ORG_CITY: CHARLESTON

ORG_NAME: RALPH H JOHNSON VA MEDICAL CENTER

ORG_STATE: SC

PHR: Abdominal aortic aneurysms (AAA) afflict ~8% of Americans and ruptured AAA carries >80% mortality. AAA screening programs have increased identification of small AAA, but there is no medical therapy to attenuate dilation and rupture rates have not decreased. Thus, the treatment paradigm of annual surveillance of growth toward the surgical threshold has not been revised in over 20 years. In retrospect, clinical trials of medical therapy for AAA may have failed to show an effect on rate of growth due to the broad inclusion criteria. We propose that easily accessible, minimally invasive techniques may be engaged to gather biomechanical data of small AAA to improve characterization of this pathology. More specifically, aortic strain and plasma pathologic matrix markers may reflect the evolving aortic wall remodeling. Using computational analysis of acquired biomechanical data, this project will establish a model to define AAA biology that will be responsive to medical therapy, thereby shifting the current surgical treatment paradigm.

PI_NAMEs: RUDDY, JEAN MARIE  (contact)

PROJECT_TERMS: abdominal aorta;Abdominal Aortic Aneurysm;American;Animals;Aorta;Attenuated;Biological Markers;Biology;Biomechanics;Blood Vessels;calcification;Cathepsins;Characteristics;Clinical;clinical application;clinical care;Clinical Trials;Complement;Computer Analysis;Computer Models;cytokine;Cytometry;Data;Dependence;Diameter;druggable target;Enrollment;Fibroblasts;Foundations;Gelatinase B;Glucocorticoids;Growth;Histologic;Image;improved;in vivo;inclusion criteria;Individual;Inflammation;Inflammatory;Inflammatory Infiltrate;inhibitor;inhibitor therapy;interest;Interleukin-6;Laboratories;Losartan;Macrophage;Measurement;mechanical force;mechanical signal;Mechanics;Medical;minimally invasive;Modeling;mortality;Mus;network models;Operative Surgical Procedures;Osteoblasts;Pathologic;Pathology;Pathway interactions;Patients;Peptide Hydrolases;Peptides;Phenotype;Phosphotransferases;Physiologic pulse;Plasma;post gamma-globulins;pre-clinical;Production;Radial;receptor;repaired;Role;Rupture;Ruptured Abdominal Aortic Aneurysm;screening program;Serum;Signal Transduction;Signaling Molecule;Specialist;specific biomarkers;stressor;System;Techniques;Technology;Tenascin;Testing;Tumor necrosis factor receptor 11b;ultrasound;Up-Regulation;Work

PROJECT_TITLE: Targeting Biomechanical Signaling in AAA

STUDY_SECTION_NAME: Special Emphasis Panel[ZRD1 SURG-P (01)]


ADMINISTERING_IC: MH

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Anxiety Disorders;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Health Services;Mental Health;Mental Illness;Post-Traumatic Stress Disorder (PTSD);Precision Medicine

ORG_CITY: BOSTON

ORG_COUNTRY: UNITED STATES

ORG_DEPT: PSYCHIATRY

ORG_FIPS: US

ORG_NAME: BOSTON UNIVERSITY MEDICAL CAMPUS

ORG_STATE: MA

PHR: Project Narrative Evidence-based treatments for posttraumatic stress disorder (PTSD) are available, but they have suboptimal rates of symptom improvement and high rates of dropout, and evidence suggests that patients' concerns about treatment and therapists' ineffective responses to these concerns prevent optimal outcomes. This trial tests an Adjunctive Writing intervention for Amplifying Response and Engagement (AWARE), which integrates findings from the health communication literature to optimize patient outcomes in evidence-based PTSD treatments via the target mechanism of improved patient-therapist communication about patients' treatment-related concerns. This trial has the potential to enhance outcomes for patients with PTSD and improve the field's knowledge of processes for enhancing PTSD treatments, and further, given that AWARE is a brief intervention that provides structure for improving patient-therapist communication during existing check-ins in evidence-based, widely disseminated treatments, AWARE can be easily scaled and implemented to enhance patient outcomes in treatments across mental health disorders.

PI_NAMEs: ALPERT, ELIZABETH ROSE (contact)

PROGRAM_OFFICER_NAME: SWEENEY, MARY MARGARET

PROJECT_TERMS: Adherence;Adult;Affect;Boston;brief intervention;Case Series;Cognitive;Communication;Competence;Conduct Clinical Trials;Data;Data Analyses;Development;Diagnosis;Disclosure;Disease;Dropout;Drops;Effectiveness;efficacy evaluation;Evaluation;evidence base;Evidence based treatment;experience;Feedback;Health;health application;health communication;Healthcare Systems;improved;improved outcome;Individual;Intervention;Investigational Therapies;Knowledge;knowledge integration;Literature;Medical;Mental disorders;Mentors;National Institute of Mental Health;novel;Outcome;outcome prediction;Participant;patient engagement;patient oriented;patient retention;patient-clinician communication;Patient-Focused Outcomes;Patients;Population;Post-Traumatic Stress Disorders;Preparation;prevent;Procedures;Process;Protocols documentation;Randomized, Controlled Trials;reduce symptoms;Reporting;Research;Research Personnel;response;satisfaction;Scientific Advances and Accomplishments;Societies;Statistical Data Interpretation;Structure;symptom treatment;symptomatic improvement;Symptoms;Testing;theories;Therapeutic;Therapeutic procedure;Training;Translating;Translations;Trauma;treatment as usual;Treatment outcome;treatment response;Writing

PROJECT_TITLE: Enhancing PTSD Treatment Outcomes by Improving Patient-Provider Communication

STUDY_SECTION: SERV

STUDY_SECTION_NAME: Mental Health Services Study Section[SERV]


ADMINISTERING_IC: VA

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: Veterans Affairs

PHR: Multiple sclerosis (MS) is a disabling neurological disease affecting individuals in their most productive years and is prevalent among US Veterans. MS is an autoimmune disease of the central nervous system where self- reactive T and B lymphocytes destroy myelin. Recently, B cell depleting anti-CD20 therapy has been approved for the treatment of patients with MS but with limited success and concerns of adverse effects/complications from global depletion of B cells. This proposal is to evaluate the preclinical potential of drugs targeting S- nitrosoglutathione reductase (GSNOR) for B cell immunomodulation that suppresses effector B cell activities (disease-causing) while inducing regulatory B cell activities (protecting against MS).

PI_NAMEs: SINGH, INDERJIT  (contact)

PROJECT_TERMS: adoptive B cell transfer;Adverse effects;Affect;Alternative Therapies;Animal Model;anti-CD20;Antibodies;asthmatic patient;Attenuated;Autoantibodies;Autoantigens;Autoimmune;Autoimmune Diseases;Autoimmune Process;Autoimmune Responses;Autoimmunity;autoreactive T cell;autoreactivity;B cell therapy;B-Lymphocytes;Catabolism;Cell Physiology;Cells;Central Nervous System Diseases;Clinical;CNS autoimmune disease;Cystic Fibrosis;cytokine;Development;Disabling;Disease;Disease Progression;Disease remission;Dose;Down-Regulation;drug efficacy;Drug Targeting;effector T cell;Enzymes;Equilibrium;Experimental Autoimmune Encephalomyelitis;Generations;Genes;Granulocyte-Macrophage Colony-Stimulating Factor;Helper-Inducer T-Lymphocyte;HIF1A gene;Homeostasis;Human;human disease;Immune response;immunoregulation;In Vitro;in vivo;Individual;Infiltration;inhibitor;Injectable;insight;Interferon Type II;Interleukin-10;Interleukin-6;IRF4 gene;Laboratories;Mediating;Modeling;Multiple Sclerosis;multiple sclerosis patient;multiple sclerosis treatment;Mus;Myelin;Nervous System Disorder;neuroprotection;neutralizing antibody;new therapeutic target;Nitric Oxide;novel;novel therapeutics;Opportunistic Infections;Oral;Oxidoreductase;Pathogenicity;Pathologic;Pathway interactions;Phase;Physiological;Play;Post-Translational Protein Processing;pre-clinical;Productivity;Recovery;Regulation;Regulatory T-Lymphocyte;Reporting;response;Role;S-Nitrosoglutathione;S-Nitrosothiols;Safety;Signal Transduction;success;T-Lymphocyte;targeted treatment;Testing;Therapeutic;tositumomab;Toxic effect;transcription factor;translational potential;treatment duration;treatment optimization;Up-Regulation;Veterans

PROJECT_TITLE: Immunomodulation and Neuroprotection in Multiple Sclerosis

STUDY_SECTION_NAME: Special Emphasis Panel[ZRD1 NURB-H (01)]


FUNDING_MECHANISM: RESEARCH CENTERS

ORG_NAME: VA BOSTON HEALTH CARE SYSTEM

PHR: Photosensitivity is common following a mild traumatic brain injury (mTBI) and can significantly impair functional rehabilitation outcomes. While sunglasses are conventionally used to treat symptoms, they are not designed to resolve issues with photosensitivity underscoring the need to develop more effective treatment options. Recent work has shown that neurofeedback interventions, such as Low Intensity Pulse-Based Transcranial Electrical Stimulation (LIP-tES) can be effective in treating post-concussive symptoms, but it remains unknown how LIP- tES interventions alter brain activity and whether this approach can help alleviate photosensitivity symptoms, specifically. This proposal will address these questions by conducting a pilot study on LIP-tES for the treatment of photosensitivity and collect resting-state functional neuroimaging scans before and after intervention. Results of this study may significantly improve functional outcomes for veterans living with photosensitivity and further our understanding of the pathophysiological mechanisms underlying photosensitivity in mTBI.

PI_NAMEs: FORTENBAUGH, FRANCESCA COWDEN (contact)

PROJECT_TERMS: acceptability and feasibility;Acute;Address;Aftercare;Anxiety;Area;Behavioral;Brain;Case Study;Center for Translational Science Activities;Cephalic;Chronic;chronic pain;chronic painful condition;Classification;Clinic;Clinical;cognitive function;comorbidity;connectome;Data;Department of Defense;Development;Diagnosis;Diagnostic;Disease;economic impact;effective therapy;Electric Stimulation;Enrollment;Evaluation;experience;Eye;Eye diseases;Eyeglasses;Feasibility Studies;feasibility testing;Functional impairment;functional improvement;Functional Magnetic Resonance Imaging;Headache;High Prevalence;Impairment;improved;Individual;Intervention;Investigation;Knowledge;Laboratories;Longitudinal cohort study;Measures;Mental Depression;Mental disorders;Meta-Analysis;mild traumatic brain injury;military veteran;Modeling;MRI Scans;Nervous System Disorder;Neurobiology;neurofeedback;neuroimaging;neurophysiology;novel;novel strategies;Outcome;Pain;Participant;participant enrollment;Patients;Photosensitivity;Physical Function;Physiologic pulse;Pilot Projects;Population;post intervention;Post-Concussion Syndrome;Post-Traumatic Stress Disorders;procedure safety;Procedures;Protocols documentation;psychiatric comorbidity;Psychological Impact;Psychopathology;Recording of previous events;Recovery;recruit;reduce symptoms;Rehabilitation Outcome;Rehabilitation therapy;remediation;Reporting;Research;research and development;response;Rest;Risk Factors;Sample Size;Sampling;Scanning;screening;Sensory;service member;Severities;Sleep;Sleep disturbances;Social Functioning;stress disorder;sunglasses;symptom treatment;Symptoms;TBI Patients;technology development;technology intervention;Testing;therapy design;Time;Traumatic Brain Injury;treatment duration;treatment effect;Treatment Efficacy;Treatment Protocols;Veterans;Veterans Health Administration;Visit;Work

PROJECT_TITLE: A Novel Neurofeedback Intervention for Photosensitivity in Mild Traumatic Brain Injury

STUDY_SECTION: RRDS

STUDY_SECTION_NAME: Rehabilitation Research and Development SPiRE Program[RRDS]


ADMINISTERING_IC: AG

IC_NAME: NATIONAL INSTITUTE ON AGING

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Brain Disorders;Dementia;Genetics;Neurodegenerative;Neurosciences;Prevention;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: SEATTLE

ORG_DEPT: PATHOLOGY

ORG_NAME: UNIVERSITY OF WASHINGTON

ORG_STATE: WA

PHR: NARRATIVE Alzheimer’s disease is a highly prevalent neurodegenerative disorder and involves deficiencies in endo- lysosomal trafficking. The AD risk gene, SORL1, is a mediator of endo-lysosomal trafficking in conjunction with the multiprotein sorting complex retromer and represents a novel therapeutic target. In this proposal we will elucidate cell-type specific actions of the SORL1-retromer pathway in human neurons and glia; we will also use patient tissue and derived cell lines to assess how a polygenic burden of endo-lysosomal risk in impacts endosomal and lysosomal morphology and neural gene expression.

PI_NAMEs: JAYADEV, SUMAN ;YOUNG, JESSICA ELAINE (contact)

PROGRAM_OFFICER_NAME: BARRETT, PAUL JOHN

PROJECT_TERMS: Affect;Alzheimer's Disease;Alzheimer's disease brain;Alzheimer's disease diagnosis;Alzheimer's disease related dementia;Alzheimer's disease risk;Alzheimer's disease therapeutic;Amyloid;Area;Automobile Driving;Autopsy;Biological Assay;brain tissue;Cause of Death;Cell Differentiation process;Cell Line;Cell Physiology;cell type;Cells;Cellular Assay;Cellular biology;Central Nervous System;Code;cohort;Complex;cytokine;Cytopathology;Data;Disease;Early Endosome;early onset;Endocytosis;Endosomes;experimental study;Functional disorder;Gene Expression;Genes;Genetic;genetic association;Genetic Risk;Genome;genome wide association study;Human;human induced pluripotent stem cells;Immune;immune function;Immune response;Immunoprecipitation;Impairment;Individual;Knowledge;Late Onset Alzheimer Disease;Lysosomes;Mediator;Microglia;Modeling;Morphology;multi-electrode arrays;Mutation;network dysfunction;neural;Neurodegenerative Disorders;Neuroglia;Neuronal Differentiation;Neurons;neuropathology;new therapeutic target;Organelles;Pathogenesis;Pathogenicity;Pathologic;Pathology;Pathway interactions;Patients;Phagocytosis;pharmacologic;Phenotype;Physiological;Process;Property;Protein Analysis;protein protein interaction;Protein Sortings;Proteins;rare variant;receptor recycling;Recycling;response;Risk;Risk Factors;risk variant;Series;small molecule;Swelling;Synapses;synaptic function;Tauopathies;Testing;Therapeutic;therapeutic development;Tissues;trafficking;transcriptome;transcriptomics;Variant;Viral Vector

PROJECT_TITLE: Characterization of AD-related endolysosomal dysfunction in human neural cells

STUDY_SECTION: CMND

STUDY_SECTION_NAME: Cellular and Molecular Biology of Neurodegeneration Study Section[CMND]


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Autoimmune Disease;Cancer;Diabetes;Digestive Diseases;Pancreatic Cancer;Pediatric;Rare Diseases

ORG_CITY: CHICAGO

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF CHICAGO

ORG_STATE: IL

PHR: Project Narrative The proposed project will precisely map the vessels that supply blood to the two tissues of the pancreas—the exocrine tissue that makes digestive enzymes to breakdown our food and the endocrine tissue that makes insulin to control blood sugar. For many years, those who study and treat patients with pancreatic disorders have been taught that the exocrine and endocrine parts of the pancreas have separate blood supplies that do not mix. However, we have discovered that these two intimately located pancreatic tissues share a common blood supply, and through mapping these blood vessels, we hope to explain how disease in one part of the pancreas often results in failure of the other part.

PI_NAMEs: HARA, MANAMI  (contact);HIBINO, NARUTOSHI

PROGRAM_OFFICER_NAME: ZAGHLOUL, NORANN

PROJECT_TERMS: 3-Dimensional;Acinar Cell;Acute;age related;Age Years;Allogenic;Anatomy;Animals;arteriole;Autoimmune Diseases;Beta Cell;Biology;Blood capillaries;Blood flow;Blood Glucose;Blood Vessels;Cell Physiology;Cells;Cellular Morphology;Characteristics;Childhood;Chronic;Clinical;Collection;Communities;Complex;Data;Dedications;Defect;density;Detection;Deterioration;Developmental Process;Diabetes Mellitus;diabetic;Diffusion;Discipline;Disease;Educational process of instructing;Endocrine;Endocrinologist;Endocrinology;Endothelial Cells;Enzymes;Erythrocytes;Exocrine pancreas;Exposure to;Failure;Family suidae;Ferrets;Food;Gastroenterologist;Gastroenterology;Genetic;Hormones;Human;Human Characteristics;Immunology;Impairment;In Situ;in situ imaging;in vivo;in vivo evaluation;in vivo Model;Inbred NOD Mice;indexing;Individual;Insulin;insulin signaling;Insulin-Dependent Diabetes Mellitus;insulitis;islet;Islet Cell;Islets of Langerhans;Islets of Langerhans Transplantation;Label;Link;Malignant neoplasm of pancreas;Maps;Measurement;Measures;Medical;Microcirculation;Modeling;Molecular;Molecular Profiling;Monitor;Monkeys;mouse model;multidisciplinary;Mus;Non-Insulin-Dependent Diabetes Mellitus;nutrient blood level;Onset of illness;Operative Surgical Procedures;Organ;Organ Donor;Oryctolagus cuniculus;Pancreas;pancreas imaging;Pancreatic Diseases;Pancreatitis;Pathogenesis;Pathology;Patients;Pattern;Physicians;Physiology;Population;Portal System;Reporting;Research;spatial relationship;Specimen;Structure;Symptoms;Technology;Testing;Thick;Three-dimensional analysis;Three-Dimensional Imaging;Tissues;transcriptomics;Vascular blood supply;Vascularization;venule;Visit

PROJECT_TITLE: Blood flow crosstalk between the endocrine and exocrine pancreas

STUDY_SECTION_NAME: Special Emphasis Panel[ZDK1 GRB-W (O2)]


FUNDING_MECHANISM: OTHERS

ORG_CITY: Aurora

ORG_NAME: VA EASTERN COLORADO HEALTH CARE SYSTEM

ORG_STATE: CO

PHR: Project Narrative Diseases of the gastrointestinal tract, including Inflammatory Bowel Disease (IBD), remain some of the most debilitating diseases among veterans. With the incidence on the rise, a fundamental understanding of IBD is essential to developing effective therapies and an eventual cure for this disease. Our ongoing research is aimed at defining new mechanisms to promote wound healing in patients with active disease. Our strategy is to use a highly collaborative, broad-spectrum approach that integrates trainees as a mechanism to bolster the next generation of biomedical veteran research scientists.

PI_NAMEs: COLGAN, SEAN P (contact)

PROJECT_TERMS: Abbreviations;Actins;American;Apical;Area;Autophagocytosis;Award;Big Data;Biological Response Modifier Therapy;Biomedical Research;Butyrates;career;Chronic Disease;Coin;Collaborations;Colon;Complex;Creatine;Creatine Kinase;creatine transporter;Crohn's disease;Development;Diet;Digestive System Disorders;Disease;Disease remission;driving force;dysbiosis;effective therapy;energy balance;Energy Metabolism;Environment;Epithelium;F-Actin;Faculty;Family;Fostering;Functional disorder;fundamental research;G Actin;Gastrointestinal Diseases;Generations;graduate student;gut microbiome;Histone Deacetylase;Hospitalization;hospitalization rates;Human;Hypoxanthines;Hypoxia;Hypoxia Inducible Factor;Hypoxia-Inducible Factor Pathway;Incidence;Indoles;Inflammatory;Inflammatory Bowel Diseases;Inflammatory Response;Infrastructure;Innate Immune System;interdisciplinary approach;Intestinal Diseases;Knowledge;Leaky Gut;Left;Life;Medical center;Medicine;Mentors;Metabolic Pathway;Metabolism;microbial;microbiota;military service;military veteran;Modeling;Molecular Target;Monocarboxylic Acid Transporters;Mucositis;Mucous Membrane;Mus;Natural Immunity;Nature;next generation;Nobel Prize;novel therapeutics;Nucleoside Transporter;nutrient absorption;Organ;Oxygen;Pathogenesis;Pathologic;Patients;Permeability;Persons;Phenotype;Phosphocreatine;Physiological;Physiology;Play;polymerization;Polymers;Postdoctoral Fellow;preservation;Prevalence;Productivity;Purines;readmission rates;Regulation;Research;Research Personnel;Research Training;Resolution;Role;Scientist;service member;Severities;Source;Starvation;stressor;Symbiosis;Syndrome;Therapeutic;Therapeutic Intervention;Tight Junctions;Tissues;Training;training opportunity;transcription factor;Translating;Tryptophan;Ulcerative Colitis;United States;United States Department of Veterans Affairs;Veterans;Volatile Fatty Acids;Work;wound healing

PROJECT_TITLE: BLRD Research Career Scientist Award Application

STUDY_SECTION_NAME: Special Emphasis Panel[ZRD1 RCSR-N (01)]


PHR: Chronic Post-amputation Pain (cPAP) is a major unsolved healthcare problem, especially prevalent in the Veteran population, and notoriously difficult to treat. We seek to answer key clinical questions that will improve patient management using the framework of the Million Veteran Program (MVP). First, we will identify a robust multi-faceted MVP-specific phenotype for cPAP that will serve future studies by our team and other researchers. The core, second aim of this proposal is to identify common and rare genetic risk factors for cPAP and its genetic overlap with related disorders such as anxiety, depression and PTSD. Finally, we will model the effects of perioperative management and psychosocial factors and Social Determinants of Health on the development of cPAP. This proposal supports a future line of research aimed to inform a comprehensive risk score to assess amputees’ risks of developing chronic pain, and to potentially identify novel therapeutic interventions via identification of pathways genetically associated with cPAP.

PI_NAMEs: OTIS, JOHN D (contact)

PROJECT_TERMS: Address;Affect;Age;Algorithms;Amputation;Amputees;Anxiety;Baseline Surveys;Biological;Biological Response Modifier Therapy;Blood Vessels;Caring;Characteristics;Chronic;Chronic low back pain;chronic pain;Classification;Clinic;Clinical;clinically relevant;clinically significant;Cluster Analysis;Code;cohort;cost;Coupled;Data;Data Set;data warehouse;Databases;demographics;Dependence;Development;diabetic;Diagnosis;Disease;Electronic Health Record;Emergency department visit;Enrollment;Environmental Risk Factor;Ethnic Origin;Functional disorder;Future;Gender;Genetic;genetic association;Genetic Drift;genetic predictors;Genetic Risk;genetic risk factor;Genetic study;genetic variant;genome wide association study;genome-wide analysis;Goals;Health;health care service utilization;Health Services Accessibility;Healthcare;high risk;holistic approach;Hospital Administration;Hospitals;Impairment;improved;Incidence;Individual;individualized prevention;insight;International Classification of Disease Codes;Intervention;Knowledge;limb amputation;Limb structure;Lower Extremity;machine learning algorithm;Manuals;Medicine;Mental Depression;Mental disorders;Mental Health Services;Methods;military veteran;Modality;Modeling;mortality;Musculoskeletal Pain;Natural Language Processing;new therapeutic target;non-genetic;novel;novel therapeutic intervention;novel therapeutics;Operative Surgical Procedures;opioid therapy;Other Genetics;Outcome Measure;Pain;Pain Measurement;Participant;Pathway interactions;patient population;Patient-Focused Outcomes;Patients;Pattern;Perioperative;Perioperative Care;Peripheral Nerves;Phantom Limb Pain;Pharmaceutical Preparations;Pharmacotherapy;Phenotype;Physical therapy;physically handicapped;Population Control;post-amputation pain;Post-Traumatic Stress Disorders;Postoperative Period;Predisposing Factor;prescription opioid;Prevalence;prevent;Prevention strategy;Preventive;primary outcome;programs;psychologic;psychosocial;Psychosocial Assessment and Care;Psychosocial Factor;Quality of life;Race;reduce symptoms;regenerative;Rehabilitation therapy;Research;Research Personnel;residual limb;Resources;Risk;Risk Factors;Role;Schizophrenia;screening;Severities;social health determinants;Societies;Solid;Substance Use Disorder;Syndrome;Therapeutic;therapeutic target;Time;trait;Treatment/Psychosocial Effects;tumor;United States Department of Veterans Affairs;Variant;Veterans;Veterans Health Administration;Well in self

PROJECT_TITLE: Identification of Procedural, Genetic and Psychosocial Risk Factors for ChronicPost-Amputation Pain

STUDY_SECTION_NAME: Special Emphasis Panel[ZRD1 NURP-N (01)]


ORG_CITY: LOS ANGELES

ORG_NAME: VA GREATER LOS ANGELES HEALTHCARE SYSTEM

ORG_STATE: CA

PHR: For Veterans with Serious Mental Illness (SMI) experiencing homelessness, obtaining permanent housing is only the first step in achieving stability and improved quality of life. Many recently housed Veterans continue to struggle with aspects of functioning and day-to-day living. Maintaining connection with providers and sustaining engagement in treatment during the transition to permanent housing are additional challenges. While the VA has made considerable efforts to provide mental health care to Veterans with SMI, few treatments designed to increase functional recovery have been applied during this key period of transition out of homelessness. In this pilot study, we will administer a brief behavioral treatment enhanced with mobile technology, conducted within the GLA Domiciliary residential treatment program. With this research we hope to learn whether such treatments can be applied to meet the unique needs of homeless Veterans with SMI and could prove effective in improving community integration so that these individuals may function more fully in their lives and society.

PI_NAMEs: JIMENEZ, AMY M (contact)

PROJECT_TERMS: acceptability and feasibility;Address;Adherence;Aftercare;Appointments and Schedules;arm;Award;barrier to care;Behavior;Behavior Therapy;Behavioral;Benchmarking;Bipolar Disorder;Caring;Cellular Phone;Clinical;clinical care;cognitive ability;Cognitive Therapy;Communities;Community Integration;community reintegration;Continuity of Patient Care;cost;Data;digital technology;digital tool;Disadvantaged;Disease;efficacy study;Enrollment;evidence base;experience;experimental arm;falls;feasibility testing;follow up assessment;follow-up;functional improvement;functional independence;Future;gaps in access;Goals;Healthcare;healthcare burden;Healthcare Systems;Homeless persons;Homelessness;Housing;Hybrids;Imprisonment;improved;improved outcome;Independent Living;indexing;Individual;innovation;Intervention;Interview;Investments;Learning;Location;Los Angeles;Maintenance;Measures;Mental Health;Mental Health Services;military veteran;mindfulness;Mindfulness Training;mobile computing;Mobile Health Application;mortality;Motivation;motivational enhancement therapy;Outcome Measure;Participant;Patient Recruitments;Persons;Pilot Projects;Population;Predisposition;primary outcome;Prognosis;Provider;psychosocial;Psychotherapy;Public Health;Quality of life;Randomized;Randomized, Controlled Trials;Recovery of Function;Recreation;recruit;remote administration;remote intervention;Research;Residential Treatment;Resources;satisfaction;Schizophrenia;screening;service utilization;Services;severe mental illness;skills;smartphone application;social;Societies;Structure;supported housing;Supportive care;Symptoms;Technology;technology intervention;Telephone;Therapeutic;Therapeutic Intervention;therapy design;Thinking;Time;Transportation;treatment arm;treatment program;United States Department of Veterans Affairs;Veterans;Veterans Health Administration;Victimization;Visit;Vocation;willingness

PROJECT_TITLE: Improving Community Integration in Homeless Veterans with Serious Mental Illness: A Pilot Study of MI-CBT Enhanced with Mobile Technology


ORG_CITY: St. Louis

ORG_NAME: ST. LOUIS VA MEDICAL CENTER

ORG_STATE: MO

PHR: 40% of veterans have hypertension (HTN), a leading modifiable cause of cardiovascular disease (CVD). However, a significant proportion of veterans do not have adequately controlled HTN despite multidrug regimens, highlighting the need for novel therapeutic approaches. Vitamin D (VD) deficiency is highly prevalent in veterans, and we have determined that disruption of VD signaling in macrophages induces HTN and promotes macrophage renin secretion, which surprisingly has the capacity to regulate systemic blood pressure and macrophage function. We propose to evaluate the mechanisms by which macrophage renin causes HTN associated with disrupted VD signaling and to characterize its impact on macrophage function. Successful completion of the proposed aims and training plan will prepare the candidate to become an independent physician scientist identifying translational therapies to reduce the risk of metabolic disease and its complications in veterans.

PI_NAMEs: BAUERLE, KEVIN T (contact)

PROJECT_TERMS: Academic skills;Address;Advisory Committees;Automobile Driving;Award;Blood Pressure;blood pressure regulation;Bone Marrow Transplantation;cardiometabolism;Cardiovascular Diseases;cardiovascular disorder risk;Cardiovascular system;career;career development;Cells;Cellular biology;Chronic Disease;Colorado;Development;Doctor of Medicine;Doctor of Philosophy;Endocrine;Endocrinology;Ensure;experience;experimental study;Fellowship;Genetic Transcription;Goals;Grant;Healthcare Systems;Human;Hypertension;hypertension control;Immune;immune function;Immunology;immunoregulation;Impairment;Inflammatory;instructor;Internal Medicine;Israel;Knockout Mice;Knowledge;Laboratories;Macrophage;Mediating;Medical center;medical schools;Medicine;Mentors;Metabolic Diseases;metabolic phenotype;military veteran;Monitor;mouse model;Mus;novel;novel therapeutic intervention;Nuclear Hormone Receptors;Outcome;Pharmaceutical Preparations;Phenotype;Physicians;Physiological;Production;programs;Publishing;Regimen;Renin;Renin-Angiotensin System;Research;Residencies;Risk Reduction;Role;Scientist;Signal Transduction;skills;Stroke;symposium;Systemic blood pressure;Systemic hypertension;systemic inflammatory response;Testing;Tissues;Training;translational therapeutics;Universities;Up-Regulation;Veterans;Vitamin D;Vitamin D Deficiency;Vitamin D3 Receptor;Washington;Work;Writing

PROJECT_TITLE: The Role of Vitamin D Deficiency-induced Macrophage Renin Angiotensin System Activation in the Development of Hypertension

STUDY_SECTION_NAME: Special Emphasis Panel[ZRD1 CARB-R (01)]


ORG_NAME: JESSE BROWN VA MEDICAL CENTER

PHR: Rheumatoid arthritis (RA) is more prominent in women and has greater severity in the Hispanic and Black populations. One in 4 veterans has arthritis (25.6%), compared to 1 in 5 civilians. RA is a disabling autoimmune disease that is associated with depression, cardiovascular disease, and psychosocial stress as well as being more prominent in women. Our clinic at the Jesse Brown VA sees around 700-900 RA patients annually. There is no cure for RA and up to 50% of RA patients do not respond to current therapies. Therefore, we aim to find a novel therapy that can slow or reverse RA pannus formation. To resolve the critical barrier in RA treatment, we have identified a novel pathway that plays a central role in pannus formation by linking immune cell activation with joint blood vessel formation. The goal of our research program is to understand the mechanism of the identified unique pathway and to evaluate whether the blockade of its function may be more effective than the current standard of care therapies.

PI_NAMEs: SHAHRARA, SHIVA  (contact)

PROJECT_TERMS: Affect;angiogenesis;Anti-Tumor Necrosis Factor Therapy;Area;Arthritis;arthritis therapy;Arthritogenic;arthropathies;Autoimmune Diseases;Autoimmunity;Award;bench to bedside;Binding;Biological Response Modifier Therapy;Biological Sciences;Black Populations;Blood;blood vessel development;Blood Vessels;bone erosion;c-myc Genes;Carbon;Cardiovascular Diseases;career;Caring;CCL21 gene;CD14 gene;CD86 gene;Cell Reprogramming;cell type;Cells;Cellular biology;Cellular Immunology;chemokine;Chronic;Circulation;Clinic;Clinical;Collagen Arthritis;Complement Factor H;cytokine;Diagnosis;Disabling;Disease;Doctor of Philosophy;Down-Regulation;editorial;effectiveness evaluation;effector T cell;Endogenous Factors;Endothelial Cells;Environment;exosome;Faculty;Family;Fibroblasts;Foundations;Frequencies;Funding;Genetic Transcription;Glucose;glucose uptake;Goals;Grant;Grant Review;Health;HIF1A gene;High Fat Diet;Hispanic Populations;Human Resources;IL7 gene;IL7R gene;Immune;immune activation;Immunology;Impairment;imprint;improved;Infiltration;Inflammatory;Inflammatory Arthritis;Infrastructure;inhibitor;inhibitor therapy;innovation;Intercept;Interleukin-12;Interleukin-6;IRAK4 gene;joint inflammation;Joints;Journals;Label;Laboratories;Leadership;Ligands;Ligation;Link;Macrophage;Mediating;Mediator;Medical Care Costs;Medical center;medical schools;Medicine;meetings;member;Mental Depression;Mentors;Metabolic;metabolic phenotype;metabolic profile;Military Personnel;Mitochondria;Modeling;Molecular;Molecular Immunology;monocyte;Monokines;mouse model;Mus;Myelogenous;Myeloid Cells;Nature;neovascularization;neovasculature;new therapeutic target;novel;novel marker;novel therapeutics;Obesity;Operative Surgical Procedures;Osteoclasts;Pain;Pathogenesis;Pathway interactions;Patients;Peer Review;Persons;Phase;phase 4 study;Phenotype;Physicians;Play;polarized cell;Postdoctoral Fellow;Pre-Clinical Model;Productivity;programs;Psoriasis;Psoriatic Arthritis;Psychosocial Stress;Publishing;Quality of life;RANTES;recruit;Regulation;Research;Research Personnel;response;restraint;Rheumatoid Arthritis;Rheumatology;Rhubarb food;Risk Factors;Role;Scientist;Secondary to;Seminal;Severities;SLC2A1 gene;Specimen;standard of care;Structure;Synovial Fluid;T cell differentiation;T-Lymphocyte;three dimensional cell culture;Time;Tissues;TLR4 gene;TLR7 gene;TNF gene;trafficking;transcriptome sequencing;Translating;translational medicine;United States National Institutes of Health;Universities;Up-Regulation;Vascularization;Veterans;Woman;Work


ORG_CITY: CORAL GABLES

ORG_NAME: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE

ORG_STATE: FL

PHR: PROJECT NARRATIVE The exocrine pancreas of patients with type 1 diabetes is smaller than the pancreas of healthy subjects and shows histological and functional anomalies. This project is aimed at generate mechanistic insight into how beta cells influence surrounding tissues to coordinate activity across pancreas compartments. By identifying the effectors and principles governing this local regulation, we will be able to understand how the progressive loss of beta cell function produces pathological changes across pancreas compartments in people with type 1 diabetes.

PI_NAMEs: ALMACA, JOANA ;BERNAL-MIZRACHI, ERNESTO ;CAICEDO, ALEJANDRO  (contact)

PROJECT_TERMS: Acinar Cell;Acute;Address;Adult;Affect;Anatomy;Atherosclerosis;autoimmune pathogenesis;Beta Cell;Blood flow;blood glucose regulation;Blood Vessels;Cell Physiology;Cells;cholinergic;Chronic;chronic pancreatitis;Data;Dedications;Deterioration;Development;Diabetes Mellitus;diabetic;Disease;Endocrine;Endothelial Cells;Enteral;Etiology;Exocrine pancreas;Fibrosis;Functional disorder;Gene Expression;Genetic;Goals;Histologic;Human;Impairment;in vivo;Individual;Infiltration;Inflammation;Inflammatory;insight;Insulin;Insulin Receptor;insulin secretion;insulin signaling;Insulin Signaling Pathway;Insulin-Dependent Diabetes Mellitus;islet;Islets of Langerhans;Knockout Mice;Knowledge;Measures;Mission;Modeling;mouse model;Mus;neural;Neurons;neurotransmission;nutrient absorption;Organ Donor;Pancreas;paracrine;Pathogenicity;Pathologic;Patients;Pericytes;Persons;Prevalence;Regulation;Regulatory Element;Research;response;Role;Secretory Cell;Signal Transduction;Site;Slice;Specimen;Testing;therapy development;Tissues;tool;United States National Institutes of Health

PROJECT_TITLE: Loss of insulin signaling across functional pancreas compartments as a major pathogenic mechanism underlying diabetic exocrine pancreatopathy


PHR: Emergence of chemoresistant disease enriched with poorly differentiated stem-like cells that escape chemotherapy and T immune cells is a leading cause of death in ovarian cancer (OC) patients. Our data suggests that these tumor cells can be attacked by another immune cell type called Natural Killer (NK) cells. Unfortunately, NK cells are defective and low in number in OC patients. To solve this problem our group has developed a novel platform that can activate and expand NK cells at clinically scalable levels for immunotherapy, called super charged NK (sNK) cells. In this study we will test the efficacy of sNK cells, alone and in combination with chemotherapy in targeting chemoresistant OCs. Biomarkers of response and mechanisms of tumor targeting will also be explored. Findings will have immediate potential for translation into therapies for women Veterans.

PI_NAMEs: MEMARZADEH, SANAZ  (contact)

PROJECT_TERMS: Activated Natural Killer Cell;Address;Aftercare;Allogenic;anti-cancer;Apoptotic;Automobile Driving;Bioinformatics;bioluminescence imaging;biomarker identification;BLT mice;Cancer Biology;cancer cell;Cancer Patient;CAR T cell therapy;Carboplatin;Cause of Death;CD8-Positive T-Lymphocytes;Cell Differentiation Induction;Cell Differentiation process;cell killing;Cell Physiology;Cell Therapy;cell type;Cells;Cellular immunotherapy;Charge;Chemoresistance;Chemosensitization;chemotherapy;Clinical;Clinical Trials;Coin;Combined Modality Therapy;cytokine;cytokine release syndrome;cytotoxic;Cytotoxic T-Lymphocytes;cytotoxicity;Data;Disease;Disease Resistance;DNA Repair;Drug Targeting;effective therapy;efficacy testing;Epithelial ovarian cancer;experimental study;Future;Genes;graft versus host disease induction;Immune;Immune checkpoint inhibitor;Immunology;Immunotherapeutic agent;Immunotherapy;In Vitro;in vivo;in vivo evaluation;innovation;Interdisciplinary Study;Interferon Type II;Interferons;Malignant neoplasm of ovary;Malignant Neoplasms;Mediating;Methods;MHC Class I Genes;Molecular;Mus;Natural Killer Cells;neoplastic cell;novel;novel therapeutic intervention;ovarian neoplasm;Ovarian Serous Adenocarcinoma;Pathway interactions;patient derived xenograft model;Patient Selection;Patients;peripheral blood;Phenotype;Platinum;potential biomarker;pre-clinical;Predisposition;Proteins;Recurrence;Recurrent disease;Recurrent tumor;Resistance;response;response biomarker;RNA;Role;Route;Safety;Sampling;Serous;single-cell RNA sequencing;Solid;stem-like cell;stemness;Syndrome;T-Lymphocyte;targeted treatment;Testing;Therapeutic;therapy resistant;TNF gene;tool;trait;translational potential;Translations;Treatment Efficacy;tumor;Tumor Burden;Veterans;Woman;women's diagnosis;Work

PROJECT_TITLE: Exploring super charged NK cells as a novel cell-based immune therapy in targeting platinum resistant ovarian cancers

STUDY_SECTION_NAME: Special Emphasis Panel[ZRD1 ONCA-S (01)]


ORG_CITY: SAN FRANCISCO

ORG_NAME: VETERANS AFFAIRS MED CTR SAN FRANCISCO

PHR: Pain worsens well-being and functioning, interferes with rehabilitative care and community integration, and contributes significantly to poorer health outcomes in Veterans with posttraumatic stress disorder (PTSD). Pain-trauma comorbidity is associated with greater utilization of medical services, greater use of psychiatric medication and increased total cost of treatment. The pathophysiology underlying pain-PTSD co-morbidity is currently unknown and current pharmacological treatments often lead to unwanted and debilitating side-effects. Identifying specific neural mechanisms for pain-PTSD co-morbidity will lead to the development of novel, scientifically based, therapeutic approaches for treating co-occurring pain in this treatment resistant population. The proposed research is relevant to Veterans health since it aims to lessen suffering and morbidity associated with co-occurring pain and trauma and decrease the total cost of treatment for the Veteran population.

PI_NAMEs: STRIGO, IRINA A (contact)

PROJECT_TERMS: Affect;Amygdaloid structure;Anxiety;Biological;Biological Markers;Brain;Brain Injuries;chronic pain;chronic painful condition;cohort;combat;combat trauma;Community Integration;comorbidity;Data;Development;disability;Disease;expectation;Functional disorder;Functional Magnetic Resonance Imaging;Funding;Goals;Graph;Health;Heterogeneity;Impairment;Individual;insight;Insula of Reil;Interoception;Intervention;Literature;Medical;Midbrain structure;military veteran;Modeling;Morbidity - disease rate;neural;neural circuit;neural network;neuroimaging;neuromechanism;novel;Opioid Analgesics;opioid use;Pain;pain perception;pain processing;pain relief;pain symptom;Personal Satisfaction;personalized intervention;Pharmaceutical Preparations;Pharmacological Treatment;poor health outcome;Population;Post-Traumatic Stress Disorders;Prevention;Process;promote resilience;psychologic;Publishing;rehabilitative care;Research;Resistance;Resort;response;Rest;Role;Sampling;Services;Severities;side effect;Stress;Subgroup;symptomatic improvement;System;Testing;Therapeutic;Training;Trauma;trauma symptom;traumatic stress;Treatment Cost;Validation;Veterans;Work

PROJECT_TITLE: The role of expectation in the pain-trauma co-morbidity among Veterans


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease Related Dementias (ADRD);Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Amyotrophic Lateral Sclerosis (ALS);Brain Disorders;Dementia;Frontotemporal Dementia (FTD);Genetics;Microbiome;Neurodegenerative;Neurosciences;Rare Diseases

ORG_CITY: CLEVELAND

ORG_NAME: CASE WESTERN RESERVE UNIVERSITY

ORG_STATE: OH

PHR: Project Narrative A mutation in C9ORF72, a gene of poorly defined function, is the most common cause of Frontotemporal dementia and Amyotrophic lateral sclerosis, neurodegenerative disorders that together affect approximately sixty thousand individuals in the United States and approximately 1.4 million people worldwide. This proposal seeks to identify pathways within T cells that contribute to neural inflammation in mice with a C9ORF72 mutation. Evaluation of T cell fate choice and function in human C9ORF72 carriers may be useful to reveal pathways important for neurodegeneration and in the future could serve as a diagnostic for risk of dementia conversion.

PI_NAMEs: BURBERRY, AARON  (contact)

PROGRAM_OFFICER_NAME: MARIC, MAJA

PROJECT_TERMS: Address;Affect;Age;ALS patients;Alzheimer's Disease;Alzheimer's disease related dementia;Amyotrophic Lateral Sclerosis;Animal Model;Autoimmunity;Autologous;bacterial community;biobank;Biological Assay;Biological Markers;Blood;C9ORF72;Caring;CD4 Positive T Lymphocytes;Cell Communication;Cell Differentiation process;Cell Physiology;Cell Separation;Cells;Cerebrospinal Fluid;Circulation;Code;Cryopreservation;cytokine;Cytoskeleton;Data;dementia risk;Diagnosis;Diagnostic;Dipeptides;Disease;Disease Progression;Emotional;Equilibrium;Evaluation;Exhibits;experimental study;FOXP3 gene;Frontotemporal Dementia;frontotemporal lobar dementia amyotrophic lateral sclerosis;Functional disorder;Future;gain of function;gene product;Genes;Genetic Transcription;Genotype;Goals;gut bacteria;gut dysbiosis;gut microbes;gut microbiome;Heritability;Human;Human Chromosomes;IL17 gene;improved;Individual;Induced Mutation;Inflammation;Inflammatory;Infusion procedures;inhibitor;insight;Interleukins;Intestines;Knockout Mice;Knowledge;loss of function;loss of function mutation;Lymphoid;Macrophage;microbial;microbiome;Motor;Motor Neurons;mouse model;Mus;mutant;Mutation;mutation carrier;Myelogenous;Nerve Degeneration;Nervous System Disorder;neural;Neurodegenerative Disorders;neuroinflammation;neuroprotection;Neutrophilia;new therapeutic target;novel;Onset of illness;Pathogenesis;Pathogenicity;Pathology;Pathway interactions;Patient-Focused Outcomes;Patients;Penetrance;Persons;Prevention strategy;Production;Prognostic Marker;Proteins;Quality of life;receptor expression;Regulation;Regulatory T-Lymphocyte;response;RNA;RNA-Binding Proteins;Role;Sampling;Serum;Severity of illness;sex;Signal Transduction;Societies;systemic inflammatory response;T cell differentiation;T cell response;T-Lymphocyte;T-Lymphocyte Subsets;Testing;therapeutic target;trafficking;transcription factor;Translating;United States;Vesicle;Work

PROJECT_TITLE: Identifying T cell determinants of heritable Frontotemporal dementia

STUDY_SECTION: CNBT

STUDY_SECTION_NAME: Clinical Neuroimmunology and Brain Tumors Study Section[CNBT]


ADMINISTERING_IC: DA

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Bioengineering;Biotechnology;Brain Disorders;Cocaine;Drug Abuse (NIDA only);Neurosciences;Stimulant Use and Misuse;Substance Misuse

ORG_CITY: DAVIS

ORG_DEPT: NEUROLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA AT DAVIS

PHR: PROJECT NARRATIVE In humans, substance use disorders (SUDs) can cause long-lasting changes in the cellular makeup of neurons in the brain. Here we propose to develop new technologies to identify changes in protein expression and localization that occur in response to substance use. These novel tools may enable the design and implementation of new pharmacological treatments to treat SUDs in patients.

PI_NAMEs: KIM, CHRISTINA  (contact)

PROGRAM_OFFICER_NAME: LE, HOANG VAN

PROJECT_TERMS: Abstinence;Acute;addiction;Animals;beta-arrestin;Binding;Biochemical;Biotin;Biotinylation;Brain;Cell membrane;cell type;Cells;Chemicals;chemoproteomics;Chronic;Cocaine;cocaine exposure;cocaine use;Collaborations;design;disease model;Dopamine;Dopamine Receptor;DRD1 gene;Drug usage;Engineering;Enzymes;experimental study;Future;G-Protein-Coupled Receptors;gene network;Human;in vivo;Injections;Label;Length;Ligand Binding;Liquid Chromatography;Maps;Methodology;Methods;Molecular;Mus;Mutagenesis;Neurons;new technology;novel;Nucleus Accumbens;Patients;Pharmaceutical Preparations;Pharmacological Treatment;Prefrontal Cortex;Protein Dynamics;Protein Engineering;protein expression;Proteins;Proteome;Proteomics;Radial;receptor;Receptor Activation;reconstitution;recruit;response;RNA;screening;substance use;Substance Use Disorder;tandem mass spectrometry;Technology;Time;tool;Up-Regulation;Withdrawal;Work

PROJECT_TITLE: Engineering chemoproteomic tools for identifying molecular mechanisms of substance use disorders

STUDY_SECTION_NAME: Special Emphasis Panel[ZDA1 SKP-N (O1)]


ORG_CITY: LEXINGTON

ORG_NAME: VA MEDICAL CENTER - LEXINGTON, KY

ORG_STATE: KY

PHR: The US Veterans are at risk to develop blood cancers due to exposure to carcinogens, such as Agent Orange, during their active military service. Many of these cancers are treated with allogeneic hematopoietic cell transplantation (allo-HCT). While allo-HCT is a life-saving therapy for hematologic malignancies, this life-saving therapy has life-threatening side effects - lethal immune activation caused by cytokine release syndrome (CRS). This proposal aims to understand the mechanism of CRS regulation, identify risk for CRS and develop preventive treatment for CRS in allo-HCT therapy, which may save the lives of both the public and veterans.

PI_NAMEs: LI, XIANG-AN  (contact)

PROJECT_TERMS: Adrenal gland hypofunction;Adrenal Glands;agent orange;Allogenic;antagonist;Antigen-Presenting Cells;biological adaptation to stress;Carcinogens;CD3 Antigens;Cells;Cessation of life;clinical translation;cost;curative treatments;cytokine;cytokine release syndrome;Data;Diagnosis;Disease;donor stem cell;Dose;Exposure to;Glucocorticoids;Goals;HDL receptor;Hematologic Neoplasms;Hematopoietic Neoplasms;Hematopoietic Stem Cell Transplantation;high risk;immune activation;Immune response;Immunologic Stimulation;Immunosuppression;improved;Individual;Inflammatory;Injections;Interleukin-6;Knockout Mice;Life;Malignant Neoplasms;military service;Modeling;mortality;multidisciplinary;Mus;organ injury;Pathogenesis;Patients;Positioning Attribute;precision medicine;preclinical study;Predisposition;prevent;Prevention;Preventive therapy;Preventive treatment;Production;Publishing;Regulation;Reporting;Risk;Risk Factors;Services;side effect;Signal Transduction;SR-BI receptor;Stress;success;systemic inflammatory response;T-Lymphocyte;Testing;Time;Translating;Transplant Recipients;transplantation therapy;Veterans;Veterans Health Administration;Work

PROJECT_TITLE: Mechanism of the adrenal stress response protection against therapy-induced lethal immune activation


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Biotechnology;Brain Disorders;Epilepsy;Gene Therapy;Genetics;Intellectual and Developmental Disabilities (IDD);Neurodegenerative;Neurosciences;Orphan Drug;Rare Diseases;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_NAME: BOSTON CHILDREN'S HOSPITAL

PHR: Project narrative (3 sentences) SSADHD is a rare inborn metabolic disorder characterized by broad spectrum encephalopathy including developmental delay, intellectual disability, seizures and a risk of sudden unexpected death in epilepsy (SUDEP). SSADH-targeted gene restoration therapy is a potential cure for this debilitating disorder, but a viable vector candidate capable of driving functionally sufficient SSADH in human neurons leading to demonstrable phenotypic curable outcome is currently unavailable. Our proposal aims to develop a novel adeno-associated virus (AAV) vector with human SSADH promoter driving functional human SSADH expressions in patient stem cell-derived neurons and determine whether systemic delivery of such clinically translatable AAV vector in SSADH-deficient mice results in safe and effective SSADH restoration with appreciable phenotypic rescue, advancing the preclinical development of SSADH gene therapy for SSADHD patients.

PI_NAMEs: LEE, HING CHEONG HENRY;ROTENBERG, ALEXANDER  (contact);SAHIN, MUSTAFA

PROGRAM_OFFICER_NAME: CONRAD, CHRISTOPHER GARNER

PROJECT_TERMS: Address;adeno-associated viral vector;adenovirus mediated delivery;Aftercare;Age;aldehyde dehydrogenases;autism symptoms;Automobile Driving;autosome;Biological Assay;Blood;blood-brain barrier penetration;Brain;brain tissue;Capsid;Catabolism;cell type;Cells;clinic ready;clinical candidate;clinical development;clinical translation;Data;Dependovirus;design;Development;Developmental Delay Disorders;Disease;DNA cassette;dosage;Dose;Down-Regulation;efficacy study;Electroencephalography;Encephalopathies;enzyme deficiency;Enzymes;Epilepsy;excitatory neuron;experimental study;extend lifespan;Family member;Future;GABA Receptor;gamma-Aminobutyric Acid;Gene Expression;gene therapy;Genes;Genetic;Genomics;Goals;Heterozygote;Human;in vivo;Induced pluripotent stem cell derived neurons;Infection;inhibitory neuron;Injections;insight;Intellectual functioning disability;Interneurons;Intractable Epilepsy;intraperitoneal;Intraperitoneal Injections;Lead;Length;Life;loss of function mutation;Measures;Medical;Metabolic Diseases;meter;Mitochondria;Molecular;mouse model;Mus;Mutation;Neurons;Neurotransmitters;novel;Outcome;Parvalbumins;Pathologic;patient derived induced pluripotent stem cells;Patients;Phase;Phenotype;Physiological;preclinical development;preclinical safety;Predisposition;proband;promoter;Property;Proteins;Protocols documentation;receptor;Recombinants;response;restoration;Risk;Route;Safety;Seizures;Serotyping;stem cells;Succinate-semialdehyde dehydrogenase deficiency;sudden unexpected death in epilepsy;Symptoms;Synapses;Syndrome;Testing;Therapeutic;Therapeutic Effect;Toxic effect;transgene expression;Transgenes;Treatment Efficacy;vector;Virus;Weight Gain;weight restoration;γ-hydroxybutyrate

PROJECT_TITLE: Gene Therapy for Succinic Semialdehyde Dehydrogenase Deficiency (SSADHD)

STUDY_SECTION: NSD

STUDY_SECTION_NAME: Neurological Sciences and Disorders A Study Section[NSD-A]


PHR: Traumatic brain injury triggers the activation of microglia and macrophages, as part of the innate immune response. This response is a first line defense against infection, but it also contributes to secondary brain injury. Recent findings indicate that microglial/macrophage activation can be suppressed by limiting glycolytic flux. Here we will evaluate targeted inhibition of microglial/macrophage glycolytic flux as an approach to improving outcome in a rodent model of traumatic brain injury. We will also evaluate the mechanism by which reduced glycolytic flux attenuates inflammatory responses in brain.

PI_NAMEs: SWANSON, RAYMOND A (contact)

PROJECT_TERMS: Affect;Anti-Inflammatory Agents;Astrocytes;Attenuated;Axon;behavioral outcome;Bioenergetics;Blood Vessels;Brain;brain cell;Brain Injuries;cell type;Cells;Clinical;Clinical Treatment;controlled cortical impact;cytokine;cytotoxic;Data;Dendrites;efficacy evaluation;functional outcomes;Gene Expression;Genes;Genetic;genetic corepressor;Genomic approach;glial activation;Glucose;glucose metabolism;Glycolysis;hexokinase;Hexokinase 2;Histologic;Hour;improved;improved outcome;In Situ;Infection;Infiltration;Inflammasome;Inflammation;Inflammatory;Inflammatory Response;inhibitor;Injury;Innate Immune Response;intervention effect;Lesion;Macrophage;Macrophage Activation;Mediating;Microglia;Modeling;mouse model;Mus;neural;Neurites;Neuronal Injury;neuronal survival;Neurons;Outcome;Oxidants;Pathogenicity;Peptide Hydrolases;Pharmaceutical Preparations;pharmacologic;Process;Production;Reactive Oxygen Species;Regulation;response;Rodent Model;Secondary to;Signal Pathway;TBI treatment;Testing;Time;transcription factor;transcriptome;Transgenic Mice;translational potential;translational study;Traumatic Brain Injury;vascular injury;Wild Type Mouse;Work

PROJECT_TITLE: Bioenergetic regulation of the innate immune response after TBI

STUDY_SECTION_NAME: Special Emphasis Panel[ZRD1 NURC-H (01)]


ORG_CITY: MATHER

ORG_NAME: VA NORTHERN CALIFORNIA HEALTH CARE SYS

PHR: Prostate cancer is still one of the leading causes of cancer-related death in men including veterans in the US. Compared to the general population, prostate cancer disease in veterans tends to more often progress to the lethal forms after anti-hormone and anti-hormone receptor treatments, therefore severely affecting the life and health of our veterans. Therefore, there is still an urgent need for development of more effective therapeutics. We recently discovered a receptor protein as a new therapeutic target for the lethal form called neuroendocrine prostate (NEPC) which develops from the current treatments. Here, we propose to develop a new strategy by targeting the receptor with small-molecule inhibitors. To make it more effective, we propose to combine the receptor inhibitors with drugs targeting a different receptor target. With the promising results from preclinical models, our studies will likely lay a solid foundation for near-future development of a new and highly efficacious strategy in treatment of advanced prostate cancer for our veteran patients.

PI_NAMEs: CHEN, HONGWU  (contact)

PROJECT_TERMS: ADRB2 gene;Adrenergic Agents;Adrenergic beta-Antagonists;Adrenergic Receptor;advanced disease;advanced prostate cancer;Affect;Androgen Antagonists;Androgen Receptor;antagonist;Automobile Driving;Cancer Etiology;cancer type;Cell Lineage;Cellular biology;Cessation of life;chemokine receptor;Chromatin;chromatin remodeling;Chromatin Structure;Clinical;Clinical Treatment;Clinical Trials;clinically significant;Coupling;CXCR4 gene;CXCR4 Receptors;Cyclic AMP-Dependent Protein Kinases;Data;Data Set;Development;Disease;drug candidate;Drug Receptors;Drug resistance;Drug Targeting;Ectopic Expression;enzalutamide;epigenomics;Family;Foundations;functional genomics;Future;gene synthesis;General Population;Genes;Genetic;genetic approach;Genomic approach;Growth;Health;Histones;Hormone Receptor;Hormones;Human;inhibitor;inhibitor therapy;innovation;insight;knock-down;Life;Ligands;Malignant neoplasm of prostate;Malignant Neoplasms;Mediating;member;men;military veteran;Modeling;Molecular;Neuroendocrine Prostate Cancer;Neurosecretory Systems;Neurotransmitter Receptor;new therapeutic target;novel;patient derived xenograft model;Patients;pharmacologic;Pre-Clinical Model;programs;Prostate;prostate cancer cell;prostate cancer progression;Prostate Neuroendocrine Neoplasm;receptor;Receptor Signaling;Resistance;response;Role;Safety;Signal Transduction;Signaling Protein;single-cell RNA sequencing;small molecule;small molecule inhibitor;Solid;Specimen;stem-like cell;Testing;Therapeutic;therapeutic candidate;Therapeutic Intervention;therapeutic target;therapeutically effective;therapy resistant;tumor;tumor growth;tumorigenic;Veterans

PROJECT_TITLE: Therapeutic targeting of a novel driver of prostate cancer progression.


ORG_CITY: Decatur

ORG_NAME: VETERANS HEALTH ADMINISTRATION

ORG_STATE: GA

PHR: Project Narrative Post-traumatic osteoarthritis (PTOA) is a debilitating condition of articular joints that is associated with pain, activity loss, and reduced quality of life. Incidence of PTOA and similar degenerative conditions is almost three times higher in the military vs civilian population by the age of 40. Intra-articular injections of cellular products, including bone marrow aspirate concentrate (BMAC), are becoming standard of care for joint preservation and pain relief. Most of our data on the best use for BMAC rely on studies using allogenic cells from young, healthy donors to treat PTOA in young, otherwise healthy rodents rather than autologous sources The objective of this proposal is to evaluate how patient factors (age, sex, PTOA) and physical interventions impact BMAC efficacy in relieving osteoarthritic pain. Successful completion of this project will provide translatable evidence whether pre-habilitation of all or a subset of Veterans prior to BMAC harvest and injection can improve relief of joint pain.

PI_NAMEs: KAISER, JARRED  (contact)

PROJECT_TERMS: Absence of pain sensation;Adipose tissue;Affect;Age;Allogenic;Animal Model;Anti-Inflammatory Agents;Arthralgia;Autologous;Blood Platelets;Bone Marrow;Bone Marrow Aspiration;Cell Therapy;Cells;chronic pain;Clinical;clinical translation;clinically relevant;contrast enhanced;cost effective;cytokine;Data;Degenerative Disorder;Degenerative polyarthritis;Disease;effective intervention;efficacy testing;endurance exercise;Enzyme-Linked Immunosorbent Assay;Exercise;exercise prescription;exercise regimen;Fatty acid glycerol esters;Female;Flow Cytometry;Future;Guidelines;Habilitation;Harvest;Health;Hematopoietic stem cells;Histology;human old age (65+);Hyaluronic Acid;Immune;Immunohistochemistry;immunoregulation;improved;in vivo;Incidence;Inflammation;Injections;Intervention;Intra-Articular Injections;Joints;Link;lipid biosynthesis;male;Marrow;Medial meniscus structure;mesenchymal stromal cell;Metabolism;microCT;middle age;Military Personnel;Modeling;Morphology;musculoskeletal injury;Obesity;Occupational;opioid misuse;osteoarthritis pain;Outcome;Pain;Pain management;pain relief;Patients;Pharmaceutical Preparations;Plasma;Population;Positioning Attribute;pre-clinical;Pre-Clinical Model;preservation;prevent;primary outcome;Proliferating;Publishing;Quality Control;Quality of life;Rattus;Regimen;Rejuvenation;Risk;Rodent;sedentary;senescence;service member;sex;Source;standard of care;Synovial Fluid;Therapeutic;therapeutically effective;Tissue Preservation;Tissues;Translations;Trauma;Traumatic Arthropathy;Traumatic injury;Variant;Veterans;Woman;Work

PROJECT_TITLE: Assessing the Impact of Patient Factors on Therapeutic Capabilities of BMAC for Osteoarthritic Pain


PHR: Heart failure and chronic obstructive pulmonary disease are extremely common in Veterans and commonly complicated by pulmonary hypertension and right heart failure. Treatment options for right heart failure are very limited. Heart failure has been the number one reason for admission among patients in the Veterans' Health Care System. Recent studies show that patients with post-traumatic stress disorder (PTSD) are at increased risk for cardiovascular disease, and PTSD is twice as prevalent in veteran populations versus the general population. The Department of Veteran Affairs Quality Enhancement Research Initiative (QUERI) is designed to improve care using research evidence to improve clinical practice for high-risk and/or highly prevalent diseases or conditions among veterans. Congestive heart failure is one of the high-risk, and highly prevalent diseases included in the QUERI program. Thus, research in cardiovascular disease, and RV failure in particular, are extremely important and relevant to the mission of the VA.

PI_NAMEs: BAKER, ANTHONY J. (contact)

PROJECT_TERMS: Acetylation;Admission activity;Adrenergic Receptor;Agonist;antioxidant enzyme;Antioxidants;Automobile Driving;Bioenergetics;Blood Pressure;Cardiac;Cardiac Myocytes;cardiac tissue engineering;cardioprotection;Cardiovascular Diseases;cardiovascular disorder risk;Caring;Cause of Death;Chronic;Chronic Disease;Chronic Obstructive Pulmonary Disease;Clinical;clinical practice;congenital heart abnormality;Congestive Heart Failure;constriction;Data;design;Disease;Dose;Failure;General Population;Health;Healthcare Systems;Heart failure;heart function;high risk;Human;Human Engineering;human induced pluripotent stem cells;improved;In Vitro;in vivo;induced pluripotent stem cell derived cardiomyocytes;Infarction;Ischemia;Link;Mediating;Microfilaments;military veteran;Mission;Mitochondria;mitochondrial dysfunction;Mitochondrial Proteins;Modeling;Modification;Muscle Proteins;Myocardial;Myocardium;novel;Pathology;Patients;Pharmacological Treatment;Play;Post-Traumatic Stress Disorders;pressure;Primary Myocardial Diseases;process improvement;Production;Prognosis;programs;protective effect;Proteins;Pulmonary artery structure;Pulmonary Fibrosis;Pulmonary Hypertension;Reactive Oxygen Species;Recovery;Reporting;Research;Respiration;right ventricular failure;Role;Stenosis;Testing;Therapeutic Effect;translational study;United States Department of Veterans Affairs;Veterans

PROJECT_TITLE: Right Heart Function in Health and Chronic Disease

STUDY_SECTION_NAME: Special Emphasis Panel[ZRD1 CARA-R (01)]


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease Related Dementias (ADRD);Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Behavioral and Social Science;Biomedical Imaging;Brain Disorders;Cerebrovascular;Clinical Research;Dementia;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Neurodegenerative;Neurosciences;Prevention;Vascular Contributions to Cognitive Impairment and Dementia (VCID)

ORG_CITY: SAINT LOUIS

ORG_NAME: WASHINGTON UNIVERSITY

PHR: PROJECT NARRATIVE Alzheimer's disease (AD) is the most common cause of dementia and currently has few disease-modifying treatments or simple, accurate diagnostic tests available in the clinic. The goal of this project is to further develop and validate amyloid, tau, and neurodegenerative blood tests for amyloid plaques (a protein thought to begin AD) and tau tangles (protein deposits closely associated with cognitive impairment) in order to diagnose AD in the clinic to enable treatment with disease-modifying drugs, which could change the course of AD. Findings from this study may enable accurate diagnoses and access to more effective treatments of AD.

PI_NAMEs: BATEMAN, RANDALL J (contact)

PROGRAM_OFFICER_NAME: LUO, YUAN

PROJECT_TERMS: Acceleration;accurate diagnosis;accurate diagnostics;Address;Age;Alzheimer's Disease;Alzheimer's disease diagnosis;Alzheimer's disease pathology;Alzheimer's disease test;Alzheimer’s disease biomarker;Amyloid;Amyloid beta-42;Amyloid beta-Protein;amyloid pathology;Apolipoprotein E;Biological;Biological Markers;Biology;Blood;Blood specimen;Blood Tests;blood-based biomarker;Caring;Clinic;Clinical;Clinical assessments;clinical diagnosis;clinical predictors;Clinical Research;Clinical Treatment;Clinical Trials;Cognition;cognitive change;cognitive testing;cohort;Communities;comorbidity;cost;Data;Dementia;demographics;Deposition;Development;Diagnosis;Diagnostic;diagnostic accuracy;Diagnostic tests;Disease;Early Diagnosis;Education;effective therapy;Electronic Health Record;Electronics;Enrollment;Excision;feasibility testing;Functional disorder;General Population;Genetic;Goals;Gold;Image;Impaired cognition;Light;Longitudinal cohort;low socioeconomic status;Measures;Medical;Medical center;medical specialties;Nerve Degeneration;Neurofibrillary Tangles;neurofilament;novel;novel marker;Participant;Pathology;patient population;Patients;Performance;Persons;Pharmaceutical Preparations;Phosphorylation Site;Plasma;polygenic risk score;Population;population based;Positron-Emission Tomography;Prevention;prognostic;Property;Prospective Studies;Proteins;Race;rate of change;Reporting;Research;Risk;Senile Plaques;Sensitivity and Specificity;sex;Socioeconomic Status;Spinal Puncture;Symptoms;tau Proteins;tau-1;Testing;tool;Underrepresented Populations;Work

PROJECT_TITLE: Blood amyloid, tau, and neurodegeneration biomarkers and prediction of clinical onset, cognitive decline, and dementia diagnosis

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 AN-D (02)]


ORG_CITY: MIAMI

ORG_NAME: MIAMI VA HEALTH CARE SYSTEM

PHR: Myocarditis associated with COVID-19 infection, long COVID syndrome and COVID mRNA vaccination have emerged as urgent unmet clinical needs. Two recent studies involving >80-million persons including national healthcare databases from the US Department of Veteran Affairs confirmed that SARS-CoV-2 infection and/or mRNA vaccination significantly predispose patients from high susceptibility as cardiovascular disease to myocarditis, constituting an urgent unmet clinical need. We propose that genetic and/or pharmacological targeting of the cardiac low-density lipoprotein receptor (LDLR) can be used to prevent and possibly attenuate COVID-19-induced myocarditis in susceptible patients. Using a new mouse model of SARS-induced myocarditis and a co-culture model with monocytes from long COVID patients, we propose two independent mechanisms of action for how LDLR causes myocarditis.

PI_NAMEs: SHEHADEH, LINA A (contact)

PROJECT_TERMS: 2019-nCoV;ACE2;Affinity;Agonist;Apoptosis;Attenuated;Autopsy;Binding;Blood;Cardiac;Cardiac Myocytes;Cardiovascular Diseases;CASP3 gene;Cell Line;Cell surface;Cells;Clinic;Clinical;Coculture Techniques;Complex;COVID-19;cytokine;cytotoxic;Data;Databases;Deposition;Diglycerides;Disease Progression;efficacy evaluation;EFRAC;Female;Genetic;Healthcare;Heart;Heart Block;Heart failure;High Pressure Liquid Chromatography;immune cell infiltrate;improved;In Vitro;in vivo;Infection;Inflammatory;Inflammatory Response;inhibitor;Integration Host Factors;intraperitoneal;intravenous injection;K-18 conjugate;LDL Cholesterol Lipoproteins;lipid metabolism;Lipids;live cell imaging;Low Density Lipoprotein Receptor;Luciferases;Macrophage;Magnetic Resonance Imaging;male;Mediating;Medical center;Metabolic Diseases;migration;Modeling;monocyte;mouse model;Mus;Myocarditis;new therapeutic target;NF-kappa B;novel;NRP1 gene;osteopontin;overexpression;Patients;Peptides;Persons;pharmacologic;post SARS-CoV-2 infection;Predisposition;prevent;Prevention;Proliferating;Protein Analysis;protein complex;Proteins;Proto-Oncogene Proteins c-akt;Publishing;receptor;receptor binding;Receptor Inhibition;Reporting;response;RNA;RNA vaccination;Role;Sampling;SARS-CoV-2 infection;SARS-CoV-2 spike protein;Severe Acute Respiratory Syndrome;Symptoms;Syndrome;therapeutic target;Tissues;United States Department of Veterans Affairs;uptake;Wild Type Mouse

PROJECT_TITLE: Role of LDLR in COVID-Induced Myocarditis


NIH_SPENDING_CATS: Aging;Basic Behavioral and Social Science;Behavioral and Social Science;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Racial and Ethnic Minority Health Research;Social Determinants of Health

ORG_CITY: NEW YORK

ORG_NAME: NEW YORK UNIVERSITY SCHOOL OF MEDICINE

ORG_STATE: NY

PHR: PROJECT NARRATIVE  Hazardous working conditions fuel socioeconomic and racial health disparities in the US; relational theories suggest such conditions are produced by upstream power imbalances between workers, managers, and employers, social classes divisible by managerial authority and business ownership. Nonetheless, while longitudinal studies have tested the effects of downstream factors like wages, none using relational theories have tested class’s cumulative effects on health over the life course, the modifying role of power dynamics, or the effects of workplace-level and state-level worker empowerment. My proposal will address these gaps, advancing the field by analyzing disparities’ overlooked root causes and identifying actionable policy solutions.

PI_NAMEs: EISENBERG-GUYOT, JERZY  (contact)

PROGRAM_OFFICER_NAME: NGUYEN, EMERALD THAI HAN

PROJECT_TERMS: Address;Adult;Aging;aging related;Area;authority;Black Populations;Black race;Businesses;career;Cessation of life;Congresses;COVID-19 pandemic;Cross-Sectional Studies;Data;Data Set;density;design;Disparity;disparity reduction;econometrics;Economics;empowerment;Excess Mortality;experience;Failure;Fostering;Gender;Goals;hazard;Health;health data;health disparity;improved;Income;income disparities;intersectionality;Labor Unions;Life Cycle Stages;Life Expectancy;Link;Longitudinal Studies;meetings;Mental disorders;Mentors;Mentorship;Methodology;Methods;Modification;mortality;mortality disparity;National Health Interview Survey;novel;Occupational;Occupations;older adult;Outcome;Ownership;pandemic disease;panel study of income dynamics;Policies;population health;Public Health Schools;Race;racial health disparity;Research;Research Personnel;Resources;Respondent;Risk;Role;Social Class;Social Power;socioeconomics;Testing;Theft;theories;Time;Training;trend;Universities;Wages;Wellness Program;Woman;Work;Workplace

PROJECT_TITLE: Analyzing the roles of social class and power dynamics in health disparities over the life course

STUDY_SECTION: AGCD

STUDY_SECTION_NAME: Career Development Facilitating The Transition to Independence Study Section[AGCD-1]


NIH_SPENDING_CATS: Aging;Basic Behavioral and Social Science;Behavioral and Social Science;Biomedical Imaging;Brain Disorders;Clinical Research;Mental Health;Mental Illness;Neurosciences;Psychosis;Schizophrenia;Serious Mental Illness

ORG_CITY: BIRMINGHAM

ORG_NAME: UNIVERSITY OF ALABAMA AT BIRMINGHAM

ORG_STATE: AL

PHR: PROJECT NARRATIVE Emerging evidence in schizophrenia spectrum disorders (SSD) support the idea that aberrant brain aging may also occur, but data on characteristic phenotypical and brain age-related signatures and their underlying mechanisms remain sparse. The principal goals, consistent with the purpose of the Funding Opportunity Announcement RFA-MH-22-270 and informed by mechanistic insights on aging in the field of geroscience, is to characterize aging phenomena in SSD across multiple units of analysis and to identify actionable targets that have the potential to ameliorate, or even prevent, aberrant aging in SSD. We will characterize age-related changes in the brain in SDD across multiple levels: brain structure (cortical thickness), brain function (nonsocial and social cognition) and metabolism (bioenergetics), which could offer mechanistic insights into aging process in SSD by focusing on multiple units of analysis and provide actionable treatment targets for aberrant aging in SSD.

PI_NAMEs: KRAGULJAC, NINA VANESSA;LAHTI, ADRIENNE C;LEE, JUNGHEE  (contact)

PROGRAM_OFFICER_NAME: ROWLAND, LAURA

PROJECT_TERMS: Address;Adult;Affect;Age;age effect;age related;age related changes;age related decline;Aging;aging brain;aging process;Anterior;Behavioral;Bioenergetics;Brain;Brain region;Characteristics;cingulate cortex;Cognition;Cognitive aging;cognitive function;cognitive performance;cognitive task;comparison control;Data;Deterioration;Dimensions;Disease;Dorsal;driving force;Energy Metabolism;Enrollment;Functional disorder;Functional Magnetic Resonance Imaging;Funding Opportunities;General Population;Geroscience;Goals;Growth;healthy volunteer;in vivo;indexing;Individual;insight;Knowledge;late life;Literature;Magnetic Resonance Spectroscopy;Measures;Metabolism;Modeling;multimodal neuroimaging;normal aging;novel;pathological aging;Patients;Pattern;Performance;Play;prevent;Psychoses;Psychotic Disorders;Role;schizophrenia spectrum disorder;social;social cognition;Structure;Techniques;therapy design;Thick;Work

PROJECT_TITLE: Multidimensional aging trajectories in mid to late-life psychosis (MAP)

STUDY_SECTION_NAME: Special Emphasis Panel[ZMH1 ERB-S (06)]


ORG_CITY: ANN ARBOR

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: PROJECT NARRATIVE Peripheral neuropathy is a common complication of type 2 diabetes, with no effective therapy and unclear mechanisms. In this proposal, we aim to determine the cellular and molecular mechanisms by which lifestyle interventions, such as diet and exercise, can be implemented to improve peripheral neuropathy using a clinically relevant mouse model of type 2 diabetes along with advanced techniques to evaluate Schwann cell- axon metabolic cross talk and energy utilization. We will also define the role of extracellular vesicle release and small RNAs in mediating the beneficial effects of diet and/or exercise to advance our understanding of the metabolic interaction of neurons with Schwann cells beyond myelination, and ultimately unlock potential avenues of investigation for treating peripheral neuropathy in type 2 diabetes to improve the quality of life in affected individuals.

PI_NAMEs: EID, STEPHANIE  (contact)

PROGRAM_OFFICER_NAME: COOKE, BRAD

PROJECT_TERMS: Affect;American;Amputation;Animal Feed;Antisense Oligonucleotides;Axon;axon growth;axon injury;Bioenergetics;Bioinformatics;Biology;career;cell injury;Cells;Clinical Data;clinically relevant;cohort;Communication;Complication;Complications of Diabetes Mellitus;Coupling;Diabetes Mellitus;Diabetic mouse;Diet;diet and exercise;dietary;Dose;Dyslipidemias;effective therapy;Evaluation;Exercise;extracellular vesicles;Foundations;Functional disorder;Genes;glycemic control;Goals;Health;High Fat Diet;Human;Impairment;improved;In Vitro;Individual;Injury;intercellular communication;Intervention;Investigation;lifestyle intervention;lipid metabolism;lipidome;lipidomics;Lipids;Mediating;Mentors;Metabolic;Metabolism;MicroRNAs;Mitochondria;Modeling;Molecular;mouse model;Mus;myelination;Nerve;nerve damage;Nerve Degeneration;nerve injury;Neuronal Dysfunction;Neurons;non-genetic;Non-Insulin-Dependent Diabetes Mellitus;Pain;Pathologic;Peripheral Nerves;Peripheral Nervous System;Peripheral Nervous System Diseases;Persons;prevent;Production;Proteins;Public Health;Quality of life;Recommendation;Research;restoration;Risk Factors;Role;Running;Schwann Cells;sex;single-cell RNA sequencing;Small RNA;Streptozocin;Stress;Techniques;Testing;therapeutic target;Tissues;Training;transcriptome;transcriptomics;Ulcer;vesicular release

PROJECT_TITLE: Schwann cell-derived extracellular vesicles maintain peripheral nerve function under homeostatic conditions and promote damage in type 2 diabetes, independent of myelination

STUDY_SECTION: DDK

STUDY_SECTION_NAME: Diabetes, Endocrinology and Metabolic Diseases B Study Section[DDK-B]


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease Related Dementias (ADRD);Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Biomedical Imaging;Brain Disorders;Cerebrovascular;Clinical Research;Clinical Trials and Supportive Activities;Dementia;Neurodegenerative;Neurosciences;Vascular Contributions to Cognitive Impairment and Dementia (VCID)

ORG_CITY: BALTIMORE

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: Project Narrative  Recent research proposed the use of biomarkers for a biological/etiological classification of Alzheimer’s disease and related dementia (ADRD). However, the current system is mainly focused on dementia of the Alzheimer’s type, but another important category of vascular cognitive impairment and dementia was not considered. The present project aims to develop and operationalize a biomarker based on brain physiology to classify vascular components in ADRD.

PI_NAMEs: LU, HANZHANG  (contact)

PROGRAM_OFFICER_NAME: ROVESCALLI, ALESSANDRA C

PROJECT_TERMS: Affect;Alzheimer's Disease;Alzheimer's disease patient;Alzheimer's disease related dementia;Amyloid;Biological;Biological Markers;Blood;Blood specimen;Blood Vessels;Brain;candidate marker;Categories;cerebrovascular;Cerebrum;Classification;Classification Scheme;Clinical;clinical diagnosis;Clinical Research;Clinical Trials;Cognitive;cognitive function;cohort;Consensus;Consumption;Dementia;Development;Diagnosis;Diagnostic;diagnostic biomarker;Disease;Enrollment;Equilibrium;Etiology;executive function;follow-up;frontal lobe;Functional disorder;Functional Imaging;Future;Goals;Growth;Hemorrhage;imaging biomarker;Impaired cognition;Impairment;indexing;International;Lacunar Infarctions;Longitudinal Studies;Magnetic Resonance Imaging;Measurement;Measures;Microvascular Dysfunction;mixed dementia;Monitor;multidisciplinary;Mus;Nature;Nerve Degeneration;novel;older adult;Older Population;Oxygen;Participant;Pathologic;Patient Monitoring;Patient Selection;Patients;Perfusion;Pharmaceutical Preparations;Physiological;Physiological Processes;Physiology;Play;Predisposition;primary endpoint;Process;processing speed;Reporting;Research;Research Personnel;research study;Risk;Role;Scanning;Scheme;Selection for Treatments;System;tau Proteins;Techniques;Technology;Testing;Time;vascular abnormality;Vascular Cognitive Impairment;vascular cognitive impairment and dementia;Vascular Dementia;vascular factor;vascular risk factor;White Matter Hyperintensity;Wild Type Mouse;Work;young adult

PROJECT_TITLE: Physiological imaging markers in vascular contributions to cognitive impairment and dementia (VCID)

STUDY_SECTION: CNN

STUDY_SECTION_NAME: Clinical Neuroscience and Neurodegeneration Study Section[CNN]


PHR: The  Veterans  Health  Administration  provides  care  to  women  servicemembers  and  mild  traumatic  brain  injury  (mTBI)  is  a  known  risk  of  military  service. Young women servicemembers  smoke  at  an alarming  rate and  are  also likely to use oral contraceptives (OC), owing to their reproductive age. Simultaneous exposure to smoking  derived- nicotine (N) and OC (N+OC) renders females more susceptible to cognitive decline, a consequence of  mTBI.  The  current proposal uses  mTBI to  model the  physiological and cognitive  consequences,  mechanisms,  and possible treatments in the setting of N+OC exposure in female rats.

PI_NAMEs: BRAMLETT, HELEN M;RAVAL, AMI P (contact)

PROJECT_TERMS: active duty;Address;Adult women;Age;Agonist;Brain;brain health;Brain Injuries;brain metabolism;care seeking;Caring;Cause of Death;Cerebrum;Cognition;Cognitive;cognitive capacity;Cognitive deficits;cognitive disability;cognitive function;Complex;complex IV;Data;Defect;Electron Transport;Electronic cigarette;Energy Metabolism;Enzymes;Estrogen Receptors;Exposure to;Female;fluid percussion injury;Genes;Healthcare;Histopathology;Hormones;Impaired cognition;Inflammasome;Inflammation;Injury;Innate Immune Response;Investigation;JUUL;Knowledge;Laboratories;Learning;male;Mediating;Memory;Metabolic Pathway;metabolomics;mild traumatic brain injury;Military Personnel;military service;Mitochondria;mitochondrial dysfunction;Modeling;Nerve Degeneration;Nicotine;nicotine exposure;nicotine use;Oral Contraceptives;Outcome;Phosphorylation;physiologic model;Predisposition;Proteins;Publishing;Rattus;receptor;reproductive;Research;Respiratory Chain;Risk;Role;Secondary to;service member;Severities;sex;Smoke;Smoking;Stress;Survivors;Testing;transcriptomics;Traumatic Brain Injury;United States Department of Veterans Affairs;Veterans;Veterans Health Administration;Woman;young woman

PROJECT_TITLE: Impact of oral contraceptives and smoking on females after traumatic brain injury


PHR: Prostate cancer (PC) is the number one cancer diagnosed in US Veterans. Almost half a million US Veterans currently undergo treatment for PC at the Veterans Health Administration. Advanced PC is treated by androgen deprivation therapy and most patients' initial response is favorable. Unfortunately, the cancer usually recurs as aggressive, incurable “castration-resistant prostate cancer” (CRPC) that often metastasizes and dramatically degrades quality of life. To combat or prevent CRPC, new therapies must be found. We identified a gene termed BUB1B (known to increase cell division) that is present at high levels in CRPC and in metastatic CRPC. Reducing BUB1B protein in genetic experiments halts the growth of CRPC cells. For clinical purposes, however, no BUB1B drugs exist. We will determine how BUB1B promotes CRPC growth, pinpoint BUB1B activity that is vulnerable to drugs, and deploy a computational and experimental approach to identify BUB1B drugs. We will validate drug effectiveness in pre-clinical CRPC models and set the stage for clinical trials.

PI_NAMEs: BURNSTEIN, KERRY L (contact)

PROJECT_TERMS: 3-Dimensional;advanced prostate cancer;androgen deprivation therapy;androgen independent prostate cancer;Androgen Receptor;androgen sensitive;antagonist;Benign;Binding Sites;Biochemical;Biological Assay;Cancer Biology;cancer diagnosis;Cancer Patient;cancer recurrence;Castration;Cell division;Cell Line;Cell Proliferation;Clinical;Clinical Trials;combat;constitutive expression;Coupled;Data;deep neural network;Development;druggable target;Effectiveness;enzalutamide;Evolution;Experimental Genetics;experimental study;Future;gene network;Generations;Genes;Genetic Transcription;Genomic Instability;Goals;Growth;Heterogeneity;Homology Modeling;human disease;inhibitor;innovation;Investigational Therapies;kinase inhibitor;knock-down;Lead;Ligands;Link;Malignant neoplasm of prostate;Malignant Neoplasms;member;Messenger RNA;Metastatic Neoplasm to the Bone;Mitotic;Mitotic Checkpoint;Modeling;Molecular;Molecular Conformation;multidisciplinary;multitask;mutant;Neoplasm Metastasis;Neuroendocrine Prostate Cancer;new therapeutic target;novel;novel therapeutics;Oncogenic;overexpression;patient derived xenograft model;patient stratification;Patients;Pharmaceutical Chemistry;Pharmaceutical Preparations;Phosphotransferases;Physics;Positioning Attribute;pre-clinical;prevent;Proliferating;Prostate;prostate cancer cell;prostate cancer cell line;prostate cancer model;Prostate Cancer therapy;Protac;Protein-Serine-Threonine Kinases;Proteins;Quality of life;Receptor Signaling;Recurrence;Resistance;response;Role;screening;Series;Serine;simulation;Site;small molecule;small molecule inhibitor;Solid Neoplasm;standard of care;Structure;Structure-Activity Relationship;Testing;Therapeutic;therapeutic target;Time;Tissues;Traction;Treatment Efficacy;tumor;Variant;Veterans;Veterans Health Administration;virtual screening;Visceral metastasis

PROJECT_TITLE: A Novel Drug Target for Aggressive Prostate Cancer


ORG_CITY: CHICAGO

PHR: Project Narrative Idiopathic pulmonary fibrosis (IPF) occurs when lungs heal abnormally after an injury and develop scarring. It is a devastating disease with treatments that are not very effective and cause intolerable side effects. The experiments in our studies are designed to identify new treatments to help Veteran’s at risk from problems related to lung scarring.

PI_NAMEs: BUDINGER, GR SCOTT ;JAIN, MANU  (contact)

PROJECT_TERMS: 2019-nCoV;Ablation;Affect;Alveolar;alveolar epithelium;Alveolar Macrophages;Animal Model;Anti-diabetic Drugs;antitumor effect;Asbestos;Attenuated;Award;Biological;biological adaptation to stress;Bleomycin;Bronchoalveolar Lavage;Bronchoscopy;cancer cell;Cells;Cessation of life;Cicatrix;Clinical;Complex;COVID-19 pandemic;COVID-19 survivors;Credentialing;CSF3 gene;Data;design;Disease;Disease Progression;Disparate;Drug Kinetics;Drug usage;Electron Transport;epithelial repair;Epithelium;experimental study;Exposure to;Fibroblasts;Fibrosis;fibrotic lung;fibrotic lung disease;Flow Cytometry;Formulation;gain of function;Gases;Gene Expression;Genes;Genetic;Human;idiopathic pulmonary fibrosis;Impaired healing;improved outcome;in vivo;injured;Injury;intraperitoneal;Laboratories;Light;loss of function;Lung;lung development;Lung Transplantation;Macrophage;Macrophage Colony-Stimulating Factor;Metabolic;Metformin;military veteran;Mitochondria;Mitochondrial Electron Transport Complex I;mitochondrial metabolism;Modeling;monocyte;mouse model;Mus;Myofibroblast;NADH dehydrogenase (ubiquinone);Natural regeneration;Non-Insulin-Dependent Diabetes Mellitus;novel;novel therapeutics;old mice;Oral;Organoids;pandemic disease;Pathway interactions;Patients;peripheral blood;Pharmaceutical Preparations;pharmacologic;Post-Acute Sequelae of SARS-CoV-2 Infection;Prevalence;prevent;programs;Proliferating;protective effect;Public Health;Publishing;Pulmonary Fibrosis;recruit;repaired;Reporting;Reproducibility;Respiratory Failure;Respiratory Signs and Symptoms;respiratory virus;response;Risk;Sampling;seal;severe COVID-19;side effect;single-cell RNA sequencing;Slice;small molecule;System;targeted treatment;Testing;therapeutic target;Tissues;tool;transcriptome;transcriptomics;Transplant Recipients;Validation;Veterans;Work;Work of Breathing;yeast protein;Yeasts

PROJECT_TITLE: Mitochondrial metabolism as a therapeutic target in pulmonary fibrosis

STUDY_SECTION_NAME: Special Emphasis Panel[ZRD1 PULM-T (01)]


ADMINISTERING_IC: EB

IC_NAME: NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING

NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Cancer;Clinical Research;Dental, Oral, and Craniofacial Disease;Neurosciences;Rare Diseases

ORG_CITY: BOSTON

ORG_NAME: BRIGHAM AND WOMEN'S HOSPITAL

PHR: PROJECT NARRATIVE Our goal is to devise clinically optimal MRI synthetic image contrasts for the skull base and face that can be tailored for field strength, gradient capabilities, spatial resolution, and desired imaging time. We propose to generate novel qualitative MRI contrasts that optimize clinically-relevant contrast-to-noise and simultaneously acquire relaxometry biomarkers that are co-registered to the anatomic images at the voxel level with markedly reduced scan times compared with current standard-of-care skull base and face MR imaging. We also propose to develop a novel pulse sequence that incorporates scanner gradient strength as a parameter to further decrease scan times and to evaluate these pulse sequences across 1.5T, 3T, and 7T field strengths.

PI_NAMEs: GUENETTE, JEFFREY P (contact)

PROGRAM_OFFICER_NAME: GATLIN, TINA L

PROJECT_TERMS: 3-Dimensional;anatomic imaging;Anatomy;Atlases;Biological Markers;Body part;Brain;Brain imaging;chemoradiation;Clinical;clinical imaging;Clinical Protocols;clinically relevant;contrast imaging;Cranial Nerves;Data;density;Derivation procedure;design;Development;Diagnosis;Disease;Face;Facial nerve structure;Fatty acid glycerol esters;Fingerprint;Funding;Future;Goals;Head and Neck Squamous Cell Carcinoma;Head and Neck Surgeon;Heart;Hospitals;Image;image processing;image reconstruction;imaging modality;improved;in vivo;K-Series Research Career Programs;Laboratories;Lead;Learning;Magnetic Resonance Imaging;magnetic resonance imaging biomarker;Mathematics;Measures;Mentors;Mentorship;Methods;Modality;Modernization;Morphologic artifacts;Motion;Neck;Nerve;Noise;Normal Range;novel;Otolaryngology;Pathology;Pathway interactions;Performance;Physicians;Physics;Physiologic pulse;Production;Property;Protocols documentation;Protons;rapid technique;Research;Research Activity;Resolution;Resources;Sampling;Scanning;Scientist;skills;skull base;standard of care;Structure;System;Techniques;Testing;Time;Tissues;Training;translational study;treatment response;tumor;United States National Institutes of Health;Vendor;Visualization;Woman;Work

PROJECT_TITLE: Rapid Anatomic and Quantitative MR Imaging of the Skull Base and Face

STUDY_SECTION_NAME: Special Emphasis Panel[ZEB1 OSR-F (O1)]


ORG_CITY: OMAHA

ORG_NAME: OMAHA VA  MEDICAL CENTER

ORG_STATE: NE

PHR: Per- and polyfluoroalkyl substances (PFAS) are a group of synthetic chemicals that are resistant to biodegradation, environmentally persistent, and have been detected in nearly every participant of the nationally representative US National Health and Nutrition Examination Survey. Little is known about the reproductive health effects of “legacy” PFAS or newer PFAS alternatives, specifically the impact on the ovary. Women Veterans are the fastest growing subgroup in the Veteran population and projected to make up 18% of the Veteran population by the year 2040. According to data from the Department of Defense, there are over 400 military installations with known/suspected releases of PFAS, leaving veterans and their families more susceptible to PFAS exposure. The results of this project will provide novel insight on pathways and processes in the ovary that are impacted by exposure to PFAS and the potential consequences on female fertility in addition to impacts on offspring developmental health.

PI_NAMEs: CLARK, KENDRA L (contact)

PROJECT_TERMS: Affect;Antral;Apoptosis;aqueous;Award;base;Biodegradation;Biological Assay;Biology;career;cell behavior;Cell Cycle;Cell Line;Cell Physiology;Cell Proliferation;Chemical Exposure;Chemicals;Communities;Competence;consumer product;Data;Department of Defense;Development;Diagnosis;Disease;Doctor of Philosophy;egg;endometriosis;Environment;Exposure to;Failure;Family;Female;female fertility;Fertility;fertility preservation;Film;folliculogenesis;Genetic;Genetic Transcription;Genomics;Goals;granulosa cell;ground water;Growth;Health;high risk;hormone regulation;Hormones;Human;Impairment;in utero;In Vitro;in vitro Model;in vivo;in vivo Model;Infertility;insight;Investigation;Life;Malignant neoplasm of ovary;manufacture;Measurable;Medical center;Menopause;Menstruation Disturbances;Mentorship;Military Personnel;military veteran;mimicry;Molecular;Mus;National Health and Nutrition Examination Survey;Nature;Nebraska;neonatal mice;novel;offspring;Oocytes;Organ Size;Osteoporosis;Ovarian;Ovarian Granulosa Cell;Ovary;ovotoxicant;ovotoxicity;Ovulation;Participant;Pathologic;Pathway interactions;Periodicity;Physiological;Poly-fluoroalkyl substances;Population;post-doctoral training;Predisposition;Pregnancy;Premature Ovarian Failure;prenatal exposure;prevent;Primordial Follicle;Process;Proliferating;Quality of life;Receptor Signaling;Regulation;Reproduction;reproductive;reproductive development;Reproductive Endocrinology;reproductive function;Reproductive Health;reproductive system disorder;Research;Research Personnel;Research Training;Resistance;Role;Sampling;Scientist;Signal Transduction;Signal Transduction Pathway;skills;stem cell self renewal;Steroid biosynthesis;Structure;Subgroup;Surface;Testing;Textiles;Tissues;Toxicology;transcription factor;Universities;Veterans;virtual;Woman;women's reproductive health

PROJECT_TITLE: Determining mechanisms of ovotoxicity from per- and polyfluoroalkyl substances

STUDY_SECTION_NAME: Special Emphasis Panel[ZRD1 ENDA-L (01)]


NIH_SPENDING_CATS: Aging;Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Epilepsy;Neurodegenerative;Neurosciences

PHR: PROJECT NARRATIVE Fifty million people have epilepsy, the incidence of epilepsy is higher after age 70 compared with any other time in life, and treatment decisions almost certainly change over the course of a person’s lifespan, yet current science poorly defines how optimal treatment strategies should change with age. This research will combine insights from a patient preferences survey with individualized seizure risk and net-benefit modeling and then plan a randomized trial, all to identify which patients with well-controlled epilepsy may benefit from deprescribing antiseizure medications. This project is directly relevant to NIA’s mission because optimizing deprescribing decisions according to a person’s age and stage in life intends to increase patients’ healthy, active years.

PI_NAMEs: TERMAN, SAMUEL W (contact)

PROGRAM_OFFICER_NAME: SALIVE, MARCEL

PROJECT_TERMS: Adult;Adverse effects;Age;age group;age related changes;Aging;aging related;Anticonvulsants;Applied Skills;Automobile Driving;Award;beneficiary;care preference;career;Caring;Central Nervous System;Central Nervous System Agents;Clinical Trials;Cognition;Cognitive;Communities;Country;Data;Data Collection;Data Set;Disease remission;Dose;Enrollment;Environment;Epilepsy;Equilibrium;evidence based guidelines;Exercise;experience;fall risk;falls;frailty;Freedom;Funding;Future;Geriatrics;Goals;Grant;Health Services;Healthcare;healthy aging;high risk;human old age (65+);Impaired cognition;improved;Incidence;individualized medicine;insight;International;Intervention;Life;Life Cycle Stages;life span;Magnetic Resonance Imaging;Measurement;Medicare;Medication Systems;Mentorship;Methods;Michigan;Mission;Modeling;Modernization;Motor Seizures;multidisciplinary;Neurologic;Neurologist;Neurology;Observation in research;older adult;older patient;optimal treatments;patient oriented;Patient Preferences;Patients;Performance;personalized medicine;personalized strategies;Persons;Pharmaceutical Preparations;pharmacologic;pilot trial;Polypharmacy;Population;Positioning Attribute;preference;Procedures;Protocols documentation;Quality of life;Quality-Adjusted Life Years;Randomized;randomized trial;Randomized, Controlled Trials;recruit;Relapse;Research;Respondent;Risk;risk prediction;Sample Size;Sampling;Science;Seizures;simulation;Site;skill acquisition;Subgroup;Surveys;Techniques;Testing;Time;Training;treatment duration;treatment strategy;trial planning;Universities;Update;willingness;Work;young adult

PROJECT_TITLE: Optimizing antiseizure medication deprescribing decisions across the lifespan by integrating seizure risk prediction and patient preferences towards individualized net-benefit assessment

STUDY_SECTION_NAME: Career Development for Clinicians/Health Professionals Study Section [AGCD-3]


ORG_CITY: SALT LAKE CITY

ORG_NAME: VA SALT LAKE CITY HEALTHCARE SYSTEM

ORG_STATE: UT

PHR: Atypical left atrial flutter seen after ablation for atrial fibrillation can be difficult to treat. Here we are going to develop a generalized computational model, which can be personalized with left atrial geometry, scar pattern, and mapping results. Such a model will enable virtual electrophysiology studies leading to the prediction of ablation points to terminate all possible such flutter pathways.

PI_NAMEs: RANJAN, RAVI  (contact)

PROJECT_TERMS: Ablation;Address;Affect;Aftercare;Area;Arrhythmia;Atrial Fibrillation;Atrial Flutter;atrioventricular node;Behavior;Cicatrix;Cities;Clinical;Complex;Computer Models;cost;Data Set;Databases;density;Development;Diagnosis;effective therapy;Electrophysiology (science);Failure;Gadolinium;Geometry;Goals;Heart Atrium;Hospitals;Image;Implant;improved;improved outcome;in silico;Incidence;insight;interdisciplinary approach;Interdisciplinary Study;Interruption;Left;Left atrial structure;Machine Learning;Magnetic Resonance Imaging;Maps;Measures;Medical Imaging;Modeling;Multi-Institutional Clinical Trial;multidisciplinary;novel;Outcome;Pacemakers;Pathway interactions;Patients;Pattern;Persons;Pharmacologic Substance;prevent;Procedures;prospective;Quality of life;Reporting;Resolution;Resources;Risk;scientific computing;Signal Transduction;simulation;Site;Sodium Chloride;Structure;success;Techniques;Testing;Time;tool;Training;Treatment outcome;Uncertainty;Universities;Utah;Veterans;virtual;voltage

PROJECT_TITLE: Computational Modeling Guided Ablation for Atrial Flutteris


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Cardiovascular;Clinical Research;Congenital Heart Disease;Congenital Structural Anomalies;Heart Disease;Pediatric;Rare Diseases

ORG_NAME: NORTHWESTERN UNIVERSITY AT CHICAGO

PHR: PROJECT NARRATIVE: This study seeks to develop new technologies to perform magnetic resonance imaging (MRI) safely and effectively in children implanted with a cardiac implantable electronic device (CIED). Specifically, this study will: (a) provide recommendations on how to perform MRI safely in these patients with existing CIEDs; (b) provide recommendations on how to configure future CIED implantations, in order to make MRI even safer; (c) deliver robust cardiac MRI methods that produce image quality in these patients that doctors can interpret with high confidence. Our study has high potential impact because it will extend MRI access to a growing number of pediatric patients with a CIED and establish an effective MRI for doctors to care for these patients.

PI_NAMEs: GOLESTANI RAD, LALEH  (contact);KIM, DANIEL

PROGRAM_OFFICER_NAME: HALLER, JOHN WAYNE

PROJECT_TERMS: Abdomen;Acceleration;Adolescent;Adopted;Adult;age related;Arrhythmia;Benefits and Risks;Body Size;Breathing;cancer risk;cardiac implant;cardiac magnetic resonance imaging;Cardiac Surgery procedures;Cardiovascular system;Caring;Characteristics;Chest;Child;Childhood;Clinical;congenital heart abnormality;Congenital Heart Defects;Consensus;Coupling;Data;data acquisition;data registry;Data Set;design;Devices;Diagnostic;Electromagnetics;Electronics;Eligibility Determination;Endocardium;Engineering;Enrollment;Ensure;Epicardium;Exclusion;FDA approved;Fever;Future;Guidelines;Heart;Heart Rate;Heating;Image;imaging modality;Implant;implantation;In Vitro;infancy;Infant;Inherited;innovation;innovative technologies;Ionizing radiation;Lead;Length;Lesion;Letters;Life;Magnetic Resonance Imaging;Methods;Modality;Modeling;Monitor;Morphologic artifacts;Myocardial;Myocardial tissue;new technology;Operating Rooms;Operative Surgical Procedures;Patients;Pectoral;Pediatric Hospitals;pediatric patients;Physics;Physiologic pulse;Population;Positioning Attribute;Prevalence;prospective;Radiation Dose Unit;radiation risk;radio frequency;radiologist;Recommendation;Reporting;repository;Research;response;Risk;risk/benefit ratio;Roentgen Rays;Safety;Scanning;Services;simulation;Syndrome;System;Techniques;Temperature;Testing;Tissues;Validation;Variant;Veins;Work;X-Ray Computed Tomography;young adult

PROJECT_TITLE: Safe and Effective MRI for Pediatric Patients with a Cardiac Implantable Electronic Device

STUDY_SECTION: EITA

STUDY_SECTION_NAME: Emerging Imaging Technologies and Applications Study Section[EITA]