NIH_SPENDING_CATS: Mental Health;Neurosciences

ORG_CITY: ATLANTA

ORG_DEPT: GENETICS

ORG_NAME: EMORY UNIVERSITY

ORG_STATE: GA

PHR: PROJECT NARRATIVE BDNF dysfunction has been observed in neurodevelopmental disorders, neurodegenerative disease, and psychiatric conditions, leading to increased interest in determining BDNF signaling mechanisms of action that may serve as therapeutic targets. Our proposal seeks to identify RhoGTPase signaling partners that are modulated by TrkB.T1 receptor activation in astrocytes, a key regulator of CNS support, homeostasis, and function. Our contributions will provide valuable information to understanding the fundamental role of developmental BDNF signaling onto astrocytes as well as identifying if novel pharmacological interventions are able to rescue astrocyte specific deficits.

PI_NAMEs: HERNANDEZ, RAYMUNDO DANIEL (contact)

PROJECT_TERMS: Actins;Adult;Affect;Affinity;Animals;Astrocytes;Award;Biological Assay;Biology;Brain;Brain-Derived Neurotrophic Factor;career;Cell Communication;Cell Physiology;cell type;Cells;Cellular Structures;Central Nervous System;Coculture Techniques;Complex;confocal imaging;Cytoskeletal Modeling;Cytoskeleton;Data Analyses;design;Development;Developmental Gene;Disease;disease model;Doctor of Philosophy;Doctor's Degree;Electrophysiology (science);Etiology;Event;experience;experimental study;Fluorescence;Functional disorder;Gene Expression;Genes;Genetic;glial cell development;Goals;Health;Homeostasis;human induced pluripotent stem cells;imaging modality;Imaging Techniques;In Situ;In Vitro;in vivo imaging;Infiltration;inhibitor;interest;Intervention;Knock-out;Knockout Mice;Link;live cell imaging;Maintenance;Measures;Medicine;Mentors;Mentorship;Methods;Modeling;Molecular;Molecular Neurobiology;Monitor;Morphogenesis;Morphology;mouse model;Mus;nervous system development;Neurodegenerative Disorders;Neurodevelopmental Disorder;neuronal growth;Neurons;Neuropil;Neurosciences;neurotransmitter uptake;neurotrophic factor;Neurotrophic Tyrosine Kinase Receptor Type 2;novel;optogenetics;Organoids;Pathologic;Pathway interactions;pharmacologic;Phase;Phenotype;Postdoctoral Fellow;postnatal;pre-doctoral;Preparation;presynaptic;Principal Investigator;Process;professor;programs;Property;Protein Isoforms;Proteins;Publications;Publishing;Receptor Activation;Reporting;Research;Research Project Grants;response;response to injury;Rett Syndrome;rho GTP-Binding Proteins;rhoB p20 GDI;Role;Signal Transduction;Structure;Supporting Cell;Synapses;synaptogenesis;targeted treatment;Technical Expertise;tenure track;Testing;Therapeutic;therapeutic target;Training Programs;transcriptome sequencing;transcriptomics;Universities;Viral;Work

PROJECT_TITLE: Investigating the role of serotonergic signaling in glial development using human iPSC-derived organoids


ADMINISTERING_IC: VA

ARRA_FUNDED: N

FUNDING_MECHANISM: OTHERS

IC_NAME: Veterans Affairs

ORG_CITY: Aurora

ORG_COUNTRY: UNITED STATES

ORG_FIPS: US

ORG_NAME: VA EASTERN COLORADO HEALTH CARE SYSTEM

ORG_STATE: CO

PHR: The goal of this proposal is to discover molecular mechanisms that link genetic factors to disease risk in Systemic Lupus Erythematosus (SLE). SLE is estimated to affect more than 200,000 people in the U.S. Treatment options for SLE are limited, as only two new therapies have received FDA approval since 1950. Available therapies cause substantial morbidity due to excess immunosuppression and infection. Thus, new therapeutic strategies are needed. The proposed research is relevant to the health of Veterans because it will define the molecular mechanisms that link genetic factors to disease risk, and provide fundamental insight into the role of the MIR146A in the etiology of Systemic Lupus Erythematosus (SLE). This insight is expected to lead to improved diagnostic, prognostic, therapeutic and preventative approaches that will improve the health of veterans and civilians with SLE and other autoimmune diseases.

PI_NAMEs: HARLEY, ISAAC T (contact)

PROJECT_TERMS: Acute;Affect;African American;Alleles;anergy;Antigen Receptors;Autoantigens;Autoimmune Diseases;Autoimmunity;autoreactive B cell;B-Cell Antigen Receptor;B-Cell Development;B-Lymphocytes;Binding;Blood Cells;career;Caring;causal variant;Cell Count;Cell Line;Cell Physiology;cell type;Cells;Chronic;Clinic;Clinical;cohort;Data;Development;Diagnostic;Disease;disorder risk;Distal;Down-Regulation;Enhancers;Environmental Risk Factor;Equilibrium;Etiology;Exhibits;experimental study;Fellowship;Flow Cytometry;follow-up;Future;Gene Expression;Genes;Genetic;genetic analysis;genetic risk factor;Genome;genome editing;genome wide association study;genome-wide;Genotype;Goals;Health;Hispanic Populations;Human;Immune;immunopathology;Immunophenotyping;Immunosuppression;improved;improved outcome;In Vitro;in vivo;Individual;Infection;innovation;insight;Interferon Type I;Intervention;Knowledge;Link;Literature;Maintenance;Maps;Mediating;Metabolism;MicroRNAs;military veteran;Modeling;Molecular;Morbidity - disease rate;mortality;Mus;Myeloid Cells;novel;novel therapeutic intervention;novel therapeutics;Pathway interactions;Patient-Focused Outcomes;Peripheral;peripheral blood;Persons;Play;Population;Population Group;prevent;Production;Productivity;prognostic;programs;Quantitative Trait Loci;rational design;Receptor Signaling;Regulation;Regulatory T-Lymphocyte;Research;restraint;Rheumatology;Risk;risk variant;RNA;Role;Serum;Signal Transduction;Site;Sjogren's Syndrome;Stimulus;Systemic Lupus Erythematosus;T-Cell Receptor;T-Lymphocyte;Testing;Therapeutic;tool;Training;transcription factor;Untranslated RNA;Variant;Veterans;Woman;Work

PROJECT_TITLE: Defining the Molecular Basis of MicroRNA-146A Risk Allele Effects in Systemic Lupus Erythematosus

STUDY_SECTION_NAME: Special Emphasis Panel[ZRD1 IMMA-G (01)]


FUNDING_MECHANISM: NON-SBIR/STTR RPGS

ORG_CITY: CHARLESTON

ORG_NAME: RALPH H JOHNSON VA MEDICAL CENTER

ORG_STATE: SC

PHR: The goal of this study is to develop an optimal mesenchymal stromal cell-based treatment protocol for reducing pain associated with chronic pancreatitis and to understand any mechanisms of protection. If proven effective, such strategy can be used as a therapeutic option for chronic pain associated with chronic pancreatitis as well as other diseases related to the health of our Veterans.

PI_NAMEs: WANG, HONGJUN  (contact)

PROJECT_TERMS: Abdominal Pain;acute pancreatitis;addiction;Adult;adult stem cell;adverse event monitoring;Affect;Aftercare;animal data;Animal Model;attributable mortality;Autologous;bench to bedside;Bone Marrow;Cell Therapy;Cells;Cessation of life;Chemistry;Chronic;chronic pain;chronic pain management;chronic pancreatitis;Clinical;clinical trial participant;Clinical Trials;cohort;critical limb Ischemia;Crossover Design;Cyclic GMP;cytokine;Diabetic Neuropathies;Diagnosis;Disease;Disease remission;Dose;Double-Blind Method;Enrollment;experience;Fibrosis;follow-up;Gene Expression;Goals;Harvest;Health;Healthcare;Human;Immunology procedure;improved;Inflammation;Inflammatory;inflammatory pain;Infusion procedures;Injury;Intervention;Knee Osteoarthritis;Measures;Medical Care Costs;Medicine;Mesenchymal;mesenchymal stromal cell;military veteran;Mission;Modeling;Morbidity - disease rate;multidisciplinary;Neurologic;Neuropathy;Neuropeptides;non-opioid analgesic;novel;novel strategies;novel therapeutics;Operative Surgical Procedures;Opiate Addiction;Overdose;Pain;Pain management;Pain Measurement;pain reduction;pain relief;pain score;painful neuropathy;Pancreas;Pancreatitis;Participant;Pathway interactions;Patient Recruitments;Patients;Peripheral Blood Mononuclear Cell;pharmacologic;Phase;Physical Examination;Placebo Control;Placebos;Population;Post-Concussion Syndrome;Post-Traumatic Stress Disorders;prescription opioid;Production;Quality Control;Randomized;Reproducibility;Research;Risk;Rodent Model;Safety;Serum;Source;stem;Stromal Cells;Syndrome;Testing;Therapeutic;Translating;Treatment Protocols;Validation;Veterans

PROJECT_TITLE: Novel Cellular Therapy for the treatment of pain associated with chronic pancreatitis

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


ADMINISTERING_IC: DA

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Drug Abuse (NIDA only);Eye Disease and Disorders of Vision;Genetics;Human Genome;Neurosciences;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human;Substance Misuse

ORG_CITY: BOSTON

ORG_NAME: BOSTON CHILDREN'S HOSPITAL

ORG_STATE: MA

PHR: Project Narrative We have identified a modular cell-type specific super-enhancer (SE) upstream of Vsx2, a transcription factor that is expressed primarily in the retina. I will examine the modularity of this SE in a human retinal organoid to understand the effect of enhancers on cell-type specification in a human model of retinal development. During my postdoctoral fellowship, I will apply this knowledge to the brain to study how epigenetic mechanisms contribute to chromatin architecture regulating gene expression and how dysregulation in these mechanisms contribute to CNS disease.

PI_NAMEs: HONNELL, VICTORIA  (contact)

PROGRAM_OFFICER_NAME: SATTERLEE, JOHN S

PROJECT_TERMS: Affect;Architecture;Binding Sites;Bipolar Neuron;blind;Blindness;Brain;cell type;Central Nervous System;Central Nervous System Diseases;Cerebellum;ChIP-seq;Chromatin;Complex;Computer Analysis;CRISPR/Cas technology;Development;Disease;Embryo;Enhancers;Epigenetic Process;Exhibits;Fellowship;gene editing technology;Gene Expression;Gene Expression Profile;Gene Expression Regulation;Genes;Genomic DNA;Genomic Segment;Genomics;Human;Human Development;human embryonic stem cell;human embryonic stem cell line;human model;Individual;innovation;insight;interest;Knock-out;knockout gene;Knockout Mice;Knowledge;Label;Learning;Measures;Microphthalmos;Modeling;Muller's cell;Mus;Mutation;Neurodegenerative Disorders;neurodevelopment;Neurodevelopmental Disorder;neurogenesis;Organoids;Pattern;Persons;Phase;Phenotype;Postdoctoral Fellow;Protocols documentation;Research;Research Project Grants;Retina;retinal bipolar neuron;retinal progenitor cell;retinogenesis;Role;single cell ATAC-seq;skills;Specific qualifier value;Spinal Cord;stem cell proliferation;Tissues;Training;transcription factor;transcriptome sequencing;Upstream Enhancer;Work

PROJECT_TITLE: Characterizing enhancers regulating transcription factor expression for cell-type specification across neurodevelopment


ADMINISTERING_IC: AG

IC_NAME: NATIONAL INSTITUTE ON AGING

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Basic Behavioral and Social Science;Behavioral and Social Science;Biomedical Imaging;Brain Disorders;Infectious Diseases;Mental Health;Neurodegenerative;Neurosciences;Social Determinants of Health

ORG_NAME: BRIGHAM AND WOMEN'S HOSPITAL

PHR: PROJECT NARRATIVE About half of all people living with HIV in the U.S. are afflicted with HIV-associated neurocognitive disorders (HAND), yet the neural mechanisms remain unknown. This project will apply structural and functional MRI to determine the role of frontostriatal neural circuits in HAND to inform the development of early diagnostic methods and help identify potential targets for therapies.

PI_NAMEs: HASSANZADEH-BEHBAHANI, SHIVA  (contact)

PROGRAM_OFFICER_NAME: SUTTERER, MATTHEW

PROJECT_TERMS: Acceleration;Adherence;Aging;aging population;antiretroviral therapy;Atlases;biopsychosocial;Brain;career;cerebral atrophy;Clinical;clinical application;Cognitive;cognitive control;cohort;Collaborations;Committee Members;comorbidity;comparison control;Computer software;Data;Data Analyses;Development;Diagnostic Procedure;Diffusion Magnetic Resonance Imaging;Educational process of instructing;Ensure;executive function;extend lifespan;Fellowship;frontal lobe;Functional disorder;Functional Magnetic Resonance Imaging;Funding;Goals;Grant;Health;High Prevalence;HIV;HIV-associated neurocognitive disorder;Hospitals;Human;Immunosuppression;Impaired cognition;improved;Injury;innovation;insight;interest;Knowledge;Lead;Magnetic Resonance Imaging;Manuscripts;Measures;Mediating;Mental Depression;Mentors;Mentorship;Methods;mild cognitive impairment;Modality;mortality;multimodality;Nature;neural circuit;neurobehavioral;Neurocognitive;Neurocognitive Deficit;neuroimaging;neuromechanism;Neurosciences;Older Population;Patients;Peripheral;Persons;Phase;Play;Positioning Attribute;Postdoctoral Fellow;pre-doctoral;Predisposition;Prefrontal Cortex;programs;Publications;Quality of life;Recording of previous events;Research;Research Personnel;Research Project Grants;Risk;Role;Severity of illness;skills;Structure;Students;success;symposium;Symptoms;targeted treatment;Techniques;Testing;therapeutic target;Thinness;timeline;tractography;Training;Unemployment;Universities;Viral;white matter;Work;Writing

PROJECT_TITLE: A Biopsychosocial Approach to Understanding the Role of White Matter in Aging


ADMINISTERING_IC: EY

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

IC_NAME: NATIONAL EYE INSTITUTE

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Bioengineering;Biomedical Imaging;Clinical Research;Eye Disease and Disorders of Vision;Neurosciences

ORG_CITY: LA JOLLA

ORG_DEPT: PSYCHOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

ORG_STATE: CA

PHR: PROJECT NARRATIVE What we perceive and hold in working memory is dependent on selective attention — a top-down cognitive ability that regulates the limited cortical resources available in the human brain from moment to moment. The proposed work will use a combination of cutting-edge non-invasive human brain imaging (fMRI and EEG), combined with computational modeling, to reveal the neural computational mechanisms through which attention regulates limited visuocortical resources. Understanding the neural substrates underlying attention in healthy adults is paramount for developing targeted interventions for brain disorders that disrupt attention, perception, and working memory — crucial cognitive functions in our everyday lives.

PI_NAMEs: RAMIREZ, LUIS DANIEL (contact)

PROGRAM_OFFICER_NAME: CLAYTON, EDWIN C

PROJECT_TERMS: Academic Training;Adult;Attention;attentional modulation;Award;Behavioral;Benchmarking;Brain;Brain Diseases;Brain imaging;BRAIN initiative;Bypass;cognitive ability;cognitive function;cognitive process;Communication;Computer Models;Data;Dependence;Detection;Development;Diagnosis;Disease;Down-Regulation;Electroencephalography;Ensure;Environment;Equity;experience;experimental study;Fostering;Functional Magnetic Resonance Imaging;functional magnetic resonance imaging/electroencephalography;Goals;Human;Impaired cognition;improved;information processing;innovation;International;Intervention;Intuition;Machine Learning;Maintenance;Manuscripts;Measures;Mentors;Mentorship;Methodology;Methods;Mission;Modeling;multimodal neuroimaging;National Institute of Neurological Disorders and Stroke;neural;neural correlate;neuroimaging;Neurons;Noise;Oral;patient population;Pattern;Perception;Phase;Play;posters;Printing;Process;process improvement;Psychophysics;Regulation;Reporting;Research;Research Personnel;Resolution;Resources;Scientist;selective attention;Short-Term Memory;Signal Detection Analysis;Signal Transduction;Stimulus;symposium;Techniques;temporal measurement;Testing;Time;Training;United States National Institutes of Health;Vision;Visual;Visual Cortex;Visual evoked cortical potential;visual information;visual memory;visual processing;Work

PROJECT_TITLE: What Mechanisms Underlie Top-Down Modulation of Human Visual Cortex?


NIH_SPENDING_CATS: Aging;Biotechnology;Eye Disease and Disorders of Vision;Genetics;Hearing Loss;Macular Degeneration;Neurodegenerative;Neurosciences

ORG_NAME: MASSACHUSETTS EYE AND EAR INFIRMARY

PHR: PROJECT NARRATIVE Age-related macular degeneration (AMD) and age-related hearing loss (ARHL) are both complex neurodegenerative disease with common causes, including age, diet, smoking, and at the tissue level, macrophage invasion and complement activation has been reported. Macrophage and complement activation creates a viscous feedback loop of inflammation. Here our study aims to develop a treatment strategy in animal models by inhibiting the alternative pathway of complement in damaged tissues to partially reduce inflammation and mitigate wet AMD and ARHL pathology.

PI_NAMEs: PARSONS, NATHANIEL BRYAN DAVID (contact)

PROJECT_TERMS: Abate;Abnormal Macrophage;adeno-associated viral vector;Age;age related;Age related macular degeneration;aged;aging auditory system;Alternative Complement Pathway;Anaphylatoxins;Animal Model;Animals;Annexin A4;Antibodies;Auditory system;Binding;Biodistribution;Biological;Biological Assay;Blindness;Cell surface;Cells;Cellular Membrane;Chimeric Proteins;Clinical;Cochlea;Competence;Complement;Complement 3 Convertase;Complement 3d Receptors;Complement Activation;Complement Factor H;Complement Membrane Attack Complex;Complex;CRISPR/Cas technology;cytokine;Deposition;Diet;Disease;Epitopes;Etiology;Exons;Expression Profiling;extracellular;Eye;Feedback;Gene Activation;gene therapy;Goals;graduate school;graduate student;Histologic;Histology;Human;human model;human old age (65+);human tissue;Immune;Immunohistochemistry;Inflammation;Inflammatory;inflammatory milieu;inhibitor;interest;Invaded;Learning;Macrophage;Macrophage Activation;Mediating;Modeling;Molecular;mouse model;Mus;natural antibodies;neoantigens;nerve damage;Nerve Degeneration;Nerve Tissue;Neurodegenerative Disorders;Neurosciences Research;Nonexudative age-related macular degeneration;novel;Ocular Pathology;old mice;Ophthalmology;Opsonin;Pathologic;Pathology;Pathway interactions;Pattern;Persons;Phase;post-doctoral training;Postdoctoral Fellow;Presbycusis;prevent;promoter;Proteins;Reporting;Research;Research Training;response to injury;RNA;Sensory;sensory neuroscience;Site;Smoke;Smoking;Stress;Structure of retinal pigment epithelium;System;Techniques;Technology;Testing;Tissue Preservation;tissue repair;Tissues;Training;Translational Research;treatment strategy;USH2A gene;vector;vector control;Viscosity;Vision;Visual System;Work

PROJECT_TITLE: Dual CRISPR/Cas9 exon deleting approach for the treatment of USH2A-associated disorders


ADMINISTERING_IC: MH

ED_INST_TYPE: SCHOOLS OF MEDICINE

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Assistive Technology;Basic Behavioral and Social Science;Behavioral and Social Science;Bioengineering;Brain Disorders;Clinical Research;Depression;Major Depressive Disorder;Mental Health;Mental Illness;Neurosciences;Rehabilitation;Serious Mental Illness

ORG_CITY: SAN FRANCISCO

ORG_DEPT: NEUROSURGERY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

PHR: PROJECT NARRATIVE Depression is a debilitating mood disorder characterized by cognitive dysfunction. Findings from the proposed research will contribute to a greater understanding of neural mechanisms underlying cognitive impairment in depression, and can be used towards optimizing neurostimulation therapy in neuropsychiatric disorders.

PI_NAMEs: ALLAWALA, ANUSHA  (contact)

PROGRAM_OFFICER_NAME: CHAVEZ, MARK RAY

PROJECT_TERMS: Amygdaloid structure;Anterior;Behavior;Behavior Control;Behavioral;behavioral impairment;Biomedical Engineering;Brain;capsule;career;cell type;cingulate cortex;Cognition;Cognitive;cognitive control;cognitive enhancement;Communication;Complement;Complex;computational neuroscience;Conflict (Psychology);Coupled;Data;Data Analyses;Data Collection;Deep Brain Stimulation;Diagnosis;disability;Disease;Dissection;Dorsal;Electric Stimulation;Electric Stimulation Therapy;Electroconvulsive Therapy;Electrodes;Electrophysiology (science);Ensure;Excision;executive function;Exertion;Experimental Designs;experimental study;flexibility;Frequencies;Functional disorder;Goals;Grain;Human;human subject;ideation;Impaired cognition;Impairment;Implanted Electrodes;improved;interdisciplinary approach;Knowledge;Major Depressive Disorder;Measurement;Measures;Mental Depression;Mental disorders;Mental Processes;Mood Disorders;Moods;Morphologic artifacts;multidisciplinary;multimodality;neural;neural circuit;neuromechanism;neurophysiology;neuropsychiatric disorder;neuroregulation;Neurosciences;novel;Outcome;Parents;Participant;Patient Self-Report;Patients;Pharmacologic Substance;Pharmacotherapy;Phase;Population;Postdoctoral Fellow;Prefrontal Cortex;Psychotherapy;recruit;Research;research clinical testing;Research Personnel;Research Project Grants;Research Proposals;Resistance;Rest;Rodent Model;Role;rumination;Schedule;Source;Stimulus;Structure;Symptoms;task analysis;Techniques;Testing;Therapeutic;Thinking;tool;Training;treatment optimization;treatment-resistant depression;Ventral Striatum;Work

PROJECT_TITLE: Modulation of network dynamics across mood states using closed-loop deep brain stimulation for depression


ORG_CITY: SAN DIEGO

ORG_NAME: VA SAN DIEGO HEALTHCARE SYSTEM

PHR: Project Narrative KRAS mutant lung adenocarcinoma remains a challenging clinical problem without specific inhibitors. We have demonstrated that alveolar Type II cells become cancer stem cells when Kras is activated. We will analyze sphingolipid pathways in these cells to identify new therapeutic targets. We will also use gene editing technology (Cas/Crispr) to find sphingolipid genes that are necessary for the survival and growth of Kras mutant stem cells. Finally, we will test new methods of activating the immune system against these cells. These approaches should allow rapid translation to the clinic to help Veterans with KRAS mutant lung cancer.

PI_NAMEs: ONAITIS, MARK  (contact)

PROJECT_TERMS: 3-Dimensional;Address;Alleles;alveolar type II cell;Biological Assay;Breeding;Cancer Etiology;cancer stem cell;Cells;ceramide 1-phosphate;ceramide kinase;Ceramides;Cessation of life;Clinic;Clinical;Complex;CRISPR/Cas technology;CTLA4 gene;Development;Distal;Enzyme Inhibition;Enzymes;Foundations;gene editing technology;Genes;Genetic;genetic approach;Genetic Recombination;Genetic Transcription;Glucosylceramides;Glycosphingolipids;Growth;Homeostasis;Immune checkpoint inhibitor;Immune system;Immunologic Surveillance;Immunosuppression;In Vitro;in vivo;Individual;inhibitor;KRAS oncogenesis;KRAS2 gene;KRASG12D;Laboratories;Lactosylceramides;Lead;LoxP-flanked allele;Lung;Lung Adenocarcinoma;lung cancer cell;lung development;Lung Neoplasms;Macrophage;Maintenance;Malignant neoplasm of lung;Metabolism;Methods;mouse genetics;Mus;mutant;Mutate;Mutation;Neoplasm Metastasis;neoplastic cell;new therapeutic target;Non-Small-Cell Lung Carcinoma;notch protein;novel;novel therapeutic intervention;Oncogenes;Pathway interactions;Patient-Focused Outcomes;Patients;Pharmaceutical Preparations;pharmacologic;Phenotype;progenitor;programmed cell death ligand 1;Pulmonary Surfactant-Associated Protein C;response;Role;Sphingolipids;sphingosine 1-phosphate;SPHK1 enzyme;stem cells;stem-like cell;Survival Rate;T cell response;Tamoxifen;Testing;Therapeutic;therapeutic target;TP53 gene;Translations;treatment response;tumor;tumor growth;tumor initiation;tumor-immune system interactions;Tumorigenicity;Type II Epithelial Receptor Cell;Urethane;Veterans

PROJECT_TITLE: Role of Sphingolipids in KRAS induced lung adenocarcinoma

STUDY_SECTION_NAME: Special Emphasis Panel[ZRD1 ONCB-A (01)]


ORG_CITY: PHOENIX

ORG_NAME: PHOENIX VA HEALTH CARE SYSTEM

ORG_STATE: AZ

PHR: Use of continuous glucose monitoring (CGM) is increasing rapidly in the VHA. However, there are major gaps in our understanding of CGM including whether it improves long-term glucose control, prevents or delays diabetes complications, and serious health events such as death. Using the VHA health records we will construct one of the largest datasets of type 1 and 2 diabetes CGM users to date. This will allow us to assess in T1D and T2D the effect of CGM initiation not just on long-term glucose control but also on a) hypoglycemia and hyperglycemia events, b) development of diabetes renal disease, a composite diabetes complication index, and c) cardiovascular outcomes and death. This study will help create an informed precision medicine based approach for the use of CGM.

PI_NAMEs: REAVEN, PETER D (contact)

PROJECT_TERMS: Accident and Emergency department;Adverse event;adverse outcome;Age;blood glucose regulation;Cardiovascular Diseases;Cardiovascular system;Caring;Cessation of life;Characteristics;Clinical;clinical development;clinically relevant;cohort;comorbidity;Complication;Complications of Diabetes Mellitus;Continuous Glucose Monitor;cost;Data;Data Collection;Data Set;Decision Making;Development;Diabetes Mellitus;Disease Outcome;early onset;Ensure;Equilibrium;ethnic identity;Ethnic Origin;Event;experience;Financial cost;follow-up;Fostering;Frequencies;Glucose;glycemic control;Glycosylated hemoglobin A;Goals;Health;Health Personnel;health record;Healthcare Systems;Heart failure;high risk;Hospitalization;hospitalization rates;Hyperglycemia;Hypoglycemia;improved;indexing;Individual;Insulin;insulin dependent diabetes mellitus onset;Insulin-Dependent Diabetes Mellitus;Ischemic Stroke;Kidney Diseases;Life;Long-Term Effects;mortality;Myocardial Infarction;Myocardial Ischemia;Non-Insulin-Dependent Diabetes Mellitus;Nurses;Observational Study;Outcome;Patients;Pattern;Perception;Physicians;precision medicine;prevent;Prevention;Race;Regimen;Renal Glycosuria;Risk;secondary analysis;Serious Adverse Event;Signal Transduction;Stroke;Subgroup;Time;type I and type II diabetes;Veterans Health Administration

PROJECT_TITLE: Use of continuous glucose monitoring and long-term diabetes outcomes within the Veteran Affairs Health Care System

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


ORG_NAME: VETERANS AFFAIRS MED CTR SAN FRANCISCO

PHR: Veterans enrolled in the VHA health care system are almost three times more likely to suffer from diabetes than the general population. Studies have shown that lowering high blood sugar (hyperglycemia) among diabetic veterans does not adequately reduce their risk of developing serious cardiovascular disease caused by fatty blockages in arteries, called atherosclerosis. Our published findings show that hyperglycemia increases atherosclerosis by enhancing the inflammatory properties of microvesicles that circulate in the bloodstream, called “exosomes”. Our publications also show that we can produce protective exosomes from cultured cells that suppress inflammation when injected into diabetic mice. Through studies of exosomes isolated from diabetic veterans, and cultured cells, we will study how hyperglycemia increases the inflammatory and atherogenic properties of exosomes. We will also seek to develop protective exosomes that could serve as new treatments to control atherosclerosis and cardiovascular disease among diabetic veterans.

PI_NAMEs: RAFFAI, ROBERT  (contact)

PROJECT_TERMS: Acceleration;Adipocytes;adipokines;Adipose tissue;aerobic glycolysis;Anti-Inflammatory Agents;antioxidant enzyme;Apoptotic;Applications Grants;Arteries;Atherosclerosis;Attenuated;Automobile Driving;Bioenergetics;Biological Markers;Biology;Blood Circulation;Blood Glucose;blood glucose regulation;Bone Marrow Stem Cell;Bone Marrow Transplantation;cardiometabolism;Cardiovascular Diseases;Cells;Cessation of life;Circulation;Communication;Cultured Cells;cytokine;Data;Diabetes Mellitus;diabetic;Diabetic mouse;disability;Enrollment;exosome;experimental study;Exposure to;fatty acid oxidation;Foam Cells;Fostering;Functional disorder;Funding;General Population;Genes;Genetic Processes;Glucose;Goals;Healthcare Systems;Hematopoietic stem cells;High Fat Diet;Human;Hyperglycemia;IL4 gene;Immune system;Immunity;Impairment;improved;Individual;Inflammation;Inflammatory;Injections;Insulin Resistance;Interleukin-10;Interleukin-4;Lesion;Leukocytes;Leukocytosis;Link;Lipids;Macrophage;Mediating;Medical;Memory;Metabolic;Metabolism;microvesicles;Mitochondria;mitochondrial dysfunction;mitochondrial metabolism;Molecular;mouse model;Mus;Myeloid Cells;Myelopoiesis;non-diabetic;Non-Insulin-Dependent Diabetes Mellitus;Obesity;Outcome;Oxidation-Reduction;Pathogenesis;Pathway interactions;Persons;Phagocytes;Plasma;Predisposition;premature;prevent;Production;programs;Property;protective effect;Publications;Publishing;Regulation;Reporting;Research;Resolution;Respiration;Risk;Role;Series;Signal Transduction;Source;stem cells;Stress;Testing;Tissue Expansion;Training;transcriptomics;uptake;vesicular release;Veterans;Visceral fat

PROJECT_TITLE: Exosomes in the Pathogenesis of Diabetic Atherosclerosis & its Treatment Opportunities

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


ORG_CITY: BIRMINGHAM

ORG_NAME: BIRMINGHAM VA MEDICAL CENTER

ORG_STATE: AL

PHR: Opioid prescribing has fallen across the US, both within and outside the US Veterans Administration. Although this change likely will prevent prescription-related harm for a number of patients, reports signal adverse events including suicide, for others. Where harm has occurred, it is crucial to know what factors, modifiable and nonmodifiable, played a role. Whereas much research has sought statistical associations between prescription opioid change and outcomes like suicide, we offer a different approach. We will recruit bereaved survivors of suicides following a prescription opioid change. We will carry out detailed survey, medical record review, and in-depth psychological autopsy interviews to learn which patient and clinical context factors could help to account for why the suicides took place. This research is descriptive. The research team includes scholarly experts and members of the affected communities. Working with VA partners, we seek actionable points of leverage for policy makers, and for health systems seeking to prevent these suicides from taking place.

PI_NAMEs: KERTESZ, STEFAN G (contact)

PROJECT_TERMS: addiction;Address;Adverse event;Affect;Ally;Anthropology;Attention;Autopsy;Caring;Cessation of life;Charge;Clinical;clinical care;clinical encounter;Collaborations;Communities;contextual factors;Data;Databases;design;Diagnosis;distrust;Dose;Ethics;Etiology;Event;experience;falls;Family;Family member;Feedback;Feeling suicidal;follow-up;Friends;Goals;Harm Reduction;hazard;Health Services Research;Health system;Healthcare;Healthcare Systems;Individual;innovation;insight;Interdisciplinary Study;Intervention;intervention mapping;Interview;Investments;Learning;Medical;Medical Records;member;Mental Health;Methodology;Methods;milligram;Morphine;Needs Assessment;Opioid;opioid tapering;Outcome;Pain;Pain management;Patients;Persons;Policies;Policy Maker;Positioning Attribute;prescription opioid;prevent;Preventive;Process;programs;prospective;protective factors;psychologic;Psychological Factors;Psychological Techniques;Randomized;recruit;Reporting;Research;Research Design;Research Personnel;response;Risk Factors;Safety;Self-Injurious Behavior;Signal Transduction;social;social stigma;Structure;Substance Use Disorder;suicidal;suicidal morbidity;suicidal risk;Suicide;Suicide prevention;Surveys;Survivors;Testing;therapy design;Time;Triage;United States Department of Veterans Affairs;United States Food and Drug Administration;Veterans;Veterans Health Administration;Work

PROJECT_TITLE: Clinical context of SuicIde following OPIOID transitionS in Veterans, CSI:OPIOIDS-V

STUDY_SECTION_NAME: Special Emphasis Panel[HSR9]


ORG_CITY: DALLAS

ORG_NAME: VA NORTH TEXAS HEALTH CARE SYSTEM

ORG_STATE: TX

PHR: Narrative Chronic musculoskeletal (MSK) pain and co-occurring depressive symptoms often result in refractory disease, worse outcomes, and additional burden on the patient and society, costing over $600 billion annually. An accessible, safe, and effective behavioral intervention targeting older Veterans with chronic MSK pain and comorbid depressive symptoms is sorely needed, especially in older populations where the efficacy and safety of pharmacologic options are less favorable. We propose to conduct a hybrid type 1 randomized controlled trial at two large VA facilities to evaluate the effectiveness, implementation processes, and cost of MOTIVATE-- a health coach, virtually delivered, behavioral intervention for older Veterans with MSK pain and depressive symptoms. Results from this research will inform the scalability and implementation of MOTIVATE to ultimately improve pain interference, depressive symptoms, among other outcomes in a rapidly growing population of older Veterans with co-occurring MSK pain and depressive symptoms.

PI_NAMEs: MAKRIS, UNA E. (contact)

PROJECT_TERMS: Address;Aging;aging population;Area;arm;Arthritis;Behavior Therapy;Behavioral;behavioral outcome;Blinded;Brief Pain Inventory;budget impact;Caring;chronic back pain;chronic musculoskeletal pain;Clinical;Clinical effectiveness;comorbidity;Complex;contextual factors;cost;Cost Analysis;cost estimate;Data;Degenerative polyarthritis;depressive symptoms;Development;Direct Expenditure;disability;Dissemination and Implementation;economic cost;Effectiveness;effectiveness evaluation;effectiveness-implementation RCT;effectiveness/implementation design;Enrollment;Evaluation;evidence base;feasibility testing;Feedback;frailty;Future;Goals;Guidelines;Health;Health Services Accessibility;Healthcare Systems;Homogeneously Staining Region;human old age (65+);Hybrids;implementation cost;implementation facilitators;implementation framework;implementation process;impression;Improve Access;improved;improved outcome;Indirect Expenditures;innovation;Intervention;intervention delivery;Interview;Measurement;medical specialties;Mental Depression;Mental Health;Mental Health Services;Methodology;military veteran;Modeling;Motivation;motivational enhancement therapy;Movement;multiple chronic conditions;Musculoskeletal;Musculoskeletal Pain;Nonpharmacologic Therapy;novel;older adult;Older Population;Operative Surgical Procedures;Outcome;Pain;pain behavior;pain catastrophizing;Pain intensity;Pain interference;Pain management;pain symptom;Patient-Focused Outcomes;Patients;Pharmaceutical Preparations;pharmacologic;Physical activity;pilot trial;Polypharmacy;Population;preference;Primary Care;primary care practice;primary endpoint;primary outcome;Promoting Action on Research Implementation in Health Services framework;Provider;Quality of life;Randomized;Randomized, Controlled Trials;Recommendation;recruit;Refractory Disease;remote delivery;Reporting;Research;Research Priority;resilience;Resources;response;Safety;secondary outcome;Self Efficacy;Services;Severities;Site;Sleep;Societies;Structure;symposium;Target Populations;telecoaching;Telephone;Testing;Treatment outcome;trial design;uptake;Veterans;virtual delivery;virtual healthcare;Waiting Lists

PROJECT_TITLE: MOTIVATE to Improve Outcomes for Older Veterans with Musculoskeletal Pain and Depression

STUDY_SECTION_NAME: HSR-6 Aging, Recovery, and Workforce[HSR6]


ED_INST_TYPE: MUSEUMS

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

NIH_SPENDING_CATS: Eye Disease and Disorders of Vision;Neurosciences

ORG_CITY: CAMBRIDGE

ORG_NAME: MASSACHUSETTS INSTITUTE OF TECHNOLOGY

PHR: Project Narrative Our brain is incredibly plastic during critical periods in development: experience reorganizes trillions of synapses between neurons, enabling neural circuits to mature and optimally process sensory information. The proposed research will determine how experience shapes the functional properties of neurons in the visual cortex by applying advanced physiological and molecular techniques to visualize synaptic modifications in functional synapses. Successful completion of this proposal will broaden our understanding of the synaptic mechanisms that underlie aberrant sensory processing and neurodevelopmental disorders, such as amblyopia, autism and schizophrenia.

PI_NAMEs: TSIMRING, KATHERINE RACHEL (contact)

PROJECT_TERMS: Amblyopia;AMPA Receptors;area striata;autism spectrum disorder;awake;Binocular Vision;Brain;Calcium;Chemosensitization;Chronic;Computer Models;Contralateral;critical developmental period;critical period;Dendritic Spines;deprivation;Development;DLG4 gene;Excision;Exhibits;experience;experimental study;Eye;Functional disorder;Functional Imaging;Future;Glutamates;Guanosine Triphosphate Phosphohydrolases;Image;Impairment;in vivo;in vivo calcium imaging;Individual;insight;Ipsilateral;Lead;Link;Maps;Measures;Mediating;Modification;Molecular;Molecular Analysis;monocular deprivation;Mus;Nature;neural circuit;Neurodevelopmental Disorder;neuron development;neuronal cell body;Neurons;novel;Ocular Dominance;orientation selectivity;Physiological;postnatal development;postsynaptic;postsynaptic neurons;presynaptic;presynaptic neurons;prevent;Property;Proteins;Proteome;Research;response;Scaffolding Protein;Schizophrenia;Sensory;Sensory Process;Shapes;structural imaging;Structure;superresolution imaging;Synapses;Synaptic plasticity;Techniques;Technology;Testing;Tissue Expansion;Tissues;two-photon;ultra high resolution;Visual;Visual Cortex;Visual impairment;visual information;Visual System;visual tracking;Visualization;Work

PROJECT_TITLE: Alignment of visual features in binocular cortical circuits through experience dependent synaptic plasticity


ORG_NAME: VA BOSTON HEALTH CARE SYSTEM

PHR: Telemental health (TMH), in which services are delivered from a distance via videoconferencing or phone, can increase Veterans’ access to high quality mental health (MH) care. Its use has skyrocketed during COVID-19 in order to reduce the infection risk of in-person care; this has provided an unprecedented opportunity to examine TMH use on a national scale. Specifically, we need to understand how the quality of TMH care compares to in-person care (as limited evidence suggests phone care may be lower quality than video and in- person), as well as which modality of care patients prefer across various clinical circumstances (e.g., medication management versus therapy appointments). These findings will be used to improve MH care modality decision-making at the patient, provider, and/or system levels, with a focus on increasing video use in circumstances where it is clinically effective and preferred by patients. Results will inform national VA clinical and operational decisions regarding how MH care is delivered well beyond the COVID-19 pandemic.

PI_NAMEs: CONNOLLY, SAMANTHA L (contact)

PROJECT_TERMS: Academy;Address;Anxiety;Appointment;Attitude;authority;caregiving;Caring;Clinic;Clinical;Clinical Services;Collaborations;Communication;comparative effectiveness;Comparative Effectiveness Research;Complex;connected care;cost;COVID-19;COVID-19 pandemic;Data;Decision Making;design;Development;Diagnosis;Effectiveness;effectiveness/implementation trial;Ensure;Equity;evidence base;experience;Future;Goals;health care delivery;Health Services;Health Services Accessibility;Health Technology;Healthcare;Home;Hospitalization;hospitalization rates;Hybrids;implementation strategy;improved;Infection;Infection prevention;infection risk;innovation;Interview;Leadership;Medication Management;Medicine;Mental Health;Mental Health Services;Mentors;Methodology;Methods;Modality;Outcome;Outpatients;pandemic disease;patient oriented;Patient Preferences;Patients;Persons;Positioning Attribute;preference;prevent;Primary Care;Process;Promoting Action on Research Implementation in Health Services framework;Provider;Psychologist;Psychotherapy;Publishing;Quality of Care;Recording of previous events;Research;Research Personnel;Research Priority;Safety;Sampling;Scientist;Services;Site;social stigma;Suicide prevention;Symptoms;System;telehealth;Telemental;Telephone;Testing;Time;Training;Travel;Veterans;Videoconferencing;Work

PROJECT_TITLE: Provision of high quality telemental health care during COVID-19 and beyond

STUDY_SECTION_NAME: Research Career Scientist[MRA0]


ORG_CITY: SAN ANTONIO

ORG_NAME: SOUTH TEXAS VETERANS HEALTH CARE SYSTEM

PHR: Among women Veterans, breast cancer (BC) is the most diagnosed cancer, accounting for 30% of female cancers and is more prevalent among older Veterans. Of great significance is the fact that BC is more common among military servicewomen, than in the general population. Further, this is particularly important for South Texas Veterans where BC prevalence is rampant. This research program is significant, as it will identify therapeutic targets and develop novel combination therapy for treating triple negative breast cancer (TNBC, a deadly subtype of BC). These treatments are urgently needed for many VA patients and will be a cost-effective approach with potential to save millions of dollars to the VA health care system.

PI_NAMEs: VADLAMUDI, RATNA K (contact)

PROJECT_TERMS: Accounting;Address;age group;Aggressive Clinical Course;Biological;Biological Assay;breast cancer metastasis;Breast Cancer Model;breast cancer progression;Breast Cancer Risk Factor;breast cancer survival;Breast Cancer therapy;cancer cell;cancer diagnosis;Caring;Cell Physiology;chemotherapy;Clinical;clinically relevant;clinically significant;Combined Modality Therapy;cost effective;Development;DNA biosynthesis;DNA Damage;DNA Double Strand Break;DNA Repair;DNA Repair Pathway;DNA-PKcs;Double Strand Break Repair;effective therapy;Estrogen receptor positive;FDA approved;Female;Foundations;Functional disorder;Gamma-H2AX;General Population;Genomic Instability;Glutamic Acid;Healthcare;Healthcare Systems;Heterogeneity;Immunoprecipitation;inhibitor;inhibitor therapy;KDM1A gene;Knowledge;Label;Leucine;Malignant Breast Neoplasm;Malignant Neoplasms;Mediating;Military Personnel;military veteran;Molecular;Molecular Mechanisms of Action;molecular subtypes;mortality;Neoplasm Metastasis;new therapeutic target;Nonhomologous DNA End Joining;novel;novel therapeutic intervention;Oncogenes;Oncogenic;Organoids;Outcome;patient derived xenograft model;Patients;Pharmaceutical Preparations;Phosphotransferases;Play;Pre-Clinical Model;Prevalence;Prevention;prognostic indicator;programs;Proliferating;Proline;Proteins;recruit;replication stress;Reporter;Research;Resistance development;response;Role;screening;Services;Signal Transduction;Site;South Texas;targeted cancer therapy;targeted treatment;Testing;Therapeutic Effect;therapeutic target;therapy resistant;TOP2A gene;Topoisomerase;Topoisomerase Inhibitors;Toxic effect;triple-negative invasive breast carcinoma;tumor progression;Veterans;Woman;women's diagnosis;Xenograft Model

PROJECT_TITLE: Targeting PELP1 oncogenic functions in DNA repair for treating triple negative breast cancer

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


ORG_CITY: PORTLAND

ORG_NAME: PORTLAND VA MEDICAL CENTER

ORG_STATE: OR

PHR: Although rates of alcohol-use disorder in women veterans have been steadily increasing, sex differences in immunological and neurobiological vulnerabilities or sex-sensitive risk factors, such as trauma or emotion regulation difficulties are rarely examined in clinical trials. As the systematic study of sex differences may provide a mechanistic understanding of biobehavioral interactions that differentially affect treatment outcome in men and women veterans, this project will leverage results from past studies of naltrexone and examine whether its anti- inflammatory or neuromodulating properties attenuate psychosocial factors and reduce alcohol use in a sex- dependent manner. As women veterans have unique vulnerabilities that contribute to disease severity, results from this study will have substantial impact in advancing the VA mission for precision medicine by providing biomarkers for tailored treatment approaches, as well as, supporting a VA priority in addressing the unique needs and improving health outcomes for female veterans.

PI_NAMEs: KOHNO, MILKY  (contact)

PROJECT_TERMS: addiction;Address;Affect;alcohol abuse therapy;Alcohol consumption;alcohol use disorder;Anti-Inflammatory Agents;Attenuated;Behavioral;binge drinking;biobehavior;Biological;Biological Assay;Biological Markers;Brain;brain abnormalities;Choline;Clinical Trials;Cognitive;combat;comparison control;Complex;Development;drinking;drinking behavior;effective therapy;Effectiveness;emotion regulation;Emotional Stress;Event;Exhibits;experience;Exposure to;Forcible intercourse;Functional Magnetic Resonance Imaging;Future;Health;High Prevalence;Immunologics;Impairment;improved;indexing;individualized medicine;Inflammation;inflammatory marker;insight;intimate partner violence;Life;Limbic System;Link;Magnetic Resonance Spectroscopy;Measures;men;Military Personnel;Mission;N-acetylaspartate;Naltrexone;negative affect;Neurobiology;neuroimaging marker;Neurons;neuroregulation;Pathway interactions;Peripheral;physical assault;Placebos;precision medicine;Prevalence;Property;psychosocial;Psychosocial Factor;Questionnaires;randomized placebo controlled trial;Recording of previous events;reduced alcohol use;relapse risk;Reporting;response;Rest;Risk Factors;Severities;Severity of illness;sex;Sex Differences;sexual assault;sexual trauma;specific biomarkers;Substance abuse problem;System;Testing;therapeutic target;Translating;Trauma;trauma exposure;traumatic event;Treatment Efficacy;Treatment outcome;treatment response;Veterans;Woman;women versus men;women's outcomes;Work

PROJECT_TITLE: Sex differences in trauma, inflammation and brain function and the implications for treatment efficacy in alcohol use disorder

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


ADMINISTERING_IC: AR

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

NIH_SPENDING_CATS: Arthritis;Clinical Research;Clinical Trials and Supportive Activities;Osteoarthritis;Transplantation

ORG_CITY: PITTSBURGH

ORG_DEPT: ORTHOPEDICS

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

ORG_STATE: PA

PHR: Project Narrative Anterior cruciate ligament reconstruction (ACLR) is complicated by high failure rates in young active individuals. The surgical methods to reconstruct the ACL-deficient knee, including graft selection (autograft bone-patellar tendon-bone or quadriceps tendon) and performance of a lateral extra-articular tenodesis may reduce the risk of graft failure in young active individuals. Improved surgical methods to reduce the risk of graft failure will minimize the need for revision ACLR and the associated decreased quality of life and socioeconomic burden that occurs because of ongoing knee instability and the increased risk for post- traumatic osteoarthritis.

PI_NAMEs: IRRGANG, JAMES JOHN (contact);MUSAHL, VOLKER

PROGRAM_OFFICER_NAME: WASHABAUGH, CHARLES H

PROJECT_TERMS: Address;adverse outcome;Affect;Age Years;anterior cruciate ligament injury;anterior cruciate ligament reconstruction;Anterolateral;Arthritis;Athletic Injuries;Autologous Transplantation;Blinded;bone;Bone Transplantation;Canada;cost;cost effective;Data;Degenerative polyarthritis;disability;Drops;Economic Burden;economic cost;Eligibility Determination;Europe;Failure;follow-up;graft failure;hamstring;Health;Health Care Costs;high risk;improved;Individual;Intention;International;Intervention;Joints;Knee;Knee bone;Knowledge;Lateral;Meniscus structure of joint;Meta-Analysis;Methods;Mission;Modeling;Morbidity - disease rate;Multi-Institutional Clinical Trial;Multicenter Studies;National Institute of Arthritis, and Musculoskeletal, and Skin Diseases;Operative Surgical Procedures;Outcome;Outcome Assessment;Participant;patellar tendon;Patient Outcomes Assessments;Patients;Performance;performance based measurement;Postoperative Period;preference;Prevention;primary outcome;Procedures;Protocols documentation;quadriceps muscle;Quality of life;Randomized;randomized trial;recruit;Rehabilitation therapy;repaired;Reporting;return to sport;Risk;Risk Reduction;Rupture;secondary outcome;sex;Site;socioeconomics;Sports;Standardization;Surgeon;Surgical Management;Symptoms;tendon graft;Tendon structure;Testing;Time;Traumatic Arthropathy;United States National Institutes of Health;Woman

PROJECT_TITLE: STABILITY 2: ACL Reconstruction +/- Lateral Tenodesis with Patellar vs. Quad Tendon

STUDY_SECTION: AMSC

STUDY_SECTION_NAME: Arthritis and Musculoskeletal and Skin Diseases Clinical Trials Study Section [AMSC]


ADMINISTERING_IC: MD

ED_INST_TYPE: SCH ALLIED HEALTH PROFESSIONS

IC_NAME: NATIONAL INSTITUTE ON MINORITY HEALTH AND HEALTH DISPARITIES

NIH_SPENDING_CATS: Aging;Behavioral and Social Science;Brain Disorders;Cerebrovascular;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Physical Rehabilitation;Racial and Ethnic Minority Health Research;Rehabilitation;Social Determinants of Health;Stroke

ORG_CITY: SALT LAKE CITY

ORG_DEPT: OTHER HEALTH PROFESSIONS

ORG_NAME: UNIVERSITY OF UTAH

ORG_STATE: UT

PHR: PROJECT NARRATIVE This project will address priorities of the US health delivery system, including those of post-acute rehabilitation care, for improving access to quality of rehabilitation services among underserved populations by 1) advancing the scientific understanding of causes of health disparities in a large national sample and 2) identifying causal pathways that can reduce rehabilitation-related health disparities for highly vulnerable stroke patients, 3) identifying facilitators and barriers to quality of care in the high-need, high-cost patients.

PI_NAMEs: KUMAR, AMIT  (contact)

PROGRAM_OFFICER_NAME: PADGETT, LYNNE SLAUGHTER

PROJECT_TERMS: access disparities;Accounting;Acute;acute care;acute stroke;Address;Admission activity;Adult;Area;Assessment tool;beneficiary;Caregivers;Caring;Characteristics;Clinical;cohort;Communities;cost;Data;Data Collection;Decision Aid;Decision Making;design;Development;Diabetes Mellitus;Discharge Plannings;Disparity;disparity reduction;Dose;dual eligible;Dual Enrollment;ethnic minority;Ethnic Origin;Evaluation;Focus Groups;functional gain;functional status;Goals;Health;health care delivery;Health care facility;health disparity;Health Services;hospital care;hospital readmission;Hospitalization;Hospitals;Hypertension;Improve Access;improved;indexing;Individual;Inequity;Inpatients;Institution;Lead;Length of Stay;low socioeconomic status;Marketing;Measures;Medicare;Medicare claim;Medicare/Medicaid;Methods;Occupational Therapy;Outcome;outcome disparities;Pathway interactions;Patient Selection;Patient-Centered Care;Patient-Focused Outcomes;Patients;Perception;Physical therapy;Population;post stroke;primary outcome;Process;Provider;provider factors;Proxy;Qualitative Methods;Quality of Care;Race;racial disparity;racial minority;Recovery;Recovery of Function;Rehabilitation Outcome;rehabilitation service;Rehabilitation therapy;rehabilitative care;Research;Sampling;Scientific Advances and Accomplishments;Selection Bias;service providers;Severities;Speech Therapy;Stroke;stroke outcome;stroke patient;Time;tool;Underserved Population;United States;United States Centers for Medicare and Medicaid Services;Work

PROJECT_TITLE: Race and Medicare-Medicaid Dual Enrollment Disparities in Access to Quality and Intensity of Post-Acute Rehabilitation Care and Health Outcomes in Patients with Stroke

STUDY_SECTION: HHD

STUDY_SECTION_NAME: Healthcare and Health Disparities Study Section[HHD]


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Assistive Technology;Bioengineering;Clinical Research;Clinical Trials and Supportive Activities;Complementary and Integrative Health;Digestive Diseases;Neurosciences;Physical Injury - Accidents and Adverse Effects;Spinal Cord Injury;Traumatic Head and Spine Injury

ORG_CITY: OKLAHOMA CITY

ORG_NAME: TRANSTIMULATION RESEARCH, INC.

ORG_STATE: OK

PHR: Narrative Neurogenic bowel dysfunction is manifested as a slow colonic motility and constipation, and it is the 2nd most common complication and 4th most common reason for re-hospitalization in people with spinal cord injury (SCI). More than 1/3 of people with SCI rate neurogenic bowel dysfunction as the most significant quality of life issue. Progress in developing effective drug treatments for improving neurogenic bowel dysfunction has been slow, despite an urgent unmet need. In our clinical studies, we discovered that transcutaneous neuromodulation applied at the ST36 acupuncture point (below the kneecap) improves neurogenic bowel dysfunction in patients with stroke chronic constipation, and other disorders. The long-term goal of this project is to develop a novel noninvasive transcutaneous neuromodulation therapy using a wearable device placed on ST36 acupuncture point for treating neurogenic bowel dysfunction in SCI. The specific aims of this project are to design and develop an easy-to-use leg-worn transcutaneous neuromodulation device AccelBand and to evaluate its clinical potential in treating neurogenic bowel dysfunction in SCI.

PI_NAMEs: CHEN, JIANDE ;MAENG, JIMIN ;PIKOV, VICTOR  (contact);RODRIGUEZ, GIANNA M;VOIT, WALTER

PROGRAM_OFFICER_NAME: GROSS, BROOKS ANDREW

PROJECT_TERMS: Acceleration;Acupuncture Points;Adverse event;Anatomy;Appearance;arm;Ataxia;Brain Stem;Caring;Cell Nucleus;Cerebral Palsy;Chronic;chronic stroke;Clinical;clinical efficacy;Clinical Research;Clinical Trials;Colon;Colorectal;Complication;Constipation;Consumption;Cutaneous;Defecation;design;Development;Device Designs;Device Safety;Devices;Disease;efficacy study;Elasticity;Electric Stimulation;Electrodes;Engineering;Enteral;External anal sphincter structure;Feces;Functional disorder;gastrointestinal symptom;Goals;Home;hospital readmission;improved;Individual;Interneurons;Intestines;Joints;laxative;Leg;Lesion;Mediating;Medical;Michigan;Monitor;Motility;Motor;Motor Neurons;Multiple Sclerosis;Nervous System Disorder;Neurons;neuroregulation;Nonpharmacologic Therapy;novel;Outcome;Pathway interactions;Patients;Persons;Pharmaceutical Preparations;Pharmacotherapy;Pilot Projects;primary outcome;Procedures;product development;Quality of life;Randomized;Rectum;Rehabilitation therapy;Research;Resort;routine care;Sacral nerve;Safety;secondary outcome;smartphone application;Spinal cord injury;spinal pathway;Stigmatization;Stroke;synergism;targeted delivery;Texas;Therapeutic Effect;Time;Universities;usability;wearable device

PROJECT_TITLE: AccelBand, a leg-worn transcutaneous neuromodulation device for treating neurogenic bowel dysfunction in individuals with spinal cord injury


ORG_CITY: Decatur

ORG_NAME: VETERANS HEALTH ADMINISTRATION

PHR: A major barrier to HIV eradication is maintenance of latently infected cells in people living with HIV (PWH). The Veteran population of PWH is nearly 2.5-fold greater versus non-Veteran individuals living in the United States, underscoring a major unmet need within the United States Veteran's population for safe, specific agents that can cure HIV and prevent or reverse associated co-morbidities. Chronic inflammation despite suppressive ART drives HIV persistence and co-morbidities, (cardiovascular disease, frailty, diabetes, and HIV-associated neurocognitive dysfunction (HAND)). We will define the multi-functional action of baricitinib, a Jak ½ inhibitor developed by our team for treatment of viral infections including HIV and COVID-19, towards reducing HIV reservoirs. We will leverage our now-enrolling Phase2a study for baricitinib towards reduction of HIV-1 reservoir in the CNS (NCT05452564) across peripheral blood and cerebral spinal fluid samples. Data will streamline translation to human studies in the Veteran PWH population, for comorbidities and eventual HIV cure.

PI_NAMEs: GAVEGNANO, CHRISTINA  (contact)

PROJECT_TERMS: AIDS clinical trial group;Antiinflammatory Effect;antiretroviral therapy;BCL2 gene;behavior change;Cardiovascular Diseases;CD4 Positive T Lymphocytes;CD8B1 gene;Cell Count;Cells;Cerebrospinal Fluid;Child;Chronic;Clinical;cohort;Collaborations;comorbidity;COVID-19;Data;Diabetes Mellitus;DNA;Dose;Drug Interactions;Enrollment;Epigenetic Process;experimental study;FDA approved;frailty;Frequencies;Functional disorder;Generations;Hepatic;HIV;HIV-1;HLA-DR Antigens;Human;Immune;immune activation;immune function;Immunologic Markers;improved;In Vitro;in vitro Model;in vivo;Individual;Infection;Inflammation;Inflammatory;inflammatory marker;inhibitor;Interruption;Investigation;Janus kinase;life span;Link;Maintenance;Measures;Memory;memory CD4 T lymphocyte;military veteran;Modeling;Modification;mouse model;Mus;Myelogenous;Neurocognitive;Patients;Peripheral;peripheral blood;Persons;Pharmaceutical Preparations;Phase;Phenotype;Population;prevent;Prevention;Renal clearance function;Research Personnel;Rheumatoid Arthritis;Safety;Sampling;Sampling Studies;Sentinel;Signal Transduction;Signal Transduction Pathway;Site;Systemic infection;T memory cell;T-Lymphocyte;terminally differentiated effector memory (TEM) T cells;Testing;Therapeutic Agents;Transducers;translation to humans;translational goal;Translations;United States;Veterans;Viral;Viral Load result;viral rebound;Virus Diseases

PROJECT_TITLE: Leveraging Jak 1/2 Inhibition with Baricitinib Towards HIV Cure in the Veteran Population

STUDY_SECTION_NAME: Special Emphasis Panel[ZRD1 INFA-K (01)]


NIH_SPENDING_CATS: Bioengineering;Neurosciences

ORG_CITY: RICHARDSON

ORG_DEPT: NEUROSCIENCES

ORG_NAME: UNIVERSITY OF TEXAS DALLAS

PHR: The ability to learn and produce specific motor movements is critical for many aspects of life and is dysregulated in a range of neurological conditions that affect the basal ganglia circuits. Our ability to help patients critically depends on a deep understanding of basal ganglia function, however, the principles of basal ganglia function and dysfunction in health and disease conditions remain elusive. The proposed work aims to provide a mechanistic, circuit-level understanding of diverse action-specific basal ganglia subcircuits that goes beyond the classical prokinetic versus antikinetic model, with profound implications for a range of brain disorders such as Parkinson's and Huntington's diseases.

PI_NAMEs: GU, ZIRONG  (contact)

PROGRAM_OFFICER_NAME: CHEN, DAOFEN

PROJECT_TERMS: Acceleration;Affect;anatomical tracing;Area;Attention deficit hyperactivity disorder;Axon;Basal Ganglia;base;Behavior;Behavioral;Brain;Brain Diseases;Brain Stem;Calcium;career development;Cell Nucleus;cell type;Clinical;Communication;Communities;computerized tools;Corpus striatum structure;Data;Development Plans;Disease;experimental study;Functional disorder;Globus Pallidus;Glutamates;Goals;Health;Heterogeneity;Huntington Disease;Image;in vivo;instrument;Investigation;kinetic model;Kinetics;Learning;Life;Light;Locomotion;Maps;Mental disorders;Mentors;Methods;Modeling;Motor;Movement;Mus;Neurodegenerative Disorders;Neurologic;Neurons;Neurosciences;new therapeutic target;novel;Obsessive-Compulsive Disorder;optogenetics;Output;Parafascicular Nucleus;Parkinson Disease;Pathway interactions;Patients;Pattern;Performance;Phase;Play;Population;prevent;Process;rabies viral tracing;Reagent;Research;response;Role;skills;Solid;Supervision;System;Technical Expertise;Testing;Textbooks;Thalamic structure;Training;Universities;Viral;Work;Writing

PROJECT_TITLE: Action-Specific Dissecting of Basal Ganglia: from the Classical Model to Diverse Action-Specific Subcircuits

STUDY_SECTION: NST

STUDY_SECTION_NAME: NST-2 Study Section [NST-2]


NIH_SPENDING_CATS: Autism;Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Genetics;Intellectual and Developmental Disabilities (IDD);Mental Health;Neurosciences;Pediatric

ORG_CITY: DURHAM

ORG_DEPT: BIOLOGY

ORG_NAME: DUKE UNIVERSITY

ORG_STATE: NC

PHR: Project Narrative Mounting evidence suggests that several neurodevelopmental disorders, including autism spectrum disorder and epilepsy, have origins in defective neural circuit formation. The goal of this proposal is to advance our understanding of how neural circuits form at the cellular and molecular level using a simpler model system. Knowledge drawn from such simple systems will build the foundation for studies aimed at understanding neural circuit formation in humans, and thus will be instrumental in the design of therapies to treat neurodevelopmental disorders in the future.

PI_NAMEs: CARREIRA-ROSARIO, ARNALDO  (contact)

PROGRAM_OFFICER_NAME: JOHNSON, KARI ANNE

PROJECT_TERMS: Address;Affect;Anatomy;autism spectrum disorder;Behavior;Behavioral;Biological Assay;Biological Models;Calcium;Calcium Binding;Candidate Disease Gene;cell type;Cells;Cognition;connectome;Data;Defect;Development;Drosophila genus;Electron Microscope;Embryo;Emotions;Epilepsy;Foundations;Future;Genes;Genetic;Goals;hatching;Human;Image;Individual;insight;Interneurons;knock-down;Knowledge;Label;larval control;Learning;Link;Locomotion;Maps;Membrane;Methods;Modeling;Molecular;Molecular Profiling;Monitor;Motor;Motor output;Musculoskeletal System;Nervous System;nervous system development;neural;neural circuit;neurodevelopment;Neurodevelopmental Disorder;neuromechanism;Neurons;Neurosciences;novel;optogenetics;Organism;Orthologous Gene;Pattern;Perception;Phase;Population;post-doctoral training;Process;programs;Property;quantitative imaging;Rapid screening;Research;RNA interference screen;Sensory;spatiotemporal;Stereotyping;stereotypy;Stimulus;Stochastic Processes;Structure;Synaptic Transmission;System;Techniques;Testing;therapy design;Time;tool;Training;transmission process;Work

PROJECT_TITLE: Structure and function of spontaneous network activity during circuit formation


PHR: Toxoplasmosis causes death and severe disability in immunocompromised Veterans. Current treatments have high rates of side effects that complicate use for treatment and prophylaxis, and fail to reduce established latent brain infection. This research will identify drug targets whose inhibition will increase the activity of ELQ-422 and identify compounds that increase the efficacy of ELQ-422 against acute and latent infection.

PI_NAMEs: DOGGETT, JOSEPH STONE (contact)

PROJECT_TERMS: Acquired Immunodeficiency Syndrome;Acute;acute infection;Adverse effects;analog;Antiparasitic Agents;atovaquone;Binding;Biological Assay;Biological Availability;Bone Marrow Transplantation;Brain;brain tissue;Carbon;Caring;Cause of Death;Cell Death;Cellular biology;Clinical;Clinical Research;Compensation;CRISPR screen;Cyst;Cytochrome bc1 Complex;disability;Dose;drug candidate;Drug Combinations;drug discovery;Drug resistance;Drug Screening;Drug Targeting;effective therapy;Enzyme Inhibitor Drugs;Excision;experimental study;Exposure to;Folic Acid Antagonists;Gene Deletion;Genes;genome sequencing;genome-wide;glucose metabolism;Glycolysis;Goals;hexokinase;HIV;Hydroquinones;Immunocompromised Host;In Vitro;in vivo;Individual;Infection;inhibitor;insight;Knock-out;Label;latent infection;Lead;Measures;Membrane;Metabolic;Metabolic Pathway;Metabolism;metabolomics;Mitochondria;Modeling;mouse model;Mus;novel therapeutic intervention;Oral;Organ;oxidation;Parasites;Pathway interactions;Pharmaceutical Preparations;Phenotype;Population;pre-clinical;Preclinical Testing;Prodrugs;Prophylactic treatment;Provider;Pyrimethamine;Qi;Quinolones;Quinones;Rattus;Recovery;Research;Risk;side effect;Site;SLC2A1 gene;Solid;Testing;Tissue-Specific Gene Expression;Tissues;Toxic effect;Toxicity Tests;Toxoplasma gondii;Toxoplasmosis;transcriptomics;Transplant Recipients;ubiquinol;Ubiquinone;United States;Veterans;whole genome

PROJECT_TITLE: Novel Therapeutic Strategies for ELQ-422, a preclinical Toxoplasmosis Drug Candidate

STUDY_SECTION_NAME: Special Emphasis Panel[ZRD1 INFB-K (01)]


ORG_CITY: Nashville

ORG_DEPT: PHARMACOLOGY

ORG_NAME: VANDERBILT UNIVERSITY

ORG_STATE: TN

PHR: A large proportion of patients with temporal lobe epilepsy suffer from chronic spontaneous seizures, which cannot be controlled with existing drug treatment options. This proposal will utilize recently developed molecular and genetic tools to investigate seizure active cellular ensembles and their associated circuits. A greater understanding of neuronal circuits controlling seizure development may lead to the identification of new targets for therapeutic intervention.

PI_NAMEs: NGUYEN, QUYNH ANH  (contact)

PROGRAM_OFFICER_NAME: CHURN, SEVERN BORDEN

PROJECT_TERMS: Acute;Adult;Advisory Committees;Anatomy;Animal Model;Animals;anti-epileptic agents;Area;Award;Behavior;Biological Markers;Brain imaging;Brain region;Calcium;career;career development;Cells;cellular targeting;Chronic;Chronic Phase;Cognitive;Cognitive deficits;comorbidity;Contralateral;Detection;Development;Disease;Early Intervention;Educational process of instructing;effective therapy;efficacious treatment;Electrophysiology (science);Environment;Epilepsy;epileptiform;Epileptogenesis;Event;Evolution;experience;Frequencies;Functional disorder;Gene Expression Profiling;Generations;Genetic;genetic approach;Goals;Grant;High Frequency Oscillation;hippocampal sclerosis;Hippocampus;Human;human model;Image;Impaired cognition;in vitro activity;in vivo;Injections;Intervention;Investigation;Ipsilateral;kainate;Knock-out;knockout gene;Knockout Mice;Label;Learning;Light;Mediating;Memory;Memory impairment;Methods;Modeling;Molecular;Molecular Profiling;mouse model;Mus;Nature;Nervous System Disorder;neural circuit;neuronal circuitry;Neurons;new therapeutic target;novel;optogenetics;Pathologic;Patients;Performance;Pharmacotherapy;Phase;Play;Population;prevent;Pyramidal Cells;receptor;Recurrence;Research;Research Personnel;Resistance;Resources;Role;Seizures;side effect;Signal Transduction;skills;social;success;System;Temporal Lobe Epilepsy;Testing;Therapeutic;Therapeutic Intervention;Tissue imaging;tool;tool development;Training;Transgenic Mice;two-photon;Work;Writing

PROJECT_TITLE: Neural circuit mechanisms controlling seizures


ORG_NAME: VA SALT LAKE CITY HEALTHCARE SYSTEM

PHR: Urothelial carcinoma (bladder cancer) is the most common cancer of the urinary tract. It represents a significant health burden to the aging Veteran population due to the cumulative effects of smoking and deployment-related carcinogen exposure. Treatment resistance and disease relapse are unfortunately very common for bladder cancer. We propose to study, narrow down and target cancer-promoting factors and devise new precise combination strategies to effectively treat bladder cancer.

PI_NAMEs: GUPTA, SUMATI  (contact)

PROJECT_TERMS: Address;aggressive therapy;Aging;Archives;ARID1A gene;Automobile Driving;Biological Assay;Biology;cancer cell;Cancer cell line;Cancer Model;Cancer Relapse;cancer stem cell;Carcinogen exposure;carcinogenesis;Carcinogens;Categories;Cell Line;Cell Maintenance;Cell Proliferation;Cells;chemotherapy;Chromatin;chromatin modification;chromatin remodeling;Chromatin Remodeling Factor;Clinical;Clinical Course of Disease;Clinical Trials;Combined Modality Therapy;Data Set;Databases;Disease;Disease Resistance;DNA Sequence Alteration;Drug Synergism;effective therapy;Epigenetic Process;epigenomics;Evolution;Gene Combinations;Gene Expression;Gene Mutation;genetic manipulation;Genetic Transcription;Genome;Growth;Health;Histones;Immunotherapy;innovation;Interdisciplinary Study;Link;loss of function mutation;Malignant neoplasm of urinary bladder;Malignant Neoplasms;MAPK1 gene;Mediating;MEK inhibition;MEKs;men;military veteran;Mitogen-Activated Protein Kinases;Modeling;Molecular;Molecular Sequence Data;Molecular Target;Multiomic Data;multiple omics;Mutate;Mutation;Nature;novel;Oncogenic;Oncology;Outcome;Pathogenesis;Pathway interactions;Patients;Pharmaceutical Preparations;Play;pre-clinical;pre-clinical assessment;precision oncology;preclinical efficacy;Process;Prognosis;programs;Proteins;Proteome;Recurrence;Recurrent disease;Relapse;Research;Research Priority;Resistance;Role;self-renewal;Signal Pathway;Signal Transduction;Site;Smoking;Source;survivorship;System;targeted treatment;Testing;The Cancer Genome Atlas;Therapeutic Agents;therapy resistant;tissue archive;transcription factor;Transitional Cell Carcinoma;Translating;Treatment Failure;Treatment outcome;treatment response;tumor;tumor initiation;tumor progression;Tumor Suppressor Genes;Tumor Suppressor Proteins;Tumor Tissue;United States Health Resources Administration;Urinary system;Urologic Cancer;Urothelium;Variant;Veterans;Veterans Health Administration

PROJECT_TITLE: Targeting ARID1A mutated Urothelial Carcinoma


NIH_SPENDING_CATS: Neurosciences

ORG_CITY: ATLANTA

ORG_NAME: GEORGIA INSTITUTE OF TECHNOLOGY

PHR: Synapses bridge communication between neurons and form the basis of neural circuits and cognitive function. This proposal will study molecularly how synapses assemble during development and how that assembly is regulated. These fundamental studies will reveal molecular components that can influence synapse formation in neurological disorders like autism or during aging.

PI_NAMEs: MCDONALD, NATHAN  (contact)

PROGRAM_OFFICER_NAME: LEENDERS, MIRIAM

PROJECT_TERMS: Actins;Action Potentials;active control;Aging;Animals;autism spectrum disorder;Automobile Driving;Award;Biological Assay;Caenorhabditis elegans;Calcium Channel;career development;Cell Adhesion Molecules;cognitive function;Common Core;Communication;Complex;Cues;Data;Defect;Degenerative Disorder;Depressed mood;Development;Educational process of instructing;Elements;Enhancers;Event;Experimental Genetics;experimental study;F-Actin;Future;Genetic Screening;genome-wide;Goals;Image;immunological synapse;In Vitro;in vitro Assay;in vivo;in vivo imaging;Individual;insight;Ion Channel;Link;Liquid substance;Location;Mass Spectrum Analysis;Membrane;Mentorship;Methods;Mission;Molecular;mutant;Mutate;Mutation;National Institute of Neurological Disorders and Stroke;Natural regeneration;Nervous System;Nervous System Disorder;neural circuit;neurodevelopment;Neurons;Neurophysiology - biologic function;Neurosciences;novel;optogenetics;Pathway interactions;Phase;phosphoproteomics;Phosphorylation;Phosphorylation Site;Phosphotransferases;Physical condensation;Play;Positioning Attribute;Post-Translational Protein Processing;postsynaptic;presynaptic;Process;Property;reconstitution;Regulation;Research;Research Methodology;Resolution;scaffold;Scaffolding Protein;screening;Side;Signal Pathway;Signaling Molecule;Site;spatiotemporal;Specific qualifier value;Structure;Synapses;Synaptic Vesicles;synaptogenesis;System;T-Lymphocyte;Testing;Thinking;Training;Universities;vesicular release;Work;Writing

PROJECT_TITLE: Spatial and temporal regulation of synapse formation through phase separation


NIH_SPENDING_CATS: Genetics;Neurosciences;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: Newark

ORG_DEPT: OTHER BASIC SCIENCES

ORG_NAME: RUTGERS BIOMEDICAL AND HEALTH SCIENCES

ORG_STATE: NJ

PHR: PROJECT NARRATIVE In diseases like Amyotrophic Lateral Sclerosis, sarcopenia, or spinal cord injury, the degeneration of specific subsets of adult motor neurons can lead to loss of muscle control, paralysis, and death. This project will produce a map of the motor neuron types found adult humans, lead to development of methods to produce adult-like motor neurons from patient cells, and generate virus based gene delivery tools that can be used to study motor neuron function and deliver therapeutics. The completion of this work will facilitate better understanding of adult motor neuron diseases and the development of treatments.

PI_NAMEs: PATEL, TULSI  (contact)

PROJECT_TERMS: adeno-associated viral vector;Adult;Affect;Age;Amyotrophic Lateral Sclerosis;ATAC-seq;Autopsy;Award;Behavior;Bioinformatics;Biological Assay;Biological Models;Brain region;candidate identification;career;career development;Cell Line;Cell Nucleus;cell type;Cells;Cessation of life;Chromatin;Communication;Data;Data Analyses;Development Plans;Dimensions;Disease;disease model;disease phenotype;Electrophysiology (science);Embryo;Embryonic Development;Gene Delivery;Gene Expression;Genetic;Genetic Transcription;Genomics;Human;human induced pluripotent stem cells;In Vitro;in vitro Model;in vivo;induced pluripotent stem cell;infancy;Laboratories;Lead;Life;Maps;Mentorship;method development;Methods;Modeling;Molecular;Molecular Profiling;Motor;Motor Neuron Disease;motor neuron function;Motor Neurons;Movement;Mus;Muscle;Muscular Atrophy;mutant;Nervous System;Nervous System Disorder;neural circuit;neuronal circuitry;Neurons;Neurophysiology - biologic function;Nucleic Acid Regulatory Sequences;Paralysed;Patients;Phase;post-doctoral training;postmitotic;postnatal;Predisposition;programs;Property;Research;Research Personnel;sarcopenia;Signal Transduction;single nucleus RNA-sequencing;skills;Sorting;Specific qualifier value;Spinal;Spinal Cord;Spinal cord injury;stem cells;System;Testing;Therapeutic;therapy development;Time;time use;timeline;tool;Training;transcription factor;transcriptome;transcriptome sequencing;transcriptomics;Universities;Viral;Virus;Work

PROJECT_TITLE: Defining motor neuron diversity from embryo to adulthood and generating tools for in vivo and in vitro access


ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

NIH_SPENDING_CATS: Aging;Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Cerebrovascular;Disability Research;Neurosciences;Physical Rehabilitation;Rehabilitation;Stroke

ORG_CITY: BERKELEY

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: UNIVERSITY OF CALIFORNIA BERKELEY

PHR: PROJECT NARRATIVE Stroke is the leading cause of disability in the United States, leaving a substantial number of survivors with permanent hand function deficits impairing dexterity. While most pre-clinical research focuses on descending movement pathways, anatomical and clinical studies underscore the critical role of somatosensory signals in recovery. This proposal uses multi-area electrophysiology to monitor functional interactions in the cortical and subcortical sensorimotor circuit during dexterous hand skill acquisition in intact and stroke-injured networks, laying the foundation for future therapies targeting normalization of somatosensory signals to enhance hand function recovery.

PI_NAMEs: KHANNA, PREEYA  (contact)

PROJECT_TERMS: Activities of Daily Living;Acute;Address;Anatomy;Animal Model;Animals;Area;Automobile Driving;Award;Behavior;Behavioral;Body mass index;Brain;BRAIN initiative;brain machine interface;Cessation of life;Clinical;Clinical Research;combat;Complex;Contralateral;Data;Data Analyses;density;Development;dexterity;disability;Dissociation;Electrophysiology (science);Evolution;experimental study;Faculty;Feedback;Foundations;Freedom;Future;Gifts;grasp;Hand;hand dysfunction;Hand functions;hand rehabilitation;haptic interface;haptics;Human;Impairment;improved;injured;Institution;Intervention;kinematics;Learning;Link;Location;Mathematics;Mentors;Methods;Modeling;Monitor;Motor;Motor Activity;Motor Cortex;Motor Pathways;Movement;neural;neuroregulation;nonhuman primate;novel;novel therapeutics;Pathway interactions;Performance;Phase;Physical therapy;Population;Positioning Attribute;post stroke;pre-clinical research;Primates;Process;Recording of previous events;Recovery;Robot;Role;sensor;sensorimotor system;Sensory;sensory cortex;sensory input;Sensory Receptors;Signal Transduction;skill acquisition;skills;somatosensory;Somatosensory Cortex;Stereotyping;stereotypy;Stroke;stroke recovery;stroke rehabilitation;stroke survivor;Survivors;TACSTD2 gene;Tactile;targeted treatment;Thalamic structure;theories;tool;Training;United States;Ventral Posterolateral Nucleus;virtual

PROJECT_TITLE: Neural dynamics of somatosensory guidance of dexterous movement in intact and stroke-injured networks


ORG_CITY: CHARLESTON

ORG_NAME: RALPH H JOHNSON VA MEDICAL CENTER

PHR: Reward seeking is normally suppressed in inappropriate conditions, yet opioid use and seeking often occur despite negative consequences in Veterans who are disproportionally vulnerable to opioid use disorder (OUD). We recently found that activity in a novel brain circuit, from paraventricular thalamus to accumbal parvalbumin interneurons, provides top-down inhibitory control over natural reward-motivated behaviors. Here we determine the influence of opioid self-administration on activity and plasticity in this thalamo-accumbal ‘brake’ for reward seeking, and further determine the function of this pathway for opioid seeking and use. Based on preliminary findings, we predict that selectively rescuing activity within cell-type specific thalamo-accumbal output circuits will prevent relapse to opioid use. Such findings would not only provide key mechanistic insight into the neurobiology of OUD, but would also provide candidate neuronal substrates that could be targeted for therapeutic intervention.

PI_NAMEs: OTIS, JAMES M (contact)

PROJECT_TERMS: Attenuated;Axon;Behavior;Behavioral;Behavioral Assay;Behavioral Paradigm;Brain;Calcium;Caring;cell type;Chronic;clinically relevant;Consumption;Cues;Dangerousness;Dependence;Disinhibition;Economics;Electrophysiology (science);Elements;Etiology;experimental study;Extinction;Fright;Genetic;genetic approach;genetic manipulation;Health;Heroin;heroin use;Image;insight;Interneurons;Knowledge;Laboratories;Laboratory Finding;Learning;learning extinction;Literature;maladaptive behavior;Measures;motivated behavior;Mus;nerve supply;Neurobiology;neuronal circuitry;Neurons;novel;Nucleus Accumbens;Opioid;opioid use;opioid use disorder;optogenetics;Output;Parvalbumins;patch clamp;Pathway interactions;Pharmaceutical Preparations;Physiology;prevent;Relapse;relapse prevention;Reporter;restoration;Rewards;Role;Self Administration;Slice;social;Stimulus;Stress;stressor;Structure of paraventricular nucleus of thalamus;Sucrose;Synapses;System;targeted treatment;Testing;Thalamic structure;Therapeutic;Therapeutic Intervention;therapy development;Time;two-photon;Veterans;Work

PROJECT_TITLE: Synapse-specific plasticity in thalamoaccumbal output circuitry disinhibits relapse to opioid seeking


ORG_CITY: NEW ORLEANS

ORG_NAME: SOUTHEAST LOUISIANA VETERANS HEALTH CARE

ORG_STATE: LA

PHR: 8. Project Narrative One fifth of the US population struggles with chronic pain, but the only effective class of drugs for treatment of severe pain also drives the opioid addiction and overdose epidemic. We have synthesized a series of opioid pain killers with reduced side effects, including abuse liability. In this project, will identify and optimize related analogs, designed for improved brain delivery, for improved treatment of pain with low abuse liability, tolerance, and respiratory depression relative to currently used opioids. Successful tests will provide proof-of-concept that the novel compounds can effectively treat pain with reduced side effects and provide support for development for clinical use.

PI_NAMEs: ZADINA, JAMES E (contact)

PROJECT_TERMS: abuse liability;Acute;ADME Study;Adverse effects;Analgesics;analog;antinociception;Behavior;behavioral study;blood-brain barrier penetration;Brain;Cessation of life;Chronic;chronic neuropathic pain;chronic pain;Clinical;clinical development;conditioned place preference;design;Development;Disease;Drug Kinetics;drug seeking behavior;effective therapy;Effectiveness;Environment;Epidemic;Exhibits;experimental study;Glycopeptides;glycosylation;Goals;Human;improved;in vivo;inflammatory pain;Lead;Methods;Modification;Morphine;Motivation;mu opioid receptors;Mus;novel;Opiate Addiction;Opioid;opioid epidemic;opioid overdose;opioid use;opioid use disorder;Outcome;Oxycodone;Pain;Pain management;pain model;pain relief;Pathway interactions;Pharmaceutical Preparations;pharmacophore;Pharmacotherapy;Population;Postoperative Period;pre-clinical assessment;preference;programs;Property;Rattus;Rewards;Rodent Model;Safety;Self Administration;Series;side effect;standard care;Testing;Ventilatory Depression;Veterans

PROJECT_TITLE: Development of Glycosylated Endomorphin Analogs with Low Abuse Liability for Treatment of Pain.


ORG_CITY: PALO ALTO

ORG_NAME: VETERANS ADMIN PALO ALTO HEALTH CARE SYS

PHR: NARRATIVE Glaucoma is a leading cause of irreversible blindness in the world, and affects over 285,000 US veterans. Lowering eye pressure remains the only treatment for glaucoma, yet the mechanisms of eye pressure regulation remain unknown. In this application, we will utilize our previous findings and preliminary data to develop a next-generation light-regulated switch that will decrease eye pressure in a mouse model of glaucoma. This optogenetic approach is significant because it will better define regulatory elements that control eye pressure and may also provide a new approach to reset eye pressure in the clinic by simply shining a light into the eyes. We anticipate that this research will ultimately lead to new treatments for VA patients with glaucoma.

PI_NAMEs: SUN, YANG  (contact)

PROJECT_TITLE: Shedding Light on Glaucoma: Next Generation of Optogenetics for Aqueous Outflow Regulation

STUDY_SECTION_NAME: Special Emphasis Panel[ZRD1 NURF-C (01)]


PHR: Heart failure (HF) is a leading cause of morbidity and mortality and is especially prevalent among US veterans. One of the pathologic hallmarks of HF is myocardial fibrosis. Fibrosis is a reparative mechanism that follows any type of injury. In the heart, it leads to reduced tissue compliance, cardiomyocyte hypertrophy and apoptosis, chamber dilation, and eventually HF. HF patients undergoing implantation of a left ventricular assist device or heart transplantation present a unique opportunity as cardiac tissue becomes available at the time of the above operations. Our studies in HF patients have identified adipocyte enhancer binding protein 1 (AEBP1) as a major node associated with myofibroblast activation, abnormal extracellular matrix (ECM) homeostasis, and impaired wound healing following cardiac injury. Our goal is to investigate the mechanisms by which the aberrant expression of AEBP1 contributes to cardiac fibrosis and to exploit its inhibition as a potential antifibrotic therapy.

PI_NAMEs: DRAKOS, STAVROS GEORGE (contact)

PROJECT_TERMS: acute myeloid leukemia 1 protein;Address;Adipocytes;Angiotensins;Animal Model;antifibrotic treatment;Apoptosis;Attenuated;Autophagocytosis;Cardiac;Cardiac Myocytes;Cardiovascular Diseases;cardiovascular disorder risk;Cardiovascular Manifestation;chromatin immunoprecipitation;Chronic;Clinical;Clinical Trials;Congestive Heart Failure;coronary fibrosis;Developed Countries;Development;Disease;enhancer binding protein;Etiology;Evolution;Extracellular Matrix;factor A;Feedback;Fibroblasts;Fibrosis;Gene Expression;Genomic Segment;Goals;Healthcare Systems;Heart;Heart failure;heart function;Heart Injuries;Heart Transplantation;Histologic;Homeobox;Homeostasis;Human;human tissue;Hypertrophy;Impaired wound healing;implantation;In Vitro;Infusion procedures;Injury;Intervention;knock-down;Knock-in Mouse;left ventricular assist device;Light;Mediating;Medical;Mesenchyme;Molecular;Molecular Target;Morbidity - disease rate;mortality;mouse model;Mus;Myocardial Infarction;Myocardial tissue;myocardin;Myocardium;Myofibroblast;new technology;novel;operation;Organ failure;organ injury;overexpression;Oxidative Stress;Pathologic;Pathway interactions;Patients;Phenylephrine;Physiological;post intervention;preservation;protein expression;public database;Regulatory Element;small hairpin RNA;targeted therapy trials;targeted treatment;Technology;Testing;Therapeutic;therapeutic evaluation;Time;Tissues;transcription factor;Transforming Growth Factor beta;Translating;Up-Regulation;Veterans;Veterans Health Administration;wound healing

PROJECT_TITLE: Understanding the mechanism of AEBP1-mediated fibrosis post-cardiac injury in heart failure

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


ORG_CITY: GAINESVILLE

ORG_STATE: FL

PHR: Approximately 5% of Veterans have heart failure and between 2014 and 2018 14.5% of those died because of it. Heart transplant is the life-saving cure for end-stage heart failure, but there are not enough hearts for the people who need them. This is often because the heart accumulates damage from lack of blood supply the longer it is out of the donor before being placed in the recipient, so it cannot be transplanted successfully. If this damage could be lessened there would be more hearts for transplant. A type of cell isolated from fat can be cultured and the factors they produce reduces this kind of damage. This study aims to test whether those factors, a particular part of the secretions or a very similar commercially available compound, could be used to treat hearts and reduce the amount of this damage They will be tested in models of a recent method to obtain hearts called donation after circulatory death during which hearts get more damaged than the traditional donation after brain death, thus potentially greatly increasing the number of suitable hearts for transplantation.

PI_NAMEs: MARCH, KEITH LEONARD (contact)

PROJECT_TERMS: Acute;Adipose tissue;Adult;angiogenesis;animation;Apoptosis;Area;Biochemical;Bioenergetics;Brain Death;Cardiac;Cardiac Myocytes;cell injury;Cell Separation;cell type;Cessation of life;circadian pacemaker;curative treatments;Data;Deterioration;Development;Diagnostic;Dose;efficacy evaluation;Enzymes;Evaluation;exosome;experience;experimental study;Exposure to;Family suidae;Fatty acid glycerol esters;functional improvement;Generations;Genes;graft function;Heart;heart allograft;Heart failure;heart function;heart preservation;Heart Transplantation;Human;human induced pluripotent stem cells;Hydrogen Peroxide;improved;In Vitro;Incubated;Infarction;Infusion procedures;Inhibition of Apoptosis;Ischemia;Kidney;Life;Mediating;Membrane Potentials;Mesenchymal;Mesenchymal Stem Cells;Metabolic;metabolic rate;Methods;Mitochondria;mitochondrial membrane;Modeling;Myocardial;Myocardial Infarction;Myocardial Reperfusion Injury;Myocardium;Organ Donor;Organ Procurements;Organ Retrievals;Organ Transplantation;Oxidoreductase;paracrine;Pathologic;Pathology;Patients;Perfusion;Persons;Physiological;Pre-Clinical Model;Preparation;preservation;Process;Production;protective effect;Protocols documentation;Reactive Oxygen Species;Recovery;Recovery of Function;Reperfusion Injury;Reperfusion Therapy;Reporting;Resolution;Rodent;Slice;Solid;Spirometry;stem;Stromal Cells;System;Testing;Therapeutic;Time;Tissues;transcriptome;Transplantation;treatment effect;Vascular blood supply;Veterans;Warm Ischemia

PROJECT_TITLE: Functional and Mechanistic Analysis of Mesenchymal Stem Cell Secretome to Ameliorate Ischemic Damage of Porcine Heart ex vivo and Human Myocardium


ORG_CITY: MINNEAPOLIS

ORG_NAME: MINNEAPOLIS VA  MEDICAL CENTER

ORG_STATE: MN

PHR: Obesity and associated comorbidities such as metabolic syndrome and diabetes affect up to 48% of Veterans, and are known risk factors for cognitive impairment and development of Alzheimer’s disease. The incidence of these neurodegenerative diseases may be higher in Veterans than in the general population. Our work supports that the onset of brain immune response (neuroinflammation) represents a link between obesity and cognitive impairment. Dietary metabolites such as fatty acids affect lipid metabolism in brain immune cells (microglia), resulting in a state change to a toxic inflammatory microglial phenotype. We hypothesize that obesity alters microglial function to directly trigger dysregulated brain immune responses and neuronal cell death, resulting in impaired cognition and altered brain circuitry. Our short term goal is to characterize regulatory changes that promote neuroinflammation and subsequent cognitive decline. Our long-term goal is to leverage this knowledge to develop targeted therapies to treat cognitive impairment and neurodegenerative disease.

PI_NAMEs: BUTTERICK, TAMMY ANGALINE (contact)

PROJECT_TERMS: abeta accumulation;Acceleration;Acids;Affect;age related neurodegeneration;age related neuroinflammation;Aging;aging brain;Alzheimer disease prevention;Alzheimer's Disease;Alzheimer's disease model;Alzheimer's disease pathology;Alzheimer's disease risk;Amyloid;Amyloid beta-Protein;attenuation;Biochemical;Biological Models;Brain;brain circuitry;brain health;Cells;Characteristics;Chronic;Clinical;clinical risk;Cognition;Communities;comorbidity;Complement;Data;Dementia;Development;Diabetes Mellitus;Diet;diet-induced obesity;dietary;Dietary Fats;Disease;Early Onset Alzheimer Disease;Environment;Etiology;Evaluation;experimental study;Exposure to;fatty acid-binding proteins;Fatty Acids;General Population;Genomics;glial activation;Glycolysis;Goals;Healthcare;High Fat Diet;high risk;Immune;Immune response;Impaired cognition;Impairment;Incidence;Inflammation;Inflammatory;Intake;Knowledge;Link;lipid metabolism;Macrophage;Mediating;Mediator;Metabolic;Metabolic Diseases;Metabolic syndrome;metabolomics;Microglia;middle age;Modification;mouse model;Mus;Neurodegenerative Disorders;neuroinflammation;neuron loss;neuropathology;neuroprotection;Neurosciences;neurotoxic;new therapeutic target;novel;Nutritional Biochemistry;obese person;Obesity;Outcome;oxidation;Oxidation-Reduction;Palmitic Acids;Pathogenesis;Pathogenicity;Pathology;Pathway interactions;Peripheral;pharmacologic;Pharmacologic Substance;Pharmacology;Phenotype;polarized cell;Primary Prevention;progressive neurodegeneration;Proteomics;Research;Resistance;Risk;Risk Factors;Role;saturated fat;Saturated Fatty Acids;Secondary Prevention;targeted treatment;Testing;Transgenic Mice;UCP2 protein;Underserved Population;Veterans;Work

PROJECT_TITLE: Impact of Obesity on Brain Immune Response and Cognition

STUDY_SECTION_NAME: Special Emphasis Panel[ZRD1 NURD-E (01)]


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Clinical Research;Clinical Trials and Supportive Activities;Immunization;Infectious Diseases;Lung;Otitis Media;Pediatric;Pneumonia;Pneumonia and Influenza;Prevention;Vaccine Related

ORG_CITY: ROCHESTER

ORG_NAME: ROCHESTER GENERAL HOSPITAL (NY)

ORG_STATE: NY

PHR: Project Narrative. In this project, a phase 2 clinical trial will be conducted in children with a killed, non-capsulated avirulent whole-cell Streptococcus pneumoniae (wSp) vaccine that elicits Th17 cell- mediated immunity and antibodies against all tested pneumococcal serotypes, and which has been tested in adults and toddlers. Nasopharyngeal (NP) colonization is a prerequisite to pneumococcal diseases and transmission. We will evaluate the efficacy of wSp vaccination in young children on pneumococcal NP colonization at times of health and onset of acute otitis media infections. The prevention of new acquisitions and/or reduction of NP colonization density may be a surrogate for prevention by wSp of pneumococcal infections. In addition, we will confirm the safety and immunogenicity of wSp.

PI_NAMEs: PICHICHERO, MICHAEL E (contact)

PROGRAM_OFFICER_NAME: UPADHYAY, MEENU MISHRA

PROJECT_TERMS: Acute;Address;Adjuvant;Adult;Adverse event;Age;Agreement;Animal Model;Antibiotics;Antibodies;Antigens;Blinded;Cells;Cellular Immunity;Child;Childhood;Clinical Research;commercialization;community acquired pneumonia;Community Health;Complement;cost;cost effectiveness;density;design;Detection;Dose;Dropout;efficacy evaluation;Enzyme-Linked Immunosorbent Assay;epidemiology study;Health;Immunity;immunogenic;immunogenicity;infancy;Infant;Infection;Injections;Licensing;Licensure;manufacture;Mucous Membrane;Nasal Lavage Fluid;Nasopharynx;Otitis Media;Periodicals;phase 2 study;phase 2 testing;Phase II Clinical Trials;phase II trial;Placebos;Pneumococcal Colonization;Pneumococcal conjugate vaccine;Pneumococcal Infections;Pneumococcal vaccine;pressure;Prevalence;Prevention;Proteins;Public Health;Research;research clinical testing;resilience;Safety;safety assessment;Saline;Sample Size;Serotyping;Serum;Sinusitis;Streptococcus pneumoniae;Testing;Toddler;transmission process;Vaccinated;Vaccination;vaccine candidate;Vaccines;Visit;Well Child Visits

PROJECT_TITLE: A Phase II Study Evaluating the Safety and Efficacy of Whole-Cell Pneumococcal Vaccine (wSp) in Reducing Nasopharyngeal Colonization by Streptococcus pneumoniae in Young Children

STUDY_SECTION_NAME: Special Emphasis Panel[ZAI1 LG-M (M1)]


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Breast Cancer;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Dissemination and Implementation Research;Health Services;Social Determinants of Health;Women's Health Research

ORG_CITY: NEW YORK

ORG_NAME: SLOAN-KETTERING INST CAN RESEARCH

PHR: PROJECT NARRATIVE In Tanzania, breast cancer is the second most common cancer and second leading cause of cancer-related death in women. Although hormone receptor testing is recommended in all breast cancers by the recently published Tanzanian National Cancer Treatment Guidelines, testing is available at only two public hospitals, resulting in pathology laboratories that are overburdened and in turnaround times of weeks to months. Using implementation science frameworks, this study aims to identify effective implementation strategies to promote routine hormone receptor testing in low resource settings, and in turn, to improve clinical outcomes by increasing access to guideline-recommended treatment.

PI_NAMEs: NG, DIANNA L. (contact)

PROGRAM_OFFICER_NAME: RADAEV, SERGEY

PROJECT_TERMS: Address;adjuvant endocrine therapy;Adopted;Adoption;Africa;Africa South of the Sahara;Biopsy;breast cancer diagnosis;Breast Cancer Patient;breast cancer survival;cancer care;Cancer Diagnostics;Cancer Etiology;cancer therapy;care delivery;career;career development;Clinical;clinical practice;Clinical Practice Guideline;Cluster randomized trial;Consolidated Framework for Implementation Research;Country;Data;Development;Development Plans;Diagnosis;Diagnostic;Diagnostic Services;Disease;disease classification;District Hospitals;Eligibility Determination;Environment;Estrogen receptor positive;Estrogen Receptors;evidence base;Evidence based practice;Faculty;Focus Groups;formative assessment;Foundations;Funding;Future;global health;Goals;Grant;Guidelines;Health Services Research;Hormone Receptor Test;hormone receptor-positive;hormone therapy;Hospital Referrals;Hospitals;implementation framework;implementation science;implementation strategy;Improve Access;improved;Income;Individual;Institution;interest;Intervention;Knowledge;Laboratories;low and middle-income countries;Malignant Breast Neoplasm;Malignant Neoplasms;Maps;member;Memorial Sloan-Kettering Cancer Center;Mentorship;Methods;mortality;multi-component intervention;multidisciplinary;National Comprehensive Cancer Network;Oncology;organizational readiness;Outcome;Outcome Measure;Pathologic;Pathologist;Pathology;Patients;Physicians;Pilot Projects;pilot test;Preparation;Progesterone Receptors;Prognosis;Progression-Free Survivals;Provider;Psychologist;Public Hospitals;Publishing;Quality of life;Reach, Effectiveness, Adoption, Implementation, and Maintenance;Recommendation;Recurrence;Research;Research Personnel;Resected;Resource-limited setting;Resources;Risk Reduction;Scientist;Services;Site;skills;Structure;Surgical Oncologist;Survival Rate;Tanzania;Testing;theories;Training;treatment guidelines;treatment planning;United States National Institutes of Health;Unnecessary Surgery;uptake;Woman;women's diagnosis;Women's mortality

PROJECT_TITLE: A multi-faceted intervention to promote breast cancer hormone receptor testing in Tanzania

STUDY_SECTION: NCI

STUDY_SECTION_NAME: Career Development Study Section (J)[NCI-J]


ADMINISTERING_IC: ES

ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

IC_NAME: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Climate-Related Exposures and Conditions;Clinical Research;Emerging Infectious Diseases;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Effects of Indoor Air Pollution;Infectious Diseases;Lung;Prevention;Rare Diseases;Social Determinants of Health;Tuberculosis

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

PHR: PROJECT NARRATIVE This project examines the role of indoor and outdoor (urban) air pollution in modulating the infectiousness of persons with pulmonary tuberculosis (TB) and the transmission of Mycobacterium tuberculosis (Mtb) to their household contacts in a major urban slum population in Kampala/Uganda, a high TB incidence environment. This project aims at understanding if, and to what extent, household and outdoor air pollution particulate matter (PM2.5) exposures affect the amount of Mtb in respiratory aerosols (source strength) and the cough frequencies of TB index cases on one side, and the transmission of Mtb from TB index cases to their household contacts on the other side. This project has important global public health and environmental justice significance as slum populations are predicted to strongly increase worldwide and air pollution regulations and interventions could help to curb Mtb transmission in poverty settings, which is the primary driver of the devastating TB pandemic.

PI_NAMEs: SCHWANDER, STEPHAN K (contact)

PROGRAM_OFFICER_NAME: HUMBLE, MICHAEL C

PROJECT_TERMS: Address;Affect;air monitoring;Air Pollution;Airborne Particulate Matter;ambient air pollution;antimicrobial;Area;Attention;Behavior;Biological;Blood Tests;case finding;Cessation of life;Characteristics;Chest;Clinical;cohort;Communities;Coughing;COVID-19 pandemic;Cross-Sectional Studies;Data;design;Development;Diabetes Mellitus;Disease;Electricity;Environment;environmental justice;Environmental Risk Factor;experimental study;Exposure to;face mask;fine particles;Frequencies;Funding;Gases;Grant;health inequalities;Home;Household;Household Air Pollution;Human;Immune;Immune response;improved;In Vitro;Incidence;indexing;Individual;Indoor Air Pollution;Industrialization;Infection;Inflammatory Response;Inhalation Exposure;Intervention;Knowledge;Laboratory Finding;Life;Linear Models;Macrophage;marginalization;Measures;Monitor;Mycobacterium tuberculosis;National Institute of Environmental Health Sciences;novel;pandemic disease;Particulate Matter;Passive Smoking;Pathway interactions;Pattern;Persons;Pollution;Population;Poverty;Predisposition;Prevention;Public Health;Pulmonary Tuberculosis;Questionnaires;Random Allocation;recruit;Regulation;Research;Research Design;respiratory aerosol;Risk;Risk Factors;Role;Sampling;Side;Slum;Smoking;solid fuel;Source;Sputum;Structure;Testing;Time;transmission process;Transportation;Tuberculin Test;Tuberculosis;Uganda;urban area;Urban Health;Urban Population;Urbanization;vulnerable community

PROJECT_TITLE: Air Pollution Effects on Transmission of Mycobacterium tuberculosis in Urban Slum Community in Uganda

STUDY_SECTION: IRAP

STUDY_SECTION_NAME: Infectious Diseases, Reproductive Health, Asthma and Pulmonary Conditions Study Section[IRAP]