Henry Ford Health System

PETS AND THE INFANT MICROBIOME: EFFECT ON IMMUNE MATURATION & ATOPIC ASTHMA

VASOACTIVE AUTACOIDS IN BLOOD PRESSURE REGULATION

CARDIAC ENERGY METABOLISM IN HEART FAILURE

BLOOD PRESSURE REGULATION: NOVEL ROLES FOR THE KIDNEY

DETROIT HCV ELIMINATION PROJECT - THE DETROIT HCV ELIMINATION PROJECT, LED BY HENRY FORD HEALTH (HFH), INTEGRATES HOSPITAL-BASED AND STREET-BASED SERVICES TO RAPIDLY DIAGNOSE, TREAT, AND SUPPORT INDIVIDUALS AFFECTED BY HEPATITIS C VIRUS (HCV), SUBSTANCE USE DISORDER (SUD), SERIOUS MENTAL ILLNESS (SMI), AND HOUSING INSTABILITY. THE OVERARCHING GOALS OF THE PROJECT ARE TO ELIMINATE HCV AS A PUBLIC HEALTH THREAT AMONG HIGH-RISK POPULATIONS IN DETROIT; REDUCE ACUTE CARE UTILIZATION AND IMPROVE LONG-TERM OUTCOMES FOR INDIVIDUALS WITH HCV AND CO-OCCURRING CONDITIONS; AND BUILD A SUSTAINABLE INFRASTRUCTURE THAT BRIDGES EMERGENCY CARE, MOBILE OUTREACH, AND COMMUNITY-BASED PRIMARY CARE TO ADDRESS THE INTERSECTING EPIDEMICS OF HCV, SUD, SMI, AND HOMELESSNESS. OVER THE GRANT PROJECT PERIOD, THE INITIATIVE WILL CURE AT LEAST 110 INDIVIDUALS OF HCV IN YEAR 1, 110 IN YEAR 2, AND 110 IN YEAR 3, ACHIEVING A MINIMUM OF 330 HCV CURES. THE INITIATIVE AIMS TO IMPROVE HEALTH FOR METRO DETROIT RESIDENTS BY EXPANDING LOW-THRESHOLD ACCESS TO CARE ACROSS HENRY FORD HOSPITAL’S EMERGENCY DEPARTMENT (ED) IN DETROIT, INFECTIOUS DISEASE (ID) DEPARTMENT, MOBILE OUTREACH, AND COMMUNITY CLINICS SUCH AS CHASS. THIS PROJECT TARGETS POPULATIONS IN METRO DETROIT WITH A HIGH INCIDENCE OF HCV AND A HIGH PREVALENCE OF CO-OCCURRING CONDITIONS SUCH AS OPIOID USE DISORDER (OUD), SMI, HIV AND HOUSING INSTABILITY. MANY INDIVIDUALS WITHIN THIS POPULATION CYCLE THROUGH EMERGENCY AND ACUTE CARE SETTINGS OR REMAIN DISENGAGED FROM TRADITIONAL HEALTH SYSTEMS. KEY STRATEGIES AND INTERVENTIONS FOR THE DETROIT HCV ELIMINATION PROJECT CENTER ON A COORDINATED, MULTI-SETTING RESPONSE TO HCV, SUBSTANCE USE, AND RELATED HEALTH CHALLENGES. AT HFH, ALL ED PATIENTS ARE SCREENED USING A STANDARDIZED SBIRT MODEL. THOSE PRESENTING WITH OUD OR OVERDOSE RECEIVE HARM REDUCTION EDUCATION, NALOXONE, CASE MANAGEMENT, AND FACILITATED REFERRAL TO CARE. POINT-OF-CARE (POC) HCV RNA TESTING USING THE CEPHEID XPERT FINGERSTICK ASSAY ENABLES REAL-TIME DIAGNOSIS AND SAME-DAY INITIATION OF TREATMENT, DIRECTLY WITHIN THE ED SETTING. PATIENTS WILL BE REFERRED TO CHASS OR ID FOR FOLLOW-UP CARE. THIS INTEGRATED CARE COORDINATION WILL BE PROVIDED BY NURSE NAVIGATORS AND PEER RECOVERY COACHES (PRCS), WHO DELIVER BEHAVIORAL HEALTH SCREENING, EDUCATION ON HCV, AND WARM HANDOFFS TO SPECIALTY OR ONGOING CARE. THE COLLABORATION WITH THE PROVIDERS OF THE EXISTING RYAN WHITE FUNDED HIV CARE INFRASTRUCTURE WITHIN THE ID DEPARTMENT WILL ENHANCE HCV TESTING, TREATMENT INITIATION, AND LONGITUDINAL CARE, INCLUDING THOSE CO-INFECTED WITH HIV. THIS INITIATIVE WILL BUILD UPON THE ID TEAM’S RYAN WHITE CLINICAL EXPERTISE OF OVER 30 YEARS, ROBUST INFRASTRUCTURE AND CARE MODEL TO RAPIDLY SCREEN, INITIATE TREATMENT, AND CURE PATIENTS WITH HCV, INCLUDING THOSE CO-INFECTED WITH HIV. COMMUNITY-BASED OUTREACH WILL BE LED BY COMMUNITY HEALTH AND SOCIAL SERVICES CENTER (CHASS) AND ITS PARTNER, THE NEIGHBORHOOD SERVICE ORGANIZATION, THROUGH MOBILE STREET MEDICINE UNITS STAFFED BY PHYSICIANS, NURSES, SOCIAL WORKERS, AND PEER WORKERS. THESE TEAMS CONDUCT POC HCV TESTING, DETERMINE ELIGIBILITY FOR SIMPLIFIED TREATMENT PATHWAYS, AND SUPPORT ADHERENCE THROUGH MODIFIED DIRECTLY OBSERVED THERAPY (DOT). CO-LOCATED SERVICES AVAILABLE THROUGH MOBILE UNITS INCLUDE MEDICATIONS FOR OPIOID USE DISORDER (MOUD), PSYCHIATRIC CARE, HOUSING NAVIGATION, AND ASSISTANCE WITH ID AND INSURANCE REACTIVATION. TO STRENGTHEN LINKAGE AND RETENTION, COMMUNITY HEALTH WORKERS (CHWS) AND PRCS ENGAGE INDIVIDUALS AND THEIR SOCIAL NETWORKS, PROVIDING CONSISTENT, CULTURALLY RESPONSIVE OUTREACH THAT BUILDS TRUST AND FACILITATES SUSTAINED CONNECTION TO CARE. PROJECT TEAMS WILL ALSO MAKE REFERRALS TO THE UNITED WAY OF SOUTHEASTERN MICHIGAN COMMUNITY INFORMATION EXCHANGE (CIE) FOR HOUSING SUPPORT AND WILL AID WITH RECOVERY HOUSING FOR A LIMITED NUMBER OF VULNERABLE PATIENTS

AN EVALUATION OF THE NATIONAL ZERO SUICIDE MODEL ACROSS LEARNING HEALTHCARE SYSTEMS

TRANS-AMERICA CONSORTIUM OF THE HEALTH CARE SYSTEMS RESEARCH NETWORK FOR THE PRECISION MEDICINE INITIATIVE COHORT PROGRAM

PERSONALIZING CARE FOR OBESE PATIENTS IN AN URBAN HEALTH SYSTEM

A NESTED CASE-CONTROL STUDY OF PROSTATE CARCINOGENESIS

PHARMACOGENOMICS OF INHALED CORTICOSTEROID RESPONSIVENESS IN PATIENTS WITH ASTHMA

CENTER FOR STROKE RESEARCH

HEALTH CARE INNOVATION CHALLENGE: MOBILITY, THE 6TH VITAL SIGN

IMPACT OF RACE AND GENETIC FACTORS ON BETA-BLOCKER EFFECTIVENESS IN HEART FAILURE

BABIES WIN. FAMILIES THRIVE. COMMUNITIES TRANSFORMED! -- DETROIT'S INNOVATIVE COLLABORATIVE FOR THE INTEGRATION OF COMMUNITY-BASED MATERNAL SUPPORT SERVICES IN PERINATAL SYSTEMS OF CARE - HENRY FORD HEALTH IN PARTNERSHIP WITH BLACK MOTHERS BREASTFEEDING ASSOCIATION AND THE UNIVERSITY OF MICHIGAN (UM) ARE PLEASED TO PRESENT THIS PROPOSAL FOR BABIES WIN. FAMILIES THRIVE. COMMUNITIES TRANSFORMED! (THE TRIPLE CROWN) WHICH WILL DEVELOP AN INNOVATIVE COLLABORATIVE TO FACILITATE THE INTEGRATION OF COMMUNITY-BASED MATERNAL SUPPORT SERVICES INTO PERINATAL SYSTEMS OF CARE IN DETROIT, MI WHERE THE POPULATION IS 76.6% BLACK AND 31.5% OF WOMEN LIVE IN POVERTY. JOINING THE TRIPLE CROWN COLLABORATION ARE A DIVERSE GROUP OF PUBLIC, PRIVATE, AND COMMUNITY PARTNERS INCLUDING BIRTH DETROIT, BRILLIANT DETROIT, COREWELL HEALTH, DETROIT HEALTH DEPARTMENT, FOCUS: HOPE, HARAMBEE CARE, MOLINA HEALTHCARE, SOUTHEAST MICHIGAN PERINATAL QUALITY IMPROVEMENT COALITION, UNITED WAY OF SOUTHEASTERN MICHIGAN, AND UM CHILD HEALTH EVALUATION AND RESEARCH CENTER. TOGETHER THESE MEDICAL, SOCIAL, COMMUNITY-BASED, ADVOCACY AND SUPPORT PARTNERS WILL ADDRESS SOCIAL DETERMINANTS OF HEALTH AND FILL GAPS THAT EXIST IN THE CONTINUUM OF CARE FOR PREGNANT AND POSTPARTUM PERSONS WHILE PURSUING THE MATERNAL INFANT CHILD HEALTH OBJECTIVES OF HEALTHY PEOPLE 2030. BY PARTNERING WITH INVESTED STAKEHOLDERS ACROSS THE CITY OF DETROIT, EXPANDING THE PERINATAL CARE TEAM WORKFORCE, AND EQUIPPING THEM WITH NEEDED RESOURCES, WE CAN ADDRESS DETROIT’S MATERNAL AND INFANT HEALTH CRISIS IN A FEASIBLE, EFFECTIVE, AND SUSTAINABLE WAY.

TRANSLATING DIGITAL WRIST TOMOSYNTHESIS AS A NOVEL DIAGNOSTIC AID TO ENABLE OSTEOPOROSIS SCREENING WITHIN THE WIDELY ACCESSIBLE MAMMOGRAPHY SETTING

ENVIRONMENTAL RISK FACTORS FOR UTERINE FIBROIDS: A PROSPECTIVE ULTRASOUND STUDY

LEVERAGING ELECTRONIC MEDICAL RECORDS TO PERFORM LARGE-SCALE DIABETES PHARMACOGENOMICS AMONG ANCESTRALLY DIVERSE PATIENT POPULATIONS

PLASMA METABOLOMICS AND MYOCARDIAL ENERGETICS IN HEART FAILURE

INTERACTION BETWEEN GLYMPHATIC AND VASCULAR SYSTEMS FOR WASTE CLEARANCE IN BRAIN

POLY-OMIC STUDY OF ASTHMA EXACERBATIONS IN DIVERSE POPULATIONS

DELIVERY MODE, ENVIRONMENT AND THE GUT MICROBIOME: INFLUENCE ON CHILDHOOD BODY SIZE

ENHANCING DIGITAL CBT-I TO IMPROVE ADHERENCE AND REDUCE DISPARITIES - PROJECT SUMMARY/ABSTRACT INSOMNIA IS A DEBILITATING CONDITION THAT ESCALATES RISK OF A MYRIAD OF DISORDERS, AND AFFECTS UP TO ONE THIRD OF ADULTS. ALTHOUGH INSOMNIA CAN BE EFFECTIVELY TREATED WITH COGNITIVE BEHAVIORAL THERAPY FOR INSOMNIA (CBT-I), THERE IS A SHORTAGE OF SPECIALTY PROVIDERS TRAINED IN CBT-I. CONSEQUENTLY, MOST PATIENTS WITH INSOMNIA ARE UNABLE TO RECEIVE CBT-I AS THE RECOMMENDED FIRST-LINE INTERVENTION FOR INSOMNIA. TO ADDRESS THIS PROBLEM, CBT-I CAN NOW BE DELIVERED DIGITALLY (DCBT-I) WITH STRONG EFFICACY; HOWEVER, THE REAL-WORLD EFFECTIVENESS OF DCBT-I IS LIMITED BY POOR ENGAGEMENT. OVER 50% OF PATIENTS DO NOT COMPLETE THE FULL COURSE OF DCBT-I, AND 40% OF THOSE WHO PERSIST IN TREATMENT DO NOT ADHERE TO CRITICAL COMPONENTS OF DCBT-I. MOREOVER, TREATMENT COMPLETION AND ADHERENCE ARE 2-3 TIMES WORSE IN THOSE WITH LOW SOCIOECONOMIC STATUS. OUR PILOT DATA INDICATE THAT THE DISPARITY IN COMPLETION AND ADHERENCE TO DCBT-I IS RELATED TO LOW HEALTH LITERACY, DEFINED AS THE ABILITY TO FIND, UNDERSTAND, AND USE INFORMATION AND SERVICES TO INFORM HEALTH-RELATED DECISIONS. HEALTH LITERACY IS ESPECIALLY CRITICAL FOR ENGAGEMENT WITH DIGITAL INTERVENTIONS THAT ARE SELF-GUIDED, SUCH AS DCBT-I. THIS PROPOSAL RESPONDS TO AN ANNOUNCEMENT FOCUSED ON IMPROVING PATIENT ADHERENCE TO TREATMENTS. WE PROPOSE A LARGE-SCALE INTERVENTION COMPARING ENHANCED DCBT-I TO CONTROL DCBT-I IN IMPROVING TREATMENT COMPLETION AND ADHERENCE IN A SAMPLE STRATIFIED BY SOCIOECONOMIC STATUS. WE ALSO PROPOSE TO TEST THE EFFECT OF ENHANCED DCBT-I ON REDUCING SOCIOECONOMIC DISPARITIES IN TREATMENT ADHERENCE AND COMPLETION. AN INNOVATIVE COMPONENT OF THIS TRIAL IS THE USE OF NON-SPECIALIST COACHES AS A SCAFFOLD FOR LOW HEALTH LITERACY, AND TO ENHANCE TREATMENT MOTIVATION AND SELF-EFFICACY. FURTHERMORE, THOSE WHO ARE AT-RISK FOR TREATMENT NON- COMPLETION ARE SHIFTED TO TELEHEALTH COACHING FOCUSED ON ONE SINGLE CRITICAL BEHAVIORAL COMPONENT TAILORED FOR EASE OF ASSIMILATION INTO THE PATIENT’S DAILY LIFE. THE ADAPTIVE COMPONENT PROVIDES PATIENTS TWO DIFFERENT TREATMENT MODALITIES TO MAXIMIZE ENGAGEMENT AND BOTH APPROACHES LEVERAGE TECHNOLOGY TO INCREASE ACCESSIBILITY. OUR LONG-TERM GOAL IS TO ENSURE EQUITABLE EFFECTIVENESS OF DIGITAL INSOMNIA TREATMENTS. TO THAT END, OUR OVERALL OBJECTIVE IS TO DETERMINE HOW ADHERENCE AND COMPLETION IN DCBT-I CAN BE IMPROVED, PARTICULARLY IN THOSE WITH LOW SES AS A HEALTH DISPARITIES POPULATION. BASED ON PILOT DATA, OUR CENTRAL HYPOTHESIS IS THAT, COMPARED TO CONTROL DCBT-I, ENHANCED DCBT-I WILL INCREASE ENGAGEMENT BY PROVIDING TARGETED SUPPORT FOR THOSE WHO NEED IT.

SHOULDER FUNCTION AFTER ROTATOR CUFF REPAIR

ADMIXTURE MAPPING OF SARCOIDOSIS GENES IN AFRICAN AMERICAN

COMBINED TRANSCRIPTOMICS AND GENOMICS TO FIND ASTHMA GENES IN ADMIXED POPULATIONS

GLYMPHATIC AND COGNITIVE IMPAIRMENT OF AGING AND DIABETES

SLEEP REACTIVITY AS A NOVEL MECHANISM IN SHIFT WORK DISORDER - PROJECT SUMMARY/ABSTRACT ALL ESSENTIAL 24-HR OPERATIONS (E.G., FIRST RESPONDERS, HOSPITAL SERVICES) RELY ON NIGHTSHIFT WORKERS WHO FORGO NOCTURNAL SLEEP FOR WORK. SHIFT WORKERS COMPRISE 20% OF THE WORKFORCE, WITH 15 MILLION REGULARLY WORKING NIGHTS. MOST DO NOT ADAPT TO THE INVERTED SLEEP-WAKE SCHEDULE, RESULTING IN SHIFT WORK DISORDER (SWD) CHARACTERIZED BY EXCESSIVE SLEEPINESS AND/OR INSOMNIA WITH SLEEP LOSS. FURTHERMORE, BECAUSE NIGHTSHIFTS ARE CRITICAL TO SAFETY- SENSITIVE OPERATIONS, THE RISK FOR CATASTROPHIC ACCIDENTS MAKES SWD A THREAT TO PUBLIC HEALTH AND SAFETY. THERE REMAIN CRITICAL GAPS IN THE CLINICAL TRANSLATION OF SHIFT WORK RESEARCH INTO VALIDATED TREATMENTS FOR SWD. ONE GAP IS A LACK OF MECHANISTIC RESEARCH IN LARGE CLINICAL SAMPLES OF SWD THAT PROBE PERTINENT TREATMENT TARGETS. AS SUCH, TREATMENTS HAVE PREDOMINANTLY FOCUSED ON SYMPTOM MANAGEMENT (E.G., STIMULANTS TO MAINTAIN ALERTNESS AND HYPNOTIC MEDICATIONS FOR SLEEP). SYMPTOM MANAGEMENT ALONE LEAVES THE UNDERLYING MECHANISMS UNABATED WHICH CAN CONTINUE TO CAUSE A MYRIAD OF ACUTE AND LONG-TERM PROBLEMS AND MORBIDITIES. TO ADDRESS THIS GAP, THE OVERALL OBJECTIVE OF THIS PROPOSAL IS TO ELUCIDATE CRITICAL AND NOVEL MECHANISMS DRIVING SWD. OUR LONG-TERM GOAL IS TO DEVELOP A TREATMENT THAT IDENTIFIES AND TARGETS THE APPROPRIATE UNDERLYING MECHANISMS IN SWD. OUR PILOT DATA INDICATES THAT IN ADDITION TO CIRCADIAN MISALIGNMENT (I.E., A MISMATCH BETWEEN THE BODY- CLOCK AND THE SLEEP-WORK SCHEDULE), ONE NOVEL AND CRITICAL MECHANISM IN SWD IS SLEEP REACTIVITY. SLEEP REACTIVITY IS A TRAIT WHERE SLEEP IS EASILY DISRUPTED BY ENVIRONMENTAL STIMULI AND STRESSORS. OUR PILOT DATA IN A CROSS-SECTIONAL SAMPLE SUGGESTS THAT SLEEP REACTIVITY PREDICTS PERSISTENT SWD SYMPTOMS EVEN AFTER REDUCING CIRCADIAN MISALIGNMENT. WE ALSO SHOW THAT SLEEP REACTIVITY CAN BE REDUCED WITH COGNITIVE BEHAVIORAL THERAPY (CBT). HOWEVER, SLEEP REACTIVITY HAS NOT BEEN EXPERIMENTALLY DISASSOCIATED FROM CIRCADIAN MISALIGNMENT AS AN INDEPENDENT CAUSAL MECHANISM OF SWD. THIS RESEARCH IS CRITICAL BECAUSE IT WOULD DEMONSTRATE THAT SWD TREATMENT SHOULD TARGET SLEEP REACTIVITY INDEPENDENTLY FROM CIRCADIAN MISALIGNMENT. TO DO THIS, WE PROPOSE A TWO-STEP MECHANISTIC RANDOMIZED CONTROLLED TRIAL IN SWD STRATIFIED BY HIGH AND LOW SLEEP REACTIVITY (N=150): THE FIRST STEP PROBES CIRCADIAN MISALIGNMENT USING TIMED BRIGHT LIGHT EXPOSURE, AND THE SECOND STEP REDUCES SLEEP REACTIVITY WITH COGNITIVE BEHAVIORAL THERAPY. OUR CENTRAL HYPOTHESIS IS THAT SYMPTOMS OF SWD WILL REDUCE PROPORTIONATELY WITH CIRCADIAN REALIGNMENT IN SWD WITH LOW SLEEP REACTIVITY; HOWEVER, BOTH INSOMNIA (AIM 1) AND SLEEPINESS (AIM 2) SYMPTOMS WILL PERSIST IN SWD WITH HIGH SLEEP REACTIVITY EVEN AFTER EXPERIMENTAL REDUCTION OF CIRCADIAN MISALIGNMENT. IN THOSE WITH PERSISTENT SYMPTOMS DESPITE REDUCED CIRCADIAN MISALIGNMENT, FURTHER REDUCING SLEEP REACTIVITY WITH CBT WOULD RESULT IN REDUCTIONS IN SYMPTOMS (AIMS 3 & 4). UPON COMPLETION, RESULTS FROM THIS STUDY WILL HAVE ESTABLISHED SLEEP REACTIVITY AS A NOVEL CAUSAL MECHANISM OF SWD TO BE INFORM FUTURE PRECISION MEDICINE APPROACHES FOR THIS HIGHLY PREVALENT AND UNDERTREATED DISORDER.

ENCOURAGING YOUNG ADULTS TO MAKE EFFECTIVE NUTRITION CHOICES: MENU GEN Y STUDY

MOLECULAR AND CLINICAL EVALUATION OF THE GLIOMA PATIENT EXPERIENCE TO ANTICIPATE MODERN OUTCOMES AND GUIDE PATIENT CARE

TREATMENT UTILIZATION BEFORE SUICIDE (TUBS)

PRAGMATIC CLUSTER RANDOMIZED TRIAL OF AN ASTHMA INTERVENTION FOR URBAN TEENS

MRI SIGNATURES OF RESPONSE TO HIGH-DOSE RADIOTHERAPY IN RAT MODELS OF CEREBRAL TUMOR

ASSESSMENT OF BONE HEALTH VIA DIGITAL WRIST TOMOSYNTHESIS IN MAMMOGRAPHY SETTING

STATINS & LYMPHOID MALIGNANCY RISK IN A LARGE MULTI-SITE POPULATION-BASED COHORT

RISKS FOR TRANSITION FROM THERAPEUTIC HYPNOTIC USE TO ABUSE

METAPLASTIC TUFT CELLS IN PANCREATIC CANCER

DISCOVERY OF ANTICANCER DRUGS FROM CYANOBACTERIA

CIRCULATING CELL-FREE DNA METHYLATION AS AN ACCURATE TOOL FOR DETECTION AND CLINICAL FOLLOW-UP OF GLIOMA - PROJECT SUMMARY/ABSTRACT DESPITE ADVANCES IN SURGICAL TECHNIQUES AND CLINICAL REGIMENS, MALIGNANT GLIOMAS USUALLY PROGRESS OR RECUR AFTER TREATMENT. CURRENTLY, VISUAL INSPECTION OF IMAGING DATA IS THE MAINSTAY TO MONITOR GLIOMA PROGRESSION; HOWEVER, THIS APPROACH MAY NOT BE ACCURATE OR REFINED ENOUGH TO MONITOR TREATMENT RESPONSE OR EVOLVING PROGNOSTIC SUBTYPES. IMAGING DATA HAS LIMITED ABILITY TO DISTINGUISH 1) GLIOMAS FROM OTHER TUMORS (E.G., PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA), 2) PROGRESSION FROM PSEUDOPROGRESSION (PSEUDOPD) RESULTING FROM THERAPY-INDUCED NECROSIS, OR 3) MINIMAL OR REMNANT TUMORAL BURDEN. RECENTLY, WE AND OTHERS FOUND THAT POTENTIAL DRIVERS OF GLIOMA PROGRESSION ARE MEDIATED BY GENE MUTATION AND EPIGENETIC ABNORMALITIES. GENERALLY, CANCER MOLECULAR SIGNATURES ARE IDENTIFIABLE IN TUMORAL TISSUE; HOWEVER, SEVERAL GROUPS HAVE REPORTED THAT TUMOR SPECIFIC SIGNATURES USING BOTH GENETICS AND DNA METHYLATION CAN BE CAPTURED BY NON- OR MINIMALLY-INVASIVE APPROACH SUCH AS LIQUID BIOPSY (LB) USING BIOSPECIMENS SUCH AS BLOOD AND CEREBROSPINAL FLUID. TO ADDRESS THIS KNOWLEDGE GAP IN THE ROLE OF LB TO MONITOR GLIOMA PROGRESSION/RECURRENCE, WE AIM TO ESTABLISH A NOVEL APPROACH TO DETECT POSTOPERATIVE MALIGNANT GLIOMA USING DNA METHYLATION OF BLOOD-DERIVED CELL-FREE DNA (CFDNA) MARKERS WITH THE ULTIMATE GOAL TO FINE-TUNE SURVEILLANCE AND TREATMENT IN REAL TIME. WITH AVAILABLE DNA METHYLATION DATA EXTRACTED FROM SERUM/PLASMA CFDNA AT INITIAL DIAGNOSIS, WE WILL DEVELOP A NON-INVASIVE GLIOMA-SCORE THAT IS ASSOCIATED WITH PROGNOSTICALLY RELEVANT SUBTYPES OF GLIOMA (E.G., G-CIMP-HIGH VS -LOW), GLIOMAS HARBORING UNIQUE AND DRUGGABLE GENETIC ALTERATIONS (FGFR3-TACC3 [F3-T3]) AND GLIOMAS DEVELOPING IN PATIENTS WITH NEUROFIBROMATOSIS TYPE 1 (NF1-GLIOMA) (AIM 1). FROM AVAILABLE COHORTS SPANNING LONGITUDINAL SPECIMENS ACCRUED FOR MORE THAN A DECADE, WE WILL PROFILE THE EPIGENOME OF PAIRED PRIMARY AND RECURRENT SETS (E.G., FIRST, SECOND /OR THIRD RECURRENCE), AND DEVELOP A GLIOMA RECURRENCE (GLIOMAR)-SCORE ASSOCIATED WITH RECURRENCE, AND RESPONSE TO THERAPY (AIM 2). BASED ON OUR DEFINED SCORES, WE WILL CLASSIFY PATIENTS INTO DEFINED PROGNOSTIC GROUPS (E.G., GOOD AND POOR OUTCOME) AND RISK TO RECUR AS A MORE AGGRESSIVE SUBTYPE UPON RECURRENCE SUBGROUPS. THIS WILL ASSESS THE ACCURACY OF LB TO MONITOR POSTOPERATIVE PROGRESSION OF DIFFERENT MOLECULAR SUBTYPES OF GLIOMA THROUGHOUT AN INDIVIDUAL’S DISEASE. WE WILL UTILIZE THE QUANTITATIVE AND SEMI-QUANTITATIVE IMAGING FEATURES ROUTINELY USED IN THE DIAGNOSIS AND MONITORING OF GLIOMA TO CORRELATE THE EPIGENOMIC MARKERS OF THE LB GLIOMA-SCORE WITH WELL ESTABLISHED GLIOMA IMAGING STANDARDS AND TAILOR THE LB SCORE TOWARDS THE RESOLUTION OF THE CURRENT LIMITATIONS OF IMAGING DATA FOR HUMAN GLIOMA (E.G., PSEUDOPD AND RADIATION NECROSIS) (AIM 3). OUR STUDY WILL BE THE FIRST TO INVESTIGATE GLIOMA WHOLE-EPIGENOME LB MARKERS TO DETECT AGGRESSIVE GLIOMAS AT INITIAL DIAGNOSIS AND DURING TUMOR PROGRESSION. ACCURATE DIAGNOSIS THROUGH A SIMPLE BLOOD TEST WILL ALLOW CLINICIANS TO DETECT THE EVOLUTION OF THE DISEASE IN REAL-TIME, THUS IDENTIFYING HIGH-RISK PATIENTS WHO MAY BENEFIT FROM MORE AGGRESSIVE THERAPY AT AN EARLIER POINT WHEN INTERVENTION COULD BE MORE EFFECTIVE.

INVESTIGATION OF D-4F EFFECTS OF NEUROVASCULAR REMODELING AFTER DIABETIC STROKE

FRUCTOSE INDUCED SALT-SENSITIVE HYPERTENSION: ROLE OF THICK ASCENDING LIMB TRANSPORT

THE IMPROVING ATTENDANCE TO CARDIAC REHABILITATION (IATTEND) TRIAL

BEHAVIORAL TREATMENT OF MENOPAUSAL INSOMNIA; SLEEP, DEPRESSION, DAYTIME OUTCOMES

IMPLEMENTING ZERO SUICIDE IN EMERGENCY DEPARTMENTS WITH DIVERSE POPULATIONS IN MICHIGAN

DEVELOPMENT OF HARDWARE AND SOFTWARE FOR CLINICAL MEG

EXOSOME THERAPY FOR ACUTE STROKE WITH LARGE ARTERY OCCLUSION

IMPLEMENTING TRAUMA-FOCUSED BEHAVIORAL HEALTH TREATMENT FOR UNDERSERVED CHILDREN IN DETROIT, MI - HENRY FORD HEALTH SYSTEM (HFHS) AIMS TO INCREASE ITS CAPACITY AND SERVICE PROVISION OF TRAUMA-FOCUSED TREATMENT VIA THE DEVELOPMENT OF A CHILD TRAUMA SPECIALTY SERVICE. TO DO SO, WE WILL IMPLEMENT TWO TRAUMA-FOCUSED TREATMENTS, THE ATTACHMENT, REGULATION AND COMPETENCY FRAMEWORK (ARC) AND TRAUMA-FOCUSED COGNITIVE BEHAVIORAL THERAPY (TF-CBT), AND INCREASE IDENTIFICATION OF AND REFERRAL TO TREATMENT FOR CHILD TRAUMATIC STRESS WITHIN PEDIATRIC PRIMARY CARE. THIS PROJECT, IMPLEMENTING TRAUMA-FOCUSED TREATMENT FOR UNDERSERVED CHILDREN IN DETROIT, MI, SEEKS TO IMPLEMENT TRAUMA-FOCUSED, EVIDENCE-BASED TREATMENTS ACROSS 5 OUTPATIENT PEDIATRIC BEHAVIORAL HEALTH AND 10 INTEGRATED CARE CLINICS IN HFHS SERVING 3 COUNTIES IN SOUTHEAST MICHIGAN (WAYNE, OAKLAND AND MACOMB). THIS CATCHMENT AREA SERVICES A RACIAL AND ETHNICALLY DIVERSE, URBAN (DETROIT) AND SUBURBAN (METRO-DETROIT) POPULATION OF CHILDREN AND FAMILIES WITH LARGE PROPORTIONS (>36% OF DETROIT RESIDENTS) LIVING UNDER THE POVERTY LINE. CHILDREN AGES 4-17 YEARS WITH TRAUMATIC STRESS (INCLUDING DIAGNOSES OF PTSD, ACUTE STRESS DISORDER AND OTHER COMPLEX OR CHRONIC STRESS AND TRAUMA CONDITIONS WHICH CAUSES IMPAIRMENTS IN SOCIAL, EMOTIONAL AND BEHAVIORAL FUNCTIONING) WILL BE SERVED THROUGH THIS PROJECT AND WILL BE IDENTIFIED AND REFERRED FOR GRANT SERVICES THROUGH SCREENING AT BOTH WELL VISITS AND BEHAVIORAL HEALTH CARE APPOINTMENTS. AS OUR GOAL IS TO BECOME THE CENTRAL HUB FOR TREATMENT OF CHILD TRAUMA IN DETROIT, THE OUTLINED GOALS OF THIS PROJECT INCLUDE 1) ESTABLISHING A LEADERSHIP TEAM WITH EXPERTISE IN CLINICAL SERVICE PROVISION, TRAINING, AND IMPLEMENTATION OF SERVICES FOR TRAUMATIZED AND VULNERABLE YOUTH, 2) INCREASING AWARENESS, KNOWLEDGE, AND TRAINING ON CHILD TRAUMA ACROSS PEDIATRIC PRIMARY CARE, BEHAVIORAL HEALTH CLINICS, AND COMMUNITY PARTNERS, 3) IMPLEMENTING THE ATTACHMENT, REGULATION AND COMPETENCY FRAMEWORK THROUGH TRAINING, CONSULTATION, SUPERVISION, AND ESTABLISHING A TRAIN-THE-TRAINER MODEL, 4) EXPANDING THE NUMBER OF PEDIATRIC TREATMENT PROVIDERS TRAINED IN TF-CBT, AND 5) DEVELOPING A HIGH-FIDELITY AND SUSTAINABLE CHILD TRAUMA SPECIALTY SERVICE THROUGH ITERATIVE QUALITY IMPROVEMENT USING THE PLAN-DO-STUDY-ACT METHOD. THIS PROJECT WILL SERVE OVER 14,000 YOUTH (BEGINNING AT 1,000 ANNUALLY IN YEAR 1 OF THE GRANT AND EXPANDING TO 4,000 ANNUALLY BY YEAR 5) THROUGH ENHANCED SCREENING FOR TRAUMATIC STRESS AT PRIMARY CARE VISITS AS WELL AS THROUGH REFERRALS FROM OUR SCHOOL-AND COMMUNITY-BASED HEALTHCARE CLINICS. GIVEN THE HIGH PREVALENCE RATES OF TRAUMATIC STRESS IN THE SURROUNDING COMMUNITIES AND HIGH LEVELS OF UNMET TRAUMA-INFORMED TREATMENT NEEDS IN THE HEALTH SYSTEM, WE ANTICIPATE IDENTIFYING, REFERRING, AND ENGAGING IN TREATMENT MINIMUM OF 580 OF CHILDREN (BEGINNING AT 80 YOUTH ANNUALLY IN YEAR 1 OF THE GRANT AND EXPANDING TO 150 ANNUALLY BY YEAR 5) BY THE END OF THE 5-YEAR PERIOD OF THE GRANT.

NOVEL REGULATION AND TARGETING OF MACROPHAGES METABOLISM IN NEUROINFLAMMATORY DISORDERS

VASCULOTIDE PROMOTES COGNITIVE IMPROVEMENT IN RATS WITH VASCULAR DEMENTIA

MICRORNAS AND NKT CELL DEVELOPMENT AND FUNCTION

DIABETIC STROKE CARDIAC DYSFUNCTION; TREATMENT WITH CD133+EXOSOMES

B-CATENIN IN VACCINE-INDUCED ANTI-TUMOR CD8 T CELL IMMUNITY

CEREBRAL ENDOTHELIAL CELLS DERIVED EXOSOMES AS A THERAPY FOR COGNITIVE IMPAIRMENT IN AGED DIABETIC RATS - ABSTRACT: DIABETES MELLITUS (DM) INDUCES CEREBRAL VASCULAR DYSFUNCTION AND IMPAIRS THE HIPPOCAMPAL NEUROGENESIS, RESULTING IN COGNITIVE DECLINE. CEREBRAL ANGIOGENESIS COUPLES WITH NEUROGENESIS. MOLECULES THAT MEDIATE THE INTERACTION BETWEEN CEREBRAL ENDOTHELIAL CELLS AND NEURAL STEM CELLS IN PARTICULAR IN DM HAVE NOT BEEN FULLY INVESTIGATED. CEREBRAL ENDOTHELIAL CELLS CONSTITUTIVELY RELEASE EXOSOMES, WHICH MEDIATE INTERCELLULAR COMMUNICATION. OUR PRELIMINARY DATA DEMONSTRATED THAT EXOSOMES DERIVED FROM DYSFUNCTIONAL CEREBRAL ENDOTHELIAL CELLS OF DM RATS COMMUNICATE WITH NEURAL STEM CELLS AND INHIBIT NEUROGENESIS. IMPORTANTLY, ADMINISTRATION OF EXOSOMES ISOLATED FROM CEREBRAL ENDOTHELIAL CELLS (CE-EXO) OF HEALTHY ADULT BRAIN TO DM RATS ROBUSTLY IMPROVED COGNITIVE FUNCTION AND MINIMIZED DM-INDUCED CEREBRAL ENDOTHELIAL CELL DYSFUNCTION AND DM- IMPAIRED HIPPOCAMPAL NEUROGENESIS. IN THIS APPLICATION, WE THEREFORE, PROPOSE TO DEVELOP CEREBRAL ENDOTHELIAL EXOSOMES AS A MECHANISM-BASED THERAPY FOR DM-INDUCED COGNITIVE DECLINE IN THE AGED RATS. THERE ARE THREE AIMS. AIM 1 TESTS THE HYPOTHESIS THAT CE-EXO TREATMENT REDUCES COGNITIVE DEFICITS IN THE DM RAT. AIM 2 TESTS THE HYPOTHESIS THAT CE-EXO TREATMENT IMPROVES CEREBRAL VASCULAR PATENCY AND INTEGRITY, AND PROMOTES NEUROGENESIS IN THE AGED-DM RAT. AIM 3 TESTS THE HYPOTHESIS THAT ENGINEERED EXOSOMES CARRYING ELEVATED SELECTIVE MIRNAS HAVE ENHANCED EFFECTS ON CEREBRAL VASCULAR FUNCTION AND NEUROGENESIS AS WELL AS COGNITIVE FUNCTION. THESE STUDIES WILL PROVIDE PRECLINICAL EVIDENCE FOR DEVELOPING CE-EXO AS AN INNOVATIVE TREATMENT FOR DM-INDUCED COGNITIVE DYSFUNCTION.

LONG TERM EFFECTIVENESS OF UTERINE SPARING FIBROID TREATMENTS - THE LIFETIME CUMULATIVE INCIDENCE OF UTERINE LEIOMYOMAS (FIBROIDS OR UF) IS >80% AMONG BLACK WOMEN AND ~70% IN WHITE WOMEN. UF ARE THE MOST COMMON REASON FOR HYSTERECTOMY IN THE U.S. AND CAN CAUSE HEAVY MENSTRUAL BLEEDING REQUIRING BLOOD TRANSFUSION(S), PELVIC PAIN, URINARY AND BOWEL PROBLEMS, INFERTILITY, AND SUBSTANTIAL IMPAIRMENT OF QUALITY OF LIFE (QOL). WHILE ALTERNATIVES TO HYSTERECTOMY ARE AVAILABLE INCLUDING MYOMECTOMY (FIBROID REMOVAL), UTERINE ARTERY EMBOLIZATION (UAE), ENDOMETRIAL ABLATION (EA), AND RADIOFREQUENCY ABLATION (RFA), THERE ARE SIGNIFICANT KNOWLEDGE GAPS THAT PRECLUDE THE DEVELOPMENT OF EVIDENCE-BASED CLINICAL GUIDELINES TO SELECT AN APPROPRIATE UF TREATMENT. PRIOR STUDIES OF UF TREATMENTS HAVE SEVERAL KEY DEFICITS INCLUDING LIMITED FOLLOW-UP TIME (<2 YEARS) AND FAILURE TO ASSESS IMPORTANT CONFOUNDERS, SUCH AS PRE-PROCEDURE FIBROID CHARACTERISTICS, BASELINE QOL, AND PREGNANCY INTENTION. TWO MULTISITE REGISTRIES WITH HARMONIZED DATA, COMPARE-UF (MYOMECTOMY, EA AND UAE PATIENTS) AND ULTRA (RFA PATIENTS), HAVE THE CAPACITY TO ADDRESS CRITICAL EVIDENCE GAPS AND SIGNIFICANTLY IMPROVE CARE FOR WOMEN WITH UF. THIS PROJECT WILL BE LED BY COMPARE-UF/ULTRA INVESTIGATORS (MPIS) AND EXTEND THE FOLLOW-UP OF 700 COMPARE-UF AND ULTRA PARTICIPANTS WHO HAVE HAD A UTERINE-SPARING FIBROID TREATMENT FOR UP TO 10 YEARS AFTER THE INDEX PROCEDURE. LONG TERM FOLLOW-UP THROUGH MENOPAUSE IS CRITICAL TO ASSESS THE DURABILITY OF SYMPTOM IMPROVEMENT AND THE RATES OF HYSTERECTOMY OR OTHER UTERINE PROCEDURES FOLLOWING THE INDEX TREATMENT. CURRENTLY, WOMEN IN COMPARE-UF/ULTRA ARE FOLLOWED ONLY FOR 1-3 YEARS POST TREATMENT; THE ADDITIONAL FOLLOW-UP IN THIS PROPOSAL, WILL HAVE A MAJOR IMPACT ON CLINICAL DECISION-MAKING, PROVIDE RELEVANT DATA IN A RACIALLY DIVERSE (>40% BLACK) POPULATION, AND INCLUDE DETAILED IMAGING INFORMATION (UF SIZE, NUMBER AND LOCATION), AND SELF-REPORTED DESIRE FOR FUTURE FERTILITY OBTAINED PRIOR TO THE INDEX FIBROID TREATMENT. AMONG WOMEN WHO HAVE UNDERGONE ONE OF FOUR UTERINE-SPARING PROCEDURES (MYOMECTOMY, EA, UAE AND RFA), VALIDATED QUESTIONNAIRES FROM PRE-PROCEDURE WILL BE REPEATED ANNUALLY UP TO 10 YEARS POST-PROCEDURE, TO ACHIEVE THE FOLLOWING: AIM 1: COMPARE CHANGES IN FIBROID SYMPTOMS AND QUALITY OF LIFE FROM PRE-PROCEDURE UP TO 10 YEARS POST-PROCEDURE AMONG FOUR UTERINE-SPARING PROCEDURES: MYOMECTOMY, EA, UAE, AND RFA. AIM 2: COMPARE THE RATE OF AND TIME UNTIL TREATMENT FAILURE UP TO 10 YEARS AFTER THE INDEX TREATMENT AMONG PARTICIPANTS WHO HAD MYOMECTOMY, EA, UAE, AND RFA. AIM 3: IDENTIFY BASELINE FACTORS THAT PREDICT CLINICAL EFFECTIVENESS AFTER MYOMECTOMY, EA, UAE, AND RFA AND WITH PATIENT AND PROVIDER INPUT, CREATE A CLINICAL PREDICTION TOOL (FIBROID TREATMENT CALCULATOR) THAT SUPPORTS INFORMED DECISION-MAKING. OUR PRELIMINARY DATA DEMONSTRATE ONGOING ACTIVE ENGAGEMENT OF THESE PARTICIPANTS. THIS PROJECT IS A TIME-LIMITED OPPORTUNITY THAT USES TWO WELL-DESIGNED LONGITUDINAL COHORTS WITH COMPREHENSIVE BASELINE INFORMATION COLLECTED WITH VALIDATED QUESTIONNAIRES AND WILL YIELD RESULTS FOR IMMEDIATE APPLICATION IN CLINICAL CARE.

EXOSOMES AND PLATINUM-INDUCED PERIPHERAL NEUROPATHY

SLEEP TO REDUCE INCIDENT DEPRESSION EFFECTIVELY (STRIDE)

SKIN BARRIER ADAPTATION - ABSTRACT THE EPIDERMIS PROVIDES SKIN BARRIER FUNCTION AGAINST THE HARSH EXTERNAL ENVIRONMENT AND IS THE PRIMARY SITE OF VITAMIN D PRODUCTION. DEFICIENCIES IN EPIDERMAL KERATINOCYTE FUNCTION LEAD TO INCREASED RISKS FOR SKIN INFECTION AND INFLAMMATION. THE EXPRESSION OF GENES ENCODED WITHIN THE EPIDERMAL DIFFERENTIATION COMPLEX (EDC) LOCUS IS CRITICAL FOR EPIDERMAL FUNCTION THAT MUST ADAPT TO DIFFERENT ENVIRONMENTS TO FURTHER ENSURE SURVIVAL. WE DISCOVERED RECENT EVOLUTION IN THE HUMAN EPIDERMIS. WE REPORT A RECENT SELECTIVE SWEEP FOR INCREASED INVOLUCRIN (IVL) EXPRESSION IN THE EPIDERMIS OF INDIVIDUALS FROM EUROPEAN POPULATIONS IN CONTRAST TO AFRICAN POPULATIONS. OUR FINDING REVEALS FUNCTIONAL DIVERSITY AND ADAPTATION IN THE HUMAN EPIDERMIS ASSOCIATED WITH HUMAN MIGRATION OUT OF AFRICA. YET THE MECHANISMS FOR INVOLUCRIN DOSAGE AND THE FUNCTIONAL IMPACT FOR ADAPTIVE EPIDERMAL FUNCTION ARE NOT KNOWN. HERE WE AIM TO RIGOROUSLY UNDERSTAND THE MECHANISMS BY WHICH IVL MODULATES VITAMIN D RECEPTOR (VDR) FUNCTION IN THE EPIDERMIS, AN EMERGING PARADIGM BASED ON OUR IN VIVO MOUSE AND HUMAN POPULATION STUDIES. IVL KNOCKOUT (IVL-/-) MICE EXPRESS LOWER LEVELS OF VITAMIN D RECEPTOR EXPRESSION IN THE EPIDERMIS RESULTING IN DECREASED LIGAND-BOUND VITAMIN D RECEPTOR SIGNALING AND DAMPENED TSLP-MEDIATED INFLAMMATION. THIS NEWLY DISCOVERED PHENOTYPE FOR IVL-/- MICE HIGHLIGHTS A FUNCTIONAL ROLE FOR IVL TO MODULATE VDR SIGNALING FOR EPIDERMAL IMMUNE CROSSTALK IN CONTRAST TO PREVIOUS WORK THAT FOUND INVOLUCRIN TO BE DISPENSABLE FOR SKIN BARRIER DEVELOPMENT. THIS FINDING IS SIGNIFICANT AS IVL AND VDR ARE BOTH INCREASED IN THE EPIDERMIS OF INDIVIDUALS OF EUROPEAN ANCESTRY IN CONTRAST TO RELATIVELY DECREASED IVL AND VDR EXPRESSION IN THE EPIDERMIS OF INDIVIDUALS OF AFRICAN ANCESTRY. TOGETHER, OUR DISCOVERIES IN MICE AND HUMAN REVEAL A FUNCTIONAL REGULATORY AXIS FOR IVL/VDR THAT UNDERLIES THE EVOLUTIONARY SELECTION AND DIVERSITY OF THE HUMAN EPIDERMIS. WE WILL TEST THE FOLLOWING OVERARCHING HYPOTHESIS IN THIS STUDY. INVOLUCRIN MODULATES VITAMIN D RECEPTOR FUNCTION AND EPIDERMAL CROSSTALK FOR ADAPTIVE EPIDERMAL FUNCTION THAT UNDERLIES HUMAN SKIN DIVERSITY AND EVOLUTION. WE WILL TEST THIS HYPOTHESIS IN THE FOLLOWING SPECIFIC AIMS. AIM 1. IDENTIFY THE REGULATORY MECHANISMS FOR INCREASED IVL. AIM 2. IDENTIFY THE MECHANISMS FOR INVOLUCRIN-MEDIATED REGULATION OF VITAMIN D RECEPTOR. AIM 3. IDENTIFY THE INVOLUCRIN PATHWAY FOR ADAPTIVE EPIDERMAL IMMUNE CROSSTALK. COMPLETION OF THE AIMS WILL GENERATE NEW KNOWLEDGE FOR IVL/VDR AXIS FUNCTION THAT UNDERLIES HUMAN SKIN DIVERSITY AND EVOLUTION. THIS KNOWLEDGE WILL FACILITATE PRECISION MEDICINE INITIATIVES DESIGNED FOR POPULATION-SPECIFIC SKIN AND CRITICAL FOR ACHIEVING GLOBAL SKIN HEALTH.

EPIDEMIOLOGY OF ALLERGIC DISEASE ENDOTYPES

DETERMINING THE MECHANISMS BY WHICH CALORIE RESTRICTION ALTERS MACROPHAGE POLARIZATION TO PROMOTE AN ANTI-TUMOR ENVIRONMENT IN EPITHELIAL OVARIAN CANCER

DECISION SUPPORT SYSTEM FOR TEMPORAL LOBE EPILEPSY

EPIDEMIOLOGY OF MULTIMORBID PEDIATRIC ATOPIC AND AIRWAY DISEASES AND THE IMPACT OF PRENATAL MATERNAL ENVIRONMENTAL EXPOSURES AND PLACENTAL EPIGENETICS - PROJECT SUMMARY WE PROPOSE TO CONTINUE TO FOLLOW THE RACIALLY AND SOCIOECONOMICALLY DIVERSE HENRY FORD HEALTH (HFH) CHILDHOOD ALLERGY AND THE NEONATAL ENVIRONMENT (CANOE) COHORT. THE INVESTIGATIVE TEAM HAS SPECIFIC INTEREST IN THE PREVENTION OF ATOPIC DISEASES – INCLUDING ATOPIC DERMATITIS (AD), FOOD ALLERGY, ASTHMA AND ALLERGIC RHINITIS – WHICH POSE A SIGNIFICANT SOCIAL, FINANCIAL, AND DEVELOPMENTAL BURDEN FOR CHILDREN AND ARE A PRIORITY FOR THE ECHO PROGRAM. THE INCIDENCE RATES AND FUNDAMENTAL DESCRIPTIVE EPIDEMIOLOGY TRENDS OF ATOPIC MULTIMORBIDITY FOR CHILDREN IN THE US ARE UNKNOWN, ALTHOUGH THE CO-EXISTENCE OF MULTIPLE ATOPIC DISORDERS CONTRIBUTES TO A SIGNIFICANT DETRIMENT IN HEALTH AND DEVELOPMENT, INCLUDING NEUROCOGNITIVE DEFICITS AND POOR GROWTH. CLINICAL PRACTICE ALSO LACKS AN EARLY BIOMARKER TO IDENTIFY THE CHILDREN WITH ATOPIC MULTIMORBIDITY PHENOTYPES, INCLUDING THOSE WITH AD, FOOD ALLERGY, AND ASTHMA WITH OR WITHOUT ALLERGIC RHINITIS (REFERRED TO HEREIN AS SEVERE ATOPIC MULTIMORBIDITY [SAMM]). ENVIRONMENTAL FACTORS MAY IMPACT RISK OF ATOPY, AND DNA METHYLATION (DNAM) IS INFLUENCED BY ENVIRONMENTAL FACTORS AND CAN PROMOTE IMMUNE PATHWAYS TOWARDS AN ALLERGIC PHENOTYPE THROUGH GENE REGULATION. LIMITED INVESTIGATIONS HAVE BEEN DONE ON PLACENTAL DNAM, A BIOLOGICALLY RELEVANT TISSUE FOR ASSESSING PRENATAL EXPOSURES THAT MAY INFLUENCE RISK OF ATOPY AND ACT AS AN EARLY BIOMARKER OF SAMM RISK. WE HYPOTHESIZE THAT THE INCIDENCE RATES OF SAMM VARY BASED ON DEMOGRAPHIC FACTORS. WE ALSO HYPOTHESIZE THAT INFANTS AT RISK OF SAMM HAVE DIFFERENTIAL PLACENTAL DNAM THAT MAY BE INFLUENCED BY ENVIRONMENTAL FACTORS. THE SPECIFIC AIMS FOR THIS PROPOSAL ARE TO: (1) DETERMINE ECHO-WIDE INCIDENCE RATES AND PREVALENCE OVER TIME OF SEVERE ATOPIC MULTIMORBIDITY (SAMM) EVIDENT BY THE AGE OF 6 YEARS BY DEMOGRAPHIC FACTORS INCLUDING AGE, SEX, RACE/ETHNICITY, AND GEOGRAPHY; (2) DETERMINE WHETHER PLACENTAL DNAM ALTERATIONS DIFFERENTIATE CHILDREN WITH SAMM AND IF THEY ARE INFLUENCED BY PRENATAL ENVIRONMENTAL EXPOSURES; AND (3) UTILIZE COMMUNITY HEALTH WORKERS AND DIVERSITY, EQUITY, AND INCLUSION PRINCIPLES TO CONNECT AND ENGAGE WITH STUDY PARTICIPANTS TO ENHANCE AND COMPLETE ECHO STUDY ACTIVITIES AND PROTOCOLS FOR AN ADDITIONAL 7 YEARS; AND UTILIZE PARTICIPANT ADVISORS TO AMPLIFY THE VOICES OF PARTICIPANTS AND OVERCOME CHALLENGES WITH ENGAGEMENT AND RETENTION. THE DATA GENERATED BY THIS PROPOSAL, COMBINED WITH ECHO-WIDE DATA, WILL ALLOW FOR ACCURATE ESTIMATES OF INCIDENCE RATES OF CO-MORBID ATOPIC DISEASE PHENOTYPES AND IS AN IMPORTANT STEP TOWARD UNDERSTANDING HOW THE PLACENTA MAY INFLUENCE ALLERGIC DISEASE RISK. MOST IMPORTANTLY, THE DATA AND BIOSPECIMENS THAT WILL BE GENERATED BY THIS COHORT AS IT AGES FROM BIRTH THROUGH MIDDLE CHILDHOOD WILL BE A FUNDAMENTAL ASSET FOR THE ECHO RESEARCH PLATFORM AS NUMEROUS INVESTIGATORS ALL OVER THE COUNTRY UTILIZE THESE DATA TO ADDRESS CHILD HEALTH AND DISEASE FOR YEARS TO COME. CONTINUED FOLLOW-UP OF THE HFH CANOE COHORT WILL ALLOW FOR SOLUTION-ORIENTED INVESTIGATIONS INTO CAUSES AND CONTRIBUTORS TO HEALTH AND DISEASE.

ROLES OF HDAC3 IN EPIDERMAL LANGERHANS CELL ONTOGENY AND FUNCTION

ENDOGENOUS METABOLITE RESTRICTS GM-CSF SIGNALING PATHWAY IN PATHOGENIC MACROPHAGES TO AMELIORATE CNS AUTOIMMUNITY

EXOSOME-BASED THERAPEUTICS IN TRAUMATIC BRAIN INJURY

TREATMENT OF TRAUMATIC BRAIN INJURY WITH VEPOLOXAMER

COMBINATION TREATMENT WITH VEPOLOXAMER AND TPA FOR ACUTE STROKE

SCHWANN CELL DERIVED EXOSOMES IMPROVE DIABETIC PERIPHERAL NEUROPATHY IN TYPE II DIABETIC MICE

MICRORNAS REGULATE SKIN LANGERHANS CELLS

MODIFYING THE MECHANOTRANSDUCTION OF BONE BY TARGETING PURINERGIC RECEPTORS

LONGITUDINAL STUDY OF PREDISOPOSITION AND LIFE EVENTS IN TRIGGERING INSOMNIA

ABCA1 REGULATES WHITE MATTER REMODELING AND OLIGODENDROGENESIS AFTER STROKE

MIR-17-92 EXOSOME TREATMENT OF STROKE

NEURORESTORATIVE THERAPY OF STROKE WITH HUCBC IN TYPE TWO DIABETIC MICE

AC-SDKP FOR TREATMENT OF ACUTE STROKE

MICRORNAS AND NEUROGENESIS AFTER STROKE

TPA WHITE MATTER AND CELL THERAPY FOR STROKE

SBI-TECH MICHIGAN: OPTIMIZING SBI IMPLEMENTATION FOR HIGH-RISK ALCOHOL USE AMONG WOMEN OF CHILDBEARING AGE

MRI BIOMARKERS OF RESPONSE IN CEREBRAL TUMORS

USE OF IPSC TO DEFINE ROLE OF ASTROCYTES IN SPECIFYING RISK FOR ONSET OF CEREBRAL ADRENOLEUKODYSTROPHY - PROJECT SUMMARY/ABSTRACT THE MECHANISM OF DISEASE PROGRESSION FROM BENIGN TO FATAL PHENOTYPES IN X-LINKED ADRENOLEUKODYSTRO- PHY REMAINS UNKNOWN AND THERE IS NO SATISFACTORY CURE FOR THE DISEASE. 60% OF MALE X-ALD PATIENTS DEVELOP FATAL CEREBRAL DISEASE (CALD) WHILE THE REMAINING 40% DEVELOP MILDER ADRENOMYELONEUROPATHY (AMN) CHARAC- TERIZED BY AXONOPATHY. THE PRIMARY GENETIC DEFECT IN X-ALD (MUTATION/DELETION IN ABCD1 GENE) AND THE BIO- CHEMICAL DEFECT (ACCUMULATION OF VERY LONG CHAIN FATTY ACID; C>22:0 IN PLASMA AND TISSUES) CANNOT PREDICT THE ONSET OF AMN OR CALD. THE LONG-TERM GOAL IS TO CONTRIBUTE TO THE DEVELOPMENT OF NOVEL CLINICALLY USEFUL, MECHA- NISM-BASED PROGNOSTIC INDICATORS AND THERAPEUTIC OPTIONS FOR X-ALD. THE OVERALL OBJECTIVE FOR THIS APPLICATION IS TO DETERMINE DIFFERENTIAL METABOLIC ENERGY METABOLISM UNDERLYING PHENOTYPE VARIABILITY (AMN VS CALD) IN THE HUMAN ASTROCYTES OF MALE X-ALD PHENOTYPES. THE CENTRAL HYPOTHESIS IS THAT ALTERED METABOLIC REPROGRAMMING UNDERLIES THE DIFFERENTIAL PHENOTYPE DEVELOPMENT IN AMN AND CALD ASTROCYTES. THESE ASTROCYTES WERE DIFFEREN- TIATED FROM INDUCED PLURIPOTENT STEM CELLS (IPSCS), WHICH, IN TURN, WERE GENERATED BY REPROGRAMMING OF HUMAN CONTROL, AMN AND CALD PATIENT-DERIVED FIBROBLASTS. THIS HYPOTHESIS IS SUPPORTED BY UNTARGETED METABOLOMICS PILOT DATA IDENTIFYING METABOLITES ALTERED BETWEEN HEALTHY-CONTROL AND CALD PHENOTYPE POSTMORTEM BRAIN AND BETWEEN AMN AND CALD ASTROCYTES. WITHIN THE CALD BRAIN WHITE MATTER, UNIQUE METABOLITE CHANGES WERE REC- ORDED BETWEEN DISTANT NORMAL LOOKING AREAS AND AREAS ADJACENT TO THE PLAQUE SUGGESTING AN ASSOCIATION WITH DISEASE PROGRESSION. OXPHOS AND GLYCOLYSIS WERE FOUND TO BE DECREASED (LOW METABOLIC STATE) IN HUMAN CALD ASTROCYTES. THIS LOW METABOLIC STATE SUGGESTS A ROLE FOR NOVEL ALTERNATIVE SOURCE(S) OF FUEL DRIVING THE PROGRESSION TO CALD PHENOTYPE IN ASTROCYTES. THE RATIONALE FOR THE PROPOSED RESEARCH IS THAT A MECHANISTIC MODELLING OF ABERRANT ENERGY METABOLISM IN AMN AND CALD ASTROCYTES WILL PROVIDE A BASIS FOR PREDICTING DISEASE PROGRESSION AND NEW OPPORTUNITIES FOR IDENTIFICATION OF TARGETS FOR NOVEL THERAPEUTIC DRUG DESIGN. THE CENTRAL HYPOTHESIS WILL BE TESTED BY PURSUING TWO SPECIFIC AIMS: 1) DETERMINE THE ROLE OF METABOLIC REPROGRAMMING IN NEWLY “FORGED” AMN AND CALD ASTROCYTES; AND 2) DETERMINE THE CONTRIBUTION OF MITOCHONDRIAL DYSFUNCTION IN METABOLIC REPRO- GRAMMING IN AMN AND CALD ASTROCYTES. THE APPROACH WILL TAKE ADVANTAGE OF CONTROL, AMN AND CALD ASTROCYTES RECENTLY GENERATED FROM IPSCS IN THE LABORATORY. THIS PROPOSAL IS INNOVATIVE BECAUSE IT DEPARTS FROM THE STATUS QUO BY IDENTIFYING FOR THE FIRST TIME, METABOLIC PATHWAYS DIFFERENTIALLY ALTERED IN HUMAN AMN AND CALD ASTROCYTES. THE PROPOSED RESEARCH IS SIGNIFICANT BECAUSE THE CELLULAR MECHANISM(S) THAT LEAD TO LESS SEVERE AMN OR FATAL CALD PHENOTYPE IN RESPONSE TO SAME ABCD1 MUTATION REMAIN UNKNOWN EVEN FOUR DECADES AFTER THE IDENTIFICA- TION OF GENE DEFECT IN X-ALD. SUCCESSFUL COMPLETION OF THE PROPOSED RESEARCH IS EXPECTED TO PROVIDE A NECESSARY CONCEPTUAL FRAMEWORK FOR THE SUBSEQUENT DEVELOPMENT OF CLINICALLY EFFECTIVE STRATEGIES FOR PREDICTING DISEASE PROGRESSION AND IMPROVING CURRENT LIMITED TREATMENT OPTIONS.

MSCS INDUCE BRAIN PLASTICITY VIA TPA

EARLY ENVIRONMENTAL HYGIENE AND PEDIATRIC ASTHMA

GENE THERAPY AND RADIATION THERAPY FOR PROSTATE CANCER

ADAM 17 AND GLIOMA-TUMOR PROGRESSION AND TREATMENT

TO QUANTIFY DEFORMABLE IMAGE REGISTRATION ERRORS IN IGRT

NEURORESTORATIVE THERAPY OF STROKE WITH AGENTS THAT INCREASE HDL

TREATMENT OF STROKE WITH A CLINICALLY APPROVED PROTEASOME INHIBITOR

A TAILORED ASTHMA EDUCATION PROGRAM FOR URBAN TEENS II

EMBEDDED MENTAL HEALTH SERVICES POSTDOCTORAL RESEARCH TRAINING IN HEALTH SYSTEMS - PROJECT SUMMARY THIS APPLICATION ESTABLISHES A NEW T32 TRAINING PROGRAM IN EMBEDDED MENTAL HEALTH SERVICES RESEARCH IN HEALTH SYSTEMS LEVERAGING THE RESOURCES OF THE NIMH-FUNDED MENTAL HEALTH RESEARCH NETWORK (MHRN). MHRN IS A CONSORTIUM OF 21 HEALTH SYSTEMS ACROSS 16 US STATES SERVING MORE THAN 30 MILLION PATIENTS PER YEAR. ESTABLISHED IN 2010, THE NETWORK PROVIDES UNIQUE DATA INFRASTRUCTURE VIA A COMMON DATA MODEL, INCLUDING ALL ELECTRONIC HEALTH RECORDS, INSURANCE CLAIMS AND ADMINISTRATIVE RECORDS ORGANIZED USING THE SAME VARIABLES AND DATA DEFINITIONS ACROSS SITES ENHANCING EFFICIENT MENTAL HEALTH SERVICES RESEARCH. IMPORTANTLY, EACH OF THE MHRN HEALTH SYSTEMS INCLUDES EMBEDDED RESEARCH CENTERS WITH EXPERIENCED MENTAL HEALTH SERVICES RESEARCHERS WITH LONG HISTORIES OF NIMH FUNDING. MHRN IS A PRACTICE-BASED RESEARCH NETWORK LEVERAGING CLOSE RELATIONSHIPS BETWEEN THESE EMBEDDED SCIENTISTS AND HEALTH SYSTEM LEADERS, CLINICIANS, AND PATIENTS TO FACILITATE AN ITERATIVE RESEARCH-PRACTICE-POLICY ECOSYSTEM FOCUSED ON STUDYING KEY MENTAL HEALTH CLINICAL AND RESEARCH QUESTIONS. THIS STRONG RELATIONSHIP DRIVES MENTAL HEALTH CARE TRANSFORMATION. THE PROPOSED PROGRAM WILL INCLUDE 2 MHRN HEALTH SYSTEMS SERVING AS POSTDOCTORAL TRAINING HOST SITES, HENRY FORD HEALTH SYSTEM (MICHIGAN) AND KAISER PERMANENTE NORTHERN CALIFORNIA, AND PROVIDE ACCESS, DATA, AND RESOURCES ACROSS ALL MHRN SITES. THIS T32 WILL SUPPORT 10 TOTAL POSTDOCTORAL FELLOWS FOR 2-YEAR TRAINING PROGRAMS DURING THE 5-YEAR AWARD PERIOD. THE PROGRAM WILL USE A NOVEL TRAINING APPROACH WITH VIRTUAL AND IN- PERSON TRAINING AND MENTORSHIP EMBEDDED WITHIN THE ESTABLISHED INFRASTRUCTURE ACROSS THE ENTIRE MHRN. THE PROGRAM WILL INTEGRATE AN EXTERNAL UNIVERSITY-BASED FACULTY ADVISORY COMMITTEE AND ADDITIONAL EXTERNAL SENIOR SCHOLARS. THE PROGRAM IS INTERDISCIPLINARY AND EXPECTS TO RECRUIT DOCTORAL-LEVEL TRAINEES FROM MANY DISCIPLINES. THE CORE TRAINING AND MENTORSHIP MODEL WILL INCLUDE THE FOLLOWING AIMS FOR ALL POSTDOCTORAL TRAINEES: 1) DIDACTIC TRAINING IN HEALTH SERVICES RESEARCH METHODS AND MENTAL HEALTH DISORDERS ETIOLOGY, PREVENTION, AND TREATMENT TAILORED FOR EMBEDDED HEALTH SYSTEM RESEARCH SETTINGS, 2) INDIVIDUALIZED TRAINING AND MENTORSHIP IN GRANT WRITING, DISSEMINATION, PROJECT MANAGEMENT AND LEADERSHIP, PROFESSIONAL DEVELOPMENT, AND MULTI-SITE STUDY COLLABORATION AND COORDINATION, AND 3) PARTICIPATION IN ALL APPLICABLE MHRN HEALTH SYSTEM ACTIVITIES. OUR LONG- TERM GOAL IS PRODUCING INDEPENDENT SCIENTISTS, WHO CAN ENGAGE IN PRACTICE-BASED RESEARCH THROUGH THE PURSUIT OF EARLY CAREER FUNDING OPPORTUNITIES FOR MENTAL HEALTH SERVICES RESEARCH.

NEUROENDOCRINE DIFFERENTIATION POST ANTI-ANDROGENIC THERAPY: ROLE OF TRIBBLES 2 - ANTI-ANDROGENIC THERAPY IS THE MAINSTAY FOR BOTH PRIMARY AND DISSEMINATED FORMS OF PROSTATE CANCER. FDA- APPROVED ENZALUTAMIDE (XTANDI) IS AT THE FOREFRONT OF ANTI-ANDROGENS WITH SUPERIOR PATIENT PROFILE AND IS THE ONE MOST PRESCRIBED. HOWEVER, ENZALUTAMIDE RESISTANT PROSTATE CANCER (ERPC) INVARIABLY DEVELOPS, WHICH IS INCURABLE AND RESPONSIBLE FOR MOST OF THE PROSTATE CANCER-RELATED DEATHS, UNDERSCORING THAT MANAGEMENT OF ERPC IS AN UNMET AND URGENT MEDICAL NEED. DEVELOPMENT OF AN EFFECTIVE THERAPY AGAINST ERPC IS SUFFERING FROM LACK OF PROPER UNDERSTANDING ABOUT CRITICAL MOLECULAR TARGETS TO EFFECTIVELY KILL ERPC CELLS. TO IDENTIFY POTENTIAL NEW TARGETS, WE DEVELOPED AN ERPC MODEL WHICH MIMICS THE CLINICAL CONDITIONS IN PATIENTS UNDERGOING STANDARD ENZALUTAMIDE THERAPY. WE TREATED ANDROGEN-SENSITIVE PROSTATE CANCER CELLS WITH ENZALUTAMIDE IN LONG- TERM CULTURE TO GENERATE CELL LINES (LNCAP-ENR, PCA-2B-ENR) WHICH ARE NO LONGER SENSITIVE TO CLINICALLY RELEVANT DOSES OF ENZALUTAMIDE. COMPREHENSIVE GENE EXPRESSION ANALYSIS REVEALED THAT THE ERPC CELLS OVEREXPRESS TRIBBLES 2 (TRIB2), A MEMBER OF THE TRIBBLES PSEUDOKINASE FAMILY. OVEREXPRESSION OF TRIB2 WAS ALSO FOUND IN PDX AND PATIENT PROSTATE TUMORS AFTER ENZALUTAMIDE TREATMENT. FORCED OVEREXPRESSION TRIB2 RESULTS IN ENHANCED PROSTATE CANCER CELL GROWTH AND RESISTANCE TO ENZALUTAMIDE, APALUTAMIDE, DAROLUTAMIDE AND ABIRATERONE. INHIBITION OF TRIB2 RE-SENSITIZES RESISTANT CELLS TO ENZALUTAMIDE AND DECREASES THEIR VIABILITY, INDICATING A POSSIBLE DIRECT LINK BETWEEN TRIB2 AND DEVELOPMENT OF ENZALUTAMIDE RESISTANCE. INTERESTINGLY, TRIB2 DOWNREGULATES RB1 AND P53, WHILE INDUCES THE NEURONAL TRANSCRIPTION FACTORS (N-MYC, BRN2) AND THE NEUROENDOCRINE (NE) MARKERS (CHROMOGRANIN A, NEURON-SPECIFIC ENOLASE AND SYNAPTOPHYSIN). INHIBITION OF N-MYC OR BRN2 RE-SENSITIZES RESISTANT CELLS TO ENZALUTAMIDE. THESE FINDINGS SUGGEST THAT TRIB2 DRIVES CELLULAR TRANS-DIFFERENTIATION FROM LUMINAL TO NE PHENOTYPE TO POSE RESISTANCE TO ANTI-ANDROGENS. THUS, TRIB2 EMERGES AS A NOVEL, PROMISING MOLECULAR TARGET FOR THERAPY OF ERPC-NE. HOWEVER, THE MECHANISM AND ROLE OF TRIB2 IN NE DIFFERENTIATION NEEDS TO BE DETERMINED USING APPROPRIATE IN VITRO AND IN VIVO MODELS. THUS, THIS PROPOSAL HAS BEEN DESIGNED WHICH WILL CHARACTERIZE HOW TRIB2 INDUCES NE DIFFERENTIATION (AIM 1), DETERMINE THE IMPACT OF TRIB2 INHIBITION IN ENHANCED ERPC TUMOR GROWTH AND DISTANT METASTASIS (AIM 2), AND TEST THE IMPACT OF TRIB2 GENE-TARGETING ON PROSTATE TUMOR PROGRESSION AND NE DIFFERENTIATION USING TRANSGENIC TRIB2 KNOCKOUT MOUSE MODELS (AIM 3). ACCOMPLISHING THESE GOALS WILL ESTABLISH TRIB2 AS A MOLECULAR DRIVER FOR TREATMENT-INDUCED NE DIFFERENTIATION AND WILL HELP DEVELOP A NEW TARGETED THERAPEUTIC STRATEGY FOR ENZALUTAMIDE RESISTANT, NE TYPE, LETHAL PROSTATE CANCER.

MOLECULAR GENE AND RADIATION THERAPIES FOR CANCER

CHRONIC HEPATITIS COHORT STUDY?II (CHECS?II)

TREATMENT OF GLIOMA WITH NANOCOMBRETASTATIN WITH MRI MONITORING

TRANSLATIONAL STUDY OF MIR-146A GENE THERAPY FOR DIABETIC PERIPHERAL NEUROPATHY

CLINICAL ASSESSMENT OF VERTEBRAL BONE QUALITY USING DIRECT BIOMECHANICAL AND TEXTURAL ANALYSIS VIA DIGITAL TOMOSYNTHESIS

REGULATION OF THE RENAL MICROCIRCULATION BY THE CONNECTING TUBULE

THYMOSIN BETA4 PROMOTES THE RECOVERY OF PERIPHERAL NEUROPATHY IN TYPE II DIABETIC

SYSTEMS CHANGE FOR EQUITABLE OUTCOMES - DRUG FREE JACKSON, SYSTEMS CHANGE FOR EQUITABLE OUTCOMES. THE SYSTEMS CHANGE FOR EQUITABLE OUTCOMES PROJECT AIMS TO IMPROVE EQUITABLE OUTCOMES IN SUBSTANCE ABUSE PREVENTION AND SUD TREATMENT AND RECOVERY IN JACKSON COUNTY, MICHIGAN. THE INFRASTRUCTURE DEVELOPMENT IN THIS PROJECT WILL PRIMARILY IMPACT YOUTH IN PUBLIC SCHOOLS IN GRADES 3-5 AND AFRICAN AMERICAN ADULTS LIVING IN THE CITY OF JACKSON. GAPS IN PREVENTION AND TREATMENT SERVICES AND FAILURE OF SYSTEMS TO ADDRESS ROOT CAUSES OF YOUTH AND ADULT SUBSTANCE USE AND MISUSE IN JACKSON COUNTY ARE PRODUCING DISPARITIES AND SUB-OPTIMAL POPULATION OUTCOMES. THE OPPORTUNITY GAP BEGINS EARLY AND IS COMPOUNDED OVER TIME BY POLICIES, PROGRAMS, AND SERVICES THAT DO NOT MEET THE NEEDS OF THOSE THEY ARE DESIGNED TO SERVE. FUNDING WILL BE USED TO INCREASE CAPACITY TO ASSESS AND TRACK POPULATION LEVEL RISK AND PROTECTIVE FACTORS IN JACKSON COUNTY ELEMENTARY SCHOOLS AND BUILD RELATIONSHIPS AND TRUST BETWEEN BLACK RESIDENTS OF THE CITY OF JACKSON AND MEDICAL, TREATMENT AND RECOVERY PROVIDERS. ADDITIONALLY THE PROJECT WILL INCREASE THE NUMBER OF SCHOOLS AND PROVIDERS WITH HUMAN-CENTERED, CULTURALLY INFORMED POLICIES AND PRACTICES BY PROVIDING TARGETED COACHING AND TECHNICAL ASSISTANCE. OUTCOMES TRACKED WILL INCLUDE NUMBER OF SCHOOLS ADMINISTERING THE DEVELOPMENTAL ASSETS SURVEY, USE OF THE HUMAN-CENTERED DESIGN MODEL TO CO-DESIGN IMPROVEMENTS IN SERVICE PROVISION, INCREASE IN ACCESS TO MEDICATION ASSISTED TREATMENT, IMPROVED YOUTH PERCEPTION OF RISK OF SUBSTANCES AND IMPROVED RATES OF YOUTH SUBSTANCE USE.

PDE5 IS A THERAPEUTIC TARGET FOR PERIPHERAL NEUROPATHY IN DIABETIC MICE

IMAGING CELL BASED TREATMENT OF TRAUMATIC BRAIN INJURY

PATHOGENESIS OF ATYPICAL FEMUR FRACTURES ON LONG TERM BISPHOSPHONATE THERAPY

SEMANTIC DATA CAPTURE INITIATIVE

MECHANISMS OF TRITERPENOIDS IN PREVENTION OF PROSTATE CANCER

EARLY LIFE VITAMIN D, RACIAL DISPARITIES, AND WHEEZING

EXOSOME TRANSFER OF MIR-133B MEDIATES MSC INDUCED NEUROLOGICAL RECOVERY AFTER STR

COMMUNITY PROJECT FUNDING/CONGRESSIONALLY DIRECTED SPENDING - CONSTRUCTION - HENRY FORD WEST BLOOMFIELD HOSPITAL IS UPGRADING OUR CARDIAC CATHETERIZATION LABORATORY (CARDIAC CATH LAB) TECHNOLOGY TO IMPROVE THE HEART HEALTH OF OUR COMMUNITY. WE PROVIDE LIFESAVING TREATMENTS TO OUR PATIENTS THROUGH TWO CARDIAC CATH LABS, WHICH HAVE SOPHISTICATED EQUIPMENT THAT ALLOWS OUR EXPERTS TO ACCESS THE HEART AND SURROUNDING STRUCTURES USING MINIMALLY INVASIVE TECHNIQUES. WE KNOW THAT HEART DISEASE IS THE LEADING CAUSE OF DEATH IN THE UNITED STATES, CONTRIBUTING TO MORE THAN 650,000 DEATHS EACH YEAR. IT IS ALSO THE LEADING CAUSE OF DEATH IN THE STATE OF MICHIGAN. IT IS ESPECIALLY PREVALENT AMONG OLDER ADULTS AND THOSE WITH CERTAIN RISK FACTORS, SUCH AS HIGH BLOOD PRESSURE, HIGH CHOLESTEROL, AND SMOKING. HEART DISEASE IS THE LEADING CAUSE OF DEATH FOR MEN, WOMEN, AND PEOPLE OF MOST RACIAL AND ETHNIC GROUPS IN THE UNITED STATES. THAT IS WHY WE ARE UPGRADING OUR CARDIAC CATH LAB TECHNOLOGY. IT WILL IMPROVE PATIENT AND PROVIDER SAFETY BY ENHANCING IMAGING QUALITY TO BETTER VISUALIZE STRUCTURES WITHIN THE HEART. IT WILL ALSO EXPAND THE HOSPITAL CARDIOLOGY TEAM’S ABILITY TO PERFORM NEW AND MORE COMPLEX PROCEDURES, INCLUDING ADDITIONAL WAYS TO CLEAR ARTERIES, REMOVE BLOOD CLOTS, AND IMPROVE BLOOD FLOW WHEN INDIVIDUALS ARE IN PAIN OR EXPERIENCING LIFE-THREATENING CONDITIONS. THIS SERVICE EXPANSION WILL ALLOW PATIENTS TO RECEIVE NEEDED CARE CLOSER TO HOME WITHOUT TRANSFERRING TO ANOTHER FACILITY. AND AS A REFERRAL CENTER, WE SEE PATIENTS FROM ALL OVER THE MIDWEST WHO CAN BENEFIT FROM THESE IMPROVEMENTS. THE FEDERAL FUNDS WILL SUPPORT THE PURCHASE OF NEW EQUIPMENT AND ITS INSTALLATION, SO THAT OUR TEAMS CAN PROVIDE STATE-OF-THE-ART CARDIOLOGY SERVICES.

4-HYDROXY-2-NONENAL IN MITOCHONDRIAL DNA DAMAGE AND CONTRACTILE DYSFUNCTION IN DIABETIC HEART: A ROLE FOR ALDEHYDE DEHYDROGENASE 2

SONOGRAPHIC ASTRONAUT VERTEBRAL EXAMINATION (SAVE) THIS PROPOSAL RESPONDS TO NRA NNJ09ZSA002N AND TEAMS WORLD EXPERTS IN MUSCULOSKELETAL (MSK) ULTRAS

TREATMENT OF 'TRAUMATIC BRAIN INJURY WITH ERYTHROPOIETIN

TRIBBLES 2, A NOVEL TARGET FOR THERAPY OF ENZALUTAMIDE-RESISTANT NEUROENDOCRINE PROSTATE CANCER

COTARGETING TELOMERE INTEGRITY AND REPAIR OF TELOMERE DAMAGE FOR CRPC THERAPY

EPIDEMIOLOGY OF MULTIMORBID PEDIATRIC ATOPIC AND AIRWAY DISEASES AND THE IMPACT OF PRENATAL MATERNAL ENVIRONMENTAL EXPOSURES AND PLACENTAL EPIGENETICS - WE PROPOSE TO CONTINUE TO FOLLOW THE HENRY FORD HEALTH (HFH) CHILDHOOD ALLERGY AND THE NEONATAL ENVIRONMENT (CANOE) COHORT. THE INVESTIGATIVE TEAM HAS SPECIFIC INTEREST IN THE PREVENTION OF ATOPIC DISEASES – INCLUDING ATOPIC DERMATITIS (AD), FOOD ALLERGY, ASTHMA AND ALLERGIC RHINITIS – WHICH POSE A SIGNIFICANT SOCIAL, FINANCIAL, AND DEVELOPMENTAL BURDEN FOR CHILDREN AND ARE A PRIORITY FOR THE ECHO PROGRAM. THE INCIDENCE RATES AND DESCRIPTIVE EPIDEMIOLOGY TRENDS OF ATOPIC MULTIMORBIDITY FOR CHILDREN IN THE US ARE UNKNOWN, ALTHOUGH THE CO-EXISTENCE OF MULTIPLE ATOPIC DISORDERS CONTRIBUTES TO A SIGNIFICANT DETRIMENT IN HEALTH AND DEVELOPMENT, INCLUDING NEUROCOGNITIVE DEFICITS AND POOR GROWTH. CLINICAL PRACTICE ALSO LACKS AN EARLY BIOMARKER TO IDENTIFY THE CHILDREN WITH ATOPIC MULTIMORBIDITY PHENOTYPES, INCLUDING THOSE WITH AD, FOOD ALLERGY, AND ASTHMA WITH OR WITHOUT ALLERGIC RHINITIS (REFERRED TO HEREIN AS SEVERE ATOPIC MULTIMORBIDITY [SAMM]). ENVIRONMENTAL FACTORS MAY IMPACT RISK OF ATOPY, AND DNA METHYLATION (DNAM) IS INFLUENCED BY ENVIRONMENTAL FACTORS AND CAN PROMOTE IMMUNE PATHWAYS TOWARDS AN ALLERGIC PHENOTYPE THROUGH GENE REGULATION. LIMITED INVESTIGATIONS HAVE BEEN DONE ON PLACENTAL DNAM, A BIOLOGICALLY RELEVANT TISSUE FOR ASSESSING PRENATAL EXPOSURES THAT MAY INFLUENCE RISK OF ATOPY AND ACT AS AN EARLY BIOMARKER OF SAMM RISK. WE HYPOTHESIZE THAT THE INCIDENCE RATES OF SAMM VARY BASED ON DEMOGRAPHIC FACTORS. WE ALSO HYPOTHESIZE THAT INFANTS AT RISK OF SAMM HAVE DIFFERENTIAL PLACENTAL DNAM THAT MAY BE INFLUENCED BY ENVIRONMENTAL FACTORS. THE SPECIFIC AIMS FOR THIS PROPOSAL ARE TO: (1) DETERMINE ECHO-WIDE INCIDENCE RATES AND PREVALENCE OVER TIME OF SEVERE ATOPIC MULTIMORBIDITY (SAMM) EVIDENT BY THE AGE OF 6 YEARS BY DEMOGRAPHIC FACTORS; (2) DETERMINE WHETHER PLACENTAL DNAM ALTERATIONS DIFFERENTIATE CHILDREN WITH SAMM AND IF THEY ARE INFLUENCED BY PRENATAL ENVIRONMENTAL EXPOSURES; AND (3); UTILIZE PARTICIPANT ADVISORS AND COMMUNITY-CENTERED ACTIVITIES TO IDENTIFY BARRIERS AND OVERCOME CHALLENGES WITH ENGAGEMENT AND RETENTION ACROSS THE DURATION OF THE STUDY. THE DATA GENERATED BY THIS PROPOSAL, COMBINED WITH ECHO-WIDE DATA, WILL ALLOW FOR ACCURATE ESTIMATES OF INCIDENCE RATES OF CO-MORBID ATOPIC DISEASE PHENOTYPES AND IS AN IMPORTANT STEP TOWARD UNDERSTANDING HOW THE PLACENTA MAY INFLUENCE ALLERGIC DISEASE RISK. MOST IMPORTANTLY, THE DATA AND BIOSPECIMENS THAT WILL BE GENERATED BY THIS COHORT AS IT AGES FROM BIRTH THROUGH MIDDLE CHILDHOOD WILL BE A FUNDAMENTAL ASSET FOR THE ECHO RESEARCH PLATFORM AS NUMEROUS INVESTIGATORS ALL OVER THE COUNTRY UTILIZE THESE DATA TO ADDRESS CHILD HEALTH AND DISEASE FOR YEARS TO COME. CONTINUED FOLLOW-UP OF THE HFH CANOE COHORT WILL ALLOW FOR SOLUTION-ORIENTED INVESTIGATIONS INTO CAUSES AND CONTRIBUTORS TO HEALTH AND DISEASE.

THE CLINCAL EFFECTIVENESS OF PHARMACY ADHERENCE INFORMATION FOR DIABETES CONTROL

HYPERTENSION AND COLLAGEN: EFFECT OF AC-SDKP

TREATMENT OF STROKE IN YOUNG AND AGED RATS USING THYMOSIN BETA4

SERUM MICRORNAS AS BIOMARKERS OF POST-TRAUMATIC OSTEOARTHRITIS

REGULATION OF PROSTATE CANCER CELL SURVIVAL BY 5-LIPOXYGENASE:ROLE OF PKC-EPSILON

MAGNETIC RESONANCE IMAGING AND LABORATORY ASSESSMENT OF STROKE RECOVERY

SIMVASTATIN TREATMENT OF EXPERIMENTAL INTRACEREBRAL HEMORRHAGE

"ULTRASOUND FRACTURE DIAGNOSIS IN SPACE"CREW MEMBERS ON LONG DURATION SPACE NLISSIONS ARE AT SIGNIFICANT RISK OF DECREASED STRENGTH OF BONES DESPITE

TARGETING MITOCHONDRIAL METABOLISM IN OVARIAN CANCER

COMMUNITY PROJECT FUNDING/CONGRESSIONALLY DIRECTED SPENDING - CONSTRUCTION - HENRY FORD WYANDOTTE HOSPITAL (HFWH) IS IMPLEMENTING AN IN-HOUSE PATIENT MONITORING SYSTEM TO IMPROVE PATIENT CARE. VIRTUAL SERVICES OFFER CONVENIENT WAYS FOR OUR PATIENTS TO SECURELY CONNECT WITH HENRY FORD CLINICIANS FROM ANY LOCATION AND AT ANY TIME. WE ALREADY DELIVER VIRTUAL CARE IN A VARIETY OF WAYS, INCLUDING VIDEO VISITS, E-VISITS AND MESSAGING, MEDICAL ADVISE PHONE LINES, AND REMOTE MONITORING. THIS PILOT PROGRAM WILL PROVIDE HFWH WILL ADDITIONAL CAPABILITIES TO OFFER VIRTUAL SUPPORT FUNCTIONS WITHIN THE HOSPITAL. SPECIFICALLY, THIS NEW VIRTUAL SYSTEM WILL UTILIZE A TWO-WAY CAMERA SYSTEM TO EXPAND REMOTE PATIENT OBSERVATION FUNCTIONS AND PROVIDE OTHER VIRTUAL SERVICES. EXPANDED CAPABILITIES INCLUDE REMOTE OBSERVATION FOR PATIENTS WHO ARE AT HIGH-RISK FOR FALLS, IN NEED OF BEHAVIORAL HEALTH SERVICES, OR REQUIRE AROUND-THE CLOCK MONITORING; CENTRALIZED MEASURING AND REVIEW OF CERTAIN METRICS BY HIGHLY QUALIFIED STAFF; NURSE BEDSIDE EDUCATION SUPPORTS TO EDUCATE PATIENTS ON AFTER-HOSPITALIZATION CARE; REAL-TIME ROUNDS WITH ATTENDING PHYSICIANS; AND SOCIAL WORK AND CASE MANAGEMENT SUPPORT. THE REMOTE HUB WILL ALSO BE TIED TO HFWH’S ELECTRONIC MEDICAL RECORD TO ENSURE COMPLETE AND UNINTERRUPTED CONTINUITY OF CARE AND REAL-TIME DOCUMENTATION INTO MEDICAL RECORDS. OVER THE PAST TWO YEARS, THE COVID-19 PUBLIC HEALTH EMERGENCY HAS ACCELERATED THE NEED FOR EXPANDED TELEHEALTH SERVICES, BOTH INSIDE AND OUTSIDE THE HOSPITAL, DUE TO THE HIGH-RISK OF IN-PERSON INTERACTIONS, LIMITED AVAILABILITY OF PERSONAL PROTECTIVE EQUIPMENT, AND STAFFING SHORTAGES. THIS UPDATED TECHNOLOGY WILL ALLOW HFWH TO PROVIDE HIGHLY RELIABLE CARE IN THE SAFEST ENVIRONMENT POSSIBLE DURING THE COVID-19 PANDEMIC AND BEYOND. THE FEDERAL FUNDS WILL SUPPORT THE PURCHASE OF EQUIPMENT FOR THE VIRTUAL CARE PROGRAM, AS WELL AS THE CONSTRUCTION AND INSTALLATION OF THE EQUIPMENT.

CHARACTERIZATION OF KELOID SPECIFIC EXOSOMES AND DETERMINATION OF EXOSOMAL CRITICAL SIGNALING PATHWAYS IN THE KELOID MICROENVIRONMENT

ROLE OF ANDROGEN RECEPTOR IN TELOMERE STABILITY: A NOVEL THERAPEUTIC STRATEGY IN POTENTIATING AR-TARGETED THERAPIES FOR THE TREATMENT OF PROSTATE CAN

INVESTIGATING CELLULAR COMMUNICATION IN THE TUMOR MICROENVIRONMENT IN PANCREATIC CANCER - PROJECT SUMMARY/ABSTRACT PANCREATIC DUCTAL ADENOCARCINOMA (PDA) IS PROJECTED TO BECOME THE 2ND LEADING CAUSE OF CANCER-RELATED DEATHS WORLD-WIDE BY 2030, LARGELY DUE A LACK OF EFFECTIVE TREATMENTS. A MAJOR BARRIER TO SUCCESSFUL THERAPY IS THE ABUNDANT FIBROTIC REACTION IN PDA, WHICH INCLUDES CANCER-ASSOCIATED FIBROBLASTS (CAFS). WHILE MANY PANCREATIC TUMORS ARE HYPOVASCULARIZED, ENDOTHELIAL CELLS REGULATE IMMUNE MATURATION AND INFILTRATION, TUMOR CELL METABOLISM, AND METASTATIC DISSEMINATION. IN PDA, HEDGEHOG (HH) SIGNALING FUNCTIONS IN A PARACRINE MANNER, WHEREBY TUMOR CELLS PRODUCE HH LIGANDS AND SIGNAL TO CAFS VIA THE CANONICAL HH RECEPTOR PTCH1, LEADING TO DOWNSTREAM PATHWAY ACTIVATION. THERE HAVE BEEN CONTRADICTORY GENETIC AND PHARMACOLOGIC STUDIES IN MOUSE MODELS, AS WELL AS DISAPPOINTING CLINICAL TRIALS WITH HH PATHWAY INHIBITORS, INDICATING THE ROLE OF HH SIGNALING IN PDA IS HIGHLY COMPLEX AND CONTEXT DEPENDENT. THIS PROPOSAL AIMS TO UNCOVER TWO KEY ASPECTS OF HH SIGNALING IN PDA: A) HH-DEPENDENT ALTERATIONS IN THE IMMUNE LANDSCAPE THROUGH FIBROBLAST-IMMUNE CROSS TALK (AIM 1), AND B) HH-DEPENDENT CHANGES IN ENDOTHELIAL CELL GENE EXPRESSION AND FUNCTION THROUGH FIBROBLAST-ENDOTHELIAL CROSS TALK (AIM 2). I HYPOTHESIZE THAT COMBINED TARGETING OF HH SIGNALING IN COMBINATION WITH THE IMMUNE RESPONSE OR THE VASCULATURE WILL BE REQUIRED TO EFFECTIVELY TREAT PDA. OUR PRELIMINARY DATA INDICATE THAT SLIT2, WHICH REGULATES ANGIOGENESIS, IS REDUCED DURING HH PATHWAY INHIBITION IN PDA. PREVIOUS WORK SHOWED THAT EPITHELIAL SLIT2 DELETION PROMOTES NEURAL INVASION AND METASTASIS IN PDA. HOWEVER, I FIND THE MAJORITY OF SLIT2 IS PRODUCED BY FIBROBLASTS, WHILE ROBO RECEPTORS ARE EXPRESSED IN ENDOTHELIAL CELLS. IN AIM 3 OF THIS PROPOSAL, I WILL DETERMINE THE FIBROBLAST-SPECIFIC CONTRIBUTION OF SLIT2 TO PANCREATIC ANGIOGENESIS AND TUMOR GROWTH. OVERALL, THE PROPOSED EXPERIMENTS WILL PROVIDE A FUNDAMENTALLY NEW UNDERSTANDING OF CELLULAR CROSS TALK WITHIN THE PANCREATIC TME, INCLUDING ADDRESSING FIBROBLAST-IMMUNE AND FIBROBLAST-ENDOTHELIAL COMMUNICATION AS WELL AS A SPECIFIC INVESTIGATION OF SLIT-ROBO SIGNALING IN PANCREATIC CANCER. THE MENTORED PHASE OF THIS AWARD WILL BE OVERSEEN BY DRS. ALLEN AND PASCA DI MAGLIANO AT THE UNIVERSITY OF MICHIGAN (UM). I HAVE DEVELOPED AN ADDITIONAL ADVISORY TEAM TO INCLUDE INTERNATIONALLY KNOWN LEADERS IN THE FIELDS OF CANCER BIOLOGY (DR. ANDRZEJ DLUGOSZ), ENDOTHELIAL BIOLOGY (DR. JASON SPENCE), AND IMMUNOLOGY (DR. BETHANY MOORE). COMBINED, THIS MENTORSHIP TEAM HAS SET FORTH A CAREER DEVELOPMENT PLAN FOCUSED ON RESEARCH, COLLABORATION, PRESENTATIONS, MENTORSHIP, GRANTSMANSHIP, AND THE FURTHERING OF MANAGEMENT SKILLS REQUIRED TO SUCCESSFULLY LEAD AN INDEPENDENT RESEARCH LABORATORY.

SLEEP TO REDUCE INCIDENT DEPRESSION EFFECTIVELY (STRIDE)

THE HENRY FORD HEALTH SYSTEM: A HUB FOR THE NETT NETWORK

INTEGRATED GENOMIC BIOMARKERS TO IDENTIFY AGGRESSIVE DISEASE IN AFRICAN AMERICANS WITH PROSTATE CANCER

CLINICAL TRANSLATION OF PHENOTYPES OF SHIFT WORK DISORDER

CELLULAR MRI IN GLIOMA AND RADIATION NECROSIS

THE PRENATAL ORIGINS OF AUTISM SPECTRUM DISORDER.

SALT ABSORPTION BY THE THAL: ROLE OF NKCC2 TRAFFICKING

PHYSICIAN RECOMMENDATION AND COLORECTAL CANCER SCREENING

REGULATION OF GLIOMA CELL MIGRATION BY RASGRP3

MRI OF ACUTE VASCULAR INJURY AND HEMORRHAGIC TRANSFORMATION IN ISCHEMIC STROKE

IMPROVING NEGATIVE STRESSFUL PERSEVERATIONS IN INSOMNIA TO REVITALIZE EXPECTING MOMS (INSPIRE) - PROJECT ABSTRACT. INSOMNIA DISORDER IMPACTS ONE IN TWO WOMEN BY THE END OF THEIR 3RD TRIMESTER, AND HALF OF PREGNANT WOMEN WITH INSOMNIA ENDORSE COMORBID DEPRESSION. THOUGH COGNITIVE-BEHAVIORAL THERAPY FOR INSOMNIA (CBTI) HAS EFFICACY IN PREGNANCY, CBTI PRODUCES SMALLER EFFECTS ON INSOMNIA AND DEPRESSION AS COMPARED TO NON-PERINATAL PATIENTS. OUR TEAM HAS IDENTIFIED A PROMISING CANDIDATE FACTOR THAT PREDICTS SUBOPTIMAL RESPONSE TO INSOMNIA THERAPY: HIGH COGNITIVE AROUSAL, A TRANSDIAGNOSTIC PHENOMENON OF HEIGHTENED COGNITIVE ACTIVITY, PARTICULARLY IN THE FORM OF PERSEVERATIVE THINKING (WORRY, RUMINATION). NEARLY ALL PREGNANT WOMEN WITH INSOMNIA HAVE HIGH COGNITIVE AROUSAL BEFORE INSOMNIA THERAPY, BUT CBTI PRODUCES MINIMAL EFFECT ON THESE SYMPTOMS. PREGNANT WOMEN WITH HIGH COGNITIVE AROUSAL AFTER INSOMNIA THERAPY ARE 4 TIMES LESS LIKELY TO REMIT FROM INSOMNIA, AND 3 TIMES MORE LIKELY TO HAVE DEPRESSION RELATIVE TO WOMEN WHOSE AROUSAL DECREASES WITH THERAPY. IN EFFORT TO ENHANCE ALLEVIATION OF COGNITIVE AROUSAL TO OPTIMIZE CLINICAL OUTCOMES, WE PLACED EFFICACIOUS BEHAVIORAL SLEEP STRATEGIES WITHIN A MINDFULNESS INTERVENTION FRAMEWORK TO DEVELOP AN INSOMNIA THERAPY SPECIFICALLY FOR PREGNANT WOMEN: PERINATAL UNDERSTANDING OF MINDFUL AWARENESS FOR SLEEP (PUMAS). UNLIKE CBTI, EFFICACY DATA SHOW THAT PUMAS PRODUCES LARGE REDUCTIONS IN INSOMNIA, DEPRESSION, AND COGNITIVE AROUSAL RELATIVE TO CONTROL. MOREOVER, EFFICACY DATA SUGGEST THAT REDUCING COGNITIVE AROUSAL MAY REPRESENT A MECHANISM BY WHICH PUMAS REDUCES INSOMNIA AND DEPRESSION. THE NEXT STEP IN THE NIMH PHASE OF INTERVENTION DEVELOPMENT IS TO TRANSLATE THESE EFFICACY DATA INTO REAL-WORLD PRACTICE. EVALUATING THE ACCEPTABILITY, FEASIBILITY, AND PRELIMINARY EFFECTIVENESS OF PUMAS IMPLEMENTED IN REAL-WORLD CLINICS IS ABSOLUTELY CRITICAL AND HAS IMMENSE POTENTIAL TO REDUCE BURDEN OF MATERNAL MENTAL ILLNESS. ALIGNED WITH NIMH EMPHASIS ON EXPERIMENTAL THERAPEUTICS APPROACH, WE WILL INVESTIGATE REDUCTIONS IN COGNITIVE AROUSAL AS A KEY MECHANISM BY WHICH PUMAS ALLEVIATES INSOMNIA AND DEPRESSION. WE PROPOSE AN EFFECTIVENESS-IMPLEMENTATION HYBRID TYPE 1 PILOT RCT WHEREIN 100 PREGNANT WOMEN WITH DSM-5 INSOMNIA DISORDER ARE RANDOMIZED TO TELEMEDICINE PUMAS OR SHAM THERAPY CONTROL. WE WILL IMPLEMENT PUMAS IN ALL 23 WOMEN’S HEALTH CLINICS ACROSS HENRY FORD HEALTH SYSTEM, CENTRALLY LOCATED IN METRO DETROIT. IMPLEMENTATION WILL REFLECT REAL-WORLD CLINIC OPERATIONS SUCH THAT WOMEN RECEIVING PRENATAL CARE WHO REPORT SLEEP DIFFICULTIES WILL BE REFERRED BY OB PHYSICIANS AND MIDWIFES TO THERAPISTS EMBEDDED IN THE WOMEN’S HEALTH CLINICS FOR EVALUATION AND TREATMENT. AFTER TREATMENT, WE WILL ASSESS PARTICIPANTS ACROSS THE FIRST POSTPARTUM YEAR TO PRELIMINARILY EVALUATE THE DURABILITY OF CLINICAL OUTCOMES. THIS PROJECT WILL NOT ONLY TEST PUMAS PRELIMINARY EFFECTIVENESS FOR INSOMNIA AND DEPRESSION, BUT WILL ALSO INVESTIGATE WHETHER PUMAS ENGAGES A KEY CANDIDATE MECHANISM (HIGH COGNITIVE AROUSAL) THAT IS OPERATIVE FOR ALLEVIATING THESE CLINICAL OUTCOMES IN THE EFFECTIVENESS CONTEXT (PAR-21-131).

IMPROVING DECISION MAKING TO PREVENT SUBSTANCE MISUSE AMONG ADOLESCENTS FROM TRADITIONALLY UNDERSERVED COMMUNITIES - EARLY CHILDHOOD ADVERSITY IS ASSOCIATED WITH SIGNIFICANT RISK FOR ENGAGING IN PROBLEMATIC SUBSTANCE USE ACROSS THE LIFESPAN. ADOLESCENTS LIVING IN LOW-INCOME NEIGHBORHOODS ARE BOTH MORE LIKELY TO EXPERIENCE ADVERSE CHILDHOOD EVENTS AND LESS LIKELY TO HAVE ACCESS TO EVIDENCE-BASED PREVENTATIVE SUBSTANCE USE INTERVENTIONS. THUS, THERE IS A CRITICAL NEED TO IDENTIFY INTERVENTIONS THAT CAN EFFECTIVELY PREVENT THE ESCALATION OF SUBSTANCE USE IN VULNERABLE YOUTH AND BE FEASIBLY DISSEMINATED IN LOW-RESOURCE, TRADITIONALLY UNDERSERVED COMMUNITIES. DELAY DISCOUNTING HAS EMERGED IN THE LITERATURE AS A CRITICAL ETIOLOGICAL MARKER OF SUBSTANCE USE RISK AND A POTENTIAL PATHWAY FROM EARLY LIFE DISADVANTAGE TO PROBLEMATIC ALCOHOL AND DRUG USE. ELEVATED DELAY DISCOUNTING IS CHARACTERIZED BY AN EXAGGERATED TENDENCY TO SELECT REWARDS THAT ARE IMMEDIATELY AVAILABLE. HIGHER (MORE PROBLEMATIC) RATES OF DELAY DISCOUNTING DURING ADOLESCENCE ARE ASSOCIATED WITH MORE SEVERE AND FREQUENT SUBSTANCE USE AND ARE PREDICTIVE OF STEEPER ESCALATIONS IN ALCOHOL, MARIJUANA AND TOBACCO USE. WORKING MEMORY, THE CAPACITY TO STORE AND MANIPULATE INFORMATION UTILIZED IN DECISION MAKING, IS CLOSELY LINKED TO DELAY DISCOUNTING AND A PLAUSIBLE NEUROCOGNITIVE MECHANISM LINKING EARLY ADVERSE ENVIRONMENTS TO PROBLEMATIC DISCOUNTING TENDENCIES AND SUBSEQUENT SUBSTANCE USE. GUIDED BY AN EXPERIMENTAL THERAPEUTICS FRAMEWORK, RECENT FINDINGS FROM OUR OWN RESEARCH TEAM AND OTHERS SUGGESTS THE EFFICACY OF UTILIZING A COMPUTER-BASED WORKING MEMORY TRAINING PROGRAM TO IMPROVE DISCOUNTING AMONG MID-LIFE ADULTS. COMPUTER-BASED TRAINING PROGRAMS MAY BE PARTICULARLY SUITABLE TO IMPLEMENT IN LOW-RESOURCE COMMUNITIES FOR AT-RISK ADOLESCENTS. SPECIFICALLY, ADOLESCENCE IS A CRITICAL PERIOD FOR THE DEVELOPMENT OF BOTH WORKING MEMORY AND DELAY DISCOUNTING, AND INTERVENTIONS TARGETING WORKING MEMORY DURING THIS LIFE STAGE HAVE EVIDENCED FAVORABLE CLINICAL RESULTS. FURTHER, COMPUTERIZED INTERVENTIONS REQUIRE LIMITED STAFF AND SPACE RESOURCES, MAKING THEM BOTH FEASIBLE AND SCALABLE IN TRADITIONALLY UNDERSERVED COMMUNITIES. BUILDING ON PROMISING FINDINGS FROM THE INVESTIGATOR TEAM’S FORMATIVE RESEARCH, THIS APPLICATION PROPOSES TO PILOT A COMPUTER-BASED WORKING MEMORY INTERVENTION AMONG ADOLESCENTS EXPOSED TO EARLY LIFE ADVERSITY IN THE LOW-RESOURCE COMMUNITY OF DETROIT, MICHIGAN. PRIMARY AIMS INCLUDE ESTABLISHING THE PRELIMINARY FEASIBILITY, ACCEPTABILITY AND APPROPRIATENESS OF DELIVERING A COMPUTERIZED WORKING MEMORY INTERVENTION IN A COMMUNITY SETTING SERVING LOW-INCOME ADOLESCENTS AS WELL AS CONDUCTING A SMALL-SCALE STAGE I RANDOMIZED CONTROL TRIAL TO EXAMINE THE EFFECTIVENESS OF THIS INTERVENTION IN REDUCING RATES OF DELAY DISCOUNTING. THE SUBSEQUENT IMPACT OF THIS INTERVENTION ON CHANGES IN ADOLESCENT SUBSTANCE USE OVER A THREE-MONTH FOLLOW-UP PERIOD WILL ALSO BE EXAMINED AS AN EXPLORATORY AIM. THE PROPOSED RESEARCH WILL PROVIDE VALUABLE INSIGHT INTO THE UTILITY OF TARGETING A SPECIFIC PATHWAY FROM EARLY ADVERSITY TO LATER SUBSTANCE USE DURING ADOLESCENCE AND WILL ESTABLISH A MODEL FOR DISSEMINATING INTERVENTIONS IN LOW-RESOURCE COMMUNITIES. RESULTS OF THIS STUDY WILL ALSO SET THE STAGE FOR FUTURE LARGE-SCALE (R01) PREVENTION RESEARCH.

REGULATION OF ENAC IN SALT-SENSITIVE HYPERTENSION VIA INFLAMMATION-INDUCED ROS PRODUCTION

FINDING THE MISSING LINK BETWEEN PANCREATIC NEOPLASIA AND CARCINOMA

TREATMENT OF ACUTE EMBOLIC STROKE WITH STATINS AND RT-PA

COMMUNITY PROJECT FUNDING/CONGRESSIONALLY DIRECTED SPENDING - CONSTRUCTION - HENRY FORD JACKSON/ALLEGIANCE HEALTH IS ESTABLISHING A NON-PROFIT HUMAN MILK DONOR BANK TO SUPPORT INFANT HEALTH. HUMAN MILK IS GENERALLY CONSIDERED THE OPTIMAL SOURCE OF NUTRITION FOR MOST INFANTS, AND IS ESPECIALLY IMPORTANT FOR PREMATURE BABIES IN NEED OF ADDITIONAL NUTRIENTS FOR DEVELOPMENT. HOWEVER, MANY DO NOT RECEIVE BREAST MILK FOR THE RECOMMENDED AMOUNT OF TIME DUE TO PHYSICAL, CULTURAL, AND SOCIETAL BARRIERS. ONE WAY TO HELP ENSURE EVERY BABY HAS ACCESS TO BREAST MILK, REGARDLESS OF THEIR CIRCUMSTANCES, IS THROUGH A MILK BANK, WHICH ALLOWS WOMEN WITH EXCESS MILK TO DONATE TO THOSE IN NEED. THERE ARE FEWER THAN 30 MILK BANKS IN THE UNITED STATES, AND ONLY ONE IN MICHIGAN. HOSPITAL CLINICIANS, AS PROPONENTS OF DONOR MILK, KNOW FIRSTHAND THE BENEFITS AND NEED FOR INCREASED AVAILABILITY. THE MILK BANK WILL OPERATE A FULL INTAKE AND DONATION PROGRAM THAT INCLUDES INTAKING MILK DONATIONS, PROCESSING MILK WITH HEAT FOR PASTEURIZATION, STORING MILK, AND QUEUING OUTGOING MILK. THE DONOR BANK WILL HAVE THE ABILITY TO SERVE PATIENTS WITHIN A 60-MILE RADIUS OF HENRY FORD JACKSON/ALLEGIANCE HEALTH’S MAIN HOSPITAL IN JACKSON COUNTY, WITH THE POTENTIAL TO EXPAND FURTHER ONCE ESTABLISHED. THE HUMAN DONOR MILK BANK WILL INCREASE ACCESS IN MICHIGAN TO A CRITICAL SOURCE OF NUTRIENTS FOR BABIES AND HELP TO CREATE A STRONG FOUNDATION FOR INFANTS AND THEIR FAMILIES AT THE START OF LIFE. THE FEDERAL FUNDS WILL SUPPORT THE SPACE RENOVATION FOR THE MILK BANK, AS WELL AS THE PURCHASE OF EQUIPMENT AND TECHNOLOGY FOR THIS EFFORT.

PRENATAL YOGA TO PREVENT POSTPARTUM DEPRESSION (PRY-D) - PROJECT ABSTRACT POSTPARTUM DEPRESSION (PPD) AFFECTS 13% OF WOMEN AND IS ASSOCIATED WITH MATERNAL, FETAL/INFANT, AND CHILDHOOD MORBIDITY. THOUGH RISK FACTORS ARE MULTIFACTORIAL, A HISTORY OF DEPRESSION STRONGLY PREDICTS RISK OF PPD, AND WOMEN OF RACIAL/ETHNIC MINORITY STATUS ARE ESPECIALLY VULNERABLE. ALTHOUGH PSYCHOLOGICAL INTERVENTIONS EXIST FOR THE PREVENTION OF PPD, A YOGA-BASED INTERVENTION TO PREVENT PPD AMONG AT-RISK WOMEN UTILIZES A SIMILAR THEORETICAL FOUNDATION (I.E., MINDFULNESS), MAY BE MORE ACCEPTABLE TO WOMEN OF MINORITY STATUS, AND MAY CONFER ADDITIONAL PHYSICAL ACTIVITY BENEFITS. YOGA INTERVENTIONS IN PREGNANCY HAVE BEEN SHOWN TO BE EFFICACIOUS FOR DEPRESSION, ALTHOUGH PRAGMATIC RESEARCH IS NEEDED TO EVALUATE THESE TYPES OF INTERVENTIONS IN A WAY THAT FACILITATES EXTERNAL VALIDITY. THE PURPOSE OF THIS R34 PILOT EFFECTIVENESS TRIAL IS TO DETERMINE THE EFFECTIVENESS OF USING A VIRTUALLY DELIVERED PRENATAL YOGA INTERVENTION FOR THE PREVENTION OF PPD AMONG AT-RISK WOMEN IN A DIVERSE HEALTH CARE SYSTEM AND EXPLORE PRELIMINARY FACTORS WHICH INFLUENCE IMPLEMENTATION OF THE INTERVENTION. TO THIS END, WE HAVE GATHERED A RESEARCH TEAM WITH CONTENT, INTERVENTION, STATISTICAL, AND METHODOLOGICAL EXPERTISE WHO WILL COLLABORATIVELY EXECUTE THE PROPOSED PROJECT. IN THE PROPOSED STUDY, PHASE 1 WILL EVALUATE FACILITATORS AND BARRIERS TO INTERVENTION IMPLEMENTATION AMONG PATIENT, CLINICIAN, AND HEALTH SYSTEM STAKEHOLDERS, FOLLOWED BY AN OPEN TRIAL, AND PHASE 2 WILL INCLUDE CONDUCTING AN 8-SESSION PILOT RANDOMIZED CONTROLLED TRIAL TO ASSESS THE FEASIBILITY AND ACCEPTABILITY OF THE PROPOSED PRENATAL YOGA INTERVENTION AMONG WOMEN WITH A HISTORY OF DEPRESSION, AS WELL AS THE ONSET AND COURSE OF PPD AND MEDIATING FACTORS. THE SPECIFIC AIMS ARE TO: 1) OPTIMIZE DELIVERY OF A YOGA INTERVENTION WITHIN A HEALTHCARE SYSTEM TO PREVENT PPD THROUGH EXAMINING FACILITATORS AND BARRIERS OF IMPLEMENTATION, 2) EXAMINE FEASIBILITY, ACCEPTABILITY AND SATISFACTION OF THE INTERVENTION WITHIN A HEALTH CARE SYSTEM, AND 3) EVALUATE PRELIMINARY EFFECTIVENESS OF THE INTERVENTION ON PPD AND PROPOSED MECHANISMS. FOR PHASE 1, SEPARATE FOCUS GROUPS WITH PATIENT STAKEHOLDERS AND CLINICIAN AND ADMINISTRATIVE STAKEHOLDERS FROM HENRY FORD HEALTH WILL INFORM INTERVENTION IMPLEMENTATION, AND AN OPEN TRIAL TO REFINE AND OPTIMIZE THE INTERVENTION. FOR PHASE 2, WOMEN WITH A HISTORY OF DEPRESSION WHO ARE 8-28 WEEKS PREGNANT WILL BE RANDOMIZED TO THE INTERVENTION GROUP (N=24) OR TREATMENT-AS-USUAL (N=24) AND WILL COMPLETE SURVEY MEASURES AT BASELINE, POST-INTERVENTION, AND 1 AND 3 MONTHS POSTPARTUM. IT IS HYPOTHESIZED THAT THE INTERVENTION WILL BE FEASIBLE AND ACCEPTABLE, ENGAGE WOMEN OF RACIAL/ETHNIC MINORITY STATUS, AND CONTRIBUTE TO LOWER RATES OF PPD ONSET. EMBODIMENT AND MINDFULNESS ARE THE PROPOSED MEDIATORS. FINDINGS FROM THIS STUDY WILL PROVIDE PRELIMINARY DATA TO INFORM A FULLY POWERED HYBRID TYPE 2 EFFECTIVENESS- IMPLEMENTATION TRIAL. THE POTENTIAL KNOWLEDGE GAINED FROM THIS STUDY CAN FACILITATE PREVENTION EFFORTS FOR PPD AND AMELIORATE THE ADVERSE PUBLIC HEALTH IMPACT OF THIS DISORDER.

FEASIBILITY OF AN ED-INITIATED ONLINE MANAGEMENT PROGRAM FOR URBAN TEENS

IN VIVO MR EVALUATION OF CELL THERAPY FOR STROKE

MICRORNA PREDICTORS OF PROSTATE CANCER OUTCOME IN AFRICAN-AMERICAN MEN

A TECHNOLOGY-BASED INTERVENTION TO REDUCE ALCOHOL USE AFTER BARIATRIC SURGERY

IMPROVING DELAY DISCOUNTING TO DECREASE HARSH PARENTING AMONG PARENTS RECEIVING SUBSTANCE USE TREATMENT IN A LOW RESOURCE COMMUNITY - ABSTRACT PARENTS WITH SUBSTANCE USE DISORDERS (SUD) ARE SIGNIFICANTLY MORE LIKELY TO ENGAGE IN HARSH PARENTING PRACTICES, INCLUDING SPANKING, HITTING, AND BELITTLING THEIR CHILDREN, THAN PARENTS WITHOUT SUD. PUNITIVE PHYSICAL AND EMOTIONAL DISCIPLINE IS, IN TURN, ASSOCIATED WITH INCREASED RATES OF CHILD MALTREATMENT AND THE SUBSEQUENT INTERGENERATIONAL TRANSMISSION OF SUBSTANCE USE DISORDERS. PARENTS IN RESIDENTIAL SUBSTANCE USE TREATMENT FACILITIES ARE AMONG THOSE AT HIGHEST RISK FOR PERPETRATING HARSH AND ABUSIVE PARENTING; YET MOST BEHAVIORALLY- BASED PARENTING INTERVENTIONS AVAILABLE WITHIN INPATIENT SETTINGS DO NOT TAKE INTO ACCOUNT THE UNIQUE MECHANISMS LINKING PARENTAL SUBSTANCE USE TO HARSH PARENTING. SPECIFICALLY, PARENTS WITH SUD MAY BE AT HEIGHTENED RISK FOR ENGAGING IN MALADAPTIVE PARENTING APPROACHES GIVEN A TENDENCY TO PRIORITIZE IMMEDIATE REWARDS (SUCH AS STOPPING A CHILD’S MISBEHAVIOR USING PHYSICAL PUNISHMENT) RELATIVE TO LARGER, BUT DELAYED REWARDS (INCLUDING SHAPING POSITIVE CHILD BEHAVIOR OVER A LONGER TERM). THIS BEHAVIORAL TENDENCY IS KNOWN AS DELAY DISCOUNTING AND RECENT FINDINGS SUGGEST THAT RATES OF DELAY DISCOUNTING PREDICT PARENTS’ USE OF HARSH PHYSICAL DISCIPLINE. EXISTING RESEARCH ALSO INDICATES A STRONG LINK BETWEEN STEEPER (MORE PROBLEMATIC) RATES OF DELAY DISCOUNTING AND THE SEVERITY OF ALCOHOL AND ILLICIT DRUG USE ACROSS THE LIFESPAN. THUS, DELAY DISCOUNTING MAY REPRESENT A SPECIFIC VULNERABILITY UNDERLYING BOTH HARSH PARENTING AND DISORDERED SUBSTANCE USE. THE CURRENT PROJECT PROPOSES TO PILOT AND FEASIBILITY TEST AN ADAPTED EPISODIC FUTURE THINKING (EFT) INTERVENTION TO TARGET THE REDUCTION OF PARENTING-RELATED DELAY DISCOUNTING AND EXAMINE ITS EFFECTS ON PARENTING PRACTICES AMONG FAMILIES IN A RESIDENTIAL SUBSTANCE USE TREATMENT SETTING. EFT MAY BE PARTICULARLY WELL-SUITED FOR DISSEMINATION IN A RESIDENTIAL SUD SETTING BECAUSE IT IS BRIEF, FLEXIBLE, AND CAN BE DELIVERED BY PEER RECOVERY COACHES (PRCS), INDIVIDUALS WITH LIVED SUBSTANCE USE AND RECOVERY EXPERIENCES. UTILIZING PRCS, WHO ARE ALREADY WIDELY EMPLOYED IN SUD TREATMENT SETTINGS, INCREASES THE SCALABILITY, ACCEPTABILITY AND COST- EFFECTIVENESS OF THIS APPROACH AND MAY REDUCE STIGMA, A CRITICAL BARRIER TO PARTICIPATION IN PARENTING PROGRAMS AMONG INDIVIDUALS WITH SUD. FOLLOWING A DEPLOYMENT-FOCUSED MODEL, WE WILL CONDUCT A SMALL CASE-SERIES TRIAL AND COLLECT DATA REGARDING CRITICAL IMPLEMENTATION OUTCOMES (INCLUDING ACCEPTABILITY, TOLERABILITY, AND DOSAGE). RESULTS FROM THIS AIM WILL INFORM MANUAL ADAPTATION. WE WILL THEN RECRUIT 72 PARENTS OF CHILDREN BETWEEN THE AGES OF 6 AND 10 RECEIVING INPATIENT SUBSTANCE USE TREATMENT IN THE LOW RESOURCE, MAJORITY-MINORITY, CITY OF FLINT, MICHIGAN. PARTICIPANTS WILL BE RANDOMIZED TO RECEIVE EFT OR A COMPARISON INTERVENTION. FINDINGS FROM THIS STUDY WILL BE USED TO PLAN A LARGE-SCALE (R01) INTERVENTION TRIAL AND WILL INFORM PUBLIC HEALTH APPROACHES FOR REDUCING CHILD MALTREATMENT AND PREVENTING INTERGENERATIONAL CYCLES OF ADDICTION.

AMPK AS A NOVEL HOST FACTOR REGULATING OVARIAN CANCER PROGRESSION

PHARMACOGENETICS OF THE B-TYPE NATRIURETIC PEPTIDE PATHWAY

DEVELOPMENT OF PLASMACYTOID DC EXOSOMES AS NEW TYPE OF CANCER VACCINES THAT OVERCOME CDC1 DEPENDENCE AND TUMOR IMMUNOSUPPRESSION

PARACRINE PATHWAYS CAUSAL IN GROWTH AND INVASION OF NEUROFIBROMAS: CONTRIBUTIONS OF CELLULAR MICROENVIRONMENT

EPIGENOMIC MASTER REGULATORS THAT DEFINE IDH1/2 MUTANT GLIOMA TUMOR PROGRESSION

TARGETING ONCOGENE AMPLIFICATION IN GLIOBLASTOMA

DEGRADATION AND RECOVERY OF BONE: OVX AND TREATMENT

MECHANISM OF ENDOTOXIN'S EFFECT ON ALLERGY RISK

UNCOVER THE NEW SUBSETS OF EPIDERMAL LANGERHANS CELLS - PROJECT SUMMARY LANGERHANS CELLS (LCS) ARE SKIN-RESIDENT DENDRITIC CELLS (DCS) EXPRESSING THE C-TYPE LECTIN LANGERIN (CD207) THAT MEDIATE BOTH ADAPTIVE IMMUNITY AND IMMUNE TOLERANCE IN SKIN AND ARE INVOLVED IN VARIOUS TYPES OF SKIN DISEASES. ADULT LCS ARE ORIGINATED FROM EMBRYONIC YOLK-SAC-DERIVED MACROPHAGES AND FETAL LIVER MONOCYTES IN THE STEADY STATE. INTERESTINGLY, LCS COULD ALSO BE DERIVED FROM THE BONE MARROW OR PERIPHERAL MONOCYTES AND REPOPULATE THE SKIN UNDER INFLAMMATORY CONDITIONS. HOWEVER, DUE TO THE LACK OF MOLECULAR PROFILES AT INDIVIDUAL LC LEVEL, A SIGNIFICANT GAP REMAINS IN OUR UNDERSTANDING ON HOW A SINGLE CD207+ EPIDERMAL LC POPULATION CAN INDUCE BOTH IMMUNITY AND TOLERANCE. FORTUNATELY, NEW TECHNOLOGIES SUCH AS THE SINGLE-CELL RNA-SEQUENCING (SCRNA-SEQ) CAN EVALUATE CELL-TO-CELL TRANSCRIPTOMIC VARIATION, WHILE THE SINGLE-CELL ASSAY FOR TRANSPOSASE- ACCESSIBLE CHROMATIN USING SEQUENCING (SCATAC-SEQ) CAN ASSESS THE EPIGENOMIC HETEROGENEITY AT SINGLE-CELL RESOLUTION IN AN UNBIASED MANNER. RECENTLY, WE IDENTIFIED TWO MAJOR LC SUBSETS IN MICE, ATF3+BAL2A1B- (MLC1) AND ATF3-BAL2A1B+(MLC2) SUBSETS, AND THREE MAJOR LC SUBSETS IN HUMAN INCLUDING ATF3+ (HLC1) SUBSET USING SCRNA-SEQ. WE ALSO FOUND IN ATF3 KNOCKOUT MICE THAT LACK OF ATF3 ENHANCES LC MATURATION AND PROMOTES LCS-INDUCED TH1 AND TH17 CELL DIFFERENTIATION SUGGESTING IMMUNE SUPPRESSIVE FUNCTION INDUCED BY ATF3+LC1. HENCE, THESE PRELIMINARY DATA SUPPORT OUR HYPOTHESIS THAT LCS ARE HETEROGENEOUS CONSISTING OF DISTINCT SUBSETS WITH DIFFERENT IMMUNE FUNCTIONS. OUR OBJECTIVE IS TO USE SINGLE-CELL ANALYSIS PLATFORMS PLUS THE LC FATE-MAPPING AND MUTATION MOUSE MODELS TO FURTHER VALIDATE THIS. WE WILL PURSUE TWO SPECIFIC AIMS IN THE R61 PHASE: AIM 1) CHARACTERIZE THE GENE SIGNATURES AND REGULATORY ELEMENTS OF MLC1 AND MLC2 BY PROFILING LCS DURING EMBRYONIC, YOUNG, AND AGING DEVELOPMENT AT STEADY-STATE AND REPOPULATED LCS AT INFLAMED STATE USING SCRNA-SEQ AND SCATAC-SEQ; AIM 2) GENERATE ATF3NEGEGFP REPORTER MICE TO FATE-MAP ATF3+LC1 EMBRYONIC DEVELOPMENT AND THE DYNAMIC CHANGE OF ATF3+LC1 AND ATF3-LC2 SUBSET AT STEADY STATE DURING ADULT AND AGING DEVELOPMENT AND AT INFLAMMATORY STATE AND FUNCTIONALLY CHARACTERIZE LC SUBSETS IN VITRO BY SORTING ATF3EGFP+ LC1 AND ATF3- LC2 CELLS AND REDERIVING ATF3.LOXP MICE, WHICH WILL BE CROSSED WITH HLANGERIN-CRE MICE TO GENERATE LC- SPECIFIC/TIME-INDUCED ATF3KO FOR IN VIVO FUNCTIONAL STUDY. IN THE R33 PHASE, WE WILL PURSUE THE FOLLOWING SPECIFIC AIM: AIM 3) FUNCTIONALLY CHARACTERIZE ATF3+LC1 SUBSET IN VIVO USING LC-SPECIFIC ATF3 DELETION HLCCRE.ATF3KO MICE TO EVALUATE THE POTENTIAL IMMUNE REGULATION FUNCTION OF ATF3+LC1 SUBSET IN THE DIFFERENT DISEASE MODELS, INCLUDING AUTOIMMUNE VITILIGO, MELANOMA, AND FUNGI INFECTION MODELS. OUR WORK WILL UNCOVER THE MYSTERY OF LC SUBSETS WITH THEIR SPECIFIC FUNCTIONS, WHICH WILL PROVIDE NEW INSIGHTS INTO THE BIOLOGY OF LCS AND LEAD TO THE DEVELOPMENT OF LC-BASED INTERVENTION STRATEGIES FOR SKIN DISEASES.

TREATMENT OF TRAUMATIC BRAIN INJURY WITH SIMVASTATIN

TRAUMATIC BRAIN INJURY AND MARROW STROMAL CELLS

UNCOVER THE NEW SUBSETS OF EPIDERMAL LANGERHANS CELLS

GENDER INFLUENCE IN MICE WITH MYOCARDIAL INFARCTION

HDAC3 AS A POTENTIAL THERAPEUTIC TARGET FOR LANGERHANS CELL HISTIOCYTOSIS

HYDROGEN PEROXIDE STIMULATES RENIN RELEASE: ROLE IN HYPERTENSION AND DIABETES

NETRIN G1 LIGAND: A NEW IMMUNOMODULATORY TARGET AND EARLY BIOMARKER IN PANCREATIC CANCER

SMALL THINGS FIRST: LEVERAGING IMPLEMENTATION SCIENCE TO INCREASE ACCESS TO INFANT DIRECTED SPEECH FOR ALL INFANTS IN NEONATAL INTENSIVE CARE UNITS - PROJECT SUMMARY/ABSTRACT ADEQUATE LANGUAGE INPUT IS REQUIRED FOR TYPICAL LANGUAGE DEVELOPMENT. HOWEVER, NICU INFANTS ARE AT PARTICULARLY HIGH RISK FOR EXPERIENCING A LANGUAGE DEPRIVED ENVIRONMENT AND MAY SPEND WEEKS-TO-MANY-MONTHS OF A CRITICAL DEVELOPMENTAL PERIOD IN THIS SETTING. IMPORTANTLY, WE KNOW THAT THE LANGUAGE ENVIRONMENT OF THE NICU MATTERS: THE QUANTITY AND QUALITY OF LANGUAGE INPUT AN INFANT RECEIVES IN THE NICU HAS BEEN ASSOCIATED WITH POSITIVE SHORT-AND-LONG-TERM OUTCOMES (E.G., ATTENTIVENESS, ALERTNESS, VOCALIZATIONS, CONVERSATIONAL TURNS, LANGUAGE, DEVELOPMENT). INFANT DIRECTED SPEECH (IDS), IS A HIGHLY PROMISING LANGUAGE CONSTRUCT, THAT IS DEFINED AS A PATTERN OF SPEAKING ADULTS USE WITH INFANTS AND YOUNG CHILDREN THAT HAS A SIMPLER PHONOLOGY, GRAMMATICAL STRUCTURE, AND FEWER LEXICAL ITEMS AS WELL AS A HIGHER PITCH AND UNUSUAL INTONATION PATTERN. INCREASED USE OF IDS HAS BEEN FOUND TO BE PREDICTIVE OF BETTER LANGUAGE OUTCOMES IN TYPICALLY DEVELOPING INFANTS. INCREASING THE QUANTITY OF IDS IN THE NICU MAY BE A SIMPLE, LOW-TRAINING, HIGH-IMPACT INTERVENTION THAT COULD BOLSTER EARLY LANGUAGE OUTCOMES FOR NICU INFANTS (E.G., VERBALIZATIONS, CONVERSATIONAL TURNS). FOR NICU INFANTS, IT IS IMPERATIVE THAT WE TASK BOTH PARENTS AND CLINICIANS AS CO-PRIMARY PROVIDERS OF ROUTINE IDS DUE TO SIGNIFICANT EXISTING BARRIERS TO PARENT VISITATION. HOWEVER, TASKING CLINICIANS TO USE IDS DURING ROUTINE CARE WILL LIKELY FACE ORGANIZATIONAL, INNOVATION, AND CLINICIAN-LEVEL BARRIERS THAT MAY IMPACT CLINICIAN INTENTIONS. TO SUCCESSFULLY INCREASE ALL INFANTS’ ACCESS TO IDS, IT IS NECESSARY TO CONDUCT PRELIMINARY IMPLEMENTATION RESEARCH PRIOR TO A HYBRID TYPE 1 (EFFECTIVENESS- IMPLEMENTATION) STUDY TO IDENTIFY AND UNDERSTAND: 1) BARRIERS TO PARENT VISITATION AND INTENTIONS TO USE IDS WITH THEIR HOSPITALIZED INFANT (WITH SEMI-STRUCTURED INTERVIEWS, SURVEYS); AND 2) IDENTIFY AND UNDERSTAND BARRIERS AND FACILITATORS TO NICU CLINICIAN USE OF IDS (WITH SURVEYS, VIDEO-ELICITATION INTERVIEWS; VIDEO SIMULATION SURVEYS). TO CONCEPTUALIZE THIS WORK, WE ARE MODIFYING THE EXPLORE PLAN IMPLEMENT SUSTAIN IMPLEMENTATION FRAMEWORK TO INCORPORATE HEALTH EQUITY FACTORS AS PART OF THE OUTER CONTEXT AND USE ORGANIZATIONAL AND PSYCHOLOGICAL THEORIES OF BEHAVIOR TO EXPLORE AND REFINE A POSSIBLE CAUSAL MODEL OF CONTRIBUTORS TO PARENT AND CLINICIAN INTENTIONS TO USE IDS WITH NICU INFANTS. COMPLETING THE PROPOSED RESEARCH WILL ALLOW US TO REFINE OUR CAUSAL MODEL BY IDENTIFYING AN EXHAUSTIVE LIST OF SOCIETAL, ORGANIZATIONAL, INNOVATION, AND INDIVIDUAL FACTORS (I.E., BARRIERS, FACILITATORS) THAT MAY IMPACT OR MODERATE PARENT INTENTIONS TO VISIT AND PARENT AND CLINICIAN INTENTIONS TO USE IDS IN THE NICU. FINALLY, THE TRAINING AND RESEARCH ACTIVITIES PROPOSED IN THE K23 APPLICATION WILL SUPPORT THE PI IN HAVING THE DATA, SKILLS, AND EXPERIENCES NECESSARY TO SUBMIT A STRONG APPLICATION FOR A MULTI-SITE HYBRID TYPE I (EFFECTIVENESS- IMPLEMENTATION) TRIAL THAT EXAMINES 1) WHETHER WE CAN SIGNIFICANTLY INCREASE ADULT USE OF IDS IN THE NICU (I.E., PARENT/VISITS, CLINICIAN/ROUTINE CARE); AND 2) WHETHER INFANTS WHO RECEIVED HIGHER LEVELS OF IDS DEMONSTRATED MORE VERBALIZATIONS, VOCALIZATIONS, AND CONVERSATIONAL TURNS AT DISCHARGE (ADJUSTING FOR GESTATIONAL AGE).

CLINICAL ASSESSMENT OF VERTEBRAL BONE QUALITY USING DIRECT BIOMECHANICAL AND TEXTURAL ANALYSIS VIA DIGITAL TOMOSYNTHESIS

GENETIC RISK OF HIDRADENITIS SUPPURATIVA IN AFRICAN AMERICANS - PROJECT SUMMARY HIDRADENITIS SUPPURATIVA (HS) IS A CHRONIC, RELAPSING, AND REMITTING INFLAMMATORY DISEASE OF THE SKIN, WITH A PREVALENCE UP TO 4% OF GENERAL POPULATION. HOWEVER, THE FACTORS THAT CONTRIBUTE TO HS RISK ARE POORLY UNDERSTOOD, AND THIS LACK OF MECHANISTIC UNDERSTANDING IS A PRINCIPAL BARRIER TO IMPROVED TREATMENTS FOR HS. THE DIFFERENCE IN THE RISK OF HS BY ETHNICITY IN THE US IS STRIKING. SPECIFICALLY, AFRICAN AMERICANS HAVE ESTABLISHED PREVALENCE AND INCIDENCE RATES THAT ARE APPROXIMATELY 3-FOLD HIGHER THAN THEIR EUROPEAN AMERICAN COUNTERPARTS. FURTHER, AFRICAN AMERICAN PATIENTS EXHIBIT HIGHER DISEASE SEVERITY AND THE GREATEST NUMBER OF CO-MORBID CONDITIONS. DESPITE THESE DIFFERENCES, THERE HAVE BEEN NO STUDIES THAT HAVE PROVIDED INSIGHT INTO THE CONTRIBUTORS TO THESE EXTREME HS RACIAL DISPARITIES. WHILE AN INHERITED GERMLINE GENETIC COMPONENT TO HS RISK IS INDICATED BY THE FACT THAT UP TO 40% OF HS PATIENTS REPORT A FAMILY HISTORY OF DISEASE, THE MAJORITY OF THE HS GENETIC STUDIES FOCUSED ON TARGETED SEQUENCING OF THREE CANDIDATE GENES WITHIN THE GAMMA-SECRETASE COMPLEX, AND REMARKABLY, THERE ARE NO GENOME- WIDE ASSOCIATION STUDIES REPORTED IN HS YET. THE OVERALL GOAL OF THIS PROJECT IS TO DEFINE THE GENETIC CONTRIBUTORS TO HS RISK IN AFRICAN AMERICANS. USING GENOME-WIDE AND CANDIDATE GENE APPROACH, WE WILL LEVERAGE THIS UNIQUE COHORT AND OTHER EXISTING GENETIC RESOURCES TO THOROUGHLY EVALUATE OUR HYPOTHESIS THROUGH THE FOLLOWING TWO AIMS. IN AIM 1, WE WILL DETERMINE WHETHER GENETIC AFRICAN ANCESTRY CONTRIBUTES TO RISK OF HS IN AFRICAN AMERICANS; IN AIM 2, WE WILL UTILIZE GENOME-WIDE AND CANDIDATE GENE APPROACHES TO IDENTIFY GENETIC VARIATION ASSOCIATED WITH HS RISK IN AFRICAN AMERICANS. SUCCESSFUL COMPLETION OF THIS PROPOSAL WILL PROVIDE THE FIRST INSIGHTS INTO THE GENETIC CONTRIBUTIONS TO RISK OF HS IN AFRICAN AMERICANS, INCLUDING MECHANISTIC EXPLORATION OF THE GENES IDENTIFIED.

ASSESSMENTS OF MULTIPLE BREAST CANCER BIOMARKERS WITH DENDRITIC MRI PROBES

PRIMARY CARE TRAINING AND ENHANCEMENT -- RESIDENCY TRAINING IN STREET MEDICINE - STREET MEDICINE, IMPACTFUL LEADERSHIP ENHANCEMENT IN FAMILY MEDICINE (SMILE-FAM) WILL DESIGN, IMPLEMENT, AND EVALUATE AN INTEGRATED LONGITUDINAL STREET MEDICINE CURRICULUM IN THE HENRY FORD HOSPITAL FAMILY MEDICINE RESIDENCY PROGRAM (HFHFMR) TO IMPROVE THE CARE FOR PEOPLE EXPERIENCING HOMELESSNESS (PEH) WHILE TRAINING FUTURE STREET MEDICINE LEADERS. TO PREPARE OUR COHORTS OF FIRST, SECOND, AND THIRD-YEAR FAMILY MEDICINE RESIDENTS TO PROVIDE CARE FOR PEH, WE WILL ACCOMPLISH THE FOLLOWING OBJECTIVES: 1. DEVELOP OR ENHANCE TRAININGS, CLINICAL ROTATIONS, AND DIDACTIC AND CLINICAL CURRICULA CONTENT TO TRAIN RESIDENTS IN STREET MEDICINE TO PROVIDE SENSITIVE AND QUALITY CARE FOR PEOPLE EXPERIENCING HOMELESSNESS WITH ATTENTION TO MENTAL HEALTH AND SUBSTANCE USE DISORDERS. 2. INCREASE RESIDENTS’ KNOWLEDGE AND SKILLS TO MEET THE UNIQUE NEEDS OF PEOPLE EXPERIENCING HOMELESSNESS AND ASSIST PATIENTS WITH NAVIGATION OF THE MEDICAL, BEHAVIORAL HEALTH, LEGAL, AND SOCIAL SUPPORT SYSTEMS RELATED TO CLINICAL CARE. 3. INCREASE RESIDENTS’ KNOWLEDGE AND SKILLS TO WORK IN INTERPROFESSIONAL TEAMS, INCLUDING CHRONIC DISEASE MANAGEMENT, MENTAL HEALTH, SUBSTANCE USE, AND MEDICAL-LEGAL INTERPROFESSIONAL TEAMS, TO ADDRESS THE SDOH THAT IMPACT PATIENT CARE. IMPLEMENTATION OF SMILE-FAM WILL BE GUIDED BY BOTH THE HFHFMR STREET MEDICINE CURRICULUM COMMITTEE AND A COMMUNITY ADVISORY BOARD. WE WILL EMPLOY VARIOUS TEACHING METHODOLOGIES, INCLUDING DIDACTIC LECTURES, MONTHLY GROUP SEMINAR SESSIONS, INTERPROFESSIONAL EDUCATION, SELF-LEARNING/E-LEARNING PLATFORMS, AND WELLNESS SUPPORT. OVER THE 5-YEAR GRANT DURATION ALL HFHFMR RESIDENTS (ESTIMATED N=64) WILL COMPLETE ONE-MONTH ROTATIONS IN PROVIDING HEALTH CARE FOR PEH, INCLUDING: INTERN ORIENTATION; HEALTHCARE EQUITY STREET MEDICINE; COMMUNITY-ORIENTED PRIMARY CARE; SENIOR STREET MEDICINE; LEADERSHIP; AND GROUP LEADERSHIP AND DEVELOPMENT ROTATIONS. SELECTED RESIDENTS WILL COMPLETE A STREET MEDICINE CONCENTRATION TRACK (ESTIMATED N=12), WHICH MAY INCLUDE PARTICIPATION IN A STREET MEDICINE CONTINUITY CLINIC, HENRY FORD HOSPITAL STREET MEDICINE CONSULT SERVICE, STREET MEDICINE OF MICHIGAN SYMPOSIUM AND OTHER CONFERENCES, STREET MEDICINE EXCHANGE OPPORTUNITIES, COMMUNITY ADVISORY BOARD, SCHOLARLY ACTIVITY, AND A CAPSTONE PROJECT. THE CURRICULUM COMMITTEE WILL USE A MIXED QUALITATIVE AND QUANTITATIVE APPROACH TO EVALUATE THESE CURRICULAR ENHANCEMENTS AND TO INFORM ITERATIVE CYCLES OF CURRICULUM IMPROVEMENT. WE WILL TRACK THE PATIENT CARE OUTCOMES BY USING THE ELECTRONIC HEALTH RECORD. THERE WILL BE FOCUS ON PATIENT DEMOGRAPHICS, REPORTED SDOH INCLUDING HOUSING STATUS, MEDICAL DIAGNOSIS, STREET MEDICINE ENCOUNTERS, AMBULATORY CLINIC VISITS, EMERGENCY DEPARTMENT UTILIZATION, HOSPITAL ADMISSION AND 30-DAY READMISSION RATES. GRADUATING RESIDENTS WILL BE FOLLOWED TO ASSESS THEIR PRACTICE CHOICES AFTER COMPLETING THE ENHANCED STREET MEDICINE CURRICULUM. SMILE-FAM AIMS TO EQUIP RESIDENTS WITH FOUNDATIONAL KNOWLEDGE AND SKILLS IN STREET MEDICINE. IN ADDITION, WE ARE NURTURING ATTITUDES THAT VALUE WELLNESS, CULTURAL HUMILITY, AND INTERPROFESSIONAL PRACTICE—ALL KEY INGREDIENTS FOR PREVENTING PROVIDER BURNOUT AND CREATING A LASTING POSITIVE INFLUENCE ON PRACTICE CHOICE. THIS WILL INCREASE THE NUMBER OF FAMILY MEDICINE RESIDENTS WHO ARE PREPARED TO PROVIDE QUALITY CARE FOR PEOPLE EXPERIENCING HOMELESSNESS. WE REQUEST A FUNDING PREFERENCE FOR A HIGH RATE OF PLACEMENT OF GRADUATES IN PRACTICE SETTINGS PRIMARILY SERVING MEDICALLY UNDERSERVED COMMUNITIES (MUCS). 53% OF HFHFMR GRADUATES PRACTICE IN MUCS FROM THE 22-23 AND 23-24 ACADEMIC YEARS. ALSO, HFHFMR HAS A SIGNIFICANT INCREASE, 33%, FOR THE PLACEMENT OF GRADUATES IN MUCS BETWEEN THE 22-23 AND 23-24 ACADEMIC YEARS. OUR UNIQUE EXCHANGE WITH THE MUNSON HEALTH, TRAVERSE CITY STREET MEDICINE PROGRAM WILL CREATE UNIQUE LEARNING OPPORTUNITIES FOR BOTH PROGRAMS. WITH THE CREATION OF A TWO-WEEK RURAL STREET MEDICINE ROTATION, WE REQUEST THE FUNDING PRIORITY IN RURAL TRAINING.

AFFORDABLE CARE ACT (ACA) GRANTS FOR SCHOOL-BASED HEALTH CENTERS CAPITAL PROGRAM

GRADUATE PSYCHOLOGY EDUCATION PROGRAMS

REDUCING MATERNAL DELAY DISCOUNTING AS A TARGET MECHANISM TO DECREASE HARSH PARENTING AND IMPROVE CHILD MENTAL HEALTH OUTCOMES IN A TRADITIONALLY UNDERSERVED COMMUNITY - ABSTRACT HARSH PARENTING IS ASSOCIATED WITH SERIOUS AND COSTLY MENTAL HEALTH PROBLEMS AMONG YOUTH, INCLUDING SUBSTANCE USE, MOOD DISORDERS, AND SUICIDAL IDEATION AND BEHAVIORS. OF CONCERN, THESE PARENTING PRACTICES ARE MOST COMMON AMONG FAMILIES FROM IMPOVERISHED COMMUNITIES; HOWEVER, MANY BEHAVIORALLY-BASED PARENTING INTERVENTIONS DO NOT TAKE INTO ACCOUNT THE UNIQUE MECHANISMS LINKING ENVIRONMENTAL DISADVANTAGE TO PARENTING APPROACHES. WHILE THE CAUSES OF HARSH PARENTING ARE COMPLEX AND VARIED, ONE SUCH MECHANISM MAY BE PARENTS' TENDENCIES TO PRIORITIZE IMMEDIATE REWARDS (SUCH AS STOPPING A CHILD'S MISBEHAVIOR VIA PHYSICAL PUNISHMENT LIKE SPANKING AND HITTING) RELATIVE TO LARGER, BUT DELAYED REWARDS (INCLUDING IMPROVED PARENT-CHILD RELATIONSHIP QUALITY). THIS BEHAVIORAL TENDENCY IS KNOWN AS DELAY DISCOUNTING AND RECENT FINDINGS FROM THIS STUDY TEAM SUGGEST THAT RATES OF DELAY DISCOUNTING PREDICT PARENTS' USE OF HARSH PHYSICAL DISCIPLINE. EXISTING RESEARCH ALSO INDICATES A STRONG LINK BETWEEN EXPOSURE TO DISADVANTAGED ENVIRONMENTS AND THE DEVELOPMENT OF DELAY DISCOUNTING. SPECIFICALLY, UNSTABLE AND LOW-RESOURCE COMMUNITIES MAY REINFORCE OPPORTUNISTIC CHOICE BEHAVIORS, SUCH THAT INDIVIDUALS EXPOSED TO THESE ENVIRONMENTS DEMONSTRATE AN EXAGGERATED TENDENCY TO DEVALUE REWARDS THAT ARE DELAYED IN THEIR RECEIPT. THUS, DELAY DISCOUNTING MAY BE AN IMPORTANT PATHWAY LINKING IMPOVERISHED ENVIRONMENTS AND HARSH PARENTING. UTILIZING AN EXPERIMENTAL THERAPEUTICS FRAMEWORK, THE CURRENT PROJECT AIMS TO ADAPT AN EPISODIC FUTURE THINKING (EFT) INTERVENTION TO TARGET THE REDUCTION OF PARENTING-RELATED DELAY DISCOUNTING. THIS APPLICATION PROPOSES TO EVALUATE PRELIMINARY IMPLEMENTATION AND EFFECTIVENESS OUTCOMES USING A HYBRID TYPE I RESEARCH DESIGN. FOLLOWING A DEPLOYMENT-FOCUSED MODEL, WE WILL CONDUCT ITERATIVE SMALL CASE-SERIES TRIALS AND COLLECT DATA FROM COMMUNITY-PARTNERS REGARDING NECESSARY INTERVENTION DOSAGE AND CRITICAL IMPLEMENTATION OUTCOMES (INCLUDING ACCEPTABILITY, TOLERABILITY, AND SAFETY). RESULTS FROM THIS AIM WILL INFORM MANUAL ADAPTATION. WE WILL THEN RECRUIT 72 MOTHERS OF CHILDREN BETWEEN THE AGES OF 5 AND 10 FROM COMMUNITY-SERVING ORGANIZATIONS IN THE LOW RESOURCE, MAJORITY-MINORITY, CITY OF FLINT, MICHIGAN. PARTICIPANTS WILL BE RANDOMIZED TO RECEIVE EFT OR A MEMORY-FOCUSED COMPARISON INTERVENTION. OUTCOMES WILL EVALUATE THE EFFECT OF EFT ON REDUCING MATERNAL DELAY DISCOUNTING AND HARSH PARENTING, AND IMPROVING CHILD CLINICAL OUTCOMES. EXPLORATORY ANALYSES WILL ALSO CONSIDER THE UTILITY OF THE ADAPTED INTERVENTION FOR IMPROVING ENGAGEMENT AND UPTAKE OF BEHAVIORAL PARENT TRAINING TECHNIQUES. FINDINGS FROM THIS STUDY WILL BE USED TO PLAN A LARGE-SCALE (R01), HYBRID TYPE II INTERVENTION TRIAL AND WILL INFORM PUBLIC HEALTH APPROACHES FOR IMPROVING YOUTH MENTAL HEALTH IN VULNERABLE COMMUNITIES.

HIGH-RESOLUTION CHARACTERIZATION OF HUMAN LEUKOCYTE ANTIGEN GENES IN DIVERSE POPULATIONS TO STUDY THE GENETICS OF FOOD ALLERGY - FOOD ALLERGIES ARE COMMON, COSTLY, AND POTENTIALLY LIFE-THREATENING. EPIDEMIOLOGIC STUDIES SUGGEST PREVALENCE IS GROWING, PARTICULARLY AMONG MINORITY POPULATIONS. TWIN STUDIES ESTIMATE THAT FOOD ALLERGIES ARE HIGHLY HERITABLE (>80%), UNDERSCORING THE IMPORTANCE OF GENETIC CAUSES. TO DATE, THERE HAS BEEN ONLY A FEW GENOME-WIDE ASSOCIATION STUDIES OF FOOD ALLERGY AND NONE WITH AFRICAN AMERICANS OR LATINOS IN THE DISCOVERY SET. MOREOVER, THE PHENOTYPES USED IN THESE STUDIES HAVE BEEN INCONSISTENT. DESPITE THESE ISSUES, THERE HAVE BEEN SOME CONSISTENT FINDINGS, SUCH AS REPEATED ASSOCIATIONS WITH HUMAN LEUKOCYTE ANTIGEN (HLA) GENES. THIS IS NOT ALTOGETHER SURPRISING GIVEN THE ROLE THAT HLA PROTEINS PLAY IN PRESENTING ANTIGENS TO EFFECTORS CELLS, RESULTING IN EITHER TOLERANCE OR SENSITIZATION. HOWEVER, OUR ABILITY TO IDENTIFY CAUSAL VARIANTS IN HLA GENES IS HAMPERED BY THE STRUCTURAL COMPLEXITY OF THE MAJOR HISTOCOMPATIBILITY COMPLEX (MHC) REGION (I.E., AN EXCEPTIONALLY HIGH DEGREE OF POLYMORPHISM, NUMEROUS PSEUDOGENES, AND LONG-RANGE LINKAGE DISEQUILIBRIUM). IN THIS APPLICATION, WE TAKE A MULTIFACETED APPROACH TO BETTER UNDERSTANDING FOOD SENSITIZATION, FOOD ALLERGY DISPARITIES, AND THE UNDERLYING RISK FACTORS. WE HAVE ASSEMBLED THREE LARGE, DIVERSE STUDY COHORTS (COMBINED N=12,882): THE STUDY OF ASTHMA PHENOTYPES AND PHARMACOGENOMIC INTERACTIONS BY RACE-ETHNICITY (SAPPHIRE); THE STUDY OF AFRICAN AMERICANS, ASTHMA, GENES & ENVIRONMENT (SAGE); AND THE GENES- ENVIRONMENTS & ADMIXTURE IN LATINO AMERICANS (GALA II). THESE MULTI-ETHNIC COHORTS HAVE A WEALTH OF EXISTING SOCIO-ENVIRONMENTAL EXPOSURE DATA AND HIGH-DEPTH SHORT-READ WHOLE-GENOME SEQUENCING (WGS). IN AIM 1, WE WILL UTILIZE IGE ARRAYS TO BROADLY CHARACTERIZE ALLERGIC SENSITIZATION FOR 94 DIFFERENT FOODS AND 77 FOOD ALLERGEN COMPONENTS. THESE DATA WILL ALLOW US TO IDENTIFY DIFFERENCES IN FOOD SENSITIZATION BETWEEN POPULATION GROUPS (I.E., AFRICAN AMERICANS, LATINOS [MEXICANS AND PUERTO RICANS], AND EUROPEAN AMERICANS) AND TO ASSESS THE RELATIONSHIP BETWEEN SOCIO-ENVIRONMENTAL EXPOSURES (E.G., AIR POLLUTION, TOBACCO SMOKE, NEIGHBORHOOD CHARACTERISTICS, AND PERINATAL EVENTS) AND FOOD ALLERGEN SENSITIZATION. IN AIM 2, WE WILL LEVERAGE THE LARGE AND DIVERSE STUDY POPULATION, EXISTING WGS, AND IGE SENSITIZATION DATA FROM AIM 1 TO INVESTIGATE FOR GENETIC VARIANTS ASSOCIATED WITH ANY FOOD SENSITIZATION AND SENSITIZATION TO SPECIFIC COMMON FOOD ALLERGENS (E.G., PEANUT, SEAFOOD, TREE NUT, DAIRY, AND EGG). ASSOCIATIONS WILL BE REPLICATED IN A LARGE PEDIATRIC COHORT FROM THE CHILDREN’S HOSPITAL OF PHILADELPHIA. TO OVERCOME THE AFOREMENTIONED CHALLENGES OF THE MHC REGION, IN AIM 3 WE PROPOSE A NOVEL APPROACH, WHICH EXPLOITS THE BENEFITS OF SHORT-READ DNA SEQUENCING (HIGH FIDELITY) AND RECENT ADVANCES IN ULTRA-LONG-READ DNA SEQUENCING. THE RESULTING DE NOVO, HIGH-RESOLUTION ASSEMBLIES OF THE MHC REGION WILL BE USED TO LOOK FOR HLA VARIANTS ASSOCIATED WITH FOOD SENSITIZATION IN A LARGE SAMPLE OF AFRICAN AMERICAN PARTICIPANTS FROM SAPPHIRE (N=1,860) AND SAGE (N=849). THESE DATA WILL PROVIDE AN UNPRECEDENTED LOOK AT THE RELATIONSHIP BETWEEN HLA VARIATION AND BOTH SEAFOOD AND PEANUT SENSITIZATION.

OVER 30% OF AMERICAN ASTRONAUTS HAVE DEVELOPED OCULAR REFRACTION CHANGE AFTER LONG DURATION SPACE FLIGHT ON THE INTERNATIONAL SPACE STATION (ISS) (65). RECENT FINDINGS HAVEALSO INCLUDED STRUCTURAL CHANGES OF THE EYE (PAPILLEDEMA GLOBE FLATTENING CHOROIDAL FOLDS) AND THE OPTIC NERVE (SHEATH DILATATION TORTUOSITY AND KINKING) AS WELL AS IMAGING SIGNS AND LUMBAR PUNCTURE DATA INDICATIVE OF ELEVATED INTRACRANIAL PRESSURE (ICP) (56; 65). WHILE SHORT DURATION SPACE FLIGHT IS ALSO CHARACTERIZED BY VISION DISTURBANCES THESE ARE GENERALLY TRANSIENT AND DO NOT APPEAR TO HAVE LASTING IMPACTS ON THE STRUCTURE OR FUNCTIONOF THE EYE. CHANGES IN VISION EYE AND ADNEXA MORPHOLOGY ARE HYPOTHESIZED TO BE THE RESULT OF SPACE FLIGHT-INDUCED CEPHALAD FLUID SHIFTS AND TRANSIENTLY ELEVATED INTRACRANIALPRESSURE (65). THIS HYPOTHESIS HOWEVER HAS NOT BEEN SYSTEMATICALLY TESTED. IN EARLIER ANECDOTAL PUBLICATIONS ICP ELEVATION IN LONG-DURATION SPACE FLIGHT HAS BEEN INFERRED BUT WITHOUT ASSOCIATION WITH STRUCTURAL OR FUNCTIONAL CHANGES OF THE EYE (74). FURTHERMORE WHILE FLUID SHIFTS AND COMPARTMENTALIZATION DURING SHORT-DURATION SPACE FLIGHT (SPACE SHUTTLE MISSIONS) HAVE BEEN STUDIED THE FLUID DISTRIBUTION PATTERNS AND THEIR EFFECTS ON INTRACRANIAL PRESSURE OR THE STRUCTURE AND FUNCTION OF THE SENSORY ORGANS IN THE COURSE OF LONG-DURATION SPACE FLIGHT ARE NOT WELL KNOWN.

REGULATORY T CELLS IN GESTATION AND CHILDHOOD ALLERGIC DISEASE

DOES PERFLUOROCARBON ATTENUATE THE SEVERITY OF SAH BY LIMITING VASOSPASM AND IMPROVING TISSUE OXYGENATION? - SUBARACHNOID HEMORRHAGE (SAH) IS ONE OF THE DEADLIEST OF HEMORRHAGIC STROKE TYPES; HOWEVER, NO EFFECTIVE THERAPEUTIC INTERVENTION IS YET AVAILABLE, OTHER THAN SUPPORTIVE CARE. VASOSPASM IS REPORTED TO TRIGGER WITHIN THE FIRST THREE DAYS AFTER THE ONSET OF SAH AND SUSTAIN FOR 1-2 WEEKS. THE VASOSPASM RESULTS IN DELAYED CEREBRAL ISCHEMIA (DCI) WHICH IS CONSIDERED AS THE MAIN CAUSE OF MORTALITY AFTER SAH. SINCE VASOSPASM LEADS TO A DECREASE IN O2 LEVEL IN THE AFFECTED REGIONS OF THE BRAIN, NOVEL METHODS TO SUPPLY O2 TO THE COMPROMISED BRAIN REGION COULD PLAY A CRITICAL ROLE IN SALVAGING THE AREA AT RISK. HYPERBARIC OXYGEN/AIR THERAPY MAY HAVE A BENEFICIAL EFFECT IN DECREASING THE PATHOPHYSIOLOGY OF SAH BY INCREASING DISSOLVED TISSUE O2. HOWEVER, SUCH TREATMENT IS COMPLEX, TIME-LIMITED (A FEW HOURS AT A TIME), EXTENSIVE MONITORING, AND TRAINED PERSONNEL. THEREFORE, HERE WE PROPOSE PERFLUOROCARBON (PFC)-BASED EMULSION OXYGENT (REFERRED TO AS PFC-OXYGENT ONWARDS), WHICH INCREASES DISSOLVED O2 IN BLOOD AND TISSUE. PFC-OXYGENT IS REPORTED TO HAVE AN EXTENDED HALF-LIFE OF ABOUT 3D. PFCS ARE EMULSIFIED COMPOUNDS THAT CAN CARRY AND RELEASE O2 FUNDAMENTALLY DIFFERENTLY THAN DOES THE HEMOGLOBIN. THE PARTICLE SIZE OF THESE EMULSIONS ALLOWS FOR PFCS TO GET TO PLACES WHERE RED BLOOD CELLS ARE BLOCKED SUCH AS CAPILLARIES AFFECTED IN SAH. IN A MODEL OF STRIATED MUSCLE AND CEREBRAL AIR EMBOLISM, WE HAVE SHOWN THAT PFC-OXYGENT INCREASED CEREBRAL BLOOD FLOW AND DELIVERED O2 TO THE AFFECTED AREA EVEN WITH LITTLE OR NO RED CELL MOVEMENT. MOREOVER, IN PRECLINICAL TBI, WE SHOWED THAT PFC-OXYGENT AUGMENTS CEREBRAL O2 LEVEL. THESE DATA INDICATE THE THERAPEUTIC POTENTIAL OF PFC-OXYGENT IN AN ACUTE CEREBRAL PATHOLOGY AND ITS POTENTIAL EFFICACY IN SAH WHERE CEREBRAL VASOSPASM PLAYS A VITAL ROLE IN THE PROGRESSION OF PATHOLOGICAL AND FUNCTIONAL OUTCOMES. SINCE PFC IS WELL TOLERATED IN HUMANS AND THE SAFETY PROFILE OF THIS COMPOUND HAS ALREADY BEEN TESTED, IT IS A PRIME CANDIDATE FOR DRUG REPURPOSING. HERE, WE ARE TESTING THE HYPOTHESIS THAT PFC-OXYGENT TREATMENT AFTER SAH CAN INCREASE O2 DELIVERY TO THE COMPROMISED AREA AFTER THE SAH, ATTENUATE OXIDATIVE STRESS, AND IMPROVE PATHOLOGICAL/FUNCTIONAL OUTCOMES. AIM 1: TO TEST WHETHER PFC RESCUES FUNCTIONAL OUTCOMES AND NEUROPATHOLOGY AFTER SAH. THIS AIM WILL TEST THE EFFECT OF PFC-OXYGENT ON FUNCTIONAL AND ANATOMICAL OUTCOMES AFTER SAH IN YOUNG AND OLD MALE AND FEMALE MICE. AIM 2: TO TEST WHETHER PFC IMPROVES TISSUE OXYGENATION AND CEREBRAL BLOOD FLOW FOLLOWING SAH. IN THIS AIM, WE WILL TEST WHETHER PFC IMPROVES LOCAL/GLOBAL CEREBRAL OXYGENATION, TISSUE SAMPLED MITOCHONDRIAL ACTIVITY, AND REDUCES OXIDATIVE STRESS AFTER SAH. THE PROPOSED STUDY WILL COLLECTIVELY PROVIDE THE ROBUSTNESS OF THE THERAPEUTIC POTENTIAL OF THIS CLINICALLY USED DRUG IN SAH. BECAUSE MOST OF THE PHARMACOKINETICS, PHARMACODYNAMICS, AND SAFETY OF PFC-OXYGENT IS KNOWN, REPURPOSING OF THIS DRUG IN REGULATING SAH OUTCOMES WOULD BE EXPEDITED AND OF HIGH TRANSLATIONAL VALUE.

CHILDHOOD HEALTH DISPARITIES: EXPLORATION OF PRENATAL EXPOSURES IN PRIMARY TEETH

COMPREHENSIVE ANALYSIS OF GENE-ENVIRONMENT INTERACTION IN SARCOIDOSIS

PLASMA BIOMARKERS OF CEREBRAL DISEASE IN X-LINKED ADRENOLEUKODYSTROPHY

EXPLORATION OF CADMIUM AS AN ENDOCRINE DISRUPTOR IN PROSTATE CANCER DISPARITIES

MODELING GLYMPHATIC SYSTEM AND APPLICATION FOR AGING - PROJECT SUMMARY BRAIN WAS LONG CONSIDERED TO BE DEVOID OF A CONVENTIONAL LYMPHATIC SYSTEM. HOWEVER, RECENT STUDIES LED TO THE CONCEPTUALIZATION OF A SYSTEM RESPONSIBLE FOR THE REMOVAL OF INTERSTITIAL SOLUTE INTO THE CEREBROSPINAL FLUID (CSF), MOSTLY AROUND THE VEINS, NAMED, THE GLYMPHATIC SYSTEM. THIS SYSTEM PROVIDES A PATHWAY OF HIGHLY ORGANIZED CONVECTIVE FLUID FLOW THAT DRIVES CLEARANCE OF INTERSTITIAL SOLUTE FROM THE BRAIN PARENCHYMA. THE GLYMPHATIC SYSTEM PLAYS AN IMPORTANT ROLE IN NEUROLOGICAL DISEASES. MAGNETIC RESONANCE IMAGING (MRI) IS A SUITABLE NON-INVASIVE TOOL FOR STUDYING THIS SYSTEM, HOWEVER, FEW STUDIES HAVE ATTEMPTED TO MODEL THE FLOW THROUGH THE GLYMPHATIC PATHWAYS IN ORDER TO DERIVE QUANTITATIVE PARAMETERS FROM MRI DATA. IN THIS PROJECT, WE WILL DEVELOP, OPTIMIZE AND VALIDATE NEW IMAGING TECHNIQUE USING MRI TO DERIVE QUANTITATIVE MAPS REPRESENTING THE DYNAMICS OF THE VASCULAR AND GLYMPHATIC SYSTEM. THEN, WE WILL INVESTIGATE AGING EFFECTS ON VASCULAR AND GLYMPHATIC SYSTEMS FOR WASTE CLEARANCE USING THE OPTIMIZED IMAGING TECHNIQUE AND ANALYSIS. AGING IN BRAIN IS ASSOCIATED WITH ARTERIAL STIFFENING AND ARTERIAL COMPLIANCE REDUCTION THAT MAY LED TO DEMENTIA AND ALZHEIMER DISEASE. DATA GENERATED FROM THIS APPLICATION WILL PROVIDE NEW INSIGHTS INTO THE EFFLUX PATHWAYS OF BRAIN WASTE CLEARANCE AND PROVIDE ADEQUATE MATERIALS PURSUING A TRANSLATIONAL INVESTIGATION OF THIS SYSTEM. IF THE AIMS OF THE PROJECT ARE ACHIEVED, SIGNIFICANT IMPROVEMENT IN PATIENT MANAGEMENT WILL BE ATTAINED BY QUANTIFYING THE GLYMPHATIC SYSTEM AND EFFLUX PATHWAYS CONTRIBUTION TO NEURODEGENERATIVE DISEASES AND FUNCTIONAL DEFICITS SUCH AS TBI, MULTIPLE SCLEROSIS, HEMORRHAGE, AND EPILEPSY.

IDENTIFYING FACTORS INFLUENCING ALCOHOL USE AFTER BARIATRIC SURGERY: AN ECOLOGICAL MOMENTARY ASSESSMENT - BARIATRIC SURGERY IS THE MOST EFFECTIVE WEIGHT LOSS TREATMENT FOR PATIENTS WHO ARE SEVERELY OBESE; HOWEVER, 1 IN 5 PATIENTS DEVELOP AN ALCOHOL USE DISORDER (AUD) AFTER UNDERGOING SURGERY. AFTER SURGERY, CHANGES IN METABOLISM, HORMONE LEVELS, AND BEHAVIORS ALTER THE REWARDING EFFECTS OF ALCOHOL WHILE CONCURRENTLY CHANGING ITS ABSORPTION RATE, PUTTING PATIENTS AT SIGNIFICANTLY ELEVATED RISK OF HAZARDOUS DRINKING. TO BETTER UNDERSTAND THE DEVELOPMENT OF AUDS AFTER BARIATRIC SURGERY, WE MUST FIRST IDENTIFY FACTORS LEADING TO RE-INITIATION OF ALCOHOL USE AND ESCALATION TO HEAVY DRINKING. PROMISING AREAS INCLUDE MOOD AND EATING BEHAVIORS. THE PURPOSE OF THE PROPOSED STUDY IS TO IDENTIFY THE DISTAL AND PROXIMAL FACTORS THAT CONTRIBUTE TO RE-INITIATION AND EPISODIC ALCOHOL USE FOLLOWING BARIATRIC SURGERY. WE WILL USE AN EXPLORATORY SEQUENTIAL MIXED METHODS APPROACH AND FIRST OBTAIN QUALITATIVE DATA TO INFORM THE QUANTITATIVE PHASE. IN THE QUALITATIVE PHASE, WE WILL CONDUCT INTERVIEWS OF PATIENTS WHO ARE BETWEEN 6 MONTHS AND 3-YEARS POST-BARIATRIC SURGERY (N= 30) TO IDENTIFY THE REASONS THEY CONSUMED ALCOHOL AFTER BARIATRIC SURGERY. WE WILL ALSO INQUIRE ABOUT THE FREQUENCY, AMOUNT, AND THE ANTECEDENTS AND CONSEQUENCES OF EPISODIC ALCOHOL USE (I.E., MOOD, EATING BEHAVIORS). THIS INFORMATION WILL BE USED TO INFORM THE QUANTITATIVE DATA PHASE (I.E., FINALIZE THE CONSTRUCTS TO ASSESS, HOW AND WHEN TO MEASURE THESE VARIABLES, AND THE FREQUENCY OF ASSESSMENT). IN THE QUANTITATIVE PHASE, PATIENTS (N= 100) WILL ALSO BE RECRUITED BETWEEN 6 MONTHS AND 3-YEARS POST-SURGERY. PARTICIPANTS WILL COMPLETE MEASURES OF SUBSTANCE USE, MOOD, AND EATING BEHAVIORS AT BASELINE AND AT 6- AND 12-WEEKS POST-BASELINE TO CAPTURE LONGER-TERM DATA TO IDENTIFY DISTAL FACTORS ASSOCIATED WITH ALCOHOL USE. WITHIN THE 12-WEEK STUDY PERIOD, PARTICIPANTS WILL ALSO BE RANDOMLY ASSIGNED A 3-WEEK PERIOD IN WHICH THEY WILL COMPLETE AN ECOLOGICAL MOMENTARY ASSESSMENT (EMA) DESIGN. THE EMA DESIGN CONSISTS OF BRIEF, DAILY MORNING AND EVENING ASSESSMENTS IN “REAL-TIME” REGARDING EMOTIONS AND BEHAVIORS (I.E., SUBSTANCE USE, AFFECT, AND EATING BEHAVIORS), WHICH WILL ALLOW US TO IDENTIFY THE FACTORS CONTRIBUTING TO EPISODIC ALCOHOL USE (I.E., PROXIMAL FACTORS). WE WILL ALSO EXAMINE INTENDED AND UNINTENDED DRINKING. OUR LONG-TERM GOAL IS TO BETTER UNDERSTAND THE PROGRESSION FROM RE-INITIATION OF ALCOHOL USE, TO HEAVY USE, TO DEVELOPMENT OF AN AUD, WHICH WILL ASSIST IN TARGETING INTERVENTIONS TO PREVENT AUDS. IN ADDITION TO BEING THE FIRST STUDY TO EXAMINE DISTAL AND PROXIMAL FACTORS OF POST-SURGICAL ALCOHOL USE, THIS PROJECT CONTAINS MULTIPLE INNOVATIVE COMPONENTS INCLUDING AN EMA DESIGN WHICH ALLOWS FOR THE EXAMINATION OF UNINTENDED DRINKING. FURTHER, GIVEN PARTICIPANTS WILL HAVE VARYING HISTORIES OF ALCOHOL USE PRIOR TO SURGERY, WE WILL EXPLORE WHETHER DISTAL AND PROXIMAL PREDICTORS ARE DIFFERENTIALLY PREDICTIVE OF DRINKING AMONG THOSE WITH AND WITHOUT A HISTORY OF HEAVY DRINKING PRIOR TO SURGERY. THE PROPOSED LINE OF RESEARCH IS SIGNIFICANT AND RELEVANT TO NIH’S MISSION BECAUSE IT WILL LEAD TO TAILORED, EFFECTIVE INTERVENTIONS TO REDUCE ALCOHOL USE AND PREVENT THE DEVELOPMENT OF AN ALCOHOL USE DISORDER AMONG PATIENTS AT HIGH RISK (I.E., THOSE WHO UNDERGO BARIATRIC SURGERY).

DECIPHERING NEUROINFLAMMATION-SPECIFIC REGULATORY RNA AND METABOLIC NETWORKS IN HUMAN IPSC-DERIVED ASTROCYTES IN CEREBRAL ADRENOLEUKODYSTROPHY

RACIAL VARIATION IN FOOD ALLERGY: MECHANISMS AND RISK

IMPAIRMENT OF THE GLYMPHATIC SYSTEM IN THE AGED DIABETIC BRAIN

THE RISK AND CLINICAL AND MOLECULAR CHARACTERISTICS OF BREAST CANCER IN WOMEN WITH NEUROFIBROMATOSIS TYPE 1

MITIGATING CUTANEOUS RADIATION INJURY WITH CXCR4 ANTAGONIST

SKIN BARRIER ADAPTATION

THE DARC SIDE OF BREAST CANCER

SCHWANN CELL DERIVED EXOSOMES IMPROVE DIABETIC PERIPHERAL NEUROPATHY IN TYPE II DIABETIC MICE

DECODING TGF-BETA SIGNALING PATHWAYS IN SKIN LANGERHANS CELLS - ABSTRACT LANGERHANS CELLS (LCS), THE SKIN RESIDING DENDRITIC CELLS (DCS), CONTROL BOTH ADAPTIVE IMMUNITY AND IMMUNE TOLERANCE IN SKIN AND ARE INVOLVED IN THE DEVELOPMENT OF A VARIETY OF SKIN DISEASES. TRANSFORMING GROWTH FACTOR-SS1 (TGFSS1) IS A CRUCIAL FACTOR FOR LC MAINTENANCE AND FUNCTION. TGFSS1 SIGNALS THROUGH INTERACTIONS WITH TGFB RECEPTORS TO ACTIVATE EITHER SMAD-DEPENDENT OR SMAD-INDEPENDENT PATHWAYS TO REGULATE TGFB1 TARGET GENES AND CELLULAR FUNCTION. HOWEVER, THE SIGNALING PATHWAYS, THE DETAILED MOLECULAR NETWORKS OF TGFB1-MEDIATED LC MAINTENANCE AND FUNCTIONAL REGULATION, AND THE SPECIFIC ROLE OF TGFB1 AND RELATED MECHANISMS IN EMBRYONIC LC DEVELOPMENT REMAIN UNCLEAR. OUR RECENT WORK AND PRELIMINARY STUDIES SHOWED THAT TGFB1 IS ABSOLUTELY REQUIRED FOR EMBRYONIC LC DEVELOPMENT, IN WHICH TGFSS-ACTIVATED KINASE 1 (TAK1), AND NOT SMADS, LEADS THE DOMINANT TGFB1 SIGNALING PATHWAY; THAT TAK1, NOT SMADS, IS INVOLVED IN LC POSTNATAL DIFFERENTIATION; AND THAT SMAD SIGNALING PATHWAYS ARE DOMINANT DURING INFLAMMATION- INDUCED LC REPOPULATION. THESE RESULTS STRONGLY SUGGEST THAT DIVERSE TGFB SIGNALING PATHWAYS MEDIATE LC REGULATIONS IN EMBRYONIC ONTOGENY VERSUS POSTNATAL HOMEOSTASIS OR INFLAMMATION- INDUCED REPOPULATION. IN THE PROPOSED STUDIES, WILL USE DIFFERENT SPATIAL- AND TEMPORAL-SPECIFIC AND TRANSIENT INDUCIBLE GENE MUTATION MOUSE MODELS COMBINED WITH RNA-SEQ, SCRNA-SEQ, CHIP-SEQ, IMAGING FACS, AND IN VIVO/IN VITRO LENTIVIRUS-MEDIATED GENE ACTIVATION AND DELETION STRATEGIES, AIMING TO DECIPHER THE CONTEXT-DEPENDENT SPECIFICITIES OF TGFB SIGNALING PATHWAYS AND RELATED MOLECULAR NETWORKS THAT REGULATE LC ONTOGENY, POSTNATAL HOMEOSTASIS, AND REPOPULATION. RESULTS FROM THE PROPOSED STUDIES WILL NOT ONLY FURTHER OUR UNDERSTANDING OF LC BIOLOGY, BUT ALSO WILL SHED NEW LIGHT ON POTENTIAL THERAPEUTIC TARGETS WITH HIGH SPECIFICITY FOR THE TREATMENT OF LC-RELATED DISEASES.

4-HYDOXY-2-NONENAL IN MITOCHONDRIAL DNA DAMAGE AND CONTRACTILE DYSFUNCTION IN DIABETIC HEART: A ROLE FOR ALDEHYDE DEHYDROGENASE 2

CEREBRAL ENDOTHELIAL DERIVED-EXOSOMES IMPROVE COGNITIVE FUNCTION IN AGED DIABETIC RAT

ABUSE LIABILITY ASSOCIATED WITH CHRONIC HYPNOTIC USE

MIRNAS AND EPIDERMAL LANGERHANS CELL DEVELOPMENT AND FUNCTION

FUNCTIONAL CHARACTERIZATION OF PSEUDOGENES AS NEW BIOMARKER IN PROSTATE CANCER

THE ROLE OF SHIP2 IN MINERALIZATION

SHEAR WAVE ELASTOGRAPHY TO PREDICT REPAIR TISSUE HEALING AND SHOULDER FUNCTION AFTER ROTATOR CUFF REPAIR

A CLINICALLY VIABLE NONINVASIVE METHOD FOR DIRECT MEASUREMENT OF MECHANICAL STRAINS IN VERTEBRAL BONE

DIGITAL TOMOSYNTHESIS-BASED MICROSTRUCTURAL MEASURES TO PREDICT VERTEBRAL FRAGILI

THE IMPROVING ATTENDANCE TO CARDIAC REHABILITATION (IATTEND) TRIAL

PROMOTING SMOKING CESSATION AMONG YOUTH EXITING FOSTER CARE

IMPROVING THE RADIATION THERAPEUTIC RATIO BY INHIBITING PROINFLAMMATORY CYTOKINES