Veterans Education And Research Association Of Michigan

RANDOMIZED CONTROLLED TRIAL OF SERTRALINE, PROLONGED EXPOSURE THERAPY AND THEIR COMBINATION OF OEF/OIF WITH PTSD

EFFECTS OF NOISE EXPOSURE ACROSS THE LIFESPAN ON BALANCE AND STABILITY IN OLDER ADULTS - ABSTRACT LOSS OF STABILITY AND FALLS IS A MAJOR RISK FACTOR FOR INJURY AND DEATH IN OLDER ADULTS. PREVIOUSLY OVERLOOKED, LIFETIME NOISE EXPOSURE HAS BEEN SHOWN TO CAUSE DAMAGE TO THE VESTIBULAR PERIPHERY; ALTHOUGH, ANIMAL MODELS AND HUMAN STUDIES THAT CAN PROVIDE A MECHANISTIC BASIS CONNECTING NOISE-INDUCED VESTIBULAR DYSFUNCTION AND AGE-RELATED FALL RISK ARE LIMITED. THE VESTIBULAR SYSTEM PLAYS A CRITICAL ROLE IN DETECTION OF HEAD MOVEMENTS AND ORIENTATION WITH RESPECT TO GRAVITY AND IS ESSENTIAL FOR NORMAL VISION AND POSTURAL CONTROL. DUE TO THEIR ANATOMICAL PROXIMITY TO THE COCHLEA, THE OTOLITH ORGANS ARE EXPOSED TO SOUND PRESSURE AND ARE AT RISK FOR NOISE OVERSTIMULATION, WHICH MAY CONTRIBUTE TO VESTIBULAR DYSFUNCTION. HOWEVER, DAMAGE MAY NOT BE LIMITED TO THE OTOLITH ORGANS. RECENT STUDIES HAVE LINKED NOISE OVERSTIMULATION TO DECREASED VESTIBULAR NERVE ACTIVITY AND LOSS OF A SPECIALIZED CLASS OF IRREGULARLY FIRING VESTIBULAR AFFERENTS WHICH EXHIBIT ENHANCED SENSITIVITY TO ACCELERATION. IT IS LIKELY THAT THESE AFFERENTS PLAY AN IMPORTANT ROLE INITIATING POSTURAL COMPENSATION FOR ABRUPT CHANGES IN HEAD OR BODY POSITION DUE TO THEIR PHYSIOLOGICAL CHARACTERISTICS AND THEIR PROJECTION TO SECONDARY VESTIBULAR NEURONS THAT PROJECT TO THE SPINAL CORD. THEREFORE, THE EFFECTS OF NOISE MAY ACCELERATE DISABILITY ASSOCIATED WITH NATURAL AGING. THE GOAL OF THIS PROPOSAL IS TO CHARACTERIZE VESTIBULAR LOSS ASSOCIATED WITH NATURAL AGING AND HOW IT IS COMPOUNDED BY CUMULATIVE NOISE EXPOSURES THROUGHOUT ONE’S LIFE. THUS, WE WILL SYSTEMATICALLY INVESTIGATE THE EFFECTS OF NOISE EXPOSURE ACROSS THE LIFESPAN ON OTOLITH AND CANAL STRUCTURE AND FUNCTION (AIM 1), SPECIFICALLY ADDRESS THE EXTENT OF IRREGULAR AFFERENT DAMAGE AND ITS FUNCTIONAL CONSEQUENCES (AIM 2), AND ASSES CHANGES IN POSTURE, MOBILITY AND BALANCE WITH NOISE EXPOSURE (AIM 3). CHANGES IN SENSORY CELL SYNAPSES WILL BE CORRELATED WITH VESTIBULAR REFLEX IMPAIRMENT AND FALL RISK ASSOCIATED WITH POSTURAL INSTABILITY AND LOSS OF BALANCE. TO IMPROVE OUR UNDERSTANDING OF HOW THESE CHANGES OCCUR OVER THE LIFETIME, WE WILL ASSESS ANATOMICAL AND FUNCTIONAL CHANGES IN EARLY-, MIDDLE-, AND LATE-ADULTHOOD. FURTHER, FUNCTIONAL EXPERIMENTS WILL BE DONE IN PARALLEL IN RATS AND HUMAN PARTICIPANTS FOR MAXIMAL TRANSLATION OF OUR RESULTS TO THE CLINIC. INDIVIDUALLY, BOTH ANIMAL AND RODENT STUDIES HAVE PROVEN INVALUABLE TO OUR UNDERSTANDING OF THE EFFECTS OF NOISE EXPOSURE ON VESTIBULAR FUNCTION. HOWEVER, BOTH HAVE LIMITATIONS THAT CAN BE BEST ADDRESSED WITH A SET OF COMPLIMENTARY STUDIES IN THE TWO SYSTEMS. THIS PROPOSAL DESCRIBES A COMPREHENSIVE, MULTIDISCIPLINARY APPROACH THAT STRIVES TO EVALUATE THE UNDERLYING MECHANISMS IN INCREASED FALLS AND FALL RISK DUE TO A HISTORY OF NOISE EXPOSURE IN OLDER ADULTS. THE SUSCEPTIBILITY OF THESE INDIVIDUALS TO POTENTIALLY FATAL FALLS UNDERSCORES THE NEED FOR A SYSTEMATIC APPROACH, THAT CAN EVENTUALLY RESULT IN IMPROVED TRAINING AND REHABILITATION METHODS TO BE USED WITH THIS POPULATION.

HARNESSING OPPORTUNITIES TO SCREEN FOR ESOPHAGEAL ADENOCARCINOMA (HOSEA)

MACHINE LEARNING ANALYSIS OF LONGITUDINAL LABORATORY AND IMAGING DATA TO PERSONALIZE THE PREDICTION OF SEVERE COMPLICATIONS IN VETERANS WITH CROHNS D

DEFINING HEPATOCELLULAR CARCINOMA SUBTYPES AND TREATMENT RESPONSES IN PATIENT-DERIVED TUMORGRAFTS