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Page 1: Mentor Name: Mentor Department Title of Proposed Project ... · Heparinoids to Determine Binding Specificity and Ultimately Prevent Tau Propagation Between Cells ... have a higher

MentorName: MentorDepartment TitleofProposedProject Hypothesis/SpecificAim RamiHallac AnalyticalImagingand

ModelingAutomaticClassificationofNormalandCleftLipPhotosusingComputerVision

HypothesisComparedtomanualhumansegmentation,theCADesystemwillaccuratelysegmentthelipinnormalsubjectsandpatientswithcleftlipand/orpalatetoautomaticallycategorizethepatients'conditionbasedonshapeanalysis,removingbiasandimprovingtheclassification,detection,andefficacyofcleftlipsurgeryprocedures,ultimatelyimprovingpatientsatisfaction.

TiffanyMoon Anesthesiology&PainManagement

OutcomesofGeneralAnesthesiainPatientswithaHistoryofCocaineUse:ARetrospectiveReview

Hypothesis:Weseektoevaluatetheclaimthatpatientswhotestpositiveforcocainemetabolites,butdonotappearacutelytoxicandhaveanormalECGandvitalsignswithinthenormalrange,willnothaveanincreasedrateofperioperativecomplicationsduringelectivesurgerycomparedtosimilarpatientswithnegativeurinecocainescreeningtests.However,itispossiblethatpatientswhoarechroniccocaineusersmayhaveahigheranestheticrequirement.SpecificAim:Thegoalofthesummerresearchfellowshipwillbetoenroll40patientsinapilotstudyatParklandMemorialHospital.Ananalysisofthepilotstudydatawillprovidecriticaldataonapatientpopulation,whichhashistoricallybeenreluctanttoself-report.TheinformationthatweobtainwillbeusedtoinformtheimplementationofagreaterIRB-approvedstudybydeterminingthetrueincidenceofthisphenomenonatourinstitution,planningfutureenrollmentthroughapoweranalysis,identifyingtrendsinthedata,andgeneratingnewhypothesesforfutureresearchefforts.

TiffanyMoon Anesthesiology&PainManagement

TheDifficultAirway:IncidenceandPredictorsinLeanvs.ObesePatientsinaLargePublicTeachingHospital

OurhypothesisisthatBMIaloneisaweakpredictorfordifficultintubationinobeseindividuals.Otherfactorssuchasneckcircumference(NC),thyromentaldistance(TMD),theNC/TMDratio,presenceofOSA,interincisordistance(IID),upperlipbitetest(ULBT)andMallampati(MP)scoremaybemorepredictiveofdifficultintubationinobeseindividuals.SpecificAim:Toassessthedifficultyofintubationusingtheintubationdifficultyscale(IDS),apreviouslyvalidatedtooltoassessthedifficultyofintubation(Adnetetal.,1997).

JarettBerry Cardiology TheAssociationbetweenPhysicalFitnessandLongevity

SpecificAim:TocharacterizetheassociationbetweenexercisetrainingonmeasuresofLVstrain.Wehypothesizethatexercisetrainingwillbeassociatedwithimprovementinleftventricularstrainaftersixmonthsofexercisetraining.

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SubhashBanerjee Cardiology VeteransAorticAneurysmCardiovascularOutcomeStudy

Secondaryendpoints:1.Tocomparetheprevalenceofatherothromboticriskfactors;concomitantnon-aorticCV)disease;PAD,andmajoradverseCVeventrates(MACE)inpatientswiththoracicorabdominalaorticaneurysms2.TocomparetheprevalenceofPAD,andmajoradverseCVeventrates(MACE)inpatientswithpatientswithaorticaneurysmsandthosewithoutaorticaneurysmHypothesis:Wehypothesizethatgiventheoverlappingrisksbetweenaorticaneurysmsandcoronaryarterydisease(CAD),especiallyhistoryoftobaccouseandhypertension,inapredominantlymaleveteranpopulation,theprevalenceofatherothromboticriskfactors;concomitantnon-aorticCV)disease;PAD,andmajoradverseCVeventrates(MACE)willbesimilarbetweenpatientswithaorticrootandotherthoracicorabdominalaneurysms.

JohnAbrams CellBiology TheRoleofTumorSuppressorp53inRestraintofRetrotransposonActivity

Hypothesis:Usingcomplementationassays,Abramslabrecentlydiscoveredthatnormalp53allelessuppresstransposonsbutmutantp53allelesfromcancerpatientscouldnot(Wylieetal,2016)..Inaddition,unrestrainedretrotransposonshavebeenobservedinp53drivenhumanandmousecancers.Thisprojectseekstoadvanceourunderstandingofthelinkbetweenthebiologyofp53andthebiologyoftransposons.Specifically,Iwilltestthehypothesisthattumorsuppressionbyp53isfundamentallycoupledtosystemsthatrestrainretrotransposonactivity.

MarcDiamond CenterforAlzheimer'sandNeurodegenerativeDiseases

TargetingDistinctTauStrainswithHeparinoidstoDetermineBindingSpecificityandUltimatelyPreventTauPropagationBetweenCells

Hypothesis:Heparinoidswilldifferentiallytargetdistincttaustrains.

RalphDeberardinis

Children'sMedicalCenterResearchInstitute

FeasibilityStudyUsingImagingBiomarkersinLungCancer

WehypothesizethatthesetumorcellsareusinglactateasanalternativefuelsourcefortheTCAcycle.Effectiveutilizationoflactatemightenabletumorcellstoresistglucosedeprivation;infact,asymbioticrelationshiphasbeenproposedbetweenwell-perfusedandpoorly-perfusedareasinthetumor,withpoorlyperfusedcellsconvertingglucosetolactateviaglycolysisandwell-perfusedcellsoxidizinglactateforenergy(5).

AmitPandya Dermatology ValidationoftheVitiligoDiseaseActivityIndex

Hypothesis:WehypothesizethatthesubjectiveVIDAscorecorrelatespoorlywithchangeinvitiligolesionsasmeasuredobjectivelybyinvestigatorsovertime.

AmitPandya Dermatology DeterminationofthelevelsofCXCL9and HypothesisWehypothesizethatchemokinelevelsdecreasein

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10intheinterstitialfluidoftheskinofpatientswithvitiligoundergoingtreatmentusinganovelblisteringtechnique

theskinofpatientswithvitiligowithtreatment.

MelissaMauskar Dermatology PredictorsofMortalityinPatientsWithSystemicCalciphylaxisandEndStageRenalDisease

Wehopetolookatclinicaldatatodetermineifthereareanypredictorsthatwouldindicatetheusefulnessofearlyinterventionordifferentmanagementprotocolsforpatientswithendstagerenaldiseasewhodevelopsystemiccalciphylaxis.Ourhypothesisisthatthesepatientshaveahighermortalityrate.

DonaldGlass Dermatology EvaluationoftheSafety,Efficacy,andIndicationsforUseofPentoxifyllineasaPost-SurgicalKeloidTreatmentOption

Hypothesis:Theuseofpentoxifyllineinpost-surgicalkeloidtreatmentwillbebeneficialindecreasingkeloidrecurrenceandwillbewell-toleratedbypatients.SpecificAims:Thisstudywillevaluatethesafetyandefficacyoforalpentoxifyllineinthetreatmentofkeloidsthroughevaluationofthefollowingfactors:1)Thenumberofpatientsgivenpentoxifyllineatoraroundthetimeofsurgery2)Thenumberofpatientswhodiscontinuedthemedication,andifso,whatwasthereason3)Therecurrencerateat6monthspost-surgeryforpatientswhotoleratedpentoxifylline,comparedtokeloidrecurrenceratescitedintheliteratureandforpost-surgicalpatientsseeninclinicwhodidnotuseortoleratepentoxifylline4)Thecriteriausedtoselectpatientsputonpentoxifyllineversusthosewhowerenot,suchashistoryofrecurrence,previoussurgery,numberoflesions,locationoflesions,andpainorpruritus

AmitPandya Dermatology Immunologicalprofileofinflammatorycellsintheskinofpatientswithvitiligoundergoingtreatment

WehypothesizethatCD8+andCD4+TcellsdiminishovertimeintheskinofpatientswithvitiligowithtreatmentwhileTregcellsincrease.

KimberlyReynolds GreenCenterforSystemsBiology,Biophysics

EvolutionofHighEfficiencyAllostericSwitches

HYPOTHESISTheengineeredDHFR/LOV2fusionswereconstructedwithoutanyoptimization,andshowedmodestregulation(2-foldchangeinenzymeactivity)inresponsetolight.Wenowaskhowthesectorarchitectureinfluencesoptimizationoftheseswitches.Wehypothesizethatthesectorarchitectureprovidesapre-wiredevolutionarypathforthegainofallostericregulation.Accordingly,shortpathsofpointmutationsshouldallowfortheoptimizationofallostericregulationdisplayedbysector-connectedDHFR/LOV2mutantswhilenon-sectorconnectedmutantsshouldremainresistanttoallostericcommunicationdespitefurthermutation.AIMS1.Measuretheeffectofeachmutationonregulationusingahighthroughputin

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vivoscreen.Todothis,IwilltransformeachlibraryintoanE.coliknock-outstrainmissingDHFR(ER2566ΔfolAΔthyA),growtheminselectivemediaunderlitanddarkconditions,andconductatimecourseexperimentinwhichsamplesareremovedfromthemixedcultureandtherelativefrequenciesofeachmutantalleleinthepopulationarequantifiedusingnext-generationsequencing.2.Identifymutantallelesthataltergrowthratesinlitversusdarkconditions,quantifytheiractivitythroughenzymekineticmeasurements,mapthesemutantallelesontotheDHFRstructure,andstatisticallycomparethesepositionstotheallostericnetworkdefinedbythesector.3.Solvehighresolutioncrystalstructuresofthemutantsdisplayingthegreatestmagnitudeinallostericregulationtobetterunderstandwhatstructuralchangesunderliethechangesinfunction.

JeffreyZigman HypothalmicResearch InvestigatingtheRoleofGhrelininPrader-WilliSyndrome

TheoverallgoalofthisSummerProjectistodirectlytestamodelpredictingnovelrolesofghrelininPWS.IncontrasttotheprevailingviewthatghrelinisdetrimentalinPWS,wenowproposethatghrelinelevationinPWSisprotective,preventingprematuredeathinchildrenwithPWSwhilealsohelpingtopreserveGHsecretionandmusclefunction,limitdepressionandanxiety,andensuresurvivalinadultswithPWS.WehypothesizethattheelevatedghrelininPWSisprotective,defendingagainstexaggerateddegreesofGHdeficiency,hypotonia,andhypoglycemia-ultimatelypreventingdeathofPWSneonates.Todirectlytestthishypothesis,wewilldetermineifcrossingSnord116delmicetoghrelin-KOmicereproducesthestrikingphenotypeobtainedusingSnord116del/GHSR-nullmice.Also,wewilldetermineifadministeringghrelinrescuesorimprovestheoutcomeofPWSmiceontheghrelin-deficientoronghrelin-repletebackgrounds,respectively.

IanNeeland InternalMedicine ImpactofVisceralAdiposityonGlycerolMetabolisminGluconeogenesisamongNon-DiabeticObeseAdults

ThefirsthypothesisisthatparticipantswithhighervisceralfatcontentbyMRIwillhaveagreaterrelativecontributionofunlabeledglyceroltoglucosecomparedwithage,sex,andbodymassindex(BMI)-matchedparticipantswithlowervisceralfat.Thesecondhypothesisisthatparticipantsinthefasting-refedstatewillhaveagreaterrelativecontributionofadiposetissuederivedglycerol(measuredby13Cnuclearmagneticresonancespectroscopyanalysis)tohepaticgluconeogenesiscomparedwithparticipantsinthefastingstate.

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RicardaLaHozDavidGreenberg

InternalMedicine EpidemiologyofBlood-BorneInfectionsinSolidOrganTransplantRecipients

HypothesisTheincidenceofbloodstreaminfectionsishigheramongsttransplantrecipientsthaninthegeneralpopulation.Wepredictthatthemostcommonmicroorganismsassociatedwithbloodstreaminfectionsamongstsolidorgantransplantrecipientstobe:CoagulasenegativeStaphylococci,Staphylococcusaureus,Enterococcusspecies,Escherichiacoli,KlebsiellaspeciesandCandidaspecies.Transplantrecipientswillhaveahigherprevalenceofmulti-drugresistantorganismsthanthegeneralpopulation.SpecificAims1.Describetheepidemiologyofbloodstreaminfectionsinsolidandstemcelltransplantrecipients.a.Identifythemostcommonorganismsresponsibleforbloodstreaminfectionsinallsolidorgantransplantrecipientsandbyorgantype(lung,heart,liver,andkidney).b.Identifythemostcommonorganismsresponsibleforbloodstreaminfectionsinstemcelltransplantrecipientsbothautologousandstemcelltransplantrecipients.c.Describetheprevalenceofmulti-drugresistantorganismsasacauseofbloodstreaminfections.

AmitSingal InternalMedicine AccuracyofUltrasoundasScreeningModalityforDetectingHepatocellularCarcinomainPatientswithCirrhosis

Specificaims/Hypothesis:Toidentifypatientcharacteristicsassociatedwithsensitivityofultrasoundforearly-stagedetectionofhepatocellularcarcinoma.Wehypothesizepatientfactorsincludingbodymassindex,presenceofascites,anddegreeofliverdysfunction/nodularityareassociatedwithlowerultrasoundsensitivityfordetectingHCCnodules.

DavidGerber InternalMedicine Clinicaltrialdesignandconducttooptimizeaccrualandquality

Aim1.ThisresearchprojectwilluseadatasetofpublicallyavailableNCI-sponsoredlungcancerclinicaltrialprotocols(N=73)andprotocolsummariesontheclinicaltrials.govwebsitetodeterminepredictorsandtrendsinthetotalnumberofeligibilitycriteriaandpharmacy-relatedeligibilitycriteria(CYP3A4metabolism,QTcprolongation).Protocolswillbecharacterizedaccordingtoactivationyear,principaltreatmentmodality,diseasehistologyandstage,trialphase,andtotalenrollmentnumber.TheassociationbetweentrialcharacteristicsandeligibilitycriteriawillbeassessedbyChi-Squareanalysis.Aim2.WorkingwithprimarymentorDr.GerberandcollaboratorDr.SimonLee,Ms.Garciawill(1)conductarelevantliteraturesearchfocusingoninteractionsbetweenclinicalresearchteamsandclinicstaff,(2)reviewtranscriptsfrompreviouslyconductedfocusgroupswithclinicalresearchandclinicstaff,and(3)developsurveysandquestionnairestobe

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administeredtostaff,providers,andpatients.Theseinstrumentswillbedesignedtodetermineperceptionsofrolesandresponsibilitiesandopportunitiestoenhancethefunctionofthismulti-teamsystem.

AnneSatterthwaite

InternalMedicine-DivisionofRheumatology

RoleofFoxo3inBCellTolerance Hypothesis:Foxo3promotesdeletionofimmatureBcellsthatremainauto-reactiveafterreceptorediting.SpecificAim1:DefinethemechanismbywhichFoxo3mediatesimmatureBcellapoptosisanddeterminetheconsequencesofthisfortheeliminationofauto-reactiveBcells.SpecificAim2:DeterminewhetheraFoxo3-deficiencyresultsinincreasedreceptoreditingduetoalongereditingwindowandassesstheconsequencesforBcellauto-reactivity.

ChrisChen Orthopedics TentativeTitle:Efficacyofintra-articularadministrationofEPOandBMP2fromHAmicroscaffoldsonautologousMSCrecruitment,localinflammatoryresponsesinsynovialspace,andcartilageregeneration.

HYPOTHESIS:Theintra-articularadministrationofEPOandBMP2fromHAmicroscaffoldswillenhanceautologousMSCrecruitment,reducelocalizedinflammatoryresponsesinthesynovialspaceandpromotecartilageregeneration.SPECIFICAIM:Totesttheabilityofintra-articularinjectionofEPO-HAandBMP2-HAmicroscaffoldsinpreventingthedevelopmentofPTOAinrabbits.

WilliamM.Lee InternalMedicine-Hepatology

HistologicalFindingsintheTwoSubtypesofHepatitisB-RelatedAcuteLiverFailure

Hypothesis:WehypothesizethatpatientswithacuteHBV-acuteliverfailurewilldemonstrate,onlivertissuestaining,qualitativeand/orquantitativedifferencesinHBcAgexpressionand/orHBsAgexpression,aswellasmorphologicaldifferencesonH&EstainfromthosewithchronicHBV-ALF.SpecificAims:Bydeterminingthatthereareantigenicand/ormorphologicaldifferencesbetweenthesubtypesofHBV-ALFandspecifyingwhattheyare,weexpandourknowledgeofthedifferencebetweenacuteandchronicHBVasitrelatestoacuteliverfailure.Thisisusefulforestablishingpotentialtherapeutictargetsthatmaymodifythecourseofthediseaseorallowforstratificationofriskwithineachcategory.

DavidGreenberg InternalMedicine,Microbiology

DevelopmentofNovelGene-SilencingTherapeuticsforPseudomonasaeruginosaBiofilms

Hypothesis:PPMOstargetingthequorumsensingproteinlasRwhenco-incubatedwithtraditionalantibioticswillprovidesynergisticeffectsinboththepreventionand/orbreakdownofP.aeruginosabiofilm.SpecificAims:1)UtilizetheLasRPPMOwithtraditionalantibioticsinastraincollectionofP.aeruginosaandmeasuretheabilitytopreventbiofilmformationinbothantibiotic-sensitiveandantibiotic-resistantstrains.2)UtilizetheLasRPPMOwithtraditionalantibioticsinastraincollectionofP.aeruginosaandmeasurethebreakdownofpre-formedbiofilms

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inbothantibiotic-sensitiveandantibiotic-resistantstrains.DavidGreenberg InternalMedicine,

MicrobiologyDevelopmentofNovelGene-SilencingTherapeuticsforAcinetobacterbaumanniiBiofilms

WehypothesizethatPPMOstargetingtheattachmentproteinCsuEwhenco-incubatedwithtraditionalantibioticswillprovidesynergisticeffectsinboththepreventionand/orbreakdownofA.baumanniibiofilm.

DharamKumbhani Cardiology AssessingthequalityoftreatmentintheuseofvascularinterventioninpatientswithPVDcomplicatedbyfootulcer

SpecificAim:TocreateandanalyzeauniquedatabaseconsistingofpatientdatafromParklandpatientsfromtheASCFootWoundClinic(includinglimiteddemographicdata,historyofdiagnosticandprognosticcareregardingvascularassessmentandintervention,dataonhemoglobinA1C,comorbidities,andoutcomes)ofapproximately600patientsovera6-monthtimeperiodtoassessdifferentoutcomesandthequalityandinclusionofvascularinterventioninpatientspresentingwithfootulcers.

PeterDouglas MolecularBiology MediatingNeuronalProtectionagainstTraumaticInjurythroughMitochondrialMetabolism

Theaimsofthisresearchprojectarethreefold.First,wewillassesswhetherapplicationofcco-1RNAiknockdowntreatmentsreversetheshort-termeffectsoftrauma,whichwillbemeasuredbyparalysisduration,ERK1/2phosphorylationlevels,levelsofoxidativedamageandrespirationratesobtainedviaaSeaHorseeffluxanalyzer.Second,wewilldetermineifthecco-1RNAitreatmentcanpreventthelong-termconsequencesofearlyadulthoodbluntforcetraumabymeasuringthedegreeofneurodegenerationinwormfood-sensingneuronsandtheaccumulationoftoxicproteinaggregatessuchasneuronalpolyglutamineexpansionproteinssuchasQ67,muscle-expressedamyloidbeta(linkedtoAlzheimer'sdisease),andtheALSlinkedgene,TDP-43.Third,wewilldeterminetheprecisespatiotemporalrequirementsforcco-1RNAitreatmentadministration.

RueylingLin MolecularBiology RoleoftheendogenoussiRNApathwayinmRNAclearanceandcellularreprogramming.

Theaimofthisprojectistobegintestingthehypothesisthattheendo-siRNApathwayhasanimportantfunctionduringthereprogrammingofmammaliancellsbygeneratingtheblankslateforthenewdevelopmentalprogram.Specifically,wewilltesttheroleofendo-siRNAinwell-developedreprogrammingprotocolsbyusingeitherectopicexpressionorknockdownofendo-siRNApathwaycomponents.Ourhypothesispredictsthatenhancingtheendo-siRNApathwayshouldimprovereprogramming(measuredasefficiencyand/ortimerequired),andconversely,inactivatingthepathwayshouldnegatively

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reprogramming.JoachimHerz MolecularGenetics InducibleMouseModelforAmyloid

PrecursorProteinHypothesis:BycreatingamousemodelthatallowsinducibleoverexpressionofendogenousAPPinatimely,regulated,andreversiblemannerweareabletocircumventseveralflawsofcurrentADmousemodels.OurtransgenicmousewillbecrossedwithwildtypeanddifferentavailableAPP-knockinmiceallowingustostudytheeffectofinducibleupanddownregulationofendogenouswildtypeandhumanAPP.SpecificAims:OurmodelmakesuseofatranscriptionfactorfusionproteinthatisdesignedtospecificallybindtothemouseendogenousAPPpromoter.Atransgenicmouseline,whichexpressessuchatranscriptionfactorinaninduciblemanner,canbeusedtostudythephysiologicalfunctionofmousewildtypeAPP,whichiscurrentlynotverywellunderstood.Geneoverexpressionstudiesandsubsequentreversiontonormallevelswillgiveimportantinsightinproteinfunctioninvivo.Thefuturemousemodelwillbesuitedtostudysynapseformationandfunction.Furthermore,breedingthistransgenicmouselinewithavailablehumanAPPknockinmicewillrevealfurtherinsightsintothepathogenesisofADundermorephysiologicalconditionsthancurrentADmousemodelsallow.Inourmousemodelwecircumventtheproblemoflackinguntranslatedregions(UTRs)intheAPPmRNAtranscript,suchimportantregulatoryelementsaredisregardedincurrentAPPoverexpressionmodels.SincethesubcellularlocalizationofmRNAandtranscriptionalregulationwillbeunaffectedinourmodelitreflectsthepathogenesisinthehumanbrainmorepreciselythancurrentmodels.Insummary,thismousemodelallowsustostudytheeffectofreversibleoverexpressionofendogenouswholelengthsAPPtodiscoverAPPfunctioninhealthanddisease.

JuanPascual Neurology&Neurotherapeutic

AnalysisoftheglucosetransportertypeIdeficiencyregistry

ThepurposeoftheGlucoseTransporterType1Deficiency(G1D)RegistryistoexpandtheknowledgeofthenaturalcourseofG1D,improveclinicalcare,andprovidedirectionforfutureresearch.TheG1DRegistryhasbeencreatedandfundedbytheDepartmentofNeurologyandNeurotherapeuticsatUTSouthwesternMedicalCenterundertheguidanceofDr.JuanPascual.Patientsandfamiliesdirectlyentertheirdataintheregistrybyansweringaseriesofquestions.Theregistrycontainsinformationaboutdiagnosis,symptoms,medicalandfamily

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history,treatmentsandmedications,laboratoryandimagingtests,andthehistoryofpatient'smedicalcare.Itisexpectedthataddressingcertainquestionsmayultimatelyresultinasignificantchangeinthestandardofcare.

CraigPowell Neurology&Neurotheraputics

Insulin-LikeGrowthFactor1(IGF-1)therapyinrestoringhippocampalneuronsinaGulfWarIllnessmodel

Objective/HypothesisWehypothesizethatthedelayed-onsetdecreaseinsynapsenumbercanbereversedwithdrugsalreadyinclinicaluseorclinicaltrials.TheneurotrophicfactorIGF-1,FDAapprovedforuseeveninchildren,stimulatessynapticspineandsynapseformationduringdevelopment,duringnormalaging,andwhenadministeredinpreclinicalstudiesofhumanneurologicaldisorders.ThisprojectwillevaluatetheeffectivenessofIGF-1therapyinrestoringnormalsynapsestructureandfunctioninourGWImousemodelusingextracellular'field'electrophysiology,neuronreconstructiontechniques,andimmunohistochemistry(IHC).

ShilpaChitnis Neurology&Neurotheraputics

PatientPerceptionsandKnowledgeofParkinsonDiseaseandTreatment

ThepurposeofthisstudyistosurveypatientsabouttheirknowledgeofPDandavailabletherapeuticoptions.Theresultsfromthissurveywillbeusefultoidentifypossibledeficienciesinpatienteducationandhelpdevelopatargetedpatienteducationprotocol,withtheultimategoalofimprovingoutcomesandprovidingreasonablequalityoflifeforPDpatientsdependingonthestageoftheirdisease.

MunroCullum Neuropsychiatry AgeofDiagnosisofMildCognitiveImpairmentbyRace:TheEffectofTraumaticBrainInjuryHistoryandApolipoproteinε4

Hypothesis:ItispredictedthattheinteractionbetweenApo-E4andahistoryofTBIwillbeassociatedwithasignificantlyearlierageofMCIdiagnosisinCaucasiansandnotinAfricanAmericannorHispanicindividuals.

JerryNiederkorn Ophthalmology MechanismsLeadingtoReducedLiverMetastasisinMicewithDefectiveFasL(CD95L)

Experiment1Hypothesis:Althoughgld/gldmicehavenon-functionalFasL,theymayhaveotheranomaliesthataffecthomingofblood-bornemelanomacellstotheliver.Rationale:Homingofblood-bornemelanomacellstothelivercorrelateswithmetastasis.Design:HomingofradiolabeledB16LS9melanomacellstotheliverwillbeassessedinWTandgld/gldmice.Outcomeifhypothesisiscorrect:LiverhomingwillbehigherinWTmice.Experiment2Hypothesis:FasL-FasRinteractionmaypromotetumormetastasisthroughincreasedliversecretionofc-met.Rationale:C-metisthemajorchemokineintheliverthatisassociatedwithlivermetastasisinhumanUMpatients.Design:LiversfromWTandgldmiceharboringlivermetastaseswillbeanalyzedbywesternblotandELISAtodeterminec-metproteinlevels.Liversupernatantsfrom

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WTandgldmicewillalsobeanalyzedfordifferencesintumorcellchemotacticresponsesinvitro.Outcomeifhypothesisiscorrect:WTmouseliverswillhavegreaterc-metlevelsandwillproducegreatertumorcellchemotacticresponses.Experiment3Hypothesis:AbsenceoffunctionalFasLmayenhanceliverNKcellcytotoxicity.Rationale:StudieshavereportedthatFasRcandampenimmuneresponsesbytransmittingsignalsintoFasL-bearingNKcells,viaamechanismknownas'reversesignaling.'Design:LiverNKcellcytotoxicitywillbeassessedinWTandgldmice.Outcomeifhypothesisiscorrect:gldmicewillhavehigherNKcytolyticactivitythanWTmice.Experiment4Hypothesis:InadditiontodefectiveFasL,gldmicemayhaveananomaloushigherproductionofinterferon-gamma(IFN-)orperforin.Rationale:IFN-andperforinareimportantmediatorsfortheanti-tumoreffectsofNKcells.Design:IFN-andperforinlevelswillbemeasuredbyELISAsintheliversremovedfromtumor-bearinggldandWTmice.Outcomeifhypothesisiscorrect:IFN-orperformlevelswillbehigheringldmice.Experiment5Hypothesis:FasL-FasRinteractionsmaypromoteangiogenesisthroughincreasedVEGFsynthesisintheliver.Rationale:AngiogenesismediatedbyVEGFisanimportantstepintheestablishmentoflivermetastases.

KaranjitKooner Ophthalmology RedefiningGlaucomaDamage Hypothesis:NFLanalysiswillprovidemoresensitive,reliableandearlyevidenceofopticnervedamagethanthecurrentVFtests.Specificaims:1.todetermineifNFLanalysisagreeswiththecurrentdefinitionsofVFdefectsbytheHodapp-Parrish-Andersoncriteria.2.DoesthethicknessoflaminacribrosacorrelatewithCCTorfamilyhistoryofglaucoma?

RonaldMancini Ophthalmology Examiningcorrelationsbetweenpreoperativebasalandsquamouscellcarcinomalesionsoftheeyelidandpostoperativerepairs

HYPOTHESIS1.Ourfirsthypothesisisthatpreoperativeappearanceofthelesionisapoorpredictoroffinallesion/defectsize.Weexpectthatthevisibletumorontheeyelidwillultimatelyrevealtobemuchlargerunderthesurface,requiringmoresurgicalinterventionthaninitiallyanticipated.2.Oursecondhypothesisisthatsquamouscellcarcinoma,amoreaggressivetumorthanbasalcellcarcinoma,willlikelyresultinalargerpostoperativedefect.3.Basalandsquamouscellcarcinomahaveapredilectionforthelowereyelidovertheuppereyelidduetomoresunexposureonthelowereyelidsurface.Wehypothesizetofindasimilarcorrelationwiththepopulationinourstudy.III.SPECIFCAIMSBylookingat

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preoperativephotographsandinitialclinicalexaminationofthepatientsinourstudy,wewilldeterminewhetherornotandtowhatdegreewewereabletopredictthedefectsizefollowingsurgicalremovalofthelesion.Wewillalsodeterminewhetherthetypeofcancer,basalvssquamouscellcarcinoma,hasaneffectontheultimatedefectsizeandourabilitytopredictdefectsizefrominitialexamination.Lastly,wewilldeterminewhetherornotourpopulationfitswithpriorreportedstudiesthatshowskincancershaveapropensityforthelowereyelidasopposedtotheuppereyelid.

DavidBirch Ophthalmology EvaluatingPossibleMechanismsofAgeRelatedMacularDegenerationwithReticularPseudodrusen

Hypothesis:RPDactsasadiffusionalblockthatphysicallylimitstheexchangeofretinolbetweenRPEandphotoreceptors.Specificaims:(1)TodeterminetheextentandprogressionofrodsensitivitylossinintermediateAMDwithRPD(2)TorelatetheextentofrodandconesensitivitylosstoenfacefdOCTstructuralmeasures.

W.MatthewPetroll

Ophthalmology ModulationofCornealWoundHealingfollowingPhotorefractiveKeratectomy

Hypothesis:WehypothesizethattopicalapplicationofQuercetinwillreducecornealfibrosisandhazefollowingphotorefractivekeratectomysurgeryintherabbit.SpecificAims:Totestthishypothesis,wewillassesstheeffectsofQuercetinonkeratocytebackscattering,alignment,morphologyandconnectivityinvivofollowingakeratectomyinjury(photorefractivekeratectomy,PRK)whichproducesafibroticresponseontopoftheinjuredstroma.CorneaswillbeevaluatedusingtheHeidelbergRetinaTomographRostockCorneaModule(HRT-RCM)clinicalconfocalmicroscope,andthesefindingswillbecorrelatedwithenbloc3-Dconfocalfluorescenceandsecondharmonicgeneration(SHG)imaging.

DanielleRobertson

Ophthalmology Impactofinsulin,IGF-1,andhyperglycemiaonautophagyinthecornealepitheliumandwouldhealing

Hypothesis:Thathyperglycemia-inducedalterationsinautophagyplaysapivotalroleinthedevelopmentofcornealepithelialcomplicationsandimpairedwoundhealingindiabetes.SpecificAims:Wewilltestthishypothesisinthefollowingtwospecificaims:1.(a)Wewillexaminetheroleofinsulininmediatingautophagyinthecornealepithelium.(b)Wewillthentesttheeffectsofhyperglycemiaonautophagyinthecornealepithelium.2.Wewillcomparethelevelofautophagyinnormalversusdiabeticcornealepithelialcellsobtainedbyprimarycultureofhumandonoreyebankcorneas.

JohnHulleman Ophthalmology Developmentofaprimaryretinalcellculturemodeltoidentifythecause(s)of

WehypothesizethathfRPEcellscanbeusedtogenerateaprimaryRPEmodelthatrecapitulatestheformationofsub-RPE

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theraremaculardystrophy,MalattiaLeventinese

proteindepositsreminiscentofML/AMD.SpecificAims.1.)ToestablishanhfRPEwhichdevelopssub-RPEproteindeposits.2.)Totestanumberofgeneticandpharmacologicmanipulationsinthiscellculturemodeltodeterminetheireffectonrescuingproteindepositformation.

RonaldMancini Ophthalmology Riskfactorscontributingtopathophysiologyofprimaryacquirednasolacrimalductobstruction

WehypothesizeriskfactorsexistthatmaycontributetothepathophysiologyofPANDO,suchasuseofglaucomamedications,environmentalfactors(i.e.cosmeticuse),gender,medicalco-morbidities,andmetabolicdisturbancesparticularlyinvolvingNa+,K+,Cl-,Ca++whichmaybeassociatedwithstoneformationsometimesnotedinPANDO.WewillaimtoidentifypotentialriskfactorsthatleadtoPANDObylookingforanypossiblestatisticallysignificantcorrelationbetweenfactorsanddisease.

DanielleRobertson

Ophthalmology PseudomonasaeruginosaTypeVIsecretionsystemonneutrophilactinpolymerization

SpecificAim:ToassesstheabilityofP.aeruginosatoevadetheinnateimmunesystembycomparingthepotentialforwildtype(PA01)andH2-T6SSmutant(PA01ΔclpV2)toinduceactinpolymerizationinhumanneutrophilsandinhibitfurtherphagocytosisinvitro.Hypothesis:ATypeVIsecretionsystemisutilizedbyPseudomonasaeruginosatointerferewithneutrophilactincytoskeleton,thushinderingitsphagocyticcapabilities.

PaulaHernandezValdez

OrthopaedicSurgery MolecularandMorphologicalResponsestoSevereBurnInjuryinRatAchillesTendonandIntervertebralDisks

Hypothesis:TheAchillestendonwillbeaffectedbysystemicexpressionofpro-inflammatorycytokinesalteringitsremodelingbalance.Also,NPcellsintheIVDswillbealteredbothmorphologicallyandinproteinexpression.SpecificAims:Aim1:Tostudygeneandproteinexpressionofpro-inflammatorycytokines,CollagenI,CollagenIIIandMMPsinAchillestendonafterskinburnaswellastocharacterizechangesinfiberalignment.Aim2:TostudyproteinexpressioninNPcellsfromIVDs,comparingareasimmediatelybelowthesiteofburninjurywiththosethataremoredistant.Wewillalsocomparetheequivalentdiscsofnon-burnedcontrolratsandobserveformorphologicalchangesinNPcellsafterburning.

MichaelKhazzam OrthopaedicSurgery EffectivenessofCorticosteroidvs.KetorolacShoulderInjections:AProspectiveDouble-BlindedRandomizedTrial

ThegoalofthisstudyistotesttheefficacyofintraarticularinjectionsofKetorolacvs.Corticosteroidonrotatorcuffshoulderpathologies,specificallyrotatorcufftearsandtendonitis.WehypothesizethatsubacromialinjectionsofKetorolacwillbemoreeffectivethancorticosteroidinjectionsinpainrelieftreatmentforshoulderpathologies.

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MohammedKhaleel

OrthopaedicSurgery SleepDisturbanceinPatientswithOperativeSpinePathology

Hypothesis:Spinepathologyhasanegativeimpactonsleepquality,andsurgicaltreatmentwillincreasethequalityofsleepinpatientswithoperativespinepathology.

MichaelHuo OrthopaedicSurgery RetrospectiveDatabaseforTotalKneeArthroplasty(TKA)

SpecificAim:TocollectclinicalandradiographicdatainconsecutivepatientswhohaveundergoneprimaryandrevisionTKAsatUTSouthwesternMedicalCenteranditsaffiliatesandParklandHealthandHospitalSystem.

HarryKim Orthopaedics Proximalfemoralgrowthmodulationusingpercutaneoustrans-physealscrewplacement

Specificaim.Wewilldeterminetheeffectsofaneccentricallyplacedtrans-physealscrewoninducingavarusorvalgusangulationoftheproximalfemurinalargegrowinganimalmodel.Hypothesis.Wehypothesizethatamediallyorlaterallyplacedproximalfemoraltrans-physealscrewwillserveasagrowthtetherandproduceavarusorvalgusangulationoftheproximalfemur,respectively.

MichaelKhazzam OrthopedicSurgery EffectivenessofCorticosteroidvs.KetorolacShoulderInjections:AProspectiveDouble-BlindedRandomizedTrial

SpecificAim:IwillbeassistingDr.MichaelKhazzaminaprospective,randomizeddouble-blindedstudythataimstocomparetheeffectivenessofketorolacorcorticosteroidinjectionsinindividualswhohaveacquiredshoulderpathologiesincludingatraumaticfullthicknessrotatorcufftearsandrotatorcufftendinitis.ThehypothesisstatesshoulderinjectionswithKetorolacwillbemoreeffectivethancorticosteroidinjections.

PaulaHernandez Orthopedics TheroleofHtrA1inthemorphologicchangesofchondrocytemorphologyseeninOsteoarthritis.

Hypothesis:chondrocytephenotypicregulationisdisruptedbyoverexpressionofHtrA1,leadingtochangesobservedinOA.SpecificAims:Aim1:tocompareOAsampleswithcontrolin(i)HtrA1expressionusingqPCRandWesternblot,(ii)HtrA1associationwithcytoskeletonusingco-immunoprecipitationandimmunofluorescence,and(iii)analysisofcellmorphologyparameterssuchascellcircularity,perimeter,andattachmentsinordertostudychangesinphenotype.Aim2:TocomparecontrolchondrocytesversusOAchondrocytesresponsetoCytochalasinDtreatment,usingcellmorphologyparameters.LowdosesofCytochalasinDwillcausecytoskeletaldisruption,particularlyinactinfilaments.

KennethLee Otolaryngology ImprovingPatientHearingOutcomesbyMinimizingInsertionTraumawithaShapeMemoryPolymerCochlearImplantArray

Hypothesis:Novelself-coilingelectrodearraysmadeofshapememorypolymerallowforatraumaticimplantationofcochlearimplants,minimizinglossofresidualhearingandmaximizinghearingoutcomesincochlearimplantpatients.

RonMitchell Otolaryngology PolysomnographicvariationandAdenotonsillectomyoutcomesinthe

Hypothesis:AmongchildrenwithDownsyndrome,obesity,ageandethnicityunfavorablypredictsoutcomesofT&Ainchildren

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pediatricpopulationwithDownsyndrome

SpecificAims:ThespecificaimsofthisprojectaretocorrelatedemographicsandespeciallyweightwiththeoutcomesofT&AinchildrenwithDownsyndromeandOSA.ThegoalisidentifypredictorsofresolutionofOSAinchildrenwithDownsyndromebasedondemographics,clinicalandpolysomnographicparameters.

RonMitchell OtolaryngologyHeadandNeckSurgery

OutcomesofT&Ainoverweightandobesepediatricpatientswithobstructivesleepapnea

WehypothesizethatT&AwillresultinimprovementorresolutionofOSAinoverweightandobesepatientsbuttheresponsewillnotbeuniform.Wealsohypothesizethatsomepredictorsofoutcomewouldincludeage,BMIz-score(specificallyweightincrease)andethnicity.

RonMitchell Otolaryngology,Pediatrics

CorrelatestoWeightGaininChildrenwithObstructiveSleepApneafollowingTonsillectomy

Manypediatriccasesofobstructivesleepapnea(OSA)occurduetotonsillitis,whichmaybetreatedwitharoutinetonsillectomy.However,manychildrenrelapseintoOSAaftertonsillectomydespitetemporaryreliefofsymptoms.Onepossiblecauseofthismaybeduetotheassociationbetweentonsillectomiesandpost-operativeweightgain,asobservedbyLewiset.al.in'Weightgainafteradenotonsillectomy:acasecontrolstudy'(2015).Inobesepatients,excessiveaccumulationofadiposetissuearoundtheneckcanleadtoairwayobstruction,thusresultinginOSA.Thegoalofthisprojectwillbetoperformaretrospectivemultivariateanalysisusingdemographicandotherpatientdata(fromtheChildren'sHealthEPICpatientrecords)toidentifyfactorsrelatingtoweightgainfollowingatonsillectomy.

JamesMalter Pathology IdentifyingrecombinantPIN1proteinsatspecificphospho-serinesitesandestablishingifsensitivetoB-amyloid

Pin1isacis-transpeptidylisomerasewithspecificityforserine-prolineorthreonine-prolinepeptidebonds,Pin1targetsincludeAPP,tau,4EBP1andavarietyofothersignalingproteinsinvolvedinneuronalfunctionandhomeostasis,leadingtothehypothesisthatPin1isinvolvedinADpathology.Pin1islostearlyinADevolutionpossiblyviaoxidationandacceleratedclearance.WhenboundtoAPPortau,Pin1acceleratesnon-amyloidogenicprocessingviaanalpha-secretasepathwayandhelpsmaintaintauinanon-phosphorylatedstate.WhetherorhowPin1enzymaticactivityisacutelyorchronicallyaffectedbyB-amyloid,thelikelycausalagentinAD,isunknown.Recently,wehaveidentifiedanewroleforPin1inthemaintenanceofdendriticspines.IntheabsenceofPin1,spinesarereducedinnumberandcomplexity.Ofnote,spinesarelostduringevolvingADthatmayaccountfortheprominentmemorylossesandbehavioralchangesseenearlyinthedisease.Therefore,itwas

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hypothesizedthatPin1loss/inhibitionwasresponsibleforthereductioninspinesseeninneuronstreatedwith/exposedtoB-amyloid.

MohammadTariqueHussain

PediatricCardiology ClinicalOutcomesandUtilityofCardiacCatheterizationPriortoFontanCompletionintheCurrentEra

Hypothesisandspecificaims:Ourgoalistoconductaretrospective,observationalstudyinwhichweexaminetheoutcomesofthepatientsatChildren'sMedicalCentereligiblefortheGlennproceduretodetermineunderwhatcircumstancespatientsproceededandunderwenttheGlenn;whatcircumstancespatientswererecommendedforandreceivedhearttransplantationandwhatcircumstancesresultedinnofurthertherapeuticoptionsbeingavailabletothem.WehypothesizethatpatientsarenotexcludedfromtheFontanprocedurebasedonhemodynamicdatathatwasnototherwisefoundinahistoryorechocardiogram.

HannahPiper PediatricSurgery Evaluationofurinarysodium,dietarysodiumintake,andsomaticgrowthinchildrenwithshortbowelsyndrome

HypothesisChildrenwithshortbowelsyndromewhoarereceivingsufficientdietarysodiumtomaintainaurinesodiumconcentration≥60meq/Lwillhavebetterweightgainandlineargrowthcomparedtochildrenwithurinesodium<60meq/Lreceivingsimilarkcal/kg.SpecificAims1.Tocorrelateurinesodiumconcentration(mmol/L)inchildrenwithSBSwithaveragedailyweightgain(g/kg/d),lineargrowth,anddailysodiumintake(mEq/kg/d)2.Todevelopaguidelineformonitoringurinarysodiumconcentrationanddietarysodiumsupplementationtoachievesufficientsomaticgrowth

FaisalQureshi PediatricSurgery AreviewofthetreatmentofspleniccystsatChildren'sMedicalCenter

Hypothesis:Wehypothesizethatthetreatmentofspleniccystswithaspirationandsclerotherapywillhavefewercomplicationsandalowerfailureratethanothertreatmentmodalities.

JosephMurphy PediatricSurgery IVCTumorThrombus-Identification,ManagementandConsequences

OurhypothesisisthosepatientswithIVCtumorthrombidoworsethanthoseIVCpatientsarewithoutthrombi.SpecificAims:Theaimofthisstudyistoidentifychildrenwithinferiorvenacava(IVC)tumorthrombi,describetheirsurgicalexperienceanddetailtheirlong-termoncologicandphysiologicoutcomes.

LindaBaker PediatricUrology NovelSurgicalTechniqueforDrainageofObstructedUterovaginalDuplication

HYPOTHESIS:Percutaneousobstructedhemivaginaaccess(POHVA)leadstominimallyinvasiveidentificationandsafeentrytothedifficultOHcomparedtoblinddissectionandsuccessfullyidentifiesthedifficultOHinover50%ofcasesSPECIFICAIMS:1.Reportthenoveltechniqueofpercutaneousobstructedhemivaginaaccess,POHVA.2.FindsuccessrateofPOHVAin

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identificationofandsafeentrytothedifficultOHinallpastcases.3.DeterminecomplicationsifanythatarosesecondarytothePOHVAtechnique

ChristyTurer Pediatrics AutomatingClinicalDecisionSupporttoImprovePediatricHypertensionIdentificationandManagement:AnEvaluationofDiagnosticSensitivity,ComputationalEfficiency,andCostofThreeProposedMethods

Wehypothesizethatthethird(Cache)methodwillbethemostsensitivefordiagnosingpediatrichypertension,followedbyuseofSDEs,andfinally,thesubstitutionofpoint-of-careheightandagemeasuresformissingorinaccuratehistoricalvalues(COCB).

DarrylMiles Pediatrics AStudyofOpticNerveSheathDiametertoPredictIntracranialHypertensioninPediatricBrainInjuredPatients

SpecificAims:Aim1:CompileastandardizednormativedatasetofONSDsinchildrenrangingfrominfancyto18years.Impact:Thisnormativedatacanbeusedbyfuturepediatricphysiciansacrossthecountrytoinformthemwhethertheirpatienthasnormallevelsofpressureornot.ThiscouldpreventunnecessarysurgicalproceduresandCTscans.Aim2:DeterminethesensitivityandspecificityoftheONSDproceduretopredictpathologicalchangesinICPinpediatricpatients.Impact:Ifproven,thisprocedurecoulddetectelevatedICPnon-invasivelyandhelpphysiciansmonitorpressurelevelsintheirpatientsonceadmittedtothePICUwithoutinvasivemonitoring.Thistechniquecouldthenbeusedonawiderangeofpediatricpatientswithacuteneurologicinjury.Hypothesis:Wehypothesizethatanultrasoundbased-measurementONSDof>4.5mminchildrenwillcorrelatewithanICPofgreaterthan20mmHgwithinvasivemonitoringmethods.

MayLau Pediatrics UniqueFactorsofDatingViolenceinAsianAmericanAdolescents

Hypothesis:1.Asian-Americanadolescentswillhavedatingviolenceratesequivalenttootherraces.2.UniquefactorswillbeidentifiedthatexplaintheequivalentdatingviolenceratesinAsian-AmericansSpecificaims:Thespecificaimsofthisstudyis:1.ToexamineratesofdatingviolenceamongAsianAmericansadolescentsandyoungadults2.Toidentifysociodemographic,academic,violence-related,drug-related,andmentalhealthfactorsthatareassociatedwithdatingviolenceinAsianAmericanadolescents

JamesCollins Pharmacology AnalysisofneoblastgeneexpressionandfunctioninSchistosomaflatworms

Wehypothesizethatneoblast-driventegumentrenewalisessentialtoprotecttheschistosomefromthehost'simmunesystem.Specificaims:Totestourmainhypothesis,werequireanin-depthunderstandingofthemoleculareventsthatcoordinatethedifferentiationofneoblastsintotegumentalcells.Therefore,wewillclonecDNAsfor20-30stemcell

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associatedgenesandperformdoublefluorescentinsituhybridizationexperimentswithknownneoblastmarkerstoconfirmthesegenesareexpressedinstemcells.

ElisabethMartinez Pharmacology TheeffectsofJumonjihistonelysinedemethylasesontheP.falciparumlifecycle

IhypothesizethatJumonjihistonelysinedemethylasesplayacriticalroleinregulatinggenetranscriptioninP.falciparumandthusmediatingparasitevirulence,andthatdisruptionofthisregulatorymechanismwilldisruptitsvirulence.SpecificAims•TodeterminehowtheredbloodcellstagesofP.falciparumareaffectedbyhistonedemethylaseinhibitors.Morespecifically,IaimtocharacterizeJIB-04-treatedbloodstageparasitestodetermine:1.whenmorphologicalchangesbecomeapparent,2.whetherthebloodcellstageoftheparasiteimpactstheabilityofdemethylaseinhibitorstoimpedelifecycleprogression3.howquicklydemethylaseinhibitorskilltheparasite•ToidentifychangesingeneexpressionmediatedbyJIB-04

JoyceRepa Physiology EvaluatingtherapiesforNiemann-PicktypeCdisease

WehypothesizethatLXRagonistsand/oranewtherapy,triglycerolacetate,mayimprovehearingfunctionandlungdiseaseinNPC.SpecificAim1.DeterminewhetherLXRactivityimpactshearing.a)PerformAuditoryBrainstemResponse(ABR)testsinwildtype,Lxralpha-/-,Lxrbeta-/-,andLxralpha/beta-/-mice.b)PerformABRtestingofNpc1+/+andNpc1-/-micetreatedwiththeLXRagonistT0901317.SpecificAim2.CharacterizethepulmonarydysfunctioninNPCdisease,andevaluatetheimpactoftherapies(T0901317,cyclodextrin,andtriglycerol-acetate)onlungphenotypesintheNpc1-/-mouse.a)PerformMS-MSALLlipidomicsanalysesonlungtissuesfromtreatedNpc1+/+andNpc1-/-mice.b)Usequantitativereal-timePCRtomeasuretheexpressionofgenesrelevanttopulmonarycelltypesandfunction(e.g.surfactants),inflammation,andlipidmetabolismusinglungtissuesfromthesemice.

ChristopherDerderian

PediatricPlasticandCraniofacialSurgery

Determiningthecraniofaciallandmarksimportantinassessingheadshape:Astudyusingeyetrackingtechnology

Wehypothesizethatthereareimportantreferencepointsintheheadandfacethatindividualscompareagainstthresholdsofnormalandabnormalandusetomakethesocialdeterminationofdeformity.Wefurtherhypothesizethatthesereferencepoints,andtheprocessofevaluation,areconservedbetweenindividuals.SpecificAims1.Assesstheeyemovementsusedinnormalheadshapeevaluationtodeterminetheoverallprocessofevaluationofnormalheadshape.2.Determinehoweyemovementsdeviatefromtheprocessofnormalheadshape

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evaluationintheevaluationofabnormalheadshape.BardiaAmirlak PlasticSurgery Retrospectivestudytomeasureefficacy

ofonabotulinumtoxinAinthecontextofchronicmigraineheadaches.

WepredictthataccurateinjectionofonabotulinumtoxinAintocarefullystudiedanatomicalsitesareeffectiveinreducingdiseaseburden.Inthisstudy,aretrospectivereviewofpatientsforheadachecharacteristicswillbeconductedtomeasurepreandposttreatmentchanges.Suchcharacteristicsincludefrequency,duration,andseverity.

NicholasHaddock PlasticSurgery Co-surgeonsinBreastReconstructiveMicrosurgery:WhatDoTheyBringtoTheTableinanAcademicInstitution?

Hypothesis:TheadditionofaCo-surgeonwebelievewillreduceoperativetime,averagepatientLOS,andsomepost-operativecomplications.Webelievethattheco-surgerymodelisassociatedwithincreasedoperativeefficiencyforBilateralDIEPBreastReconstruction.

JeffreyKenkel PlasticSurgery ClinicalAssessmentofthePerformanceofCombination1470nm/2940nmLaserTherapyforImprovedFacialSkinTexture,Tone,andReductionofSkinPoreSize

Ideally,non-surgicalskinrejuvenationwillmovetowardslasertreatmentsthatachievetheresultsofablativetherapieswithouttheunfavorablerecoverytimesandrisks.Inoursummerproject,wewillinitiallydefinewhatyouthfulskinlookslikeusingnon-invasivetechniquessuchashighresolutionphotography,3-dimensionalphotography,UVlightevaluation,high-resolutionultrasound(HRUS),elasticitymeasurements,andvariouspolarizedlights.Specifically,3D-photographywillbeusedtoevaluateimprovementsinskintone,texture,andporesize.UVlightevaluationwillbeusedtoassessimprovementsinactinicsundamage.HRUSwillbeusedtomeasureincreasesincollagenthickness.Wewilltheninvestigateskinultrastructureevaluatingcollagen,elastin,andglycosaminoglycansusingelectronandconfocalmicroscopy.Inaddition,wewillconsiderthegeneexpressionusingRNAsequencingandMassspectroscopy.

SumeetTeotaNicholasHaddock

PlasticSurgery The2stagedimplantbasedreconstructionwithanatomictexturedimplantsinNipple-sparingmastectomy

Wehypothesizethatstrictadherancetoprotocolfortexturedimplantsisnecessarytooptimizepatientoutcome.Furthermorecertaintechniquesofmanipulationofexpandersizemayreducethecomplicationrateandresultinhigherpatientsatisfaction.

SumeetTeotia PlasticSurgery Challengesinradiationofpatientswithbreastcancer,QuantitativeAnalysisinoutcomesofseven-hundredconsecutiveautologousbreastreconstructionsatUTSW

Hypothesis:Refinementsinmultiple-freeflapbreastreconstructionsproducebetteraestheticoutcomesandpatientsatisfactioninpost-radiation,post-mastectomy,patients.

CarolNorth Psychiatry SecondaryAnalysisSUNCODAStudyDataonHomelessServiceUse

ScientificaimsandhypothesesAim1.ToexaminetheSUNCODAmodel,exploringtherelationshipsamongpredisposing,enabling,andneedfactors,serviceuse,andcostof

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servicesassociatedwithdrugabuseandotherhealthconditions,andhowthesefactorsandserviceuseareassociatedwithchangesinstatusovertimeinadrugabusinghomelesspopulation.These'changeinstatus'variablesincludeddruguse,housing,consequencesofdruguse,andHIVriskbehaviors.Aim1pertainstotheSUNCODAmodel'sabilitytopredictserviceuseandsubsequentstatuschanges.Thesestatuschangesincludeachievementofstablehousing,changesinsubstanceusepatternsandtheirconsequences,changesinpsychiatricstatus,changesinHIVriskbehaviors,andchangesinotherbehaviorsassociatedwithhomelessnessandsubstanceusedisordersandtheirconsequences(e.g.,employment,entitlementuse,childcustodystatus).ThedatasetcollectedfortheSUNCODAprojectprovidesarichsourceofmaterialforinvestigationoftherelativedirectcostsofserviceuseandtheirrelationtostatuschanges.AnalysesrelatedtospecificcomponentsoftheSUNCODAmodelarepredictionofhousingoutcomesfromdrugabusestatusandtreatmentutilized.AnalysisofdatafortheSUNCODAhomelessmodelonwhichthedatafromthisprojectarestructuredpermitscombiningattributesofstructuralanalysis(pathanalytic)modelswithrepeatedmeasurestoexaminecomponentsofthemodelsimultaneously.TheseanalysesareongoingandwillprovideyearsofproductiveanalysisandpublicationoffindingsfromtheSUNCODAdatabases.Aim2.Toexaminetheassociationofdrugabuseandthecourseofhomelessnessbycomparingdrugabusingandnon-drugabusinghomelessindividualsovertimeintermsofstatuschangeassociatedwithserviceusewithintheSUNCODAhomelessmodel.Hypothesis1:Drugabusinghomelessindividualswillnotonlybemorelikelytousedrug-relatedservices,theseindividualswillalsobemorelikelytouseavarietyofservicesmoreextensivelythanwilltheirnon-drugabusingcounterparts,includingalcoholtreatmentandotherpsychiatric,medical,andsocialservices.Hypothesis2:Controllingfortheextentandtypesofservicesused,drugabusingindividualswillhaveworseconsequencesthantheirnon-drugabusingcounterparts.Serviceuseandextentofusewillbelesspredictiveofstatuschanges(e.g.,exitinghomelessness)indrugabusinghomelessindividualsthaninthenon-drugabusinghomelesscomparisonpopulation.

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SherwoodBrown Psychiatry RelationshipBetweenDepressionandBoneDensityintheDallasHeartStudy.

Hypothesis:CurrentdepressivesymptomseveritywillbeinverselyrelatedtoBMDSpecificAims:PrimaryAim:DeterminewhethercurrentdepressivesymptomseverityisinverselyrelatedtoBMDinparticipantsintheDHS.SecondaryAims:1)ExploreracialandethnicdifferencesintherelationshipbetweencurrentdepressivesymptomseverityandBMD.2)DeterminewhetherantidepressantuseinfluencestherelationshipbetweendepressivesymptomsandBMD.

XuejunGu RadiationOncology AutomaticSegmentationforBrainTumorsinStereotacticRadiosurgeryApplications

SpecificAims:Thegoalofthisprojectistodevelopanauto-segmentationclinicaltoolthatcanhelpalleviatetheworkloadofmanualcontouringduringSRSplanning,providegoodbasecontoursforphysicianstorefine,andreduceinter-observercontouringvariability.

KevinAlbuquerque

RadiationOncology HematologicToxicityinIntactCervicalCancerPatientswhohaveUndergoneIntensity-ModulatedRadiationTherapywithandwithoutBoneMarrowSparing

SpecificAimsAim1:ComparetheHToccurrenceratebetweenpatientsirradiatedbynormal-IMRT,BMS-IMRTand3D-CRTinanindigentpatientpopulation.Aim2:DeterminethepredictorsofHTincervicalcancerpatientsreceivingIMRT.Aim3:ReportoutcomesofpatientsreceivingIMRTforintactcervicalcancer.HypothesisWehypothesizethatBMS-IMRTpatientswillhavetheleastriskofHTwhile3D-CRTpatientswillhavethehighestriskforHT,becauseBMS-IMRTwillirradiateaslittleofthebonemarrowaspossiblewhereasthe3D-CRTpatientswillreceivethegreatestamountofirradiationtothepelvicbonemarrow.WehypothesizethattheoutcomeofpatientsreceivingIMRTforintactcervicalcancerwillnotbeasfavorableasthosereceiving3D-CRT,becausewhileIMRTisveryeffectiveindefiningthebordersofthetumor,thetumorcouldmoveduringtreatment,leadingtoineffectiveirradiationofthetumorsincetheboundarieshavechanged.

IvanPedrosa Radiology Identifyinghistologicandgeneticfactorsexplainingcorrelationbetweenmagneticresonanceimagingphenotypesandpapillaryrenalcellcarcinomaprognosis

Hypothesis:BecauseithasbeenshownthatimagingphenotypesarebetterpredictorsforassessingprognosisofpapillaryRCCs,thehypothesisunderstudyisthattherearespecificMRIimagingphenotypesthatcorrelatewithspecifichistologicalfindingsindicativeofpapillaryRCCs,suchasthepresenceofinfiltrationoftheadjacentrenalparenchymaand/orperirenalfatathistopathology.ArecentstudyhasalsoelucidatedacollectionofgeneticmutationsthatcorrelatewithdiagnosisofpRCC.AnotherhypothesistobeinvestigatedinthisprojectiswhethertherearespecificmolecularandgeneticfeaturesthatcanbeidentifiedandcorrelatedwiththeMRimagingphenotypesandtheir

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prognosticpredictions.ByidentifyingthesehistologicalandgeneticfeaturesandexplainingiftheycorrelatewithMRimagingphenotypes,wecanbetterunderstandandexplainwhyMRIphenotypesmaybeaccurateandeffectiveindicatorsofpapillaryRCCprognosis.

DanielCosta Radiology Anovelmodel-independentDWIinterpretationmethodforthediagnosisofprostatecancer

HypothesisThemodel-independentDWIratioimage(lowbvaluedividedbyhighbvalue)isnoninferiortothatofthecurrentgoldstandardofADCfordiagnosisofprostatecancer.SpecificAimsInordertosupporttheuseoftheb-valueratioasamethodforevaluationofprostatecancer,theinvestigationmustcomparetheaccuracyofGleasonscoringbetweenusingtheb-valueratioandADCmeasurement.

RalphMason Radiology Evaluatingphotoacoustictomography(PAT)inbreasttumoroxygenation

HypothesisPhotoacoustictomographywillrevealheterogeneityintumoroxygenationwithrespecttorespiratorychallenges.SpecificaimsAssessabilityofphotoacoustictomographytodetectchangesinbreasttumoroxygenation

DavidBoothman SimmonsComprehensiveCancerCenter,Pharmacology,RadiationOncology

RoleofMTH1inpotentiatingb-lapachonetumorselectivedeathinpancreaticductaladenocarcinomas

Hypothesis:Webelievethatinhibitionofproteinsparticipatinginbaseexcisionrepair(BER),specificallyMTH1,willenhanceb-lapachoneefficacyandimprovepatientoutcomeswithpancreaticductaladenocarcinomasbyallowingustouselowerdosesofb-lapachoneandtherebyreducepatienttoxicityintheformofmethemaglobinemia.ThisprojectwillfocusonthemechanismofactionofMTH1potentiatingb-lapachoneusingPDAcelllinecultures.SpecificAims:InhibitingBERspecificproteins,mainlyMTH1,andallowingforprolongedapyrimidinic/apurinic(AP)sitehalf-lifewhichwillfurtherpotentiatePARP1hyperactivationandtumorcelldeath.SinceMTH1isinvolvedinpreventingtheincorporationofDNAdamagingmolecules,weexpecttoseeincreasedDNAdamage,subsequenthyperactivationofPARP1,andeventualcelldeathbyknockingdownMTH1activity.SpecificAim1:ToexploretheinvitroeffectofMTH1inhibitiononb-lapachoneefficacyinPDAtumorsusingNQO1+vsNQO1-MiaPaca2celllines.OtherPDAcelllineswithvariedNQO1levelswillalsobeexplored.SpecificAim2:ToelucidatethemechanismofactionofMTH1inhibitiontoincreasethepotencyofb-lapachoneinNQO1+PDAcellsinvitro.Aim1:MTH1expressionwillbeknockeddownintheNQO1+vsNQO1-MiaPaca2pancreatictumorcelllineusingthreedifferentmethods:transientsiRNA,stableshRNA,andMTH1inhibitor.Knockdownwillthenbeconfirmedusing

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WesternblottingorReal-TimePCRexpressionanalyses.Cellsurvivalassays,includingDNAandcolonyformingassessmentswillthenbeperformedtoascertaintheeffectsthatknockdownofMTH1willhaveon-lapachoneactivity.OtherPDAcells(12totalcelllines)willthenbetested.IexpectNQO1+,MTH1-cellswillhavethegreatestlossofoverallsurvival,withnoalterationsincellcyclestatusesasnotedpreviously.Aim2:CelldeathpotentiatedbyMTH1inhibitionincombinationwithsub-lethaldosesb-lapachoneshouldbeaccompaniedbyincreasedDNAdamage.Usingnontoxicdosesofb-lapachone,IwilltestforexpectedlossesinglycolysisandTCAcyclemetabolism.Additionally,Iwillmonitorforarisein8-oxo-dGTPincorporation,increasedDNAdamage(bycometandyH2AX/53BP1fociformationassays),andelevatedlevelsofPARformation.

StevenWolf Surgery Combinationtherapeuticstrategyofmusclefunctionimprovement

Hypothesis:AgrowthresponseintheskeletalmusclecellswithfunctionalimprovementthroughtheuseofmesenchymalstemcellsandUBM,characterizedthroughsystemicmorphologicalchangesincludinglipogenesis,fibrosis,musclefiberstructure,andangiogenesis.

PatricioM.Polanco

Surgery FailuretoRescueafterCytoreductiveSurgeryandHyperthermicIntraperitonealChemotherapytoTreatPeritonealCarcinomatosis

WeaimtodefinetherelationshipbetweensurgeonandhospitaloperativevolumesofCRS/HIPECandFTRafterthisprocedureusingtheNationalInpatientSample(NIS)dataset.Wealsoaimtoidentifypatients'riskfactorsandcomorbiditiesassociatedwithFTRfollowingCRS/HIPECusingtheNationalSurgicalQualityImprovementProgramdatabase(NSQIP).NISandNSQIParetwolargenationaldatasets.WehypothesizethatmorbidityandmortalityfollowingCRS/HIPECareassociatedwithindividualsurgeons'andinstitutionalpatientvolumes.WealsohypothesizethatFTRispredictableinpatientspresentingwithspecificriskfactorsandco-morbiditiesundergoingCRS/HIPEC.

StevenWolf Surgery Theroleofmyokinemusclininmuscleatrophyafterburn

Theaimofthestudyistoinvestigatetheroleofmusclininmuscleatrophyinresponsetosevereinjury.Thehypothesisofthestudyisthatmusclinisnecessaryformusclehomeostasis,muscleatrophyfollowingmuscleatrophyisatleastpartlythroughmusclinsignaling.Thespecificaimsofstudyareto1)todetectmusclinlevelinresponsetoburn;2)toidentifythemusclininregulatingmitochondrialimpairmentinmuscleafterburn;3)toinvestigatetheeffectofmuscledisuse,exerciseandinsulininmusclinexpressions.

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StevenWolf Surgery CholecystitisandtheMicrobiomeoftheGallBladder

HYPOTHESIS:Themicrobiotacompositioninsevereacutecholecystitiswillbecomplexandtheseveritygradesofcholecystitiswillhavesignificantdifferencesintheirmicrobiotaprofiles.SPECIFICAIM:Determinethemicrobiomeprofileofthegallbladderinacutecholecystitis.

Stevenwolf Surgery ChangesinWeightDuringAcuteHospitalisationintheSeverelyBurned:ModernClinicalPracticeandPotentialPitfalls

Ourgeneralhypothesisisthatweightlossiscommonintheseverelyburnedandfollowsapredictablepattern.

AdamAlder Surgery AReviewofIntervalAppendectomy Weaimtouseamatchedcase-controlapproachtocomparetheclinicaloutcomesofpatientswithcomplicatedappendicitiswhowereselectedforfirst-lineantibioticversusfirst-lineappendectomyapproachestomanagement.Wehypothesizethatafirst-lineantibioticapproachtocomplicatedacuteappendicitisinchildrenwillnotbeassociatedwithanincreaseinEDvisitsandCTscanscomparedtoafirst-lineappendectomyapproach.

SergioHuerta Surgery Predictorsofmorbidityandmortalityinpatientsundergoingcholecystectomyinveteranpatients

ThemaingoalofthisstudyistoidentifyoutcomesofveteranpatientsundergoingcholecystectomiesattheVAhospital.Wehypothesizethatwhilethenumberofcomorbidconditionsinourpatientpopulationisincreasing,thecomplicationrateandmortalityremainsthesame.Further,thisanalysiswillallowustoidentifyfactorsthatmightpreventadverseoutcomesinthosethathavethem.

StevenWolf Surgery Testinginflammatorycytokinesandmitochondrialproteinsandhowtheyaffectmitochondrialdynamicsinresponsetoburn

Hypothesis:BurnresultedmusclecelldeathisdependofIL-6andTNF-alphastimulation;intracellularpathwayisassociatedwithmitochondrialfission/fusioncycleregulatedbyDrp1/Mfn1signals.Forspecificaim1,wearegoingtorepeatburnserumstimulationofnormalC2C12musclecells,butaddanIL-6andTNF-alphapostburnserumstimulation,sothatwemayobservetheeffectsonmitochondrialmorphology.Inadditional,wearegoingtotestmitochondrialdynamicsinprimarymurinemyoblast.Forspecificaim2,wearegoingtoknockoutDrp1andMfn1inC2C12musclecelllinesbyusingcrispr/cas9andlentiviraltransfectioninvitro.

MichaelChoti Surgery Theroleoftheintestinalmicrobiotainpostoperativeoutcomesfollowingpancreaticcancersurgery

Inthisstudy,wewillinvestigatewhetherthereisacorrelationbetweenintestinaldysbiosisandpost-operativeclinicalsymptomsafterpancreaticsurgery.Todeterminethiswewillusestepwiseforwardlogisticregressionanalysisofclinical

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characteristicstomodeltheindependentpredictorsforpost-operativegastrointestinalsymptoms.Inthisstudy,wewillalsocharacterizetheintestinalmicrobiotainpatientsthathaveundergonepancreaticoduodenectomycomparedtopatientswhohaveundergodistalpancreatectomy.

RoshniRao Surgery EvaluationoftheCedilleIncisioninSkin-SparingTotalMastectomy

Purpose:ToevaluatewhethertheCédilleincisionforperformanceofskinsparingmastectomyprovidessuperiorresultswhencomparedtostandard'tennisracket'incisions.

JoselinAnandamArtiBarnes

SurgeryandInfectiousDiseases

InvestigationofeffectivenessofscreeningforanalcanceramongHIVpatientsintheParklandpatientpopulation

SpecificAims:Thefollowingspecificaimsaredefinedforthisproject1.Estimatethecurrentannual-screeningrateachieved(viaanalPaptesting)forParklandHIVpatientsanddetermineifthatscreeningratevariesacrossprovidersand/oracrosspatientdemographicsubgroups.2.EstimatethefractionofpatientswithpositiveanalPapresultsthathaveappropriateandtimelyfollow-upfordiagnosticconfirmation.3.EstimatethedistributionofstageatdiagnosisforHIVpatientsscreenedviaPaptestingandultimatelydiagnosedwithanalcancer,andcomparethatstagedistribution(afterdemographicadjustment)tounscreenedHIVpatientswithanalcancerdiagnoses.4.Estimatetheeffectoflife-yearsofannualanalcancerscreeningviaanalPaptesting,ascomparedtonoanalPaptesting.

BrianWilliams Surgery,DivisionofBurn/Trauma/CriticalCare

PosttraumaticStressDisorder(PTSD)intheprimarycaregiverofcriticallypatientsintheSurgical/TraumaICU

Individualswhowitness,orlearnof,traumaticeventshappeningtoaclosefamilymemberorfriendarealsoatriskofdevelopingPTSDsymptoms.ThismayincludefamilymembersoftraumapatientswhoareadmittedtoIntensiveCareUnits.Inthisprospectivepilotstudy,wewillestimatetheprevalenceofPTSDinthefamilymemberwhoistheprimarycaregiverofcriticallyillpatientsintheSurgical/TraumaIntensiveCareUnit(SICU).ThisobservationalpilotstudywilldetermineifusingavalidatedPTSDself-reportquestionnaireforthemaincaregiverofcriticallyillSICUpatientsisfeasibleandinvestigatewhetherthereisanotableprevalenceofPTSDwithinthispopulation.Withthisdata,wewillexpandourinvestigationtoevaluatepatternsofPTSDbasedonsocioeconomicstatus,immigrantstatus,mechanismoftrauma,andneedforemergencysurgery.Theprimarygoalistoimproveoutcomesforpatientsandfamilymembersofcriticallyillpatients.

MalcolmMacConmara

SurgicalTransplant 'DiscardedDonorOrgans-CanWeDoBetter?'

Thisresearchprojectaimstoexaminetheimpactofemployingsurgeonsdedicatedonlytotheprocurementoftheseorgansandtoseeifthishasledtoimprovedutilizationbytransplant

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programsinthearea,especiallyatUTSouthwesternMedicalCenter.Thespecificaimsoftheprojectareto:(1)identifytheincidenceoforgandiscardandthecausativefactorsintheNorthTexasDSA,(2)examinetheimpactofanindependentdonorsurgeonontherateandpatternsoforgandiscards,and(3)determineintheeventoforganreallocationiftheindependentsurgeonmodelhasimprovedrecipientoutcomes.Thegoalofthisresearchistobetterunderstandtheeventsandfactorsthatleadtoorgansbeingdiscardedandspecificallytoassessifbetterorganizationwithintheorgansharingsystemmightincreasethenumberoforgansused.

KempKernstine ThoracicSurgery CostandClinicalOutcomesforPulmonaryLobectomy:AssessingtheComparativeEffectivenessforOpen,Video-Assisted,andRoboticProcedures

Ourspecificaimforthisprojectistoprovideagreaterunderstandingoftheapplicationoftheseprocedurestoachieveoptimalcosteffectiveoutcomesinpulmonarylobectomy,perhapsofferinginsightintothelevelanddepthoftrainingrequiredtomaximizeproficiency.Onalargerscale,thisstudywillattempttobetterinformbothsurgeonsandinstitutionsofthebenefitsofparticulartechniquesthatimpactpatientsafety,performance,andcost-of-care.

GaryLemack Urology RiskFactorsPredictingComplicationsintheAdultSpinaBifidaPatient

Hypothesis:Wehypothesizethatadultpatientswithspinabifidapresentingwithcomplexpriorurologichistoryareatincreasedriskofcomplicationslong-term.SpecificAims:Theaimofthisprojectistoidentifymodifiableriskfactorsinthispopulationtopredictlong-termcomplications.Asecondaryaimistocharacterizetheurologicmanagement,qualityoflife(QOL)andsexualfunctioninthispopulationtoassistinguidelinesfortheirevaluationandmanagement.

PhilippeZimernn Urology CollegialityandTransparency:Howtoinformacolleagueaboutadelayedcomplicationofameshimplanteddevicetocorrectstressurinaryincontinenceand/orpelvicorganprolapse?

Itisourbeliefthatlong-termoutcomedataiscrucialforre-evaluationofcurrentsurgicalpracticeandwefeelsurgeonswithadverseeventsmaybenefitfromthisfeedback.

PhilippeZimmern Urology UrinaryAntibioticConcentrationInWomenNotRespondingtoUrinaryCulture-GuidedAntibioticTherapy

Unresolvedinfectionscouldbeduetoavarietyoffactorssuchas:-anincreaseinantibiotic-resistantUPEC,-adifferentbacteriaserotypethantheoneoriginallyidentified,-thedevelopmentofintracellularbacterialcommunities(IBC)asprovenintheurinesedimentofwomenexperiencingacuteandrecurrentUTI's,-anunder-dosingoftheadministeredantibiotic-oratreatmenttooshort.Severalmechanismsmaybeatplaytoexplainthissurprisingandunexpectedcourseofantibioticnon-

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responsedespiteanappropriatelyselectedurineculture-directedantibioticselection.AmongtheplausibleexplanationsforthislackofclinicaleffectivenessleadingtoanunresolvedUTIisthepossibilitythattheantibioticdosingisinsufficient,resultinginnon-bactericidalurinaryconcentrations.Itisnotcleariftheroleoffluidintakeandurinedilutioncouldbeaffectingtheefficacyoftheantibiotictreatmentatthebladderlevelaswell.AcreatinineurinevaluetoevaluatethelevelofurinaryconcentrationandurinaryantibioticconcentrationwillbeobtainedonaurinesampleatthecompletionofantibiotictreatmenttoverifyresolutionofinfectionandstudytheantibioticconcentrationvariabilityinalargecohortofolderwomenwithRUTI.

PhilippeZimmern Urology BacterialandPhageSurveyofUrinefromPostmenopausalUTIpatients

Studyaims/hypothesisWeareinterestedinthefollowingissues:ArebacteriainUTIclonal?WhilemanyUTIpathogenshavebeencharacterizedheretofore,thegeneticrelatednessofpathogensinthesamebladderisnotknown.If,forinstance,aUTIincludesmultipleUPECstrains,thenphage-basedantibacterialinterventionswouldneedtobeinformedbythisknowledge.Doesthepresenceofprophageinanystrainmakeitlesssusceptibletolyticbacteriophage?CRISPRandrestrictionsystemsarecommoninphageresistantstrains.ThemovementofCRISPRonprophageisnotknown,butCRISPRelementsdoinfluencetheretentionofpathogenicityislands,whichfacilitatephageresistance.Thesimultaneouspresenceofactiveprophageinphageresistantstrainswillprovideopportunitiestoexploremechanismsoflateraltransferofphageresistancebyprophage.Doprophageshaverecipientstrainsinthesamebladderisolatesastheirhosts?Thepresenceofsusceptiblestrainswillfacilitatecharacterizationofprophages,butmoreoveritmaysuggestpathwaysofgenetransmissionandsharingamonglike/unlikespecies.Whatistherateofspontaneousinductionofurine-derived-prophage-carrier-strains?TheabilityofphageDNAtobemobilizedthroughtransductionissalienttotheevolutionoflong-termandchronicinfectionsinpatients.Iftransductionhappensinthebladder,thenaresidentinfectionmaybecomemorerecalcitranttotherapywhenlysogenizedbyatransientandlessadaptedpathogenthatactsasaprophagedonor.

GregoryModrall VascularSurgery Renalatrophyandlong-termsurvivalinpatientswithrenalarterystenosisand

Hypothesis.Wehypothesizethatrenalarterystentingisassociatedwithlessrenalparenchymalatrophy,comparedto

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renalstenting patientswithrenalarterystenosisandnostenting.Wefurtherhypothesizethattherewillbenodifferenceinlong-termrenalfunctionorsurvivalbetweenthetwogroups(stentedversusunstented).SpecificAims.ThetwoSpecificAimsoftheprojectareto:1)Comparelongitudinalrenalvolume(overtime)intwogroupswithrenalarterystenosis:stentedversusunstentedgroups.2)Comparechangesinrenalfunctionovertimeandlong-termsurvivaloftwogroupswithrenalarterystenosis:stentedversusunstentedgroups.