简介:Axonaldegenerationisapivotalfeatureofmanyneurodegenerativeconditionsandsubstantiallyaccountsforneurologicalmorbidity.AwidelyusedexperimentalmodeltostudythemechanismsofaxonaldegenerationisWalleriandegeneration(WD),whichoccursafteracuteaxonalinjury.Intheperipheralnervoussystem(PNS),WDischaracterizedbyswiftdismantlingandclearanceofinjuredaxonswiththeirmyelinsheaths.Thisisaprerequisiteforsuccessfulaxonalregeneration.Inthecentralnervoussystem(CNS),WDismuchslower,whichsignificantlycontributestofailedaxonalregeneration.Althoughitiswell-documentedthatSchwanncells(SCs)haveacriticalroleintheregenerativepotentialofthePNS,todatewehaveonlyscarceknowledgeastohowSCs‘sense'axonalinjuryandimmediatelyrespondtoit.Inthisregard,itremainsunknownastowhetherSCsplaytheroleofapassivebystanderoranactivedirectorduringtheexecutionofthehighlyorchestrateddisintegrationprogramofaxons.Olderreports,togetherwithmorerecentstudies,suggestthatSCsmountdynamicinjuryresponsesminutesafteraxonalinjury,longbeforeaxonalbreakdownoccurs.TheswiftSCresponsetoaxonalinjurycouldplayeitherapro-degenerativerole,oralternativelyasupportiverole,totheintegrityofdistressedaxonsthathavenotyetcommittedtodegenerate.Indeed,supportingthelatterconcept,recentfindingsinachronicPNSneurodegenerationmodelindicatethatdeactivationofakeymoleculepromotingSCinjuryresponsesexacerbatesaxonalloss.Ifthisholdstrueinabroaderspectrumofconditions,itmayprovidethegroundsforthedevelopmentofnewglia-centrictherapeuticapproachestocounteractaxonalloss.
简介:Theriskofbreastcancer(BC)overdiagnosisattributedtomammographyscreeningisanunresolvedissue,complicatedbyheterogeneityinthemethodologyofquantifyingitsmagnitude,andbothpoliticalandscientificelementssurroundinginterpretationoftheevidenceonthisphenomenon.EvidencefromrandomizedtrialsandalsofromobservationalstudiesshowsthatmammographyscreeningreducestheriskofBCdeath;similarly,thesestudiesprovidesufficientevidencethatoverdiagnosisrepresentsaseriousharmfrompopulationbreastscreening.Forboththeseoutcomesofscreening,BCmortalityreductionandoverdiagnosis,estimatesofmagnitudevarybetweenstudieshoweveroverdiagnosisestimatesareassociatedwithsubstantialuncertainty.Thetrade-offbetweenthebenefitandthecollectiveharmsofBCscreening,includingfalse-positivesandoverdiagnosis,ismorefinelybalancedthaninitiallyrecognized,howeverthesnapshotofevidencepresentedonoverdiagnosisdoesnotmeanthatbreastscreeningisworthless.Futureeffortsshouldbedirectedtowards(a)ensuringthatanychangesintheimplementationofBCscreeningoptimizethebalancebetweenbenefitandharms,includingassessinghowplannedoractualchangesmodifytheriskofoverdiagnosis;(b)informingwomenofalltheoutcomesthatmayaffectthemwhentheyparticipateinscreeningusingwell-craftedandbalancedinformation;and(c)investinginresearchthatwillhelpdefineandreducetheensuingovertreatmentofscreen-detectedBC.
简介:摘要综合实践活动是集综合性、实践性、开放性、生成性、自主性为一体的一门必修课程,是一种实践性的综合课程,是着眼于发展学生的综合实践能力、创新精神和探究精神的发展性课程。它为学生提供了一个相对独立的学习生态化空间,让学生以主导者的身份学习,通过享受各种活动的乐趣,达到让学生在快乐中学习的目的。