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This Provisional PDF corresponds to the article as it appeared upon acceptance. Fully formattedPDF and full text (HTML) versions will be made available soon.
Extremely short duration high intensity training substantially improves insulinaction in young sedentary males
BMC Endocrine Disorders 2009, 9:3 doi:10.1186/1472-6823-9-3
John A Babraj ([email protected])Niels BJ Vollaard ([email protected])
Cameron Keast ([email protected])Fergus M Guppy ([email protected])
Greg Cottrell ([email protected])James A Timmons ([email protected])
ISSN 1472-6823
Article type Research article
Submission date 10 September 2008
Acceptance date 28 January 2009
Publication date 28 January 2009
Article URL http://www.biomedcentral.com/1472-6823/9/3
Like all articles in BMC journals, this peer-reviewed article was published immediately uponacceptance. It can be downloaded, printed and distributed freely for any purposes (see copyright
notice below).
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BMC Endocrine Disorders
2009 Babraj et al. , licensee BioMed Central Ltd.This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0),
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
mailto:[email protected]:[email protected]:[email protected]:[email protected]:[email protected]:[email protected]://www.biomedcentral.com/1472-6823/9/3http://www.biomedcentral.com/info/authors/http://creativecommons.org/licenses/by/2.0http://creativecommons.org/licenses/by/2.0http://www.biomedcentral.com/info/authors/http://www.biomedcentral.com/1472-6823/9/3mailto:[email protected]:[email protected]:[email protected]:[email protected]:[email protected]:[email protected]7/29/2019 DIABETE ESERCIZIO FISICO.pdf
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Extremelyshortdurationhighintensityintervaltrainingsubstantiallyimproves
insulinactioninyounghealthymales
1JohnABabraj*,1NielsBJVollaardNBJ*,1CameronKeast,1FergusM
Guppy,1GregCottrelland1,2JamesATimmons
1TranslationalBiomedicine,SchoolofEngineeringandPhysicalSciences,
Heriot-WattUniversityEdinburgh,Scotlandand2TheWenner-GrenInstitute,
ArrheniusLaboratories,StockholmUniversity,Sweden.
*Theseauthorscontributedequallytothiswork
E-mailaddresses
JAB [email protected]@hw.ac.ukCK [email protected] [email protected] [email protected] [email protected]:
ProfessorJamesATimmons
TranslationalBiomedicine,
Heriot-WattUniversityEdinburgh
RiccartonEH144AS
Scotland,UK
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Abstract
Background: Traditional high volume aerobic exercise training reduces
cardiovascular and metabolic disease risk but involves a substantial time
commitment.Extremely lowvolumehigh-intensity interval training(HIT) has
recentlybeendemonstratedtoproduceimprovementstoaerobicfunction,but
it is unknown whether HIT has the capacity to improve insulin action and
henceglycemiccontrol.
Methods:Sixteenyoungmen(age:212y;BMI:23.73.1kgm -2;VO2peak:
489mlkg-1min-1)performed2weeksofsupervisedHITcomprisingofatotal
of 15 min of exercise (6 sessions; 4-6 x 30-s cycle sprints per session).
Aerobic performance (250-kJ self-paced cycling time trial), and glucose,
insulin and NEFA responses to a 75-g oral glucose load (oral glucose
tolerancetest;OGTT)weredeterminedbeforeandaftertraining.
Results:Following2weeksofHIT,theareaundertheplasmaglucose,insulin
and NEFA concentration-time curves were all reduced (12%, 37%, 26%
respectively,allP
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middleagedsedentarypopulationswhootherwisewouldnotadheretotime
consumingtraditionalaerobicexerciseregimes.
Background
Theprevalenceoftype2diabetes(T2D)israpidlyincreasingworld-wideand,
forexample,intheUnitedStatesitreached17.5millionpeoplein2007[1].
Aside from the associated reduction in quality-of-life and the increase in
morbidityandmortalityfortheaffectedindividuals,theeconomicburdenwas
estimated at$116 billion inexcessmedical expenditures and $58 billion in
reducedproductivity[1].Similarly,theestimateddirectandindirecteconomic
costsofcardiovascular disease (CVD) in theUSfor 2008are estimatedat
$287billion[2].
The risk of developingCVD andT2D can be modified by regular physical
activity[3].However,thereisnoconsensusonthenatureofexercisetherapy
required toprovideadequatehealth benefits, particularly with regard to the
volume-intensity relationship. Furthermore, as we do not understand the
precise mechanisms which link physical activity and a reduced risk of
developing CVD or T2D, the scientific rationale for current health guides
needstobeimproved[4].Forexerciseguidelinestoyieldapositiveeconomic
benefit for society, as well as a health benefit for the individual, not only
should the regime reliablymodify key disease risk factors, itmust also be
plausibletoimplement.
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Metabolic adaptations associated with traditional aerobic exercise training
correlate with improved insulin action and glycemic control [5, 6]. These
effects appear to be independent of changes inbody composition [7], and
someevidencesuggeststhatgreaterimprovementsininsulinsensitivitymay
beachievedwithhigher trainingintensities[8-10].Current recommendations
for improving glycemic control involve performing moderate to vigorous
intensityaerobicandresistanceexerciseforseveralhoursperweek[11,12].
However, the generalpopulation fails to followsuch regimesdue to lackof
time,motivationandadherence[13].Thissuggeststhatthecurrentfocuson
time-consumingmoderateintensityphysicalactivity,aimedatincreasingtotal
energyexpenditure,may not beoptimal for reducing the riskofdeveloping
T2D.
Recently an extremely low volume high-intensity interval training paradigm
(HIT),consistingofnomorethan7.5minutesofexerciseperweek,hasbeen
proposed as a novel, time-efficient exercise regime for improving aerobic
fitness [4, 14]. We speculated that it should be possible to substantially
improve insulin action using HIT despite a negligible contribution to total
energyexpenditureasthistrainingmodelwouldsubstantially reducemuscle
glycogen stores. Compared to traditional strategies for reduction of risk
factorsofCVDandT2D,theextremelylowvolumeofexerciserequiredwith
HIT may promote adherence and thus represent a genuinely preventative
publichealthstrategy.
Methods
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Subjects
Twenty-five young healthy sedentary or recreationally active men were
recruited to participate in this study, with none engaged in a structured
endurancetrainingprogram.Subjectswererandomlyallocatedtooneoftwo
partsofthestudy.Sixteensubjects(meanSD:212y;8217kg;1.830.08
m;BMI:23.73.1kgm-2;VO2max:489mlkg-1min-1)wereallocated tothe
mainpartofthestudy,andcompletedthefullexperimentalprocedures.The
remainingninesubjects(meanSD:238y;739kg;1.780.09m;23.01.4
kgm-2;VO2max: 4711mlkg-1min-1) tookpart ina separateexperiment to
determine intra-individual variation in response toanoralglucose tolerance
test,anddidnotperformHIT.Therewerenosignificantdifferencesintheage,
height,weight,BMIorVO 2maxbetweenthetwogroupsofsubjects.Subjects
wereinformedoftheexperimentalprotocolbothverballyandinwritingbefore
givinginformedconsent.Furthermore,allsubjectswereinformedabouthow
potential life-style changes could affect the results of the study, and were
requested tomaintaintheir normaldietandlevelsofphysicalactivity (apart
from the training program) throughout the durationof the study. The study
protocolwasapprovedbytheinstitutionalEthicsCommitteeandconductedin
accordancewiththeHelsinkiDeclaration.
Experimentalprocedures
Baselineaerobicperformanceandhealthparametersweredeterminedovera
2-weekperiodpriortocommencementofthetrainingprogram.
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Oralglucosetolerancetest(OGTT)
Subjectsrefrainedfromperforminganystrenuousphysicalactivityfor2days
prior to the OGTT, and attended the laboratory having fasted overnight.
Venous bloodsampleswere collected byvenepuncture before, and 60, 90
and120minafteringestionof75gglucose(FisherScientific,Loughborough,
UK)dissolvedin100mlofwater.Plasmawasseparatedbycentrifugation(10
minat1600g)andstoredat-20Cuntilanalysisofglucose,insulinandNEFA
concentrations. Plasma glucose concentrations were measured using an
automaticanalyzer(YSIStat2300,YellowSpringInstruments,YellowSpring,
OH) and plasma insulin concentrations were determined by ELISA
(Invitrogen,UK).Plasmainsulinwasmeasuredonlyforsamplestakenat0,
60, and 90 min. Plasma NEFA concentrations were determined by a
colorimetric assay (Wako Chemicals, Germany) using a modified protocol.
Briefly,3.75lofplasmasamplesandstandardsofknownconcentrationwere
pipettedintoa96-wellplate.75lofcolourreagentAwasaddedtoeachwell
andincubatedat37Cfor10min.150lofcolourreagentBwasaddedand
incubatedfora further10minat37C.Theplatewasthenremovedfromthe
incubator and allowed tocool to roomtemperature prior to theabsorbance
being read at 550 nm. Coefficients of variation (CV) for duplicate samples
were3%forglucose,5%forinsulin,and8%forNEFAs.
VO2peaktest
On a separate occasion, subjects performed an exhaustive incremental
cyclingtest(LodeExcaliburSport,Groningen,theNetherlands)todetermine
maximal power output (Wmax) and maximal oxygen uptake capacity
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(VO2peak)usinganonlinegasanalysissystem(SensorMedics,Bilthoven,the
Netherlands).Aftercyclingat30Wfor1min,poweroutputwasincreasedby
30Wmin-1untilvolitionalexhaustion.VO2peakwasdeterminedasthehighest
valueachievedovera20-speriod.
Timetrials
Endurance performance was determined to provide an integrated
physiological readout to facilitate comparison of the present study with
previous studies which provided data from muscle biopsy samples [15].
Subjects performed two self-paced cycling time trials in which they were
instructedtocomplete250 kJ ofworkas fastaspossible.The linear factor
waschosentoproduceapoweroutputcorrespondingto75%ofWmaxata
pedal rate of 90 rpm. No encouragement was given, and subjects were
blinded from information on time, power output and pedal frequency. The
amountofwork(kJ)completedwascalledoutevery25kJ.Timetrialswere
spacedatleasttwodaysapart.Althoughthefirstofthetwopre-trainingtrials
wasmainlyusedasafamiliarisationtrial,thefastesttimeachievedinthetwo
trialswasconsideredtobestrepresentthepre-trainingperformanceleveland
usedintheanalysis(19outof25subjectsperformedbetterinthesecondtrial
thaninthefamiliarisationtrial).
Sprintintervaltraining
The sprint training protocol was similar to that used previously by
Burgomasteretal.[4,14].Sixsessionsofsprintintervalexercisewerespread
over14days,with1or2daysofrestbetweeneachsession.Each training
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session consisted of 4-6 repeated 30-s all-out cycling efforts against a
resistanceequivalent to7.5%ofbodyweight (Wingate tests),with4minof
recoverybetweensprints.Duringrecovery,subjectsremainedonthebikeand
either rested orcycledata lowcadencewithout resistance.Thenumberof
sprints increased from4during the first twosessions, to5 in the thirdand
fourthsessions,and6inthelasttwosessions.Totaltimecommitmentwas
17-26minpersession,involvingonly2-3minutessprintexercise.
Post-trainingassessment
AsecondOGTTwasperformedaftercompletionofthetrainingprogram.In
order to determine whether potential changes were due to acute effects
attributabletothelasttrainingsession,subjectsweretestedeithertwo(n=10),
orthree(n=6)daysafterthelastboutofexercise.Onedayafterthesecond
OGTT subjects performed a third cycling time trial in order to determine
changesinaerobicperformance.
Intra-individualvariabilityintimetrialperformanceandOGTT-response
Inordertoassessnormalintra-individualvariationinresponsetoanOGTT
overaperiodof severalweeksas used inthepresentstudy,ninesubjects
performedan identical protocol to thetraininggroupbutwithoutperforming
the six training sessions. Coefficients of variation (CV) for repeated
measurements within individual subjects were determined for baseline
glucose and NEFA levels, for glucose and NEFA area under the plasma
curve,andfortimetrialperformance.
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Calculationsandstatisticalanalysis
Areaunder the plasmacurve(AUC)was calculated using the conventional
trapezoid rule. The Cederholm index, which represents peripheral insulin
sensitivity[16],wascalculatedusingtheformula:
ISICederholm=75000+(G0-G120)1.151800.19BW/120Gmeanlog
(Imean)
WhereBWisbodyweight,G0andG120areplasmaglucoseconcentrationat0
and120min(mmoll-1),andImeanandGmeanarethemeaninsulin(mUl-1)and
glucose(mmoll-1)concentrationsduringtheOGTT.
AlldataarepresentedasmeansSEM.Plasmaglucose,insulin,andNEFA
responsestothepre-trainingandpost-trainingOGTTswereanalyzedusing
two-way repeatedmeasuresANOVAwith post hoc StudentNewman-Keuls
tests. Differences between pre-training and post-training data for time trial
performance,AUCsforplasmaglucose,insulin,andNEFAlevels,andinsulin
sensitivityasmeasuredbytheCederholmindexwereanalyzedusingpaired
samplet-tests.Pearsonscorrelationcoefficientwasusedtoassessbivariate
correlations between baseline values of, and changes in the variables
performance, AUCs of glucose, insulin, and NEFAs, and the Cederholm
Index.SignificancewasacceptedatP
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Fastingplasmaglucoseconcentrationswereunalteredafter2weeksofHIT.
Inthepre-trainingOGTT,plasmaglucoseconcentrationwaselevated60min
afterthe75gglucosebolus(Figure1A;0min:5.00.1v60min:6.50.4
mmoll-1;P
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There was a trend towards a decrease in baseline plasma NEFA
concentrationsfollowingHIT(Figure1C;pre:35036moll-1vpost:290
39moll-1,P=0.058).Inthepre-trainingOGTT,plasmaNEFAconcentration
wasdecreased60minafterthe75gglucosebolus(Figure1C;0min:350
36moll-1v60min:25548moll-1;P
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Improvementsinglucose,insulin,andNEFAresponsesweresimilarwhether
assessed two or three days following the final training session (mean
reductioninglucoseAUC:2dpost1210%,3dpost194%;insulinAUC:2
dpost349%,3dpost389%;NEFAAUC,2dpost2321%,3dpost27
9%).
Intra-individualvariationintimetrialperformanceandresponsetoanOGTT
In subjects not performing the HIT program, no significant differences
between the first and second OGTTs were observed for plasma glucose
(AUC:67147v65940mmolminl-1)andNEFAs(AUC:240351611v
22599 2544 molminl-1), nor for time trial performance (1477214 v
1491245s).Coefficientsof variationfor the repeatedmeasurementswere
2.1% for the time trial, 4.9% and 7.0% for fasting glucose and NEFA
concentrations,and8.1%and8.2%forglucoseandNEFAAUCsrespectively.
Discussion
Whileregularexercisetrainingrepresentsoneofthemostpowerfulstrategies
toreducethedevelopmentofmetabolicdiseaseinhealthyadults[17],most
adults failtomeet currentguidelinesforparticipation [18].Theseguidelines
largely focus on the time spent carrying out moderately intense activity (or
totalenergyexpenditure),typicallyrequiremanyhoursofexerciseeachweek
and can fail to modify risk factors relevant for disease prevention [19]. In
addition, as time commitment is perceived as a major barrier, driving or
contributing to low compliance, then these guidelinesmaynot be themost
logical approach for improving public health. In the present study we
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demonstrateforthefirsttimethatonlyafewminutesofhighintensityinterval
exerciseperformedovertwoweeksisrequiredtosubstantially improveboth
insulin action and glucose homeostasis in sedentary youngmales. This is
both a physiologically important observation and potentially useful as it
highlightsapreventativeinterventionthatcouldlogicallybeimplementedas
an early strategy to prevent age related development of cardiovascular
disease.
Interestingly,despiteemployinglong-termtraininginterventions(2-16months)
the majority of studies investigating classic aerobic [10, 20-25] or strength
training programs [26-28] have observed only a reduction in insulin area
under the curve (AUC) in response to a glucose load following training,
without a concomitant reduction in glucose AUC, indicating only a partial
improvementininsulinaction.Furthermore,walkingbasedinterventionsmay
not reduce risk factors in the target populationwhereprevention is the key
objective[19].Somelongitudinalexercisestudieshaveshownreductionsin
glucose AUC [29-31], but post-training OGTTs were performed within 24
hoursofthelastexerciseboutandthereforereflectthecombinedimpactof
acute and chronic exercise [32]. In contrast, Hughes et al demonstrated
reduced glucose AUC in elderly subjectswithout a concomitant change in
insulinAUC[33].
Thelowvolume,highintensitytrainingutilizedinthecurrentstudysignificantly
reducedbothglucoseAUC(-12%)and insulinAUC(-37%),withasustained
improvedinsulinactionuntilatleastdaythreeafterthelastexercisesession.
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Thiswasachievedwithoutchangesinbodyweight,andwithaweeklyenergy-
cost of training of ~225 kcal during the first trainingweek and ~275 kcal
during the second training week. This very modest increase in calorie
consumption is in stark contrast to the ~2000-3000 kcalweek-1 consumed
duringatypicalaerobictrainingprogram[25,34].Thisimplies,butdoesnot
prove,thatthemechanismunderpinningthebenefitsweobservedwithHIT,
maybedistinctfromthoseresponsibleforthemoremodestimprovementsin
insulinactionwithclassictime-consumingaerobictraining.Whilemuchfocus
isbeinggiventoincreasingcalorieconsumptiontowardoffweightgain,itis
clear that improving metabolic fitnessmay be just as important as limiting
gainsbodymassindex.
Failure for insulin to adequately control blood glucose following a meal is
knownasinsulinresistance.Skeletalmuscle isconsideredthemajortissue
responsiblefortheuptakeofglucosefollowingameal,oraglucoseorinsulin
challenge [35] such that it is entirely reasonable to assume that the
improvement in glucose and insulin AUC observed in the present study
reflected improved muscle glucose uptake. The limiting step in glucose
disposal is considered to be its transport into the skeletal muscle [6] and
GLUT4 is the most abundant glucose transporter in skeletal muscle.
IncreasedGLUT4concentrationwithendurancetraininghasbeensuggested
tobeanimportantfactorregulatinginsulinsensitivity[6,33].Burgomasteret
al. reportedthatskeletalmuscleGLUT4 levels increaseby ~20%afterone
weekofHIT,andremarkablyremainedelevatedover6weeksoftrainingand
asubsequent6-weekperiodofdetraining[14].Giventhesimilaritybetween
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ourstudyandtheaerobicperformanceimprovement,protocolsandsubjects
in the Burgomasteret al studies, these studies shouldbecomparable and
thus an increase in GLUT4 may partly explain our findings. However,
increasedGLUT4concentrationdoesnotalwaysfullyexplaintraining-induced
improvementsininsulinsensitivityandkeyregulatoryproteinsdown-streamin
the insulin signalling pathway are more activated in response to insulin
following aerobic training [36]. HIT produces similar changes in skeletal
musclemarkersofcarbohydrateandlipidmetabolismtoaerobictraining[37],
soitshouldbeinvestigatedwhetherHITalsoproducessimilaradaptationsof
the insulin signalling pathway as seen following traditional aerobic training
[36].
Improvedwholebodyglucosedisposalfollowingtraininghasbeenassociated
withanincreaseininsulinstimulatedglycogensynthesis[38].HIThasatleast
twonovelfeatures,firstlyunlikewalkingormoderateintensityaerobictraining,
it involves the activation of a large muscle mass and secondly this is
associatedwithaveryhighglycogenbreakdown-turnover.Thecombinationof
thesetwofactorsmeansthatagreaterproportionofmusclefibreswillneedto
replenish their carbohydrate stores, compared with what would be
encounteredfollowingmoderateintensityaerobictraining.Musclecontraction
underconditionsofmetabolicstress(suchasincurredduringHIT)resultsin
veryrapidglycogendegradation[39]andthiswouldalmostcertainlyalterthe
bindingofavarietyofglycogenassociatedproteins[40,41].Thuswesuspect
that remodelling of the glycogen pool, altering the molecules branching
architecture[38],maywellbeimportantinregulatingskeletalmuscleinsulin
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sensitivity following HIT. Currently, high intensity muscle contraction is the
only feasiblestrategy for remodellingof the entiremuscle glycogenpool in
humans.
Insulin sensitivity may also be regulated by plasma NEFA concentration.
Pharmacological lowering of plasma NEFA levels has been shown to
positively regulate insulin sensitivity during anOGTT [39], whereas raising
plasmaNEFA concentration, through lipid infusion, lowers glucose infusion
rateduringperipheralinsulinemia-euglycemiainyoungmen[40].Incontrast,
exercisetraininghasbeenshowntohavelittleornoeffectonfastingplasma
NEFA concentration, insulin mediated lipolysis or NEFA release during
exercise [41-44]. In the present study, HIT was associated with a 17%
decrease in fasting plasma NEFA concentration without a concomitant
changeinfastinginsulin.Furthermore,therewasa26%reductioninNEFA
AUC during OGTT following HIT despite a 37% reduction in the plasma
insulinAUC.Thissuggeststhatinsulinwasabletoinhibitlipolysistoagreater
extent followingHIT andwhile these changesaremoremodest than those
observedwith lipidpoweringdrugs, the long termsbenefitsmay still beof
significance.
Conclusion
We demonstrate for the first time that low volume, high intensity interval
exerciseinvolvingonly~250kcalofwork,issufficienttoachievesignificant
improvements in glycemic control in sedentary young adults. This study is
limitedtothemeasurementofwholebodyinsulinsensitivitywhichmakesthe
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interpretation of our data incomplete. Analysis of tissue specific responses
through biopsy studies would enhance the present study by allowing
determinationofthemechanisms involvedin theimprovementsobservedat
thewholebodylevel.Nevertheless,ourdataandthefindingsbytheGibala
lab[4,37,45-49]suggestthatcurrentguidelines,withregardstooptimizing
exerciseprescription toyield thebest healthoutcomes,maynotbeoptimal
andcertainly requirefurtherdiscussion.Ourfindingswarrant furtherstudies
investigatingtheeffectivenessofHITinimprovingglycemiccontrolinhealthy
middleagedindividualsatriskofdevelopingT2DandinpatientswithT2D.
CompetingInterests
Noauthorsreportanycompetinginterests
Authorscontribution
JBandNBJVparticipatedinthestudydesign,analysis,writingandeditingof
themanuscript,CK,FMGandGCparticipatedindatagenerationandstudy
analysis.JATconceivedthestudyideaandparticipatedinthestudydesign,
writingandeditingofthemanuscript.
Acknowledgements
WewouldliketothanksMartinJGibalaforhisinsightfulcommentsduringthe
preparationofthisstudyandmanuscript.
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Figure1 Responsetoanoralglucoseloadpre-andpost-HIT.PlasmaconcentrationsandAUCforA:glucose,B:insulinandC:NEFAs.(*:P
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