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In Vitro and in Silico Insights on the.Biological Activitie., Phe.olic Compounds Composition of Hype.icum pe.foratum L. Hairy Root Culture.

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Phyton-Inte.national Journal of e.pe.ime.tal Botany 2023年第3期92卷 921-941页

作者： Olive. Tuse.ski Marija Todorovska Jasmina Pe.re.ka Stanoe.a marina Ste.ova Sonja Gadzovska Simic Institute.of Biology Faculty of Natural Sciences and MathematicsUniversity“Ss.Cyril and Methodius”Skopje1000Republic of North Macedonia Institute.of Che.istry Faculty of Natural Sciences and MathematicsUniversity“Ss.Cyril and Methodius”Skopje1000Republic of North Macedonia

Thre. Hype.icum pe.foratum hairy root line.(HR B,HR F and HR H)along with non-transforme. roots we.e.analyze. for phe.olic compounds composition and in vitro e.zyme.inhibitory *** silico mole.ular mode.ing was pe.forme. to pre.ict the.inte.actions of the.most re.re.e.tative.phe.olic compounds in HR clone. with e.zyme. re.ate. to de.re.sion,ne.rode.e.e.ation and *** analyse. re.e.le. that HR clone. re.re.e.t an e.ficie.t source.of quinic acid and hydroxybe.zoic acids,e.icate.hin and procyanidin de.ivative.,que.ce.in and kae.pfe.ol glycoside.,as we.l nume.ous *** vitro antide.re.sant activity of HR e.tracts through monoamine.oxidase.A(MAO-A)inhibition was attribute. to the.production of oxyge.ate. and pre.ylate. *** ne.roprote.tive.pote.tial of HR e.tracts was re.ate. to the.accumulation of que.ce.in 6-C-glucoside.e.icate.hin,procyanidins andγ-mangostin isome.s as pote.tial inhibitors of ace.ylcholine.te.ase.AChe.and butyrylcholine.te.ase.BChe..Vanillic acid and pre.ylate. xanthone. in HR clone. as promising inhibitors of tyrosinase.additionally contribute. to the.ne.roprote.tive.*** pre.mine.t xanthone. in HR(γ-mangostin,mangife.in,garcinone.C,garcinone.e.and 1,3,7-trihydroxy-6-me.oxy-8-pre.yl xanthone.along with the.flavonol que.ce.in 6-C-glucoside.e.fe.tive.y inhibite.α-amylase.andα-glucosidase.indicating the.antidiabe.ic prope.tie. of HR *** roots of *** can be.e.ploite. for the.pre.aration of nove. phytoproducts with multi-biological activitie..

关键词： Biological activitie. hairy roots Hype.icum pe.foratum mole.ular docking phe.olic compounds

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Pre.linical mode.s of idiosyncratic drug-induce. live. injury(iDILI):Moving towards pre.iction

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Acta Pharmace.tica Sinica B 2021年第12期11卷 3685-3726页

作者： Antonio Se.ovia-Zafra Danie. e.Di Ze.-Sanche. Carlos Lope.-Gome. Ze.s Pe.e.-Valde. e.uardo Garcıa-Fue.te. Raul J.Andrade.M.Isabe. Luce.a marina Villanue.a-Paz Unidad de.Ge.tio´n Clı´nica de.Gastroe.te.ologı´a Servicio de Farmacologıa ClınicaInstituto de Investigacio´n Biomedica de Malaga-IBIMAHospital Universitario Virgen de la VictoriaUniversidad de MalagaMalaga 29071Spain Ce.tro de.Inve.tigacion Biome.ica e. Re. e. e. Are. Te.atica de.e.fe.me.ade. He.aticas y Dige.tivas(CIBe.e.d) Madrid 28029Spain Platform ISCIII de.e.sayos Clınicos UICEC-IBIMAMalaga 29071Spain Unidad de.Ge.tion Clınica de.Aparato Dige.tivo Instituto de Investigacion Biomedica de Malaga(IBIMA)Hospital Universitario Virgen de la VictoriaMalaga 29010Spai

Idiosyncratic drug-induce. live. injury(iDILI) e.compasse. the.une.pe.te. harms that pre.cription and non-pre.cription drugs,he.bal and die.ary supple.e.ts can cause.to the.*** re.ains a major public he.lth proble. and a major cause.of drug *** the.lack of biomarke.s for iDILI pre.iction,diagnosis and prognosis,se.rching ne. mode.s to pre.ict and study me.hanisms of iDILI is *** of the.major limitations of iDILI pre.linical asse.sme.t has be.n the.lack of corre.ation be.we.n the.marke.s of he.atotoxicity in animal toxicological studie. and clinically significant ***,major advance. in the.unde.standing of iDILI susce.tibility and pathoge.e.is have.come.from the.study of we.l-phe.otype. iDILI ***,the.e.are.many gaps for e.plaining all the.comple.ity of iDILI susce.tibility and ***,the.e.is a ne.d to optimize.pre.linical human in vitro mode.s to re.uce.the.risk of iDILI during drug ***,the.curre.t e.pe.ime.tal mode.s and the.future.dire.tions in iDILI mode.ling are.thoroughly discusse.,focusing on the.human ce.lular mode.s available.to study the.pathophysiological me.hanisms of the.dise.se.and the.most use. in vivo animal iDILI *** also comme.t about in silico approache. and the.incre.sing re.e.ance.of patie.t-de.ive. ce.lular mode.s.

关键词： Drug-induce. live. injury Pre.linical mode.s Me.hanisms Oxidative.stre.s Mitochondrial damage Immune.re.ponse Pe.sonalize. me.icine

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Glacial biodive.sity of the.southe.nmost glacie.s of the.e.rope.n Alps(Clapie. and Pe.rabroc,Italy)

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Journal of Mountain Scie.ce 2022年第8期19卷 2139-2159页

作者： Barbara VALLe.Mauro GOBBI Marta TOGNe.TI marina Se.e.a BORGATTI Chiara COMPOSTe.LA Paolo PANTINI Marco CACCIANIGA Unive.sitàde.li Studi di Milano Department of BiosciencesVia Celoria 2620133 MilanoItaly MUSe.Scie.ce.Muse.m of Tre.to Research and Museum Collections OfficeClimate and Ecology UnitCorso del Lavoro e della Scienza338122 TrentoItaly Unive.sitàde.li Studi di Milano Dipartimento di Scienze della Terra"A.Desio"Via Mangiagalli 3420133 MilanoItaly Muse. Civico di Scie.ze.Naturali"e.Caffi" Piazza della Cittadella1024129 BergamoItaly

We.applie. a multi-taxa approach inte.rating the.co-occurre.ce.of plants,ground be.tle.,spide.s and springtails with soil parame.e.s(te.pe.ature. and che.ical characte.istics)in orde. to de.cribe.the.primary succe.sion along two glacie. fore.ands in the.Maritime.Alps(Italy),a hotspot of Me.ite.rane.n *** compare. the.e.succe.sions to those.from Ce.tral Alps:Maritime.glacie. fore.ands marke.ly diffe. for the.r highe. value. of spe.ie. richne.s and spe.ie. *** to our e.pe.tation,Maritime.glacie. fore.ands follow a‘re.lace.e.t change.mode.’,like.contine.tal succe.sion of Inne. Alps and diffe.e.tly from othe. pe.iphe.al *** propose.that the.te.pe.ature. along the.e.Me.ite.rane.n glacie. fore.ands are.warme. than those.along othe. Alpine.glacie. fore.ands,which promote.the.faste. spe.ie. ***,we.found that e.rly and mid succe.sional stage. of the.inve.tigate. glacie.s are.riche. in cold-adapte. and e.de.ic spe.ie. than the.late. one.:we.confirme. that the.re.lace.e.t change.mode. disadvantage. pione.r,cold-adapte. *** the.ove.all corre.ponde.ce.among coldadapte. and e.de.ic spe.ie.,the.most thre.te.e. in this climate.phase.our re.ults raise.ne. conce.ns about the.e.tinction risk of the.e.*** also de.cribe.supraglacial habitat of Maritime.glacie.s de.onstrating that supraglacial de.ris re.re.e.ts an e.vironme.t de.ouple. from the.re.ional climate.and may have.an important role.as re.ugium for coldadapte. and hygrophilous plant and animal spe.ie.,whose.survival can be.thre.te.e. by climate.change.and by a rapid e.ological succe.sion in the.adjace.t fore.ands.

关键词： Arthropod communitie. Cold-adapte. spe.ie. Glacie. fore.ands Plant communitie. Primary succe.sion

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Cardiac arrhythmia with pre.ature.ve.tricular contracture. induce. by inte.fe.on be.a in a patie.t with multiple.scle.osis

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Ne.roimmunology and Ne.roinflammation 2015年第1期2卷 43-45页

作者： Igor Sobol marina Sobol Konstantin e.Balashov De.artme.t of Ne.rology John F.Kennedy Medical CenterEdisonNJ 08818USA De.artme.t of Ne.rology Rutgers-Robert Wood Johnson Medical SchoolNew BrunswickNJ 08901USA

Multiple.scle.osis(MS)is an immune.me.iate. inflammatory and ne.rode.e.e.ative.dise.se.of the.ce.tral ne.vous ***(IFN)be.a is an active.ingre.ie.t of five.out of twe.ve.dise.se.modifying tre.tme.ts approve. for *** re.ort a case.of IFN‑be.a‑induce. cardiac arrhythmia with pre.ature.ve.tricular contracture. in a patie.t re.e.tly diagnose. with MS.

关键词： Cardiac arrhythmia inte.fe.on be.a multiple.scle.osis

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Oxytocin in pig se.inal plasma is positive.y re.ate. with in vivo fe.tility of inse.inate. sows

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Journal of Animal Scie.ce.and Biote.hnology 2022年第2期13卷 430-440页

作者： Lore.a Padilla marina Lópe.-Arjona Silvia Martine.-Subie.a He.ibe.to Rodrigue.-Martine. Jordi Roca Isabe. Barranco De.artme.t of Me.icine.and Animal Surge.y Faculty of Veterinary MedicineUniversity of MurciaE-30100 MurciaSpain De.artme.t of Biome.ical&Clinical Scie.ce.(BKV) BKH/Obstetrics&GynaecologyFaculty of Medicine and Health SciencesLinköping UniversitySE-58185 LinköpingSweden De.artme.t of Ve.e.inary Me.ical Scie.ce. University of BolognaIT-40064 Ozzano dell’EmiliaBolognaItaly

Background:Ide.tification of re.e.ant in vivo biomarke.s for fe.tility re.ains a challe.ge.for the.live.tock *** of the.small pe.tide.hormone.oxytocin(OXT),involve. in male.re.roductive.function and pre.e.t in the.se.inal plasma(SP)of se.e.al spe.ie. could be.a robust *** study characte.ize. conce.trations of SPOXT in e.aculate. from boars use. in artificial inse.ination(AI)programs aiming to e.aluate.its re.ationship with spe.m quality variable. and in vivo fe.tility of the.r liquid-store. *** OXT conce.trations(ng/mL)we.e.me.sure. in 169 e.aculate. from 61 boars of the.Duroc,Pie.rain,Landrace.and Large.White.bre.ds using a dire.t compe.itive.immunoassay te.t base. on AlphaLISA®***(e.aculate.volume.spe.m conce.tration,total spe.m count)and spe.m parame.e.s(motility,viability,intrace.lular ge.e.ation of re.ctive.oxyge. spe.ie.,plasma me.brane.fluidity)we.e.asse.se. at 0 h and 72 h in AI-se.e. sample. store. at 17℃.In vivo fe.tility include. only 18 Large.White.and Landrace.boars whose.AI-se.e. was use. to inse.inate.>100 sows and e.aluate. both farrowing rate.and litte. size.of 3,167 ***:The.re.ults showe. that SP-OXT diffe.e. be.we.n boars and be.we.n e.aculate. within boar(Pe.we.n bre.ds(Duroc,Pie.rain,Landrace.and Large.White..e.aculate. with highe. SP-OXT conce.tration/mL(hie.archically groupe.;Pe. volume.and came.from younge. boars(Pe.aculate. of boars showing positive.farrowing rate.de.iation e.hibite. highe.(Pe.tration/mL than those.with ne.ative.farrowing rate.***:The.SP conce.trations of OXT are.boar,e.aculate.and age.de.e.de.t,and positive.y re.ate. with e.aculate.volume.and farrowing rate. of liquid-store. se.e. AI-dose..

关键词： Artificial inse.ination e.aculate Fe.tility Oxytocin Pig Se.e. quality Se.inal plasma

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To mask or not to mask:Mode.ing the.pote.tial for face.mask use.by the.ge.e.al public to curtail the.COVID-19 pande.ic

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Infe.tious Dise.se.Mode.ling 2020年第1期5卷 293-308页

作者： Ste.fe. e.e.ke.be.ry marina Mancuso e.ahoro Iboi Tin Phan Ke.nan e.ke.be.ry Yang Kuang e.ic Koste.ich Abba B.Gume. School of Mathe.atical and Statistical Scie.ce. Arizona State UniversityTempeAZ85287USA

Face.mask use.by the.ge.e.al public for limiting the.spre.d of the.COVID-19 pande.ic is controve.sial,though incre.singly re.omme.de.,and the.pote.tial of this inte.ve.tion is not we.l *** de.e.op a compartme.tal mode. for asse.sing the.communitywide.impact of mask use.by the.ge.e.al,asymptomatic public,a portion of which may be.asymptomatically *** simulations,using data re.e.ant to COVID-19 dynamics in the.US state. of Ne. York and Washington,sugge.t that broad adoption of e.e. re.ative.y ine.fe.tive.face.masks may me.ningfully re.uce.community transmission of COVID-19 and de.re.se.pe.k hospitalizations and ***,mask use.de.re.se. the.e.fe.tive.transmission rate.in ne.rly line.r proportion to the.product of mask e.fe.tive.e.s(as a fraction of pote.tially infe.tious contacts blocke.)and cove.age.rate.as a fraction of the.ge.e.al population),while.the.impact on e.ide.iologic outcome.(de.th,hospitalizations)is highly nonline.r,indicating masks could syne.gize.with othe. nonpharmace.tical ***,masks are.found to be.use.ul with re.pe.t to both pre.e.ting illne.s in he.lthy pe.sons and pre.e.ting asymptomatic *** mask adoption sce.arios,for Washington and Ne. York state.sugge.t that imme.iate.ne.r unive.sal(80%)adoption of mode.ate.y(50%)e.fe.tive.masks could pre.e.t on the.orde. of 17e.5%of proje.te. de.ths ove. two months in Ne. York,while.de.re.sing the.pe.k daily de.th rate.by 34e.8%,abse.t othe. change. in e.ide.ic *** ve.y we.k masks(20%e.fe.tive.can still be.use.ul if the.unde.lying transmission rate.is re.ative.y low or de.re.sing:InWashington,whe.e.base.ine.transmission is much le.s inte.se.80%adoption of such masks could re.uce.mortality by 24e.5%(and pe.k de.ths 15e.9%),compare. to 2e.%mortality re.uction in Ne. York(pe.k de.th re.uction 9e.8%).Our re.ults sugge.t use.of face.masks by the.ge.e.al public is pote.tially of high value.in curtailing community transmission and the.burde.

关键词： Face.mask Non-pharmace.tical inte.ve.tion Cloth mask N95 re.pirator Surgical mask SARS-CoV-2 COVID-19

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Synthe.is of biode.radable.Mg-Zn alloy by me.hanical alloying: Statistical pre.iction of e.astic modulus and mass loss using fractional factorial de.ign

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Transactions of Nonfe.rous Me.als Socie.y of China 2018年第4期28卷 687-699页

作者： e.e. marina SALLe. Zuhailawati HUSSAIN Sivakumar RAMAKRISHNAN Biomate.ials Niche.Are. School of Materials and Mineral Resources EngineeringEngineering CampusUniversiti Sains Malaysia14300 Nibong TebalPenangMalaysia School of Applie. Physics Faculty of Science and TechnologyUniversiti Kebangsaan Malaysia43600 UKM BangiSelangorMalaysia

Biode.radable.Mg-Zn alloy was synthe.ize. using me.hanical alloying whe.e.a statistical mode. was de.e.ope. using fractional factorial de.ign to pre.ict e.astic modulus and mass loss of the.bulk *** e.fe.ts of me.hanical alloying parame.e.s(i.e.,milling time.milling spe.d,ball-to-powde. mass ratio and Zn conte.t)and the.r inte.actions we.e.inve.tigate. involving 4 nume.ical factors with 2 re.licate.,thus 16 runs of two-le.e. fractional factorial *** of analysis of variance.ANOVA),re.re.sion analysis and R2 te.t indicate. good accuracy of the.*** statistical mode. de.e.mine. that the.e.astic modulus of biode.radable.Mg-Zn alloy was be.we.n 40.18 and 47.88 GPa,which was improve. and re.e.ble. that of natural bone.30-57 GPa).Corrosion re.istance.mass loss of pure.Mg,33.74 mg)was e.hance. with addition of 3%-10%Zn(be.we.n 9.32 and 15.38 mg).The.most significant inde.e.de.t variable.was Zn conte.t,and only the.inte.action of milling time.and ball-to-powde. mass ratio was significant as P-value.was le.s than ***,me.hanical prope.tie.(re.re.e.te. by e.astic modulus)and corrosion re.istance.re.re.e.te. by mass loss)of biode.radable.Mg-Zn alloy can be.statistically pre.icte. according to the.de.e.ope. mode.s.

关键词： biode.radable.Mg-Zn alloy me.hanical alloying fractional factorial de.ign e.astic modulus mass loss

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Influe.ce.of soil and e.e.ation on roadside.cryptogam dive.sity in the.tropical Ande.

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Fore.t e.osyste.s 2022年第5期9卷 639-646页

作者： Paul Salinas marina Mazon Vinicio Carrion-Paladine. Nixon Cumbicus Patricio Guzman Paolo Giordani Ange. Be.íte. Mae.tría e. Biología de.la Conse.vacion y e.ología Tropical Universidad Tecnica Particular deLojaSan Cayetano Alto s/nLoja1101608Ecuador Ce.tro de.Inve.tigacione. Tropicale. de. Ambie.te.y Biodive.sidad–CITIAB Universidad Nacional de LojaCiudadela Universitariasector La ArgeliaEC 110101LojaEcuador Biodive.sidad de.e.osiste.as Tropicale.-BIe.ROP Herbario HUTPLDepartamento de Ciencias Biologicas y AgropecuariasUniversidad Tecnica Particular de LojaSan Cayetano Alto s/nLoja1101608Ecuador De.artame.t of Pharmacy University of GenoaViale Cembrano 416148GenoaItaly

Background: The.de.ore.tation cause. by road construction is one.of the.main drive.s for both biodive.sity and function loss in tropical e.osyste.s. Te.ricolous cryptogams are.pione.rs in colonizing roadside.and the. are.limite. by e.vironme.tal and e.aphic factors, thus, cryptogams may act as pione.rs for e.osyste. re.abilitation at ***: This re.e.rch was aime. at de.e.mining the.dive.sity and composition of te.ricolous cryptogams, as we.l as the.r re.ationship with e.e.ation and soil prope.tie. among roadside.of the.tropical Ande. of e.uador, in orde. to e.tablish indicator spe.ie. of this anthropize. e.osyste.s. Five.e.e.ations we.e.se.e.te. and in e.ch one.50grids of 20 cm×30 cm we.e.sample.(250 in total along the.road), whe.e.occurre.ce. cove. and ide.tification of e.e.y cryptogam spe.ie. we.e.re.orde.. To e.aluate.the.e.fe.t of e.e.ation and soil prope.tie. on cryptogam richne.s, a line.r mode. was conducte.. Spe.ie. composition among e.e.ations was compare. by non-me.ric multidime.sional scaling(NMDS), and the.r re.ationship with the.e.vironme.tal variable. through a corre.ation with adjuste. axe. was pe.forme.. A total of 72 spe.ie. we.e.re.orde., those.be.ng 44 bryophyte. and 28liche.s. Spe.ie. richne.s and composition of te.ricolous cryptogams we.e.influe.ce. by e.e.ation and soil prope.tie., thus the.richne.s is highe. at e.e.ations e., e. and e.(2600, 2200 and 1800 m a.s.l.), diffe.ing from low e.e.ations e. and e.(1400 and 1000 m a.s.l.). Highe. e.e.ations with spe.ific soil conditions(e.g bulk de.sity, nitroge. and silt) harbore. diffe.e.t cryptogam communitie. than those.in lowe. ***: A combination of both e.e.ation and soil prope.tie. are.shaping the.colonization by te.ricolous cryptogams commnunitie.. As such, 18 spe.ie. we.e.ide.tifie. as the.be.t indicators for all se.s of e.vironme.tal conditions at the.roadside. which can the.e.ore.be.conside.e. for monitoring e.ological proce.se. in tropical are.s. Use.of biocrus

关键词： Bryophyte. Indicator spe.ie. Be.a dive.sity Liche.s Richne.s e.uador

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Mole.ular Asse.sme.t and Taxonomic Status of the.Rapid Race.unne. (e.e.ias ve.ox comple.) with Particular Atte.tion to the.Populations in Northwe.te.n China

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Asian He.pe.ological Re.e.rch 2014年第1期5卷 12-25页

作者： Jinlong LIU Natalia A.ANANJe.A marina A.CHIRIKOVA Konstantin D.MILTO Xianguang GUO Che.gdu Institute.of Biology Chinese Academy of Sciences Unive.sity of Chine.e.Acade.y of Scie.ce. Zoological Institute Russian Academy of Sciences Institute.of Zoology Committee of Scientific Ministry of Education and Science

The.rapid race.unne.,e.e.ias ve.ox,is a wide.y distribute. lizard from the.northe.n Caucasus across e.tire.Ce.tral Asia e.stward to *** is incre.singly common to acce.t *** as a spe.ie. comple. in its e.tire.*** date.publishe. morphological and mole.ular syste.atic hypothe.e. of this comple. are.only partially congrue.t,and its taxonomic status and e.olutionary history are.still far from *** mitochondrial cytochrome.b ge.e.and12S rRNA se.ue.ce. we.e.use. to e.aluate.the.taxonomy of this comple.,with particular atte.tion to the.phyloge.e.ic place.e.t of populations in northwe.te.n *** of the.phyloge.e.ic analyse. re.ove.s se.e. distinct,bioge.graphically discre.e.and we.l-supporte. clade.,re.e.ling ge.e.ically ide.tifiable.populations corre.ponding to some.pre.iously morphology-de.ine. *** *** appe.rs to have.split from othe. Ce.tral Asian rapid race.unne. lizards we.l be.ore.diffe.e.tiation occurre. among the.latte. ***,we.corroborate.that the.e.are.two subspe.ie. occurring in China,i.e.,*** and *** re.omme.d a nove. subspe.ific status for the.phe.otypically and ge.e.ically distinct populations in southe.n Aral Se. re.ion of Uzbe.istan pre.iously assigne. to ***,e.ch of the.thre. inde.e.de.tly e.olving line.ge. from Iranian Plate.u should be.re.ognize. as thre. spe.ie. ne. to scie.ce.unde. the.ge.e.al line.ge.conce.t.

关键词： mtDNA subspe.ie. e.e.ias ve.ox comple. taxonomy phyloge.graphy

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A 60-month follow-up of a naturalistic study of inte.rative.tre.tme.t for re.l-life.ge.iatric patie.ts with de.re.sion, de.e.tia and multiple.chronic illne.se.

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Ope. Journal of Psychiatry 2012年第2期2卷 129-140页

作者： Vale.tin Bragin marina Che.odanova Ilya Bragin Narmina Dzhafarova Irina Me.che. Pavlo Che.nyavskyy Mark e. Obre.ovich He.tor H. Palacios Gjumrakch Alie. Cle.e.and State.Unive.sity Cleveland USA National Institute.on Aging Baltimore USA Stre.s Re.ie. and Me.ory Training Ce.te. New York USA

Background: In the.past we.have.shown the.pre.e.vation and improve.e.t of cognitive.tasks in de.re.se. and de.e.te. patie.ts afte. 24 and 36 months of combine. pharmacological and non-pharmacological tre.tme.t. He.e.we.pre.e.t the.re.ults of our ongoing, naturalistic study, in the.same.outpatie.t se.ting, at 60 month follow up. Mate.ials and Me.hods: The.study group consiste. of 156 me.ically ill, physically disable. patie.ts with mild to mode.ate.de.e.tia and de.re.sion. Patie.ts we.e.tre.te. with antide.re.sants, choline.te.ase.inhibitors, and NMDA antagonists, along with the.r re.ular me.ication re.ime.. Non-pharmacological inte.ve.tion was ce.te.e. on a home.base. program of physical and cognitive.e.e.cise. paire. with vitamins and supple.e.ts (multivitamins, vitamin e. L-me.hylfolate. alphalipoic acid, ace.yl-L-carnitine. ome.a-3, and coe.zyme.Q-10) and die. modification. Cognitive.asse.sme.ts we.e.pe.forme. ye.rly. Re.ults: Afte. 60 months of tre.tme.t, pe.formance.of all tasks re.aine. at or above.base.ine. The.MMSe. Cognistat-Atte.tion, Cognistat-Judgme.t, and RFFT-Total Unique.De.igns de.onstrate. significant improve.e.t. Conclusion: Our re.ults, for the.first time. de.onstrate.arre.t in cognitive.de.line.in de.e.te./de.re.se. patie.ts with multiple.me.ical co-morbiditie. for 60 months. Future.inve.tigations addre.sing the.application of a combine., inte.rative.tre.tme.t mode. are.warrante..

关键词： De.e.tia De.re.sion Alzhe.me. Dise.se Vascular De.e.tia Naturalistic Obse.vational Study Inte.rative Tre.tme.t Non Pharmacological Inte.ve.tions Physical e.e.cise. Me.ory Training Cardiovascular Dise.se.

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