Tekanyetso ea insulin ke eng? Insulin e na le phello efe?
Li-receptor tsa insulin li fumanoa haholo ka har'a sebete, mesifa le lithane tsa adipose. Li na le likarolo tse peli tsa "α -unun" tse ka ntle ho sele, 'me ke likarolo tse peli tse hlokoang tse phunyeletsang lera kahare ea lisele mme li na le ts'ebetso ea tyrosine kinase. Insulin e tlama ho α-subunits, e eketsa ts'ebetso ea tyrosine kinase ea β-subunits, e lebisang ho phosphorylation ea liprotheine tse kahare ho sele: liprotheine tse tsamaisang glucose, liprotheine tse tsamaisang potasiamo le phosphate ion ho sele, hexokinase, glycogen synthetase le tse ling, e lebisang phetohong ea lits'ebetso tsa metabolism. Ebe mochine oa "insulin" o nang le receptor o kena ka seleng, moo o robehang. Receptor e boetse e kenella kahara membrane, 'me insulin e phahamisa ho amoheloa ha li-amino acid ka lisele, e kenya tšebetsong mesebetsi ea protheine ea ribosomal, ebe e chekoa ka lysosomes.
(glucose transporter, tsamaiso ea tsoekere e thusang tsoekere)
Ho bokelloa ha lisele hoa eketseha
Liphello tsa 'mele tsa insulin.
Phello ea Hypoglycemic: e eketsa ho tsamaisoa ha tsoekere ho pholletsa le li-membrane tsa sele, e kenya phosphorylation ea tsoekere, e eketsa tlhahiso ea glycogen, e thibela glycogenolysis le gluconeogeneis.
Kameho ho metabolism ea mafura:e ts'ehetsa ho theoa le ho hlahisoa ha triglycerides, e thibela phetoho ea mafura acid ho keto acid, e fokotsa lipolysis, e thibelang lipase tsa methapo.
Kameho ea metabolism ea protheine:eketsa tlhahiso ea liprotheine ho tloha ho amino acid, e thibela ho fetoloa ha li-amino acid ho li-keto acid.
Bakeng sa kalafo ea lefu la tsoekere.
Bana ba nts'etsapele mofuta oa 1 lefu la tsoekere, le bakoang ke ho felisoa ha lisele tsa pancreatic le ho haella ka botlalo ha insulin (autoimmune, idiopathic).
Tekanyetso ea "insulin"ho latela boemo ba tsoekere maling, glucosuria, acetonuria. 1 yuniti ea "insulin" e sebelisa 2,5-5 g ea tsoekere. Ka nepo: 1 yuniti ea "insulin" e fokotsa glycemia ka 2.2 mmol / l (glucose e tloaelehileng ea ho itima lijo = 3.3-5.5 mmol / l) kapa 0,3 - 0.8 unit / kg ea boima ba 'mele ka letsatsi.
Taba ea pele, palo e phahameng e nkuoa, ebe lethalamo le khethoa ka bonngoe. Nakong ea khetho ea tekanyetso ea insulin, boemo ba tsoekere maling bo lekanyetsoa ho fihla ho makhetlo a 7-9 ka letsatsi. Boikutlo ba bana ba ho fumana insulin bo phahameng haholo ho feta ba batho ba baholo.
Merero ea ts'ebeliso ea insulin.
- Tloaelo: "insulin" e sebetsang ka nako e khuts'oane e tšeloa ka makhetlo a 4-5 ka letsatsi ka metsotso e 30 pele ho lijo.
- motheo-bolus (o matlafalitsoe): insulin e khutšoanyane e sebetsang ka nako ea metsotso e 30 pele ho lijo + tsa ente ea insulin le ea nako e telele, e fana ka litekanyetso tsa insulin, empa ha e felise hyperglycemia ea postprandial, eo li-insulin tse sebetsanang le nako e khutšoanyane li e felisang (ho feta tsohle, humalogue).
Li-insulin le tsona lia sebetsa
- ho eketsa takatso ea lijo le bofokoli ba boima ba 'mele,
- e le karolo ea kalafo ea polarizing,
- Le lefu la tsoekere la mofuta oa 2,
-e na le schizophrenia (kalafo ea coma).
Hypoglycemia(e mamelletsoe ho feta hyperglycemia):
Tachycardia, mofufutso, ho thothomela, ho nyekeloa, tlala, ho se sebetse hantle ha tsamaiso ea methapo (pherekano, boits'oaro bo sa tloaelehang), encephalopathy, tsitsipano ea mmele, komisi.
Thuso: lijo tsa hoseng tse halikiloeng, monate. Ka coma iv, tharollo ea tsoekere ea 40%.
Lipodystrophylibakeng tsa tsamaiso ea insulin - ho nyamela kapa keketseho ea ho beoa hoa mafura a subcutaneous. E hlaha ka lebaka la kenyelletso ea li-insulin tse sa hloekisitsoeng hampe, ka ho tlola mokhoa oa tsamaiso ea lithethefatsi (tsamaiso e batang, e phahameng ka ho fetesisa (e tlameha ho ba ka botebo), ho tsebisa sebakeng se le seng. Ka potlako le ka botlalo, insulin e nkuoa ho tsoa lithong tse ka tlase tsa mpa ea mpa ea mpa, butle butle ho tloha mahetleng, kapele ho serope mme butle butle ho tsoa sebakeng se subscapular le buttocks. Ho feta 16 IU ea insulin ha e tsamaisoe sebakeng se le seng, hang ka matsatsi a 60.
Litla-morao (ho hlohlona, ho soetseha, ho ts'oha hoa anaphylactic). Sena ke sephetho sa ho itlhoekisa insulin, ho li-preservatives, ho insulin ea liphoofolo. Hoa hlokahala ho fetisetsa mokuli ho lithethefatsi tse fokolang tsa immunogenic (insulin ea motho), ho fana ka antihistamines, HA.
Ho ruruha ha boko, matšoafo, litho tsa ka hare.
Ho phahamisa boima ba 'mele (botenya).
Β-cell atrophy, ho hanyetsa insulin(e hlaha ha insulin e hloka ho feta 2 PIECES / kg ya boima ba mmele, ka ho hlahisoa ha PIERES tse fetang 60 ka letsatsi).
Ho fetoha ha li-electrolyte, mathata a metabolism, ho felloa ke kelello, thibelo ea maikutlo, ho hlohlona, mathata a hemodynamic.
Phapang e rarahane: tharollo ea tsoekere ea 40%.
Intravenous drip insulin e etsang nakoana (10-20 IU) + tsoekere e hlokahalang.
Ho feta moo, subcutaneally kapa i / m 5-10 IU ea insulin bakeng sa taolo ea tsoekere.
Phekolo ea infusion - tharollo ea isotonic ea sodium chloride, chloride ea potasiamo.
Ka pH ea tharollo e tlase ho 7.0 w / w sodium bicarbonate.
Cocarboxylase ho fokotsa maemo a ketone.
Type 2 lefu la tsoekere
Li-agents tsa molomo tse hlalositsoeng ha li sebelisoe ho bana.
Basebeletsi ba molomo oa hypoglycemic
Ketso ea pharmacological
Insulin e maling a rona ke hormone e laolang metabolism ea lik'habohaedreite, e theola tsoekere e maling, hape e thusa ho monya tsoekere.
Motho o hloka ho amohela insulin ho tsoa kantle maemong ao ha makhopho a khaotsa ho a hlahisa ka bongata bo lekaneng kapa a hlahisa haholo. Tekanyo ea "insulin" maling a motho ea phetseng hantle ke 3-20 mkU / ml. Ka ho senyeha, lefu la tsoekere la mofuta oa 1 le fetoha ho isa tlase, 'me lefu la tsoekere la 2 le hlaha ka insulin.
Insulin ea maiketsetso bakeng sa bongaka e etsoa ho tsoa litšoelesa tsa manyeme, likhomo le boenjiniere ba liphatsa tsa lefutso.
Matšoao a sebelisang insulin
Sesebelisoa se ka sehloohong sa kalafo ke kalafo ea mofuta oa 1 lefu la tsoekere. Maemong a mang, e sebelisoa le lefu la tsoekere la mofuta oa 2.
Tekanyetso e nyane ea insulin (5-10ED) e sebelisetsoa ho alafa hepatitis, cirrhosis sethaleng sa pele, ka mokhathala, furunculosis, acidosis, khaello ea phepo e nepahetseng, thyrotoxicosis.
Setlhare se ka sebelisoa ho felisa ts'ebetso ea methapo, ho phekola bokhoba ba joala, mefuta e meng ea schizophrenia.
Mokhoa oa kopo
Ha e le hantle, lithethefatsi li kenella ka har'a mesifa kapa ka tlasa letlalo, maemong a matla a nang le lefu la tsoekere le fanoa kahare.
Tekanyetso e hlokahalang ea moriana e khethoa ka bomong ho latela litholoana tsa tlhahlobo, incl. ya data ka boemo ba tsoekere, insulin maling, kahoo o ka fana feela ka litekanyetso tse amohelehang tse tloaelehileng.
Tekanyetso e hlokahalang ea insulin bakeng sa lefu la tsoekere le tsoa ho 10-40 ED ka letsatsi.
Ka komello ea lefu la tsoekere, ha ho na likarolo tse fetang 100 ka letsatsi tse ka tsamaisoang ka mokhoa o ikhethileng, 'me ka tsamaiso ea methapo e sa feteng 50 unit ka letsatsi.
Bakeng sa matšoao a mang, moriana o laetsoe ka tekanyetso e nyane - 6-10ED / letsatsi.
Bakeng sa ente ea insulin, ho sebelisoa syringe e khethehileng, ka nale e hahiloeng, moralo oa eona o fana ka tlhahiso ea tsohle tsa eona ntle le masala, e o lumellang ho latela tekanyetso e nepahetseng ea lithethefatsi.
Pele o bokella insulin ka mokhoa oa ho emisoa ka syringe, lintho tse kahare tsa vial li lokela ho tsukutleha ho etsa emishene e tšoanang
Ka tloaelo, tekanyetso ea letsatsi le letsatsi e fanoa ka litekanyetso tse peli ho isa ho tse tharo. Ente e etsoa halofo ea hora, hora pele ho lijo. Ketso ea insulin, lethal e le 'ngoe ea eona, e qala kamora halofo ea hora, hora' me e nka lihora tse 4,8.
Ketso ea insulin e kenngoeng kahare kahare e qala kamora metsotso e 20-30. Boemo ba tsoekere bo theohela boemong ba pele kamora hora e le 'ngoe ho isa ho tse peli.
Litlamorao
Ha moriana o fanoa ka mokhoa o sa tsamaeang hantle, lipodystrophy e ka ba teng. Hape, lithethefatsi li ka baka allergies.
Insulin e phahamisitsoeng ka lebaka la ho fetella ha eona e ka lebisa ho tsitsinyeho ea hypoglycemic. Matšoao: ho sesefa ho eketsehileng, ho fufuleloa, bofokoli, ho hema ka thata, ho tsekela, ho tsofala, ka seoelo - komello, makhopho, ho nyehla, ho lahleheloa ke letsoalo.
Insulin: litheko tsa litlhare tsa inthanete
Syringe sfm insulin 3x comp 1ml n20 (u40 / u100 26g 0.45x12)
Syringe bd insulin e ntle haholo + 0.5ml n10 (u100 g29 0.33x12.7)
Syringe bd "insulin" e na le "1ml n10 (u40 30g 0.3x8)
Syringe bd "insulin" e hantle feela 1ml n10 (u100 g30 0.3x8)
Syringe bd "insulin" e hantle demi 0,3ml n10 (u100 g30 0.3x8)
Insulin Protafan NM emisoa. d / inject 100ME / ml 10ml
Tharollo ea insulin Actrapid NM ea ente ea 100ME / ml 10ml
Syringe sfm insulin 3x comp 1ml n100 (u100 29g 0.33x12.7)
Syringe sfm insulin 3x comp 1ml n100 (u40 29g 0.33x12.7 ind pack)
Tharollo ea insulin Actrapid NM penfill ea likarete tsa 100 IU / ml tsa 3ml No. 5
Insulin Protafan NM Penfill Susp. d / inject100ME / ml likarete tsa 3ml N5
Insulin Humulin M3 Susp. d / jara likarete tsa 100 IU / ml. 3ml №5
Tharollo ea insulin ea kamehla ea insulin r / d likarete tsa 100 IU / ml. 3ml №5
Insulin Humalog rr d / jara likarete tsa 100ME / ml. 3ml №5
Tharollo ea Insulin Apidra Solostar ea ente ea 100ME / ml 3ml No. 5 spr-pen.
Tlhahisoleseling mabapi le sethethefatsi e akaretsoa ka kakaretso, e fanoa molemong oa tlhahisoleseling mme ha e nke sebaka sa litaelo tsa semmuso. Ho ikoetlisa ho kotsi bophelong!
Basali ba bangata ba khona ho natefeloa ke ho nahanisisa ka 'mele oa bona o motle ka seiponeng ho fapana le ho etsa thobalano. Kahoo, basali, loanang ka kutloano.
Motho ea nkang khatello ea maikutlo maemong a mangata o tla boela a be le khatello ea maikutlo. Haeba motho a sebetsana le khatello ea maikutlo a le mong, o na le monyetla o mong le o mong oa ho lebala ka boemo bona ka ho sa feleng.
E ne e le tloaelo eo e ruisa 'mele le oksijene. Leha ho le joalo, pono ena e ile ea hlakoloa. Bo-rasaense ba pakile hore ho hahola, motho ho folisa kelello le ho ntlafatsa ts'ebetso ea eona.
Libaktheria tse limilione li tsoaloa, li phela 'me li shoa ka mpeng ea rona. Li ka bonoa feela ka matla a phahameng, empa haeba li ka kopana, li ne li tla lekana ka senoelo sa kofi se tloaelehileng.
Linoko tse 'ne tsa chokolete e lefifi li na le likhalori tse ka bang makholo a mabeli. Kahoo haeba u sa batle ho phela hantle, ho molemo hore u se ke ua ja li-lobules tse fetang tse peli ka letsatsi.
Ho bua le mantsoe a makhuts'oane le a bonolo haholo, re sebelisa mesifa ea 72.
Ho 5% ea bakuli, "antidepressant clomipramine e baka" orgasm.
Haeba sebete sa hau se khaotsa ho sebetsa, lefu le ne le tla ba teng ka mor'a letsatsi.
Madi a motho "a" tsamaea "ka har'a lijana tlas'a khatello e kholo, mme haeba bots'epehi ba hae bo tlotsoe, bo ka thunya ho fihlela ho limithara tse 10.
Sebete ke setho se boima haholo 'meleng oa rona. Boima ba hae bo itekanetseng ke 1.5 kg.
Lefu le sa tloaelehang haholo ke lefu la Kuru. Ke baemeli ba morabe oa Fore New New New ba kulang le eena. Mokuli o shoa ka lebaka la litšeho. Ho lumeloa hore sesosa sa lefu lena se ja kelello ea motho.
Qalong lithethefatsi tse ngata li ne li rekisoa ka lithethefatsi. Ka mohlala, qalong heroin e ile ea rekisoa e le moriana oa khohlela. Mme cocaine e ile ea khothalletsoa ke lingaka e le mokhoa oa ho ikoetlisa le mokhoa oa ho eketsa mamello.
Ka ho etela khafetsa betheng ea letlalo le lecha, monyetla oa ho tšoaroa ke kankere ea letlalo o eketseha ka 60%.
Nakong ea bophelo, motho ea tloaelehileng ha a hlahise matamo a maholo a ka tlase ho a mabeli.
Liphio tsa rona li ka hlatsoa litha e tharo tsa mali ka motsotso o le mong.
Palo ea basebetsi ba sebetsang ofising e eketsehile haholo. Tloaelo ena e tsebahala haholo metseng e meholo. Mosebetsi oa ofisi o hohela banna le basali.
Nako ea ketso ea lithethefatsi
Ka moriana, litlhare tsa linako tse latelang li khetholloa:
- haufinyane
- khutšoanyane haholo
- nako e telele ea ho pepeseha
- nako e telele ea ho pepeseha.
Ho sebelisoa ha mofuta o mong kapa o mong oa insulin ho latela litšobotsi tsa mokuli le kalafo ea lefu la tsoekere. Mefuta e fapaneng ea "insulin" e fapana hara bona ka mokhoa oa motsoako le sebopeho. Bakeng sa mofuta o mong le o mong oa lithethefatsi, litaelo tsa tšebeliso li ntlafatsoa ho latela likarolo tsena.
Ntle le moo, ho na le litlhoko tse ling tse akaretsang tse lokelang ho bonoa ha u etsa kalafo ea insulin. Moriana o mong le o mong oa insulin o na le matšoao a itseng a ho sebelisoa le a contraindication.
Sena ke eng
Insulin ke tlhophiso ea lihormone-peptide. E sebelisoa e le moriana o itseng kalafong ea lefu la tsoekere. Ena ke hormone e sebetsang ka mafolofolo ho metabolism ea carbohydrate mme e fokotsa khatello ea tsoekere maling. Phokotso ea lik'habohaedreite e fihlella ka ho eketsa tekanyo ea tsoekere ka linama tse itšetlehileng ka insulin tlasa ts'usumetso ea insulin, e khothalletsang ho hlophisoa ha glycogen ka lisele tsa sebete mme e thibela phetoho ea li-amino acid le mafura ho lik'habohaedreite.
Empa ho na le litlamorao tsa insulin 'meleng.
Haeba a lahlehile?
Ka lebaka la khaello ea eona, ho bonoa keketseho ea maemo a tsoekere, e leng se bakang ho hlaha ha lefu la tsoekere le mathata a mang. Ho haella ha insulin ho etsahala ka lebaka la liphetoho mokhoapong, tse bakoang ke ho sitisoa hoa tšebetso ea tsamaiso ea endocrine, kamora ho lemala kapa nakong ea khatello e phahameng ea kelello e amanang le maemo a sithabetsang.
Meriana e entsoe ka lisele tsa manyeme a liphoofolo.
Pheko ea lefu la tsoekere
Insulin e nkoa e le eona moriana o ka sehloohong kalafong ea lefu la tsoekere, hobane e fokotsa hyperglycemia, e pheta phepelo ea glycogen ka har'a lisele le mesifa, e fokotsa sebopeho sa glucose, e nolofatsa lefu la tsoekere. Insulin bakeng sa ts'ebeliso ea bongaka e fumanoa ho manyeme a likolobe le likhomo. Ho na le mokhoa oa tlhahiso ea lik'hemik'hale ka insulin, empa hajoale e ka fumaneha. Mekhoa ea biotechnological bakeng sa tlhahiso ea insulin ea motho e hlahisitsoe. Insulin e fumanoeng ke boenjiniere ba liphatsa tsa lefutso e lumellana ka botlalo le letoto la amino acid ea insulin ea motho.
Maemong moo ntho ena e fumanoang ho tsoa ho litšoelesa tsa liphoofolo, litšila tse fapaneng (glucagon, proinsulin, liprotheine, "statin", polypeptides, jj) li ka bonoa sehlahisoa ka lebaka la tlhoekiso e sa lekanang. Lijo tse se nang phepo e ntle li ka baka litlamorao tse fapaneng.
Insulin ea nama ea pancreas insulin e atile haholo kajeno. Crystalline insulin ea motho le eona e sebelisitsoe haholo.
Ts'ebetso ea ntho ena e khethiloe ka tlhaho. Bakeng sa yuniti e le 'ngoe ea tšebetso (yuniti ea machabeng), ts'ebetso ea 0.04082 mg ea insulin e nkoa.
Pele re nka hore na insulin e ama 'mele joang le litlamorao tsa ntho ena, rea tseba hore na e behiloe maemong afe.
Matšoao a ho khethoa
Matšoao a ho khethoa ke ho ba teng ha 'mele oa mefuta e tsoelang pele ea mofuta o itšetlehileng ka lefu la tsoekere. Ka litekanyetso tse nyane, e ka sebelisoa kalafo ea li-pathologies tsa sebete. Haeba ho hlokahala, ho ka etsahala ho sebelisa lithethefatsi tse joalo kalafong ea mafu a kelello le a neuropsychiatric.
Insulin e ka ba le matšoao a latelang a ts'ebeliso:
- kalafo le thibelo ea acidosis,
- thibelo ea ho fokola hoa mmele
- thyrotooticosis,
- furunculosis,
- lefu la tsoekere,
- urticaria, eczema, jj.
Ka botaoa ba joala le schizophrenia
Tšebeliso ea insulin kalafong ea joala le mefuta e meng ea schizophrenia e bontšitse litholoana tse ntle. Nakong ea kalafo ea schizophrenia, kalafo ea insulinocomatous e beoa, eo ho eona lethaliti la insulin le kenngang 'meleng oa mokuli le sa khone ho baka ho thothomela ha hypoglycemic. Maemong a mang, lithethefatsi tse nang le insulin li fuoa bakuli nakong ea ho phomola ha tsamaiso ea methapo.
Contraindication le litlamorao tsa insulin li tla hlahisoa ka tlase.
Insulin e hatelloa neng?
Insulin e na le meeli le li-contraindication tse ling bakeng sa tšebeliso.Maemo a latelang a pathological a kenyelelitsoe lenaneng la li-contraindication:
- pancreatitis
- hepatitis
- jade
- ho ba teng ha calculi ka liphio le nako ea ho mpefala ha lefu la lejoe la liphio,
- lefu le bolaeang la pelo,
- lesapo la mokokotlo.
Ntle le maloetse a kaholimo, li-insulin li ngotsoe maemong a latelang:
- ho ba teng ho mokuli ea nang le lefu la tsoekere la mofuta oa "insulin" o itšetlehileng ka insulin ho li-insulin tsa maiketsetso,
- hypoglycemia kapa litlamorao tsa pele tsa teng,
Litlhahiso tse khethehileng
Taba e amanang le tšebeliso ea meriana ena ke ho ba teng ha litla-morao tse matla tsa lithethefatsi tseo ho tsona insulin e leng teng.
Meriana e mengata e nang le insulin ha e khothalletsoe bakeng sa kalafo ea lefu la tsoekere nakong ea kemolo le lactation. Ka nako ena, meriana e entsoeng motheong oa insulin ea tlhaho ea liphoofolo e lokela ho sebelisoa.
Litla-morao tsa insulin
Litla-morao tse hlahang nakong ea ts'ebeliso ea insulin li bonahala maemong a ho fetella nakong ea ente. Tabeng ena, keketseho ea litekanyetso tsa mali tsa ntho e ka bonoa. Sena se ka kenya letsoho kholisong ea boemo ba hypoglycemia, bo lebisang ho tsitsinyeho ea hypoglycemic.
Hona ke litlamorao tse ka sehloohong tsa insulin 'meleng oa motho, empa ho na le tse ling.
Ho eketsa boemo ba eona ho etsa hore mofufutso o eketsehe, ho tsekela, ho eketsa tšebetso ea lekunutu ea litšoelesa tse thellang le nts'etsopele ea ho hema. Ka ho sebelisa mokhoa o feteletseng oa ho sebelisa lithethefatsi kapa lijo tse nang le lik'habohaedreite tse ngata tse boletsoeng ka nako, ho ka etsahala hore u lahleheloe ke letsoalo le ho tsietsana. Ho senyeha ho latelang ho halefisa komello ea hypoglycemic.
U ka thibela see joang?
Ho felisa matšoao a bosholu ba joala, o hloka ho ja 100 g ea bohobe bo tšoeu, likhaba tse 'maloa tsa tsoekere kapa kopi ea tee e tsoekere, o ka ja apole.
Haeba matšoao a tšohanyetso a hlaha, mokuli o lokela ho enta glucose kahare. Haeba ho hlokahala, tsamaiso e potolohileng ea adrenaline le eona e ka sebelisoa.
Litla-morao tsa insulin li lokela ho tsejoa ke motho e mong le e mong ea nang le lefu la tsoekere.
Ho hlokahala tlhokomeliso e 'ngoe ha u sebelisa lithethefatsi tsena tsa maiketsetso tsa lefu la tsoekere, haholoholo ha li fetoha le bothata ba ho fokola ha' mele le ha ho ka ba le tsitiso ea ho potoloha ha lisele. Tabeng ea tšebeliso ea mefuta e telele ea litokisetso tsa insulin, ho lokela hore ho hlahlojoe moroto oa boemo ba mokuli le boemo ba mali le qeto ea boemo ba tsoekere ho tsona. Boithuto bona bo tla u thusa ho utloisisa hore na ke nako efe e tla ba loketseng bakeng sa ho fana ka moriana ho theola litla-morao tsa insulin.
Ho tsamaisa lithethefatsi tse thehiloeng ho insulin, ho sebelisoa li-syringe tse khethehileng tsa insulin kapa liponche, ho latela mofuta oa insulin e sebelisitsoeng kalafo ea insulin.
U ka sebelisa ntho ee joang ho qoba litlamorao tsa insulin ho lefu la tsoekere?