ΕΡΙΕ ΟΜΕΝ ΕΝΗΜΕΡΩΤΙΚΟ ΔΕΛΤΙΟ 15 ΙΟΥΝΙΟΣ 2015 ΕΜ ΛΟΚΗ ΤΟΥ Ρ ΟΝΤ ΕΝΕΡ Ο ΟΙΗΣΗΣ ΙΜΟ ΕΤ ΛΙΩΝ ΣΤΗΝ ΗΡΩΜ ΤΩΣΗ

ΕΝΗΜΕΡΩΤΙΚΟ ΔΕΛΤΙΟ 15 ΙΟΥΝΙΟΣ 2015 ΕΡΙΕ ΟΜΕΝ ΕΜ ΛΟΚΗ ΤΟΥ Ρ ΟΝΤ ΕΝΕΡ Ο ΟΙΗΣΗΣ ΙΜΟ ΕΤ ΛΙΩΝ ΣΤΗΝ ΗΡΩΜ ΤΩΣΗ Η ΛΕ ΤΙΝΗ ΩΣ ΔΙ ΝΩΣΤΙΚΟΣ ΔΕΙΚΤΗΣ ΣΕ ΤΟΜ ΜΕ Σ Κ ΡΩΔΗ ΔΙ ΗΤΗ Κ Ι ΝΤΙΣΤ ΣΗ ΣΤΗΝ ΙΝΣΟΥΛΙΝΗ ΣΥΣ ΕΤΙΣΗ ΥΣ ΡΚΙ Σ ΜΕ ΤΟ Υ Ρ ΕΙ ΣΥΣ ΕΤΙΣΗ ΤΗΣ Σ Ι Ο ΡΕΝΕΙ Σ Κ Ι ΤΗΣ ΟΜΟΚΥΣΤΕ ΝΗΣ ΣΤΟΝ ΟΡΟ ΤΩΝ Σ ΕΝΩΝ Η Ο Ι 1 Ο ΝΕΛΛΗΝΙΟ ΣΥΝΕΔΡΙΟ ΚΛΙΝΙΚΗΣ ΗΜΕΙ Σ ΚΟΣΜΙ ΗΜΕΡ ΝΕ ΡΟΥ 1

1 Σ Κ 2 1 Ο 2015 1 Σ Κ ΣΗΜ ΝΤΙΚΕΣ ΗΜΕΡΟΜΗΝΙΕΣ 20 Σ 2015 Ο 2015 0 Σ 2015 0 0 20 0 ΕΕΚ Κ 10 210 5 51 210 5 2 2

ΕΜ ΛΟΚΗ ΤΟΥ Ρ ΟΝΤ ΕΝΕΡ Ο ΟΙΗΣΗΣ ΙΜΟ ΕΤ ΛΙΩΝ ΣΤΗΝ ΗΡΩΜ ΤΩΣΗ Κ πό Μ ι 1, π λ Μ ί 2 1 Π υχι ύχ μ μ Ι ικώ Ε γ ίω, ΕΙ Αθ,2 μικό, PhD, MSc ά Η ϊ [1] LDL HDL ΐ Η HDL Ap A I LDL Η Η [2] LDL MCP 1 Η MCP 1 [3] ϊ ϊ [4] [5] [6] [7] [8] Η [9] Η Η [10] Η [11] άγ γ 1966 Barbar Zvaifler 1970 Benveniste 1971 Siraganian Olser 1972 Benveniste Hens n C chrane 3

1974 1977 1979 [12] Ό PAF PAF 10 14 [13] Η PAF G ΐ Η G ΐ ϊ 1 4 5 ϊ C [14] O PAF de n v rem deling de n v 1 sn 3 C A 1 2 PAF DTT PAF Η rem deling 2 1 2 PAF Η PAF PAF C A Η PAF PAF [15] Η PAF PAF AH sn 2 2 HDL LDL ϊ LDL [16] Ε A A AH ά Η PAF vw O vw [17] PAF LDL [18] PAF AH [19] Η LPC ΐ C [20] Η PAF AH PAF AH [21] G994àT [22] 379V ϊ [23] [19] Η γ 1 V Mallika ''Ather scler sis Path physi l gy and the le vel isk Fact rs A Clinic bi chemical Perspec ve '' Angiology 5 2007 513 522 2 er Mar n F Br dde Beate ehrel ''High density lip pr teins platelets and the path genesis ather scler sis '' CEPP 7 2010 226 735 3 Falk ''Path genesis Ather scler sis '' JAAC 8s1 2006 C7 C12 4

4 G Guyt n F lemp ''Devel pment the lipid rich c re in human ather scler sis '' Pubmed 1 1996 4 11 5 T D Li le d D Trev r Benne Mar n ''Ap pt c cell death in ather scler sis '' Current opinion in lipidology 5 2003 469 475 6 Ale p ul s P aggi ''Calci ca n in ather scler sis '' Nature Reviews Cardiology 6 2009 681 688 7 P M ren Purush thaman M Sir l A P Levy V Fuster '' e vasculari a n in human ather scler sis '' Circula on 113 2006 2245 2252 8 Z S Galis hatri ''Matri Metall pr teinases in Vascular em deling and ther genesis '' Circula on research 90 2002 251 262 9 Marutsuka Hatakeyama A Yamashita Y Asada ather scler sis '' Pubmed 1 2005 1 8 '' le thr mb genic act rs in the devel pment 10 L Mart rell Mar ne G n le C dr gue M Gen le O Calvayrac L Badim n ''Thr mbin and pr tease ac vated recept rs PA s in ather thr mb sis '' Thrombosis and Haemostasis 2 2008 249 455 11 S P Mars S Mehta A Frutkin A H use McCrary ulkarni '' L adip nec n levels are ass ciated ith ather genic dyslipidemia and lipid rich pla ue in n ndiabe c c r nary arteries '' Pubmed 5 2008 989 94 12 S s uena i H P Ba an '' le Platelet Ac va ng Fact r in Cell Death Signaling in the C rnea A evie '' Molecular neurobiology 1 2010 32 38 13 ''Platelet ac va ng act r '' Κ δι λ γικ γ ώμ 2012 2 7 15 24 14 L Liu S H Xia '' le platelet ac va ng act r in path genesis acute pancrea s '' World journal of gastroenterology 4 2006 539 545 15 G M ntrucchi G All a G Gamussi '' le platelet ac va ng act r in cardi vascular path physi l gy'' APS 4 2000 1671 1682 16 M P e e W A Buurman G amsay W M Greve ''Mul ple rgan ailure Springer e Y rk 2000 ISB 0 387 98733 9 17 P Grant ''Diabetes mellitus as a pr thr mb c c ndi n '' Journal of internal medicine 2 2007 157 172 18 D C Ts ukat s ''C pper Cataly ed O ida n Mediates PAF F rma n in Human LDL Subspecies '' Arteriosclerosis, Thrombosis, and Vascular Biology 17 1997 3505 3512 19 A Th ms n Danesh ''Lip pr tein ass ciated ph sph lipase A2 and risk c r nary disease str ke and m rtality c llab ra ve analysis 32 pr spec ve studies '' The Lancet 2010 375 9725 1536 1544 20 T Matsum t T bayashi amata '' le lys ph spha dylch line LPC in ather scler sis '' Pubmed 2007 14(30):3209-20. 21. Unn T akamura H anek T Uchiyama Yamam t Sugatani M Mi a S akamura ''Plasma platelet ac va ng act r acetylhydr lase de ciency is ass ciated ith ather scler c cclusive disease in apan '' Journal of vascular surgery 2000 32 2 263 267 5

22 Unn T Saka uchi T akamura Yamam t Su atani M Mi a nn H ''A single nucle de p lym rphism in the plasma PAF acetylhydr lase gene and risk ather scler sis in apanese pa ents ith peripheral artery cclusive disease '' Pubmed 2006 134 1 36 43 23 P Y Liu Y H Li W L Wu T H Cha L M Tsai L Lin G Y Shi H Chen '' Platelet ac va ng act r acetylhydr lase A379V e n 11 gene p lym rphism is an independent and unc nal risk act r r premature my cardial in arc n '' Pubmed 2006 4 5 1023 8 6

Η ΛΕ ΤΙΝΗ ΩΣ ΔΙ ΝΩΣΤΙΚΟΣ ΔΕΙΚΤΗΣ ΣΕ ΤΟΜ ΜΕ Σ Κ ΡΩΔΗ ΔΙ ΗΤΗ Κ Ι ΝΤΙΣΤ ΣΗ ΣΤΗΝ ΙΝΣΟΥΛΙΝΗ Μ ι Αλί Αμπδελ χμ, εχ λόγ Ι ικώ Ε γ ίω, ΕΙ Αθ, Μ ί π λ, μικό, MSc Κλι ικ μεί, PhD Βι χ μεί 1 7 M rales A 2004 I II 2 Oda 2008 3 G kulakrishnan 2013 4 Maghb li Ζ 2007 5 Baban 2010 61 63 Η 6 2010 7 Silha 2003 Η 7

8 Ι ΛΙΟ Ρ Ί 1 M Huerta Adip nectin and leptin p tential t ls in the di erential diagn sis pediatric diabetes? 2006 Sep 7 3 187 96 [PubMed] http ncbi nlm nih g v pubmed 17131205 2 A M rales C Wasser all T Brusk C Carter D Schat Silverstein T llis and M Atkins n Adip nectin and leptin c ncentrati ns may aid in discriminating disease rms in children and ad lescents ith type 1 and type 2diabetes 2004Aug 27 8 2010 4 http ncbi nlm nih g v pubmed 15277432 3 Oda S Imamura T Fujita Y Uchida Inagaki H aki a a Hayaka a A Su uki Takeda Y H rika a and M It h The rati leptin t adip nectin can be used as an inde insulin resistance 2008 Feb 57 2 268 73 http ncbi nlm nih g v pubmed 18191059 4 G kulakrishnan V Aravindhan A Amutha S Abhijit H anjani Anjana Unnikrishnan P Miranda arayan and V M han Serum adip nectin helps t di erentiate type 1 and type 2 diabetes am ng y ung AsianIndians 2013Aug 15 8 696 702 http ncbi nlm nih g v pubmed 23902401 5 Z Maghb li A H ssein M ahmani Sha aei B Larijani elati nship bet een leptin c ncentrati n and insulin resistance 2007 Dec 39 12 903 7 [PubMed] http ncbi nlm nih g v pubmed 18075970 6 Baban asar and I Al ara i Fasting Gluc se t Leptin ati as a e Diagn stic Marker in Patients ith Diabetes Mellitus Oman Medical urnal 2010Oct 25 4 269 275[PubMed] http ncbi nlm nih g v pmc articles PMC3191658 7 2010 Η 23 2 182 186 http ngda gr innet UsersFiles ngda d cuments Xr nika 2010_2 08_Sarigianni pd 8 Silha M rsek Skrha P Sucharda B y mba and L Murphy Plasma resistin adip nectin and leptin levels in lean and bese subjects c rrelati ns ithinsulinresistance 2003Oct 149 4 331 5 http ncbi nlm nih g v pubmed 14514348 8

ΣΥΣ ΕΤΙΣΗ ΥΣ ΡΚΙ Σ ΜΕ ΤΟ Π Γεω γί 1, π λ Μ ί 2 1. Π υχι ύχ μ μ Ι ικώ Ε γ ίω, ΕΙ Αθ,2. μικό, PhD, MSc Y eur peptide Y PY GAD2 PY PY2 PY2 Y PY GAD2 4 PY stress PY 5 Y Y 5 60 0% ΐ PFG ϊ Y PY 2 Y PY PY PY LH AC VTA PY PY VTA AC PY AC LH VTA PY 1 9

Η POMC C Y C LA cp cp 6 Η Y PY POMC m A C LA cp FF Lean FF 10 21 25 8 12 PF FF 10 FF FF Ω FF FF PY POMC POMC POMC C POMC PY 3 PY 2 7 8 La s n Western Ontari ΐ PY ΐ Ω ΐ ΐ ΐ 9 10 10

Ρ Φ 1 Pandit Luijendijk M Vanderschuren L Fleur S Adan Limbic substrates the e ects neur peptide Y n intake and m tivati n r palatable d Obesity Silver Spring 2014 Feb 6 d i 10 1002 by 20718 2 cha M Fernandes P L tu B Manhães A Barradas P Ten ri F Undernutriti n during early li e alters neur peptide Y distributi n al ng the arcuate paraventricular path ay eur science 2014 an 3 256 379 91 3 Diané A Pierce W ussell Heth C Vine D ichard D Pr ct r S D n regulati n hyp thalamic pr pi melan c rtin POMC e pressi n a ter eaning is ass ciated ith hyperphagia induced besity in C rats vere pressing neur peptide Y Br utr 2014 Mar 111 5 924 32 d i 10 1017 S0007114513003061 pub 2013 Oct 7 4 ensha D Batterham Peptide YY A p tential therapy r besity Curr Drug Targets 2005 6 171 179 5 Dube MG arla SP arla PS L abundance PY in the hyp thalamus can pr duce hyperphagia and besity Peptides 2007 2 475 479 6 ussell Graham S ichards n M Cardi vascular disease in the C LA cp rat M l Cell Bi chem 1998 v 188 1 2 113 26 7 rashes M Shah B da S L ell B apid versus delayed stimulati n eeding by the end gen usly released Ag P neur n mediat rs GABA PY and Ag P Cell Metab 2013 Oct 1 18 4 588 95 d i 10 1016 j cmet 2013 09 009 8 Beck B eur peptide Y in n rmal eating and in genetic and dietary induced besity Phil s Trans S c L nd B Bi l Sci 2006 361 1159 1185 9 Diané A Pierce W ussell Heth C Vine D ichard D Pr ct r S D n regulati n hyp thalamic pr pi melan c rtin POMC e pressi n a ter eaning is ass ciated ith hyperphagia induced besity in C rats vere pressing neur peptide Y Br utr 2014 Mar 111 5 924 32 d i 10 1017 S0007114513003061 pub 2013 Oct 7 10 Hsieh Y Chen P Yu C Lia u D The neur peptide Y Y1 recept r kn ckd n m dulates activat r pr tein 1 inv lved eeding behavi r in amphetamine treated rats M l Brain 2013 v 13 6 46 d i 10 1186 1756 6606 6 46 11

Υ Ρ ΕΙ ΣΥΣ ΕΤΙΣΗ ΤΗΣ Σ Ι Ο ΡΕΝΕΙ Σ Κ Ι ΤΗΣ ΟΜΟΚΥΣΤΕ ΝΗΣ ΣΤΟΝ ΟΡΟ ΤΩΝ Σ ΕΝΩΝ Η Ο Ι Γεώ γι Μπ κ ύλι, εχ λόγ Ι ικώ Ε γ ίω, ΕΙ Αθ, Μ ί π λ μικό, MSc. Κλι ικ μεί, Ph.D Βι χ μεί. ψ ΐ Ε γ γ ΐ [1 2] ΐ [3 4] ΐ ϊ [5 6] [7 8 9] 1960 [10 11] Σ χ Ah d A M ust t (201 ) [12] 6 ( ) ΐ ( ) Φ FOLH1 (γ) ΐ 12

( ) ( ) ΐ ( ) ( y S K t 201 ) [13] 40 40 ΐ 10 ICD 10 ( ) ΐ ( ) (γ) ( ) A sh t (201 ) [14] 1379 ΐ 381 998 2 4 DSM IV S d s v c t (201 ) [15] ( ) ΐ ( ) Φ (γ) T H K & S W M (2011) [16] ΐ 2 Φ H M u t (2010) [17] ΐ Ο / Μ Τ ό Λά Υγ Μά (p) Ο ΐ 16 1µm l L 10 9µm l L p = 0 028 ό Οξύ 4 2 g L 8 2 g L p < 0 001 ( M t 200 ) [18] 250 250 ΐ ΐ ύ / Μ Τ ό Λά Υγ Μά (p) Ά 12 26µm l L 1 11 40µm l L 1 p = 0 026 9 61µm l L 1 8 33µm l L 1 p < 0 001 13

J s ph L v t (200 ) [19] Φ ϊ ΐ S G dy t (200 ) [20] 12 ϋ γ Ad Wys s & Iw Kł sz ws (201 ) [21] 48 ΐ BMI HDL Μ Τ / ύ Ά ό Λά (p) 17 0µm l L 12 1µm l L p = 0 009 Υγ Μά 16 0µm l L 11 2µm l L Σύ 16 5µm l L 11 6µm l L p < 0 001 ΐ ύ / Μ Τ Υγ Μά ό Λά (p) Ά 17 0µm l L 16 0µm l L p = 0 4 12 1µm l L 11 2µm l L p = 0 6 Σύ 14 5µm l L 13 6µm l L p = 0 48 (Δ Κό t 2010) [22] 153 92 61 ΐ MTHF COMT (J s ph L v t 2005) [23] ΐ ΐ CSF V s C t (1 ) [24] Ku u H t (1 ) [24] ΐ MTHF Σ ζ Σ ά Μ Σ όχ 14

ϊ Ό ΐ ϊ Η ϊ ϊ Η ϊ Η Φ Ό γ 1 2008 2013 Δι χέ Σχιζ φ έ ει, h p kantart is s ri s gr html s i reneia html 16 2014 2 Michel Hersen Deb rah C Beidel 2011 Adult Psychopathology and Diagnosis, hn Wiley & S ns ISB 13 978 1118138847 l gical c nsidera ns 3 2001 Η Ομ κυ εΐ ω π γ κι δύ υ κ δι γγει κώ ό ω κ ι θ μβώ εω, 18 5 526 536 4 2000 Υπε μ κυ εϊ ιμί, 17 4 348 351 5 2008 ΕΠΙΠΕΔΑ ΟΜΟΚΥΣ ΕΪΝΗΣ, ΦΥΛΛΙΚΟΥ ΟΞΕΟΣ ΚΑΙ ΒΙ ΑΜΙΝΗΣ Β 12 Σ ΟΝ ΟΡΟ ΠΑΙΔΙΩΝ ΗΛΙΚΙΑΣ 6-15 ΡΟΝΩΝ ΚΑΙ ΣΥΣ Ε ΙΣΗ ΟΥΣ ΜΕ Η ΔΙΑ ΡΟΦΗ, Θ Θ 17 75 6 2005 Η μ ί μ κυ εϊ εγκυμ ύ, Η Η Η & 37 1 37 42 15

7 2011 Σχιζ φ έ ει κ ι ί Ηλικί Η Ί 3 48 8 2012 Συγκ ι ικ μελέ π ϊκ μ φ Σχιζ φ έ ει π ώιμ κ ι όψιμ έ ξ, 5 12 9 2007 Σχιζ φ έ ει με έ ξ π ιδικ λικί : χ κ ι ικ κ ι ιδι ι ε ό ε, 44 2 10 P llin W Card n PV r ety SS 1961 E ects of amino acid feedings in schi ophrenic pa ents treated with ipronia id, Science 133 3446 104 105 11 Spir H Schimke Welch P 1965 Schi ophrenia in a pa ent with a defect in methionine metabolism, The urnal nerv us and mental disease 141 3 285 290 12 M usta a A A He edi D H issa A M Frydecka D Misiak B 2014 Homocysteine levels in schi ophrenia and a ec ve disorders focus on cogni on, Fr n ers in Behavi ral eur science 8 343 d i 10 3389 nbeh 2014 00343 13 arayan S Verman A a mani S Ananthanarayanan P H Adithan C 2014 Plasma homocysteine levels in depression and schi ophrenia in South ndian Tamilian popula on, Indian urnal Psychiatry 56 1 46 53 d i 10 4103 0019 5545 124746 14 Akira ishi Shusuke umata Atsushi Tajima Mak t in shita umik ikuchi Shinji Shim dera Masahit T m take a utaka Ohi y ta Hashim t Issei Im t Masat shi Takeda Tetsur Ohm ri 2014 Meta-analyses of Blood Homocysteine Levels for Gender and Gene c Associa on Studies of the MTH R C677T Polymorphism in Schi ophrenia, Schi phrenia Bulle n Advance Access d i 10 1093 schbul sbt154 15 Saida Fisek vic a ja Serdarevic Amra Memic ai Serdarevic Sabina Sahbeg vic Abdulah ucukalic 2013 Correla on between serum concentra ons of homocysteine, folate and vitamin B12 in pa ents with schi ophrenia, urnal Health Sciences 3 2 138 144 16 Tae H im Se k W M n 2011 Serum Homocysteine and olate Levels in orean Schi ophrenic Pa ents, Psychiatry Inves ga n 8 134 140 d i 10 4306 pi 2011 8 2 134 17 Mabr uk H D uki W Mechri A Y unes M Ome ine A B uslama A Gaha L ajjar MF 2010 Hyperhomocystéinémie et schi ophrénie : étude cas témoin, L' ncéphale 37 4 308 313 d i 10 1016 j encep 2010 12 004 18 Yin Ying Ma Chi Chung Shek Ma C W ng a Chee Yip ger M g Desm nd G H guyen Ting eung P n 2009 Homocysteine level in schi ophrenia pa ents, Australian and e Zealand urnal Psychiatry V lume 43 Issue 8 pp 760 765 d i 10 1080 00048670903001935 19 seph Levine Ziva Stahl Ben Ami Sela Vladimir uderman Oleg Shumaic Ivgeny Babushkin Yamima Osher Yuly Bersudsky H Belmaker 2006 Homocysteine-Reducing Strategies mprove Symptoms in Chronic Schi ophrenic Pa ents with Hyperhomocysteinemia, Bi l gical Psychiatry V lume 60 Issue 3 pp 265 269 d i 10 1016 j bi psych 2005 10 009 20 Sim n Gilb dy Sarah Le is Tracy Ligh t 2006 Μethylenetetrahydrofolate Reductase ( MTH R ) Gene c Polymorphisms and Psychiatric Disorders: A HuGE Review, American urnal pidemi l gy d i 10 1093 aje k j347 21 Adam Wys kinski I na ł s e ska 2013 Homocysteine Levels in Pa ents with Schi ophrenia on Clo apine Monotherapy, eur chemical esearch 38 2056 2062 d i 10 1007 s11064 013 1113 1 22 Φ Θ 2010 Κλι ικ ί, βι χ μικ ί κ ι γε ε ικ ί υ ελε έ γ ω ικ δυ λει υ γί χιζ φ έ ει, Ί 23 Levine G Agam B A Sela D L Garver F T rrey H Belmaker 2005 CS homocysteine is not elevated in schi ophrenia, urnal eural Transmissi n V lume 112 Issue 2 pp 297 302 d i 10 1007 s00702 004 0269 24 Chris na B lander G uaille Té d r B glieri 2007 Homocysteine: Related Vitamins and Neuropsychiatric Disorders, Springer Science & Business Media ISB 13 978 2287225581 p 154 16

12 Μ ΡΤΙΟΥ 2015 ΚΟΣΜΙ ΗΜΕΡ ΝΕ ΡΟΥ Σύ Υγ γ ό - έω Π κευ ι Μικ βι λ γικ ύ Ε γ ί υ ζ εί υ, Ν κ μεί υ Πει ι -Γε ικ Γ μμ έ υ Π λι ι ικ ύ Συλλόγ υ ω Λι ύμ Αιγ λεω -Γε ικ Γ μμ έ υ Π ελλ ί υ Αθλ ικ ύ Συλλόγ υ, Με μ χευμέ ω ΔΡΟΜΕΑΣ -Λ π ι Νεφ ικ ύ Μ χεύμ - Αθλ ι μ δ Με μ χευμέ ω κ ι Ιδ υ ικό Μέλ πό 197 2006 Η Η Φ 10 12 Μ χ ύ γ ό Η Ν ύ ό Ν Νό ( ΝΝ) ό Ν ά γ γ ό 17

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Η Θ Η ` Ρ Ο Ν ζίμ ικμέ (Nâ ım Hikmet, Θε λ ίκ 15 Ι υ ί υ 1902 Μό χ 2 Ι υ ί υ 1963) ύ κ π ι κ ι δ μ υ γό, έ γ υ π ί υ με φ κ ε π λλέ γλώ ε. Υπ ξε μέλ υ Κ μμ υ ι ικ ύ Κόμμ υ κί. Πέθ ε Μό χ πό κ δι κ π β λ ε λικί 61 ε ώ. Α κ ι π ώ υ π ι μ γ φ κ με π δ ι κό μέ, ικμέ δι κ π μ κ ύ θ κε πό πλ ί ι υ μέ υ κ ι μ ι κ λ ξί κ ι χι ε ζ εί έ μ φ γι π ι μ υ. Κ δι κει ω π ώ ω χ ό ω δι μ υ Σ βιε ικ Έ ω, ζ υ έφ ε π κ ύφωμ. Π ίμ ε ελεύθε ίχ, π ί ί ι ζε κ ι με πλ ύ ι φω λ γί υ κικ γλώ. Επ ε κε κυ ίω πό Βλ ιμί Μ γι κόφ κι. http thessal nikiartsandculture gr 23