259:
to the 4- to 5-fold increase in glutamate release in nucleus accumbens during the acute withdrawal state between binges but only in dose 3 g/kg, in 2 g/kg there is no increase in glutamate release. In contrast, during withdrawal from chronic alcoholism only a 2- to 3-fold increase in glutamate release occurs. The high levels of glutamate release causes a chain reaction in other neurotransmitter systems. The reason that chronic sustained alcoholism is thought by some researchers to be less brain damaging than binge drinking is because tolerance develops to the effects of alcohol and unlike binge drinking repeated periods of acute withdrawal does not occur, but there are also many alcoholics who typically drink in binges followed by periods of no drinking. Excessive glutamate release is a known major cause of neuronal cell death. Glutamate causes
288:
and alcoholics. Neural kindling may explain the advancing pathogenesis and progressively deteriorating course of alcoholism and explain continued alcohol abuse as due to avoidance of distressing acute withdrawal symptoms which get worse with each withdrawal. Multiple withdrawals from alcohol is associated with long-term nonverbal memory impairment in adolescents and to poor memory in adult alcoholics. Adult alcoholics who experienced two or more withdrawals showed more frontal lobe impairments than alcoholics who had a history of one or no prior alcohol withdrawals. The finding of kindling in alcoholism is consistent with the mechanism of brain damage due to binge drinking and subsequent withdrawal.
240:
which are a subtype of glutamate receptors being altered by repeated withdrawals from benzodiazepines. The changes which occur after withdrawal in AMPA receptors in animals have been found in regions of the brain which govern anxiety and seizure threshold; thus kindling may result in increased severity of anxiety and a lowered seizure threshold during repeated withdrawal. Changes in the glutamate system and GABA system may play an important role at different time points during
287:
Repeated acute withdrawal from alcohol which occurs in heavy binge drinkers has been shown in several studies to be associated with cognitive deficits as a result of neural kindling; neural kindling due to repeated withdrawals is believed to be the mechanism of cognitive damage in both binge drinkers
258:
Binge drinking may induce brain damage due to the repeated cycle of acute intoxication followed by an acute abstinence withdrawal state. Based on animal studies, regular binge drinking in the long-term is thought to be more likely to result in brain damage than chronic (daily) alcoholism. This is due
118:
properly; this is believed to be due to kindling of the amygdala with resultant distortion of neurotransmission. Adolescents, females and young adults are most sensitive to the neuropsychological effects of binge drinking. Adolescence, particularly early adolescence, is a developmental stage which is
239:
Repeated benzodiazepine withdrawal episodes may result in similar neuronal kindling as that seen after repeated withdrawal episodes from alcohol, with resultant increased neuro-excitability. The glutamate system is believed to play an important role in this kindling phenomenon with AMPA receptors
139:
Repeated acute intoxication followed by acute withdrawal is associated with profound behavioural changes and neurobiological alterations in several brain regions. Much of the documented evidence of kindling caused by repeated detoxification regards increased seizure frequency. Increased fear and
135:
deficiency. It is possible in some cases that alcohol abuse via a kindling mechanism can cause the development of a chronic substance-induced psychotic disorder (e.g., schizophrenia). The effects of an alcohol-related psychosis include an increased risk of depression and suicide as well as
176:
release in the central nervous system, which increases neurotoxicity; this may result in cognitive impairments, psychological problems, and may cause irreversible brain damage in both adolescent and adult long-term binge drinkers. Similar to binge drinkers, individuals suffering from
267:
and oxidative glutamate toxicity. Evidence from animal studies suggests that some people may be more genetically sensitive to the neurotoxic and brain damage associated with binge drinking regimes. Binge drinking activates microglial cells which leads to the release of inflammatory
217:
explains long-term potentiation as well as neuro-kindling phenomena. There is some evidence that a prior history of CNS depressant dependence (e.g. alcohol) increases the risk of dependence on benzodiazepines. Tolerance to drugs is commonly believed to be due to receptor
152:
and increases the risk of an abstaining alcoholic relapsing. This impairment may also result in long-term adverse effects on emotional behavior. Impaired associative learning may make behavioural therapies involving conditioning approaches for alcoholics less effective.
77:
Each withdrawal leads to more severe withdrawal symptoms than in previous episodes. Individuals who have had more withdrawal episodes are at an increased risk of very severe withdrawal symptoms, up to and including seizures and death. Long-term activation of the
301:
Kindling refers to the phenomenon of increasingly severe withdrawal symptoms, including an increased risk of seizures, that occurs as a result of repeated withdrawal from alcohol or other sedative–hypnotics with related modes of action.
113:
is believed to increase impulsivity due to altered functioning of prefrontal–subcortical and orbitofrontal circuits. Binge drinking in alcoholics who have undergone repeated detoxification is associated with an inability to interpret
122:
Approximately 3 percent of people who are alcohol dependent experience psychosis during acute intoxication or withdrawal. Alcohol-related psychosis may manifest itself through a kindling mechanism. The mechanism of alcohol-related
185:
and cognitive impairments, leading to altered neurological function. The changes in activity of excitatory and inhibitory neurotransmitter systems is similar to that which occurs in individuals suffering from limbic or
226:, may play a more important role in the development of benzodiazepine dependence; this may lead to prolonged conformational changes in the receptors or altered subunit composition of the receptors.
322:, but the majority of research into kindling has primarily focused on alcohol. An intensification of anxiety and other psychological symptoms of alcohol withdrawal also occurs.
939:
181:
develop changes to neurotransmitter systems, which occur as a result of kindling and sensitization during withdrawal. This progressively lowers the threshold needed to cause
144:
experiences. The impairments induced by binge drinking or repeated detoxification of alcoholics cause a loss of behavioural inhibition of the prefrontal cortex; the
222:; however, there is very limited evidence to support this, and this hypothesis comes from animal studies using very high doses. Instead, other mechanisms, such as
1861:
1489:
829:
De Witte P, Littleton J, Parot P, Koob G (2005). "Neuroprotective and abstinence-promoting effects of acamprosate: elucidating the mechanism of action".
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particularly vulnerable to the neurotoxic and neurocognitive adverse effects of binge drinking due to it being a time of significant brain development.
932:
340:
drug, reduces excessive glutamate activity in the central nervous system and thereby may reduce excitotoxicity and withdrawal related brain damage.
1762:
148:
is mediated by subcortical systems such as the amygdala. This loss of behavioral control due to brain impairment predisposes an individual to
1286:
223:
140:
anxiety and cognitive impairments are also associated with alcohol withdrawal kindling due to binge drinking or alcoholics with repeated
925:
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1089:
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1342:
445:"Biochemical and neurotransmitter changes implicated in alcohol-induced brain damage in chronic or 'binge drinking' alcohol abuse"
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1261:
1352:
1244:
602:
Allison C, Pratt JA (May 2003). "Neuroadaptive processes in GABAergic and glutamatergic systems in benzodiazepine dependence".
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Mirijello A, D'Angelo C, Ferrulli A, Vassallo G, Antonelli M, Caputo F, Leggio L, Gasbarrini A, Addolorato G (March 2015).
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Failure to manage the alcohol withdrawal syndrome appropriately can lead to permanent brain damage or death.
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374:"Review. Cognitive and emotional consequences of binge drinking: role of amygdala and prefrontal cortex"
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306:(alcohol) has a very similar mechanism of tolerance and withdrawal to benzodiazepines, involving the
1705:
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540:"Epileptiform activity in alcohol dependent patients and possibilities of its indirect measurement"
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17:
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520:
466:
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281:
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from benzodiazepines. Other receptor complexes may be involved; in particular, the excitatory
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115:
38:
741:"Acute withdrawal, protracted abstinence and negative affect in alcoholism: are they linked?"
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is the neurological condition which results from repeated withdrawal episodes from
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Binge drinking regimes are associated with causing an imbalance between
1733:
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303:
182:
178:
149:
141:
1546:
707:
692:"Binge drinking in young adults: Data, definitions, and determinants"
638:
921:
874:"Identification and management of alcohol withdrawal syndrome"
677:"Alcohol – Special Subjects – Merck Manuals Consumer Version"
639:"Are binge drinkers more at risk of developing brain damage?"
443:
Ward, RJ.; Lallemand, F.; de Witte, P. (March–April 2009).
90:
overactivity, which can lead to drug and neurotransmitter
213:
system is implicated. The involvement of glutamate in
739:
Heilig M, Egli M, Crabbe JC, Becker HC (April 2010).
336:, a drug used to promote abstinence from alcohol, an
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benzodiazepine receptor complex do not fully explain
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538:Bob, P.; Jasova, D.; Bizik, G.; Raboch, J. (2011).
491:"Impulsivity, frontal lobes and risk for addiction"
37:
32:
1485:Acute intoxication from hallucinogens (bad trip)
367:
365:
82:by sedative–hypnotic drugs causes chronic GABA
597:
595:
593:
933:
127:is due to distortions to neuronal membranes,
8:
484:
482:
480:
1490:Hallucinogen persisting perception disorder
1085:
1078:
940:
926:
918:
29:
897:
805:
764:
715:
573:
563:
514:
460:
397:
1620:Kindling (sedative–hypnotic withdrawal)
489:Crews, FT.; Boettiger, CA. (Sep 2009).
438:
436:
434:
361:
33:Kindling (sedative–hypnotic withdrawal)
1763:Chronic solvent-induced encephalopathy
690:Courtney, KE.; Polich, J. (Jan 2009).
1862:Adverse effects of psychoactive drugs
1287:Alcohol-induced respiratory reactions
7:
788:Hanwella R, de Silva V (June 2009).
372:Stephens, DN.; Duka, T. (Oct 2008).
1794:Anabolic-androgenic steroids abuse
1423:Synthetic cannabinoid use disorder
378:Philos Trans R Soc Lond B Biol Sci
242:benzodiazepine withdrawal syndrome
25:
1343:Caffeine-induced anxiety disorder
790:"Treatment of alcohol dependence"
284:leading to neuronal destruction.
1396:Cannabinoid hyperemesis syndrome
843:10.2165/00023210-200519060-00004
757:10.1111/j.1369-1600.2009.00194.x
193:Adaptational changes at the GABA
1353:Caffeine-induced sleep disorder
1245:Fetal alcohol spectrum disorder
18:Kindling (substance withdrawal)
1747:Sudden sniffing death syndrome
1402:Intravenous marijuana syndrome
996:Post-acute-withdrawal syndrome
1:
1574:Opioid-induced endocrinopathy
616:10.1016/S0163-7258(03)00029-9
1787:Anabolic-androgenic steroids
1314:(alcohol use disorder (AUD))
1256:Positional alcohol nystagmus
1221:Alcohol-related brain damage
655:10.1016/0741-8329(93)90083-Z
565:10.1371/journal.pone.0018678
254:Alcohol-related brain damage
183:alcohol-related brain damage
1651:Benzodiazepine use disorder
1580:Opioid-induced constipation
1568:Opioid-induced hyperalgesia
1262:Wernicke–Korsakoff syndrome
1226:Alcohol withdrawal syndrome
1015:Substance-related disorders
980:Substance-induced psychosis
952:substance-related disorders
1878:
1348:Caffeine-induced psychosis
1279:Respiratory tract diseases
1264:(WKS, Korsakoff psychosis)
1061:Combined drug intoxication
251:
136:psychosocial impairments.
1657:Benzodiazepine dependence
1641:Benzodiazepine withdrawal
1451:Prenatal cocaine exposure
1114:Gastrointestinal diseases
890:10.1007/s40265-015-0358-1
507:10.1016/j.pbb.2009.04.018
422:Alcohol-Related Psychosis
215:benzodiazepine dependence
1216:Alcoholic polyneuropathy
1180:Alcohol-related dementia
1098:Alcoholic cardiomyopathy
1051:Polysubstance dependence
1024:Psychological dependence
1636:Benzodiazepine overdose
1268:Wernicke encephalopathy
1122:Alcoholic liver disease
1090:Cardiovascular diseases
495:Pharmacol Biochem Behav
98:hyperexcitability, and
84:receptor downregulation
64:sedative–hypnotic drugs
1722:Amphetamine dependence
1683:Barbiturate dependence
1514:Green Tobacco Sickness
1412:Amotivational syndrome
1292:Alcoholic lung disease
1232:Alcoholic hallucinosis
1211:Alcoholic hallucinosis
1159:Alcoholic ketoacidosis
1103:Alcohol flush reaction
971:Substance intoxication
390:10.1098/rstb.2008.0097
274:tumour necrosis factor
272:and mediators such as
188:temporal lobe epilepsy
96:central nervous system
1837:Clinical pharmacology
1417:Cannabis use disorder
1140:Auto-brewery syndrome
807:10.4038/cmj.v54i2.877
462:10.1093/alcalc/agn100
1857:Withdrawal syndromes
1822:Addiction psychiatry
1673:Barbiturate overdose
1446:Cocaine intoxication
1186:Alcohol intoxication
1028:Substance dependence
60:substance withdrawal
1706:Stimulant psychosis
1591:Opioid use disorder
1535:Nicotine dependence
1525:Nicotine withdrawal
1368:Caffeine dependence
1128:Alcoholic hepatitis
1020:Physical dependence
991:Neonatal withdrawal
556:2011PLoSO...618678B
224:receptor uncoupling
1520:Nicotine poisoning
1462:Cocaine dependence
1391:Cannabis arteritis
1251:Korsakoff syndrome
1151:Endocrine diseases
637:Hunt, WA. (1993).
179:alcohol dependence
142:alcohol withdrawal
116:facial expressions
1809:
1808:
1563:Opioid withdrawal
1326:
1325:
1300:
1299:
384:(1507): 3169–79.
282:neuroinflammation
146:prefrontal cortex
53:
52:
27:Medical condition
16:(Redirected from
1869:
1753:Toluene toxicity
1237:Delirium tremens
1133:Zieve's syndrome
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708:10.1037/a0014414
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1832:Causes of death
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1558:Opioid overdose
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1172:system diseases
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1011:Substance abuse
954:
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604:Pharmacol. Ther
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449:Alcohol Alcohol
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338:NMDA antagonist
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235:Benzodiazepines
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230:Pathophysiology
220:down-regulation
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172:and changes in
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129:gene expression
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72:benzodiazepines
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1768:Inhalant abuse
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350:Kindling model
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320:AMPA receptors
316:NMDA receptors
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265:excitotoxicity
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111:Binge drinking
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100:excitotoxicity
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1309:
1307:
1303:
1293:
1290:
1288:
1285:
1284:
1282:
1280:
1276:
1269:
1266:
1263:
1260:
1257:
1254:
1252:
1249:
1246:
1243:
1238:
1235:
1233:
1230:
1229:
1227:
1224:
1222:
1219:
1217:
1214:
1212:
1209:
1208:
1206:
1204:
1198:
1192:
1189:
1187:
1184:
1181:
1178:
1177:
1175:
1173:
1167:
1160:
1157:
1156:
1154:
1152:
1148:
1141:
1138:
1134:
1131:
1129:
1126:
1125:
1123:
1120:
1119:
1117:
1115:
1111:
1104:
1101:
1099:
1096:
1095:
1093:
1091:
1087:
1084:
1080:
1077:
1075:
1071:
1062:
1059:
1058:
1056:
1052:
1049:
1048:
1046:
1045:
1043:
1041:substance use
1037:
1029:
1025:
1021:
1018:
1016:
1012:
1009:
1008:
1007:
1004:
997:
994:
992:
989:
988:
986:
983:
981:
978:
976:
975:Drug overdose
972:
969:
968:
967:
964:
963:
961:
957:
953:
950:
943:
938:
936:
931:
929:
924:
923:
920:
909:
905:
900:
895:
891:
887:
884:(4): 353–65.
883:
879:
875:
868:
865:
860:
856:
852:
848:
844:
840:
837:(6): 517–37.
836:
832:
825:
822:
817:
813:
808:
803:
799:
795:
791:
784:
781:
776:
772:
767:
762:
758:
754:
751:(2): 169–84.
750:
746:
742:
735:
732:
727:
723:
718:
713:
709:
705:
702:(1): 142–56.
701:
697:
693:
686:
683:
678:
672:
669:
664:
660:
656:
652:
649:(6): 559–61.
648:
644:
640:
633:
630:
625:
621:
617:
613:
610:(2): 171–95.
609:
605:
598:
596:
594:
590:
585:
581:
576:
571:
566:
561:
557:
553:
550:(4): e18678.
549:
545:
541:
534:
531:
526:
522:
517:
512:
508:
504:
501:(3): 237–47.
500:
496:
492:
485:
483:
481:
477:
472:
468:
463:
458:
455:(2): 128–35.
454:
450:
446:
439:
437:
435:
431:
428:
424:
423:
417:
414:
409:
405:
400:
395:
391:
387:
383:
379:
375:
368:
366:
362:
355:
351:
348:
347:
343:
341:
339:
335:
331:
325:
323:
321:
317:
313:
305:
296:
291:
289:
285:
283:
279:
275:
271:
266:
262:
261:neurotoxicity
255:
247:
245:
243:
234:
229:
227:
225:
221:
216:
212:
208:
204:
200:
191:
189:
184:
180:
175:
171:
168:
164:
156:
154:
151:
147:
143:
137:
134:
131:, as well as
130:
126:
120:
117:
112:
105:
103:
101:
97:
93:
92:sensitization
89:
85:
81:
80:GABA receptor
75:
73:
69:
65:
61:
57:
49:
45:
42:
40:
36:
31:
19:
1785:
1712:
1663:
1626:
1619:
1474:Hallucinogen
1201:Neurological
949:Psychoactive
881:
877:
867:
834:
830:
824:
797:
794:Ceylon Med J
793:
783:
748:
744:
734:
699:
696:Psychol Bull
695:
685:
671:
646:
642:
632:
607:
603:
547:
543:
533:
498:
494:
452:
448:
420:
416:
381:
377:
332:
329:
300:
286:
278:nitric oxide
257:
238:
192:
160:
138:
121:
109:
76:
59:
55:
54:
1714:amphetamine
1665:barbiturate
800:(2): 63–5.
745:Addict Biol
334:Acamprosate
170:amino acids
86:as well as
1816:Categories
1695:Stimulants
1358:Caffeinism
1312:Alcoholism
985:Withdrawal
356:References
297:Definition
252:See also:
207:withdrawal
203:dependence
167:excitatory
163:inhibitory
150:alcoholism
48:psychiatry
1852:Sedatives
1847:Neurology
1842:Hypnotics
1801:Chocolate
1203:disorders
831:CNS Drugs
427:eMedicine
326:Treatment
312:receptors
292:Diagnosis
270:cytokines
211:glutamate
199:tolerance
174:monoamine
125:psychosis
88:glutamate
44:Neurology
39:Specialty
1734:Volatile
1609:hypnotic
1604:Sedative
1503:Nicotine
1380:Cannabis
1332:Caffeine
1191:Hangover
1039:Combined
908:25666543
859:11563216
851:15963001
816:19670554
775:20148778
726:19210057
624:12725868
584:21541318
544:PLOS ONE
525:19410598
471:19155229
408:18640918
344:See also
280:causing
133:thiamine
106:Symptoms
66:such as
56:Kindling
1779:Related
1736:solvent
1547:Opioids
1435:Cocaine
1228:(AWS):
1170:Nervous
1124:(ALD):
1074:Alcohol
959:General
899:4978420
766:3268458
717:2748736
663:8123218
643:Alcohol
575:3082533
552:Bibcode
516:2730661
399:2607328
304:Ethanol
263:due to
248:Alcohol
68:alcohol
58:due to
1790:: SUD
1749:(SSDS)
1492:(HPPD)
1247:(FASD)
998:(PAWS)
906:
896:
857:
849:
814:
773:
763:
724:
714:
661:
622:
582:
572:
523:
513:
469:
406:
396:
276:, and
205:, and
157:Causes
1653:(BUD)
1593:(OUD)
1582:(OIC)
1576:(OIE)
1570:(OIH)
1516:(GTS)
1453:(PCE)
1419:(CUD)
1398:(CHS)
1258:(PAN)
1239:(DTs)
1182:(ARD)
1161:(AKA)
1142:(ABS)
1105:(AFR)
1063:(CDI)
878:Drugs
855:S2CID
1759:SUD
1743:SID
1718:SUD
1702:SID
1679:SUD
1669:SID
1647:SUD
1632:SID
1616:SID
1587:SUD
1554:SID
1531:SUD
1510:SID
1481:SID
1458:SUD
1442:SID
1408:SUD
1387:SID
1364:SUD
1339:SID
1270:(WE)
1057:SID
1047:SUD
904:PMID
847:PMID
812:PMID
771:PMID
722:PMID
659:PMID
620:PMID
580:PMID
521:PMID
467:PMID
404:PMID
318:and
308:GABA
165:and
70:and
1305:SUD
1082:SID
1006:SUD
966:SID
894:PMC
886:doi
839:doi
802:doi
761:PMC
753:doi
712:PMC
704:doi
700:135
651:doi
612:doi
570:PMC
560:doi
511:PMC
503:doi
457:doi
425:at
394:PMC
386:doi
382:363
1818::
1026:/
1022:/
1013:/
987::
973:/
902:.
892:.
882:75
880:.
876:.
853:.
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835:19
833:.
810:.
798:54
796:.
792:.
769:.
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743:.
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710:.
698:.
694:.
657:.
647:10
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641:.
618:.
608:98
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592:^
578:.
568:.
558:.
546:.
542:.
519:.
509:.
499:93
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493:.
479:^
465:.
453:44
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447:.
433:^
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380:.
376:.
364:^
314:,
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201:,
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46:,
1716::
1667::
1630::
1606:/
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927:v
910:.
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861:.
841::
818:.
804::
777:.
755::
728:.
706::
679:.
665:.
653::
626:.
614::
586:.
562::
554::
548:6
527:.
505::
473:.
459::
410:.
388::
310:A
195:A
20:)
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