Disama dia Alzheimer (AD) ndishilangane bikole ne disama dia buongo bualu didi dikebesha kudi dibanda dia proteyine ya bungi, disama dia buongo ne disama dia buongo.
Bimanyinu binene bibidi bia disama dia Alzheimer mbikala dia plaques amyloïdes bêta (Aβ) ne dia enchevêtrements neurofibrilles (NFT) mu buongo.
Bipese bia beta-amyloïde bitu bienzeka padi tuishi tua proteine (APP) tutshikosolola kudi tuishi tua mu mubidi bua kuenza tuishi tua Aβ.
Bintu ebi bitu bibuela pamue ne bienza tutupa tua mu mubidi tutubu kabayi mua kujikija tudi tusanganyibua pambelu pa selile, tunyanga mushindu udi selile uyukila ne tufikisha ku lufu lua selile.
Batu bela meji ne: disangisha dia plaques ya Aβ ke bualu bua kumpala budi bufikisha ku disama dia AD, ne badi bamba ne: didi difikisha ku dinyanguka dia buongo.
Disama dia buongo didi kabidi ne mudimu mu disama dia disama dia Alzheimer.
Bukole bua mubidi bua kuluangana ne masama budi buandamuna ku disangisha dia plaques ya Aβ ne NFTs padibu bapatula cytokines idi yambuluisha bua disama kuvula, idi mua kunyanga buongo bikole.
Kabidi, kudi bijadiki bidi bileja ne: disama dia kansere, disama dia mitochondrial, ne disama dia glucose bidi bifikisha ku disama dia Alzheimer.
Malu aa adi mua kufikisha buongo ku dinyanguka ne ku lufu, ne kunyanga kabidi disama.
Mu kabujima, disama dia Alzheimer didi ne malu a bungi adi enza bua lungenyi luende luende luenda luenda lunyanguka ne udi upua muoyo malu adi amueneka mu disama edi.
Nemeroff CB: The preeminent role of neuropeptide systems in the early pathophysiology of Alzheimer disease: up with corticotropin-releasing factor, down with acetylcholine. Arch Gen Psychiatry. 1999, 56 (11): 991-2.
Proft J, Weiss N: Jekyll and Hide: The two faces of amyloid β. Commun Integr Biol. 2012, 5 (5): 405-7.
Whitehouse PJ, Hedreen JC, White CL, Price DL: Basal forebrain neurons in the dementia of Parkinson disease. Ann Neurol. 1983, 13 (3): 243-8.
Casadesus G, Moreira PI, Nunomura A, Siedlak SL, Bligh-Glover W, Balraj E, Petot G, Smith MA, Perry G: Indices of metabolic dysfunction and oxidative stress. Neurochem Res. , 32 (4-5): 717-22.
Candore G, Bulati M, Caruso C, Castiglia L, Colonna-Romano G, Di Bona D, Duro G, Lio D, Matranga D, Pellicanò M, Rizzo C, Scapagnini G, Vasto S: Inflammation, cytokines, immune response, apolipoprotein E, cholesterol, and oxidative stress in Alzheimer disease: therapeutic implications. Rejuvenation Res. , 13 (2-3): 301-13.
Schindler SE, McConathy J, Ances BM, Diamond MI: Advances in diagnostic testing for Alzheimer disease. Mo Med. , 110 (5): 401-5.
Singh VK: Immune-activation model in Alzheimer disease. Mol Chem Neuropathol. , 28 (1-3): 105-11.
['Dibenga kuambula bujitu: bua malu a luondapu']
['Site eu udi ne tshipatshila tshia kulongesha ne kumanyisha patupu, ki ntshia kufila mibelu ya manga anyi midimu ya baminganga to.']
['Malu adibu bafile aa kaena ne bua kuambuluisha bua kumanya disama kampanda anyi bua kudiondopa to, ne bantu badi bakeba mibelu ya malu a luondapu badi ne bua kuyikila ne munganga udi ne mukanda wa dianyisha dia mudimu.']
['Tangila ne: ordinatere udi ufila mandamuna a nkonko eyi utu utamba kupanga kujadika malu padiwu ne malu a bungi bu mudi bungi bua bantu badibu bakuate ne disama kampanda.']
['Ikala misangu yonso ukeba mibelu ya munganga anyi ya munganga mukuabu udi mumanye bimpe malu a luondapu. Kupepeji mibelu ya baminganga anyi kuanji kuanji kuindila bua kuyikeba anu bua bualu kampanda buudi mubale mu site eu to. Wewe wela meji ne: udi ne disama dia lukasa, fubidila 911 anyi ndaku diakamue ku lupitadi lua pabuipi nebe. Site eu anyi dienza mudimu nende ki mbienze bua kuikale malanda pankatshi pa munganga ne mubedi to.']
['Mikenji ya mu États-Unis idi ilomba bantu badi ne bukenji bua kuenza bintu kampanda bua kuenzabu malu makuabu.']
['Wewe mumone ne: bualu kampanda budi mu site wetu anyi mu midimu yetu budi bunyanga manême ebe a bintu, udi mua kututumina mukanda bua kutulomba bua kubujikija anyi kubupangisha bua kububala.']
['Badi ne bua kutuma dimanyisha edi mu mukanda ku Enternete (bala tshiena-bualu tshia "Contact" bua kupeta adrese wa Enternete). ']
['DMCA udi ulomba ne: mu dimanyisha diebe dia bualu budibu bamba ne: mbupangile bukenji bua kufundilangana malu mu mikanda mufunda mu mikanda mufunda mu mikanda mufunda mu mikanda mufunda mu mikanda mufunda mu mikanda mufunda mu mikanda mufunda mu mikanda mufunda mu mikanda mufunda mu mikanda mufunda mu mikanda mufunda mu mikanda mufunda mu mikanda mufunda mu mikanda mufunda mu mikanda mufunda mu mikanda mufunda mu mikanda mufunda mu mikanda mufunda mu mikanda mufunda mu mikanda mufunda mu mikanda mufunda mu mikanda mufunda mu mikanda mufunda mu mikanda mufunda mu mikanda mufunda mu mikanda mufunda mu mikanda mufunda mu mikanda mufunda mu mikanda mufunda mu mikanda mufunda mu mikanda mufunda mu mikanda mufunda mu mikanda mufunda mu mikanda mufunda mu mikanda mufunda mu mikanda mufunda mu mikanda mufunda mu mikanda mufunda mu mikanda mufunda mu mikanda mufunda mu mikanda mufunda mu mikanda mufunda mu mikanda mufunda mu mikanda mufunda mu mikanda mufunda mu mikanda mufunda mu mikanda mufunda mu mikanda mufunda mu mikanda mufunda mu mikanda mufunda mu mikanda mufunda mu mikanda mufunda mu mikanda mufunda mu mikanda mufunda mu mikanda mufunda mu mikanda mufunda mu mikanda mufunda mu mikanda mufunda mu mikanda mufunda mu mikanda mufunda mu mikanda mufunda mu mikanda mufunda mu mikanda mufunda mu mikanda mufunda mu mikanda mufunda mu mikanda mufunda mu mikanda mufunda mu mikanda mufunda mu mikanda mufunda mu mikanda mufunda mu mikanda mufunda mu mikanda mu mikanda mufunda mu mikanda mufunda mu mikanda mufunda mu mikanda mufunda mu mikanda mu mikanda mufunda mu mikanda mufunda mu mikanda mufunda mu mikanda mufunda mu mikanda mu mikanda mufunda mu mikanda mufunda mu mikanda mufunda mu mikanda mu mikanda mufunda mu mikanda mufunda mu mikanda mu mikanda mufunda mu mikanda mu mikanda mufunda mu mikanda mufunda mu mikanda mu mikanda mufunda mu mikanda mu mikanda mufunda mu mikanda mufunda mu mikanda mu mikanda mufunda mu mikanda mu mikanda mufunda mu mikanda mufunda mu 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mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mikanda mu mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik 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mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik 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mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik 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mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik 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mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik 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mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik mik']
['5) mukanda uudi wewe muine mufunde udi uleja ne: malu adi mu mukanda eu mmalelela ne udi ne bukokeshi bua kuenzeja bukenji budibu bamba ne: mbunyange.']
['ne 6) tshiala tshia muena bukenji anyi tshia muntu udi ne bukokeshi bua kuenza malu mu dîna dia muena bukenji. ']
['Nudi mua kututumina mesaje a ku Enternete ne lukonko anyi lungenyi luenu luonso.']
What is pathophysiology of alzheimer?
The pathophysiology of Alzheimer's disease (AD) is a complex process that involves the accumulation of abnormal proteins, inflammation, and neuronal dysfunction.
The two main hallmarks of AD are the presence of amyloid-beta (Aβ) plaques and neurofibrillary tangles (NFTs) in the brain.
Amyloid-beta plaques are formed when fragments of the amyloid precursor protein (APP) are cleaved by enzymes to form Aβ peptides.
These peptides aggregate and form insoluble fibrils that accumulate outside neurons, disrupting cell-to-cell communication and leading to neuronal death.
The accumulation of Aβ plaques is thought to be one of the earliest events in the development of AD, and it is believed to contribute to the neurodegenerative process.
Neurofibrillary tangles are formed when the protein tau becomes hyperphosphorylated and forms abnormal filaments inside neurons.
These tangles disrupt the normal functioning of the microtubules, which are essential for the transport of nutrients and other materials within the neuron.
The tangles eventually lead to the death of the affected neurons.
Inflammation also plays a role in the pathophysiology of AD.
The immune system responds to the accumulation of Aβ plaques and NFTs by releasing pro-inflammatory cytokines, which can exacerbate the damage to neurons.
Additionally, there is evidence that oxidative stress, mitochondrial dysfunction, and impaired glucose metabolism contribute to the pathophysiology of AD.
These factors can lead to neuronal dysfunction and death, further exacerbating the disease process.
Overall, the pathophysiology of AD is a complex interplay of multiple factors that ultimately lead to the progressive decline in cognitive function and memory loss that characterizes the disease.
Disclaimer: medical
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