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Montalban-Bravo G, Huang X, Naqvi K, Jabbour E, Borthakur G , DiNardo CD, Pemmaraju N, Cortes J, Verstovsek S, Kadia T, Daver N, Wierda W, Alvarado Y, Konopleva M, Ravandi F, Estrov Z, Jain N, Alfonso A, Brandt M, Sneed T, Chen HC, Yang H, Bueso-Ramos C, Pierce S, Estey E, Bohannan Z, Kantarjian HM, Garcia-Manero G

Protocol 4: nasal spray approach Goal: Needle-free administration with acceptable bioavailability trade-off Duration: 20 days active, then 4-6 months off Schedule: Days 1-20: 10-15 mg epitalon intranasally, divided into 2-3 daily doses Days 21-180: Off cycle Repeat 1-2 times per year Formulation: Reconstitute in saline with 3 percent DMSO for improved nasal absorption

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Indirect astrocyte state transitions: astrocytes are the modulator of neuronal plasticity It is well established that astrocytes modulate neuronal plasticity indirectly by secreting synaptogenic and anti-synaptogenic cues