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and gluconeogenesis is suppressed 38 in part due to depletion of pyruvate and lactate 39

In certain embodiments, tonicity agents are added to the formulations described herein in an amount as to provide a practical osmolality of an otic formulation of about 100 mOsm/kg to about 1000 mOsm/kg, from about 200 mOsm/kg to about 800 mOsm/kg, from about 250 mOsm/kg to about 500 mOsm/kg, from about 250 mOsm/kg to about 350 mOsm/kg, or from about 280 mOsm/kg to about 320 mOsm/kg

doi: 10.1111/j.2042-7158.1987.tb07154.x

An FEI Vitrobot Mark IV (Thermo Fisher Scientific) was used to plunge-freeze the grids into liquid ethane after sample application at 4 C and 100% humidity, with a blot time of 3 s and a blot force of 5