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While several studies have revealed the relationship between ED and diabetes, the specific physiological mechanisms remain unclear, especially the interactions between different mechanisms

In certain embodiments, any controlled-release otic formulation described herein increases the exposure of an active agent and increases the Area Under the Curve (AUC) in otic fluids (e.g., endolymph and/or perilymph) by about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, about 90%, about 100%, or higher than 100%, compared to an otic formulation that is not a controlled-release otic formulation

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An early clue came from the research of Selye ( A R action

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