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Jenkins AB, et al

Pyo et al., Arch Pharm Res, 2007)

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When this fluid pools in the lower legs and feet due to gravity, it creates a feeling of tight, heavy fullness and can stretch the skin, causing a dull, persistent ache

Changes occurring in the midface and to the orbital rim lead to a tightening of ligaments and to the overlying skin

The foundational mechanism work has been complemented by translational-research investigations in disease-model systems and by recent contemporary reviews compiling the broader research framework