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The SURMOUNT-4 trial provides the clearest long-term data

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Additionally, the increase in hemichannel activation due to an increase in pro-inflammatory cytokines [e.g., tumor necrosis factor- (TNF-) and interleukin-1 (IL-1)] in primary cell cultures and mice results in an increase in the release of various ions (i.e., K + , Ca 2+ ) and gliotransmitters (i.e., ATP, glutamate) into the extracellular space, further disrupting homeostasis and possibly contributing to neuronal death (Retamal et al., 2007