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Modified-release (MR) metformin is now the preferred formulation to improve gastrointestinal tolerability and patient adherence

Many different causative agents, not associated with elevated IOP or glaucomatous optic nerve disease, may result in pathological optic nerve excavation

When elevated levels are identified, systematic investigation is required to determine the underlying cause

ZIP13 dysregulation has further been implicated in myocardial ischemiareperfusion injury and broader connective-tissue pathologies 63,143

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Ethics declarations Ethics Approval and Consent to Participate All experiments were conducted by the Ethical Principles in Animal Experimentation and were accepted by the Ethics Committee on the Use of Animals of the Aggeu Magalhes Institute (CEUA 135/2018-IAM)