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If patients report such episodes, the clinician should further inquire about the average frequency of these episodes over the past 3 months

5 m-thick sections were stained with hematoxylin and eosin (H&E) or picrosirius red solution (Abcam #ab150681) following manufacturers protocol as previously described ( 2.8 Statistical analyses All the data are presented as mean SEM and analysed by unpaired two-tailed Students t-test or two-way ANOVA with Bonferroni or Tukeys post-hoc test as appropriate using GraphPad Prism

Options for managing tolerance include a brief dose reduction for 4 to 8 weeks ("drug holiday" at a lower dose, not complete cessation), lifestyle optimization to maximize the medication effect, evaluation for other contributing factors (thyroid function, cortisol, sleep quality, medication interactions), and consideration of adding a complementary compound to address specific aspects of the plateau

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