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Like many other nutrient deficiencies and complex medical problems, it boils down to physician and patient oversimplification of the problem

This is part of why B12 has a strong safety record, and it is also why levels sometimes need regular replenishment during active treatment

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Currently, when oral MTX is not tolerated or shows insufficient clinical response, SC MTX treatment is advised (Visser and van der Heijde 2009

Although the complex remains highly dynamic upon binding, we were able to obtain a set of distance restraints from these experiments