Hardus Viljoen hit an unbeaten 60, his highest score for Derbyshire, as the hosts enjoyed the better of the opening day versus Middlesex at The 3aaa County Ground.
Wayne Madsen scored 47, before Viljoen and Palladino (35) shared an 81-run partnership for the eighth wicket to help Derbyshire recover from 167-7 to 265 all out.
Ravi Rampaul (1-8), Duanne Olivier (1-4) and Hardus Viljoen (1-19) all took a wicket apiece in the final stages of the day to leave Middlesex 45-3 at stumps, still trailing by 220 runs.
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