Musculoskeletal Pain in Older Adults: A Clinical Review.

Persistent pain in older adults is a widely prevalent and disabling condition that is the manifestation of multiple contributing physical, mental, social, and age-related factors. To effectively treat pain, the clinician must assess and address contributing factors using a comprehensive approach that includes pharmacologic and nonpharmacologic therapies within the context of a strong therapeutic relationship among the patient, caregivers, and a multidisciplinary team. This article reviews the current understanding of persistent pain in older adults and suggests a general approach to its assessment and management, followed by specific considerations for musculoskeletal pain conditions commonly seen in older adults.

I86A/C295A mutant secondary alcohol dehydrogenase from Thermoanaerobacter ethanolicus has broadened substrate specificity for aryl ketones.

Thermoanaerobacter ethanolicus secondary alcohol dehydrogenase (SADH) reduces aliphatic ketones according to Prelog's Rule, with binding pockets for small and large substituents. It was shown previously that the I86A mutant SADH reduces acetophenone, which is not a substrate of wild-type SADH, to give the anti-Prelog R-product (Musa, M. M.; Lott, N.; Laivenieks, M.; Watanabe, L.; Vieille, C.; Phillips, R. S. ChemCatChem2009, 1, 89-93.). However, I86A SADH did not reduce aryl ketones with substituents larger than fluorine. We have now expanded the small pocket of the active site of I86A SADH by mutation of Cys-295 to alanine to allow reaction of substituted acetophenones. As predicted, the double mutant I86A/C295A SADH has broadened substrate specificity for meta-substituted, but not para-substituted, acetophenones. However, the increase of the substrate specificity of I86A/C295A SADH is accompanied by a decrease in the kcat/Km values of acetophenones, possibly due to the substrates fitting loosely inside the more open active site. Nevertheless, I86A/C295A SADH gives high conversions and very high enantiomeric excess of the anti-Prelog R-alcohols from the tested substrates.