Using step cadence goals to increase moderate-to-vigorous-intensity physical activity.

BACKGROUND: Increasing moderate-to-vigorous-intensity physical activity (MVPA) is an important public health goal. Pedometers are evidence-based devices for increasing daily activity, but studies have not evaluated the comparative efficacy of step cadence goals for increasing MVPA. PURPOSE: This study aimed to evaluate the efficacy of three pedometer-based step goals for increasing MVPA. METHODS: Latina women (n = 180; 18-55 yr, mean body mass index = 31.1, SD = 6.5) were recruited to 12 community centers, which were randomly assigned to one of three conditions. Each group received an identical 12-wk theory-based physical activity (PA) intervention that differed only on the type of daily step goal: 1) a self-selected goal (SELF); 2) a goal of 10,000 steps per day (FREQUENCY); or 3) a goal of 3000 steps in 30 min (CADENCE). Accelerometer-based PA was measured at baseline and after 12 wk. RESULTS: Adjusted multilevel pattern-mixture models using generalized estimating equations revealed that participants in the CADENCE condition engaged in similar levels of postintervention MVPA to those in the SELF and FREQUENCY goal conditions. However, MVPA of participants in the CADENCE condition was more likely to occur in bouts lasting greater than 10 consecutive minutes compared with the MVPA of participants in the SELF (P = 0.01) or FREQUENCY (P = 0001) conditions. CONCLUSIONS: PA interventions should consider including a step cadence goal to help individuals accumulate bout-based MVPA and meet national PA guidelines.

Fragment-based screen against HIV protease.

We have employed a fragment-based screen against wild-type (NL4-3) HIV protease (PR) using the Active Sight fragment library and X-ray crystallography. The experiments reveal two new binding sites for small molecules. PR was co-crystallized with fragments, or crystals were soaked in fragment solutions, using five crystal forms, and 378 data sets were collected to 2.3-1.3 A resolution. Fragment binding induces a distinct conformation and specific crystal form of TL-3 inhibited PR during co-crystallization. One fragment, 2-methylcyclohexanol, binds in the 'exo site' adjacent to the Gly(16)Gly(17)Gln(18)loop where the amide of Gly(17)is a specific hydrogen bond donor, and hydrophobic contacts occur with the side chains of Lys(14)and Leu(63). Another fragment, indole-6-carboxylic acid, binds on the 'outside/top of the flap' via hydrophobic contacts with Trp(42), Pro(44), Met(46), and Lys(55), a hydrogen bond with Val(56), and a salt-bridge with Arg(57). 2-acetyl-benzothiophene also binds at this site. This study is the first fragment-based crystallographic screen against HIV PR, and the first time that fragments were screened against an inhibitor-bound drug target to search for compounds that both bind to novel sites and stabilize the inhibited conformation of the target.