Palbociclib (PD 0332991) Interaction with Kinases. Theoretical and Comparative Molecular Docking Study.

The optimized geometry of palbociclib, (PD 0332991) (8-cyclopentyl-6-ethanoyl-5-methyl-2-(5-(piperazin-1-yl)pyridin-2-ylamino)pyrido[2,3-d]pyrimidin-7(8H)-one), electrostatic potential map, molecular orbitals were calculated using the density functional theory. The geometry was used in a molecular docking study of palbociclib-kinase complexes, results could be explained by the charge of the nitrogen and oxygen atoms within the palbociclib. Energy gap of HOMO-LUMO surfaces, could help to explain the reactivity of the ligand and the hydrogen bonding with three different kinases, two of CDK6 and one of CDK4 type. Docking results are similar and complementary with literature reports using molecular dynamics, were hydrogen bonding was obtained and analyzed. The promiscuity of three kinases with palbociclib was detected by the docking results, thus, palbociclib could be used in other types of cancer besides myeloid leukemia. Some similarities are found with CDK4/CDK6 kinases which allow us to determine that palbociclib could be used to control other resistant inhibitor types of cancer.

Scaffolding depth cues and perceptual learning in VR to train stereovision: a proof of concept pilot study.

Stereopsis is a valuable feature of human visual perception, which may be impaired or absent in amblyopia and/or strabismus but can be improved through perceptual learning (PL) and videogames. The development of consumer virtual reality (VR) may provide a useful tool for improving stereovision. We report a proof of concept study, especially useful for strabismic patients and/or those with reduced or null stereoacuity. Our novel VR PL strategy is based on a principled approach which included aligning and balancing the perceptual input to the two eyes, dichoptic tasks, exposure to large disparities, scaffolding depth cues and perception for action. We recruited ten adults with normal vision and ten with binocular impairments. Participants played two novel PL games (DartBoard and Halloween) using a VR-HMD. Each game consisted of three depth cue scaffolding conditions, starting with non-binocular and binocular cues to depth and ending with only binocular disparity. All stereo-anomalous participants improved in the game and most (9/10) showed transfer to clinical and psychophysical stereoacuity tests (mean stereoacuity changed from 569 to 296 arc seconds, P < 0.0001). Stereo-normal participants also showed in-game improvement, which transferred to psychophysical tests (mean stereoacuity changed from 23 to a ceiling value of 20 arc seconds, P = 0.001). We conclude that a VR PL approach based on depth cue scaffolding may provide a useful method for improving stereoacuity, and the in-game performance metrics may provide useful insights into principles for effective treatment of stereo anomalies.This study was registered as a clinical trial on 04/05/2010 with the identifier NCT01115283 at ClinicalTrials.gov.

G-loading and vibration effects on heart and respiration rates.

BACKGROUND: Operational environments expose pilots and astronauts to sustained acceleration (G loading) and whole-body vibration, alone and in combination. Separately, the physiological effects of G loading and vibration have been well studied; both have effects similar to mild exercise. The few studies of combined G loading and vibration have not reported an interaction between these factors on physiological responses. METHODS: We tested the effects of G loading (+1 and +3.8 G(x)) and vibration (0.5 gx at 8, 12, and 16 Hz), alone and in combination, on heart and respiration rate. RESULTS: We observed an effect of G loading on heart rate (average increase of 23 bpm, SD 12) and respiration rate (average increase of 5 breaths per minute, SD 5), an effect of vibration on heart rate, and an interaction on heart rate. With vibration, we observed heart rate increases of 4 bpm (SD: 3) with no increase in respiration rate. In the +1 G(x) condition, the largest heart rate increase occurred during low-frequency (8 Hz) vibration, while at +3.8 G(x), the largest heart rate increase occurred during high-frequency (16 Hz) vibration, demonstrating interaction. DISCUSSION: Consistent with previous reports, our G-loading and vibration effects are similar to mild exercise. In addition, we observed an interaction between G loading and vibration on heart rate, with maximum heart rates occurring at a higher vibration frequency at +3.8 G(x) compared to +1 G(x). The observed interaction demonstrates that G-loading and vibration effects are not independent and can only be properly assessed during combined exposure.