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Background and Objectives: Topical drug delivery can be increased by pretreatment of the skin with ablative fractional laser (AFXL). Several physical penetration enhancement techniques have been investigated to further improve AFXL-assisted drug delivery. This study investigated the influence of three of these techniques, namely massage, acoustic pressure wave treatment, and pressure vacuum alterations (PVP) on the distribution of the fluorescent drug indocyanine green (ICG) at different depths in the skin after topical application on AFXL pretreated skin., Materials and Methods: In ex vivo human skin, test regions were pretreated with AFXL (10,600 nm, channel depth 300 μm, channel width 120 μm, density 15%). Subsequently, ICG was applied, followed by massage, acoustic pressure wave treatment or PVP. ICG fluorescence intensity (FI) was assessed after 1, 3, and 24 hours at several depths using fluorescence photography., Results: FI was higher when using enhancement techniques compared to control (AFXL-only) up to 3 hours application time (P < 0.05). After 3 hours, mean surface FI was highest after acoustic pressure wave treatment (61.5 arbitrary units; AU), followed by massage (57.5AU) and PVP (46.9AU), respectively (for comparison: AFXL-only 31.6AU, no pretreatment 14.9AU). Comparable or higher FI was achieved already after 1 hour with enhancement techniques compared to 3-24 hours application time without. After 24 hours, no significant differences between enhancement techniques and AFXL-only were observed (P = 0.31)., Conclusion: Penetration enhancement techniques, especially acoustic pressure wave treatment and massage, result in improved drug accumulation in AFXL-pretreated skin and reduce the application time needed. Lasers Surg. Med. © 2019 The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals, Inc., (© 2019 The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals, Inc.)

Background: Attention problems are among the most prominent behavioral deficits reported in very preterm children (below 32 wk of gestation) at school age. In this study, we aimed to elucidate the brain abnormalities underlying attention problems in very preterm children by investigating the role of abnormalities in white and gray brain matter during interference control, using functional magnetic resonance imaging (fMRI)-guided probabilistic diffusion tensor tractography., Methods: Twenty-nine very preterm children (mean (SD) age: 8.6 (0.3) y), and 47 term controls (mean (SD) age: 8.7 (0.5) y), performed a fMRI version of the Eriksen Flanker task measuring interference control., Results: Very preterm children showed slower reaction times than term controls when interfering stimuli were presented, indicating poorer interference control. Very preterm children and term controls did not differ in mean activation of the cortical regions involved in interference control. However, impaired fractional anisotropy (FA) was found in very preterm children in specifically those fiber tracts that innervate the cortical regions involved in interference control. Lower FA was related to poorer interference control in very preterm children., Conclusion: White matter alterations have a crucial role in the interference control problems of very preterm children at school age.