A Thioacetal Photocage Designed for Dual Release: Application in the Quantitation of Therapeutic Release by Synchronous Reporter Decaging

Despite the immense potential of existing photocaging technology, its application is limited by the paucity of advanced caging tools. Here, we report on the design of a novel thioacetal ortho‐nitrobenzaldehyde (TNB) dual arm photocage that enabled control of the simultaneous release of two payloads linked to a single TNB unit. By using this cage, which was prepared in a single step from commercial 6‐nitroverataldehyde, three drug–fluorophore conjugates were synthesized: Taxol‐TNB‐fluorescein, Taxol‐TNB‐coumarin, and doxorubicin‐TNB‐coumarin, and long‐wavelength UVA light‐triggered release experiments demonstrated that dual payload release occurred with rapid decay kinetics for each conjugate. In cell‐based assays performed in vitro, dual release could also be controlled by UV exposure, resulting in increased cellular fluorescence and cytotoxicity with potency equal to that of unmodified drug towards the KB carcinoma cell line. The extent of such dual release was quantifiable by reporter fluorescence measured in situ and was found to correlate with the extent of cytotoxicity. Thus, this novel dual arm cage strategy provides a valuable tool that enables both active control and real‐time monitoring of drug activation at the delivery site.Binary photocage: An ortho‐nitrobenzaldehyde‐derived dual arm photocage was developed for real‐time monitoring of the simultaneous release of two payloads linked to a single cage unit. Light‐controlled uncaging of the drug–fluorophore conjugate resulted in increased cellular fluorescence, which was found to correlate with cytotoxicity.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135367/1/cbic201600494.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/135367/2/cbic201600494-sup-0001-misc_information.pd

Determining crystal structures through crowdsourcing and coursework

We show here that computer game players can build high-quality crystal structures. Introduction of a new feature into the computer game Foldit allows players to build and real-space refine structures into electron density maps. To assess the usefulness of this feature, we held a crystallographic model-building competition between trained crystallographers, undergraduate students, Foldit players and automatic model-building algorithms. After removal of disordered residues, a team of Foldit players achieved the most accurate structure. Analysing the target protein of the competition, YPL067C, uncovered a new family of histidine triad proteins apparently involved in the prevention of amyloid toxicity. From this study, we conclude that crystallographers can utilize crowdsourcing to interpret electron density information and to produce structure solutions of the highest quality

Severe penile necrotizing infection with subsequent glandular gangrene after distal corporal aspiration and irrigation procedure for ischemic priapism

Necrotizing penile infection following ischemic priapism takedown is a rare complication. A 60-year-old man presented with 1-week history of green and pink purulent discharge, penile swelling, and inability to void. Computed tomography demonstrated gas and fluid accumulation within the corporal bodies, suggestive for bilateral penile necrotizing corporal infection with possibility of intra-corporal abscesses. The patient underwent extensive serial surgical debridement of the penile and corporal tissues which was complicated with poly-microbial tissue cultures, growing Candida albicans and Staphylococcus epidermidis. Despite maximal penile drainage, glans penis gangrene was developed to level of mid penile shaft necessitating a partial penectomy

Inside Cover: A Thioacetal Photocage Designed for Dual Release: Application in the Quantitation of Therapeutic Release by Synchronous Reporter Decaging (ChemBioChem 1/2017)

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135406/1/cbic201600661.pd

Effects of Music Therapy on Quality of Life in Adults with Sickle Cell Disease (MUSIQOLS): A Mixed Methods Feasibility Study.

PURPOSE: To investigate the feasibility, acceptability, and preliminary efficacy of a 6-session music therapy protocol on self-efficacy, quality of life, and coping skills in adults with sickle cell disease (SCD). PATIENTS AND METHODS: Using a mixed-methods intervention design, adults with SCD (ages 21-57; mean age 32.33) were randomized (1:1) to either 1) a 6-session music therapy (MT) intervention (n = 12) or 2) waitlist control (WLC) (n = 12) using stratified randomization where factors were age in years (≤30 vs >30), and sex (male, female). All participants completed two weeks of daily electronic pain diary entries and self-efficacy, quality of life, and coping skills measures before and after their assigned study condition to explore preliminary efficacy. MT participants were taught music exercises accessed via smartphone and subsequently interviewed to determine feasibility and acceptability. RESULTS: The enrollment rate was 89%. All study measures were completed, with high rates of electronic pain diary completion at baseline (70%) and 2-week follow-up (66%). Interviews revealed two overall themes related to MT participants experience: 1) participants learned new self-management skills and 2) MT improved participants ability to cope with pain. MT participants demonstrated 100% attendance. In preliminary analyses, MT participants demonstrated significant improvements (means ± SD) in self-efficacy (5.42 ± 5.43, p = 0.008, d = 1.20), PROMIS sleep disturbance (-1.49 ± 6.68, p = 0.023, d = -0.99), PROMIS pain interference (-2.10 ± 4.68, p = 0.016, d = -1.06), and ASCQ-Me social functioning impact scores (2.97 ± 6.91, p = 0.018, d = 1.05) compared to WLC participants. CONCLUSION: Preliminary findings support the feasibility and acceptability of music therapy for home use in adults with SCD. While music therapy may assist adults with SCD in improving self-efficacy and quality of life, subsequent, fully-powered clinical research is needed to determine its efficacy