A Prospective, Multicenter, Randomized, Evaluator-Blinded, Split-Hand Study to Evaluate the Effectiveness and Safety of Large-Gel-Particle Hyaluronic Acid with Lidocaine for the Correction of Volume Deficits in the Dorsal Hand.

BACKGROUND: Hand rejuvenation has become increasingly popular, but there are few reports published on the use of hyaluronic acid gels for correction of volume deficits in the dorsal hand. METHODS: This study evaluated the efficacy and safety of large-gel-particle hyaluronic acid with lidocaine, a 20-mg/ml hyaluronic acid gel with 0.3% lidocaine, compared to no treatment for the correction of volume deficits in the dorsal hand. This was a prospective, multicenter, split-hand study in 90 subjects who received treatment with product in one hand. The primary efficacy endpoint was based on a 1 point of improvement with treatment versus no treatment according to the Merz Hand Grading Scale at week 12. Other assessments included Central Independent Photographic Reviewers evaluations of hand photographs, Global Aesthetic Improvement Scale, subject satisfaction, and safety. RESULTS: The mean injection volume was 2.1 ml at the first treatment. Subjects demonstrated significantly higher response rates with treatment compared to no treatment at week 12 (85.9 percent versus 21.2 percent) and at weeks 16, 20, and 24 (p < 0.0001). Photographic Reviewers assessments showed consistently greater improvements in the treated hands compared with the untreated hands from week 12 to week 24. Most subjects and investigators (≥92.8 percent) reported improvements in Global Aesthetic Improvement Scale score across all time points with treatment. Treatment-related adverse events were reported in seven subjects (7.9 percent). Most of these were mild, and none were serious. CONCLUSION: Hyaluronic acid with lidocaine is safe, effective, and well tolerated for the correction of volume deficits in the dorsal hand. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

Assessment of the Stoichiometry of Multicomponent Crystals Using Only X-ray Powder Diffraction Data.

Knowledge of the unit cell volume of a crystalline form and the expected space filling requirements of an API molecule can be used to determine if a crystalline material is likely to be multicomponent, such as a solvate, hydrate, salt, or a co-crystal. The unit cell information can be readily accessed from powder diffraction data alone utilizing powder indexing methodology. If the unit cell has additional space not likely attributable to the API entity, then there is either a void or another component within the crystal lattice. This "leftover" space can be used to determine the likely stoichiometry of the additional component. A simple approach for calculating the expected required volume for a given molecule within a crystal using an atom based additive approach will be discussed. Coupling this estimation with the actual unit cell volumes and space group information obtained from powder indexing allows for the rapid evaluation of the likely stoichiometry of multicomponent crystals using diffraction data alone. This approach is particularly useful for the early assessment of new phases during salt, co-crystal, and polymorph screening, and also for the characterization of stable and unstable solvates.

Molecular regulation of histone H3 trimethylation by COMPASS and the regulation of gene expression.

The Set1-containing complex COMPASS, which is the yeast homolog of the human MLL complex, is required for mono-, di-, and trimethylation of lysine 4 of histone H3. We have performed a comparative global proteomic screen to better define the role of COMPASS in histone trimethylation. We report that both Cps60 and Cps40 components of COMPASS are required for proper histone H3 trimethylation, but not for proper regulation of telomere-associated gene silencing. Purified COMPASS lacking Cps60 can mono- and dimethylate but is not capable of trimethylating H3(K4). Chromatin immunoprecipitation (ChIP) studies indicate that the loss subunits of COMPASS required for histone trimethylation do not affect the localization of Set1 to chromatin for the genes tested. Collectively, our results suggest a molecular requirement for several components of COMPASS for proper histone H3 trimethylation and regulation of telomere-associated gene expression, indicating multiple roles for different forms of histone methylation by COMPASS.