Treatment of Imiquimod Resistant Epidermodysplasia Verruciformis With Ingenol Mebutate.

BACKGROUND: Epidermodysplasia verruciformis (EV) is a rare genetic disorder characterized by widespread human papillomavirus (HPV) associated lesions and an increase susceptibility to cutaneous malignancies. A host of medications traditionally used to treat warty lesions have been used with variable results and limited success. To our knowledge, we describe the first reported case of a patient with Imiquimod resistant EV successfully treated with topical ingenol mebutate (Picato). CASE: A patient with a 5 year history of EV failed to respond to a 6 week course of 5% imiquimod on the forehead and was subsequently treated with a 3 day course of 0.015% Picato gel which resulted in significant clinical improvement. A one month follow-up examination showed no reoccurrence of the lesions with the patient reporting continued satisfaction of the outcome. CONCLUSION: Our case provides insight into the potential use of ingenol mebutate for EV patients unresponsive to traditional medical treatments.

A highly redundant gene network controls assembly of the outer spore wall in S. cerevisiae.

The spore wall of Saccharomyces cerevisiae is a multilaminar extracellular structure that is formed de novo in the course of sporulation. The outer layers of the spore wall provide spores with resistance to a wide variety of environmental stresses. The major components of the outer spore wall are the polysaccharide chitosan and a polymer formed from the di-amino acid dityrosine. Though the synthesis and export pathways for dityrosine have been described, genes directly involved in dityrosine polymerization and incorporation into the spore wall have not been identified. A synthetic gene array approach to identify new genes involved in outer spore wall synthesis revealed an interconnected network influencing dityrosine assembly. This network is highly redundant both for genes of different activities that compensate for the loss of each other and for related genes of overlapping activity. Several of the genes in this network have paralogs in the yeast genome and deletion of entire paralog sets is sufficient to severely reduce dityrosine fluorescence. Solid-state NMR analysis of partially purified outer spore walls identifies a novel component in spore walls from wild type that is absent in some of the paralog set mutants. Localization of gene products identified in the screen reveals an unexpected role for lipid droplets in outer spore wall formation.

A visual screen of protein localization during sporulation identifies new components of prospore membrane-associated complexes in budding yeast.

During ascospore formation in Saccharomyces cerevisiae, the secretory pathway is reorganized to create new intracellular compartments, termed prospore membranes. Prospore membranes engulf the nuclei produced by the meiotic divisions, giving rise to individual spores. The shape and growth of prospore membranes are constrained by cytoskeletal structures, such as septin proteins, that associate with the membranes. Green fluorescent protein (GFP) fusions to various proteins that associate with septins at the bud neck during vegetative growth as well as to proteins encoded by genes that are transcriptionally induced during sporulation were examined for their cellular localization during prospore membrane growth. We report localizations for over 100 different GFP fusions, including over 30 proteins localized to the prospore membrane compartment. In particular, the screen identified IRC10 as a new component of the leading-edge protein complex (LEP), a ring structure localized to the lip of the prospore membrane. Localization of Irc10 to the leading edge is dependent on SSP1, but not ADY3. Loss of IRC10 caused no obvious phenotype, but an ady3 irc10 mutant was completely defective in sporulation and displayed prospore membrane morphologies similar to those of an ssp1 strain. These results reveal the architecture of the LEP and provide insight into the evolution of this membrane-organizing complex.

Fractional CO2 laser and adjunctive therapies in skin of color melasma patients.

Background: Ablative lasers have long been considered an unfavorable option for melasma in patients with skin of color and continue to be underutilized. Objective: To evaluate the safety and outcomes of ablative fractional CO2 lasers on refractory melasma in patients with skin of color. Methods: A retrospective chart review of 12 patients from a single-center dermatology clinic. The study included refractory melasma patients receiving ablative fractional CO2 laser therapy alone or with laser toning and/or tranexamic acid (TXA). A validated modified Melasma Area and Severity Index (mMASI) scoring scale was used to assess disease severity at baseline and approximately 1 month after each treatment session. Results: Among the 12 patients, 41.7% patients showed >50% reduction in mMASI scores with 33.3% of patients showing statistical significance (P < .05). The CO2 laser therapy with the TXA cohort showed the largest decrease in the mean mMASI scores and the CO2 laser with laser toning showed the lowest decrease in scores. Patients who started on oral TXA earlier, after their initial ablative laser session, showed better clinical improvement. Limitations: Retrospective study design with short follow-up period and a small sample size. Conclusion: Ablative CO2 laser treatment may be a reasonable option for refractory melasma in patients with skin of color, though future research is needed.