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Laccase activity in plants results in the formation of a number of brown pigments, often referred to as tannins. Laccase-dependent pigment production is also catalogued in numerous fungal and bacterial species. The laccase of the haploid yeast Cryptococcus neoformans forms melanin-like pigmentation outside the cell wall in the presence of exogenous substrates. While this process is a contributing factor to its virulence in humans, the evolutionary intent for the laccase function remains a mystery. We show here that C. neoformans and Bacillus subtilis have the ability to create melanin-like pigments from a variety of flavonoid molecules across a range of conformations, preferring those with 3',4'-dihydroxylations. Since flavonoids are ubiquitous plant molecules and often-considered antimicrobial agents, we postulate that they are the intended natural targets of laccase activity and result in the formation of a defensive melanin-like coat. These results suggests a new mechanism by which flavonoid-melanin formation may occur, using not only A- and C-ring linkages, but also monomer links through the B-ring of the flavonoid structure. We also show that resveratrol and other non- and mono-hydroxylated polyphenol substrates have the ability to restrict pigment formation and may be potent inhibitors of laccase activity.

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Complex lymphatic anomalies (CLAs) are rare, pediatric developmental lymphatic anomalies that include a spectrum of overlapping clinical presentations, imaging findings, and symptoms. Owing to their rarity, diagnosis and treatment can be challenging. CLAs have significant risk of morbidity and mortality and require multimodal, comprehensive management. New molecular insights into the pathogenesis of CLAs will likely change classification and therapeutic options in the future. We describe herein 2 children with CLAs with distinct presentations and clinical courses but with some overlapping features. These cases highlight the spectrum of disease presentation in CLAs as well as the need for continued use of molecular data to drive diagnosis, classification, and management of these rare disorders.

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Our study findings indicate that the diagnostic value of total lower extremity radiography is similar to dedicated tibia radiography in the workup of the nonweight-bearing young child without trauma history or localizing signs. Radiation and cost savings can be realized by reserving additional radiographs for patients with high clinical suspicion and normal findings on dedicated tibia radiography.

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