andibular distraction osteogenesis was made popular in the modern era by Joseph McCarthy in the 1990s. 1 The process consists of three components 1,2 : (1) performing a mandibular osteotomy to create a gap in the bone, (2) placement of hardware across the osteotomy that is attached to both the mesial and distal pieces of bone, and (3) the gradual activation

Introduction: Acne vulgaris is the most common skin condition worldwide, and it is associated with substantial psychological comorbidity. Topical therapies-including retinoids, antibiotics, and benzoyl peroxide-are the cornerstones of treatment for patients with acne. The main barriers to care in the treatment of acne are poor adherence to therapy and lack of tolerability.Areas covered: Herein, the authors review the safety and efficacy of adapalene/benzoyl peroxide combination gel (0.1%/2.5% and 0.3%/2.5%), as well as its specific mechanisms of action that target acne vulgaris. The authors also offer an expert opinion on the use of adapalene/benzoyl peroxide gel compared with other topical therapies.Information Classification: General Expert opinion: Adapalene/benzoyl peroxide gel is safe and highly effective in the treatment of acne vulgaris. Its efficacy, tolerability, and ease-of-use are superior to other topical acne therapies, and its use does not contribute to antibiotic resistance. However, the cost of adapalene/benzoyl peroxide gel and lack of available generics may prohibit its use.

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We have shown that Alphaviruses can enter cells by direct penetration at the plasma membrane (R. Vancini, G. Wang, D. Ferreira, R. Hernandez, and D. Brown, J Virol, 87:4352–4359, 2013). Direct penetration removes the requirement for receptor-mediated endocytosis exposure to low pH and membrane fusion in the process of RNA entry. Endosomal pH as well as the pH of the cell cytoplasm is maintained by the activity of the vacuolar ATPase (V-ATPase). Bafilomycin is a specific inhibitor of V-ATPase. To characterize the roll of the V-ATPase in viral replication we generated a Bafilomycin A1(BAF) resistant mutant of Sindbis virus (BRSV). BRSV produced mature virus and virus RNA in greater amounts than parent virus in BAF-treated cells. Sequence analysis revealed mutations in the E2 glycoprotein, T15I/Y18H, were responsible for the phenotype. These results show that a functional V-ATPase is required for efficient virus RNA synthesis and virus maturation in Alphavirus infection.

The rates of refractory pediatric psoriasis and atopic dermatitis (AD) have steadily risen over the last few decades, demanding newer and more effective therapies. This review aims to explore the reasons for resistant disease, as well as its management; this includes the indications for, efficacy of, and safety of current therapies for refractory pediatric dermatologic disease. A PubMed search for key phrases was performed. Poor medication adherence is the most common cause of resistant disease and may be managed with techniques such as simplified treatment regimens, more follow-ups and educational workshops, as well as framing and tailoring. Once problems with adherence are ruled out, escalating treatment to stronger biologic therapy may be indicated. Development of anti-drug antibodies (ADAs) can cause patients’ disease to be refractory in the presence of potent biologics, which may be addressed with regular medication use or concomitant methotrexate. If patients with AD fail to respond to biologic therapy, a biopsy to rule out mycosis fungoides, or patch testing to rule out allergic contact dermatitis, may be indicated. A limitation of this study is the absence of more techniques for the management of poor medication adherence. Managing medication adherence, escalating treatment when appropriate, and addressing possible anti-drug antibodies will help assure control and relief for patients with resistant disease.

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Background: The process by which drugs leave the bloodstream to enter the skin compartments is important in determining appropriate routes of delivery and developing more efficacious medications. We conducted a general literature review on percutaneous egression mechanisms. Summary: Studies demonstrate that the stratum corneum (SC) is a compartment for systemically delivered drugs. Upon reviewing the available literature, it became apparent that there may be multiple mechanisms of percutaneous egression dependent upon drug physiochemical properties. These mechanisms include, but are not limited to, desquamation, sebum secretion, sweat transport and passive diffusion. While drugs often utilize one major pathway, it is possible that all mechanisms may play a role to varying extents. Key Messages: Available literature suggests that hydrophilic substances tended to travel from blood to the upper layers of the skin via sweat, whereas lipophilic substances utilized sebum secretion to reach the SC. Upon reaching the skin surface, the drugs spread laterally before penetrating back into the skin as if they were topically administered. More data are warranted to identify additional percutaneous egression mechanisms, precise drug action sites and accelerate drug development.