The aetiopathogenic mechanisms of vitiligo are still poorly understood, and this has held back progress in diagnosis and treatment. Up until now, treatment guidelines have existed at national levels, but no common European viewpoint has emerged. This guideline for the treatment of segmental and nonsegmental vitiligo has been developed by the members of the Vitiligo European Task Force and other colleagues. It summarizes evidence-based and expert-based recommendations (S1 level)

Alpha-MSH is a tridecapeptide derived from proopiomelanocortin. Many studies over the last few years have provided evidence that alpha-MSH has potent protective and antiinflammatory effects. These effects can be elicited via centrally expressed melanocortin receptors that orchestrate descending neurogenic antiinflammatory pathways. alpha-MSH can also exert antiinflammatory and protective effects on cells of the immune system and on peripheral nonimmune cell types expressing melanocortin receptors. At the molecular level, alpha-MSH affects various pathways implicated in regulation of inflammation and protection, i.e., nuclear factor-kappaB activation, expression of adhesion molecules and chemokine receptors, production of proinflammatory cytokines and mediators, IL-10 synthesis, T cell proliferation and activity, inflammatory cell migration, expression of antioxidative enzymes, and apoptosis. The antiinflammatory effects of alpha-MSH have been validated in animal models of experimentally induced fever; irritant and allergic contact dermatitis, vasculitis, and fibrosis; ocular, gastrointestinal, brain, and allergic airway inflammation; and arthritis, but also in models of organ injury. One obstacle limiting the use of alpha-MSH in inflammatory disorders is its pigmentary effect. Due to its preserved antiinflammatory effect but lack of pigmentary action, the C-terminal tripeptide of alpha-MSH, KPV, has been delineated as an alternative for antiinflammatory therapy. KdPT, a derivative of KPV corresponding to amino acids 193-195 of IL-1beta, is also emerging as a tripeptide with antiinflammatory effects. The physiochemical properties and expected low costs of production render both agents suitable for the future treatment of immune-mediated inflammatory skin and bowel disease, fibrosis, allergic and inflammatory lung disease, ocular inflammation, and arthritis.

Three-dimensional quantitative structure-activity relationship (3D QSAR) methods were applied using a training set of 72 inhibitors of the benzamidine type with respect to their binding affinities (Ki values) toward thrombin, trypsin, and factor Xa to yield statistically reliable models of good predictive power. Two methods were compared: the widely used comparative molecular field analysis (CoMFA) and the recently reported CoMSIA approach (comparative molecular similarity indices analysis). CoMSIA produced significantly better results for all correlations. Furthermore, in contrast to CoMFA, CoMSIA is not sensitive to changes in orientation of the superimposed molecules in the lattice. The correlation results obtained by CoMSIA were graphically interpreted in terms of field contribution maps allowing physicochemical properties relevant for binding to be easily mapped back onto molecular structures. The advantage of this feature is demonstrated using the maps to design new molecules. Finally, the CoMSIA method was applied to elucidate structural features among ligands which are responsible for affinity differences toward thrombin and trypsin. These selectivity-determining features were interpreted graphically in terms of spatial regions responsible for affinity discrimination. Such indicators are highly informative for the lead optimization process with respect to selectivity enhancement.

Digital platforms are an omnipresent phenomenon that challenges incumbents by changing how we consume and provide digital products and services. Whereas traditional firms create value within the boundaries of a company or a supply chain, digital platforms utilize an ecosystem of autonomous agents to co-create value. Scholars from various disciplines, such as economics, technology management, and information systems have taken different perspectives on digital platform ecosystems. In this Fundamentals article, we first synthesize research on digital platforms and digital platform ecosystems to provide a definition that integrates both concepts. Second, we use this definition to explain how different digital platform ecosystems vary according to three core building blocks: (1) platform ownership, (2) value-creating mechanisms, and (3) complementor autonomy. We conclude by giving an outlook on four overarching research areas that connect the building blocks: (1) technical properties and value creation; (2) complementor interaction with the ecosystem; (3) value capture; and (4) the make-or-join decision in digital platform ecosystems.

As the outermost barrier of the body, the skin is exposed to multiple environmental factors, including temperature, humidity, mechanical stress, and chemical stimuli such as odorants that are often used in cosmetic articles. Keratinocytes, the major cell type of the epidermal layer, express a variety of different sensory receptors that enable them to react to various environmental stimuli and process information in the skin. Here we report the identification of a novel type of chemoreceptors in human keratinocytes, the olfactory receptors (ORs). We cloned and functionally expressed the cutaneous OR, OR2AT4, and identified Sandalore, a synthetic sandalwood odorant, as an agonist of this receptor. Sandalore induces strong Ca(2+) signals in cultured human keratinocytes, which are mediated by OR2AT4, as demonstrated by receptor knockdown experiments using RNA interference. The activation of OR2AT4 induces a cAMP-dependent pathway and phosphorylation of extracellular signal-regulated kinases (Erk1/2) and p38 mitogen-activated protein kinases (p38 MAPK). Moreover, the long-term stimulation of keratinocytes with Sandalore positively affected cell proliferation and migration, and regeneration of keratinocyte monolayers in an in vitro wound scratch assay. These findings combined with our studies on human skin organ cultures strongly indicate that the OR 2AT4 is involved in human keratinocyte re-epithelialization during wound-healing processes.