A Web-Based Tool for Patient Triage in Emergency Department Settings: Validation Using the Emergency Severity Index.

Background: We evaluated the concordance between triage scores generated by a novel Internet clinical decision support tool, Clinical GPS (cGPS) (Lumiata Inc, San Mateo, CA), and the Emergency Severity Index (ESI), a well-established and clinically validated patient severity scale in use today. Although the ESI and cGPS use different underlying algorithms to calculate patient severity, both utilize a five-point integer scale with level 1 representing the highest severity.

Objective: The objective of this study was to compare cGPS results with an established gold standard in emergency triage.

Receptors, cells and circuits involved in pruritus of systemic disorders.

Pruritus is a sensory phenomenon accompanying a broad range of systemic disorders including hematologic and lymphoproliferative disorders, metabolic and endocrine diseases, solid tumours, and infectious diseases. The molecular mechanisms involved in itch sensation remain enigmatic in most of these diseases. However, from studies in patients and animal models a large number of mediators and receptors responsible for scratching behaviour have been identified in recent years.

Psychoneuroimmunology of psychological stress and atopic dermatitis: pathophysiologic and therapeutic updates.

Atopic dermatitis is a chronic inflammatory skin disease characterized by impaired epidermal barrier function, inflammatory infiltration, extensive pruritus and a clinical course defined by symptomatic flares and remissions. The mechanisms of disease exacerbation are still poorly understood. Clinical occurrence of atopic dermatitis is often associated with psychological stress.

Angioinvasive Fusarium and concomitant Enterococcus infection arising in association with leukemia cutis.

Leukemia cutis represents the cutaneous infiltration of neoplastic leukocytes or their precursors that results in clinically identifiable skin lesions. For patients with myelodysplastic syndrome, developing such a lesion may indicate impending leukemic transition. These patients are also often immunocompromised, putting them at risk for infection by opportunistic fungal pathogens such as Fusarium.

Genetics for the practicing dermatologist.

In the era of robust genome sequencing, a working understanding of genetics has become important for the clinician. For the dermatologist, understanding the flow of genetic information from genotype to phenotype can aid in the delivery of effective patient care. In this article, we will review concepts in genetics and the human genome and how they contribute to clinical dermatology.

Innovative management of pruritus.

Pruritus remains a significant problem facing dermatologists and can be associated with various dermatoses and systemic derangements. At times, one can treat the underlying cutaneous or systemic process to alleviate itch. However, it is frequently challenging to identify the cause of a patient's itch and, in this situation, even more difficult to manage the symptom effectively.

Eruptive angiokeratomas on the glans penis.

Angiokeratomas are benign proliferations of dilated thin-walled blood vessels in the upper dermis with overlying epidermal hyperkeratosis. There are several clinical variants of angiokeratomas: 1. Fordyce: smooth reddish-purple papules on scrotum or vulva; 2.

Phenotypic categorization of genetic skin diseases reveals new relations between phenotypes, genes and pathways.

Motivation: Systematic analysis of connection between proteins, their cellular function and phenotypic manifestations in disease is a central problem of biological and clinical research. The solution to this problem requires the development of new approaches to link the rapidly growing dataset of gene-disease associations with the many complex and overlapping phenotypes of human disease.

Results: We analyze genetic skin disorders and suggest a manually designed set of elementary phenotypes whose combinations define diseases as points in a multidimensional space, providing a basis for phenotypic disease clustering.

Phenotypic and genotypic analyses of genetic skin disease through the Online Mendelian Inheritance in Man (OMIM) database.

Despite unprecedented gains in genomic technologies and genotype resolution, there remain tremendous challenges in our ability to capture disease "phenomes." We propose a previously unreported method for deconvolving human disease into elemental features, thereby creating a third space that interacts with both the disease and genotypic spaces. Using cutaneous and noncutaneous clinical findings available through Johns Hopkins University's Online Mendelian Inheritance in Man (OMIM) database, we set out to deconstruct genetic skin disease (GSD) into its various components, to more fully explore the relationship between these features within the complex phenotypic space and to characterize the genotypic space within which these disorders exist.

A gender gap in the dermatology literature? Cross-sectional analysis of manuscript authorship trends in dermatology journals during 3 decades.

Background: Despite a dramatic influx of female dermatologists during the last 30 years, women in academic dermatology departments remain relatively clustered in junior faculty positions. Research in other specialties showing a disparity in the academic productivity of women has led to many hypotheses regarding factors that may place them at a competitive disadvantage. It is unknown, however, whether similar differences in academic productivity might also serve as barriers to advancement in dermatology, or whether any productivity gap actually exists in this specialty that experienced a more substantial entry of women.

Unsaturated fatty acids inhibit proteasomal degradation of Insig-1 at a postubiquitination step.

Proteasomes mediate the regulated degradation of Insig-1, a membrane protein of the endoplasmic reticulum (ER) that plays a crucial role in lipid metabolism. We showed previously that sterols inhibit this degradation by blocking ubiquitination of Insig-1. Here we show that unsaturated fatty acids stabilize Insig-1 without affecting its ubiquitination.

Congenital atrophic dermatofibrosarcoma protuberans in a 7-month-old boy treated with Mohs micrographic surgery.

Dermatofibrosarcoma protuberans is a rare, malignant, slow-growing, locally invasive tumor of the skin. Although most cases are acquired and diagnosed in adulthood, there have been an increasing number of congenital dermatofibrosarcoma protuberans mimicking benign birthmarks described in the literature. The clinical presentation of this tumor is often one of an indurated exophytic plaque or nodule; however, a rare variant can present as atrophic or sclerotic in nature.

Intramembrane aspartic acid in SCAP protein governs cholesterol-induced conformational change.

The polytopic membrane protein SCAP transports sterol regulatory element-binding proteins (SREBPs) from the endoplasmic reticulum (ER) to the Golgi, thereby activating cholesterol synthesis. Cholesterol accumulation in the ER membranes changes SCAP to an alternate conformation in which it binds ER retention proteins called Insigs, thereby terminating cholesterol synthesis. Here, we show that the conserved Asp-428 in the sixth transmembrane helix of SCAP is essential for SCAP's dissociation from Insigs.

Cholesterol and 25-hydroxycholesterol inhibit activation of SREBPs by different mechanisms, both involving SCAP and Insigs.

The current paper demonstrates that cholesterol and its hydroxylated derivative, 25-hydroxycholesterol (25-HC), inhibit cholesterol synthesis by two different mechanisms, both involving the proteins that control sterol regulatory element-binding proteins (SREBPs), membrane-bound transcription factors that activate genes encoding enzymes of lipid synthesis. Using methyl-beta-cyclodextrin as a delivery vehicle, we show that cholesterol enters cultured Chinese hamster ovary cells and elicits a conformational change in SREBP cleavage-activating protein (SCAP), as revealed by the appearance of a new fragment in tryptic digests. This change causes SCAP to bind to Insigs, which are endoplasmic reticulum retention proteins that abrogate movement of the SCAP.

Membrane topology of human insig-1, a protein regulator of lipid synthesis.

Insig-1 is an intrinsic protein of the endoplasmic reticulum (ER) that regulates the proteolytic processing of membrane-bound sterol regulatory element-binding proteins (SREBPs), transcription factors that activate the synthesis of cholesterol and fatty acids in mammalian cells. When cellular levels of sterols rise, Insig-1 binds to the membranous sterol-sensing domain of SREBP cleavage-activating protein (SCAP), retaining the SCAP/SREBP complex in the ER and preventing it from moving to the Golgi for proteolytic processing. Under conditions of sterol excess, Insig-1 also binds to the ER enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, facilitating its ubiquitination and proteasomal degradation.

Cholesterol addition to ER membranes alters conformation of SCAP, the SREBP escort protein that regulates cholesterol metabolism.

Sterol accumulation in membranes blocks the exit of SCAP from the ER, preventing SREBP cleavage and reducing cholesterol synthesis. Sterols act through SCAP's sterol-sensing domain by an obscure mechanism. Here, we show that addition of cholesterol to ER membranes in vitro causes a conformational change in SCAP, detected by the unmasking of closely spaced trypsin cleavage sites.