Tradeoffs and decision-making in moderate to severe psoriasis for oral versus injectable treatments: data from patients and dermatologists in Australia.

Background: Oral systemic and injectable biologic treatments are available in Australia to treat moderate to severe psoriasis.

Objective: To examine how patients and dermatologists in Australia choose between oral and injectable treatments for psoriasis.

Methods: In this discrete choice experiment (DCE), adults with moderate to severe psoriasis and dermatologists were asked to choose between 2 treatments labeled by mode of administration ('oral' or 'subcutaneous injection'), each with randomly assigned levels for 9 treatment attributes.

Type III cutaneous atypical meningioma of the scalp.

Meningiomas occur rarely in extracranial sites, including the skin, where they may pose a diagnostic challenge because of their histopathologic overlap with several other spindle-cell tumors. Cutaneous meningiomas are divided into type I (congenital), type II (ectopic), and type III (via direct extension) lesions. We present a rare case of atypical meningioma of the skin in a 71-year-old woman who presented with a painful and enlarging lesion on the left central frontal scalp.

Assessment of disability in idiopathic inflammatory myopathy: a call for linearity.

Objectives: To evaluate the clinimetric properties of the Academic Medical Centre Disability Score (ALDS) in patients with idiopathic inflammatory myopathy (IIM).

Methods: We used prospectively collected data of IIM patients who completed a phase-2 study with first-line IVIG monotherapy. The ALDS is a patient-reported questionnaire which contains 25 items relevant for disability in myositis.

Functional constipation in infancy and early childhood: epidemiology, risk factors, and healthcare consultation.

Background: Functional constipation (FC) is a pediatric problem that is seen frequently. However, its prevalence in Asia remains undetermined. In this study we attempted to determine the prevalence, risk factors and therapeutic modalities of FC in infants and toddlers in Sri Lanka.

Molecular structures of cdc2-like kinases in complex with a new inhibitor chemotype.

Cdc2-like kinases (CLKs) represent a family of serine-threonine kinases involved in the regulation of splicing by phosphorylation of SR-proteins and other splicing factors. Although compounds acting against CLKs have been described, only a few show selectivity against dual-specificity tyrosine phosphorylation regulated-kinases (DYRKs). We here report a novel CLK inhibitor family based on a 6,7-dihydropyrrolo[3,4-g]indol-8(1H)-one core scaffold.

Association of Facial Exercise With the Appearance of Aging.

This pilot study assesses the association of a 20-week facial exercise program with the facial appearance of middle-aged women.

Migratory CD11b conventional dendritic cells induce T follicular helper cell-dependent antibody responses.

T follicular helper (Tfh) cells are a subset of CD4 T cells that promote antibody production during vaccination. Conventional dendritic cells (cDCs) efficiently prime Tfh cells; however, conclusions regarding which cDC instructs Tfh cell differentiation have differed between recent studies. We found that these discrepancies might exist because of the unusual sites used for immunization in murine models, which differentially bias which DC subsets access antigen.

Antimicrobial stewardship: a qualitative study of the development of national guidelines for antibiotic use in hospitals.

Background: As effective antibiotics are becoming a scarce resource, governmental regulation is needed to promote responsible use. Implementation of antibiotic stewardship and practice guidelines in health care facilities seems to be crucial to this effort. Empirical studies suggest, however, that guidelines have limited influence on health professionals' behavior and practice.

Genome-wide functional analysis reveals central signaling regulators of lymphatic endothelial cell migration and remodeling.

Lymphatic vessels constitute a specialized vasculature that is involved in development, cancer, obesity, and immune regulation. The migration of lymphatic endothelial cells (LECs) is critical for vessel growth (lymphangiogenesis) and vessel remodeling, processes that modify the lymphatic network in response to developmental or pathological demands. Using the publicly accessible results of our genome-wide siRNA screen, we characterized the migratome of primary human LECs and identified individual genes and signaling pathways that regulate LEC migration.

Infection Programs Sustained Lymphoid Stromal Cell Responses and Shapes Lymph Node Remodeling upon Secondary Challenge.

Lymph nodes (LNs) are constructed of intricate networks of endothelial and mesenchymal stromal cells. How these lymphoid stromal cells (LSCs) regulate lymphoid tissue remodeling and contribute to immune responses remains poorly understood. We performed a comprehensive functional and transcriptional analysis of LSC responses to skin viral infection and found that LSC subsets responded robustly, with different kinetics for distinct pathogens.

Identification of CLK1 Inhibitors by a Fragment-linking Based Virtual Screening.

Alternative splicing plays an important role in the regulation of protein biosynthesis. CDC2-like kinases (CLKs) phosphorylate splicing factors rendering them a potential target for treating diseases caused by splicing dysregulation. As selective and potent inhibitors of CLK1 are still lacking, a fragment-linking based virtual screening campaign was successfully applied to identify new inhibitors showing activity on CLK1.

The closely related CD103+ dendritic cells (DCs) and lymphoid-resident CD8+ DCs differ in their inflammatory functions.

Migratory CD103+ and lymphoid-resident CD8+ dendritic cells (DCs) share many attributes, such as dependence on the same transcription factors, cross-presenting ability and expression of certain surface molecules, such that it has been proposed they belong to a common sub-lineage. The functional diversity of the two DC types is nevertheless incompletely understood. Here we reveal that upon skin infection with herpes simplex virus, migratory CD103+ DCs from draining lymph nodes were more potent at inducing Th17 cytokine production by CD4+ T cells than CD8+ DCs.

Aldara activates TLR7-independent immune defence.

Aldara is a cream used for topical treatment of non-melanoma skin cancer, and is thought to act through stimulation of anti-tumour immunity. The active ingredient, imiquimod, has been shown to stimulate toll-like receptor 7. Aldara also induces psoriasis-like lesions when applied to naive murine skin, and as such is used as a mouse model for psoriasis.

Hybridization detection of enzyme-labeled DNA at electrically heated electrodes.

In this report we describe an electrochemical DNA hybridization sensor approach, in which signal amplification is achieved using heated electrodes together with an enzyme as DNA-label. On the surface of the heatable low temperature co-fired ceramic (LTCC) gold electrode, an immobilized thiolated capture probe was hybridized with a biotinylated target using alkaline phosphatase (SA-ALP) as reporter molecule. The enzyme label converted the redox-inactive substrate 1-naphthyl phosphate (NAP) into the redox-active 1-naphthol voltammetrically determined at the modified gold LTCC electrode.

CD24 Ala57Val polymorphism predicts pathologic complete response to sequential anthracycline- and taxane-based neoadjuvant chemotherapy for primary breast cancer.

Overexpression of CD24 is an independent prognostic factor for breast cancer. Recently, two polymorphisms in the CD24 gene were linked to disease risk and progression in autoimmune diseases. Here, we evaluated the clinical relevance of these polymorphisms with respect to their potential to predict a pathologic complete response (pCR) to neoadjuvant chemotherapy (NCT) for primary breast cancer (PBC), one of the strongest prognostic factors in this setting.

Human CD271-positive melanoma stem cells associated with metastasis establish tumor heterogeneity and long-term growth.

Human melanoma is composed of distinct cell types reminiscent of neural crest derivatives and contains multipotent cells that express the neural crest stem cell markers CD271(p75(NTR)) and Sox10. When isolated from solid tumors by using a method that leaves intact cell surface epitopes, CD271-positive, but not CD271-negative, cells formed tumors on transplantation into nude or nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice. These tumors fully mirrored the heterogeneity of the parental melanoma and could be passaged more than 5 times.

Redox cycling amplified electrochemical detection of DNA hybridization: application to pathogen E. coli bacterial RNA.

An electrochemical genosensor in which signal amplification is achieved using p-aminophenol (p-AP) redox cycling by nicotinamide adenine dinucleotide (NADH) is presented. An immobilized thiolated capture probe is combined with a sandwich-type hybridization assay, using biotin as a tracer in the detection probe, and streptavidin-alkaline phosphatase as reporter enzyme. The phosphatase liberates the electrochemical mediator p-AP from its electrically inactive phosphate derivative.

Cancer-testis antigens and immunosurveillance in human cutaneous squamous cell and basal cell carcinomas.

Purpose: Nonmelanoma skin cancer is the most common cancer and comprises basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). The incidence of SCC increases drastically in immunosuppressed individuals, suggesting a critical role of the immune system in controlling SCC. To find an explanation for the selective immunosurveillance of SCC, we investigated the expression of cancer-testis (CT) antigens and MHC class I (MHC-I) and the infiltration by immune cells in BCC and SCC.

Amplified potentiometric transduction of DNA hybridization using ion-loaded liposomes.

Amplified potentiometric transduction of DNA hybridization based on using liposome 'nanocarriers' loaded with the signaling ions is reported. The liposome-amplified potentiometric bioassay involved the duplex formation, followed by the capture of calcium-loaded liposomes, a surfactant-induced release and highly-sensitive measurements of the calcium signaling ions using a Ca(2+) ion-selective electrode (ISE). The high loading yield of nearly one million signaling ions per liposome leads to sub-fmol DNA detection limits.

Spatial organization of a ubiquitous eukaryotic kinetochore protein network in Drosophila chromosomes.

Chromosome segregation during meiosis and mitosis depends on the assembly of functional kinetochores within centromeric regions. Centromeric DNA and kinetochore proteins show surprisingly little sequence conservation despite their fundamental biological role. However, our identification in Drosophila melanogaster of the most diverged orthologs identified so far, which encode components of a kinetochore protein network including the Ndc80 and Mis complexes, further emphasizes the notion of a shared eukaryotic kinetochore design.