Estrogen modulation of endosome-associated toll-like receptor 8: An IFNα-independent mechanism of sex-bias in systemic lupus erythematosus

Females of child-bearing age are more resistant to infectious disease and have an increased risk of systemic lupus erythematosus (SLE). We hypothesized that estrogen-induced gene expression could establish an immunoactivated state which would render enhanced defense against infection, but may be deleterious in autoimmune development. Using peripheral blood mononuclear cells (PBMCs), we demonstrate enhanced responses with immunogen stimulation in the presence of 17β-estradiol (E2) and gene array analyses reveal toll-like receptor 8 (TLR8) as an E2-responsive candidate gene. TLR8 expression levels are up-regulated in SLE and PBMCs stimulated with TLR8 agonist display a female sex-biased, E2-sensitive response. Moreover, we identify a putative ERα-binding region near the TLR8 locus and blocking ERα expression significantly decreases E2-mediated TLR8 induction. Our findings characterize TLR8 as a novel estrogen target gene that can lower the inflammatory threshold and implicate an IFNα-independent inflammatory mechanism that could contribute to higher SLE incidence in women.     

Transthyretin cardiac amyloidosis: a review of the nuclear imaging findings with emphasis on the radiotracers mechanisms

Annals of Nuclear Medicine - Cardiac amyloidosis is a protein deposition disease characterized by the infiltration of the myocardium and coronary arteries resulting in a progressive thickening of...     

Elevated Expression Levels of Lung Complement Anaphylatoxin,Neutrophil Chemoattractant Chemokine IL-8, and RANTES in MERS-CoV-Infected Patients: Predictive Biomarkers for Disease Severity and Mortality

Journal of Clinical Immunology - The complement system, a network of highly-regulated proteins, represents a vital part of the innate immune response. Over-activation of the complement system plays...     

Stress free configuration of the human eye

Numerical simulations of eye globes often rely on topographies that have been measured in vivo using devices such as the Pentacam or OCT. The topographies, which represent the form of the already stressed eye under the existing intraocular pressure, introduce approximations in the analysis. The accuracy of the simulations could be improved if either the stress state of the eye under the effect of intraocular pressure is determined, or the stress-free form of the eye estimated prior to conducting the analysis. This study reviews earlier attempts to address this problem and assesses the performance of an iterative technique proposed by Pandolfi and Holzapfel [1], which is both simple to implement and promises high accuracy in estimating the eye's stress-free form. A parametric study has been conducted and demonstrated reliance of the error level on the level of flexibility of the eye model, especially in the cornea region. However, in all cases considered 3–4 analysis iterations were sufficient to produce a stress-free form with average errors in node location <10^?6 mm and a maximal error <10^?4 mm. This error level, which is similar to what has been achieved with other methods and orders of magnitude lower than the accuracy of current clinical topography systems, justifies the use of the technique as a pre-processing step in ocular numerical simulations.     

Epithelial sheath neuroma: be aware of benign perineural invasion!

Perineural involvement by epithelial cells is usually considered as a sign of malignancy and is seen in a variety of malignant skin neoplasms. However, there are other benign conditions characterized by the presence of perineural involvement by epithelial cells. We present a case of epithelial sheath neuroma in a 43-year-old male. The clinicopathological features of this newly described entity are discussed together with the differential diagnosis and the different hypotheses of pathogenesis. Both pathologists and dermatologists should be aware of this entity to avoid misdiagnosis of malignancy.