Psoriasis and Hypertension Severity: Results from a Case-Control Study

BACKGROUND: Epidemiologic studies have provided new insights into the association between psoriasis and cardiovascular diseases. Previous population studies have examined hypertension frequency in psoriasis patients. However, the relationship between severity of hypertension and psoriasis has not been characterized. OBJECTIVE: We sought to investigate whether patients with psoriasis have more difficult-to-manage hypertension compared to non-psoriatic hypertensive patients. APPROACH: We performed a case-control study using the University of California Davis electronic medical records. The cases were defined as patients diagnosed with both psoriasis and hypertension, and controls were defined as patients with hypertension and without psoriasis. In this identified population, 835 cases were matched on age, sex, and body mass index (BMI) to 2418 control patients. KEY RESULTS: Treatment with multiple anti-hypertensives was significantly associated with the presence of psoriasis using univariate (p < 0.0001) and multivariable analysis, after adjusting for diabetes, hyperlipidemia, and race (p < 0.0001). Compared to hypertensive patients without psoriasis, psoriasis patients with hypertension were 5 times more likely to be on a monotherapy antihypertensive regimen (95% CI 3.607.05), 9.5 times more likely to be on dual antihypertensive therapy (95% CI 6.68-13.65), 16.5 times more likely to be on triple antihypertensive regimen (95% CI 11.01-24.84), and 19.9 times more likely to be on quadruple therapy or centrally-acting agent (95% CI 10.58-37.33) in multivariable analysis after adjusting for traditional cardiac risk factors. CONCLUSIONS: Psoriasis patients appear to have more difficult-to-control hypertension compared to non-psoriatic, hypertensive patients

Novel Sulfated Polysaccharides Disrupt Cathelicidins, Inhibit RAGE and Reduce Cutaneous Inflammation in a Mouse Model of Rosacea

Rosacea is a common disfiguring skin disease of primarily Caucasians characterized by central erythema of the face, with telangiectatic blood vessels, papules and pustules, and can produce skin thickening, especially on the nose of men, creating rhinophyma. Rosacea can also produce dry, itchy eyes with irritation of the lids, keratitis and corneal scarring. The cause of rosacea has been proposed as over-production of the cationic cathelicidin peptide LL-37.We tested a new class of non-anticoagulant sulfated anionic polysaccharides, semi-synthetic glycosaminoglycan ethers (SAGEs) on key elements of the pathogenic pathway leading to rosacea. SAGEs were anti-inflammatory at ng/ml, including inhibition of polymorphonuclear leukocyte (PMN) proteases, P-selectin, and interaction of the receptor for advanced glycation end-products (RAGE) with four representative ligands. SAGEs bound LL-37 and inhibited interleukin-8 production induced by LL-37 in cultured human keratinocytes. When mixed with LL-37 before injection, SAGEs prevented the erythema and PMN infiltration produced by direct intradermal injection of LL-37 into mouse skin. Topical application of a 1% (w/w) SAGE emollient to overlying injected skin also reduced erythema and PMN infiltration from intradermal LL-37.Anionic polysaccharides, exemplified by SAGEs, offer potential as novel mechanism-based therapies for rosacea and by extension other LL-37-mediated and RAGE-ligand driven skin diseases

Principles of Hand Fracture Management

The hand is essential in humans for physical manipulation of their surrounding environment. Allowing the ability to grasp, and differentiated from other animals by an opposing thumb, the main functions include both fine and gross motor skills as well as being a key tool for sensing and understanding the immediate surroundings of their owner

A framework for evolutionary systems biology

<p>Abstract</p> <p>Background</p> <p>Many difficult problems in evolutionary genomics are related to mutations that have weak effects on fitness, as the consequences of mutations with large effects are often simple to predict. Current systems biology has accumulated much data on mutations with large effects and can predict the properties of knockout mutants in some systems. However experimental methods are too insensitive to observe small effects.</p> <p>Results</p> <p>Here I propose a novel framework that brings together evolutionary theory and current systems biology approaches in order to quantify small effects of mutations and their epistatic interactions <it>in silico</it>. Central to this approach is the definition of fitness correlates that can be computed in some current systems biology models employing the rigorous algorithms that are at the core of much work in computational systems biology. The framework exploits synergies between the realism of such models and the need to understand real systems in evolutionary theory. This framework can address many longstanding topics in evolutionary biology by defining various 'levels' of the adaptive landscape. Addressed topics include the distribution of mutational effects on fitness, as well as the nature of advantageous mutations, epistasis and robustness. Combining corresponding parameter estimates with population genetics models raises the possibility of testing evolutionary hypotheses at a new level of realism.</p> <p>Conclusion</p> <p>EvoSysBio is expected to lead to a more detailed understanding of the fundamental principles of life by combining knowledge about well-known biological systems from several disciplines. This will benefit both evolutionary theory and current systems biology. Understanding robustness by analysing distributions of mutational effects and epistasis is pivotal for drug design, cancer research, responsible genetic engineering in synthetic biology and many other practical applications.</p