The association of PTPN22 rs2476601 with juvenile idiopathic arthritis is specific to females.

A preponderance of females develop autoimmune disease, including juvenile idiopathic arthritis (JIA), yet the reason for this bias remains elusive. Evidence suggests that genetic risk of disease may be influenced by sex. PTPN22 rs2476601 is associated with JIA and numerous other autoimmune diseases, and has been reported to show female-specific association with type 1 diabetes. We performed main effect and sex-stratified association analyses to determine whether a sex-specific association exists in JIA. As expected, rs2476601 was associated with JIA in our discovery (413 cases and 690 controls) and replication (1008 cases and 9284 controls) samples. Discovery sample sex-stratified analyses demonstrated an association specifically in females (odds ratio (OR)=2.35, 95% confidence interval (CI)=1.52-3.63, P=0.00011) but not males (OR=0.91, 95% CI=0.52-1.60, P=0.75). This was similarly observed in the replication sample. There was evidence for genotype-by-sex interaction (Pinteraction=0.009). The association between rs2476601 and JIA appears restricted to females, partly accounting for the predominance of females with this disease.

A study on the interfacial chemistry of magnesium hydroxide surfaces in aqueous phosphate solutions: influence of Ca2+, Cl- and protein.

In recent years, magnesium based materials have been proposed as a potential biodegradable metallic implant material for orthopedic applications. Magnesium alloys are an excellent material for this purpose because they have mechanical properties that are similar to bone, have been shown to dissolve in biological fluids and are non-toxic. However, there is still relatively little information on the surface chemistry of these materials in physiological solutions. The interaction of phosphates with magnesium alloys is of particular interest because the deposition of calcium phosphate at implant surfaces is critical to the healing process in orthopedic applications. In the present work, the chemistry at the magnesium hydroxide/solution interface for model solutions containing physiologically relevant ions and protein was investigated using in situ ATR-FTIR. These studies are complemented by ex situ analysis of magnesium alloy coupons exposed to similar solutions. Our results demonstrate that precipitation of phosphate minerals at the solid/liquid interface dominates the observed changes in surface chemistry. The mineralization process was further observed to be strongly affected by the presence of chloride salts and protein in solution.

Influence of coating bath chemistry on the deposition of 3-mercaptopropyl trimethoxysilane films deposited on magnesium alloy.

Magnesium alloys have a low specific density and a high strength to weight ratio. This makes them sought after light weight construction materials for automotive and aerospace applications. These materials have also recently become of interest for biomedical applications. Unfortunately, the use of magnesium alloys in many applications has been limited due to its high susceptibility to corrosion. One way to improve the corrosion resistance of magnesium alloys is through the deposition of protective coatings. Many of the current pretreatments/coatings available use toxic chemicals such as chromates and hydrofluoric acid. One possible environmentally friendly alternative is organosilane coatings which have been shown to offer significant corrosion protection to both aluminum alloys and steels. Organosilanes are ambifunctional molecules that are capable of covalent bonding to metal hydroxide surfaces. In order for covalent bonding to occur, the organosilane must undergo hydrolysis in the coating bath followed by a condensation reaction with the surface. There are a number of factors that influence the rates of these reactions such as pH and concentration of reactants. These factors can also influence competing reactions in solution such as oligomerization. The rates of hydrolysis and condensation of 3-mercaptopropyltrimethoxy silane in methanol have been analyzed with (1)H NMR and ATR-FTIR. The results indicate that organosilane oligomers begin to form in solution before the molecules are fully hydrolyzed. The organosilane films deposited on magnesium alloy AZ91 at a variety of concentrations and pre-hydrolysis times were characterized with a combination of ATR-FTIR, ellipsometry and SEM/EDS. The results show that both organosilane film thickness and uniformity are affected by the chemistry occurring in the coating bath prior to deposition.

The mechanism of deposition of calcium phosphate coatings from solution onto magnesium alloy AZ31.

In recent years, magnesium alloys have been proposed as a new class of metallic bioabsorbable implant material. Unfortunately, hydrogen gas evolution and an increase in alkalinity are both byproducts of the degradation process. This necessitates the development of magnesium alloys with controlled degradation rates. The development of biocompatible coatings that can delay the onset of corrosion is essential for improving the lifetime and performance of these materials in vivo. Calcium phosphate coatings have been shown to improve the biocompatibility of metallic implants for orthopedic applications. In this article, we report a solution chemistry technique for depositing calcium phosphate coatings on magnesium alloy surfaces. Our kinetic studies indicate that the deposition of the coating is related to the anodic dissolution of the substrate. Characterization of the coating by XPS, SEM/EDS, and XRD reveal that the coating produced is a poorly crystalline calcium magnesium hydroxyapatite material.

Advances in paediatric rheumatology: beyond NSAIDs and joint replacement.

Over the previous three decades there have been a number of dramatic changes in our understanding of both the pathogenesis and epidemiology of the rheumatic diseases of childhood. Improvements in the classification of paediatric-onset arthritides and international collaboration in terms of multicentre research have led to the development of new therapeutic agents and better methods of outcome assessment for these chronic and often disabling conditions. Fortunately for children with paediatric rheumatic diseases treatment regimes are now available that provide excellent disease control for many and remission induction for some. Challenges include clearer definition of the genetics and pathogenesis of the diseases, delineation of reliable biological markers for diagnosis and monitoring of disease activity. The future should also herald early identification of those with a poorer prognosis, together with the design of more powerful, safer and cheaper remission-inducing agents, given to the right patients at the right time.