Selection of restorative materials for the atraumatic restorative treatment (ART) approach: a review

The atraumatic restorative treatment (ART) technique or approach for the restoration of primary and permanent teeth has been widely adopted in, but not limited to, developing countries. However, the requirement for the placement of the restorative materials under often less-than-ideal conditions imposes significant restrictions on their selection; and there have been very few randomized clinical trials or reports comparing different types of restorative materials and treatments. Although conventional glass-ionomer cements (GICs) have relatively poor mechanical and adhesive strengths, their satisfactory biological features, ease of use, and low costs are distinct advantages. Most of the published reports of the clinical performance of the newer, high-strength esthetic conventional GICs specifically marketed for the ART approach have been from short-term studies. Satisfactory clinical performance has been demonstrated for single-surface posterior restorations only, over three years. Findings indicate that further improvements in restorative materials are still required for their use with the ART approach, together with further clinical investigations of the remineralization of shallow open caries lesions, as an alternative to placing definitive restorations.link_to_subscribed_fulltex

Copper is required for oncogenic BRAF signalling and tumorigenesis

The BRAF kinase is mutated, typically V600E, to induce an active oncogenic state in a large fraction of melanoma, thyroid, hairy cell leukemia, and to a lesser extent, a wide spectrum of other cancers1,2. BRAFV600E phosphorylates and activates the kinases MEK1 and MEK2, which in turn phosphorylate and activate the kinases ERK1 and ERK2, stimulating the MAPK pathway to promote cancer3. Targeting MEK1/2 is proving to be an important therapeutic strategy, as a MEK1/2 inhibitor provides a survival advantage in metastatic melanoma4, which is increased when co-administered with a BRAFV600E inhibitor5. In this regard, we previously found that copper (Cu) influx enhances MEK1 phosphorylation of ERK1/2 through a Cu-MEK1 interaction6. We now show that genetic loss of the high affinity Cu transporter Ctr1 or mutations in MEK1 that disrupt Cu binding reduced BRAFV600E-driven signaling and tumorigenesis. Conversely, a MEK1-MEK5 chimera that phosphorylates ERK1/2 independent of Cu or an active ERK2 restored tumor growth to cells lacking Ctr1. Importantly, Cu chelators used in the treatment of Wilson disease7 reduced tumor growth of both BRAFV600E-transformed cells and cells resistant to BRAF inhibition. Taken together, these results suggest that Cu-chelation therapy could be repurposed to treat BRAFV600E mutation-positive cancers

Badger macrophages fail to produce nitric oxide, a key anti-mycobacterial effector molecule

The European badger is recognised as a wildlife reservoir for bovine tuberculosis (bTB); the control of which is complex, costly and controversial. Despite the importance of badgers in bTB and the well-documented role for macrophages as anti-mycobacterial effector cells, badger macrophage (bdMij) responses remain uncharacterised. Here, we demonstrate that bdMij fail to produce nitric oxide (NO) or upregulate inducible nitric oxide synthase (iNOS) mRNA following Toll-like receptor (TLR) agonist treatment. BdMij also failed to make NO after stimulation with recombinant badger interferon gamma (bdIFNȖ) or a combination of bdIFNȖ and lipopolysaccharide. Exposure of bdMij to TLR agonists and/or bdIFNȖ resulted in upregulated cytokine (IL1ȕ, IL6, IL12 and TNFĮ) mRNA levels indicating that these critical pathways were otherwise intact. Although stimulation with most TLR agonists resulted in strong cytokine mRNA responses, weaker responses were evident after exposure to TLR9 agonists, potentially due to very low expression of TLR9 in bdMij. Both NO and TLR9 are important elements of innate immunity to mycobacteria, and these features of bdMij biology would impair their capacity to resist bTB infection. These findings have significant implications for the development of bTB management strategies, and support the use of vaccination to reduce bTB infection in badgers