Whole-methylome analysis of circulating monocytes in acute diabetic Charcot foot reveals differentially methylated genes involved in the formation of osteoclasts.

AIM: To assess whether DNA methylation of monocytes play a role in the development of acute diabetic Charcot foot (CF). PATIENTS & METHODS: We studied the whole methylome (WM) of circulating monocytes in 18 patients with Type 2 diabetes (T2D) and acute CF, 18 T2D patients with equivalent neuropathy and 18 T2D patients without neuropathy, using the enhanced reduced representation bisulfite sequencing technique. RESULTS & CONCLUSION: WM analysis demonstrated that CF monocytes are differentially methylated compared with non-CF monocytes, in both CpG-site and gene-mapped analysis approaches. Among the methylated genes, several are involved in the migration process during monocyte differentiation into osteoclasts or are indirectly involved through the regulation of inflammatory pathways. Finally, we demonstrated an association between methylation and gene expression in cis- and trans-association.

Circulating microparticles in acute diabetic Charcot foot exhibit a high content of inflammatory cytokines, and support monocyte-to-osteoclast cell induction.

Circulating microparticles (MPs) are major mediators in cardiovascular complications of type 2 diabetes (T2D); however, their contribution to Charcot foot (CF) disease is not known. Here, we purified and assessed the origin, concentration and content of circulating MPs from 33 individuals: 11 with T2D and acute CF, 11 T2D patients with equivalent neuropathy and 11 non-diabetic controls. First, we demonstrated that there were no differences in the distribution of MPs of endothelial, platelet origin among the 3 groups. However, MPs from leukocytes and monocytes origin were increased in CF patients. Moreover, we demonstrated that monocytes-derived MPs originated more frequently from intermediate and non-classical monocytes in CF patients. Five cytokines (G-CSF, GM-CSF, IL-1-ra, IL-2 and IL-16) were significantly increased in MPs from acute CF patients. Applying ingenuity pathways analysis, we found that those cytokines interacted well and induced the activation of pathways that are involved in osteoclast formation. Further, we treated THP-1 monocytes and monocytes sorted from healthy patients with CF-derived MPs during their differentiation into osteoclasts, which increased their differentiation into multinucleated osteoclast-like cells. Altogether, our study suggests that circulating MPs in CF disease have a high content of inflammatory cytokines and could increase osteoclast differentiation in vitro.

Systematic thematic review of e-health research in the Gulf Cooperation Council (Arabian Gulf): Bahrain, Kuwait, Oman, Qatar, Saudi Arabia and United Arab Emirates.

Introduction The Gulf Cooperation Council (GCC or 'Arabian Gulf'), comprising Bahrain, Kuwait, Oman, Qatar, Saudi Arabia and United Arab Emirates, is a political organization sharing a common history and culture. All GCC nations have made substantial investments in telecommunications and electronic health infrastructure since 2000. Methods We conducted a literature search in English and Arabic on peer-reviewed e-health research up to December 2014 originating in the GCC. The objective was to retrieve all research on e-health in the GCC and to categorize and analyse it qualitatively to reveal the current state of e-health research and development in the region. Inclusion criteria included peer-reviewed articles, books, book chapters, conference papers and graduate theses written on e-health in the GCC. Blogs, health websites and non-peer-reviewed literature were excluded. Results Three hundred and six articles were retrieved, categorized and analysed qualitatively to reveal the state of e-health research in the GCC. Both country-specific and GCC-wide major themes were identified using NVivo 10.0 qualitative software and summarized. The most common type of study was an overview (35.0%), with common study designs of case studies (26.8%) and descriptive articles (46.4%). Significant themes were: prospective national benefits from e-health, implementation and satisfaction with electronic health records, online technologies in medical education, innovative systems (case studies), and information security and personal health information. Discussion This is the first comprehensive analytical literature review of e-health in the GCC. Important research gaps were identified: few cost-benefit analyses, controlled interventional studies, or research targeting gender and religious issues were retrieved.