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.
Cognitive impairment is prevalent but still poorly diagnosed in hemodialysis adults, mainly because of the impracticality of current tools. This study examined whether remotely monitoring mobility performance can help identifying digital measures of cognitive impairment in hemodialysis patients. Sixty-nine diabetes mellitus hemodialysis patients (age = 64.1
Background: Balance, mobility, falls, and foot problems are serious detriments for the diabetic patients undergoing hemodialysis (HD) treatment. In addition, the HD process often leaves them too fatigued to engage in any physical activity or daily exercise, further deteriorating their motor functions. Exercise would be effective for this population. However, due to the time availability, post-dialysis fatigue, as well as limitation of transportation to exercise facility, the conventional exercise is impractical. Objective: We are developing an interactive foot and ankle exercise game that can be played during HD sessions to improve mobility and balance, as well as reduce foot problems. In this study, we examined the feasibility and effectiveness of this innovative wearable sensor based non-weight bearing exercise (Exergame) to improve daily physical activity in diabetic patients undergoing HD treatment. Methods: Thirty-three diabetic subjects receiving HD treatment were recruited and randomized into an intervention group (IG: n = 15, age = 62.2 ± 7.6 years, BMI = 29.1 ± 6.1 kg/m2) and a control group (CG: n = 18, age = 66.6 ± 8.7 years, BMI = 32.5 ± 9.0 kg/m2). Both groups underwent a 4-week ankle and foot exercise program (30 minutes per session, two sessions per week) during HD process. The IG received exercise via the Exergame program, which uses wearable sensors attached on subject's feet. The subject's 3-dementional ankle and foot movements were visualized in real-time on a computer screen placed in front of him/her. The subject played some game-like tasks by moving and rotating the foot and ankle. The difficulty level of the task was gradually increased depends on ability of the subject (like a game) from a simple flexion-extension movement to more complex movements including medial-lateral movement with different range of motion. The CG received traditional foot and ankle exercise without technology. Daily physical activity data was assessed for 48 hours (day and night) at baseline and post 4-week exercise, using a validated wearable sensor (PAMSysTM). Daily physical activity was quantified by duration spent in each main posture (i.e. lying, sitting, standing, and walking) and activities (e.g. postural transition, sedentary behavior, etc). Results: All IG subjects achieved to complete all exercise tasks indicating the feasibility of the Exergame platform. No adverse event or difficulty were reported indicating practicality of the exercise program. None subject in the IG was dropped out during the 4-week exercise program. Low dropout rate may indicate acceptability of the proposed Exergame platform. At the end of intervention, subjects in the IG were more active than subjects in the CG. In summary, the IG performed 53% more posture transitions to walking (Cohen's d effect size = 0.5) and 39% more posture transitions between sitting and walking (d = 0.5), when compared to the CG. Subjects in the IG also had significant less sedentary behavior than subjects in the CG. In summary, subjects in the IG spent 5% less time on sitting and lying (p = 0.049, d = 0.7), as well as 47% more time on standing and walking (p = 0.049, d = 0.7), when compared to subjects in the CG. Conclusions: This study demonstrated feasibility, acceptability, and effectiveness of an innovative Exergame program to improve daily physical activity in diabetic patients undergoing HD treatment. The key innovation of the proposed intervention is its practicality to be done during HD process, which could address the limitations of prior exercise interventions in HD patients, for example the low adherence of therapeutic exercise. Further studies should be addressed to confirm the observation with larger sample sizes.
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.
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