Electrochemical Sodium Storage in Hard Carbon Powder Electrodes Implemented in an Improved Cell Assembly: Insights from In‐Situ and Ex‐Situ Solid‐State NMR

In this work, we report on an improved cell assembly of cylindrical electrochemical cells for ²³Na in‐situ solid‐state NMR (ssNMR) investigations. The cell set‐up is suitable for using powder electrode materials. Reproducibility of our cell assembly is analyzed by preparing two cells containing hard carbon (HC) powder as working electrode and sodium metal as reference electrode. Electrochemical storage properties of HC powder electrode derived from carbonization of sustainable cellulose are studied by ssNMR. ²³Na in‐situ ssNMR monitors the sodiation/desodiation of a Na|NaPF₆|HC cell (cell 1) over a period of 22 days, showing high cell stability. After the galvanostatic process, the HC powder material is investigated by high resolution ²³Na ex‐situ MAS NMR. The formation of ionic sodium species in different chemical environments is obtained. Subsequently, a second Na|NaPF₆|HC cell (cell 2) is sodiated for 11 days achieving a capacity of 220 mAh/g. ²³Na ex‐situ MAS NMR measurements of the HC powder material extracted from this cell clearly indicate the presence of quasi‐metallic sodium species next to ionic sodium species. This observation of quasi‐metallic sodium species is discussed in terms of the achieved capacity of the cell as well as of side reactions of sodium in this electrode material

A proposal for a study on treatment selection and lifestyle recommendations in chronic inflammatory diseases:A danish multidisciplinary collaboration on prognostic factors and personalised medicine

Chronic inflammatory diseases (CIDs), including Crohn’s disease and ulcerative colitis (inflammatory bowel diseases, IBD), rheumatoid arthritis, psoriasis, psoriatic arthritis, spondyloarthritides, hidradenitis suppurativa, and immune-mediated uveitis, are treated with biologics targeting the pro-inflammatory molecule tumour necrosis factor-α (TNF) (i.e., TNF inhibitors). Approximately one-third of the patients do not respond to the treatment. Genetics and lifestyle may affect the treatment results. The aims of this multidisciplinary collaboration are to identify (1) molecular signatures of prognostic value to help tailor treatment decisions to an individual likely to initiate TNF inhibitor therapy, followed by (2) lifestyle factors that support achievement of optimised treatment outcome. This report describes the establishment of a cohort that aims to obtain this information. Clinical data including lifestyle and treatment response and biological specimens (blood, faeces, urine, and, in IBD patients, intestinal biopsies) are sampled prior to and while on TNF inhibitor therapy. Both hypothesis-driven and data-driven analyses will be performed according to pre-specified protocols including pathway analyses resulting from candidate gene expression analyses and global approaches (e.g., metabolomics, metagenomics, proteomics). The final purpose is to improve the lives of patients suffering from CIDs, by providing tools facilitating treatment selection and dietary recommendations likely to improve the clinical outcome

Metabonomics of human fecal extracts characterize ulcerative colitis, Crohn's disease and healthy individuals

This study employs spectroscopy-based metabolic profiling of fecal extracts from healthy subjects and patients with active or inactive ulcerative colitis (UC) and Crohn’s disease (CD) to substantiate the potential use of spectroscopy as a non-invasive diagnostic tool and to characterize the fecal metabolome in inflammatory bowel disease (IBD). Stool samples from 113 individuals (UC 48, CD 44, controls 21) were analyzed by (1)H nuclear magnetic resonance (NMR) spectroscopy (Bruker 600 MHz, Bruker BioSpin, Rheinstetten, Germany). Data were analyzed with principal component analysis and orthogonal-projection to latent structure-discriminant analysis using SIMCA-P + 12 and MATLAB. Significant differences were found in the metabolic profiles making it possible to differentiate between active IBD and controls and between UC and CD. The metabolites holding differential power primarily belonged to a range of amino acids, microbiota-related short chain fatty acids, and lactate suggestive of an inflammation-driven malabsorption and dysbiosis of the normal bacterial ecology. However, removal of patients with intestinal surgery and anti-TNF-α antibody treatment eliminated the discriminative power regarding UC versus CD. This study consequently demonstrates that (1)H NMR spectroscopy of fecal extracts is a potential non-invasive diagnostic tool and able to characterize the inflammation-driven changes in the metabolic profiles related to malabsorption and dysbiosis. Intestinal surgery and medication are to be accounted for in future studies, as it seems to be factors of importance in the discriminative process. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11306-014-0677-3) contains supplementary material, which is available to authorized users

18F-FDG and 18F-FLT-PET Imaging for Monitoring Everolimus Effect on Tumor-Growth in Neuroendocrine Tumors:Studies in Human Tumor Xenografts in Mice

The mTOR inhibitor everolimus has shown promising results in some but not all neuroendocrine tumors. Therefore, early assessment of treatment response would be beneficial. In this study, we investigated the in vivo and in vitro treatment effect of everolimus in neuroendocrine tumors and evaluated the performance of 18F-FDG and the proliferation tracer 18F-FLT for treatment response assessment by PET imaging.The effect of everolimus on the human carcinoid cell line H727 was examined in vitro with the MTT assay and in vivo on H727 xenograft tumors. The mice were scanned at baseline with 18F-FDG or 18F-FLT and then treated with either placebo or everolimus (5 mg/kg daily) for 10 days. PET/CT scans were repeated at day 1,3 and 10.Everolimus showed significant inhibition of H727 cell proliferation in vitro at concentrations above 1 nM. In vivo tumor volumes measured relative to baseline were significantly lower in the everolimus group compared to the control group at day 3 (126±6% vs. 152±6%; p = 0.016), day 7 (164±7% vs. 226±13%; p<0.001) and at day 10 (194±10% vs. 281±18%; p<0.001). Uptake of 18F-FDG and 18F-FLT showed little differences between control and treatment groups, but individual mean uptake of 18F-FDG at day 3 correlated with tumor growth day 10 (r2 = 0.45; P = 0.034), 18F-FLT mean uptake at day 1 correlated with tumor growth day 7 (r2 = 0.63; P = 0.019) and at day 3 18F-FLT correlated with tumor growth day 7 (r2 = 0.87; P<0.001) and day 10 (r2 = 0.58; P = 0.027).Everolimus was effective in vitro and in vivo in human xenografts lung carcinoid NETs and especially early 18F-FLT uptake predicted subsequent tumor growth. We suggest that 18F-FLT PET can be used for tailoring therapy for neuroendocrine tumor patients through early identification of responders and non-responders

PET uptake in H727 xenografts.

<p>Uptake of FDG (upper panel) and FLT (lower panel) after treatment of H727 xenografts with everolimus or vehicle. N = 8–10 tumors/group. *) P<0.05 vs. control group on same day, #) P<0.05 and ##) P<0.01 vs. baseline of same group. P-values are Bonferroni corrected.</p

MTT Assay.

<p><i>In vitro</i> inhibition of neuroendocrine tumor cell proliferation by everolimus using MTT assay.</p

Early PET correlated to later tumorgrowth.

<p>Correlations of individual tumor uptake (SUVmean) day 1 and day 3 and subsequent tumor growth until day 7 and 10. Left panel: mean uptake of FDG at day 3 correlated significantly with tumor growth until day 10, (n = 10). Right panel: mean uptake of FLT at day 1 correlated significantly with tumor growth until day 7 and FLT uptake at day 3 correlated with tumor growth until both day 7 and 10 (n = 8 tumors). Tumor growth is expressed as volume relative to baseline, 95% confidence intervals are shown. Correlations with SUVmax show same trend (not shown).</p

Study design.

<p>Study design.</p