Rationale Autologous bone marrow- or cardiac-derived stem cell therapy for heart disease has demonstrated safety and efficacy in clinical trials but functional improvements have been limited. Finding the optimal stem cell type best suited for cardiac regeneration is key toward improving clinical outcomes. Objective To determine the mechanism by which novel bone-derived stem cells support the injured heart. Methods and Results Cortical bone stem cells (CBSCs) and cardiac-derived stem cells (CDCs) were isolated from EGFP+ transgenic mice and were shown to express c-kit and Sca-1 as well as 8 paracrine factors involved in cardioprotection, angiogenesis and stem cell function. Wild-type C57BL/6 mice underwent sham operation (n=21) or myocardial infarction (MI) with injection of CBSCs (n=67), CDCs (n=36) or saline (n=60). Cardiac function was monitored using echocardiography. Only 2/8 paracrine factors were detected in EGFP+ CBSCs in vivo (basic fibroblast growth factor and vascular endothelial growth factor) and this expression was associated with increased neovascularization of the infarct border zone. CBSC therapy improved survival, cardiac function, regional strain, attenuated remodeling, and decreased infarct size relative to CDC- or saline-treated MI controls. By 6 weeks, EGFP+ cardiomyocytes, vascular smooth muscle and endothelial cells could be identified in CBSC- but not in CDC-treated animals. EGFP+ CBSC-derived isolated myocytes were smaller and more frequently mononucleated, but were functionally indistinguishable from EGFP- myocytes. Conclusions CBSCs improve survival, cardiac function, and attenuate remodeling through two mechanisms:1) secretion of pro-angiogenic factors that stimulate endogenous neovascularization, and 2) differentiation into functional adult myocytes and vascular cells.

Rationale and Objectives The aims of this study were to determine the feasibility of diffusion-weighted magnetic resonance imaging (DWI) in the detection of bowel inflammation and to investigate the changes in apparent diffusion coefficient (ADC) values in the inflamed bowel in patients with Crohn's disease. Materials and Methods Eleven patients who underwent magnetic resonance enterography (including DWI) for Crohn's disease and colonoscopy or surgery within 4 weeks of examination were recruited. Two radiologists reviewed diffusion-weighted images and ADC maps to evaluate for inflammation in each bowel segment (terminal ileum, cecum, ascending colon, transverse colon, descending colon, and rectosigmoid colon) and measured the ADC values of each bowel segment. Endoscopic and pathologic results were correlated with DWI findings. Results Fifty-three segments (19 with inflammation, 34 normal) were included. DWI detected inflammation in 18 of 19 segments (94.7%) and showed normal results in 28 of 34 segments (82.4%). On diffusion-weighted images, bowel segments with inflammation revealed higher signal compared to normal segments. Artifact levels were none or minimal in 10 of 11 patients (90.9%) and moderate in one patient. On quantitative analysis, ADC values of inflamed and normal bowel were measured as 0.47 – 2.60 × 10−3 and 1.39 – 4.03 × 10−3 mm2/s, respectively (P < .05). Conclusion DWI with parallel imaging is a feasible technique for the detection of inflammation in patients with Crohn's disease. ADC values are decreased in inflamed bowel segments, indicating restricted diffusion.

To achieve a consistent contrast enhancement in cardiac CT angiography (CTA), contrast-medium dose should be adjusted with the body weight or the BSA (which accounts for both the body weight and height factors) to provide adjustment of iodine dose over a wide range of body sizes.

Whereas both leaflets tethering is related to preoperative ischemic MR, both leaflets tethering but with predominant contribution from augmented and progressive PML tethering is related to recurrent/persistent ischemic/functional MR late after surgical annuloplasty.

Resistance to TKI treatment is a major obstacle in effective treatment of NSCLC. Besides EGFR mutation status, the mechanisms involved are largely unknown. Some evidence supports a role for microRNA 21 in modulating drug sensitivity of chemotherapy but its role in NSCLC TKI resistance still remains unexplored. This study aimed to investigate whether NSCLC miR-21 mediated resistance to TKIs also results from Pten targeting. Here, we show miR-21 promotes cancer by negatively regulating Pten expression in human NSCLC tissues: high miR-21 expression levels were associated with shorter DFS in 47 NSCLC patients; high miR-21/low Pten expression levels indicated a poor TKI clinical response and shorter overall survival in another 46 NSCLC patients undergoing TKI treatment. In vitro assays showed that miR-21 was up-regulated concomitantly to down-regulation of Pten in pc-9/GR cells in comparison with pc-9 cells. Moreover, over-expression of miR-21 significantly decreased gefitinib sensitivity by down-regulating Pten expression and activating Akt and ERK pathways in pc-9 cells, while miR-21 knockdown dramatically restored gefitinib sensitivity of pc-9/GR cells by up-regulation of Pten expression and inactivation of AKT and ERK pathways, in vivo and in vitro. We propose alteration of miR-21/Pten expression as a novel mechanism for TKI resistance in NSCLC cancer. Our findings provide a new basis for using miR 21/Pten-based therapeutic strategies to reverse gefitinib resistance in NSCLC.

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Purpose To determine whether ketamine added to morphine or hydromorphone patient-controlled analgesia (PCA) provides clinically relevant reductions in postoperative pain, opioid requirements, and adverse events when compared with morphine or hydromorphone PCA in adults undergoing surgery.Source We systematically searched six databases up to June 2, 2015 for randomized controlled trials (RCTs) comparing ketamine plus morphine/hydromorphone PCA vs morphine/hydromorphone PCA for postoperative pain in adults. Principal findings Thirty-six RCTs including 2,502 patients proved eligible, and 22 of these were at low risk of bias. The addition of ketamine to morphine/

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