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We previously reported that syndecan-2 expression is increased on the colonic epithelium during chronic inflammation. Here, we report that syndecan-2 exhibits a different pattern of site-specific colonic expression during acute inflammation. Syndecan-2 expression was up-regulated predominantly in the proximal colon of dextran sulfate sodium-induced colitis mice. The colitis-associated up-regulation of syndecan-2 was barely detected in Rag-1-/- (recombination activating gene 1 knockout) mice under colitis-inducing conditions. Increased syndecan-2 expression correlated with increased levels of infiltrated CD4+ IL-17A+ T cells in the proximal colon. Serum levels of IL-17A were increased during the acute inflammatory response in normal mice but not Rag-1-/- mice. IL-17A directly induced IL-17 receptor (IL-17RA) and syndecan-2 expression in ex vivo-cultured proximal colon tissues and adenoma cell lines from proximal colon. IL-17RA knockdown reduced the IL-17A-mediated syndecan-2 expression in SNU1235 cells. No elevation of syndecan-2 or IL-17RA was observed in colonic tissues from IL-17A-/- mice during colitis induction. Finally, increased expression of syndecan-2 and IL-17RA was observed in the proximal colons of cecal ligation and puncture-induced sepsis mice and infectious pan colitis patients. Together, these data suggest that acute inflammation induces syndecan-2 expression predominantly in the proximal colon via IL-17A-IL-17RA signaling during the early stage of the inflammatory response and that proximal colonic syndecan-2 might be a biomarker for acute inflammation.-Hong, H., Song, H.-K., Hwang, E. S., Lee, A. R., Han, D. S., Kim, S.-E., Oh, E.-S. Up-regulation of syndecan-2 in proximal colon correlates with acute inflammation.

Recent studies have shown that exercise improves skeletal muscle and cognitive function by stimulating the secretion of numerous molecules. In particular, previous studies have suggested that exercise‐induced beta‐hydroxybutyrate (BHB) release might improve skeletal muscle and cognitive function, but to date these studies have been limited to cell and animal models. Therefore, we aimed to determine how an exercise‐induced increase in BHB affects skeletal muscle and cognitive function at a cellular level, in an animal model, and in humans. The effects of BHB on skeletal muscle and cognitive function were determined by treating C2C12 and C6 cell lines with BHB, and by measuring the skeletal muscle and serum BHB concentrations in aged mice after endurance or resistance exercise. In addition, serum BHB concentration was measured before and after high‐speed band exercise in elderly people, and its relationships with muscle and cognitive function were analyzed. We found that BHB increased cell viability and brain‐derived neurotrophic factor expression level in C6 cells, and endurance exercise, but not resistance exercise, increased the muscle BHB concentration in aged mice. Furthermore, the BHB concentration was positively related to skeletal muscle and cognitive function. Exercise did not increase the serum BHB concentration in the elderly people and BHB did not correlate with cognitive function, but after excluding the five people with the highest preexisting serum concentrations of BHB, the BHB concentrations of the remaining participants were increased by exercise, and the concentration showed a tendency toward a positive correlation with cognitive function. Thus, the BHB released by skeletal muscle following endurance exercise may improve muscle and cognitive function in animals and humans., Exercise upregulated DBHB level in skeletal muscle in mice and skeletal muscle cell. Also, DBHB effected to cognitive function as well.

Many bone diseases, such as osteoporosis and rheumatoid arthritis, are attributed to an increase in osteoclast number or activity; therefore, control of osteoclasts has significant clinical implications. This study shows how skullcapflavone II (SFII), a flavonoid with anti-inflammatory activity, regulates osteoclast differentiation, survival, and function. SFII inhibited osteoclastogenesis with decreased activation of MAPKs, Src, and cAMP response element-binding protein (CREB), which have been known to be redox sensitive. SFII decreased reactive oxygen species by scavenging them or activating nuclear factor-erythroid 2-related factor 2 (Nrf2), and its effects were partially reversed by hydrogen peroxide cotreatment or Nrf2 deficiency. In addition, SFII attenuated survival, migration, and bone resorption, with a decrease in the expression of integrin β3, Src, and p130 Crk-associated substrate, and the activation of RhoA and Rac1 in differentiated osteoclasts. Furthermore, SFII inhibited osteoclast formation and bone loss in an inflammation- or ovariectomy-induced osteolytic mouse model. These findings suggest that SFII inhibits osteoclastogenesis through redox regulation of MAPKs, Src, and CREB and attenuates the survival and resorption function by modulating the integrin pathway in osteoclasts. SFII has therapeutic potential in the treatment and prevention of bone diseases caused by excessive osteoclast activity.-Lee, J., Son, H. S., Lee, H. I., Lee, G.-R., Jo, Y.-J., Hong, S.-E., Kim, N., Kwon, M., Kim, N. Y., Kim, H. J., Lee, Y. J., Seo, E. K., Jeong, W. Skullcapflavone II inhibits osteoclastogenesis by regulating reactive oxygen species and attenuates the survival and resorption function of osteoclasts by modulating integrin signaling.

Purpose To demonstrate the interchangeable neck shape-specific (NSS) coil concept that supplements standard commercial spine and head/neck coils to provide simultaneous high-resolution (hi-res) head/neck imaging with high signal-to-noise ratio (SNR). Methods Two NSS coils were constructed on formers designed to fit two different neck shapes. A 7-channel (7ch) ladder array was constructed on a medium neck former, and a 9-channel (9ch) ladder array was constructed on large neck former. Both coils were interchangeable with the same preamp housing. Results The 7ch and 9ch coils demonstrate SNR gains of approximately 4 times and 3 times over the Siemens 20-channel head/neck coil in the carotid arteries of our volunteers, respectively. Coupling between the Siemens 32-channel spine coil, Siemens 20-channel head/neck coil, and the NSS coils was negligible, allowing for simultaneous hi-res head/neck imaging with high SNR. Conclusions This study demonstrates that supplementing existing commercial spine and head/neck coils with an NSS coil allows uniform simultaneous hi-res imaging with high SNR in the anterior neck, while maintaining SNR of the commercial coil in the head and posterior neck. Magn Reson Med 78:2460-2468, 2017. © 2017 International Society for Magnetic Resonance in Medicine.

Chronic inflammation is known to be a key causative factor in tumor progression, but we do not yet fully understand the molecular mechanism through which inflammation leads to cancer. Here, we report that the dextran sulfate sodium (DSS)-induced mouse model of chronic colitis is associated with increases in the serum level of IL-1β and the colonic epithelial expression of the cell-surface heparan sulfate proteoglycan, syndecan-2. We further show that IL-1β stimulated the transcription of syndecan-2 via NF-κB-dependent FOXO3a activation in CCD841CoN normal colonic epithelial cells and early-stage HT29 colon cancer cells. Inflammatory hypoxia was observed in the colonic epithelia of mice with chronic colitis, suggesting that hypoxic stress is involved in the regulation of syndecan-2 expression. Consistently, experimental inflammatory hypoxia induced hypoxia inducible factor-1α-dependent FOXO3a expression and the p38 MAPK-mediated nuclear localization of FOXO3a. FOXO3a directly mediated syndecan-2 expression in both cell lines and the colonic epithelia of mice with DSS-induced colitis. Moreover, syndecan-2 expression was detected in azoxymethane/DSS-induced colon tumors. Together, these data demonstrate that inflammatory hypoxia up-regulates syndecan-2 via the IL-1β-NF-κB-FOXO3a pathway. These findings provide new mechanistic insights into inflammatory hypoxia-mediated syndecan-2 expression to connect chronic inflammation and the development of colon cancer.-Choi, S., Chung, H., Hong, H., Kim, S. Y., Kim, S.-E., Seoh, J.-Y., Moon, C. M., Yang, E. G., Oh, E.-S. Inflammatory hypoxia induces syndecan-2 expression through IL-1β-mediated FOXO3a activation in colonic epithelia.

AIM The present study aimed to investigate the risk factors and prognostic implications of aspiration pneumonia in older hip fracture patients. METHODS A total of 394 female and 125 male hip fracture patients aged ≥60 years who underwent surgery between 2015 and 2018 were retrospectively analyzed. To identify risk factors of aspiration pneumonia, demographic factors, the American Society of Anesthesiologists classification, past medical history, known risk factors of aspiration and factors associated with surgery were compared between the aspiration pneumonia group and the control group. Regression analysis was also carried out. To assess the prognostic implications of aspiration pneumonia, hospital stay, frequency of the intensive care unit admission and in-hospital mortality rates were compared between groups. RESULTS Aspiration pneumonia was diagnosed in 8.8% of the hip fracture patients. Increased age, low body mass index, malnutrition, longer duration of surgery and delayed surgery were identified as risk factors of aspiration pneumonia. Regarding prognostic implications, hospital stay, the frequency of intensive care unit care and in-hospital mortality rates were significantly higher in the aspiration pneumonia group (P < 0.001

PURPOSE Carotid artery imaging is important in the clinical management of patients at risk for stroke. Carotid intraplaque hemorrhage (IPH) presents an important diagnostic challenge. 3D magnetization prepared rapid acquisition gradient echo (MPRAGE) has been shown to accurately image carotid IPH; however, this sequence can be limited due to motion- and flow-related artifact. The purpose of this work was to develop and evaluate an improved 3D carotid MPRAGE sequence for IPH detection. We hypothesized that a radial-based k-space trajectory sequence such as "Stack of Stars" (SOS) incorporated with inversion recovery preparation would offer reduced motion sensitivity and more robust flow suppression by oversampling of central k-space. MATERIALS AND METHODS A total of 31 patients with carotid disease (62 carotid arteries) were imaged at 3T magnetic resonance imaging (MRI) with 3D IR-prep Cartesian and SOS sequences. Image quality was determined between SOS and Cartesian MPRAGE in 62 carotid arteries using t-tests and multivariable linear regression. Kappa analysis was used to determine interrater reliability. RESULTS In all, 25 among 62 carotid plaques had carotid IPH by consensus from the reviewers on SOS compared to 24 on Cartesian sequence. Image quality was significantly higher with SOS compared to Cartesian (mean 3.74 vs. 3.11, P < 0.001). SOS acquisition yielded sharper image features with less motion (19.4% vs. 45.2%, P < 0.002) and flow artifact (27.4% vs. 41.9%, P < 0.089). There was also excellent interrater reliability with SOS (kappa = 0.89), higher than that of Cartesian (kappa = 0.84). CONCLUSION By minimizing flow and motion artifacts and retaining high interrater reliability, the SOS MPRAGE has important advantages over Cartesian MPRAGE in carotid IPH detection. LEVEL OF EVIDENCE 1 J. Magn. Reson. Imaging 2017;45:410-417.

Purpose To compare the clinical outcomes of intravitreal bevacizumab (IVB) injection, with different dosing (0.25 mg/0.01 ml versus 0.625 mg/0.025 ml) in each eye of the same patient with retinopathy of prematurity (ROP). Methods Intravitreal bevacizumab (IVB) was injected into eight patients with stage 3+ in zone I or posterior zone II ROP (16 eyes). Bevacizumab, with different dosing (0.25 mg/0.01 ml and 0.625 mg/0.025 ml), was injected into the vitreous cavity of each eye. Results Among the 16 eyes treated with IVB, six eyes had zone I ROP and 10 eyes had zone II ROP. The mean birthweight was 800 ± 139 g (range, 533–955 g), and the mean gestational age was 25.9 ± 1.2 gestational weeks (range, 24.4–28.7 weeks). The postmenstrual age at initial treatment was 37.2 gestational weeks (range, 33.7–41 weeks). The mean follow-up was 312 ± 50 days (median, 305 days; range, 238–376 days). All eyes showed regression of plus sign after IVB injection within 1 week and revascularization to the ora serrata at the time of final visit. There was no difference in the time of anatomical achievement between the eyes with different doses. None of the patients received any additional IVB injection or laser photocoagulation. After the regression of ROP, tractional retinal detachment and macular ectopia were not observed in any patients during follow-up. Conclusions There was no difference in the short-term clinical outcomes of stage 3+ ROP in zone I or II between the eyes with low dose and conventional dose of IVB.

Objectives The aim of the present study was to measure brain phosphorus-31 magnetic resonance spectroscopy (31P MRS) metabolite levels and the creatine kinase reaction forward rate constant (kf) in subjects with bipolar disorder (BD). Methods Subjects with bipolar euthymia (n = 14) or depression (n = 11) were recruited. Healthy comparison subjects (HC) (n = 23) were recruited and matched to subjects with BD on age, gender, and educational level. All studies were performed on a 3-Tesla clinical magnetic resonance imaging system using a 31P/1H double-tuned volume head coil. 31P spectra were acquired without 1H-decoupling using magnetization-transfer image-selected in vivo spectroscopy. Metabolite ratios from a brain region that includes the frontal lobe, corpus callosum, thalamus, and occipital lobe are expressed as a percentage of the total phosphorus (TP) signal. Brain pH was also investigated. Results Beta-nucleoside-triphosphate (β-NTP/TP) in subjects with bipolar depression was positively correlated with kf (p = 0.039, r2 = 0.39); similar correlations were not observed in bipolar euthymia or HC. In addition, no differences in kf and brain pH were observed among the three diagnostic groups. A decrease in the ratio of phosphomonoesters to phosphodiesters (PME/PDE) was observed in subjects with bipolar depression relative to HC (p = 0.032). We also observed a trend toward an inverse correlation in bipolar depression characterized by decreased phosphocreatine and increased depression severity. Conclusions In our sample, kf was not altered in the euthymic or depressed mood state in BD. However, decreased PME/PDE in subjects with bipolar depression was consistent with differences in membrane turnover. These data provide preliminary support for alterations in phospholipid metabolism and mitochondrial function in bipolar depression.