Volumetric Measurement of Relative CBV Using T1-Perfusion-Weighted MRI with High Temporal Resolution Compared with Traditional T2*-Perfusion-Weighted MRI in Postoperative Patients with High-Grade Gliomas.

BACKGROUND AND PURPOSE: T1-PWI with high temporal resolution may provide a reliable relative CBV value as a valid alternative to T2*-PWI under increased susceptibility. The purpose of this study was to assess the technical and clinical performance of T1-relative CBV in patients with postoperative high-grade gliomas. MATERIALS AND METHODS: Forty-five MRIs of 34 patients with proved high-grade gliomas were included. In all MRIs, T1- and T2*-PWIs were both acquired and processed semiautomatically to generate relative CBV maps using a released commercial software. Lesion masks were overlaid on the relative CBV maps, followed by a histogram of the whole VOI. The intraclass correlation coefficient and Bland-Altman plots were used for quantitative and qualitative comparisons. Signal loss from both methods was compared using the Wilcoxon signed-rank test of zero voxel percentage. The MRIs were divided into a progression group (n = 20) and a nonprogression group (n = 14) for receiver operating characteristic curve analysis. RESULTS: Fair intertechnique consistency was observed between the 90th percentiles of the T1- and T2*-relative CBV values (intraclass correlation coefficient = 0.558, P < .001). T2*-PWI revealed a significantly higher percentage of near-zero voxels than T1-PWI (17.7% versus 3.1%, P < .001). There was no statistically significant difference between the area under the curve of T1- and T2*-relative CBV (0.811 versus 0.793, P = .835). T1-relative CBV showed 100% sensitivity and 57.1% specificity for the detection of progressive lesions. CONCLUSIONS: T1-relative CBV demonstrated exquisite diagnostic performance for detecting progressive lesions in postoperative patients with high-grade gliomas, suggesting the potential role of T1-PWI as a valid alternative to the traditional T2*-PWI.

Extended approach or usage of nasoseptal flap is a risk factor for olfactory dysfunction after endoscopic anterior skullbase surgery: results from 928 patients in a single tertiary center.

BACKGROUND: The aim of this study was to compare olfactory function change in patients who underwent endoscopic skull-base surgery. METHODOLOGY: A total of 928 patients were included in this retrospective study. Olfactory function was measured using the non- validated Likert scale (0â€"100), the Cross-Cultural Smell Identification Test (CC-SIT) and the butanol threshold test (BTT). Patients were divided into two groups: an endoscopic trans-sellar approach group (ETA, n = 768) and an extended endoscopic endonasal approach group (EEEA, n = 160). The ETA group was sub-divided into Nasoseptal flap (NSF) and no NSF groups. RESULTS: Non-validated olfactory function significantly worsened in the EEEA and ETA-NSF groups compared with that in the ETA- no NSF group for at least 6 months post-operatively. Validated olfactory impairment (BTT and CC-SIT) was also significantly worse in the EEEA and NSF groups compared with that in the ETA-no NSF group 3 months post-operatively. Additionally, the degrees of non-validated and validated olfactory deterioration were not significantly different between the EEEA and ETA-NSF groups. We also found that CC-SIT score changes were significantly impaired in tuberculum sellae meningioma patients than in craniopharyn- gioma patients. CONCLUSIONS: We conclude that NSF was the key factor that led to olfactory impairment after endoscopic skull-base surgery.

Therapeutic effects of kefir grain Lactobacillus-derived extracellular vesicles in mice with 2,4,6-trinitrobenzene sulfonic acid-induced inflammatory bowel disease.

Kefir is a fermented product from yeast and lactic acid bacteria, and has been associated with various health benefits including relieving inflammatory bowel disease. Recently, it has been shown that gram-positive bacteria produce extracellular vesicles (EV). The EV could be appearing as potentially important mediators of cell to cell interaction. In this study, we explored the role of kefir grain Lactobacillus-derived EV in modulating inflammation responses via alleviating the production of inflammatory cytokines in tumor necrosis factor-α (TNF-α)-induced inflammation in Caco-2 cells and the 2,4,6-trinitrobenzene sulfonic acid-induced inflammatory bowel disease mouse model. Kefir-derived Lactobacillus EV were isolated by ultracentrifugation of the culture medium of 3 different kefir-derived strains (i.e., Lactobacillus kefir, Lactobacillus kefiranofaciens, and Lactobacillus kefirgranum). Nanoparticle tracking analysis showed that the size of isolated kefir-derived Lactobacillus EV was within 80 to 400 nm, and kefir-derived Lactobacillus EV uptake into recipient Caco-2 cells was confirmed by fluorescence labeling. Treatment of each kefir-derived Lactobacillus EV onto TNF-α-stimulated Caco-2 cells significantly reduced the level of both mRNA expression and secretion of IL-8, and Western blot analysis revealed that such an effect was related to inhibition of TNF-α signaling mediated by reducing the phosphorylation of p65, a subunit of NF-kB. Subsequent administration of kefir-derived Lactobacillus EV into inflammatory bowel disease-induced mice significantly alleviated the body weight loss and rectal bleeding, and enhanced stool consistency. Histological examination showed that kefir-derived Lactobacillus EV substantially reduced the infiltration of transmural leukocytes and loss of goblet cells within the colon, and the serum level of myeloperoxidase was significantly lower in the EV-treated group than control group. Our study demonstrates that kefir-derived Lactobacillus EV can be potentially used for developing innovative strategies for alleviating inflammatory bowel disease.

Acute anti-obesity effects of intracerebroventricular 11ß-HSD1 inhibitor administration in diet-induced obese mice.

The hypothalamus is the regulatory centre of both appetite and energy balance and endoplasmic reticulum (ER) stress in the hypothalamus is involved in the pathogenesis of obesity. Recently, inhibition of 11 ß hydroxysteroid dehydrogenase type1 (11ß-HSD1) was reported to have an anti-obesity effect by reducing fat mass. However, the link between the role of 11ß-HSD1 in the hypothalamus and obesity has yet to be determined. In the present study, embryonal primary hypothalamic neurones and high-fat diet (HFD) fed mice were used to investigate the anorexigenic effects of 11ß-HSD1 inhibitors both in vitro and in vivo. In hypothalamic neurones, carbenoxolone (a non selecitve 11ß-HSD inhibitor) alleviated ER stress and ER stress-induced neuropeptide alterations. In HFD mice, i.c.v. administration of carbenoxolone or KR67500 (nonselective and selective 11ß-HSD1 inhibitors, respectively) was associated with less weight gain compared to control mice for 24 hours after treatment, presumably by reducing food intake. Furthermore, glucose regulated protein (Grp78), spliced X-box binding protein (Xbp-1s), c/EBP homologous protein (chop) and ER DnaJ homologue protein (Erdj4) expression was decreased in the hypothalami of mice administrated 11ß-HSD1 inhibitors compared to controls. Conversely, the phosphorylation of protein kinase B (PKB/Akt), signal transducer and activator of transcription 3 (Stat3), mitogen-activated protein kinase (MAPK/ERK) and S6 kinase1 (S6K1) in the hypothalamus was induced more in mice treated using the same regimes. In conclusion, acute 11ß-HSD1 inhibition in the hypothalamus could reduce food intake by decreasing ER stress and increasing insulin, leptin, and mammalian target of rapamycin complex 1 (mTORC1) signalling.

Comparison of 3D and 2D shear-wave elastography for differentiating benign and malignant breast masses: focus on the diagnostic performance.

AIM: To evaluate the diagnostic performance of three-dimensional (3D) image shear-wave elastography (SWE) for differentiating benign from malignant breast masses compared to two-dimensional (2D) SWE and B-mode ultrasound (US). MATERIALS AND METHODS: This study consisted of 205 breast lesions from 199 patients who underwent B-mode US and SWE before biopsy from January 2014 to March 2016. Quantitative elasticity values (maximum and mean elasticity, Emax and Emean) obtained from 2D and 3D SWE (axial, sagittal, and coronal images) were reviewed retrospectively, in addition to the histopathological findings including immunohistochemistry profiles (luminal A, luminal B, human epidermal growth factor receptor 2 (HER2)-enriched, and triple-negative breast cancer) in cases of malignancy. Histopathological findings were regarded as the reference standard. The diagnostic performance of each data set was evaluated using the area under the receiver operating characteristic (ROC) curve (AUC) analysis to compare sensitivity and specificity. RESULTS: Among 205 lesions, 105 (51.22%) were malignant and 100 (48.78%) were benign. Compared to benign masses, malignant masses had higher values of Emax and Emean on both 2D and 3D SWE, the differences of which were statistically significant (p<0.001). The AUCs of 2D, 3D axial, and sagittal SWE were significantly higher than that of 3D coronal SWE (p<0.05). In addition, the sensitivities of axial, sagittal, and coronal 3D SWE were all higher than that of 2D SWE for Emean (81.9%, 87.6%, and 89.5% versus 70.5%, respectively, p<0.05). Conversely, the specificity of 2D and 3D axial SWE was higher than that of 3D sagittal and coronal SWE (Emax, 84%, 83% versus 76%, 73%; Emean, 85%, 81% versus 68%, 50%, respectively, p<0.05). We also assessed changes in Breast Imaging-Reporting and Data System (BI-RADS) category 3 and category 4a lesions by adding each of the parameters for 2D and 3D SWE in B-mode US. The specificity, PPV, and accuracy of combined 2D or combined 3D SWE with B-mode US was statistically higher than that of B-mode US alone for differentiating benign and malignant lesions (p<0.05). CONCLUSIONS: Among SWE images, 2D SWE, and 3D SWE axial and sagittal images exhibited superior diagnostic performance compared to 3D coronal images. Addition of 3D SWE images to B-mode US improved the diagnostic performance for distinguishing benign from malignant masses.

Calling the patient's own name facilitates recovery from general anaesthesia: a randomised double-blind trial.

People can hear and pay attention to familiar terms such as their own name better than general terms, referred to as the cocktail party effect. We performed a prospective, randomised, double-blind trial to investigate whether calling the patient's name compared with a general term facilitated a patient's response and recovery from general anaesthesia. We enrolled women having breast cancer surgery with general anaesthesia using propofol and remifentanil. Patients were randomly allocated into two groups depending on whether the patient's name or a general term was called, followed by the verbal command - 'open your eyes!' - during emergence from anaesthesia; this pre-recorded sentence was played to the patient using headphones. Fifty patients were allocated to the name group and 51 to the control group. Our primary outcome was the time from discontinuation of anaesthesia until eye opening. The mean (SD) time was 337 (154) s in the name group and 404 (170) s in the control group (p = 0.041). The time to i-gel® removal was 385 (152) vs. 454 (173) s (p = 0.036), the time until achieving a bispectral index of 60 was 174 (133) vs. 205 (160) s (p = 0.3), and the length of stay in the postanaesthesia care unit was 43.8 (3.4) vs. 47.3 (7.1) min (p = 0.005), respectively. In conclusion, using the patient's name may be an easy and effective method to facilitate recovery from general anaesthesia.

Differentiation of benign and metastatic axillary lymph nodes in breast cancer: additive value of MRI computer-aided evaluation.

AIM: To retrospectively determine the qualitative and quantitative cut-off values of the magnetic resonance computer-aided evaluation (MR CAE) parameters to differentiate between benign and metastatic axillary lymph nodes (ALNs) and to investigate the combined diagnostic performance of MR CAE imaging. MATERIALS AND METHODS: From July 2011 to June 2014, 124 patients who underwent preoperative conventional MR, diffusion-weighted (DW), and MR CAE imaging were included. Computer-generated qualitative and quantitative features for ALNs were recorded, and two breast imaging radiologists interpreted the MR images for the presence of metastatic ALNs using conventional MR and DW, and in combination with MR CAE images by consensus. The cut-off values of MR CAE and diagnostic performance were derived from the receiver operating characteristic (ROC) curve. RESULTS: Thirty-four (26.4%) were ALN positive and 90 (73.6%) were ALN negative on the final histopathological result. On qualitative analysis, visualization on the colour map (p=0.007) and kinetic curve type (p<0.001) were significantly different between the groups. On quantitative analysis, mean values (%) of persistent, plateau, and washout ratios differed significantly (p<0.001). Of these significant parameters, a washout ratio of >49% showed the greatest diagnostic accuracy (area under the ROC curve, 0.909). With conventional MR and DW images, sensitivity, specificity, and accuracy were 82.4%, 85.6%, and 84.7%, respectively. With added information from MR CAE images, accuracy significantly improved to 93.5% (p=0.043). The sensitivity and specificity improved to 91.2% (p=0.403) and 94.4% (p=0.086), respectively. CONCLUSION: The additive use of MR CAE improved diagnostic performance and can be helpful for differentiating benign from metastatic ALNs.

Spectral study of metabolism-based autofluorescence and white-light reflectance for endoscopic tumor imaging.

Metabolism-based autofluorescence redox imaging is one of the promising options for non-invasive screening of digestive tumors. In this paper, autofluorescence from fluorescent coenzymes such as NADH and FAD related to cellular metabolism as well as total hemoglobin and oxygen saturation are analyzed based on a point spectrum. As a redox index based on the metabolism, the ratio of the 450nm-490nm fluorescence intensities for 365nm and 405nm excitation wavelengths (F365/F405) is used. Although F365/F405 is a good index in many samples, inversion and weakened contrast are observed. A Simplified models with and without collagen based on Lambert-Beer law are built to explain how F365/F405 depicts the tumor region.

Ascites associated with uterine leiomyoma in a 22-year-old woman with systemic lupus erythematosus.

Ascites in systemic lupus erythematosus (SLE) patients has a variety of etiologies, which usually require different treatment options. Our case was a 22-year-old patient with an unusual combination of ascites, uterine leiomyoma and SLE. The patient presented with painless ascites of an inflammatory nature. However, the ascites was not related to peritonitis and SLE disease activity. The ascites disappeared following laparotomy and tumor resection without additional medication. Gynecologic benign tumors including uterine leiomyoma can be the cause of ascites in SLE patients. Clinicians should be aware of that possibility in case painless ascites occurs in females with SLE.

Dual-band multi-aperture enhanced redox imaging of colonic adenomas for endoscopes with a high-performance CMOS imager.

Dual-band multi-aperture imaging of colonic adenomas based on the redox condition of mucosal cells for next-generation endoscopes is proposed. A low-noise and high-dynamic-range CMOS imager with the folding integration and the cyclic ADC is utilized in the single-imager multi-aperture camera system with 475-nm and 530-nm band-pass filters. A redox image is calculated from four kinds of images, 475-nm and 530-nm fluorescence images for 365-nm and 405-nm excitation lights. Dark current and random noise are reduced with a selective averaging method. The contrast of the redox image has been successfully enhanced.

Nonmuscle myosin heavy chain and histone H3 are intracellular binding partners of lithospermic acid B and mediate its antiproliferative effect on VSMCs.

Lithospermic acid B (LAB), an active component of danshen, is known to inhibit the proliferation of vascular smooth muscle cells (VSMCs) and has pharmacological activity scavenging free radicals in VSMCs. However, the precise mechanism through which LAB exerts its antiproliferative effect is unclear. Therefore, we investigated how LAB regulates cellular proliferation in primary cultured rat VSMCs. Using fluorescein isothiocyanate (FITC)-conjugated LAB to track its cellular localization, we show that LAB localizes to the nucleus, specifically to the nucleolus, where it binds to histone H3, leading to the inhibition of the platelet-derived growth factor (PDGF)- induced phosphorylation of histone H3. LAB also only moves into the nucleus during the normal expression of nonmuscle myosin heavy chain (NMHC-IIA), which is associated with LAB in VSMCs. Notably, LAB suppressed the PDGF-induced phosphorylation of Akt and the expression of cyclin D2 in the presence of NMHC-IIA expression. Knockdown of NMHC-IIA expression impeded the function of LAB, which was then unable to inhibit the PDGF-induced proliferation of VSMCs. We conclude that LAB modulates the PDGF-induced proliferation of VSMCs by interacting with NMHC-IIA, which allows LAB to localize in the nucleus and to suppress the PDGF-induced proliferation of VSMCs.

SOX2 has a crucial role in the lineage determination and proliferation of mesenchymal stem cells through Dickkopf-1 and c-MYC.

SOX2 is a well-known core transcription factor in embryonic stem cells (ESCs) and has an important role in the maintenance of pluripotency. Recently, SOX2 expression has also been reported in adult stem cells (ASCs), but the role of SOX2 in ASCs remains unknown. In this study, we examined the molecular mechanisms of SOX2 in human mesenchymal stem cells (hMSCs), a type of ASCs, by performing inhibition studies. SOX2 inhibition resulted in altered cell growth and differentiation capabilities. These changes coincided with a decrease in Dickkopf-1 (DKK1), a soluble inhibitor of WNT signaling. Chromatin immunoprecipitation and luciferase assays showed that SOX2 binds to DKK1 and has a positive regulatory role in transcription. The enforced expression of DKK1 in SOX2-inhibited hMSCs reversed the differentiation deformities, but could not abrogate the cell proliferation defect. Proliferation was regulated by c-MYC, whose expression can also be controlled by SOX2. Our study shows that SOX2 directly regulates DKK1 expression and, as a consequence, determines the differentiation lineage of hMSCs. Moreover, SOX2 also regulates proliferation by affecting c-MYC. Therefore, these results suggest that SOX2 might have a specific function by regulating DKK1 and c-MYC in the differentiation and growth of ASCs, which is separate from its roles in ESCs.

Genistein and daidzein repress adipogenic differentiation of human adipose tissue-derived mesenchymal stem cells via Wnt/ß-catenin signalling or lipolysis.

OBJECTIVES: One aspect of the effects of isoflavones against fat deposition might be at least associated with the mechanism by which Wnt/ß-catenin signalling inhibits adipocyte differentiation. However, it remains completely unknown as to whether isoflavones might influence Wnt signalling during commitment of pluripotent mesenchymal stem cells (MSCs) to adipose lineages. In the present study, we have investigated the mechanisms underlying effects of genistein and daidzein, the major soy isoflavones, on anti-adipogenic Wnt/ß-catenin signalling. MATERIALS AND METHODS: Adipose tissue-derived (AD) MSCs were exposed continuously to genistein and daidzein (0.01-100 µm) during adipogenic differentiation (21 days). An oestrogen antagonist, ICI 182,780, was used to determine whether or not the isoflavones activated Wnt signalling via oestrogen receptors (ERs). RESULTS: Genistein and daidzein suppressed adipogenic differentiation of AD-MSCs in a dose-dependent manner and inhibited expression of adipogenic markers, PPARγ, SREBP-1c and Glut 4, from mid-phase differentiation. Microarrays showed that anti-adipogenic effects of genistein were principally attributable to activation of Wnt signalling via ERs-dependent pathway, such as Erk/JNK signalling and LEF/TCF4 co-activators. These findings were supported by evidence that the effects of genistein were offset by ICI182,780. Unlike genistein, daidzein inhibited adipogenesis through stimulation of lipolysis, with for example, PKA-mediated hormone sensitive lipase. This is consistent with the increase in glycerol released from AD-MSCs. In conclusion, understanding that different sets of mechanisms of the two isoflavones on adipogenesis will help the design of novel strategies to prevent observed current epidemic levels of obesity, using isoflavones.

Community-acquired Clostridium difficile-associated diarrhea in a patient on chronic peritoneal dialysis.

A 66-year-old woman on chronic peritoneal dialysis was admitted because of intermittent diarrhea and abdominal pain, and anorexia for 1 month. She had not been given antibiotics nor hospitalized for at least 6 months prior to the onset of symptoms. Clostridium difficile and its toxin were detected in the stool and Clostridium difficile-associated diarrhea (CDAD) was diagnosed. Colonoscopic examination revealed pseudomembrane formation and colitis in the whole colon. Clostridium difficile and its toxin became negative 12 days after vancomycin administration. Thus, clinical suspicion to CDAD is important in dialysis patients presenting with abdominal symptoms even if it is apparently community-acquired with no history of antibiotic use and hospitalization.

DNER modulates adipogenesis of human adipose tissue-derived mesenchymal stem cells via regulation of cell proliferation.

OBJECTIVES: In recent years, obesity has become a global epidemic, highlighting the necessity for basic research into mechanisms underlying growth of adipose tissue and differentiation of stem cells into adipocytes, in humans. For better understanding of cell signalling in adipogenesis, the role of DNER (delta/Notch-like EGF-related receptor) in adipogenic differentiation of human adipose tissue-derived mesenchymal stem cells (hAMSC) was investigated. MATERIALS AND METHODS: To assess the role of DNER in hAMSC adipogenesis, hAMSCs were transfected with DNER small interfering RNA (siDNER). Real-time quantitative reverse transcriptase polymerase chain reactions to assess expression levels of adipogenesis-related genes regulated by siDNER, cell cycle and immunoblot analyses were performed. RESULTS: First, it was determined that DNER mRNA was profoundly expressed in hAMSCs and reduced during adipogenic differentiation. Knockdown of DNER altered cell morphology, inhibited proliferation and increased frequency and efficiency of adipogenesis in hAMSC. Expression of CCAAT/enhancer-binding protein delta increased and proportion of cells in S phase decreased by knockdown of DNER, using specific siRNA. Moreover, adipocyte-specific genes including peroxisome proliferator-activated receptor gamma, fatty acid binding protein 4 and perilipin were up-regulated in siDNER compared to the siControl group during adipogenesis in hAMSC. CONCLUSIONS: These results indicate that DNER knockdown in hAMSC accelerated onset of adipogenic differentiation by bypassing mitotic clonal expansion during the early stages of adipogenesis.

Histone deacetylase inhibitors decrease proliferation potential and multilineage differentiation capability of human mesenchymal stem cells.

OBJECTIVES: Histone deacetylase (HDAC) is an important therapeutic target in cancer. Two of the main anticancer mechanisms of HDAC inhibitors are induction of terminal differentiation and inhibition of cell proliferation. To investigate the role of HDAC in maintenance of self-renewal and cell proliferation, we treated mesenchymal stem cells (MSCs) that originated from adipose tissue or umbilical cord blood with valproic acid (VPA) and sodium butyrate (NaBu). MATERIALS AND METHODS: Human MSCs were isolated from mammary fat tissue and cord blood. We performed MTT assay and flow cytometry-based cell cycle analysis to assess self-renewal of MSCs. In vitro differentiation assays into osteogenic, adipogenic, neurogenic and chondrogenic lineages were conducted to investigate MSC multipotency. Immunocytochemistry, Western blot and reverse transcription-polymerase chain reaction were used to interrogate molecular pathways. RESULTS: VPA and NaBu flattened the morphology of MSCs and inhibited their growth. VPA and NaBu activated the transcription of p21(CIP1/WAF1) by increasing the acetylation of histone H3 and H4 and eventually blocked the cell cycle at G2/M phase. The expression level of p16(INK4A), a cdk inhibitor that is closely related to cellular senescence, was not changed by HDAC inhibitor treatment. We performed controlled differentiation into bone, fat, cartilage and nervous tissue to elucidate the role of HDAC in the pluripotency of MSC to differentiate into functional tissues. VPA and NaBu decreased the efficiency of adipogenic, chondrogenic, and neurogenic differentiation as visualized by specific staining and reverse transcription-polymerase chain reaction. In contrast, osteogenic differentiation was elevated by HDAC inhibitor treatment. CONCLUSION: HDAC activity is essential for maintaining the self-renewal and pluripotency of MSCs.

Radioresistance of Anisakis simplex third-stage larvae and the possible role of superoxide dismutase.

The radioresistance of Anisakis simplex third-stage larvae and the possible role of sublethal radiation on superoxide dismutase (SOD) were investigated. Larvae were isolated from the viscera of the sea eel Anago anago; irradiated with 10, 100, 200, 500, or 1,000 Gy; and then given orally to rats. Worms were recovered at 16 hr postinoculation. Most larvae were found to have invaded the gastric wall, omentum, and abdominal cavity, suggesting that their viability and infectivity were not controlled by irradiation with the doses used. To determine the relationship between SOD activities in parasites and their radiosensitivities, the larvae of A. simplex and the metacercariae of Neodiplostomum seoulense (a radiosensitive control) were irradiated with 0, 30, 100, or 500 Gy, and parasite SOD levels were measured. In nonirradiated A. simplex larvae, the average SOD level was 38.9 U/mg, and this increased to 51.3 U/mg at 500 Gy. However, at all radiation doses applied, SOD activities of N. seoulense metacercariae were significantly (P < 0.05) lower than those of A. simplex larvae. Our results demonstrate that A. simplex third-stage larvae are radioresistant, and suggest that SOD plays a role in this radioresistance.