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In our previous work, we characterized the in vitro biofunctionality and evaluated the biosafety of exopolysaccharide (EPS)-producing Weissella confusa VP30 (VP30), newly isolated from healthy children’s feces. Since the purified EPS (pEPS) from fermented milk with VP30 (VP30-EPS) showed significant water holding capacity, it was theorized that its consumption would relieve constipation. In this work, the in vivo functionalities of VP30-EPS and pEPS were evaluated for their effect on constipation using an experimental constipated rat model. Rats were randomly divided into four groups: (i) negative control (PBS administered normal group), (ii) loperamide treated positive control (constipation group), (iii) constipation with loperamide plus VP30-EPS (1 g/kg) and (iv) constipation with loperamide plus pEPS (0.6 g/kg) groups. Loperamide treatment induced animal constipation and significantly reduced the frequency of defecation, intestinal transit ratio, and water content of feces. However, all four fecal parameters were improved in both the loperamide plus VP30-EPS and pEPS administered groups as compared to the loperamide treated positive control group. No significant changes in dietary intake or serum hepatocellular necrosis maker levels were observed in any experimental group. These results suggest that the addition of VP30-EPS or pEPS potentially improves the functional laxative effects of commercial products. No other published research relating in vivo functional effects of EPS from Weissella spp. on constipation could be identified. This study suggests the possibility that VP30-EPS and pEPS can be applied to fermented and/or functional foods to relieve constipation.

To identify the risk factors leading to new brain metastases (BM) following brain-directed treatment for initial BM resulting from breast cancer (BC). In this multi-institutional study, 538 BC patients with available follow-up imaging after brain-directed treatment for initial BM were analyzed. Tumor molecular subtypes were classified as follows: hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2−, n = 136), HER2-positive (HER2+, n = 253), or triple-negative BC (TNBC, n = 149). In 37.4% of patients, new BM emerged at a median of 10.5 months after brain-directed treatment for initial BM. The 1-year actuarial rate of new BM for HR+/HER2−, HER2+, and TNBC were 51.9%, 44.0%, and 69.6%, respectively (p = 0.008). Initial whole-brain radiotherapy (WBRT) reduced new BM rates (22.5% reduction at 1 year, p 4) (p

In active matrix organic light emitting diode (AMOLED) displays, when a variable refresh rate is applied and the frame rate changes, the image’s color and luminance quality in AMOLED displays deteriorates. The frequency-dependent cognitive differences were experimentally demonstrated by using 6.76″ AMOLED displays. This phenomenon is dependent on the emission time and the data programming time on the frame rate. This degradation of the image quality during the frequency switch could be prevented by applying a variable initial voltage (VINI) to the OLED anode. For a frequency change between 60 and 120 Hz, the measured just noticeable color difference (JNCD) decreased from 7.50 to less than 1.00 in luminance, and from 2.34 to 0.02 in color. As our approach can prevent image quality distortion by utilizing an existing compensation pixel structure without additional compensation steps, it will be a promising technique for improving the picture quality in AMOLED displays.

Background The continuum of anti-HER2 agents is a standard treatment of HER2 + metastatic breast cancer (MBC). This study evaluated the efficacy of lapatinib plus vinorelbine in patients progressed on both trastuzumab and lapatinib treatments. Methods A total of 149 patients were randomly assigned to lapatinib with vinorelbine (LV) (n = 75; lapatinib, 1000 mg daily; vinorelbine 20 mg/m2 D1, D8 q3w) or vinorelbine (V) (n = 74; 30 mg/m2 D1, D8 q3w). The primary endpoint was progression-free survival (PFS) rate at 18 weeks. Results The median number of previous anti-HER2 therapies was 2 (range 2–5). There was no significant difference in PFS rate at 18 weeks between LV and V arms (45.9% vs 38.9%, p = 0.40). ORR was 19.7% in LV arm, and 16.9% in V arm (p = 0.88). PFS and OS did not differ between two arms (LV vs V; median PFS, 16 vs 12 weeks, HR = 0.86, 95% CI 0.61–1.22; median OS, 15.0 vs 18.9 months, HR = 1.07, 95% CI 0.72–1.58). Toxicity profiles were similar in both arms and all were manageable. Conclusions Lapatinib plus vinorelbine treatment was tolerable; however, it failed to demonstrate the clinical benefits over vinorelbine alone in patients with HER2 + MBC after progression on both trastuzumab and lapatinib. Clinical trial registration ClinicalTrials.gov number NCT01730677.

Challenges for better treatment of slaughterhouse wastewater (SWW) stem from too strong organic pollutants as well as the potential existence of various pathogen but conventional biological treatment still has shown its limitation. Using cold plasma, this study investigates the physicochemical deactivation of pathogens while treating organic and inorganic pollutants of slaughterhouse wastewater (SWW). Experiments were conducted by decreasing the hydraulic retention time from 0.16 to 1 L/day to derive the best operating condition based on the performance in the cold plasma oxidation. While operating the continuous plasma process, this study identifies the main mechanisms for nitrogen, phosphorus, and iron removal. The results show that chemical oxygen demand (COD), total nitrogen (TN), and total phosphorus (TP) recorded the removal efficiencies of 78~93, 51~92, and 35~83%, respectively. A slight increase in pH via cold plasma influence total iron (T-Fe) removal up to 93%. Cell counting confirms that bacteria could be removed as much as 98% or more in all the operating conditions tested. Toxicity unit dramatically decreased to less than 1 (~ 96% removal). These results suggest that the cold plasma treatment of SWW might be a viable option to manage organic pollutants, pathogen, and toxicity simultaneously.

Background Oxaliplatin is a platinum derivative that has shown efficacy in advanced hepatocellular carcinoma. S-1 is an oral fluoropyrimidine that has substituted for 5-fluorouracil in many cancers. This was a multicenter, open-label, single-arm phase II trial that evaluated the efficacy of S-1 and oxaliplatin (SOX) in advanced hepatocellular carcinoma. All patients included in the present study were systemic treatment-naïve. Prior treatment with sorafenib was allowed, but other treatments were not. Methods Patients received S-1 (40 mg/m2 twice daily from day 1–14) and oxaliplatin (130 mg/m2 on day 1) every 3 weeks. The primary end point was time to progression (TTP). Secondary end points included progression-free survival, overall survival (OS), response rate, and safety profile. Results Thirty six patients with advanced hepatocellular carcinoma were included in this study. The median TTP was 3.0 months (95% confidence interval (CI), 0.75–5.25), and the median OS was 10.3 months (95% CI, 6.4–14.3). Bone metastasis was associated with poorer TTP and OS. The efficacy of SOX was unaffected by prior sorafenib or locoregional therapy. The objective response rate was 13.9%. No grade 4 toxicity or death from adverse events occurred. The most common grade 3 toxicities were neutropenia (13.9%), thrombocytopenia (13.9%), and diarrhea (8.3%). Conclusions Although this trial did not meet its primary end point, the SOX regimen showed comparable efficacy and safety to the 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) regimen. As the SOX regimen is easier for patients, SOX may be a reasonable substitute for FOLFOX in hepatocellular carcinoma. Trial registration Clinicaltrials.gov NCT01429961. Registered 7 September 2011.

We aimed to investigate the prognostic factors that can predict terminal stage survival (TSS) at the time of terminal cancer diagnosis. We prospectively evaluated 141 patients immediately after the diagnosis of terminal cancer by their attending oncologists. A total of 32 factors, including performance status, clinical prediction of survival, time to terminal cancer (TTC), clinical symptoms, signs, and laboratory tests including the neutrophil–lymphocyte ratio (NLR), were analyzed. TSS was defined as the time from the diagnosis of terminal cancer to death. The mean age of the 141 patients studied was 58.7 years, and 53 were female (38 %). The median TSS was 1.7 months (95 % confidence interval [CI] 1.43–1.97). In the univariate analyses, the TSS was significantly associated with 16 of the 32 factors tested. In the multivariate analysis, a lower Karnofsky performance status (KPS), a shorter TTC (

Hybrid electric vehicles (HEV) utilize electric power and a mechanical engine for propulsion; therefore, the performance of HEVs is directly influenced by the characteristics of the energy storage system (ESS). The ESS for an HEV generally requires high power performance, long cycle life, reliability and cost effectiveness; thus, a hybrid energy storage system (HESS) that combines different types of storage devices has been considered to fulfill both performance and cost requirements. To improve the operating efficiency and cycle life of a HESS, an advanced dynamic control regime in which pertinent storage devices in the HESS can be selectively operated based on their status is presented. Verification tests were performed to confirm the degree of improvement in energy efficiency. In this paper, an advanced HESS with a battery management system (BMS) that includes an optimal switching control function based on the estimated state of charge (SOC) is presented and verified.

Purpose Neoadjuvant chemotherapy may modify the yield of involved axillary lymph nodes. The purpose of this study was to identify the clinical significance of the involved nodal ratios in patients with stage II/III breast cancer treated with neoadjuvant chemotherapy. Methods Two hundred and five stage II and III breast cancer patients who received neoadjuvant docetaxel/doxorubicin chemotherapy were enrolled in this prospective study. The patients received three cycles of neoadjuvant chemotherapy followed by curative surgery, either breast-conserving surgery or mastectomy with axillary lymph node dissection, and received three additional cycles of docetaxel/doxorubicin chemotherapy as adjuvant. Adjuvant radiotherapy and hormonal therapy were given after adjuvant chemotherapy when indicated. Results The median follow-up duration was 28.9 months. The overall response rate (RR) for neoadjuvant chemotherapy was 77.6%. The mean nodal ratio was 0.29 (range, 0–1.0; nodal ratio ≤0.25, 121 [59.0%] vs. >0.25, 84 [41.0%]). Relapse free survival (RFS) of the patients who had a nodal ratio >0.25 was significantly shorter (Hazard Ratio (HR) = 2.701, P = 0.001). A nodal ratio >0.25 was also associated with a shorter overall survival (OS) (HR = 4.109, P = 0.006). However, RFS and OS were not different according to the absolute number of involved nodes (ANIN) (P = 0.166, P = 0.248, respectively). In multivariate analysis, the nodal ratio was an independent prognostic factor for RFS and OS (HR = 4.246, P

The cellular prion protein (PrPC) is a highly conserved glycosylphosphatidylinositol (GPI)-anchored membrane protein that is involved in the signal transduction during the initial phase of neurite outgrowth. The Ras homolog gene family member A (RhoA) is a small GTPase that is known to have an essential role in regulating the development, differentiation, survival, and death of neurons in the central nervous system. Although recent studies have shown the dysregulation of RhoA in a variety of neurodegenerative diseases, the role of RhoA in prion pathogenesis remains unclear. Here, we investigated the regulation of RhoA-mediated signaling by PrPC using both in vitro and in vivo models and found that overexpression of PrPC significantly induced RhoA inactivation and RhoA phosphorylation in hippocampal neuronal cells and in the brains of transgenic mice. Using siRNA-mediated depletion of endogenous PrPC and overexpression of disease-associated mutants of PrPC, we confirmed that PrPC induced RhoA inactivation, which accompanied RhoA phosphorylation but reduced the phosphorylation levels of LIM kinase (LIMK), leading to cofilin activation. In addition, PrPC colocalized with RhoA, and the overexpression of PrPC significantly increased neurite outgrowth in nerve growth factor-treated PC12 cells through RhoA inactivation. However, the disease-associated mutants of PrPC decreased neurite outgrowth compared with wild-type PrPC. Moreover, inhibition of Rho-associated kinase (ROCK) substantially facilitated neurite outgrowth in NGF-treated PC12 cells, similar to the effect induced by PrPC. Interestingly, we found that the induction of RhoA inactivation occurred through the interaction of PrPC with RhoA and that PrPC enhanced the interaction between RhoA and p190RhoGAP (a GTPase-activating protein). These findings suggest that the interactions of PrPC with RhoA and p190RhoGAP contribute to neurite outgrowth by controlling RhoA inactivation and RhoA-mediated signaling and that disease-associated mutations of PrPC impair RhoA inactivation, which in turn leads to prion-related neurodegeneration.

Rat pheochromocytoma (PC12) cells have been used to investigate neurite outgrowth. Nerve growth factor (NGF) has been well known to induce neurite outgrowth from PC12 cells. RhoA belongs to Ras-related small GTP-binding proteins, which regulate a variety of cellular processes, including cell morphology alteration, actin dynamics, and cell migration. NGF suppressed GTP-RhoA levels after 12 h in PC12 cells and was consistently required for a long time to induce neurite outgrowth. Constitutively active (CA)-RhoA suppressed neurite outgrowth from PC12 cells in response to NGF, whereas dominant-negative (DN)-RhoA stimulated it, suggesting that RhoA inactivation is essential for neurite outgrowth. Here, we investigated the mechanism of RhoA inactivation. DN-p190RhoGAP abrogated neurite outgrowth, whereas wild-type (WT)-p190RhoGAP and WT-Src synergistically stimulated it along with accelerating RhoA inactivation, suggesting that p190RhoGAP, which can be activated by Src, is a major component in inhibiting RhoA in response to NGF in PC12 cells. Contrary to RhoA, Rap1 was activated by NGF, and DN-Rap1 suppressed neurite outgrowth, suggesting that Rap1 is also essential for neurite outgrowth. RhoA was co-immunoprecipitated with Rap1, suggesting that Rap1 interacts with RhoA. Furthermore, a DN-Rap-dependent RhoGAP (ARAP3) prevented RhoA inactivation, abolishing neurite formation from PC12 cells in response to NGF. These results suggest that NGF activates Rap1, which, in turn, up-regulates ARAP3 leading to RhoA inactivation and neurite outgrowth from PC12 cells. Taken together, p190RhoGAP and ARAP3 seem to be two main factors inhibiting RhoA activity during neurite outgrowth in PC12 cells in response to NGF.