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Sample records for survival increased significantly

  1. Continues administration of Nano-PSO significantly increased survival of genetic CJD mice.

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    Binyamin, Orli; Keller, Guy; Frid, Kati; Larush, Liraz; Magdassi, Shlomo; Gabizon, Ruth

    2017-12-01

    We have shown previously that Nano-PSO, a nanodroplet formulation of pomegranate seed oil, delayed progression of neurodegeneration signs when administered for a designated period of time to TgMHu2ME199K mice, modeling for genetic prion disease. In the present work, we treated these mice with a self-emulsion formulation of Nano-PSO or a parallel Soybean oil formulation from their day of birth until a terminal disease stage. We found that long term Nano-PSO administration resulted in increased survival of TgMHu2ME199K lines by several months. Interestingly, initiation of treatment at day 1 had no clinical advantage over initiation at day 70, however cessation of treatment at 9months of age resulted in the rapid loss of the beneficial clinical effect. Pathological studies revealed that treatment with Nano-PSO resulted in the reduction of GAG accumulation and lipid oxidation, indicating a strong neuroprotective effect. Contrarily, the clinical effect of Nano-PSO did not correlate with reduction in the levels of disease related PrP, the main prion marker. We conclude that long term administration of Nano-PSO is safe and may be effective in the prevention/delay of onset of neurodegenerative conditions such as genetic CJD. Copyright © 2017. Published by Elsevier Inc.

  2. Significant prolongation of segmental pancreatic allograft survival in two species

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    Du Toit, D.F.; Heydenrych, J.J.

    1988-06-01

    A study was conducted to assess the suppression of segmental pancreatic allograft rejection by cyclosporine (CSA) alone in baboons and dogs, and subtotal marrow irradiation (TL1) alone and TL 1 in combination with CSA in baboons. Total pancreatectomy in the dog and primate provided a reliable diabetic model, induced an absolute deficiency of insulin and was uniformly lethal if not treated. Continuous administration of CSA in baboons resulted in modest allograft survival. As in baboons, dogs receiving CSA 25 mg/kg/d rendered moderate graft prolongation but a dose of 40 mg/kg/d resulted in significant graft survival (greater than 100 days) in 5 of 8 allograft recipients. Irradiation alone resulted in minimal baboon pancreatic allograft survival of 20 baboons receiving TL1 1,000 rad and CSA, 3 had graft survival greater than of 100 days. Of 15 baboons receiving TL1 800 rad and CSA, 6 had graft survival of greater than 100 days. In conclusion, CSA administration in dogs and TL1 in combination with CSA in baboons resulted in highly significant segmental pancreatic allograft survival.

  3. Analysis of Prognostic Values of Various PET Metrics in Preoperative 18F-FDG PET for Early-Stage Bronchial Carcinoma for Progression-Free and Overall Survival: Significantly Increased Glycolysis Is a Predictive Factor.

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    Steiger, Seraina; Arvanitakis, Michael; Sick, Beate; Weder, Walter; Hillinger, Sven; Burger, Irene A

    2017-12-01

    The purpose of this study was to assess various volume-based PET quantification metrics, including metabolic tumor volume and total lesion glycolysis (TLG) with different thresholds, as well as background activity-based PET metrics (background-subtracted lesion activity [BSL] and background-subtracted volume) as prognostic markers for progression-free and overall survival (PFS and OS, respectively) in early-stage I and II non-small cell lung cancer (NSCLC) after resection. Methods: Patients (n = 133) underwent an adequate 18F-FDG PET/CT scan before surgery between January 2003 and December 2010. All PET activity metrics showed a skewed distribution and were log-transformed before calculation of the Pearson correlation coefficients. Survival tree analysis was used to discriminate between high- and low-risk patients and to select the most important prognostic markers. The Akaike information criterion was used to compare 2 univariate models. Results: Within the study time, 36 patients died from NSCLC and 26 patients from other causes. At the end of follow-up, 70 patients were alive, with 67 patients being free of disease. All log-transformed PET metrics showed a strong linear association, with a Pearson correlation coefficient between 0.703 and 0.962. After multiple testing corrections, only 1 prognostic marker contributed a significant split point in the survival tree analysis. Of 10 potential predictors including 7 PET metrics, a BSL greater than 6,852 (P = 0.017) was chosen as split point, assigning 13 patients into a high-risk group. If BSL was removed from the set of predictors, a 42% TLG (TLG42%) of greater than 4,204 (P = 0.023) was chosen as split point. When a dichotomized BSL or TLG42% variable was used for a univariate Cox model, the Akaike information criterion difference of both models was smaller than 2; therefore, the data do not provide evidence that 1 of the 2 prognostic factors is superior. Conclusion: Volume-based PET metrics correlate with PFS and

  4. Significantly increased visceral adiposity index in prehypertension.

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    Yanan Ding

    Full Text Available The prevalence of prehypertension has increased in China, and prehypertension frequently progress to hypertension over a short time period; both have become public health problems. Therefore, this study was conducted to determine the relationship between the Visceral Adiposity Index (VAI and blood pressure (BP in China.A cross-sectional epidemiological survey was conducted in China using a stratified random cluster sampling method. Sex-specific VAI quartile cut-off points were used as follows: 0.88, 1.41, 2.45 in males and 0.85, 1.33, 2.22 in females. Prehypertension and hypertension were each defined according to The Seventh Report of the Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7 guidelines. A multivariate logistic analysis was conducted to analyze the relationship among VAI, prehypertension and hypertension.The ORs for prehypertension and hypertension in the upper quartiles of the VAI were 1.514 (1.074-2.133, P=0.018 and 1.660 (1.084-2.542, P=0.020, in males, after adjusting for age, education, smoking habits, alcohol consumption, physical activity, serum creatinine, fasting glucose, and plasma insulin. Following further adjustments for the above confounders, chronic kidney disease, and diabetes, the ORs for prehypertension and hypertension in the upper quartile of the VAI were 1.660 1.533 (1.086-2.165, P=0.015, and 1.743 (1.133-2.680, P=0.011, in males. The ORs for prehypertension and hypertension in the upper quartile of the VAI were 1.691 (1.223-2.338, P=0.001, and 1.682 (1.162-2.435, P=0.006, in females, after adjusting for age, education, smoking habits, alcohol consumption, physical activity, serum creatinine, fasting glucose, and plasma insulin. Following further adjustments for the above confounders, chronic kidney disease, and diabetes, the ORs for prehypertension and hypertension in the upper quartile of the VAI were 1.688 (1.220-2.334, P=0.002, and 1.657 (1

  5. Intravenous hemostatic nanoparticles increase survival following blunt trauma injury.

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    Shoffstall, Andrew J; Atkins, Kristyn T; Groynom, Rebecca E; Varley, Matthew E; Everhart, Lydia M; Lashof-Sullivan, Margaret M; Martyn-Dow, Blaine; Butler, Robert S; Ustin, Jeffrey S; Lavik, Erin B

    2012-11-12

    Trauma is the leading cause of death for people ages 1-44, with blood loss comprising 60-70% of mortality in the absence of lethal CNS or cardiac injury. Immediate intervention is critical to improving chances of survival. While there are several products to control bleeding for external and compressible wounds, including pressure dressings, tourniquets, or topical materials (e.g., QuikClot, HemCon), there are no products that can be administered in the field for internal bleeding. There is a tremendous unmet need for a hemostatic agent to address internal bleeding in the field. We have developed hemostatic nanoparticles (GRGDS-NPs) that reduce bleeding times by ~50% in a rat femoral artery injury model. Here, we investigated their impact on survival following administration in a lethal liver resection injury in rats. Administration of these hemostatic nanoparticles reduced blood loss following the liver injury and dramatically and significantly increased 1 h survival from 40 and 47% in controls (inactive nanoparticles and saline, respectively) to 80%. Furthermore, we saw no complications following administration of these nanoparticles. We further characterized the nanoparticles' effect on clotting time (CT) and maximum clot firmness (MCF) using rotational thromboelastometry (ROTEM), a clinical measurement of whole-blood coagulation. Clotting time is significantly reduced, with no change in MCF. Administration of these hemostatic nanoparticles after massive trauma may help staunch bleeding and improve survival in the critical window following injury, and this could fundamentally change trauma care.

  6. Metastatic breast cancer - age has a significant effect on survival

    African Journals Online (AJOL)

    1991-03-02

    Mar 2, 1991 ... months for patients aged 55 - 64 years (P= 0,08; Cox model). The median survival improves again to 24,6 months ... in the very old (aged 75 - 84 years) (P = 0,52; Cox model). The more favourable prognosis in the elderly ... po Box 667, Pretoria, 0001 RSA. Accepted 18 Ocr 1990. tic breast cancer seen in ...

  7. Metastatic breast cancer - age has a significant effect on survival ...

    African Journals Online (AJOL)

    The data on 217 elderly (aged ≥ 65 years) and 209 middleaged postmenopausal patients with metastatic breast cancer treated in the Department of Medical Oncology, University of Pretoria, from 1976 to 1985 were analysed to determine the effect of age on survival. When considered as a group, the elderly have a more ...

  8. Always follow your nose: the functional significance of social chemosignals in human reproduction and survival.

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    Lübke, Katrin T; Pause, Bettina M

    2015-02-01

    This article is part of a Special Issue "Chemosignals and Reproduction" Across phyla, chemosensory communication is crucial for mediating a variety of social behaviors, which form the basis for ontogenetic and phylogenetic survival. In the present paper, evidence on chemosensory communication in humans, with special reference to reproduction and survival, will be presented. First, the impact of chemosignals on human reproduction will be reviewed. Work will be presented, showing how chemosensory signals are involved in mate choice and partnership formation by communicating attractiveness and facilitating a partner selection, which is of evolutionary advantage, and furthermore providing information about the level of sexual hormones. In addition to direct effects on phylogenetic survival, chemosignals indirectly aid reproductive success by fostering harm protection. Results will be presented, showing that chemosensory communication aids the emotional bond between mother and child, which in turn motivates parental caretaking and protection, leading to infant survival. Moreover, the likelihood of group survival can be increased through the use of stress-related chemosignals. Stress-related chemosignals induce a stress-related physiology in the perceiver, thereby priming a fight-flight-response, which is necessary for an optimum adaption to environmental harm. Finally, effects of sexual orientation on chemosensory communication will be discussed in terms of their putative role in stabilizing social groups, which might indirectly provide harm protection and foster survival. An integrative model of the presented data will be introduced. In conclusion, an outlook, focusing on the involvement of chemosensory communication in human social behavior and illustrating a novel approach to the significance of chemosensory signals in human survival, will be given. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Physical activity increases survival after heart valve surgery

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    Lund, K.; Sibilitz, Kirstine Lærum; Kikkenborg Berg, Selina

    2016-01-01

    physical activity levels 6-12 months after heart valve surgery and (1) survival, (2) hospital readmission 18-24 months after surgery and (3) participation in exercise-based cardiac rehabilitation. METHODS: Prospective cohort study with registry data from The CopenHeart survey, The Danish National Patient...... of physical activity after heart valve surgery are positively associated with higher survival rates and participation in cardiac rehabilitation.......OBJECTIVES: Increased physical activity predicts survival and reduces risk of readmission in patients with coronary heart disease. However, few data show how physical activity is associated with survival and readmission after heart valve surgery. Objective were to assess the association between...

  10. FUEL PRICE INCREASE AND MANUFACTURING FIRMS SURVIVAL IN INDONESIA

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    Eko Atmadji

    2014-03-01

    Full Text Available The administered price of fuel has increased quite frequently since 1970. It has raised a concern on the survival ability of manufacturing firms that could be weakened by such policy. This research objective is for confirming whether the policy of increasing fuel price affects the survival of manufacturing firms in Indonesia. By using Instrumental Variable Probit Model, it demonstrates that increasing fuel price does not affect firms’ survival in the short-run, middle-run, as well as long-run. Nevertheless, the z-statistics increase when the period of estimation is expanded. It means that if the time span of sample observation is widened, the result might be different.Keywords: Fuel price, survival ability, instrumental variable probit modelJEL classification numbers: H27, D22AbstrakHarga bahan bakar minyak (BBM selalu meningkat sejak 1970. Kenaikan harga ini telah menimbulkan kekhawatiran pada kemampuan kelangsungan hidup perusahaan manufaktur di Indonesia yang bisa dilemahkan oleh kebijakan tersebut. Penelitian ini dilakukan dengan tujuan mengonfirmasi apakah kebijakan kenaikan harga BBM mempengaruhi kelangsungan hidup perusahaan industri manufaktur di Indonesia. Dengan menggunakan Instrumental Variable Probit Model, hasil penelitian menunjukkan bahwa peningkatan harga BBM tidak mempengaruhi kelangsungan hidupperusahaan dalam jangka pendek, menengah, serta jangka panjang. Namun demikian, z-statistik meningkat ketika periode estimasi diperluas. Ini berarti bahwa jika rentang waktu pengamatan sampel melebar, hasilnya mungkin akan berbeda.Kata kunci: Harga BBM, kemampuan bertahan hidup, instrumental variable probit modelJEL classification numbers: H27, D22

  11. Increased Sleep Promotes Survival during a Bacterial Infection in Drosophila

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    Kuo, Tzu-Hsing; Williams, Julie A.

    2014-01-01

    Study Objectives: The relationship between sleep and immune function is not well understood at a functional or molecular level. We therefore used a genetic approach in Drosophila to manipulate sleep and evaluated effects on the ability of flies to fight bacterial infection. Setting: Laboratory. Participants: Drosophila melanogaster. Methods and Results: We used a genetic approach to transiently alter neuronal excitability in the mushroom body, a region in the central brain that is known to regulate sleep. Flies with increased sleep for up to two days prior to a bacterial infection showed increased resistance to the infection and improved survival. These flies also had increased expression levels of a subset of anti-microbial peptide mRNA prior to infection, as well as increased NFκB activity during infection as indicated by in vivo luciferase reporter activity. In contrast, flies that experienced reduced sleep for up to two days prior to infection had no effect on survival or on NFκB activity during infection. However, flies with reduced sleep showed an altered defense mechanism, such that resistance to infection was increased, but at the expense of reduced tolerance. This effect was dependent on environmental condition. Conclusions: Increasing sleep enhanced activity of an NFκB transcription factor, increased resistance to infection, and strongly promoted survival. Together, these findings support the hypothesis that sleep is beneficial to the host by maintaining a robust immune system. Citation: Kuo TH, Williams JA. Increased sleep promotes survival during a bacterial infection in Drosophila. SLEEP 2014;37(6):1077-1086. PMID:24882902

  12. Significance of platelet and AFP levels and liver function parameters for HCC size and survival.

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    Carr, Brian I; Guerra, Vito; Giannini, Edoardo G; Farinati, Fabio; Ciccarese, Francesca; Rapaccini, Gian Ludovico; Di Marco, Maria; Benvegnù, Luisa; Zoli, Marco; Borzio, Franco; Caturelli, Eugenio; Chiaramonte, Maria; Trevisani, Franco

    2014-09-30

    Hepatocellular carcinoma (HCC) is a heterogeneous disease with both tumor and liver factors being involved. To investigate HCC clinical phenotypes and factors related to HCC size. Prospectively-collected HCC patients' data from a large Italian database were arranged according to the maximum tumor diameter (MTD) and divided into tumor size terciles, which were then compared in terms of several common clinical parameters and patients' survival. An higer MTD tercile was significantly associated with increased blood alpha-fetoprotein (AFP), gamma-glutamyl transpeptidase (GGTP), and platelet levels. Patients with higher platelet levels had larger tumors and higher GGTP levels, with lower bilirubin levels. However, patients with the highest AFP levels had larger tumors and higher bilirubin levels, reflecting an aggressive biology. AFP correlation analysis revealed the existence of 2 different groups of patients: those with higher and with lower AFP levels, each with different patient and tumor characteristics. The Cox proportional-hazard model showed that a higher risk of death was correlated with GGTP and bilirubin levels, tumor size and number, and portal vein thrombosis (PVT), but not with AFP or platelet levels. An increased tumor size was associated with increased blood platelet counts, AFP and GGTP levels. Platelet and AFP levels were important indicators of tumor size, but not of survival.

  13. Evaluating the use of enhanced oak seedlings for increased survival and growth: first-year survival

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    Joshua L. Moree; Andrew W. Ezell; John D. Hodges; Andrew J. Londo; K. David Godwin

    2010-01-01

    Oaks (Quercus spp.) are very important in the southern landscape for timber production and wildlife habitat. More landowners are attempting to establish oak plantations as the demand for wood products and wildlife habitat continues to increase. These attempts are not always successful with early growth and survival becoming major concerns. In this...

  14. Climate impacts of oil extraction increase significantly with oilfield age

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    Masnadi, Mohammad S.; Brandt, Adam R.

    2017-08-01

    Record-breaking temperatures have induced governments to implement targets for reducing future greenhouse gas (GHG) emissions. Use of oil products contributes ~35% of global GHG emissions, and the oil industry itself consumes 3-4% of global primary energy. Because oil resources are becoming increasingly heterogeneous, requiring different extraction and processing methods, GHG studies should evaluate oil sources using detailed project-specific data. Unfortunately, prior oil-sector GHG analysis has largely neglected the fact that the energy intensity of producing oil can change significantly over the life of a particular oil project. Here we use decades-long time-series data from twenty-five globally significant oil fields (>1 billion barrels ultimate recovery) to model GHG emissions from oil production as a function of time. We find that volumetric oil production declines with depletion, but this depletion is accompanied by significant growth--in some cases over tenfold--in per-MJ GHG emissions. Depletion requires increased energy expenditures in drilling, oil recovery, and oil processing. Using probabilistic simulation, we derive a relationship for estimating GHG increases over time, showing an expected doubling in average emissions over 25 years. These trends have implications for long-term emissions and climate modelling, as well as for climate policy.

  15. Veratridine increases the survival of retinal ganglion cells in vitro

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    S.P.F. Pereira

    1997-12-01

    Full Text Available Neuronal cell death is an important phenomenon involving many biochemical pathways. This degenerative event has been studied to understand how the cells activate the mechanisms that lead to self-destruction. Target cells and afferent cells play a relevant role in the regulation of natural cell death. We studied the effect of veratridine (1.5, 3.0, 4.5 and 6.0 µM on the survival of neonatal rat retinal ganglion cells in vitro. Veratridine (3.0 µM, a well-known depolarizing agent that opens the Na+ channel, promoted a two-fold increase in the survival of retinal ganglion cells kept in culture for 48 h. This effect was dose-dependent and was blocked by 1.0 µM tetrodotoxin (a classical voltage-dependent Na+ channel blocker and 30.0 µM flunarizine (a Na+ and Ca2+ channel blocker. These results indicate that electrical activity is also important for the maintenance of retinal ganglion cell survival in vitro

  16. Significant Impacts of Increasing Aridity on the Arid Soil Microbiome.

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    Neilson, Julia W; Califf, Katy; Cardona, Cesar; Copeland, Audrey; van Treuren, Will; Josephson, Karen L; Knight, Rob; Gilbert, Jack A; Quade, Jay; Caporaso, J Gregory; Maier, Raina M

    2017-01-01

    Global deserts occupy one-third of the Earth's surface and contribute significantly to organic carbon storage, a process at risk in dryland ecosystems that are highly vulnerable to climate-driven ecosystem degradation. The forces controlling desert ecosystem degradation rates are poorly understood, particularly with respect to the relevance of the arid-soil microbiome. Here we document correlations between increasing aridity and soil bacterial and archaeal microbiome composition along arid to hyperarid transects traversing the Atacama Desert, Chile. A meta-analysis reveals that Atacama soil microbiomes exhibit a gradient in composition, are distinct from a broad cross-section of nondesert soils, and yet are similar to three deserts from different continents. Community richness and diversity were significantly positively correlated with soil relative humidity (SoilRH). Phylogenetic composition was strongly correlated with SoilRH, temperature, and electrical conductivity. The strongest and most significant correlations between SoilRH and phylum relative abundance were observed for Acidobacteria, Proteobacteria, Planctomycetes, Verrucomicrobia, and Euryarchaeota (Spearman's rank correlation [rs] = >0.81; false-discovery rate [q] = ≤0.005), characterized by 10- to 300-fold decreases in the relative abundance of each taxon. In addition, network analysis revealed a deterioration in the density of significant associations between taxa along the arid to hyperarid gradient, a pattern that may compromise the resilience of hyperarid communities because they lack properties associated with communities that are more integrated. In summary, results suggest that arid-soil microbiome stability is sensitive to aridity as demonstrated by decreased community connectivity associated with the transition from the arid class to the hyperarid class and the significant correlations observed between soilRH and both diversity and the relative abundances of key microbial phyla typically

  17. Significance of increased leptin expression in osteoarthritis patients.

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    Ping Zhang

    Full Text Available Alterations in leptin expression contributes to the progression of various diseases, including cancers. This meta-analysis investigated the clinical significance of leptin levels in osteoarthritis (OA patients, with the goal of building a leptin-based diagnostic criterion for OA.Multiple scientific databases in English and Chinese languages, such as the Cochrane Library Database, CINAHL, Chinese Biomedical (CBM, EMBASE, PubMed, and Web of Science, were exhaustively searched, without any language restrictions, to identify high-quality studies relevant to leptin and OA. Version 12.0 STATA software was used for data analysis. We used odds ratios (OR and 95% confidence intervals (CI to test the correlation between serum leptin levels and OA progression.A total of 11 clinical studies were finally selected for their high quality and relevance to the topic in this meta-analysis. The 11 case-control studies contained a combined total of 3,625 subjects. The meta-analysis results showed that leptin expression was significantly increased in OA patients, compared with the controls (SMD = 0.87, 95%CI: 0.72-1.02, P < 0.001, and there was also a strong association between leptin expression levels and gender (SMD = 8.55, 95%CI: 4.74-12.35, P < 0.001. In ethnicity-stratified subgroup analysis, all the study populations, irrespective of ethnicity, showed remarkably high leptin expression levels in females and in OA patients (all P < 0.05, compared to their respective counterparts.The present study revealed that increased leptin expression levels are associated with disease severity in OA patients, especially among the female OA patients. Based on our results, we propose that leptin level may be a useful biomarker for the assessment of the clinical status in OA patients.

  18. Significance of increased leptin expression in osteoarthritis patients.

    Science.gov (United States)

    Zhang, Ping; Zhong, Zhi-Hong; Yu, Hao-Tao; Liu, Bin

    2015-01-01

    Alterations in leptin expression contributes to the progression of various diseases, including cancers. This meta-analysis investigated the clinical significance of leptin levels in osteoarthritis (OA) patients, with the goal of building a leptin-based diagnostic criterion for OA. Multiple scientific databases in English and Chinese languages, such as the Cochrane Library Database, CINAHL, Chinese Biomedical (CBM), EMBASE, PubMed, and Web of Science, were exhaustively searched, without any language restrictions, to identify high-quality studies relevant to leptin and OA. Version 12.0 STATA software was used for data analysis. We used odds ratios (OR) and 95% confidence intervals (CI) to test the correlation between serum leptin levels and OA progression. A total of 11 clinical studies were finally selected for their high quality and relevance to the topic in this meta-analysis. The 11 case-control studies contained a combined total of 3,625 subjects. The meta-analysis results showed that leptin expression was significantly increased in OA patients, compared with the controls (SMD = 0.87, 95%CI: 0.72-1.02, P leptin expression levels and gender (SMD = 8.55, 95%CI: 4.74-12.35, P leptin expression levels in females and in OA patients (all P leptin expression levels are associated with disease severity in OA patients, especially among the female OA patients. Based on our results, we propose that leptin level may be a useful biomarker for the assessment of the clinical status in OA patients.

  19. Elevated fasting insulin level significantly increases the risk of microalbuminuria.

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    Ryoo, Jae-Hong; Park, Sung Keun; Jung, Ju Young

    2015-01-01

    Microalbuminuria is significantly associated with long-term prognosis in the general population as well as in diabetic patients. It is well known that insulin resistance (IR) can induce microalbuminuria, but an elevated fasting insulin level, which is an early clinical manifestation of IR, as a risk factor for microalbuminuria has not been clarified, so we investigated the association between fasting insulin level and the development of microalbuminuria in a general population. A total of 1,192 non-diabetic Korean men without microalbuminuria in 2005 were followed until 2010. They were categorized into 3 groups according to their fasting insulin levels and monitored for the development of microalbuminuria. The incidence of microalbuminuria was compared among groups, and Cox proportional hazards models were used to calculate the hazard ratios for microalbuminuria according to the fasting insulin levels. During 4,013.0 person-years of follow-up, 51 incident cases of microalbuminuria developed between 2006 and 2010. The incidence of microalbuminuria increased in proportion to the fasting insulin levels (tertile 1: 1.8%, tertile 2: 4.5%, tertile 3: 6.5%, Pfasting insulin levels [tertile 1: reference, tertile 2: 2.44 (1.01-5.89), tertile 3: 3.30 (1.40-7.78), respectively, P for trend 0.013]. Elevated fasting insulin level was associated with the future development of microalbuminuria.

  20. Prognostic significance of tumour vascularisation on survival of patients with advanced ovarian carcinoma.

    Science.gov (United States)

    Labiche, Alexandre; Elie, Nicolas; Herlin, Paulette; Denoux, Yves; Crouet, Hubert; Heutte, Natacha; Joly, Florence; Héron, Jean-François; Gauduchon, Pascal; Henry-Amar, Michel

    2009-04-01

    The prognostic significance of microvessel density in ovarian cancer is still a matter of debate. Classically, the degree of vascularisation is assessed in areas of high vascular density (hot spots), considered as regions of increased probability of metastasis. Since ovarian tumours have a particular progression and dissemination behaviour, vascularisation outside hot spots may also contribute to their evolution. In the present study, the degree of tumour vascularisation was estimated both in whole histogical sections and in hot spots, in 235 patients with ovarian carcinoma, using fully automatic image analysis methods. Six parameters were estimated: mean microvessel density (MVD) and mean microvessel surface fraction (MSP) on the whole section, mean and maximum values of MVD and MSP inside hot spots (MVDHS1, MSPHS1 and MVDHS2, MSPHS2). Relationships between vascular parameters and clinicopathologic features were analysed. In stage III-IV patients multivariate analysis showed that stage IV disease (hazards ratio (HR)=1.72, p=0.001), post-surgical residual disease 1cm (HR=2.86, p<0.001), upper MVD tercile (HR=1.45, p<0.022) and medial MVDHS1 tercile (HR=1.36, p=0.060) retained an independent prognostic value upon overall survival. Our results suggest that quantification of blood vessels, both on the whole histological section and in hot spots might be helpful in evaluating prognosis in advanced ovarian carcinomas.

  1. The Wildland-Urban Interface: Increasing Significance, Complexity and Contribution

    Science.gov (United States)

    John F. Dwyer; Sarah M. McCaffrey

    2002-01-01

    During the past two decades, presentations at International Symposia on Society and Resource Management (ISSRM) have covered an increasingly broad scope of topics on natural resource issues. The wildland-urban interface (WUI) was a key topic of discussion at the ninth ISSRM in 2002: a reflection of the response by social scientists to increasing residential development...

  2. CONTINUING THE REFORMS IN MAJOR SIGNIFICANCE FIELDS FOR ECONOMIC INCREASE

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    CECILIA ELENA VĂDUVA

    2008-01-01

    Full Text Available The macroeconomic framework has to focus on structural reforms, tax and budgetary policy, agriculture and rural development, and the macroeconomic framework has to follow IMMs preservation. Form the convergence view the macroeconomic framework supports the durability of the economic increase including by financing the development of physical infrastructures of the human capital.

  3. Chemotherapy increases long-term survival in patients with adult medulloblastoma

    DEFF Research Database (Denmark)

    Kocakaya, Selin; Beier, Christoph Patrick; Beier, Dagmar

    2016-01-01

    parts of treatment regimes; however, established prognostic factors and data clarifying the role of chemotherapy are missing. METHODS: We investigated 227 publications from 1969-2013, with 907 identifiable, individual patients being available for meta-analysis. Demographic data, risk stratification...... chemotherapy first-line survived significantly longer (mOS: 108 mo, 95% CI: 68.6-148.4) than patients treated with radiation alone (mOS: 57 mo, 95% CI: 39.6-74.4) or patients who received chemotherapy at tumor recurrence. This effect was not biased by tumor stage or decade of treatment. Importantly, (neo......)adjuvant chemotherapy also significantly increased the chance for long-term survival (>5 y) compared with radiotherapy alone or chemotherapy at tumor recurrence. CONCLUSIONS: This meta-analysis clarifies relevant prognostic factors and suggests that chemotherapy as part of first-line therapy improves overall survival...

  4. Heterogeneity of aquatic sediment significantly increases nitrogen removal

    Science.gov (United States)

    Sawyer, A. H.

    2014-12-01

    In recent decades, nitrate loads to rivers and coasts have increased dramatically and contributed to eutrophication and hypoxia in coastal waters. A major sink for nitrate in the environment is denitrification in aquatic sediments. Here, I show that nitrate removal rates are as much as 100 times more efficient in heterogeneous than equivalent homogeneous aquatic sediments. Numerical experiments quantify nitrate removal from groundwater discharging through shallow columns of heterogeneous aquatic sediment. The steady groundwater flow equation was coupled to the advection-dispersion-reaction equations for dissolved oxygen, nitrate, and dissolved organic carbon (DOC). Bimodal sediments composed of sand and clay were simulated using TPROGS for a wide range of clay fractions. Small (centimeter-scale) sedimentary structures were intended to represent infilled burrows or clay rip-up clasts. Clay structures were assigned a relatively high organic carbon content (2%). The local source of DOC fuels oxygen consumption in clay structures and promotes restricted zones of denitrification in otherwise aerobic sediments. As a result, redox transformations do not strictly depend on residence times but rather on distributions of organic carbon in aquatic sediments. Furthermore, bimodal sand and clay deposits are more efficient than either clean sand or homogeneous sandy-clay at removing nitrate. These results help explain observations of efficient nitrate removal in relatively sandy, oxygenated aquatic sediments when small organic-rich structures are present. The results also suggest that models of reactive transport in homogeneous sediment underestimate biogeochemical transformation rates relative to heterogeneous sediment. Similarly, laboratory-derived denitrification rates on homogenized cores are likely underestimated relative to intact cores.

  5. Rubber dam may increase the survival time of dental restorations.

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    Keys, William; Carson, Susan J

    2017-03-01

    Data sourcesCochrane Oral Health's Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), Medline, Embase, LILACS, SciELO, Chinese BioMedical Literature Database, VIP, China National Knowledge Infrastructure, ClinicalTrials.gov, World Health Organization International Clinical Trials Registry Platform, OpenGrey and Sciencepaper Online databases. Handsearches in a number of journals.Study selectionRandomised controlled trials, including split-mouth studies assessing the effects of rubber dam isolation for restorative treatments in dental patients.Data extraction and synthesisTwo review authors independently screened the results of the electronic searches, extracted data and assessed the risk of bias of the included studies.ResultsFour studies involving a total of 1,270 patients were included. The studies were at high risk of bias. One trial was excluded from the analysis due to inconsistencies in the presented data. Restorations had a significantly higher survival rate in the rubber dam isolation group compared to the cotton roll isolation group at six months in participants receiving composite restorative treatment of non-carious cervical lesions (risk ratio (RR) 1.19, 95% confidence interval (CI) 1.04 to 1.37, very low-quality evidence). The rubber dam group had a lower risk of failure at two years in children undergoing proximal atraumatic restorative treatment in primary molars (hazard ratio (HR) 0.80, 95% CI 0.66 to 0.97, very low-quality evidence). One trial reported limited data showing that rubber dam usage during fissure sealing might shorten the treatment time. None of the included studies mentioned adverse effects or reported the direct cost of the treatment, or the level of patient acceptance/satisfaction. There was also no evidence evaluating the effects of rubber dam usage on the quality of the restorations.ConclusionsWe found some very low-quality evidence, from single studies, suggesting that rubber dam usage in dental direct

  6. Increasing incidence and survival in oral cancer: a nationwide Danish study from 1980 to 2014.

    Science.gov (United States)

    Karnov, Kirstine Kim Schmidt; Grønhøj, Christian; Jensen, David Hebbelstrup; Wessel, Irene; Charabi, Birgitte Wittenborg; Specht, Lena; Kjaer, Andreas; von Buchwald, Christian

    2017-09-01

    Oral carcinomas (OCs) make up a significant proportion of head and neck carcinomas (HNCs) and are an important cause of morbidity and mortality globally. The purpose of this population-based study was to determine trends in incidence and survival in OC in the Danish population from 1980 to 2014. This study covered all patients registered in the nationwide Danish cancer registry (DCR) in the period 1980-2014. Age-adjusted incidence rate (AAIR) per 100,000 and annual percentage change (APC) were evaluated. Also, 5-year overall survival (OS) was calculated with Cox regression analysis in relation to location, gender, age, and calendar year at diagnosis. Altogether, 8299 patients with oral cancer were identified, 5062 (61%) of whom were males and 3237 (39%) were females. The median age at diagnosis was 63 years. The AAIR of patients with OC increased from 1.9 per 100,000 in 1980 to 3.5 per 100,000 in 2014, and we observed a significant increase in 5-year OS of 12% points (a relative increase of 38%) from the period 1980-1984 to 2005-2009. Women were found to have a better prognosis than men. We found an unexpected increase in the age-standardized incidence of OC during the last 30 years in Denmark, and also an improvement in survival. The 5-year OS was significantly better in recent years even when we adjusted the analysis for relevant covariates.

  7. Plant circadian clocks increase photosynthesis, growth, survival, and competitive advantage.

    Science.gov (United States)

    Dodd, Antony N; Salathia, Neeraj; Hall, Anthony; Kévei, Eva; Tóth, Réka; Nagy, Ferenc; Hibberd, Julian M; Millar, Andrew J; Webb, Alex A R

    2005-07-22

    Circadian clocks are believed to confer an advantage to plants, but the nature of that advantage has been unknown. We show that a substantial photosynthetic advantage is conferred by correct matching of the circadian clock period with that of the external light-dark cycle. In wild type and in long- and short-circadian period mutants of Arabidopsis thaliana, plants with a clock period matched to the environment contain more chlorophyll, fix more carbon, grow faster, and survive better than plants with circadian periods differing from their environment. This explains why plants gain advantage from circadian control.

  8. Increased pancreatic cancer survival with greater lymph node retrieval in the National Cancer Data Base.

    Science.gov (United States)

    Contreras, Carlo M; Lin, Chee Paul; Oster, Robert A; Reddy, Sushanth; Wang, Thomas; Vickers, Selwyn; Heslin, Martin

    2017-09-01

    We evaluated the role of lymph node (LN) retrieval in pancreatic adenocarcinoma (PA) patients undergoing pancreaticoduodenectomy (PD). We utilized the National Cancer Data Base; Cox regression models and logistic regression models were used for statistical evaluation. We evaluated 26,792 patients with PA who underwent PD. The mean LN retrieved in LN(-) patients was 10.8 vs 14.4 for LN(+) patients (P < 0.0001). Greater LN retrieval is an independent predictor of a negative microscopic margin and decreased length of stay. The median survival of LN(-) patients exceeded that of LN(+) patients (24.5 vs 15.1 months, P < 0.0001). Increasing LN retrieval is a significant predictor of survival in all patients, and in LN(-) patients. The relationship of increased LN retrieval and enhanced survival is a nearly linear trend. Rather than demonstrating an inflection point that defines the extent of adequate lymphadenectomy, this dataset demonstrates an incremental relationship between LN retrieval and survival. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Significant increase of Echinococcus multilocularis prevalence in foxes, but no increased predicted risk for humans.

    Science.gov (United States)

    Maas, M; Dam-Deisz, W D C; van Roon, A M; Takumi, K; van der Giessen, J W B

    2014-12-15

    The emergence of the zoonotic tapeworm Echinococcus multilocularis, causative agent of alveolar echinococcosis (AE), poses a public health risk. A previously designed risk map model predicted a spread of E. multilocularis and increasing numbers of alveolar echinococcosis patients in the province of Limburg, The Netherlands. This study was designed to determine trends in the prevalence and worm burden of E. multilocularis in foxes in a popular recreational area in the southern part of Limburg to assess the risk of infection for humans and to study the prevalence of E. multilocularis in dogs in the adjacent city of Maastricht. Thirty-seven hunted red foxes were tested by the intestinal scraping technique and nested PCR on colon content. Additionally, 142 fecal samples of domestic dogs from Maastricht were analyzed by qPCR for the presence of E. multilocularis. In foxes, a significantly increased prevalence of 59% (95% confidence interval 43-74%) was found, compared to the prevalence of 11% (95% CI 7-18%) in 2005-2006. Average worm burden increased to 37 worms per fox, the highest since the first detection, but consistent with the prediction about the parasite population for this region. Updated prediction on the number of AE cases did not lead to an increase in previous estimates of human AE cases up to 2018. No dogs in the city of Maastricht tested positive, but results of questionnaires showed that deworming schemes were inadequate, especially in dogs that were considered at risk for infection. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Variation in dicer gene is associated with increased survival in T-cell lymphoma.

    Directory of Open Access Journals (Sweden)

    Xi Li

    Full Text Available Dicer, an endonuclease in RNase III family, is essential for the RNA interference (RNAi pathway. Aberrant expression of Dicer has been shown in various cancers including some subtypes of T cell lymphoma (TCL, which influences patient prognosis. A single-nucleotide polymorphism (SNP rs3742330A>G has been identified in the Dicer gene, located in the 3' untranslated region (3' UTR that is important for mRNA transcript stability. We investigated whether rs3742330 is associated with the survival in 163 TCL patients. Significant association between Dicer rs3742330 and TCL survival were found. Patients carrying the GG genotype (n = 12 had a significantly increased overall survival (OS compared with those carrying the GA and AA genotypes (n = 70 and n = 81, respectively; p = 0.031. Moreover, the significant association was maintained for patients with mature T type (n = 134; p = 0.026. In multivariate Cox-regression analysis, rs3742330 proved to be an independent predictor for OS, together with the commonly used International Prognostic Index (IPI and BAFF rs9514828, another SNP we have previously reported to be associated with TCL survival, with hazard ratios (HRs for patient death rate of 8.956 (95% CI, 1.210 to 66.318; p = 0.032 for the GA genotype and 10.145 (95% CI, 1.371 to 75.084; p = 0.023 for the AA genotype. Furthermore, we observed cumulative effects of Dicer rs3742330 and BAFF rs9514828 on TCL survival. Compared with patients carrying zero unfavorable genotype, those carrying one and two unfavorable genotypes had an increased risk of death with a HR of 7.104 (95% CI, 0.969-53.086; p = 0.054 and 14.932 (95% CI, 1.950-114.354; p = 0.009, respectively, with a significant dose-response trend (p(trend  = 0.004. In conclusion, Dicer rs3742330 is associated with TCL survival, suggesting that genetic variation might play a role in predicting prognosis of TCL patients.

  11. Functionalized Scaffold-mediated Interleukin 10 Gene Delivery Significantly Improves Survival Rates of Stem Cells In Vivo

    Science.gov (United States)

    Holladay, Carolyn; Power, Karen; Sefton, Michael; O'Brien, Timothy; Gallagher, William M.; Pandit, Abhay

    2011-01-01

    While stem cell transplantation could potentially treat a variety of disorders, clinical studies have not yet demonstrated conclusive benefits. This may be partly because transplanted stem cells have low survival rates, potentially due to host inflammation. The system described herein used two different gene therapy techniques to improve retention of rat mesenchymal stem cells. In the first, stem cells were transfected with interleukin-10 (IL-10) before being loaded into a collagen scaffold. In the second, unmodified stem cells were loaded into a collagen scaffold along with polymer-complexed IL-10 plasmids. The scaffolds were surgically implanted into the dorsum of syngeneic rats. At each endpoint, the scaffolds were explanted and cell retention, IL-10 level and inflammatory response were quantified. All treatment groups had statistically significant increases in cell retention after 7 days, but the group treated with 2 µg of IL-10 polyplexes had a significant improvement even at 21 days. This cell retention was associated with increased IL-10 and decreased levels of proinflammatory cytokines and apoptosis. The primary effect on the inflammatory response appeared to be on macrophage differentiation, encouraging the regulatory phenotype over the cytotoxic lineage. Improving cell survival may be an important step toward realization of the therapeutic potential of stem cells. PMID:21266957

  12. Humic substances increase survival of freshwater shrimp Caridina sp. D to acid mine drainage.

    Science.gov (United States)

    Holland, Aleicia; Duivenvoorden, Leo J; Kinnear, Susan H W

    2013-02-01

    Humic substances (HS) are known to decrease the toxicity of heavy metals to aquatic organisms, and it has been suggested that they can provide buffering protection in low pH conditions. Despite this, little is known about the ability for HS to increase survival to acid mine drainage (AMD). In this study, the ability of HS to increase survival of the freshwater shrimp (Caridina sp. D sensu Page et al. in Biol Lett 1:139-142, 2005) to acid mine drainage was investigated using test waters collected from the Mount Morgan open pit in Central Queensland with the addition of Aldrich humic acid (AHA). The AMD water from the Mount Morgan open pit is highly acidic (pH 2.67) as well as contaminated with heavy metals (1780 mg/L aluminum, 101 mg/L copper [Cu], 173 mg/L manganese, 51.8 mg/L zinc [Zn], and 51.8 mg/L iron). Freshwater shrimp were exposed to dilutions in the range of 0.5 % to 5 % AMD water with and without the addition of 10 or 20 mg/L AHA. In the absence of HS, all shrimp died in the 2.5 % AMD treatment. In contrast, addition of HS increased survival in the 2.5 % AMD treatment by ≤66 % as well as significantly decreased the concentration of dissolved Cu, cobalt, cadmium, and Zn. The decreased toxicity of AMD in the presence of HS is likely to be due to complexation and precipitation of heavy metals with the HS; it is also possible that HS caused changes to the physiological condition of the shrimp, thus increasing their survival. These results are valuable in contributing to an improved understanding of potential role of HS in ameliorating the toxicity of AMD environments.

  13. Increasing incidence and survival in oral cancer: a nationwide Danish study from 1980 to 2014

    DEFF Research Database (Denmark)

    Karnov, Kirstine Kim Schmidt; Grønhøj, Christian; Jensen, David Hebbelstrup

    2017-01-01

    regression analysis in relation to location, gender, age, and calendar year at diagnosis. Results: Altogether, 8299 patients with oral cancer were identified, 5062 (61%) of whom were males and 3237 (39%) were females. The median age at diagnosis was 63 years. The AAIR of patients with OC increased from 1......Background: Oral carcinomas (OCs) make up a significant proportion of head and neck carcinomas (HNCs) and are an important cause of morbidity and mortality globally. The purpose of this population-based study was to determine trends in incidence and survival in OC in the Danish population from 1980...... to 2014. Material and methods: This study covered all patients registered in the nationwide Danish cancer registry (DCR) in the period 1980–2014. Age-adjusted incidence rate (AAIR) per 100,000 and annual percentage change (APC) were evaluated. Also, 5-year overall survival (OS) was calculated with Cox...

  14. Prognostic significance of tumour vascularisation on survival of patients with advanced ovarian carcinoma

    OpenAIRE

    Labiche, Alexandre; Elie, Nicolas; Herlin, Paulette; Denoux, Yves; Crouet, Hubert; Heutte, Natacha; Joly, Florence; Héron, Jean-François; Gauduchon, Pascal; Henry-Amar, Michel

    2009-01-01

    Objective. The prognostic significance of microvessel density in ovarian cancer is still a matter of debate. Classically, the degree of vascularisation is assessed in areas of high vascular density (hot spots), considered as regions of increased probability of metastasis. Since ovarian tumours have a particular progression and dissemination behaviour, vascularisation outside hot spots may also contribute to their evolution. Methods. In the present study, the degree of ...

  15. Significant increase of Echinococcus multilocularis prevalencein foxes, but no increased predicted risk for humans

    NARCIS (Netherlands)

    Maas, M.; Dam-Deisz, W.D.C.; Roon, van A.M.; Takumi, K.; Giessen, van der J.W.B.

    2014-01-01

    The emergence of the zoonotic tapeworm Echinococcus multilocularis, causative agent ofalveolar echinococcosis (AE), poses a public health risk. A previously designed risk mapmodel predicted a spread of E. multilocularis and increasing numbers of alveolar echinococ-cosis patients in the province of

  16. Local-regional radiotherapy and surgery is associated with a significant survival advantage in metastatic breast cancer patients.

    Science.gov (United States)

    Ly, Bevan Hong; Vlastos, Georges; Rapiti, Elisabetta; Vinh-Hung, Vincent; Nguyen, Nam Phong

    2010-01-01

    There is growing evidence of a survival benefit for metastatic breast cancer patients receiving surgery of the primary tumor. We investigated whether or not adjuvant radiotherapy can improve survival. Women diagnosed between 1988 and 2003 with metastatic, histologically confirmed unilateral primary breast cancer were selected from the SEER Program. Overall survival and specific survival were computed by the Kaplan-Meier method. Treatment hazard ratios of breast-conserving surgery or mastectomy versus no surgery, and radiotherapy versus none, were computed by Cox regression adjusting for period of diagnosis, age, marital status, race, histology, grade, and hormone receptors. Of 8761 women, radiotherapy was given to 1473 of 3905 who did not undergo surgery, to 882 of 2070 who underwent breast-conserving surgery, and to 1103 of 2786 mastectomy patients. Median overall survival was: for no surgery, 14 months; for breast-conserving surgery, 23 months; and for mastectomy, 28 months (P < 0.0001). The median overall survival of radiotherapy versus none was respectively 16 vs. 13 months without surgery (P = 0.0003), 28 vs. 20 months for breast-conserving surgery patients (P < 0.0001), and 28 vs. 28 months among mastectomy patients (P = 0.895). Multivariate analysis showed relative mortality reductions of 28% by breast-conserving surgery, 42% by mastectomy, and 10% by radiotherapy. Specific survival showed comparable results. Surgery and radiotherapy were associated with a significant survival advantage. We argue that local therapy should be considered even in metastatic disease.

  17. Histological Subtype Remains a Significant Prognostic Factor for Survival Outcomes in Patients With Appendiceal Mucinous Neoplasm With Peritoneal Dissemination.

    Science.gov (United States)

    Huang, Yeqian; Alzahrani, Nayef A; Chua, Terence C; Morris, David L

    2017-04-01

    It has been increasingly recognized that appendiceal mucinous neoplasm with peritoneal dissemination is not a homogenous disease. This study aimed to examine the impact of different histological subtypes on survival of a large cohort of patients with appendiceal mucinous neoplasms uniformly treated by cytoreductive surgery and intraperitoneal chemotherapy. This was a retrospective study of prospectively collected data of patients with peritoneal dissemination of appendiceal neoplasm who underwent cytoreductive surgery and intraperitoneal chemotherapy. The study was conducted by 1 surgical team at St. George Hospital. A total of 444 patients formed the cohort of this study. Histological diagnoses were categorized based on Carr criteria to include acellular mucin, disseminated peritoneal adenomucinosis, peritoneal mucinous neoplasms without signet ring cells, and peritoneal mucinous carcinomatosis with signet cells. Patients with low-grade appendiceal mucinous neoplasms with neoplastic epithelium absent tended to have lower CEA, CA19-9, and CA125 levels preoperatively (p = 0.109, 0.008, and 0.034). Factor analysis showed that histological diagnosis was an independent prognostic factor for survival outcomes (HR = 3.13 (95% CI, 2.34-4.39); p 20, completeness of cytoreductive score ≥2, use of early postoperative intraperitoneal chemotherapy, transfusion units, CEA >7.0 mg/L, CA19-9 >24.0 U/mL, and CA125 >24 U/mL. This study was limited by its retrospective nature, lack of uniform classifications of appendiceal mucinous neoplasms in early years, and the heterogeneity of this study cohort given the long study period. Histological subtype remains a significant prognostic factor for survival outcomes in patients with appendiceal mucinous neoplasms. It should be taken into account when selecting patients for cytoreductive surgery, tailoring appropriate adjuvant therapies and follow-up surveillance plan.

  18. Protein kinase G1 α overexpression increases stem cell survival and cardiac function after myocardial infarction.

    Directory of Open Access Journals (Sweden)

    Linlin Wang

    Full Text Available We hypothesized that overexpression of cGMP-dependent protein kinase type 1α (PKG1α could mimic the effect of tadalafil on the survival of bone marrow derived mesenchymal stem cells (MSCs contributing to regeneration of the ischemic heart.MSCs from male rats were transduced with adenoviral vector encoding for PKG1α ((PKG1αMSCs.Controls included native MSCs ((NatMSCs and MSCs transduced with an empty vector ((NullMSCs. PKG1α activity was increased approximately 20, 5 and 16 fold respectively in (PKG1αMSCs. (PKG1αMSCs showed improved survival under oxygen and glucose deprivation (OGD which was evidenced by lower LDH release, caspase-3/7 activity and number of positive TUNEL cells. Anti-apoptotic proteins pAkt, pGSK3β, and Bcl-2 were significantly increased in (PKG1αMSCs compared to (NatMSCs and (NullMSCs. Higher release of multiple prosurvival and angiogenic factors such as HGF, bFGF, SDF-1 and Ang-1 was observed in (PKG1αMSCs before and after OGD. In a female rat model of acute myocardial infarction, (PKG1αMSCs group showed higher survival compared with (NullMSCs group at 3 and 7 days after transplantation as determined by TUNEL staining and sry-gene quantitation by real-time PCR. Increased anti-apoptotic proteins and paracrine factors in vitro were also identified. Immunostaining for cardiac troponin I combined with GFP showed increased myogenic differentiation of (PKG1αMSCs. At 4 weeks after transplantation, compared to DMEM group and (NullMSCs group, (PKG1αMSCs group showed increased blood vessel density in infarct and peri-infarct areas (62.5±7.7; 68.8±7.3 per microscopic view, p<0.05 and attenuated infarct size (27.2±2.5%, p<0.01. Heart function indices including ejection fraction (52.1±2.2%, p<0.01 and fractional shortening (24.8%±1.3%, p<0.01 were improved significantly in (PKG1αMSCs group.Overexpression of PKG1α transgene could be a powerful approach to improve MSCs survival and their angiomyogenic potential in the

  19. Increasing vaginal progesterone gel supplementation after frozen-thawed embryo transfer significantly increases the delivery rate

    DEFF Research Database (Denmark)

    Alsbjerg, Birgit; Polyzos, Nikolaos P; Elbaek, Helle Olesen

    2013-01-01

    The aim of this study was to evaluate the reproductive outcome in patients receiving frozen-thawed embryo transfer before and after doubling of the vaginal progesterone gel supplementation. The study was a retrospective study performed in The Fertility Clinic, Skive Regional Hospital, Denmark....... A total of 346 infertility patients with oligoamenorrhoea undergoing frozen-thawed embryo transfer after priming with oestradiol and vaginal progesterone gel were included. The vaginal progesterone dose was changed from 90mg (Crinone) once a day to twice a day and the reproductive outcome during the two...... rate (8.7% versus 20.5%, respectively; P=0.002). Doubling of the vaginal progesterone gel supplementation during frozen-thawed embryo transfer cycles decreased the early pregnancy loss rate, resulting in a significantly higher delivery rate. This study evaluated the reproductive outcome of 346 women...

  20. Mortality of acute mesenteric ischemia remains unchanged despite significant increase in utilization of endovascular techniques.

    Science.gov (United States)

    Eslami, Mohammad H; Rybin, Denis; Doros, Gheorghe; McPhee, James T; Farber, Alik

    2016-02-01

    In this study, we evaluated if increase in utilization of endovascular surgery has affected in-hospital mortality rates among patients with acute mesenteric ischemia. The National Inpatient Sample (2003-2011) was queried for acute mesenteric ischemia using ICD-9 code for acute mesenteric ischemia (557.1). This cohort was divided into patients treated with open vascular surgery (open vascular group) and by endovascular therapies (endovascular group) based on the ICD-9CM procedure codes. Multivariable logistic regression was used to determine temporal trend for mortality while adjusting for confounding variables. There was 1.45-fold increase in utilization of endovascular techniques in this study. In-hospital mortality rate, total median charges and length of stay were significantly lower among the endovascular group than the open vascular group despite having significantly higher Elixhauser comorbidities index (3 ± 0.1 vs. 2.7 ± 0.1, p = .003). Over the course of the study period, there was no change in the overall mortality rate despite higher endovascular utilization. Factors associated with increased mortality included age, open surgical repair (Odds ratio: 1.45, 95% Confidence Interval: 1.10-1.91, p = .016) and bowel resection Odds ratio: 2.88, 95% Confidence Interval: 2.01-4.12). The mortality rate for acute mesenteric ischemia remains unchanged throughout this contemporary study. Open surgical intervention, bowel resection and age were associated with increased mortality. Endovascular group patients had better survival despite higher morbidity indices. © The Author(s) 2015.

  1. Sweet waste extract uptake by a mosquito vector: Survival, biting, fecundity responses, and potential epidemiological significance.

    Science.gov (United States)

    Dieng, Hamady; Satho, Tomomitsu; Abang, Fatimah; Meli, Nur Khairatun Khadijah Binti; Ghani, Idris A; Nolasco-Hipolito, Cirilo; Hakim, Hafijah; Miake, Fumio; Ahmad, Abu Hassan; Noor, Sabina; Zuharah, Wan Fatma; Ahmad, Hamdan; Majid, Abdul Hafiz A; Morales Vargas, Ronald E; Morales, Noppawan P; Attrapadung, Siriluck; Noweg, Gabriel Tonga

    2017-05-01

    In nature, adult mosquitoes typically utilize nectar as their main energy source, but they can switch to other as yet unidentified sugary fluids. Contemporary lifestyles, with their associated unwillingness to consume leftovers and improper disposal of waste, have resulted in the disposal of huge amounts of waste into the environment. Such refuse often contains unfinished food items, many of which contain sugar and some of which can collect water from rain and generate juices. Despite evidence that mosquitoes can feed on sugar-rich suspensions, semi-liquids, and decaying fruits, which can be abundant in garbage sites, the impacts of sweet waste fluids on dengue vectors are unknown. Here, we investigated the effects of extracts from some familiar sweet home waste items on key components of vectorial capacity of Aedes aegypti. Adult mosquitoes were fed one of five diets in this study: water (WAT); sucrose (SUG); bakery product (remnant of chocolate cake, BAK); dairy product (yogurt, YOG); and fruit (banana (BAN). Differences in survival, response time to host, and egg production were examined between groups. For both males and females, maintenance on BAK extract resulted in marked survival levels that were similar to those seen with SUG. Sweet waste extracts provided better substrates for survival compared to water, but this superiority was mostly seen with BAK. Females maintained on BAK, YOG, and BAN exhibited shorter response times to a host compared to their counterparts maintained on SUG. The levels of egg production were equivalent in waste extract- and SUG-fed females. The findings presented here illustrate the potential of sweet waste-derived fluids to contribute to the vectorial capacity of dengue vectors and suggest the necessity of readdressing the issue of waste disposal, especially that of unfinished sweet foods. Such approaches can be particularly relevant in dengue endemic areas where rainfall is frequent and waste collection infrequent. Copyright

  2. Amantadine improves cognitive outcome and increases neuronal survival after fluid percussion traumatic brain injury in rats.

    Science.gov (United States)

    Wang, Tao; Huang, Xian-Jian; Van, Ken C; Went, Gregory T; Nguyen, Jack T; Lyeth, Bruce G

    2014-02-15

    This study evaluated the effects of clinically relevant concentrations of amantadine (AMT) on cognitive outcome and hippocampal cell survival in adult rats after lateral fluid percussion traumatic brain injury (TBI). AMT is an antagonist of the N-methyl-D-aspartate-type glutamate receptor, increases dopamine release, blocks dopamine reuptake, and has an inhibitory effect on microglial activation and neuroinflammation. Currently, AMT is clinically used as an antiparkinsonian drug. Amantadine or saline control was administered intraperitoneally, starting at 1 h after TBI followed by dosing three times daily for 16 consecutive days at 15, 45, and 135 mg/kg/day. Terminal blood draws were obtained from TBI rats at the time of euthanasia at varying time points after the last amantadine dose. Pharmacokinetics analysis confirmed that the doses of AMT achieved serum concentrations similar to those observed in humans receiving therapeutic doses (100-400 mg/day). Acquisition of spatial learning and memory retention was assessed using the Morris water maze (MWM) on days 12-16 after TBI. Brain tissues were collected and stained with Cresyl-violet for long-term cell survival analysis. Treatment with 135mg/kg/day of AMT improved acquisition of learning and terminal cognitive performance on MWM. The 135-mg/kg/day dosing of AMT increased the numbers of surviving CA2-CA3 pyramidal neurons at day 16 post-TBI. Overall, the data showed that clinically relevant dosing schedules of AMT affords neuroprotection and significantly improves cognitive outcome after experimental TBI, suggesting that it has the potential to be developed as a novel treatment of human TBI.

  3. Ciprofloxacin Derivatives Affect Parasite Cell Division and Increase the Survival of Mice Infected with Toxoplasma gondii.

    Directory of Open Access Journals (Sweden)

    Erica S Martins-Duarte

    Full Text Available Toxoplasmosis, caused by the protozoan Toxoplasma gondii, is a worldwide disease whose clinical manifestations include encephalitis and congenital malformations in newborns. Previously, we described the synthesis of new ethyl-ester derivatives of the antibiotic ciprofloxacin with ~40-fold increased activity against T. gondii in vitro, compared with the original compound. Cipro derivatives are expected to target the parasite's DNA gyrase complex in the apicoplast. The activity of these compounds in vivo, as well as their mode of action, remained thus far uncharacterized. Here, we examined the activity of the Cipro derivatives in vivo, in a model of acute murine toxoplasmosis. In addition, we investigated the cellular effects T. gondii tachyzoites in vitro, by immunofluorescence and transmission electron microscopy (TEM. When compared with Cipro treatment, 7-day treatments with Cipro derivatives increased mouse survival significantly, with 13-25% of mice surviving for up to 60 days post-infection (vs. complete lethality 10 days post-infection, with Cipro treatment. Light microscopy examination early (6 and 24h post-infection revealed that 6-h treatments with Cipro derivatives inhibited the initial event of parasite cell division inside host cells, in an irreversible manner. By TEM and immunofluorescence, the main cellular effects observed after treatment with Cipro derivatives and Cipro were cell scission inhibition--with the appearance of 'tethered' parasites--malformation of the inner membrane complex, and apicoplast enlargement and missegregation. Interestingly, tethered daughter cells resulting from Cipro derivatives, and also Cipro, treatment did not show MORN1 cap or centrocone localization. The biological activity of Cipro derivatives against C. parvum, an apicomplexan species that lacks the apicoplast, is, approximately, 50 fold lower than that in T. gondii tachyzoites, supporting that these compounds targets the apicoplast. Our results

  4. Cardiopulmonary Bypass has No Significant Impact on Survival in Patients Undergoing Nephrectomy and Level III-IV Inferior Vena Cava Thrombectomy: Multi-Institutional Analysis.

    Science.gov (United States)

    Nguyen, Hao G; Tilki, Derya; Dall'Era, Marc A; Durbin-Johnson, Blythe; Carballido, Joaquín A; Chandrasekar, Thenappan; Chromecki, Thomas; Ciancio, Gaetano; Daneshmand, Siamak; Gontero, Paolo; Gonzalez, Javier; Haferkamp, Axel; Hohenfellner, Markus; Huang, William C; Espinós, Estefania Linares; Mandel, Philipp; Martinez-Salamanca, Juan I; Master, Viraj A; McKiernan, James M; Montorsi, Francesco; Novara, Giacomo; Pahernik, Sascha; Palou, Juan; Pruthi, Raj S; Rodriguez-Faba, Oscar; Russo, Paul; Scherr, Douglas S; Shariat, Shahrokh F; Spahn, Martin; Terrone, Carlo; Vergho, Daniel; Wallen, Eric M; Xylinas, Evanguelos; Zigeuner, Richard; Libertino, John A; Evans, Christopher P

    2015-08-01

    The impact of cardiopulmonary bypass in level III-IV tumor thrombectomy on surgical and oncologic outcomes is unknown. We determine the impact of cardiopulmonary bypass on overall and cancer specific survival, as well as surgical complication rates and immediate outcomes in patients undergoing nephrectomy and level III-IV tumor thrombectomy with or without cardiopulmonary bypass. We retrospectively analyzed 362 patients with renal cell cancer and with level III or IV tumor thrombus from 1992 to 2012 at 22 U.S. and European centers. Cox proportional hazards models were used to compare overall and cancer specific survival between patients with and without cardiopulmonary bypass. Perioperative mortality and complication rates were assessed using logistic regression analyses. Median overall survival was 24.6 months in noncardiopulmonary bypass cases and 26.6 months in cardiopulmonary bypass cases. Overall survival and cancer specific survival did not differ significantly in both groups on univariate analysis or when adjusting for known risk factors. On multivariate analysis no significant differences were seen in hospital length of stay, Clavien 1-4 complication rate, intraoperative or 30-day mortality and cancer specific survival. Limitations include the retrospective nature of the study. In our multi-institutional analysis the use of cardiopulmonary bypass did not significantly impact cancer specific survival or overall survival in patients undergoing nephrectomy and level III or IV tumor thrombectomy. Neither approach was independently associated with increased mortality on multivariate analysis. Greater surgical complications were not independently associated with the use of cardiopulmonary bypass. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  5. SPARCL1 Expression Increases With Preoperative Radiation Therapy and Predicts Better Survival in Rectal Cancer Patients

    Energy Technology Data Exchange (ETDEWEB)

    Kotti, Angeliki, E-mail: angkotti@yahoo.gr; Holmqvist, Annica; Albertsson, Maria; Sun, Xiao-Feng, E-mail: xiao-feng.sun@liu.se

    2014-04-01

    Purpose: The secreted protein acidic and rich in cysteine-like 1 (SPARCL1) is expressed in various normal tissues and many types of cancers. The function of SPARCL1 and its relationship to a patient's prognosis have been studied, whereas its relationship to radiation therapy (RT) is not known. Our aim was to investigate the expression of SPARCL1 in rectal cancer patients who participated in a clinical trial of preoperative RT. Methods and Materials: The study included 136 rectal cancer patients who were randomized to undergo preoperative RT and surgery (n=63) or surgery alone (n=73). The expression levels of SPARCL1 in normal mucosa (n=29), primary tumor (n=136), and lymph node metastasis (n=35) were determined by immunohistochemistry. Results: Tumors with RT had stronger SPARCL1 expression than tumors without RT (P=.003). In the RT group, strong SPARCL1 expression was related to better survival than weak expression in patients with stage III tumors, independent of sex, age, differentiation, and margin status (P=.022; RR = 18.128; 95% confidence interval, 1.512-217.413). No such relationship was found in the non-RT group (P=.224). Further analysis of interactions among SPARCL1 expression, RT, and survival showed statistical significance (P=.024). In patients with metastases who received RT, strong SPARCL1 expression was related to better survival compared to weak expression (P=.041) but not in the non-RT group (P=.569). Conclusions: SPARCL1 expression increases with RT and is related to better prognosis in rectal cancer patients with RT but not in patients without RT. This result may help us to select the patients best suited for preoperative RT.

  6. Myriocin Significantly Increases the Mortality of a Non-Mammalian Model Host during Candida Pathogenesis

    Science.gov (United States)

    de Melo, Nadja Rodrigues; Abdrahman, Ahmed; Greig, Carolyn; Mukherjee, Krishnendu; Thornton, Catherine; Ratcliffe, Norman A.; Vilcinskas, Andreas; Butt, Tariq M.

    2013-01-01

    Candida albicans is a major human pathogen whose treatment is challenging due to antifungal drug toxicity, drug resistance and paucity of antifungal agents available. Myrocin (MYR) inhibits sphingosine synthesis, a precursor of sphingolipids, an important cell membrane and signaling molecule component. MYR also has dual immune suppressive and antifungal properties, potentially modulating mammalian immunity and simultaneously reducing fungal infection risk. Wax moth (Galleria mellonella) larvae, alternatives to mice, were used to establish if MYR suppressed insect immunity and increased survival of C. albicans-infected insects. MYR effects were studied in vivo and in vitro, and compared alone and combined with those of approved antifungal drugs, fluconazole (FLC) and amphotericin B (AMPH). Insect immune defenses failed to inhibit C. albicans with high mortalities. In insects pretreated with the drug followed by C. albicans inoculation, MYR+C. albicans significantly increased mortality to 93% from 67% with C. albicans alone 48 h post-infection whilst AMPH+C. albicans and FLC+C. albicans only showed 26% and 0% mortalities, respectively. MYR combinations with other antifungal drugs in vivo also enhanced larval mortalities, contrasting the synergistic antifungal effect of the MYR+AMPH combination in vitro. MYR treatment influenced immunity and stress management gene expression during C. albicans pathogenesis, modulating transcripts putatively associated with signal transduction/regulation of cytokines, I-kappaB kinase/NF-kappaB cascade, G-protein coupled receptor and inflammation. In contrast, all stress management gene expression was down-regulated in FLC and AMPH pretreated C. albicans -infected insects. Results are discussed with their implications for clinical use of MYR to treat sphingolipid-associated disorders. PMID:24260135

  7. Myriocin significantly increases the mortality of a non-mammalian model host during Candida pathogenesis.

    Directory of Open Access Journals (Sweden)

    Nadja Rodrigues de Melo

    Full Text Available Candida albicans is a major human pathogen whose treatment is challenging due to antifungal drug toxicity, drug resistance and paucity of antifungal agents available. Myrocin (MYR inhibits sphingosine synthesis, a precursor of sphingolipids, an important cell membrane and signaling molecule component. MYR also has dual immune suppressive and antifungal properties, potentially modulating mammalian immunity and simultaneously reducing fungal infection risk. Wax moth (Galleria mellonella larvae, alternatives to mice, were used to establish if MYR suppressed insect immunity and increased survival of C. albicans-infected insects. MYR effects were studied in vivo and in vitro, and compared alone and combined with those of approved antifungal drugs, fluconazole (FLC and amphotericin B (AMPH. Insect immune defenses failed to inhibit C. albicans with high mortalities. In insects pretreated with the drug followed by C. albicans inoculation, MYR+C. albicans significantly increased mortality to 93% from 67% with C. albicans alone 48 h post-infection whilst AMPH+C. albicans and FLC+C. albicans only showed 26% and 0% mortalities, respectively. MYR combinations with other antifungal drugs in vivo also enhanced larval mortalities, contrasting the synergistic antifungal effect of the MYR+AMPH combination in vitro. MYR treatment influenced immunity and stress management gene expression during C. albicans pathogenesis, modulating transcripts putatively associated with signal transduction/regulation of cytokines, I-kappaB kinase/NF-kappaB cascade, G-protein coupled receptor and inflammation. In contrast, all stress management gene expression was down-regulated in FLC and AMPH pretreated C. albicans-infected insects. Results are discussed with their implications for clinical use of MYR to treat sphingolipid-associated disorders.

  8. Splenectomy increases the survival time of heart allograft via developing immune tolerance

    Science.gov (United States)

    2013-01-01

    Background The spleen is an active lymphoid organ. The effect of splenectomy on the immune response remains unclear. This study investigated whether splenectomy can induce immune tolerance and has a beneficial role in cardiac allograft. Methods Wistar rats were used for heart donors. The Sprague–Dawley (SD) rats designated as the recipients of heart transplantation (HT) were randomly assigned into four groups: sham, splenectomy, HT, splenectomy + HT. The survival of transplanted hearts was assessed by daily checking of abdominal palpation. At various time points after transplantation, the transplanted hearts were collected and histologically examined; the level of CD4+CD25+ T regulatory lymphocytes (Tregs) and rate of lymphocyte apoptosis (annexin-v+ PI+ cells) in the blood were analyzed by using flow cytometric method. Results 1) Splenectomy significantly prolonged the mean survival time of heart allografts (7 ± 1.1 days and 27 ± 1.5 days for HT and splenectomy + HT, respectively; n = 12-14/group, HT vs. splenectomy + HT, p Splenectomy delayed pathological changes (inflammatory cell infiltration, myocardial damage) of the transplanted hearts in splenectomy + HT rats; 3) The level of CD4+CD25+ Tregs in the blood of splenectomized rats was significantly increased within 7 days (2.4 ± 0.5%, 4.9 ± 1.3% and 5.3 ± 1.0% for sham, splenectomy and splenectomy + HT, respectively; n = 15/group, sham vs. splenectomy or splenectomy + HT, p splenectomy surgery and gradually decreased to baseline level; 4) Splenectomy increased the rate of lymphocyte apoptosis (day 7: 0.3 ± 0.05%, 3.9 ± 0.9% and 4.1 ± 0.9% for sham, splenectomy and splenectomy + HT, respectively; n = 15/group, sham vs. splenectomy or splenectomy + HT, p Splenectomy inhibits the development of pathology and prolongs the survival time of cardiac allograft. The responsible mechanism is associated with induction of immune

  9. Increased rate of survival in Streptococcus pneumoniae-infected rats treated with the new immunomodulator Pidotimod.

    Science.gov (United States)

    di Marco, R; Condorelli, F; Girardello, R; Uslenghi, C; Chisari, G; di Mauro, M; Speciale, A M; Meroni, P L; Nicoletti, F

    1992-01-01

    Wistar rats infected with Streptococcus pneumoniae (type III ATCC) rapidly develop an acute form of experimental lobar pneumonia (ELP) with death of 80-90% of the animals by 6 days after the infection. Prophylactic treatment of these animals with the novel immunomodulator Pidotimod, at the dose of 25 mg/kg bw, significantly increased their rate of survival as compared to the control group (50 vs. 90% respectively). Recovery from the infection appeared definitive since all the Pidotimod-treated survivors were alive and in good condition at the end of the observation period (45 days post infection). Prophylactic treatment with higher or lower doses of the drug was ineffective. Therapy with Pidotimod was not effective. This preliminary study suggests that Pidotimod may have contributed to activation of specific and non-specific immune effectors involved in the host response to S. pneumoniae infection.

  10. Increasing Calcium Oxide (Cao) to Accelerate Moulting and Survival Rate Vannamei Shrimp (Litopenaeus Vannamei))

    OpenAIRE

    Erlando, Gito; ', Rusliadi; Mulyadi,

    2016-01-01

    The research about the increasing Calcium Oxide (CaO) to accelerate moulting and survival rate vannamei shrimp (Litopenaeus vannamei) was conducted from Agustus until September 2015 at Balai Perikanan Budidaya Air Payau, Instalasi Pembenihan Udang (IPU) Gelung, Situbondo Provinsi Jawa Timur. The purpose of this research was to investigate optimum doses calcium oxide to accelerate moulting and the survival rate vannamei shrimp (Litopenaeus vannamei). Vannamei shrimp with size PL25 were used in...

  11. Cardiopulmonary bypass (CPB) has no significant impact on survival in patients undergoing nephrectomy and level III-IV inferior vena cava thrombectomy; a multi-institutional analysis

    Science.gov (United States)

    Dall'Era, Marc A.; Durbin-Johnson, Blythe; Carballido, Joaquín A.; Chandrasekar, Thenappan; Chromecki, Thomas; Ciancio, Gaetano; Daneshmand, Siamak; Gontero, Paolo; Gonzalez, Javier; Haferkamp, Axel; Hohenfellner, Markus; Huang, William C.; Espinós, Estefania Linares; Mandel, Philipp; Martinez-Salamanca, Juan I.; Master, Viraj A.; McKiernan, James M.; Montorsi, Francesco; Novara, Giacomo; Pahernik, Sascha; Palou, Juan; Pruthi, Raj S.; Rodriguez-Faba, Oscar; Russo, Paul; Scherr, Douglas S.; Shariat, Shahrokh F.; Spahn, Martin; Terrone, Carlo; Vergho, Daniel; Wallen, Eric M.; Xylinas, Evanguelos; Zigeuner, Richard; Libertino, John A.; Evans, Christopher P.

    2016-01-01

    Purpose The impact of cardiopulmonary bypass (CPB) usage in level III-IV tumor thrombectomy on surgical and oncologic outcomes is unknown. We sought to determine the impact of cardiopulmonary bypass (CPB) on overall and cancer specific survival, as well as surgical complication rates, and immediate outcomes in patients undergoing nephrectomy and level III-IV tumor thrombectomy with or without CPB. Patients and Methods We retrospectively analyzed 362 patients with RCC and with level III or IV tumor thrombus from 1992 to 2012 in 22 US and European centers. Cox proportional hazards models were used to compare overall and cancer-specific survival between patients with and without CPB. Perioperative mortality and complications rates were assessed using logistic regression analyses. Results The median overall survival was 24.6 months in non-CPB patients and 26.6 months in CPB patients. Overall survival and cancer-specific survival (CSS) did not differ significantly in both groups, neither in univariate analysis nor when adjusting for known risk factors. In multivariate analysis, no significant differences were seen in hospital LOS, Clavien 1-4 complication rate, intraoperative or 30 day mortality, and CSS between both groups. Limitations include the retrospective nature of the study. Conclusions In our multi-institutional analysis, the use of cardiopulmonary bypass did not significantly impact cancer specific survival or overall survival in patients undergoing nephrectomy and level III or IV tumor thrombectomy. Neither approach was independently associated with increased mortality in the multivariate analysis. Higher surgical complications were not independently associated with the use of CPB. PMID:25797392

  12. Survival

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — These data provide information on the survival of California red-legged frogs in a unique ecosystem to better conserve this threatened species while restoring...

  13. Physical skill training increases the number of surviving new cells in the adult hippocampus.

    Directory of Open Access Journals (Sweden)

    Daniel M Curlik

    Full Text Available The dentate gyrus is a major site of plasticity in the adult brain, giving rise to thousands of new neurons every day, through the process of adult neurogenesis. Although the majority of these cells die within two weeks of their birth, they can be rescued from death by various forms of learning. Successful acquisition of select types of associative and spatial memories increases the number of these cells that survive. Here, we investigated the possibility that an entirely different form of learning, physical skill learning, could rescue new hippocampal cells from death. To test this possibility, rats were trained with a physically-demanding and technically-difficult version of a rotarod procedure. Acquisition of the physical skill greatly increased the number of new hippocampal cells that survived. The number of surviving cells positively correlated with performance on the task. Only animals that successfully mastered the task retained the cells that would have otherwise died. Animals that failed to learn, and those that did not learn well did not retain any more cells than those that were untrained. Importantly, acute voluntary exercise in activity wheels did not increase the number of surviving cells. These data suggest that acquisition of a physical skill can increase the number of surviving hippocampal cells. Moreover, learning an easier version of the task did not increase cell survival. These results are consistent with previous reports revealing that learning only rescues new neurons from death when acquisition is sufficiently difficult to achieve. Finally, complete hippocampal lesions did not disrupt acquisition of this physical skill. Therefore, physical skill training that does not depend on the hippocampus can effectively increase the number of surviving cells in the adult hippocampus, the vast majority of which become mature neurons.

  14. Viral vector-mediated downregulation of RhoA increases survival and axonal regeneration of retinal ganglion cells.

    Science.gov (United States)

    Koch, Jan Christoph; Tönges, Lars; Michel, Uwe; Bähr, Mathias; Lingor, Paul

    2014-01-01

    The Rho/ROCK pathway is a promising therapeutic target in neurodegenerative and neurotraumatic diseases. Pharmacological inhibition of various pathway members has been shown to promote neuronal regeneration and survival. However, because pharmacological inhibitors are inherently limited in their specificity, shRNA-mediated approaches can add more information on the function of each single kinase involved. Thus, we generated adeno-associated viral vectors (AAV) to specifically downregulate Ras homologous member A (RhoA) via shRNA. We found that specific knockdown of RhoA promoted neurite outgrowth of retinal ganglion cells (RGC) grown on the inhibitory substrate chondroitin sulfate proteoglycan (CSPG) as well as neurite regeneration of primary midbrain neurons (PMN) after scratch lesion. In the rat optic nerve crush (ONC) model in vivo, downregulation of RhoA significantly enhanced axonal regeneration compared to control. Moreover, survival of RGC transduced with AAV expressing RhoA-shRNA was substantially increased at 2 weeks after optic nerve axotomy. Compared to previous data using pharmacological inhibitors to target RhoA, its upstream regulator Nogo or its main downstream target ROCK, the specific effects of RhoA downregulation shown here were most pronounced in regard to promoting RGC survival but neurite outgrowth and axonal regeneration were also increased significantly. Taken together, we show here that specific knockdown of RhoA substantially increases neuronal survival after optic nerve axotomy and modestly increases neurite outgrowth in vitro and axonal regeneration after optic nerve crush.

  15. Forced mastication increases survival of adult neural stem cells in the hippocampal dentate gyrus.

    Science.gov (United States)

    Akazawa, Yuki; Kitamura, Takamasa; Fujihara, Yuri; Yoshimura, Yoshitaka; Mitome, Masato; Hasegawa, Tomokazu

    2013-02-01

    In this study, we examined the effect of forced mastication on neurogenesis in the hippocampal dentate gyrus (DG) of adult mice. Six-week-old mice were subjected to either a hard or normal diet for 13 weeks. They received a daily injection of bromodeoxyuridine (BrdU) for 12 consecutive days beginning at 14 weeks of age. The number of BrdU-positive cells in the DG was counted 1 day after and 5 weeks after the final BrdU injection. The number of BrdU-positive cells 1 day after injection did not differ between the 2 diet groups. However, the number of BrdU-positive cells in the group fed the hard diet was significantly increased 5 weeks after BrdU injection compared to the group fed the normal diet. The results of the Morris water maze test showed that mice fed a hard diet required significantly less time to reach the platform than the control mice when tested at 10 days. Moreover, mice in the group fed the hard diet spent significantly more time in the former platform area than the group fed the normal diet, indicating that hard diet feeding improved spatial memory compared to normal diet feeding. Real-time PCR analysis showed that the expression of glutamate receptor 1 mRNA was significantly increased in the group fed the hard diet compared with the group fed the normal diet. These results suggest that mastication increases the survival of adult neural stem cells in the hippocampal DG.

  16. Significantly improved survival time in pigs with complete liver ischemia treated with a novel bioartificial liver.

    Science.gov (United States)

    Flendrig, L M; Calise, F; Di Florio, E; Mancini, A; Ceriello, A; Santaniello, W; Mezza, E; Sicoli, F; Belleza, G; Bracco, A; Cozzolino, S; Scala, D; Mazzone, M; Fattore, M; Gonzales, E; Chamuleau, R A

    1999-10-01

    Aim of the study was to evaluate treatment efficacy and safety of a scaled-up version of our porcine hepatocytes based BAL system in pigs with complete liver ischemia (LIS). Thirty-one pigs underwent total devascularization of the liver (LIS) by termino-lateral porta-caval shunts and sutures around the bile duct, the common hepatic and gastroduodenal arteries and their accessory branches. The hepato-duodenal ligament was completely transected. Four experimental groups were studied: the first control group (LIS Control, n = 10) received glucose infusion only, the second control group (LIS Plasmapheresis, n = 8) was connected to a centrifugal plasma-separator with a bottle representing the bioreactor volume, the third control group (LIS Empty-BAL, n = 5) received BAL treatment without cells, and the treated group (LIS Cell-BAL, n = 8) was connected for a maximum period of 24 hours to our scaled-up BAL seeded with around 14 billion viable primary porcine hepatocytes. BAL treatment significantly prolonged life in large animals (approximately 35 kg) with complete LIS (Controls, mean +/- SEM: 33.1 +/- 3 h, Cell-BAL: 51.1 +/- 3.4 h; p = 0.001; longest survivor 63 h). In addition, blood ammonia and total bilirubin levels decreased significantly, indicating metabolic activity of porcine hepatocytes in the bioreactor. No significant differences were noticed among the three control groups, indicating that there was no device effect and that the plasmapheresis procedure was well tolerated. No important adverse effects were observed.

  17. Outbreeding increases offspring survival in wild greater horseshoe bats (Rhinolophus ferrumequinum).

    Science.gov (United States)

    Rossiter, S J; Jones, G; Ransome, R D; Barratt, E M

    2001-05-22

    The factors influencing the survival of greater horseshoe bat (Rhinolophus ferrumequinum) offspring born over seven years at a maternity colony in south-west Britain were studied. The effects of a range of phenotypic and maternal variables were analysed using a historical data set. In addition, the influence of two genetic measures on mortality, individual heterozygosity and a new measure of outbreeding, termed mean d(2), was assessed. Logistic regressions were undertaken with survival modelled as a binary response variable. Survival to two life stages was studied for each variable and all models were developed for both sexes separately and together. Only one variable, mean d(2), was significantly associated with survival. Male offspring with high mean d(2) scores were more likely to survive to their first and second summers. The influence of mean d(2) was not due to a single locus under selection but a wider multilocus effect and probably represents heterosis as opposed to solely inbreeding depression. Therefore, the extent to which an individual is outbred may determine survival more than widely used phenotypic characteristics such as size and mass. Mean d(2) may reflect immunocompetence, which influences mortality. Protection of mating sites in order to facilitate gene flow and, therefore, outbreeding may help to promote population stability and growth.

  18. Neurogenesis and Increase in Differentiated Neural Cell Survival via Phosphorylation of Akt1 after Fluoxetine Treatment of Stem Cells

    Directory of Open Access Journals (Sweden)

    Anahita Rahmani

    2013-01-01

    Full Text Available Fluoxetine (FLX is a selective serotonin reuptake inhibitor (SSRI. Its action is possibly through an increase in neural cell survival. The mechanism of improved survival rate of neurons by FLX may relate to the overexpression of some kinases such as Akt protein. Akt1 (a serine/threonine kinase plays a key role in the modulation of cell proliferation and survival. Our study evaluated the effects of FLX on mesenchymal stem cell (MSC fate and Akt1 phosphorylation levels in MSCs. Evaluation tests included reverse transcriptase polymerase chain reaction, western blot, and immunocytochemistry assays. Nestin, MAP-2, and β-tubulin were detected after neurogenesis as neural markers. Ten μM of FLX upregulated phosphorylation of Akt1 protein in induced hEnSC significantly. Also FLX did increase viability of these MSCs. Continuous FLX treatment after neurogenesis elevated the survival rate of differentiated neural cells probably by enhanced induction of Akt1 phosphorylation. This study addresses a novel role of FLX in neurogenesis and differentiated neural cell survival that may contribute to explaining the therapeutic action of fluoxetine in regenerative pharmacology.

  19. Green tea increases the survival yield of Bifidobacteria in simulated gastrointestinal environment and during refrigerated conditions

    Directory of Open Access Journals (Sweden)

    Vodnar Dan C

    2012-06-01

    Full Text Available Abstract Background The well–known prebiotics are carbohydrates but their effects may not always be beneficial, as they can also encourage the growth of non-probiotic bacteria such as Eubacterium biforme and Clostridium perfringens. Therefore, new alternatives such as non-carbohydrate sources to stimulate the growth of probiotics are needed. The aim of this work was to evaluate (I the green tea polyphenols by HPLC-LC/MS and (II the protective effect of green tea extract on viability and stability of B. infantis ATCC 15697 and B. breve ATCC 15700 microencapsulated in chitosan coated alginate microcapsules during exposure to simulated gastrointestinal conditions and refrigerated storage. Results The major compound identified by HPLC-LC/MS in green tea was epigallocatechin gallate followed by caffeine and epigallocatechin. The survival yield of probiotic bacteria in microcapsules with 10% GT during storage at 4°C, demonstrated significantly (P B.infantis and B. breve with 5% and 10% GT showed a significantly (P  Conclusions The results of this study suggest that green tea coencapsulated with B. infantis or B. breve exert a protective effect of bacteria during exposure to gastrointestinal conditions and refrigerated storage. For a health perspective, the results confirm the growing interest probiotic bacteria and the perceived benefit of increasing their numbers in the gastrointestinal tract by microencapsulation.

  20. Tumor-infiltrating lymphocytes are significantly associated with better overall survival and disease-free survival in triple-negative but not estrogen receptor-positive breast cancers.

    Science.gov (United States)

    Krishnamurti, Uma; Wetherilt, Ceyda Sonmez; Yang, Jing; Peng, Limin; Li, Xiaoxian

    2017-06-01

    Correlation between tumor-infiltrating lymphocytes (TILs) and complete pathological response (pCR) in breast cancers in neoadjuvant settings have been reported. In this study, we analyzed the association between TILs and diagnostic and prognostic parameters in estrogen receptor-positive (ER+) and triple-negative breast cancer (TNBC) without neoadjuvant treatments. Three hundred forty-four (344) patients who underwent mastectomy for breast cancer (187 ER+ and 157 TNBC) without neoadjuvant treatments were evaluated. Percentage of overall and peripheral TILs were correlated with lymphovascular invasion (LVI), Nottingham histologic grade (NHG, 1/2 versus 3), stage, lymph node status (LN), overall survival (OS), and disease-free survival (DFS). In TNBC, both peripheral and overall TILs were significantly associated with NHG 3 (PP=.0354) and DFS (HR: 0.95; 95% CI: 0.91-1.00; P=.0314) in univariate and multivariate analysis. In ER+ breast cancer, only peripheral TILs were associated with NHG 3 (P=.018) but not with OS or DFS (both P>.05). In ER+ breast cancer, there was a negative association between Oncotype DX recurrence score and both overall (P=.0007) and peripheral TILs (P=.0119). In conclusion, peripheral but not overall TILs correlate with better OS and DFS in TNBC, indicating the location of TILs may be important in TNBC. The negative association between TILs and Oncotype DX score in ER+ may indicate the possible prognostic value of TILs in ER+ breast cancer. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Viral vector-mediated downregulation of RhoA increases survival and axonal regeneration of retinal ganglion cells

    Directory of Open Access Journals (Sweden)

    Jan Christoph Koch

    2014-09-01

    Full Text Available The Rho/ROCK pathway is a promising therapeutic target in neurodegenerative and neurotraumatic diseases. Pharmacological inhibition of various pathway members has been shown to promote neuronal regeneration and survival. However, because pharmacological inhibitors are inherently limited in their specificity, shRNA-mediated approaches can add more information on the function of each single kinase involved. Thus, we generated adeno-associated viral vectors (AAV to specifically downregulate RhoA via shRNA. We found that specific knockdown of RhoA promoted neurite outgrowth of retinal ganglion cells (RGC grown on the inhibitory substrate CSPG as well as neurite regeneration of primary midbrain neurons after scratch lesion. In the rat optic nerve crush model in vivo, downregulation of RhoA significantly enhanced axonal regeneration compared to control. Moreover, survival of RGCs transduced with AAV expressing RhoA-shRNA was substantially increased at two weeks after optic nerve axotomy.Compared to previous data using pharmacological inhibitors to target RhoA, its upstream regulator Nogo or its main downstream target ROCK2, the specific effects of RhoA downregulation shown here were more pronounced in regard to promoting RGC survival while the stimulatory effects on neurite outgrowth were rather moderate. Taken together, we show here that specific knockdown of RhoA substantially increases neuronal survival after optic nerve axotomy and modestly increases neurite outgrowth in vitro and axonal regeneration after optic nerve crush.

  2. The number of positive nodes and the ratio of positive to excised nodes are significant predictors of survival in women with micrometastatic node-positive breast cancer.

    Science.gov (United States)

    Truong, Pauline T; Vinh-Hung, Vincent; Cserni, Gabor; Woodward, Wendy A; Tai, Patricia; Vlastos, Georges

    2008-08-01

    To evaluate the prognostic impact of the number of positive nodes and the lymph node ratio (LNR) of positive to excised nodes on survival in women diagnosed with nodal micrometastatic breast cancer before the era of widespread sentinel lymph node biopsy. Subjects were 62,551 women identified by the Surveillance Epidemiology and End Results database, diagnosed with pT1-2pN0-1 breast cancer between 1988 and 1997. Kaplan-Meier breast cancer-specific survival (BCSS) and overall survival (OS) were compared between three cohorts: node-negative (pN0, n=57,980) nodal micrometastasis all 2mm but or= 4) and the LNR (0.25). Median follow-up was 7.3 yr. Ten-year BCSS and OS in pNmic breast cancer were significantly lower compared to pN0 disease (BCSS 82.3% versus 91.9%, p<0.001 and OS 68.1% versus 75.7%, p<0.001). BCSS and OS with pNmic disease progressively declined with increasing number of positive nodes and increasing LNR. OS with pNmic was similar to pNmac disease when matched by the number of positive nodes and by the LNR. Both pN-based and LNR-based classifications were significantly prognostic of BCSS and OS on Cox regression multivariate analysis. Nodal micrometastasis is associated with poorer survival compared to pN0 disease. Mortality hazards with nodal micrometastasis increased with increasing number of positive nodes and increasing LNR. The number of positive nodes and the LNR should be considered in risk estimates for patients with nodal micrometastatic breast cancer.

  3. Survival and population size of a resident bird species are declining as temperature increases.

    Science.gov (United States)

    Santisteban, Leonard; Benkman, Craig W; Fetz, Trevor; Smith, Julie W

    2012-03-01

    1. A large number of migratory bird species appear to be declining as the result of climate change, but whether resident bird species have or will be adversely affected by climate change is less clear. We focus on the South Hills crossbill (Loxia curvirostra complex), which is endemic to about 70 km(2) of Rocky Mountain lodgepole pine (Pinus contorta latifolia) forest in southern Idaho, USA. 2. Our results indicate that the South Hills crossbill has declined by over 60% between 2003 and 2008, and that decreasing adult survival drives this population decline. 3. We evaluated the relative support for multiple hypotheses linking crossbill survival to climate, an ectoparasitic mite (scaly-leg mites Knemidokoptes jamaicensis), and the recent emergence of West Nile virus. Changes in adult apparent survival rate were closely associated with average spring and annual temperatures, and with high temperatures (≥32 °C) during summer, which have increased during the last decade. In contrast, there was little evidence that scaly-leg mites or West Nile virus contributed to recent declines in adult survival. 4. The most probable mechanism causing the decline in adult survival and population size is a decrease in the availability of their primary food resource, seeds in serotinous pine cones. Cone production has declined with increasing annual temperatures, and these cones appear to be prematurely opening owing to increasingly hot summer conditions releasing their seeds and reducing the carrying capacity for crossbills later in the year. 5. In light of regional climate change forecasts, which include an increase in both annual temperature and hot days (>32 °C), and the likely disappearance of lodgepole pine from southern Idaho by the end of this century, additional research is needed to determine how to maintain lodgepole pine forests and their supply of seeds to conserve one of the few bird species endemic to the continental United States. © 2011 The Authors. Journal of

  4. Minimally invasive esophagectomy provides significant survival advantage compared with open or hybrid esophagectomy for patients with cancers of the esophagus and gastroesophageal junction.

    Science.gov (United States)

    Palazzo, Francesco; Rosato, Ernest L; Chaudhary, Asadulla; Evans, Nathaniel R; Sendecki, Jocelyn A; Keith, Scott; Chojnacki, Karen A; Yeo, Charles J; Berger, Adam C

    2015-04-01

    Minimally invasive esophagectomy (MIE) is increasingly being used to treat patients with cancer of the esophagus and gastroesophageal junction. We previously reported that oncologic efficacy may be improved with MIE compared with open or hybrid esophagectomy (OHE). We compared survival of patients undergoing MIE and OHE. Our contemporary series of patients who underwent MIE (2008 to 2013) was compared with a cohort undergoing OHE (3-hole [n = 39], Ivor Lewis [n = 16], hybrid [n = 13], 2000 to 2013). Summary statistics were calculated by operation type; Kaplan-Meier methods were used to compare survival. Cox regression was used to assess the impact of operation type (MIE vs OHE) on mortality, adjusting for age, sex, total lymph nodes, lymph node ratio (LNR), neoadjuvant chemoradiotherapy (CRT), and stage. The MIE (n = 104) and OHE (n = 68) groups were similar with respect to age and sex. The MIE group tended to have higher BMI, earlier stage disease, and was less likely to receive CRT. The MIE group experienced lower operative mortality (3.9% vs 8.8%, p = 0.35) and significantly fewer major complications. Five-year survival between groups was significantly different (MIE, 64%, OHE, 35%, p analysis demonstrated that patients undergoing OHE had a significantly worse survival compared with MIE independent of age, LNR, CRT, and pathologic stage (hazard ratio 2.00, p = 0.019). This study supports MIE for EC as a superior procedure with respect to overall survival, perioperative mortality, and severity of postoperative complications. Several biases may have affected these results: earlier stage in the MIE group and disparity in timing of the procedures. These results will need to be confirmed in future prospective studies with longer follow-up. Copyright © 2015 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

  5. Aromatase expression increases the survival and malignancy of estrogen receptor positive breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Keya De Mukhopadhyay

    Full Text Available In postmenopausal women, local estrogen produced by adipose stromal cells in the breast is believed to support estrogen receptor alpha (ERα positive breast cancer cell survival and growth. This raises the question of how the ERα positive metastatic breast cancer cells survive after they enter blood and lymph circulation, where estrogen level is very low in postmenopausal women. In this study, we show that the aromatase expression increased when ERα positive breast cancer cells were cultured in suspension. Furthermore, treatment with the aromatase substrate, testosterone, inhibited suspension culture-induced apoptosis whereas an aromatase inhibitor attenuated the effect of testosterone suggesting that suspended circulating ERα positive breast cancer cells may up-regulate intracrine estrogen activity for survival. Consistent with this notion, a moderate level of ectopic aromatase expression rendered a non-tumorigenic ERα positive breast cancer cell line not only tumorigenic but also metastatic in female nude mice without exogenous estrogen supplementation. The increased malignant phenotype was confirmed to be due to aromatase expression as the growth of orthotopic tumors regressed with systemic administration of an aromatase inhibitor. Thus, our study provides experimental evidence that aromatase plays an important role in the survival of metastatic ERα breast cancer cells by suppressing anoikis.

  6. Plasmodium Parasitemia Associated With Increased Survival in Ebola Virus-Infected Patients.

    Science.gov (United States)

    Rosenke, Kyle; Adjemian, Jennifer; Munster, Vincent J; Marzi, Andrea; Falzarano, Darryl; Onyango, Clayton O; Ochieng, Melvin; Juma, Bonventure; Fischer, Robert J; Prescott, Joseph B; Safronetz, David; Omballa, Victor; Owuor, Collins; Hoenen, Thomas; Groseth, Allison; Martellaro, Cynthia; van Doremalen, Neeltje; Zemtsova, Galina; Self, Joshua; Bushmaker, Trenton; McNally, Kristin; Rowe, Thomas; Emery, Shannon L; Feldmann, Friederike; Williamson, Brandi N; Best, Sonja M; Nyenswah, Tolbert G; Grolla, Allen; Strong, James E; Kobinger, Gary; Bolay, Fatorma K; Zoon, Kathryn C; Stassijns, Jorgen; Giuliani, Ruggero; de Smet, Martin; Nichol, Stuart T; Fields, Barry; Sprecher, Armand; Massaquoi, Moses; Feldmann, Heinz; de Wit, Emmie

    2016-10-15

    The ongoing Ebola outbreak in West Africa has resulted in 28 646 suspected, probable, and confirmed Ebola virus infections. Nevertheless, malaria remains a large public health burden in the region affected by the outbreak. A joint Centers for Disease Control and Prevention/National Institutes of Health diagnostic laboratory was established in Monrovia, Liberia, in August 2014, to provide laboratory diagnostics for Ebola virus. All blood samples from suspected Ebola virus-infected patients admitted to the Médecins Sans Frontières ELWA3 Ebola treatment unit in Monrovia were tested by quantitative real-time polymerase chain reaction for the presence of Ebola virus and Plasmodium species RNA. Clinical outcome in laboratory-confirmed Ebola virus-infected patients was analyzed as a function of age, sex, Ebola viremia, and Plasmodium species parasitemia. The case fatality rate of 1182 patients with laboratory-confirmed Ebola virus infections was 52%. The probability of surviving decreased with increasing age and decreased with increasing Ebola viral load. Ebola virus-infected patients were 20% more likely to survive when Plasmodium species parasitemia was detected, even after controlling for Ebola viral load and age; those with the highest levels of parasitemia had a survival rate of 83%. This effect was independent of treatment with antimalarials, as this was provided to all patients. Moreover, treatment with antimalarials did not affect survival in the Ebola virus mouse model. Plasmodium species parasitemia is associated with an increase in the probability of surviving Ebola virus infection. More research is needed to understand the molecular mechanism underlying this remarkable phenomenon and translate it into treatment options for Ebola virus infection. Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  7. Prognostic significance of increased bone marrow microcirculation in newly diagnosed multiple myeloma: results of a prospective DCE-MRI study

    Energy Technology Data Exchange (ETDEWEB)

    Merz, Maximilian; Hillengass, Jens [Department of Radiology, German Cancer Research Center, Heidelberg (Germany); University of Heidelberg, Department of Hematology, Oncology and Rheumatology, Heidelberg (Germany); Moehler, Thomas M.; Ritsch, Judith; Delorme, Stefan [Department of Radiology, German Cancer Research Center, Heidelberg (Germany); Baeuerle, Tobias [University of Erlangen-Nuremberg, Department of Radiology, Erlangen (Germany); Zechmann, Christian M. [Rinecker Proton Therapy, Muenchen (Germany); Wagner, Barbara; Hose, Dirk [University of Heidelberg, Department of Hematology, Oncology and Rheumatology, Heidelberg (Germany); Jauch, Anna [University of Heidelberg, Institute of Human Genetics, Heidelberg (Germany); Kunz, Christina; Hielscher, Thomas [German Cancer Research Center, Department of Biostatistics, Heidelberg (Germany); Laue, Hendrik [Fraunhofer MEVIS, Bremen (Germany); Goldschmidt, Hartmut [University of Heidelberg, Department of Hematology, Oncology and Rheumatology, Heidelberg (Germany); National Center for Tumor Diseases, Heidelberg (Germany)

    2016-05-15

    Aim of this prospective study was to investigate prognostic significance of increased bone marrow microcirculation as detected by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for survival and local complications in patients with multiple myeloma (MM). We performed DCE-MRI of the lumbar spine in 131 patients with newly diagnosed MM and analysed data according to the Brix model to acquire amplitude A and exchange rate constant k{sub ep}. In 61 patients a second MRI performed after therapy was evaluated to assess changes in vertebral height and identify vertebral fractures. Correlation analysis revealed significant positive association between beta2-microglobulin as well as immunoparesis with DCE-MRI parameters A and k{sub ep}. Additionally, A was negatively correlated with haemoglobin levels and k{sub ep} was positively correlated with LDH levels. Higher baseline k{sub ep} values were associated with decreased vertebral height in a second MRI (P = 0.007) and A values were associated with new vertebral fractures in the lower lumbar spine (P = 0.03 for L4). Pre-existing lytic bone lesions or remission after therapy had no impact on the occurrence of vertebral fractures. Multivariate analysis revealed that amplitude A is an independent adverse risk factor for overall survival. DCE-MRI is a non-invasive tool with significance for systemic prognosis and vertebral complications. (orig.)

  8. Cost of wound treatment to increase significantly in Denmark over the next decade

    DEFF Research Database (Denmark)

    Hjort, Anne Mette; Gottrup, F

    2010-01-01

    To demonstrate that changes in demography, life expectancy and incidence of background diseases (including type 2 diabetes mellitus) during the period 2009-2020 will significantly increase the costs of wound care in Denmark.......To demonstrate that changes in demography, life expectancy and incidence of background diseases (including type 2 diabetes mellitus) during the period 2009-2020 will significantly increase the costs of wound care in Denmark....

  9. Recombinant human erythropoietin increases survival and reduces neuronal apoptosis in a murine model of cerebral malaria

    DEFF Research Database (Denmark)

    Wiese, Lothar; Hempel, Casper; Penkowa, Milena

    2008-01-01

    BACKGROUND: Cerebral malaria (CM) is an acute encephalopathy with increased pro-inflammatory cytokines, sequestration of parasitized erythrocytes and localized ischaemia. In children CM induces cognitive impairment in about 10% of the survivors. Erythropoietin (Epo) has - besides of its well known...... with recombinant human Epo (rhEpo; 50-5000 U/kg/OD, i.p.) at different time points. The effect on survival was measured. Brain pathology was investigated by TUNEL (Terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP)-digoxigenin nick end labelling), as a marker of apoptosis. Gene...... expression in brain tissue was measured by real time PCR. RESULTS: Treatment with rhEpo increased survival in mice with CM in a dose- and time-dependent manner and reduced apoptotic cell death of neurons as well as the expression of pro-inflammatory cytokines in the brain. This neuroprotective effect...

  10. Gastrin activates autophagy and increases migration and survival of gastric adenocarcinoma cells.

    Science.gov (United States)

    Rao, Shalini V; Solum, Guri; Niederdorfer, Barbara; Nørsett, Kristin G; Bjørkøy, Geir; Thommesen, Liv

    2017-01-21

    The peptide hormone gastrin exerts a growth-promoting effect in both normal and malignant gastrointestinal tissue. Gastrin mediates its effect via the cholecystokinin 2 receptor (CCKBR/CCK2R). Although a substantial part of the gastric adenocarcinomas express gastrin and CCKBR, the role of gastrin in tumor development is not completely understood. Autophagy has been implicated in mechanisms governing cytoprotection, tumor growth, and contributes to chemoresistance. This study explores the role of autophagy in response to gastrin in gastric adenocarcinoma cell lines. Immunoblotting, survival assays and the xCELLigence system were used to study gastrin induced autophagy. Chemical inhibitors of autophagy were utilized to assess the role of this process in the regulation of cellular responses induced by gastrin. Further, knockdown studies using siRNA and immunoblotting were performed to explore the signaling pathways that activate autophagy in response to gastrin treatment. We demonstrate that gastrin increases the expression of the autophagy markers MAP1LC3B-II and SQSTM1 in gastric adenocarcinoma cells. Gastrin induces autophagy via activation of the STK11-PRKAA2-ULK1 and that this signaling pathway is involved in increased migration and cell survival. Furthermore, gastrin mediated increase in survival of cells treated with cisplatin is partially dependent on induced autophagy. This study reveals a novel role of gastrin in the regulation of autophagy. It also opens up new avenues in the treatment of gastric cancer by targeting CCKBR mediated signaling and/or autophagy in combination with conventional cytostatic drugs.

  11. β-Catenin Signaling Increases during Melanoma Progression and Promotes Tumor Cell Survival and Chemoresistance

    Science.gov (United States)

    Sinnberg, Tobias; Menzel, Moritz; Ewerth, Daniel; Sauer, Birgit; Schwarz, Michael; Schaller, Martin; Garbe, Claus; Schittek, Birgit

    2011-01-01

    Beta-catenin plays an important role in embryogenesis and carcinogenesis by controlling either cadherin-mediated cell adhesion or transcriptional activation of target gene expression. In many types of cancers nuclear translocation of beta-catenin has been observed. Our data indicate that during melanoma progression an increased dependency on the transcriptional function of beta-catenin takes place. Blockade of beta-catenin in metastatic melanoma cell lines efficiently induces apoptosis, inhibits proliferation, migration and invasion in monolayer and 3-dimensional skin reconstructs and decreases chemoresistance. In addition, subcutaneous melanoma growth in SCID mice was almost completely inhibited by an inducible beta-catenin knockdown. In contrast, the survival of benign melanocytes and primary melanoma cell lines was less affected by beta-catenin depletion. However, enhanced expression of beta-catenin in primary melanoma cell lines increased invasive capacity in vitro and tumor growth in the SCID mouse model. These data suggest that beta-catenin is an essential survival factor for metastatic melanoma cells, whereas it is dispensable for the survival of benign melanocytes and primary, non-invasive melanoma cells. Furthermore, beta-catenin increases tumorigenicity of primary melanoma cell lines. The differential requirements for beta-catenin signaling in aggressive melanoma versus benign melanocytic cells make beta-catenin a possible new target in melanoma therapy. PMID:21858114

  12. Increased survival of experimentally evolved antimicrobial peptide-resistant Staphylococcus aureus in an animal host

    Science.gov (United States)

    Dobson, Adam J; Purves, Joanne; Rolff, Jens

    2014-01-01

    Antimicrobial peptides (AMPs) have been proposed as new class of antimicrobial drugs, following the increasing prevalence of bacteria resistant to antibiotics. Synthetic AMPs are functional analogues of highly evolutionarily conserved immune effectors in animals and plants, produced in response to microbial infection. Therefore, the proposed therapeutic use of AMPs bears the risk of ‘arming the enemy’: bacteria that evolve resistance to AMPs may be cross-resistant to immune effectors (AMPs) in their hosts. We used a panel of populations of Staphylococcus aureus that were experimentally selected for resistance to a suite of individual AMPs and antibiotics to investigate the ‘arming the enemy’ hypothesis. We tested whether the selected strains showed higher survival in an insect model (Tenebrio molitor) and cross-resistance against other antimicrobials in vitro. A population selected for resistance to the antimicrobial peptide iseganan showed increased in vivo survival, but was not more virulent. We suggest that increased survival of AMP-resistant bacteria almost certainly poses problems to immune-compromised hosts. PMID:25469169

  13. History of autoimmune disease is associated with impaired survival in multiple myeloma and monoclonal gammopathy of undetermined significance: a population-based study.

    Science.gov (United States)

    Lindqvist, Ebba K; Landgren, Ola; Lund, Sigrún H; Turesson, Ingemar; Hultcrantz, Malin; Goldin, Lynn; Björkholm, Magnus; Kristinsson, Sigurdur Y

    2017-02-01

    Multiple myeloma (MM) is a plasma cell disorder preceded by monoclonal gammopathy of undetermined significance (MGUS). Incidence of MM and MGUS is higher among patients with autoimmune disease. The aim of this study was to determine whether a history of autoimmunity has an impact on survival in MM and MGUS. Using high-quality national Swedish registries, we identified 8367 patients with MM, 18,768 patients with MGUS, and 110,251 matched control subjects, and obtained information on previous autoimmune disease in patients and controls. Cox regression was used to calculate hazard ratios (HRs) for overall survival with 95 % confidence intervals (CIs). In patients with MM and a prior autoimmune disease, the risk of death was significantly increased, HR = 1.2 (95 % CI 1.2-1.3) compared to MM patients with no history of autoimmunity. In MGUS patients, a prior autoimmune disease was associated with a significantly 1.4-fold elevated risk of death (95 % CI 1.3-1.4). When analyzing different types of autoimmune diseases, a history of ulcerative colitis had a stronger impact on survival in MM than in controls. Our findings that a history of autoimmune disease has a negative impact on survival in MM and MGUS could be due to shared underlying common genetic factors, or that patients with a history of autoimmunity develop more severe cases of MM and MGUS, or cumulative comorbidity in the individual. Our results suggest that more attention should be paid to comorbidity as a prognostic factor in MGUS and MM, and underlines the need for studies aimed at tailoring therapy according to comorbidity.

  14. Increased Expression of the GLUT-1 Gene is Associated With Worse Overall Survival in Resected Pancreatic Adenocarcinoma

    Science.gov (United States)

    Davis-Yadley, Ashley H.; Abbott, Andrea M.; Pimiento, Jose M.; Chen, Dung-Tsa; Malafa, Mokenge P.

    2015-01-01

    Objectives There is currently no reliable method to predict the risk of relapse after curative resection of early-stage pancreatic adenocarcinoma. Increased glucose metabolism observed on 18F-fluorodeoxyglucose positron emission tomography (PET) by malignant cells, the Warburg effect, is a well-known characteristic of the malignant phenotype. We investigated the role of glucose transporter type 1 (GLUT-1) gene expression, a glucose cell plasma membrane transporter, in early-stage pancreatic cancer. Methods Associations between GLUT-1 gene expression with PET maximum standardized uptake values (SUVmax) and histologic grade were investigated in early-stage pancreatic adenocarcinoma patients. Multivariate analysis was conducted to determine predictors of prognosis. Cox proportional hazards model was used for survival analysis. Results Sixty-three patients had GLUT-1 gene analysis performed, and 50 patients had both GLUT-1 analysis and PET scan. Patients with high GLUT-1 gene expression had a decreased overall survival by univariate analysis using Cox proportional hazards model (HR=2.82, p=0.001) and remained significant on multivariate analysis (HR=2.54, p=0.03). There was no correlation of GLUT-1 gene expression with histologic grade or PET SUVmax. Conclusion Increased GLUT-1 gene expression was associated with a decreased overall survival in pancreatic adenocarcinoma. This supports increased GLUT-1 gene expression as a potential prognostic marker in resected pancreatic adenocarcinoma. PMID:26692443

  15. Continuous background light significantly increases flashing-light enhancement of photosynthesis and growth of microalgae.

    Science.gov (United States)

    Abu-Ghosh, Said; Fixler, Dror; Dubinsky, Zvy; Iluz, David

    2015-01-01

    Under specific conditions, flashing light enhances the photosynthesis rate in comparison to continuous illumination. Here we show that a combination of flashing light and continuous background light with the same integrated photon dose as continuous or flashing light alone can be used to significantly enhance photosynthesis and increase microalgae growth. To test this hypothesis, the green microalga Dunaliella salina was exposed to three different light regimes: continuous light, flashing light, and concomitant application of both. Algal growth was compared under three different integrated light quantities; low, intermediate, and moderately high. Under the combined light regime, there was a substantial increase in all algal growth parameters, with an enhanced photosynthesis rate, within 3days. Our strategy demonstrates a hitherto undescribed significant increase in photosynthesis and algal growth rates, which is beyond the increase by flashing light alone. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Two-step grafting significantly enhances the survival of foetal dopaminergic transplants and induces graft-derived vascularisation in a 6-OHDA model of Parkinson's disease.

    Science.gov (United States)

    Büchele, Fabian; Döbrössy, Máté; Hackl, Christina; Jiang, Wei; Papazoglou, Anna; Nikkhah, Guido

    2014-08-01

    GFP+ vessels - completely absent in control grafts - in regions where the two grafts overlap, indicating second-graft derived angiogenesis. In summary, the study shows that two-step grafting with a 2days time interval significantly increases DAergic cell survival compared to the standard protocol. Furthermore, our results demonstrate, for the first time, a donor-derived neoangiogenesis, leading to a new understanding of graft survival and development in the field of cell-replacement therapies for neurodegenerative diseases. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Immunotherapy with subcutaneous immunogenic autologous tumor lysate increases murine glioblastoma survival.

    Science.gov (United States)

    Belmans, Jochen; Van Woensel, Matthias; Creyns, Brecht; Dejaegher, Joost; Bullens, Dominique M; Van Gool, Stefaan W

    2017-10-24

    Immunotherapeutic strategies for glioblastoma, the most frequent malignant primary brain tumor, aim to improve its disastrous consequences. On top of the standard treatment, one strategy uses T cell activation by autologous dendritic cells (DC) ex vivo loaded with tumor lysate to attack remaining cancer cells. Wondering whether 'targeting' in vivo DCs could replace these ex vivo ones, immunogenic autologous tumor lysate was used to treat glioma-inoculated mice in the absence of ex vivo loaded DCs. Potential immune mechanisms were studied in two orthotopic, immunocompetent murine glioma models. Pre-tumoral subcutaneous lysate treatment resulted in a survival benefit comparable to subcutaneous DC therapy. Focussing on the immune response, glioma T cell infiltration was observed in parallel with decreased amounts of regulatory T cells. Moreover, these results were accompanied by the presence of strong tumor-specific immunological memory, shown by complete survival of a second glioblastoma tumor, inoculated 100 days after the first one. Finally, in combination with temozolomide, survival of established glioma in mice could be increased. Our results show the potential of immunogenic autologous tumor lysate used to treat murine glioblastoma, which will be worthwhile to study in clinical trials as it has potential as a cost-efficient adjuvant treatment strategy for gliomas.

  18. Pretreatment direct bilirubin and total cholesterol are significant predictors of overall survival in advanced non-small-cell lung cancer patients with EGFR mutations.

    Science.gov (United States)

    Zhang, Yanwei; Xu, Jianlin; Lou, Yuqing; Hu, Song; Yu, Keke; Li, Rong; Zhang, Xueyan; Jin, Bo; Han, Baohui

    2017-04-01

    This study was designed to examine the prediction of pretreatment circulating bilirubin and cholesterol for overall survival in 459 advanced non-small-cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations. Circulating total bilirubin, direct bilirubin (DB), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) levels were measured at baseline. The mean age (standard deviation) of all study patients was 58.7 (10.5) years, and 42.9% of them was males. Ever smokers accounted for 27.0% and lung adenocarcinoma for 90.4%. The median follow-up time and survival time were 29.5 and 34.9 months, respectively. Patients with higher DB had a 1.68-fold increased risk of death compared with patients with lower DB (hazard ratio [HR] = 1.68, 95% confidence interval [CI]: 1.22-2.30, p = 0.001), while patients with higher TC were at a 63% reduced risk of death compared with patients with lower TC (HR = 0.37, 95% CI: 0.20-0.67, p = 0.001). As for HDL-C, patients with higher levels had the risk of death reduced by 46% (HR = 0.54, 95% CI: 0.29-1.00, p = 0.049) compared with patients with lower levels. After the Bonferroni correction, only DB and TC were significantly associated with NSCLC survival. Our findings demonstrate for the first time that pretreatment DB was identified as a significant risk factor, yet TC as a protective factor, for overall survival in NSCLC patients with EGFR mutations. © 2016 UICC.

  19. Do Increased Doses to Stem-Cell Niches during Radiation Therapy Improve Glioblastoma Survival?

    Directory of Open Access Journals (Sweden)

    Sebastian Adeberg

    2016-01-01

    Full Text Available Background and Purpose. The reasons for the inevitable glioblastoma recurrence are yet understood. However, recent data suggest that tumor cancer stem cells (CSCs in the stem-cell niches, with self-renewing capacities, might be responsible for tumor initiation, propagation, and recurrence. We aimed to analyze the effect of higher radiation doses to the stem-cell niches on progression-free survival (PFS and overall survival (OS in glioblastoma patients. Materials and Methods. Sixty-five patients with primary glioblastoma treated with radiation therapy were included in this retrospective analysis. The SVZ and DG were segmented on treatment planning magnetic resonance imaging, and the dose distributions to the structures were calculated. The relationship of dosimetry data and survival was evaluated using the Cox regression analysis. Results. Conventionally fractionated patients (n=54 who received higher doses (Dmean ≥ 40 Gy to the IL SVZ showed improved PFS (8.5 versus 5.2 months; p=0.013. Furthermore, higher doses (Dmean ≥ 30 Gy to the CL SVZ were associated with increased PFS (10.1 versus 6.9 months; p=0.025. Conclusion. Moderate higher IL SVZ doses (≥40 Gy and CL SVZ doses (≥30 Gy are associated with improved PFS. Higher doses to the DG, the second stem-cell niche, did not influence the survival. Targeting the potential cancer stem cells in the SVZ might be a promising treatment approach for glioblastoma and should be addressed in a prospective randomized trial.

  20. Survival outcomes of obese patients in type II endometrial cancer: Defining the prognostic impact of increasing BMI.

    Science.gov (United States)

    Billingsley, Caroline C; Cansino, Catherine; O'Malley, David M; Cohn, David E; Fowler, Jeffrey M; Copeland, Larry J; Backes, Floor J; Salani, Ritu

    2016-03-01

    To investigate the role of obesity as a risk factor for type II endometrial cancer (EC), as well as the prognostic significance of increasing body mass index (BMI) on survival. A single institution retrospective analysis of 154 type II EC cases from 1987 to 2010 was conducted. Patients were categorized into cohorts by BMI (normal (obese class I (30-34.9), and obese class II-III (≥35)). Descriptive, regression and ANOVA analyses were performed. Kaplan-Meier curves were compared with log rank tests. The BMI distribution was 22.8% normal BMI; 24% overweight; 17.5% class I; and 35.7% class II-III. The median follow up was 41 months. The median progression-free survival (PFS) was 45.4, 36.0, 35.3 and 42.0 months and overall survival (OS) was 54.7, 44.7, 44.8 and 49.7 months, among the respective groups. There was no association between BMI and PFS (p=0.71), OS (p=0.72), or time to recurrence (p=0.71). There were no differences among the increasing BMI groups compared to normal weight women for the risk of death. Our analysis did not reveal any differences in outcomes by BMI group. Our data reveals that obesity is highly prevalent in type II ECs, though obesity has not historically been described as a risk factor. While BMI as a single variable may not be prognostic for survival outcomes, the role of obesity as a risk factor for type II EC should be further investigated, given the increasing prevalence of obesity in type II ECs. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Therapeutic doses of oral methylphenidate significantly increase extracellular dopamine in the human brain.

    Science.gov (United States)

    Volkow, N D; Wang, G; Fowler, J S; Logan, J; Gerasimov, M; Maynard, L; Ding, Y; Gatley, S J; Gifford, A; Franceschi, D

    2001-01-15

    Methylphenidate (Ritalin) is the most commonly prescribed psychoactive drug in children for the treatment of attention deficit hyperactivity disorder (ADHD), yet the mechanisms responsible for its therapeutic effects are poorly understood. Whereas methylphenidate blocks the dopamine transporter (main mechanism for removal of extracellular dopamine), it is unclear whether at doses used therapeutically it significantly changes extracellular dopamine (DA) concentration. Here we used positron emission tomography and [(11)C]raclopride (D2 receptor radioligand that competes with endogenous DA for binding to the receptor) to evaluate whether oral methylphenidate changes extracellular DA in the human brain in 11 healthy controls. We showed that oral methylphenidate (average dose 0.8 +/- 0.11 mg/kg) significantly increased extracellular DA in brain, as evidenced by a significant reduction in B(max)/K(d) (measure of D2 receptor availability) in striatum (20 +/- 12%; p methylphenidate at doses within the therapeutic range significantly increases extracellular DA in human brain. This result coupled with recent findings of increased dopamine transporters in ADHD patients (which is expected to result in reductions in extracellular DA) provides a mechanistic framework for the therapeutic efficacy of methylphenidate. The increase in DA caused by the blockade of dopamine transporters by methylphenidate predominantly reflects an amplification of spontaneously released DA, which in turn is responsive to environmental stimulation. Because DA decreases background firing rates and increases signal-to-noise in target neurons, we postulate that the amplification of weak DA signals in subjects with ADHD by methylphenidate would enhance task-specific signaling, improving attention and decreasing distractibility. Alternatively methylphenidate-induced increases in DA, a neurotransmitter involved with motivation and reward, could enhance the salience of the task facilitating the "interest that

  2. Significant alterations in reported clinical practice associated with increased oversight of organ transplant center performance.

    Science.gov (United States)

    Schold, Jesse D; Arrington, Charlotte J; Levine, Greg

    2010-09-01

    In the past several years, emphasis on quality metrics in the field of organ transplantation has increased significantly, largely because of the new conditions of participation issued by the Centers for Medicare and Medicaid Services. These regulations directly associate patients' outcomes and measured performance of centers with the distribution of public funding to institutions. Moreover, insurers and marketing ventures have used publicly available outcomes data from transplant centers for business decision making and advertisement purposes. We gave a 10-question survey to attendees of the Transplant Management Forum at the 2009 meeting of the United Network for Organ Sharing to ascertain how centers have responded to the increased oversight of performance. Of 63 responses, 55% indicated a low or near low performance rating at their center in the past 3 years. Respondents from low-performing centers were significantly more likely to indicate increased selection criteria for candidates (81% vs 38%, P = .001) and donors (77% vs 31%, P vs 52%, P = .007). Among respondents indicating lost insurance contracts (31%), these differences were also highly significant. Based on respondents' perceptions, outcomes of performance evaluations are associated with significant changes in clinical practice at transplant centers. The transplant community and policy makers should practice vigilance that performance evaluations and regulatory oversight do not inadvertently lead to diminished access to care among viable candidates or decreased transplant volume.

  3. Denosumab significantly increases DXA BMD at both trabecular and cortical sites: results from the FREEDOM study.

    Science.gov (United States)

    Bolognese, Michael A; Teglbjærg, Christence Stubbe; Zanchetta, Jose R; Lippuner, Kurt; McClung, Michael R; Brandi, Maria Luisa; Høiseth, Arne; Lakatos, Péter; Moffett, Alfred H; Lorenc, Roman S; Wang, Andrea; Libanati, Cesar

    2013-01-01

    Denosumab is an approved therapy for postmenopausal women with osteoporosis at high or increased risk for fracture. In the FREEDOM study, denosumab reduced fracture risk and increased bone mineral density (BMD). We report the spine and hip dual-energy X-ray absorptiometry (DXA) BMD responses from the overall study of 7808 women and from a substudy of 441 participants in which more extensive spine and hip assessments as well as additional skeletal sites were evaluated. Significant BMD improvements were observed as early as 1 mo at the lumbar spine, total hip, and trochanter (all p<0.005 vs placebo and baseline). BMD increased progressively at the lumbar spine, total hip, femoral neck, trochanter, 1/3 radius, and total body from baseline to months 12, 24, and 36 (all p<0.005 vs placebo and baseline). BMD gains above the least significant change of more than 3% at 36 months were observed in 90% of denosumab-treated subjects at the lumbar spine and 74% at the total hip, and gains more than 6% occurred in 77% and 38%, respectively. In conclusion, denosumab treatment resulted in significant, early, and continued BMD increases at both trabecular and cortical sites throughout the skeleton over 36 mo with important gains observed in most subjects. Copyright © 2013 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.

  4. Increased Body Mass Index Is Associated With Improved Survival in United States Veterans With Diffuse Large B-Cell Lymphoma

    Science.gov (United States)

    Carson, Kenneth R.; Bartlett, Nancy L.; McDonald, Jay R.; Luo, Suhong; Zeringue, Angelique; Liu, Jingxia; Fu, Qiang; Chang, Su-Hsin; Colditz, Graham A.

    2012-01-01

    Purpose Obesity increases the risk of death from many malignancies, including non-Hodgkin's lymphoma (NHL). In diffuse large B-cell lymphoma (DLBCL), the most common form of NHL, the association between body mass index (BMI) at diagnosis and survival is unclear. Patients and Methods We evaluated the association between BMI at diagnosis and overall survival in a retrospective cohort of 2,534 United States veterans diagnosed with DLBCL between October 1, 1998 and December 31, 2008. Cox modeling was used to control for patient- and disease-related prognostic variables. Results Mean age at diagnosis was 68 years (range, 20 to 100 years); 64% of patients were overweight (BMI, 25 to < 30) or obese (BMI, ≥ 30). Obese patients were significantly younger, had significantly fewer B symptoms, and trended toward lower-stage disease, compared with other BMI groups. Cox analysis showed reduced mortality in overweight and obese patients (overweight: hazard ratio [HR], 0.73; 95% CI, 0.65 to 0.83; obese: HR, 0.68; 95% CI, 0.58 to 0.80), compared with normal-weight patients (BMI, 18.5 to < 25). Treatment during the rituximab era reduced the risk of death without affecting the association between BMI and survival. Disease-related weight loss occurred in 29% of patients with weight data 1 year before diagnosis. Cox analysis based on BMI 1 year before diagnosis continued to demonstrate reduced risk of death in overweight and obese patients. Conclusion Being overweight or obese at the time of DLBCL diagnosis is associated with improved overall survival. Understanding the mechanisms responsible for this association will require further study. PMID:22649138

  5. Non-viral VEGF165 gene therapy ? magnetofection of acoustically active magnetic lipospheres (?magnetobubbles?) increases tissue survival in an oversized skin flap model

    OpenAIRE

    Holzbach, Thomas; Vlaskou, Dialekti; Neshkova, Iva; Konerding, Moritz A.; W?rtler, Klaus; Mykhaylyk, Olga; G?nsbacher, Bernd; Machens, H-G; Plank, Christian; Giunta, Riccardo E

    2008-01-01

    Abstract Adenoviral transduction of the VEGF gene in an oversized skin flap increases flap survival and perfusion. In this study, we investigated the potential of magnetofection of magnetic lipospheres containing VEGF165-cDNA on survival and perfusion of ischemic skin flaps and evaluated the method with respect to the significance of applied magnetic field and ultrasound. We prepared perfluoropropane-filled magnetic lipospheres (?magnetobubbles?) from Tween60-coated magnetic nanoparticles, Me...

  6. Lovastatin delays infection and increases survival rates in AG129 mice infected with dengue virus serotype 2.

    Directory of Open Access Journals (Sweden)

    Marlen Martinez-Gutierrez

    Full Text Available BACKGROUND: It has been reported that treatment of DENV-infected cultures with Lovastatin (LOV, can affect viral assembly. The objective of this study was to evaluate the effect of LOV on the survival rate and viremia levels of DENV-2-infected AG129 mice. METHODOLOGY/PRINCIPAL FINDINGS: Mice were inoculated with 1 × 10(6 plaque-forming units (PFU/ml of DENV-2 and treated with LOV (200 mg/kg/day. Pre-treatment with one or three doses of LOV increased the survival rate compared to untreated mice (7.3 and 7.1 days, respectively, compared to 4.8 days. Viremia levels also decreased by 21.8% compared to untreated mice, but only in the group administered three doses prior to inoculation. When LOV was administered after viral inoculation, the survival rate increased (7.3 days in the group treated at 24 hpi, 6.8 days in the group treated at 48 hpi and 6.5 days in the group treated with two doses compared to the untreated group (4.8 days. Interestingly, the serum viral titer increased by 24.6% in mice treated at 48 hpi with a single dose of LOV and by 21.7% in mice treated with two doses (at 24 and 48 hpi of LOV compared to untreated mice. Finally histopathological changes in the liver and spleen in infected and untreated mice included massive extramedullary erythropoiesis foci and inflammatory filtration, and these characteristics were decreased or absent in LOV-treated mice. CONCLUSIONS/SIGNIFICANCE: Our results suggest that the effect of LOV on viremia depends on the timing of treatment and on the number of doses administered. We observed a significant increase in the survival rate in both schemes due to a delay in the progression of the disease. However, the results obtained in the post-treatment scheme must be handled carefully because this treatment scheme increases viremia and we do not know how this increase could affect disease progression in humans.

  7. Overall survival of patients with advanced pancreatic cancer improved with an increase in second-line chemotherapy after gemcitabine-based therapy.

    Science.gov (United States)

    Zhang, Yuan Dong; Yang, Qiong; Jiang, Zhi Min; Ma, Wen; Zhou, Si Wei; Xie, De Rong

    2011-03-09

    In the last decade, gemcitabine-based regimen as first-line therapy has demonstrated low efficacy regarding overall survival benefit for patients with advanced pancreatic cancer. The purpose of this study was to explore a new strategy, such as an increased second-line chemotherapy rate, in order to improve overall survival. Retrospective data analysis. The data in the literature on gemcitabine-based therapy for patients with advanced pancreatic cancer were collected by searching databases, such as MEDLINE, EMBASE, the Chinese Biomedical Literature Analysis and Retrieval System, and EBM Reviews (Cochrane Database of Systematic Reviews). Linear regression was used to explore the relationship between overall survival and second-line chemotherapy. The primary endpoint was overall survival. The secondary endpoints were progression-free survival and residual survival. Ten randomized controlled trials, involving 2,679 patients, were included in the present study. The results indicated that overall survival was positively correlated with a combination of chemotherapy, stage of disease and second-line chemotherapy in patients with advanced pancreatic cancer (r = 0.753; P = 0.003). Meanwhile median overall survival would be prolonged about 1.56 days if second-line chemotherapy was increased by 1% (t = 4.33; P = 0.001). Progression-free survival was not significantly correlated with second-line chemotherapy (r = 0.092; P = 0.701); in contrast, residual survival was positively correlated with second-line chemotherapy (r = 0.717; P chemotherapy in patients with advanced pancreatic cancer; more attention should be paid after first-line therapy which must be administered skillfully in order to improve overall survival, and this is worthy of further study.

  8. Increased survival in the red flour beetle after oral priming with bacteria-conditioned media.

    Science.gov (United States)

    Milutinović, Barbara; Fritzlar, Svenja; Kurtz, Joachim

    2014-01-01

    Immune priming is defined as enhanced protection upon secondary exposure to a pathogen. Such enhanced resistance after prior exposure has been demonstrated for a number of insect species including the red flour beetle, Tribolium castaneum. In testing this phenomenon, the majority of studies have focused on introducing the pathogen into the insect's hemocoel via septic wounding through the cuticle. Although such septic injury can occur in nature, many pathogens enter their hosts via the oral route, i.e. by ingestion. Bacillus thuringiensis bacteria are well-known insect pathogens that infect their host orally. We found that T. castaneum larvae showed increased survival after oral exposure to B. thuringiensis, when they had been orally primed with filter-sterilized media in which spores of B. thuringiensis had been raised. Such priming was achieved only with a naturally pathogenic strain of B. thuringiensis and a strain that was made pathogenic by transfer of plasmids. Moreover, primed larvae were smaller in size 24 h after priming and had a longer developmental time, indicating that investment in such a response comes at a cost. However, the increased survival in primed larvae was not caused by larval size differences upon challenge. © 2013 S. Karger AG, Basel.

  9. Measles Vaccination Supports Millennium Development Goal 4: Increasing Coverage and Increasing Child Survival in Northern Ghana, 1996–2012

    Directory of Open Access Journals (Sweden)

    Paul Welaga

    2018-02-01

    Full Text Available BackgroundMeasles vaccine (MV administered as the last vaccine after the third dose of diphtheria-tetanus-pertussis (DTP may be associated with better child survival unrelated to prevention of measles infection. Other studies have shown that MV administered after DTP was more beneficial and was associated with lower mortality compared with DTP administered after MV or DTP administered simultaneously with MV. We compared the difference in mortality between measles vaccinated after DTP3 and measles-unvaccinated children in Navrongo, Ghana.MethodsThis was a follow-up study involving annual cohort of children aged 9–23 months from 1996 to 2012. We assessed survival in relation to the measles vaccination status within the first 12 months from interview date and until 5 years of age using Cox proportional hazards models.ResultsIn all, 38,333 children were included in the study. The proportion of children vaccinated with MV-after-DTP3 increased from 45% in 1996 to 95% in 2012. The adjusted hazard ratio (HR for measles unvaccinated compared with MV-after-DTP3 vaccinated children was 1.38 (1.15–1.66 in the first 12 months after assessment of vaccination status and 1.22 (1.05–1.41 with follow-up to 5 years of age. The national immunization days campaigns with oral polio vaccine or MV might have reduced the effect of being MV-after-DTP3 vaccinated vs MV-unvaccinated. For 12 months of follow-up, the HR before a campaign for MV-unvaccinated children was 1.63 (1.23–2.17 compared to those who received MV-after-DTP3. After the campaign, the HR reduced to 1.23 (0.97–1.54. Stratifying the analysis by sex, measles-unvaccinated boys had a HR of 1.69 (1.33–2.61 compared to measles-unvaccinated girls who had a HR 1.06 (0.79–1.40 during 1-year follow-up. In 1989, only 7% of children in the area had received MV-after-DTP3; the increase in MV-after-DTP3 coverage from 1989 to 2012 may have lowered mortality rate among children aged 9 months to

  10. Distributing tasks via multiple input pathways increases cellular survival in stress.

    Science.gov (United States)

    Granados, Alejandro A; Crane, Matthew M; Montano-Gutierrez, Luis F; Tanaka, Reiko J; Voliotis, Margaritis; Swain, Peter S

    2017-05-17

    Improving in one aspect of a task can undermine performance in another, but how such opposing demands play out in single cells and impact on fitness is mostly unknown. Here we study budding yeast in dynamic environments of hyperosmotic stress and show how the corresponding signalling network increases cellular survival both by assigning the requirements of high response speed and high response accuracy to two separate input pathways and by having these pathways interact to converge on Hog1, a p38 MAP kinase. Cells with only the less accurate, reflex-like pathway are fitter in sudden stress, whereas cells with only the slow, more accurate pathway are fitter in increasing but fluctuating stress. Our results demonstrate that cellular signalling is vulnerable to trade-offs in performance, but that these trade-offs can be mitigated by assigning the opposing tasks to different signalling subnetworks. Such division of labour could function broadly within cellular signal transduction.

  11. Effect of oral administration of Lactobacillus reuteri in increased survival and resistance to neoplasm in mice breast cancer

    Directory of Open Access Journals (Sweden)

    Soltan Dallal MM

    2013-02-01

    Full Text Available Background: Several reports indicate that the probiotics can increase body resistance against malignant tumors. The aim of this study is to evaluate the effect of Lactobaci-llus reuteri Persian type culture collection (PTCC 1655 in preventing tumor growth, improving weight and survival rate in mice with breast cancer.Methods: Twenty mice, the BALB/c at six weeks age, weighing approximately 17 gram were divided into two groups. Oral administration of 500 micro liters of Lactobacillus reuteri suspension performed for the first group 14 days before tumor transplantation. The second group (control received the same volume of phosphate buffer saline (PBS. Then the mice had tumor transplantation surgery. Lactobacillus reuteri was prescribed in the first group in seven-day period and three-day interruption pattern. At the same time the second group (control received PBS. This process was continued until 45 day. The tumor growth, histology and body weight were evaluated in both group and the mortality of mice was recorded.Results: In the mice transplanted tumors that had received probiotics, tumor growth decreased in comparison with control group. In this group the body weight increased (P>0/05. In addition, the survival of these mice had significantly increased compared to control group (P=0.002. The evaluation of tumor tissue also showed increased immune system function in mice receiving the probiotic (P>0/05.Conclusion: Lactobacillus reuteri can improve immune system function and have an important role to help treatment of cancer.

  12. Exam anxiety induces significant blood pressure and heart rate increase in college students.

    Science.gov (United States)

    Zhang, Zhihong; Su, Hai; Peng, Qiang; Yang, Qing; Cheng, Xiaoshu

    2011-01-01

    To investigate the relationship between the anxiety and blood pressure (BP) and heart rate (HR) increase in peri-exam period. Sixty-four college students(20.0 ± 0.1 year old) were included in this study. The BP and HR were measured in the morning and in the evening for 3 days during the prereview (ba), review, and exam periods. The BP and HR increase amplitudes (HRIA) of review and exam periods were from the difference of corresponding values and basic values, and the BPIA/baBP and HRIA/baHR were calculated. All of the students completed the Self-Rating Anxiety score (SAS) questionnaire the first day of the exam period. Scores over 50 points were used as the standard for anxiety. From the prereview to exam periods, the BP and HR increased gradually. The exam SBPIA (4.3 ± 1.3 vs. 0.3 ± 0.5 mmHg, P anxiety group than in the no-anxiety group. The SBPIA/DBPIA and HRIA showed a similar profile also(9.7 ± 2.1 vs. 1.9 ± 0.9 bpm, P anxiety score; meanwhile, their exam BPIAs and HRIAs were significantly higher than their corresponding group. The BP and HR increase in the review and exam period, anxiety is an important factor of BP and HR increase.

  13. Inhibition of CDK4/6 by Palbociclib Significantly Extends Survival in Medulloblastoma Patient-Derived Xenograft Mouse Models.

    Science.gov (United States)

    Cook Sangar, Michelle L; Genovesi, Laura A; Nakamoto, Madison W; Davis, Melissa J; Knobluagh, Sue E; Ji, Pengxiang; Millar, Amanda; Wainwright, Brandon J; Olson, James M

    2017-10-01

    Purpose: Bioinformatics analysis followed by in vivo studies in patient-derived xenograft (PDX) models were used to identify and validate CDK 4/6 inhibition as an effective therapeutic strategy for medulloblastoma, particularly group 3 MYC-amplified tumors that have the worst clinical prognosis.Experimental Design: A protein interaction network derived from a Sleeping Beauty mutagenesis model of medulloblastoma was used to identify potential novel therapeutic targets. The top hit from this analysis was validated in vivo using PDX models of medulloblastoma implanted subcutaneously in the flank and orthotopically in the cerebellum of mice.Results: Informatics analysis identified the CDK4/6/CYCLIN D/RB pathway as a novel "druggable" pathway for multiple subgroups of medulloblastoma. Palbociclib, a highly specific inhibitor of CDK4/6, was found to inhibit RB phosphorylation and cause G1 arrest in PDX models of medulloblastoma. The drug caused rapid regression of Sonic hedgehog (SHH) and MYC-amplified group 3 medulloblastoma subcutaneous tumors and provided a highly significant survival advantage to mice bearing MYC-amplified intracranial tumors.Conclusions: Inhibition of CDK4/6 is potentially a highly effective strategy for the treatment of SHH and MYC-amplified group 3 medulloblastoma. Clin Cancer Res; 23(19); 5802-13. ©2017 AACR. ©2017 American Association for Cancer Research.

  14. Cyclin D1 is significantly associated with stage of tumor and predicts poor survival in endometrial carcinoma patients.

    Science.gov (United States)

    Khabaz, Mohamad Nidal; Abdelrahman, Amer Shafie; Butt, Nadeem Shafique; Al-Maghrabi, Basim; Al-Maghrabi, Jaudah

    2017-10-01

    Cyclin D1 overexpression has been described to have oncogenic role and association with diagnosis, prognosis and survival in various tumors. This study will describe the immunohistochemical phenotype of cyclin D1, and investigate the correlation between these patterns of expression and clinicopathological parameters of endometrial carcinomas, to conclude the clinical relevance of cyclin D1 expression in the evolution of endometrial neoplasms. This study employed 101 endometrial tissue samples which include 71 endometrial carcinomas and thirty normal and benign endometrium cases. All these tissue samples were used in the assembly of tissue microarrays which have been utilized afterward in immunohistochemistry staining to detect cyclin D1 expression. Forty (56.3%) cases of endometrial carcinomas showed brown nuclear expression of cyclin D1 including 36 (61%) cases of endometrioid carcinomas, and 3 (33.3%) cases of serous carcinomas. Twenty three (76.6%) cases of control group demonstrated nuclear expression. High score cyclin D1 immunohistochemical staining has been significantly linked with patient age (P=0.0001). Large proportion of high score cyclin D1 immunohistochemical staining was observed in females who are endometrial tissues in comparison with carcinomas. The distribution pattern of cyclin D1 immunoexpression suggests poor prognoses in endometrial carcinoma patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Endurance training significantly increases serum endocan but not osteoprotegerin levels: a prospective observational study.

    Science.gov (United States)

    Sponder, Michael; Campean, Ioana-Alexandra; Emich, Michael; Fritzer-Szekeres, Monika; Litschauer, Brigitte; Bergler-Klein, Jutta; Graf, Senta; Strametz-Juranek, Jeanette

    2017-01-05

    Endocan (EN) was suggested a potential inflammatory and cardiovascular disease (CVD) marker which might also be involved in renal failure and/or renal failure-associated vascular events. It is not clear whether osteoprotegerin (OPG) is a pro- or anti-atherogenic factor, however, it is agreed upon that OPG is elevated in subjects with increased calcification status. The aim of the study was to investigate the influence of long-term physical activity on serum endocan (EN) and osteoprotegerin-levels. One hundred nine subjects were told to increase their amount of physical activity for 8 months by performing 150min/week moderate or 75min/week vigorous exercise. Incremental cycle ergometer tests were performed at the beginning and the end of the study to prove and quantify the performance gain. Blood samples were drawn at baseline and every 2 months for the determination of EN and OPG. To investigate the difference between baseline and 8 months levels of EN and OPG we used a paired sample t-test. To investigate the significance of the tendency of the progression (baseline/2 months/4 months/6 months/8 months) we used a Friedman test. Thirty-eight female and 60 male subjects completed the study. In the group of 61 subjects who had a performance gain by >4,9% EN-levels increased from 146 ± 110 to 196 ± 238 pg/ml (p = 0,036) equivalent to an increase of 33,5% but there was no significant change in OPG (4,4 ± 2,4 pmol/l vs. 4,3 ± 2,1 pmol/l; p = 0,668). Physical activity increases significantly EN-levels relativizing the status of EN as proinflammatory factor. EN should rather be considered as a mediator which is involved in several physiological (e.g., angiogenesis) but also pathological processes (e.g., CVD, tumour progression or endothelium-dependent inflammation) and whose expression can be significantly influenced by long term endurance training. Clinical trial registration number: NCT02097199 Date of trial registration at Clinical Trials

  16. Bromelain and N-acetylcysteine inhibit proliferation and survival of gastrointestinal cancer cells in vitro: significance of combination therapy.

    Science.gov (United States)

    Amini, Afshin; Masoumi-Moghaddam, Samar; Ehteda, Anahid; Morris, David Lawson

    2014-11-12

    Bromelain and N-acetylcysteine are two natural, sulfhydryl-containing compounds with good safety profiles which have been investigated for their benefits and application in health and disease for more than fifty years. As such, the potential values of these agents in cancer therapy have been variably reported in the literature. In the present study, the efficacy of bromelain and N-acetylcysteine in single agent and combination treatment of human gastrointestinal carcinoma cells was evaluated in vitro and the underlying mechanisms of effect were explored. The growth-inhibitory effects of bromelain and N-acetylcysteine, on their own and in combination, on a panel of human gastrointestinal carcinoma cell lines, including MKN45, KATO-III, HT29-5F12, HT29-5M21 and LS174T, were assessed by sulforhodamine B assay. Moreover, the influence of the treatment on the expression of a range of proteins involved in the regulation of cell cycle and survival was investigated by Western blot. The presence of apoptosis was also examined by TUNEL assay. Bromelain and N-acetylcysteine significantly inhibited cell proliferation, more potently in combination therapy. Drug-drug interaction in combination therapy was found to be predominantly synergistic or additive. Mechanistically, apoptotic bodies were detected in treated cells by TUNEL assay. Furthermore, Western blot analysis revealed diminution of cyclins A, B and D, the emergence of immunoreactive subunits of caspase-3, caspase-7, caspase-8 and cleaved PARP, withering or cleavage of procaspase-9, overexpression of cytochrome c, reduced expression of anti-apoptotic Bcl-2 and pro-survival phospho-Akt, the emergence of the autophagosomal marker LC3-II and deregulation of other autophagy-related proteins, including Atg3, Atg5, Atg7, Atg12 and Beclin 1. These results were more prominent in combination therapy. We report for the first time to our knowledge the growth-inhibitory and cytotoxic effects of bromelain and N-acetylcysteine, in

  17. Increased cardiac arrest survival and bystander intervention in enclosed pedestrian walkway systems.

    Science.gov (United States)

    Lee, Minha; Demirtas, Derya; Buick, Jason E; Feldman, Michael J; Cheskes, Sheldon; Morrison, Laurie J; Chan, Timothy C Y

    2017-09-01

    Cities worldwide have underground or above-ground enclosed walkway systems for pedestrian travel, representing unique environments for studying out-of-hospital cardiac arrests (OHCAs). The characteristics and outcomes of OHCAs that occur in such systems are unknown. To determine whether OHCAs occurring in enclosed pedestrian walkway systems have differing demographics, prehospital intervention, and survival outcomes compared to the encompassing city, by examining the PATH walkway system in Toronto. We identified all atraumatic, public-location OHCAs in Toronto from April 2006 to March 2016. Exclusion criteria were obvious death, existing DNR, and EMS-witnessed OHCAs. OHCAs were classified into mutually exclusive location groups: Toronto, Downtown, and PATH-accessible. PATH-accessible OHCAs were those that occurred within the PATH system between the first basement and third floor. We analyzed demographic, prehospital intervention, and survival data using t-tests and chi-squared tests. We identified 2172 OHCAs: 1752 Toronto, 371 Downtown, and 49 PATH-accessible. Compared to Toronto, a significantly higher proportion of PATH-accessible OHCAs was bystander-witnessed (62.6% vs 83.7%, p=0.003), had bystander CPR (56.6% vs 73.5%, p=0.019), bystander AED use (11.0% vs 42.6%, pinfrastructure systems worldwide should consider these findings when determining AED placement and public engagement strategies. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Adaptive Memory: Survival Processing Increases Both True and False Memory in Adults and Children

    Science.gov (United States)

    Otgaar, Henry; Smeets, Tom

    2010-01-01

    Research has shown that processing information in a survival context can enhance the information's memorability. The current study examined whether survival processing can also decrease the susceptibility to false memories and whether the survival advantage can be found in children. In Experiment 1, adults rated semantically related words in a…

  19. Frequent shopping by men and women increases survival in the older Taiwanese population.

    Science.gov (United States)

    Chang, Yu-Hung; Chen, Rosalind Chia-Yu; Wahlqvist, Mark L; Lee, Meei-Shyuan

    2012-07-01

    Active ageing is a key to healthy ageing; shopping behaviour is an economically relevant activity of the elderly. Analysis was based on the NAHSIT 1999-2000 dataset. A total of 1841 representative free-living elderly Taiwanese people were selected and information included demographics, socioeconomic status, health behaviours, shopping frequencies, physical function and cognitive function. These data were linked to official death records. Cox proportional hazard models were used to evaluate shopping frequency on death from 1999-2008 with possible covariate adjustment. Highly frequent shopping compared to never or rarely predicted survival (HR 0.54, 95% CI 0.43 to 0.67) with adjustment for physical function and cognitive function and other covariates HR was 0.73 (95% CI 0.56 to 0.93). Elderly who shopped every day have 27% less risk of death than the least frequent shoppers. Men benefited more from everyday shopping than women with decreased HR 28% versus 23% compared to the least. Shopping behaviour favourably predicts survival. Highly frequent shopping may favour men more than women. Shopping captures several dimensions of personal well-being, health and security as well as contributing to the community's cohesiveness and economy and may represent or actually confer increased longevity.

  20. Ant Mutualism Increases Long-Term Growth and Survival of a Common Amazonian Tree.

    Science.gov (United States)

    Báez, Selene; Donoso, David A; Queenborough, Simon A; Jaramillo, Liliana; Valencia, Renato; Dangles, Olivier

    2016-11-01

    How ecological context shapes mutualistic relationships remains poorly understood. We combined long-term tree census data with ant censuses in a permanent 25-ha Amazonian forest dynamics plot to evaluate the effect of the mutualistic ant Myrmelachista schumanni (Formicinae) on the growth and survival of the common Amazonian tree Duroia hirsuta (Rubiaceae), considering its interactions with tree growth, population structure, and habitat. We found that the mutualist ant more than doubled tree relative growth rates and increased odds of survival. However, host tree size and density of conspecific neighbors modified the effect of the ant. Smaller trees hosting the mutualist ant consistently grew faster when surrounded by higher densities of conspecifics, suggesting that the benefit to the tree outweighs any negative effects of high conspecific densities. Moreover, our findings suggest that the benefit afforded by the ant diminishes with plant age and also depends on the density of conspecific neighbors. We provide the first long-term large-scale evidence of how mutualism affects the population biology of an Amazonian tree species.

  1. Clinicopathological significance of increased ZIC1 expression in human endometrial cancer.

    Science.gov (United States)

    Gu, Xing; Liu, Qin; Yang, Ning; Shen, Jian-fang; Zhang, Xue-gang; Cao, Fang; Ding, Hou-zhong

    2015-12-01

    Zinc finger of the cerebellum (ZIC1), one of ZIC family genes, has been shown to play important roles in many cancers such as gastric cancer and breast cancer. However, there is little known about the expression and significance of ZIC1 in endometrial cancer. The aim of this study was to determine the expression pattern and clinicopathological significance of ZIC1 in endometrial cancer. The mRNA and protein expression of ZIC1 in endometrial cancer tissues was detected using the reverse-transcription polymerase chain reaction and Western blotting, respectively. Immunostaining of ZIC1 in 99 endometrial cancer samples was examined and its associations with clinicopathological parameters were analyzed. Hec-1-B cells were transfected with ZIC1-shRNA or sc-shRNA, and cell proliferation was assayed. Hec-1-B cells stably transfected with ZIC1-shRNA or sc-shRNA were subcutaneously inoculated into nude mice, and the tumor weight was measured. A significantly increased expression of ZIC1 mRNA and protein was observed in endometrial cancer tissues compared to that in normal endometrial tissues (Pendometrial cancer samples (90/99) while light and moderate immunostaining of ZIC1 was only detected in 17 of 30 (56.7%) normal tissues. Moreover, up-regulation of ZIC1 was significantly correlated with age, disease stage, TNM stage and FIGO stage (Pendometrial cancer tissue but not in normal tissue, and positively correlated to the malignant biological behavior of endometrial carcinogenesis.

  2. Increased Subventricular Zone Radiation Dose Correlates With Survival in Glioblastoma Patients After Gross Total Resection

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    Chen, Linda [Department of Neurosurgery, The Johns Hopkins University, Baltimore, Maryland (United States); Duke University School of Medicine, Durham, North Carolina (United States); Guerrero-Cazares, Hugo [Department of Neurosurgery, The Johns Hopkins University, Baltimore, Maryland (United States); Ye, Xiaobu [Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, The Johns Hopkins University, Baltimore, Maryland (United States); Ford, Eric [Department of Radiation Oncology, University of Washington, Seattle, Washington (United States); McNutt, Todd; Kleinberg, Lawrence [Department of Radiation Oncology and Molecular Radiation Sciences, The Johns Hopkins University, Baltimore, Maryland (United States); Lim, Michael; Chaichana, Kaisorn [Department of Neurosurgery, The Johns Hopkins University, Baltimore, Maryland (United States); Quinones-Hinojosa, Alfredo, E-mail: aquinon2@jhmi.edu [Department of Neurosurgery, The Johns Hopkins University, Baltimore, Maryland (United States); Redmond, Kristin, E-mail: kjanson3@jhmi.edu [Department of Radiation Oncology and Molecular Radiation Sciences, The Johns Hopkins University, Baltimore, Maryland (United States)

    2013-07-15

    Purpose: Neural progenitor cells in the subventricular zone (SVZ) have a controversial role in glioblastoma multiforme (GBM) as potential tumor-initiating cells. The purpose of this study was to examine the relationship between radiation dose to the SVZ and survival in GBM patients. Methods and Materials: The study included 116 patients with primary GBM treated at the Johns Hopkins Hospital between 2006 and 2009. All patients underwent surgical resection followed by adjuvant radiation therapy with intensity modulated radiation therapy (60 Gy/30 fractions) and concomitant temozolomide. Ipsilateral, contralateral, and bilateral SVZs were contoured on treatment plans by use of coregistered magnetic resonance imaging and computed tomography. Multivariate Cox regression was used to examine the relationship between mean SVZ dose and progression-free survival (PFS), as well as overall survival (OS). Age, Karnofsky Performance Status score, and extent of resection were used as covariates. The median age was 58 years (range, 29-80 years). Results: Of the patients, 12% underwent biopsy, 53% had subtotal resection (STR), and 35% had gross total resection (GTR). The Karnofsky Performance Status score was less than 90 in 54 patients and was 90 or greater in 62 patients. The median ipsilateral, contralateral, and bilateral mean SVZ doses were 48.7 Gy, 34.4 Gy, and 41.5 Gy, respectively. Among patients who underwent GTR, a mean ipsilateral SVZ dose of 40 Gy or greater was associated with a significantly improved PFS compared with patients who received less than 40 Gy (15.1 months vs 10.3 months; P=.028; hazard ratio, 0.385 [95% confidence interval, 0.165-0.901]) but not in patients undergoing STR or biopsy. The subgroup of GTR patients who received an ipsilateral dose of 40 Gy or greater also had a significantly improved OS (17.5 months vs 15.6 months; P=.027; hazard ratio, 0.385 [95% confidence interval, 0.165-0.895]). No association was found between SVZ radiation dose and PFS

  3. Head and neck cooling decreases tympanic and skin temperature, but significantly increases blood pressure.

    Science.gov (United States)

    Koehn, Julia; Kollmar, Rainer; Cimpianu, Camelia-Lucia; Kallmünzer, Bernd; Moeller, Sebastian; Schwab, Stefan; Hilz, Max J

    2012-08-01

    Localized head and neck cooling might be suited to induce therapeutic hypothermia in acute brain injury such as stroke. Safety issues of head and neck cooling are undetermined and may include cardiovascular autonomic side effects that were identified in this study. Ten healthy men (age 35±13 years) underwent 120 minutes of combined head and neck cooling (Sovika, HVM Medical). Before and after onset of cooling, after 60 and 120 minutes, we determined rectal, tympanic, and forehead skin temperatures, RR intervals, systolic and diastolic blood pressures (BP), laser-Doppler skin blood flow at the index finger and cheek, and spectral powers of mainly sympathetic low-frequency (0.04-0.15 Hz) and parasympathetic high-frequency (0.15-0.5 Hz) RR interval oscillations and sympathetic low-frequency oscillations of BP. We compared values before and during cooling using analysis of variance with post hoc analysis; (significance, Pskin temperature dropped by 5.5±2.2°C with cooling onset and by 12.4±3.2°C after 20 minutes. Tympanic temperature decreased by 4.7±0.7°C within 40 minutes, and rectal temperature by only 0.3±0.3°C after 120 minutes. Systolic and diastolic BP increased immediately on cooling onset and rose by 15.3±20.8 mm Hg and 16.5±13.4 mm Hg (P=0.004) after 120 minutes, whereas skin blood flow fell significantly during cooling. RR intervals and parasympathetic RR interval high-frequency powers increased with cooling onset and were significantly higher after 60 and 120 minutes than they were before cooling. Head and neck cooling prominently reduced tympanic temperature and thus might also induce intracerebral hypothermia; however, it did not significantly lower body core temperature. Profound skin temperature decrease induced sympathetically mediated peripheral vasoconstriction and prominent BP increases that are not offset by simultaneous parasympathetic heart rate slowing. Prominent peripheral vasoconstriction and BP increase must be considered as

  4. Kinematic and Microphysical Significance of Lightning Jumps versus Non-Jump Increases in Total Flash Rate.

    Science.gov (United States)

    Schultz, Christopher J; Carey, Lawrence D; Schultz, Elise V; Blakeslee, Richard J

    2017-02-01

    Thirty-nine thunderstorms are examined using multiple-Doppler, polarimetric and total lightning observations to understand the role of mixed phase kinematics and microphysics in the development of lightning jumps. This sample size is larger than those of previous studies on this topic. The principal result of this study is that lightning jumps are a result of mixed phase updraft intensification. Larger increases in intense updraft volume (≥ 10 m s-1) and larger changes in peak updraft speed are observed prior to lightning jump occurrence when compared to other non-jump increases in total flash rate. Wilcoxon-Mann-Whitney Rank Sum testing yields p-values ≤0.05, indicating statistical independence between lightning jump and non-jump distributions for these two parameters. Similar changes in mixed phase graupel mass magnitude are observed prior to lightning jumps and non-jump increases in total flash rate. The p-value for graupel mass change is p=0.096, so jump and non-jump distributions for graupel mass change are not found statistically independent using the p=0.05 significance level. Timing of updraft volume, speed and graupel mass increases are found to be 4 to 13 minutes in advance of lightning jump occurrence. Also, severe storms without lightning jumps lack robust mixed phase updrafts, demonstrating that mixed phase updrafts are not always a requirement for severe weather occurrence. Therefore, the results of this study show that lightning jump occurrences are coincident with larger increases in intense mixed phase updraft volume and peak updraft speed than smaller non-jump increases in total flash rate.

  5. Trade-off mediated effects on the genetics of human survival caused by increasingly benign living conditions.

    Science.gov (United States)

    Drenos, Fotios; Westendorp, Rudi G J; Kirkwood, Thomas B L

    2006-08-01

    It is sometimes suggested that modern life, with its planned fertility and medically assisted compensation for genetic disadvantage, has greatly reduced the power of natural selection to produce significant further human evolution. However, this overlooks the very recent and dramatic changes that have occurred in the patterns of human mortality, driven by the development of increasingly benign living conditions. Where the genetics of survival are significantly influenced by life history trade-offs, as is now thought to be the case for ageing and longevity, a change in the environment can shift the optimal balance that was established through natural selection under previous conditions. We examine this possibility in the context of the dramatic recent change in the mortality pressure exerted by infectious disease using a model of a hypothetical immunogenetic trade-off that weighs survival against fecundity. Our results predict that such a change might have a significant effect on population genetics over relatively short-timescales, and they may also resolve the paradox of genes that impair fertility in present-day populations by showing how such genes might be a legacy from a powerful trade-off that has acted until very recently.

  6. Processes involved in assisted reproduction technologies significantly increase sperm DNA fragmentation and phosphatidylserine translocation.

    Science.gov (United States)

    Balasuriya, A; Serhal, P; Doshi, A; Harper, J C

    2014-03-01

    Sperm preparation techniques in assisted reproduction technologies (ART) are potential generators of exogenous stresses that cause additional DNA damage. DNA fragmentation tests, such as the sperm chromatin structure assay, involve freezing sperm samples in the absence of cryoprotectant. Thermal, oxidative stress (OS) and freezing are detrimental to sperm DNA fragmentation and phosphatidylserine (PS) translocation. The primary aim of this study was to subject mature sperm to environmental insults that normally occur during ART. We tested the hypotheses that OS, thermal stress and freeze-thawing caused sperm nuclear and membrane damage and that a positive correlation exists between PS translocation and DNA fragmentation. Sperm DNA integrity deteriorates in semen samples from men with advancing age and a sperm concentration of <15 m ml(-1) . The significant increase in sperm DNA fragmentation at 37 °C after merely 1 h is important clinically as semen liquefaction and short-term sperm storage in an ART cycle involve incubating samples at this temperature. Freezing without a cryoprotectant significantly increases the level of sperm nuclear damage, so it is important not to freeze neat semen prior to DNA fragmentation testing. This study highlights the importance of minimising the production of exogenous stresses during sperm preparation in ART. © 2012 Blackwell Verlag GmbH.

  7. Significant increase in ecosystem C can be achieved with sustainable forest management in subtropical plantation forests.

    Science.gov (United States)

    Wei, Xiaohua; Blanco, Juan A

    2014-01-01

    Subtropical planted forests are rapidly expanding. They are traditionally managed for intensive, short-term goals that often lead to long-term yield decline and reduced carbon sequestration capacity. Here we show how it is possible to increase and sustain carbon stored in subtropical forest plantations if management is switched towards more sustainable forestry. We first conducted a literature review to explore possible management factors that contribute to the potentials in ecosystem C in tropical and subtropical plantations. We found that broadleaves plantations have significantly higher ecosystem C than conifer plantations. In addition, ecosystem C increases with plantation age, and reaches a peak with intermediate stand densities of 1500-2500 trees ha⁻¹. We then used the FORECAST model to simulate the regional implications of switching from traditional to sustainable management regimes, using Chinese fir (Cunninghamia lanceolata) plantations in subtropical China as a study case. We randomly simulated 200 traditional short-rotation pure stands and 200 sustainably-managed mixed Chinese fir--Phoebe bournei plantations, for 120 years. Our results showed that mixed, sustainably-managed plantations have on average 67.5% more ecosystem C than traditional pure conifer plantations. If all pure plantations were gradually transformed into mixed plantations during the next 10 years, carbon stocks could rise in 2050 by 260.22 TgC in east-central China. Assuming similar differences for temperate and boreal plantations, if sustainable forestry practices were applied to all new forest plantation types in China, stored carbon could increase by 1,482.80 TgC in 2050. Such an increase would be equivalent to a yearly sequestration rate of 40.08 TgC yr⁻¹, offsetting 1.9% of China's annual emissions in 2010. More importantly, this C increase can be sustained in the long term through the maintenance of higher amounts of soil organic carbon and the production of timber products

  8. Significant increase in ecosystem C can be achieved with sustainable forest management in subtropical plantation forests.

    Directory of Open Access Journals (Sweden)

    Xiaohua Wei

    Full Text Available Subtropical planted forests are rapidly expanding. They are traditionally managed for intensive, short-term goals that often lead to long-term yield decline and reduced carbon sequestration capacity. Here we show how it is possible to increase and sustain carbon stored in subtropical forest plantations if management is switched towards more sustainable forestry. We first conducted a literature review to explore possible management factors that contribute to the potentials in ecosystem C in tropical and subtropical plantations. We found that broadleaves plantations have significantly higher ecosystem C than conifer plantations. In addition, ecosystem C increases with plantation age, and reaches a peak with intermediate stand densities of 1500-2500 trees ha⁻¹. We then used the FORECAST model to simulate the regional implications of switching from traditional to sustainable management regimes, using Chinese fir (Cunninghamia lanceolata plantations in subtropical China as a study case. We randomly simulated 200 traditional short-rotation pure stands and 200 sustainably-managed mixed Chinese fir--Phoebe bournei plantations, for 120 years. Our results showed that mixed, sustainably-managed plantations have on average 67.5% more ecosystem C than traditional pure conifer plantations. If all pure plantations were gradually transformed into mixed plantations during the next 10 years, carbon stocks could rise in 2050 by 260.22 TgC in east-central China. Assuming similar differences for temperate and boreal plantations, if sustainable forestry practices were applied to all new forest plantation types in China, stored carbon could increase by 1,482.80 TgC in 2050. Such an increase would be equivalent to a yearly sequestration rate of 40.08 TgC yr⁻¹, offsetting 1.9% of China's annual emissions in 2010. More importantly, this C increase can be sustained in the long term through the maintenance of higher amounts of soil organic carbon and the production

  9. Metformin Increases Overall Survival in Patients with Diabetes Undergoing Surgery for Colorectal Cancer

    DEFF Research Database (Denmark)

    Fransgaard, Tina; Thygesen, Lau Caspar; Gögenur, Ismail

    2015-01-01

    BACKGROUND: Emerging evidence suggests that metformin decreases the risk of developing colorectal cancer in patients with diabetes, but only few studies have examined potential survival benefits after surgery for colorectal cancer (CRC). The purpose of the study was to examine the association......-Meier estimator and the Cox regression model adjusted for important clinical risk factors were used. RESULTS: A total of 30,493 patients were included in the study, of which 3391 were diagnosed with diabetes and 1962 were treated with metformin. The adjusted HR of all-cause mortality for the diabetes group was 1.......12 (1.06-1.18, p metformin-treated group compared with the insulin-treated group. CONCLUSIONS: A 12 % increase in all-cause mortality among patients with CRC and diabetes was found. Treatment...

  10. Haemodynamic unloading increases the survival and affects the differentiation of cardiac stem cells after implantation into an infarcted heart.

    Science.gov (United States)

    Kurazumi, Hiroshi; Li, Tao-Sheng; Takemoto, Yoshihiro; Suzuki, Ryo; Mikamo, Akihito; Guo, Chang-Ying; Murata, Tomoaki; Hamano, Kimikazu

    2014-06-01

    It has been anticipated that stem cell therapy is capable of repairing an injured heart but is currently limited by its marginal efficacy. We believe that mechanical stress due to haemodynamic loading may negate the therapeutic potency of stem cells and therefore investigated how haemodynamic unloading affects the survival and differentiation of stem cells after implantation into an infarcted heart. A left ventricular (LV) haemodynamic unloading model was implemented by heterotopic transplantation of an infarcted donor heart into another healthy mouse. An in situ infarcted heart with general haemodynamic loading was used as control. A total of 5 million cardiac stem cells expanded from green fluorescence protein (GFP)-transgenic mouse were intramyocardially implanted into the infarcted LVs of haemodynamically unloaded donor heart or general haemodynamic loaded heart. The survival and differentiation of the implanted cardiac stem cells were evaluated by histological analyses at 3 and 21 days after cell implantation (n = 5-6 in each time points per group). Compared with the general haemodynamic loading condition, haemodynamic unloading of the infarcted hearts significantly improved the survival, increased the proliferation and inhibited the apoptosis of cardiac stem cells at 21 days after cell implantation (P cells was much higher in the unloaded hearts than in the loaded hearts at 21 days after cell implantation, although the difference was not statistically significant (5.67 ± 5.10 vs 0.75 ± 0.50, P = 0.051). Among the surviving GFP(+) donor cells 21 days after implantation, the expressions of platelet endothelial cell adhesion molecule-1, smooth muscle actin and sarcomeric alpha actin were ~7, 38 and 27% in the loaded heart and ~19, 14 and 55% in the unloaded heart, respectively. Haemodynamic unloading favours the survival/engraftment of donor stem cells and affects their differentiation after implantation into an infarcted heart. Although further studies in a

  11. Brief overdose education can significantly increase accurate recognition of opioid overdose among heroin users.

    Science.gov (United States)

    Jones, Jermaine D; Roux, Perrine; Stancliff, Sharon; Matthews, William; Comer, Sandra D

    2014-01-01

    In an effort to increase effective intervention following opioid overdose, the New York State Department of Health (NYSDOH) has implemented programs where bystanders are given brief education in recognizing the signs of opioid overdose and how to provide intervention, including the use of naloxone. The current study sought to assess the ability of NYSDOH training to increase accurate identification of opioid and non-opioid overdose, and naloxone use among heroin users. Eighty-four participants completed a test on overdose knowledge comprised of 16 putative overdose scenarios. Forty-four individuals completed the questionnaire immediately prior to and following standard overdose prevention training. A control group (n=40), who opted out of training, completed the questionnaire just once. Overdose training significantly increased participants' ability to accurately identify opioid overdose (pnaloxone administration was indicated (poverdose or non-overdose situations where naloxone should not be administered. The data indicate that overdose prevention training improves participants' knowledge of opioid overdose and naloxone use, but naloxone may be administered in some situations where it is not warranted. Training curriculum could be improved by teaching individuals to recognize symptoms of non-opioid drug over-intoxication. Copyright © 2013 Elsevier B.V. All rights reserved.

  12. Type VI collagen increases cell survival and prevents anti-beta 1 integrin-mediated apoptosis.

    Science.gov (United States)

    Howell, S J; Doane, K J

    1998-05-25

    Cell-matrix interactions are important in the development of the avian cornea. Type VI collagen is present within the periocular mesenchyme prior to the migration of cells into the corneal stroma and is abundant in the mature stroma. Whether the interaction of cells with type VI collagen is essential for cellular survival in the cornea is not known. In the present study, we examined the interaction of corneal cells with type VI collagen in vitro to determine if it can increase cell proliferation and decrease apoptosis. In vivo analysis demonstrated that apoptosis occurs in the periocular region during early stages of avian corneal development, but in fully mature corneas apoptosis only occurs in the corneal epithelium and not in the stroma. In vitro analysis examined the importance of beta 1 integrin interactions with type VI collagen in mature corneal fibroblasts and the precursor cells. Using an anti-beta 1 integrin blocking antibody, CSAT, integrin/matrix interactions were disrupted. Results indicated that viability of both corneal fibroblasts and periocular mesenchyme cells was greater on type VI collagen than on type I collagen or BSA-blocked glass. In addition, less apoptosis was observed for both cell types on type VI collagen when beta 1 integrin--matrix interactions were disrupted. These data indicated that these cells require intact beta 1 interactions with type I collagen and with BSA-coated glass controls to remain viable. Thus, type VI collagen may play a role in the rescue of corneal cells from anti-beta 1 integrin-induced apoptosis by increasing cell survival, probably via a non-beta 1 integrin-dependent mechanism.

  13. Intermittent hypoxia selects for genotypes and phenotypes that increase survival, invasion, and therapy resistance.

    Directory of Open Access Journals (Sweden)

    Daniel Verduzco

    Full Text Available Hypoxia in tumors correlates with greater risk of metastases, increased invasiveness, and resistance to systemic and radiation therapy. The evolutionary dynamics that links specific adaptations to hypoxia with these observed tumor properties have not been well investigated. While some tumor populations may experience fixed hypoxia, cyclical and stochastic transitions from normoxia to hypoxia are commonly observed in vivo. Although some phenotypic adaptations to this cyclic hypoxia are likely reversible, we hypothesize that some adaptations may become fixed through mutations promoted by hypoxia-induced genomic instability. Here we seek to identify genetic alterations and corresponding stable phenotypes that emerge following cyclic hypoxia. Although these changes may originate as adaptations to this specific environmental stress, their fixation in the tumor genome may result in their observation in tumors from regions of normoxia, a condition known as pseudohypoxia. We exposed several epithelial cell lines to 50 cycles of hypoxia-normoxia, followed by culture in normoxia over a period of several months. Molecular analyses demonstrated permanent changes in expression of several oncogenes and tumor-suppressors, including p53, E-cadherin, and Hif-1α. These changes were associated with increased resistance to multiple cytotoxins, increased survival in hypoxia and increased anchorage-independent growth. These results suggest cycles of hypoxia encountered in early cancers can select for specific and stable genotypic and phenotypic properties that persist even in normoxic conditions, which may promote tumor progression and resistance to therapy.

  14. Application of Bioorganic Fertilizer Significantly Increased Apple Yields and Shaped Bacterial Community Structure in Orchard Soil.

    Science.gov (United States)

    Wang, Lei; Li, Jing; Yang, Fang; E, Yaoyao; Raza, Waseem; Huang, Qiwei; Shen, Qirong

    2017-02-01

    and Rhodospirillaceae, were found to be the significantly increased by the BOF addition and the genus Lysobacter may identify members of this group effective in biological control-based plant disease management and the members of family Rhodospirillaceae had an important role in fixing molecular nitrogen. These results strengthen the understanding of responses to the BOF and possible interactions within bacterial communities in soil that can be associated with disease suppression and the accumulation of carbon and nitrogen. The increase of apple yields after the application of BOF might be attributed to the fact that the application of BOF increased SOM, and soil total nitrogen, and changed the bacterial community by enriching Rhodospirillaceae, Alphaprotreobateria, and Proteobacteria.

  15. Dietary Curcumin Increases Antioxidant Defenses in Lung, Ameliorates Radiation-Induced Pulmonary Fibrosis, and Improves Survival in Mice

    Science.gov (United States)

    Lee, James C.; Kinniry, Paul A.; Arguiri, Evguenia; Serota, Matthew; Kanterakis, Stathis; Chatterjee, Shampa; Solomides, Charalambos C.; Javvadi, Prashanthi; Koumenis, Constantinos; Cengel, Keith A.; Christofidou-Solomidou, Melpo

    2010-01-01

    The effectiveness of lung radiotherapy is limited by radiation tolerance of normal tissues and by the intrinsic radiosensitivity of lung cancer cells. The chemopreventive agent curcumin has known antioxidant and tumor cell radiosensitizing properties. Its usefulness in preventing radiation-induced pneumonopathy has not been tested previously. We evaluated dietary curcumin in radiation-induced pneumonopathy and lung tumor regression in a murine model. Mice were given 1%or 5%(w/w) dietary curcumin or control diet prior to irradiation and for the duration of the experiment. Lungs were evaluated at 3 weeks after irradiation for acute lung injury and inflammation by evaluating bronchoalveolar lavage (BAL) fluid content for proteins, neutrophils and at 4 months for pulmonary fibrosis. In a separate series of experiments, an orthotopic model of lung cancer using intravenously injected Lewis lung carcinoma (LLC) cells was used to exclude possible tumor radioprotection by dietary curcumin. In vitro, curcumin boosted antioxidant defenses by increasing heme oxygenase 1 (HO-1) levels in primary lung endothelial and fibroblast cells and blocked radiation-induced generation of reactive oxygen species (ROS). Dietary curcumin significantly increased HO-1 in lungs as early as after 1 week of feeding, coinciding with a steady-state level of curcumin in plasma. Although both 1% and 5% w/w dietary curcumin exerted physiological changes in lung tissues by significantly decreasing LPS-induced TNF-α production in lungs, only 5%dietary curcumin significantly improved survival of mice after irradiation and decreased radiation-induced lung fibrosis. Importantly, dietary curcumin did not protect LLC pulmonary metastases from radiation killing. Thus dietary curcumin ameliorates radiation-induced pulmonary fibrosis and increases mouse survival while not impairing tumor cell killing by radiation. PMID:20426658

  16. Biofilms Formed by Gram-Negative Bacteria Undergo Increased Lipid A Palmitoylation, Enhancing In Vivo Survival

    Science.gov (United States)

    Chalabaev, Sabina; Chauhan, Ashwini; Novikov, Alexey; Iyer, Pavithra; Szczesny, Magdalena; Beloin, Christophe; Caroff, Martine

    2014-01-01

    ABSTRACT Bacterial biofilm communities are associated with profound physiological changes that lead to novel properties compared to the properties of individual (planktonic) bacteria. The study of biofilm-associated phenotypes is an essential step toward control of deleterious effects of pathogenic biofilms. Here we investigated lipopolysaccharide (LPS) structural modifications in Escherichia coli biofilm bacteria, and we showed that all tested commensal and pathogenic E. coli biofilm bacteria display LPS modifications corresponding to an increased level of incorporation of palmitate acyl chain (palmitoylation) into lipid A compared to planktonic bacteria. Genetic analysis showed that lipid A palmitoylation in biofilms is mediated by the PagP enzyme, which is regulated by the histone-like protein repressor H-NS and the SlyA regulator. While lipid A palmitoylation does not influence bacterial adhesion, it weakens inflammatory response and enhances resistance to some antimicrobial peptides. Moreover, we showed that lipid A palmitoylation increases in vivo survival of biofilm bacteria in a clinically relevant model of catheter infection, potentially contributing to biofilm tolerance to host immune defenses. The widespread occurrence of increased lipid A palmitoylation in biofilms formed by all tested bacteria suggests that it constitutes a new biofilm-associated phenotype in Gram-negative bacteria. PMID:25139899

  17. Deletion of the DNA Ligase IV Gene in Candida glabrata Significantly Increases Gene-Targeting Efficiency.

    Science.gov (United States)

    Cen, Yuke; Fiori, Alessandro; Van Dijck, Patrick

    2015-08-01

    Candida glabrata is reported as the second most prevalent human opportunistic fungal pathogen in the United States. Over the last decades, its incidence increased, whereas that of Candida albicans decreased slightly. One of the main reasons for this shift is attributed to the inherent tolerance of C. glabrata toward the commonly used azole antifungal drugs. Despite a close phylogenetic distance to Saccharomyces cerevisiae, homologous recombination works with poor efficiency in C. glabrata compared to baker's yeast, in fact limiting targeted genetic alterations of the pathogen's genome. It has been shown that nonhomologous DNA end joining is dominant over specific gene targeting in C. glabrata. To improve the homologous recombination efficiency, we have generated a strain in which the LIG4 gene has been deleted, which resulted in a significant increase in correct gene targeting. The very specific function of Lig4 in mediating nonhomologous end joining is the reason for the absence of clear side effects, some of which affect the ku80 mutant, another mutant with reduced nonhomologous end joining. We also generated a LIG4 reintegration cassette. Our results show that the lig4 mutant strain may be a valuable tool for the C. glabrata research community. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  18. [Significant increase in the colonisation of Staphylococcus aureus among medical students during their hospital practices].

    Science.gov (United States)

    Rodríguez-Avial, Carmen; Alvarez-Novoa, Andrea; Losa, Azucena; Picazo, Juan J

    2013-10-01

    Staphylococcus aureus is a pathogen of major concern. The emergence of methicillin-resistant S. aureus (MRSA) has increasingly complicated the therapeutic approach of hospital-acquired infections. Surveillance of MRSA and control measures must be implemented in different healthcare settings, including screening programs for carriers. Our first aim was to determine the prevalence of methicillin-susceptible S. aureus (MSSA) and MRSA nasal carriage in medical students from the Clínico San Carlos Hospital (Madrid). As the MRSA carrier rate in healthcare workers is higher than in the general population, we hypothesised that carrier rate could be increased during their clinical practice in their last three years. We performed an epidemiologic al study of the prevalence of S. aureus colonisation among a group of medical students, who were sampled in 2008 in their third-year, and in 2012 when this class was in its sixth year. We have found a significant increase in MSSA carriage, from 27% to 46%. There were no MRSA colonisations in the third-year, but one was found in the sixth-year group. The large majority of strains (89%) of strains were resistant to penicillin, and 27% to erythromycin and clindamycin. As 19 coagulase-negative Staphylococcus MR were also identified, a horizontal transfer of genes, such as mecA gene to S. aureus, could have occurred. Medical students are both, at risk for acquiring, and a potential source of nosocomial pathogens, mainly MSSA. Therefore, they should take special care for hygienic precautions, such as frequent and proper hand washing, while working in the hospital. Copyright © 2012 Elsevier España, S.L. All rights reserved.

  19. Minocycline prevents cerebral malaria, confers neuroprotection and increases survivability of mice during Plasmodium berghei ANKA infection.

    Science.gov (United States)

    Apoorv, Thittayil Suresh; Babu, Phanithi Prakash

    2017-02-01

    Cerebral malaria (CM) is a neurological complication arising due to Plasmodium falciparum or Plasmodium vivax infection. Minocycline, a semi-synthetic tetracycline, has been earlier reported to have a neuroprotective role in several neurodegenerative diseases. In this study, we investigated the effect of minocycline treatment on the survivability of mice during experimental cerebral malaria (ECM). The currently accepted mouse model, C57BL/6 mice infected with Plasmodium berghei ANKA, was used for the study. Infected mice were treated with an intra-peritoneal dose of minocycline hydrochloride, 45mg/kg daily for ten days that led to parasite clearance in blood, brain, liver and spleen on 7th day post-infection; and the mice survived until experiment ended (90days) without parasite recrudescence. Evans blue extravasation assay showed that blood-brain barrier integrity was maintained by minocycline. The tumor necrosis factor-alpha protein level and caspase activity, which is related to CM pathogenesis, was significantly reduced in the minocycline-treated group. Fluoro-Jade® C and hematoxylin-eosin staining of the brains of minocycline group revealed a decrease in degenerating neurons and absence of hemorrhages respectively. Minocycline treatment led to decrease in gene expressions of inflammatory mediators like interferon-gamma, CXCL10, CCL5, CCL2; receptors CXCR3 and CCR2; and hence decrease in T-cell-mediated cerebral inflammation. We also proved that this reduction in gene expressions is irrespective of the anti-parasitic property of minocycline. The distinct ability of minocycline to modulate gene expressions of CXCL10 and CXCR3 makes it effective than doxycycline, a tetracycline used as chemoprophylaxis. Our study shows that minocycline is highly effective in conferring neuroprotection during ECM. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Cell-delivered magnetic nanoparticles caused hyperthermia-mediated increased survival in a murine pancreatic cancer model.

    Science.gov (United States)

    Basel, Matthew T; Balivada, Sivasai; Wang, Hongwang; Shrestha, Tej B; Seo, Gwi Moon; Pyle, Marla; Abayaweera, Gayani; Dani, Raj; Koper, Olga B; Tamura, Masaaki; Chikan, Viktor; Bossmann, Stefan H; Troyer, Deryl L

    2012-01-01

    Using magnetic nanoparticles to absorb alternating magnetic field energy as a method of generating localized hyperthermia has been shown to be a potential cancer treatment. This report demonstrates a system that uses tumor homing cells to actively carry iron/iron oxide nanoparticles into tumor tissue for alternating magnetic field treatment. Paramagnetic iron/ iron oxide nanoparticles were synthesized and loaded into RAW264.7 cells (mouse monocyte/ macrophage-like cells), which have been shown to be tumor homing cells. A murine model of disseminated peritoneal pancreatic cancer was then generated by intraperitoneal injection of Pan02 cells. After tumor development, monocyte/macrophage-like cells loaded with iron/ iron oxide nanoparticles were injected intraperitoneally and allowed to migrate into the tumor. Three days after injection, mice were exposed to an alternating magnetic field for 20 minutes to cause the cell-delivered nanoparticles to generate heat. This treatment regimen was repeated three times. A survival study demonstrated that this system can significantly increase survival in a murine pancreatic cancer model, with an average post-tumor insertion life expectancy increase of 31%. This system has the potential to become a useful method for specifically and actively delivering nanoparticles for local hyperthermia treatment of cancer.

  1. Increased incidence of cerebral metastases in sarcoma patients with prolonged survival from chemotherapy. Report of cases of leiomysarcoma and chondrosarcoma.

    Science.gov (United States)

    Gercovich, F G; Luna, M A; Gottlieb, J A

    1975-11-01

    Soft tissue and bony sarcomas rarely metastasize to the central nervous system, particularly to the cerebral hemispheres. In 456 patients with metastatic sarcoma, only 6 (1.3%) had cerebral metastases documented by brain scan at the time of referral for chemotherapy. Adriamycin-containing combination chemotherapeutic regimens have led to a significant increase in the median survival of patients from the start of chemotherapy (18 + months for responders compared, to 7 months in nonresponders). Of 14 patients relapsing after a response or stabilization of disease of 6 months or greater, the cause of relapse was the development of cerebral metastases in 5 (36%). Two of these cases, one a patient with leiomyosarcoma and one with chondrosarcoma, were documented by autopsy and are reported in detail because of their rarity in the medical literature. Although the numbers are small, the increased incidence of cerebral metastases in the group relapsing after a lengthy response suggests that improved chemotherapy for sarcomas resulting in improved survival may be chaning the pattern of metastatic disease, and may require new the;apeutic approaches.

  2. Maternal investment, sibling competition, and offspring survival with increasing litter size and parity in pigs (Sus scrofa).

    Science.gov (United States)

    Andersen, Inger Lise; Nævdal, Eric; Bøe, Knut Egil

    2011-06-01

    The aim of this study was to examine the effects of litter size and parity on sibling competition, piglet survival, and weight gain. It was predicted that competition for teats would increase with increasing litter size, resulting in a higher mortality due to maternal infanticide (i.e., crushing) and starvation, thus keeping the number of surviving piglets constant. We predicted negative effects on weight gain with increasing litter size. Based on maternal investment theory, we also predicted that piglet mortality would be higher for litters born late in a sow's life and thus that the number of surviving piglets would be higher in early litters. As predicted, piglet mortality increased with increasing litter size both due to an increased proportion of crushed piglets, where most of them failed in the teat competition, and due to starvation caused by increased sibling competition, resulting in a constant number of survivors. Piglet weight at day 1 and growth until weaning also declined with increasing litter size. Sows in parity four had higher piglet mortality due to starvation, but the number of surviving piglets was not affected by parity. In conclusion, piglet mortality caused by maternal crushing of piglets, many of which had no teat success, and starvation caused by sibling competition, increased with increasing litter size for most sow parities. The constant number of surviving piglets at the time of weaning suggests that 10 to 11 piglets could be close to the upper limit that the domestic sow is capable of taking care of.

  3. Effect of mitochondrially targeted carboxy proxyl nitroxide on Akt-mediated survival in Daudi cells: Significance of a dual mode of action.

    Directory of Open Access Journals (Sweden)

    Gokul Variar

    Full Text Available Vicious cycles of mutations and reactive oxygen species (ROS generation contribute to cancer progression. The use of antioxidants to inhibit ROS generation promotes cytostasis by affecting the mutation cycle and ROS-dependent survival signaling. However, cancer cells select mutations to elevate ROS albeit maintaining mitochondrial hyperpolarization (Δψm, even under hypoxia. From this perspective, the use of drugs that disrupt both ROS generation and Δψm is a viable anticancer strategy. Hence, we studied the effects of mitochondrially targeted carboxy proxyl nitroxide (Mito-CP and a control ten carbon TPP moiety (Dec-TPP+ in the human Burkitt lymphoma cell line (Daudi and normal peripheral blood mononuclear cells under hypoxia and normoxia. We found preferential localization, Δψm and adenosine triphosphate loss, and significant cytotoxicity by Mito-CP in Daudi cells alone. Interestingly, ROS levels were decreased and maintained in hypoxic and normoxic cancer cells, respectively, by Mito-CP but not Dec-TPP+, therefore preventing any adaptive signaling. Moreover, dual effects on mitochondrial bioenergetics and ROS by Mito-CP curtailed the cancer survival via Akt inhibition, AMPK-HIF-1α activation and promoted apoptosis via increased BCL2-associated X protein and poly (ADP-ribose polymerase expression. This dual mode of action by Mito-CP provides a better explanation of the application of antioxidants with specific relevance to cancerous transformation and adaptations in the Daudi cell line.

  4. Biofilms formed by gram-negative bacteria undergo increased lipid a palmitoylation, enhancing in vivo survival.

    Science.gov (United States)

    Chalabaev, Sabina; Chauhan, Ashwini; Novikov, Alexey; Iyer, Pavithra; Szczesny, Magdalena; Beloin, Christophe; Caroff, Martine; Ghigo, Jean-Marc

    2014-08-19

    Bacterial biofilm communities are associated with profound physiological changes that lead to novel properties compared to the properties of individual (planktonic) bacteria. The study of biofilm-associated phenotypes is an essential step toward control of deleterious effects of pathogenic biofilms. Here we investigated lipopolysaccharide (LPS) structural modifications in Escherichia coli biofilm bacteria, and we showed that all tested commensal and pathogenic E. coli biofilm bacteria display LPS modifications corresponding to an increased level of incorporation of palmitate acyl chain (palmitoylation) into lipid A compared to planktonic bacteria. Genetic analysis showed that lipid A palmitoylation in biofilms is mediated by the PagP enzyme, which is regulated by the histone-like protein repressor H-NS and the SlyA regulator. While lipid A palmitoylation does not influence bacterial adhesion, it weakens inflammatory response and enhances resistance to some antimicrobial peptides. Moreover, we showed that lipid A palmitoylation increases in vivo survival of biofilm bacteria in a clinically relevant model of catheter infection, potentially contributing to biofilm tolerance to host immune defenses. The widespread occurrence of increased lipid A palmitoylation in biofilms formed by all tested bacteria suggests that it constitutes a new biofilm-associated phenotype in Gram-negative bacteria. Bacterial communities called biofilms display characteristic properties compared to isolated (planktonic) bacteria, suggesting that some molecules could be more particularly produced under biofilm conditions. We investigated biofilm-associated modifications occurring in the lipopolysaccharide (LPS), a major component of all Gram-negative bacterial outer membrane. We showed that all tested commensal and pathogenic biofilm bacteria display high incorporation of a palmitate acyl chain into the lipid A part of LPS. This lipid A palmitoylation is mediated by the PagP enzyme, whose

  5. Increased immunogenicity of surviving tumor cells enables cooperation between liposomal doxorubicin and IL-18

    Directory of Open Access Journals (Sweden)

    Danet-Desnoyers Gwen-äel

    2009-12-01

    Full Text Available Abstract Background Liposomal doxorubicin (Doxil is a cytotoxic chemotherapy drug with a favorable hematologic toxicity profile. Its active drug, doxorubicin, has interesting immunomodulatory properties. Here, the effects of Doxil on surviving tumor cell immunophenotype were investigated. Methods Using ID8 murine ovarian cancer cells, the immunomodulatory effects of Doxil were studied by measuring its impact on ovarian cancer cell expression of MHC class-I and Fas, and susceptibility to immune attack in vitro. To evaluate the ability of Doxil to cooperate with cancer immunotherapy, the interaction between Doxil and Interleukin 18 (IL-18, a pleiotropic immunostimulatory cytokine, was investigated in vivo in mice bearing ID8-Vegf tumors. Results While Doxil killed ID8 tumor cells in a dose-dependent manner, tumor cells escaping Doxil-induced apoptosis upregulated surface expression of MHC-I and Fas, and were sensitized to CTL killing and Fas-mediated death in vitro. We therefore tested the hypothesis that the combination of immunotherapy with Doxil provides positive interactions. Combination IL-18 and Doxil significantly suppressed tumor growth compared with either monotherapy in vivo and uniquely resulted in complete tumor regression and long term antitumor protection in a significant proportion of mice. Conclusion These data demonstrate that Doxil favorably changes the immunophenotype of a large fraction of the tumor that escapes direct killing thus creating an opportunity to expand tumor killing by immunotherapy, which can be capitalized through addition of IL-18 in vivo.

  6. Increased Fracture Collapse after Intertrochanteric Fractures Treated by the Dynamic Hip Screw Adversely Affects Walking Ability but Not Survival.

    Science.gov (United States)

    Fang, Christian; Gudushauri, Paata; Wong, Tak-Man; Lau, Tak-Wing; Pun, Terence; Leung, Frankie

    2016-01-01

    In osteoporotic hip fractures, fracture collapse is deliberately allowed by commonly used implants to improve dynamic contact and healing. The muscle lever arm is, however, compromised by shortening. We evaluated a cohort of 361 patients with AO/OTA 31.A1 or 31.A2 intertrochanteric fracture treated by the dynamic hip screw (DHS) who had a minimal follow-up of 3 months and an average follow-up of 14.6 months and long term survival data. The amount of fracture collapse and shortening due to sliding of the DHS was determined at the latest follow-up and graded as minimal (2 cm). With increased severity of collapse, more patients were unable to maintain their premorbid walking function (minimal collapse = 34.2%, moderate = 33.3%, severe = 62.8%, and p = 0.028). Based on ordinal regression of risk factors, increased fracture collapse was significantly and independently related to increasing age (p = 0.037), female sex (p = 0.024), A2 fracture class (p = 0.010), increased operative duration (p = 0.011), poor reduction quality (p = 0.000), and suboptimal tip-apex distance of >25 mm (p = 0.050). Patients who had better outcome in terms of walking function were independently predicted by younger age (p = 0.036), higher MMSE marks (p = 0.000), higher MBI marks (p = 0.010), better premorbid walking status (p = 0.000), less fracture collapse (p = 0.011), and optimal lag screw position in centre-centre or centre-inferior position (p = 0.020). According to Kaplan-Meier analysis, fracture collapse had no association with mortality from 2.4 to 7.6 years after surgery. In conclusion, increased fracture collapse after fixation of geriatric intertrochanteric fractures adversely affected walking but not survival.

  7. Defense against dermal exposures is only skin deep: significantly increased penetration through slightly damaged skin.

    Science.gov (United States)

    Nielsen, Jesper Bo; Nielsen, Flemming; Sørensen, Jens Ahm

    2007-11-01

    The OECD guideline for studies on percutaneous penetration to be used in hazard and risk evaluations prescribes experimental conditions with optimal barrier integrity of the skin, which in many occupational settings probably is not true. Thus, workers may have compromised skin due to chemical or mechanical damage, due to different medical conditions (eczema, dermatitis, skin irritation) or related to occupational scenarios involving prolonged wet work. The present study used the OECD guideline procedures to study the in vitro percutaneous penetration through human skin of a number of model substances (glyphosat, caffeine, benzoic acid, malathion) covering a range of solubilities. Further, we studied the extent to which a slightly damaged skin would change the rate, the amount absorbed during dermal exposure and the distribution of chemical deposition between epidermis and dermis. The present study demonstrates that a limited damage to the skin significantly increases the permeability coefficient (K (p)) as well as total percutaneous penetration of chemicals, and most significantly for those compounds that due to their physicochemical characteristics (the most hydrophilic as well as the most lipophilic) have low penetration rates through intact skin. The present experiment not only confirms the proportionality between lipophilicity and potential for percutaneous penetration, but also illustrates that at a certain degree of lipophilicity of a model compound, the different skin compartments become more attractive for temporary deposition of model compounds. Moreover, a clear change from epidermal deposition towards a dominating dermis deposition of chemicals temporarily deposited within the skin is seen following damage to the skin barrier. Thus, the distribution of chemicals within the skin compartments is affected by the physicochemical characteristics of the chemicals as well as by the integrity of the skin. This observation may have implications when evaluating

  8. Improved bowel preparation increases polyp detection and unmasks significant polyp miss rate

    Science.gov (United States)

    Papanikolaou, Ioannis S; Sioulas, Athanasios D; Magdalinos, Nektarios; Beintaris, Iosif; Lazaridis, Lazaros-Dimitrios; Polymeros, Dimitrios; Malli, Chrysoula; Dimitriadis, George D; Triantafyllou, Konstantinos

    2015-01-01

    AIM: To retrospectively compare previous-day vs split-dose preparation in terms of bowel cleanliness and polyp detection in patients referred for polypectomy. METHODS: Fifty patients underwent two colonoscopies: one diagnostic in a private clinic and a second for polypectomy in a University Hospital. The latter procedures were performed within 12 wk of the index ones. Examinations were accomplished by two experienced endoscopists, different in each facility. Twenty-seven patients underwent screening/surveillance colonoscopy, while the rest were symptomatic. Previous day bowel preparation was utilized initially and split-dose for polypectomy. Colon cleansing was evaluated using the Aronchick scale. We measured the number of detected polyps, and the polyp miss rates per-polyp. RESULTS: Excellent/good preparation was reported in 38 cases with previous-day preparation (76%) vs 46 with split-dose (92%), respectively (P = 0.03). One hundred and twenty-six polyps were detected initially and 169 subsequently (P < 0.0001); 88 vs 126 polyps were diminutive (P < 0.0001), 25 vs 29 small (P = 0.048) and 13 vs 14 equal or larger than 10 mm. The miss rates for total, diminutive, small and large polyps were 25.4%, 30.1%, 13.7% and 6.6%, respectively. Multivariate analysis revealed that split-dose preparation was significantly associated (OR, P) with increased number of polyps detected overall (0.869, P < 0.001), in the right (0.418, P = 0.008) and in the left colon (0.452, P = 0.02). CONCLUSION: Split-dose preparation improved colon cleansing, enhanced polyp detection and unmasked significant polyp miss rates. PMID:26488024

  9. Effect of sludge retention on UF membrane fouling: The significance of sludge crystallization and EPS increase.

    Science.gov (United States)

    Yu, Wenzheng; Graham, Nigel; Yang, Yunjia; Zhou, Zhiqi; Campos, Luiza C

    2015-10-15

    This paper concerns a previously unreported mechanism of membrane ultrafiltration (UF) fouling when a UF process with coagulation pre-treatment is used in drinking water treatment. The significance of settled coagulant solids (sludge) with different age within the membrane tank on UF fouling has been investigated at laboratory-scale, using model micro-polluted surface water. The process of floc crystallization and increasing bacterial EPS with solids (sludge) retention time may be detrimental to UF operation by causing an increased rate of membrane fouling. In this study the performance of two alum pre-treated hollow-fibre UF units, operated in parallel but with different settled sludge retention times (1 and 7 days), was compared. The results showed that over 34 days of operation the extent of reversible and irreversible fouling was much greater for the 7-day solids retention time. This was attributed to the greater extent of bacterial activity and the presence of Al-nanoparticles, arising from sludge crystallization, at the longer retention time. In particular, greater quantities of organic matter, particularly EPS (proteins and polysaccharides), were found in the UF cake layer and pores for the 7-day retention time. The addition of chlorine later in the membrane run substantially reduced the rate of membrane fouling for both sludge retention times, and this corresponded to reduced quantities of organic substances, including EPS, in the cake layer and pores of both membranes. The results suggest that bacterial activity (and EPS production) is more important than the production of Al-nanoparticles from solids crystallization in causing membrane fouling. However, it is likely that both phenomena are interactive and possibly synergistic. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Significantly increased risk of carotid atherosclerosis with arsenic exposure and polymorphisms in arsenic metabolism genes

    Energy Technology Data Exchange (ETDEWEB)

    Hsieh, Yi-Chen [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wusing St., Taipei 11031, Taiwan (China); Lien, Li-Ming [Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); School of Medicine, Taipei Medical University, Taipei, Taiwan (China); Department of Neurology, Shin Kong WHS Memorial Hospital, Taipei, Taiwan (China); Chung, Wen-Ting [Department of Neurology, Wanfang Hospital, Taipei Medical University, Taipei, Taiwan (China); Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei, Taiwan (China); Hsieh, Fang-I; Hsieh, Pei-Fan [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wusing St., Taipei 11031, Taiwan (China); Wu, Meei-Maan [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wusing St., Taipei 11031, Taiwan (China); Graduate Institute of Basic Medicine, College of Medicine, Fu-Jen Catholic University, Taipei, Taiwan (China); Tseng, Hung-Pin [Department of Neurology, Lotung Poh-Ai Hospital, I-Lan, Taiwan (China); Chiou, Hung-Yi, E-mail: hychiou@tmu.edu.tw [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wusing St., Taipei 11031, Taiwan (China); Chen, Chien-Jen [Genomics Research Center, Academia Sinica, Taipei, Taiwan (China)

    2011-08-15

    Individual susceptibility to arsenic-induced carotid atherosclerosis might be associated with genetic variations in arsenic metabolism. The purpose of this study is to explore the interaction effect on risk of carotid atherosclerosis between arsenic exposure and risk genotypes of purine nucleoside phosphorylase (PNP), arsenic (+3) methyltransferase (As3MT), and glutathione S-transferase omega 1 (GSTO1) and omega 2 (GSTO2). A community-based case-control study was conducted in northeastern Taiwan to investigate the arsenic metabolic-related genetic susceptibility to carotid atherosclerosis. In total, 863 subjects, who had been genotyped and for whom the severity of carotid atherosclerosis had been determined, were included in the present study. Individual well water was collected and arsenic concentration determined using hydride generation combined with flame atomic absorption spectrometry. The result showed that a significant dose-response trend (P=0.04) of carotid atherosclerosis risk associated with increasing arsenic concentration. Non-significant association between genetic polymorphisms of PNP Gly51Ser, Pro57Pro, As3MT Met287Thr, GSTO1 Ala140Asp, and GSTO2 A-183G and the risk for development of carotid atherosclerosis were observed. However, the significant interaction effect on carotid atherosclerosis risk was found for arsenic exposure (>50 {mu}g/l) and the haplotypes of PNP (p=0.0115). A marked elevated risk of carotid atherosclerosis was observed in subjects with arsenic exposure of >50 {mu}g/l in drinking water and those who carried the PNP A-T haplotype and at least either of the As3MT risk polymorphism or GSTO risk haplotypes (OR, 6.43; 95% CI, 1.79-23.19). In conclusion, arsenic metabolic genes, PNP, As3MT, and GSTO, may exacerbate the formation of atherosclerosis in individuals with high levels of arsenic concentration in well water (>50 {mu}g/l). - Highlights: {yields}Arsenic metabolic genes might be associated with carotid atherosclerosis. {yields

  11. Greater mass increases annual survival of Prothonotary Warblers wintering in northeastern Costa Rica

    Science.gov (United States)

    Jared D. Wolfe; Matthew D. Johnson; C. John Ralph

    2013-01-01

    Estimates of survival of nearctic-neotropic migrants have broadened our understanding of life-history variation across taxa and latitudes. Despite the importance of assessing migrants' survival through all phases of their life-cycle, data from their tropical winter ranges are few. In this study we used 14 years of data on captured birds to quantify the influence...

  12. Templated assembly of photoswitches significantly increases the energy-storage capacity of solar thermal fuels.

    Science.gov (United States)

    Kucharski, Timothy J; Ferralis, Nicola; Kolpak, Alexie M; Zheng, Jennie O; Nocera, Daniel G; Grossman, Jeffrey C

    2014-05-01

    Large-scale utilization of solar-energy resources will require considerable advances in energy-storage technologies to meet ever-increasing global energy demands. Other than liquid fuels, existing energy-storage materials do not provide the requisite combination of high energy density, high stability, easy handling, transportability and low cost. New hybrid solar thermal fuels, composed of photoswitchable molecules on rigid, low-mass nanostructures, transcend the physical limitations of molecular solar thermal fuels by introducing local sterically constrained environments in which interactions between chromophores can be tuned. We demonstrate this principle of a hybrid solar thermal fuel using azobenzene-functionalized carbon nanotubes. We show that, on composite bundling, the amount of energy stored per azobenzene more than doubles from 58 to 120 kJ mol(-1), and the material also maintains robust cyclability and stability. Our results demonstrate that solar thermal fuels composed of molecule-nanostructure hybrids can exhibit significantly enhanced energy-storage capabilities through the generation of template-enforced steric strain.

  13. Templated assembly of photoswitches significantly increases the energy-storage capacity of solar thermal fuels

    Science.gov (United States)

    Kucharski, Timothy J.; Ferralis, Nicola; Kolpak, Alexie M.; Zheng, Jennie O.; Nocera, Daniel G.; Grossman, Jeffrey C.

    2014-05-01

    Large-scale utilization of solar-energy resources will require considerable advances in energy-storage technologies to meet ever-increasing global energy demands. Other than liquid fuels, existing energy-storage materials do not provide the requisite combination of high energy density, high stability, easy handling, transportability and low cost. New hybrid solar thermal fuels, composed of photoswitchable molecules on rigid, low-mass nanostructures, transcend the physical limitations of molecular solar thermal fuels by introducing local sterically constrained environments in which interactions between chromophores can be tuned. We demonstrate this principle of a hybrid solar thermal fuel using azobenzene-functionalized carbon nanotubes. We show that, on composite bundling, the amount of energy stored per azobenzene more than doubles from 58 to 120 kJ mol-1, and the material also maintains robust cyclability and stability. Our results demonstrate that solar thermal fuels composed of molecule-nanostructure hybrids can exhibit significantly enhanced energy-storage capabilities through the generation of template-enforced steric strain.

  14. Increased Mortality in Diabetic Foot Ulcer Patients: The Significance of Ulcer Type.

    Science.gov (United States)

    Chammas, N K; Hill, R L R; Edmonds, M E

    2016-01-01

    Diabetic foot ulcer (DFU) patients have a greater than twofold increase in mortality compared with nonulcerated diabetic patients. We investigated (a) cause of death in DFU patients, (b) age at death, and (c) relationship between cause of death and ulcer type. This was an eleven-year retrospective study on DFU patients who attended King's College Hospital Foot Clinic and subsequently died. A control group of nonulcerated diabetic patients was matched for age and type of diabetes mellitus. The cause of death was identified from death certificates (DC) and postmortem (PM) examinations. There were 243 DFU patient deaths during this period. Ischaemic heart disease (IHD) was the major cause of death in 62.5% on PM compared to 45.7% on DC. Mean age at death from IHD on PM was 5 years lower in DFU patients compared to controls (68.2 ± 8.7 years versus 73.1 ± 8.0 years, P = 0.015). IHD as a cause of death at PM was significantly linked to neuropathic foot ulcers (OR 3.064, 95% CI 1.003-9.366, and P = 0.049). Conclusions. IHD is the major cause of premature mortality in DFU patients with the neuropathic foot ulcer patients being at a greater risk.

  15. Offspring schooling associated with increased parental survival in rural KwaZulu-Natal, South Africa.

    Science.gov (United States)

    De Neve, Jan-Walter; Harling, Guy

    2017-03-01

    Investing in offspring's human capital has been suggested as an effective strategy for parents to improve their living conditions at older ages. A few studies have assessed the role of children's schooling in parental survival in high-income countries, but none have considered lower-resource settings with limited public wealth transfers and high adult mortality. We followed 17,789 parents between January 2003 and August 2015 in a large population-based open cohort in rural KwaZulu-Natal, South Africa. We used Cox proportional hazards models to investigate the association between offspring's schooling and time to parental death. We assessed the association separately by parental sex and for four cause of death groups. A one year increase in offspring's schooling attainment was associated with a 5% decline in the hazard of maternal death (adjusted Hazard Ratio [aHR]: 0.95, 95%CI: 0.94-0.97) and a 6% decline in the hazard of paternal death (aHR: 0.94, 95%CI: 0.92-0.96), adjusting for a wide range of demographic and socio-economic variables of the parent and their children. Among mothers, the association was strongest for communicable, maternal, perinatal and nutritional conditions (aHR: 0.87, 95%CI: 0.82-0.92) and AIDS and tuberculosis (aHR: 0.92, 95%CI: 0.89-0.96), and weakest for injuries. Among fathers, the association was strongest for injuries (aHR: 0.87, 95%CI: 0.79-0.95) and AIDS and tuberculosis (aHR: 0.92, 95%CI: 0.89-0.96), and weakest for non-communicable diseases. Higher levels of schooling in offspring are associated with increased parental survival in rural South Africa, particularly for mothers at risk of communicable disease mortality and fathers at risk of injury mortality. Offspring's human capital may be an important factor for health disparities, particularly in lower-resource settings. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  16. I171V germline mutation in the NBS1 gene significantly increases risk of breast cancer.

    Science.gov (United States)

    Roznowski, Krzysztof; Januszkiewicz-Lewandowska, Danuta; Mosor, Maria; Pernak, Monika; Litwiniuk, Maria; Nowak, Jerzy

    2008-07-01

    Nijmegen Breakage Syndrome (NBS) is a rare autosomal, recessive disease caused by homozygous mutations in the NBS1 gene. The most common deletion of 5 bp (657del5) in exon 6, which affects mostly the population of Central Europe is observed. Among the typical features of this disorder is that NBS patients experience a high incidence of lymphoid malignancies as well. An increased risk of solid tumors development for 657del5 carriers was the reason to investigate the role of NBS1 gene as a susceptible one for the breast cancer. The purpose of this work is to identify mutations in all 16 exons of the NBS1 gene in the group of the patients with diagnosed breast cancer and the control group of healthy individuals. In the group of 270 women with breast cancer, seven cases of mutated NBS1 gene were revealed. In the subgroup presenting mutated NBS1 gene, the mutation I171V in 5th exon occurred in five cases. It is the first such a discovery concerning breast cancer patients because this mutation had been previously observed only in the course of lymphoid or hematological malignancies. The rate of I171V mutation in the group of breast cancer patients was significantly higher than in the controls (OR: 9.42; 95% CI: 1.09-81.05; P = 0.02). The conclusion is that heterozygous germline mutation I171V in NBS1 gene is a significant risk factor for breast cancer development. It concerns especially the women whose first degree relatives had a previously diagnosed breast cancer (OR: 6.00; 95% CI: 0.98-38.07; P = 0.04). The histopathological and clinical features of breast cancer with I171V mutation suggest accumulation of the negative prognostic factors. The treatment's results however were unexpectedly satisfactory, that is why further investigations are necessary to assess the role of I171V mutation in NBS1 gene as a prognostic and predictive factor for breast cancer.

  17. Mandible-Powered Escape Jumps in Trap-Jaw Ants Increase Survival Rates during Predator-Prey Encounters.

    Directory of Open Access Journals (Sweden)

    Fredrick J Larabee

    Full Text Available Animals use a variety of escape mechanisms to increase the probability of surviving predatory attacks. Antipredator defenses can be elaborate, making their evolutionary origin unclear. Trap-jaw ants are known for their rapid and powerful predatory mandible strikes, and some species have been observed to direct those strikes at the substrate, thereby launching themselves into the air away from a potential threat. This potential escape mechanism has never been examined in a natural context. We studied the use of mandible-powered jumping in Odontomachus brunneus during their interactions with a common ant predator: pit-building antlions. We observed that while trap-jaw ant workers escaped from antlion pits by running in about half of interactions, in 15% of interactions they escaped by mandible-powered jumping. To test whether escape jumps improved individual survival, we experimentally prevented workers from jumping and measured their escape rate. Workers with unrestrained mandibles escaped from antlion pits significantly more frequently than workers with restrained mandibles. Our results indicate that some trap-jaw ant species can use mandible-powered jumps to escape from common predators. These results also provide a charismatic example of evolutionary co-option, where a trait that evolved for one function (predation has been co-opted for another (defense.

  18. Mandible-Powered Escape Jumps in Trap-Jaw Ants Increase Survival Rates during Predator-Prey Encounters.

    Science.gov (United States)

    Larabee, Fredrick J; Suarez, Andrew V

    2015-01-01

    Animals use a variety of escape mechanisms to increase the probability of surviving predatory attacks. Antipredator defenses can be elaborate, making their evolutionary origin unclear. Trap-jaw ants are known for their rapid and powerful predatory mandible strikes, and some species have been observed to direct those strikes at the substrate, thereby launching themselves into the air away from a potential threat. This potential escape mechanism has never been examined in a natural context. We studied the use of mandible-powered jumping in Odontomachus brunneus during their interactions with a common ant predator: pit-building antlions. We observed that while trap-jaw ant workers escaped from antlion pits by running in about half of interactions, in 15% of interactions they escaped by mandible-powered jumping. To test whether escape jumps improved individual survival, we experimentally prevented workers from jumping and measured their escape rate. Workers with unrestrained mandibles escaped from antlion pits significantly more frequently than workers with restrained mandibles. Our results indicate that some trap-jaw ant species can use mandible-powered jumps to escape from common predators. These results also provide a charismatic example of evolutionary co-option, where a trait that evolved for one function (predation) has been co-opted for another (defense).

  19. Evolution of invasive traits in nonindigenous species: increased survival and faster growth in invasive populations of rusty crayfish (Orconectes rusticus).

    Science.gov (United States)

    Sargent, Lindsey W; Lodge, David M

    2014-09-01

    The importance of evolution in enhancing the invasiveness of species is not well understood, especially in animals. To evaluate evolution in crayfish invasions, we tested for differences in growth rate, survival, and response to predators between native and invaded range populations of rusty crayfish (Orconectes rusticus). We hypothesized that low conspecific densities during introductions into lakes would select for increased investment in growth and reproduction in invasive populations. We reared crayfish from both ranges in common garden experiments in lakes and mesocosms, the latter in which we also included treatments of predatory fish presence and food quality. In both lake and mesocosm experiments, O. rusticus from invasive populations had significantly faster growth rates and higher survival than individuals from the native range, especially in mesocosms where fish were present. There was no influence of within-range collection location on growth rate. Egg size was similar between ranges and did not affect crayfish growth. Our results, therefore, suggest that growth rate, which previous work has shown contributes to strong community-level impacts of this invasive species, has diverged since O. rusticus was introduced to the invaded range. This result highlights the need to consider evolutionary dynamics in invasive species mitigation strategies.

  20. Polymyalgia rheumatica without significantly increased erythrocyte sedimentation rate. A more benign syndrome.

    Science.gov (United States)

    González-Gay, M A; Rodríguez-Valverde, V; Blanco, R; Fernández-Sueiro, J L; Armona, J; Figueroa, M; Martínez-Taboada, V M

    1997-02-10

    An erythrocyte sedimentation rate (ESR) of at least 40 mm/h is considered an important requisite for the diagnosis of polymyalgia rheumatica (PMR). However, the relative frequency and clinical features of PMR in patients without a significantly increased ESR are unclear. We performed a retrospective study of patients diagnosed as having PMR at the rheumatology divisions of 3 teaching hospitals. The diagnosis of PMR was established, regardless of the ESR, in 201 consecutive patients fulfilling the following criteria: (1) age 50 years or older, (2) severe proximal pain for more than 1 month in at least 2 of 3 areas: neck, shoulder, and/or pelvic girdles, and (3) rapid resolution of the syndrome while taking low-dose prednisone. Patients with giant cell arteritis were previously excluded from the study. The frequency and clinical features of patients with PMR and an ESR lower than 40 mm/h were analyzed. A comparative study between these patients and those with high ESRs was performed. An ESR lower than 40 mm/h was found in 41 patients (20.4%). These patients were younger (P = .02), were more frequently men (P = .006), and experienced a lower frequency of fever (P = .003) and weight loss (P = .07). Furthermore, these patients were characterized by an absence of anemia (P = .002) and a lower frequency of abnormal protein electrophoresis results (P fever, weight loss, and laboratory test result abnormalities, but it was unrelated to the duration of the illness prior to diagnosis. It is not uncommon to find a patient with PMR with an ESR lower than 40 mm/h. This syndrome is more frequent in men and it is clinically less severe than the classic form of PMR. Its recognition will allow these patients to benefit from an effective treatment with low-dose corticosteroids.

  1. TIMP-1 Is Significantly Associated with Objective Response and Survival in Metastatic Colorectal Cancer Patients Receiving Combination of Irinotecan, 5-Fluorouracil, and Folinic Acid

    DEFF Research Database (Denmark)

    Sørensen, Nanna M; Byström, Per; Christensen, Ib Jarle

    2007-01-01

    the curve 0.66) butmuchless so. PlasmaTIMP-1was the only significant covariate in a multivariable analysis of best objective response (OR, 3.6; 95%CI,1.4-9.5; P = 0.001). PlasmaTIMP-1scoredas a continuous variable on the log scale (loge) was significantly associatedwith overall survival [OS; hazardr atio...

  2. Physical activity level significantly affects the survival of patients with end-stage lung disease on a waiting list for lung transplantation.

    Science.gov (United States)

    Komatsu, Teruya; Oshima, Ayako; Chen-Yoshikawa, Toyofumi F; Harashima, Shin-Ichi; Aoyama, Akihiro; Inagaki, Nobuya; Date, Hiroshi

    2017-12-01

    Our objective was to investigate the factors predicting the survival of patients on the waiting list for lung transplantation (LT) during the waiting period, with a special emphasis on the physical activity level. The study included 70 patients with end-stage pulmonary disease who were on the waiting list for LT at Kyoto University Hospital. We examined the association between the baseline characteristics, including the body mass index and body composition, serum albumin, serum C-reactive protein (CRP), steroid administration, physical activity level (calculated by the food frequency questionnaire) and survival during the waiting period using Kaplan-Meier curves and Cox proportional hazard regression models. A physical activity level of ≤1.2 was correlated with significantly decreased survival (1-year survival: 68 vs. 90.9%, p = 0.0089), with a hazard ratio (HR) of 2.24 (95% confidence interval (CI) 1.22-4.19, p = 0.0001). Hypo-albumin (HR 2.024, 95% CI 1.339-6.009, p = 0.004), a high level of CRP (HR 2.551, CI 1.229-4.892, p = 0.02), and the administration of steroids (HR 2.258, CI 1.907-5.032, p = 0.024) were also significant predictors of survival. Low levels of physical activity during the waiting period for LT led to decreased survival times among LT candidates.

  3. Sugar administration to newly emerged Aedes albopictus males increases their survival probability and mating performance.

    Science.gov (United States)

    Bellini, Romeo; Puggioli, Arianna; Balestrino, Fabrizio; Brunelli, Paolo; Medici, Anna; Urbanelli, Sandra; Carrieri, Marco

    2014-04-01

    Aedes albopictus male survival in laboratory cages is no more than 4-5 days when kept without any access to sugar indicating their need to feed on a sugar source soon after emergence. We therefore developed a device to administer energetic substances to newly emerged males when released as pupae as part of a sterile insect technique (SIT) programme, made with a polyurethane sponge 4 cm thick and perforated with holes 2 cm in diameter. The sponge was imbibed with the required sugar solution and due to its high retention capacity the sugar solution was available for males to feed for at least 48 h. When evaluated in lab cages, comparing adults emerged from the device with sugar solution vs the device with water only (as negative control), about half of the males tested positive for fructose using the Van Handel anthrone test, compared to none of males in the control cage. We then tested the tool in semi-field and in field conditions with different sugar concentrations (10%, 15%, and 20%) and compared results to the controls fed with water only. Males were recaptured by a battery operated manual aspirator at 24 and 48 h after pupae release. Rather high share 10-25% of captured males tested positive for fructose in recollections in the vicinity of the control stations, while in the vicinity of the sugar stations around 40-55% of males were positive, though variability between replicates was large. The sugar positive males in the control test may have been released males that had access to natural sugar sources found close to the release station and/or wild males present in the environment. Only a slight increase in the proportion of positive males was obtained by increasing the sugar concentration in the feeding device from 10% to 20%. Surprisingly, modification of the device to add a black plastic inverted funnel above the container reduced rather than increased the proportion of fructose positive males collected around the station. No evidence of difference in the

  4. Increased Rrm2 gene dosage reduces fragile site breakage and prolongs survival of ATR mutant mice

    DEFF Research Database (Denmark)

    Lopez-Contreras, Andres J; Specks, Julia; Barlow, Jacqueline H

    2015-01-01

    of the RNR regulatory subunit RRM2 (Rrm2(TG)) present supraphysiological RNR activity and reduced chromosomal breakage at fragile sites. Moreover, increased Rrm2 gene dosage significantly extends the life span of ATR mutant mice. Our study reveals the first genetic condition in mammals that reduces fragile...

  5. Survival sex work and increased HIV risk among sexual minority street-involved youth.

    Science.gov (United States)

    Marshall, Brandon D L; Shannon, Kate; Kerr, Thomas; Zhang, Ruth; Wood, Evan

    2010-04-01

    Exchanging sex for money, drugs, or other commodities for survival is associated with an array of HIV risks. We sought to determine if street-involved drug-using sexual minority youth are at greater risk for survival sex work and are more likely to engage in risk behaviors with clients. We examined factors associated with survival sex work among participants enrolled in the At Risk Youth Study using logistic regression. Self-reported risk behaviors with clients were also examined. Of 558 participants eligible for this analysis, 75 (13.4%) identified as a sexual minority and 63 (11.3%) reported survival sex work in the past 6 months. Sexual minority males (adjusted odds ratio = 16.1, P exchange sex are urgently required.

  6. Major histocompatibility complex I upregulation in clear cell renal cell carcinoma is associated with increased survival

    Directory of Open Access Journals (Sweden)

    Rishi R. Sekar

    2016-04-01

    Conclusion: Our data demonstrate that high MHCI expression confers improved overall and recurrence free survival in patients with clear cell RCC and could serve as an important prognostic tool in identifying high-risk patients.

  7. Blockade of cannabinoid CB1 receptors improves renal function, metabolic profile, and increased survival of obese Zucker rats.

    Science.gov (United States)

    Janiak, P; Poirier, B; Bidouard, J-P; Cadrouvele, C; Pierre, F; Gouraud, L; Barbosa, I; Dedio, J; Maffrand, J-P; Le Fur, G; O'Connor, S; Herbert, J-M

    2007-12-01

    Obesity is a major risk factor in the development of chronic renal failure. Rimonabant, a cannabinoid CB1 receptor antagonist, improves body weight and metabolic disorders; however, its effect on mortality and chronic renal failure associated with obesity is unknown. Obese Zucker rats received either rimonabant or vehicle for 12 months and were compared to a pair-fed but untreated group of obese rats. Mortality in the obese rats was significantly reduced by rimonabant along with a sustained decrease in body weight, transient reduction in food intake, and an increase in plasma adiponectin. This was associated with significant reduction in plasma total cholesterol, low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio, triglycerides, glucose, norepinephrine, plasminogen activator inhibitor 1, and preservation of pancreatic weight and beta-cell mass index. The cannabinoid antagonist attenuated the increase in proteinuria, urinary N-acetylglucosaminidase excretion, plasma creatinine, and urea nitrogen levels while improving creatinine clearance. Renal hypertrophy along with glomerular and tubulointerstitial lesions were reduced by rimonabant. Although the drug did not modify hemodynamics, it normalized the pressor response to angiotensin II. Our study suggests that in a rat model of chronic renal failure due to obesity, rimonabant preserves renal function and increases survival.

  8. Aggressive Treatment of Patients with Metastatic Colorectal Cancer Increases Survival: A Scandinavian Single-Center Experience

    Directory of Open Access Journals (Sweden)

    Kristoffer Watten Brudvik

    2013-01-01

    Full Text Available Background. We examined overall and disease-free survivals in a cohort of patients subjected to resection of liver metastasis from colorectal cancer (CRLM in a 10-year period when new treatment strategies were implemented. Methods. Data from 239 consecutive patients selected for liver resection of CRLM during the period from 2002 to 2011 at a single center were used to estimate overall and disease-free survival. The results were assessed against new treatment strategies and established risk factors. Results. The 5-year cumulative overall and disease-free survivals were 46 and 24%. The overall survival was the same after reresection, independently of the number of prior resections and irrespectively of the location of the recurrent disease. The time intervals between each recurrence were similar (11 ± 1 months. Patients with high tumor load given neoadjuvant chemotherapy had comparable survival to those with less extensive disease without neoadjuvant chemotherapy. Positive resection margin or resectable extrahepatic disease did not affect overall survival. Conclusion. Our data support that one still, and perhaps to an even greater extent, should seek an aggressive therapeutic strategy to achieve resectable status for recurrent hepatic and extrahepatic metastases. The data should be viewed in the context of recent advances in the understanding of cancer biology and the metastatic process.

  9. Significant Historical and Projected Increases in Evaporative Demand in the United States

    Science.gov (United States)

    Ficklin, D. L.; Novick, K. A.

    2016-12-01

    Climate change will modify vapor pressure deficit (VPD) via increases in air temperature and changes in relative humidity. VPD is the difference between the water vapor the air can hold at saturation (es) and the actual amount of water vapor (ea) and is a critical determinant for the exchange of water vapor and CO2 between the land surface and the atmosphere. Over non-vegetated surfaces, increases in VPD will increase the evapotranspiration (ET) rate; however, over vegetated ecosystems, stomata close when VPD is high, modifying the rates of ET and reducing carbon uptake. This work assesses how VPD, es, ea, and their underlying climatic components (maximum and minimum air temperature, relative humidity) have been changing in the United States for the recent, observed past (1979-2013) and how these components may change in the future (2065-2099) using 18 downscaled General Circulation Models (GCMs). An increase in historic VPD was observed for all seasons, and was especially apparent in the southwestern United States. The increases in VPD are a result of directional or divergent changes in es and ea, where es is increasing for a large portion of the United States from increases in air temperature while ea is decreasing from decreases in relative humidity. GCM projections indicate similar, but stronger patterns into future. There is GCM agreement that VPD will increase compared to the historical time period due to temperature-driven increases in es that are not matched by concomitant increases in ea, reflecting a general pattern of declining relative humidity moving forward.

  10. Significant survival improvement of patients with recurrent breast cancer in the periods 2001-2008 vs. 1992-2000

    Directory of Open Access Journals (Sweden)

    Nishimura Sumiko

    2011-03-01

    Full Text Available Abstract Background It is unclear whether individualized treatments based on biological factors have improved the prognosis of recurrent breast cancer. The purpose of this study is to evaluate the survival improvement of patients with recurrent breast cancer after the introduction of third generation aromatase inhibitors (AIs and trastuzumab. Methods A total of 407 patients who received first diagnosis of recurrent breast cancer and treatment at National Kyushu Cancer Center between 1992 and 2008 were retrospectively evaluated. As AIs and trastuzumab were approved for clinical use in Japan in 2001, the patients were divided into two time cohorts depending on whether the cancer recurred before or after 2001. Cohort A: 170 patients who were diagnosed between 1992 and 2000. Cohort B: 237 patients who were diagnosed between 2001 and 2008. Tumor characteristics, treatments, and outcome were compared. Results Fourteen percent of cohort A and 76% of cohort B received AIs and/or trastuzumab (P Conclusions The prognosis of patients with recurrent breast cancer was improved over time following the introduction of AIs and trastuzumab and the survival improvement was apparent in HR- and/or HER-2-positive tumors.

  11. Adaptive Significance of Quorum Sensing-dependent Regulation of Rhamnolipids by Integration of Growth Rate in Burkholderia glumae: A Trade-off between Survival and Efficiency

    Directory of Open Access Journals (Sweden)

    Arvin Nickzad

    2016-08-01

    Full Text Available Quorum sensing (QS is a cell density-dependent mechanism which enables a population of bacteria to coordinate cooperative behaviors in response to the accumulation of self-produced autoinducer signals in their local environment. An emerging framework is that the adaptive significance of QS in the regulation of production of costly extracellular metabolites («public goods» is to maintain the homeostasis of cooperation. We investigated this model using the phytopathogenic bacterium Burkholderia glumae, which we have previously demonstrated uses QS to regulate the production of rhamnolipids, extracellular surface-active glycolipids promoting the social behavior called «swarming motility». Using mass spectrometric quantification and chromosomal lux-based gene expression, we made the unexpected finding that when unrestricted nutrient resources are provided, production of rhamnolipids is carried out completely independently of QS regulation. This is a unique observation among known QS-controlled factors in bacteria. On the other hand, under nutrient-limited conditions, QS then becomes the main regulating mechanism, significantly enhancing the specific rhamnolipids yield. Accordingly, decreasing nutrient concentrations amplifies rhamnolipid biosynthesis gene expression, revealing a system where QS-dependent regulation is specifically triggered by the growth rate of the population, rather than by its cell density. Furthermore, a gradual increase in QS signal specific concentration upon decrease of specific growth rate suggests a reduction in quorum threshold, which reflects an increase in cellular demand for production of QS-dependent target gene product at low density populations. Integration of growth rate with QS as a decision-making mechanism for biosynthesis of costly metabolites, such as rhamnolipids, could serve to assess the demand and timing for expanding the carrying capacity of a population through spatial expansion mechanisms, such as

  12. The effect of salinity increase on the photosynthesis, growth and survival of the Mediterranean seagrass Cymodocea nodosa

    Science.gov (United States)

    Sandoval-Gil, José M.; Marín-Guirao, Lázaro; Ruiz, Juan M.

    2012-12-01

    There are major concerns in the Mediterranean Sea over the effects of hypersaline effluents from seawater desalination plants on seagrass communities. However, knowledge concerning the specific physiological capacities of seagrasses to tolerate or resist salinity increases is still limited. In this study, changes in the photosynthetic characteristics, pigment content, leaf light absorption, growth and survival of the seagrass Cymodocea nodosa were examined across a range of simulated hypersaline conditions. To this end, large plant fragments were maintained under salinities of 37 (control ambient salinity), 39, 41 and 43 (practical salinity scale) in a laboratory mesocosm system for 47 days. At the end of the experimental period, net photosynthesis exhibited a modest, but significant, decline (12-17%) in all tested hypersaline conditions (39-43). At intermediate salinity levels (39-41), the decline in photosynthetic rates was mainly accounted for by substantial increases in respiratory losses (approximately 98% of the control), the negative effects of which on leaf carbon balance were offset by an improved capacity and efficiency of leaves to absorb light, mainly through changes in accessory pigments, but also in optical properties related to leaf anatomy. Conversely, inhibition of gross photosynthesis (by 19.6% compared to the control mean) in the most severe hypersaline conditions (43) reduced net photosynthesis. In this treatment, the respiration rate was limited in order to facilitate a positive carbon balance (similar to that of the control plants) and shoot survival, although vitality would probably be reduced if such metabolic alterations persisted. These results are consistent with the ecology of Mediterranean C. nodosa populations, which are considered to have high morphological and physiological plasticity and a capacity to grow in a wide variety of coastal environments with varying salinity levels. The results from this study support the premise that C

  13. Chronic stress increases experimental pancreatic cancer growth, reduces survival and can be antagonised by beta-adrenergic receptor blockade.

    Science.gov (United States)

    Partecke, Lars Ivo; Speerforck, Sven; Käding, André; Seubert, Florian; Kühn, Sandra; Lorenz, Eric; Schwandke, Sebastian; Sendler, Matthias; Keßler, Wolfram; Trung, Dung Nguyen; Oswald, Stefan; Weiss, Frank Ulrich; Mayerle, Julia; Henkel, Christin; Menges, Pia; Beyer, Katharina; Lerch, Markus M; Heidecke, Claus-Dieter; von Bernstorff, Wolfram

    2016-01-01

    Chronic stress could promote tumour growth and reduce survival of pancreatic cancer patients via beta-adrenergic receptors of tumour cells. We have tested the impact of chronic acoustic and restraint stress on tumour development in an orthotopic syngeneic murine model of pancreatic cancer. Tumour-bearing C57BL/6 mice exposed to chronic stress had 45% (p = 0.0138) higher circulating steroid and 111% (p = 0.0052) higher adrenal tyrosine hydroxylase levels. Their immune response was significantly suppressed: The in vitro LPS response of splenocytes was significantly reduced regarding Th1- and Th2-cytokines including IFN-gamma, IL-6, IL-10 and MCP-1 (0.0011  0.05). TGF-beta in vitro was increased by 23.4% using catecholamines (p Beta-catecholamines increased proliferation in tumour cells by 18% (p beta-blocker propranolol reduced these effects by 25% (p beta-blockers of patients with pancreatic cancer or other malignancies should be further evaluated as an adjuvant anti-neoplastic agent in clinical trials. Copyright © 2016 IAP and EPC. Published by Elsevier B.V. All rights reserved.

  14. Increased Lymph Node Yield Is Associated with Improved Survival in Rectal Cancer Irrespective of Neoadjuvant Treatment

    DEFF Research Database (Denmark)

    Lykke, Jakob; Jess, Per; Roikjaer, Ole

    2015-01-01

    BACKGROUND: It has been proposed that the lymph node yield achieved during rectal cancer resection is associated with survival. It is debated whether a high lymph node yield improves survival, per se, or whether it does so by diminishing the International Union Against Cancer stage drifting effect....... OBJECTIVE: The purpose of this study was to evaluate the prognostic implications of the lymph node yield in curative resected rectal cancer. DESIGN: This study was based on data from a prospectively maintained colorectal cancer database. SETTINGS: This was a national cohort study. PATIENTS: All 6793...... patients in Denmark who were diagnosed with International Union Against Cancer stage I to III adenocarcinoma of the rectum and so treated in the period from 2003 to 2011 were included in the analysis. MAIN OUTCOME MEASURES: The primary outcome measure was overall survival. RESULTS: The observed percentages...

  15. The Earth's Population Can Reach 14 Billion in the 23rd Century without Significant Adverse Effects on Survivability.

    Science.gov (United States)

    Krapivin, Vladimir F; Varotsos, Costas A; Soldatov, Vladimir Yu

    2017-08-07

    This paper presents the results obtained from the study of the sustainable state between nature and human society on a global scale, focusing on the most critical interactions between the natural and anthropogenic processes. Apart from the conventional global models, the basic tool employed herein is the newly proposed complex model entitled "nature-society system (NSS) model", through which a reliable modeling of the processes taking place in the global climate-nature-society system (CNSS) is achieved. This universal tool is mainly based on the information technology that allows the adaptive conformance of the parametric and functional space of this model. The structure of this model includes the global biogeochemical cycles, the hydrological cycle, the demographic processes and a simple climate model. In this model, the survivability indicator is used as a criterion for the survival of humanity, which defines a trend in the dynamics of the total biomass of the biosphere, taking into account the trends of the biocomplexity dynamics of the land and hydrosphere ecosystems. It should be stressed that there are no other complex global models comparable to those of the CNSS model developed here. The potential of this global model is demonstrated through specific examples in which the classification of the terrestrial ecosystem is accomplished by separating 30 soil-plant formations for geographic pixels 4° × 5°. In addition, humanity is considered to be represented by three groups of economic development status (high, transition, developing) and the World Ocean is parameterized by three latitude zones (low, middle, high). The modelling results obtained show the dynamics of the CNSS at the beginning of the 23rd century, according to which the world population can reach the level of 14 billion without the occurrence of major negative impacts.

  16. The Earth’s Population Can Reach 14 Billion in the 23rd Century without Significant Adverse Effects on Survivability

    Science.gov (United States)

    Krapivin, Vladimir F.; Varotsos, Costas A.; Soldatov, Vladimir Yu.

    2017-01-01

    This paper presents the results obtained from the study of the sustainable state between nature and human society on a global scale, focusing on the most critical interactions between the natural and anthropogenic processes. Apart from the conventional global models, the basic tool employed herein is the newly proposed complex model entitled “nature-society system (NSS) model”, through which a reliable modeling of the processes taking place in the global climate-nature-society system (CNSS) is achieved. This universal tool is mainly based on the information technology that allows the adaptive conformance of the parametric and functional space of this model. The structure of this model includes the global biogeochemical cycles, the hydrological cycle, the demographic processes and a simple climate model. In this model, the survivability indicator is used as a criterion for the survival of humanity, which defines a trend in the dynamics of the total biomass of the biosphere, taking into account the trends of the biocomplexity dynamics of the land and hydrosphere ecosystems. It should be stressed that there are no other complex global models comparable to those of the CNSS model developed here. The potential of this global model is demonstrated through specific examples in which the classification of the terrestrial ecosystem is accomplished by separating 30 soil-plant formations for geographic pixels 4° × 5°. In addition, humanity is considered to be represented by three groups of economic development status (high, transition, developing) and the World Ocean is parameterized by three latitude zones (low, middle, high). The modelling results obtained show the dynamics of the CNSS at the beginning of the 23rd century, according to which the world population can reach the level of 14 billion without the occurrence of major negative impacts. PMID:28783136

  17. Increased HDAC1 deposition at hematopoietic promoters in AML and its association with patient survival

    DEFF Research Database (Denmark)

    Tickenbrock, Lara; Klein, Hans-Ulrich; Trento, Cristina

    2011-01-01

    was established, that revealed an AML specific pattern of HDAC1 distribution. Many of the HDAC1-binding altered promoters regulate genes involved in hematopoiesis, transcriptional regulation and signal transduction. HDAC1 binding patterns were associated with patients' event free survival. This is the first study...... to determine HDAC1 modification patterns in a large number of AML and ALL specimens. Our findings suggest that dyslocalization of HDAC1 is a common feature in AML. Importantly, HDAC1 modifications possess prognostic power for patient survival. Our findings suggest that altered HDAC1 localization...

  18. Presence of gingivitis and periodontitis significantly increases hospital charges in patients undergoing heart valve surgery.

    Science.gov (United States)

    Allareddy, Veerasathpurush; Elangovan, Satheesh; Rampa, Sankeerth; Shin, Kyungsup; Nalliah, Romesh P; Allareddy, Veerajalandhar

    2015-01-01

    To examine the prevalence and impact of gingivitis and periodontitis in patients having heart valve surgical procedures. Nationwide Inpatient Sample for the years 2004-2010 was used. All patients who had heart valve surgical procedures were selected. Prevalence of gingivitis/periodontitis was examined in these patients. Impact of gingivitis/periodontitis on hospital charges, length of stay, and infectious complications was examined. 596,190 patients had heart valve surgical procedures. Gingivitis/periodontitis was present in 0.2 percent. Outcomes included: median hospital charges ($175,418 with gingivitis/ periodontitis versus $149,353 without gingivitis/periodontitis) and median length of stay (14 days with gingivitis/periodontitis versus 8 days without gingivitis/periodontitis). After adjusting for the effects of patient- and hospital-level confounding factors, hospital charges and length of stay were significantly higher (p gingivitis/periodontitis compared to their counterparts. Further, patients with gingivitis/periodontitis had significantly higher odds for having bacterial infections (OR = 3.41, 95% CI = 2.33-4.98, p gingivitis/periodontitis. Presence of gingivitis and periodontitis is associated with higher risk for bacterial infections and significant hospital resource utilization.

  19. Transglutaminase 2 expression is significantly increased in cyclosporine-induced gingival overgrowth

    OpenAIRE

    Asioli, Sofia; Righi, Alberto; Cardone, Pietro; Aimetti, Mario; Maletta, Francesca; Coda, Renato; Carossa, Stefano; Navone, Roberto; Cassoni, Paola

    2011-01-01

    Cyclosporine A is a potent immunosuppressant used to prevent organ transplant rejection and treat various autoimmune diseases. However, cyclosporine A can also induce gingival overgrowth, which is characterized by increased extracellular matrix due to an altered balance between collagen synthesis and degradation. This study proposed to verify whether trans-glutaminase 2, an enzyme thought to be responsible for the assembly and remodelling of extracellular matrix, plays any role in the path...

  20. Dietary Omega-3 Fatty Acids Increase Survival and Decrease Bacterial Load in Mice Subjected to Staphylococcus aureus-Induced Sepsis.

    Science.gov (United States)

    Svahn, Sara L; Ulleryd, Marcus A; Grahnemo, Louise; Ståhlman, Marcus; Borén, Jan; Nilsson, Staffan; Jansson, John-Olov; Johansson, Maria E

    2016-04-01

    Sepsis caused by Staphylococcus aureus is increasing in incidence. With the alarming use of antibiotics,S. aureus is prone to become methicillin resistant. Antibiotics are the only widely used pharmacological treatment for sepsis. Interestingly, mice fed high-fat diet (HFD) rich in polyunsaturated fatty acids have better survival of S. aureus-induced sepsis than mice fed HFD rich in saturated fatty acids (HFD-S). To investigate what component of polyunsaturated fatty acids, i.e., omega-3 or omega-6 fatty acids, exerts beneficial effects on the survival of S. aureus-induced sepsis, mice were fed HFD rich in omega-3 or omega-6 fatty acids for 8 weeks prior to inoculation with S. aureus Further, mice fed HFD-S were treated with omega-3 fatty acid metabolites known as resolvins. Mice fed HFD rich in omega-3 fatty acids had increased survival and decreased bacterial loads compared to those for mice fed HFD-S after S. aureus-induced sepsis. Furthermore, the bacterial load was decreased in resolvin-treated mice fed HFD-S after S. aureus-induced sepsis compared with that in mice treated with vehicle. Dietary omega-3 fatty acids increase the survival of S. aureus-induced sepsis by reversing the deleterious effect of HFD-S on mouse survival. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  1. DHA-supplemented diet increases the survival of rats following asphyxia-induced cardiac arrest and cardiopulmonary bypass resuscitation.

    Science.gov (United States)

    Kim, Junhwan; Yin, Tai; Shinozaki, Koichiro; Lampe, Joshua W; Becker, Lance B

    2016-11-04

    Accumulating evidence illustrates the beneficial effects of dietary docosahexaenoic acid (DHA) on cardiovascular diseases. However, its effects on cardiac arrest (CA) remain controversial in epidemiological studies and have not been reported in controlled animal studies. Here, we examined whether dietary DHA can improve survival, the most important endpoint in CA. Male Sprague-Dawley rats were randomized into two groups and received either a control diet or a DHA-supplemented diet for 7-8 weeks. Rats were then subjected to 20 min asphyxia-induced cardiac arrest followed by 30 min cardiopulmonary bypass resuscitation. Rat survival was monitored for additional 3.5 h following resuscitation. In the control group, 1 of 9 rats survived for 4 h, whereas 6 of 9 rats survived in the DHA-treated group. Surviving rats in the DHA-treated group displayed moderately improved hemodynamics compared to rats in the control group 1 h after the start of resuscitation. Rats in the control group showed no sign of brain function whereas rats in the DHA-treated group had recurrent seizures and spontaneous respiration, suggesting dietary DHA also protects the brain. Overall, our study shows that dietary DHA significantly improves rat survival following 20 min of severe CA.

  2. Significant yield increases from control of leaf diseases in maize - an overlooked problem?!

    DEFF Research Database (Denmark)

    Jørgensen, Lise Nistrup

    2012-01-01

    maize have often grown maize consecutively for several years. This leads to significant amounts of debris building up in the fields, which serves as an important source of inoculum for diseases when new crops are grown. In recent years, leaf diseases have caused production problems over several seasons....... Two major diseases have been identified: Eyespot (Kabatiella zeae) and Northern leaf blotch (Exserohilum turcicum). Other diseases, including Southern maize leaf blight or maydis leaf blight, caused by Bipolaris maydis, and Northern corn leaf spot, caused by Bipolaris zeicola, may potentially play...

  3. Strong Selection Significantly Increases Epistatic Interactions in the Long-Term Evolution of a Protein.

    Directory of Open Access Journals (Sweden)

    Aditi Gupta

    2016-03-01

    Full Text Available Epistatic interactions between residues determine a protein's adaptability and shape its evolutionary trajectory. When a protein experiences a changed environment, it is under strong selection to find a peak in the new fitness landscape. It has been shown that strong selection increases epistatic interactions as well as the ruggedness of the fitness landscape, but little is known about how the epistatic interactions change under selection in the long-term evolution of a protein. Here we analyze the evolution of epistasis in the protease of the human immunodeficiency virus type 1 (HIV-1 using protease sequences collected for almost a decade from both treated and untreated patients, to understand how epistasis changes and how those changes impact the long-term evolvability of a protein. We use an information-theoretic proxy for epistasis that quantifies the co-variation between sites, and show that positive information is a necessary (but not sufficient condition that detects epistasis in most cases. We analyze the "fossils" of the evolutionary trajectories of the protein contained in the sequence data, and show that epistasis continues to enrich under strong selection, but not for proteins whose environment is unchanged. The increase in epistasis compensates for the information loss due to sequence variability brought about by treatment, and facilitates adaptation in the increasingly rugged fitness landscape of treatment. While epistasis is thought to enhance evolvability via valley-crossing early-on in adaptation, it can hinder adaptation later when the landscape has turned rugged. However, we find no evidence that the HIV-1 protease has reached its potential for evolution after 9 years of adapting to a drug environment that itself is constantly changing. We suggest that the mechanism of encoding new information into pairwise interactions is central to protein evolution not just in HIV-1 protease, but for any protein adapting to a changing

  4. Survival of male Tengmalm’s owls increases with cover of old forest in the territory

    NARCIS (Netherlands)

    Hakkarainen, H.; Korpimäki, E.; Laaksonen, T.; Nikula, A.; Suorsa, P.

    2008-01-01

    The loss and fragmentation of forest habitats have been considered to pose a worldwide threat to the viability of forest-dwelling animals, especially to species that occupy old forests. We investigated whether the annual survival of sedentary male Tengmalm’s owls Aegolius funereus was associated

  5. Modern environmental health hazards: a public health issue of increasing significance in Africa.

    Science.gov (United States)

    Nweke, Onyemaechi C; Sanders, William H

    2009-06-01

    Traditional hazards such as poor sanitation currently account for most of Africa's environmentally related disease burden. However, with rapid development absent appropriate safeguards for environment and health, modern environmental health hazards (MEHHs) may emerge as critical contributors to the continent's disease burden. We review recent evidence of human exposure to and health effects from MEHHs, and their occurrence in environmental media and consumer products. Our purpose is to highlight the growing significance of these hazards as African countries experience urbanization, industrial growth, and development. We reviewed published epidemiologic, exposure, and environmental studies of chemical agents such as heavy metals and pesticides. The body of evidence demonstrates ongoing environmental releases of MEHHs and human exposures sometimes at toxicologically relevant levels. Several sources of MEHHs in environmental media have been identified, including natural resource mining and processing and automobile exhaust. Biomonitoring studies provided direct evidence of human exposure to metals such as mercury and lead and pesticides such as p,p'-dichlorodiphenyltrichloroethane (DDT) and organophosphates. Land and water resource pollution and industrial air toxics are areas of significant data gaps, notwithstanding the presence of several emitting sources. Unmitigated MEHH releases and human exposure have implications for Africa's disease burden. For Africans encumbered by conditions such as malnutrition that impair resilience to toxicologic challenges, the burden may be higher. A shift in public health policy toward accommodating the emerging diversity in Africa's environmental health issues is necessary to successfully alleviate the burden of avoidable ill health and premature death for all its communities now and in the future.

  6. Longer duration of asthma is significantly associated with increased RV/TLC ratio.

    Science.gov (United States)

    Tiwari, Anupama; Rahman, Kazi; Abejie, Belayneh; Jain, Vipul V; Vempilly, Jose Joseph

    2017-03-01

    Although FEV1/FVC ratio has been shown to be negatively associated with longer duration of asthma; an association between RV/TLC ratio and longer duration of asthma has not been explored. Patients with established asthma for more than a year and met inclusion and exclusion criteria were recruited. Data obtained by questionnaire after informed consent was obtained, Pulmonary function tests and laboratory results were collected through chart review. Correlation and multiple linear regressions were used to analyze the data. Among the 93 subjects, 61 were women. The mean age of patients was 58 ± 15 years, and the mean duration of asthma was 21 ± 18 years. The ethnic composition included: Caucasians 64%, Hispanics 28% and other groups 8%. The FEV1/FVC ratio was not significantly associated with duration of asthma (R2 = 0.15, p = 0.05). However, the RV/TLC ratio was significantly associated with duration of asthma (R2 = 0.46, p TLC ratio may be a better indicator than FEV1/FVC ratio to detect airway obstruction related to longer duration of asthma. Lung volume measurements should be done in addition to spirometry to detect changes related to airway obstruction in patients with longer duration of asthma. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Combining modularity, conservation, and interactions of proteins significantly increases precision and coverage of protein function prediction.

    Science.gov (United States)

    Jaeger, Samira; Sers, Christine T; Leser, Ulf

    2010-12-20

    While the number of newly sequenced genomes and genes is constantly increasing, elucidation of their function still is a laborious and time-consuming task. This has led to the development of a wide range of methods for predicting protein functions in silico. We report on a new method that predicts function based on a combination of information about protein interactions, orthology, and the conservation of protein networks in different species. We show that aggregation of these independent sources of evidence leads to a drastic increase in number and quality of predictions when compared to baselines and other methods reported in the literature. For instance, our method generates more than 12,000 novel protein functions for human with an estimated precision of ~76%, among which are 7,500 new functional annotations for 1,973 human proteins that previously had zero or only one function annotated. We also verified our predictions on a set of genes that play an important role in colorectal cancer (MLH1, PMS2, EPHB4 ) and could confirm more than 73% of them based on evidence in the literature. The combination of different methods into a single, comprehensive prediction method infers thousands of protein functions for every species included in the analysis at varying, yet always high levels of precision and very good coverage.

  8. Dietary phosphorus is associated with a significant increase in left ventricular mass

    Science.gov (United States)

    Yamamoto, Kalani T.; Robinson-Cohen, Cassianne; de Oliveira, Marcia C.; Kostina, Alina; Nettleton, Jennifer A.; Ix, Joachim H.; Nguyen, Ha; Eng, John; Lima, Joao A.C.; Siscovick, David; Weiss, Noel S.; Kestenbaum, Bryan

    2012-01-01

    Dietary phosphorus consumption has risen steadily in the United States. Oral phosphorus loading alters key regulatory hormones and impairs vascular endothelial function which may lead to an increase in left ventricular mass (LVM). We investigated the association of dietary phosphorus with LVM in 4,494 participants from the Multi-Ethnic Study of Atherosclerosis, a community-based study of individuals free of known cardiovascular disease. The intake of dietary phosphorus was estimated using a 120-item food frequency questionnaire and the LVM was measured using magnetic resonance imaging. Regression models were used to determine associations of estimated dietary phosphorus with LVM and left ventricular hypertrophy (LVH). Mean estimated dietary phosphorus intake was 1,167 mg/day in men and 1,017 mg/day in women. After adjustment for demographics, dietary sodium, total calories, lifestyle factors, comorbidities, and established LVH risk factors, each quintile increase in the estimated dietary phosphate intake was associated with an estimated 1.1 gram greater LVM. The highest gender-specific dietary phosphorus quintile was associated with an estimated 6.1 gram greater LVM compared to the lowest quintile. Higher dietary phosphorus intake was associated with greater odds of LVH among women, but not men. These associations require confirmation in other studies. PMID:23283134

  9. Current and past cigarette smoking significantly increase risk for microscopic colitis.

    Science.gov (United States)

    Yen, Eugene F; Pokhrel, Bhupesh; Du, Hongyan; Nwe, Steven; Bianchi, Laura; Witt, Benjamin; Hall, Curtis

    2012-10-01

    Cigarette smoking is an important environmental factor affecting inflammatory bowel disease. The role of smoking has not been rigorously studied in microscopic colitis (MC). The aim of this study was to compare the association of cigarette smoking in individuals with MC compared to a control population without MC. We reviewed the records of patients with a clinical and histologic diagnosis of collagenous colitis (CC) or lymphocytic colitis (LC). Clinical history, including alcohol and smoking status at the time of diagnosis of MC, were reviewed. In this case-control study, age- and gender-matched patients without diarrhea presenting for outpatient colonoscopy served as the control population. We analyzed a total of 340 patients with MC: 124 with CC and 216 with LC. Overall, any smoking status (former or current) was associated with MC (odds ratio [OR] 2.12, 95% confidence interval [CI]: 1.56-2.88). This risk was more prominent in current smokers (adjusted OR 5.36, 3.81, and 4.37 for CC, LC, and all MC, respectively, 95% CI all greater than 1). The association of smoking was not significantly affected by gender or average alcohol consumption. In our study population, cigarette smoking is a risk factor for the development of both forms of microscopic colitis. There were no significant differences between LC and CC, and current smoking and the development of microscopic colitis affected men and women similarly. We feel that these data are sufficient to discuss the potential risks of tobacco use in patients with microscopic colitis. Copyright © 2011 Crohn's & Colitis Foundation of America, Inc.

  10. Fasting increases survival to cold in FOXO, DIF, autophagy mutants and in other genotypes of Drosophila melanogaster.

    Science.gov (United States)

    Le Bourg, Éric; Massou, Isabelle

    2015-08-01

    Fasting increases survival to a severe cold stress in young and middle-aged wild-type flies, this effect being lowered or absent at old age. As an attempt to determine the mechanisms of this effect, genes involved in metabolism (dFOXO), autophagy (Atg7), innate immunity (Dif (1) ), and resistance to cold (Frost) were studied. The 12 mutant, RNAi and control lines tested in this study displayed an increased survival to cold after fasting. This shows that fasting has a robust effect on survival to cold in many genotypes, but the mechanism of this effect remains unknown. This mechanism does not seem to be linked to metabolic pathways often considered to play a critical role in ageing and longevity determinations (insulin/insulin-like growth factor-1 pathway and autophagy).

  11. Memory T Cells Are Significantly Increased in Rejecting Liver Allografts of Rhesus Monkeys.

    Science.gov (United States)

    Kim, Hwajung; Kim, Hyeyoung; Lee, Sun-Kyung; Jin, Xue-Li; Kim, Tae Jin; Park, Chanho; Lee, Jae-Il; Kim, Hyo-Sin; Hong, Suk Kyun; Yoon, Kyung Chul; Ahn, Sung Woo; Lee, Kyoung-Bun; Yi, Nam-Joon; Yang, Jaeseok; Lee, Kwang-Woong; Hawthorne, Wayne J; Suh, Kyung-Suk

    2017-11-18

    The Rhesus monkey (RM) is an excellent preclinical model in kidney, heart and islet transplantation that has provided the basis for new immunosuppressive protocols for clinical studies. However, there remain relatively few liver transplantation (LT) models in nonhuman primates. In this study, we analyzed the immune cell populations of PBMCs and secondary lymphoid organs along with livers of normal rhesus monkeys and compared them to those of rejecting liver transplanted recipient's following withdrawal of immunosuppression. We undertook five allogeneic ABO compatible orthotopic LT in monkeys using five normal donor monkey livers. We collected tissues including lymph nodes, spleens, blood, recipient livers and performed flow cytometric analysis using isolated immune cells. We found that CD4 or CD8 naïve T cells were normally seen at low levels and memory T cells were seen at high levels in the liver rather than lymphoid organs or PBMC. However, regulatory cells such as CD4+FoxP-3(+)T cells and CD8+CD28- cells remained in high numbers in the liver, but not in lymph node or PBMC. The comparison of CD4/8 T sub-populations in normal and rejected livers and the various tissues showed that naïve cells were dramatically decreased in spleen, lymph node and PBMC of rejected liver transplanted monkeys, but rather memory CD4/8 T cells were increased in all tissues and PBMC. The normal liver has large numbers of CD4 Tregs, CD8+CD28- and myeloid-derived suppressor cells, which are known immunosuppressive cells occurring at much higher levels than those seen in lymph node or peripheral blood. Memory T cells are dramatically increased in rejecting liver allografts of rhesus monkeys compared to those seen in normal RM tissues. This article is protected by copyright. All rights reserved. © 2017 by the American Association for the Study of Liver Diseases.

  12. Nanospray FAIMS Fractionation Provides Significant Increases in Proteome Coverage of Unfractionated Complex Protein Digests*

    Science.gov (United States)

    Swearingen, Kristian E.; Hoopmann, Michael R.; Johnson, Richard S.; Saleem, Ramsey A.; Aitchison, John D.; Moritz, Robert L.

    2012-01-01

    High-field asymmetric waveform ion mobility spectrometry (FAIMS) is an atmospheric pressure ion mobility technique that can be used to reduce sample complexity and increase dynamic range in tandem mass spectrometry experiments. FAIMS fractionates ions in the gas-phase according to characteristic differences in mobilities in electric fields of different strengths. Undesired ion species such as solvated clusters and singly charged chemical background ions can be prevented from reaching the mass analyzer, thus decreasing chemical noise. To date, there has been limited success using the commercially available Thermo Fisher FAIMS device with both standard ESI and nanoLC-MS. We have modified a Thermo Fisher electrospray source to accommodate a fused silica pulled tip capillary column for nanospray ionization, which will enable standard laboratories access to FAIMS technology. Our modified source allows easily obtainable stable spray at flow rates of 300 nL/min when coupled with FAIMS. The modified electrospray source allows the use of sheath gas, which provides a fivefold increase in signal obtained when nanoLC is coupled to FAIMS. In this work, nanoLC-FAIMS-MS and nanoLC-MS were compared by analyzing a tryptic digest of a 1:1 mixture of SILAC-labeled haploid and diploid yeast to demonstrate the performance of nanoLC-FAIMS-MS, at different compensation voltages, for post-column fractionation of complex protein digests. The effective dynamic range more than doubled when FAIMS was used. In total, 10,377 unique stripped peptides and 1649 unique proteins with SILAC ratios were identified from the combined nanoLC-FAIMS-MS experiments, compared with 6908 unique stripped peptides and 1003 unique proteins with SILAC ratios identified from the combined nanoLC-MS experiments. This work demonstrates how a commercially available FAIMS device can be combined with nanoLC to improve proteome coverage in shotgun and targeted type proteomics experiments. PMID:22186714

  13. Significance of baseline bone markers on disease progression and survival in hormone-sensitive prostate cancer with bone metastasis.

    Science.gov (United States)

    Nozawa, Masahiro; Hara, Isao; Matsuyama, Hideyasu; Iki, Masayuki; Nagao, Kazuhiro; Nishioka, Tsukasa; Komura, Takahiro; Esa, Atsunobu; Uejima, Shigeya; Imanishi, Masaaki; Uekado, Yasunari; Ogawa, Takatoshi; Kajikawa, Hiroshi; Uemura, Hirotsugu

    2015-09-01

    This study evaluated the baseline patient characteristics associated with the time to biochemical progression and overall survival in patients who participated in a phase II trial on zoledronic acid combined with the initial androgen-deprivation therapy for treatment-naïve bone-metastatic prostate cancer. Patients received zoledronic acid 4 mg intravenously every 4 weeks for up to 24 months, concomitantly started with bicalutamide 80 mg orally every day and goserelin acetate 10.8 mg subcutaneously every 12 weeks. A total of 53 Japanese patients were enrolled between July 2008 and April 2010, and 52 patients were evaluable. Median follow-up period was 41.6 months. Updated median time to biochemical progression was 25.9 months (95 % confidence interval 14.5-49.9). Higher serum bone-specific alkaline phosphatase was an independent risk factor for time to biochemical progression based on multivariate analysis (hazard ratio 6.51; 95 % confidence interval 2.71-15.62; P prostate cancer treated with upfront zoledronic acid concomitantly started with androgen-deprivation therapy.

  14. Reduced-dose cyclosporine with mycophenolate mofetil and prednisone significantly improves the long-term glomerular filtration rate and graft survival.

    Science.gov (United States)

    Wang, Rending; Xu, Ying; Wu, Jianyong; Wang, Yimin; He, Qiang; Chen, Jianghua

    2013-01-01

    It remains debated whether reduced doses of chronic calcineurin inhibitors benefit graft survival. This retrospective study analyzed 60 first cadaveric renal transplant recipients who received cyclosporine (CSA), mycophenolate mofetil (MMF) and prednisone (CMP group) and 71 recipients who received reduced-dose CSA with prednisone and MMF (RCMP group). All recipients were followed for at least 96 months. The Modification of Diet in Renal Disease (MDRD) glomerular filtration rate (GFR) calculated at different time points, graft survival, the incidence of chronic allograft nephropathy (CAN) and the acute rejection rate within six months were analyzed and compared between the two groups. The incidence of acute rejection within six months post-transplant was 15.5% (11/71) in the RCMP group and 13.3% (8/60) in the CMP group. This difference was not significant (p=0.727). The MDRD-calculated GFR in the CMP group reached a peak at 24 months post-transplant (66.6 ± 20.2 mL/min/1.73 m(2)) then decreased gradually. In contrast, in the RCMP group, the GFR reached a peak at 36 months post-transplant (76.9 ± 19.6 mL/min/1.73 m(2)). The GFR from month 36 to month 96 was significantly higher in the RCMP group than in the CMP group. The Kaplan-Meier calculated death-censored graft survival in the RCMP group was significantly higher than that observed in the CMP group, with an estimated cumulative proportion surviving at 96 months of 95.5% in the RCMP group and 83.5% in the CMP group. The incidence of CAN within 96 months was 5.6% (4/71) in the RCMP group vs. 16.7% (10/60) in the CMP group (p=0.042). An RCMP regimen can significantly improve the long-term GFR level and benefit graft survival.

  15. Distinct Effects of miR-210 Reduction on Neurogenesis: Increased Neuronal Survival of Inflammation But Reduced Proliferation Associated with Mitochondrial Enhancement.

    Science.gov (United States)

    Voloboueva, Ludmila A; Sun, Xiaoyun; Xu, Lijun; Ouyang, Yi-Bing; Giffard, Rona G

    2017-03-15

    Neurogenesis is essential to brain development and plays a central role in the response to brain injury. Stroke and head trauma stimulate proliferation of endogenous neural stem cells (NSCs); however, the survival of young neurons is sharply reduced by postinjury inflammation. Cellular mitochondria are critical to successful neurogenesis and are a major target of inflammatory injury. Mitochondrial protection was shown to improve survival of young neurons. This study tested whether reducing cellular microRNA-210 (miR-210) would enhance mitochondrial function and improve survival of young murine neurons under inflammatory conditions. Several studies have demonstrated the potential of miR-210 inhibition to enhance and protect mitochondrial function through upregulation of mitochondrial proteins. Here, miR-210 inhibition significantly increased neuronal survival and protected the activity of mitochondrial enzymes cytochrome c oxidase and aconitase in differentiating NSC cultures exposed to inflammatory mediators. Unexpectedly, we found that reducing miR-210 significantly attenuated NSC proliferation upon induction of differentiation. Further investigation revealed that increased mitochondrial function suppressed the shift to primarily glycolytic metabolism and reduced mitochondrial length characteristic of dividing cells. Activation of AMP-regulated protein kinase-retinoblastoma signaling is important in NSC proliferation and the reduction of this activation observed by miR-210 inhibition is one mechanism contributing to the reduced proliferation. Postinjury neurogenesis occurs as a burst of proliferation that peaks in days, followed by migration and differentiation over weeks. Our studies suggest that mitochondrial protective miR-210 inhibition should be delayed until after the initial burst of proliferation, but could be beneficial during the prolonged differentiation stage.SIGNIFICANCE STATEMENT Increasing the success of endogenous neurogenesis after brain injury

  16. Gangrenous cholecystitis: Deceiving ultrasounds, significant delay in surgical consult, and increased postoperative morbidity!

    Science.gov (United States)

    Yeh, Daniel Dante; Cropano, Catrina; Fagenholz, Peter; King, David R; Chang, Yuchiao; Klein, Eric N; DeMoya, Marc; Kaafarani, Haytham; Velmahos, George

    2015-11-01

    Gangrenous cholecystitis (GC) is difficult to diagnose preoperatively in the patient with suspected acute cholecystitis. We sought to characterize preoperative risk factors and post-operative complications. Pathology reports of all patients undergoing cholecystectomy for suspected acute cholecystitis from June 2010 to January 2014 and admitted through the emergency department were examined. Patients with GC were compared with those with acute/chronic cholecystitis (AC/CC). Data collected included demographics, preoperative signs and symptoms, radiologic studies, operative details, and clinical outcomes. Thirty-eight cases of GC were identified and compared with 171 cases of AC/CC. Compared with AC/CC, GC patients were more likely to be older (57 years vs. 41 years, p < 0.001), of male sex (63% vs. 31%, p < 0.001), hypertensive (47% vs. 22%, p = 0.002), hyperlipidemic (29% vs. 14%, p = 0.026), and diabetic (24% vs. 8%, p = 0.006). GC patients were more likely to have a fever (29% vs. 12%, p = 0.007) and less likely to have nausea/vomiting (61% vs. 80%, p = 0.019) or an impacted gallstone on ultrasound (US) (8% vs. 26%, p = 0.017). Otherwise, there was no significant difference in clinical or US findings. Among GC patients, US findings were absent (8%, n = 3) or minimal (42%, n = 16). Median time from emergency department registration to US (3.3 hours vs. 2.8 hours, p = 0.28) was similar, but US to operation was longer (41.2 hours vs. 18.4 hours, p < 0.001), conversion to open cholecystectomy was more common (37% vs. 10%, p < 0.001), and hospital stay was longer (median, 4 days vs. 2 days, p < 0.0001). Delay in surgical consultation occurred in 16% of GC patients compared with 1% of AC patients (p < 0.001). Demographic features may be predictive of GC. Absent or minimal US signs occur in 50%, and delay in surgical consultation is common. Postoperative morbidity is greater for patients with GC compared with those with AC/CC. Epidemiologic study, level III; therapeutic

  17. Offspring schooling associated with increased parental survival in rural KwaZulu-Natal, South Africa

    OpenAIRE

    De Neve, Jan-Walter; Harling, Guy

    2017-01-01

    Background Investing in offspring's human capital has been suggested as an effective strategy for parents to improve their living conditions at older ages. A few studies have assessed the role of children's schooling in parental survival in high-income countries, but none have considered lower-resource settings with limited public wealth transfers and high adult mortality. Methods We followed 17,789 parents between January 2003 and August 2015 in a large population-based open cohort in rural ...

  18. From utopia to reality: increased survival in peritoneal carcinomatosis treated with cytoreduction and hyperthermic intraperitoneal chemotherapy.

    Science.gov (United States)

    Segura-Sampedro, Juan José; Morales-Soriano, Rafael

    2017-11-01

    We have read with great interest the article by Illán et al.1 entitled "Long survival in a patient with metastatic colorectal carcinoma: reality or utopia?" This article describes the case of a 42 year old patient with mucinous-type colon adenocarcinoma who had tumor recurrence with peritoneal metastases 18 months after resection of the primary tumor and adjuvant chemotherapy. After multiple metastasectomies and several lines of chemotherapy, the patient died 27 months after the recurrence.

  19. Improvements in logistics could increase survival after out-of-hospital cardiac arrest in Sweden.

    Science.gov (United States)

    Strömsöe, A; Afzelius, S; Axelsson, C; Södersved Källestedt, M L; Enlund, M; Svensson, L; Herlitz, J

    2013-06-01

    In a review based on estimations and assumptions, to report the estimated number of survivors after out-of-hospital cardiac arrest (OHCA) in whom cardiopulmonary resuscitation (CPR) was started and to speculate about possible future improvements in Sweden. An observational study. All ambulance organisations in Sweden. Patients included in the Swedish Cardiac Arrest Registry who suffered an OHCA between January 1, 2008 and December 31, 2010. Approximately 80% of OHCA cases in Sweden in which CPR was started are included. None In 11 005 patients, the 1-month survival rate was 9.4%. There are approximately 5000 OHCA cases annually in which CPR is started and 30-day survival is achieved in up to 500 patients yearly (6 per 100 000 inhabitants). Based on findings on survival in relation to the time to calling for the Emergency Medical Service (EMS) and the start of CPR and defibrillation, it was estimated that, if the delay from collapse to (i) calling EMS, (ii) the start of CPR, and (iii) the time to defibrillation were reduced to <2 min, <2 min, and <8 min, respectively, 300-400 additional lives could be saved. Based on findings relating to the delay to calling for the EMS and the start of CPR and defibrillation, we speculate that 300-400 additional OHCA patients yearly (4 per 100 000 inhabitants) could be saved in Sweden. © 2013 The Association for the Publication of the Journal of Internal Medicine.

  20. The capacity of seagrasses to survive increased turbidity and siltation: The significance of growth form and light use

    NARCIS (Netherlands)

    Vermaat, J.E.; Agawin, N.S.R.; Fortes, M.D.; Uri, J.; Duarte, C.M.; Marbà, N.; Enriquez, S.; Van Vierssen, W.

    1997-01-01

    Seagrasses are submerged or intertidal angiosperms that form extensive meadows in shallow coastal waters. Tropical as well as temperate seagrass beds are subject to man's interference. Most human activities affect seagrasses either through reductions in light availability or changes in sediment

  1. Effect of Increased Radiotoxicity on Survival of Patients with Non-small Cell Lung Cancer Treated with Curatively Intended Radiotherapy.

    Science.gov (United States)

    Holgersson, Georg; Bergström, Stefan; Liv, Per; Nilsson, Jonas; Edlund, Per; Blomberg, Carl; Nyman, Jan; Friesland, Signe; Ekman, Simon; Asklund, Thomas; Henriksson, Roger; Bergqvist, Michael

    2015-10-01

    To elucidate the impact of different forms of radiation toxicities (esophagitis, radiation pneumonitis, mucositis and hoarseness), on the survival of patients treated with curatively intended radiotherapy for non-small cell lung cancer (NSCLC). Data were individually collected retrospectively for all patients diagnosed with NSCLC subjected to curatively intended radiotherapy (≥50 Gy) in Sweden during the time period 1990 to 2000. Esophagitis was the only radiation-induced toxicity with an impact on survival (hazard ratio=0.83, p=0.016). However, in a multivariate model, with clinical- and treatment-related factors taken into consideration, the impact of esophagitis on survival was no longer statistically significant (hazard ratio=0.88, p=0.17). The effect on survival seen in univariate analysis may be related to higher radiation dose and to the higher prevalence of chemotherapy in this group. The results do not suggest that the toxicities examined have any detrimental effect on overall survival. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  2. Non-viral VEGF165 gene therapy – magnetofection of acoustically active magnetic lipospheres (‘magnetobubbles’) increases tissue survival in an oversized skin flap model

    Science.gov (United States)

    Holzbach, Thomas; Vlaskou, Dialekti; Neshkova, Iva; Konerding, Moritz A; Wörtler, Klaus; Mykhaylyk, Olga; Gänsbacher, Bernd; Machens, H-G; Plank, Christian; Giunta, Riccardo E

    2010-01-01

    Abstract Adenoviral transduction of the VEGF gene in an oversized skin flap increases flap survival and perfusion. In this study, we investigated the potential of magnetofection of magnetic lipospheres containing VEGF165-cDNA on survival and perfusion of ischemic skin flaps and evaluated the method with respect to the significance of applied magnetic field and ultrasound. We prepared perfluoropropane-filled magnetic lipospheres (‘magnetobubbles’) from Tween60-coated magnetic nanoparticles, Metafectene, soybean-oil and cDNA and studied the effect in an oversized random-pattern-flap model in the rats (n= 46). VEGF-cDNA-magnetobubbles were administered under a magnetic field with simultaneously applied ultrasound, under magnetic field alone and with applied ultrasound alone. Therapy was conducted 7 days pre-operative. Flap survival and necrosis were measured 7 days post-operatively. Flap perfusion, VEGF-protein concentration in target and surrounding tissue, formation and appearance of new vessels were analysed additionally. Magnetofection with VEGF-cDNA-magnetobubbles presented an increased flap survival of 50% and increased flap perfusion (P < 0.05). Without ultrasound and without magnetic field, the effect is weakened. VEGF concentration in target tissue was elevated (P < 0.05), while underlying muscle was not affected. Our results demonstrate the successful VEGF gene therapy by means of magnetobubble magnetofection. Here, the method of magnetofection of magnetic lipospheres is equally efficient as adenoviral transduction, but has a presumable superior safety profile. PMID:19040418

  3. Non-viral VEGF(165) gene therapy--magnetofection of acoustically active magnetic lipospheres ('magnetobubbles') increases tissue survival in an oversized skin flap model.

    Science.gov (United States)

    Holzbach, Thomas; Vlaskou, Dialekti; Neshkova, Iva; Konerding, Moritz A; Wörtler, Klaus; Mykhaylyk, Olga; Gänsbacher, Bernd; Machens, H-G; Plank, Christian; Giunta, Riccardo E

    2010-03-01

    Adenoviral transduction of the VEGF gene in an oversized skin flap increases flap survival and perfusion. In this study, we investigated the potential of magnetofection of magnetic lipospheres containing VEGF(165)-cDNA on survival and perfusion of ischemic skin flaps and evaluated the method with respect to the significance of applied magnetic field and ultrasound. We prepared perfluoropropane-filled magnetic lipospheres ('magnetobubbles') from Tween60-coated magnetic nanoparticles, Metafectene, soybean-oil and cDNA and studied the effect in an oversized random-pattern-flap model in the rats (n= 46). VEGF-cDNA-magnetobubbles were administered under a magnetic field with simultaneously applied ultrasound, under magnetic field alone and with applied ultrasound alone. Therapy was conducted 7 days pre-operative. Flap survival and necrosis were measured 7 days post-operatively. Flap perfusion, VEGF-protein concentration in target and surrounding tissue, formation and appearance of new vessels were analysed additionally. Magnetofection with VEGF-cDNA-magnetobubbles presented an increased flap survival of 50% and increased flap perfusion (P < 0.05). Without ultrasound and without magnetic field, the effect is weakened. VEGF concentration in target tissue was elevated (P < 0.05), while underlying muscle was not affected. Our results demonstrate the successful VEGF gene therapy by means of magnetobubble magnetofection. Here, the method of magnetofection of magnetic lipospheres is equally efficient as adenoviral transduction, but has a presumable superior safety profile.

  4. Sumatran tiger survival threatened by deforestation despite increasing densities in parks.

    Science.gov (United States)

    Luskin, Matthew Scott; Albert, Wido Rizki; Tobler, Mathias W

    2017-12-05

    The continuing development of improved capture-recapture (CR) modeling techniques used to study apex predators has also limited robust temporal and cross-site analyses due to different methods employed. We develop an approach to standardize older non-spatial CR and newer spatial CR density estimates and examine trends for critically endangered Sumatran tigers (Panthera tigris sumatrae) using a meta-regression of 17 existing densities and new estimates from our own fieldwork. We find that tiger densities were 47% higher in primary versus degraded forests and, unexpectedly, increased 4.9% per yr from 1996 to 2014, likely indicating a recovery from earlier poaching. However, while tiger numbers may have temporarily risen, the total potential island-wide population declined by 16.6% from 2000 to 2012 due to forest loss and degradation and subpopulations are significantly more fragmented. Thus, despite increasing densities in smaller parks, we conclude that there are only two robust populations left with >30 breeding females, indicating Sumatran tigers still face a high risk of extinction unless deforestation can be controlled.

  5. Gemtuzumab Ozogamicin (GO Inclusion to Induction Chemotherapy Eliminates Leukemic Initiating Cells and Significantly Improves Survival in Mouse Models of Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Cathy C Zhang

    2018-01-01

    Full Text Available Gemtuzumab ozogamicin (GO is an anti-CD33 antibody-drug conjugate for the treatment of acute myeloid leukemia (AML. Although GO shows a narrow therapeutic window in early clinical studies, recent reports detailing a modified dosing regimen of GO can be safely combined with induction chemotherapy, and the combination provides significant survival benefits in AML patients. Here we tested whether the survival benefits seen with the combination arise from the enhanced reduction of chemoresidual disease and leukemic initiating cells (LICs. Herein, we use cell line and patient-derived xenograft (PDX AML models to evaluate the combination of GO with daunorubicin and cytarabine (DA induction chemotherapy on AML blast growth and animal survival. DA chemotherapy and GO as separate treatments reduced AML burden but left significant chemoresidual disease in multiple AML models. The combination of GO and DA chemotherapy eliminated nearly all AML burden and extended overall survival. In two small subsets of AML models, chemoresidual disease following DA chemotherapy displayed hallmark markers of leukemic LICs (CLL1 and CD34. In vivo, the two chemoresistant subpopulations (CLL1+/CD117− and CD34+/CD38+ showed higher ability to self-renewal than their counterpart subpopulations, respectively. CD33 was coexpressed in these functional LIC subpopulations. We demonstrate that the GO and DA induction chemotherapy combination more effectively eliminates LICs in AML PDX models than either single agent alone. These data suggest that the survival benefit seen by the combination of GO and induction chemotherapy, nonclinically and clinically, may be attributed to the enhanced reduction of LICs.

  6. Increasing Calcium Carbonate (Caco3) To Growt And Survival Rate Vannamei Shrimp (Litopenaeus Vannamei))

    OpenAIRE

    Heriadi, Unggul Fitrah; ', Mulyadi; Putra, Iskandar

    2016-01-01

    This research was conducted in March 2016 - April 2016 for 21 days at the NationalBroodstock Center For Shrimp and Mollusk Karangasem Bali. The purpose of this study todetermine the effect of calcium carbonate (CaCO3) on the growth and survival rate vanameishrimp (Litopeneaus vannamei). Vanamei shrimp size PL25 were used in the research. Thecontainer used fiber tub with capacity 250 liters and the volume of water used is 100 liters.The treatment is giving of calcium carbonate 20 mg, 35mg, 50m...

  7. Pancreatic Digestive Enzyme Blockade in the Intestine Increases Survival After Experimental Shock

    Science.gov (United States)

    DeLano, Frank A.; Hoyt, David B.; Schmid-Schönbein, Geert W.

    2015-01-01

    Shock, sepsis, and multiorgan failure are associated with inflammation, morbidity, and high mortality. The underlying pathophysiological mechanism is unknown, but evidence suggests that pancreatic enzymes in the intestinal lumen autodigest the intestine and generate systemic inflammation. Blocking these enzymes in the intestine reduces inflammation and multiorgan dysfunction. We investigated whether enzymatic blockade also reduces mortality after shock. Three rat shock models were used here: hemorrhagic shock, peritonitis shock induced by placement of cecal material into the peritoneum, and endotoxin shock. One hour after initiation of hemorrhagic, peritonitis, or endotoxin shock, animals were administered one of three different pancreatic enzyme inhibitors—6-amidino-2-naphtyl p-guanidinobenzoate di-methanesulfate, tranexamic acid, or aprotinin—into the lumen of the small intestine. In all forms of shock, blockade of digestive proteases with protease inhibitor attenuated entry of digestive enzymes into the wall of the intestine and subsequent autodigestion and morphological damage to the intestine, lung, and heart. Animals treated with protease inhibitors also survived in larger numbers than untreated controls over a period of 12 weeks. Surviving animals recovered completely and returned to normal weight within 14 days after shock. The results suggest that the active and concentrated digestive enzymes in the lumen of the intestine play a central role in shock and multi-organ failure, which can be treated with protease inhibitors that are currently available for use in the clinic. PMID:23345609

  8. Recognising out-of-hospital cardiac arrest during emergency calls increases bystander cardiopulmonary resuscitation and survival

    DEFF Research Database (Denmark)

    Viereck, Søren; Møller, Thea Palsgaard; Ersbøll, Annette Kjær

    2017-01-01

    BACKGROUND: Initiation of early bystander cardiopulmonary resuscitation (CPR) depends on bystanders' or medical dispatchers' recognition of out-of-hospital cardiac arrest (OHCA). The primary aim of our study was to investigate if OHCA recognition during the emergency call was associated with byst......BACKGROUND: Initiation of early bystander cardiopulmonary resuscitation (CPR) depends on bystanders' or medical dispatchers' recognition of out-of-hospital cardiac arrest (OHCA). The primary aim of our study was to investigate if OHCA recognition during the emergency call was associated...... with bystander CPR, return of spontaneous circulation (ROSC), and 30-day survival. Our secondary aim was to identify patient-, setting-, and dispatcher-related predictors of OHCA recognition. METHODS: We performed an observational study of all OHCA patients' emergency calls in the Capital Region of Denmark from...... the association between OHCA recognition and bystander CPR, ROSC, and 30-day survival. Univariable logistic regression analyses were applied to identify predictors of OHCA recognition. RESULTS: We included 779 emergency calls in the analyses. During the emergency calls, 70.1% (n=534) of OHCAs were recognised...

  9. Increased tumour ADC value during chemotherapy predicts improved survival in unresectable pancreatic cancer

    Energy Technology Data Exchange (ETDEWEB)

    Nishiofuku, Hideyuki; Tanaka, Toshihiro; Kichikawa, Kimihiko [Nara Medical University, Department of Radiology and IVR Center, Kashihara-city, Nara (Japan); Marugami, Nagaaki [Nara Medical University, Department of Endoscopy and Ultrasound, Kashihara-city, Nara (Japan); Sho, Masayuki; Akahori, Takahiro; Nakajima, Yoshiyuki [Nara Medical University, Department of Surgery, Kashihara-city, Nara (Japan)

    2016-06-15

    To investigate whether changes to the apparent diffusion coefficient (ADC) of primary tumour in the early period after starting chemotherapy can predict progression-free survival (PFS) or overall survival (OS) in patients with unresectable pancreatic adenocarcinoma. Subjects comprised 43 patients with histologically confirmed unresectable pancreatic cancer treated with first-line chemotherapy. Minimum ADC values in primary tumour were measured using the selected area ADC (sADC), which excluded cystic and necrotic areas and vessels, and the whole tumour ADC (wADC), which included whole tumour components. Relative changes in ADC were calculated from baseline to 4 weeks after initiation of chemotherapy. Relationships between ADC and both PFS and OS were modelled by Cox proportional hazards regression. Median PFS and OS were 6.1 and 11.0 months, respectively. In multivariate analysis, sADC change was the strongest predictor of PFS (hazard ratio (HR), 4.5; 95 % confidence interval (CI), 1.7-11.9; p = 0.002). Multivariate Cox regression analysis for OS revealed sADC change and CRP as independent predictive markers, with sADC change as the strongest predictive biomarker (HR, 6.7; 95 % CI, 2.7-16.6; p = 0.001). Relative changes in sADC could provide a useful imaging biomarker to predict PFS and OS with chemotherapy for unresectable pancreatic adenocarcinoma. (orig.)

  10. Surgical fusion of early onset severe scoliosis increases survival in Rett syndrome: a cohort study.

    Science.gov (United States)

    Downs, Jenny; Torode, Ian; Wong, Kingsley; Ellaway, Carolyn; Elliott, Elizabeth J; Izatt, Maree T; Askin, Geoffrey N; Mcphee, Bruce I; Cundy, Peter; Leonard, Helen

    2016-06-01

    Scoliosis is a common comorbidity in Rett syndrome and spinal fusion may be recommended if severe. We investigated the impact of spinal fusion on survival and risk of severe lower respiratory tract infection in Rett syndrome. Data were ascertained from hospital medical records, the Australian Rett Syndrome Database, a longitudinal and population-based registry, and from the Australian Institute of Health and Welfare National Death Index database. Cox regression and generalized estimating equation models were used to estimate the effects of spinal surgery on survival and severe respiratory infection respectively in 140 females who developed severe scoliosis (Cobb angle ≥45°) before adulthood. After adjusting for mutation type and age of scoliosis onset, the rate of death was lower in the surgery group (hazard ratio [HR] 0.30, 95% confidence interval [CI] 0.12-0.74; p=0.009) compared to those without surgery. Rate of death was particularly reduced for those with early onset scoliosis (HR 0.17, 95% CI 0.06-0.52; p=0.002). There was some evidence to suggest that spinal fusion was associated with a reduction in risk of severe respiratory infection among those with early onset scoliosis (risk ratio 0.41, 95% CI 0.16-1.03; p=0.06). With appropriate cautions, spinal fusion confers an advantage to life expectancy in Rett syndrome. © 2015 Mac Keith Press.

  11. Lundep, a sand fly salivary endonuclease increases Leishmania parasite survival in neutrophils and inhibits XIIa contact activation in human plasma.

    Directory of Open Access Journals (Sweden)

    Andrezza C Chagas

    2014-02-01

    Full Text Available Neutrophils are the host's first line of defense against infections, and their extracellular traps (NET were recently shown to kill Leishmania parasites. Here we report a NET-destroying molecule (Lundep from the salivary glands of Lutzomyia longipalpis. Previous analysis of the sialotranscriptome of Lu. longipalpis showed the potential presence of an endonuclease. Indeed, not only was the cloned cDNA (Lundep shown to encode a highly active ss- and dsDNAse, but also the same activity was demonstrated to be secreted by salivary glands of female Lu. longipalpis. Lundep hydrolyzes both ss- and dsDNA with little sequence specificity with a calculated DNase activity of 300000 Kunitz units per mg of protein. Disruption of PMA (phorbol 12 myristate 13 acetate- or parasite-induced NETs by treatment with recombinant Lundep or salivary gland homogenates increases parasite survival in neutrophils. Furthermore, co-injection of recombinant Lundep with metacyclic promastigotes significantly exacerbates Leishmania infection in mice when compared with PBS alone or inactive (mutagenized Lundep. We hypothesize that Lundep helps the parasite to establish an infection by allowing it to escape from the leishmanicidal activity of NETs early after inoculation. Lundep may also assist blood meal intake by lowering the local viscosity caused by the release of host DNA and as an anticoagulant by inhibiting the intrinsic pathway of coagulation.

  12. Flexible survival strategies of Pseudomonas aeruginosa in biofilms result in increased fitness compared with Candida albicans.

    Science.gov (United States)

    Purschke, Frauke Gina; Hiller, Ekkehard; Trick, Iris; Rupp, Steffen

    2012-12-01

    The majority of microorganisms persist in nature as surface-attached communities often surrounded by an extracellular matrix, called biofilms. Most natural biofilms are not formed by a single species but by multiple species. Microorganisms not only cooperate as in some multispecies biofilms but also compete for available nutrients. The Gram-negative bacterium Pseudomonas aeruginosa and the polymorphic fungus Candida albicans are two opportunistic pathogens that are often found coexisting in a human host. Several models of mixed biofilms have been reported for these organisms showing antagonistic behavior. To investigate the interaction of P. aeruginosa and C. albicans in more detail, we analyzed the secretome of single and mixed biofilms of both organisms using MALDI-TOF MS/MS at several time points. Overall 247 individual proteins were identified, 170 originated from P. aeruginosa and 77 from C. albicans. Only 39 of the 131 in mixed biofilms identified proteins were assigned to the fungus whereby the remaining 92 proteins belonged to P. aeruginosa. In single-species biofilms, both organisms showed a higher diversity of proteins with 73 being assigned to C. albicans and 154 to P. aeruginosa. Most interestingly, P. aeruginosa in the presence of C. albicans secreted 16 proteins in significantly higher amounts or exclusively among other virulence factors such as exotoxin A and iron acquisition systems. In addition, the high affinity iron-binding siderophore pyoverdine was identified in mixed biofilms but not in bacterial biofilms, indicating that P. aeruginosa increases its capability to sequester iron in competition with C. albicans. In contrast, C. albicans metabolism was significantly reduced, including a reduction in detectable iron acquisition proteins. The results obtained in this study show that microorganisms not only compete with the host for essential nutrients but also strongly with the present microflora in order to gain a competitive advantage.

  13. Flexible Survival Strategies of Pseudomonas aeruginosa in Biofilms Result in Increased Fitness Compared with Candida albicans *

    Science.gov (United States)

    Purschke, Frauke Gina; Hiller, Ekkehard; Trick, Iris; Rupp, Steffen

    2012-01-01

    The majority of microorganisms persist in nature as surface-attached communities often surrounded by an extracellular matrix, called biofilms. Most natural biofilms are not formed by a single species but by multiple species. Microorganisms not only cooperate as in some multispecies biofilms but also compete for available nutrients. The Gram-negative bacterium Pseudomonas aeruginosa and the polymorphic fungus Candida albicans are two opportunistic pathogens that are often found coexisting in a human host. Several models of mixed biofilms have been reported for these organisms showing antagonistic behavior. To investigate the interaction of P. aeruginosa and C. albicans in more detail, we analyzed the secretome of single and mixed biofilms of both organisms using MALDI-TOF MS/MS at several time points. Overall 247 individual proteins were identified, 170 originated from P. aeruginosa and 77 from C. albicans. Only 39 of the 131 in mixed biofilms identified proteins were assigned to the fungus whereby the remaining 92 proteins belonged to P. aeruginosa. In single-species biofilms, both organisms showed a higher diversity of proteins with 73 being assigned to C. albicans and 154 to P. aeruginosa. Most interestingly, P. aeruginosa in the presence of C. albicans secreted 16 proteins in significantly higher amounts or exclusively among other virulence factors such as exotoxin A and iron acquisition systems. In addition, the high affinity iron-binding siderophore pyoverdine was identified in mixed biofilms but not in bacterial biofilms, indicating that P. aeruginosa increases its capability to sequester iron in competition with C. albicans. In contrast, C. albicans metabolism was significantly reduced, including a reduction in detectable iron acquisition proteins. The results obtained in this study show that microorganisms not only compete with the host for essential nutrients but also strongly with the present microflora in order to gain a competitive advantage. PMID

  14. Molecular subtype and tumor characteristics of breast cancer metastases as assessed by gene expression significantly influence patient post-relapse survival.

    Science.gov (United States)

    Tobin, N P; Harrell, J C; Lövrot, J; Egyhazi Brage, S; Frostvik Stolt, M; Carlsson, L; Einbeigi, Z; Linderholm, B; Loman, N; Malmberg, M; Walz, T; Fernö, M; Perou, C M; Bergh, J; Hatschek, T; Lindström, L S

    2015-01-01

    We and others have recently shown that tumor characteristics are altered throughout tumor progression. These findings emphasize the need for re-examination of tumor characteristics at relapse and have led to recommendations from ESMO and the Swedish Breast Cancer group. Here, we aim to determine whether tumor characteristics and molecular subtypes in breast cancer metastases confer clinically relevant prognostic information for patients. The translational aspect of the Swedish multicenter randomized trial called TEX included 111 patients with at least one biopsy from a morphologically confirmed locoregional or distant breast cancer metastasis diagnosed from December 2002 until June 2007. All patients had detailed clinical information, complete follow-up, and metastasis gene expression information (Affymetrix array GPL10379). We assessed the previously published gene expression modules describing biological processes [proliferation, apoptosis, human epidermal receptor 2 (HER2) and estrogen (ER) signaling, tumor invasion, immune response, and angiogenesis] and pathways (Ras, MAPK, PTEN, AKT-MTOR, PI3KCA, IGF1, Src, Myc, E2F3, and β-catenin) and the intrinsic subtypes (PAM50). Furthermore, by contrasting genes expressed in the metastases in relation to survival, we derived a poor metastasis survival signature. A significant reduction in post-relapse breast cancer-specific survival was associated with low-ER receptor signaling and apoptosis gene module scores, and high AKT-MTOR, Ras, and β-catenin module scores. Similarly, intrinsic subtyping of the metastases provided statistically significant post-relapse survival information with the worst survival outcome in the basal-like [hazard ratio (HR) 3.7; 95% confidence interval (CI) 1.3-10.9] and HER2-enriched (HR 4.4; 95% CI 1.5-12.8) subtypes compared with the luminal A subtype. Overall, 25% of the metastases were basal-like, 32% HER2-enriched, 10% luminal A, 28% luminal B, and 5% normal-like. We show that tumor

  15. Increased expression of interleukin-21 along colorectal adenoma-carcinoma sequence and its predicating significance in patients with sporadic colorectal cancer.

    Science.gov (United States)

    Cui, Guanglin; Yuan, Aping; Zhu, Li; Florholmen, Jon; Goll, Rasmus

    2017-10-01

    The role and significance of interleukin (IL)-21 in the development of sporadic CRC have not been well defined. The aim of this study is therefore to investigate the dynamics of the IL-21 along colorectal adenoma-carcinoma sequence and to evaluate the impact of IL-21 on clinicopathological parameters and CRC prognosis. The real-time PCR results showed that the level of IL-21 in adenomas (n=50) and sporadic CRC (n=50) were significantly higher than that in normal controls (n=18), which were predominately observed in the adenoma/CRC stroma. Analysis revealed that IL-21 level was correlated with the overall survival time in CRC patients. Double immunofluorescence observations confirmed that IL-21 positive cells were mostly natural killer cells and T lymphocytes in the tumor stroma. These results indicate that significant increased IL-21 expression present within the adenoma/CRC microenvironment might have a potential predicating significance for survival time in patients with CRC. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Prognostic significance of electrical alternans versus signal averaged electrocardiography in predicting the outcome of electrophysiological testing and arrhythmia-free survival

    Science.gov (United States)

    Armoundas, A. A.; Rosenbaum, D. S.; Ruskin, J. N.; Garan, H.; Cohen, R. J.

    1998-01-01

    OBJECTIVE: To investigate the accuracy of signal averaged electrocardiography (SAECG) and measurement of microvolt level T wave alternans as predictors of susceptibility to ventricular arrhythmias. DESIGN: Analysis of new data from a previously published prospective investigation. SETTING: Electrophysiology laboratory of a major referral hospital. PATIENTS AND INTERVENTIONS: 43 patients, not on class I or class III antiarrhythmic drug treatment, undergoing invasive electrophysiological testing had SAECG and T wave alternans measurements. The SAECG was considered positive in the presence of one (SAECG-I) or two (SAECG-II) of three standard criteria. T wave alternans was considered positive if the alternans ratio exceeded 3.0. MAIN OUTCOME MEASURES: Inducibility of sustained ventricular tachycardia or fibrillation during electrophysiological testing, and 20 month arrhythmia-free survival. RESULTS: The accuracy of T wave alternans in predicting the outcome of electrophysiological testing was 84% (p antiarrhythmic agents. The accuracy of T wave alternans in predicting the outcome of arrhythmia-free survival was 86% (p < 0.030). Neither SAECG-I (accuracy 65%; p < 0.21) nor SAECG-II (accuracy 71%; p < 0.48) was a statistically significant predictor of arrhythmia-free survival. CONCLUSIONS: T wave alternans was a highly significant predictor of the outcome of electrophysiological testing and arrhythmia-free survival, while SAECG was not a statistically significant predictor. Although these results need to be confirmed in prospective clinical studies, they suggest that T wave alternans may serve as a non-invasive probe for screening high risk populations for malignant ventricular arrhythmias.

  17. Prognostic significance of electrical alternans versus signal averaged electrocardiography in predicting the outcome of electrophysiological testing and arrhythmia-free survival

    Science.gov (United States)

    Armoundas, A. A.; Rosenbaum, D. S.; Ruskin, J. N.; Garan, H.; Cohen, R. J.

    1998-01-01

    OBJECTIVE: To investigate the accuracy of signal averaged electrocardiography (SAECG) and measurement of microvolt level T wave alternans as predictors of susceptibility to ventricular arrhythmias. DESIGN: Analysis of new data from a previously published prospective investigation. SETTING: Electrophysiology laboratory of a major referral hospital. PATIENTS AND INTERVENTIONS: 43 patients, not on class I or class III antiarrhythmic drug treatment, undergoing invasive electrophysiological testing had SAECG and T wave alternans measurements. The SAECG was considered positive in the presence of one (SAECG-I) or two (SAECG-II) of three standard criteria. T wave alternans was considered positive if the alternans ratio exceeded 3.0. MAIN OUTCOME MEASURES: Inducibility of sustained ventricular tachycardia or fibrillation during electrophysiological testing, and 20 month arrhythmia-free survival. RESULTS: The accuracy of T wave alternans in predicting the outcome of electrophysiological testing was 84% (p data were available in 36 patients while not on class I or III antiarrhythmic agents. The accuracy of T wave alternans in predicting the outcome of arrhythmia-free survival was 86% (p < 0.030). Neither SAECG-I (accuracy 65%; p < 0.21) nor SAECG-II (accuracy 71%; p < 0.48) was a statistically significant predictor of arrhythmia-free survival. CONCLUSIONS: T wave alternans was a highly significant predictor of the outcome of electrophysiological testing and arrhythmia-free survival, while SAECG was not a statistically significant predictor. Although these results need to be confirmed in prospective clinical studies, they suggest that T wave alternans may serve as a non-invasive probe for screening high risk populations for malignant ventricular arrhythmias.

  18. Increased flexibility for modeling telemetry and nest-survival data using the multistate framework

    Science.gov (United States)

    Devineau, Olivier; Kendall, William L.; Doherty, Paul F.; Shenk, Tanya M.; White, Gary C.; Lukacs, Paul M.; Burnham, Kenneth P.

    2014-01-01

    Although telemetry is one of the most common tools used in the study of wildlife, advances in the analysis of telemetry data have lagged compared to progress in the development of telemetry devices. We demonstrate how standard known-fate telemetry and related nest-survival data analysis models are special cases of the more general multistate framework. We present a short theoretical development, and 2 case examples regarding the American black duck and the mallard. We also present a more complex lynx data analysis. Although not necessary in all situations, the multistate framework provides additional flexibility to analyze telemetry data, which may help analysts and biologists better deal with the vagaries of real-world data collection.

  19. Cardiomyocyte Differentiation Promotes Cell Survival During Nicotinamide Phosphoribosyltransferase Inhibition Through Increased Maintenance of Cellular Energy Stores.

    Science.gov (United States)

    Kropp, Erin M; Broniowska, Katarzyna A; Waas, Matthew; Nycz, Alyssa; Corbett, John A; Gundry, Rebekah L

    2017-04-01

    To address concerns regarding the tumorigenic potential of undifferentiated human pluripotent stem cells (hPSC) that may remain after in vitro differentiation and ultimately limit the broad use of hPSC-derivatives for therapeutics, we recently described a method to selectively eliminate tumorigenic hPSC from their progeny by inhibiting nicotinamide phosphoribosyltransferase (NAMPT). Limited exposure to NAMPT inhibitors selectively removes hPSC from hPSC-derived cardiomyocytes (hPSC-CM) and spares a wide range of differentiated cell types; yet, it remains unclear when and how cells acquire resistance to NAMPT inhibition during differentiation. In this study, we examined the effects of NAMPT inhibition among multiple time points of cardiomyocyte differentiation. Overall, these studies show that in vitro cardiomyogenic commitment and continued culturing provides resistance to NAMPT inhibition and cell survival is associated with the ability to maintain cellular ATP pools despite depletion of NAD levels. Unlike cells at earlier stages of differentiation, day 28 hPSC-CM can survive longer periods of NAMPT inhibition and maintain ATP generation by glycolysis and/or mitochondrial respiration. This is distinct from terminally differentiated fibroblasts, which maintain mitochondrial respiration during NAMPT inhibition. Overall, these results provide new mechanistic insight into how regulation of cellular NAD and energy pools change with hPSC-CM differentiation and further inform how NAMPT inhibition strategies could be implemented within the context of cardiomyocyte differentiation. Stem Cells Translational Medicine 2017;6:1191-1201. © 2017 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

  20. Increased Severe Trauma Patient Volume is Associated With Survival Benefit and Reduced Total Health Care Costs: A Retrospective Observational Study Using a Japanese Nationwide Administrative Database.

    Science.gov (United States)

    Endo, Akira; Shiraishi, Atsushi; Fushimi, Kiyohide; Murata, Kiyoshi; Otomo, Yasuhiro

    2017-06-07

    The aim of this study was to evaluate the associations of severe trauma patient volume with survival benefit and health care costs. The effect of trauma patient volume on survival benefit is inconclusive, and reports on its effects on health care costs are scarce. We conducted a retrospective observational study, including trauma patients who were transferred to government-approved tertiary emergency hospitals, or hospitals with an intensive care unit that provided an equivalent quality of care, using a Japanese nationwide administrative database. We categorized hospitals according to their annual severe trauma patient volumes [1 to 50 (reference), 51 to 100, 101 to 150, 151 to 200, and ≥201]. We evaluated the associations of volume categories with in-hospital survival and total cost per admission using a mixed-effects model adjusting for patient severity and hospital characteristics. A total of 116,329 patients from 559 hospitals were analyzed. Significantly increased in-hospital survival rates were observed in the second, third, fourth, and highest volume categories compared with the reference category [94.2% in the highest volume category vs 88.8% in the reference category, adjusted odds ratio (95% confidence interval, 95% CI) = 1.75 (1.49-2.07)]. Furthermore, significantly lower costs (in US dollars) were observed in the second and fourth categories [mean (standard deviation) for fourth vs reference = $17,800 ($17,378) vs $20,540 ($32,412), adjusted difference (95% CI) = -$2559 (-$3896 to -$1221)]. Hospitals with high volumes of severe trauma patients were significantly associated with a survival benefit and lower total cost per admission.

  1. Hypothermia after cardiac arrest as a novel approach to increase survival in cardiopulmonary cerebral resuscitation: a review.

    Science.gov (United States)

    Soleimanpour, Hassan; Rahmani, Farzad; Safari, Saeid; Golzari, Samad Ej

    2014-07-01

    The aim of this review study was to evaluate therapeutic mild hypothermia, its complications and various methods for induced mild hypothermia in patients following resuscitation after out-of-hospital cardiac arrest. Studies conducted on post-cardiac arrest cares, history of induced hypothermia, and therapeutic hypothermia for patients with cardiac arrest were included in this study. We used the valid databases (PubMed and Cochrane library) to collect relevant articles. According to the studies reviewed, induction of mild hypothermia in patients after cardiopulmonary resuscitation would lead to increased survival and better neurological outcome; however, studies on the complications of hypothermia or different methods of inducing hypothermia were limited and needed to be studied further. This study provides strategic issues concerning the induction of mild hypothermia, its complications, and different ways of performing it on patients; using this method helps to increase patients' neurological survival rate.

  2. Calcineurin inhibition at the clinical phase of prion disease reduces neurodegeneration, improves behavioral alterations and increases animal survival.

    Directory of Open Access Journals (Sweden)

    Abhisek Mukherjee

    2010-10-01

    Full Text Available Prion diseases are fatal neurodegenerative disorders characterized by a long pre-symptomatic phase followed by rapid and progressive clinical phase. Although rare in humans, the unconventional infectious nature of the disease raises the potential for an epidemic. Unfortunately, no treatment is currently available. The hallmark event in prion diseases is the accumulation of a misfolded and infectious form of the prion protein (PrP(Sc. Previous reports have shown that PrP(Sc induces endoplasmic reticulum stress and changes in calcium homeostasis in the brain of affected individuals. In this study we show that the calcium-dependent phosphatase Calcineurin (CaN is hyperactivated both in vitro and in vivo as a result of PrP(Sc formation. CaN activation mediates prion-induced neurodegeneration, suggesting that inhibition of this phosphatase could be a target for therapy. To test this hypothesis, prion infected wild type mice were treated intra-peritoneally with the CaN inhibitor FK506 at the clinical phase of the disease. Treated animals exhibited reduced severity of the clinical abnormalities and increased survival time compared to vehicle treated controls. Treatment also led to a significant increase in the brain levels of the CaN downstream targets pCREB and pBAD, which paralleled the decrease of CaN activity. Importantly, we observed a lower degree of neurodegeneration in animals treated with the drug as revealed by a higher number of neurons and a lower quantity of degenerating nerve cells. These changes were not dependent on PrP(Sc formation, since the protein accumulated in the brain to the same levels as in the untreated mice. Our findings contribute to an understanding of the mechanism of neurodegeneration in prion diseases and more importantly may provide a novel strategy for therapy that is beneficial at the clinical phase of the disease.

  3. Increase of Intracellular Cyclic AMP by PDE4 Inhibitors Affects HepG2 Cell Cycle Progression and Survival.

    Science.gov (United States)

    Massimi, Mara; Cardarelli, Silvia; Galli, Francesca; Giardi, Maria Federica; Ragusa, Federica; Panera, Nadia; Cinque, Benedetta; Cifone, Maria Grazia; Biagioni, Stefano; Giorgi, Mauro

    2017-06-01

    Type 4 cyclic nucleotide phosphodiesterases (PDE4) are major members of a superfamily of enzymes (PDE) involved in modulation of intracellular signaling mediated by cAMP. Broadly expressed in most human tissues and present in large amounts in the liver, PDEs have in the last decade been key therapeutic targets for several inflammatory diseases. Recently, a significant body of work has underscored their involvement in different kinds of cancer, but with no attention paid to liver cancer. The present study investigated the effects of two PDE4 inhibitors, rolipram and DC-TA-46, on the growth of human hepatoma HepG2 cells. Treatment with these inhibitors caused a marked increase of intracellular cAMP level and a dose- and time-dependent effect on cell growth. The concentrations of inhibitors that halved cell proliferation to about 50% were used for cell cycle experiments. Rolipram (10 μM) and DC-TA-46 (0.5 μM) produced a decrease of cyclin expression, in particular of cyclin A, as well as an increase in p21, p27 and p53, as evaluated by Western blot analysis. Changes in the intracellular localization of cyclin D1 were also observed after treatments. In addition, both inhibitors caused apoptosis, as demonstrated by an Annexin-V cytofluorimetric assay and analysis of caspase-3/7 activity. Results demonstrated that treatment with PDE4 inhibitors affected HepG2 cell cycle and survival, suggesting that they might be useful as potential adjuvant, chemotherapeutic or chemopreventive agents in hepatocellular carcinoma. J. Cell. Biochem. 118: 1401-1411, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  4. Aggressive Treatment of Performance Status 1 and 2 HCC Patients Significantly Improves Survival - an Egyptian Retrospective Cohort Study of 524 Cases.

    Science.gov (United States)

    Aziz, Ashraf Omar Abdel; Omran, Dalia; Nabeel, Mohamed Mahmoud; Elbaz, Tamer Mahmoud; Abdelmaksoud, Ahmed Hosni; Attar, Inas El; Shousha, Hend Ibrahim

    2016-01-01

    In the Barcelona Clinic Liver Cancer (BCLC) system, only sorafenib is suggested for HCC patients having performance status (PS) 1 or 2 even if they have treatable lesions. In the current study, we aimed to explore the outcome of using aggressive treatment for HCC patients with PS 1 and 2. Five hundred and twenty four patients with HCC were enrolled in this study and divided into 2 groups: 404 PS 1 and 120 PS 2. Of the included 524 patients, 136 recceived non-aggressive supportive treatment and sorafenib, while 388 patients were offered aggressive treatment in the form of surgical resection, transplantation, percutaneous ablation, trans-arterial chemoembolization and/or chemoperfusion. All the patients were followed up for a period of 2 years to determine their survival. Most HCC patients were CHILD A and B grades (89.4% versus 85.0%, for PS1 and PS2, respectively). Patients with PS1 were significantly younger. Out of the enrolled 524 patients, 388 were offered aggressive treatment, 253 (65.2%) having their lesions fully ablated, 94 (24.2%) undergoing partial ablation and 41 patients with no ablation (10.6%). The median survival of the patients with PS 1 who were offered aggressive treatment was 20 months versus 9 months only for those who were offered supportive treatment and sorafenib (<0.001). Regarding HCC patients with PS 2, the median survivals were similarly 19.7 months versus 8.7 months only (<0.001). Aggressive treatment of HCC patients with PS 1 and 2 significantly improves their survival. Revising the BCLC guidelines regarding such patients is recommended.

  5. Edema-induced increase in tumour cell survival for {sup 125}I and {sup 103}Pd prostate permanent seed implants - a bio-mathematical model

    Energy Technology Data Exchange (ETDEWEB)

    Yue Ning; Chen Zhe; Nath, Ravinder [Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT (United States)

    2002-04-01

    with the increase of edema magnitude and EHL. For a typical edema of a half-life of 10 days and a magnitude of 50%, the edema increased tumour cell survival by about 1 and 2 orders of magnitude for {sup 125}I and {sup 103}Pd seed implants respectively. At the extreme (95% edema magnitude and an edema half-life of 30 days), the increase was more than 3 and 5 orders of magnitude for {sup 125}I and {sup 103}Pd seed implants respectively. The absolute increases were almost independent of TPDT and the prostate edema did not significantly change the effective treatment time. Tumour cell survival for prostate undergoing CLDRI using {sup 125}I or {sup 103}Pd seeds may be increased substantially due to the presence of edema caused by surgical trauma. This effect appears to be more pronounced for {sup 103}Pd than {sup 125}I because of the shorter half-life of {sup 103}Pd. If significant edema is observed post implantation, then a boost to the prostate using external beam radiotherapy may be considered as a part of the treatment strategy. (author)

  6. Effect of increased ovulation rate on embryo and foetal survival as a model for selection by ovulation rate in rabbits

    Directory of Open Access Journals (Sweden)

    A.Y. Badawy

    2016-06-01

    Full Text Available Selection for ovulation rate in prolific species has not improved litter size, due to an increase in prenatal mortality, with most mortality observed in the foetal period. The aim of this study was to investigate the magnitude and timing of embryo and early foetal survival in females with high ovulation rate using hormonal treatment as a model for selection by ovulation rate. Two groups of females (treated and untreated were used. Treated females were injected with 50 IU equine chorionic gonadotropin 48 h before mating. Females were slaughtered at 18 d of gestation. Ovulation rate (OR, number of implanted embryos (IE, number of live foetuses at 12 and 18 d (LF12 and LF18, respectively were recorded. In addition, embryo survival (ES=IE/OR, foetal survival at 18 d of gestation (FSLF18=LF18/IE, foetal survival between 12 and 18 d of gestation (FSLF18/LF12=LF18/LF12 and prenatal survival (PSLF18=LF18/OR were estimated. For each female, the mean and variability of the weight for live foetuses (LFWm and LFWv, respectively and their placentas (LFPWm and LFPWv, respectively were calculated. Treated females had a higher ovulation rate (+3.02 ova than untreated females, with a probability of 0.99. An increase in the differences (D between treated and untreated females was observed from implantation to 18 d of gestation (D=–0.33, –0.70 and –1.28 for IE, LF12 and LF18, respectively. These differences had a low accuracy and the probability that treated females would have a lower number of foetuses also increased throughout gestation (0.60, 0.70 and 0.86 for IE, LF12 and LF18, respectively. According to the previous results for OR and LF18, treated females showed a lower survival rate from ovulation to 18 d of gestation (D=–0.12, P=0.98 for PSLF18. Treated females also had lower embryo and foetal survival (D=–0.10 and P=0.94 for ES and D=–0.08 and P=0.93 for FSLF18. Main differences in foetal survival appeared from 12 to 18 d of gestation (D=–0

  7. The small-molecule TNF-α inhibitor, UTL-5g, delays deaths and increases survival rates for mice treated with high doses of cisplatin.

    Science.gov (United States)

    Shaw, Jiajiu; Media, Joseph; Chen, Ben; Valeriote, Fredrick

    2013-09-01

    UTL-5g is a novel small-molecule chemoprotector that lowers hepatotoxicity, nephrotoxicity, and myelotoxicity induced by cisplatin through TNF-α inhibition among other factors. The objective of this study was to investigate whether UTL-5g can reduce the overall acute toxicity of cisplatin and increase cisplatin tolerability in mice. BDF1 female mice were treated individually with UTL-5g (suspended in Ora-Plus) by oral gavage at 60 mg/kg, 30 min before i.p. injection of cisplatin at 10, 15, and 20 mg/kg, respectively, on Day 0. Starting from Day 1, individual mice were again treated daily by the same dose of UTL-5g for 4 consecutive days. Survivals and body weights were monitored. UTL-5g treatment increased the survival rate and delayed the time to death for mice treated with 150 % of the maximum tolerated dose (MTD) of cisplatin (15 mg/kg). Likewise, at 200 % of the MTD of cisplatin (20 mg/kg), treatment of UTL-5g increased the survival rate and delayed the time to death. Treatment of UTL-5g did not have a significant effect on weight loss induced by cisplatin, indicating that body weight may not be a sensitive-enough measure for chemoprotection of UTL-5g against cisplatin. In summary, UTL-5g delayed deaths and increased survival rates of mice treated by high doses of cisplatin, indicating that UTL-5g is capable of reducing the overall acute toxicity of cisplatin and increased cisplatin tolerability in mice; this is in line with the specific chemoprotective effects of UTL-5g previously reported. Further investigation of UTL-5g in combination with cisplatin is warranted.

  8. Coffee consumption protects against progression in liver cirrhosis and increases long-term survival after liver transplantation.

    Science.gov (United States)

    Friedrich, Kilian; Smit, Mark; Wannhoff, Andreas; Rupp, Christian; Scholl, Sabine G; Antoni, Christoph; Dollinger, Matthias; Neumann-Haefelin, Christoph; Stremmel, Wolfgang; Weiss, Karl Heinz; Schemmer, Peter; Gotthardt, Daniel Nils

    2016-08-01

    Therapeutic options to treat progression of end-stage liver disease (ESLD) or improve long-term survival after liver transplantation remain scarce. We investigated the impact of coffee consumption under these conditions. We recorded coffee consumption habits of 379 patients with ESLD awaiting liver transplantation and 260 patients after liver transplantation. Survival was analyzed based on coffee intake. One hundred ninety-five patients with ESLD consumed coffee on a daily basis, while 184 patients did not. Actuarial survival was impaired (P = 0.041) in non-coffee drinkers (40.4 ± 4.3 months, 95% confidence interval [CI]: 32.0-48.9) compared with coffee drinkers (54.9 ± 5.5 months, 95% CI: 44.0-65.7). In subgroup analysis, the survival of patients with alcoholic liver disease (ALD; P = 0.020) and primary sclerosing cholangitis (PSC; P = 0.017) was increased with coffee intake while unaffected in patients with chronic viral hepatitis (P = 0.517) or other liver disease entities (P = 0.652). Multivariate analysis showed that coffee consumption of PSC and ALD patients retained as an independent risk factor (odds ratio [OR]: 1.94; 95% CI: 1.15-3.28; P = 0.013) along with MELD score (OR: 1.13; 95% CI: 1.09-1.17; P = 0.000). Following liver transplantation, long-term survival was longer in coffee drinkers (coffee: 61.8 ± 2.0 months, 95% CI: 57.9-65.8) than non-drinkers (52.3 ± 3.5 months, 95% CI: 45.4-59.3; P = 0.001). Coffee consumption delayed disease progression in ALD and PSC patients with ESLD and increased long-term survival after liver transplantation. We conclude that regular coffee intake might be recommended for these patients. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  9. Empiric potassium supplementation and increased survival in users of loop diuretics.

    Directory of Open Access Journals (Sweden)

    Charles E Leonard

    Full Text Available The effectiveness of the clinical strategy of empiric potassium supplementation in reducing the frequency of adverse clinical outcomes in patients receiving loop diuretics is unknown. We sought to examine the association between empiric potassium supplementation and 1 all-cause death and 2 outpatient-originating sudden cardiac death (SD and ventricular arrhythmia (VA among new starters of loop diuretics, stratified on initial loop diuretic dose.We conducted a one-to-one propensity score-matched cohort study using 1999-2007 US Medicaid claims from five states. Empiric potassium supplementation was defined as a potassium prescription on the day of or the day after the initial loop diuretic prescription. Death, the primary outcome, was ascertained from the Social Security Administration Death Master File; SD/VA, the secondary outcome, from incident, first-listed emergency department or principal inpatient SD/VA discharge diagnoses (positive predictive value = 85%.We identified 654,060 persons who met eligibility criteria and initiated therapy with a loop diuretic, 27% of whom received empiric potassium supplementation (N = 179,436 and 73% of whom did not (N = 474,624. The matched hazard ratio for empiric potassium supplementation was 0.93 (95% confidence interval, 0.89-0.98, p = 0.003 for all-cause death. Stratifying on initial furosemide dose, hazard ratios for empiric potassium supplementation with furosemide < 40 and ≥ 40 milligrams/day were 0.93 (0.86-1.00, p = 0.050 and 0.84 (0.79-0.89, p < 0.0001. The matched hazard ratio for empiric potassium supplementation was 1.02 (0.83-1.24, p = 0.879 for SD/VA.Empiric potassium supplementation upon initiation of a loop diuretic appears to be associated with improved survival, with a greater apparent benefit seen with higher diuretic dose. If confirmed, these findings support the use of empiric potassium supplementation upon initiation of a loop diuretic.

  10. Chelerythrine delayed tumor growth and increased survival duration of Dalton′s lymphoma bearing BALB/c H 2d mice by activation of NK cells in vivo

    Directory of Open Access Journals (Sweden)

    Sanjay Kumar

    2015-01-01

    Full Text Available Aim: The aims of the present investigation were to evaluate the antitumor effect of chelerythrine (CHE on in vivo growth and survival duration of BALB/c (H 2d mice bearing Dalton′s lymphoma (DL and enhanced function of tumor associated NK cells (TANK cells. Materials and Methods: BALB/c (H 2d mice at 8-10 weeks of age of either sex were used. Increasing concentration of CHE (1.25, 2.5, and 5.0 mg/kg, staurosporine (0.625, 1.0, 1.5, and 2.0 mg/kg and cyclophosphamide (25, 50, 100, and 200 mg/kg were administered intraperitoneally and tumor regression and survival duration of tumor bearing host were determined, and thereafter expression of NKG2D and NKG2A on TANK cells were detected. Results: Our results show that treatment with 2.5 mg/kg of CHE results in a significant reduction in mean tumor volume and increased survival duration of DL bearing BALB/c (H 2d mice when compared to control. Activating receptor NKG2D on TANK cells were observed upregulated in contrast to inhibitory receptor NKG2A. Conclusions: CHE reduced mean tumor volume and increased survival duration of DL bearing BALB/c (H 2d mice. Increased expression of activating receptor NKG2D on TANK cells results in recovery of immunosuppression during tumor progression. Therefore, CHE could be a potential anticancer therapeutic agent that may be used to replace chemo-radio-therapy in future.

  11. Mobile zinc increases rapidly in the retina after optic nerve injury and regulates ganglion cell survival and optic nerve regeneration.

    Science.gov (United States)

    Li, Yiqing; Andereggen, Lukas; Yuki, Kenya; Omura, Kumiko; Yin, Yuqin; Gilbert, Hui-Ya; Erdogan, Burcu; Asdourian, Maria S; Shrock, Christine; de Lima, Silmara; Apfel, Ulf-Peter; Zhuo, Yehong; Hershfinkel, Michal; Lippard, Stephen J; Rosenberg, Paul A; Benowitz, Larry

    2017-01-10

    Retinal ganglion cells (RGCs), the projection neurons of the eye, cannot regenerate their axons once the optic nerve has been injured and soon begin to die. Whereas RGC death and regenerative failure are widely viewed as being cell-autonomous or influenced by various types of glia, we report here that the dysregulation of mobile zinc (Zn(2+)) in retinal interneurons is a primary factor. Within an hour after the optic nerve is injured, Zn(2+) increases several-fold in retinal amacrine cell processes and continues to rise over the first day, then transfers slowly to RGCs via vesicular release. Zn(2+) accumulation in amacrine cell processes involves the Zn(2+) transporter protein ZnT-3, and deletion of slc30a3, the gene encoding ZnT-3, promotes RGC survival and axon regeneration. Intravitreal injection of Zn(2+) chelators enables many RGCs to survive for months after nerve injury and regenerate axons, and enhances the prosurvival and regenerative effects of deleting the gene for phosphatase and tensin homolog (pten). Importantly, the therapeutic window for Zn(2+) chelation extends for several days after nerve injury. These results show that retinal Zn(2+) dysregulation is a major factor limiting the survival and regenerative capacity of injured RGCs, and point to Zn(2+) chelation as a strategy to promote long-term RGC protection and enhance axon regeneration.

  12. Increased serum sTRAIL levels were correlated with survival in bevacizumab-treated metastatic colon cancer

    Directory of Open Access Journals (Sweden)

    Bisgin Atil

    2012-02-01

    Full Text Available Abstract Background Colorectal cancer is the third most common cancer and the third leading cause of cancer-related death. Bevacizumab is a humanized monoclonal antibody developed against vascular endothelial growth factor (VEGF for the treatment of metastatic cancer. The parameters of RECIST (Response Evaluation Criteria for Solid Tumors are not adequate to detect important treatment effects and response. Our goal was to evaluate the possibility of using sTRAIL (serum-soluble TNF-related apoptosis-inducing ligand and VEGF as markers of treatment efficacy and prognosis in patients with metastatic colon cancer. Methods sTRAIL and VEGF levels were measured by ELISA in the sera of 16 bevacizumab-treated metastatic colon cancer patients and 10 presumably healthy age-matched controls. The measurements were taken before and after treatment for comparison purposes. Results Elevated levels of sTRAIL were found in seven out of 16 patients after bevacizumab treatment. Although these patients had a median survival time of 20.6 months, the remaining bevacizumab-treated patients who did not show an increase in sTRAIL had a median survival time of 9.4 months. As expected, serum VEGF levels were decreased in all patients who received bevacizumab therapy and showed no correlation between serum VEGF levels and patient survival (data not shown. Conclusions Serum sTRAIL levels might be a useful predictor of prognosis in metastatic colon cancer, in the early evaluation stages following bevacizumab treatment.

  13. Increased expression of fatty acid synthase provides a survival advantage to colorectal cancer cells via upregulation of cellular respiration.

    Science.gov (United States)

    Zaytseva, Yekaterina Y; Harris, Jennifer W; Mitov, Mihail I; Kim, Ji Tae; Butterfield, D Allan; Lee, Eun Y; Weiss, Heidi L; Gao, Tianyan; Evers, B Mark

    2015-08-07

    Fatty acid synthase (FASN), a lipogenic enzyme, is upregulated in colorectal cancer (CRC). Increased de novo lipid synthesis is thought to be a metabolic adaptation of cancer cells that promotes survival and metastasis; however, the mechanisms for this phenomenon are not fully understood. We show that FASN plays a role in regulation of energy homeostasis by enhancing cellular respiration in CRC. We demonstrate that endogenously synthesized lipids fuel fatty acid oxidation, particularly during metabolic stress, and maintain energy homeostasis. Increased FASN expression is associated with a decrease in activation of energy-sensing pathways and accumulation of lipid droplets in CRC cells and orthotopic CRCs. Immunohistochemical evaluation demonstrated increased expression of FASN and p62, a marker of autophagy inhibition, in primary CRCs and liver metastases compared to matched normal colonic mucosa. Our findings indicate that overexpression of FASN plays a crucial role in maintaining energy homeostasis in CRC via increased oxidation of endogenously synthesized lipids. Importantly, activation of fatty acid oxidation and consequent downregulation of stress-response signaling pathways may be key adaptation mechanisms that mediate the effects of FASN on cancer cell survival and metastasis, providing a strong rationale for targeting this pathway in advanced CRC.

  14. Honey bee (Apis mellifera) drones survive oxidative stress due to increased tolerance instead of avoidance or repair of oxidative damage.

    Science.gov (United States)

    Li-Byarlay, Hongmei; Huang, Ming Hua; Simone-Finstrom, Michael; Strand, Micheline K; Tarpy, David R; Rueppell, Olav

    2016-10-01

    Oxidative stress can lead to premature aging symptoms and cause acute mortality at higher doses in a range of organisms. Oxidative stress resistance and longevity are mechanistically and phenotypically linked; considerable variation in oxidative stress resistance exists among and within species and typically covaries with life expectancy. However, it is unclear whether stress-resistant, long-lived individuals avoid, repair, or tolerate molecular damage to survive longer than others. The honey bee (Apis mellifera L.) is an emerging model system that is well-suited to address this question. Furthermore, this species is the most economically important pollinator, whose health may be compromised by pesticide exposure, including oxidative stressors. Here, we develop a protocol for inducing oxidative stress in honey bee males (drones) via Paraquat injection. After injection, individuals from different colony sources were kept in common social conditions to monitor their survival compared to saline-injected controls. Oxidative stress was measured in susceptible and resistant individuals. Paraquat drastically reduced survival but individuals varied in their resistance to treatment within and among colony sources. Longer-lived individuals exhibited higher levels of lipid peroxidation than individuals dying early. In contrast, the level of protein carbonylation was not significantly different between the two groups. This first study of oxidative stress in male honey bees suggests that survival of an acute oxidative stressor is due to tolerance, not prevention or repair, of oxidative damage to lipids. It also demonstrates colony differences in oxidative stress resistance that might be useful for breeding stress-resistant honey bees. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Extended hypoxia in the alfalfa leafcutting bee, Megachile rotundata, increases survival but causes sub-lethal effects.

    Science.gov (United States)

    Abdelrahman, H; Rinehart, J P; Yocum, G D; Greenlee, K J; Helm, B R; Kemp, W P; Schulz, C H; Bowsher, J H

    2014-05-01

    Many insects are tolerant of hypoxic conditions, but survival may come at a cost to long-term health. The alfalfa leaf-cutting bee, Megachile rotundata, develops in brood cells inside natural cavities, and may be exposed to hypoxic conditions for extended periods of time. Whether M. rotundata is tolerant of hypoxia, and whether exposure results in sub-lethal effects, has never been investigated. Overwintering M. rotundata prepupae were exposed to 10%, 13%, 17%, 21% and 24% O2 for 11 months. Once adults emerged, five indicators of quality - emergence weight, body size, feeding activity, flight performance, and adult longevity, - were measured to determine whether adult bees that survived past exposure to hypoxia were competent pollinators. M. rotundata prepupae are tolerant of hypoxic condition and have higher survival rates in hypoxia, than in normoxia. Under hypoxia, adult emergence rates did not decrease over the 11 months of the experiment. In contrast, bees reared in normoxia had decreased emergence rates by 8 months, and were dead by 11 months. M. rotundata prepupae exposed to extended hypoxic conditions had similar emergence weight, head width, and cross-thorax distance compared to bees reared in standard 21% oxygen. Despite no significant morphological differences, hypoxia-exposed bees had lower feeding rates and shorter adult lifespans. Hypoxia may play a role in post-diapause physiology of M. rotundata, with prepupae showing better survival under hypoxic conditions. Extended exposure to hypoxia, while not fatal, causes sub-lethal effects in feeding rates and longevity in the adults, indicating that hypoxia tolerance comes at a cost. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  16. Increased Expression of Periplasmic Cu,Zn Superoxide Dismutase Enhances Survival of Escherichia coli Invasive Strains within Nonphagocytic Cells

    Science.gov (United States)

    Battistoni, Andrea; Pacello, Francesca; Folcarelli, Silvia; Ajello, Maria; Donnarumma, Giovanna; Greco, Rita; Grazia Ammendolia, Maria; Touati, Danièle; Rotilio, Giuseppe; Valenti, Piera

    2000-01-01

    We have studied the influence of periplasmic Cu,Zn superoxide dismutase on the intracellular survival of Escherichia coli strains able to invade epithelial cells by the expression of the inv gene from Yersinia pseudotuberculosis but unable to multiply intracellularly. Intracellular viability assays, confirmed by electron microscopy observations, showed that invasive strains of E. coli engineered to increase Cu,Zn superoxide dismutase production are much more resistant to intracellular killing than strains containing only the chromosomal sodC copy. However, we have found only a slight difference in survival within HeLa cells between a sodC-null mutant and its isogenic wild-type strain. Such a small difference in survival correlates with the very low expression of this enzyme in the wild-type strain. We have also observed that acid- and oxidative stress-sensitive E. coli HB101(pRI203) is more rapidly killed in epithelial cells than E. coli GC4468(pRI203). The high mortality of E. coli HB101(pRI203), independent of the acidification of the endosome, is abolished by the overexpression of sodC. Our data suggest that oxyradicals are involved in the mechanisms of bacterial killing within epithelial cells and that high-level production of periplasmic Cu,Zn superoxide dismutase provides bacteria with an effective protection against oxidative damage. We propose that Cu,Zn superoxide dismutase could offer an important selective advantage in survival within host cells to bacteria expressing high levels of this enzyme. PMID:10603365

  17. Cannabidiol increases survival and promotes rescue of cognitive function in a murine model of cerebral malaria.

    Science.gov (United States)

    Campos, A C; Brant, F; Miranda, A S; Machado, F S; Teixeira, A L

    2015-03-19

    Cerebral malaria (CM) is a severe complication resulting from Plasmodium falciparum infection that might cause permanent neurological deficits. Cannabidiol (CBD) is a nonpsychotomimetic compound of Cannabis sativa with neuroprotective properties. In the present work, we evaluated the effects of CBD in a murine model of CM. Female mice were infected with Plasmodium berghei ANKA (PbA) and treated with CBD (30mg/kg/day - 3 or 7days i.p.) or vehicle. On 5th day-post-infection (dpi), at the peak of the disease), animals were treated with single or repeated doses of Artesunate, an antimalarial drug. All groups were tested for memory impairment (Novel Object Recognition or Morris Water Maze) and anxiety-like behaviors (Open field or elevated plus maze test) in different stages of the disease (at the peak or after the complete clearance of the disease). Th1/Th2 cytokines and neurotrophins (brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF)) were measured in the prefrontal cortex and hippocampus of experimental groups. PbA-infected mice displayed memory deficits and exhibited increase in anxiety-like behaviors on the 5dpi or after the clearance of the parasitemia, effects prevented by CBD treatment. On 5dpi, TNF-α and IL-6 increased in the hippocampus, while only IL-6 increased in the prefrontal cortex. CBD treatment resulted in an increase in BDNF expression in the hippocampus and decreased levels of proinflammatory cytokines in the hippocampus (TNF-α) and prefrontal cortex (IL-6). Our results indicate that CBD exhibits neuroprotective effects in CM model and might be useful as an adjunctive therapy to prevent neurological symptoms following this disease. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  18. Sodium chloride inhibits the growth and infective capacity of the amphibian chytrid fungus and increases host survival rates.

    Directory of Open Access Journals (Sweden)

    Michelle Pirrie Stockwell

    Full Text Available The amphibian chytrid fungus Batrachochytrium dendrobatidis is a recently emerged pathogen that causes the infectious disease chytridiomycosis and has been implicated as a contributing factor in the global amphibian decline. Since its discovery, research has been focused on developing various methods of mitigating the impact of chytridiomycosis on amphibian hosts but little attention has been given to the role of antifungal agents that could be added to the host's environment. Sodium chloride is a known antifungal agent used routinely in the aquaculture industry and this study investigates its potential for use as a disease management tool in amphibian conservation. The effect of 0-5 ppt NaCl on the growth, motility and survival of the chytrid fungus when grown in culture media and its effect on the growth, infection load and survivorship of infected Peron's tree frogs (Litoria peronii in captivity, was investigated. The results reveal that these concentrations do not negatively affect the survival of the host or the pathogen. However, concentrations greater than 3 ppt significantly reduced the growth and motility of the chytrid fungus compared to 0 ppt. Concentrations of 1-4 ppt NaCl were also associated with significantly lower host infection loads while infected hosts exposed to 3 and 4 ppt NaCl were found to have significantly higher survival rates. These results support the potential for NaCl to be used as an environmentally distributed antifungal agent for the prevention of chytridiomycosis in susceptible amphibian hosts. However, further research is required to identify any negative effects of salt exposure on both target and non-target organisms prior to implementation.

  19. Increased actin polymerization and stabilization interferes with neuronal function and survival in the AMPKγ mutant Loechrig.

    Directory of Open Access Journals (Sweden)

    Mandy Cook

    Full Text Available loechrig (loe mutant flies are characterized by progressive neuronal degeneration, behavioral deficits, and early death. The mutation is due to a P-element insertion in the gene for the γ-subunit of the trimeric AMP-activated protein kinase (AMPK complex, whereby the insertion affects only one of several alternative transcripts encoding a unique neuronal isoform. AMPK is a cellular energy sensor that regulates a plethora of signaling pathways, including cholesterol and isoprenoid synthesis via its downstream target hydroxy-methylglutaryl (HMG-CoA reductase. We recently showed that loe interferes with isoprenoid synthesis and increases the prenylation and thereby activation of RhoA. During development, RhoA plays an important role in neuronal outgrowth by activating a signaling cascade that regulates actin dynamics. Here we show that the effect of loe/AMPKγ on RhoA prenylation leads to a hyperactivation of this signaling pathway, causing increased phosphorylation of the actin depolymerizating factor cofilin and accumulation of filamentous actin. Furthermore, our results show that the resulting cytoskeletal changes in loe interfere with neuronal growth and disrupt axonal integrity. Surprisingly, these phenotypes were enhanced by expressing the Slingshot (SSH phosphatase, which during development promotes actin depolymerization by dephosphorylating cofilin. However, our studies suggest that in the adult SSH promotes actin polymerization, supporting in vitro studies using human SSH1 that suggested that SSH can also stabilize and bundle filamentous actin. Together with the observed increase in SSH levels in the loe mutant, our experiments suggest that in mature neurons SSH may function as a stabilization factor for filamentous actin instead of promoting actin depolymerization.

  20. Prostaglandin E2 increases hematopoietic stem cell survival and accelerates hematopoietic recovery after radiation injury

    Science.gov (United States)

    Porter, Rebecca L.; Georger, Mary; Bromberg, Olga; McGrath, Kathleen E.; Frisch, Benjamin J.; Becker, Michael W.; Calvi, Laura M.

    2013-01-01

    Hematopoietic stem and progenitor cells (HSPCs), which continuously maintain all mature blood cells, are regulated within the marrow microenvironment. We previously reported that pharmacologic treatment of naïve mice with prostaglandin E2 (PGE2) expands HSPCs. However, the cellular mechanisms mediating this expansion remain unknown. Here we demonstrate that PGE2 treatment in naïve mice inhibits apoptosis of HSPCs without changing their proliferation rate. In a murine model of sub-lethal total body irradiation (TBI), in which HSPCs are rapidly lost, treatment with a long-acting PGE2 analogue (dmPGE2) reversed the apoptotic program initiated by TBI. dmPGE2 treatment in vivo decreased the loss of functional HSPCs following radiation injury, as demonstrated both phenotypically and by their increased reconstitution capacity. The antiapoptotic effect of dmPGE2 on HSPCs did not impair their ability to differentiate in vivo, resulting instead in improved hematopoietic recovery after TBI. dmPGE2 also increased microenvironmental cyclooxygenase-2 expression and expanded the α-SMA+ subset of marrow macrophages, thus enhancing the bone marrow microenvironmental response to TBI. Therefore, in vivo treatment with PGE2 analogues may be particularly beneficial to HSPCs in the setting of injury by targeting them both directly and also through their niche. The current data provide rationale for in vivo manipulation of the HSPC pool as a strategy to improve recovery after myelosuppression. PMID:23169593

  1. Light Fractionation Significantly Increases the Efficacy of Photodynamic Therapy Using BF-200 ALA in Normal Mouse Skin.

    NARCIS (Netherlands)

    H.S. de Bruijn (Riette); S. Brooks (Sander); A. van der Ploeg-van den Heuvel (Angélique); T.L.M. ten Hagen (Timo); E.R.M. de Haas (Ellen); D.J. Robinson (Dominic)

    2016-01-01

    markdownabstractBACKGROUND: Light fractionation significantly increases the efficacy of 5-aminolevulinic acid (ALA) based photodynamic therapy (PDT) using the nano-emulsion based gel formulation BF-200. PDT using BF-200 ALA has recently been clinically approved and is under investigation in several

  2. Increasing the probability of surviving loss of consciousness underwater when using a rebreather.

    Science.gov (United States)

    Haynes, Paul

    2016-12-01

    Re-circulating underwater breathing apparatus (rebreathers) have become increasingly popular amongst sport divers. In comparison to open-circuit scuba, rebreathers are complex life support equipment that incorporates many inherent failure modes and potential for human error. This individually or in combination can lead to an inappropriate breathing gas. Analysis of rebreather diving incidents suggests that inappropriate breathing gas is the most prevalent disabling agent. This can result in spontaneous loss of consciousness (LoC), water aspiration and drowning. Protecting the airway by maintaining the diver/rebreather oral interface may delay water aspiration following LoC underwater; the possibility of a successful rescue is, thus, increased. One means of protecting the airway following LoC underwater is the use of a full-face mask (FFM). However, such masks are complex and expensive; therefore, they have not been widely adopted by the sport diving community. An alternative to the FFM used extensively throughout the global military diving community is the mouthpiece retaining strap (MRS). A recent study documented 54 LoC events in military rebreather diving with only three consequent drownings; all divers were reported to be using a MRS. Even allowing for the concomitant use of a tethered diving partner system in most cases, the low number of fatalities in this large series is circumstantially supportive of the efficacy of the MRS. Despite drowning featuring as a final common pathway in the vast majority of rebreather fatalities, the MRS has not been widely adopted by the sport rebreather diving community.

  3. Long-term use of amiodarone before heart transplantation significantly reduces early post-transplant atrial fibrillation and is not associated with increased mortality after heart transplantation.

    Science.gov (United States)

    Rivinius, Rasmus; Helmschrott, Matthias; Ruhparwar, Arjang; Schmack, Bastian; Erbel, Christian; Gleissner, Christian A; Akhavanpoor, Mohammadreza; Frankenstein, Lutz; Darche, Fabrice F; Schweizer, Patrick A; Thomas, Dierk; Ehlermann, Philipp; Bruckner, Tom; Katus, Hugo A; Doesch, Andreas O

    2016-01-01

    Amiodarone is a frequently used antiarrhythmic drug in patients with end-stage heart failure. Given its long half-life, pre-transplant use of amiodarone has been controversially discussed, with divergent results regarding morbidity and mortality after heart transplantation (HTX). The aim of this study was to investigate the effects of long-term use of amiodarone before HTX on early post-transplant atrial fibrillation (AF) and mortality after HTX. Five hundred and thirty patients (age ≥18 years) receiving HTX between June 1989 and December 2012 were included in this retrospective single-center study. Patients with long-term use of amiodarone before HTX (≥1 year) were compared to those without long-term use (none or amiodarone). Primary outcomes were early post-transplant AF and mortality after HTX. The Kaplan-Meier estimator using log-rank tests was applied for freedom from early post-transplant AF and survival. Of the 530 patients, 74 (14.0%) received long-term amiodarone therapy, with a mean duration of 32.3±26.3 months. Mean daily dose was 223.0±75.0 mg. Indications included AF, Wolff-Parkinson-White syndrome, ventricular tachycardia, and ventricular fibrillation. Patients with long-term use of amiodarone before HTX had significantly lower rates of early post-transplant AF (P=0.0105). Further, Kaplan-Meier analysis of freedom from early post-transplant AF showed significantly lower rates of AF in this group (P=0.0123). There was no statistically significant difference between patients with and without long-term use of amiodarone prior to HTX in 1-year (P=0.8596), 2-year (P=0.8620), 5-year (P=0.2737), or overall follow-up mortality after HTX (P=0.1049). Moreover, Kaplan-Meier survival analysis showed no statistically significant difference in overall survival (P=0.1786). Long-term use of amiodarone in patients before HTX significantly reduces early post-transplant AF and is not associated with increased mortality after HTX.

  4. Cytoplasmic BRMS1 expression in malignant melanoma is associated with increased disease-free survival

    Directory of Open Access Journals (Sweden)

    Slipicevic Ana

    2012-02-01

    Full Text Available Abstract Background/aims Breast cancer metastasis suppressor 1 (BRMS1 blocks metastasis in melanoma xenografts; however, its usefulness as a biomarker in human melanomas has not been widely studied. The goal was to measure BRMS1 expression in benign nevi, primary and metastatic melanomas and evaluate its impact on disease progression and prognosis. Methods Paraffin-embedded tissue from 155 primary melanomas, 69 metastases and 15 nevi was examined for BRMS1 expression using immunohistochemistry. siRNA mediated BRMS1 down-regulation was used to study impact on invasion and migration in melanoma cell lines. Results A significantly higher percentage of nevi (87%, compared to primary melanomas (20% and metastases (48%, expressed BRMS1 in the nucelus (p Waf1/Cip1 (p = 0.009. Cytoplasmic score index was inversely associated with nuclear p-Akt (p = 0.013 and positively associated with cytoplasmic p-ERK1/2 expression (p = 0.033. Nuclear BRMS1 expression in ≥ 10% of primary melanoma cells was associated with thicker tumors (p = 0.016 and decreased relapse-free period (p = 0.043. Nuclear BRMS1 was associated with expression of fatty acid binding protein 7 (FABP7; p = 0.011, a marker of invasion in melanomas. In line with this, repression of BRMS1 expression reduced the ability of melanoma cells to migrate and invade in vitro. Conclusion Our data suggest that BRMS1 is localized in cytoplasm and nucleus of melanocytic cells and that cellular localization determines its in vivo effect. We hypothesize that cytoplasmic BRMS1 restricts melanoma progression while nuclear BRMS1 possibly promotes melanoma cell invasion. Please see related article: http://www.biomedcentral.com/1741-7015/10/19

  5. Triglyceride content in remnant lipoproteins is significantly increased after food intake and is associated with plasma lipoprotein lipase.

    Science.gov (United States)

    Nakajima, Katsuyuki; Tokita, Yoshiharu; Sakamaki, Koji; Shimomura, Younosuke; Kobayashi, Junji; Kamachi, Keiko; Tanaka, Akira; Stanhope, Kimber L; Havel, Peter J; Wang, Tao; Machida, Tetsuo; Murakami, Masami

    2017-02-01

    Previous large population studies reported that non-fasting plasma triglyceride (TG) reflect a higher risk for cardiovascular disease than TG in the fasting plasma. This is suggestive of the presence of higher concentration of remnant lipoproteins (RLP) in postprandial plasma. TG and RLP-TG together with other lipids, lipoproteins and lipoprotein lipase (LPL) in both fasting and postprandial plasma were determined in generally healthy volunteers and in patients with coronary artery disease (CAD) after consuming a fat load or a more typical moderate meal. RLP-TG/TG ratio (concentration) and RLP-TG/RLP-C ratio (particle size) were significantly increased in the postprandial plasma of both healthy controls and CAD patients compared with those in fasting plasma. LPL/RLP-TG ratio demonstrated the interaction correlation between RLP concentration and LPL activity The increased RLP-TG after fat consumption contributed to approximately 90% of the increased plasma TG, while approximately 60% after a typical meal. Plasma LPL in postprandial plasma was not significantly altered after either type of meal. Concentrations of RLP-TG found in the TG along with its particle size are significantly increased in postprandial plasma compared with fasting plasma. Therefore, non-fasting TG determination better reflects the presence of higher RLP concentrations in plasma. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  6. Significant social events and increasing use of life-sustaining treatment: trend analysis using extracorporeal membrane oxygenation as an example.

    Science.gov (United States)

    Chen, Yen-Yuan; Chen, Likwang; Huang, Tien-Shang; Ko, Wen-Je; Chu, Tzong-Shinn; Ni, Yen-Hsuan; Chang, Shan-Chwen

    2014-03-04

    Most studies have examined the outcomes of patients supported by extracorporeal membrane oxygenation as a life-sustaining treatment. It is unclear whether significant social events are associated with the use of life-sustaining treatment. This study aimed to compare the trend of extracorporeal membrane oxygenation use in Taiwan with that in the world, and to examine the influence of significant social events on the trend of extracorporeal membrane oxygenation use in Taiwan. Taiwan's extracorporeal membrane oxygenation uses from 2000 to 2009 were collected from National Health Insurance Research Dataset. The number of the worldwide extracorporeal membrane oxygenation cases was mainly estimated using Extracorporeal Life Support Registry Report International Summary July 2012. The trend of Taiwan's crude annual incidence rate of extracorporeal membrane oxygenation use was compared with that of the rest of the world. Each trend of extracorporeal membrane oxygenation use was examined using joinpoint regression. The measurement was the crude annual incidence rate of extracorporeal membrane oxygenation use. Each of the Taiwan's crude annual incidence rates was much higher than the worldwide one in the same year. Both the trends of Taiwan's and worldwide crude annual incidence rates have significantly increased since 2000. Joinpoint regression selected the model of the Taiwan's trend with one joinpoint in 2006 as the best-fitted model, implying that the significant social events in 2006 were significantly associated with the trend change of extracorporeal membrane oxygenation use following 2006. In addition, significantly social events highlighted by the media are more likely to be associated with the increase of extracorporeal membrane oxygenation use than being fully covered by National Health Insurance. Significant social events, such as a well-known person's successful extracorporeal membrane oxygenation use highlighted by the mass media, are associated with the use of

  7. Lack of potassium channel induces proliferation and survival causing increased neurogenesis and two-fold hippocampus enlargement

    DEFF Research Database (Denmark)

    Almgren, Malin; Persson, Ann-Sophie; Fenghua, Chen

    2007-01-01

    and the second week of life. To investigate the hyperplasia, cell proliferation was studied within the subgranular zone of the DG using BrdU and Ki67. There was a three-fold increase in proliferation in mceph/mceph mice compared to wild type mice at an age before onset of epileptic symptoms (3 weeks...... was lower in mceph/mceph supporting additional overgrowth mechanism than induced by seizures. In conclusion, lack of a functional Kv1.1 ion channel subunit in the mceph/mceph mice causes a unique neuronal hyperplasia in distinct hippocampal regions and consequently hippocampal enlargement from 2 to 3 weeks...... of age. This phenotype is a result, at least in DG, from increased proliferation, neurogenesis, and enhanced general hippocampal cell survival. Udgivelsesdato: 2007-null...

  8. The metastatic infiltration at the metastasis/brain parenchyma-interface is very heterogeneous and has a significant impact on survival in a prospective study

    Science.gov (United States)

    Siam, Laila; Bleckmann, Annalen; Chaung, Han-Ning; Mohr, Alexander; Klemm, Florian; Barrantes-Freer, Alonso; Blazquez, Raquel; Wolff, Hendrik A.; Lüke, Florian; Rohde, Veit; Stadelmann, Christine; Pukrop, Tobias

    2015-01-01

    The current approach to brain metastases resection is macroscopic removal of metastasis until reaching the glial pseudo-capsule (gross total resection (GTR)). However, autopsy studies demonstrated infiltrating metastatic cells into the parenchyma at the metastasis/brain parenchyma (M/BP)-interface. Aims/Methods: To analyze the astrocyte reaction and metastatic infiltration pattern at the M/BP-interface with an organotypic brain slice coculture system. Secondly, to evaluate the significance of infiltrating metastatic tumor cells in a prospective biopsy study. Therefore, after GTR, biopsies were obtained from the brain parenchyma beyond the glial pseudo-capsule and analyzed histomorphologically. Results: The coculture revealed three types of cancer cell infiltration. Interestingly, the astrocyte reaction was significantly different in the coculture with a benign, neuroectodermal-derived cell line. In the prospective biopsy study 58/167 (34.7%) samples revealed infiltrating metastatic cells. Altogether, 25/39 patients (64.1%) had proven to exhibit infiltration in at least one biopsy specimen with significant impact on survival (OS) (3.4 HR; p = 0.009; 2-year OS was 6.6% versus 43.5%). Exceptionally, in the non-infiltrating cohort three patients were long-term survivors. Conclusions: Metastatic infiltration has a significant impact on prognosis. Secondly, the astrocyte reaction at the M/BP-interface is heterogeneous and supports our previous concept of the organ-specific defense against metastatic (organ-foreign) cells. PMID:26299612

  9. Personalized axillary dissection: the number of excised lymph nodes of nodal-positive breast cancer patients has no significant impact on relapse-free and overall survival.

    Science.gov (United States)

    Ebner, Florian; Wöckel, Achim; Janni, Wolfgang; Kreienberg, Rolf; Schwentner, Lukas; Wischnewsky, Manfred

    2017-04-24

    Sentinel lymph node (SLN) biopsy has replaced axillary lymph node dissection (ALND) for the staging of clinically node-negative breast cancer patients (BCP), demonstrating equivalent survival to ALND while resulting in reduced morbidity. ALND has remained the standard of care for the majority of BCP with clinical axillary metastases or metastases found on SLN biopsy. More recently, it is debated whether ALND could be avoided not only in SLN-negative BCP but also in selected SLN-positive disease or even in all patients. This analysis of pN+ BCP shows the impact of the number of excised lymph nodes on RFS and OAS adjusted by age, tumor size, intrinsic subtypes and adjuvant systemic therapy. In this retrospective, multicenter cohort study, we investigated data from 2992 pN+ primary BCP recruited from 17 participating certified breast cancer centers in Germany between 2001 and 2008 within the BRENDA study group. The median number of excised lymph nodes was 17. The number of excised lymph nodes was neither significant for RFS (p = 0.085) nor for OAS (p = 0.285). Adjustments were made for age, tumor size and intrinsic subtypes. The most important significant parameters for RFS were intrinsic subtypes (p < 0.001) and tumor size (p < 0.001) and for OAS age (p < 0.001) and intrinsic subtypes (p < 0.001). There were no significant differences in RFS and OAS in any subgroup stratified by the number of excised lymph nodes. Only for T3/T4 tumors, there is a very small significant advantage of ALND for RFS but not for OAS. After adjusting in addition by guideline adherence of adjuvant systemic therapy (AST), intrinsic subtypes and guideline-adherent AST are the most important significant (p < 0.001) parameters for RFS and OAS. The number of excised lymph nodes of pN+ BCP neither correlates with RFS nor with OAS. Survival of pN+ BCP is primarily determined by the biology and the guideline-adherent AST based on the corresponding intrinsic subtypes. These results

  10. Increased drying rate lowers the critical water content for survival in embryonic axes of English oak (Quercus robur L.) seeds.

    Science.gov (United States)

    Ntuli, Tobias M; Finch-Savage, William E; Berjak, Patricia; Pammenter, Norman W

    2011-04-01

    The potential to cryopreserve embryonic axes of desiccation-sensitive (recalcitrant) seeds is limited by damage during the desiccation necessary for low temperature survival, but the basis of this injury and how to reduce it is not well understood. The effects of drying rate on the viability, respiratory metabolism and free radical-mediated processes were therefore investigated during dehydration of Quercus robur L. embryonic axes. Viability, assessed by evidence of germination and tetrazolium staining, showed a sharp decline at 0.27 and 0.8 g/g during rapid (<12 h) or slow (3 d) dehydration, respectively. Rapid dehydration therefore lowered the critical water content for survival. At any given water content rapid dehydration was associated with higher activities of the free radical processing enzymes, superoxide dismutase, catalase and glutathione reductase and lower levels of hydroperoxide and membrane damage. Rapid dehydration was also associated with lower malate dehydrogenase activity, and a reduced decline in phosphofructokinase activity and in levels of the oxidized form of nicotinamide dinucleotide. Ageing may have contributed to increased damage during slow dehydration, since viability declined even in hydrated storage after 3 d. The results presented are consistent with rapid dehydration reducing the accumulation of damage resulting from desiccation induced aqueous-based deleterious reactions. © 2011 Institute of Botany, Chinese Academy of Sciences.

  11. CD14+ cells from peripheral blood positively regulate hematopoietic stem and progenitor cell survival resulting in increased erythroid yield

    Science.gov (United States)

    Heideveld, Esther; Masiello, Francesca; Marra, Manuela; Esteghamat, Fatemehsadat; Yağcı, Nurcan; von Lindern, Marieke; Migliaccio, Anna Rita F.; van den Akker, Emile

    2015-01-01

    Expansion of erythroblasts from human peripheral blood mononuclear cells is 4- to 15-fold more efficient than that of CD34+ cells purified from peripheral blood mononuclear cells. In addition, purified CD34+ and CD34− populations from blood do not reconstitute this erythroid yield, suggesting a role for feeder cells present in blood mononuclear cells that increase hematopoietic output. Immunodepleting peripheral blood mononuclear cells for CD14+ cells reduced hematopoietic stem and progenitor cell expansion. Conversely, the yield was increased upon co-culture of CD34+ cells with CD14+ cells (full contact or transwell assays) or CD34+ cells re-constituted in conditioned medium from CD14+ cells. In particular, CD14++CD16+ intermediate monocytes/macrophages enhanced erythroblast outgrowth from CD34+ cells. No effect of CD14+ cells on erythroblasts themselves was observed. However, 2 days of co-culturing CD34+ and CD14+ cells increased CD34+ cell numbers and colony-forming units 5-fold. Proliferation assays suggested that CD14+ cells sustain CD34+ cell survival but not proliferation. These data identify previously unrecognized erythroid and non-erythroid CD34− and CD34+ populations in blood that contribute to the erythroid yield. A flow cytometry panel containing CD34/CD36 can be used to follow specific stages during CD34+ differentiation to erythroblasts. We have shown modulation of hematopoietic stem and progenitor cell survival by CD14+ cells present in peripheral blood mononuclear cells which can also be found near specific hematopoietic niches in the bone marrow. PMID:26294724

  12. Cancer in adolescents and young adults in north Netherlands (1989-2003) : increased incidence, stable survival and high incidence of second primary tumours

    NARCIS (Netherlands)

    van Gaal, J. C.; Bastiaannet, E.; Schaapveld, M.; Otter, R.; Kluin-Nelemans, J. C.; de Bont, E. S. J. M.; van der Graaf, W. T. A.

    Background: Lack of survival improvement in adolescents and young adults (AYA) with cancer has led to increased awareness of this young population. Design: We carried out a population-based study of incidence and survival of primary tumours and second primary tumours in patients aged 12-24 in north

  13. Do mycorrhizal network benefits to survival and growth of interior Douglas-fir seedlings increase with soil moisture stress?

    Science.gov (United States)

    Bingham, Marcus A; Simard, Suzanne W

    2011-11-01

    Facilitation of tree establishment by ectomycorrhizal (EM) networks (MNs) may become increasingly important as drought stress increases with climate change in some forested regions of North America. The objective of this study was to determine (1) whether temperature, CO(2) concentration ([CO(2)]), soil moisture, and MNs interact to affect plant establishment success, such that MNs facilitate establishment when plants are the most water stressed, and (2) whether transfer of C and water between plants through MNs plays a role in this. We established interior Douglas-fir (Pseudotsuga menziesiivar.glauca) seedlings in root boxes with and without the potential to form MNs with nearby conspecific seedlings that had consistent access to water via their taproots. We varied temperature, [CO(2)], and soil moisture in growth chambers. Douglas-fir seedling survival increased when the potential existed to form an MN. Growth increased with MN potential under the driest soil conditions, but decreased with temperature at 800 ppm [CO(2)]. Transfer of (13)C to receiver seedlings was unaffected by potential to form an MN with donor seedlings, but deuterated water (D(2)O) transfer increased with MN potential under ambient [CO(2)]. Chlorophyll fluorescence was reduced when seedlings had the potential to form an MN under high [CO(2)] and cool temperatures. We conclude that Douglas-fir seedling establishment in laboratory conditions is facilitated by MN potential where Douglas-fir seedlings have consistent access to water. Moreover, this facilitation appears to increase as water stress potential increases and water transfer via networks may play a role in this. These results suggest that conservation of MN potential may be important to forest regeneration where drought stress increases with climate change.

  14. Hen's egg allergen in house and bed dust is significantly increased after hen's egg consumption-A pilot study.

    Science.gov (United States)

    Trendelenburg, V; Tschirner, S; Niggemann, B; Beyer, K

    2017-09-02

    Environmental exposure to food allergens may be a risk factor for cutaneous sensitization. Previous studies could detect peanut allergen in house dust. In this pilot study, we wanted to investigate whether hen's egg allergen is detectable in house dust collected from different household areas and whether levels are increased after intentional hen's egg consumption. Hen's egg protein levels of dust samples were measured using ELISA. In 8 of 8 households, hen's egg was detectable in dust samples of eating area and bed. Forty-eight hours after intentional hen's egg consumption, hen's egg protein levels were significantly increased in both. Still, further research is necessary to investigate whether hen's egg allergen in house and bed dust plays a role in sensitization via skin. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

  15. A significant increase in the frequency of hand-foot-mouth disease in İstanbul in June 2012

    Directory of Open Access Journals (Sweden)

    Algün Polat Ekinci

    2013-12-01

    Full Text Available We have reviwed that there is a dramatic increase in the frequency of hand-foot-mouth disease at Dermatovenerology Department of İstanbul Medical Faculty in June 2013 compared to previous years. When we compared these data with those of June 2011, we have determined a significant difference statistically. We have learned from the authorities of City Health Administrative that they had not been reported about this issue. Although it is difficult to comment based on the data of a single clinic, we want to draw attention that there is a possibility for epidemic disease and a need for national data about this disease.

  16. Tetramethylpyrazine protects Schwann cells from ischemia-like injury and increases cell survival in cold ischemic rat nerves

    Directory of Open Access Journals (Sweden)

    Ming-Ming Yang

    2015-03-01

    Full Text Available Tetramethylpyrazine (TMP, a major active ingredient of Ligusticum wallichi Franchat extract (a Chinese herb, exhibits neuroprotective properties in ischemia. In this study, we assessed its protective effects on Schwann cells (SCs by culturing them in the presence of oxygen glucose deprivation (OGD conditions and measuring cell survival in cold ischemic rat nerves. In the OGD-induced ischemic injury model of SCs, we demonstrated that TMP treatment not only reduced OGD-induced cell viability losses, cell death, and apoptosis of SCs in a dose-dependent manner, and inhibited LDH release, but also suppressed OGD-induced downregulation of Bcl-2 and upregulation of Bax and caspase-3, as well as inhibited the consequent activation of caspase-3. In the cold ischemic nerve model, we found that prolonged cold ischemic exposure for four weeks was markedly associated with the absence of SCs, a decrease in cell viability, and apoptosis in preserved nerve segments incubated in University of Wisconsin solution (UWS alone. However, TMP attenuated nerve segment damage by preserving SCs and antagonizing the decrease in nerve fiber viability and increase in TUNEL-positive cells in a dose-dependent manner. Collectively, our results indicate that TMP not only provides protective effects in an ischemia-like injury model of cultured rat SCs by regulating Bcl-2, Bax, and caspase-3, but also increases cell survival and suppresses apoptosis in the cold ischemic nerve model after prolonged ischemic exposure for four weeks. Therefore, TMP may be a novel and effective therapeutic strategy for preventing peripheral nervous system ischemic diseases and improving peripheral nerve storage.

  17. Analysis of a large dataset of mycorrhiza inoculation field trials on potato shows highly significant increases in yield.

    Science.gov (United States)

    Hijri, Mohamed

    2016-04-01

    An increasing human population requires more food production in nutrient-efficient systems in order to simultaneously meet global food needs while reducing the environmental footprint of agriculture. Arbuscular mycorrhizal fungi (AMF) have the potential to enhance crop yield, but their efficiency has yet to be demonstrated in large-scale crop production systems. This study reports an analysis of a dataset consisting of 231 field trials in which the same AMF inoculant (Rhizophagus irregularis DAOM 197198) was applied to potato over a 4-year period in North America and Europe under authentic field conditions. The inoculation was performed using a liquid suspension of AMF spores that was sprayed onto potato seed pieces, yielding a calculated 71 spores per seed piece. Statistical analysis showed a highly significant increase in marketable potato yield (ANOVA, P < 0.0001) for inoculated fields (42.2 tons/ha) compared with non-inoculated controls (38.3 tons/ha), irrespective of trial year. The average yield increase was 3.9 tons/ha, representing 9.5 % of total crop yield. Inoculation was profitable with a 0.67-tons/ha increase in yield, a threshold reached in almost 79 % of all trials. This finding clearly demonstrates the benefits of mycorrhizal-based inoculation on crop yield, using potato as a case study. Further improvements of these beneficial inoculants will help compensate for crop production deficits, both now and in the future.

  18. Expression of a bacterial catalase in a strictly anaerobic methanogen significantly increases tolerance to hydrogen peroxide but not oxygen

    Science.gov (United States)

    Jennings, Matthew E.; Schaff, Cody W.; Horne, Alexandra J.; Lessner, Faith H.

    2014-01-01

    Haem-dependent catalase is an antioxidant enzyme that degrades H2O2, producing H2O and O2, and is common in aerobes. Catalase is present in some strictly anaerobic methane-producing archaea (methanogens), but the importance of catalase to the antioxidant system of methanogens is poorly understood. We report here that a survey of the sequenced genomes of methanogens revealed that the majority of species lack genes encoding catalase. Moreover, Methanosarcina acetivorans is a methanogen capable of synthesizing haem and encodes haem-dependent catalase in its genome; yet, Methanosarcina acetivorans cells lack detectable catalase activity. However, inducible expression of the haem-dependent catalase from Escherichia coli (EcKatG) in the chromosome of Methanosarcina acetivorans resulted in a 100-fold increase in the endogenous catalase activity compared with uninduced cells. The increased catalase activity conferred a 10-fold increase in the resistance of EcKatG-induced cells to H2O2 compared with uninduced cells. The EcKatG-induced cells were also able to grow when exposed to levels of H2O2 that inhibited or killed uninduced cells. However, despite the significant increase in catalase activity, growth studies revealed that EcKatG-induced cells did not exhibit increased tolerance to O2 compared with uninduced cells. These results support the lack of catalase in the majority of methanogens, since methanogens are more likely to encounter O2 rather than high concentrations of H2O2 in the natural environment. Catalase appears to be a minor component of the antioxidant system in methanogens, even those that are aerotolerant, including Methanosarcina acetivorans. Importantly, the experimental approach used here demonstrated the feasibility of engineering beneficial traits, such as H2O2 tolerance, in methanogens. PMID:24222618

  19. The adipokine leptin increases skeletal muscle mass and significantly alters skeletal muscle miRNA expression profile in aged mice

    Energy Technology Data Exchange (ETDEWEB)

    Hamrick, Mark W., E-mail: mhamrick@mail.mcg.edu [Department of Cellular Biology and Anatomy, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); Department of Orthopaedic Surgery, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); Herberg, Samuel; Arounleut, Phonepasong [Department of Cellular Biology and Anatomy, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); Department of Orthopaedic Surgery, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); He, Hong-Zhi [Henry Ford Immunology Program, Henry Ford Health System, Detroit, MI (United States); Department of Dermatology, Henry Ford Health System, Detroit, MI (United States); Shiver, Austin [Department of Cellular Biology and Anatomy, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); Department of Orthopaedic Surgery, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); Qi, Rui-Qun [Henry Ford Immunology Program, Henry Ford Health System, Detroit, MI (United States); Department of Dermatology, Henry Ford Health System, Detroit, MI (United States); Zhou, Li [Henry Ford Immunology Program, Henry Ford Health System, Detroit, MI (United States); Department of Dermatology, Henry Ford Health System, Detroit, MI (United States); Department of Internal Medicine, Henry Ford Health System, Detroit, MI (United States); Isales, Carlos M. [Department of Cellular Biology and Anatomy, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); Department of Orthopaedic Surgery, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); and others

    2010-09-24

    Research highlights: {yields} Aging is associated with muscle atrophy and loss of muscle mass, known as the sarcopenia of aging. {yields} We demonstrate that age-related muscle atrophy is associated with marked changes in miRNA expression in muscle. {yields} Treating aged mice with the adipokine leptin significantly increased muscle mass and the expression of miRNAs involved in muscle repair. {yields} Recombinant leptin therapy may therefore be a novel approach for treating age-related muscle atrophy. -- Abstract: Age-associated loss of muscle mass, or sarcopenia, contributes directly to frailty and an increased risk of falls and fractures among the elderly. Aged mice and elderly adults both show decreased muscle mass as well as relatively low levels of the fat-derived hormone leptin. Here we demonstrate that loss of muscle mass and myofiber size with aging in mice is associated with significant changes in the expression of specific miRNAs. Aging altered the expression of 57 miRNAs in mouse skeletal muscle, and many of these miRNAs are now reported to be associated specifically with age-related muscle atrophy. These include miR-221, previously identified in studies of myogenesis and muscle development as playing a role in the proliferation and terminal differentiation of myogenic precursors. We also treated aged mice with recombinant leptin, to determine whether leptin therapy could improve muscle mass and alter the miRNA expression profile of aging skeletal muscle. Leptin treatment significantly increased hindlimb muscle mass and extensor digitorum longus fiber size in aged mice. Furthermore, the expression of 37 miRNAs was altered in muscles of leptin-treated mice. In particular, leptin treatment increased the expression of miR-31 and miR-223, miRNAs known to be elevated during muscle regeneration and repair. These findings suggest that aging in skeletal muscle is associated with marked changes in the expression of specific miRNAs, and that nutrient

  20. Association with pregnancy increases the risk of local recurrence but does not impact overall survival in breast cancer: A case-control study of 87 cases.

    Science.gov (United States)

    Genin, A S; De Rycke, Y; Stevens, D; Donnadieu, A; Langer, A; Rouzier, R; Lerebours, F

    2016-12-01

    Pregnancy-associated breast cancer (PABC) constitutes 7% of all BCs in young women. The prognosis of PABC remains controversial. In this study, we evaluated the impact of the association of pregnancy with BC on the rates of overall survival (OS), disease free survival (DFS), and distant and local recurrence-free survival. We conducted a retrospective unicenter case-control study. We enrolled PABC patients treated at our institution between 1992 and 2009. For each case, 2 BC controls were matched for age and year of diagnosis. Univariate and multivariate analyses were performed to assess the parameters associated with prognosis. Eighty-seven PABC patients were enrolled and matched with 174 controls. The univariate analysis did not reveal any significant differences in OS, DFS or distant recurrence rates between the 2 groups. Pregnancy associated status, a tumor larger than T2 and neoadjuvant chemotherapy as the primary treatment were significantly associated with an increased risk of local relapse. The multivariate analysis showed that the pregnancy associated status and the tumor size were strong prognostic factors of local recurrence. Pregnancy associated status negates the prognostic value of tumor size, as both T0-T2 and T3-T4 PABC patients have the same poor prognosis as control BC patients with T3-T4 tumors. Interestingly, although PABC patients have more locally advanced tumors, they did not have a higher rate of radical surgery than the control BC patients. Pregnancy associated status is a strong prognostic factor of local relapse in BC. In PABC patients, when possible, radical surgery should be the preferred first treatment step. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. The contribution of human agricultural activities to increasing evapotranspiration is significantly greater than climate change effect over Heihe agricultural region.

    Science.gov (United States)

    Zou, Minzhong; Niu, Jun; Kang, Shaozhong; Li, Xiaolin; Lu, Hongna

    2017-08-18

    Evapotranspiration (ET) is a major component linking the water, energy, and carbon cycles. Understanding changes in ET and the relative contribution rates of human activity and of climate change at the basin scale is important for sound water resources management. In this study, changes in ET in the Heihe agricultural region in northwest China during 1984-2014 were examined using remotely-sensed ET data with the Soil and Water Assessment Tool (SWAT). Correlation analysis identified the dominant factors that influence change in ET per unit area and those that influence change in total ET. Factor analysis identified the relative contribution rates of the dominant factors in each case. The results show that human activity, which includes factors for agronomy and irrigation, and climate change, including factors for precipitation and relative humidity, both contribute to increases in ET per unit area at rates of 60.93% and 28.01%, respectively. Human activity, including the same factors, and climate change, including factors for relative humidity and wind speed, contribute to increases in total ET at rates of 53.86% and 35.68%, respectively. Overall, in the Heihe agricultural region, the contribution of human agricultural activities to increased ET was significantly greater than that of climate change.

  2. HIV-1 Structural Proteins Serve as PAMPs for TLR2 Heterodimers Significantly Increasing Infection and Innate Immune Activation.

    Science.gov (United States)

    Henrick, Bethany M; Yao, Xiao-Dan; Rosenthal, Kenneth Lee

    2015-01-01

    Immune activation is critical to HIV infection and pathogenesis; however, our understanding of HIV innate immune activation remains incomplete. Recently we demonstrated that soluble TLR2 (sTLR2) physically inhibited HIV-induced NFκB activation and inflammation, as well as HIV-1 infection. In light of these findings, we hypothesized that HIV-1 structural proteins may serve as pathogen-associated molecular patterns (PAMPs) for cellular TLR2 heterodimers. These studies made use of primary human T cells and TZMbl cells stably transformed to express TLR2 (TZMbl-2). Our results demonstrated that cells expressing TLR2 showed significantly increased proviral DNA compared to cells lacking TLR2, and mechanistically this may be due to a TLR2-mediated increased CCR5 expression. Importantly, we show that HIV-1 structural proteins, p17, p24, and gp41, act as viral PAMPs signaling through TLR2 and its heterodimers leading to significantly increased immune activation via the NFκB signaling pathway. Using co-immunoprecipitation and a dot blot method, we demonstrated direct protein interactions between these viral PAMPs and TLR2, while only p17 and gp41 bound to TLR1. Specifically, TLR2/1 heterodimer recognized p17 and gp41, while p24 lead to immune activation through TLR2/6. These results were confirmed using TLR2/1 siRNA knock down assays which ablated p17 and gp41-induced cellular activation and through studies of HEK293 cells expressing selected TLRs. Interestingly, our results show in the absence of TLR6, p24 bound to TLR2 and blocked p17 and gp41-induced activation, thus providing a novel mechanism by which HIV-1 can manipulate innate sensing. Taken together, our results identified, for the first time, novel HIV-1 PAMPs that play a role in TLR2-mediated cellular activation and increased proviral DNA. These findings have important implications for our fundamental understanding of HIV-1 immune activation and pathogenesis, as well as HIV-1 vaccine development.

  3. Little evidence for significant increases of methane emissions from oil and gas operations in the U.S.

    Science.gov (United States)

    Lan, X.; Tans, P. P.; Sweeney, C.; Andrews, A. E.; Dlugokencky, E. J.; Lang, P. M.; Crotwell, M.; Miller, B.; Kofler, J.; Newberger, T.; McKain, K.; Wolter, S.; Montzka, S. A.

    2016-12-01

    Recent studies on whether methane (CH4) emissions from oil and natural gas (ONG) operations in the U.S. have increased are still inconclusive. To provide observational evidence we carefully analyzed the in-situ CH4 measurements from the NOAA/ESRL Global Greenhouse Gas Reference Network (GGGRN) for the best estimates of CH4 trends for 2006-2016. Methane data from more than 20 surface and aircraft sites across the U.S. were included in this study. Variations of sampling frequencies in different seasons were taken into account for accurate trend detection. Correlations among measurements within short sampling intervals were also considered for uncertainty estimates. We found that most of our sites had similar CH4 trends of 6 ppb/yr, which was comparable with the recent global background CH4 trend. Substantially higher growth rates were found at the Southern Great Plain site in Oklahoma (SGP, downwind of the Eagle Ford, Barnett Shale and Woodford ONG fields) and the Dahlen sites in North Dakota (DND, downwind of the Bakken ONG field), which indicated influences from regional ONG activities. Ethane (C2H6) measurements from SGP (C2H6 measurements were not available from DND) and propane (C3H8) measurements from both SPG and DND exhibited significant increasing trends, while trends at other sites were either non-significant (trend ONG emissions) on CH4 trend estimates, we would infer much larger surface CH4 trends than what we actually observed at these two sites. This discrepancy suggests that using enhancement ratios of C3H8 /CH4 is not likely a reliable approach to compute CH4 emission trends.

  4. A Prolonged Time Interval Between Trauma and Prophylactic Radiation Therapy Significantly Increases the Risk of Heterotopic Ossification

    Energy Technology Data Exchange (ETDEWEB)

    Mourad, Waleed F., E-mail: Waleed246@gmail.com [Department of Radiation Oncology, University of Mississippi Medical Center, Jackson, MS (United States); Department of Radiation Oncology, Beth Israel Medical Center, New York, NY (Israel); Packianathan, Satyaseelan [Department of Radiation Oncology, University of Mississippi Medical Center, Jackson, MS (United States); Shourbaji, Rania A. [Department of Epidemiology and Biostatistics, Jackson State University, Jackson, MS (United States); Zhang Zhen; Graves, Mathew [Department of Orthopedic Surgery, University of Mississippi Medical Center, Jackson, MS (United States); Khan, Majid A. [Department of Radiology, University of Mississippi Medical Center, Jackson, MS (United States); Baird, Michael C. [Department of Radiation Oncology, University of Mississippi Medical Center, Jackson, MS (United States); Russell, George [Department of Orthopedic Surgery, University of Mississippi Medical Center, Jackson, MS (United States); Vijayakumar, Srinivasan [Department of Radiation Oncology, University of Mississippi Medical Center, Jackson, MS (United States)

    2012-03-01

    Purpose: To ascertain whether the time from injury to prophylactic radiation therapy (RT) influences the rate of heterotopic ossification (HO) after operative treatment of displaced acetabular fractures. Methods and Materials: This is a single-institution, retrospective analysis of patients referred for RT for the prevention of HO. Between January 2000 and January 2009, 585 patients with displaced acetabular fractures were treated surgically followed by RT for HO prevention. We analyzed the effect of time from injury on prevention of HO by RT. In all patients, 700 cGy was prescribed in a single fraction and delivered within 72 hours postsurgery. The patients were stratified into five groups according to time interval (in days) from the date of their accident to the date of RT: Groups A {<=}3, B {<=}7, C {<=}14, D {<=}21, and E >21days. Results: Of the 585 patients with displaced acetabular fractures treated with RT, (18%) 106 patients developed HO within the irradiated field. The risk of HO after RT increased from 10% for RT delivered {<=}3 days to 92% for treatment delivered >21 days after the initial injury. Wilcoxon test showed a significant correlation between the risk of HO and the length of time from injury to RT (p < 0.0001). Chi-square test and multiple logistic regression analysis showed no significant association between all other factors and the risk of HO (race, gender, cause and type of fracture, surgical approach, or the use of indomethacin). Conclusions: Our data suggest that there is higher incidence and risk of HO if prophylactic RT is significantly delayed after a displaced acetabular fracture. Thus, RT should be administered as early as clinically possible after the trauma. Patients undergoing RT >3 weeks from their displaced acetabular fracture should be informed of the higher risk (>90%) of developing HO despite prophylaxis.

  5. Student Acceptance of Plain Milk Increases Significantly 2 Years after Flavored Milk Is Removed from School Cafeterias: An Observational Study.

    Science.gov (United States)

    Schwartz, Marlene B; Henderson, Kathryn E; Read, Margaret; Cornelius, Talea

    2017-07-13

    Previous studies document decreases in lunchtime milk consumption immediately after flavored milk is removed. Less is known about longer-term effects. Plain milk selection and consumption were measured the first year flavored milk was removed in a school district (2010 to 2011 [Time 1]) and 2 years later (2012 to 2013 [Time 2]). Four behavioral economic interventions to promote milk were tested in one school at Time 2. This was a longitudinal, observational study. Participants were kindergarten through grade 8 students in two schools in an urban district. Primary data were collected 10 times per school year at Time 1 and Time 2, yielding 40 days of data and 13,883 student observations. The milk promotion interventions were tested on 6 additional days. Outcomes were the percentage of students selecting milk at lunch, the ounces of milk consumed per carton, and the ounces of milk consumed school-wide per student. Logistic regressions were used to assess how sex, grade, time, availability of 100% juice, and behavioral interventions affected milk selection and consumption. At Time One, 51.5% of students selected milk and drank 4 oz (standard deviation=3.2 oz) per carton, indicating school-wide per-student consumption of 2.1 oz (standard deviation=3.0 oz). At Time Two, 72% of students selected milk and consumed 3.4 oz per carton (standard deviation=3.2 oz), significantly increasing the school-wide per-student consumption to 2.5 oz (standard deviation=3.1 oz). Older students and boys consumed significantly more milk. Availability of 100% fruit juice was associated with a 16-percentage point decrease in milk selection. None of the behavioral economic interventions significantly influenced selection. These data suggest that after flavored milk is removed from school cafeterias, school-wide per-student consumption of plain milk increases over time. In addition, the presence of 100% juice is associated with lower milk selection. Copyright © 2017 Academy of Nutrition and

  6. An incomplete TCA cycle increases survival of Salmonella Typhimurium during infection of resting and activated murine macrophages.

    Science.gov (United States)

    Bowden, Steven D; Ramachandran, Vinoy K; Knudsen, Gitte M; Hinton, Jay C D; Thompson, Arthur

    2010-11-08

    In comparison to the comprehensive analyses performed on virulence gene expression, regulation and action, the intracellular metabolism of Salmonella during infection is a relatively under-studied area. We investigated the role of the tricarboxylic acid (TCA) cycle in the intracellular replication of Salmonella Typhimurium in resting and activated macrophages, epithelial cells, and during infection of mice. We constructed deletion mutations of 5 TCA cycle genes in S. Typhimurium including gltA, mdh, sdhCDAB, sucAB, and sucCD. We found that the mutants exhibited increased net intracellular replication in resting and activated murine macrophages compared to the wild-type. In contrast, an epithelial cell infection model showed that the S. Typhimurium ΔsucCD and ΔgltA strains had reduced net intracellular replication compared to the wild-type. The glyoxylate shunt was not responsible for the net increased replication of the TCA cycle mutants within resting macrophages. We also confirmed that, in a murine infection model, the S. Typhimurium ΔsucAB and ΔsucCD strains are attenuated for virulence. Our results suggest that disruption of the TCA cycle increases the ability of S. Typhimurium to survive within resting and activated murine macrophages. In contrast, epithelial cells are non-phagocytic cells and unlike macrophages cannot mount an oxidative and nitrosative defence response against pathogens; our results show that in HeLa cells the S. Typhimurium TCA cycle mutant strains show reduced or no change in intracellular levels compared to the wild-type. The attenuation of the S. Typhimurium ΔsucAB and ΔsucCD mutants in mice, compared to their increased net intracellular replication in resting and activated macrophages suggest that Salmonella may encounter environments within the host where a complete TCA cycle is advantageous.

  7. Chemotherapy Significantly Improves Survival for Patients with T1c-T2N0M0 Medullary Breast Cancer: 3739 Cases From the National Cancer Data Base.

    Science.gov (United States)

    Mateo, Alina M; Pezzi, Todd A; Sundermeyer, Mark; Kelley, Cynthia A; Klimberg, V Suzanne; Pezzi, Christopher M

    2017-04-01

    Medullary breast cancer (MBC) is a rare tumor associated with a better prognosis compared with other breast cancers. The role of adjuvant chemotherapy has not been extensively studied. Female patients with invasive MBC reported to the National Cancer Data Base from 2004 to 2012 were analyzed. Overall survival (OS) and treatment were studied using the Kaplan-Meier method and the Cox proportional hazard model. Patients who had node-negative (N0), non-metastatic (M0) tumors 10 to 50 mm in size (T1cN0M0 and T2N0M0) treated with and without chemotherapy were analyzed using propensity score matching. Of 3739 patients with MBC, 2642 (71%) had T1b-T2N0M0 disease treated with and without chemotherapy. Multivariable analysis showed that for all MBC patients, the significant predictors of OS were age older than 65 years, one or more comorbidities, tumor larger than 2 cm, positive nodes, distant metastasis, and treatment with chemotherapy or radiation therapy. Patients with T1cN0M0 and T2N0M0 had improved OS if they received chemotherapy (p < 0.0005). Patients with T1bN0M0 who received chemotherapy did not show better OS than those who did not. Patients with T1c-T2N0M0 were then matched by propensity score based on age, presence of comorbidities, tumor size, and treatment methods used. After matching, the group receiving chemotherapy showed an improved OS (hazard ratio [HR], 0.40; 95% confidence interval [CI], 0.26-0.62; p < 0.0005) compared to the group that did not receive chemotherapy. For patients with T1c-T2N0M0 MBC, chemotherapy significantly improves OS.

  8. Unequivocal detection of ozone recovery in the Antarctic Ozone Hole through significant increases in atmospheric layers with minimum ozone

    Science.gov (United States)

    de Laat, Jos; van Weele, Michiel; van der A, Ronald

    2015-04-01

    An important new landmark in present day ozone research is presented through MLS satellite observations of significant ozone increases during the ozone hole season that are attributed unequivocally to declining ozone depleting substances. For many decades the Antarctic ozone hole has been the prime example of both the detrimental effects of human activities on our environment as well as how to construct effective and successful environmental policies. Nowadays atmospheric concentrations of ozone depleting substances are on the decline and first signs of recovery of stratospheric ozone and ozone in the Antarctic ozone hole have been observed. The claimed detection of significant recovery, however, is still subject of debate. In this talk we will discuss first current uncertainties in the assessment of ozone recovery in the Antarctic ozone hole by using multi-variate regression methods, and, secondly present an alternative approach to identify ozone hole recovery unequivocally. Even though multi-variate regression methods help to reduce uncertainties in estimates of ozone recovery, great care has to be taken in their application due to the existence of uncertainties and degrees of freedom in the choice of independent variables. We show that taking all uncertainties into account in the regressions the formal recovery of ozone in the Antarctic ozone hole cannot be established yet, though is likely before the end of the decade (before 2020). Rather than focusing on time and area averages of total ozone columns or ozone profiles, we argue that the time evolution of the probability distribution of vertically resolved ozone in the Antarctic ozone hole contains a better fingerprint for the detection of ozone recovery in the Antarctic ozone hole. The advantages of this method over more tradition methods of trend analyses based on spatio-temporal average ozone are discussed. The 10-year record of MLS satellite measurements of ozone in the Antarctic ozone hole shows a

  9. Increased motoneuron survival and improved neuromuscular function in transgenic ALS mice after intraspinal injection of an adeno-associated virus encoding Bcl-2.

    Science.gov (United States)

    Azzouz, M; Hottinger, A; Paterna, J C; Zurn, A D; Aebischer, P; Büeler, H

    2000-03-22

    Mutations in the gene encoding Cu/Zn superoxide dismutase (SOD1) underlie some familial cases of amyotrophic lateral sclerosis (ALS), a neurodegenerative disorder characterized by loss of cortical, brainstem and spinal motoneurons. Transgenic mice over- expressing a mutated form of human SOD1 containing a Gly-->Ala substitution at position 93 (SOD1(G93A)) develop a severe, progressive motoneuron disease. We investigated the potential of recombinant adeno-associated virus (rAAV) to transfer neuroprotective molecules in this animal ALS model. Initial experiments showed that injection of an rAAV vector encoding green fluorescent protein unilaterally into the lumbar spinal cord of wild-type mice leads to expression of the reporter gene in 34.7 +/- 5.2% of the motoneurons surrounding the injection site. Intraspinal injection of an rAAV encoding the anti-apoptotic protein bcl-2 in SOD1 (G93A) mice resulted in sustained bcl-2 expression in motoneurons and significantly increased the number of surviving motoneurons at the end-stage of disease. Moreover, the compound muscle action potential amplitude elicited by nerve stimulation and recorded by electromyographic measurements was higher in the rAAV-bcl-2-treated group than in controls. Local bcl-2 expression in spinal motoneurons delayed the appearance of signs of motor deficiency but was not sufficient to prolong the survival of SOD1 (G93A) mice. To our know-ledge, this study describes the first successful transduction and protection of spinal motoneurons by direct gene transfer in a model of progressive motoneuron disease. Our results support the use of AAVs for the delivery of protective genes to spinal cord moto-neurons as a possible way to enhance motoneuron survival and repair.

  10. The significance of increased fluid signal on magnetic resonance imaging in lumbar facets in relationship to degenerative spondylolisthesis.

    Science.gov (United States)

    Chaput, Christopher; Padon, Derek; Rush, Jeremy; Lenehan, Eric; Rahm, Mark

    2007-08-01

    Retrospective radiographic review of consecutive patients with universally applied standard. To define MRI findings at the facet joints that may suggest abnormal sagittal plane translation seen on standing lateral flexion-extension (SLFE) radiographs. MRI findings, including facet joint orientation, facet joint osteoarthritis, and the presence of synovial cysts, have all been linked with degenerative spondylolisthesis (DS). MRI can also detect facet joint effusion; however, there has not been a study specifically addressing the association of facet fluid signal to degenerative spondylolisthesis (DS). MRI and SLFE films of all patients seen at a single institution for an orthopedic spine consultation over a 2-year period were analyzed. The presence of facet effusions, synovial cysts, increased intensity within the interspinous ligament, degenerative changes at the facets, and anterior sagittal plane translation were all recorded. The data were analyzed to determine if there was a significant association between the presence of DS and the following: facet effusion, degenerative changes of the facets, synovial cysts, increased signal in the interspinous ligament, age, and gender. There were 139 patients without DS at (NegDS) and 54 with DS (PosDS) on SLFE films at L4-L5 (n = 193). PosDS patients were more likely to be older (P 1.5 mm) facet effusions are highly predictive of degenerative spondylolisthesis at L4-L5 in the absence of measurable anterolisthesis on supine MRI. A clinically measurable facet effusion (> or = 1 mm) suggests the need for SLFE films to diagnose degenerative spondylolisthesis that can be missed with supine positioning on MRI.

  11. Overexpression of GPC6 and TMEM132D in Early Stage Ovarian Cancer Correlates with CD8+ T-Lymphocyte Infiltration and Increased Patient Survival

    Directory of Open Access Journals (Sweden)

    Athanasios Karapetsas

    2015-01-01

    Full Text Available Infiltration of cytotoxic T-lymphocytes in ovarian cancer is a favorable prognostic factor. Employing a differential expression approach, we have recently identified a number of genes associated with CD8+ T-cell infiltration in early stage ovarian tumors. In the present study, we validated by qPCR the expression of two genes encoding the transmembrane proteins GPC6 and TMEM132D in a cohort of early stage ovarian cancer patients. The expression of both genes correlated positively with the mRNA levels of CD8A, a marker of T-lymphocyte infiltration [Pearson coefficient: 0.427 (p=0.0067 and 0.861 (p<0.0001, resp.]. GPC6 and TMEM132D expression was also documented in a variety of ovarian cancer cell lines. Importantly, Kaplan-Meier survival analysis revealed that high mRNA levels of GPC6 and/or TMEM132D correlated significantly with increased overall survival of early stage ovarian cancer patients (p=0.032. Thus, GPC6 and TMEM132D may serve as predictors of CD8+ T-lymphocyte infiltration and as favorable prognostic markers in early stage ovarian cancer with important consequences for diagnosis, prognosis, and tumor immunobattling.

  12. Survival from Traumatic Injury Does Not End at Hospital Discharge: Hospital-Acquired Infections Increase Post-Discharge Mortality.

    Science.gov (United States)

    Dhiman, Nitasha; Rimal, Ram C; Hamill, Mark; Love, Katie M; Lollar, Daniel; Collier, Bryan

    2017-07-01

    Hospital-acquired infections (HAI) in trauma patients increase inpatient morbidity and mortality. However, their impact on long-term mortality is not well understood. A retrospective trauma registry analysis of all patients admitted to an academic level I trauma center between July 1, 2008 and December 31, 2012 was performed. Patients included survived to discharge and were 18 years of age or older. Age, gender, Injury Severity Score (ISS), ventilator use, history of chronic obstructive pulmonary disease (COPD), and HAI were reviewed. Name, social security number, and date of birth were used to extract National Death Index data from 2008-2013 for an outcome of mortality after discharge, time to death, and cause of death. Unadjusted logistic regression was performed. Multiple logistic regression was used to adjust for patient and injury characteristics and to determine odds of mortality in the post-discharge period. A total of 8,275 patients met inclusion criteria; 65.4% were male and the median age was 47. The mean ISS was 11 ± 8.9. Nine hundred seventeen patients (11.1%) died after discharge; 4.8% of patients had hospital-acquired pneumonia (HAP) and 4.2% had a urinary tract infection (UTI). The unadjusted odds ratio (OR) of mortality after discharge in patients who had pneumonia and UTI were 1.77 (1.35, 2.31, p injuries and HAI. Further characterization of HAP and its subsequent treatment strategies are needed.

  13. Knocking down of the KCC2 in rat hippocampal neurons increases intracellular chloride concentration and compromises neuronal survival

    Science.gov (United States)

    Pellegrino, Christophe; Gubkina, Olena; Schaefer, Michael; Becq, Hélène; Ludwig, Anastasia; Mukhtarov, Marat; Chudotvorova, Ilona; Corby, Severine; Salyha, Yuriy; Salozhin, Sergey; Bregestovski, Piotr; Medina, Igor

    2011-01-01

    Abstract KCC2 is a neuron-specific potassium–chloride co-transporter controlling intracellular chloride homeostasis in mature and developing neurons. It is implicated in the regulation of neuronal migration, dendrites outgrowth and formation of the excitatory and inhibitory synaptic connections. The function of KCC2 is suppressed under several pathological conditions including neuronal trauma, different types of epilepsies, axotomy of motoneurons, neuronal inflammations and ischaemic insults. However, it remains unclear how down-regulation of the KCC2 contributes to neuronal survival during and after toxic stress. Here we show that in primary hippocampal neuronal cultures the suppression of the KCC2 function using two different shRNAs, dominant-negative KCC2 mutant C568A or DIOA inhibitor, increased the intracellular chloride concentration [Cl−]i and enhanced the toxicity induced by lipofectamine-dependent oxidative stress or activation of the NMDA receptors. The rescuing of the KCC2 activity using over-expression of the active form of the KCC2, but not its non-active mutant Y1087D, effectively restored [Cl−]i and enhanced neuronal resistance to excitotoxicity. The reparative effects of KCC2 were mimicked by over-expression of the KCC3, a homologue transporter. These data suggest an important role of KCC2-dependent potassium/chloride homeostasis under neurototoxic conditions and reveal a novel role of endogenous KCC2 as a neuroprotective molecule. PMID:21486764

  14. Different loci and mRNA copy number of the increased serum survival gene of Escherichia coli.

    Science.gov (United States)

    Xu, Wang-Ye; Li, Yi-Jing; Fan, Chen

    2018-02-01

    The increased serum survival gene (iss) has been identified as a virulence trait associated with the virulence of Escherichia coli, causing colibacillosis in poultry. However, it remains unclear as to whether iss mRNA copy number and sequence affect virulence. To examine these influences, we assessed the presence of iss, sequence analysis, iss mRNA copy number, and serum resistance. The iss gene was detected in 88 (all) E. coli isolates from different sources, and sequencing identified 16 alleles (32 different loci) and 10 amino acid sequences (10 different loci). Nested polymerase chain reaction improved iss detection. The isolates from sick chickens had >68% livability in serum resistance tests and higher iss mRNA copy number. The iss mRNA copy number highly correlated with mortality and E. coli livability. Student's t tests confirmed the relationship between the different loci to iss transcription, serum resistance, and virulence. These data suggest that iss mRNA copy number and different loci affect the virulence and serum resistance. These findings could be useful in further studies on the prevalence of iss among E. coli isolates and other virulence factors.

  15. Trauma-induced coagulopathy upon emergency room arrival: still a significant problem despite increased awareness and management?

    Science.gov (United States)

    Fröhlich, Matthias; Mutschler, Manuel; Caspers, Michael; Nienaber, Ulrike; Jäcker, Vera; Driessen, Arne; Bouillon, Bertil; Maegele, Marc

    2017-11-23

    Over the last decade, the pivotal role of trauma-induced coagulopathy has been described and principal drivers have been identified. We hypothesized that the increased knowledge on coagulopathy of trauma would translate into a more cautious treatment, and therefore, into a reduced overall incidence rate of coagulopathy upon ER admission. Between 2002 and 2013, 61,212 trauma patients derived from the TraumaRegister DGU® had a full record of coagulation parameters and were assessed for the presence of coagulopathy. Coagulopathy was defined by a Quick's value  50), the incidence of coagulopathy was reduced by 7%. Regardless of the injury severity, the amount of pre-hospital i.v.-fluids declined during the observed period by 51%. Simultaneously, morbidity and mortality of severely injured patients were on the decrease. During the 12 years observed, a substantial decline of coagulopathy has been observed. This was paralleled by a significant decrease of i.v.-fluids administered in the pre-hospital treatment. The reduced presence of coagulopathy translated into decreased transfusion requirements and mortality. Nevertheless, especially in the most severely injured patients, posttraumatic coagulopathy remains a frequent and life-threatening syndrome.

  16. Pioglitazone treatment increases survival and prevents body weight loss in tumor-bearing animals: possible anti-cachectic effect.

    Science.gov (United States)

    Beluzi, Mércia; Peres, Sidney B; Henriques, Felipe S; Sertié, Rogério A L; Franco, Felipe O; Santos, Kaltinaitis B; Knobl, Pâmela; Andreotti, Sandra; Shida, Cláudio S; Neves, Rodrigo X; Farmer, Stephen R; Seelaender, Marília; Lima, Fábio B; Batista, Miguel L

    2015-01-01

    Cachexia is a multifactorial syndrome characterized by profound involuntary weight loss, fat depletion, skeletal muscle wasting, and asthenia; all symptoms are not entirely attributable to inadequate nutritional intake. Adipose tissue and skeletal muscle loss during cancer cachexia development has been described systematically. The former was proposed to precede and be more rapid than the latter, which presents a means for the early detection of cachexia in cancer patients. Recently, pioglitazone (PGZ) was proposed to exhibit anti-cancer properties, including a reduction in insulin resistance and adipose tissue loss; nevertheless, few studies have evaluated its effect on survival. For greater insight into a potential anti-cachectic effect due to PGZ, 8-week-old male Wistar rats were subcutaneously inoculated with 1 mL (2×107) of Walker 256 tumor cells. The animals were randomly assigned to two experimental groups: TC (tumor + saline-control) and TP5 (tumor + PGZ/5 mg). Body weight, food ingestion and tumor growth were measured at baseline and after removal of tumor on days 7, 14 and 26. Samples from different visceral adipose tissue (AT) depots were collected on days 7 and 14 and stored at -80o C (5 to 7 animals per day/group). The PGZ treatment showed an increase in the survival average of 27.3% (P< 0.01) when compared to TC. It was also associated with enhanced body mass preservation (40.7 and 56.3%, p< 0.01) on day 14 and 26 compared with the TC group. The treatment also reduced the final tumor mass (53.4%, p<0.05) and anorexia compared with the TC group during late-stage cachexia. The retroperitoneal AT (RPAT) mass was preserved on day 7 compared with the TC group during the same experimental period. Such effect also demonstrates inverse relationship with tumor growth, on day 14. Gene expression of PPAR-γ, adiponectin, LPL and C/EBP-α from cachectic rats was upregulated after PGZ. Glucose uptake from adipocyte cells (RPAT) was entirely re-established due to

  17. Pioglitazone treatment increases survival and prevents body weight loss in tumor-bearing animals: possible anti-cachectic effect.

    Directory of Open Access Journals (Sweden)

    Mércia Beluzi

    Full Text Available Cachexia is a multifactorial syndrome characterized by profound involuntary weight loss, fat depletion, skeletal muscle wasting, and asthenia; all symptoms are not entirely attributable to inadequate nutritional intake. Adipose tissue and skeletal muscle loss during cancer cachexia development has been described systematically. The former was proposed to precede and be more rapid than the latter, which presents a means for the early detection of cachexia in cancer patients. Recently, pioglitazone (PGZ was proposed to exhibit anti-cancer properties, including a reduction in insulin resistance and adipose tissue loss; nevertheless, few studies have evaluated its effect on survival. For greater insight into a potential anti-cachectic effect due to PGZ, 8-week-old male Wistar rats were subcutaneously inoculated with 1 mL (2×107 of Walker 256 tumor cells. The animals were randomly assigned to two experimental groups: TC (tumor + saline-control and TP5 (tumor + PGZ/5 mg. Body weight, food ingestion and tumor growth were measured at baseline and after removal of tumor on days 7, 14 and 26. Samples from different visceral adipose tissue (AT depots were collected on days 7 and 14 and stored at -80o C (5 to 7 animals per day/group. The PGZ treatment showed an increase in the survival average of 27.3% (P< 0.01 when compared to TC. It was also associated with enhanced body mass preservation (40.7 and 56.3%, p< 0.01 on day 14 and 26 compared with the TC group. The treatment also reduced the final tumor mass (53.4%, p<0.05 and anorexia compared with the TC group during late-stage cachexia. The retroperitoneal AT (RPAT mass was preserved on day 7 compared with the TC group during the same experimental period. Such effect also demonstrates inverse relationship with tumor growth, on day 14. Gene expression of PPAR-γ, adiponectin, LPL and C/EBP-α from cachectic rats was upregulated after PGZ. Glucose uptake from adipocyte cells (RPAT was entirely re

  18. Differences in p53 status significantly influence the cellular response and cell survival to 1,25-dihydroxyvitamin D3-metformin cotreatment in colorectal cancer cells.

    Science.gov (United States)

    Abu El Maaty, Mohamed A; Strassburger, Wendy; Qaiser, Tooba; Dabiri, Yasamin; Wölfl, Stefan

    2017-11-01

    Mutations in the tumor suppressor p53 are highly prevalent in cancers and are known to influence the sensitivity of cells to various chemotherapeutics including the anti-cancer candidates 1,25-dihydrovitamin D3 [1,25D3] and metformin. Previous studies have demonstrated additive/synergistic anti-cancer effects of the 1,25D3-metformin combination in different models, however, the influence of p53 status on the efficacy of this regimen has not been investigated. The CRC colorectal cancer (CRC) cell lines HCT116 wild-type (wt), HCT116 p53-/-, and HT-29 (mutant; R273H) were employed, covering three different p53 variations. Synergistic effects of the combination were confirmed in all cell lines using MTT assay. Detailed evaluation of the combination's effects was performed, including on-line measurements of cellular metabolism (glycolysis/respiration) using a biosensor chip system, analyses of mitochondrial activity (membrane potential and ATP/ROS production), mRNA expression analysis of WNT/β-catenin pathway players, and a comprehensive proteomic screen using immunoblotting and ELISA microarrays. AMPK signaling was found to be more strongly induced in response to all treatments in HCT116 wt cells compared to other cell lines, an observation that was coupled to a stronger accumulation of intracellular ROS in response to metformin/combination, and finally an induction in autophagy, depicted by an increase in LC3II:LC3I ratio in combination-treated cells compared to mono-treatments. An induction in apoptotic signaling was observed in the other cell lines in response to the combination, illustrated by a decrease in expression of pro-survival Bcl2 family members. P53 status impacts cellular responses to the combination but does not hamper its anti-proliferative synergy. © 2017 Wiley Periodicals, Inc.

  19. Demographic consequences of chromatic leaf defence in tropical tree communities: do red young leaves increase growth and survival?

    Science.gov (United States)

    Queenborough, Simon A.; Metz, Margaret R.; Valencia, Renato; Wright, S. Joseph

    2013-01-01

    Background Many tropical forest tree species delay greening their leaves until full expansion. This strategy is thought to provide newly flushing leaves with protection against damage by herbivores by keeping young leaves devoid of nutritive value. Because young leaves suffer the greatest predation from invertebrate herbivores, delayed greening could prevent costly tissue loss. Many species that delay greening also produce anthocyanin pigments in their new leaves, giving them a reddish tint. These anthocyanins may be fungicidal, protect leaves against UV damage or make leaves cryptic to herbivores blind to the red part of the spectrum. Methods A comprehensive survey was undertaken of seedlings, saplings and mature trees in two diverse tropical forests: a rain forest in western Amazonia (Yasuní National Park, Ecuador) and a deciduous forest in Central America (Barro Colorado Island, Panamá). A test was made of whether individuals and species with delayed greening or red-coloured young leaves showed lower mortality or higher relative growth rates than species that did not. Key results At both Yasuní and Barro Colorado Island, species with delayed greening or red young leaves comprised significant proportions of the seedling and tree communities. At both sites, significantly lower mortality was found in seedlings and trees with delayed greening and red-coloured young leaves. While there was little effect of leaf colour on the production of new leaves of seedlings, diameter relative growth rates of small trees were lower in species with delayed greening and red-coloured young leaves than in species with regular green leaves, and this effect remained when the trade-off between mortality and growth was accounted for. Conclusions Herbivores exert strong selection pressure on seedlings for the expression of defence traits. A delayed greening or red-coloured young leaf strategy in seedlings appears to be associated with higher survival for a given growth rate, and may

  20. Six Year Refractive Change among White Children and Young Adults: Evidence for Significant Increase in Myopia among White UK Children.

    Directory of Open Access Journals (Sweden)

    Sara J McCullough

    Full Text Available To determine six-year spherical refractive error change among white children and young adults in the UK and evaluate differences in refractive profiles between contemporary Australian children and historical UK data.Population-based prospective study.The Northern Ireland Childhood Errors of Refraction (NICER study Phase 1 examined 1068 children in two cohorts aged 6-7 years and 12-13 years. Prospective data for six-year follow-up (Phase 3 are available for 212 12-13 year olds and 226 18-20 year olds in each cohort respectively.Cycloplegic refractive error was determined using binocular open-field autorefraction (Shin-Nippon NVision-K 5001, cyclopentolate 1%. Participants were defined by spherical equivalent refraction (SER as myopic SER ≤-0.50D, emmetropic -0.50Dsignificantly increased between 6-7 years (1.9% and 12-13 years (14.6% (p<0.001 but not between 12-13 and 18-20 years (16.4% to 18.6%, p = 0.51. The estimated annual incidence of myopia was 2.2% and 0.7% for the younger and older cohorts respectively. There were significantly more myopic children in the UK at age 12-13 years in the NICER study (16.4% than reported in Australia (4.4% (p<0.001. However by 17 years the proportion of myopia neared equivalence in the two populations (NICER 18.6%, Australia 17.7%, p = 0.75. The proportion of myopic children aged 12-13 years in the present study (2006-2008 was 16.4%, significantly greater than that reported for children aged 10-16 years in the 1960's (7.2%, p = 0.01. The proportion of hyperopes in the younger NICER cohort decreased significantly over the six year period (from 21.7% to 14.2%, p = 0.04. Hyperopes with SER ≥+3.50D in both NICER age cohorts demonstrated persistent hyperopia.The incidence and proportion of myopia are relatively low in this contemporary white UK population in comparison to other worldwide studies. The proportion of

  1. Mesenterico-portal vein resection in patients with pancreatico-duodenal cancer is safe and may increase survival

    DEFF Research Database (Denmark)

    Storkholm, Jan Henrik; Hansen, Carsten Palnæs

    2014-01-01

    INTRODUCTION: Pancreatic cancer is one of the most serious gastrointestinal cancers, and in the US and Europe it is a leading cause of cancer-related mortality. Radical surgery is the only option available for long-term survival. The aim of this study was to describe the surgical technique...... high-volume centres. The median survival was far better than expected, especially since our material included a considerable number of patients with lymph node metastases. FUNDING: not relevant. TRIAL REGISTRATION: not relevant....

  2. Increased mortality among HIV-positive men on antiretroviral therapy: survival differences between sexes explained by late initiation in Uganda

    Directory of Open Access Journals (Sweden)

    Kanters S

    2013-05-01

    Full Text Available Steve Kanters,1,3 Margaret Nansubuga,2 Daniel Mwehire,2 Mary Odiit,2 Margaret Kasirye,2 William Musoke,2 Eric Druyts,3 Sanni Yaya,3 Anna Funk,3 Nathan Ford,4,5 Edward J Mills3,61Faculty of Health Science, Simon Fraser University, Burnaby, BC, Canada, 2Mildmay Uganda, Kampala, Uganda; 3Faculty of Health Sciences, University of Ottawa, Ottawa, ON, Canada; 4Médecins Sans Frontières, Geneva, Switzerland; 5Centre for Infectious Disease Epidemiology and Research, University of Cape Town, South Africa; 6Stanford Prevention Research Center, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USABackground: We aimed to assess the relationship between gender and survival among adult patients newly enrolled on antiretroviral therapy (ART in Uganda. We also specifically examined the role of antenatal services in favoring women's access to HIV care.Methods: From an observational cohort study, we assessed survival and used logistic regression and differences in means to compare men and women who did not access care through antenatal services. Differences were assessed on measures of disease progression (WHO stage and CD4 count and demographic (age, marital status, and education, behavioral (sexual activity, disclosure to partner, and testing, and clinical variables (hepatitis B and C, syphilis, malaria, and anemia. A mediational analysis that considered gender as the initial variable, time to death as the outcome, initial CD4 count as the mediator, and age as a covariate was performed using an accelerated failure time model with a Weibull distribution.Results: Between 2004 and 2011, a total of 4775 patients initiated ART, and after exclusions 4537 (93.2% were included in analysis. Men initiating ART were more likely to have a WHO disease stage III or IV (odds ratio: 1.46, 95% confidence interval [CI]: 1.29–1.66, and lower CD4 cell counts compared to women (median baseline CD4 124 cells/mm3, interquartile range [IQR]: 43–205

  3. Squamous Cancers of the Rectum Demonstrate Poorer Survival and Increased Need for Salvage Surgery Compared With Squamous Cancers of the Anus.

    Science.gov (United States)

    Kulaylat, Audrey S; Hollenbeak, Christopher S; Stewart, David B

    2017-09-01

    Squamous cell cancers of the anus are rare GI malignancies for which neoadjuvant chemoradiation is the first-line treatment for nonmetastatic disease. Squamous cancers of the rectum are far less common, and it is unclear to what degree chemoradiotherapy improves their outcomes. The purpose of this study was to compare stage-specific survival for anal and rectal squamous cancers stratified by treatment approach. This was a retrospective cohort study. The study was conducted at Commission on Cancer designated hospitals. Patients (2006-2012) identified in the National Cancer Database with pretreatment clinical stage I to III cancers who underwent chemoradiotherapy, with and without subsequent salvage surgical resection (low anterior resection or abdominoperineal resection), ≥12 weeks after chemoradiotherapy were included in the study. Overall survival and the need for salvage surgery were measured. Anal cancers (n = 11,224) typically presented with stage II (45.7%) or III (36.3%) disease, whereas rectal cancer stages (n = 1049) were more evenly distributed (p cancer underwent low anterior or abdominoperineal resections 12 weeks or later after chemoradiotherapy versus those undergoing abdominoperineal resection for anal cancer (3.8% versus 1.2%; p cancer was associated with poorer survival compared with anal cancer (stage I, p = 0.017; stage II, p cancer was associated with worse survival for stage I to III cancers; salvage surgery did not significantly affect survival for rectal cancer. This was a retrospective study without cancer-specific survival measures. Squamous rectal cancers are associated with significantly worse survival than squamous cancers of the anus for clinical stage I and II disease. Despite both cancers exhibiting squamous histology, rectal cancers may be less radiosensitive than anal cancers, as suggested by the greater incidence of salvage surgery that does not appear to significantly improve overall survival. See Video Abstract at http

  4. Prognostic significance of K-ras and TP53 mutations in the role of adjuvant chemotherapy on survival in patients with Dukes C colon cancer

    NARCIS (Netherlands)

    Bleeker, W A; Hayes, V M; Karrenbeld, A; Hofstra, R M; Verlind, E; Hermans, J; Poppema, S; Buys, C H; Plukker, J T

    PURPOSE: Mutations in K-ras and TP53 genes are common in colorectal cancer. They affect biologic behavior and might influence chemotherapy susceptibility in these tumors. We investigated whether the survival of patients with Dukes C colon cancer treated with adjuvant chemotherapy is influenced by

  5. Treatment of rheumatoid arthritis with tumor necrosis factor inhibitors may predispose to significant increase in tuberculosis risk: a multicenter active-surveillance report.

    Science.gov (United States)

    Gómez-Reino, Juan J; Carmona, Loreto; Valverde, Vicente Rodríguez; Mola, Emilio Martín; Montero, Maria Dolores

    2003-08-01

    The long-term safety of therapeutic agents that neutralize tumor necrosis factor (TNF) is uncertain. Recent evidence based on spontaneous reporting shows an association with active tuberculosis (TB). We undertook this study to determine and describe the long-term safety of 2 of these agents, infliximab and etanercept, in rheumatic diseases based on a national active-surveillance system following the commercialization of the drugs. We analyzed the safety data actively collected in the BIOBADASER (Base de Datos de Productos Biológicos de la Sociedad Española de Reumatología) database, which was launched in February 2000 by the Spanish Society of Rheumatology. For the estimation of TB risk, the annual incidence rate in patients treated with these agents was compared with the background rate and with the rate in a cohort of patients with rheumatoid arthritis (RA) assembled before the era of anti-TNF treatment. Seventy-one participating centers sent data on 1,578 treatments with infliximab (86%) or etanercept (14%) in 1,540 patients. Drug survival rates (reported as the cumulative percentage of patients still receiving medication) for infliximab and etanercept pooled together were 85% and 81% at 1 year and 2 years, respectively. Instances of discontinuation were essentially due to adverse events. Seventeen cases of TB were found in patients treated with infliximab. The estimated incidence of TB associated with infliximab in RA patients was 1,893 per 100,000 in the year 2000 and 1,113 per 100,000 in the year 2001. These findings represent a significant increased risk compared with background rates. In the first 5 months of 2002, after official guidelines were established for TB prevention in patients treated with biologics, only 1 new TB case was registered (in January). Therapy with infliximab is associated with an increased risk of active TB. Proper measures are needed to prevent and manage this adverse event.

  6. Splenic vein thrombosis is associated with an increase in pancreas-specific complications and reduced survival in patients undergoing distal pancreatectomy for pancreatic exocrine cancer.

    Science.gov (United States)

    Dedania, Nishi; Agrawal, Nidhi; Winter, Jordan M; Koniaris, Leonidas G; Rosato, Ernest L; Sauter, Patricia K; Leiby, Ben; Pequignot, Edward; Yeo, Charles J; Lavu, Harish

    2013-08-01

    Distal pancreatectomy and splenectomy (DPS) is the procedure of choice for the surgical treatment of pancreatic exocrine cancer localized to the body and tail of the pancreas. Splenic vein thrombosis (SVT) can occur in patients with malignant pancreatic exocrine tumors secondary to direct tumor invasion or compression of the splenic vein by mass effect. This study examines the effect of preoperative SVT on postoperative outcomes. In this retrospective cohort study, we queried our pancreatic surgery database to identify patients who underwent DPS from October 2005 to June 2011. These cases were evaluated for evidence of preoperative SVT on clinical records and cross-sectional imaging (CT,MRI, endoscopic US). Outcomes for patients with and without SVT were compared. From an overall cohort of 285 consecutive patients who underwent DPS during the study period, data were evaluated for 70 subjects who underwent surgery for pancreatic exocrine cancer (27 with SVT, 43 without SVT). The preoperative demographics and co-morbidities were similar between the groups, except the average age was higher for those without SVT (pSVT group (675 versus 250 ml, p=SVT versus 56% no SVT, p=NS), the group with SVT had a significantly higher rate of pancreas-specific complications, including pancreatic fistula (33 versus 7 %,pSVT had a trend toward longer median survival (40 versus 20.8 months),although the difference was not statistically significant (p=0.1). DPS for pancreatic ductal adenocarcinoma can be performed safely in patients with SVT, but with higher intraoperative blood loss, increased pancreas-specific complications, and a trend towards lower long-term survival rates. This paper was presented as a poster at the 53rd annual meeting of the Society for Surgery of the Alimentary Tract and at the 46th annual meeting of the Pancreas Club, San Diego, CA, May 2012.

  7. Preliminary Study on Intrasplenic Implantation of Artificial Cell Bioencapsulated Stem Cells to Increase the Survival of 90% Hepatectomized Rats

    Science.gov (United States)

    Liu, Zun Chang; Chang, Thomas M.S.

    2012-01-01

    We implanted artificial cell bioencapsulated bone marrow mesenchymal stem cells into the spleens of 90% hepatectomized (PH) rats. The resulting 14 days survival rate was 91%. This is compared to a survival rate of 21% in 90% hepatectomized rats and 25% for those receiving free MSCs transplanted the same way. Unlike free MSCs, the bioencapsulated MSCs are retained in the spleens and their hepatotrophic factors can continue to drain directly into the liver without dilution resulting in improved hepatic regeneration. In addition, with time the transdifferentiation of MSCs into hepatocyte-like cells in the spleen renders the spleen as a ectopic liver support. PMID:19132579

  8. Was there significant tax evasion after the 1999 50 cent per pack cigarette tax increase in California?

    OpenAIRE

    Emery, S.; White, M.; Gilpin, E; Pierce, J.

    2002-01-01

    Objectives: Several states, including California, have implemented large cigarette excise tax increases, which may encourage smokers to purchase their cigarettes in other lower taxed states, or from other lower or non-taxed sources. Such tax evasion thwarts tobacco control objectives and may cost the state substantial tax revenues. Thus, this study investigates the extent of tax evasion in the 6–12 months after the implementation of California's $0.50/pack excise tax increase.

  9. Prognostic significance of repeat biopsy in lupus nephritis: Histopathologic worsening and a short time between biopsies is associated with significantly increased risk for end stage renal disease and death.

    Science.gov (United States)

    Arriens, Cristina; Chen, Sixia; Karp, David R; Saxena, Ramesh; Sambandam, Kamalanathan; Chakravarty, Eliza; James, Judith A; Merrill, Joan T

    2017-12-01

    Approximately half of patients with systemic lupus erythematosus (SLE) develop lupus nephritis (LN), a major cause of morbidity and early mortality in that disease. Prolonged renal inflammation is associated with irreversible kidney damage which confers a 30% risk of end stage renal disease (ESRD), making early, aggressive treatment mandatory. Failure to achieve therapeutic response or recurrence of renal flare often prompts repeat biopsy. However, the role of repeat biopsy in determining long-term renal prognosis remains controversial. For this reason repeat biopsies are usually not utilized unless clinical evidence of refractory or recurrent disease is already present, despite known mismatches between clinical and biopsy findings. The current study quantifies the degree to which histopathologic worsening between first and second biopsies and duration between them predicts ESRD and death. Medical records of 141 LN patients with more than one biopsy were obtained from a single large urban medical center. Cases were attained using billing codes for diagnosis and procedures from 1/1999-1/2015. Biopsy worsening was defined as unfavorable histopathologic classification transitions and/or increased chronicity; if neither were present, the patient was defined as non-worsening. We used Cox proportional hazard models to study the relationship between ESRD and survival adjusting for covariates which included age at first biopsy, gender, race, initial biopsy class, and initial induction therapy. Of 630 patients screened, 141 had more than one biopsy. Advancing chronicity was detected in 48 (34.0%) and a renal class switch to worse grade of pathology was found in 54 (38.3%). At least one of these adverse second biopsy features was reported in 79 (56.0%) patients. Five years following initial biopsy, 28 (35.4%) of those with worsening histopathology on second biopsy developed ESRD, compared to 6 (9.7%) of non-worsening patients and 10 (12.7%) of patients with worsening

  10. Increasing significance of advanced physical/chemical processes in the development and application of sustainable wastewater treatment systems

    NARCIS (Netherlands)

    Rulkens, W.H.

    2008-01-01

    The awareness of the problem of the scarcity of water of high quality has strongly changed the approach of wastewater treatment. Currently, there is an increasing need for the beneficial reuse of treated wastewater and to recover valuable products and energy from the wastewater. Because

  11. Emerged HA and NA mutants of the pandemic influenza H1N1 viruses with increasing epidemiological significance in Taipei and Kaohsiung, Taiwan, 2009-10.

    Directory of Open Access Journals (Sweden)

    Chuan-Liang Kao

    Full Text Available The 2009 influenza pandemic provided an opportunity to observe dynamic changes of the hemagglutinin (HA and neuraminidase (NA of pH1N1 strains that spread in two metropolitan areas--Taipei and Kaohsiung. We observed cumulative increases of amino acid substitutions of both HA and NA that were higher in the post-peak than in the pre-peak period of the epidemic. About 14.94% and 3.44% of 174 isolates had one and two amino acids changes, respective, in the four antigenic sites. One unique adaptive mutation of HA2 (E374K was first detected three weeks before the epidemic peak. This mutation evolved through the epidemic, and finally emerged as the major circulated strain, with significantly higher frequency in the post-peak period than in the pre-peak (64.65% vs 9.28%, p<0.0001. E374K persisted until ten months post-nationwide vaccination without further antigenic changes (e.g. prior to the highest selective pressure. In public health measures, the epidemic peaked at seven weeks after oseltamivir treatment was initiated. The emerging E374K mutants spread before the first peak of school class suspension, extended their survival in high-density population areas before vaccination, dominated in the second wave of class suspension, and were fixed as herd immunity developed. The tempo-spatial spreading of E374K mutants was more concentrated during the post-peak (p = 0.000004 in seven districts with higher spatial clusters (p<0.001. This is the first study examining viral changes during the naïve phase of a pandemic of influenza through integrated virological/serological/clinical surveillance, tempo-spatial analysis, and intervention policies. The vaccination increased the percentage of E374K mutants (22.86% vs 72.34%, p<0.001 and significantly elevated the frequency of mutations in Sa antigenic site (2.36% vs 23.40%, p<0.001. Future pre-vaccination public health efforts should monitor amino acids of HA and NA of pandemic influenza viruses isolated at

  12. Simulation of Jack-Up Overturning Using the Monte Carlo Method with Artificially Increased Significant Wave Height

    DEFF Research Database (Denmark)

    Jensen, Jørgen Juncher

    2010-01-01

    It is well known from linear analyses in stochastic seaway that the mean out-crossing rate of a level r is given through the reliability index, defined as r divided by the standard deviation. Hence, the reliability index becomes inversely proportional to the significant wave height. For non......-linear processes the mean out-crossing rate depends non-linearly on the response level r and a good estimate can be found using the First Order Reliability Method (FORM), see e.g. Jensen and Capul (2006). The FORM analysis also shows that the reliability index is strictly inversely proportional to the significant...... wave height irrespectively of the non-linearity in the system. However, the FORM analysis only gives an approximation to the mean out-crossing rate. A more exact result can be obtained by Monte Carlo simulations, but the necessary length of the time domain simulations for very low out-crossing rates...

  13. Increased Risk of Clinically Significant Gallstones following an Appendectomy: A Five-Year Follow-Up Study.

    Directory of Open Access Journals (Sweden)

    Shiu-Dong Chung

    Full Text Available Although the vermiform appendix is commonly considered a vestigial organ, adverse health consequences after an appendectomy have garnered increasing attention. In this study, we investigated the risks of gallstone occurrence during a 5-year follow-up period after an appendectomy, using a population-based dataset. We used data from the Taiwan Longitudinal Health Insurance Database 2005. The exposed cohort included 4916 patients who underwent an appendectomy. The unexposed cohort was retrieved by randomly selecting 4916 patients matched with the exposed cohort in terms of sex, age, and year. We individually tracked each patient for a 5-year period to identify those who received a diagnosis of gallstones during the follow-up period. Cox proportional hazard regressions were performed for the analysis. During the 5-year follow-up period, the incidence rate per 1000 person-years was 4.71 for patients who had undergone an appendectomy, compared to a rate of 2.59 for patients in the unexposed cohort (p<0.001. Patients who had undergone an appendectomy were independently associated with a 1.79 (95% CI = 1.29~2.48-fold increased risk of being diagnosed with gallstones during the 5-year follow-up period. We found that among female patients, the adjusted hazard ratio of gallstones was 2.25 (95% CI = 1.41~3.59 for patients who underwent an appendectomy compared to unexposed patients. However, for male patients, we failed to observe an increased hazard for gallstones among patients who underwent an appendectomy compared to unexposed patients. We found an increased risk of a subsequent gallstone diagnosis within 5 years after an appendectomy.

  14. A cell-delivered and cell-activated SN38-dextran prodrug increases survival in a murine disseminated pancreatic cancer model.

    Science.gov (United States)

    Basel, Matthew T; Balivada, Sivasai; Shrestha, Tej B; Seo, Gwi-Moon; Pyle, Marla M; Tamura, Masaaki; Bossmann, Stefan H; Troyer, Deryl L

    2012-03-26

    Enzyme-activated prodrugs have been investigated and sought after as highly specific, low-side-effect treatments, especially for cancer therapy. Unfortunately, excellent targets for enzyme-activated therapy are rare. Here a system based on cell delivery that can carry both a prodrug and an activating enzyme to the cancer site is demonstrated. Raw264.7 cells (mouse monocyte/macrophage-like cells, Mo/Ma) are engineered to express intracellular rabbit carboxylesterase (InCE), which is a potent activator of the prodrug irinotecan to SN38. InCE expression is regulated by the TetOn® system, which silences the gene unless a tetracycline, such as doxycycline, is present. Concurrently, an irinotecan-like prodrug, which is conjugated to dextran and can be loaded into the cytoplasm of Mo/Ma, is synthesized. To test the system, a murine pancreatic cancer model is generated by intraperitoneal (i.p.) injection of Pan02 cells. Engineered Mo/Ma are loaded with the prodrug and are injected i.p. Two days later, doxycycline was given i.p. to activate InCE, which activated the prodrug. A survival study demonstrates that this system significantly increased survival in a murine pancreatic cancer model. Thus, for the first time, a prodrug/activating enzyme system, which is self-contained within tumor-homing cells and can prolong the life of i.p. pancreatic tumor bearing mice, is demonstrated. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Nation-Scale Adoption of Shorter Breast Radiation Therapy Schedules Can Increase Survival in Resource Constrained Economies: Results From a Markov Chain Analysis.

    Science.gov (United States)

    Khan, Atif J; Rafique, Raza; Zafar, Waleed; Shah, Chirag; Haffty, Bruce G; Vicini, Frank; Jamshed, Arif; Zhao, Yao

    2017-02-01

    Hypofractionated whole breast irradiation and accelerated partial breast irradiation (APBI) offer women options for shorter courses of breast radiation therapy. The impact of these shorter schedules on the breast cancer populations of emerging economies with limited radiation therapy resources is unknown. We hypothesized that adoption of these schedules would improve throughput in the system and, by allowing more women access to life-saving treatments, improve patient survival within the system. We designed a Markov chain model to simulate the different health states that a postlumpectomy or postmastectomy patient could enter over the course of a 20-year follow-up period. Transition rates between health states were adapted from published data on recurrence rates. We used primary data from a tertiary care hospital in Lahore, Pakistan, to populate the model with proportional use of mastectomy versus breast conservation and to estimate the proportion of patients suitable for APBI. Sensitivity analyses on the use of APBI and relative efficacy of APBI were conducted to study the impact on the population. The shorter schedule resulted in more women alive and more women remaining without evidence of disease (NED) compared with the conventional schedule, with an absolute difference of about 4% and 7% at 15 years, respectively. Among women who had lumpectomies, the chance of remaining alive and with an intact breast was 62% in the hypofractionation model and 54% in the conventional fractionation model. Increasing throughput in the system can result in improved survival, improved chances of remaining without evidence of disease, and improved chances of remaining alive with a breast. These findings are significant and suggest that adoption of hypofractionation in emerging economies is not simply a question of efficiency and cost but one of access to care and patient survivorship. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Nation-Scale Adoption of Shorter Breast Radiation Therapy Schedules Can Increase Survival in Resource Constrained Economies: Results From a Markov Chain Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Khan, Atif J., E-mail: atif.j.khan@rutgers.edu [Department of Radiation Oncology, Robert Wood Johnson Medical School/Cancer Institute of New Jersey, New Brunswick, New Jersey (United States); Rafique, Raza [Suleman Dawood School of Business, Lahore University of Management Sciences, Lahore (Pakistan); Zafar, Waleed [Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore (Pakistan); Shah, Chirag [Department of Radiation Oncology, Cleveland Clinic, Cleveland, Ohio (United States); Haffty, Bruce G. [Department of Radiation Oncology, Robert Wood Johnson Medical School/Cancer Institute of New Jersey, New Brunswick, New Jersey (United States); Vicini, Frank [Michigan HealthCare Professionals, Farmington Hills, Michigan (United States); Jamshed, Arif [Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore (Pakistan); Zhao, Yao [Rutgers University School of Business, Newark, New Jersey (United States)

    2017-02-01

    Purpose: Hypofractionated whole breast irradiation and accelerated partial breast irradiation (APBI) offer women options for shorter courses of breast radiation therapy. The impact of these shorter schedules on the breast cancer populations of emerging economies with limited radiation therapy resources is unknown. We hypothesized that adoption of these schedules would improve throughput in the system and, by allowing more women access to life-saving treatments, improve patient survival within the system. Methods and Materials: We designed a Markov chain model to simulate the different health states that a postlumpectomy or postmastectomy patient could enter over the course of a 20-year follow-up period. Transition rates between health states were adapted from published data on recurrence rates. We used primary data from a tertiary care hospital in Lahore, Pakistan, to populate the model with proportional use of mastectomy versus breast conservation and to estimate the proportion of patients suitable for APBI. Sensitivity analyses on the use of APBI and relative efficacy of APBI were conducted to study the impact on the population. Results: The shorter schedule resulted in more women alive and more women remaining without evidence of disease (NED) compared with the conventional schedule, with an absolute difference of about 4% and 7% at 15 years, respectively. Among women who had lumpectomies, the chance of remaining alive and with an intact breast was 62% in the hypofractionation model and 54% in the conventional fractionation model. Conclusions: Increasing throughput in the system can result in improved survival, improved chances of remaining without evidence of disease, and improved chances of remaining alive with a breast. These findings are significant and suggest that adoption of hypofractionation in emerging economies is not simply a question of efficiency and cost but one of access to care and patient survivorship.

  17. Love is the triumph of the imagination: Daydreams about significant others are associated with increased happiness, love and connection.

    Science.gov (United States)

    Poerio, Giulia L; Totterdell, Peter; Emerson, Lisa-Marie; Miles, Eleanor

    2015-05-01

    Social relationships and interactions contribute to daily emotional well-being. The emotional benefits that come from engaging with others are known to arise from real events, but do they also come from the imagination during daydreaming activity? Using experience sampling methodology with 101 participants, we obtained 371 reports of naturally occurring daydreams with social and non-social content and self-reported feelings before and after daydreaming. Social, but not non-social, daydreams were associated with increased happiness, love and connection and this effect was not solely attributable to the emotional content of the daydreams. These effects were only present when participants were lacking in these feelings before daydreaming and when the daydream involved imagining others with whom the daydreamer had a high quality relationship. Findings are consistent with the idea that social daydreams may function to regulate emotion: imagining close others may serve the current emotional needs of daydreamers by increasing positive feelings towards themselves and others. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  18. The abundant free-living amoeba, Acanthamoeba polyphaga, increases the survival of Campylobacter jejuni in milk and orange juice

    Directory of Open Access Journals (Sweden)

    Jenny Olofsson

    2015-09-01

    Full Text Available Background: Campylobacter jejuni is a common cause of human bacterial diarrhea in most parts of the world. Most C. jejuni infections are acquired from contaminated poultry, milk, and water. Due to health care costs and human suffering, it is important to identify all possible sources of infection. Unpasteurized milk has been associated with several outbreaks of C. jejuni infection. Campylobacter has been identified on fresh fruit, and other gastrointestinal pathogens such as Salmonella, E. coli O157:H7 and Cryptosporidium have been involved in fruit juice outbreaks. C. jejuni is sensitive to the acidic environment of fruit juice, but co-cultures with the amoeba, Acanthamoeba polyphaga, have previously been shown to protect C. jejuni at low pH. Methods: To study the influence of A. polyphaga on the survival of C. jejuni in milk and juice, the bacteria were incubated in the two products at room temperature and at 4°C with the following treatments: A C. jejuni preincubated with A. polyphaga before the addition of product, B C. jejuni mixed with A. polyphaga after the addition of product, and C C. jejuni in product without A. polyphaga. Bacterial survival was assessed by colony counts on blood agar plates. Results: Co-culture with A. polyphaga prolonged the C. jejuni survival both in milk and juice. The effect of co-culture was most pronounced in juice stored at room temperature. On the other hand, A. polyphaga did not have any effect on C. jejuni survival during pasteurization of milk or orange juice, indicating that this is a good method for eliminating C. jejuni in these products. Conclusion: Amoebae-associated C. jejuni in milk and juice might cause C. jejuni infections.

  19. Increased survival of normal cells during laser photodynamic therapy: implications for ex vivo autologous bone marrow purging

    Energy Technology Data Exchange (ETDEWEB)

    Gulliya, K.S.; Matthews, J.L.; Fay, J.W.; Dowben, R.M.

    1988-01-01

    Laser light-induced, dye-mediated photolysis of leukemic cells was tested in an in vitro model for its efficacy in eliminating occult tumor cells for ex vivo autologous bone marrow purging. Merocyanine 540 (MC540) was mixed with acute promyelocytic leukemia (HL-60) cells in the presence of human albumin. This cell-dye mixture was irradiated with 514 nm argon laser light. Results show that in the presence of 0.1%, 0.25% and 0.5% albumin, laser light doses of 62.4 J/cm/sup 2/, 93.6 J/cm/sup 2/ and 109.2 J/cm/sup 2/, respectively, were required for a 5 log reduction in the survival of leukemic cells. Under identical conditions, 80% to 84% of the normal bone marrow cells and 41% of the granulocyte-macrophage colony forming cells survived. The number of surviving stromal cells was reduced (1+) compared to the untreated control (4+). Mixing of irradiated bone marrow cells with equal number of HL-60 cells did not interfere with the killing of HL-60 cells treated with MC540 and laser light. The non-specific cytotoxicity of laser light alone was less than 6% for normal bone marrow cells. These results suggest that the concentration of human albumin plays an important role in laser light-induced phototoxicity. This laser light-induced selective photolysis of leukemic cells can be used in ex vivo purging of tumor cell-contaminated bone marrow grafts to achieve very high survival rates of normal bone marrow cells and granulocyte-macrophage colony forming cells.

  20. Increased survival of western corn rootworm on transgenic corn within three generations of on-plant greenhouse selection.

    Science.gov (United States)

    Meihls, Lisa N; Higdon, Matthew L; Siegfried, Blair D; Miller, Nicholas J; Sappington, Thomas W; Ellersieck, Mark R; Spencer, Terence A; Hibbard, Bruce E

    2008-12-09

    To delay evolution of insect resistance to transgenic crops producing Bacillus thuringiensis (Bt) toxins, nearby "refuges" of host plants not producing Bt toxins are required in many regions. Such refuges are expected to be most effective in slowing resistance when the toxin concentration in Bt crops is high enough to kill all or nearly all insects heterozygous for resistance. However, Bt corn, Zea mays, introduced recently does not meet this "high-dose" criterion for control of western corn rootworm (WCR), Diabrotica virgifera virgifera. A greenhouse method of rearing WCR on transgenic corn expressing the Cry3Bb1 protein was used in which approximately 25% of previously unexposed larvae survived relative to isoline survival (compared to 1-4% in the field). After three generations of full larval rearing on Bt corn (Constant-exposure colony), WCR larval survival was equivalent on Bt corn and isoline corn in greenhouse trials, and the LC(50) was 22-fold greater for the Constant-exposure colony than for the Control colony in diet bioassays with Cry3Bb1 protein on artificial diet. After six generations of greenhouse selection, the ratio of larval recovery on Bt corn to isoline corn in the field was 11.7-fold greater for the Constant-exposure colony than the Control colony. Removal from selection for six generations did not decrease survival on Bt corn in the greenhouse. The results suggest that rapid response to selection is possible in the absence of mating with unexposed beetles, emphasizing the importance of effective refuges for resistance management.

  1. 'Knowledge for better health' revisited - the increasing significance of health research systems: a review by departing Editors-in-Chief.

    Science.gov (United States)

    Hanney, Stephen R; González-Block, Miguel A

    2017-10-02

    How can nations organise research investments to obtain the best bundle of knowledge and the maximum level of improved health, spread as equitably as possible? This question was the central focus of a major initiative from WHO led by Prof Tikki Pang, which resulted in a range of developments, including the publication of a conceptual framework for national health research systems - Knowledge for better health - in 2003, and in the founding of the journal Health Research Policy and Systems (HARPS). As Editors-in-Chief of the journal since 2006, we mark our retirement by tracking both the progress of the journal and the development of national health research systems. HARPS has maintained its focus on a range of central themes that are key components of a national health research system in any country. These include building capacity to conduct and use health research, identifying appropriate priorities, securing funds and allocating them accountably, producing scientifically valid research outputs, promoting the use of research in polices and practice in order to improve health, and monitoring and evaluating the health research system. Some of the themes covered in HARPS are now receiving increased attention and, for example, with the assessment of research impact and development of knowledge translation platforms, the journal has covered their progress throughout that expansion of interest. In addition, there is increasing recognition of new imperatives, including the importance of promoting gender equality in health research if benefits are to be maximised. In this Editorial, we outline some of the diverse and developing perspectives considered within each theme, as well as considering how they are held together by the growing desire to build effective health research systems in all countries.From 2003 until mid-June 2017, HARPS published 590 articles on the above and related themes, with authors being located in 76 countries. We present quantitative data tracing

  2. Functional significance of extent and timing of muscle activation during double poling on-snow with increasing speed.

    Science.gov (United States)

    Zoppirolli, Chiara; Boccia, Gennaro; Bortolan, Lorenzo; Schena, Federico; Pellegrini, Barbara

    2017-11-01

    To evaluate the level of activation and timing of upper- and lower-body muscles during double poling at different speeds on snow. Nineteen well-trained cross-country skiers volunteered to double pole on a flat snowy track at different speeds (15, 18, 21 km h -1 ). The target speeds could be maintained by the skiers thanks to the use of an audio-pace system in combination with cones spaced equally alongside the track. Only 11 subjects were finally included in the analysis, since their actual speeds, calculated through a photocell system, were within ±0.5 km h -1 from those requested. Cycle and poling durations were measured from the recordings of an accelerometer attached to a wrist, while the pattern and the level of muscle activation were evaluated from electromyographyc signals. Double poling speed did not alter the sequence of muscle activation that started with hip flexors, continued with trunk flexors, shoulder, elbow and trunk extensors and ended with ankle plantar-flexors. However, higher speeds required an increasing involvement of thigh, trunk and shoulder muscles (P < 0.05) as well as an anticipation of their activation before pole plant (P < 0.05). A progressively earlier activation of trunk and lower limb muscles is a coordinative strategy that allows rapid achievement of optimal body posture prior to the exertion of poling phase. Moreover, earlier activation of these muscles as the speed increases provides adequate muscle stiffness in the shoulder and core regions for the acceptance of the poling load.

  3. Human papillomavirus-16 infection in advanced oral cavity cancer patients is related to an increased risk of distant metastases and poor survival.

    Directory of Open Access Journals (Sweden)

    Li-Ang Lee

    Full Text Available BACKGROUND: Human papillomavirus (HPV is an oncogenic virus causing oropharyngeal cancers and resulting in a favorable outcome after the treatment. The role of HPV in oral cavity squamous cell carcinoma (OSCC remains ambiguous. OBJECTIVE: This study aimed to examine the effect of HPV infection on disease control among patients with OSCC following radical surgery with radiation-based adjuvant therapy. PATIENTS AND METHOD: We prospectively followed 173 patients with advanced OSCC (96% were stage III/IV who had undergone radical surgery and adjuvant therapy between 2004 and 2006. They were followed between surgery and death or up to 60 months. Surgical specimens were examined using a PCR-based HPV blot test. The primary endpoints were the risk of relapse and the time to relapse; the secondary endpoints were disease-free survival, disease-specific survival, and overall survival. RESULTS: The prevalence of HPV-positive OSCC was 22%; HPV-16 (9% and HPV-18 (7% were the genotypes most commonly encountered. Solitary HPV-16 infection was a poor predictor of 5-year distant metastases (hazard ratio, 3.4; 95% confidence interval, 1.4-8.0; P = 0.005, disease-free survival (P = 0.037, disease-specific survival (P = 0.006, and overall survival (P = 0.010, whereas HPV-18 infection had no impact on 5-year outcomes. The rate of 5-year distant metastases was significantly higher in the HPV-16 or level IV/V metastasis group compared with both the extracapsular spread or tumor depth ≥ 11-mm group and patients without risk factors (P<0.001. CONCLUSIONS: HPV infections in advanced OSCC patients are not uncommon and clinically relevant. Compared with HPV-16-negative advanced OSCC patients, those with a single HPV-16 infection are at higher risk of distant metastases and poor survival despite undergoing radiation-based adjuvant therapy and require a more aggressive adjuvant treatment and a more thorough follow-up.

  4. Growth hormone significantly increases the adult height of children with idiopathic short stature: comparison of subgroups and benefit

    Science.gov (United States)

    2014-01-01

    Background Children with Idiopathic Short Stature do not attain a normal adult height. The improvement of adult height with treatment with recombinant human growth hormone (rhGH), at doses of 0.16 to 0.28 mg/kg/week is modest, usually less that 4 cm, and they remain short as adults. The benefit obtained seems dose dependent and benefits of 7.0 to 8.0 cm have been reported with higher doses of 0.32 to 0.4 mg/kg/week, but the number of studies is limited. The topic has remained controversial. Objective The objective was to conduct a retrospective analysis of our experience with 123 children with ISS treated with 0.32 ± 0.03 mg/kg/week of rhGH, with the aim of comparing the different subgroups of non-familial short stature, familial short stature, normal puberty, and delayed puberty and to assess the benefit by comparison with 305 untreated historical controls, from nine different randomized and nonrandomized controlled studies. Results Eighty eight of our children (68 males and 20 females) attained an adult height or near adult height of -0.71 SDS (0.74 SD) (95% CI, -0.87 to -0.55) with a benefit over untreated controls of 9.5 cm (7.4 to 11.6 cm) for males and 8.6 cm (6.7 to 10.5 cm) for females. In the analysis of the subgroups, the adult height and adult height gain of children with non-familial short stature were significantly higher than of familial short stature. No difference was found in the cohorts with normal or delayed puberty in any of the subgroups, except between the non-familial short stature and familial short stature puberty cohorts. This has implications for the interpretation of the benefit of treatment in studies where the number of children with familial short stature in the controls or treated subjects is not known. The treatment was safe. There were no significant adverse events. The IGF-1 values were essentially within the levels expected for the stages of puberty. Conclusion Our experience was quite positive with normalization of

  5. [Multi-disciplinary treatment increases the survival rate of late stage pharyngeal, laryngeal or cervical esophageal cancers treated by free jejunal flap reconstruction after cancer resection].

    Science.gov (United States)

    Zhu, Y M; Zhang, H; Ni, S; Wang, J; Li, D Z; Liu, S Y

    2016-05-23

    To investigate the survival status of patients with pharyngeal, laryngeal or cervical esophageal cancers, who received free jejunal flap (FJF) to repair the defects following tumor resection, and to analyze the effect of multi-disciplinary treatment on their survival. Fifty-eight patients with pharyngeal, laryngeal or cervical esophageal cancer underwent free jejunal flap (FJF) reconstruction after cancer resection between 2010 and 2013. All their clinical records were reviewed and analyzed. The success rate of flap transplantation was 91.4% (53/58). The 2-year overall survival rates (OSR) of cervical esophageal cancer and hypopharyngeal cancer patients were 67.5% and 49.3%, respectively, both were significantly better than that of laryngeal cancer. The main causes of death were local recurrence and distant metastases. The group with no short-term complications had a better two-year OSR (59.0%) than the group with short-term complications (46.6%), however, the difference between them was not significant (P=0.103). The 2-year survival rate of the initial treatment group was 65.0%, better than that of the salvage treatment group (49.4%), but the difference was not significant (P=0.051). For the stage III and IV patients, the multi-disciplinary treatment group had a significantly better 2-year OSR (64.7%) than the single or sequential treatment group (37.0%, P=0.016). Free jejunal flap reconstruction is an ideal option for repairing the cervical digestive tract circumferential defects caused by tumor resection with a high success rate and a low mortality. Compared with the single or sequential treatment, multi-disciplinary treatment can significantly improve the survival rate of late-stage hypopharyngeal and cervical esophageal cancer patients.

  6. Plant Explants Grown on Medium Supplemented with Fe3O4 Nanoparticles Have a Significant Increase in Embryogenesis

    Directory of Open Access Journals (Sweden)

    Inese Kokina

    2017-01-01

    Full Text Available Development of nanotechnology leads to the increasing release of nanoparticles in the environment that results in accumulation of different NPs in living organisms including plants. This can lead to serious changes in plant cultures which leads to genotoxicity. The aims of the present study were to detect if iron oxide NPs pass through the flax cell wall, to compare callus morphology, and to estimate the genotoxicity in Linum usitatissimum L. callus cultures induced by different concentrations of Fe3O4 nanoparticles. Two parallel experiments were performed: experiment A, where flax explants were grown on medium supplemented with 0.5 mg/l, 1 mg/l, and 1.5 mg/l Fe3O4 NPs for callus culture obtaining, and experiment B, where calluses obtained from basal MS medium were transported into medium supplemented with concentrations of NPs identical to experiment A. Obtained results demonstrate similarly in both experiments that 25 nm Fe3O4 NPs pass into callus cells and induce low toxicity level in the callus cultures. Nevertheless, calluses from experiment A showed 100% embryogenesis in comparison with experiment B where 100% rhizogenesis was noticed. It could be associated with different stress levels and adaptation time for explants and calluses that were transported into medium with Fe3O4 NPs supplementation.

  7. High Dose Atorvastatin Associated with Increased Risk of Significant Hepatotoxicity in Comparison to Simvastatin in UK GPRD Cohort.

    Directory of Open Access Journals (Sweden)

    Alan T Clarke

    Full Text Available Occasional risk of serious liver dysfunction and autoimmune hepatitis during atorvastatin therapy has been reported. We compared the risk of hepatotoxicity in atorvastatin relative to simvastatin treatment.The UK GPRD identified patients with a first prescription for simvastatin [164,407] or atorvastatin [76,411] between 1997 and 2006, but with no prior record of liver disease, alcohol-related diagnosis, or liver dysfunction. Incident liver dysfunction in the following six months was identified by biochemical value and compared between statin groups by Cox regression model adjusting for age, sex, year treatment started, dose, alcohol consumption, smoking, body mass index and comorbid conditions.Moderate to severe hepatotoxicity [bilirubin >60μmol/L, AST or ALT >200U/L or alkaline phosphatase >1200U/L] developed in 71 patients on atorvastatin versus 101 on simvastatin. Adjusted hazard ratio [AHR] for all atorvastatin relative to simvastatin was 1.9 [95% confidence interval 1.4-2.6]. High dose was classified as 40-80mg daily and low dose 10-20mg daily. Hepatotoxicity occurred in 0.44% of 4075 patients on high dose atorvastatin [HDA], 0.07% of 72,336 on low dose atorvastatin [LDA], 0.09% of 44,675 on high dose simvastatin [HDS] and 0.05% of 119,732 on low dose simvastatin [LDS]. AHRs compared to LDS were 7.3 [4.2-12.7] for HDA, 1.4 [0.9-2.0] for LDA and 1.5 [1.0-2.2] for HDS.The risk of hepatotoxicity was increased in the first six months of atorvastatin compared to simvastatin treatment, with the greatest difference between high dose atorvastatin and low dose simvastatin. The numbers of events in the analyses were small.

  8. Rare extragonadal teratomas in children: complete tumor excision as a reliable and essential procedure for significant survival. Clinical experience and review of the literature.

    Science.gov (United States)

    Paradies, Guglielmo; Zullino, Francesca; Orofino, Antonio; Leggio, Samuele

    2014-01-01

    Extragonadal teratomas are rare tumors in neonates and infants and can sometimes show unusual, distinctive feature such as an unusual location, a clinical sometimes acute, presentation and a "fetiform" histotype of the lesion. We have extrapolated, from our entire experience of teratomas, 4 unusual cases, mostly operated as emergencies; 2 of them were treated just after birth. Aim of this paper is to report the clinical and pathological findings, to evaluate the surgical approach and the long-term biological behaviour in these cases, in the light of survival and current insights reported in the literature. The Authors reviewed the most significant (Tables I and II) clinical, laboratory, radiologic, and pathologic findings, surgical procedures, early and long-term results in 4 children, 1 male and 3 females (M/F ratio: 1/3), suffering from extragonadal teratomas, located in the temporo-zygomatic region of the head (Case n. 1, Fig. 1), retroperitoneal space (Case n. 2, Fig. 2) ,liver (Case n. 3, Figg. 3-5), kidney (Case n. 4, Fig. 6, 7), respectively. Of the 4 patients, 2 were treated neonatally (1 T. of the head, 1 retroperitoneal T.) A prenatal diagnosis had already been made in 2 of the 4 patients, between the 2nd and 3rd trimester of pregnancy, All the infants were born by scheduled caesarean section in a tertiary care hospital and were the immediately referred to thew N.I.C.Us. Because of a mostly acute clinical presentation, the 4 patients were then referred to the surgical unit at different ages: 7 days, 28 days, 7 months, and 4 years respectively. The initial clinical presentation (Table II) was consistent with the site of the mass and/or its side effects. The 2 newborns (Case 1 and 2) both with a prenatally diagnosed mass located at the temporozygomatic region and in the abdominal cavite respectively, already displayed, at birth a mass with a tendency to further growth. The symptoms and signs described to the primary care physician by the parents of the 2

  9. A significant increase in the pepsinogen I/II ratio is a reliable biomarker for successful Helicobacter pylori eradication.

    Directory of Open Access Journals (Sweden)

    Hiroki Osumi

    Full Text Available Helicobacter pylori (H. pylori eradication is usually assessed using the 13C-urea breath test (UBT, anti-H. pylori antibody and the H. pylori stool antigen test. However, a few reports have used pepsinogen (PG, in particular, the percentage change in the PG I/II ratio. Here, we evaluated the usefulness of the percentage changes in serum PG I/II ratios for determining the success of eradication therapy for H. pylori.In total, 650 patients received eradication therapy from October 2008 to March 2013 in our Cancer Institute Hospital. We evaluated the relationship between H. pylori eradication and percentage changes in serum PG I/II ratios before and 3 months after treatment with CLEIA® (FUJIREBIO Inc, Tokyo, Japan. The gold standard of H. pylori eradication was defined as negative by the UBT performed 3 months after completion of eradication treatment. Cut-off values for percentage changes in serum PG I/II ratios were set as +40, +25 and +10% when the serum PG I/II ratio before treatment was below 3.0, above 3.0 but below 5.0 and 5.0 or above, respectively.Serum PG I and PG II levels were measured in 562 patients with H. pylori infection before and after eradication therapy. Eradication of H. pylori was achieved in 433 patients studied (77.0%. The ratios of first, second, third-line and penicillin allergy eradication treatment were 73.8% (317/429, 88.3% (99/112, 75% (12/16 and 100% (5/5, respectively. An increasing percentage in the serum levels of the PG I/II ratios after treatment compared with the values before treatment clearly distinguished success from failure of eradication (108.2±57.2 vs. 6.8±30.7, p<0.05. Using the above cut-off values, the sensitivity, specificity and validity for determination of H. pylori were 93.1, 93.8 and 93.2%, respectively.In conclusion, the percentage changes in serum PG I/II ratios are useful as evaluation criteria for assessing the success of eradication therapy for H. pylori.

  10. Photodynamic therapy activated signaling from epidermal growth factor receptor and STAT3: Targeting survival pathways to increase PDT efficacy in ovarian and lung cancer

    OpenAIRE

    Edmonds, Christine; Hagan, Sarah; Gallagher-Colombo, Shannon M.; Busch, Theresa M.; Cengel, Keith A.

    2012-01-01

    Patients with serosal (pleural or peritoneal) spread of malignancy have few definitive treatment options and consequently have a very poor prognosis. We have previously shown that photodynamic therapy (PDT) can be an effective treatment for these patients, but that the therapeutic index is relatively narrow. Here, we test the hypothesis that EGFR and STAT3 activation increase survival following PDT, and that inhibiting these pathways leads to increased PDT-mediated direct cellular cytotoxicit...

  11. First feeding of Eugerres brasilianus (Carapeva larvae with Acartia tonsa (Copepod nauplii increases survival and resistance to acute stress

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    Wanessa de Melo Costa

    2016-01-01

    Full Text Available The rotifer Brachionus sp. is commonly used for larval feeding in marine fish hatcheries. The aim of this study was to evaluate whether the inclusion of Acartia tonsa nauplii in the initial diet of carapeva larvae improves their survival, growth and resistance to stress when compared to the regimen containing only rotifers. Adult copepods were collected in the wild and cultured with the microalgae Chaetoceros muelleri, Isochrysis galbana and Nannochloropsis oculata to obtain nauplii. Carapeva larvae were grown for 15 days using four treatments and three replicates: 1 Brachionus plicatilis rotifers (10 to 15/mL; 2 A. tonsa nauplii (0.25 to 0.5/mL; 3 Brachionus plicatilis rotifers (5 to 7.5/mL + A. tonsa nauplii (0.12 to 0.25/mL, and 4 no supply of live feed. After 15 days, the carapeva larvae were subjected to stress by exposure to air for 10 seconds and then returned to the source tank to evaluate survival after 24 h. Survival and stress resistance were higher in carapeva larvae fed B. plicatilis + A. tonsa nauplii (P<0.05, 20.9 ± 11.2% and 88.9%, respectively. These results confirm the positive effect of the inclusion of copepod nauplii in the diet of fish larvae. However, more research is needed to validate these results.

  12. Escin Increases the Survival Rate of LPS-Induced Septic Mice Through Inhibition of HMGB1 Release from Macrophages

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    Yajun Cheng

    2015-07-01

    Full Text Available Background: Previous studies have described the effects of Escin on improving the survival rate of endotoxemic animals. The purpose of this study was to explore the molecular mechanisms of this potentially beneficial treatment. Methods: First, the survival rate of endotoxemic mice was monitored for up to 2 weeks after Escin pretreatment, Escin post-treatment, or Escin post-treatment + rHMGB1. The effects of Escin on the release of pro-inflammatory cytokines such as TNF-a, IL-1ß, IL-6 and HMGB1 in the serum of endotoxemic mice and LPS-induced macrophages were evaluated by ELISA. Furthermore, the mRNA and protein levels of HMGB1 in LPS-induced macrophages were measured by qRT-PCR and Western blot, respectively. Additionally, the release of pro-inflammatory cytokines such as TNF-a, IL-1ß, IL-6 was evaluated by ELISA in rHMGB1-induced macrophages. Finally, the protein levels and the activity of NF-κB in macrophages were checked by Western blot and ELISA, respectively. Results: Both pretreatment and post-treatment with Escin could improve the survival rate of endotoxemic mice, while exogenous rHMGB1 reversed this effect. In addition, Escin decreased the level of the pro-inflammatory cytokines TNF-a, IL-1ß, IL-6 and HMGB1 in endotoxemic mice and in LPS-induced macrophages. Escin could also inhibit the mRNA levels and activity of HMGB1. The release of the pro-inflammatory cytokines TNF-a, IL-1ß, IL-6 could be suppressed in rHMGB1-induced macrophages by Escin. Finally, Escin could suppress the activation of NF-κB in LPS-induced macrophages. Conclusion: Escin could improve the survival of mice with LPS-induced endotoxemia. This effect maybe meditated by reducing the release of HMGB1, resulting in the suppression of the release of pro-inflammatory cytokines.

  13. Glutamate Increases In Vitro Survival and Proliferation and Attenuates Oxidative Stress-Induced Cell Death in Adult Spinal Cord-Derived Neural Stem/Progenitor Cells via Non-NMDA Ionotropic Glutamate Receptors.

    Science.gov (United States)

    Hachem, Laureen D; Mothe, Andrea J; Tator, Charles H

    2016-08-15

    Traumatic spinal cord injury (SCI) leads to a cascade of secondary chemical insults, including oxidative stress and glutamate excitotoxicity, which damage host neurons and glia. Transplantation of exogenous neural stem/progenitor cells (NSPCs) has shown promise in enhancing regeneration after SCI, although survival of transplanted cells remains poor. Understanding the response of NSPCs to the chemical mediators of secondary injury is essential in finding therapies to enhance survival. We examined the in vitro effects of glutamate and glutamate receptor agonists on adult rat spinal cord-derived NSPCs. NSPCs isolated from the periventricular region of the adult rat spinal cord were exposed to various concentrations of glutamate for 96 h. We found that glutamate treatment (500 μM) for 96 h significantly increased live cell numbers, reduced cell death, and increased proliferation, but did not significantly alter cell phenotype. Concurrent glutamate treatment (500 μM) in the setting of H2O2 exposure (500 μM) for 10 h increased NSPC survival compared to H2O2 exposure alone. The effects of glutamate on NSPCs were blocked by the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate receptor antagonist GYKI-52466, but not by the N-methyl-D-aspartic acid receptor antagonist MK-801 or DL-AP5, or the mGluR3 antagonist LY-341495. Furthermore, treatment of NSPCs with AMPA, kainic acid, or the kainate receptor-specific agonist (RS)-2-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl)propanoic acid mimicked the responses seen with glutamate both alone and in the setting of oxidative stress. These findings offer important insights into potential mechanisms to enhance NSPC survival and implicate a potential role for glutamate in promoting NSPC survival and proliferation after traumatic SCI.

  14. Hemangiosarcoma in a Dog: Unusual Presentation and Increased Survival Using a Complementary/Holistic Approach Combined with Metronomic Chemotherapy

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    Philip Chaikin

    2018-01-01

    Full Text Available This case report documents the clinical and pathologic findings in a 12-year-old terrier mix with intraocular and splenic hemangiosarcoma. Pathologic findings in both the spleen and globe were consistent with hemangiosarcoma with a low mitotic count. Initial treatment consisted of enucleation and then splenectomy followed by one cycle of conventional doxorubicin chemotherapy. Due to poor tolerance, a subsequent treatment regimen consisted of metronomic chemotherapy with chlorambucil combined with an alternative/complementary regimen of I’m-Yunity (polysaccharopeptide and Yunnan Baiyao. Follow-up thoracic radiographs and abdominal ultrasounds over a period of 24 months showed no evidence of pulmonary, hepatic, or right atrial metastases, during which time the patient had an excellent quality of life. However, shortly after achieving two-year survival, the patient developed new onset seizures unresponsive to anticonvulsant therapy. Therefore, a decision was made to euthanize the dog given that the most likely etiology of the seizures was a brain tumor. Overall, this is an exceptional treatment response given the poor survival statistics of hemangiosarcoma even with conventional chemotherapy. However, additional clinical pharmacology and clinical trial data are needed to further support the use of a complementary/holistic approach in combination with metronomic chemotherapy.

  15. G-CSF and Exenatide Might Be Associated with Increased Long-Term Survival of Allogeneic Pancreatic Islet Grafts.

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    Alessia Zoso

    Full Text Available Allogeneic human islet transplantation is an effective therapy for the treatment of patients with Type 1 Diabetes (T1D. The low number of islet transplants performed worldwide and the different transplantation protocols used limit the identification of the most effective therapeutic options to improve the efficacy of this approach.We present a retrospective analysis on the data collected from 44 patients with T1D who underwent islet transplantation at our institute between 2000 and 2007. Several variables were included: recipient demographics and immunological characteristics, donor and transplant characteristics, induction protocols, and additional medical treatment received. Immunosuppression was induced with anti-CD25 (Daclizumab, alone or in association with anti-tumor necrosis factor alpha (TNF-α treatments (Etanercept or Infliximab, or with anti-CD52 (Alemtuzumab in association with anti-TNF-α treatments (Etanercept or Infliximab. Subsets of patients were treated with Filgrastim for moderate/severe neutropenia and/or Exenatide for post prandial hyperglycemia.The analysis performed indicates a negative association between graft survival (c-peptide level ≥ 0.3 ng/ml and islet infusion volume, with the caveat that, the progressive reduction of infusion volumes over the years has been paralleled by improved immunosuppressive protocols. A positive association is instead suggested between graft survival and administration of Exenatide and Filgrastim, alone or in combination.This retrospective analysis may be of assistance to further improve long-term outcomes of protocols for transplant of islets and other organs.

  16. G-CSF and Exenatide Might Be Associated with Increased Long-Term Survival of Allogeneic Pancreatic Islet Grafts.

    Science.gov (United States)

    Zoso, Alessia; Serafini, Paolo; Lanzoni, Giacomo; Peixoto, Eduardo; Messinger, Shari; Mantero, Alejandro; Padilla-Téllez, Nathalia D; Baidal, David A; Alejandro, Rodolfo; Ricordi, Camillo; Inverardi, Luca

    2016-01-01

    Allogeneic human islet transplantation is an effective therapy for the treatment of patients with Type 1 Diabetes (T1D). The low number of islet transplants performed worldwide and the different transplantation protocols used limit the identification of the most effective therapeutic options to improve the efficacy of this approach. We present a retrospective analysis on the data collected from 44 patients with T1D who underwent islet transplantation at our institute between 2000 and 2007. Several variables were included: recipient demographics and immunological characteristics, donor and transplant characteristics, induction protocols, and additional medical treatment received. Immunosuppression was induced with anti-CD25 (Daclizumab), alone or in association with anti-tumor necrosis factor alpha (TNF-α) treatments (Etanercept or Infliximab), or with anti-CD52 (Alemtuzumab) in association with anti-TNF-α treatments (Etanercept or Infliximab). Subsets of patients were treated with Filgrastim for moderate/severe neutropenia and/or Exenatide for post prandial hyperglycemia. The analysis performed indicates a negative association between graft survival (c-peptide level ≥ 0.3 ng/ml) and islet infusion volume, with the caveat that, the progressive reduction of infusion volumes over the years has been paralleled by improved immunosuppressive protocols. A positive association is instead suggested between graft survival and administration of Exenatide and Filgrastim, alone or in combination. This retrospective analysis may be of assistance to further improve long-term outcomes of protocols for transplant of islets and other organs.

  17. Increased ID4 expression, accompanied by mutant p53 accumulation and loss of BRCA1/2 proteins in triple-negative breast cancer, adversely affects survival.

    Science.gov (United States)

    Thike, Aye A; Tan, Puay H; Ikeda, Murasaki; Iqbal, Jabed

    2016-04-01

    Breast cancer 1 (BRCA1) expression is down-regulated in a significant proportion of non-hereditary breast cancers, in the absence of any mutation. This phenomenon is more pronounced in oestrogen (ER)-negative tumours. Recent studies have suggested that inhibitor of DNA binding 4 (ID4), as well as p53, participate in the transcriptional regulation of BRCA1. Immunohistochemical expression of ID4, BRCA1, BRCA2 and p53 in 699 women with triple-negative breast cancer was investigated using tissue microarrays. The prognostic role of these biomarkers was also evaluated. Survival outcomes were estimated with the Kaplan-Meier method and compared between groups with log-rank statistics. Loss of BRCA1 and BRCA2 expression and overexpression of ID4 and p53 was observed in 75%, 90%, 95% and 66% of tumours, respectively. ID4 expression was increased in higher tumour grade (P P P = 0.037) and p53 accumulation (P triple-negative breast cancers (P = 0.041) and basal-like triple-negative breast cancers (P = 0.026). There is frequent ID4 expression and concomitant loss of BRCA proteins in triple-negative breast cancer. We hypothesize that strong ID4 expression could be useful as a prognostic marker in triple-negative breast cancer, predicting early tumour recurrence. © 2015 John Wiley & Sons Ltd.

  18. Photothermal Therapy Using Gold Nanorods and Near-Infrared Light in a Murine Melanoma Model Increases Survival and Decreases Tumor Volume

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    Mary K. Popp

    2014-01-01

    Full Text Available Photothermal therapy (PTT treatments have shown strong potential in treating tumors through their ability to target destructive heat preferentially to tumor regions. In this paper we demonstrate that PTT in a murine melanoma model using gold nanorods (GNRs and near-infrared (NIR light decreases tumor volume and increases animal survival to an extent that is comparable to the current generation of melanoma drugs. GNRs, in particular, have shown a strong ability to reach ablative temperatures quickly in tumors when exposed to NIR light. The current research tests the efficacy of GNRs PTT in a difficult and fast growing murine melanoma model using a NIR light-emitting diode (LED light source. LED light sources in the NIR spectrum could provide a safer and more practical approach to photothermal therapy than lasers. We also show that the LED light source can effectively and quickly heat in vitro and in vivo models to ablative temperatures when combined with GNRs. We anticipate that this approach could have significant implications for human cancer therapy.

  19. Elevated plasma YKL-40 predicts increased risk of gastrointestinal cancer and decreased survival after any cancer diagnosis in the general population

    DEFF Research Database (Denmark)

    Johansen, J.S.; Bojesen, S.E.; Mylin, A.K.

    2009-01-01

    to plasma YKL-40 in sex and 10 years age percentile categories: 0% to 33%, 34% to 66%, 67% to 90%, 91% to 95%, and 96% to 100%. RESULTS: The cumulative incidence of gastrointestinal cancer increased with increasing YKL-40 (trend P gastrointestinal cancer were 1...... a median survival time after the diagnosis of 1 year versus 4 years in participants with YKL-40 category 0% to 33% (P gastrointestinal cancer were 6 months versus 1 year (P = .007). Multifactorially adjusted HRs for early death were 1.8 (95% CI, 1.3 to 2.5; P ...) after any cancer and 2.4 (95% CI, 1.3 to 4.3; P = .005) after gastrointestinal cancer in participants with YKL-40 category 91% to 100% versus 0% to 33%. CONCLUSION: In the general population, elevated plasma YKL-40 predicts increased risk of gastrointestinal cancer and decreased survival after any...

  20. Hydroxyurea-Increased Fetal Hemoglobin Is Associated with Less Organ Damage and Longer Survival in Adults with Sickle Cell Anemia.

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    Courtney D Fitzhugh

    Full Text Available Adults with sickle cell anemia (HbSS are inconsistently treated with hydroxyurea.We retrospectively evaluated the effects of elevating fetal hemoglobin with hydroxyurea on organ damage and survival in patients enrolled in our screening study between 2001 and 2010.An electronic medical record facilitated development of a database for comparison of study parameters based on hydroxyurea exposure and dose. This study is registered with ClinicalTrials.gov, number NCT00011648.Three hundred eighty-three adults with homozygous sickle cell disease were analyzed with 59 deaths during study follow-up. Cox regression analysis revealed deceased subjects had more hepatic dysfunction (elevated alkaline phosphatase, Hazard Ratio = 1.005, 95% CI 1.003-1.006, p<0.0.0001, kidney dysfunction (elevated creatinine, Hazard Ratio = 1.13, 95% CI 1.00-1.27, p = 0.043, and cardiopulmonary dysfunction (elevated tricuspid jet velocity on echocardiogram, Hazard Ratio = 2.22, 1.23-4.02, p = 0.0082. Sixty-six percent of subjects were treated with hydroxyurea, although only 66% of those received a dose within the recommended therapeutic range. Hydroxyurea use was associated with improved survival (Hazard Ratio = 0.58, 95% CI 0.34-0.97, p = 0.040. This effect was most pronounced in those taking the recommended dose of 15-35 mg/kg/day (Hazard Ratio 0.36, 95% CI 0.17-0.73, p = 0.0050. Hydroxyurea use was not associated with changes in organ function over time. Further, subjects with higher fetal hemoglobin responses to hydroxyurea were more likely to survive (p = 0.0004. While alkaline phosphatase was lowest in patients with the best fetal hemoglobin response (95.4 versus 123.6, p = 0.0065 and 96.1 versus 113.6U/L, p = 0.041 at first and last visits, respectively, other markers of organ damage were not consistently improved over time in patients with the highest fetal hemoglobin levels.Our data suggest that adults should be treated with the maximum tolerated hydroxyurea dose

  1. Photothermal Therapy Using Gold Nanorods and Near-Infrared Light in a Murine Melanoma Model Increases Survival and Decreases Tumor Volume

    OpenAIRE

    Popp, Mary K.; Imane Oubou; Colin Shepherd; Zachary Nager; Courtney Anderson; Len Pagliaro

    2014-01-01

    Photothermal therapy (PTT) treatments have shown strong potential in treating tumors through their ability to target destructive heat preferentially to tumor regions. In this paper we demonstrate that PTT in a murine melanoma model using gold nanorods (GNRs) and near-infrared (NIR) light decreases tumor volume and increases animal survival to an extent that is comparable to the current generation of melanoma drugs. GNRs, in particular, have shown a strong ability to reach ablative temperatur...

  2. Endovascular Thrombectomy for Ischemic Stroke Increases Disability-Free Survival, Quality of Life, and Life Expectancy and Reduces Cost

    Directory of Open Access Journals (Sweden)

    Bruce C. V. Campbell

    2017-12-01

    Full Text Available BackgroundEndovascular thrombectomy improves functional outcome in large vessel occlusion ischemic stroke. We examined disability, quality of life, survival and acute care costs in the EXTEND-IA trial, which used CT-perfusion imaging selection.MethodsLarge vessel ischemic stroke patients with favorable CT-perfusion were randomized to endovascular thrombectomy after alteplase versus alteplase-only. Clinical outcome was prospectively measured using 90-day modified Rankin scale (mRS. Individual patient expected survival and net difference in Disability/Quality-adjusted life years (DALY/QALY up to 15 years from stroke were modeled using age, sex, 90-day mRS, and utility scores. Level of care within the first 90 days was prospectively measured and used to estimate procedure and inpatient care costs (US$ reference year 2014.ResultsThere were 70 patients, 35 in each arm, mean age 69, median NIHSS 15 (IQR 12–19. The median (IQR disability-weighted utility score at 90 days was 0.65 (0.00–0.91 in the alteplase-only versus 0.91 (0.65–1.00 in the endovascular group (p = 0.005. Modeled life expectancy was greater in the endovascular versus alteplase-only group (median 15.6 versus 11.2 years, p = 0.02. The endovascular thrombectomy group had fewer simulated DALYs lost over 15 years [median (IQR 5.5 (3.2–8.7 versus 8.9 (4.7–13.8, p = 0.02] and more QALY gained [median (IQR 9.3 (4.2–13.1 versus 4.9 (0.3–8.5, p = 0.03]. Endovascular patients spent less time in hospital [median (IQR 5 (3–11 days versus 8 (5–14 days, p = 0.04] and rehabilitation [median (IQR 0 (0–28 versus 27 (0–65 days, p = 0.03]. The estimated inpatient costs in the first 90 days were less in the thrombectomy group (average US$15,689 versus US$30,569, p = 0.008 offsetting the costs of interhospital transport and the thrombectomy procedure (average US$10,515. The average saving per patient treated with thrombectomy was US$4

  3. Changes in rocket salad phytochemicals within the commercial supply chain: Glucosinolates, isothiocyanates, amino acids and bacterial load increase significantly after processing.

    Science.gov (United States)

    Bell, Luke; Yahya, Hanis Nadia; Oloyede, Omobolanle Oluwadamilola; Methven, Lisa; Wagstaff, Carol

    2017-04-15

    Five cultivars of Eruca sativa and a commercial variety of Diplotaxis tenuifolia were grown in the UK (summer) and subjected to commercial growth, harvesting and processing, with subsequent shelf life storage. Glucosinolates (GSL), isothiocyanates (ITC), amino acids (AA), free sugars, and bacterial loads were analysed throughout the supply chain to determine the effects on phytochemical compositions. Bacterial load of leaves increased significantly over time and peaked during shelf life storage. Significant correlations were observed with GSL and AA concentrations, suggesting a previously unknown relationship between plants and endemic leaf bacteria. GSLs, ITCs and AAs increased significantly after processing and during shelf life. The supply chain did not significantly affect glucoraphanin concentrations, and its ITC sulforaphane significantly increased during shelf life in E. sativa cultivars. We hypothesise that commercial processing may increase the nutritional value of the crop, and have added health benefits for the consumer. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  4. Bee bread increases honeybee haemolymph protein and promote better survival despite of causing higher Nosema ceranae abundance in honeybees.

    Science.gov (United States)

    Basualdo, Marina; Barragán, Sergio; Antúnez, Karina

    2014-08-01

    Adequate protein nutrition supports healthy honeybees and reduces the susceptibility to disease. However little is known concerning the effect of the diet on Nosema ceranae development, an obligate intracellular parasite that disturbs the protein metabolism of honeybees (Apis mellifera). Here we tested the effect of natural (bee bread) and non-natural protein diets (substitute) on haemolymph proteins titers of honeybee and N. ceranae spore production. The natural diet induced higher levels of protein and parasite development, but the survival of bees was also higher than with non-natural diets. The data showed that the administration of an artificially high nutritious diet in terms of crude protein content is not sufficient to promote healthy bees; rather the protein ingested should be efficiently assimilated. The overall results support the idea that the physiological condition of the bees is linked to protein levels in the haemolymph, which affects the tolerance to parasite; consequently the negative impact of the parasite on host fitness is not associated only with the level of infection. © 2014 Society for Applied Microbiology and John Wiley & Sons Ltd.

  5. Blood lactate levels differ significantly between surviving and nonsurviving patients within the same risk-adjusted Classification for Congenital Heart Surgery (RACHS-1) group after pediatric cardiac surgery.

    Science.gov (United States)

    Molina Hazan, Vered; Gonen, Yael; Vardi, Amir; Keidan, Ilan; Mishali, David; Rubinshtein, Marina; Yakov, Yusim; Paret, Gideon

    2010-10-01

    This study aimed to examine the association between lactate levels in the first hours after surgery for congenital heart defects and the results of Risk-Adjusted Classification for Congenital Heart Surgery (RACHS-1) scoring and to evaluate serial lactate levels over time to determine whether they can serve as a supplementary tool for postoperative assessment within the same RACHS-1 group of patients. A retrospective cohort study was performed using data retrieved from a clinical database of 255 children who had surgery for congenital heart defects between 1999 and 2001 at Sheba Medical Center. Lactate levels were measured postoperatively four times (mg/dL units). The last sample was taken at the end of the surgical procedure, and lactate levels were measured at admission to the pediatrics critical care unit, then 6 and 12 h after admission. The lactate level was measured via arterial blood gases. A total of 27 deaths occurred, yielding a mortality rate of 7.4% when Norwood operations were excluded and 10.16% when they were included. The mean initial postoperative lactate level was significantly lower for survivors (42.2 ± 32.0 mg/dL) than for nonsurvivors (85.4 ± 54.1 mg/dL) (p 0.96 for all). The Pearson correlations between postoperative lactate levels (last lactate measurement taken in the operating room) and cardiopulmonary bypass (CPB) duration (r = 0.549), clamp duration (r = 0.586), and the inotropic score (r = 0.466) (p maximum lactate levels (during the first 12 postoperative hours) and CPB duration (r = 0.496), clamp duration (r = 0.509), and the inotropic score (r = 0.633) (p < 0.001 for all) were extremely positive. The early elevation of lactate levels in RACHS-1 subgroups 1 to 3 were highly correlated with poor prognosis and death (p < 0.03). In addition, the lactate levels differed significantly between survivors and nonsurvivors within the same RACHS-1 subgroup. The survivors in RACHS-1 subgroups 1 to 3 had lower mean lactate levels than the

  6. Trade-off between increased survival and reduced growth for blue mussels living on Pacific oyster reefs

    DEFF Research Database (Denmark)

    Eschweiler, Nina; Christensen, Helle Torp

    2011-01-01

    22days. Shell growth was significantly reduced for mussels placed on the bottom compared to mussels at the top of an oyster reef. Condition index was lower for mussels on the bottom of the reef irrespective of whether placed between dead or living oysters. We conclude that mussels experience a trade...

  7. Saving The Savable: Using Bystanders To Increase Survival From Out Of Hospital Cardiac Arrest (Ohca) In New York City

    Science.gov (United States)

    2016-03-01

    results also confirm that workplace training and CPR in school are effective for training large segments of the community. However, the survey also...increasingly a part of everyday life for millions of Americans. Further, it can be expected that future generations will follow the lead of millennials

  8. Serum Antioxidant Parameters are Significantly Increased in Patients with Type 2 Diabetes Mellitus after Consumption of Chinese Propolis: A Randomized Controlled Trial Based on Fasting Serum Glucose Level.

    Science.gov (United States)

    Gao, Weina; Pu, Lingling; Wei, Jingyu; Yao, Zhanxin; Wang, Yawen; Shi, Tala; Zhao, Liting; Jiao, Changya; Guo, Changjiang

    2018-02-01

    Propolis is a natural product with many biological activities. The present study was designed to evaluate the effects of Chinese propolis on glucose metabolism, antioxidant function, and inflammatory cytokines in patients with type 2 diabetes mellitus (T2DM). In the 18-week study, recruited T2DM patients were randomly divided into a Chinese propolis group (900 mg/day) (n = 31) and a control group (n = 30) according to fasting serum glucose levels at baseline. At the end of the study, no significant difference was found between the groups in serum glucose, glycosylated hemoglobin, insulin, aldose reductase, or adiponectin. However, serum GSH, flavonoids, and polyphenols were significantly increased, and serum lactate dehydrogenase activity was significantly reduced in the Chinese propolis group. Meanwhile, serum IL-6 was significantly increased in the Chinese propolis group. Chinese propolis is effective at improving antioxidant function in T2DM patients, partly by increasing serum antioxidant parameters.

  9. Increased tolerance and resistance to virus infections: a possible factor in the survival of Varroa destructor-resistant honey bees (Apis mellifera).

    Science.gov (United States)

    Locke, Barbara; Forsgren, Eva; de Miranda, Joachim R

    2014-01-01

    The honey bee ectoparasitic mite, Varroa destructor, has a world-wide distribution and inflicts more damage than all other known apicultural diseases. However, Varroa-induced colony mortality is more accurately a result of secondary virus infections vectored by the mite. This means that honey bee resistance to Varroa may include resistance or tolerance to virus infections. The aim of this study was to see if this is the case for a unique population of mite-resistant (MR) European honey bees on the island of Gotland, Sweden. This population has survived uncontrolled mite infestation for over a decade, developing specific mite-related resistance traits to do so. Using RT-qPCR techniques, we monitored late season virus infections, Varroa mite infestation and honey bee colony population dynamics in the Gotland MR population and compared this to mite-susceptible (MS) colonies in a close by apiary. From summer to autumn the deformed wing virus (DWV) titres increased similarly between the MR and MS populations, while the black queen cell virus (BQCV) and sacbrood virus (SBV) titres decreased substantially in the MR population compared to the MS population by several orders of magnitude. The MR colonies all survived the following winter with high mite infestation, high DWV infection, small colony size and low proportions of autumn brood, while the MS colonies all perished. Possible explanations for these changes in virus titres and their relevance to Varroa resistance and colony winter survival are discussed.

  10. Increased tolerance and resistance to virus infections: a possible factor in the survival of Varroa destructor-resistant honey bees (Apis mellifera.

    Directory of Open Access Journals (Sweden)

    Barbara Locke

    Full Text Available The honey bee ectoparasitic mite, Varroa destructor, has a world-wide distribution and inflicts more damage than all other known apicultural diseases. However, Varroa-induced colony mortality is more accurately a result of secondary virus infections vectored by the mite. This means that honey bee resistance to Varroa may include resistance or tolerance to virus infections. The aim of this study was to see if this is the case for a unique population of mite-resistant (MR European honey bees on the island of Gotland, Sweden. This population has survived uncontrolled mite infestation for over a decade, developing specific mite-related resistance traits to do so. Using RT-qPCR techniques, we monitored late season virus infections, Varroa mite infestation and honey bee colony population dynamics in the Gotland MR population and compared this to mite-susceptible (MS colonies in a close by apiary. From summer to autumn the deformed wing virus (DWV titres increased similarly between the MR and MS populations, while the black queen cell virus (BQCV and sacbrood virus (SBV titres decreased substantially in the MR population compared to the MS population by several orders of magnitude. The MR colonies all survived the following winter with high mite infestation, high DWV infection, small colony size and low proportions of autumn brood, while the MS colonies all perished. Possible explanations for these changes in virus titres and their relevance to Varroa resistance and colony winter survival are discussed.

  11. Increased neutrophil-to-lymphocyte ratio after neoadjuvant therapy is associated with worse survival after resection of borderline resectable pancreatic ductal adenocarcinoma.

    Science.gov (United States)

    Glazer, Evan S; Rashid, Omar M; Pimiento, Jose M; Hodul, Pamela J; Malafa, Mokenge P

    2016-11-01

    The neutrophil-to-lymphocyte ratio (neutrophil count divided by lymphocyte count) is a marker of inflammation associated with poor cancer outcomes. The role of neutrophil-to-lymphocyte ratio in borderline resectable pancreatic ductal adenocarcinoma is unknown. We hypothesized that increased neutrophil-to-lymphocyte ratio in patients with borderline resectable pancreatic ductal adenocarcinoma after neoadjuvant therapy is inversely associated with survival. We used our borderline resectable pancreatic ductal adenocarcinoma database to identify patients who had completed neoadjuvant therapy and underwent resection. The neutrophil-to-lymphocyte ratio difference was calculated as the neutrophil-to-lymphocyte ratio after neoadjuvant therapy minus the neutrophil-to-lymphocyte ratio before neoadjuvant therapy. Patients were assigned to the increased neutrophil-to-lymphocyte ratio cohort if the difference was ≥2.5 units; all others were assigned to the stable neutrophil-to-lymphocyte ratio cohort. Statistical analyses were performed with t test and regression. Of 62 patients identified, 43 were assigned to the stable neutrophil-to-lymphocyte ratio cohort, and 19 to the increased neutrophil-to-lymphocyte ratio cohort. There were no differences in stage, age, or sex. The preneoadjuvant neutrophil-to-lymphocyte ratio was 3.1 ± 2.4, whereas the postneoadjuvant neutrophil-to-lymphocyte ratio was 4.4 ± 3.5 (P = .002). Overall survival was worse in the increased neutrophil-to-lymphocyte ratio cohort compared with the stable neutrophil-to-lymphocyte ratio cohort (P = .009) with a Cox hazard ratio of 2.9 (P = .02). N0 disease conferred a survival advantage over N1 disease (Cox hazard ratio = 0.3, P = .01). On multivariate Cox hazard regression analysis, both increased neutrophil-to-lymphocyte ratio and N1 stage were associated with worse survival (P ratio in patients with borderline resectable pancreatic ductal adenocarcinoma. These findings support exploring

  12. CD14+ cells from peripheral blood positively regulate hematopoietic stem and progenitor cell survival resulting in increased erythroid yield

    OpenAIRE

    Heideveld, Esther; Masiello, Francesca; Marra, Manuela; Esteghamat, Fatemehsadat; Yağcı, Nurcan; von Lindern, Marieke; Migliaccio, Anna Rita F.; van den Akker, Emile

    2015-01-01

    Expansion of erythroblasts from human peripheral blood mononuclear cells is 4- to 15-fold more efficient than that of CD34+ cells purified from peripheral blood mononuclear cells. In addition, purified CD34+ and CD34− populations from blood do not reconstitute this erythroid yield, suggesting a role for feeder cells present in blood mononuclear cells that increase hematopoietic output. Immunodepleting peripheral blood mononuclear cells for CD14+ cells reduced hematopoietic stem and progenitor...

  13. Up-regulation of cell cycle arrest protein BTG2 correlates with increased overall survival in breast cancer, as detected by immunohistochemistry using tissue microarray

    Directory of Open Access Journals (Sweden)

    Jirström Karin

    2010-06-01

    Full Text Available Abstract Background Previous studies have shown that the ADIPOR1, ADORA1, BTG2 and CD46 genes differ significantly between long-term survivors of breast cancer and deceased patients, both in levels of gene expression and DNA copy numbers. The aim of this study was to characterize the expression of the corresponding proteins in breast carcinoma and to determine their correlation with clinical outcome. Methods Protein expression was evaluated using immunohistochemistry in an independent breast cancer cohort of 144 samples represented on tissue microarrays. Fisher's exact test was used to analyze the differences in protein expression between dead and alive patients. We used Cox-regression multivariate analysis to assess whether the new markers predict the survival status of the patients better than the currently used markers. Results BTG2 expression was demonstrated in a significantly lower proportion of samples from dead patients compared to alive patients, both in overall expression (P = 0.026 and cell membrane specific expression (P = 0.013, whereas neither ADIPOR1, ADORA1 nor CD46 showed differential expression in the two survival groups. Furthermore, a multivariate analysis showed that a model containing BTG2 expression in combination with HER2 and Ki67 expression along with patient age performed better than a model containing the currently used prognostic markers (tumour size, nodal status, HER2 expression, hormone receptor status, histological grade, and patient age. Interestingly, BTG2 has previously been described as a tumour suppressor gene involved in cell cycle arrest and p53 signalling. Conclusions We conclude that high-level BTG2 protein expression correlates with prolonged survival in patients with breast carcinoma.

  14. Physician presence in an ambulance car is associated with increased survival in out-of-hospital cardiac arrest: a prospective cohort analysis.

    Directory of Open Access Journals (Sweden)

    Akihito Hagihara

    increased short- and long-term survival.

  15. Surviving workplace adversity: a qualitative study of nurses and midwives and their strategies to increase personal resilience.

    Science.gov (United States)

    Mcdonald, Glenda; Jackson, Debra; Vickers, Margaret H; Wilkes, Lesley

    2016-01-01

    To explore the experiences of Australian nurses and midwives who perceived themselves as resilient. The focus of this paper is to report the strategies used by a group of nurses and midwives to develop and maintain their resilience, despite encountering serious workplace adversity. Despite the potentially adverse effects of nursing work, many nurses and midwives thrive through exercising self-efficacy and coping skills. The relationship between thriving and resilience is clear, as resilience refers to the ability to cope well with adversity and change. The participants were part of an instrumental, collective case study investigation of personal resilience amongst nurses and midwives. Prior to an innovative, work-based intervention including workshops and mentoring, participants were interviewed to collect baseline perceptions and experiences of personal resilience and workplace adversity. Interview transcripts were analysed thematically. Participants attributed their ability to thrive in the workplace to three major influences: support networks, personal characteristics and ability to organise work for personal resilience. Participant insights contributed to a deeper understanding of personal resilience and highlight future initiatives to enhance the ability of nurses and midwives to thrive within health organisations and systems. It is vital that resilience-enhancing initiatives, such as peer mentoring and tailored work options to increase autonomy, are implemented at earlier career phases. © 2015 John Wiley & Sons Ltd.

  16. Cardiac-specific expression of the tetracycline transactivator confers increased heart function and survival following ischemia reperfusion injury.

    Directory of Open Access Journals (Sweden)

    Laila Elsherif

    Full Text Available Mice expressing the tetracycline transactivator (tTA transcription factor driven by the rat α-myosin heavy chain promoter (α-MHC-tTA are widely used to dissect the molecular mechanisms involved in cardiac development and disease. However, these α-MHC-tTA mice exhibit a gain-of-function phenotype consisting of robust protection against ischemia/reperfusion injury in both in vitro and in vivo models in the absence of associated cardiac hypertrophy or remodeling. Cardiac function, as assessed by echocardiography, did not differ between α-MHC-tTA and control animals, and there were no noticeable differences observed between the two groups in HW/TL ratio or LV end-diastolic and end-systolic dimensions. Protection against ischemia/reperfusion injury was assessed using isolated perfused hearts where α-MHC-tTA mice had robust protection against ischemia/reperfusion injury which was not blocked by pharmacological inhibition of PI3Ks with LY294002. Furthermore, α-MHC-tTA mice subjected to coronary artery ligation exhibited significantly reduced infarct size compared to control animals. Our findings reveal that α-MHC-tTA transgenic mice exhibit a gain-of-function phenotype consisting of robust protection against ischemia/reperfusion injury similar to cardiac pre- and post-conditioning effects. However, in contrast to classical pre- and post-conditioning, the α-MHC-tTA phenotype is not inhibited by the classic preconditioning inhibitor LY294002 suggesting involvement of a non-PI3K-AKT signaling pathway in this phenotype. Thus, further study of the α-MHC-tTA model may reveal novel molecular targets for therapeutic intervention during ischemic injury.

  17. Hypoxic Preconditioning Increases Survival and Pro-Angiogenic Capacity of Human Cord Blood Mesenchymal Stromal Cells In Vitro.

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    Andreas Matthäus Bader

    preconditioning might be a translationally relevant strategy to increase the tolerance of cord blood MSCs to ischemia and improve their therapeutic efficacy in clinical applications.

  18. In situ normoxia enhances survival and proliferation rate of human adipose tissue-derived stromal cells without increasing the risk of tumourigenesis.

    Directory of Open Access Journals (Sweden)

    Jane Ru Choi

    Full Text Available Adipose tissue-derived stromal cells (ASCs natively reside in a relatively low-oxygen tension (i.e., hypoxic microenvironment in human body. Low oxygen tension (i.e., in situ normoxia, has been known to enhance the growth and survival rate of ASCs, which, however, may lead to the risk of tumourigenesis. Here, we investigated the tumourigenic potential of ASCs under their physiological condition to ensure their safe use in regenerative therapy. Human ASCs isolated from subcutaneous fat were cultured in atmospheric O2 concentration (21% O2 or in situ normoxia (2% O2. We found that ASCs retained their surface markers, tri-lineage differentiation potential, and self-renewal properties under in situ normoxia without altering their morphology. In situ normoxia displayed a higher proliferation and viability of ASCs with less DNA damage as compared to atmospheric O2 concentration. Moreover, low oxygen tension significantly up-regulated VEGF and bFGF mRNA expression and protein secretion while reducing the expression level of tumour suppressor genes p16, p21, p53, and pRb. However, there were no significant differences in ASCs telomere length and their relative telomerase activity when cultured at different oxygen concentrations. Collectively, even with high proliferation and survival rate, ASCs have a low tendency of developing tumour under in situ normoxia. These results suggest 2% O2 as an ideal culture condition for expanding ASCs efficiently while maintaining their characteristics.

  19. The Silencing of a 14-3-3ɛ Homolog in Tenebrio molitor Leads to Increased Antimicrobial Activity in Hemocyte and Reduces Larval Survivability.

    Science.gov (United States)

    Seo, Gi Won; Jo, Yong Hun; Seong, Jeong Hwan; Park, Ki Beom; Patnaik, Bharat Bhusan; Tindwa, Hamisi; Kim, Sun-Am; Lee, Yong Seok; Kim, Yu Jung; Han, Yeon Soo

    2016-08-20

    The 14-3-3 family of phosphorylated serine-binding proteins acts as signaling molecules in biological processes such as metabolism, division, differentiation, autophagy, and apoptosis. Herein, we report the requirement of 14-3-3ɛ isoform from Tenebrio molitor (Tm14-3-3ɛ) in the hemocyte antimicrobial activity. The Tm14-3-3ɛ transcript is 771 nucleotides in length and encodes a polypeptide of 256 amino acid residues. The protein has the typical 14-3-3 domain, the nuclear export signal (NES) sequence, and the peptide binding residues. The Tm14-3-3ɛ transcript shows a significant three-fold expression in the hemocyte of T. molitor larvae when infected with Escherichia coli Tm14-3-3ɛ silenced larvae show significantly lower survival rates when infected with E. coli. Under Tm14-3-3ɛ silenced condition, a strong antimicrobial activity is elicited in the hemocyte of the host inoculated with E. coli. This suggests impaired secretion of antimicrobial peptides (AMP) into the hemolymph. Furthermore, a reduction in AMP secretion under Tm14-3-3ɛ silenced condition would be responsible for loss in the capacity to kill bacteria and might explain the reduced survivability of the larvae upon E. coli challenge. This shows that Tm14-3-3ɛ is required to maintain innate immunity in T. molitor by enabling antimicrobial secretion into the hemolymph and explains the functional specialization of the isoform.

  20. The Silencing of a 14-3-3ɛ Homolog in Tenebrio molitor Leads to Increased Antimicrobial Activity in Hemocyte and Reduces Larval Survivability

    Directory of Open Access Journals (Sweden)

    Gi Won Seo

    2016-08-01

    Full Text Available The 14-3-3 family of phosphorylated serine-binding proteins acts as signaling molecules in biological processes such as metabolism, division, differentiation, autophagy, and apoptosis. Herein, we report the requirement of 14-3-3ɛ isoform from Tenebrio molitor (Tm14-3-3ɛ in the hemocyte antimicrobial activity. The Tm14-3-3ɛ transcript is 771 nucleotides in length and encodes a polypeptide of 256 amino acid residues. The protein has the typical 14-3-3 domain, the nuclear export signal (NES sequence, and the peptide binding residues. The Tm14-3-3ɛ transcript shows a significant three-fold expression in the hemocyte of T. molitor larvae when infected with Escherichia coli Tm14-3-3ɛ silenced larvae show significantly lower survival rates when infected with E. coli. Under Tm14-3-3ɛ silenced condition, a strong antimicrobial activity is elicited in the hemocyte of the host inoculated with E. coli. This suggests impaired secretion of antimicrobial peptides (AMP into the hemolymph. Furthermore, a reduction in AMP secretion under Tm14-3-3ɛ silenced condition would be responsible for loss in the capacity to kill bacteria and might explain the reduced survivability of the larvae upon E. coli challenge. This shows that Tm14-3-3ɛ is required to maintain innate immunity in T. molitor by enabling antimicrobial secretion into the hemolymph and explains the functional specialization of the isoform.

  1. Thermal tolerances of reef corals in the Gulf: a review of the potential for increasing coral survival and adaptation to climate change through assisted translocation.

    Science.gov (United States)

    Coles, Steve L; Riegl, Bernhard M

    2013-07-30

    Corals in the Gulf withstand summer temperatures up to 10 °C higher than corals elsewhere and have recovered from extreme temperature events in 10 years or less. This heat-tolerance of Gulf corals has positive implications for the world's coral populations to adapt to increasing water temperatures. However, survival of Gulf corals has been severely tested by 35-37 °C temperatures five times in the last 15 years, each time causing extensive coral bleaching and mortality. Anticipated future temperature increases may therefore challenge survival of already highly stressed Gulf corals. Previously proposed translocation of Gulf corals to introduce temperature-adapted corals outside of the Gulf is assessed and determined to be problematical, and to be considered a tool of last resort. Coral culture and transplantation within the Gulf is feasible for helping maintain coral species populations and preserving genomes and adaptive capacities of Gulf corals that are endangered by future thermal stress events. Copyright © 2012 Elsevier Ltd. All rights reserved.

  2. Human circulating plasma DNA significantly decreases while lymphocyte DNA damage increases under chronic occupational exposure to low-dose gamma-neutron and tritium β-radiation

    Energy Technology Data Exchange (ETDEWEB)

    Korzeneva, Inna B., E-mail: inna.korzeneva@molgen.vniief.ru [Russian Federal Nuclear Center – All-Russian Research Institute of Experimental Physics (RFNC-VNIIEF) 607190, Sarov, 37 Mira ave., Nizhniy Novgorod Region (Russian Federation); Kostuyk, Svetlana V.; Ershova, Liza S. [Research Centre for Medical Genetics, Russian Academy of Medical Sciences, 115478 Moscow, 1 Moskvorechye str. (Russian Federation); Osipov, Andrian N. [Federal Medial and Biological Center named after Burnazyan of the Federal Medical and Biological Agency (FMBTz named after Burnazyan of FMBA), Moscow (Russian Federation); State Research Center - Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency, Zhivopisnaya, 46, Moscow, 123098 (Russian Federation); Zhuravleva, Veronika F.; Pankratova, Galina V. [Russian Federal Nuclear Center – All-Russian Research Institute of Experimental Physics (RFNC-VNIIEF) 607190, Sarov, 37 Mira ave., Nizhniy Novgorod Region (Russian Federation); Porokhovnik, Lev N.; Veiko, Natalia N. [Research Centre for Medical Genetics, Russian Academy of Medical Sciences, 115478 Moscow, 1 Moskvorechye str. (Russian Federation)

    2015-09-15

    Highlights: • The chronic exposure to low-dose IR induces DSBs in human lymphocytes (TM index). • Exposure to IR decreases the level of human circulating DNA (cfDNA index). • IR induces an increase of DNase1 activity (DNase1 index) in plasma. • IR induces an increase of the level of antibodies to DNA (Ab DNA index) in plasma. • The ratio cfDNA/(DNase 1 × Ab DNA × TM) is a potential marker of human exposure to IR. - Abstract: The blood plasma of healthy people contains cell-fee (circulating) DNA (cfDNA). Apoptotic cells are the main source of the cfDNA. The cfDNA concentration increases in case of the organism’s cell death rate increase, for example in case of exposure to high-dose ionizing radiation (IR). The objects of the present research are the blood plasma and blood lymphocytes of people, who contacted occupationally with the sources of external gamma/neutron radiation or internal β-radiation of tritium N = 176). As the controls (references), blood samples of people, who had never been occupationally subjected to the IR sources, were used (N = 109). With respect to the plasma samples of each donor there were defined: the cfDNA concentration (the cfDNA index), DNase1 activity (the DNase1 index) and titre of antibodies to DNA (the Ab DNA index). The general DNA damage in the cells was defined (using the Comet assay, the tail moment (TM) index). A chronic effect of the low-dose ionizing radiation on a human being is accompanied by the enhancement of the DNA damage in lymphocytes along with a considerable cfDNA content reduction, while the DNase1 content and concentration of antibodies to DNA (Ab DNA) increase. All the aforementioned changes were also observed in people, who had not worked with the IR sources for more than a year. The ratio cfDNA/(DNase1 × Ab DNA × TM) is proposed to be used as a marker of the chronic exposure of a person to the external low-dose IR. It was formulated the assumption that the joint analysis of the cfDNA, DNase1, Ab

  3. Photodynamic therapy activated signaling from epidermal growth factor receptor and STAT3: Targeting survival pathways to increase PDT efficacy in ovarian and lung cancer.

    Science.gov (United States)

    Edmonds, Christine; Hagan, Sarah; Gallagher-Colombo, Shannon M; Busch, Theresa M; Cengel, Keith A

    2012-12-01

    Patients with serosal (pleural or peritoneal) spread of malignancy have few definitive treatment options and consequently have a very poor prognosis. We have previously shown that photodynamic therapy (PDT) can be an effective treatment for these patients, but that the therapeutic index is relatively narrow. Here, we test the hypothesis that EGFR and STAT3 activation increase survival following PDT, and that inhibiting these pathways leads to increased PDT-mediated direct cellular cytotoxicity by examining BPD-PDT in OvCa and NSCLC cells. We found that BPD-mediated PDT stimulated EGFR tyrosine phosphorylation and nuclear translocation, and that EGFR inhibition by erlotinib resulted in reduction of PDT-mediated EGFR activation and nuclear translocation. Nuclear translocation and PDT-mediated activation of EGFR were also observed in response to BPD-mediated PDT in multiple cell lines, including OvCa, NSCLC and head and neck cancer cells, and was observed to occur in response to porfimer sodium-mediated PDT. In addition, we found that PDT stimulates nuclear translocation of STAT3 and STAT3/EGFR association and that inhibiting STAT3 signaling prior to PDT leads to increased PDT cytotoxicity. Finally, we found that inhibition of EGFR signaling leads to increased PDT cytotoxicity through a mechanism that involves increased apoptotic cell death. Taken together, these results demonstrate that PDT stimulates the nuclear accumulation of both EGFR and STAT3 and that targeting these survival pathways is a potentially promising strategy that could be adapted for clinical trials of PDT for patients with serosal spread of malignancy.

  4. A pre-partum lift in ewe nutrition from a high-energy lick or maize or by grazing Lotus uliginosus pasture, increases colostrum production and lamb survival.

    Science.gov (United States)

    Banchero, G E; Quintans, G; Lindsay, D R; Milton, J T B

    2009-08-01

    This experiment tested the hypothesis that a lift in the nutrition of ewes, before lambing, to increase colostrum production would enhance lamb survival. In all, 261 mature Corriedale ewes, each with a single fetus from a synchronised mating, grazed native pasture to day 130 after mating; at which point they were weighed, condition scored and allocated to graze either native pasture or a pasture dominant with Lotus uliginosus. Five days later (14 days before the expected start of lambing) the ewes were allocated to one of four treatments and fed: (i) native pasture alone, (ii) native pasture plus a commercial high-energy lick, (iii) L. uliginosus pasture alone or (iv) L. uliginosus pasture plus whole maize. The weight, viscosity and concentration of components and immunoglobulin G in the colostrum that had accumulated at parturition, were measured for 10 ewes in each treatment. The lambs that survived to 20 days of age from the 221 ewes that were not milked, were recorded. The ewes supplemented with the lick or maize grain and those that grazed the L. uliginosus pasture alone accumulated two to three times more colostrum at birth than the ewes that grazed native pasture alone (396, 635 and 662 g v. 206 g; P < 0.01). The colostrum from the ewes that grazed only native pasture was more viscous (lower score) than that from the ewes supplemented with the lick or maize grain or the ewes that grazed the L. uliginosus pasture alone (scores of 4.1 v. 6.2, 6.5 and 6.4, P < 0.001) and, not surprisingly, the concentration of lactose in the colostrum of the ewes fed only native pasture was also much lower (1.1% v. 3.0%, 2.8% and 2.6%; P < 0.001)he survival of lambs from the ewes fed only native pasture was less than that of the lambs from ewes fed native pasture plus the commercial lick (81.8% v. 95.5%; P < 0.05) or the L. uliginosus pasture alone (92.4%, P < 0.05), and also tended to be lower than that for lambs born to ewes fed L. uliginosus pasture plus maize (91.8%, P = 0

  5. Fluorescence-guided surgery of retroperitoneal-implanted human fibrosarcoma in nude mice delays or eliminates tumor recurrence and increases survival compared to bright-light surgery.

    Directory of Open Access Journals (Sweden)

    Fuminari Uehara

    Full Text Available The aim of this study is to determine if fluorescence-guided surgery (FGS can eradicate human fibrosarcoma growing in the retroperitoneum of nude mice. One week after retroperitoneal implantation of human HT1080 fibrosarcoma cells, expressing green fluorescent protein (GFP (HT-1080-GFP, in nude mice, bright-light surgery (BLS was performed on all tumor-bearing mice (n = 22. After BLS, mice were randomized into 2 treatment groups; BLS-only (n = 11 or the combination of BLS + FGS (n = 11. The residual tumors remaining after BLS were resected with FGS using a hand-held portable imaging system under fluorescence navigation. The average residual tumor area after BLS + FGS was significantly smaller than after BLS-only (0.4 ± 0.4 mm(2 and 10.5 ± 2.4 mm(2, respectively; p = 0.006. Five weeks after surgery, the fluorescent-tumor areas of BLS- and BLS + FGS-treated mice were 379 ± 147 mm(2 and 11.7 ± 6.9 mm(2, respectively, indicating that FGS greatly inhibited tumor recurrence compared to BLS. The combination of BLS + FGS significantly decreased fibrosarcoma recurrence compared to BLS-only treated mice (p < 0.001. Mice treated with BLS+FGS had a significantly higher disease-free survival rate than mice treated with BLS-only at five weeks after surgery. These results suggest that combination of BLS + FGS significantly reduced the residual fibrosarcoma volume after BLS and improved disease-free survival.

  6. Induction chemotherapy for T3N0M0 non-small-cell lung cancer increases the rate of complete resection but does not confer improved survival.

    Science.gov (United States)

    Anderson, Kevin L; Mulvihill, Michael S; Yerokun, Babatunde A; Speicher, Paul J; D'Amico, Thomas A; Tong, Betty C; Berry, Mark F; Hartwig, Matthew G

    2017-08-01

    The objective of this study was to evaluate outcomes of induction therapy prior to an operation in patients with cT3 non-small-cell lung cancer (NSCLC). Patients diagnosed with cT3N0M0 NSCLC from 2006 to 2011 in the National Cancer Database who were treated with lobectomy or pneumonectomy were stratified by treatment strategy: an operation first versus induction chemotherapy. Propensity scores were developed and matched cohorts were generated. Short-term outcomes included margin status, 30- and 90-day mortality rates, readmission and length of stay. Survival analyses using Kaplan-Meier methods were performed on both the unadjusted and propensity matched cohorts. A total of 3791 cT3N0M0 patients were identified for inclusion, of which 580 (15%) were treated with induction chemotherapy. Prior to adjustment, patients treated with induction chemotherapy were younger, had a higher comorbidity burden and were more likely to have private insurance (all P  induction chemotherapy were more likely to subsequently undergo an open procedure (87.3 vs 77.8%, P  = 0.005). These patients were more likely to obtain R0 resection (93.1% vs 90.0%, P  = 0.04) and were thereby less likely to have positive margins at the time of resection (6.9% vs 10.0%, P  = 0.03). Patients who received induction therapy had higher rates of 90-day mortality (6.6% vs 3.4%) but there was no difference in long-term survival between the groups. Despite yielding increased rates of R0 resection, induction chemotherapy for cT3N0M0 NSCLC is not associated with improved survival and should not be considered routinely. Further studies are warranted to elucidate cohorts that may benefit from induction therapy.

  7. BDNF Increases Survival and Neuronal Differentiation of Human Neural Precursor Cells Cotransplanted with a Nanofiber Gel to the Auditory Nerve in a Rat Model of Neuronal Damage

    Directory of Open Access Journals (Sweden)

    Yu Jiao

    2014-01-01

    Full Text Available Objectives. To study possible nerve regeneration of a damaged auditory nerve by the use of stem cell transplantation. Methods. We transplanted HNPCs to the rat AN trunk by the internal auditory meatus (IAM. Furthermore, we studied if addition of BDNF affects survival and phenotypic differentiation of the grafted HNPCs. A bioactive nanofiber gel (PA gel, in selected groups mixed with BDNF, was applied close to the implanted cells. Before transplantation, all rats had been deafened by a round window niche application of β-bungarotoxin. This neurotoxin causes a selective toxic destruction of the AN while keeping the hair cells intact. Results. Overall, HNPCs survived well for up to six weeks in all groups. However, transplants receiving the BDNF-containing PA gel demonstrated significantly higher numbers of HNPCs and neuronal differentiation. At six weeks, a majority of the HNPCs had migrated into the brain stem and differentiated. Differentiated human cells as well as neurites were observed in the vicinity of the cochlear nucleus. Conclusion. Our results indicate that human neural precursor cells (HNPC integration with host tissue benefits from additional brain derived neurotrophic factor (BDNF treatment and that these cells appear to be good candidates for further regenerative studies on the auditory nerve (AN.

  8. Human circulating plasma DNA significantly decreases while lymphocyte DNA damage increases under chronic occupational exposure to low-dose gamma-neutron and tritium β-radiation.

    Science.gov (United States)

    Korzeneva, Inna B; Kostuyk, Svetlana V; Ershova, Liza S; Osipov, Andrian N; Zhuravleva, Veronika F; Pankratova, Galina V; Porokhovnik, Lev N; Veiko, Natalia N

    2015-09-01

    The blood plasma of healthy people contains cell-fee (circulating) DNA (cfDNA). Apoptotic cells are the main source of the cfDNA. The cfDNA concentration increases in case of the organism's cell death rate increase, for example in case of exposure to high-dose ionizing radiation (IR). The objects of the present research are the blood plasma and blood lymphocytes of people, who contacted occupationally with the sources of external gamma/neutron radiation or internal β-radiation of tritium N = 176). As the controls (references), blood samples of people, who had never been occupationally subjected to the IR sources, were used (N = 109). With respect to the plasma samples of each donor there were defined: the cfDNA concentration (the cfDNA index), DNase1 activity (the DNase1 index) and titre of antibodies to DNA (the Ab DNA index). The general DNA damage in the cells was defined (using the Comet assay, the tail moment (TM) index). A chronic effect of the low-dose ionizing radiation on a human being is accompanied by the enhancement of the DNA damage in lymphocytes along with a considerable cfDNA content reduction, while the DNase1 content and concentration of antibodies to DNA (Ab DNA) increase. All the aforementioned changes were also observed in people, who had not worked with the IR sources for more than a year. The ratio cfDNA/(DNase1×Ab DNA × TM) is proposed to be used as a marker of the chronic exposure of a person to the external low-dose IR. It was formulated the assumption that the joint analysis of the cfDNA, DNase1, Ab DNA and TM values may provide the information about the human organism's cell resistivity to chronic exposure to the low-dose IR and about the development of the adaptive response in the organism that is aimed, firstly, at the effective cfDNA elimination from the blood circulation, and, secondly - at survival of the cells, including the cells with the damaged DNA. Copyright © 2015. Published by Elsevier B.V.

  9. The Impact of Agricultural Bank Advertisement and Identification of the Most Significant Factors in Increasing Impact of Advertisement in Mazandaran Province

    OpenAIRE

    Seyed Reza Mousavizadeh; Vahid Esmailpour Souteh

    2016-01-01

    The aim of this study is a survey about the impact of Agricultural bank advertisement and identification of the most significant factors in increasing impact of advertisement in Mazandaran province. The fundamental hypothesis of this study consists the commercial advertisement of Agricultural bank in Mazandaran province is influential. The applied model in order to assay the impact of advertisement is A.I.D.A model that includes 4 aspects of attracting attention, making interest, making tende...

  10. Interferon gamma increases survival in urine experimental cryptococcosis El Interferon gamma incrementa la sobrevida de un modelo experimental murino de criptococosis

    Directory of Open Access Journals (Sweden)

    Amadeo J. Bava

    1995-10-01

    Full Text Available Systemic disease by Cryptococcus neoformans (C. neoformans is a common opportunistic infection in immunodeficient patients. Cellular immunity seems to be the most important determinant of resistance. The aim of this study was to assess the effect of recombinant rat interferon gamma (IFN-gamma in murine cryptococcosis (Balb/c mice infected by IP route with the Rivas strain of C. neoformans, evaluating survival time, macroscopic and microscopic examination of the organs, and massive seeding of brain homogenate. IFN-gamma treatment, at a daily dose of 10,000 IU, did not modify significantly these variables when mice were challenged with a high inoculum (10(7 yeasts and treatment was delayed to 5 days after infection (median survival 21 days in control mice vs. 23 days in IFN-treated. Another set of experiments suggested that IFN-gamma treatment, at a dose of 10,000 IU/day, begun at the moment of infection could be useful (it prolonged survival from 20 to 28 days, although the difference did not achieve statistical signification. When used simultaneously with infection by 3.5 x 10(5 yeasts, IFN-gamma at 10,000 IU/day for 15 days significantly prolonged survival of mice (p = 0.004. These results suggest that, depending on the experimental conditions, IFN-gamma can improve survival of mice infected with a lethal dose of C. neoformans.Se evaluó la efectividad del interferon-gamma (IFN-gamma recombinante de rata en un modelo experimental de criptococosis desarollado en ratones Balb/C inoculados por vía intraperitoneal con la cepa Rivas de Cryptococcus neoformans (C. neoformans. Se tuvieron en cuenta el tiempo de sobrevida de los animales, el aspecto macroscópico de los órganos en la autopsia, la presencia de levaduras capsuladas en los tejidos y la siembra masiva de un homogenato de cerebro. El tratamiento con IFN-gamma, en dosis diarias de 10.000 UI, no modificó estos parámetros cuando la dosis infectante fue de 10(7 levaduras y el tratamiento se

  11. Significant increases in pulping efficiency in C4H-F5H-transformed poplars: improved chemical savings and reduced environmental toxins.

    Science.gov (United States)

    Huntley, Shannon K; Ellis, Dave; Gilbert, Margarita; Chapple, Clint; Mansfield, Shawn D

    2003-10-08

    The gene encoding ferulate 5-hydroxylase (F5H) was overexpressed in poplar (Populus tremula x Populus alba) using the cinnamate-4-hydroxylase (C4H) promoter to drive expression specifically in cells involved in the lignin biosynthetic pathway and was shown to significantly alter the mole percentage of syringyl subunits in the lignin, as determined by thioacidolysis. Analysis of poplar transformed with a C4H-F5H construct demonstrated significant increases in chemical (kraft) pulping efficiency from greenhouse-grown trees. Compared to wild-type wood, decreases of 23 kappa units and increases of >20 ISO brightness units were observed in trees exhibiting high syringyl monomer concentrations. These changes were associated with no significant modification in total lignin content and no observed phenotypic differences. C4H-F5H-transformed trees could increase pulp throughputs at mills by >60% while concurrently decreasing chemicals employed during processing (chemical pulping and bleaching) and, consequently, the amount of deleterious byproducts released into the environment.

  12. Liver-Specific Deletion of Phosphatase and Tensin Homolog Deleted on Chromosome 10 Significantly Ameliorates Chronic EtOH-Induced Increases in Hepatocellular Damage.

    Directory of Open Access Journals (Sweden)

    Colin T Shearn

    Full Text Available Alcoholic liver disease is a significant contributor to global liver failure. In murine models, chronic ethanol consumption dysregulates PTEN/Akt signaling. Hepatospecific deletion of phosphatase and tensin homolog deleted on chromosome 10 (PTENLKO mice possess constitutive activation of Akt(s and increased de novo lipogenesis resulting in increased hepatocellular steatosis. This makes PTENLKO a viable model to examine the effects of ethanol in an environment of preexisting steatosis. The aim of this study was to determine the impact of chronic ethanol consumption and the absence of PTEN (PTENLKO compared to Alb-Cre control mice (PTENf/f on hepatocellular damage as evidenced by changes in lipid accumulation, protein carbonylation and alanine amino transferase (ALT. In the control PTENf/f animals, ethanol significantly increased ALT, liver triglycerides and steatosis. In contrast, chronic ethanol consumption in PTENLKO mice decreased hepatocellular damage when compared to PTENLKO pair-fed controls. Consumption of ethanol elevated protein carbonylation in PTENf/f animals but had no effect in PTENLKO animals. In PTENLKO mice, overall hepatic mRNA expression of genes that contribute to GSH homeostasis as well as reduced glutathione (GSH and oxidized glutathione (GSSG concentrations were significantly elevated compared to respective PTENf/f counterparts. These data indicate that during conditions of constitutive Akt activation and steatosis, increased GSH homeostasis assists in mitigation of ethanol-dependent induction of oxidative stress and hepatocellular damage. Furthermore, data herein suggest a divergence in EtOH-induced hepatocellular damage and increases in steatosis due to polyunsaturated fatty acids downstream of PTEN.

  13. Quality of life is significantly associated with survival in women with advanced epithelial ovarian cancer: An ancillary data analysis of the NRG Oncology/Gynecologic Oncology Group (GOG-0218) study.

    Science.gov (United States)

    Phippen, N T; Secord, A A; Wolf, S; Samsa, G; Davidson, B; Abernethy, A P; Cella, D; Havrilesky, L J; Burger, R A; Monk, B J; Leath, C A

    2017-10-01

    Evaluate association between baseline quality of life (QOL) and changes in QOL measured by FACT-O TOI with progression-free disease (PFS) and overall survival (OS) in advanced epithelial ovarian cancer (EOC). Patients enrolled in GOG-0218 with completed FACT-O TOI assessments at baseline and at least one follow-up assessment were eligible. Baseline FACT-O TOI scores were sorted by quartiles (Q1-4) and outcomes compared between Q1 and Q2-4 with log-rank statistic and multivariate Cox regression adjusting for age, stage, post-surgical residual disease size, and performance status (PS). Trends in FACT-O TOI scores from baseline to the latest follow-up assessment were evaluated for impact on intragroup (Q1 or Q2-4) outcome by log-rank analysis. Of 1152 eligible patients, 283 formed Q1 and 869 formed Q2-4. Mean baseline FACT-O TOI scores were 47.5 for Q1 vs. 74.7 for Q2-4 (P<0.001). Q1 compared to Q2-4 had worse median OS (37.5 vs. 45.6months, P=0.001) and worse median PFS (12.5 vs. 13.1months, P=0.096). Q2-4 patients had decreased risks of disease progression (HR 0.974, 95% CI 0.953-0.995, P=0.018), and death (HR 0.963, 95% CI 0.939-0.987, P=0.003) for each five-point increase in baseline FACT-O TOI. Improving versus worsening trends in FACT-O TOI scores were associated with longer median PFS (Q1: 12.7 vs. 8.6months, P=0.001; Q2-4: 16.7 vs. 11.1months, P<0.001) and median OS (Q1: 40.8 vs. 16months, P<0.001; Q2-4: 54.4 vs. 33.6months, P<0.001). Baseline FACT-O TOI scores were independently prognostic of PFS and OS while improving compared to worsening QOL was associated with significantly better PFS and OS in women with EOC. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Increasing levels of wild-type CREB up-regulates several activity-regulated inhibitor of death (AID genes and promotes neuronal survival

    Directory of Open Access Journals (Sweden)

    Tan Yan-Wei

    2012-05-01

    Full Text Available Abstract Background CREB (cAMP-response element binding protein is the prototypical signal-regulated transcription factor. In neurons, it is the target of the synaptic activity-induced nuclear calcium-calcium/calmodulin dependent protein kinase (CaMK IV signaling pathway that controls the expression of genes important for acquired neuroprotection as well as other long-lasting adaptive processes in the nervous system. The function of CREB as a transcriptional activator is controlled by its phosphorylation on serine 133, which can be catalyzed by CaMKIV and leads to the recruitment of the co-activator, CREB binding protein (CBP. Activation of CBP function by nuclear calcium-CaMKIV signaling is a second regulatory step required for CREB/CBP-mediated transcription. Results Here we used recombinant adeno-associated virus (rAAV to increase the levels of wild type CREB or to overexpress a mutant version of CREB (mCREB containing a serine to alanine mutation at position amino acid 133 in mouse hippocampal neurons. Increasing the levels of CREB was sufficient to boost neuroprotective activity even under basal conditions (i.e., in the absence of stimulation of synaptic activity. In contrast, overexpression of mCREB increased cell death. The ratio of phospho(serine 133CREB to CREB immunoreactivity in unstimulated hippocampal neurons was similar for endogenous CREB and overexpressed wild type CREB and, as expected, dramatically reduced for overexpressed mCREB. A gene expression analysis revealed that increased expression of CREB but not that of mCREB in hippocampal neurons led to elevated expression levels of bdnf as well as that of several members of a previously characterized set of Activity-regulated Inhibitor of Death (AID genes, which include atf3, btg2, gadd45β, and gadd45γ. Conclusions Our findings indicate that the expression levels of wild type CREB are a critical determinant of the ability of hippocampal neurons to survive harmful conditions

  15. Increased Biological Effective Dose of Radiation Correlates with Prolonged Survival of Patients with Limited-Stage Small Cell Lung Cancer: A Systematic Review.

    Directory of Open Access Journals (Sweden)

    Lucheng Zhu

    Full Text Available Thoracic radiotherapy (TRT is a critical component of the treatment of limited-stage small cell lung cancer (LS-SCLC. However, the optimal radiation dose/fractionation remains elusive. This study reviewed current evidence and explored the dose-response relationship in patients with LS-SCLC who were treated with radiochemotherapy.A quantitative analysis was performed through a systematic search of PubMed, Web of Science, and the Cochrane Library. The correlations between the biological effective dose (BED and median overall survival (mOS, median progression-free survival (mPFS, 1-, 3-, and 5-year overall survival (OS as well as local relapse (LR were evaluated.In all, 2389 patients in 19 trials were included in this study. Among these 19 trials, seven were conducted in Europe, eight were conducted in Asia and four were conducted in the United States. The 19 trials that were included consisted of 29 arms with 24 concurrent and 5 sequential TRT arms. For all included studies, the results showed that a higher BED prolonged the mOS (R2 = 0.198, p<0.001 and the mPFS (R2 = 0.045, p<0.001. The results also showed that increased BED improved the 1-, 3-, and 5-year OS. A 10-Gy increment added a 6.3%, a 5.1% and a 3.7% benefit for the 1-, 3-, and 5-year OS, respectively. Additionally, BED was negatively correlated with LR (R2 = 0.09, p<0.001. A subgroup analysis of concurrent TRT showed that a high BED prolonged the mOS (p<0.001 and the mPFS (p<0.001, improved the 1-, 3-, and 5-year OS (p<0.001 and decreased the rate of LR (p<0.001.This study showed that an increased BED was associated with improved OS, PFS and decreased LR in patients with LS-SCLC who were treated with combined chemoradiotherapy, which indicates that the strategy of radiation dose escalation over a limited time frame is worth exploring in a prospective clinical trial.

  16. Significance of targeted therapy and genetic alterations in EGFR, ALK, or KRAS on survival in patients with non-small cell lung cancer treated with radiotherapy for brain metastases.

    Science.gov (United States)

    Mak, Kimberley S; Gainor, Justin F; Niemierko, Andrzej; Oh, Kevin S; Willers, Henning; Choi, Noah C; Loeffler, Jay S; Sequist, Lecia V; Shaw, Alice T; Shih, Helen A

    2015-02-01

    We determined the impact of genetic alterations in EGFR, ALK, or KRAS on survival after radiotherapy for brain metastases in non-small cell lung cancer (NSCLC). Of 172 genotyped NSCLC patients treated with radiotherapy for brain metastases in 2005-2012, 54 had cancers with EGFR mutations, 12 had ALK rearrangements, 38 had KRAS mutations, and 68 were wild-type (WT). Overall survival (OS) was determined. Median follow-up was 8.6 months. Median OS was 13.6 months for patients with EGFR mutations and 26.3 months for patients with ALK rearrangements, in contrast to 5.7 months for KRAS-mutant patients and 5.5 months for WT patients (P = .001). On multivariate analysis, adjusting for receipt of targeted therapy after cranial radiotherapy, ALK rearrangements were associated with improved OS (HR, 0.31; 95% CI, 0.13-0.74; P = .008). EGFR mutations were not significantly associated with improved OS on multivariate analysis (HR, 0.71; 95% CI, 0.37-1.38; P = .3). KRAS mutations were also not associated with improved OS (HR, 0.93; 95% CI, 0.59-1.47; P = .8). Receipt of targeted therapy after cranial radiotherapy was independently associated with improved OS (HR, 0.30; 95% CI, 0.17-0.54; P genetic alterations in ALK have improved survival outcomes after radiotherapy for brain metastases compared with EGFR, KRAS, or WT. Subsequent receipt of targeted therapy was associated with additional improvement in OS. © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  17. Significant survival advantage of high pulmonary vein index and the presence of native pulmonary artery in pulmonary atresia with ventricular septal defect and major aortopulmonary collateral arteries: results from preoperative computed tomography angiography.

    Science.gov (United States)

    Jia, Qianjun; Cen, Jianzheng; Zhuang, Jian; Zhong, Xiaomei; Liu, Xiaoqing; Li, Jiahua; Liang, Changhong; Huang, Meiping

    2017-08-01

    The prognosis of pulmonary atresia with ventricular septal defect and major aortopulmonary collateral arteries (PA-VSD-MAPCAs) after surgery shows substantial clinical heterogeneity and predictors for outcomes are lacking. This study aimed to assess the predictive value of preoperative cardiac computed tomography angiography (CTA) for survival in patients with PA-VSD-MAPCAs. We retrospectively analysed PA-VSD-MAPCA patients with preoperative CTA who underwent both right ventricular outflow tract reconstruction and MAPCA unifocalization ( n  = 24) or pulmonary artery rehabilitation ( n  = 28). The end-point was overall survival. Prognostic values of CTA were assessed using Cox univariate and multivariate analyses. The significant threshold of independent parameters was calculated using receiver-operating characteristic (ROC) curves. During a median follow-up of 1145 days, a total of 13 deaths were observed. Multivariate analysis identified a high pulmonary vein index (PVI) [hazard ratio (HR) = 0.03; 95% confidence interval (CI): 0.03, 0.28; P  advantage in PA-VSD-MAPCA patients. A PVI ≥438 mm 2 /m 2 may be a reliable positive prognosticator that could improve the decision-making strategy for PA-VSD-MAPCA patients.

  18. Increasing Radiation Therapy Dose Is Associated With Improved Survival in Patients Undergoing Stereotactic Body Radiation Therapy for Stage I Non–Small-Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Koshy, Matthew, E-mail: mkoshy@radonc.uchicago.edu [Department of Radiation Oncology, University of Illinois at Chicago, Chicago, Illinois (United States); Department of Radiation and Cellular Oncology, The University of Chicago, Chicago, Illinois (United States); Malik, Renuka [Department of Radiation and Cellular Oncology, The University of Chicago, Chicago, Illinois (United States); Weichselbaum, Ralph R. [Department of Radiation Oncology, University of Illinois at Chicago, Chicago, Illinois (United States); Department of Radiation and Cellular Oncology, The University of Chicago, Chicago, Illinois (United States); Sher, David J. [Department of Radiation Oncology, Rush University Medical Center, Chicago, Illinois (United States)

    2015-02-01

    Purpose: To determine the comparative effectiveness of different stereotactic body radiation therapy (SBRT) dosing regimens for early-stage non–small-cell lung cancer, using a large national database, focusing on the relative impact of dose as a function of tumor stage. Methods and Materials: The study included patients in the National Cancer Database from 2003 to 2006 with T1-T2N0M0 inoperable lung cancer (n=498). The biologically effective dose (BED) was calculated according to the linear quadratic formula using an α/β ratio of 10. High versus lower-dose (HD vs LD) SBRT was defined as a calculated BED above or below 150 Gy. Overall survival was estimated using Kaplan-Meier methods and Cox proportional hazard regression. Results: The 5 most common dose fractionation schemes (percentage of cohort) used were 20 Gy × 3 (34%), 12 Gy × 4 (16%), 18 Gy × 3 (10%), 15 Gy × 3 (10%), and 16 Gy × 3 (4%). The median calculated BED was 150 Gy (interquartile range 106-166 Gy). The 3-year overall survival (OS) for patients who received HD versus LD was 55% versus 46% (log–rank P=.03). On subset analysis of the T1 cohort there was no association between calculated BED and 3-year OS (61% vs 60% with HD vs LD, P=.9). Among the T2 cohort, patients receiving HD experienced superior 3-year OS (37% vs 24%, P=.01). On multivariable analysis, factors independently prognostic for mortality were female gender (hazard ratio [HR] 0.76, P=.01), T2 tumor (HR 1.99, P=.0001), and HD (HR 0.68, P=.001). Conclusions: This comparative effectiveness analysis of SBRT dose for patients with stage I non–small-cell lung cancer suggests that higher doses (>150 Gy BED) are associated with a significant survival benefit in patients with T2 tumors.

  19. Murine Cerebral Malaria Is Associated with a Vasospasm-Like Microcirculatory Dysfunction, and Survival upon Rescue Treatment Is Markedly Increased by Nimodipine

    Science.gov (United States)

    Cabrales, Pedro; Zanini, Graziela M.; Meays, Diana; Frangos, John A.; Carvalho, Leonardo J.M.

    2010-01-01

    Brain hemodynamics in cerebral malaria (CM) is poorly understood, with apparently conflicting data showing microcirculatory hypoperfusion and normal or even increased blood flow in large arteries. Using intravital microscopy to assess the pial microvasculature through a closed cranial window in the murine model of CM by Plasmodium berghei ANKA, we show that murine CM is associated with marked decreases (mean: 60%) of pial arteriolar blood flow attributable to vasoconstriction and decreased blood velocity. Leukocyte sequestration further decreased perfusion by narrowing luminal diameters in the affected vessels and blocking capillaries. Remarkably, vascular collapse at various degrees was observed in 44% of mice with CM, which also presented more severe vasoconstriction. Coadministration of artemether and nimodipine, a calcium channel blocker used to treat postsubarachnoid hemorrhage vasospasm, to mice presenting CM markedly increased survival compared with artemether plus vehicle only. Administration of nimodipine induced vasodilation and increased pial blood flow. We conclude that vasoconstriction and vascular collapse play a role in murine CM pathogenesis and nimodipine holds potential as adjunctive therapy for CM. PMID:20110412

  20. Orally administered indomethacin acutely reduces cellular prion protein in the small intestine and modestly increases survival of mice exposed to infectious prions.

    Science.gov (United States)

    Martin, Gary R; Sharkey, Keith A; Jirik, Frank R

    2015-05-01

    The oral uptake of infectious prions represents a common way to acquire a prion disease; thus, host factors, such as gut inflammation and intestinal "leakiness", have the potential to influence infectivity. For example, the ingestion of nonsteroidal anti-inflammatory drugs (NSAIDs) is known to induce intestinal inflammation and increase intestinal permeability. Previously, we reported that normal cellular prion protein (PrP(C)) expression was increased in experimental colitis, and since the level of PrP(C) expressed is a determinant of prion disease propagation, we hypothesized that NSAID administration prior to the oral inoculation of mice with infectious prions would increase intestinal PrP(C) expression and accelerate the onset of neurological disease. In the long-term experiments, one group of mice was gavaged with indomethacin, followed by a second gavage with brain homogenate containing mouse-adapted scrapie (ME7). Control mice received ME7 brain homogenate alone. Brain and splenic tissues were harvested at several time points for immunoblotting, including at the onset of clinical signs of disease. In a second series of experiments, mice were gavaged with indomethacin to assess the acute effects of this treatment on intestinal PrP(C) expression. Acutely, NSAID treatment reduced intestinal PrP(C) expression, and chronically, there was a modest delay in the onset of neurological disease. In contrast to our hypothesis, brief exposure to an NSAID decreased intestinal PrP(C) expression and led to a modest survival advantage following oral ingestion of infectious prions.

  1. Prenatal prochloraz treatment significantly increases pregnancy length and reduces offspring weight but does not affect social-olfactory memory in rats

    DEFF Research Database (Denmark)

    Dmytriyeva, Oksana; Klementiev, Boris; Berezin, Vladimir

    2013-01-01

    the perinatal period. Pregnant Wistar rats were administered a 200mg/kg dose of prochloraz on gestational day (GD) 7, GD11, and GD15. The social recognition test (SRT) was performed on 7-week-old male rat offspring. We found an increase in pregnancy length and a significantly reduced pup weight on PND15 and PND......Metabolites of the commonly used imidazole fungicide prochloraz are androgen receptor antagonists. They have been shown to block androgen-driven development and compromise reproductive function. We tested the effect of prochloraz on cognitive behavior following exposure to this fungicide during...

  2. Decidual Macrophages Are Significantly Increased in Spontaneous Miscarriages and Over-Express FasL: A Potential Role for Macrophages in Trophoblast Apoptosis

    Directory of Open Access Journals (Sweden)

    Antonis Makrigiannakis

    2012-07-01

    Full Text Available Decidual macrophages (DM are the second most abundant population in the fetal-maternal interface. Their role has been so far identified as being local immuno-modulators favoring the maternal tolerance to the fetus. Herein we investigated tissue samples from 11 cases of spontaneous miscarriages and from 9 cases of elective terminations of pregnancy. Using immunohistochemistry and dual immunofluorescence we have demonstrated that in spontaneous miscarriages the DM are significantly increased. Additionally, we noted a significant up-regulation of macrophage FasL expression. Our results further support a dual role for DM during pregnancy and miscarriages. We hypothesize that the baseline DM population in normal pregnancy is in line with an M2 phenotype supporting the ongoing gestation. In contrast, during spontaneous miscarriages, the increased FasL-expressing population could be a part of an M1 phenotype participating in Fas/FasL-related apoptosis. Our results highlight a new aspect of macrophage biology in pregnancy physiology and pathophysiology. Further studies with larger samples are needed to verify the current results and evaluate their clinical impact.

  3. Somatic Copy Number Abnormalities and Mutations in PI3K/AKT/mTOR Pathway Have Prognostic Significance for Overall Survival in Platinum Treated Locally Advanced or Metastatic Urothelial Tumors.

    Directory of Open Access Journals (Sweden)

    Joaquim Bellmunt

    Full Text Available An integrative analysis was conducted to identify genomic alterations at a pathway level that could predict overall survival (OS in patients with advanced urothelial carcinoma (UC treated with platinum-based chemotherapy.DNA and RNA were extracted from 103 formalin-fixed paraffin embedded (FFPE invasive high-grade UC samples and were screened for mutations, copy number variation (CNV and gene expression analysis. Clinical data were available from 85 cases. Mutations were analyzed by mass-spectrometry based on genotyping platform (Oncomap 3 and genomic imbalances were detected by comparative genomic hybridization (CGH analysis. Regions with threshold of log2 ratio ≥0.4, or ≤0.6 were defined as either having copy number gain or loss and significantly recurrent CNV across the set of samples were determined using a GISTIC analysis. Expression analysis on selected relevant UC genes was conducted using Nanostring. To define the co-occurrence pattern of mutations and CNV, we grouped genomic events into 5 core signal transduction pathways: 1 TP53 pathway, 2 RTK/RAS/RAF pathway, 3 PI3K/AKT/mTOR pathway, 4 WNT/CTNNB1, 5 RB1 pathway. Cox regression was used to assess pathways abnormalities with survival outcomes.35 samples (41% harbored mutations on at least one gene: TP53 (16%, PIK3CA (9%, FGFR3 (2%, HRAS/KRAS (5%, and CTNNB1 (1%. 66% of patients had some sort of CNV. PIK3CA/AKT/mTOR pathway alteration (mutations+CNV had the greatest impact on OS (p=0.055. At a gene level, overexpression of CTNNB1 (p=0.0008 and PIK3CA (p=0.02 were associated with shorter OS. Mutational status on PIK3CA was not associated with survival. Among other individually found genomic alterations, TP53 mutations (p=0.07, mTOR gain (p=0.07 and PTEN overexpression (p=0.08 have a marginally significant negative impact on OS.Our study suggests that targeted therapies focusing on the PIK3CA/AKT/mTOR pathway genomic alterations can generate the greatest impact in the overall patient

  4. Suicide plus immune gene therapy prevents post-surgical local relapse and increases overall survival in an aggressive mouse melanoma setting.

    Science.gov (United States)

    Villaverde, Marcela S; Combe, Kristell; Duchene, Adriana G; Wei, Ming X; Glikin, Gerardo C; Finocchiaro, Liliana M E

    2014-09-01

    In an aggressive B16-F10 murine melanoma model, we evaluated the effectiveness and antitumor mechanisms triggered by a surgery adjuvant treatment that combined a local suicide gene therapy (SG) with a subcutaneous genetic vaccine (Vx) composed of B16-F10 cell extracts and lipoplexes carrying the genes of human interleukin-2 and murine granulocyte and macrophage colony stimulating factor. Pre-surgical SG treatment, neither alone nor combined with Vx was able to slow down the fast evolution of this tumor. After surgery, both SG and SG + Vx treatments, significantly prevented (in 50% of mice) or delayed (in the remaining 50%) post-surgical recurrence, as well as significantly prolonged recurrence-free (SG and SG + Vx) and overall median survival (SG + Vx). The treatment induced the generation of a pseudocapsule wrapping and separating the tumor from surrounding host tissue. Both, SG and the subcutaneous Vx, induced this envelope that was absent in the control group. On the other hand, PET scan imaging of the SG + Vx group suggested the development of an effective systemic immunostimulation that enhanced (18)FDG accrual in the thymus, spleen and vertebral column. When combined with surgery, direct intralesional injection of suicide gene plus distal subcutaneous genetic vaccine displayed efficacy and systemic antitumor immune response without host toxicity. This suggests the potential value of the assayed approach for clinical purposes. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Using Interferon Alfa Before Tyrosine Kinase Inhibitors May Increase Survival in Patients With Metastatic Renal Cell Carcinoma: A Turkish Oncology Group (TOG) Study.

    Science.gov (United States)

    Artaç, Mehmet; Çoşkun, Hasan Şenol; Korkmaz, Levent; Koçer, Murat; Turhal, Nazım Serdar; Engin, Hüseyin; Dede, İsa; Paydaş, Semra; Öksüzoğlu, Berna; Bozcuk, Hakan; Demirkazık, Ahmet

    2016-08-01

    We aimed to investigate the outcomes of interferon alfa and sequencing tyrosine kinase inhibitors (TKIs) in patients with metastatic renal cell carcinoma. This multicenter study assessing the efficacy of TKIs after interferon alfa therapy in the first-line setting in patients with metastatic renal cell carcinoma. Patients (n = 104) from 8 centers in Turkey, who had been treated with interferon alfa in the first-line setting, were included in the study. Prognostic factors were evaluated for progression-free survival (PFS). The median age of the patients was 57 years. The median PFS of the patients treated with interferon alfa in the first-line was 3.6 months. A total of 61 patients received TKIs (sunitinib, n = 58; sorafenib, n = 3) after progression while on interferon alfa. The median PFS among the TKI-treated patients was 13.2 months. In the univariate analysis for interferon alfa treatment, neutrophil and hemoglobin level, platelet count, and Karnofsky performance status were the significant factors associated with PFS. In the univariate analysis for TKI treatment, neutrophil and hemoglobin levels were the significant factors for PFS. The median total PFS of the patients who had been treated with first-line interferon alfa and second-line TKIs was 24.9 months. This study showed that first-line interferon alfa treatment before TKIs may improve the total PFS in patients with metastatic renal cell carcinoma. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Fluorescence-guided surgery of retroperitoneal-implanted human fibrosarcoma in nude mice delays or eliminates tumor recurrence and increases survival compared to bright-light surgery.

    Science.gov (United States)

    Uehara, Fuminari; Hiroshima, Yukihiko; Miwa, Shinji; Tome, Yasunori; Yano, Shuya; Yamamoto, Mako; Matsumoto, Yasunori; Maehara, Hiroki; Tanaka, Kazuhiro; Bouvet, Michael; Kanaya, Fuminori; Hoffman, Robert M

    2015-01-01

    The aim of this study is to determine if fluorescence-guided surgery (FGS) can eradicate human fibrosarcoma growing in the retroperitoneum of nude mice. One week after retroperitoneal implantation of human HT1080 fibrosarcoma cells, expressing green fluorescent protein (GFP) (HT-1080-GFP), in nude mice, bright-light surgery (BLS) was performed on all tumor-bearing mice (n = 22). After BLS, mice were randomized into 2 treatment groups; BLS-only (n = 11) or the combination of BLS + FGS (n = 11). The residual tumors remaining after BLS were resected with FGS using a hand-held portable imaging system under fluorescence navigation. The average residual tumor area after BLS + FGS was significantly smaller than after BLS-only (0.4 ± 0.4 mm(2) and 10.5 ± 2.4 mm(2), respectively; p = 0.006). Five weeks after surgery, the fluorescent-tumor areas of BLS- and BLS + FGS-treated mice were 379 ± 147 mm(2) and 11.7 ± 6.9 mm(2), respectively, indicating that FGS greatly inhibited tumor recurrence compared to BLS. The combination of BLS + FGS significantly decreased fibrosarcoma recurrence compared to BLS-only treated mice (p fibrosarcoma volume after BLS and improved disease-free survival.

  7. Effect of repetitive daily ethanol intoxication on adult rat brain: significant changes in phospholipase A2 enzyme levels in association with increased PARP-1 indicate neuroinflammatory pathway activation.

    Science.gov (United States)

    Tajuddin, Nuzhath F; Przybycien-Szymanska, Magdalena M; Pak, Toni R; Neafsey, Edward J; Collins, Michael A

    2013-02-01

    Collaborating on studies of subchronic daily intoxication in juvenile and adult rats, we examined whether the repetitive ethanol treatments at these two life stages altered levels of key neuroinflammation-associated proteins-aquaporin-4 (AQP4), certain phospholipase A2 (PLA2) enzymes, PARP-1 and caspase-3-in hippocampus (HC) and entorhinal cortex (EC). Significant changes in the proteins could implicate activation of specific neuroinflammatory signaling pathways in these rats as well as in severely binge-intoxicated adult animals that are reported to incur degeneration of vulnerable neurons in HC and EC. Male Wistar rats, ethanol-intoxicated (3 g/kg i.p.) once daily for 6 days over an 8-day interval beginning at 37 days old and repeated at age 68-75 days, were sacrificed 1 h after the day 75 dose (blood ethanol, 200- 230 mg/dl). Analysis of HC with an immunoblot technique showed that AQP4, Ca(+2)-dependent PLA2 (cPLA2 IVA), phosphorylated (activated) p-cPLA2, cleaved (89 kD) PARP (c-PARP), and caspase-3 levels were significantly elevated over controls, whereas Ca(+2)-independent PLA2 (iPLA2 VIA) was reduced ∼70%; however, cleaved caspase-3 was undetectable. In the EC, AQP4 was unchanged, but cPLA2 and p-cPLA2 were significantly increased while iPLA2 levels were diminished (∼40%) similar to HC, although just outside statistical significance (p = 0.06). In addition, EC levels of PARP-1 and c-PARP were significantly increased. The ethanol-induced activation of cPLA2 in association with reduced iPLA2 mirrors PLA2 changes in reports of neurotrauma and also of dietary omega-3 fatty acid depletion. Furthermore, the robust PARP-1 elevations accompanied by negligible caspase-3 activation indicate that repetitive ethanol intoxication may be potentiating non-apoptotic neurodegenerative processes such as parthanatos. Overall, the repetitive ethanol treatments appeared to instigate previously unappreciated neuroinflammatory pathways in vivo. The data provide insights

  8. Addition of a third field significantly increases dose to the brachial plexus for patients undergoing tangential whole-breast therapy after lumpectomy

    Energy Technology Data Exchange (ETDEWEB)

    Stanic, Sinisa; Mathai, Mathew; Mayadev, Jyoti S.; Do, Ly V.; Purdy, James A. [Department of Radiation Oncology, University of California, Davis, Sacramento, CA (United States); Chen, Allen M., E-mail: allen.chen@ucdmc.ucdavis.edu [Department of Radiation Oncology, University of California, Davis, Sacramento, CA (United States)

    2012-07-01

    Our goal was to evaluate brachial plexus (BP) dose with and without the use of supraclavicular (SCL) irradiation in patients undergoing breast-conserving therapy with whole-breast radiation therapy (RT) after lumpectomy. Using the standardized Radiation Therapy Oncology Group (RTOG)-endorsed guidelines delineation, we contoured the BP for 10 postlumpectomy breast cancer patients. The radiation dose to the whole breast was 50.4 Gy using tangential fields in 1.8-Gy fractions, followed by a conedown to the operative bed using electrons (10 Gy). The prescription dose to the SCL field was 50.4 Gy, delivered to 3-cm depth. The mean BP volume was 14.5 {+-} 1.5 cm{sup 3}. With tangential fields alone, the median mean dose to the BP was 0.57 Gy, the median maximum dose was 1.93 Gy, and the irradiated volume of the BP receiving 40, 45, and 50 Gy was 0%. When the third (SCL field) was added, the dose to the BP was significantly increased (P = .01): the median mean dose to the BP was 40.60 Gy, and the median maximum dose was 52.22 Gy. With 3-field RT, the median irradiated volume of the BP receiving 40, 45, and 50 Gy was 83.5%, 68.5%, and 24.6%, respectively. The addition of the SCL field significantly increases dose to the BP. The possibility of increasing the risk of BP morbidity should be considered in the context of clinical decision making.

  9. Clinical significance of increased cerebellar default-mode network connectivity in resting-state patients with drug-naive somatization disorder.

    Science.gov (United States)

    Wang, Houliang; Guo, Wenbin; Liu, Feng; Chen, Jindong; Wu, Renrong; Zhang, Zhikun; Yu, Miaoyu; Li, Lehua; Zhao, Jingping

    2016-07-01

    The cerebellum has been proven to be connected to the brain network, as in the default-mode network (DMN), among healthy subjects and patients with psychiatric disorders. However, whether or not abnormal cerebellar DMN connectivity exists and what its clinical significance is among drug-naive patients with somatization disorder (SD) at rest remain unclear.A total of 25 drug-naive patients with SD and 28 healthy controls were enrolled for a resting-state scan. The imaging data were analyzed using the seed-based functional connectivity (FC) method.Compared with the controls, patients with SD showed increased left/right Crus I-left/right angular gyrus (AG) connectivity and Lobule IX-left superior medial prefrontal cortex (MPFC) connectivity. The FC values of the left/right Crus I-right AG connectivity of the patients were positively correlated with their scores in the somatization subscale of the symptom checklist-90 (Scl-90). A trend level of correlations was observed between the FC values of the left Crus I-left AG connectivity of the patients and their scores for the somatization subscale of Scl-90, as well as between the FC values of their Lobule IX-left superior MPFC connectivity and their scores for the Eysenck personality questionnaire (EPQ) extraversion.Our findings show the increased cerebellar DMN connectivity in patients with SD and therefore highlight the importance of the DMN in the neurobiology of SD. Increased cerebellar DMN connectivities are also correlated with their somatization severity and personality, both of which bear clinical significance.

  10. Elevated levels of transferrin receptor 2 mRNA, not transferrin receptor 1 mRNA, are associated with increased survival in acute myeloid leukaemia.

    Science.gov (United States)

    Nakamaki, Tsuyoshi; Kawabata, Hiroshi; Saito, Bungo; Matsunawa, Manabu; Suzuki, Junko; Adachi, Daisuke; Tomoyasu, Shigeru; Phillip Koeffler, H

    2004-04-01

    Transferrin receptor 1 (TfR1) is a type II membrane protein that mediates cellular iron uptake. Transferrin receptor 2(TfR2), another receptor for transferrin (Tf), has recently been cloned. We examined expression levels of TfR1, TfR2-alpha (membrane form) and TfR2-beta (non-membrane form) transcripts in cells from 67 patients with de novo acute myeloid leukaemia (AML) using reverse transcription-polymerase chain reaction (RT-PCR), and correlated the results with a variety of clinical features and disease outcomes of these patients. Significant correlations were noted between the levels of both TfR1 and TfR2-alpha (r = 0.771, P TfR2-beta (r = 0.534, P TfR2-alpha (r = -0.486, P TfR2-beta (r = -0.435, P = 0.0003). Only TfR2 expression was significantly associated with either serum iron (r = -0.270, P = 0.045) or serum ferritin (r = -0.364, P = 0.008). Multivariate analyses using Cox's proportional hazard model showed that elevated TfR2-alpha, but not TfR1 or TfR2-beta mRNA levels significantly contributed to a better prognosis for AML patients. Furthermore, a group with high expression levels of both TfR2-alpha and TfR2-beta survived significantly longer than a group without high expression of both of them (P TfR2 (especially the alpha form) is a novel prognostic factor for patients with AML.

  11. Insights on the antitumor effects of kahweol on human breast cancer: Decreased survival and increased production of reactive oxygen species and cytotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Cárdenas, Casimiro [Department of Molecular Biology and Biochemistry, Faculty of Sciences, University of Málaga, E-29071 Málaga (Spain); IBIMA (Biomedical Research Institute of Málaga), E-29071 Málaga (Spain); Research Support Central Services (SCAI) of the University of Málaga, E-29071 Málaga (Spain); Quesada, Ana R. [Department of Molecular Biology and Biochemistry, Faculty of Sciences, University of Málaga, E-29071 Málaga (Spain); IBIMA (Biomedical Research Institute of Málaga), E-29071 Málaga (Spain); CIBER de Enfermedades Raras (CIBERER), E-29071 Málaga (Spain); Medina, Miguel Ángel, E-mail: medina@uma.es [Department of Molecular Biology and Biochemistry, Faculty of Sciences, University of Málaga, E-29071 Málaga (Spain); IBIMA (Biomedical Research Institute of Málaga), E-29071 Málaga (Spain); CIBER de Enfermedades Raras (CIBERER), E-29071 Málaga (Spain)

    2014-05-09

    Highlights: • Kahweol inhibits growth and attachment-independent proliferation of tumor cells. • Kahweol induces apoptosis in MDA-MB231 human breast cancer cells. • Kahweol-induced apoptosis involves caspase activation and cytochrome c release. • Kahweol does not protect against hydrogen peroxide cytotoxicity. • Kahweol increases hydrogen peroxide production by human breast cancer cells. - Abstract: The present study aims to identify the modulatory effects of kahweol, an antioxidant diterpene present in coffee beans, on a panel of human tumor cell lines. Kahweol inhibits tumor cell proliferation and clonogenicity and induces apoptosis in several kinds of human tumor cells. In the estrogen receptor-negative MDA-MB231 human breast cancer, the mentioned effects are accompanied by caspases 3/7 and 9 activation and cytochrome c release. On the other hand, kahweol increases the production of reactive oxygen species and their cytotoxicity in human breast cancer cells but not in normal cells. Taken together, our data suggest that kahweol is an antitumor compound with inhibitory effects on tumor cell growth and survival, especially against MDA-MB231 breast cancer cells.

  12. MaquiBright™ standardized maqui berry extract significantly increases tear fluid production and ameliorates dry eye-related symptoms in a clinical pilot trial.

    Science.gov (United States)

    Hitoe, S; Tanaka, J; Shimoda, H

    2014-09-01

    Dry eye symptoms, resulting from insufficient tear fluid generation, represent a considerable burden for a largely underestimated number of people. We concluded from earlier pre-clinical investigations that the etiology of dry eyes encompasses oxidative stress burden to lachrymal glands and that antioxidant MaquiBright™ Aristotelia chilensis berry extract helps restore glandular activity. In this pilot trial we investigated 13 healthy volunteers with moderately dry eyes using Schirmer test, as well as a questionnaire which allows for estimating the impact of dry eyes on daily routines. Study participants were assigned to one of two groups, receiving MaquiBright™ at daily dosage of either 30 mg (N.=7) or 60 mg (N.=6) over a period of 60 days. Both groups presented with significantly (PDry Eye-related Quality of life Score" (DEQS), with values spanning from zero (impact) to a maximum score of 60. Participants had comparable baseline values of 41.0±7.7 (30 mg) and 40.2±6.3 (60 mg). With 30 mg treatment the score significantly decreased to 21.8±3.9 and 18.9±3.9, after 30 and 60 days, respectively. With 60 mg treatment the DEQS significantly decreased to 26.9±5.3 and 11.1±2.7, after 30 and 60 days, respectively. Blood was drawn for safety analyses (complete blood rheology and -chemistry) at all three investigative time points without negative findings. In conclusion, while daily supplementation with 30 mg MaquiBright™ is effective, the dosage of 60 significantly increased tear fluid volume at all investigative time points and decreased dry eye symptoms to almost a quarter from initial values after two months treatment.

  13. The in vitro mass-produced model mycorrhizal fungus, Rhizophagus irregularis, significantly increases yields of the globally important food security crop cassava.

    Directory of Open Access Journals (Sweden)

    Isabel Ceballos

    Full Text Available The arbuscular mycorrhizal symbiosis is formed between arbuscular mycorrhizal fungi (AMF and plant roots. The fungi provide the plant with inorganic phosphate (P. The symbiosis can result in increased plant growth. Although most global food crops naturally form this symbiosis, very few studies have shown that their practical application can lead to large-scale increases in food production. Application of AMF to crops in the tropics is potentially effective for improving yields. However, a main problem of using AMF on a large-scale is producing cheap inoculum in a clean sterile carrier and sufficiently concentrated to cheaply transport. Recently, mass-produced in vitro inoculum of the model mycorrhizal fungus Rhizophagus irregularis became available, potentially making its use viable in tropical agriculture. One of the most globally important food plants in the tropics is cassava. We evaluated the effect of in vitro mass-produced R. irregularis inoculum on the yield of cassava crops at two locations in Colombia. A significant effect of R. irregularis inoculation on yield occurred at both sites. At one site, yield increases were observed irrespective of P fertilization. At the other site, inoculation with AMF and 50% of the normally applied P gave the highest yield. Despite that AMF inoculation resulted in greater food production, economic analyses revealed that AMF inoculation did not give greater return on investment than with conventional cultivation. However, the amount of AMF inoculum used was double the recommended dose and was calculated with European, not Colombian, inoculum prices. R. irregularis can also be manipulated genetically in vitro, leading to improved plant growth. We conclude that application of in vitro R. irregularis is currently a way of increasing cassava yields, that there is a strong potential for it to be economically profitable and that there is enormous potential to improve this efficiency further in the future.

  14. Exercise significantly increases plasma adrenaline and oxidized low-density lipoprotein in normal healthy subjects but not in persons with spinal cord injury.

    Science.gov (United States)

    Mitsui, Toshihito; Nakamura, Takeshi; Ito, Tomoyuki; Umemoto, Yasunori; Sakamoto, Keiko; Kinoshita, Tokio; Nakagawa, Masafumi; Tajima, Fumihiro

    2012-04-01

    To compare plasma concentrations of oxidized low-density lipoprotein (oxLDL) and adrenaline during exercise between persons with spinal cord injury (SCI) and able-bodied (AB) individuals. Randomized controlled study. Human laboratory at a medical university. Persons with SCI (n=7) and AB individuals (n=9). Two-hour arm crank ergometer exercise at 60% maximum oxygen consumption. Plasma oxLDL and adrenaline levels. Exercise significantly increased plasma adrenaline levels in AB persons (mean ± SD: rest, 45.4±32.2 pg/mL; exercise, 200.9±113.7 pg/mL; Pplasma oxLDL levels in AB persons (mean ± SD: rest, 102.2±30.2 U/L; exercise, 179.7±60.0 U/L; Pplasma adrenaline levels during exercise contribute to the increase in plasma oxLDL levels. Copyright © 2012 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  15. Changes in epidemiologic features of testicular germ cell cancer: age at diagnosis and relative frequency of seminoma are constantly and significantly increasing.

    Science.gov (United States)

    Ruf, Christian G; Isbarn, Hendrik; Wagner, Walter; Fisch, Margit; Matthies, Cord; Dieckmann, Klaus-Peter

    2014-01-01

    Testicular germ cell tumors (GCTs) have their incidence peak in the third and fourth decades of life. Histologically, GCTs comprise of seminoma and nonseminoma at almost equal proportions with a slight preponderance of nonseminoma in most of the major series. Since decades, there is a shift toward decreasing age at presentation. Recently, there are suggestions of a reversal of the age trend, and also, the histologic subtype ratio appears to shift toward seminoma. We retrospectively looked to our patient populations to verify these recent trends. A total of 2,482 patients with histologically proven GCT diagnosed between 1976 and 2010 were retrospectively evaluated regarding the year of diagnosis, histology of primary tumor, and age at presentation. Patients were categorized according to the following time periods of treatment: before 1990, 1990 to 1994, 1995 to 1999, 2000 to 2004, and 2005 to 2010. Mean age and relative proportion of seminoma were compared among patient categories by employing the chi-square test and analysis of variance, respectively. The mean age significantly increased from 28 to 36 years. The age difference between the 2 histologic subtypes remained constant between 6 and 8 years during the entire observation period. The relative proportion of seminoma continuously increased from 30.9% to 56% (P theories regarding the pathogenesis of GCT may receive support from our results: first, the theory of divergent pathogenetic pathways of seminoma and nonseminoma and second, the involvement of postnatal environmental factors in the pathogenesis of GCTs. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Symmetric dimeric bisbenzimidazoles DBP(n reduce methylation of RARB and PTEN while significantly increase methylation of rRNA genes in MCF-7 cancer cells.

    Directory of Open Access Journals (Sweden)

    Svetlana V Kostyuk

    Full Text Available Hypermethylation is observed in the promoter regions of suppressor genes in the tumor cancer cells. Reactivation of these genes by demethylation of their promoters is a prospective strategy of the anticancer therapy. Previous experiments have shown that symmetric dimeric bisbenzimidazoles DBP(n are able to block DNA methyltransferase activities. It was also found that DBP(n produces a moderate effect on the activation of total gene expression in HeLa-TI population containing epigenetically repressed avian sarcoma genome.It is shown that DBP(n are able to penetrate the cellular membranes and accumulate in breast carcinoma cell MCF-7, mainly in the mitochondria and in the nucleus, excluding the nucleolus. The DBP(n are non-toxic to the cells and have a weak overall demethylation effect on genomic DNA. DBP(n demethylate the promoter regions of the tumor suppressor genes PTEN and RARB. DBP(n promotes expression of the genes RARB, PTEN, CDKN2A, RUNX3, Apaf-1 and APC "silent" in the MCF-7 because of the hypermethylation of their promoter regions. Simultaneously with the demethylation of the DNA in the nucleus a significant increase in the methylation level of rRNA genes in the nucleolus was detected. Increased rDNA methylation correlated with a reduction of the rRNA amount in the cells by 20-30%. It is assumed that during DNA methyltransferase activity inhibition by the DBP(n in the nucleus, the enzyme is sequestered in the nucleolus and provides additional methylation of the rDNA that are not shielded by DBP(n.It is concluded that DBP (n are able to accumulate in the nucleus (excluding the nucleolus area and in the mitochondria of cancer cells, reducing mitochondrial potential. The DBP (n induce the demethylation of a cancer cell's genome, including the demethylation of the promoters of tumor suppressor genes. DBP (n significantly increase the methylation of ribosomal RNA genes in the nucleoli. Therefore the further study of these compounds is needed

  17. Increased Circulating Level of the Survival Factor GP88 (Progranulin in the Serum of Breast Cancer Patients When Compared to Healthy Subjects

    Directory of Open Access Journals (Sweden)

    Katherine Rak Tkaczuk

    2011-01-01

    Full Text Available Introduction GP88 (PC-Cell Derived Growth Factor, progranulin is a glycoprotein overexpressed in breast tumors and involved in their proliferation and survival. Since GP88 is secreted, an exploratory study was established to compare serum GP88 level between breast cancer patients (BC and healthy volunteers (HV. Methods An IRB approved prospective study enrolled 189 stage 1–4 BC patients and 18 HV. GP88 serum concentration was determined by immunoassay. Results Serum GP88 level was 28.7+ 5.8 ng/ml in HV and increased to 40.7+ 16.0 ng/ml ( P = 0.007 for stage 1-3 and 45.3 +23.3 ng/ml ( P = 0.0007 for stage 4 BC patients. There was no correlation between the GP88 level and BC characteristics such as age, race, tumor grade, ER, PR and HER-2 expression. Conclusion These data suggest that serial testing of serum GP88 levels may have value as a circulating biomarker for detection, monitoring and follow up of BC.

  18. Pretreatment with Cry1Ac Protoxin Modulates the Immune Response, and Increases the Survival of Plasmodium-Infected CBA/Ca Mice

    Directory of Open Access Journals (Sweden)

    Martha Legorreta-Herrera

    2010-01-01

    Full Text Available Malaria is a major global health problem that kills 1-2 million people each year. Despite exhaustive research, naturally acquired immunity is poorly understood. Cry1A proteins are potent immunogens with adjuvant properties and are able to induce strong cellular and humoral responses. In fact, it has been shown that administration of Cry1Ac protoxin alone or with amoebic lysates induces protection against the lethal infection caused by the protozoa Naegleria fowleri. In this work, we studied whether Cry1Ac is able to activate the innate immune response to induce protection against Plasmodium berghei ANKA (lethal and P. chabaudi AS (nonlethal parasites in CBA/Ca mice. Treatment with Cry1Ac induced protection against both Plasmodium species in terms of reduced parasitaemia, longer survival time, modulation of pro- and anti-inflammatory cytokines, and increased levels of specific antibodies against Plasmodium. Understanding how to boost innate immunity to Plasmodium infection should lead to immunologically based intervention strategies.

  19. Population-based survival of patients with peritoneal carcinomatosis from colorectal origin in the era of increasing use of palliative chemotherapy.

    NARCIS (Netherlands)

    Klaver, Y.L.B.; Lemmens, V.E.; Creemers, G.J.; Rutten, H.J.; Nienhuijs, S.W.; Hingh, I.H.J.T. de

    2011-01-01

    BACKGROUND: Palliative chemotherapy improves survival in patients with metastasised colorectal cancer. However, there is a lack of data regarding the effectiveness of modern chemotherapy in patients with isolated peritoneal carcinomatosis (PC). PATIENTS AND METHODS: All patients with synchronous PC

  20. N- and C-terminal truncations of a GH10 xylanase significantly increase its activity and thermostability but decrease its SDS resistance.

    Science.gov (United States)

    Zheng, Fei; Huang, Jingxuan; Liu, Xingchen; Hu, Hang; Long, Liangkun; Chen, Kaixiang; Ding, Shaojun

    2016-04-01

    XynII from Volvariella volvacea has high sodium dodecyl sulfate (SDS) resistance, with the potential for industrial applications under harsh conditions. It consists of a single glycoside hydrolase family 10 (GH10) catalytic domain but contains an additional unique 10 and 4 amino acid residues at the N- and C-terminus, respectively. In this study, five XynII derivatives with N- and/or C-terminus deletions were constructed to determine the effects of these regions on enzyme activity, substrate specificity, thermostability, and SDS resistance. Our results revealed that N- and/or C-terminal truncations significantly increased enzyme activity and thermostability, but reduced SDS resistance. Specifically, the XynIIΔNC4 mutant had 2.53-fold more catalytic efficiency (k cat/K m) towards beechwood xylan than wild-type and 3.0-fold more thermostability (t 1/2 [55°C]). XynIIΔNC4 displayed 3.33-, 4.38-, 1.37-, and 1.98-fold more activity against xylotriose, xylotetraose, xylopentaose, and xylohexaose, respectively, than XynII did. However, its half-life (t 1/2) in 4 % SDS was only 1.72 h, while that of XynII was 4.65 h. Circular dichroism analysis revealed that deletion of N- and C-terminal segments caused minor changes in secondary structure. Our observations suggest that the extra N- and C-terminal segments in wild-type XynII evolved to strengthen the interaction between these regions of the protein, making the local structure more rigid and reducing structural flexibility. In this way, N- and C-terminal truncations increased the thermostability and activity of XynII on different xylans and linear xylooligosaccharides, but reduced its resistance to SDS.

  1. Epilepsy by the Numbers: Epilepsy deaths by age, race/ethnicity, and gender in the United States significantly increased from 2005 to 2014.

    Science.gov (United States)

    Greenlund, Sujay F; Croft, Janet B; Kobau, Rosemarie

    2017-04-01

    To inform public health efforts to prevent epilepsy-related deaths, we used the Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research (WONDER; Wonder.cdc.gov) to examine any-listed epilepsy deaths for the period 2005-2014 by age groups (≤24, 25-44, 45-64, 65-84, ≥85years), sex, and race/ethnicity (non-Hispanic White, non-Hispanic African American, Hispanic, Asian/Pacific Islander, or American Indian/Alaska Native). Epilepsy deaths were defined by the International Classification of Diseases, Tenth Revision (ICD-10) codes G40.0-G40.9. The total number of deaths per year with epilepsy as any listed cause ranged from 1760 in 2005 to 2962 in 2014. Epilepsy was listed as the underlying cause of death for about 54% of all deaths with any mention of epilepsy in 2005 and for 43% of such deaths in 2014. Age-adjusted epilepsy mortality rates (as any-listed cause of death) per 100,000 significantly increased from 0.58 in 2005 to 0.85 in 2014 (47% increase). In 2014, deaths among the non-Hispanic Black population (1.42 deaths per 100,000) were higher than among non-Hispanic White (0.86 deaths per 100,000) and Hispanic populations (0.70 deaths per 100,000). Males had a higher mortality rate than females (1.01 per 100,000 versus 0.74 per 100,000 in 2014), and those aged 85years or older had the highest mortality among age groups. Results highlight the need for heightened action to prevent and monitor epilepsy-associated mortality. Published by Elsevier Inc.

  2. Significant increase in factual knowledge with web-assisted problem-based learning as part of an undergraduate cardio-respiratory curriculum.

    Science.gov (United States)

    Raupach, T; Münscher, C; Pukrop, T; Anders, S; Harendza, S

    2010-08-01

    In recent years, increasing attention has been paid to web-based learning although the advantages of computer-aided instruction over traditional teaching formats still need to be confirmed. This study examined whether participation in an online module on the differential diagnosis of dyspnoea impacts on student performance in a multiple choice examination of factual knowledge in cardiology and pneumology. A virtual problem-based learning environment for medical students supervised by postgraduate teachers was created. Seventy-four out of 183 fourth-year medical students volunteered to use the online module while attending a 6-week cardio-respiratory curriculum in summer 2007. Of these, 40 were randomly selected to be included (intervention group); the remaining 34 served as an internal control group. Analysis of all written exams taken during the preceding term showed that both groups were comparable (86.4 ± 1.1 vs. 85.9 ± 1.1%; p = 0.751). Students in the intervention group scored significantly higher in the final course assessment than students allocated to the control group (84.8 ± 1.3 vs. 79.5 ± 1.4%; p = 0.006; effect size 0.67). Thus, additional problem-based learning with an online module as part of an undergraduate cardio-respiratory curriculum lead to higher students' scores in an exam testing factual knowledge. Whether using this teaching format increases overall student motivation to engage in the learning process needs to be further investigated.

  3. Precision intrauterine contraception may significantly increase continuation of use: a review of long-term clinical experience with frameless copper-releasing intrauterine contraception devices

    Directory of Open Access Journals (Sweden)

    Wildemeersch D

    2013-04-01

    Full Text Available Dirk Wildemeersch,1 Ansgar Pett,2 Sohela Jandi,2 Thomas Hasskamp,3 Patrick Rowe,4 Marc Vrijens5 1Gynecological Outpatient Clinic and IUD Training Center, Ghent, Belgium; 2Gynecological Outpatient Clinic, Berlin, Germany; 3Gynecological Outpatient Clinic, Münster, Germany; 4Formely IUD Research Group at the UNDP/UNFPA/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction, World Health Organization, Geneva, Switzerland; 5Gynecological Outpatient Clinic, Ghent, Belgium Objective: The purpose of this paper is to review the experience with the frameless, anchored, GyneFix copper-releasing intrauterine contraceptive devices (IUCDs/IUDs (Contrel Europe, Belgium, and to demonstrate their high acceptability and low rate of discontinuation of use, which could contribute to current efforts that aim to reduce radically the high number of unintended pregnancies and induced abortions, particularly in young women. Materials and methods: This paper is based on studies that examined the differences in uterine volume and cavity size, related to age and parity, and on original clinical research data and practical experience with frameless copper IUDs, as well as on literature data on the IUD–endometrial cavity relationship of conventional IUDs, with special reference to side effects and user discontinuation. Results: The mean transverse diameter in nulliparous and parous women is significantly less than the length of the transverse arm of the TCu380A IUD (ParaGard, Duramed, NY, USA or the levonorgestrel intrauterine system (Mirena, Bayer, Germany. Small, frameless, flexible, and unidimensional copper IUDs appear to be well tolerated, with less impact on menstrual bleeding, resulting in low discontinuation rates when compared with standard-size conventional IUDs, which often result in increased expulsion rates, complaints of pain and erratic or increased menstrual bleeding, and subsequent high rates of

  4. The Clinical Significance of Increased Serum Proinflammatory Cytokines, C-Reactive Protein, and Erythrocyte Sedimentation Rate in Patients with Hidradenitis Suppurativa

    Directory of Open Access Journals (Sweden)

    D. Jiménez-Gallo

    2017-01-01

    Full Text Available Objectives. To assess inflammatory serum markers including serum proinflammatory cytokines, C-reactive protein (CRP, and erythrocyte sedimentation rate (ESR according to the clinical inflammatory activity of patients with hidradenitis suppurativa (HS. Patients and Methods. Seventy-four patients with HS were studied based on the Hidradenitis Suppurativa-Physician Global Assessment (HS-PGA score and Hurley staging system. Proinflammatory cytokines were measured using a multiplex cytokine assay. Twenty-two healthy volunteers were recruited. Results. Serum interleukin- (IL- 6, IL-23, soluble tumour necrosis factor alpha (TNF-α receptor I (sTNF-RI, CRP, and ESR were different in the patients with HS compared with those in the healthy controls (P0.25, P<0.05. The levels of IL-6 (r=0.53, P<0.001, CRP (r=0.54, P<0.001, and ESR (r=0.60, P<0.001 were especially well correlated with clinical inflammatory activity based on HS-PGA scores. The levels of IL-6, IL-8, sTNF-RI, sTNF-RII, CRP, and ESR were significantly elevated according to Hurley staging system. Conclusions. Serum proinflammatory cytokines, CRP, and ESR are increased in relation to the clinical inflammatory activity of patients with HS compared with healthy controls. Serum IL-6, CRP, and ESR are effective biomarkers for evaluating the severity of HS.

  5. Significantly increased detection rate of drugs of abuse in urine following the introduction of new German driving licence re-granting guidelines.

    Science.gov (United States)

    Agius, Ronald; Nadulski, Thomas; Kahl, Hans-Gerhard; Dufaux, Bertin

    2012-02-10

    In this paper we present the first assessment of the new German driving licence re-granting medical and psychological assessment (MPA) guidelines by comparing over 3500 urine samples tested under the old MPA cut-offs to over 5000 samples tested under the new MPA cut-offs. Since the enzyme multiplied immunoassay technique (EMIT) technology used previously was not sensitive enough to screen for drugs at such low concentrations, as suggested by the new MPA guidelines, enzyme-linked immunosorbent assay (ELISA) screening kits were used to screen for the drugs of abuse at the new MPA cut-offs. The above comparison revealed significantly increased detection rates of drug use or exposure during the rehabilitation period as follows: 1.61, 2.33, 3.33, and 7 times higher for 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid (THC-COOH), morphine, benzoylecgonine and amphetamine respectively. The present MPA guidelines seem to be more effective to detect non-abstinence from drugs of abuse and hence to detecting drivers who do not yet fulfil the MPA requirements to regain their revoked driving licence. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  6. Time to recurrence is a significant predictor of cancer-specific survival after recurrence in patients with recurrent renal cell carcinoma--results from a comprehensive multi-centre database (CORONA/SATURN-Project).

    Science.gov (United States)

    Brookman-May, Sabine D; May, Matthias; Shariat, Shahrokh F; Novara, Giacomo; Zigeuner, Richard; Cindolo, Luca; De Cobelli, Ottavio; De Nunzio, Cosimo; Pahernik, Sascha; Wirth, Manfred P; Longo, Nicola; Simonato, Alchiede; Serni, Sergio; Siracusano, Salvatore; Volpe, Alessandro; Morgia, Giuseppe; Bertini, Roberto; Dalpiaz, Orietta; Stief, Christian; Ficarra, Vincenzo

    2013-11-01

    To assess the prognostic impact of time to recurrence (TTR) on cancer-specific survival (CSS) after recurrence in patients with renal cell carcinoma (RCC) undergoing radical nephrectomy or nephron-sparing surgery. To analyse differences in clinical and histopathological criteria between patients with early and late recurrence. Of 13,107 patients with RCC from an international multicentre database, 1712 patients developed recurrence in the follow-up (FU), at a median (interquartile range) of 50.1 (25-106) months. In all, 1402 patients had recurrence at ≤5 years (Group A) and 310 patients beyond this time (Group B). Differences in clinical and histopathological variables between patients with early and late recurrence were analysed. The influence of TTR and further variables on CSS after recurrence was assessed by Cox regression analysis. Male gender, advanced age, tumour diameter and stage, Fuhrman grade 3-4, lymphovascular invasion (LVI), and pN + stage were significantly more frequent in patients with early recurrence, who had a significantly reduced 3-year CSS of 30% compared with patients in Group B (41%; P = 0.001). Age, gender, tumour histology, pT stage, and continuous TTR (hazard ratio 0.99, P = 0.006; monthly interval) independently predicted CSS. By inclusion of dichotomised TTR in the multivariable model, a significant influence of this variable on CSS was present until 48 months after surgery, but not beyond this time. Advanced age, male gender, larger tumour diameters, LVI, Fuhrman grade 3-4, pN + stage, and advanced tumour stages are associated with early recurrence. Up to 4 years from surgery, a shorter TTR independently predicts a reduced CSS after recurrence. © 2013 The Authors. BJU International © 2013 BJU International.

  7. Context-dependent codon partition models provide significant increases in model fit in atpB and rbcL protein-coding genes.

    Science.gov (United States)

    Baele, Guy; Van de Peer, Yves; Vansteelandt, Stijn

    2011-05-27

    Accurate modelling of substitution processes in protein-coding sequences is often hampered by the computational burdens associated with full codon models. Lately, codon partition models have been proposed as a viable alternative, mimicking the substitution behaviour of codon models at a low computational cost. Such codon partition models however impose independent evolution of the different codon positions, which is overly restrictive from a biological point of view. Given that empirical research has provided indications of context-dependent substitution patterns at four-fold degenerate sites, we take those indications into account in this paper. We present so-called context-dependent codon partition models to assess previous empirical claims that the evolution of four-fold degenerate sites is strongly dependent on the composition of its two flanking bases. To this end, we have estimated and compared various existing independent models, codon models, codon partition models and context-dependent codon partition models for the atpB and rbcL genes of the chloroplast genome, which are frequently used in plant systematics. Such context-dependent codon partition models employ a full dependency scheme for four-fold degenerate sites, whilst maintaining the independence assumption for the first and second codon positions. We show that, both in the atpB and rbcL alignments of a collection of land plants, these context-dependent codon partition models significantly improve model fit over existing codon partition models. Using Bayes factors based on thermodynamic integration, we show that in both datasets the same context-dependent codon partition model yields the largest increase in model fit compared to an independent evolutionary model. Context-dependent codon partition models hence perform closer to codon models, which remain the best performing models at a drastically increased computational cost, compared to codon partition models, but remain computationally interesting

  8. Innovations’ Survival

    Directory of Open Access Journals (Sweden)

    Jakub Tabas

    2016-01-01

    Full Text Available Innovations currently represent a tool of maintaining the going concern of a business entity and its competitiveness. However, effects of innovations are not infinite and if an innovation should constantly preserve a life of business entity, it has to be a continual chain of innovations, i.e. continual process. Effective live of a single innovation is limited while the limitation is derived especially from industry. The paper provides the results of research on innovations effects in the financial performance of small and medium-sized enterprises in the Czech Republic. Objective of this paper is to determine the length and intensity of the effects of technical innovations in company’s financial performance. The economic effect of innovations has been measured at application of company’s gross production power while the Deviation Analysis has been applied for three years’ time series. Subsequently the Survival Analysis has been applied. The analyses are elaborated for three statistical samples of SMEs constructed in accordance to the industry. The results obtained show significant differences in innovations’ survival within these three samples of enterprises then. The results are quite specific for the industries, and are confronted and discussed with the results of authors’ former research on the issue.

  9. Survival after blood transfusion

    DEFF Research Database (Denmark)

    Kamper-Jørgensen, Mads; Ahlgren, Martin; Rostgaard, Klaus

    2008-01-01

    of transfusion recipients in Denmark and Sweden followed for up to 20 years after their first blood transfusion. Main outcome measure was all-cause mortality. RESULTS: A total of 1,118,261 transfusion recipients were identified, of whom 62.0 percent were aged 65 years or older at the time of their first...... the SMR remained significantly 1.3-fold increased. CONCLUSION: The survival and relative mortality patterns among blood transfusion recipients were characterized with unprecedented detail and precision. Our results are relevant to assessments of the consequences of possible transfusion-transmitted disease...... as well as for cost-benefit estimation of new blood safety interventions....

  10. Nuclear War Survival Skills

    Energy Technology Data Exchange (ETDEWEB)

    Kearny, C.H.

    2002-06-24

    The purpose of this book is to provide Americans with information and instructions that will significantly increase their chances of surviving a possible nuclear attack. It brings together field-tested instructions that, if followed by a large fraction of Americans during a crisis that preceded an attack, could save millions of lives. The author is convinced that the vulnerability of our country to nuclear threat or attack must be reduced and that the wide dissemination of the information contained in this book would help achieve that objective of our overall defense strategy.

  11. Targeting CXCR1/2 Significantly Reduces Breast Cancer Stem Cell Activity and Increases the Efficacy of Inhibiting HER2 via HER2-dependent and -independent Mechanisms

    Science.gov (United States)

    Singh, Jagdeep K.; Farnie, Gillian; Bundred, Nigel J.; Simões, Bruno M; Shergill, Amrita; Landberg, Göran; Howell, Sacha; Clarke, Robert B.

    2012-01-01

    Purpose Breast cancer stem-like cells (CSCs) are an important therapeutic target as they are predicted to be responsible for tumour initiation, maintenance and metastases. Interleukin-8 (IL-8) is upregulated in breast cancer and associated with poor prognosis. Breast cancer cell line studies indicate that IL-8 via its cognate receptors, CXCR1 and CXCR2, is important in regulating breast CSC activity. We investigated the role of IL-8 in the regulation of CSC activity using patient-derived breast cancers and determined the potential benefit of combining CXCR1/2 inhibition with HER2-targeted therapy. Experimental design CSC activity of metastatic and invasive human breast cancers (n=19) was assessed ex vivo using the mammosphere colony forming assay. Results Metastatic fluid IL-8 level correlated directly with mammosphere formation (r=0.652; Pbreast cancers (n=17). IL-8 induced activation of EGFR/HER2 and downstream signalling pathways and effects were abrogated by inhibition of SRC, EGFR/HER2, PI3K or MEK. Furthermore, lapatinib inhibited the mammosphere-promoting effect of IL-8 in both HER2-positive and negative patient-derived cancers. CXCR1/2 inhibition also blocked the effect of IL-8 on mammosphere formation and added to the efficacy of lapatinib in HER2-positive cancers. Conclusions These studies establish a role for IL-8 in the regulation of patient-derived breast CSC activity and demonstrate that IL-8/CXCR1/2 signalling is partly mediated via a novel SRC and EGFR/HER2-dependent pathway. Combining CXCR1/2 inhibitors with current HER2-targeted therapies has potential as an effective therapeutic strategy to reduce CSC activity in breast cancer and improve the survival of HER2-positive patients. PMID:23149820

  12. Increased litter survival rates, reduced clinical illness and better lactogenic immunity against TGEV in gilts that were primed as neonates with porcine respiratory coronavirus (PRCV).

    Science.gov (United States)

    Wesley, Ronald D; Lager, Kelly M

    2003-09-01

    Establishing immunological memory in female piglets at a young age with PRCV was effective in inducing a secondary immune response to a limiting dose of virulent TGEV given orally 13-18 days prior to farrowing. Subsequently, because of passive antibody transfer, the offspring of these primed gilts were more efficient in surviving a lethal TGEV challenge. An average survival rate of 89% occurred in 6 litters of piglets from primed gilts that were boosted with 2.8 x 10(6) plaque forming units (PFU) of TGEV whereas 76% of the piglets survived in three litters that suckled primed gilts boosted with 3.0 x 10(5)PFU of TGEV. Non-primed gilts given identical pre-farrowing doses of TGEV had litter survival rates of 63 and 55%, respectively. Moreover, both groups of litters from primed gilts suffered less clinical illness (as measured by the extent of weight loss post-challenge) than control litters. Priming of the piglets as neonates and boosting the pregnant gilts produced an anamnestic systemic immune response and correspondingly higher milk titers in the primed gilts compared to control animals. Thus, priming piglets with PRCV was beneficial in providing resistance to TGEV and could be incorporated into a vaccine strategy that yields better protection against TGEV.

  13. Increasing CPR duration prior to first defibrillation does not improve return of spontaneous circulation or survival in a swine model of prolonged ventricular fibrillation

    Science.gov (United States)

    Rittenberger, Jon C.; Suffoletto, Brian; Salcido, David; Logue, Eric; Menegazzi, James J.

    2008-01-01

    Introduction The optimum duration of cardiopulmonary resuscitation (CPR) prior to first rescue shock is unknown. Clinical trials have used 90s and 180s. Neither of these durations may be optimal. We sought to determine the optimum duration of CPR prior to first defibrillation attempt and whether this varied depending on the duration of ventricular fibrillation (VF). In this porcine model of basic life support, our outcomes were rates of return of spontaneous circulation (ROSC), survival, and coronary perfusion pressure (CPP). Methods We anesthetized and instrumented 45 swine and then induced VF. After 5 or 8 minutes of untreated VF, we randomized the swine to mechanical CPR for 90, 180, or 300s. A single rescue shock (150J biphasic) was then administered. If this shock failed, 2 minutes of mechanical CPR were completed prior to the next rescue shock. CPP was calculated for each 30 second epoch. ROSC was defined as a blood pressure >80mmHg sustained for 60s. Survival was defined as sustained ROSC for 20 minutes. Data were analyzed with descriptive statistics, Fisher’s exact test, and ANOVA. Results In the 5 minute VF cohort, the rate of ROSC did not differ between the three groups (90s: 25%; 180s: 38%; 300s: 38%, p>.05). Survival rates did not differ (90s: 25%; 180s: 25%; 300s: 25%, p>0.05). In the 8 minute VF cohort, no animals experienced ROSC or survival. CPP were calculated by 30 second epoch and did not differ between the three groups (p>0.05). CPPs decline after 180s of CPR. Conclusions ROSC and survival were equivalent regardless of VF duration and CPR duration. When CPR begins late, CPPs are low, stressing the importance of early CPR. We do not recommend 300s of CPR unless a defibrillator is unavailable. PMID:18620793

  14. Microencapsulation increases survival of the probiotic L .plantarum IS-10506, but not E. faecium IS-27526 in a dynamic, computer-controlled in vitro model of the upper gastrointestinal tract.

    Science.gov (United States)

    Surono, Ingrid; Verhoeven, Jessica; Verbruggen, Sanne; Venema, Koen

    2018-02-23

    to test the effect of microencapsulation on the survival of two probiotic strains isolated from Dadih, Indonesian fermented buffalo milk, in a dynamic, computer controlled in vitro model of the upper gastrointestinal (GI) tract (TIM-1), simulating human adults. Free or microencapsulated probiotics, L.plantarum IS-10506 or E.faecium IS-27526, resuspended in milk were studied for survival in the complete TIM-1 system (stomach + small intestine) or in the gastric compartment of TIM-1 only. Hourly samples collected after the ileal-cecal valve or after the pylorus were plated on MRS agar (for Lactobacillus) or S&B agar (for Enterococcus). Survival of the free cells after transit through the complete TIM-1 system was on average for the E. faecium and L. plantarum 15.0% and 18.5%, respectively. Survival of the microencapsulated E. faecium and L. plantarum was 15.7% and 84.5%, respectively. The free cells were further assessed in only the gastric compartment of TIM-1. E. faecium and L. plantarum showed an average survival of 39% and 32%, respectively, after gastric passage. There is similar sensitivity to gastric acid as well as survival after complete upper GI tract transit of free cells, but microencapsulation only protected L. plantarum. Survival of microencapsulated L. plantarum IS-10506 is increased compared to free cells in a validated in vitro model of the upper GI tract. It increases its use as ingredient of functional foods. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  15. Community reinforcement training for family and significant others of drug abusers: a unilateral intervention to increase treatment entry of drug users.

    Science.gov (United States)

    Kirby, K C; Marlowe, D B; Festinger, D S; Garvey, K A; La Monaca, V

    1999-08-02

    We randomly assigned 32 concerned family members and significant others (FSOs) of drug users (DUs) to a community reinforcement training intervention or a popular 12-step self-help group. We measured problems arising from the DU's behavior, social functioning of the DU and FSO, and mood of the FSO at baseline and 10 weeks later. We also monitored the FSOs' treatment attendance and treatment entry of the DUs. The treatment groups showed equal reductions from baseline to follow-up in problems and improvements in social functioning and mood of the FSO. However the community reinforcement intervention was significantly better at retaining FSOs in treatment and inducing treatment entry of the DUs.

  16. Experimentally-induced immune activation in natural hosts of SIV induces significant increases in viral replication and CD4+ T cell depletion

    Energy Technology Data Exchange (ETDEWEB)

    Ribeiro, Ruy M [Los Alamos National Laboratory

    2008-01-01

    Chronically SIVagm-infected African green monkeys (AGMs) have a remarkably stable non-pathogenic disease course, with levels of immune activation in chronic SIVagm infection similar to those observed in uninfected monkeys and stable viral loads (VLs) for long periods of time. In vivo administration of lipopolysaccharide (LPS) or an IL-2/diphtheria toxin fusion protein (Ontak) to chronically SIVagm-infected AGMs triggered increases in immune activation and subsequently of viral replication and depletion of intestinal CD4{sup +} T cells. Our study indicates that circulating microbial products can increase viral replication by inducing immune activation and increasing the number of viral target cells, thus demonstrating that immune activation and T cell prolifeation are key factors in AIDS pathogenesis.

  17. A diet with 3% of energy from a mixture of Omega-3 fatty acids significantly increases in vivo lipid peroxidation in postmenopausal women

    Science.gov (United States)

    Dietary omega-3 polyunsaturated fatty acids (n-3 PUFA) are recommended by public health organizations to reduce the risk of disease. However, n-3 PUFA are susceptible to an increase in lipid peroxidation in the human body. As part of a crossover dietary intervention study of a diet (20% of energy ...

  18. The significance of the European beaver (Castor fibre activity for the process of renaturalization of river valleys in the era of increasing

    Directory of Open Access Journals (Sweden)

    Kusztal Piotr

    2017-03-01

    Full Text Available Changes in the environment that are caused by the activity of beavers bring numerous advantages. They affect the increase in biodiversity, contribute to improving the condition of cleanliness of watercourses, improve local water relations and restore the natural landscape of river valleys.

  19. Significant Increase in Factual Knowledge with Web-Assisted Problem-Based Learning as Part of an Undergraduate Cardio-Respiratory Curriculum

    Science.gov (United States)

    Raupach, T.; Munscher, C.; Pukrop, T.; Anders, S.; Harendza, S.

    2010-01-01

    In recent years, increasing attention has been paid to web-based learning although the advantages of computer-aided instruction over traditional teaching formats still need to be confirmed. This study examined whether participation in an online module on the differential diagnosis of dyspnoea impacts on student performance in a multiple choice…

  20. Co-downregulation of the hydroxycinnamoyl-CoA:shikimate hydroxycinnamoyl transferase and coumarate 3-hydroxylase significantly increases cellulose content in transgenic alfalfa (Medicago sativa L.).

    Science.gov (United States)

    Tong, Zongyong; Li, Heng; Zhang, Rongxue; Ma, Lei; Dong, Jiangli; Wang, Tao

    2015-10-01

    Lignin is a component of the cell wall that is essential for growth, development, structure and pathogen resistance in plants, but high lignin is an obstacle to the conversion of cellulose to ethanol for biofuel. Genetically modifying lignin and cellulose contents can be a good approach to overcoming that obstacle. Alfalfa (Medicago sativa L.) is rich in lignocellulose biomass and used as a model plant for the genetic modification of lignin in this study. Two key enzymes in the lignin biosynthesis pathway-hydroxycinnamoyl -CoA:shikimate hydroxycinnamoyl transferase (HCT) and coumarate 3-hydroxylase (C3H)-were co-downregulated. Compared to wild-type plants, the lignin content in the modified strain was reduced by 38%, cellulose was increased by 86.1%, enzyme saccharification efficiency was increased by 10.9%, and cell wall digestibility was increased by 13.0%. The modified alfalfa exhibited a dwarf phenotype, but normal above ground biomass. This approach provides a new strategy for reducing lignin and increasing cellulose contents and creates a new genetically modified crop with enhanced value for biofuel. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  1. Increased levels of IL-6 in the cerebrospinal fluid of patients with chronic schizophrenia — significance for activation of the kynurenine pathway

    Science.gov (United States)

    Schwieler, Lilly; Larsson, Markus K.; Skogh, Elisabeth; Kegel, Magdalena E.; Orhan, Funda; Abdelmoaty, Sally; Finn, Anja; Bhat, Maria; Samuelsson, Martin; Lundberg, Kristina; Dahl, Marja-Liisa; Sellgren, Carl; Schuppe-Koistinen, Ina; Svensson, Camilla I.; Erhardt, Sophie; Engberg, Göran

    2015-01-01

    Background Accumulating evidence indicates that schizophrenia is associated with brain immune activation. While a number of reports suggest increased cytokine levels in patients with schizophrenia, many of these studies have been limited by their focus on peripheral cytokines or confounded by various antipsychotic treatments. Here, well-characterized patients with schizophrenia, all receiving olanzapine treatment, and healthy volunteers were analyzed with regard to cerebrospinal fluid (CSF) levels of cytokines. We correlated the CSF cytokine levels to previously analyzed metabolites of the kynurenine (KYN) pathway. Methods We analyzed the CSF from patients and controls using electrochemiluminescence detection with regard to cytokines. Cell culture media from human cortical astrocytes were analyzed for KYN and kynurenic acid (KYNA) using high-pressure liquid chromatography or liquid chromatography/mass spectrometry. Results We included 23 patients and 37 controls in our study. Patients with schizophrenia had increased CSF levels of interleukin (IL)-6 compared with healthy volunteers. In patients, we also observed a positive correlation between IL-6 and the tryptophan:KYNA ratio, indicating that IL-6 activates the KYN pathway. In line with this, application of IL-6 to cultured human astrocytes increased cell medium concentration of KYNA. Limitations The CSF samples had been frozen and thawed twice before analysis of cytokines. Median age differed between patients and controls. When appropriate, all present analyses were adjusted for age. Conclusion We have shown that IL-6, KYN and KYNA are elevated in patients with chronic schizophrenia, strengthening the idea of brain immune activation in patients with this disease. Our concurrent cell culture and clinical findings suggest that IL-6 induces the KYN pathway, leading to increased production of the N-methyl-d-aspartate receptor antagonist KYNA in patients with schizophrenia. PMID:25455350

  2. Significant association of increased PD-L1 and PD-1 expression with nodal metastasis and a poor prognosis in oral squamous cell carcinoma.

    Science.gov (United States)

    Maruse, Y; Kawano, S; Jinno, T; Matsubara, R; Goto, Y; Kaneko, N; Sakamoto, T; Hashiguchi, Y; Moriyama, M; Toyoshima, T; Kitamura, R; Tanaka, H; Oobu, K; Kiyoshima, T; Nakamura, S

    2018-01-26

    Programmed cell death ligand 1 (PD-L1) and its receptor PD-1 are immune checkpoint molecules that attenuate the immune response. Blockade of PD-L1 enhances the immune response in a variety of tumours and thus serves as an effective anti-cancer treatment. However, the biological and prognostic roles of PD-L1/PD-1 signalling in oral squamous cell carcinoma (OSCC) remain to be elucidated. The purpose of this study was to examine the correlation of PD-L1/PD-1 signalling with the prognosis of OSCC patients to assess its potential therapeutic relevance. The expression of PD-L1 and of PD-1 was determined immunohistochemically in 97 patients with OSCC and the association of this expression with clinicopathological characteristics was examined. Increased expression of PD-L1 was found in 64.9% of OSCC cases and increased expression of PD-1 was found in 61.9%. Univariate and multivariate analysis revealed that increased expression of PD-L1 and PD-1 positively correlated with cervical lymph node metastasis. The expression of CD25, an activated T-cell marker, was negatively correlated with the labelling index of PD-L1 and PD-1. Moreover, the patient group with PD-L1-positive and PD-1-positive expression showed a more unfavourable prognosis than the group with PD-L1-negative and PD-1-negative expression. These data suggest that increased PD-L1 and PD-1 expression is predictive of nodal metastasis and a poor prognosis and is possibly involved in cancer progression via attenuating the immune response. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  3. Seed-Specific Expression of a Lysine-Rich Protein Gene, GhLRP, from Cotton Significantly Increases the Lysine Content in Maize Seeds

    Directory of Open Access Journals (Sweden)

    Jing Yue

    2014-03-01

    Full Text Available Maize seed storage proteins are a major source of human and livestock consumption. However, these proteins have poor nutritional value, because they are deficient in lysine and tryptophan. Much research has been done to elevate the lysine content by reducing zein content or regulating the activities of key enzymes in lysine metabolism. Using the naturally lysine-rich protein genes, sb401 and SBgLR, from potato, we previously increased the lysine and protein contents of maize seeds. Here, we examined another natural lysine-rich protein gene, GhLRP, from cotton, which increased the lysine content of transgenic maize seeds at levels varying from 16.2% to 65.0% relative to the wild-type. The total protein content was not distinctly different, except in the six transgenic lines. The lipid and starch levels did not differ substantially in Gossypium hirsutum L. lysine-rich protein (GhLRP transgenic kernels when compared to wild-type. The agronomic characteristics of all the transgenic maize were also normal. GhLRP is a high-lysine protein candidate gene for increasing the lysine content of maize. This study provided a valuable model system for improving maize lysine content.

  4. Significantly increased expression of OCT4 and ABCG2 in spheroid body-forming cells of the human gastric cancer MKN-45 cell line.

    Science.gov (United States)

    Liu, Jianming; Wang, Lei; Ma, Lilin; Xu, Junfei; Liu, Chun; Zhang, Jianguo; Liu, Jie; Chen, Ruixin

    2013-10-01

    The cancer stem cell (CSC) theory hypothesizes that CSCs are the cause of tumor formation, recurrence and metastasis. Key to the study of CSCs is their isolation and identification. The present study investigated whether spheroid body-forming cells in the human gastric cancer (GC) MKN-45 cell line are enriched for CSC properties, and also assessed the expression of the candidate CSC markers, octamer-binding transcription factor-4 (OCT4) and adenosine triphosphate-binding cassette transporter G2 (ABCG2) in the MKN-45 spheroid body cells. The MKN-45 cells were plated in a stem cell-conditioned culture system to allow for spheroid body formation. The expression levels of OCT4 and ABCG2 in the spheroid body cells were assessed by qPCR, western blot analysis and immunofluorescence staining, while the tumorigenicity of the spheroid body-forming cells was assessed by in vivo xenograft studies in nude mice. The MKN-45 cells were able to form spheroid bodies when cultured in stem cell-conditioned medium. The spheroid body-forming cells showed a significantly higher (Pspheroid body cells from the MKN-45 GC cell line cultured in stem cell-conditioned medium possessed gastric CSC properties. The co-expression of OCT4 and ABCG2 by these cells may represent the presence of a subpopulation of gastric CSCs.

  5. Conjugation of the CRM197-inulin conjugate significantly increases the immunogenicity of Mycobacterium tuberculosis CFP10-TB10.4 fusion protein.

    Science.gov (United States)

    Hu, Shun; Yu, Weili; Hu, Chunyang; Wei, Dong; Shen, Lijuan; Hu, Tao; Yi, Youjin

    2017-11-01

    Mycobacterium tuberculosis (Mtb) is a serious fatal pathogen that causes tuberculosis (TB). Effective vaccination is urgently needed to deal with the serious threat from TB. Mtb-secreted protein antigens are important virulence determinants of Mtb with poor immunogenicity. Adjuvants and antigen delivery systems are thus highly desired to improve the immunogenicity of protein antigens. Inulin is a biocompatible polysaccharide (PS) adjuvant that can stimulate a strong cellular and humoral immunity. Bacterial capsular PS and haptens have been conjugated with cross-reacting material 197 (CRM 197 ) to improve their immunogenicity. CFP10 and TB10.4 were two Mtb-secreted immunodominant protein antigens. A CFP10-TB10.4 fusion protein (CT) was used as the antigen for covalent conjugation with the CRM 197 -inulin conjugate (CRM-inu). The resultant conjugate (CT-CRM-inu) elicited high CT-specific IgG titers, stimulated splenocyte proliferation and provoked the secretion of Th1-type and Th2-type cytokines. Conjugation with CRM-inu significantly prolonged the systemic circulation of CT and exposure to the immune system. Moreover, CT-CRM-inu showed no apparent toxicity to cardiac, hepatic and renal functions. Thus, conjugation of CT with CRM-inu provided an effective strategy for development of protein-based vaccines against Mtb infection. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. A new polymorphism biomarker rs629367 associated with increased risk and poor survival of gastric cancer in chinese by up-regulated miRNA-let-7a expression.

    Directory of Open Access Journals (Sweden)

    Qian Xu

    Full Text Available BACKGROUND: Variant in pri-miRNA could affect miRNA expression and mature process or splicing efficiency, thus altering the hereditary susceptibility and prognosis of cancer. We aimed to assess miRNA-let-7 single nucleotide polymorphisms (SNP associated with the risk and prognosis of gastric cancer (GC as predicting biomarkers, and furthermore, its possible mechanisms. METHODS: A two-stage case-control study was designed to screen four miRNA SNPs (pri-let-7a-2 rs629367 and rs1143770, pri-let-7a-1 rs10739971, pri-let-7f-2 rs17276588 in 107 GC patients, 107 atrophic gastritis (AG, and matched 124 controls using PCR-RFLP. Two promising SNPs were validated in another independent 1949 samples (including 579 gastric cancer patients, 649 atrophic gastritis and 721 controls using Sequenom MassARRAY platform and sequencing. RESULTS: We found that pri-let-7a-2 rs629367 CC variant genotype was associated with increased risks of gastric cancer and atrophic gastritis by 1.83-fold and 1.86-fold, respectively. For gastric cancer prognosis, patients with rs629367 CC genotype had significantly poorer survival than patients with AA genotype (log-rank P = 0.004. We further investigated the let-7a expression levels in serum and found that let-7a expression elevated gradually for rs629367 AA, CA, CC genotype in the atrophic gastritis group (P = 0.043. Furthermore, we confirmed these findings in vitro study by overexpressing let-7a carrying pri-let-7a-2 wild-type A or polymorphic-type C allele (P<0.001. CONCLUSIONS: pri-let-7a-2 rs629367 CC genotype could increase the risks of gastric cancer as well as atrophic gastritis and was also associated with poor survival of gastric cancer, which possibly by affecting the mature let-7a expression, and could serve as a predicting biomarker for high-risk and poor prognosis of gastric cancer.

  7. High fasting blood glucose and obesity significantly and independently increase risk of breast cancer death in hormone receptor-positive disease.

    Science.gov (United States)

    Minicozzi, Pamela; Berrino, Franco; Sebastiani, Federica; Falcini, Fabio; Vattiato, Rosa; Cioccoloni, Francesca; Calagreti, Gioia; Fusco, Mario; Vitale, Maria Francesca; Tumino, Rosario; Sigona, Aurora; Budroni, Mario; Cesaraccio, Rosaria; Candela, Giuseppa; Scuderi, Tiziana; Zarcone, Maurizio; Campisi, Ildegarda; Sant, Milena

    2013-12-01

    We investigated the effect of fasting blood glucose and body mass index (BMI) at diagnosis on risk of breast cancer death for cases diagnosed in five Italian cancer registries in 2003-2005 and followed up to the end of 2008. For 1607 Italian women (≥15 years) with information on BMI or blood glucose or diabetes, we analysed the risk of breast cancer death in relation to glucose tertiles (≤84.0, 84.1-94.0, >94.0 mg/dl) plus diabetic and unspecified categories; BMI tertiles (≤23.4, 23.5-27.3, >27.3 kg/m(2), unspecified), stage (T1-3N0M0, T1-3N+M0 plus T4anyNM0, M1, unspecified), oestrogen (ER) and progesterone (PR) status (ER+PR+, ER-PR-, ER and PR unspecified, other), age, chemotherapy and endocrine therapy, using multiple regression models. Separate models for ER+PR+ and ER-PR- cases were also run. Patients often had T1-3N0M0, ER+PR+ cancers and received chemotherapy or endocrine therapy; only 6% were M1 and 17% ER-PR-. Diabetic patients were older and had more often high BMI (>27 kg/m(2)), ER-PR-, M1 cancers than other patients. For ER+PR+ cases, with adjustment for other variables, breast cancer mortality was higher in women with high BMI than those with BMI 23.5-27.3 kg/m(2) (hazard ratio (HR)=2.9, 95% confidence interval (CI) 1.2-6.9). Breast cancer mortality was also higher in women with high (>94 mg/dl) blood glucose compared to those with glucose 84.1-94.0mg/dl (HR=2.6, 95% CI 1.2-5.7). Our results provide evidence that in ER+PR+ patients, high blood glucose and high BMI are independently associated with increased risk of breast cancer death. Detection and correction of these factors in such patients may improve prognosis. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. Body size and survival in premenopausal breast cancer.

    Science.gov (United States)

    Greenberg, E. R.; Vessey, M. P.; McPherson, K.; Doll, R.; Yeates, D.

    1985-01-01

    The survival experience of 582 women with premenopausal breast cancer was examined to determine whether prognosis was related to body size or to demographic and reproductive factors. During the follow-up period 228 patients died and 18 emigrated or were lost to follow-up. Usual body weight, reported at the time of diagnosis, was a strong predictor of survival, with a statistically significant trend towards lower survival with increasing weight. Height and obesity (Quetelet index) were not significantly related to survival, although the tallest women and the most obese women appeared to fare worst. Other characteristics of prognostic importance were disease stage and reproductive history (women who were older when their first child was born fared better). Women aged 46-50 when diagnosed also appeared more likely to survive but no clear trend with age was evident. Other characteristics of the women including social class, cigarette use and oral contraceptive use were not significantly related to survival probability. PMID:3994912

  9. Increased survival of human free fat grafts with varying densities of human adipose-derived stem cells and platelet-rich plasma.

    Science.gov (United States)

    Li, Kun; Li, Feng; Li, Jie; Wang, Hang; Zheng, Xiaohui; Long, Jie; Guo, Weihua; Tian, Weidong

    2017-01-01

    The high absorption rate of transplanted fat has limited the application of autogenous fat grafts in the clinical setting. Therefore, this study aimed to evaluate the effects of platelet-rich plasma (PRP) and adipose-derived stem cells (ASCs) on fat regeneration by investigating the impact of PRP and conditioned medium on the biological characteristics of ASCs. Fat grafts were prepared with ASCs at densities of 107 /ml, 106 /ml, 105 /ml, 104 /ml and 0/ml with and without PRP and injected subcutaneously into nude mice. Liquid overflow method, haematoxylin and eosin staining, and immunohistochemical analyses were used to examine the fat grafts. The residual fat volume of the 105 /ml ASC + PRP group was significantly higher than that of other treatment conditions after 90 days. Furthermore, histological examination revealed that in 105 /ml ASCs-treated grafts normal adipocyte area and capillary formation were increased dramatically compared with other treatment conditions. It is concluded that fat grafts consisting of PRP and 105 /ml ASCs constitute an ideal transplant strategy, which may result in decreased absorption and accelerated fat regeneration. This simple and reliable method could provide a valuable and needed tool in plastic and reconstructive surgery. Copyright © 2014 John Wiley & Sons, Ltd. Copyright © 2014 John Wiley & Sons, Ltd.

  10. Implementing a simplified neonatal resuscitation protocol-helping babies breathe at birth (HBB - at a tertiary level hospital in Nepal for an increased perinatal survival

    Directory of Open Access Journals (Sweden)

    KC Ashish

    2012-10-01

    Full Text Available Abstract Background Reducing neonatal death has been an emerging challenge in low and middle income countries in the past decade. The development of the low cost interventions and their effective delivery are needed to reduce deaths from birth asphyxia. This study will assess the impact of a simplified neonatal resuscitation protocol provided by Helping Babies Breathe (HBB at a tertiary hospital in Nepal. Perinatal outcomes and performance of skilled birth attendants on management of intrapartum-related neonatal hypoxia will be the main measurements. Methods/Design The study will be carried out at a tertiary level maternity hospital in Nepal. A prospective cohort-study will include a six-month baseline a six month intervention period and a three-month post intervention period. A quality improvement process cycle will introduce the neonatal resuscitation protocol. A surveillance system, including CCD cameras and pulse oximeters, will be set up to evaluate the intervention. Discussion Along with a technique to improve health workers performance on the protocol, the study will generate evidence on the research gap on the effectiveness of the simplified neonatal resuscitation protocol on intrapartum outcome and early neonatal survival. This will generate a global interest and inform policymaking in relation to delivery care in all income settings. Trial registration ISRCTN97846009

  11. Survival in Women with NSCLC

    Science.gov (United States)

    Katcoff, Hannah; Wenzlaff, Angela S.; Schwartz, Ann G.

    2014-01-01

    Introduction Although lung cancer is the leading cause of cancer death in women, few studies have investigated the hormonal influence on survival after a lung cancer diagnosis and results have been inconsistent. We evaluated the role of reproductive and hormonal factors in predicting overall survival in women with non–small-cell lung cancer (NSCLC). Methods Population-based lung cancer cases diagnosed between November 1, 2001 and October 31, 2005 were identified through the Metropolitan Detroit Surveillance, Epidemiology, and End Results Registry. Interview and follow-up data were collected for 485 women. Cox proportional hazard regression models were used to determine hazard ratios (HRs) for death after an NSCLC diagnosis associated with reproductive and hormonal variables. Results Use of hormone therapy (HT) was associated with improved survival (HR, 0.69; 95% confidence interval, 0.54–0.89), adjusting for stage, surgery, radiation, education level, pack-years of smoking, age at diagnosis, race, and a multiplicative interaction between stage and radiation. No other reproductive or hormonal factor was associated with survival after an NSCLC diagnosis. Increased duration of HT use before the lung cancer diagnosis (132 months or longer) was associated with improved survival (HR, 0.54; 95% confidence interval, 0.37–0.78), and this finding remained significant in women taking either estrogen alone or progesterone plus estrogen, never smokers, and smokers. Conclusion These findings suggest that HT use, in particular use of estrogen plus progesterone, and long-term HT use are associated with improved survival of NSCLC. PMID:24496005

  12. RX-207, a Small Molecule Inhibitor of Protein Interaction with Glycosaminoglycans (SMIGs), Reduces Experimentally Induced Inflammation and Increases Survival Rate in Cecal Ligation and Puncture (CLP)-Induced Sepsis.

    Science.gov (United States)

    Juhas, Stefan; Harris, Nicholas; Il'kova, Gabriela; Rehák, Pavol; Zsila, Ferenc; Yurgenzon Kogan, Faina; Lahmy, Orly; Zhuk, Regina; Gregor, Paul; Koppel, Juraj

    2018-02-01

    The fused quinazolinone derivative, RX-207, is chemically and functionally related to small molecule inhibitors of protein binding to glycosaminoglycans (SMIGs). Composed of a planar aromatic amine scaffold, it inhibits protein binding to glycosaminoglycans (GAGs). RX-207 reduced neutrophil migration in thioglycollate-induced peritonitis (37%), inhibited carrageenan-induced paw edema (32%) and cerulein-induced pancreatitis (28%), and increased animal survival in the mouse model of cecal ligation and puncture (CLP)-induced sepsis (60%). The mechanism of RX-207 action, analyzed by UV spectroscopy, confirmed that which was elucidated for chemically related anti-inflammatory SMIGs. RX-207 binding to cell surface GAGs can account for the inhibition of neutrophil recruitment via the micro-vasculature and as a consequence, the reduction of neutrophil mediated tissue damage in the animal models of inflammation and improved survival of mice in CLP-induced sepsis.

  13. Zebrafish fed on recombinant Artemia expressing epinecidin-1 exhibit increased survival and altered expression of immunomodulatory genes upon Vibrio vulnificus infection.

    Science.gov (United States)

    Jheng, Yu-Hsuan; Lee, Lin-Han; Ting, Chen-Hung; Pan, Chieh-Yu; Hui, Cho-Fat; Chen, Jyh-Yih

    2015-01-01

    Artemia has been used extensively in aquaculture as fodder for larval fish, shrimp, and shellfish. Epinecidin-1, an antimicrobial peptide, was isolated from grouper (Epinephelus coioides) in 2005. Epinecidin-1 has been previously reported to possess antimicrobial activity against several Gram-positive and Gram-negative bacterial species, including Staphylococcus coagulase, Pseudomonas aeruginosa, Streptococcus pyogenes, and Vibrio vulnificus. In this study, we used electroporation to introduce plasmid DNA encoding a green fluorescent protein (EGFP)-epinecidin-1 fusion protein under the control of the cytomegalovirus (CMV) promoter into decapsulated Artemia cysts. Optimization of various properties (including cyst weight (0.2 g), plasmid concentration (50 μg/100 μl), and pulse voltage (150 V), length (10 ms), and number (2)) resulted in a hatching rate of 41.15%, a transfection efficiency of 49.81%, and a fluorescence intensity (A.U.) of 47.46. The expression of EGFP-epinecidin-1 was first detected by quantitative RT-PCR at 120 h post-electroporation, and protein was identified by Western blot at the same time. Furthermore, the EGFP-epinecidin-1 protein inhibited V. vulnificus (204) growth, as demonstrated by zone of inhibition studies. Zebrafish fed on transgenic Artemia expressing CMV-gfp-epi combined with commercial fodder were more resistant to infection by V. vulnificus (204): survival rate was enhanced by over 70% at 7, 14, and 21 days post-infection, and bacterial numbers in the liver and intestine were reduced. In addition, feeding of transgenic Artemia to zebrafish affected the immunomodulatory response to V. vulnificus (204) infection; expression of immune-responsive genes, including hepcidin and defbl2, was altered, as shown by qPCR. These findings suggest that feeding transgenic Artemia expressing CMV-gfp-epi to larval fish has antimicrobial effects, without the drawbacks of introducing drug residues or inducing bacterial drug resistance

  14. Oxidative stress-mediated NFκB phosphorylation upregulates p62/SQSTM1 and promotes retinal pigmented epithelial cell survival through increased autophagy.

    Directory of Open Access Journals (Sweden)

    Chunjuan Song

    Full Text Available p62 is a scaffolding adaptor implicated in the clearance of protein aggregates by autophagy. Reactive oxygen species (ROS can either stimulate or inhibit NFκB-mediated gene expression influencing cellular fate. We studied the effect of hydrogen peroxide (H2O2-mediated oxidative stress and NFκB signaling on p62 expression in the retinal pigment epithelium (RPE and investigated its role in regulation of autophagy and RPE survival against oxidative damage. Cultured human RPE cell line ARPE-19 and primary human adult and fetal RPE cells were exposed to H2O2-induced oxidative stress. The human apolipoprotein E4 targeted-replacement (APOE4 mouse model of AMD was used to study expression of p62 and other autophagy proteins in the retina. p62, NFκB p65 (total, phosphorylated, nuclear and cytoplasmic and ATG10 expression was assessed by mRNA and protein analyses. Cellular ROS and mitochondrial superoxide were measured by CM-H2DCFDA and MitoSOX staining respectively. Mitochondrial viability was determined using MTT activity. qPCR-array system was used to investigate autophagic genes affected by p62. Nuclear and cytoplasmic levels of NFκB p65 were evaluated after cellular fractionation by Western blotting. We report that p62 is up-regulated in RPE cells under H2O2-induced oxidative stress and promotes autophagic activity. Depletion of endogenous p62 reduces autophagy by downregulation of ATG10 rendering RPE more susceptible to oxidative damage. NFκB p65 phosphorylation at Ser-536 was found to be critical for p62 upregulation in response to oxidative stress. Proteasome inhibition by H2O2 causes p62-NFκB signaling as antioxidant pre-treatment reversed p62 expression and p65 phosphorylation when RPE was challenged by H2O2 but not when by Lactacystin. p62 protein but not RNA levels are elevated in APOE4-HFC AMD mouse model, suggesting reduction of autophagic flux in disease conditions. Our findings suggest that p62 is necessary for RPE cytoprotection

  15. Probiotic yogurts manufactured with increased glucose oxidase levels: postacidification, proteolytic patterns, survival of probiotic microorganisms, production of organic acid and aroma compounds.

    Science.gov (United States)

    Cruz, A G; Castro, W F; Faria, J A F; Lollo, P C B; Amaya-Farfán, J; Freitas, M Q; Rodrigues, D; Oliveira, C A F; Godoy, H T

    2012-05-01

    We investigated the effect of increased glucose oxidase concentration as a technological option to decrease oxidative stress during the processing of probiotic yogurts. Probiotic yogurts were produced with increased concentrations of glucose oxidase (0, 250, 500, 750, or 1,000 mg/kg) and submitted to physicochemical and microbiological analysis at 1, 15, and 30 d of refrigerated storage. Higher concentrations of glucose oxidase (750 and 1,000 mg/kg) and a longer storage time were found to have an influence on the characteristics of the probiotic yogurt, contributing to more extensive postacidification, an increase in the dissolved oxygen level, and higher proteolysis. In addition, increased production of aroma compounds (diacetyl and acetaldehyde) and organic acids (mainly lactic acid) and a decrease in the probiotic bacteria count were reported. The use of glucose oxidase was a feasible option to minimize oxidative stress in probiotic yogurts. However, supplementation with excessive amounts of the enzyme may be ineffective, because insufficient substrate (glucose) is present for its action. Consumer tests should be performed to evaluate changes in the sensory attributes of the probiotic yogurts with increased supplementation of glucose oxidase. In addition, packaging systems with different permeability to oxygen should be evaluated. Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  16. Survival Analysis

    CERN Document Server

    Miller, Rupert G

    2011-01-01

    A concise summary of the statistical methods used in the analysis of survival data with censoring. Emphasizes recently developed nonparametric techniques. Outlines methods in detail and illustrates them with actual data. Discusses the theory behind each method. Includes numerous worked problems and numerical exercises.

  17. Modelling survival

    DEFF Research Database (Denmark)

    Ashauer, Roman; Albert, Carlo; Augustine, Starrlight

    2016-01-01

    well GUTS, calibrated with short-term survival data of Gammarus pulex exposed to four pesticides, can forecast effects of longer-term pulsed exposures. Thirdly, we tested the ability of GUTS to estimate 14-day median effect concentrations of malathion for a range of species and use these estimates...

  18. Inhibition of IL-32 activation by alpha-1 antitrypsin suppresses alloreactivity and increases survival in an allogeneic murine marrow transplantation model.

    NARCIS (Netherlands)

    Marcondes, A.M.; Li, X.; Tabellini, L.; Bartenstein, M.; Kabacka, J.; Sale, G.E.; Hansen, J.A.; Dinarello, C.A.; Deeg, H.J.

    2011-01-01

    Interleukin (IL)-32 was originally identified in natural killer cells and IL-2-activated human T lymphocytes. As T cells are activated in allogeneic transplantation, we determined the role of IL-32 in human mixed lymphocyte cultures (MLCs) and GVHD. In allogeneic MLCs, IL-32 increased two-fold in

  19. Artists’ Survival Rate

    DEFF Research Database (Denmark)

    Bille, Trine; Jensen, Søren

    2017-01-01

    The literature of cultural economics generally finds that an artistic education has no significant impact on artists’ income and careers in the arts. In our research, we have readdressed this question by looking at the artists’ survival in the arts occupations. The results show that an artistic...... education has a significant impact on artists’ careers in the arts and we find important industry differences....

  20. Network ties and survival

    DEFF Research Database (Denmark)

    Acheampong, George; Narteh, Bedman; Rand, John

    2017-01-01

    Poultry farming has been touted as one of the major ways by which poverty can be reduced in low-income economies like Ghana. Yet, anecdotally there is a high failure rate among these poultry farms. This current study seeks to understand the relationship between network ties and survival chances...... of small commercial poultry farms (SCPFs). We utilize data from a 2-year network survey of SCPFs in rural Ghana. The survival of these poultry farms are modelled using a lagged probit model of farms that persisted from 2014 into 2015. We find that network ties are important to the survival chances...... but this probability reduces as the number of industry ties increases but moderation with dynamic capability of the firm reverses this trend. Our findings show that not all network ties aid survival and therefore small commercial poultry farmers need to be circumspect in the network ties they cultivate and develop....

  1. Individual social capital and survival

    DEFF Research Database (Denmark)

    Ejlskov, Linda; Mortensen, Rikke N; Overgaard, Charlotte

    2014-01-01

    BACKGROUND: The concept of social capital has received increasing attention as a determinant of population survival, but its significance is uncertain. We examined the importance of social capital on survival in a population study while focusing on gender differences. METHODS: We used data from...... a Danish regional health survey with a five-year follow-up period, 2007-2012 (n = 9288, 53.5% men, 46.5% women). We investigated the association between social capital and all-cause mortality, performing separate analyses on a composite measure as well as four specific dimensions of social capital while...... controlling for covariates. Analyses were performed with Cox proportional hazard models by which hazard ratios and 95% confidence intervals were calculated. RESULTS: For women, higher levels of social capital were associated with lower all-cause mortality regardless of age, socioeconomic status, health...

  2. Survival and clinical outcome of dogs with ischaemic stroke

    DEFF Research Database (Denmark)

    Gredal, Hanne Birgit; Toft, Nils; Westrup, Ulrik

    2013-01-01

    The objectives of the present study were to investigate survival time, possible predictors of survival and clinical outcome in dogs with ischaemic stroke. A retrospective study of dogs with a previous diagnosis of ischaemic stroke diagnosed by magnetic resonance imaging (MRI) was performed....... The association between survival and the hypothesised risk factors was examined using univariable exact logistic regression. Survival was examined using Kaplan-Meier and Cox regression. Twenty-two dogs were identified. Five dogs (23%) died within the first 30days of the stroke event. Median survival in 30-day...... survivors was 505days. Four dogs (18%) were still alive by the end of the study. Right-sided lesions posed a significantly increased risk of mortality with a median survival time in dogs with right-sided lesions of 24days vs. 602days in dogs with left sided lesions (P=0.006). Clinical outcome was considered...

  3. Meta-analysis of survival prediction with Palliative Performance Scale.

    Science.gov (United States)

    Downing, Michael; Lau, Francis; Lesperance, Mary; Karlson, Nicholas; Shaw, Jack; Kuziemsky, Craig; Bernard, Steve; Hanson, Laura; Olajide, Lola; Head, Barbara; Ritchie, Christine; Harrold, Joan; Casarett, David

    2007-01-01

    This paper aims to reconcile the use of Palliative Performance Scale (PPSv2) for survival prediction in palliative care through an international collaborative study by five research groups. The study involves an individual patient data meta-analysis on 1,808 patients from four original datasets to reanalyze their survival patterns by age, gender, cancer status, and initial PPS score. Our findings reveal a strong association between PPS and survival across the four datasets. The Kaplan-Meier survival curves show each PPS level as distinct, with a strong ordering effect in which higher PPS levels are associated with increased length of survival. Using a stratified Cox proportional hazard model to adjust for study differences, we found females lived significantly longer than males, with a further decrease in hazard for females not diagnosed with cancer. Further work is needed to refine the reporting of survival times/probabilities and to improve prediction accuracy with the inclusion of other variables in the models.

  4. Significance of ERBB2 Overexpression in Therapeutic Resistance and Cancer-Specific Survival in Muscle-Invasive Bladder Cancer Patients Treated With Chemoradiation-Based Selective Bladder-Sparing Approach

    Energy Technology Data Exchange (ETDEWEB)

    Inoue, Masaharu [Department of Urology, Tokyo Medical and Dental University, Graduate School, Tokyo (Japan); Koga, Fumitaka, E-mail: f-koga@cick.jp [Department of Urology, Tokyo Medical and Dental University, Graduate School, Tokyo (Japan); Yoshida, Soichiro [Department of Urology, Tokyo Medical and Dental University, Graduate School, Tokyo (Japan); Tamura, Tomoki [Department of Pathology, Tokyo Medical and Dental University, Graduate School, Tokyo (Japan); Fujii, Yasuhisa [Department of Urology, Tokyo Medical and Dental University, Graduate School, Tokyo (Japan); Ito, Eisaku [Department of Pathology, Tokyo Medical and Dental University, Graduate School, Tokyo (Japan); Kihara, Kazunori [Department of Urology, Tokyo Medical and Dental University, Graduate School, Tokyo (Japan)

    2014-10-01

    Purpose: To investigate the associations of ERBB 2 overexpression with chemoradiation therapy (CRT) resistance and cancer-specific survival (CSS) in muscle-invasive bladder cancer (MIBC) patients treated with the CRT-based bladder-sparing protocol. Methods and Materials: From 1997 to 2012, 201 patients with cT2-4aN0M0 bladder cancer were treated with CRT (40 Gy with concurrent cisplatin) following transurethral resection of bladder tumor (TURBT). Basically, patients with tumors that showed good CRT response and were amenable to segmental resection underwent partial cystectomy (PC) with pelvic lymph node dissection for bladder preservation; otherwise, radical cystectomy (RC) was recommended. Included in this study were 119 patients in whom TURBT specimens were available for immunohistochemical analysis of ERBB 2 expression. Following CRT, 30 and 65 patients underwent PC or RC, respectively; the remaining 24 patients did not undergo cystectomy. Tumors were defined as CRT-resistant when patients did not achieve complete response after CRT. Associations of ERBB 2 overexpression with CRT resistance and CSS were evaluated. Results: CRT resistance was observed clinically in 56% (67 of 119 patients) and pathologically (in cystectomy specimens) in 55% (52 of 95 patients). ERBB 2 overexpression was observed in 45 patients (38%). On multivariate analysis, ERBB 2 overexpression was an independent predictor for CRT resistance clinically (odds ratio, 3.6; P=.002) and pathologically (odds ratio, 2.9; P=.031). ERBB 2 overexpression was associated with shorter CSS (5-year CSS rates, 56% vs 87% for the ERBB 2 overexpression group vs the others; P=.001). ERBB 2 overexpression was also an independent risk factor for bladder cancer death at all time points of our bladder-sparing protocol (pre-CRT, post-CRT, and post-cystectomy). Conclusions: ERBB 2 overexpression appears relevant to CRT resistance and unfavorable CSS in MIBC patients treated with the CRT-based bladder

  5. Obinutuzumab (GA101) compared to rituximab significantly enhances cell death and antibody-dependent cytotoxicity and improves overall survival against CD20(+) rituximab-sensitive/-resistant Burkitt lymphoma (BL) and precursor B-acute lymphoblastic leukaemia (pre-B-ALL): potential targeted therapy in patients with poor risk CD20(+) BL and pre-B-ALL.

    Science.gov (United States)

    Awasthi, Aradhana; Ayello, Janet; Van de Ven, Carmella; Elmacken, Mona; Sabulski, Anthony; Barth, Matthew J; Czuczman, Myron S; Islam, Humayun; Klein, Christian; Cairo, Mitchell S

    2015-12-01

    Obinutuzumab is a novel glycoengineered Type-II CD20 monoclonal antibody. CD20 is expressed in approximately 100% of children and adolescents with Burkitt lymphoma (BL) and 40% with precursor B-cell acute lymphoblastic leukaemia (pre-B-ALL). We evaluated the anti-tumour activity of obinutuzumab versus rituximab against rituximab-resistant (Raji 4RH) and -sensitive (Raji) BL and pre-B-ALL (U698-M) cells in vitro and in human BL or Pre-B-ALL xenografted mice. We demonstrated that obinutuzumab compared to rituximab significantly enhanced cell death against Raji 35·6 ± 3·1% vs. 25·1 ± 2·0%, (P = 0·001), Raji4RH 19·7 ± 2·2% vs. 7·9 ± 1·5% (P = 0·001) and U-698-M 47·3 ± 4·9% vs. 23·2 ± 0·5% (P = 0·001), respectively. Obinutuzumab versus rituximab also induced a significant increase in antibody-dependent cellular cytotoxicity (ADCC) with K562-IL15-41BBL expanded NK cells against Raji 73·8 ± 8·1% vs. 56·81 ± 4·6% (P = 0·001), Raji-4RH 40·0 ± 1·6% vs. 0·5 ± 1·1% (P = 0·001) and U-698-M 70·0 ± 1·6% vs. 45·5 ± 0·1% (P = 0·001), respectively. Overall survival in tumour xenografted mice receiving 30 mg/kg of obinutuzumab was significantly increased when compared to those receiving 30 mg/kg of rituximab in BL; Raji (P = 0·05), Raji4RH (P = 0·02) and U698-M (P = 0·03), respectively. These preclinical data suggest obinutuzumab is significantly superior to rituximab in inducing cell death, ADCC and against rituximab-sensitive/-resistant BL and pre-B-ALL xenografted mice. Taken together, these preclinical results provide evidence to suggest that future investigation of obinutuzumab is warranted in patients with relapsed/refractory CD20(+) BL and/or pre-B-ALL. © 2015 John Wiley & Sons Ltd.

  6. Dietary fats significantly influence the survival of penumbral neurons in a rat model of chronic ischemic by modifying lipid mediators, inflammatory biomarkers, NOS production, and redox-dependent apoptotic signals.

    Science.gov (United States)

    Lausada, Natalia; Arnal, Nathalie; Astiz, Mariana; Marín, María Cristina; Lofeudo, Juan Manuel; Stringa, Pablo; Tacconi de Alaniz, María J; Tacconi de Gómez Dumm, Nelva; Hurtado de Catalfo, Graciela; Cristalli de Piñero, Norma; Pallanza de Stringa, María Cristina; Illara de Bozzolo, Eva María; Bozzarello, Enrique Gustavo; Cristalli, Diana Olga; Marra, Carlos Alberto

    2015-01-01

    Brain stroke is the third most important cause of death in developed countries. We studied the effect of different dietary lipids on the outcome of a permanent ischemic stroke rat model. Wistar rats were fed diets containing 7% commercial oils (S, soybean; O, olive; C, coconut; G, grape seed) for 35 d. Stroke was induced by permanent middle cerebral artery occlusion. Coronal slices from ischemic brains and sham-operated animals were supravitally stained. Penumbra and core volumes were calculated by image digitalization after 24, 48, and 72 h poststroke. Homogenates and mitochondrial fractions were prepared from different zones and analyzed by redox status, inflammatory markers, ceramide, and arachidonate content, phospholipase A2, NOS, and proteases. Soybean (S) and G diets were mainly prooxidative and proinflammatory by increasing the liberation of arachidonate and its transformation into prostaglandins. O was protective in terms of redox homeostatic balance, minor increases in lipid and protein damage, conservation of reduced glutathione, protective activation of NOS in penumbra, and net ratio of anti-to proinflammatory cytokines. Apoptosis (caspase-3, milli- and microcalpains) was less activated by O than by any other diet. Dietary lipids modulate NOS and PLA2 activities, ceramide production, and glutathione import into the mitochondrial matrix, finally determining the activation of the two main protease systems involved in programmed cell death. Olive oil appears to be a biological source for the isolation of protective agents that block the expansion of brain core at the expense of penumbral neurons. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Effects of provenance and seed size on seedling survival and mophology of Quercus pontica

    Directory of Open Access Journals (Sweden)

    Yusuf Aksu

    2015-11-01

    Full Text Available This study was designed to investigate the effect of provenance and seed size on seedling survival and growth of Quercus pontica. The study showed that seed parameters showed significant differences among provenances. Provenance and seed size affected seedling survival and seedling morphology. Bigger seed size increased seedling survival, and also the large sized seed showed significant higher seedling height, root dry weight, shoot dry weight, and Dickson Quality Index in 1+0 seedlings.

  8. Duration of one-lung ventilation stage, POSSUM value and the quality of post-operative analgesia significantly affect survival and length of stay on intensive care unit of patients undergoing two-stage esophagectomy.

    Science.gov (United States)

    Almakadma, Yasin Said; Riad, Tamer Hunein; Ayad, Ismaei I; Ibrahim, Tamer Hussein

    2013-07-01

    To analyze different factors affecting the outcome of patients undergoing Two Stage Esophagectomy (TSE) for the treatment of esophageal carcinoma (EC) while relating these factors to the length of stay on Intensive Care Unit (ILOS), mortality, and morbidity. Retrospective study of case-notes of 45 patients who underwent a TSE for resection of EC at a general district hospital in the United Kingdom (UK). These procedures were performed by the same surgical team and followed same approach, known as the Ivor-Lewis procedure. The duration of One Lung Ventilation (OLV) during TSE was found to be critical for patient's outcome. Statistical analysis suggested a potentially strong effect of the duration of OLV (range: 90-320 minutes) on the ILOS (P=0.001). The ratio OLV: Total duration of surgery (TOT) was significantly different in early post-operative (PO) deaths (within 3 months) and late deaths after the third month (P=0.032). The POSSUM value (Physiological and Operative Severity Score for Enumeration of Mortality) correlated well with ILOS (P=0.05). Regression analysis showed a strong relationship between the two variables (P=0.03). An excellent to good quality of PO analgesia allowed for shorter ILOS (P=0.023). Duration of the OLV appears as an important factor in the outcome of patients. POSSUM value could help in planning the post-operative critical care need of patients undergoing TSE. A well managed post-operative pain allowed to reduce the ILOS.

  9. Actuarial survival of a large Canadian cohort of preterm infants

    Directory of Open Access Journals (Sweden)

    Ohlsson Arne

    2005-11-01

    Full Text Available Abstract Background The increased survival of preterm and very low birth weight infants in recent years has been well documented but continued surveillance is required in order to monitor the effects of new therapeutic interventions. Gestation and birth weight specific survival rates most accurately reflect the outcome of perinatal care. Our aims were to determine survival to discharge for a large Canadian cohort of preterm infants admitted to the neonatal intensive care unit (NICU, and to examine the effect of gender on survival and the effect of increasing postnatal age on predicted survival. Methods Outcomes for all 19,507 infants admitted to 17 NICUs throughout Canada between January 1996 and October 1997 were collected prospectively. Babies with congenital anomalies were excluded from the study population. Gestation and birth weight specific survival for all infants with birth weight Results Survival to discharge at 24 weeks gestation was 54%, compared to 82% at 26 weeks and 95% at 30 weeks. In infants with birth weights 600–699, survival to discharge was 62%, compared to 79% at 700–799 g and 96% at 1,000–1,099 g. In infants born at 24 weeks gestational age, survival was higher in females but there were no significant gender differences above 24 weeks gestation. Actuarial analysis showed that risk of death was highest in the first 5 days. For infants born at 24 weeks gestation, estimated survival probability to 48 hours, 7 days and 4 weeks were 88 (CI 84,92%, 70 (CI 64, 76% and 60 (CI 53,66% respectively. For smaller birth weights, female survival probabilities were higher than males for the first 40 days of life. Conclusion Actuarial analysis provides useful information when counseling parents and highlights the importance of frequently revising the prediction for long term survival particularly after the first few days of life.

  10. Tooth survival after root canal treatment.

    Science.gov (United States)

    Balto, Khaled

    2011-01-01

    Medline, the Cochrane Library, hand searches of the International Endodontic Journal, Journal of Endodontics, Oral Surgery Oral Medicine Oral Pathology Oral Radiology and Endodontics, Dental Traumatology (& Endodontics) and bibliographies of all relevant articles and review articles. Unpublished studies were identified by searching abstracts and conference proceedings. Personal contacts were used to identify ongoing or unpublished studies. Two reviewers independently assessed and selected the studies with disagreements being resolved by discussion. Clinical studies of RCTx on more than 30 teeth and of at least six-month duration, where the success was based on survival of tooth and the proportion of teeth surviving was given, or could be calculated from the raw data, were included. Data were extracted by two reviewers independently using custom-designed forms. The weighted pooled proportion of teeth surviving after treatment and the combined effects (expressed as odds ratio) of clinical factors on tooth survival were estimated using fixed and random effects meta-analyses using DerSimonean and Laird's methods. The survival data were pooled into three groups based on the duration after treatment: 2 or 3 years; 4 or 5 years; and 8, 9 or 10 years. Statistical heterogeneity amongst the studies was assessed by Cochran's (Q) test. Of the 31 articles identified, 14 studies were included. The majority (10) were retrospective. The reported survival is shown in Table 1. Substantial differences in study characteristics were found to hinder effective direct comparison of findings. Evidence for the effect of prognostic factors on tooth survival was weak. Based on the data available for meta-analysis, four conditions were found to significantly improve tooth survival. In descending order of influence, the conditions increasing observed proportion of survival were as follows: (i) a crown restoration after RCTx; (ii) tooth having both mesial and distal proximal contacts; (iii

  11. Colorectal Cancer in Jordan: Survival Rate and Its Related Factors.

    Science.gov (United States)

    Sharkas, Ghazi Faisal; Arqoub, Kamal H; Khader, Yousef S; Tarawneh, Mohammad R; Nimri, Omar F; Al-Zaghal, Marwan J; Subih, Hadil S

    2017-01-01

    Objectives. To estimate the survival rate of colorectal cancer (CRC) and determine its predictors among Jordanian patients who were diagnosed in the period of 2005-2010. Methods. This study was based on Jordan cancer registry. All CRC cases that were registered in cancer registry during 2005-2010 were analyzed using the survival analysis. The last date for follow-up was 1st Oct 2016. Results. A total of 3005 patients with CRC were registered during 2005-2010. The overall 5-year and 10-year survival rates for patients with CRC were 58.2% and 51.8%, respectively. The 5-year survival rate decreased significantly from 60.4% for the age <50 years to 49.3% for the age ≥70 years (p < 0.005). The 5-year survival rate was 72.1% for the localized stage, 53.8% for the regional stage, and 22.6% for the distant metastasis. In the multivariate analysis, the only factors that were significantly associated with survival were age, grade, stage, and location of tumor. Conclusions. The overall 5-year and ten-year survival rates for CRC were 58.2% and 51.8%, respectively. Increased age, poor differentiation, advanced cancer stage, and right-sided cancers were associated with lower survival rates. Screening strategies are needed for early detection of colon adenomas and colorectal cancer in Jordan.

  12. Colorectal Cancer in Jordan: Survival Rate and Its Related Factors

    Directory of Open Access Journals (Sweden)

    Ghazi Faisal Sharkas

    2017-01-01

    Full Text Available Objectives. To estimate the survival rate of colorectal cancer (CRC and determine its predictors among Jordanian patients who were diagnosed in the period of 2005–2010. Methods. This study was based on Jordan cancer registry. All CRC cases that were registered in cancer registry during 2005–2010 were analyzed using the survival analysis. The last date for follow-up was 1st Oct 2016. Results. A total of 3005 patients with CRC were registered during 2005–2010. The overall 5-year and 10-year survival rates for patients with CRC were 58.2% and 51.8%, respectively. The 5-year survival rate decreased significantly from 60.4% for the age <50 years to 49.3% for the age ≥70 years (p<0.005. The 5-year survival rate was 72.1% for the localized stage, 53.8% for the regional stage, and 22.6% for the distant metastasis. In the multivariate analysis, the only factors that were significantly associated with survival were age, grade, stage, and location of tumor. Conclusions. The overall 5-year and ten-year survival rates for CRC were 58.2% and 51.8%, respectively. Increased age, poor differentiation, advanced cancer stage, and right-sided cancers were associated with lower survival rates. Screening strategies are needed for early detection of colon adenomas and colorectal cancer in Jordan.

  13. Growth and survival of Mudfish (Clarias anguillaris) hatchlings fed ...

    African Journals Online (AJOL)

    All fish in treatment C (fishmeal only) and H (no feeding) died after the first week of the experiment. Survival in the other treatments ranged between 84.0% and 88.0% but no significant differences (P > 0.05) were observed in the survival values. The greatest increases in body weight (222.5 mg) and total length (25.8 mm) ...

  14. Infections and mixed infections with the selected species of Borrelia burgdorferi sensu lato complex in Ixodes ricinus ticks collected in eastern Poland: a significant increase in the course of 5 years.

    Science.gov (United States)

    Wójcik-Fatla, Angelina; Zając, Violetta; Sawczyn, Anna; Sroka, Jacek; Cisak, Ewa; Dutkiewicz, Jacek

    2016-02-01

    In the years 2008-2009 and 2013-2014, 1620 and 1500 questing Ixodes ricinus ticks, respectively, were examined on the territory of the Lublin province (eastern Poland). The presence of three pathogenic species causing Lyme disease was investigated: Borrelia burgdorferi sensu stricto, B. afzelii and B. garinii. The proportion of I. ricinus ticks infected with B. burgdorferi sensu lato showed a highly significant increase between 2008-2009 and 2013-2014, from 6.0 to 15.3%. A significant increase was noted with regard to all types of infections with individual species: single (4.7-7.8%), dual (1.2-6.6%), and triple (0.1-0.9%). When expressed as the percent of all infections, the frequency of mixed infections increased from 21.4 to 49.2%. Statistical analysis performed with two methods (by calculating of odds ratios and by Fisher's exact test) showed that the frequencies of mixed infections in most cases proved to be significantly greater than expected. The strongest associations were found between B. burgdorferi s. s. and B. afzelii, and between B. burgdorferi s. s. and B. garinii. They appeared to be highly significant (P < 0.0001) when assessed by two methods for 2013-2014, and for the sum of findings for both time periods. The proportions of the individual species detected in the mixed infections in 2008-2009 and 2013-2014 revealed highly significant increases for B. burgdorferi s. s. and B. garinii (from 33.9 to 71.1% and from 18.2 to 82.9%, respectively), and an insignificant decrease for B. afzelii (from 51.4 to 41.6%). The proportions of the species B. burgdorferi s. s., B. afzelii and B. garinii (with combined single and mixed infections) for 2008-2009 and 2013-2014 were: 51.2/44.0 %, 30.6/24.9% and 18.2/31.1%, respectively. In conclusion, our results seem to indicate the detrimental trend of the increasing infection rate of I. ricinus ticks with B. burgdorferi s. l. in eastern Poland, and dramatic enhancement of mixed infections with individual species, which

  15. Long-term omeprazole and esomeprazole treatment does not significantly increase gastric epithelial cell proliferation and epithelial growth factor receptor expression and has no effect on apoptosis and p53 expression.

    Science.gov (United States)

    Hritz, Istvan; Herszenyi, Laszlo; Molnar, Bela; Tulassay, Zsolt; Pronai, Laszlo

    2005-08-14

    To study the effect of proton pump inhibitor (PPI) treatment on patients with reflux esophagitis and its in vivo effect on apoptosis, p53- and epidermal growth factor receptor (EGFR) expression. After informed consent was obtained, gastric biopsies of the antrum were taken from patients with reflux oesophagitis prior to and after 6 mo of 20 mg omeprazole (n = 14) or 40 mg esomeprazole (n = 12) therapy. Patients did not take any other medications known to affect the gastric mucosa. All patients were Helicobacter pylori negative as confirmed by rapid urease test and histology, respectively. Cell proliferation, apoptosis, EGFR, and p53 expression were measured by immunohistochemical techniques. At least 600 glandular epithelial cells were encountered and results were expressed as percentage of total cells counted. Was considered statistically significant. Although there was a trend towards increase of cell proliferation and EGFR expression both in omeprazole and esomeprazole treated group, the difference was not statistically significant. Neither apoptosis nor p53 expression was affected. Long-term PPI treatment does not significantly increase gastric epithelial cell proliferation and EGFR expression and has no effect on apoptosis and p53 expression.

  16. CD36 mRNA and Protein Expression Levels Are Significantly Increased in the Heart and Testis of apoE Deficient Mice in Comparison to Wild Type (C57BL/6

    Directory of Open Access Journals (Sweden)

    Kazem Zibara

    2002-01-01

    Full Text Available CD36, an 88kd-adhesion molecule, plays a major role as a scavenging receptor implicated in cellular lipid metabolism. Secretory mammary epithelium, microvasculature endothelium, adipocytes, smooth muscle cells, and platelets express CD36. In addition, CD36 expression is significantly enhanced in macrophages differentiating into foam cells. The effect of pathological levels of cholesterol, as observed in apoE−/−, on vascular CD36 expression is, at this stage, not known. In this study, a quantitative analysis of CD36 transcription and protein expression levels, present in tissues of male C57BL/6 and apolipoprotein-E (apoE deficient mice was carried out by Northern and Western blots. Four-week-old animals were fed a chow diet over different periods of time (0, 6, 16, or 20 weeks. Immunohistochemistry was used to localize CD36 protein expression in the heart and testis. Results indicate that CD36 transcription is increased in hearts of apoE deficient animals (100% higher at 6 weeks, and 30% higher at 16 and 20 weeks in comparison to wild type. This was confirmed at the protein level, which showed an increase of at least 100% at 6 weeks, and between 40% to 50% increase at 16 and 20 weeks of apoE−/− mice compared to controls. In addition, CD36 transcription levels were significantly increased in testis of apoE animals (at least 100% at 6, 16, and 20 weeks compared to C57BL/6 wild type. Such an increase was also confirmed at the protein level (65% increase at 16 weeks in apoE mice compared to control. Finally, localization of CD36 protein expression by immunohistochemistry showed that it was expressed in the capillaries of heart and testis endothelial cells and also at the head of spermatozoid during spermatogenesis. These results indicate that high circulating cholesterol levels, in apoE deficient mice, significantly enhance the expression of CD36 in the heart and testis. Such enhanced CD36 expression might lead to organ remodeling and

  17. Incidence and overall survival of malignant ameloblastoma.

    Directory of Open Access Journals (Sweden)

    Alexandra Rizzitelli

    Full Text Available Malignant ameloblastoma, comprising metastasizing ameloblastoma and ameloblastic carcinoma, represents 1.6-2.2% of all odontogenic tumors. Due to its rare nature, malignant ameloblastoma has only been reported in the literature in small case series or case reports. Using the Surveillance, Epidemiology and End-Results (SEER database, we have performed a population-based study to determine the incidence rate and the absolute survival of malignant ameloblastoma.Using the International Classification of Diseases for Oncology (ICD-O codes 9310/3 and 9270/3, data from the SEER database were used to calculate the incidence rate and absolute survival rate of population with malignant ameloblastoma.The overall incidence rate of malignant ameloblastoma was 1.79 per 10 million person/year. The incidence rate was higher in males than females and also higher in black versus white population. The median overall survival was 17.6 years from the time of diagnosis and increasing age was associated with a statistically significant poorer survival.To our best knowledge, we report the largest population-based series of malignant ameloblastoma. The incidence rate was 1.79 per 10 million person/year and the overall survival was 17.6 years.

  18. Surviving cyberwar

    CERN Document Server

    Stiennon, Richard

    2010-01-01

    This book examines in depth the major recent cyber attacks that have taken place around the world, discusses the implications of such attacks, and offers solutions to the vulnerabilities that made these attacks possible. Through investigations of the most significant and damaging cyber attacks, the author introduces the reader to cyberwar, outlines an effective defense against cyber threats, and explains how to prepare for future attacks.

  19. A single amino acid change (Y318F) in the L-arabitol dehydrogenase (LadA) from Aspergillus niger results in a significant increase in affinity for D-sorbitol.

    Science.gov (United States)

    Rutten, Lucy; Ribot, Cecile; Trejo-Aguilar, Blanca; Wösten, Han A B; de Vries, Ronald P

    2009-08-12

    L-arabitol dehydrogenase (LAD) and xylitol dehydrogenase (XDH) are involved in the degradation of L-arabinose and D-xylose, which are among the most abundant monosaccharides on earth. Previous data demonstrated that LAD and XDH not only differ in the activity on their biological substrate, but also that only XDH has significant activity on D-sorbitol and may therefore be more closely related to D-sorbitol dehydrogenases (SDH). In this study we aimed to identify residues involved in the difference in substrate specificity. Phylogenetic analysis demonstrated that LAD, XDH and SDH form 3 distinct groups of the family of dehydrogenases containing an Alcohol dehydrogenase GroES-like domain (pfam08240) and likely have evolved from a common ancestor. Modelling of LadA and XdhA of the saprobic fungus Aspergillus niger on human SDH identified two residues in LadA (M70 and Y318), that may explain the absence of activity on D-sorbitol. While introduction of the mutation M70F in LadA of A. niger resulted in a nearly complete enzyme inactivation, the Y318F resulted in increased activity for L-arabitol and xylitol. Moreover, the affinity for D-sorbitol was increased in this mutant. These data demonstrates that Y318 of LadA contributes significantly to the substrate specificity difference between LAD and XDH/SDH.

  20. A single amino acid change (Y318F in the L-arabitol dehydrogenase (LadA from Aspergillus niger results in a significant increase in affinity for D-sorbitol

    Directory of Open Access Journals (Sweden)

    Ribot Cecile

    2009-08-01

    Full Text Available Abstract Background L-arabitol dehydrogenase (LAD and xylitol dehydrogenase (XDH are involved in the degradation of L-arabinose and D-xylose, which are among the most abundant monosaccharides on earth. Previous data demonstrated that LAD and XDH not only differ in the activity on their biological substrate, but also that only XDH has significant activity on D-sorbitol and may therefore be more closely related to D-sorbitol dehydrogenases (SDH. In this study we aimed to identify residues involved in the difference in substrate specificity. Results Phylogenetic analysis demonstrated that LAD, XDH and SDH form 3 distinct groups of the family of dehydrogenases containing an Alcohol dehydrogenase GroES-like domain (pfam08240 and likely have evolved from a common ancestor. Modelling of LadA and XdhA of the saprobic fungus Aspergillus niger on human SDH identified two residues in LadA (M70 and Y318, that may explain the absence of activity on D-sorbitol. While introduction of the mutation M70F in LadA of A. niger resulted in a nearly complete enzyme inactivation, the Y318F resulted in increased activity for L-arabitol and xylitol. Moreover, the affinity for D-sorbitol was increased in this mutant. Conclusion These data demonstrates that Y318 of LadA contributes significantly to the substrate specificity difference between LAD and XDH/SDH.

  1. Common germline polymorphisms associated with breast cancer-specific survival.

    Science.gov (United States)

    Pirie, Ailith; Guo, Qi; Kraft, Peter; Canisius, Sander; Eccles, Diana M; Rahman, Nazneen; Nevanlinna, Heli; Chen, Constance; Khan, Sofia; Tyrer, Jonathan; Bolla, Manjeet K; Wang, Qin; Dennis, Joe; Michailidou, Kyriaki; Lush, Michael; Dunning, Alison M; Shah, Mitul; Czene, Kamila; Darabi, Hatef; Eriksson, Mikael; Lambrechts, Dieter; Weltens, Caroline; Leunen, Karin; van Ongeval, Chantal; Nordestgaard, Børge G; Nielsen, Sune F; Flyger, Henrik; Rudolph, Anja; Seibold, Petra; Flesch-Janys, Dieter; Blomqvist, Carl; Aittomäki, Kristiina; Fagerholm, Rainer; Muranen, Taru A; Olsen, Janet E; Hallberg, Emily; Vachon, Celine; Knight, Julia A; Glendon, Gord; Mulligan, Anna Marie; Broeks, Annegien; Cornelissen, Sten; Haiman, Christopher A; Henderson, Brian E; Schumacher, Frederick; Le Marchand, Loic; Hopper, John L; Tsimiklis, Helen; Apicella, Carmel; Southey, Melissa C; Cross, Simon S; Reed, Malcolm Wr; Giles, Graham G; Milne, Roger L; McLean, Catriona; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Grip, Mervi; Hooning, Maartje J; Hollestelle, Antoinette; Martens, John Wm; van den Ouweland, Ans Mw; Marme, Federick; Schneeweiss, Andreas; Yang, Rongxi; Burwinkel, Barbara; Figueroa, Jonine; Chanock, Stephen J; Lissowska, Jolanta; Sawyer, Elinor J; Tomlinson, Ian; Kerin, Michael J; Miller, Nicola; Brenner, Hermann; Butterbach, Katja; Holleczek, Bernd; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M; Li, Jingmei; Brand, Judith S; Humphreys, Keith; Devilee, Peter; Tollenaar, Robert Aem; Seynaeve, Caroline; Radice, Paolo; Peterlongo, Paolo; Manoukian, Siranoush; Ficarazzi, Filomena; Beckmann, Matthias W; Hein, Alexander; Ekici, Arif B; Balleine, Rosemary; Phillips, Kelly-Anne; Benitez, Javier; Zamora, M Pilar; Perez, Jose Ignacio Arias; Menéndez, Primitiva; Jakubowska, Anna; Lubinski, Jan; Gronwald, Jacek; Durda, Katarzyna; Hamann, Ute; Kabisch, Maria; Ulmer, Hans Ulrich; Rüdiger, Thomas; Margolin, Sara; Kristensen, Vessela; Nord, Siljie; Evans, D Gareth; Abraham, Jean; Earl, Helena; Poole, Christopher J; Hiller, Louise; Dunn, Janet A; Bowden, Sarah; Yang, Rose; Campa, Daniele; Diver, W Ryan; Gapstur, Susan M; Gaudet, Mia M; Hankinson, Susan; Hoover, Robert N; Hüsing, Anika; Kaaks, Rudolf; Machiela, Mitchell J; Willett, Walter; Barrdahl, Myrto; Canzian, Federico; Chin, Suet-Feung; Caldas, Carlos; Hunter, David J; Lindstrom, Sara; Garcia-Closas, Montserrat; Couch, Fergus J; Chenevix-Trench, Georgia; Mannermaa, Arto; Andrulis, Irene L; Hall, Per; Chang-Claude, Jenny; Easton, Douglas F; Bojesen, Stig E; Cox, Angela; Fasching, Peter A; Pharoah, Paul Dp; Schmidt, Marjanka K

    2015-04-22

    Previous studies have identified common germline variants nominally associated with breast cancer survival. These associations have not been widely replicated in further studies. The purpose of this study was to evaluate the association of previously reported SNPs with breast cancer-specific survival using data from a pooled analysis of eight breast cancer survival genome-wide association studies (GWAS) from the Breast Cancer Association Consortium. A literature review was conducted of all previously published associations between common germline variants and three survival outcomes: breast cancer-specific survival, overall survival and disease-free survival. All associations that reached the nominal significance level of P value <0.05 were included. Single nucleotide polymorphisms that had been previously reported as nominally associated with at least one survival outcome were evaluated in the pooled analysis of over 37,000 breast cancer cases for association with breast cancer-specific survival. Previous associations were evaluated using a one-sided test based on the reported direction of effect. Fifty-six variants from 45 previous publications were evaluated in the meta-analysis. Fifty-four of these were evaluated in the full set of 37,954 breast cancer cases with 2,900 events and the two additional variants were evaluated in a reduced sample size of 30,000 samples in order to ensure independence from the previously published studies. Five variants reached nominal significance (P <0.05) in the pooled GWAS data compared to 2.8 expected under the null hypothesis. Seven additional variants were associated (P <0.05) with ER-positive disease. Although no variants reached genome-wide significance (P <5 x 10(-8)), these results suggest that there is some evidence of association between candidate common germline variants and breast cancer prognosis. Larger studies from multinational collaborations are necessary to increase the power to detect associations, between

  2. Surviving downsizing

    Energy Technology Data Exchange (ETDEWEB)

    Crawford, A.C. [Colorado Public Service Co., Platteville, CO (United States); Schulz, J.W. [Applied Behavioral Sciences, Englewood, CO (United States); Holmes, M.H. [Colorado Public Service Co., Platteville, CO (United States)

    1996-12-31

    Utilities along with other companies are under increasing pressure to operate in a leaner, more efficient way. Companies with excess personnel costs consider downsizing as one solution. Developments in communication and technology along with more team-oriented management approaches further fuel the move to downsize as these developments permit smaller, flatter organizations. Downsizing is often, however, a difficult and even hazardous path. Reducing the size of a workforce does not automatically translate into lower costs or improved operations. The hidden costs of downsizing, i.e., the psychological impacts on the entire organization, may, in fact, overwhelm the anticipated gains. Yet, utilities facing deregulation and increasing competition ma be forced to follow this difficult course.

  3. Survival After Relapse of Medulloblastoma.

    Science.gov (United States)

    Koschmann, Carl; Bloom, Karina; Upadhyaya, Santhosh; Geyer, J Russell; Leary, Sarah E S

    2016-05-01

    Survival after recurrence of medulloblastoma has not been reported in an unselected cohort of patients in the contemporary era. We reviewed 55 patients diagnosed with medulloblastoma between 2000 and 2010, and treated at Seattle Children's Hospital to evaluate patterns of relapse treatment and survival. Fourteen of 47 patients (30%) over the age of 3 experienced recurrent or progressive medulloblastoma after standard therapy. The median time from diagnosis to recurrence was 18.0 months (range, 3.6 to 62.6 mo), and site of recurrence was metastatic in 86%. The median survival after relapse was 10.3 months (range, 1.3 to 80.5 mo); 3-year survival after relapse was 18%. There were trend associations between longer survival and having received additional chemotherapy (median survival 12.8 vs. 1.3 mo, P=0.16) and radiation therapy (15.4 vs. 5.9 mo, P=0.20). Isolated local relapse was significantly associated with shorter survival (1.3 vs. 12.8 mo, P=0.009). Recurrence of medulloblastoma is more likely to be metastatic than reported in previous eras. Within the limits of our small sample, our data suggest a potential survival benefit from retreatment with cytotoxic chemotherapy and radiation even in heavily pretreated patients. This report serves as a baseline against which to evaluate novel therapy combinations.

  4. Withania somnifera chemotype NMITLI 101R significantly increases the efficacy of antileishmanial drugs by generating strong IFN-γ and IL-12 mediated immune responses in Leishmania donovani infected hamsters.

    Science.gov (United States)

    Tripathi, Chandra Dev Pati; Kushawaha, Pramod Kumar; Sangwan, Rajender Singh; Mandal, Chitra; Misra-Bhattacharya, Shailja; Dube, Anuradha

    2017-01-15

    Withania somnifera (L.) Dunal (Solanaceae), commonly known as Ashwagandha, is one of the most important medicinal plant in the traditional Indian medical systems. Pharmacological studies have established that root extracts of W. somnifera contain several bioactive constituents called withanolides. The plant has long been used for its several beneficial properties and recently as an immunomodulator. A combination therapy including a potential and safe immunostimulant with lower doses of effective drug, which can reduce the parasitic burden and simultaneously can produce an enhancement of adaptive immunity, has proven to be significantly a more effective approach than immunotherapy or drug therapy alone. Evaluation of the immunostimulatory effect of W. somnifera chemotype NMITLI 101R when used in combination with ED50 doses of antileishmanial drugs in Leishmania donovani infected hamsters. Infected animals were administered with chemotype 101R(30mg/kg × 15 days) either alone or in combination with ED50 doses of miltefosine (10mg/kg × 5 days), paromomycin (30mg/kg × 5 days) or amphotericin B (0.5mg/kg × 5 days). The treated animals were euthanized on days 30 and 60 post-treatment (p.t.) and checked for parasite clearance, delayed type hypersensitivity (DTH) response, cytokine and inducible nitric oxide synthase levels by real-time PCR, nitric oxide (NO) production, reactive oxygen species (ROS) generation, lymphoproliferative and antibody responses. The group of animals that received 101R and ED50 dose of miltefosine showed optimum inhibition of parasite multiplication (∼98%) by day 60 p.t. followed by the group that received 101R plus paromomycin (∼94%) and 101R plus amphotericin B (∼93%). The efficacy was well supported by the increased inducible NO synthase mRNA transcript, strong IFN-γand IL-12 mediated Th1 immune responses and significantly suppressed levels of Th2 cytokines (IL-4, IL-10 and TGF-β). Additionally, same therapy

  5. Surviving secondments.

    Science.gov (United States)

    Kedward, Alison; Jones, Eiri

    2008-11-01

    In the current climate of organisational and financial change in the NHS, new job opportunities along traditional pathways for senior staff are becoming fewer. Increasing competition for posts requires that senior staff acquire new professional expertise, and one of the best ways of doing so is to undertake secondments. The two authors of this case study have both held senior substantive positions in nursing management and clinical leadership: Eiri Jones at the former Bio Morgannwg NHS Trust and Alison Kedward at the former Swansea NHS Trust. These trusts have now merged to form Abertawe Bro Morgannwg University NHS Trust. After completing a national executive development programme for aspiring nurse directors run by the National Leadership and Innovation Agency for Healthcare (NLIAH), they both obtained secondments to interim nurse director posts. Ms Kedward was seconded to Pembrokeshire Local Health Board, a commissioning organisation, for nine months and Ms Jones was seconded to Ceredigion and Mid Wales NHS Trust, an integrated NHS service provider, for 14 months. This article provides a case study of the authors' experiences on secondment, and recommendations for nurse managers who are considering whether to undertake this form of career development.

  6. Disparities in Survival with Bystander CPR following Cardiopulmonary Arrest Based on Neighborhood Characteristics

    Directory of Open Access Journals (Sweden)

    Nina Thakkar Rivera

    2016-01-01

    Full Text Available The American Heart Association reports the annual incidence of out-of-hospital cardiopulmonary arrests (OHCA is greater than 300,000 with a survival rate of 9.5%. Bystander cardiopulmonary resuscitation (CPR saves one life for every 30, with a 10% decrease in survival associated with every minute of delay in CPR initiation. Bystander CPR and training vary widely by region. We conducted a retrospective study of 320 persons who suffered OHCA in South Florida over 25 months. Increased survival, overall and with bystander CPR, was seen with increasing income (p=0.05, with a stronger disparity between low- and high-income neighborhoods (p=0.01 and p=0.03, resp.. Survival with bystander CPR was statistically greater in white- versus black-predominant neighborhoods (p=0.04. Increased survival, overall and with bystander CPR, was seen with high- versus low-education neighborhoods (p=0.03. Neighborhoods with more high school age persons displayed the lowest survival. We discovered a significant disparity in OHCA survival within neighborhoods of low-income, black-predominance, and low-education. Reduced survival was seen in neighborhoods with larger populations of high school students. This group is a potential target for training, and instruction can conceivably change survival outcomes in these neighborhoods, closing the gap, thus improving survival for all.

  7. Serum hCG-β levels of postovulatory day 12 and 14 with the sequential application of hCG-β fold change significantly increased predictability of pregnancy outcome after IVF-ET cycle.

    Science.gov (United States)

    Sung, Nayoung; Kwak-Kim, Joanne; Koo, H S; Yang, K M

    2016-09-01

    To investigate hCG-β level on postovulatory day (POD) 12 and its fold increase as predictors for pregnancy outcome after in vitro fertilization (IVF) cycles. A retrospective cohort study was performed in total 1408 fresh and 598 frozen cycles between November 2008 and October 2011, which resulted in biochemical pregnancy, early pregnancy loss, or live birth of singleton pregnancy. The serum hCG-β levels of POD 12 and 14 were compared among biochemical pregnancy, early pregnancy loss, and live birth groups. The cutoff values of POD 12 and 14 hCG-β levels and the degree of hCG-β increase from POD 12 to 14 were determined for each pregnancy outcome. POD 12 and 14 hCG-β levels stratified based on pregnancy outcomes were significantly different among the biochemical pregnancy, early pregnancy loss, and live birth in both fresh and frozen cycles. Serum hCG-β levels of POD 12 and 14 and the fold increase of hCG-β levels from POD 12 to 14 significantly predict pregnancy outcomes after fresh and frozen cycles. Among these, the cutoff value of POD 14 hCG-β had the highest sensitivity and positive predictive value (PPV). In fresh cycles, the cutoff values of POD 12 and 14 serum hCG-β levels for clinical pregnancies were 30.2 mIU/mL (sensitivity 81.3 %, specificity 79.6 %, and PPV 92.3 %) and 70.5 mIU/mL (sensitivity 88.4 %, specificity 85.2 %, and PPV 94.7 %). In pregnancies with POD 12 serum hCG-β levels ≥30.2 mIU/mL, the cutoff level of increase of hCG-β for clinical pregnancy was 2.56 (sensitivity 73.6 %, specificity 72.4 %, and PPV 97.8 %). Sequential application of cutoff values such as POD 12 hCG-β and fold increase of hCG-β improved predictability of pregnancy outcome as compared with that of POD 12 hCG-β alone. The cutoff values of POD 12 and 14 serum hCG-β levels for live birth were 40.5 mIU/mL (sensitivity 75.2 %, specificity 72.6 %, PPV 78.9 %) and 104.5 mIU/mL (sensitivity 80.3 %, specificity 74.1 %, PPV 80.8 %). In the frozen

  8. Global Activities and Plant Survival

    DEFF Research Database (Denmark)

    Bandick, Roger

    2014-01-01

    This chapter provides an extensive review of the empirical evidence found for Sweden concerning plant survival. The result reveals that foreign MNE plants and exporting non-MNE plants have the lowest exit rates, followed by purely domestic-oriented plants, and that domestic MNE plants have...... the highest exit rates. Moreover, the exit rates of globally engaged plants seem to be unaffected by increased foreign presence, whereas there appears to be a negative impact on the survival rates of non-exporting non-MNE plants. Finally, the result reveals that the survival ratio of plants of acquired...... exporters, but not other types of plants, improves post acquisition....

  9. Operational slack and venture survival

    OpenAIRE

    Azadegan, Arash; Patel, Pankaj; Parida, Vinit

    2013-01-01

    Slack can act as a double-edged sword. While it can buffer against environmental threats to help ensure business continuity, slack canalso be costly and reduce profitability. In this study, we focus on operational slack, the form related to the firm’s production processes. We investigate the role of operational slack on firm survival during its venture stage, when its survival is significantly challenged by environmental threats. Specifically, we explore how change in three types of environme...

  10. In Vivo Imaging Reveals Significant Tumor Vascular Dysfunction and Increased Tumor Hypoxia-Inducible Factor-1α Expression Induced by High Single-Dose Irradiation in a Pancreatic Tumor Model

    Energy Technology Data Exchange (ETDEWEB)

    Maeda, Azusa [Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario (Canada); Department of Medical Biophysics, University of Toronto, Toronto, Ontario (Canada); Chen, Yonghong; Bu, Jiachuan; Mujcic, Hilda [Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario (Canada); Wouters, Bradly G. [Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario (Canada); Department of Medical Biophysics, University of Toronto, Toronto, Ontario (Canada); Department of Radiation Oncology, University of Toronto, Toronto, Ontario (Canada); DaCosta, Ralph S., E-mail: rdacosta@uhnres.utoronto.ca [Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario (Canada); Department of Medical Biophysics, University of Toronto, Toronto, Ontario (Canada); Techna Institute, University Health Network, Toronto, Ontario (Canada)

    2017-01-01

    Purpose: To investigate the effect of high-dose irradiation on pancreatic tumor vasculature and microenvironment using in vivo imaging techniques. Methods and Materials: A BxPC3 pancreatic tumor xenograft was established in a dorsal skinfold window chamber model and a subcutaneous hind leg model. Tumors were irradiated with a single dose of 4, 12, or 24 Gy. The dorsal skinfold window chamber model was used to assess tumor response, vascular function and permeability, platelet and leukocyte adhesion to the vascular endothelium, and tumor hypoxia for up to 14 days after 24-Gy irradiation. The hind leg model was used to monitor tumor size, hypoxia, and vascularity for up to 65 days after 24-Gy irradiation. Tumors were assessed histologically to validate in vivo observations. Results: In vivo fluorescence imaging revealed temporary vascular dysfunction in tumors irradiated with a single dose of 4 to 24 Gy, but most significantly with a single dose of 24 Gy. Vascular functional recovery was observed by 14 days after irradiation in a dose-dependent manner. Furthermore, irradiation with 24 Gy caused platelet and leukocyte adhesion to the vascular endothelium within hours to days after irradiation. Vascular permeability was significantly higher in irradiated tumors compared with nonirradiated controls 14 days after irradiation. This observation corresponded with increased expression of hypoxia-inducible factor-1α in irradiated tumors. In the hind leg model, irradiation with a single dose of 24 Gy led to tumor growth delay, followed by tumor regrowth. Conclusions: Irradiation of the BxPC3 tumors with a single dose of 24 Gy caused transient vascular dysfunction and increased expression of hypoxia-inducible factor-1α. Such biological changes may impact tumor response to high single-dose and hypofractionated irradiation, and further investigations are needed to better understand the clinical outcomes of stereotactic body radiation therapy.

  11. Extended-spectrum β-lactamase-producing Escherichia coli contributes to the survival of cefotaxime-susceptible E. coli under high concentrations of cefotaxime by acquisition of increased AmpC expression.

    Science.gov (United States)

    Nakayama, Tatsuya; Kawahara, Ryuji; Kumeda, Yuko; Yamamoto, Yoshimasa

    2018-01-18

    Extended-spectrum β-lactamase-producing Escherichia coli (ESBL-E) are becoming increasingly widespread in Vietnam. Antibiotics are detected in many Vietnamese foods; however, the effect of ESBL-E and antibiotic consumption on intestinal bacteria has not been studied sufficiently. Here, we investigated the effect of oral administration of ESBL-E (TB19) and cefotaxime on luminescence-emitting cefotaxime-sensitive E. coli (X14). Mice were given water containing TB19 and then received three injections of 1.0 × 108 CFU of X14 harboring a luciferase gene. The mice were administered 100 μg of cefotaxime and luminescent bacteria were monitored over 24 h, following which luminescent bacteria were isolated from mouse feces. Luminescence continued to be detected in mice administered TB19 24 h after cefotaxime ingestion. Fecal analysis revealed two types of luminescent colonies, cefoxitin-resistant E. coli (X14-R) and Pseudomonas aeruginosa. Pulse-field gel electrophoresis confirmed that X14-R was a clonal strain of X14, suggesting that X14 survived using ESBLs originating from TB19 and acquired cefoxitin resistance due to cefotaxime consumption. Moreover, in vitro analysis of X14 indicated that expression of the ampC gene was upregulated by cefotaxime. Overall, ESBL-E and cefotaxime promoted the expansion of cefoxitin-resistant E. coli in the absence of plasmid-mediated gene transfer. © FEMS 2018. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  12. Fusion of Epstein-Barr virus nuclear antigen-1-derived glycine-alanine repeat to trans-dominant HIV-1 Gag increases inhibitory activities and survival of transduced cells in vivo.

    Science.gov (United States)

    Hammer, Diana; Wild, Jens; Ludwig, Christine; Asbach, Benedikt; Notka, Frank; Wagner, Ralf

    2008-06-01

    Trans-dominant human immunodeficiency virus type 1 (HIV-1) Gag derivatives have been shown to efficiently inhibit late steps of HIV-1 replication in vitro by interfering with Gag precursor assembly, thus ranking among the interesting candidates for gene therapy approaches. However, efficient antiviral activities of corresponding transgenes are likely to be counteracted in particular by cell-mediated host immune responses toward the transgene-expressing cells. To decrease this potential immunogenicity, a 24-amino acid Gly-Ala (GA) stretch derived from Epstein-Barr virus nuclear antigen-1 (EBNA1) and known to overcome proteasomal degradation was fused to a trans-dominant Gag variant (sgD1). To determine the capacity of this fusion polypeptide to repress viral replication, PM-1 cells were transduced with sgD1 and GAsgD1 transgenes, using retroviral gene transfer. Challenge of stably transfected permissive cell lines with various viral strains indicated that N-terminal GA fusion even enhanced the inhibitory properties of sgD1. Further studies revealed that the GA stretch increased protein stability by blocking proteasomal degradation of Gag proteins. Immunization of BALB/c mice with a DNA vaccine vector expressing sgD1 induced substantial Gag-specific immune responses that were, however, clearly diminished in the presence of GA. Furthermore, recognition of cells expressing the GA-fused transgene by CD8(+) T cells was drastically reduced, both in vitro and in vivo, resulting in prolonged survival of the transduced cells in recipient mice.

  13. Red cell survival time in chronic renal failure

    Energy Technology Data Exchange (ETDEWEB)

    Rath, R.N.; Das, R.K.; Panda, R.K.; Mahakur, A.C.; Patnaik, S.R. (M.K.C.G. Medical College, Berhampur (India))

    1979-10-01

    The red cell survival time was estimated in 50 cases of chronic renal failure and 20 healthy subjects, using radioactive chromium /sup 51/Cr. The mean value of red cell survival half time (T1/2/sup 51/Cr) was determined to be 25.9 +- 1.1 days in control subjects. The red cell survival half time (17.9 +- 4.67 days) was found to be significantly decreased in cases of chronic renal failure, when compared to the control group. An inverse relationship was observed between T1/2/sup 51/Cr value and blood urea, serum creatinine, the magnitude of hypertension, and duration of illness, whereas, creatinine clearance showed a direct relationship. There was no increased splenic uptake of radioactive chromium, indicating that haemolysis occurred elsewhere in the circulation other than spleen. The possible mechanism for the reduction of red cell survival time and the effect of uraemic environment on it has been di