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Sample records for cilengitide enhances efficacy

  1. The integrin antagonist cilengitide activates alphaVbeta3, disrupts VE-cadherin localization at cell junctions and enhances permeability in endothelial cells.

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    Gian Carlo Alghisi

    Full Text Available Cilengitide is a high-affinity cyclic pentapeptdic alphaV integrin antagonist previously reported to suppress angiogenesis by inducing anoikis of endothelial cells adhering through alphaVbeta3/alphaVbeta5 integrins. Angiogenic endothelial cells express multiple integrins, in particular those of the beta1 family, and little is known on the effect of cilengitide on endothelial cells expressing alphaVbeta3 but adhering through beta1 integrins. Through morphological, biochemical, pharmacological and functional approaches we investigated the effect of cilengitide on alphaVbeta3-expressing human umbilical vein endothelial cells (HUVEC cultured on the beta1 ligands fibronectin and collagen I. We show that cilengitide activated cell surface alphaVbeta3, stimulated phosphorylation of FAK (Y(397 and Y(576/577, Src (S(418 and VE-cadherin (Y(658 and Y(731, redistributed alphaVbeta3 at the cell periphery, caused disappearance of VE-cadherin from cellular junctions, increased the permeability of HUVEC monolayers and detached HUVEC adhering on low-density beta1 integrin ligands. Pharmacological inhibition of Src kinase activity fully prevented cilengitide-induced phosphorylation of Src, FAK and VE-cadherin, and redistribution of alphaVbeta3 and VE-cadherin and partially prevented increased permeability, but did not prevent HUVEC detachment from low-density matrices. Taken together, these observations reveal a previously unreported effect of cilengitide on endothelial cells namely its ability to elicit signaling events disrupting VE-cadherin localization at cellular contacts and to increase endothelial monolayer permeability. These effects are potentially relevant to the clinical use of cilengitide as anticancer agent.

  2. Cilengitide in patients with recurrent glioblastoma: the results of NABTC 03-02, a phase II trial with measures of treatment delivery.

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    Gilbert, Mark R; Kuhn, John; Lamborn, Kathleen R; Lieberman, Frank; Wen, Patrick Y; Mehta, Minesh; Cloughesy, Timothy; Lassman, Andrew B; Deangelis, Lisa M; Chang, Susan; Prados, Michael

    2012-01-01

    Cilengitide is a cyclic pentapeptide that is a specific inhibitor of the αvβ3 and αvβ5 integrins. Preclinical studies demonstrate antiangiogenic activity and anti-invasive activity in a number of glioma models. This study was designed to evaluate the efficacy and tumor delivery of cilengitide in patients with recurrent glioblastoma. Patients with recurrent glioblastoma who require a surgical resection for optimal clinical care received 3 intravenous doses of cilengitide at either 500 or 2000 mg (day -8, -4, -1) prior to undergoing tumor resection with corresponding blood samples for plasma to tumor comparisons. After recovery from surgery, patients were treated with cilengitide (2000 mg i.v. twice weekly, maximum of 2 years of treatment). The study accrued 30 patients with recurrent glioblastoma, 26 were evaluable for efficacy. The 6-month progression free survival rate was 12%. Cilengitide was detected in all tumor specimens with higher levels in the group receiving 2000 mg dosing while corresponding plasma concentrations were low, often below the lower limit of detection. These results confirm drug delivery and possibly retention in tumor. This study provides evidence that with established dosing, cilengitide is adequately delivered to the tumor, although as a single agent, efficacy in recurrent glioblastoma is modest. However, these results demonstrating drug delivery to tumor do support continued investigation of this agent as preliminary results from recent studies combining cilengitide with cytotoxic therapies are promising.

  3. The effect of cilengitide in combination with irradiation and chemotherapy in head and neck squamous cell carcinoma cell lines

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    Heiduschka, G. [Medical University of Vienna, Department of Otorhinolaryngology, Head and Neck Surgery, Comprehensive Cancer Center, Vienna (Austria); Medical University of Vienna, Clinical Pharmacology, Vienna (Austria); Lill, C.; Schneider, S.; Kotowski, U.; Thurnher, D. [Medical University of Vienna, Department of Otorhinolaryngology, Head and Neck Surgery, Comprehensive Cancer Center, Vienna (Austria); Seemann, R. [Medical University of Vienna, Craniomaxillofacial and Oral Surgery, Vienna (Austria); Kornek, G. [Medical University of Vienna, Internal Medicine, Vienna (Austria); Schmid, R. [Medical University of Vienna, Radiotherapy and Radiobiology, Vienna (Austria)

    2014-05-15

    Integrins are highly attractive targets in oncology due to their involvement in angiogenesis in a wide spectrum of cancer entities. Among several integrin inhibitors under clinical evaluation, cilengitide is the most promising compound. However, little is known about the cellular processes induced during cilengitide therapy in combination with irradiation and cisplatin in head and neck squamous cell carcinoma (HNSCC). The cytostatic effect of cilengitide was assessed by proliferation assay in the three HNSCC cell lines SCC25, FaDu and CAL27. Combination experiments with cisplatin and irradiation were performed. Possible synergistic effects were calculated in combination index (CI) analyses. Colony forming inhibition was investigated in clonogenic assays. Real-time PCR arrays were used to evaluate target protein gene expression patterns. Flow cytometry was used to detect apoptosis. Used alone, cilengitide has only minor cytotoxic effects in HNSCC cell lines. However, combination with cisplatin resulted in synergistic growth inhibition in all three cell lines. Irradiation showed synergism in short-term experiments and in colony forming assays, an additive effect was detected. Real-time PCR assay detected downregulation of the antiapoptotic protein Bcl-2 after exposure of cells to cilengitide. Cilengitide in combination with cisplatin and irradiation may be a feasible option for the treatment of patients with head and neck cancer. However, further investigations are required to understand the exact mechanism that leads to synergistic cytotoxicity. (orig.) [German] Durch ihre Rolle bei der Angiogenese sind Integrine ein attraktives Ziel in der onkologischen Forschung. Der derzeit vielversprechendste Inhibitor dieser Molekuele ist Cilengitide, welches bereits in klinischen Studien getestet wird. Dennoch ist erst wenig ueber die zellulaeren Vorgaenge bekannt, welche durch Cilengitide in Kopf-Hals-Karzinomen (HNSCC) insbesondere in Kombination mit Strahlentherapie und

  4. 西仑吉肽的固相合成%Solid phase synthesis of cilengitide

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    张波; 王卫国; 康武; 智小霞; 姚忠; 徐红岩

    2012-01-01

    Fully-protected linear peptide was synthesized by Fmoc solid phase peptide synthesis methods. The solid phase carrier was 2-chlorotrityl chloride resin. HATU/HOBt and HBTU/HOBt were used as the coupling reagents. The synthesis of fully-protected cyclic peptide used THF/DCM ( at a ratio of 1: 1 by volume) as the solvent and HATU/HOBt as the coupling reagents. Finally cilengitide could be obtained by deprotection reaction.%采用Fmoc固相合成法,选用2-氯三苯甲基氯树脂作为固相载,HBTU/HOBt和HATU/HOBt为缩合剂,合成全保护线性肽.以V(DCM)∶V(THF)= 1∶1为溶剂,HATU/HOBt为缩合剂,合成全保护环肽.最后脱除保护基得终产物西仑吉肽.

  5. Efficacy of enhanced external counterpulsation: our experience

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    Chandra Mani Adhikari

    2014-11-01

    Full Text Available Aims Enhanced external counterpulsation therapy is a non-invasive, non-pharmacological outpatient treatment option for refractory angina pectoris. Our aim is to evaluate its efficacy in Nepalese refractory angina pectoris patients. Materials and methods It was single centre prospective study conducted from 2010 August to 2013 December. All thirty one (n=31 consecutive patients, referred for and received 35 hours of treatment were included in this study. The distance covered in six minute walk test before and after the treatment was recorded and compared. Patients were followed each with the questionnaires about their anginal symptoms before and after the treatment. Results In our study 19(61.3% were male and 12(38.7% female. The mean age was 65.7±9.3 years. Most patients had multi vessel disease. Twelve patients had previous history of revascularization. In 6 minute walk test there was significant difference in mean distance covered before and after the treatment. Most patients experienced decrease in the angina symptom. They had decreased in severity and frequency of angina, resulting in decreased use of sublingual nitrates. Conclusion EECP can be safe and effective treatment option for patients with RAP.

  6. Cilengitide inhibits attachment and invasion of malignant pleural mesothelioma cells through antagonism of integrins αvβ3 and αvβ5.

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    Ngan Ching Cheng

    Full Text Available Malignant pleural mesothelioma (MPM is an almost invariably fatal, asbestos-related malignancy arising from the mesothelial membrane lining the thoracic cavities. Despite some improvements in treatment, therapy is not considered curative and median survival following diagnosis is less than 1 year. Although still classed as a rare cancer, the incidence of MPM is increasing, and the limited progress in treating the disease makes the identification of new therapies a priority. As there is evidence for expression of the integrins αvβ3 and αvβ5 in MPM, there is a rationale for investigating the effects on MPM of cilengitide, a synthetic peptide inhibitor of integrin αv heterodimer with high specificity for αvβ3 and αvβ5. In mesothelial cells (MC and 7 MPM cell lines, growth inhibition by cilengitide was associated with the expression level of its target integrins. Furthermore, cilengitide caused cell detachment and subsequent death of anoikis-sensitive cells. It also suppressed invasion of MPM cells in monolayer and three-dimensional cultures. Gene knockdown experiments indicated that these effects of cilengitide were, at least partly, due to antagonism of αvβ3 and αvβ5.

  7. Bt toxin modification for enhanced efficacy.

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    Deist, Benjamin R; Rausch, Michael A; Fernandez-Luna, Maria Teresa; Adang, Michael J; Bonning, Bryony C

    2014-10-22

    Insect-specific toxins derived from Bacillus thuringiensis (Bt) provide a valuable resource for pest suppression. Here we review the different strategies that have been employed to enhance toxicity against specific target species including those that have evolved resistance to Bt, or to modify the host range of Bt crystal (Cry) and cytolytic (Cyt) toxins. These strategies include toxin truncation, modification of protease cleavage sites, domain swapping, site-directed mutagenesis, peptide addition, and phage display screens for mutated toxins with enhanced activity. Toxin optimization provides a useful approach to extend the utility of these proteins for suppression of pests that exhibit low susceptibility to native Bt toxins, and to overcome field resistance.

  8. Leadership and Leader Developmental Self-Efficacy: Their Role in Enhancing Leader Development Efforts.

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    Murphy, Susan Elaine; Johnson, Stefanie K

    2016-01-01

    This chapter describes the role of two types of self-efficacy-leader self-efficacy and leader developmental efficacy-for enhancing leadership development. Practical implications for designing and developing leadership programs that take into account these two types of self-efficacy are discussed.

  9. Pirfenidone enhances the efficacy of combined radiation and sunitinib therapy

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    Choi, Seo-Hyun; Nam, Jae-Kyung; Jang, Junho; Lee, Hae-June, E-mail: hjlee@kcch.re.kr; Lee, Yoon-Jin, E-mail: yjlee8@kcch.re.kr

    2015-06-26

    Radiotherapy is a widely used treatment for many tumors. Combination therapy using anti-angiogenic agents and radiation has shown promise; however, these combined therapies are reported to have many limitations in clinical trials. Here, we show that radiation transformed tumor endothelial cells (ECs) to fibroblasts, resulting in reduced vascular endothelial growth factor (VEGF) response and increased Snail1, Twist1, Type I collagen, and transforming growth factor (TGF)-β release. Irradiation of radioresistant Lewis lung carcinoma (LLC) tumors greater than 250 mm{sup 3} increased collagen levels, particularly in large tumor vessels. Furthermore, concomitant sunitinib therapy did not show a significant difference in tumor inhibition versus radiation alone. Thus, we evaluated multimodal therapy that combined pirfenidone, an inhibitor of TGF-induced collagen production, with radiation and sunitinib treatment. This trimodal therapy significantly reduced tumor growth, as compared to radiation alone. Immunohistochemical analysis revealed that radiation-induced collagen deposition and tumor microvessel density were significantly reduced with trimodal therapy, as compared to radiation alone. These data suggest that combined therapy using pirfenidone may modulate the radiation-altered tumor microenvironment, thereby enhancing the efficacy of radiation therapy and concurrent chemotherapy. - Highlights: • Radiation changes tumor endothelial cells to fibroblasts. • Radio-resistant tumors contain collagen deposits, especially in tumor vessels. • Pirfenidone enhances the efficacy of combined radiation and sunitinib therapy. • Pirfenidone reduces radiation-induced collagen deposits in tumors.

  10. Enhancement of anticancer efficacy using modified lipophilic nanoparticle drug encapsulation

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    Lee P

    2012-02-01

    Full Text Available Puiyan Lee1, Ruizhong Zhang1, Vincent Li1, Xuelai Liu1, Raymond WY Sun2, Chi-Ming Che2, Kenneth KY Wong11Department of Surgery, Li Ka Shing Faculty of Medicine, 2Department of Chemistry and Open Laboratory of Chemical Biology of the Institute of Molecular Technology for Drug Discovery and Synthesis, The University of Hong Kong, Hong KongBackground: Development of anticancer drugs is challenging. Indeed, much research effort has been spent in the development of new drugs to improve clinical outcomes with minimal toxicity. We have previously reported that a formulation of lipid gold porphyrin nanoparticles reduced systemic drug toxicity when compared with free gold porphyrin. In this study, we investigated the delivery and treatment efficiency of PEG surface-modified lipid nanoparticles as a carrier platform.Methods: We encapsulated antitumor drugs into PEG-modified lipid nanoparticles and these were characterized by size, zeta potential, and encapsulation efficiency. The delivery efficiency into tumor tissue was evaluated using a biodistribution study. To evaluate antitumor efficacy, gold porphyrin or camptothecin (a DNA topoisomerase I inhibitor were encapsulated and compared using an in vivo neuroblastoma (N2A model.Results: We showed that drug encapsulation into PEG-modified lipid nanoparticles enhanced the preferential uptake in tumor tissue. Furthermore, higher tumor killing efficiency was observed in response to treatment with PEG-modified lipid nanoparticles encapsulating gold porphyrin or camptothecin when compared with free gold porphyrin or free camptothecin. The in vivo antitumor effect was further confirmed by study of tumor inhibition and positive apoptosis activity. Surface modification of lipophilic nanoparticles with PEG increased the efficiency of drug delivery into tumor tissue and subsequently more effective antitumor activity.Conclusion: This specific design of a chemotherapeutic agent using nanotechnology is important in the

  11. Validation of an instrument for mathematics enhancement teaching efficacy of Pacific Northwest agricultural educators

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    Jansen, Daniel J.

    Teacher efficacy continues to be an important area of study in educational research. This study tested an instrument designed to assess the perceived efficacy of agricultural education teachers when engaged in lessons involving mathematics instruction. The study population of Oregon and Washington agricultural educators utilized in the validation of the instrument revealed important demographic findings and specific results related to teacher efficacy for the study population. An instrument was developed from the assimilation of three scales previously used and validated in efficacy research. Participants' mathematics teaching efficacy was assessed using a portion of the Mathematics Teaching Efficacy Beliefs Instrument (MTEBI), and personal mathematics efficacy was evaluated by the mathematics self-belief instrument which was derived from the Betz and Hackett's Mathematics Self-Efficacy Scale. The final scale, the Teachers' Sense of Efficacy Scale (TSES) created by Tschannen-Moran and Woolfolk Hoy, examined perceived personal teaching efficacy. Structural equation modeling was used as the statistical analyses tool to validate the instrument and examine correlations between efficacy constructs used to determine potential professional development needs of the survey population. As part of the data required for validation of the Mathematics Enhancement Teaching Efficacy instrument, demographic information defining the population of Oregon and Washington agricultural educators was obtained and reported. A hypothetical model derived from teacher efficacy literature was found to be an acceptable model to verify construct validity and determine strength of correlations between the scales that defined the instrument. The instrument produced an alpha coefficient of .905 for reliability. Both exploratory and confirmatory factor analyses were used to verify construct and discriminate validity. Specifics results related to the survey population of agricultural educators

  12. Biofilm disruption with rotating microrods enhances antimicrobial efficacy

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    Mair, Lamar O.; Nacev, Aleksandar; Hilaman, Ryan; Stepanov, Pavel Y.; Chowdhury, Sagar; Jafari, Sahar; Hausfeld, Jeffrey; Karlsson, Amy J.; Shirtliff, Mark E.; Shapiro, Benjamin; Weinberg, Irving N.

    2017-04-01

    Biofilms are a common and persistent cause of numerous illnesses. Compared to planktonic microbes, biofilm residing cells often demonstrate significant resistance to antimicrobial agents. Thus, methods for dislodging cells from the biofilm may increase the antimicrobial susceptibility of such cells, and serve as a mechanical means of increasing antimicrobial efficacy. Using Aspergillus fumigatus as a model microbe, we magnetically rotate microrods in and around biofilm. We show that such rods can improve the efficacy of antimicrobial Amphotericin B treatments in vitro. This work represents a first step in using kinetic magnetic particle therapy for disrupting fungal biofilms.

  13. Mentoring Program as an Instrument of Enhancing Mentees’ Self- Efficacy

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    Azman Ismail

    2015-06-01

    Full Text Available This study investigates the correlation between mentoring program and mentees‘ selfefficacy. Self-report questionnaires were employed to collect data from undergraduate business students at a research university in Malaysia. The results of SmartPLS path model showed two essential findings: firstly, communication was positively and significantly correlated with mentees‘ self-efficacy. Secondly, support was positively and significantly correlated with mentees‘ selfefficacy. The result demonstrates that mentoring program does act as an important determinant of mentees‘ self-efficacy in the organizational sample. Further, the paper provides discussion, implications and conclusion.

  14. The use of self-efficacy enhancing methods in diabetes education in the Netherlands.

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    Koopman-van den Berg, D J; van der Bijl, J J

    2001-01-01

    According to the social cognitive theory of Bandura, self-efficacy predicts behavorial change. Bandura notes that self-efficacy is based on four major sources of information: performance accomplishments, vicarious experience, verbal persuasion and self-evaluation. This exploratory study examined the use of these four sources of information by Dutch nurse diabetes educators to enhance self-efficacy among people with diabetes mellitus. A survey questionnaire was sent to all Dutch nurse members of the European Association of Diabetes Educators (EADE) asking about the use of self-efficacy-enhancing methods, and four different educational programs were observed. Survey respondents said that performance accomplishments and verbal persuasion were often used, vicarious experience was hardly ever used, and the use of self-evaluation varied. The observations gave a different picture: only verbal persuasion was observed often; the other three sources were hardly ever used. Clearly, self-efficacy-enhancing educational methods are not systematically used in the Netherlands and there is little variety in the methods used. More varied methods of enhancing self-efficacy need to be developed and implemented in diabetes education programs.

  15. Tumor vessel normalization after aerobic exercise enhances chemotherapeutic efficacy.

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    Schadler, Keri L; Thomas, Nicholas J; Galie, Peter A; Bhang, Dong Ha; Roby, Kerry C; Addai, Prince; Till, Jacob E; Sturgeon, Kathleen; Zaslavsky, Alexander; Chen, Christopher S; Ryeom, Sandra

    2016-10-04

    Targeted therapies aimed at tumor vasculature are utilized in combination with chemotherapy to improve drug delivery and efficacy after tumor vascular normalization. Tumor vessels are highly disorganized with disrupted blood flow impeding drug delivery to cancer cells. Although pharmacologic anti-angiogenic therapy can remodel and normalize tumor vessels, there is a limited window of efficacy and these drugs are associated with severe side effects necessitating alternatives for vascular normalization. Recently, moderate aerobic exercise has been shown to induce vascular normalization in mouse models. Here, we provide a mechanistic explanation for the tumor vascular normalization induced by exercise. Shear stress, the mechanical stimuli exerted on endothelial cells by blood flow, modulates vascular integrity. Increasing vascular shear stress through aerobic exercise can alter and remodel blood vessels in normal tissues. Our data in mouse models indicate that activation of calcineurin-NFAT-TSP1 signaling in endothelial cells plays a critical role in exercise-induced shear stress mediated tumor vessel remodeling. We show that moderate aerobic exercise with chemotherapy caused a significantly greater decrease in tumor growth than chemotherapy alone through improved chemotherapy delivery after tumor vascular normalization. Our work suggests that the vascular normalizing effects of aerobic exercise can be an effective chemotherapy adjuvant.

  16. Enhancing antibiofilm efficacy in antimicrobial photodynamic therapy: effect of microbubbles

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    Kishen, Anil; George, Saji

    2013-02-01

    In this study, we tested the hypothesis that a microbubble containing photosensitizer when activated with light would enable comprehensive disinfection of bacterial biofilms in infected root dentin by antimicrobial photodynamic therapy (APDT). Experiments were conducted in two stages. In the stage-1, microbubble containing photosensitizing formulation was tested for its photochemical properties. In the stage-2, the efficacy of microbubble containing photosensitizing formulation was tested on in vitro infected root canal model, developed with monospecies biofilm models of Enterococcus faecalis on root dentin substrate. The findings from this study showed that the microbubble containing photosensitizing formulation was overall the most effective formulation for photooxidation, generation of singlet oxygen, and in disinfecting the biofilm bacteria in the infected root canal model. This modified photosensitizing formulation will have potential advantages in eliminating bacterial biofilms from infected root dentin.

  17. Enhancing elementary-school mathematics teachers' efficacy beliefs: a qualitative action research

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    Katz, Sara; Stupel, Moshe

    2016-04-01

    Individuals and societies that can use mathematics effectively in this period of rapid changes will have a voice on increasing the opportunities and potentials which can shape their future. This has brought affective characteristics, such as self-efficacy, that affect mathematics achievement into focus of the research. Teacher efficacy refers to the extent to which a teacher feels capable to help students learn, influence students' performance and commitment, and thus plays a crucial role in developing the student in all aspects. In this study, we used two sources of efficacy beliefs, mastery experiences and physiological and emotional states, in an interesting and challenging seven month workshop, as tools to foster teacher efficacy for six elementary-school teachers who were frustrated and wanted to leave their job. Our aim was to study the nature of these teachers' efficacy in order to change it. In this qualitative action research, we used open interviews, non-participant observations and field notes. Results show that these teachers became efficacious, their students' achievements and motivation were enhanced, and the school climate was changed. Qualitative inquiry of this construct sheds light on efficacy beliefs of mathematics teachers. Nurturing teacher efficacy has borne much fruit in the field of mathematics in school.

  18. Efficacy of an Unsaturated Soil Flushing/Enhanced Bioremediation Technology

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    Smith, J. E.; Badley, J. A.; Crowe, A. S.

    2003-12-01

    Undesirably high concentrations of DDT and its daughter products DDE and DDD in some soils at Point Pelee National Park (PPNP) in Leamington, Ontario, Canada has resulted in restricted access to relatively large areas of the park. The contamination occurs primarily within the upper 20 cm thick Ah horizon, and has been linked to elevated levels within numerous local fauna. The common solution of "dig-and-dump" is not practical in this case since it would destroy the local protected ecosystem. Field trials conducted by McMaster University in partnership with Environment Canada, and Parks Canada have indicated that the application of solutions of cyclodextrin as a low-impact soil flushing/enhanced biodegradation remediation technology can remove a large proportion of DDT, DDE and DDD from the soil within a few months. Based upon previous studies at PPNP, the naturally occurring degradation processes would take decades to achieve the same mass loss. The cyclodextrin solutions exhibited a strong "tailing-effect" after approximately ten pore-volumes had passed through the Ah. There was an effect on soil hydraulic properties with decreased hydraulic conductivities and higher soil water retention, particularly where the higher concentration solutions were applied. The results indicate that soil flushing with cyclodextrin is highly effective to remediate pesticide contaminated soils. Additional work will quantify the relative amount of enhanced degradation versus mobilisation.

  19. Gold nanoshell mediated hyperthermia enhances the efficacy of radiation therapy

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    Diagaradjane, Parmeswaran; Shetty, Anil; Wang, James; Elliot, Andrew; Schwartz, Jon; Shentu, Shujun; Park, Chul; Deorukhkar, Amit; Stafford, Jason; Cho, Sang; Tunnell, James; Hazle, John; Krishnan, Sunil

    2008-02-01

    Despite convincing evidence for hyperthermic radiosensitization, the invasive means of achieving and monitoring hyperthermia and the lack of good thermal dosimetry have hindered its use in routine clinical practice. A non-invasive method to generate and monitor hyperthermia would provide renewed enthusiasm for such treatments. Near-infrared absorbing gold nanoshells have been shown to accumulate preferentially in tumors via the enhanced permeability and retention effect and have been used for thermal ablation of tumors. We evaluated the use of these nanoshells to generate hyperthermia to evaluate the anti-tumor effects of combining gold nanoshell mediated hyperthermia with radiotherapy. Laser settings were optimized for hyperthermia in a mouse xenograft model to achieve a temperature rise of 40- 41°C in the tumor periphery and 37-38°C (ΔT=4-5°C) deeper within the tumors. The ΔT measurements were verified using both thermocouple and magnetic resonance thermal imaging (MRTI) temperature measurements. Tumor re-growth delay was estimated by measuring tumor size after treatment with radiation (10Gy single dose), hyperthermia (15 minutes at 40°C), and hyperthermia followed by radiation and control. Significant difference (p time was observed between the radiation group (13 days) and combination treatment group (25 days). The immunofluorescence staining for the hypoxic, proliferating cells and the vasculature corroborated our hypothesis that the radiosensitization is in part mediated by increased initial perfusion and subsequent collapse of vasculature that leads to acute inflammatory response in the tumor. The increased vascular perfusion immediately after gold nanoshell mediated hyperthermia is confirmed by dynamic contrast enhanced magnetic resonance imaging.

  20. Enhancing HIV Communication between Parents and Children: Efficacy of the Parents Matter! Program

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    Miller, Kim S.; Lin, Carol Y.; Poulsen, Melissa N.; Fasula, Amy; Wyckoff, Sarah C.; Forehand, Rex; Long, Nicholas; Armistead, Lisa

    2011-01-01

    We examine efficacy of the Parents Matter! Program (PMP), a program to teach African-American parents of preadolescents sexual communication and HIV-prevention skills, through a multicenter, randomized control trial. A total of 1115 parent-child participants were randomized to one of three intervention arms (enhanced, brief, control). Percentages…

  1. Using Acetaminophen's Toxicity Mechanism to Enhance Cisplatin Efficacy in Hepatocarcinoma and Hepatoblastoma Cell Lines

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    Alexander J. Neuwelt

    2009-10-01

    Conclusions: Our results suggest that a chemotherapeutic regimen containing both AAP and CDDP with delayed NAC rescue has the potential to enhance chemotherapeutic efficacy while decreasing adverse effects. This would be a promising approach particularly for hepatoblastomas regardless of cellular CYP2E1 protein level but could also be beneficial in other malignancies.

  2. Recombinant, catalytically inactive juvenile hormone esterase enhances efficacy of baculovirus insecticides

    NARCIS (Netherlands)

    Meer, van M.M.M.; Bonning, B.C.; Ward, V.K.; Vlak, J.M.; Hammock, B.D.

    2000-01-01

    The insecticidal efficacy of baculoviruses can be enhanced by engineering the viral genome to express proteins that disrupt the physiology of the host insect. Here we describe the development of a genetically engineered Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV) which expresses

  3. Enhanced in vivo antitumor efficacy of doxorubicin encapsulated within laponite nanodisks.

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    Li, Kai; Wang, Shige; Wen, Shihui; Tang, Yueqin; Li, Jipeng; Shi, Xiangyang; Zhao, Qinghua

    2014-08-13

    Development of various nanoscale drug carriers for enhanced antitumor therapy still remains a great challenge. In this study, laponite (LAP) nanodisks encapsulated with anticancer drug doxorubicin (DOX) at an exceptionally high loading efficiency (98.3 ± 0.77%) were used for tumor therapy applications. The long-term in vivo antitumor efficacy and toxicology of the prepared LAP/DOX complexes were analyzed using a tumor-bearing mouse model. Long-term tumor appearance, normalized tumor volume, CD31 staining, and hematoxylin and eosin (H&E)-stained tumor sections were used to evaluate the tumor therapy efficacy, while long-term animal body weight changes and H&E-stained tissue sections of different major organs were used to evaluate the toxicology of LAP/DOX complexes. Finally, the in vivo biodistribution of magnesium ions and DOX in different organs was analyzed. We showed that under the same DOX concentration, LAP/DOX complexes displayed enhanced tumor inhibition efficacy and afforded the treated mice with dramatically prolonged survival time. In vivo biodistribution data revealed that the reticuloendothelial systems (especially liver) had significantly higher magnesium uptake than other major organs, and the LAP carrier was able to be cleared out of the body at 45 days post treatment. Furthermore, LAP/DOX afforded a higher DOX uptake in the tumor region than free DOX, presumably due to the known enhanced permeability and retention effect. The developed LAP-based drug delivery system with an exceptionally high DOX payload, enhanced in vivo antitumor efficacy, and low systemic toxicity may be used as a promising platform for enhanced tumor therapy.

  4. Adjuvants Based on Hybrid Antibiotics Overcome Resistance in Pseudomonas aeruginosa and Enhance Fluoroquinolone Efficacy.

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    Gorityala, Bala Kishan; Guchhait, Goutam; Fernando, Dinesh M; Deo, Soumya; McKenna, Sean A; Zhanel, George G; Kumar, Ayush; Schweizer, Frank

    2016-01-11

    The use of adjuvants that rescue antibiotics against multidrug-resistant (MDR) pathogens is a promising combination strategy for overcoming bacterial resistance. While the combination of β-lactam antibiotics and β-lactamase inhibitors has been successful in restoring antibacterial efficacy in MDR bacteria, the use of adjuvants to restore fluoroquinolone efficacy in MDR Gram-negative pathogens has been challenging. We describe tobramycin-ciprofloxacin hybrid adjuvants that rescue the activity of fluoroquinolone antibiotics against MDR and extremely drug-resistant Pseudomonas aeruginosa isolates in vitro and enhance fluoroquinolone efficacy in vivo. Structure-activity studies reveal that the presence of both tobramycin and ciprofloxacin, which are separated by a C12 tether, is critical for the function of the adjuvant. Mechanistic studies indicate that the antibacterial modes of ciprofloxacin are retained while the role of tobramycin is limited to destabilization of the outer membrane in the hybrid.

  5. Enhanced radioimmunotherapeutic efficacy of a monoclonal antibody cocktail against SMMC—7721 human hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    SONGYIQIANG; GENFENGWANG; 等

    1998-01-01

    The improved tumoricidal effect of the radioantibody mixture (“cocktail”)has been reported recently for the treatment of colon tumor.In the present study,we demonstrated the enhanced radioimmunotherapeutic efficacy of a monoclonal antibody (MAb) cocktail against human hepatocellular carcinoma.Therapeutic efficacy was determined by measuring the change in tumor size over a period,determining the percentage of growth inhibition of each treatment at various times after radioantibody therapy.Radioimmunotherapy of SMMC-7721 human hepatoma xenografts in athymic unde mice with combination of 131Ilabeled Hepama-1 and 131 I-labeled 9403 mouse MAbs was more effective than using either Hepeam-1 or 9403 MAb alone The MAb cocktail could target a greater number of hepatoma cells and increase the magnitude of hepatoma cell uptake of radioantibodies.The in vitro results explain the enhanced effect of the MAb cocktail in in vivo model system.

  6. Chemical Modifications of Antisense Morpholino Oligomers Enhance Their Efficacy against Ebola Virus Infection

    Science.gov (United States)

    2009-05-01

    specific PMOs in infected cells and mice during lethal Ebola virus challenge. Members of the Filoviridae family of viruses , Ebola virus (EBOV) and Marburg ...American Society for Microbiology. All Rights Reserved. Chemical Modifications of Antisense Morpholino Oligomers Enhance Their Efficacy against Ebola Virus ...sequence is complementary to a region spanning the start codon of VP24 mRNA were protected against lethal Ebola virus challenge. In the present study, we

  7. Enhancing the Breadth and Efficacy of Therapeutic Vaccines for Breast Cancer

    Science.gov (United States)

    2015-10-01

    single antigen such as HER2 in breast cancer is likely to be insufficient - instead we need a repertoire of multiple immunologically validated T cell...Award Number: W81XWH-11-1-0548 TITLE: Enhancing the Breadth and Efficacy of Therapeutic Vaccines for Breast Cancer PRINCIPAL INVESTIGATOR...for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection

  8. Cortical EEG oscillations and network connectivity as efficacy indices for assessing drugs with cognition enhancing potential.

    Science.gov (United States)

    Ahnaou, A; Huysmans, H; Jacobs, T; Drinkenburg, W H I M

    2014-11-01

    Synchronization of electroencephalographic (EEG) oscillations represents a core mechanism for cortical and subcortical networks, and disturbance in neural synchrony underlies cognitive processing deficits in neurological and neuropsychiatric disorders. Here, we investigated the effects of cognition enhancers (donepezil, rivastigmine, tacrine, galantamine and memantine), which are approved for symptomatic treatment of dementia, on EEG oscillations and network connectivity in conscious rats chronically instrumented with epidural electrodes in different cortical areas. Next, EEG network indices of cognitive impairments with the muscarinic receptor antagonist scopolamine were modeled. Lastly, we examined the efficacy of cognition enhancers to normalize those aberrant oscillations. Cognition enhancers elicited systematic ("fingerprint") enhancement of cortical slow theta (4.5-6 Hz) and gamma (30.5-50 Hz) oscillations correlated with lower activity levels. Principal component analysis (PCA) revealed a compact cluster that corresponds to shared underlying mechanisms as compared to different drug classes. Functional network connectivity revealed consistent elevated coherent slow theta activity in parieto-occipital and between interhemispheric cortical areas. In rats instrumented with depth hippocampal CA1-CA3 electrodes, donepezil elicited similar oscillatory and coherent activities in cortico-hippocampal networks. When combined with scopolamine, the cognition enhancers attenuated the leftward shift in coherent slow delta activity. Such a consistent shift in EEG coherence into slow oscillations associated with altered slow theta and gamma oscillations may underlie cognitive deficits in scopolamine-treated animals, whereas enhanced coherent slow theta and gamma activity may be a relevant mechanism by which cognition enhancers exert their beneficial effect on plasticity and cognitive processes. The findings underscore that PCA and network connectivity are valuable tools to

  9. Amorphous Silica Based Nanomedicine with Safe Carrier Excretion and Enhanced Drug Efficacy

    Science.gov (United States)

    Zhang, Silu

    With recent development of nanoscience and nanotechnology, a great amount of efforts have been devoted to nanomedicine development. Among various nanomaterials, silica nanoparticle (NP) is generally accepted as non-toxic, and can provide a versatile platform for drug loading. In addition, the surface of the silica NP is hydrophilic, being favorable for cellular uptake. Therefore, it is considered as one of the most promising candidates to serve as carriers for drugs. The present thesis mainly focuses on the design of silica based nanocarrier-drug systems, aiming at achieving safe nanocarrier excretion from the biological system and enhanced drug efficacy, which two are considered as most important issues in nanomedicine development. To address the safe carrier excretion issue, we have developed a special type of selfdecomposable SiO2-drug composite NPs. By creating a radial concentration gradient of drug in the NP, the drug release occurred simultaneously with the silica carrier decomposition. Such unique characteristic was different from the conventional dense SiO2-drug NP, in which drug was uniformly distributed and can hardly escape the carrier. We found that the controllable release of the drug was primarily determined by diffusion, which was caused by the radial drug concentration gradient in the NP. Escape of the drug molecules then triggered the silica carrier decomposition, which started from the center of the NP and eventually led to its complete fragmentation. The small size of the final carrier fragments enabled their easy excretion via renal systems. Apart from the feature of safe carrier excretion, we also found the controlled release of drugs contribute significantly to the drug efficacy enhancement. By loading an anticancer drug doxorubicin (Dox) to the decomposable SiO 2-methylene blue (MB) NPs, we achieved a self-decomposable SiO 2(MB)-Dox nanomedicine. The gradual escape of drug molecules from NPs and their enabled cytosolic release by optical

  10. HemoHIM enhances the therapeutic efficacy of ionizing radiation treatment in tumor-bearing mice.

    Science.gov (United States)

    Park, Hae-Ran; Ju, Eun-Jin; Jo, Sung-Kee; Jung, Uhee; Kim, Sung-Ho

    2010-02-01

    Although radiotherapy is commonly used for a variety of cancers, radiotherapy alone does not achieve a satisfactory therapeutic outcome. In this study, we examined the possibility that HemoHIM can enhance the anticancer effects of ionizing radiation (IR) in melanoma-bearing mice. The HemoHIM was prepared by adding the ethanol-insoluble fraction to the total water extract of a mixture of three edible herbs-Angelica Radix, Cnidium Rhizoma, and Paeonia Radix. Anticancer effects of HemoHIM were evaluated in melanoma-bearing mice exposed to IR. IR treatment (5 Gy at 7 days after melanoma cell injection) reduced the weight of the solid tumors, and HemoHIM supplementation with IR enhanced the decreases in tumor weight (P < .03). In the melanoma-bearing mice treated with IR, HemoHIM administration also increased the activity of natural killer cells and cytotoxic T cells, although the proportions of these cells in spleen were not different. In addition, HemoHIM administration increased the interleukin-2 and tumor necrosis factor-alpha secretion from lymphocytes stimulated with concanavalin A, which seemed to contribute to the enhanced efficacy of HemoHIM in tumor-bearing mice treated with IR. In conclusion, HemoHIM may be a beneficial supplement during radiotherapy for enhancing the antitumor efficacy.

  11. Middle School Students' Self-Efficacy, Attitudes, and Achievement in a Computer-Enhanced Problem-Based Learning Environment

    Science.gov (United States)

    Liu, Min; Hsieh, Peggy (Pei-Hsuan); Cho, Yoonjung; Schallert, Diane

    2006-01-01

    This study examined the effect of a computer-enhanced problem-based learning (PBL) environment on middle school students' learning, investigating the relationship among students' self-efficacy, attitude toward science, and achievement. As Bandura defined it (1986), self-efficacy refers to the beliefs people have about whether or not they can…

  12. Immunosuppression enhances oncolytic adenovirus replication and antitumor efficacy in the Syrian hamster model.

    Science.gov (United States)

    Thomas, Maria A; Spencer, Jacqueline F; Toth, Karoly; Sagartz, John E; Phillips, Nancy J; Wold, William S M

    2008-10-01

    We recently described an immunocompetent Syrian hamster model for oncolytic adenoviruses (Ads) that permits virus replication in tumor cells as well as some normal tissues. This model allows exploration of interactions between the virus, tumor, normal organs, and host immune system that could not be examined in the immunodeficient or nonpermissive animal models previously used in the oncolytic Ad field. Here we asked whether the immune response to oncolytic Ad enhances or limits antitumor efficacy. We first determined that cyclophosphamide (CP) is a potent immunosuppressive agent in the Syrian hamster and that CP alone had no effect on tumor growth. Importantly, we found that the antitumor efficacy of oncolytic Ads was significantly enhanced in immunosuppressed animals. In animals that received virus therapy plus immunosuppression, significant differences were observed in tumor histology, and in many cases little viable tumor remained. Notably, we also determined that immunosuppression allowed intratumoral virus levels to remain elevated for prolonged periods. Although favorable tumor responses can be achieved in immunocompetent animals, the rate of virus clearance from the tumor may lead to varied antitumor efficacy. Immunosuppression, therefore, allows sustained Ad replication and oncolysis, which leads to substantially improved suppression of tumor growth.

  13. The mechanism of methylated seed oil on enhancing biological efficacy of topramezone on weeds.

    Science.gov (United States)

    Zhang, Jinwei; Jaeck, Ortrud; Menegat, Alexander; Zhang, Zongjian; Gerhards, Roland; Ni, Hanwen

    2013-01-01

    Methylated seed oil (MSO) is a recommended adjuvant for the newly registered herbicide topramezone in China and also in other countries of the world, but the mechanism of MSO enhancing topramezone efficacy is still not clear. Greenhouse and laboratory experiments were conducted to determine the effects of MSO on efficacy, solution property, droplet spread and evaporation, active ingredient deposition, foliar absorption and translocation of topramezone applied to giant foxtail (Setaria faberi Herrm.) and velvetleaf (Abutilon theophrasti Medic.). Experimental results showed that 0.3% MSO enhanced the efficacy of topramezone by 1.5-fold on giant foxtail and by 1.0-fold on velvetleaf. When this herbicide was mixed with MSO, its solution surface tension and leaf contact angle decreased significantly, its spread areas on weed leaf surfaces increased significantly, its wetting time was shortened on giant foxtail but not changed on velvetleaf, and less of its active ingredient crystal was observed on the treated weed leaf surfaces. MSO increased the absorption of topramezone by 68.9% for giant foxtail and by 45.9% for velvetleaf 24 hours after treatment. It also apparently promoted the translocation of this herbicide in these two weeds.

  14. The mechanism of methylated seed oil on enhancing biological efficacy of topramezone on weeds.

    Directory of Open Access Journals (Sweden)

    Jinwei Zhang

    Full Text Available Methylated seed oil (MSO is a recommended adjuvant for the newly registered herbicide topramezone in China and also in other countries of the world, but the mechanism of MSO enhancing topramezone efficacy is still not clear. Greenhouse and laboratory experiments were conducted to determine the effects of MSO on efficacy, solution property, droplet spread and evaporation, active ingredient deposition, foliar absorption and translocation of topramezone applied to giant foxtail (Setaria faberi Herrm. and velvetleaf (Abutilon theophrasti Medic.. Experimental results showed that 0.3% MSO enhanced the efficacy of topramezone by 1.5-fold on giant foxtail and by 1.0-fold on velvetleaf. When this herbicide was mixed with MSO, its solution surface tension and leaf contact angle decreased significantly, its spread areas on weed leaf surfaces increased significantly, its wetting time was shortened on giant foxtail but not changed on velvetleaf, and less of its active ingredient crystal was observed on the treated weed leaf surfaces. MSO increased the absorption of topramezone by 68.9% for giant foxtail and by 45.9% for velvetleaf 24 hours after treatment. It also apparently promoted the translocation of this herbicide in these two weeds.

  15. Co-administration of a Tumor-Penetrating Peptide Enhances the Efficacy of Cancer Drugs

    Science.gov (United States)

    Sugahara, Kazuki N.; Teesalu, Tambet; Karmali, Priya Prakash; Kotamraju, Venkata Ramana; Agemy, Lilach; Greenwald, Daniel R.; Ruoslahti, Erkki

    2010-01-01

    Poor penetration of anti-cancer drugs into tumors can be an important factor limiting their efficacy. Studying mouse tumor models, we show that a previously characterized tumor-penetrating peptide, iRGD (CRGDK/RGPD/EC), increased vascular and tissue permeability in a tumor-specific and neuropilin-1-dependent manner, allowing co-administered drugs to penetrate into extravascular tumor tissue. Importantly, this effect did not require the drugs to be chemically conjugated to the peptide. Systemic injection with iRGD improved the therapeutic index of drugs of various compositions including a small molecule (doxorubicin), nanoparticles (nab-paclitaxel and doxorubicin liposomes), and a monoclonal antibody (trastuzumab). Thus, co-administration of iRGD may be a valuable way to enhance the efficacy of anti-cancer drugs while reducing their side effects, a primary goal of cancer therapy research. PMID:20378772

  16. Curcumin enhances the lung cancer chemopreventive efficacy of phospho-sulindac by improving its pharmacokinetics.

    Science.gov (United States)

    Cheng, Ka-Wing; Wong, Chi C; Mattheolabakis, George; Xie, Gang; Huang, Liqun; Rigas, Basil

    2013-09-01

    Phospho-sulindac (PS) is a safe sulindac derivative with promising anticancer efficacy in colon cancer. We evaluated whether its combination with curcumin could enhance the efficacy in the treatment of lung cancer. Curcumin, the principal bioactive component in turmeric, has demonstrated versatile capabilities to modify the therapeutic efficacy of a wide range of anticancer agents. Here, we evaluated the effect of co-administration of curcumin on the anticancer activity of PS in a mouse xenograft model of human lung cancer. Curcumin enhanced the cellular uptake of PS in human lung and colon cancer cell lines. To assess the potential synergism between curcumin and PS in vivo, curcumin was suspended in 10% Tween-80 or formulated in micellar nanoparticles and given to mice by oral gavage prior to the administration of PS. Both formulations of curcumin significantly improved the pharmacokinetic profiles of PS, with the 10% Tween-80 suspension being much more effective than the nanoparticle formation. However, curcumin did not exhibit any significant modification of the metabolite profile of PS. Furthermore, in a mouse subcutaneous xenograft model of human lung cancer, PS (200 mg/kg) in combination with curcumin (500 mg/kg) suspended in 10% Tween-80 (51% inhibition, p<0.05) was significantly more efficacious than PS plus micelle curcumin (30%) or PS (25%) or curcumin alone (no effect). Consistent with the improved pharmacokinetics, the combination treatment group had higher levels of PS and its metabolites in the xenografts compared to PS alone. Our results show that curcumin substantially improves the pharmacokinetics of PS leading to synergistic inhibition of the growth of human lung cancer xenografts, representing a promising drug combination.

  17. The Application of Interpersonal Relationship Poll to the Enhancement of Management Efficacy

    Directory of Open Access Journals (Sweden)

    Kuo-Wei Lin

    2012-01-01

    Full Text Available Problem statement: Every employee needs to directly face their different superiors and subordinates that he must have ability to get along with other people or teams. It is the ability that he could communicate, coordinate, convince, negotiate and inspire his working partners smoothly and the organization, leadership and control could be implemented in accordance with the established plans. So the interpersonal relationship of employees may severely affect an organization. Although many enterprises have developed their own assessment systems, most of the systems focus on performance evaluation and few of them explore the efficacy of organization from the angle of employee’s interpersonal relationship. Approach: This study aims to develop a well-rounded model for the interpersonal relationship poll that every employee could receive poll for his own interpersonal relationship. Through the questionnaire poll that includes self-assessment and other’s assessment, one could systematically and methodically see himself from the eyes of others and understand whether he is an asset or a liability in the operation of organization, a resistance force or a boosting force that he could modify his own interpersonal relationship and in turn enhance the operational efficacy in organization. Results: The model for interpersonal relationship poll developed by the study has been practically applied. After an employee understand his working partners’ views on him in the poll, his relationship with other colleagues is improved and his performance is enhanced. Conclusion: The interpersonal relationship poll made full use of the approaches in raising questions to the persons involved for self-evaluation and assessed by others, jumped out passive and slow one-way self-examination and turned to positive, quick two-way communications that were substantially helpful in harmonizing interpersonal relationship and enhancing the operational efficacy in

  18. Enhanced antitumor efficacy of cisplatin in combination with HemoHIM in tumor-bearing mice

    Directory of Open Access Journals (Sweden)

    Kim Sung-Ho

    2009-03-01

    Full Text Available Abstract Background Although cisplatin is one of the most effective chemotherapeutic agents, cisplatin alone does not achieve a satisfactory therapeutic outcome. Also cisplatin accumulation shows toxicity to normal tissues. In this study, we examined the possibility of HemoHIM both to enhance anticancer effect with cisplatin and to reduce the side effects of cisplatin in melanoma-bearing mice. Methods HemoHIM was prepared by adding the ethanol-insoluble fraction to the total water extract of a mixture of 3 edible herbs, Angelica Radix, Cnidium Rhizoma and Paeonia Radix. Anticancer effects of HemoHIM with cisplatin were evaluated in melanoma-bearing mice. We used a Cr51-release assay to measure the activity of NK/Tc cell and ELISA to evaluate the production of cytokines. Results In melanoma-bearing mice, cisplatin (4 mg/kg B.W. reduced the size and weight of the solid tumors, and HemoHIM supplementation with cisplatin enhanced the decrease of both the tumor size (p in vitro, and did not disturb the effects of cisplatin in vitro. However HemoHIM administration enhanced both NK cell and Tc cell activity in mice. Interestingly, HemoHIM increased the proportion of NK cells in the spleen. In melanoma-bearing mice treated with cisplatin, HemoHIM administration also increased the activity of NK cells and Tc cells and the IL-2 and IFN-γ secretion from splenocytes, which seemed to contribute to the enhanced efficacy of cisplatin by HemoHIM. Also, HemoHIM reduced nephrotoxicity as seen by tubular cell of kidney destruction. Conclusion HemoHIM may be a beneficial supplement during cisplatin chemotherapy for enhancing the anti-tumor efficacy and reducing the toxicity of cisplatin.

  19. Enhancement of the anti-damping spin torque efficacy of platinum by interface modification

    Energy Technology Data Exchange (ETDEWEB)

    Nguyen, Minh-Hai; Pai, Chi-Feng; Nguyen, Kayla X.; Buhrman, R. A., E-mail: buhrman@cornell.edu [Cornell University, Ithaca, New York 14853 (United States); Muller, David A.; Ralph, D. C. [Cornell University, Ithaca, New York 14853 (United States); Kavli Institute at Cornell, Ithaca, New York 14853 (United States)

    2015-06-01

    We report a strong enhancement of the efficacy of the spin Hall effect (SHE) of Pt for exerting anti-damping spin torque on an adjacent ferromagnetic layer by the insertion of ≈0.5 nm layer of Hf between a Pt film and a thin, ≤2 nm, Fe{sub 60}Co{sub 20}B{sub 20} ferromagnetic layer. This enhancement is quantified by measurement of the switching current density when the ferromagnetic layer is the free electrode in a magnetic tunnel junction. The results are explained as the suppression of spin pumping through a substantial decrease in the effective spin-mixing conductance of the interface, but without a concomitant reduction of the ferromagnet's absorption of the SHE generated spin current.

  20. Solid lipid nanoparticle suspension enhanced the therapeutic efficacy of praziquantel against tapeworm

    Directory of Open Access Journals (Sweden)

    Xie S

    2011-10-01

    Full Text Available Shuyu Xie1,*, Baoliang Pan1,*, Baoxin Shi2, Zhuangzhi Zhang2, Xu Zhang2, Ming Wang1, Wenzhong Zhou11Department of Preventive Veterinary Medicine, College of Veterinary Medicine, China Agricultural University, Beijing, People’s Republic of China; 2Veterinary Research Institute, Xinjiang Academy of Animal Science, Xinjiang, People’s Republic of China *These authors contributed equally to this study Abstract: Hydatid disease caused by tapeworm is an increasing public health and socioeconomic concern. In order to enhance the therapeutic efficacy of praziquantel (PZQ against tapeworm, PZQ-loaded hydrogenated castor oil solid lipid nanoparticle (PZQ-HCO-SLN suspension was prepared by a hot homogenization and ultrasonication method. The stability of the suspension at 4°C and room temperature was evaluated by the physicochemical characteristics of the nanoparticles and in-vitro release pattern of the suspension. Pharmacokinetics was studied after subcutaneous administration of the suspension in dogs. The therapeutic effect of the novel formulation was evaluated in dogs naturally infected with Echinococcus granulosus. The results showed that the drug recovery of the suspension was 97.59% ± 7.56%. Nanoparticle diameter, polydispersivity index, and zeta potential were 263.00 ± 11.15 nm, 0.34 ± 0.06, and -11.57 ± 1.12 mV, respectively and showed no significant changes after 4 months of storage at both 4°C and room temperature. The stored suspensions displayed similar in-vitro release patterns as that of the newly prepared one. SLNs increased the bioavailability of PZQ 5.67-fold and extended the mean residence time of the drug from 56.71 to 280.38 hours. Single subcutaneous administration of PZQ-HCO-SLN suspension obtained enhanced therapeutic efficacy against tapeworm in infected dogs. At the dose of 5 mg/kg, the stool-ova reduction and negative conversion rates and tapeworm removal rate of the suspension were 100%, while the native PZQ were 91

  1. Enhanced photodynamic therapy efficacy of methylene blue-loaded calcium phosphate nanoparticles.

    Science.gov (United States)

    Seong, Da-Young; Kim, Young-Jin

    2015-05-01

    Although methylene blue (MB) is the most inexpensive photosensitizer with promising applications in the photodynamic therapy (PDT) for its high quantum yield of singlet oxygen generation, the clinical use of MB has been limited by its rapid enzymatic reduction in the biological environment. To enhance PDT efficacy of MB by preventing the enzymatic reduction, we have developed a new mineralization method to produce highly biocompatible MB-loaded calcium phosphate (CaP-MB) nanoparticles in the presence of polymer templates. The resulting CaP-MB nanoparticles exhibited spherical shape with a size of under 50 nm. Fourier transform infrared (FT-IR) and zeta-potential analyses confirmed the insertion of MB into the CaP-MB nanoparticles. The encapsulation of MB in CaP nanoparticles could effectively protect MB from the enzymatic reduction. In addition, the CaP-MB nanoparticles exhibited a good biocompatibility in the dark condition and significantly enhanced PDT efficacy due to apoptotic cell death against human breast cancer cells as compared with free MB, implying that CaP-MB nanoparticle system might be potentially applicable in PDT.

  2. Quantum dots as enhancers of the efficacy of bacterial lethal photosensitization

    Science.gov (United States)

    Narband, N.; Mubarak, M.; Ready, D.; Parkin, I. P.; Nair, S. P.; Green, M. A.; Beeby, A.; Wilson, M.

    2008-11-01

    Because of the increasing resistance of bacteria to antibiotics there is considerable interest in light-activated antimicrobial agents (LAAAs) as alternatives to antibiotics for treating localized infections. The purpose of this study was to determine whether CdSe/ZnS quantum dots (QD) could enhance the antibacterial activity of the LAAA, toluidine blue O (TBO). Suspensions of Staphylococcus aureus and Streptococcus pyogenes were exposed to white light (3600 lux) and TBO (absorbance maximum = 630 nm) in the presence and absence of 25 nm diameter QD (emission maximum = 627 nm). When the TBO:QD ratio was 2667:1, killing of Staph. aureus was enhanced by 1.72log10 units. In the case of Strep. pyogenes, an enhanced kill of 1.55log10 units was achieved using TBO and QD in the ratio 267:1. Singlet oxygen and fluorescence measurements showed that QD suppress the formation of singlet oxygen from TBO and that QD fluorescence is significantly quenched in the presence of TBO (70-90%). Enhanced killing appears to be attributable to a non-Förster resonance energy transfer mechanism, whereby the QD converts part of the incident light to the absorption maximum for TBO; hence more light energy is harvested, resulting in increased concentrations of bactericidal radicals. QD may, therefore, be useful in improving the efficacy of antimicrobial photodynamic therapy.

  3. Enhancement of cisplatin efficacy by thalidomide in a 9L rat gliosarcoma model.

    Science.gov (United States)

    Murphy, Susan; Davey, Ross A; Gu, Xiao-Qing; Haywood, Miriam C; McCann, Lauren A; Mather, Laurence E; Boyle, Frances M

    2007-11-01

    With the aim of improving the treatment of glioblastoma multiforme, we investigated the potential of thalidomide to enhance the effectiveness of cisplatin chemotherapy in a rat glioma model. Female F344 rats were implanted with 9L gliosarcoma tumors either intracranially or subcutaneously and treated with 1 mg/kg cisplatin injected i.p. or with 1% thalidomide in the food or with these treatments combined. Cisplatin in combination with thalidomide significantly reduced both the subcutaneous tumor volume at 30 days to 22 +/- 5% (mean +/- SEM, P < 0.001) and the intracranial tumor volume at 18 days to 44 +/- 15% (P < 0.05) of that with cisplatin alone. Thalidomide selectively increased the cisplatin concentration 10-fold in intracranial tumors (P < 0.05) and 2-fold in the subcutaneous tumors (P < 0.05) without increasing its concentration in major organs including brain and kidney. Cisplatin combined with thalidomide caused a significant decrease in vascular endothelial growth factor (VEGF) levels by 73% in intracranial tumors (P < 0.05) and by 50% in subcutaneous tumors (P < 0.05) and caused the level of active hepatic growth factor (a-HGF) to double in both the subcutaneous and intracranial tumors (P < 0.05), suggesting this treatment altered the vasculature in these tumors. We conclude the increased efficacy of cisplatin in the presence of thalidomide was due to the selective increase in cisplatin concentration within the tumors and speculate that this is the result of thalidomide or the cisplatin/thalidomide combination, selectively altering the tumor vasculature. Based on the selective effects of thalidomide on tumor cisplatin concentrations and the resulting increase in efficacy, thalidomide may also increase the efficacy of other drugs that are presently considered ineffective against glioma.

  4. Augmenting the Efficacy of Immunotoxins and Other Targeted Protein Toxins by Endosomal Escape Enhancers

    Directory of Open Access Journals (Sweden)

    Hendrik Fuchs

    2016-07-01

    Full Text Available The toxic moiety of almost all protein-based targeted toxins must enter the cytosol of the target cell to mediate its fatal effect. Although more than 500 targeted toxins have been investigated in the past decades, no antibody-targeted protein toxin has been approved for tumor therapeutic applications by the authorities to date. Missing efficacy can be attributed in many cases to insufficient endosomal escape and therefore subsequent lysosomal degradation of the endocytosed toxins. To overcome this drawback, many strategies have been described to weaken the membrane integrity of endosomes. This comprises the use of lysosomotropic amines, carboxylic ionophores, calcium channel antagonists, various cell-penetrating peptides of viral, bacterial, plant, animal, human and synthetic origin, other organic molecules and light-induced techniques. Although the efficacy of the targeted toxins was typically augmented in cell culture hundred or thousand fold, in exceptional cases more than million fold, the combination of several substances harbors new problems including additional side effects, loss of target specificity, difficulties to determine the therapeutic window and cell type-dependent variations. This review critically scrutinizes the chances and challenges of endosomal escape enhancers and their potential role in future developments.

  5. Anti-invasive adjuvant therapy with imipramine blue enhances chemotherapeutic efficacy against glioma.

    Science.gov (United States)

    Munson, Jennifer M; Fried, Levi; Rowson, Sydney A; Bonner, Michael Y; Karumbaiah, Lohitash; Diaz, Begoña; Courtneidge, Sara A; Knaus, Ulla G; Brat, Daniel J; Arbiser, Jack L; Bellamkonda, Ravi V

    2012-03-28

    The invasive nature of glioblastoma (GBM) represents a major clinical challenge contributing to poor outcomes. Invasion of GBM into healthy tissue restricts chemotherapeutic access and complicates surgical resection. Here, we test the hypothesis that an effective anti-invasive agent can "contain" GBM and increase the efficacy of chemotherapy. We report a new anti-invasive small molecule, Imipramine Blue (IB), which inhibits invasion of glioma in vitro when tested against several models. IB inhibits NADPH (reduced form of nicotinamide adenine dinucleotide phosphate) oxidase-mediated reactive oxygen species generation and alters expression of actin regulatory elements. In vivo, liposomal IB (nano-IB) halts invasion of glioma, leading to a more compact tumor in an aggressively invasive RT2 syngeneic astrocytoma rodent model. When nano-IB therapy was followed by liposomal doxorubicin (nano-DXR) chemotherapy, the combination therapy prolonged survival compared to nano-IB or nano-DXR alone. Our data demonstrate that nano-IB-mediated containment of diffuse glioma enhanced the efficacy of nano-DXR chemotherapy, demonstrating the promise of an anti-invasive compound as an adjuvant treatment for glioma.

  6. Itraconazole IV nanosuspension enhances efficacy through altered pharmacokinetics in the rat.

    Science.gov (United States)

    Rabinow, Barrett; Kipp, James; Papadopoulos, Pavlos; Wong, Joseph; Glosson, Jill; Gass, Jerome; Sun, Chong-Son; Wielgos, Todd; White, Randy; Cook, Chyung; Barker, Kerry; Wood, Kristy

    2007-07-18

    The goal of this research was to evaluate an intravenous itraconazole nanosuspension dosage form, relative to a solution formulation, in the rat. Itraconazole was formulated as a nanosuspension by a tandem process of microcrystallization followed by homogenization. Acute toxicity, pharmacokinetics, and distribution were studied in the rat, and compared with a solution formulation of itraconazole. Efficacy was studied in an immunocompromised rat model, challenged with a lethal dose of either itraconazole-sensitive or itraconazole-resistant C. albicans. Itraconazole nanosuspension was tolerated at significantly higher doses compared with a solution formulation. Pharmacokinetics of the nanosuspension were altered relative to the solution formulation. C(max) was reduced and t(1/2) was much prolonged. This occurred due to distribution of the nanosuspension to organs of the monocyte phagocytic system (MPS), followed by sustained release from this IV depot. The higher dosing of the drug, enabled in the case of the nanosuspension, led to higher kidney drug levels and reduced colony counts. Survival was also shown to be superior relative to the solution formulation. Thus, formulation of itraconazole as a nanosuspension enhances efficacy of this antifungal agent relative to a solution formulation, because of altered pharmacokinetics, leading to increased tolerability, permitting higher dosing and resultant tissue drug levels.

  7. Blockade of IL-18 signaling diminished neuropathic pain and enhanced the efficacy of morphine and buprenorphine.

    Science.gov (United States)

    Pilat, Dominika; Piotrowska, Anna; Rojewska, Ewelina; Jurga, Agnieszka; Ślusarczyk, Joanna; Makuch, Wioletta; Basta-Kaim, Agnieszka; Przewlocka, Barbara; Mika, Joanna

    2016-03-01

    Currently, the low efficacy of antinociceptive drugs for the treatment of neuropathic pain is a major therapeutic problem. Here, we show the potential role of interleukin (IL)-18 signaling in this phenomenon. IL-18 is an important molecule that performs various crucial functions, including the alteration of nociceptive transmission in response to neuropathic pain. We have studied the changes in the mRNA and protein levels (qRT-PCR and Western blot analysis, respectively) of IL-18, IL-18-binding protein (IL-18BP) and the IL-18 receptor (IL-18R) over time in rats following chronic constriction injury (CCI) of the sciatic nerve. Our study demonstrated that the spinal levels of IL-18BP were slightly downregulated at days 7 and 14 in the rats subjected to CCI. In contrast, the IL-18 and IL-18R mRNA expression and protein levels were elevated in the ipsilateral spinal cord on days 2, 7 and 14. Moreover, in rats exposed to a single intrathecal administration of IL-18BP (50 and 100 ng) 7 or 14 days following CCI, symptoms of neuropathic pain were attenuated, and the analgesia pursuant to morphine and buprenorphine (0.5 and 2.5 μg) was enhanced. In summary, the restoration of the analgesic activity of morphine and buprenorphine via the blockade of IL-18 signaling suggests that increased IL-18 pathway may account for the decreased analgesic efficacy of opioids for neuropathic pain.

  8. The efficacy of diazepam in enhancing motor function in children with spastic cerebral palsy.

    Science.gov (United States)

    Mathew, Anna; Mathew, M C; Thomas, Molly; Antonisamy, B

    2005-04-01

    Muscle spasm and hypertonia limit mobility in children with spastic cerebral palsy. This double-blind, placebo-controlled, randomized controlled clinical trial studies the clinical efficacy of a low dose of diazepam in enhancing movement in children with spastic cerebral palsy. One hundred and eighty children fulfilled the criteria and were randomly allocated to receive one of two doses of diazepam or placebo at bedtime; 173 completed the study. There was a significant reduction of hypertonia, improvement in the range of passive movement, and an increase in spontaneous movement in the children who received diazepam. There was no report of daytime drowsiness. In developing countries, where cost factors often determine choice of drug, diazepam is a cheap and effective way of relieving spasm and stiffness, optimizing physical therapy and facilitating movement in children with spasticity.

  9. Cyclooxygenase-2 inhibitor enhances the efficacy of a breast cancer vaccine: role of IDO.

    Science.gov (United States)

    Basu, Gargi D; Tinder, Teresa L; Bradley, Judy M; Tu, Tony; Hattrup, Christine L; Pockaj, Barbara A; Mukherjee, Pinku

    2006-08-15

    We report that administration of celecoxib, a specific cyclooxygenase-2 (COX-2) inhibitor, in combination with a dendritic cell-based cancer vaccine significantly augments vaccine efficacy in reducing primary tumor burden, preventing metastasis, and increasing survival. This combination treatment was tested in MMTV-PyV MT mice that develop spontaneous mammary gland tumors with metastasis to the lungs and bone marrow. Improved vaccine potency was associated with an increase in tumor-specific CTLs. Enhanced CTL activity was attributed to a significant decrease in levels of tumor-associated IDO, a negative regulator of T cell activity. We present data suggesting that inhibiting COX-2 activity in vivo regulates IDO expression within the tumor microenvironment; this is further corroborated in the MDA-MB-231 human breast cancer cell line. Thus, a novel mechanism of COX-2-induced immunosuppression via regulation of IDO has emerged that may have implications in designing future cancer vaccines.

  10. Self-efficacy enhancing intervention increases light physical activity in people with chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Larson JL

    2014-10-01

    Full Text Available Janet L Larson,1,2 Margaret K Covey,2 Mary C Kapella,2 Charles G Alex,3,4 Edward McAuley,5 1Division of Acute, Critical and Long-Term Care Programs, School of Nursing, University of Michigan, Ann Arbor, MI, 2Department of Biobehavioral Health Science, College of Nursing, University of Illinois at Chicago, Chicago, IL, 3Division of Pulmonary and Critical Care Medicine, Edward Hines Jr VA Hospital, Hines, IL, 4Advocate Christ Medical Center, Oaklawn, IL, 5Department of Kinesiology and Community Health, College of Applied Health Sciences, University of Illinois Urbana-Champagne, Urbana, IL, USA Background: People with chronic obstructive pulmonary disease lead sedentary lives and could benefit from increasing their physical activity. The purpose of this study was to determine if an exercise-specific self-efficacy enhancing intervention could increase physical activity and functional performance when delivered in the context of 4 months of upper body resistance training with a 12-month follow-up. Methods: In this randomized controlled trial, subjects were assigned to: exercise-specific self-efficacy enhancing intervention with upper body resistance training (SE-UBR, health education with upper body resistance training (ED-UBR, or health education with gentle chair exercises (ED-Chair. Physical activity was measured with an accelerometer and functional performance was measured with the Functional Performance Inventory. Forty-nine people with moderate to severe chronic obstructive pulmonary disease completed 4 months of training and provided valid accelerometry data, and 34 also provided accelerometry data at 12 months of follow-up. The self-efficacy enhancing intervention emphasized meeting physical activity guidelines and increasing moderate-to-vigorous physical activity. Results: Differences were observed in light physical activity (LPA after 4 months of training, time by group interaction effect (P=0.045. The SE-UBR group increased time spent in

  11. Mechanisms mediating enhanced neutralization efficacy of staphylococcal enterotoxin B by combinations of monoclonal antibodies.

    Science.gov (United States)

    Dutta, Kaushik; Varshney, Avanish K; Franklin, Matthew C; Goger, Michael; Wang, Xiaobo; Fries, Bettina C

    2015-03-13

    Staphylococcal enterotoxin B (SEB) is a superantigen that cross-links the major histocompatibility complex class II and specific V-β chains of the T-cell receptor, thus forming a ternary complex. Developing neutralizing mAb to disrupt the ternary complex and abrogate the resulting toxicity is a major therapeutic challenge because SEB is effective at very low concentrations. We show that combining two SEB-specific mAbs enhances their efficacy, even though one of the two mAbs by itself has no effect on neutralization. Crystallography was employed for fine-mapping conformational epitopes in binary and ternary complexes between SEB and Fab fragments. NMR spectroscopy was used to validate and identify subtle allosteric changes induced by mAbs binding to SEB. The mapping of epitopes established that a combination of different mAbs can enhance efficacy of mAb-mediated protection from SEB induced lethal shock by two different mechanisms: one mAb mixture promoted clearance of the toxin both in vitro and in vivo by FcR-mediated cross-linking and clearance, whereas the other mAb mixture induced subtle allosteric conformational changes in SEB that perturbed formation of the SEB·T-cell receptor·major histocompatibility complex class II trimer. Finally structural information accurately predicted mAb binding to other superantigens that share conformational epitopes with SEB. Fine mapping of conformational epitopes is a powerful tool to establish the mechanism and optimize the action of synergistic mAb combinations.

  12. Doxorubicin conjugated functionalizable carbon dots for nucleus targeted delivery and enhanced therapeutic efficacy

    Science.gov (United States)

    Yang, Lei; Wang, Zheran; Wang, Ju; Jiang, Weihua; Jiang, Xuewei; Bai, Zhaoshi; He, Yunpeng; Jiang, Jianqi; Wang, Dongkai; Yang, Li

    2016-03-01

    Carbon dots (CDs) have shown great potential in imaging and drug/gene delivery applications. In this work, CDs functionalized with a nuclear localization signal peptide (NLS-CDs) were employed to transport doxorubicin (DOX) into cancer cells for enhanced antitumor activity. DOX was coupled to NLS-CDs (DOX-CDs) through an acid-labile hydrazone bond, which was cleavable in the weakly acidic intracellular compartments. The cytotoxicity of DOX-CD complexes was evaluated by the MTT assay and the cellular uptake was monitored using flow cytometry and confocal laser scanning microscopy. Cell imaging confirmed that DOX-CDs were mainly located in the nucleus. Furthermore, the complexes could efficiently induce apoptosis in human lung adenocarcinoma A549 cells. The in vivo therapeutic efficacy of DOX-CDs was investigated in an A549 xenograft nude mice model and the complexes exhibited an enhanced ability to inhibit tumor growth compared with free DOX. Thus, the DOX-CD conjugates may be exploited as promising drug delivery vehicles in cancer therapy.Carbon dots (CDs) have shown great potential in imaging and drug/gene delivery applications. In this work, CDs functionalized with a nuclear localization signal peptide (NLS-CDs) were employed to transport doxorubicin (DOX) into cancer cells for enhanced antitumor activity. DOX was coupled to NLS-CDs (DOX-CDs) through an acid-labile hydrazone bond, which was cleavable in the weakly acidic intracellular compartments. The cytotoxicity of DOX-CD complexes was evaluated by the MTT assay and the cellular uptake was monitored using flow cytometry and confocal laser scanning microscopy. Cell imaging confirmed that DOX-CDs were mainly located in the nucleus. Furthermore, the complexes could efficiently induce apoptosis in human lung adenocarcinoma A549 cells. The in vivo therapeutic efficacy of DOX-CDs was investigated in an A549 xenograft nude mice model and the complexes exhibited an enhanced ability to inhibit tumor growth compared

  13. The efficacy of contrast-enhanced harmonic endoscopic ultrasonography in diagnosing gallbladder cancer.

    Science.gov (United States)

    Sugimoto, Mitsuru; Takagi, Tadayuki; Konno, Naoki; Suzuki, Rei; Asama, Hiroyuki; Hikichi, Takuto; Watanabe, Ko; Waragai, Yuichi; Kikuchi, Hitomi; Takasumi, Mika; Ohira, Hiromasa

    2016-01-01

    The aim of this study was to review the efficacy of contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS) in diagnosing gallbladder (GB)-protruded lesions. Thirty-eight patients underwent CH-EUS for the diagnosis of GB-protruded lesions. Twenty-four patients whose major axes of their largest lesions were longer than 10 mm were recruited. The ability of CH-EUS to diagnose malignant or benign lesions was reviewed. We treated lesions with brindled enhanced patterns as malignant and those with uniformly enhanced or unenhanced patterns as benign. Furthermore, three gastroenterologists who were not familiar with pancreaticobiliary EUS compared the diagnostic abilities of CH-EUS and conventional EUS using photographs. The sensitivity, specificity, and malignant accuracy of CH-EUS were 100, 94.4, and 95.8%, respectively. The number of lesions that presented with enhanced patterns was significantly different between the malignant lesions and the benign lesions (P < 0.001). In the comparison of diagnostic abilities between CH-EUS and conventional EUS by the three gastroenterologists, CH-EUS was significantly superior to conventional EUS in terms of sensitivity, specificity, and accuracy (76.1 vs. 42.9%, P = 0.029; 66.7 vs. 39.2%, P = 0.005; and 69.4 vs. 40.3%, P < 0.001; respectively). In conclusion, CH-EUS was useful for diagnosing malignant and benign GB-protruded lesions.

  14. Surface decoration by Spirulina polysaccharide enhances the cellular uptake and anticancer efficacy of selenium nanoparticles

    Science.gov (United States)

    Yang, Fang; Tang, Quanming; Zhong, Xueyun; Bai, Yan; Chen, Tianfeng; Zhang, Yibo; Li, Yinghua; Zheng, Wenjie

    2012-01-01

    A simple and solution-phase method for functionalization of selenium nanoparticles (SeNPs) with Spirulina polysaccharides (SPS) has been developed in the present study. The cellular uptake and anticancer activity of SPS-SeNPs were also evaluated. Monodisperse and homogeneous spherical SPS-SeNPs with diameters ranging from 20 nm to 50 nm were achieved under optimized conditions, which were stable in the solution phase for at least 3 months. SPS surface decoration significantly enhanced the cellular uptake and cytotoxicity of SeNPs toward several human cancer cell lines. A375 human melanoma cells were found extremely susceptible to SPS-SeNPs with half maximal (50%) inhibitory concentration value of 7.94 μM. Investigation of the underlying mechanisms revealed that SPS-SeNPs inhibited cancer cell growth through induction of apoptosis, as evidenced by an increase in sub-G1 cell population, deoxyribonucleic acid fragmentation, chromatin condensation, and phosphatidylserine translocation. Results suggest that the strategy to use SPS as a surface decorator could be an effective way to enhance the cellular uptake and anticancer efficacy of nanomaterials. SPS-SeNPs may be a potential candidate for further evaluation as a chemopreventive and chemotherapeutic agent against human cancers. PMID:22359460

  15. Novel curcumin diclofenac conjugate enhanced curcumin bioavailability and efficacy in streptococcal cell wall-induced arthritis

    Directory of Open Access Journals (Sweden)

    S K Jain

    2014-01-01

    Full Text Available Curcumin-diclofenac conjugate as been synthesized by esterification of phenolic group of curcumin with the acid moiety of diclofenac, and characterized by mass spectrometry, NMR, FTIR, DSC, thermogravimetric analysis and X-ray diffraction analysis. The relative solubility of curcumin-diclofenac conjugate, curcumin and diclofenac; stability of curcumin-diclofenac conjugate in intestinal extract; permeability study of curcumin-diclofenac conjugate using the everted rat intestinal sac method; stability of curcumin-diclofenac conjugate in gastrointestinal fluids and in vitro efficacy have been evaluated. In vivo bioavailability of curcumin-diclofenac conjugate and curcumin in Sprague-Dawley rats, and antiarthritic activity of curcumin-diclofenac conjugate, curcumin and diclofenac in modified streptococcal cell wall-induced arthritis model in Balb/c mice to mimic rheumatoid arthritis in humans have also been studied. In all of the above studies, curcumin-diclofenac conjugate exhibited enhanced stability as compared to curcumin; its activity was twice that of diclofenac in inhibiting thermal protein denaturation taken as a measure of in vitro antiinflammatory activity; it enhanced the bioavailability of curcumin by more than five folds, and significantly (P<0.01 alleviated the symptoms of arthritis in streptococcal cell wall-induced arthritis model as compared to both diclofenac and curcumin.

  16. Liposomal photofrin enhances therapeutic efficacy of photodynamic therapy against the human gastric cancer.

    Science.gov (United States)

    Igarashi, Akira; Konno, Hiroyuki; Tanaka, Tatsuo; Nakamura, Satoshi; Sadzuka, Yasuyuki; Hirano, Toru; Fujise, Yutaka

    2003-11-30

    Photodynamic therapy (PDT) has been established as a potent and less invasive treatment for gastrointestinal tumors. The aim of the present study was to investigate whether or not liposomalization of the photosensitizer enhanced the therapeutic efficacy of PDT. Photofrin (PF) was entrapped in multilammelar liposomes. Mice implanted with a human gastric cancer xenograft, were divided into a PF group and a liposomal photofrin (LPF) group and intravenously administered 10 mg/kg of PF or LPF (as a dose of PF), respectively. At 8 h after injection PF level in tumor tissue in the LPF group was significantly higher level by 2.4-fold of that in the PF group, whereas the PF levels in the skin were almost equal. Irradiation was performed with the excimer dye laser at 150 mW/cm(2), total dose 40 J, at 8 h after PF or LPF administration. The results revealed that the volume of necrotic tumor tissue was significantly higher in the LPF group than in the PF group. The apoptotic index of the tumor was also significantly higher in the LPF group. In conclusion, the liposomalization of the photosensitizer increased its tumor accumulation, with a resulting enhancement of the therapeutic effect of PDT.

  17. The Development of a Cultural-Based Educational Program to Enhance Breast Self-Examination (BSE Self-Efficacy

    Directory of Open Access Journals (Sweden)

    Juanita Juanita

    2012-08-01

    Full Text Available Purpose: To develop the educational program which is appropriate with Islamic culture in order to enhance BSE self-efficacy of nursing students and thus promote BSE practice. Method: This study is a development research study which is consisting of three phases including: 1 reviewing several existing BSE educational programs; 2 program design based on SCT and Islamic culture; and 3 program validation by three experts. Result: Based on previous studies, the most appropriate theory to enhance self-efficacy was Social Cognitive Theory (SCT because this theory provides several strategies to increase the self-efficacy. Further, the program that used Islamic culture was more appropriate to increase BSE practice among Muslim women. As a result, the newly developed program was developed used SCT and Islamic culture. This program was comprised of four sessions including: 1 exploring Islamic mandate on prevention and individual responsibility in health promotion, and culture-related beliefs toward BSE, 2 health education by conducting lecturing session and watching a video about BSE procedures, 3 BSE training activities including BSE demonstration and return demonstration, 4 follow-up by conducting a meeting. Conclusion: The cultural-based educational program for enhancing BSE self-efficacy and promoting BSE is a program using multifaceted methods. It designed based on a review of the literature from previous studies and were supported by research findings on experimental studies in other population. Keywords: Cultural, Educational program development, Breast self-examination, Self-efficacy.

  18. Inspiring Instructional Change in Elementary School Science: The Relationship Between Enhanced Self-efficacy and Teacher Practices

    Science.gov (United States)

    Sandholtz, Judith Haymore; Ringstaff, Cathy

    2014-10-01

    This longitudinal study examined the extent to which teachers' participation in a 3-year professional development program enhanced their self-efficacy and prompted changes in science instruction in the early elementary grades. The study used a mixed-methods design, and included 39 teachers who taught in kindergarten, first grade, or second grade classrooms in rural school districts. Data sources, administered pre-program and at the end of each year, included a self-efficacy assessment and teacher survey. Interviews and classroom observations provided corroborating data about teachers' beliefs and science instruction. Results showed significant increases in teachers' overall self-efficacy in teaching science, personal efficacy, and outcome expectancy efficacy during the 3 years. Gains in self-efficacy were correlated with changes in reported instructional practices, particularly student participation activities. However, changes in self-efficacy tended not to be correlated with changes in instructional time. Contextual factors beyond teachers' direct control, such as curricular and testing requirements in mathematics and language arts influenced time allotted to science instruction.

  19. Enhancing self-efficacy improves episodic future thinking and social-decision making in combat veterans with posttraumatic stress disorder.

    Science.gov (United States)

    Brown, Adam D; Kouri, Nicole A; Rahman, Nadia; Joscelyne, Amy; Bryant, Richard A; Marmar, Charles R

    2016-08-30

    Posttraumatic Stress Disorder (PTSD) is associated with maladaptive changes in self-identity, including impoverished perceived self-efficacy. This study examined if enhancing perceptions of self-efficacy in combat veterans with and without symptoms of PTSD promotes cognitive strategies associated with positive mental health outcomes. Prior to completing a future thinking and social problem-solving task, sixty-two OEF/OIF veterans with and without symptoms of PTSD were randomized to either a high self-efficacy (HSE) induction in which they were asked to recall three autobiographical memories demonstrating self-efficacy or a control condition in which they recalled any three autobiographical events. An interaction between HSE and PTSD revealed that individuals with symptoms of PTSD in the HSE condition generated future events with more self-efficacious statements than those with PTSD in the control condition, whereas those without PTSD did not differ in self-efficacy content across the conditions. In addition, individuals in the HSE condition exhibited better social problem solving than those in the control condition. Increasing perceptions of self-efficacy may promote future thinking and problem solving in ways that are relevant to overcoming trauma and adversity.

  20. The Effectiveness of Group Motivational Interviewing Sessions on Enhancing of Addicted Women’s Self-Esteem and Self Efficacy

    Directory of Open Access Journals (Sweden)

    Samireh Dehghani F

    2013-07-01

    Full Text Available Objective: The aim of present research was to study of the effectiveness of motivational interviewing on enhancing of self-esteem and self-efficacy in addicted women who were under therapy. Method: The research method was semi experimental research design namely: pretest-posttest with witness group. The population consisted of all addicted women who were referred to Ayandeh Roshan recovery addiction camp of Isfahan city during summer in 1391. By available sampling, 30 women selected and divided randomly to two experimental and witness groups (N= 15, per group. Experimental group received eight sessions of 90 minutes based on group counseling sessions following motivational interviewing style. For gathering data, Cooper Smith’s self-esteem and general self-efficacy questionnaires administered among two groups. Results: The results indicated the effectiveness of motivational interviewing. Conclusion: It can be concluded that motivational interviewing has had enhancing effect on self-esteem and self-efficacy among experimental group.

  1. Downregulation of XPF-ERCC1 enhances cisplatin efficacy in cancer cells.

    Science.gov (United States)

    Arora, Sanjeevani; Kothandapani, Anbarasi; Tillison, Kristin; Kalman-Maltese, Vivian; Patrick, Steve M

    2010-07-01

    Bulky cisplatin lesions are repaired primarily by nucleotide excision repair (NER), in which the structure specific endonuclease XPF-ERCC1 is a critical component. It is now known that the XPF-ERCC1 complex has repair functions beyond NER and plays a role in homologous recombination (HR). It has been suggested that expression of ERCC1 correlates with cisplatin drug resistance in non-small cell lung cancer (NSCLC). In our study, using NSCLC, ovarian, and breast cancer cells, we show that the XPF-ERCC1 complex is a valid target to increase cisplatin cytotoxicity and efficacy. We targeted XPF-ERCC1 complex by RNA interference and assessed the repair capacity of cisplatin intrastrand and interstrand crosslinks by ELISA and alkaline comet assay, respectively. We also assessed the repair of cisplatin-ICL-induced double-strand breaks (DSBs) by monitoring gamma-H2AX focus formation. Interestingly, XPF protein levels were significantly reduced following ERCC1 downregulation, but the converse was not observed. The transcript levels were unaffected suggesting that XPF protein stability is likely affected. The repair of both types of cisplatin-DNA lesions was decreased with downregulation of XPF, ERCC1 or both XPF-ERCC1. The ICL-induced DSBs persist in the absence of XPF-ERCC1. The suppression of the XPF-ERCC1 complex significantly decreases the cellular viability which correlates well with the decrease in DNA repair capacity. A double knockdown of XPF-ERCC1 displays the greatest level of cellular cytotoxicity when compared with XPF or ERCC1 alone. The difference in cytotoxicity observed is likely due to the level of total protein complex remaining. These data demonstrate that XPF-ERCC1 is a valid target to enhance cisplatin efficacy in cancer cells by affecting cisplatin-DNA repair pathways.

  2. Ultrasound enhanced sanitizer efficacy in reduction of Escherichia coli O157:H7 population on spinach leaves

    Science.gov (United States)

    The use of ultrasound to enhance the efficacy of selected sanitizers in reduction of Escherichia coli O157:H7 populations on spinach was investigated. Spot-inoculated spinach samples were treated with water, chlorine, acidified sodium chlorite (ASC), peroxyacetic acid (POAA), and acidic electrolyzed...

  3. Light fractionation does not enhance the efficacy of methyl 5-aminolevulinate mediated photodynamic therapy in normal mouse skin.

    NARCIS (Netherlands)

    Bruijn, H.S. de; Haas, E.R. de; Hebeda, K.M.; Ploeg-van den Heuvel, A. van der; Sterenborg, H.J.C.M.; Neumann, H.A.; Robinson, D.J.

    2007-01-01

    Previous work demonstrated that fractionated illumination using two fractions separated by a dark interval of 2 h, significantly enhanced the clinical efficacy of photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA). Considering the increasing clinical use of methyl 5-aminolevulinate (MAL) an

  4. Does computerized working memory training with game elements enhance motivation and training efficacy in children with ADHD?

    NARCIS (Netherlands)

    Prins, P.J.M.; Dovis, S.; Ponsioen, A.; ten Brink, E.; van der Oord, S.

    2011-01-01

    This study examined the benefits of adding game elements to standard computerized working memory (WM) training. Specifically, it examined whether game elements would enhance motivation and training performance of children with ADHD, and whether it would improve training efficacy. A total of 51 child

  5. Nanoparticulated docetaxel exerts enhanced anticancer efficacy and overcomes existing limitations of traditional drugs

    Directory of Open Access Journals (Sweden)

    Choi J

    2015-09-01

    Full Text Available Jinhyang Choi,1,2 Eunjung Ko,1 Hye-Kyung Chung,3 Jae Hee Lee,1 Eun Jin Ju,1 Hyun Kyung Lim,4 Intae Park,1 Kab-Sig Kim,5 Joo-Hwan Lee,5 Woo-Chan Son,6 Jung Shin Lee,1,7 Joohee Jung,1,4 Seong-Yun Jeong,1,2 Si Yeol Song,1,8 Eun Kyung Choi1,3,8 1Institute for Innovative Cancer Research, 2Asan Institute for Life Sciences, 3Center for Development and Commercialization of Anti-cancer Therapeutics, 4College of Pharmacy, Duksung Women’s University, 5Bio-Synectics, 6Department of Pathology, 7Department of Internal Medicine, 8Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea Abstract: Nanoparticulation of insoluble drugs improves dissolution rate, resulting in increased bioavailability that leads to increased stability, better efficacy, and reduced toxicity of drugs. Docetaxel (DTX, under the trade name Taxotere™, is one of the representative anticancer chemotherapeutic agents of this era. However, this highly lipophilic and insoluble drug has many adverse effects. Our novel and widely applicable nanoparticulation using fat and supercritical fluid (NUFS™ technology enabled successful nanoscale particulation of DTX (Nufs-DTX. Nufs-DTX showed enhanced dissolution rate and increased aqueous stability in water. After confirming the preserved mechanism of action of DTX, which targets microtubules, we showed that Nufs-DTX exhibited similar effects in proliferation and clonogenic assays using A549 cells. Interestingly, we observed that Nufs-DTX had a greater in vivo tumor growth delay effect on an A549 xenograft model than Taxotere™, which was in agreement with the improved drug accumulation in tumors according to the biodistribution result, and was caused by the enhanced permeability and retention (EPR effect. Although both Nufs-DTX and Taxotere™ showed negative results for our administration dose in the hematologic toxicity test, Nufs-DTX showed much less toxicity than Taxotere™ in

  6. Enhancing the efficacy of cisplatin in ovarian cancer treatment – could arsenic have a role

    Directory of Open Access Journals (Sweden)

    Helm C William

    2009-01-01

    Full Text Available Abstract Ovarian cancer affects more than 200,000 women each year around the world. Most women are not diagnosed until the disease has already metastasized from the ovaries with a resultant poor prognosis. Ovarian cancer is associated with an overall 5 year survival of little more than 50%. The mainstay of front-line therapy is cytoreductive surgery followed by chemotherapy. Traditionally, this has been by the intravenous route only but there is more interest in the delivery of intraperitoneal chemotherapy utilizing the pharmaco-therapeutic advantage of the peritoneal barrier. Despite three large, randomized clinical trials comparing intravenous with intraperitoneal chemotherapy showing improved outcomes for those receiving at least part of their chemotherapy by the intraperitoneal route. Cisplatin has been the most active drug for the treatment of ovarian cancer for the last 4 decades and the prognosis for women with ovarian cancer can be defined by the tumor response to cisplatin. Those whose tumors are innately platinum-resistant at the time of initial treatment have a very poor prognosis. Although the majority of patients with ovarian cancer respond to front-line platinum combination chemotherapy the majority will develop disease that becomes resistant to cisplatin and will ultimately succumb to the disease. Improving the efficacy of cisplatin could have a major impact in the fight against this disease. Arsenite is an exciting agent that not only has inherent single-agent tumoricidal activity against ovarian cancer cell lines but also multiple biochemical interactions that may enhance the cytotoxicity of cisplatin including inhibition of deoxyribose nucleic acid (DNA repair. In vitro studies suggest that arsenite may enhance the activity of cisplatin in other cell types. Arsenic trioxide is already used clinically to treat acute promyelocytic leukemia demonstrating its safety profile. Further research in ovarian cancer is warranted to define

  7. Enhanced protective efficacy of a chimeric form of the schistosomiasis vaccine antigen Sm-TSP-2.

    Directory of Open Access Journals (Sweden)

    Mark S Pearson

    Full Text Available The large extracellular loop of the Schistosoma mansoni tetraspanin, Sm-TSP-2, when fused to a thioredoxin partner and formulated with Freund's adjuvants, has been shown to be an efficacious vaccine against murine schistosomiasis. Moreover, Sm-TSP-2 is uniquely recognised by IgG(1 and IgG(3 from putatively resistant individuals resident in S. mansoni endemic areas in Brazil. In the present study, we expressed Sm-TSP-2 at high yield and in soluble form in E. coli without the need for a solubility enhancing fusion partner. We also expressed in E. coli a chimera called Sm-TSP-2/5B, which consisted of Sm-TSP-2 fused to the immunogenic 5B region of the hookworm aspartic protease and vaccine antigen, Na-APR-1. Sm-TSP-2 formulated with alum/CpG showed significant reductions in adult worm and liver egg burdens in two separate murine schistosomiasis challenge studies. Sm-TSP-2/5B afforded significantly greater protection than Sm-TSP-2 alone when both antigens were formulated with alum/CpG. The enhanced protection obtained with the chimeric fusion protein was associated with increased production of anti-Sm-TSP-2 antibodies and IL-4, IL-10 and IFN-γ from spleen cells of vaccinated animals. Sera from 666 individuals from Brazil who were infected with S. mansoni were screened for potentially deleterious IgE responses to Sm-TSP-2. Anti-Sm-TSP-2 IgE to this protein was not detected (also shown previously for Na-APR-1, suggesting that the chimeric antigen Sm-TSP-2/5B could be used to safely and effectively vaccinate people in areas where schistosomes and hookworms are endemic.

  8. Surface decoration by Spirulina polysaccharide enhances the cellular uptake and anticancer efficacy of selenium nanoparticles

    Directory of Open Access Journals (Sweden)

    Li Y

    2012-02-01

    Full Text Available Fang Yang1*, Quanming Tang1,2*, Xueyun Zhong3, Yan Bai1, Tianfeng Chen1, Yibo Zhang1, Yinghua Li1, Wenjie Zheng11Department of Chemistry, Jinan University, Guangzhou, China; 2South China Seas Institute of Oceanology, Chinese Academy of Sciences, Guangzhou, China; 3Department of Pathology, Jinan University, Guangzhou, China*These authors contributed equally to this workAbstract: A simple and solution-phase method for functionalization of selenium nanoparticles (SeNPs with Spirulina polysaccharides (SPS has been developed in the present study. The cellular uptake and anticancer activity of SPS-SeNPs were also evaluated. Monodisperse and homogeneous spherical SPS-SeNPs with diameters ranging from 20 nm to 50 nm were achieved under optimized conditions, which were stable in the solution phase for at least 3 months. SPS surface decoration significantly enhanced the cellular uptake and cytotoxicity of SeNPs toward several human cancer cell lines. A375 human melanoma cells were found extremely susceptible to SPS-SeNPs with half maximal (50% inhibitory concentration value of 7.94 µM. Investigation of the underlying mechanisms revealed that SPS-SeNPs inhibited cancer cell growth through induction of apoptosis, as evidenced by an increase in sub-G1 cell population, deoxyribonucleic acid fragmentation, chromatin condensation, and phosphatidylserine translocation. Results suggest that the strategy to use SPS as a surface decorator could be an effective way to enhance the cellular uptake and anticancer efficacy of nanomaterials. SPS-SeNPs may be a potential candidate for further evaluation as a chemopreventive and chemotherapeutic agent against human cancers.Keywords: selenium nanoparticles, Spirulina polysaccharide, cellular uptake, anticancer, apoptosis

  9. SAMHD1 enhances nucleoside-analogue efficacy against HIV-1 in myeloid cells

    Science.gov (United States)

    Ordonez, Paula; Kunzelmann, Simone; Groom, Harriet C. T.; Yap, Melvyn W.; Weising, Simon; Meier, Chris; Bishop, Kate N.; Taylor, Ian A.; Stoye, Jonathan P.

    2017-01-01

    SAMHD1 is an intracellular enzyme that specifically degrades deoxynucleoside triphosphates into component nucleoside and inorganic triphosphate. In myeloid-derived dendritic cells and macrophages as well as resting T-cells, SAMHD1 blocks HIV-1 infection through this dNTP triphosphohydrolase activity by reducing the cellular dNTP pool to a level that cannot support productive reverse transcription. We now show that, in addition to this direct effect on virus replication, manipulating cellular SAMHD1 activity can significantly enhance or decrease the anti-HIV-1 efficacy of nucleotide analogue reverse transcription inhibitors presumably as a result of modulating dNTP pools that compete for recruitment by viral polymerases. Further, a variety of other nucleotide-based analogues, not normally considered antiretrovirals, such as the anti-herpes drugs Aciclovir and Ganciclovir and the anti-cancer drug Clofarabine are now revealed as potent anti-HIV-1 agents, under conditions of low dNTPs. This in turn suggests novel uses for nucleotide analogues to inhibit HIV-1 in differentiated cells low in dNTPs. PMID:28220857

  10. [Evolving 5-Fluorouracil Therapy to Achieve Enhanced Efficacy-Past and Current Efforts of Researchers].

    Science.gov (United States)

    Maehara, Yoshihiko; Oki, Eiji; Saeki, Hiroshi; Tokunaga, Eriko; Kitao, Hiroyuki; Iimori, Makoto; Niimi, Shinichiro; Kataoka, Yuki; Emi, Yasunori; Kakeji, Yoshihiro; Baba, Hideo; Shirasaka, Tetsuhiko

    2016-07-01

    5-fluorouracil(5-FU)therapy has advanced greatly over the past 50 years, achieving enhanced therapeutic effects and reduced adverse effects. By taking advantage of the metabolism of 5-FU, researchers have made efforts to develop prodrugs, combination drug products, and combination therapy regimens via biochemical modulation(BCM)with alteration of the drug metabolism. Examples include the advent of the prodrug tegafur(FT), followed by tegafur-uracil(UFT)and tegafurgimeracil- potassium oxonate(S-1)as combined products based on BCM. In the current standard treatment for gastrointestinal cancers, anticancer 5-FU derivatives serve as a platform for combination regimens with other cytotoxic agents or molecular- targeted drugs. To provide further improvements in anticancer therapy outcomes, novel molecular-targeted agents, immune checkpoint inhibitors, and other drugs are being developed, but 5-FU remains an attractive target that shows further potential for increased efficacy. In the future, the evolution of anticancer therapy with 5-FU derivatives is expected to continue via a variety of approaches.

  11. Development and Evaluation of Mouth Dissolving Films of Amlodipine Besylate for Enhanced Therapeutic Efficacy

    Directory of Open Access Journals (Sweden)

    K. M. Maheswari

    2014-01-01

    Full Text Available The present investigation was undertaken with an objective of formulating mouth dissolving films (MDFs of Amlodipine Besylate (AMLO to enhance convenience and compliance of the elderly and pediatric patients for better therapeutic efficacy. Film formers like hydroxy propyl methyl cellulose (HPMC and methyl cellulose (MC along with film modifiers like poly vinyl pyrrolidone K30 (PVP K30, and sodium lauryl sulphate (SLS as solubilizing agents were evaluated. The prepared MDFs were evaluated for in vitro dissolution characteristics, in vitro disintegration time, and their physicomechanical properties. All the prepared MDFs showed good mechanical properties like tensile strength, folding endurance, and % elongation. MDFs were evaluated by means of FTIR, SEM, and X-RD studies. MDFs with 7.5% (w/w of HPMC E3 gave better dissolution properties when compared to HPMC E5, HPMC E15, and MC. MDFs with PVP K30 and SLS gave superior dissolution properties when compared to MDFs without PVP K30 and SLS. The dissolution properties of MDFs with PVP K30 were superior when compared to MDFs with SLS. In the case of F3 containing 7.5% of HPMC E3 and 0.04% of PVP K30, complete and faster release was observed within 60 sec when compared to other formulations. Release kinetics data reveals diffusion is the release mechanism.

  12. Enhanced anticancer efficacy and tumor targeting through folate-PEG modified nanoliposome loaded with 5-fluorouracil

    Science.gov (United States)

    Le, Van Minh; Tran Nho, Trung Duc; Trieu Ly, Hai; Vo, Thanh Sang; Dung Nguyen, Hoang; Thu Huong Phung, Thi; Zou, Aihua; Liu, Jianwen

    2017-03-01

    Cancer targeted therapies have attracted considerable attention over the past year. Recently, 5-fluouracil (5-FU), which has high toxicity to normal cells and short half-life associated with rapid metabolism, is one of the most commonly used therapies in the treatment of cancer. In this study the folic acid-conjugated pegylated nanoliposomes were synthesized and then loaded into them with 5-FU to improve the anti-tumor efficacy. The average size of liposomes (LPs) was about 52.7 nm which was identified by TEM. In the liposome uptake studies, the level uptake of folate-conjugated liposomes has increased compared to non-conjugated LPs according to LPs concentration, incubation time and presence of concentration of free folic acid (FA). The MTT assay and apoptotic test were carried out in HCT116 and MCF-7 cells for 24 or 48 h. The results revealed that the folate-PEG modified 5-Fu loaded nanoliposomes had strong cytotoxicity to cancer cell compared to pure 5-FU or PEG modified 5-FU loaded liposomes in a concentration- and time-dependent manner, and mainly enhanced the cancer cell death through folate-mediated endocytosis. Hence, the folate-PEG modified nanoliposome is a potential targeted drug-delivery system for the treatment of FR-positive cancers.

  13. Modern adjuvants do not enhance the efficacy of an inactivated African swine fever virus vaccine preparation.

    Science.gov (United States)

    Blome, Sandra; Gabriel, Claudia; Beer, Martin

    2014-06-30

    African swine fever (ASF) is among the most devastating viral diseases of pigs. In recent years, the disease has spread alarmingly. Despite intensive research activities, promising vaccine candidates are still lacking. For this reason, a study was undertaken to re-assess inactivated ASFV preparations with state-of-the-art adjuvants. Inactivated preparations of ASF virus (ASFV) "Armenia08" were adjuvanted with either Polygen™ or Emulsigen(®)-D, respectively, and used to immunize six weaner pigs two times with a three-week interval. Six weeks after the first immunization, animals were challenged with the homologues highly virulent ASFV. Although ASFV-specific antibodies were detectable in all but one vaccinated animal prior to challenge, no protective effect of immunization was observed. All animals developed acute-lethal ASF and had to be euthanized within eleven days post challenge. A slightly accelerated clinical course in vaccinees could even indicate an antibody dependent enhancement, which could also influence efficacy of other vaccine approaches.

  14. Development and Evaluation of Mouth Dissolving Films of Amlodipine Besylate for Enhanced Therapeutic Efficacy.

    Science.gov (United States)

    Maheswari, K M; Devineni, Pavan Kumar; Deekonda, Sravanthi; Shaik, Salma; Uppala, Naga Pravallika; Nalluri, Buchi N

    2014-01-01

    The present investigation was undertaken with an objective of formulating mouth dissolving films (MDFs) of Amlodipine Besylate (AMLO) to enhance convenience and compliance of the elderly and pediatric patients for better therapeutic efficacy. Film formers like hydroxy propyl methyl cellulose (HPMC) and methyl cellulose (MC) along with film modifiers like poly vinyl pyrrolidone K30 (PVP K30), and sodium lauryl sulphate (SLS) as solubilizing agents were evaluated. The prepared MDFs were evaluated for in vitro dissolution characteristics, in vitro disintegration time, and their physicomechanical properties. All the prepared MDFs showed good mechanical properties like tensile strength, folding endurance, and % elongation. MDFs were evaluated by means of FTIR, SEM, and X-RD studies. MDFs with 7.5% (w/w) of HPMC E3 gave better dissolution properties when compared to HPMC E5, HPMC E15, and MC. MDFs with PVP K30 and SLS gave superior dissolution properties when compared to MDFs without PVP K30 and SLS. The dissolution properties of MDFs with PVP K30 were superior when compared to MDFs with SLS. In the case of F3 containing 7.5% of HPMC E3 and 0.04% of PVP K30, complete and faster release was observed within 60 sec when compared to other formulations. Release kinetics data reveals diffusion is the release mechanism.

  15. Enhanced efficacy of CTLA-4 fusion anti-caries DNA vaccines in gnotobiotic hamsters

    Institute of Scientific and Technical Information of China (English)

    Feng ZHANG; Yu-hong LI; Ming-wen FAN; Rong JIA; Qing-an XU; Ji-hua GUO; Fei YU; Qi-wei TIAN

    2007-01-01

    Aim:To evaluate the comparative immunogenicity and protective efficacy of the cytotoxic T-lymphocyte.associated antigen 4(CTLA-4)fusion anti-caries DNA vaccines pGJA-P/VAX1,pGJA-P,and non-fusion anti-caries DNA construct pGLUA-P in hamsters.In addition,the ability of CTLA-4 to target pGJA-P/VAX1-encoding antigen to dendritic cells was tested in vitro.Methods:All DNA constructs contain genes encoding the A-P regions of a cell surface protein(PAc) and the glucan binding(GLU) domain of glucosyltransferases(GTFs)of cari-ogenic organism Streptococcus mutans.Human dendritic cells were mixed with the CTLA-4-Ig-GLU-A-P protein expressed by pGJA-P/VAX1-transfected cells and analyzed by flow cytometry.Gnotobiotic hamsters were immunized with anti-caries DNA vaccines by intramuscular injection or intranasal administration.Antibody responses to a representative antigen PAc were assayed by ELlSA,and caries protection was evaluated by Keyes caries scores.Results:A flow cytometric analysis demonstrated that CTLA-4-Ig-GLU-A-P protein was capable of bind-ing to human dendritic cells.pGJA-P/VAX1 and pGJA-P induced significantly higher specific salivary and serum anti-PAc antibody responses than pGLUA-R.Significantly fewet caries lesions were alSO observed in hamsters immunized with pGJA-P/VAX1 and pGJA-p There was no significant difference in the anti-PAC antibody level or caries scores between pGJA-P/VAX1 and pGJA-P-immunized groups.Conclusion:Antigen encoded by CTLA-4 fusion anti-caries DNA vac-cine pGJA-P/VAX1 could specifically bind to human dendritic cells through the interaction of CTLA-4 and B7 molecules.Fusing antigen to CTLA-4 has been proven to greatly enhance the immunogenicity and protective efficacy of anti-caries DNA vaccines.

  16. Liposomal glucocorticosteroids in treatment of chronic autoimmune demyelination: long-term protective effects and enhanced efficacy of methylprednisolone formulations.

    Science.gov (United States)

    Linker, Ralf A; Weller, Charlotte; Lühder, Fred; Mohr, Alexander; Schmidt, Jens; Knauth, Michael; Metselaar, Josbert M; Gold, Ralf

    2008-06-01

    Liposomal encapsulation leads to enhanced efficacy of glucocorticosteroids (GS) in treatment of autoimmune diseases. Here we compare liposomal prednisolone (PL) to liposomal methylprednisolone (MPL) in chronic-relapsing myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis (EAE), a model closely reflecting aspects of multiple sclerosis (MS). At the maximum of the first relapse, a single dose of PL or MPL was applied at 10 mg/kg or at 4 mg/kg and compared to classical methylprednisolone (MP) pulse therapy. PL at 10 mg/kg was superior to free MP with long-term efficacy and a sustained protection even during the second and third relapse. At the same time, in vivo magnetic resonance imaging of rat brains revealed a significant reduction of T2-lesions after PL application. Comparison of PL and MPL at 10 mg/kg disclosed superior effects for MPL with an enhanced reduction of inflammatory infiltration as well as preservation of myelin and axons. Dose titration experiments underscored a dose-dependent efficacy of liposomal GS with a sustained efficacy especially of the higher dosage. In histological analyses, PL10 was superior in reducing macrophage and T cell infiltration as well as demyelination and axonal loss while the lower dosages were still at least as effective as free MP. FACS analyses revealed an effect of liposome formulations on T cell numbers, the CD4/CD8 ratio, frequencies of regulatory T cells and adhesion molecule expression. In summary, liposomal GS and especially methylprednisolone formulations display an enhanced efficacy not only in acute inflammatory, but also in chronic demyelinating models of MS and confer long-term protection from relapses. These findings lay the groundwork for applying liposomal GS in clinical MS trials in the near future.

  17. Enhancing Elementary-School Mathematics Teachers' Efficacy Beliefs: A Qualitative Action Research

    Science.gov (United States)

    Katz, Sara; Stupel, Moshe

    2016-01-01

    Individuals and societies that can use mathematics effectively in this period of rapid changes will have a voice on increasing the opportunities and potentials which can shape their future. This has brought affective characteristics, such as self-efficacy, that affect mathematics achievement into focus of the research. Teacher efficacy refers to…

  18. Role of contrast-enhanced ultrasonography in percutaneous radiofrequency ablation of liver metastases and efficacy evaluation

    Institute of Scientific and Technical Information of China (English)

    Jie Wu; Wei Yang; Shanshan Yin; Jinyu Wu; Wei Wu; Kun Yan; Minhua Chen

    2013-01-01

    Objective:To retrospectively investigate the role of contrast-enhanced ultrasonography (CEUS) in percutaneous radiofrequency ablation (RFA) in patients with liver metastases and evaluate the therapeutic efficacy of RFA assisted by CEUS.Methods:From May 2004 to September 2010,136 patients with 219 liver metastatic lesions received CEUS examination 1 h before RFA (CEUS group),and other 126 patients with 216 lesions without CEUS examination in the earlier period were served as a historical control group.The mean tumor size was 3.2 cm and the mean tumor number was 1.6 in the CEUS group,while 3.4 cm and 1.7 in the control group,respectively (P>0.05).The clinical characteristics,recurrence results and survival outcomes were compared between two groups.Results:In the CEUS group,two isoechoic tumors were not demonstrated on unenhanced ultrasonography (US),and 63 (47%) of 134 tumors examined with CEUS were 0.3 cm larger than with unenhanced US.Furthermore,in 18.4% of 136 patients,additional 1-3 tumors were detected on CEUS.The CEUS group showed higher early tumor necrosis and lower intrahepatic recurrence than the control group.The 3-year overall survival (OS) rate and the 3-year local recurrence-free survival (LRFS) rate in the CEUS group were 50.1% and 38.3%,in contrast to 25.3% and 19.3% in the control group,respectively (P=0.002 and P<0.001).Conclusions:CEUS provides important information for RFA treatment in patients with liver metastases and better therapeutic effect could be attained.

  19. Replication Study: Coadministration of a tumor-penetrating peptide enhances the efficacy of cancer drugs

    Science.gov (United States)

    Mantis, Christine; Kandela, Irawati; Aird, Fraser

    2017-01-01

    In 2015, as part of the Reproducibility Project: Cancer Biology, we published a Registered Report (Kandela et al., 2015) that described how we intended to replicate selected experiments from the paper “Coadministration of a tumor-penetrating peptide enhances the efficacy of cancer drugs“ (Sugahara et al., 2010). Here we report the results of those experiments. We found that coadministration with iRGD peptide did not have an impact on permeability of the chemotherapeutic agent doxorubicin (DOX) in a xenograft model of prostate cancer, whereas the original study reported that it increased the penetrance of this cancer drug (Figure 2B; Sugahara et al., 2010). Further, in mice bearing orthotopic 22Rv1 human prostate tumors, we did not find a statistically significant difference in tumor weight for mice treated with DOX and iRGD compared to DOX alone, whereas the original study reported a decrease in tumor weight when DOX was coadministered with iRGD (Figure 2C; Sugahara et al., 2010). In addition, we did not find a statistically significant difference in TUNEL staining in tumor tissue between mice treated with DOX and iRGD compared to DOX alone, while the original study reported an increase in TUNEL positive staining with iRGD coadministration (Figure 2D; Sugahara et al., 2010). Similar to the original study (Supplemental Figure 9A; Sugahara et al., 2010), we did not observe an impact on mouse body weight with DOX and iRGD treatment. Finally, we report meta-analyses for each result. DOI: http://dx.doi.org/10.7554/eLife.17584.001 PMID:28100395

  20. Enhancing the Inclusive Self-Efficacy of Preservice Teachers through Embedded Course Design

    Directory of Open Access Journals (Sweden)

    Lucia Zundans-Fraser

    2012-01-01

    Full Text Available This study was an initial investigation into the effects of Embedded Design on the self-efficacy of pre-service teachers studying inclusive education. Forty-one participants completed pre- and postquestionnaires to determine differences in self-efficacy prior to and again at completion of an inclusive education course in an undergraduate teaching degree. A modified version of the scale developed by Hickson (1995, the “Self-Efficacy toward Future Interactions with People with Disabilities” (SEIPD was employed for data collection. This data was supplemented by way of anonymous formal student feedback collected from the university. Findings indicate that the theoretically designed course did in fact significantly improve self-efficacy between pre- and postoccasions. Limitations of the present study are discussed as well as implications for future practice in the design of preservice courses for inclusive education.

  1. Enhanced chemoprophylactic and clinical efficacy of albendazole formulated as solid dispersions in experimental cystic echinococcosis.

    Science.gov (United States)

    Pensel, Patricia E; Castro, Silvina; Allemandi, Daniel; Bruni, Sergio Sánchez; Palma, Santiago D; Elissondo, María Celina

    2014-06-16

    Cystic echinococcosis is a chronic, complex, and still neglected disease. Although albendazole has demonstrated efficacy, only about one-third of patients experience complete remission or cure and 30-50% of treated patients develop some evidence of a therapeutic response. Different strategies have been developed in order to improve the albendazole water solubility and dissolution rate. The aim of the current work was to investigate the chemoprophylactic and clinical efficacy of an albendazole:poloxamer 188 solid dispersion formulation on mice infected with Echinococcus granulosus metacestodes. Albendazole formulated as solid dispersion had greater chemoprophylactic and clinical efficacy than albendazole alone. The improved in therapeutic efficacy could be a consequence of the increase in the systemic availability of albendazole sulfoxide. The work reported here demonstrates that in vivo treatment with albendazole:poloxamer 188 impairs the development of the hydatid cysts. This new pharmacotechnically based strategy could be a suitable alternative for treating cystic echinococcosis in humans.

  2. Pre- and post-exposure safety and efficacy of attenuated rabies virus vaccines are enhanced by their expression of IFNγ

    Energy Technology Data Exchange (ETDEWEB)

    Barkhouse, Darryll A. [Department of Cancer Biology, 1020 Locust St., Jefferson Alumni Hall, Room 454, Philadelphia, PA 19107 (United States); Center for Neurovirology 1020 Locust St., Jefferson Alumni Hall, Room 454, Philadelphia, PA 19107 (United States); Faber, Milosz [Center for Neurovirology 1020 Locust St., Jefferson Alumni Hall, Room 454, Philadelphia, PA 19107 (United States); Department of Microbiology and Immunology 1020 Locust St., Jefferson Alumni Hall, Room 465, Philadelphia, PA 19107 (United States); Hooper, D. Craig, E-mail: douglas.hooper@jefferson.edu [Department of Cancer Biology, 1020 Locust St., Jefferson Alumni Hall, Room 454, Philadelphia, PA 19107 (United States); Department of Neurological Surgery, 1020 Locust St., Jefferson Alumni Hall, Room 454, Philadelphia, PA 19107 (United States); Center for Neurovirology 1020 Locust St., Jefferson Alumni Hall, Room 454, Philadelphia, PA 19107 (United States)

    2015-01-01

    Consistent with evidence of a strong correlation between interferon gamma (IFNγ) production and rabies virus (RABV) clearance from the CNS, we recently demonstrated that engineering a pathogenic RABV to express IFNγ highly attenuates the virus. Reasoning that IFNγ expression by RABV vaccines would enhance their safety and efficacy, we reverse-engineered two proven vaccine vectors, GAS and GASGAS, to express murine IFNγ. Mortality and morbidity were monitored during suckling mice infection, immunize/challenge experiments and mixed intracranial infections. We demonstrate that GASγ and GASγGAS are significantly attenuated in suckling mice compared to the GASGAS vaccine. GASγ better protects mice from lethal DRV4 RABV infection in both pre- and post-exposure experiments compared to GASGAS. Finally, GASγGAS reduces post-infection neurological sequelae, compared to control, during mixed intracranial infection with DRV4. These data show IFNγ expression by a vaccine vector can enhance its safety while increasing its efficacy as pre- and post-exposure treatment. - Highlights: • IFNγ expression improves attenuated rabies virus safety and immunogenicity. • IFNγ expression is safer and more immunogenic than doubling glycoprotein expression. • Co-infection with IFNγ-expressing RABV prevents wild-type rabies virus lethality. • Vaccine safety and efficacy is additive for IFNγ and double glycoprotein expression.

  3. Communicative social capital and collective efficacy as determinants of access to health-enhancing resources in residential communities.

    Science.gov (United States)

    Matsaganis, Matthew D; Wilkin, Holley A

    2015-04-01

    This article contributes to the burgeoning literature on the social determinants of health disparities. The authors investigate how communication resources and collective efficacy, independently and in combination, shape residents' access to health enhancing resources (including healthcare services, sources of healthier food options, and public recreation spaces) in their communities. Using random digit dial telephone survey data from 833 residents of South Los Angeles communities the authors show that communicative social capital-that is, an information and problem-solving resource that accrues to residents as they become more integrated into their local communication network of neighbors, community organizations, and local media-plays a significant role in access to health resources. This relationship is complicated by individuals' health insurance and health status, as communicative social capital magnifies the sense of absence of resources for those who are in worse health and lack insurance. Communicative social capital builds collective efficacy, which is positively related to access to health-enhancing resources, but it also mediates the negative relationship between communicative social capital and access to health resources. Residents with richer stores of communicative social capital and collective efficacy report better access to health resources. The authors conclude with a discussion of implications of these findings and suggestions for future research.

  4. Enhancing Self-Efficacy in Elementary Science Teaching With Professional Learning Communities

    Science.gov (United States)

    Mintzes, Joel J.; Marcum, Bev; Messerschmidt-Yates, Christl; Mark, Andrew

    2013-11-01

    Emerging from Bandura's Social Learning Theory, this study of in-service elementary school teachers examined the effects of sustained Professional Learning Communities (PLCs) on self-efficacy in science teaching. Based on mixed research methods, and a non-equivalent control group experimental design, the investigation explored changes in personal self-efficacy and outcome expectancy among teachers engaged in PLCs that featured Demonstration Laboratories, Lesson Study, and annual Summer Institutes. Significant changes favoring the experimental group were found on all quantitative measures of self-efficacy. Structured clinical interviews revealed that observed changes were largely attributable to a wide range of direct (mastery) and vicarious experiences, as well as emotional reinforcement and social persuasion.

  5. How Setting Goals Enhances Learners’ Self-Efficacy Beliefs in Listening Comprehension

    Directory of Open Access Journals (Sweden)

    Liliana Ballesteros Muñoz

    2014-04-01

    Full Text Available This article outlines a study that explores the relationship between SMART goal setting (Specific, Measurable, Attainable, Relevant, and Time-based and learning English in Colombia concerning a foreign language learners’ self-efficacy beliefs in listening. The participants were seventh and ninth grade students of two schools in Bogotá, Colombia. The results revealed that self-efficacy was highly positive when related to goal setting as students were able to set SMART goals to improve their listening comprehension and learners showed improvement in self-efficacy beliefs and felt more motivated while completing listening tasks related to songs. Furthermore this study shows that goal setting training can be incorporated successfully into the English as a foreign language classroom.

  6. Clavulanic acid enhances glutamate transporter subtype I (GLT-1) expression and decreases reinforcing efficacy of cocaine in mice.

    Science.gov (United States)

    Kim, Jae; John, Joel; Langford, Dianne; Walker, Ellen; Ward, Sara; Rawls, Scott M

    2016-03-01

    The β-lactam antibiotic ceftriaxone (CTX) reduces cocaine reinforcement and relapse in preclinical assays through a mechanism involving activation of glutamate transporter subtype 1 (GLT-1). However, its poor brain penetrability and intravenous administration route may limit its therapeutic utility for indications related to CNS diseases. An alternative is clavulanic acid (CA), a structural analog of CTX that retains the β-lactam core required for GLT-1 activity but displays enhanced brain penetrability and oral activity relative to CTX. Here, we tested the hypothesis that CA (1, 10 mg/kg ip) would enhance GLT-1 expression and decrease cocaine self-administration (SA) in mice, but at lower doses than CTX. Experiments revealed that GLT-1 transporter expression in the nucleus accumbens of mice treated with repeated CA (1, 10 mg/kg) was enhanced relative to saline-treated mice. Repeated CA treatment (1 mg/kg) reduced the reinforcing efficacy of cocaine (0.56 mg/kg/inf) in mice maintained on a progressive-ratio (PR) schedule of reinforcement but did not affect acquisition of cocaine SA under fixed-ratio responding or acquisition or retention of learning. These findings suggest that the β-lactamase inhibitor CA can activate the cellular glutamate reuptake system in the brain reward circuit and reduce cocaine's reinforcing efficacy at 100-fold lower doses than CTX.

  7. Extinction learning as a moderator of d-cycloserine efficacy for enhancing exposure therapy in posttraumatic stress disorder.

    Science.gov (United States)

    de Kleine, Rianne A; Smits, Jasper A J; Hendriks, Gert-Jan; Becker, Eni S; van Minnen, Agnes

    2015-08-01

    Augmentation of exposure therapy with d-cycloserine (DCS) has proven efficacious across anxiety disorders, although results in PTSD have been mixed. Work in animals and anxiety-disordered patients suggest that the potentiating effects of DCS are dependent on the level of extinction learning during extinction training and exposure treatment, respectively. The aim of the current study was to replicate and extend previous work by examining the association between the degree of extinction learning and DCS efficacy in our randomized clinical trial on DCS (50 mg) versus placebo enhancement of exposure therapy in a chronic mixed-trauma PTSD sample (N=67; de Kleine, Hendriks, Kusters, Broekman, & van Minnen, 2012). The decline in subjective units of distress ratings collected during and across the exposure sessions were evaluated as indices of extinction learning. First, we examined whether extinction learning during an exposure session moderated DCS effects on self-reported PTSD symptoms at the next session. Second, we examined whether averaged extinction learning over the course of treatment interacted with group assignment to predict change over time and post treatment outcome. We did not find evidence that DCS effects were moderated by the degree of extinction learning, although, extinction learning was related to outcome regardless of group assignment. In PTSD, not one extinction-learning index has been consistently linked to DCS enhanced exposure treatment outcome. More (experimental) work needs to been done to unravel the complex interplay between extinction learning and DCS enhancement, especially in PTSD patients.

  8. Enhancing Students' Learning and Self- Efficacy through Blended Learning in a Teachers' Program

    Science.gov (United States)

    Abdelraheem, Ahmed Yousif

    2014-01-01

    Blended Learning (BL) strategies play an important role in collaboration, communication skills, motivation, attitudes, interaction with the subject and practical skills. However, their relationship with students' learning and self efficacy were not studied enough and this was the focus of this study. Therefore, the aim of the study was to…

  9. Perceptual Training Methods Compared: The Relative Efficacy of Different Approaches to Enhancing Sport-Specific Anticipation

    Science.gov (United States)

    Abernethy, Bruce; Schorer, Jorg; Jackson, Robin C.; Hagemann, Norbert

    2012-01-01

    The comparative efficacy of different perceptual training approaches for the improvement of anticipation was examined using a goalkeeping task from European handball that required the rapid prediction of shot direction. Novice participants (N = 60) were assigned equally to four different training groups and two different control groups (a placebo…

  10. Enhancing Self-Efficacy in Elementary Science Teaching with Professional Learning Communities

    Science.gov (United States)

    Mintzes, Joel J.; Marcum, Bev; Messerschmidt-Yates, Christl; Mark, Andrew

    2013-01-01

    Emerging from Bandura's Social Learning Theory, this study of in-service elementary school teachers examined the effects of sustained Professional Learning Communities (PLCs) on self-efficacy in science teaching. Based on mixed research methods, and a non-equivalent control group experimental design, the investigation explored changes in…

  11. Integrating Motivational Interviewing into a Basic Counseling Skills Course to Enhance Counseling Self-Efficacy

    Science.gov (United States)

    Iarussi, Melanie H.; Tyler, Jessica M.; Littlebear, Sarah; Hinkle, Michelle S.

    2013-01-01

    Motivational interviewing (MI), a humanistic counseling style used to help activate clients' motivation to change, was integrated into a basic counseling skills course. Nineteen graduate-level counseling students completed the Counselor Estimate of Self-Efficacy at the start and conclusion of the course. Significant differences were found between…

  12. Metronomic Doses of Temozolomide Enhance the Efficacy of Carbon Nanotube CpG Immunotherapy in an Invasive Glioma Model

    Science.gov (United States)

    Guo, Qin; Zhang, Ian; Gao, Hang; Yanyan, Song; Chen, Xuebo; Weng, Yiming; Da Fonseca, Anna; Shah, Sunny; Manuel, Edwin R.; Zhang, Leying; Vonderfecht, Steven L.; Alizadeh, Darya; Berlin, Jacob M.; Badie, Behnam

    2016-01-01

    Even when treated with aggressive current therapies, most patients with glioblastoma survive less than two years. Rapid tumor growth, an invasive nature, and the blood-brain barrier, which limits the penetration of large molecules into the brain, all contribute to the poor tumor response associated with conventional therapies. Immunotherapy has emerged as a therapeutic approach that may overcome these challenges. We recently reported that single-walled carbon nanotubes (SWCNTs) can be used to dramatically increase the immunotherapeutic efficacy of CpG oligonucleotides in a mouse model of glioma. Following implantation in the mouse brain, the tumor cell line used in these previous studies (GL261) tends to form a spherical tumor with limited invasion into healthy brain. In order to evaluate SWCNT/CpG therapy under more clinically-relevant conditions, here we report the treatment of a more invasive mouse glioma model (K-Luc) that better recapitulates human disease. In addition, a CpG sequence previously tested in humans was used to formulate the SWCNT/CpG which was combined with temozolomide, the standard of care chemotherapy for glioblastoma patients. We found that, following two intracranial administrations, SWCNT/CpG is well-tolerated and improves the survival of mice bearing invasive gliomas. Interestingly, the efficacy of SWCNT/CpG was enhanced when combined with temozolomide. This enhanced anti-tumor efficacy was correlated to an increase of tumor-specific cytotoxic activity in splenocytes. These results reinforce the emerging understanding that immunotherapy can be enhanced by combining it with chemotherapy and support the continued development of SWCNT/CpG. PMID:26829221

  13. Metronomic Doses of Temozolomide Enhance the Efficacy of Carbon Nanotube CpG Immunotherapy in an Invasive Glioma Model.

    Directory of Open Access Journals (Sweden)

    Mao Ouyang

    Full Text Available Even when treated with aggressive current therapies, most patients with glioblastoma survive less than two years. Rapid tumor growth, an invasive nature, and the blood-brain barrier, which limits the penetration of large molecules into the brain, all contribute to the poor tumor response associated with conventional therapies. Immunotherapy has emerged as a therapeutic approach that may overcome these challenges. We recently reported that single-walled carbon nanotubes (SWCNTs can be used to dramatically increase the immunotherapeutic efficacy of CpG oligonucleotides in a mouse model of glioma. Following implantation in the mouse brain, the tumor cell line used in these previous studies (GL261 tends to form a spherical tumor with limited invasion into healthy brain. In order to evaluate SWCNT/CpG therapy under more clinically-relevant conditions, here we report the treatment of a more invasive mouse glioma model (K-Luc that better recapitulates human disease. In addition, a CpG sequence previously tested in humans was used to formulate the SWCNT/CpG which was combined with temozolomide, the standard of care chemotherapy for glioblastoma patients. We found that, following two intracranial administrations, SWCNT/CpG is well-tolerated and improves the survival of mice bearing invasive gliomas. Interestingly, the efficacy of SWCNT/CpG was enhanced when combined with temozolomide. This enhanced anti-tumor efficacy was correlated to an increase of tumor-specific cytotoxic activity in splenocytes. These results reinforce the emerging understanding that immunotherapy can be enhanced by combining it with chemotherapy and support the continued development of SWCNT/CpG.

  14. Association with amino acids does not enhance efficacy of polymerized liposomes as a system for lung gene delivery

    Directory of Open Access Journals (Sweden)

    Elga eBernardo Bandeira De Melo

    2016-04-01

    Full Text Available Development of improved drug and gene delivery systems directly into the lungs is highly desirable given the important burden of respiratory diseases. We aimed to evaluate the safety and efficacy of liposomes composed of photopolymerized lipids (1,2-bis-(tricosa-10,12-diynoyl-sn-glycero-3-phosphocholine associated with amino acids as vectors for gene delivery into the lungs of healthy animals. Lipopolymer vesicles, in particular, are more stable than other types of liposomes. In this study, lipopolymers were associated with L-arginine, L-tryptophan, or L-cysteine. We hypothesized that the addition of these amino acids would enhance the efficacy of gene delivery to the lungs by the lipopolymers. L-Arginine showed the highest association efficiency due to its positive charge and better surface interactions. None of the formulations caused inflammation or altered lung mechanics, suggesting that these lipopolymers can be safely administered as aerosols. All formulations were able to induce eGFP mRNA expression in lung tissue, but the addition of amino acids reduced delivery efficacy when compared with the simple lipopolymer particle. These results indicate that this system could be further explored for gene or drug delivery targeting lung diseases.

  15. Pretreatment with 5-Fluorouracil Cream Enhances the Efficacy of Daylight-mediated Photodynamic Therapy for Actinic Keratosis.

    Science.gov (United States)

    Nissen, Christoffer V; Heerfordt, Ida Marie; Wiegell, Stine R; Mikkelsen, Carsten S; Wulf, Hans C

    2017-01-17

    The efficacy of photodynamic therapy (PDT) with methyl aminolevulinate is reduced when treating actinic keratosis (AK) on the extremities in comparison with the face and scalp. Studies indicate that PDT efficacy can be improved by combining PDT with other treatment modalities. This randomized intra-individual study investigated whether pretreatment with topical 5% 5-fluorouracil (5-FU) enhanced the treatment efficacy of daylight-mediated PDT in 24 patients with AKs on the hands. One hand of each patient was given 7 days of pretreatment with 5-FU twice daily before daylight-PDT, whereas the other hand was treated with daylight-PDT alone. At 3-month follow-up the overall lesion response rate was significantly higher for the combination of 5-FU and daylight-PDT (62.7%) than for daylight-PDT alone (51.8%) (p = 0.001). Furthermore, pain and erythema in relation to treatment were similar in the 2 groups (p = 1.0 and p = 0.2, respectively). Combination therapy is a safe and effective method to improve daylight-PDT for acral AKs.

  16. Digital Self-Efficacy and Language Learning Enhancement in an Online Setting

    OpenAIRE

    2013-01-01

    The importance of personal factors such as personality traits, learning strategies, self-esteem, and self-efficacy in the complicated task of language learning has been established for years. However, the introduction of computers, networks and their wide communication affordances, seem to impact many aspects of learning and teaching and particularly language learning and teaching. The storage place, manner, and magnitude of learning materials for example, have shifted from the human mind to ...

  17. Enhancing the Breadth and Efficacy of Therapeutic Vaccines for Breast Cancer

    Science.gov (United States)

    2015-10-01

    emulsion RT- PCR . Additional modifications were made to our epitope discovery workflow to increase efficacy of transcript and neoantigen candidate...resource of normal transcript expression levels across all tissues against which tumors are compared for identification of uniquely expressed...license via GitHub. Statistical analysis was carried out by our team to determining the false discovery rate of shared clonotypes, comparing those

  18. Co-administration of a Tumor-Penetrating Peptide Enhances the Efficacy of Cancer Drugs

    OpenAIRE

    Sugahara, Kazuki N.; Teesalu, Tambet; Karmali, Priya Prakash; Kotamraju, Venkata Ramana; Agemy, Lilach; Greenwald, Daniel R.; Ruoslahti, Erkki

    2010-01-01

    Poor penetration of anti-cancer drugs into tumors can be an important factor limiting their efficacy. Studying mouse tumor models, we show that a previously characterized tumor-penetrating peptide, iRGD (CRGDK/RGPD/EC), increased vascular and tissue permeability in a tumor-specific and neuropilin-1-dependent manner, allowing co-administered drugs to penetrate into extravascular tumor tissue. Importantly, this effect did not require the drugs to be chemically conjugated to the peptide. Systemi...

  19. Enhancing Predicted Efficacy of Tumor Treating Fields Therapy of Glioblastoma Using Targeted Surgical Craniectomy: A Computer Modeling Study

    Science.gov (United States)

    Korshoej, Anders Rosendal; Saturnino, Guilherme Bicalho; Rasmussen, Line Kirkegaard; von Oettingen, Gorm; Sørensen, Jens Christian Hedemann; Thielscher, Axel

    2016-01-01

    Objective The present work proposes a new clinical approach to TTFields therapy of glioblastoma. The approach combines targeted surgical skull removal (craniectomy) with TTFields therapy to enhance the induced electrical field in the underlying tumor tissue. Using computer simulations, we explore the potential of the intervention to improve the clinical efficacy of TTFields therapy of brain cancer. Methods We used finite element analysis to calculate the electrical field distribution in realistic head models based on MRI data from two patients: One with left cortical/subcortical glioblastoma and one with deeply seated right thalamic anaplastic astrocytoma. Field strength was assessed in the tumor regions before and after virtual removal of bone areas of varying shape and size (10 to 100 mm) immediately above the tumor. Field strength was evaluated before and after tumor resection to assess realistic clinical scenarios. Results For the superficial tumor, removal of a standard craniotomy bone flap increased the electrical field strength by 60–70% in the tumor. The percentage of tissue in expected growth arrest or regression was increased from negligible values to 30–50%. The observed effects were highly focal and targeted at the regions of pathology underlying the craniectomy. No significant changes were observed in surrounding healthy tissues. Median field strengths in tumor tissue increased with increasing craniectomy diameter up to 50–70 mm. Multiple smaller burr holes were more efficient than single craniectomies of equivalent area. Craniectomy caused no significant field enhancement in the deeply seated tumor, but rather a focal enhancement in the brain tissue underlying the skull defect. Conclusions Our results provide theoretical evidence that small and clinically feasible craniectomies may provide significant enhancement of TTFields intensity in cerebral hemispheric tumors without severely compromising brain protection or causing unacceptable heating in

  20. Capsaicin enhances anti-proliferation efficacy of pirarubicin via activating TRPV1 and inhibiting PCNA nuclear translocation in 5637 cells.

    Science.gov (United States)

    Zheng, Long; Chen, Jiaqi; Ma, Zhenkun; Liu, Wei; Yang, Fei; Yang, Zhao; Wang, Ke; Wang, Xinyang; He, Dalin; Li, Lei; Zeng, Jin

    2016-01-01

    The recurrence of bladder cancer after surgery with or without chemotherapy remains a major challenge in bladder cancer treatment. Previous studies have shown that transient receptor potential vanilloid 1 (TRPV1) acts as a tumor suppressor through inducing apoptosis in bladder cancer cells. However, whether activation of TRPV1 has any synergistic effects with pirarubicin (THP), one of main drugs used in urinary bladder instillation chemotherapy to improve chemotherapeutic efficacy has remained elusive. The present study verified that TRPV1 was differentially expressed in bladder cancer cell lines. Furthermore, activation of TRPV1 by capsaicin was shown to induce growth inhibition of 5637 cells in which TRPV1 was highly expressed, while the growth of T24 cells, which express TRPV1 at low levels, was not affected. In addition, the present study demonstrated that activation of TRPV1 enhanced the anti‑proliferative effects of pirarubicin using an MTT assay and cell cycle analysis. Finally, immunofluorescent microscopy revealed that activation of TRPV1 prevented the translocation of proliferating cell nuclear antigen to the nucleus. This phenomenon was reversed by pre‑treatment with capsazepine, a specific TRPV1 antagonist. In conclusion, the present study confirmed the anti‑tumor activity of TRPV1 against bladder cancer. Activation of TRPV1 may be applied as a novel strategy to treat bladder cancer or enhance the therapeutic efficacy of traditional chemotherapeutic drugs.

  1. Cystic echinococcosis therapy: Albendazole-loaded lipid nanocapsules enhance the oral bioavailability and efficacy in experimentally infected mice.

    Science.gov (United States)

    Pensel, Patricia E; Ullio Gamboa, Gabriela; Fabbri, Julia; Ceballos, Laura; Sanchez Bruni, Sergio; Alvarez, Luis I; Allemandi, Daniel; Benoit, Jean Pierre; Palma, Santiago D; Elissondo, María C

    2015-12-01

    Therapeutic failures attributed to medical management of cystic echinococcosis (CE) with albendazole (ABZ) have been primarily linked to the poor drug absorption rate resulting in low drug level in plasma and hydatid cysts. Lipid nanocapsules (LNCs) represent nanocarriers designed to encapsulate lipophilic drugs, such as ABZ. The goals of the current work were: (i) to characterize the plasma and cyst drug exposure after the administration of ABZ as ABZ-LNCs or ABZ suspension (ABZ-SUSP) in mice infected with Echinococcus granulosus, and ii) to compare the clinical efficacies of both ABZ formulations. Enhanced ABZ sulphoxide (ABZ-SO) concentration profiles were obtained in plasma and cysts from ABZ-LNC treated animals. ABZSO exposure (AUC0-LOQ) was significantly higher in plasma and cyst after the ABZ-LNC treatments, both orally and subcutaneously, compared to that observed after oral administration of ABZ-SUSP. Additionally, ABZSO concentrations measured in cysts from ABZ-LNC treated mice were 1.7-fold higher than those detected in plasma. This enhanced drug availability correlated with an increased efficacy against secondary CE in mice observed for the ABZ-LNCs, while ABZ-SUSP did not reach differences with the untreated control group. This new pharmacotechnically-based strategy could be a potential alternative to improve the treatment of human CE.

  2. Anticancer Drug-Incorporated Layered Double Hydroxide Nanohybrids and Their Enhanced Anticancer Therapeutic Efficacy in Combination Cancer Treatment

    Directory of Open Access Journals (Sweden)

    Tae-Hyun Kim

    2014-01-01

    Full Text Available Objective. Layered double hydroxide (LDH nanoparticles have been studied as cellular delivery carriers for anionic anticancer agents. As MTX and 5-FU are clinically utilized anticancer drugs in combination therapy, we aimed to enhance the therapeutic performance with the help of LDH nanoparticles. Method. Anticancer drugs, MTX and 5-FU, and their combination, were incorporated into LDH by reconstruction method. Simply, LDHs were thermally pretreated at 400°C, and then reacted with drug solution to simultaneously form drug-incorporated LDH. Thus prepared MTX/LDH (ML, 5-FU/LDH (FL, and (MTX + 5-FU/LDH (MFL nanohybrids were characterized by X-ray diffractometer, scanning electron microscopy, infrared spectroscopy, thermal analysis, zeta potential measurement, dynamic light scattering, and so forth. The nanohybrids were administrated to the human cervical adenocarcinoma, HeLa cells, in concentration-dependent manner, comparing with drug itself to verify the enhanced therapeutic efficacy. Conclusion. All the nanohybrids successfully accommodated intended drug molecules in their house-of-card-like structures during reconstruction reaction. It was found that the anticancer efficacy of MFL nanohybrid was higher than other nanohybrids, free drugs, or their mixtures, which means the multidrug-incorporated LDH nanohybrids could be potential drug delivery carriers for efficient cancer treatment via combination therapy.

  3. Investigation of the Efficacy of Transdermal Penetration Enhancers Through the Use of Human Skin and a Skin Mimic Artificial Membrane.

    Science.gov (United States)

    Balázs, Boglárka; Vizserálek, Gábor; Berkó, Szilvia; Budai-Szűcs, Mária; Kelemen, András; Sinkó, Bálint; Takács-Novák, Krisztina; Szabó-Révész, Piroska; Csányi, Erzsébet

    2016-03-01

    The aim of this study was to investigate the behavior of promising penetration enhancers through the use of 2 different skin test systems. Hydrogel-based transdermal formulations were developed with ibuprofen as a nonsteroidal anti-inflammatory drug. Transcutol and sucrose esters were used as biocompatible penetration enhancers. The permeability measurements were performed with ex vivo Franz diffusion cell methods and a newly developed Skin Parallel Artificial Membrane Permeability Assays (PAMPA) model. Franz diffusion measurement is commonly used as a research tool in studies of diffusion through synthetic membranes in vitro or penetration through ex vivo human skin, whereas Skin PAMPA involves recently published artificial membrane-based technology for the fast prediction of skin penetration. It is a 96-well plate-based model with optimized artificial membrane structure containing free fatty acid, cholesterol, and synthetic ceramide analog compounds to mimic the stratum corneum barrier function. Transdermal preparations containing 2.64% of different sucrose esters and/or Transcutol and a constant (5%) of ibuprofen were investigated to determine the effects of these penetration enhancers. The study demonstrated the good correlation of the permeability data obtained through use of human skin membrane and the in vitro Skin PAMPA system. The Skin PAMPA artificial membrane serves as quick and relatively deep tool in the early stages of transdermal delivery systems, through which the enhancing efficacy of excipients can be screened so as to facilitate the choice of effective penetration components.

  4. Therapeutic Strategies to Enhance the Anticancer Efficacy of Histone Deacetylase Inhibitors

    Directory of Open Access Journals (Sweden)

    Claudia P. Miller

    2011-01-01

    Full Text Available Histone acetylation is a posttranslational modification that plays a role in regulating gene expression. More recently, other nonhistone proteins have been identified to be acetylated which can regulate their function, stability, localization, or interaction with other molecules. Modulating acetylation with histone deacetylase inhibitors (HDACi has been validated to have anticancer effects in preclinical and clinical cancer models. This has led to development and approval of the first HDACi, vorinostat, for the treatment of cutaneous T cell lymphoma. However, to date, targeting acetylation with HDACi as a monotherapy has shown modest activity against other cancers. To improve their efficacy, HDACi have been paired with other antitumor agents. Here, we discuss several combination therapies, highlighting various epigenetic drugs, ROS-generating agents, proteasome inhibitors, and DNA-damaging compounds that together may provide a therapeutic advantage over single-agent strategies.

  5. Enhanced sialylation and in vivo efficacy of recombinant human α-galactosidase through in vitro glycosylation

    Directory of Open Access Journals (Sweden)

    Youngsoo Sohn

    2013-03-01

    Full Text Available Human α-galactosidase A (GLA has been used in enzymereplacement therapy for patients with Fabry disease. Weexpressed recombinant GLA from Chinese hamster ovary cellswith very high productivity. When compared to an approvedGLA (agalsidase beta, its size and charge were found to besmaller and more neutral. These differences resulted from thelack of terminal sialic acids playing essential roles in the serumhalf-life and proper tissue targeting. Because a simplesialylation reaction was not enough to increase the sialic acidcontent, a combined reaction using galactosyltransferase,sialyltransferase, and their sugar substrates at the same timewas developed and optimized to reduce the incubation time.The product generated by this reaction had nearly the samesize, isoelectric points, and sialic acid content as agalsidasebeta. Furthermore, it had better in vivo efficacy to degrade theaccumulated globotriaosylceramide in target organs of Fabrymice compared to an unmodified version. [BMB Reports 2013;46(3: 157-162

  6. Enhanced photodynamic efficacy towards melanoma cells by encapsulation of Pc4 in silica nanoparticles.

    Science.gov (United States)

    Zhao, Baozhong; Yin, Jun-Jie; Bilski, Piotr J; Chignell, Colin F; Roberts, Joan E; He, Yu-Ying

    2009-12-01

    Nanoparticles have been explored recently as an efficient means of delivering photosensitizers for cancer diagnosis and photodynamic therapy (PDT). Silicon phthalocyanine 4 (Pc4) is currently being clinically tested as a photosensitizer for PDT. Unfortunately, Pc4 aggregates in aqueous solutions, which dramatically reduces its PDT efficacy and therefore limits its clinical application. We have encapsulated Pc4 using silica nanoparticles (Pc4SNP), which not only improved the aqueous solubility, stability, and delivery of the photodynamic drug but also increased its photodynamic efficacy compared to free Pc4 molecules. Pc4SNP generated photo-induced singlet oxygen more efficiently than free Pc4 as measured by chemical probe and EPR trapping techniques. Transmission electron microscopy and dynamic light scattering measurements showed that the size of the particles is in the range of 25-30 nm. Cell viability measurements demonstrated that Pc4SNP was more phototoxic to A375 or B16-F10 melanoma cells than free Pc4. Pc4SNP photodamaged melanoma cells primarily through apoptosis. Irradiation of A375 cells in the presence of Pc4SNP resulted in a significant increase in intracellular protein-derived peroxides, suggesting a Type II (singlet oxygen) mechanism for phototoxicity. More Pc4SNP than free Pc4 was localized in the mitochondria and lysosomes. Our results show that these stable, monodispersed silica nanoparticles may be an effective new formulation for Pc4 in its preclinical and clinical studies. We expect that modifying the surface of silicon nanoparticles encapsulating the photosensitizers with antibodies specific to melanoma cells will lead to even better early diagnosis and targeted treatment of melanoma in the future.

  7. Enhanced efficacy and sensory properties of an anti-dandruff shampoo containing zinc pyrithione and climbazole.

    Science.gov (United States)

    Turner, G A; Matheson, J R; Li, G-Z; Fei, X-Q; Zhu, D; Baines, F L

    2013-02-01

    Dandruff is a common complaint and is suffered by as much as half of the population at some time post puberty. The condition is characterized by the presence of flakes on the scalp and in the hair, and is often accompanied by itch. The most common treatment for dandruff is the use of shampoo formulations that contain fungistatic agents such as zinc pyrithione (ZPT) and octopirox. Whilst most antidandruff shampoos are effective in resolving the symptoms of dandruff these shampoos can often result in hair condition that is less than acceptable to consumers which can lead to a tendency for them to revert to use of a non-antidandruff shampoo. This can result in a rapid return of dandruff symptoms. The aim of this investigation was to study the impact of using a combination of antidandruff actives and silicones on the resolution of dandruff and to deliver superior sensory properties to the hair. We have demonstrated that shampoo containing the dual active system of ZPT/Climbazole deposits both active agents onto a model skin surface (VitroSkin) and reduces Malassezia furfur regrowth in vitro. Clinical evaluation of the dual active shampoo demonstrated superior efficacy and retained superiority during a regression phase where all subjects reverted to using a non-antidandruff shampoo. We have also demonstrated that it is possible to deposit silicone materials from antidandruff shampoo uniformly over both virgin and damaged hair fibres that results in smoother hair fibres (as evidenced by reduced dry friction). This combination of antidandruff agents and conditioning silicones delivered from a shampoo provides subjects with superior antidandruff efficacy and desired end sensory benefits ensuring compliance and longer term dandruff removal.

  8. From Burdens to Benefits: The Societal Impact of PDL-Enriched, Efficacy-Enhanced Educators

    Science.gov (United States)

    Shaha, Steven H.; Glassett, Kelly F.; Rosenlund, David; Copas, Aimee; Huddleston, T. Lisa

    2016-01-01

    Societies continue to absorb increased burdens in cost for helping citizens unable to achieve at optimal levels. Building on past research, we project educational benefits to offset current societal burdens through enhanced educator capabilities. Studies reviewed show participation in a high-impact professional development and learning solution…

  9. Cold storage enhances the efficacy and margin of security in postharvest irradiation treatments against fruit flies (Diptera: Tephritidae).

    Science.gov (United States)

    Follett, Peter A; Snook, Kirsten

    2013-10-01

    Cold storage is used to preserve fruit quality after harvest during transportation in marketing channels. Low temperature can be a stressor for insects that reduces survivorship, and cold storage may contribute to the efficacy of postharvest quarantine treatments such as irradiation against quarantine insect pests. The combined effect of irradiation and cold storage was examined in a radiation-tolerant fruit fly, Bactrocera cucurbitae Coquillet (melon fly), and a radiation-intolerant fruit fly, Ceratitis capitata (Wiedemann) (Mediterranean fruit fly) (Diptera: Tephritidae). Third instars on diet or in papaya were treated with a sublethal radiation dose of 30 Gy and stored at 4 or 11 degrees C for 3-13 d and held for adult emergence. For both fruit fly species, survival of third instars to the adult stage generally decreased with increasing cold storage duration at 4 or 11 degrees C in diet or papaya. Survivorship differences were highly significant for the effects of substrate (diet > papaya), temperature (11 > 4 degrees C),and irradiation (0 > 30 Gy). Few Mediterranean fruit flies survived in any cold storage treatment after receiving a radiation dose of 30 Gy. No melon fly larvae survived to the adult stage after irradiation and 11 d cold storage at 4 or 11 degrees C in papayas. Cold storage enhances the efficacy and widens the margin of security in postharvest irradiation treatments. Potentially irradiation and cold storage can be used in combination to reduce the irradiation exposure requirements of quarantine treatments.

  10. Immobilized silver nanoparticles enhance contact killing and show highest efficacy: elucidation of the mechanism of bactericidal action of silver.

    Science.gov (United States)

    Agnihotri, Shekhar; Mukherji, Soumyo; Mukherji, Suparna

    2013-08-21

    Antimicrobial materials with immobilized/entrapped silver nanoparticles (AgNPs) are of considerable interest. There is significant debate on the mode of bactericidal action of AgNPs, and both contact killing and/or ion mediated killing have been proposed. In this study, AgNPs were immobilized on an amine-functionalized silica surface and their bactericidal activity was studied concurrently with the silver release profile over time. This was compared with similar studies performed using colloidal AgNPs and AgCl surfaces that released Ag ions. We conclude that contact killing is the predominant bactericidal mechanism and surface immobilized nanoparticles show greater efficacy than colloidal AgNPs, as well as a higher concentration of silver ions in solution. In addition, the AgNP immobilized substrate was used multiple times with good efficacy, indicating this immobilization protocol is effective for retaining AgNPs while maintaining their disinfection potential. The antibacterial surface was found to be extremely stable in aqueous medium and no significant leaching (∼1.15% of total silver deposited) of the AgNPs was observed. Thus, immobilization of AgNPs on a surface may promote reuse, reduce environmental risks associated with leaching of AgNPs and enhance cost effectiveness.

  11. A bacterial protein enhances the release and efficacy of liposomal cancer drugs.

    Science.gov (United States)

    Cheong, Ian; Huang, Xin; Bettegowda, Chetan; Diaz, Luis A; Kinzler, Kenneth W; Zhou, Shibin; Vogelstein, Bert

    2006-11-24

    Clostridium novyi-NT is an anaerobic bacterium that can infect hypoxic regions within experimental tumors. Because C. novyi-NT lyses red blood cells, we hypothesized that its membrane-disrupting properties could be exploited to enhance the release of liposome-encapsulated drugs within tumors. Here, we show that treatment of mice bearing large, established tumors with C. novyi-NT plus a single dose of liposomal doxorubicin often led to eradication of the tumors. The bacterial factor responsible for the enhanced drug release was identified as a previously unrecognized protein termed liposomase. This protein could potentially be incorporated into diverse experimental approaches for the specific delivery of chemotherapeutic agents to tumors.

  12. Enhanced antitumor efficacy of cisplatin in combination with HemoHIM in tumor-bearing mice

    OpenAIRE

    Kim Sung-Ho; Jung Uhee; Jo Sung-Kee; Ju Eun-Jin; Park Hae-Ran; Yee Sung-Tae

    2009-01-01

    Abstract Background Although cisplatin is one of the most effective chemotherapeutic agents, cisplatin alone does not achieve a satisfactory therapeutic outcome. Also cisplatin accumulation shows toxicity to normal tissues. In this study, we examined the possibility of HemoHIM both to enhance anticancer effect with cisplatin and to reduce the side effects of cisplatin in melanoma-bearing mice. Methods HemoHIM was prepared by adding the ethanol-insoluble fraction to the total water extract of ...

  13. Harnessing structure-activity relationship to engineer a cisplatin nanoparticle for enhanced antitumor efficacy.

    Science.gov (United States)

    Paraskar, Abhimanyu S; Soni, Shivani; Chin, Kenneth T; Chaudhuri, Padmaparna; Muto, Katherine W; Berkowitz, Julia; Handlogten, Michael W; Alves, Nathan J; Bilgicer, Basar; Dinulescu, Daniela M; Mashelkar, Raghunath A; Sengupta, Shiladitya

    2010-07-13

    Cisplatin is a first line chemotherapy for most types of cancer. However, its use is dose-limited due to severe nephrotoxicity. Here we report the rational engineering of a novel nanoplatinate inspired by the mechanisms underlying cisplatin bioactivation. We engineered a novel polymer, glucosamine-functionalized polyisobutylene-maleic acid, where platinum (Pt) can be complexed to the monomeric units using a monocarboxylato and an O --> Pt coordinate bond. We show that at a unique platinum to polymer ratio, this complex self-assembles into a nanoparticle, which releases cisplatin in a pH-dependent manner. The nanoparticles are rapidly internalized into the endolysosomal compartment of cancer cells, and exhibit an IC50 (4.25 +/- 0.16 microM) comparable to that of free cisplatin (3.87 +/- 0.37 microM), and superior to carboplatin (14.75 +/- 0.38 microM). The nanoparticles exhibited significantly improved antitumor efficacy in terms of tumor growth delay in breast and lung cancers and tumor regression in a K-ras(LSL/+)/Pten(fl/fl) ovarian cancer model. Furthermore, the nanoparticle treatment resulted in reduced systemic and nephrotoxicity, validated by decreased biodistribution of platinum to the kidney as quantified using inductively coupled plasma spectroscopy. Given the universal need for a better platinate, we anticipate this coupling of nanotechnology and structure-activity relationship to rationally reengineer cisplatin could have a major impact globally in the clinical treatment of cancer.

  14. Efficacy and Effectiveness of Physical Therapy in Enhancing Postural Control in Children With Cerebral Palsy

    Directory of Open Access Journals (Sweden)

    Susan R. Harris

    2005-01-01

    Full Text Available The purpose of this article was to conduct a systematic review of studies that examined the efficacy and effectiveness of postural control intervention strategies for children with CP. Only physical therapy interventions were included, e.g. adaptive seating devices, ankle foot orthoses, neurodevelopmental treatment. A multifaceted search strategy was employed to identify all potential studies published between 1990 and 2004. The search strategy included electronic databases, reference list scanning, author and citation tracking of relevant studies, and hand searching of pediatric physical therapy journals and conference proceedings. Twelve studies (1991–2004, comprising ten group design studies and two single subject studies, met our inclusion criteria. A variety of age ranges and severity of children with cerebral palsy (n = 132 participated in the studies. The study quality scores ranged from 2 to 7 (total possible range of 0 to 7 with a median score of 5.5 and a mode of 6. As was true in an earlier systematic review on adaptive seating, most of the 12 ‘experimental’ studies published since 1990 that were aimed at evaluating the effectiveness of postural control strategies provided lower levels of evidence, i.e. Sackett Levels III to V. Additional studies with stronger designs are needed to establish that postural control interventions for children with CP are effective.

  15. Novel nitric oxide generating compound glycidyl nitrate enhances the therapeutic efficacy of chemotherapy and radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Ning, Shoucheng [Department of Radiation Oncology, Stanford University Medical Center, Stanford, CA 94305 (United States); Bednarski, Mark [Department of Radiology, Stanford University Medical Center, Stanford, CA 94305 (United States); Oronsky, Bryan; Scicinski, Jan [RadioRx, Inc., Mountain View, CA 94040 (United States); Knox, Susan J., E-mail: sknox@stanford.edu [Department of Radiation Oncology, Stanford University Medical Center, Stanford, CA 94305 (United States)

    2014-05-09

    Highlights: • Glycidyl nitrate (GLYN) is a NO generating small molecule and has ability to release NO on bioactivation in tumor cells. • GLYN-induced intracellular NO generation was attenuated by NO scavengers. • GLYN increases tumor blood flow in tumor-bearing animal model. • GLYN significantly increased the anti-tumor efficacy of cisplatin and radiation therapy in mice. • GLYN is well tolerated with no obvious systemic toxicities at its effective therapeutic doses in preclinical animal studies. - Abstract: Selective release of nitric oxide (NO) in tumors could improve the tumor blood flow and drug delivery for chemotherapeutic agents and radiotherapy, thereby increasing the therapeutic index. Glycidyl nitrate (GLYN) is a NO generating small molecule, and has ability to release NO on bioactivation in SCC VII tumor cells. GLYN-induced intracellular NO generation was significantly attenuated by NO scavenger carboxy-PTIO (cPTIO) and NAC. GLYN significantly increases tumor blood flow, but has no effect on the blood flow of normal tissues in tumor-bearing mice. When used with cisplatin, GLYN significantly increased the tumor growth inhibition effect of cisplatin. GLYN also had a modest radiosensitizing effect in vitro and in vivo. GLYN was well tolerated and there were no acute toxicities found at its effective therapeutic doses in preclinical studies. These results suggest that GLYN is a promising new drug for use with chemotherapy and radiotherapy, and provide a compelling rationale for future studies of GLYN and related compounds.

  16. The iron chelator deferasirox enhances liposomal amphotericin B efficacy in treating murine invasive pulmonary aspergillosis

    Science.gov (United States)

    Ibrahim, Ashraf S.; Gebremariam, Teclegiorgis; French, Samuel W.; Edwards, John E.; Spellberg, Brad

    2010-01-01

    Objectives Increased bone marrow iron levels in patients with haematological malignancies is an independent risk factor for developing invasive pulmonary aspergillosis (IPA), suggesting an important role for iron uptake in the pathogenesis of IPA. We sought to determine the potential for combination therapy with the iron chelator deferasirox + liposomal amphotericin B (LAmB) to improve the outcome of murine IPA compared with LAmB monotherapy. Methods In vitro MIC and minimum fungicidal concentration (MFC) values of the iron chelator, deferasirox, for Aspergillus fumigatus were determined by microdilution assay. In addition, we studied the efficacy of deferasirox alone or combined with LAmB in treating immunocompromised mice infected with A. fumigatus via inhalation. Results Deferasirox was cidal in vitro against A. fumigatus, with an MIC and MFC of 25 and 50 mg/L, respectively. Deferasirox monotherapy modestly prolonged survival of mice with IPA. Combination deferasirox + LAmB therapy synergistically improved survival and reduced lung fungal burden compared with either monotherapy alone. Conclusions Iron chelation therapy with deferasirox alone or in combination with LAmB is effective in treating experimental IPA. Further study of deferasirox is warranted as adjunctive therapy for IPA infections. PMID:19942619

  17. Berberine Nanosuspension Enhances Hypoglycemic Efficacy on Streptozotocin Induced Diabetic C57BL/6 Mice

    Directory of Open Access Journals (Sweden)

    Zhiping Wang

    2015-01-01

    Full Text Available Berberine (Ber, an isoquinoline derivative alkaloid and active ingredient of Coptis, has been demonstrated to possess antidiabetic activities. However its low oral bioavailability restricts its clinical application. In this report, Ber nanosuspension (Ber-NS composed of Ber and D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS was prepared by high pressure homogenization technique. Antidiabetic effects of Ber-NS relative to efficacy of bulk Ber were evaluated in streptozotocin (STZ induced diabetic C57BL/6 mice. The particle size and zeta potential of Ber-NS were 73.1 ± 3.7 nm and 6.99 ± 0.17 mV, respectively. Ber-NS (50 mg/kg treatment via oral gavage for 8 weeks resulted in a superior hypoglycemic and total cholesterol (TC and body weight reduction effects compared to an equivalent dose of bulk Ber and metformin (Met, 300 mg/kg. These data indicate that a low dosage Ber-NS decreases blood glucose and improves lipid metabolism in type 2 diabetic C57BL/6 mice. These results suggest that the delivery of Ber as a nanosuspension is a promising approach for treating type 2 diabetes.

  18. Berberine nanosuspension enhances hypoglycemic efficacy on streptozotocin induced diabetic C57BL/6 mice.

    Science.gov (United States)

    Wang, Zhiping; Wu, Junbiao; Zhou, Qun; Wang, Yifei; Chen, Tongsheng

    2015-01-01

    Berberine (Ber), an isoquinoline derivative alkaloid and active ingredient of Coptis, has been demonstrated to possess antidiabetic activities. However its low oral bioavailability restricts its clinical application. In this report, Ber nanosuspension (Ber-NS) composed of Ber and D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) was prepared by high pressure homogenization technique. Antidiabetic effects of Ber-NS relative to efficacy of bulk Ber were evaluated in streptozotocin (STZ) induced diabetic C57BL/6 mice. The particle size and zeta potential of Ber-NS were 73.1 ± 3.7 nm and 6.99 ± 0.17 mV, respectively. Ber-NS (50 mg/kg) treatment via oral gavage for 8 weeks resulted in a superior hypoglycemic and total cholesterol (TC) and body weight reduction effects compared to an equivalent dose of bulk Ber and metformin (Met, 300 mg/kg). These data indicate that a low dosage Ber-NS decreases blood glucose and improves lipid metabolism in type 2 diabetic C57BL/6 mice. These results suggest that the delivery of Ber as a nanosuspension is a promising approach for treating type 2 diabetes.

  19. Biphasic pulses enhance bleomycin efficacy in a spontaneous canine genital tumor model of chemoresistance: Sticker sarcoma

    Directory of Open Access Journals (Sweden)

    Citro Gennaro

    2008-11-01

    Full Text Available Abstract Sticker's sarcoma (also known as transmissible venereal tumor is a horizontally transmitted neoplasm of the dog, that is passed with coitus. It is a locally aggressive tumor with a low tendency to metastatic spread. The most common locations are the genitals, the nose, the perianal area. Standard treatment consists with chemotherapy with vincristine, however other therapies such as, cryotherapy, immunotherapy or, in selected cases, radiation therapy, have been reported. In this article we describe the outcome of a small cohort of canine patients, with chemotherapy resistant transmissible venereal tumor (TVT, treated with bleomycin selectively driven by trains of biphasic pulses (electrochemotherapy. Three canine patients, with refractory TVT, entered the study and received two sessions of ECT under sedation. The pets had local injection of bleomycin at the concentration of 1.5 mg/ml and five minutes after the chemotherapy, trains of 8 biphasic electric pulses lasting 50 + 50 μs each, with 1 ms interpulse intervals, were delivered by means of modified caliper or, for difficult districts, through paired needle electrode. All the patients responded to the treatment and are still in remission at different times. Electrochemotherapy appears as a safe and efficacious modality for the treatment of TVT and warrants further investigations.

  20. A Radio Frequency Electric Current Enhances Antibiotic Efficacy against Bacterial Biofilms

    Science.gov (United States)

    Caubet, R.; Pedarros-Caubet, F.; Chu, M.; Freye, E.; de Belém Rodrigues, M.; Moreau, J. M.; Ellison, W. J.

    2004-01-01

    Bacterial biofilms are notably resistant to antibiotic prophylaxis. The concentration of antibiotic necessary to significantly reduce the number of bacteria in the biofilm matrix can be several hundred times the MIC for the same bacteria in a planktonic phase. It has been observed that the addition of a weak continuous direct electric current to the liquid surrounding the biofilm can dramatically increase the efficacy of the antibiotic. This phenomenon, known as the bioelectric effect, has only been partially elucidated, and it is not certain that the electrical parameters are optimal. We confirm here the bioelectric effect for Escherichia coli biofilms treated with gentamicin and with oxytetracycline, and we report a new bioelectric effect with a radio frequency alternating electric current (10 MHz) instead of the usual direct current. None of the proposed explanations (transport of ions within the biofilm, production of additional biocides by electrolysis, etc.) of the direct current bioelectric effect are applicable to the radio frequency bioelectric effect. We suggest that this new phenomenon may be due to a specific action of the radio frequency electromagnetic field upon the polar parts of the molecules forming the biofilm matrix. PMID:15561841

  1. Enhanced antifungal efficacy of tebuconazole using gated pH-driven mesoporous nanoparticles

    Science.gov (United States)

    Mas, Núria; Galiana, Irene; Hurtado, Silvia; Mondragón, Laura; Bernardos, Andrea; Sancenón, Félix; Marcos, María D; Amorós, Pedro; Abril-Utrillas, Nuria; Martínez-Máñez, Ramón; Murguía, José Ramón

    2014-01-01

    pH-sensitive gated mesoporous silica nanoparticles have been synthesized. Increased extracellular pH and internalization into living yeast cells triggered molecular gate aperture and cargo release. Proper performance of the system was demonstrated with nanodevices loaded with fluorescein or with the antifungal agent tebuconazole. Interestingly, nanodevices loaded with tebuconazole significantly enhanced tebuconazole cytotoxicity. As alterations of acidic external pH are a key parameter in the onset of fungal vaginitis, this nanodevice could improve the treatment for vaginal mycoses. PMID:24920897

  2. Enhanced efficacy of clindamycin hydrochloride encapsulated in PLA/PLGA based nanoparticle system for oral delivery.

    Science.gov (United States)

    Rauta, Pradipta Ranjan; Das, Niladri Mohan; Nayak, Debasis; Ashe, Sarbani; Nayak, Bismita

    2016-08-01

    Clindamycin hydrochloride (CLH) is a clinically important oral antibiotic with wide spectrum of antimicrobial activity that includes gram-positive aerobes (staphylococci, streptococci etc.), most anaerobic bacteria, Chlamydia and certain protozoa. The current study was focused to develop a stabilised clindamycin encapsulated poly lactic acid (PLA)/poly (D,L-lactide-co-glycolide) (PLGA) nano-formulation with better drug bioavailability at molecular level. Various nanoparticle (NPs) formulations of PLA and PLGA loaded with CLH were prepared by solvent evaporation method varying drug: polymer concentration (1:20, 1:10 and 1:5) and characterised (size, encapsulation efficiency, drug loading, scanning electron microscope, differential scanning calorimetry [DSC] and Fourier transform infrared [FTIR] studies). The ratio 1:10 was found to be optimal for a monodispersed and stable nano formulation for both the polymers. NP formulations demonstrated a significant controlled release profile extended up to 144 h (both CLH-PLA and CLH-PLGA). The thermal behaviour (DSC) studies confirmed the molecular dispersion of the drug within the system. The FTIR studies revealed the intactness as well as unaltered structure of drug. The CLH-PLA NPs showed enhanced antimicrobial activity against two pathogenic bacteria Streptococcus faecalis and Bacillus cereus. The results notably suggest that encapsulation of CLH into PLA/PLGA significantly increases the bioavailability of the drug and due to this enhanced drug activity; it can be widely applied for number of therapies.

  3. Synergistic efficacy of salicylic acid with a penetration enhancer on human skin monitored by OCT and diffuse reflectance spectroscopy

    Science.gov (United States)

    Zhao, Qingliang; Dai, Cuixia; Fan, Shanhui; Lv, Jing; Nie, Liming

    2016-10-01

    Salicylic acid (SA) has been frequently used as a facial chemical peeling agent (FCPA) in various cosmetics for facial rejuvenation and dermatological treatments in the clinic. However, there is a tradeoff between therapeutic effectiveness and possible adverse effects caused by this agent for cosmetologists. To optimize the cosmetic efficacy with minimal concentration, we proposed a chemical permeation enhancer (CPE) azone to synergistically work with SA on human skin in vivo. The optical properties of human skin after being treated with SA alone and SA combined with azone (SA@azone) were successively investigated by diffuse reflectance spectroscopy (DRS) and optical coherence tomography (OCT). Our results revealed that as the SA concentration increased, the light reflectance decreased and the absorption increased. We also found that SA@azone exhibited a synergistic effect on enhancing light penetration and OCT imaging depth. We demonstrated that the combination of DRS and OCT techniques could be used as a noninvasive, rapid and accurate measurement method to monitor the subtle changes of skin tissue after treatment with FCPA and CPE. The approach will greatly benefit the development of clinical cosmetic surgery, dermatosis diagnosis and therapeutic effect inspection in related biomedical studies.

  4. A dual TLR agonist adjuvant enhances the immunogenicity and protective efficacy of the tuberculosis vaccine antigen ID93.

    Directory of Open Access Journals (Sweden)

    Mark T Orr

    Full Text Available With over eight million cases of tuberculosis each year there is a pressing need for the development of new vaccines against Mycobacterium tuberculosis. Subunit vaccines consisting of recombinant proteins are an attractive vaccine approach due to their inherent safety compared to attenuated live vaccines and the uniformity of manufacture. Addition of properly formulated TLR agonist-containing adjuvants to recombinant protein vaccines enhances the antigen-specific CD4(+ T cell response characterized by IFN-γ and TNF, both of which are critical for the control of TB. We have developed a clinical stage vaccine candidate consisting of a recombinant fusion protein ID93 adjuvanted with the TLR4 agonist GLA-SE. Here we examine whether ID93+GLA-SE can be improved by the addition of a second TLR agonist. Addition of CpG containing DNA to ID93+GLA-SE enhanced the magnitude of the multi-functional TH1 response against ID93 characterized by co-production of IFN-γ, TNF, and IL-2. Addition of CpG also improved the protective efficacy of ID93+GLA-SE. Finally we demonstrate that this adjuvant synergy between GLA and CpG is independent of TRIF signaling, whereas TRIF is necessary for the adjuvant activity of GLA-SE in the absence of CpG.

  5. Synergistic efficacy of salicylic acid with a penetration enhancer on human skin monitored by OCT and diffuse reflectance spectroscopy

    Science.gov (United States)

    Zhao, Qingliang; Dai, Cuixia; Fan, Shanhui; Lv, Jing; Nie, Liming

    2016-01-01

    Salicylic acid (SA) has been frequently used as a facial chemical peeling agent (FCPA) in various cosmetics for facial rejuvenation and dermatological treatments in the clinic. However, there is a tradeoff between therapeutic effectiveness and possible adverse effects caused by this agent for cosmetologists. To optimize the cosmetic efficacy with minimal concentration, we proposed a chemical permeation enhancer (CPE) azone to synergistically work with SA on human skin in vivo. The optical properties of human skin after being treated with SA alone and SA combined with azone (SA@azone) were successively investigated by diffuse reflectance spectroscopy (DRS) and optical coherence tomography (OCT). Our results revealed that as the SA concentration increased, the light reflectance decreased and the absorption increased. We also found that SA@azone exhibited a synergistic effect on enhancing light penetration and OCT imaging depth. We demonstrated that the combination of DRS and OCT techniques could be used as a noninvasive, rapid and accurate measurement method to monitor the subtle changes of skin tissue after treatment with FCPA and CPE. The approach will greatly benefit the development of clinical cosmetic surgery, dermatosis diagnosis and therapeutic effect inspection in related biomedical studies. PMID:27721398

  6. Enhancement of chemotherapeutic efficacy in hypermethylator breast cancer cells through targeted and pharmacologic inhibition of DNMT3b.

    Science.gov (United States)

    Sandhu, Rupninder; Rivenbark, Ashley G; Coleman, William B

    2012-01-01

    A subset of primary breast cancers and breast cancer cell lines express a hypermethylation defect (characterized by DNMT hyperactivity and DNMT3b overexpression) which contributes to chemotherapy resistance and provides a target for development of new treatment strategies. The objective of the current study was to determine if targeting the epigenome enhances the sensitivity of breast cancer cells to cytotoxic chemotherapy. Hypermethylator breast cancer cell lines (MDA-MB-453, BT549, and Hs578T) were treated with 250 or 500 nM 5-aza-2'-deoxycytidine (5-aza) and/or were subjected to RNAi-mediated DNMT3b knockdown (KD), and then tested for sensitivity to doxorubicin hydrochloride (DOX), paclitaxel (PAX), and 5-fluorouracil (5-FU). In MDA-MB-453 cells, DNMT3b KD reduces the IC(50) for DOX from 0.086 to 0.048 μM (44% reduction), for PAX from 0.497 to 0.376 nM (24%), and for 5-FU from 0.817 to 0.145 mM (82%). Treatment with 250 nM 5-aza for 7 days did not increase the efficacy of DOX, PAX, or 5-FU, but 7-day treatment with 500 nM 5-aza sensitized cells, reducing the IC(50) for DOX to 0.035 μM (60%), PAX to 0.311 nM (37%), and 5-FU to 0.065 mM (92%). 5-aza treatment of DNMT3b KD cells reduced the IC(50) for DOX to 0.036 μM (59%), for PAX to 0.313 nM (37%) and for 5-FU to 0.067 (92%). Similar trends of enhancement of cell kill were seen in BT549 (13-60%) and Hs578T (29-70%) cells after RNAi-mediated DNMT3b KD and/or treatment with 5-aza. The effectiveness of DOX, PAX, and 5-FU is enhanced through targeted and/or pharmacological inhibition of DNMT3b, strongly suggesting that combined epigenetic and cytotoxic treatment will improve the efficacy of breast cancer chemotherapy.

  7. Use of biotin targeted methotrexate–human serum albumin conjugated nanoparticles to enhance methotrexate antitumor efficacy

    Directory of Open Access Journals (Sweden)

    Taheri A

    2011-09-01

    Full Text Available Azade Taheri1, Rassoul Dinarvand1,2, Faranak Salman Nouri1, Mohammad Reza Khorramizadeh3, Atefeh Taheri Borougeni4, Pooria Mansoori5, Fatemeh Atyabi1,21Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; 2Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical sciences, Tehran, Iran; 3Department of Pathobiology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran; 4Department of Oral and Maxillofacial Pathology, Faculty of Dentistry, Tehran University of Medical Sciences, Tehran, Iran; 5Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IranAbstract: Biotin molecules could be used as suitable targeting moieties in targeted drug delivery systems against tumors. To develop a biotin targeted drug delivery system, we employed human serum albumin (HSA as a carrier. Methotrexate (MTX molecules were conjugated to HSA. MTX-HSA nanoparticles (MTX-HSA NPs were prepared from these conjugates by cross-linking the HSA molecules. Biotin molecules were then conjugated on the surface of MTX-HSA NPs. The anticancer efficacy of biotin targeted MTX-HSA NPs was evaluated in mice bearing 4T1 breast carcinoma. A single dose of biotin targeted MTX-HSA NPs showed stronger in vivo antitumor activity than non-targeted MTX-HSA NPs and free MTX. By 7 days after treatment, average tumor volume in the biotin targeted MTX-HSA NPs-treated group decreased to 17.6% of the initial tumor volume when the number of attached biotin molecules on MTX-HSA-NPs was the highest. Average tumor volume in non-targeted MTX-HSA NPs-treated mice grew rapidly and reached 250.7% of the initial tumor volume. Biotin targeted MTX-HSA NPs increased the survival of tumor-bearing mice to 47.5 ± 0.71 days and increased their life span up to 216.7%. Mice treated with biotin targeted MTX-HSA NPs showed slight body weight loss (8% 21 days after treatment, whereas non-targeted MTX

  8. Enhanced in vitro and in vivo therapeutic efficacy of codrug-loaded nanoparticles against liver cancer

    Directory of Open Access Journals (Sweden)

    Li X

    2012-10-01

    Full Text Available Xiaolin Li,1,* Hua’e Xu,2,* Xinzheng Dai,3,4,* Zhenshu Zhu,5 Baorui Liu,6 Xiaowei Lu11Department of Geriatrics, 2Department of Pharmacy, the First Affiliated Hospital to Nanjing Medical University, Nanjing; 3Key Laboratory of Living Donor Liver Transplantation, Ministry of Public Health, 4Liver Transplantation Center, the First Affiliated Hospital to Nanjing Medical University, Nanjing; 5Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing; 6The Comprehensive Cancer Center of Drum Tower Hospital, Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University, Nanjing, China*These authors contributed equally to this workAbstract: Paclitaxel (Ptx, one of the most widely used anticancer agents, has demonstrated extraordinary activities against a variety of solid tumors. However, the therapeutic response of Ptx is often associated with severe side effects caused by its nonspecific cytotoxic effects and special solvents (Cremophor EL®. The current study reports the stable controlled release of Ptx/tetrandrine (Tet-coloaded nanoparticles by amphilic methoxy poly(ethylene glycol–poly(caprolactone block copolymers. There were three significant findings. Firstly, Tet could effectively stabilize Ptx-loaded nanoparticles with the coencapsulation of Tet and Ptx. The influence of different Ptx/Tet feeding ratios on the size and loading efficiency of the nanoparticles was also explored. Secondly, the encapsulation of Tet and Ptx into nanoparticles retains the synergistic anticancer efficiency of Tet and Ptx against mice hepatoma H22 cells. Thirdly, in the in vivo evaluation, intratumoral administration was adopted to increase the site-specific delivery. Ptx/Tet nanoparticles, when delivered intratumorally, exhibited significantly improved antitumor efficacy; moreover, they substantially increased the overall survival in an established H22-transplanted mice model. Further investigation into the

  9. beta 1 integrin inhibition dramatically enhances radiotherapy efficacy in human breast cancer xenografts

    Energy Technology Data Exchange (ETDEWEB)

    Park, Catherine C.; Park, Catherine C.; Zhang, Hui J.; Yao, Evelyn S.; Park, Chong J.; Bissell, Mina J.

    2008-06-02

    {beta}1 integrin signaling has been shown to mediate cellular resistance to apoptosis after exposure to ionizing radiation (IR). Other signaling molecules that increase resistance include Akt, which promotes cell survival downstream of {beta}1 integrin signaling. We showed previously that {beta}1 integrin inhibitory antibodies, AIIB2, enhance apoptosis and decrease growth in human breast cancer cells in 3 dimensional laminin-rich extracellular matrix (3D lrECM) cultures and in vivo. Here we asked whether AIIB2 could synergize with IR to modify Akt-mediated IR resistance. We used 3D lrECM cultures to test the optimal combination of AIIB2 with IR treatment of two breast cancer cell lines, MCF-7 and HMT3522-T4-2, as well as T4-2 myr-Akt breast cancer colonies or HMT3522-S-1, which form normal organotypic structures in 3D lrECM. Colonies were assayed for apoptosis and {beta}1 integrin/Akt signaling pathways were evaluated using western blot. In addition, mice bearing MCF-7 xenografts were used to validate the findings in 3D lrECM. We report that AIIB2 increased apoptosis optimally post-IR by down regulating Akt in breast cancer colonies in 3D lrECM. In vivo, addition of AIIB2 after IR significantly enhanced tumor growth inhibition and apoptosis compared to either treatment alone. Remarkably, the degree of tumor growth inhibition using AIIB2 plus 2 Gy radiation was similar to that of 8 Gy alone. We showed previously that AIIB2 had no discernible toxicity in mice; here, its addition allowed for a significant reduction in the IR dose that was necessary to achieve comparable growth inhibition and apoptosis in breast cancer xenografts in vivo.

  10. Photosensitive Pt(IV)-azide prodrug-loaded nanoparticles exhibit controlled drug release and enhanced efficacy in vivo.

    Science.gov (United States)

    Xiao, Haihua; Noble, Gavin T; Stefanick, Jared F; Qi, Ruogu; Kiziltepe, Tanyel; Jing, Xiabin; Bilgicer, Basar

    2014-01-10

    Cisplatin has long been the first line of treatment for a variety of solid tumors. However, poor pharmacokinetics and high incidences of resistance in the clinic have motivated the production of numerous alternative Pt-based anticancer species. Recently, photosensitive Pt(IV) complexes have garnered much interest because they offer a method of selective induction of active Pt(II) at the tumor site by UVA irradiation. Here, we report the first synthesis, in vitro and in vivo characterization of a novel series of photosensitive Pt(IV)–azide prodrugs and micellar nanoparticle formulations thereof. Upon mild UVA irradiation, both free Pt(IV) complexes and micellar nanoparticles rapidly released biologically active Pt(II), capable of binding to 5′-GMP,while remaining extremely stable in the dark. In vitro, uptake of photosensitive Pt(IV) prodrugs by ovarian cancer SKOV-3 cells was greatly enhanced with the micellar nanoparticles compared to their free prodrug analogs, as well as cisplatin and oxaliplatin. Increased cytotoxicity was observed upon UVA treatment, with up to a 13-fold enhancement over oxaliplatin for the micellar nanoparticles. In vivo bioavailability of micellar nanoparticles was enhanced ~10 fold over free Pt(IV) prodrugs. Importantly, micellar nanoparticles demonstrated significantly improved efficacy against H22 murine hepatocarcinoma, showing decreased systemic toxicity and increased tumor growth inhibition relative to small molecule drugs. These findings establish that photosensitive Pt(IV) complexes, specifically when formulated into micellar nanoparticles, have the potential to offer a robust platform for the controlled delivery and selective activation of Pt-based anticancer therapeutics.

  11. Immobilized silver nanoparticles enhance contact killing and show highest efficacy: elucidation of the mechanism of bactericidal action of silver

    Science.gov (United States)

    Agnihotri, Shekhar; Mukherji, Soumyo; Mukherji, Suparna

    2013-07-01

    Antimicrobial materials with immobilized/entrapped silver nanoparticles (AgNPs) are of considerable interest. There is significant debate on the mode of bactericidal action of AgNPs, and both contact killing and/or ion mediated killing have been proposed. In this study, AgNPs were immobilized on an amine-functionalized silica surface and their bactericidal activity was studied concurrently with the silver release profile over time. This was compared with similar studies performed using colloidal AgNPs and AgCl surfaces that released Ag ions. We conclude that contact killing is the predominant bactericidal mechanism and surface immobilized nanoparticles show greater efficacy than colloidal AgNPs, as well as a higher concentration of silver ions in solution. In addition, the AgNP immobilized substrate was used multiple times with good efficacy, indicating this immobilization protocol is effective for retaining AgNPs while maintaining their disinfection potential. The antibacterial surface was found to be extremely stable in aqueous medium and no significant leaching (~1.15% of total silver deposited) of the AgNPs was observed. Thus, immobilization of AgNPs on a surface may promote reuse, reduce environmental risks associated with leaching of AgNPs and enhance cost effectiveness.Antimicrobial materials with immobilized/entrapped silver nanoparticles (AgNPs) are of considerable interest. There is significant debate on the mode of bactericidal action of AgNPs, and both contact killing and/or ion mediated killing have been proposed. In this study, AgNPs were immobilized on an amine-functionalized silica surface and their bactericidal activity was studied concurrently with the silver release profile over time. This was compared with similar studies performed using colloidal AgNPs and AgCl surfaces that released Ag ions. We conclude that contact killing is the predominant bactericidal mechanism and surface immobilized nanoparticles show greater efficacy than colloidal Ag

  12. Efficacy of cognitive enhancers for Alzheimer’s disease: protocol for a systematic review and network meta-analysis

    Directory of Open Access Journals (Sweden)

    Tricco Andrea C

    2012-06-01

    Full Text Available Abstract Background Approximately 35 million people world-wide have Alzheimer’s disease and this is projected to nearly double by 2030. Cognitive enhancers, including cholinesterase inhibitors (for example, donepezil, galantamine and rivastigmine and memantine (N-methyl-D-aspartic acid (NMDA receptor antagonist have been approved for the treatment of Alzheimer’s disease in many countries. Our objective is to evaluate the comparative effectiveness, safety, and cost of cognitive enhancers for Alzheimer’s disease through a systematic review. Methods/design Studies examining the efficacy, safety, and cost of cognitive enhancers compared to placebo, supportive care, and other cognitive enhancers for Alzheimer’s patients will be included. The primary outcome is cognition and secondary outcomes include function, behavior, quality of life, safety, and cost. Experimental studies (randomized controlled trials, quasi-randomized controlled trials, controlled clinical trials, quasi-experimental studies (controlled before-after, interrupted time series, and observational studies (cohort, case–control studies will be eligible for inclusion. Inclusion will not be limited by publication status, time period or language of dissemination. We will search electronic databases (for example, MEDLINE, Cochrane Central Register of Controlled Trials, EMBASE, CINAHL, Ageline from inception onwards. The electronic database search will be supplemented by searching for grey literature (for example, conference proceedings, searches in Google and relevant organization websites. Two reviewers will independently screen the studies for inclusion using the eligibility criteria established a priori and independently extract data. Risk of bias will be assessed using the Cochrane Risk of Bias tool for experimental and quasi-experimental studies and the Newcastle Ottawa Scale for observational studies. If deemed appropriate, meta-analysis and network (that is, indirect

  13. Teacher Self-Efficacy Enhancement and School Location: Implication for Students' Achievement in Economics in Senior Secondary School in Ibadan, Oyo State, Nigeria

    Science.gov (United States)

    Durowoju, Esther O.; Onuka, Adams O. U.

    2015-01-01

    The paper investigated the effect of teacher self-efficacy enhancement and school location on students' achievement in Economics in Senior Secondary School in Ibadan Metropolis of Oyo State, Nigeria. Three hypotheses were tested at 0.05 level of significance. Multi-stage sampling technique was adopted in the study. Four Local Government Areas (two…

  14. Evaluating the Efficacy of an Animation to Enhance Understanding of First Motion Diagrams

    Science.gov (United States)

    Farmer, E. C.

    2011-12-01

    Having taught the interpretation of first motion diagrams (sometimes referred to as "beach ball diagrams" due to their appearance) in an Introduction to Physical Geology class over many semesters, I was frustrated with the hand-waving this effort entailed when describing static diagrams. I searched for a computer animation that would show how the initial ground motions in an earthquake correspond to the various shaded regions in each first motion diagram, but was not able to find such a pedagogical tool in existence. I decided to work with the staff of my University's Faculty Computing Services to create something that would serve this need. We designed and constructed an animation of strike-slip motions, which can be seen at http://people.hofstra.edu/alex_smiros/earthquake/grid_22march2011.swf. A still image of the animation appears in Figure 1. In order to see if utilizing this visualization enhanced student understanding of the difficult concepts involved in interpreting first motion diagrams, I compared scores on test questions involving first motion diagrams from two different semester iterations of the course: one was taught without utilizing the animation, and one was taught with utilization of the animation.

  15. Cetuximab enhanced the efficacy of chemotherapeutic agent in ABCB1/P-glycoprotein-overexpressing cancer cells.

    Science.gov (United States)

    Wang, Fang; Chen, Yifan; Huang, Lihua; Liu, Tao; Huang, Yue; Zhao, Jianming; Wang, Xiaokun; Yang, Ke; Ma, Shaolin; Huang, Liyan; To, Kenneth Kin Wah; Gu, Yong; Fu, Liwu

    2015-12-01

    The overexpression of ATP-binding cassette (ABC) transporters is closely associated with the development of multidrug resistance (MDR) in certain types of cancer, which represents a formidable obstacle to the successful cancer chemotherapy. Here, we investigated that cetuximab, an EGFR monoclonal antibody, reversed the chemoresistance mediated by ABCB1, ABCG2 or ABCC1. Our results showed that cetuximab significantly enhanced the cytotoxicity of ABCB1 substrate agent in ABCB1-overexpressing MDR cells but had no effect in their parental drug sensitive cells and ABCC1, ABCG2 overexpressing cells. Furthermore, cetuximab markedly increased intracellular accumulation of doxorubicin (DOX) and rhodamine 123 (Rho 123) in ABCB1-overexpressing MDR cancer cells in a concentration-dependent manner. Cetuximab stimulated the ATPase activity but did not alter the expression level of ABCB1 or block phosphorylation of AKT and ERK. Interestingly, cetuximab decreased the cell membrane fluidity which was known to decrease the function of ABCB1. Our findings advocate further clinical investigation of combination chemotherapy of cetuximab and conventional chemotherapeutic drugs in ABCB1 overexpressing cancer patients.

  16. A Novel Agent Enhances the Chemotherapeutic Efficacy of Doxorubicin in MCF-7 Breast Cancer Cells

    Science.gov (United States)

    Wang, Liang; Chan, Judy Y.; Zhou, Xinhua; Cui, Guozhen; Yan, Zhixiang; Wang, Li; Yan, Ru; Di, Lijun; Wang, Yuqiang; Hoi, Maggie P.; Shan, Luchen; Lee, Simon M.

    2016-01-01

    We have previously demonstrated that DT-010, a novel conjugate of danshensu (DSS) and tetramethylpyrazine (TMP), displays anti-tumor effects in breast cancer cells both in vitro and in vivo. In the present study, we investigated whether DT-010 enhances the chemotherapeutic effect of doxorubicin (Dox) in MCF-7 breast cancer cells and exerts concurrent cardioprotective benefit at the same time. Our findings showed that DT-010 was more potent than TMP, DSS, or their combination in potentiating Dox-induced toxicity in MCF-7 cells. Co-treatment with DT-010 and Dox increased apoptosis in MCF-7 cells relative to Dox alone. Further study indicated that glycolytic capacity, glycolytic reserve and lactate level of MCF-7 cells were significantly inhibited after DT-010 treatment. DT-010 also increased the expression of the pro-survival protein GRP78, which was inhibited by co-treatment with Dox. Both endoplasmic reticulum stress inhibitor 4-PBA and knockdown of the expression of GRP78 protein potentiated DT-010-mediated apoptosis in MCF-7 cells. Moreover, DT-010 inhibited Dox-induced cardiotoxicity in H9c2 myoblasts. In conclusion, DT-010 and Dox confer synergistic anti-tumor effect in MCF-7 breast cancer cells through downregulation of the glycolytic pathway and inhibition of the expression of GRP78. Meanwhile, DT-010 also protects against Dox-induced cardiotoxicity. PMID:27559313

  17. Rationale for a multimodality strategy to enhance the efficacy of dendritic cell-based cancer immunotherapy

    Directory of Open Access Journals (Sweden)

    Jashodeep eDatta

    2015-06-01

    Full Text Available Dendritic cells (DC, master antigen-presenting cells that orchestrate interactions between the adaptive and innate immune arms, are increasingly utilized in cancer immunotherapy. Despite remarkable progress in our understanding of DC immunobiology, as well as several encouraging clinical applications — such as DC-based sipuleucel-T for metastatic castration-resistant prostate cancer — clinically effective DC-based immunotherapy as monotherapy for a majority of tumors remains a distant goal. The complex interplay between diverse molecular and immune processes that govern resistance to DC-based vaccination compels a multimodality approach, encompassing a growing arsenal of antitumor agents which target these distinct processes and synergistically enhance DC function. These include antibody-based targeted molecular therapies, immune checkpoint inhibitors, therapies that inhibit immunosuppressive cellular elements, conventional cytotoxic modalities, and immune potentiating adjuvants. It is likely that in the emerging era of precision cancer therapeutics, tangible clinical benefits will only be realized with a multifaceted—and personalized—approach combining DC-based vaccination with adjunctive strategies.

  18. Combined blockade of Tim-3 and MEK inhibitor enhances the efficacy against melanoma.

    Science.gov (United States)

    Liu, Yang; Cai, Pengcheng; Wang, Ning; Zhang, Qianwen; Chen, Fenghua; Shi, Liang; Zhang, Yang; Wang, Lin; Hu, Lihua

    2017-03-04

    Insights into the role of the mitogen-activated protein kinase (MAPK) pathway and immune checkpoints have led combined targeted therapy and immunotherapy to be a promising regimen. Trametinib, as a mitogen-activated extracellular signal-regulated kinase (MEK) inhibitor, has demonstrated effectiveness in patients with advanced melanoma. T cell immunoglobulin- and mucin-domain-containing molecule-3 (Tim-3), an immune checkpoint molecule, participates in multiple negative regulation of antitumor immunity. We for the first time to our knowledge reported the combination of trametinib and anti-Tim-3 monoclonal antibody (mAb) in treating B16-F10 melanoma mice. We discovered that trametinib remarkably promoted apoptosis and inhibited cell proliferation while inhibition of MEK improved the expression of Tim-3 and caused the decrease of CD8(+) T cells; to the contrary, anti-Tim-3 mAb enhanced antitumor immunity by stimulating CD8(+) T cells, thus the combined therapy produced potent antitumor effect cooperatively. Taken together, our study provides compelling evidence for combining trametinib and anti-Tim-3 mAb as a potential valuable regimen in treating melanoma.

  19. Selenium enhances the efficacy of Radachlorin mediated-photodynamic therapy in cervical cancer model

    Science.gov (United States)

    Bae, Dong Han; Wen, Lan Ying; Bae, Su Mi; Kang, Uk; Kim, Keun Hee; Jheon, Sang Hoon; Lee, Jeong Sang; Ahn, Woong Shick

    2009-06-01

    Selenium, an essential trace element possessing anti-carcinogenic properties, can induce apoptosis in cancer cells. Our goal was to investigate the enhanced anti-tumor effects of photodynamic therapy (PDT) plus selenium in TC-1 tumor cells implanted into mice. The MTT assay and tumor growth inhibition study were evaluated at various time intervals after the PDT plus a various dose of selenium. Following Radachlorin injections after 3 hr, the mice were then administrated selenium (2ug/kg b.w.) and then, tumors were treated with external light treatment (300 J/cm2). The selenium was administered daily for 20 days. PDT or selenium was found to be more compared to control groups. Moreover, the PDT combined with selenium demonstrated a significant suppression of tumor growth in vitro and in vivo. The tumor growth by the PDT combined with selenium was significantly reduced. These data suggest that selenium plus PDT can induce a significant tumor suppression response compared with PDT alone. Also, it can be an effective approach to induce anti-cancer therapy strategy.

  20. Enhanced tolerance and antitumor efficacy by docetaxel-loaded albumin nanoparticles.

    Science.gov (United States)

    Tang, Xiaolei; Wang, Guijun; Shi, Runjie; Jiang, Ke; Meng, Lingtong; Ren, Hao; Wu, Jinhui; Hu, Yiqiao

    2016-10-01

    Docetaxel is one of the most active chemotherapeutic agents for cancer treatment. The traditional docetaxel injection (TAXOTERE®) is currently formulated in the surfactant polysorbate 80, which has been associated with severe adverse reactions. To avoid the use of polysorbate 80 as well as to reduce the systemic toxicity of docetaxel, in this study, docetaxel-loaded albumin nanoparticles were fabricated by a novel simple self-assembly method. The resulting nanoparticles showed a mean diameter size of 150 nm. After being encapsulated into nanoparticles, docetaxel displayed similar cytotoxicity to traditional injection. Since polysorbate 80 was not involved in nanoparticles, the hemolysis was completely eliminated. The maximal tolerance dose of nanoparticles was also increased, which allowed a higher dose to be safely intravenously injected and produced ideal antitumor effects. The 150 nm diameter also allowed the nanoparticles to accumulate in tumor tissue via the enhanced permeability and retention effect. The passive targeting ability further caused the higher antitumor effects of nanoparticles than that of traditional injection at the same dose (7.5 mg/kg). Therefore, docetaxel-loaded albumin nanoparticles fabricated by our strategy showed higher promise in their safety and effectiveness than the traditional docetaxel injection.

  1. Hormonal enhancement of insecticide efficacy in Tribolium castaneum: oxidative stress and metabolic aspects.

    Science.gov (United States)

    Plavšin, Ivana; Stašková, Tereza; Šerý, Michal; Smýkal, Vlastimil; Hackenberger, Branimir K; Kodrík, Dalibor

    2015-04-01

    Insect anti-stress responses, including those induced by insecticides, are controlled by adipokinetic hormones (AKHs). We examined the physiological consequences of Pyrap-AKH application on Tribolium castaneum adults (AKH-normal and AKH-deficient prepared by the RNAi technique) treated by two insecticides, pirimiphos-methyl and deltamethrin. Co-application of pirimiphos-methyl and/or deltamethrin with AKH significantly increased beetle mortality compared with application of the insecticides alone. This co-treatment was accompanied by substantial stimulation of general metabolism, as monitored by carbon dioxide production. Further, the insecticide treatment alone affected some basic markers of oxidative stress: it lowered total antioxidative capacity as well as the activity of superoxide dismutase in the beetle body; in addition, it enhanced the activity of catalase and glutathione-S-transferase. However, these discrepancies in oxidative stress markers were eliminated/reduced by co-application with Pyrap-AKH. We suggest that the elevation of metabolism, which is probably accompanied with faster turnover of toxins, might be responsible for the higher mortality that results after AKH and insecticide co-application. Changes in oxidative stress markers are probably not included in the mechanisms responsible for increased mortality.

  2. Bifunctional Crosslinking Agents Enhance Anion Exchange Membrane Efficacy for Vanadium Redox Flow Batteries.

    Science.gov (United States)

    Wang, Wenpin; Xu, Min; Wang, Shubo; Xie, Xiaofeng; Lv, Yafei; Ramani, Vijay K

    2014-06-01

    A series of cross-linked fluorinated poly (aryl ether oxadiazole) membranes (FPAEOM) derivatized with imidazolium groups were prepared. Poly (N-vinylimidazole) (PVI) was used as the bifunctional cross-linking agent to: a) lower vanadium permeability, b) enhance dimensional stability, and c) concomitantly provide added ion exchange capacity in the resultant anion exchange membranes. At a molar ratio of PVI to FPAEOM of 1.5, the resultant membrane (FPAEOM-1.5 PVI) had an ion exchange capacity of 2.2 meq g-1, a vanadium permeability of 6.8×10-7 cm2 min-1, a water uptake of 68 wt.%, and an ionic conductivity of 22.0 mS cm-1, all at 25°C. Single cells prepared with the FPAEOM-1.5 PVI membrane exhibited a higher coulombic efficiency (> 92%) and energy efficiency (> 86%) after 40 test cycles in vanadium redox flow battery. The imidazolium cation showed high chemical stability in highly acidic and oxidizing vanadium solution as opposed to poor stability in alkaline solutions. Based on our DFT studies, this was attributed to the lower HOMO energy (-7.265 eV) of the HSO4- ion (compared to the OH- ion; -5.496 eV) and the larger HOMO-LUMO energy gap (6.394 eV) of dimethylimidazolium bisulfate ([DMIM] [HSO4]) as compared to [DMIM] [OH] (5.387 eV).

  3. Enhanced efficacy and reduced side effects of diazepam by kava combination.

    Science.gov (United States)

    Tawfiq, Rasha A; Nassar, Noha N; El-Eraky, Wafaa I; El-Denshary, Ezzeldein S

    2014-09-01

    The long term use of antiepileptic drugs possesses many unwanted effects; thus, new safe combinations are urgently mandated. Hence, the present study aimed to investigate the anticonvulsant effect of kava alone or in combination with a synthetic anticonvulsant drug, diazepam (DZ). To this end, female Wistar rats were divided into two subsets, each comprising 6 groups as follows: group (i) received 1% Tween 80 p.o. and served as control, while groups (ii) and (iii) received kava at two dose levels (100 and 200 mg/kg, p.o.). The remaining three groups received (iv) DZ alone (10 mg/kg p.o.) or kava in combination with DZ (v) (5 mg/kg, p.o.) or (vi) (10 mg/kg, p.o.). Results of the present study revealed that kava increased the maximal electroshock seizure threshold (MEST) and enhanced the anticonvulsant effect of diazepam following both acute and chronic treatment. Moreover, neither kava nor its combination with DZ impaired motor co-ordination either acutely or chronically. Furthermore, kava ameliorated both the reduction in locomotor activity as well as changes in liver function tests induced by chronic administration of DZ. Moreover, no elevation was shown in the creatinine concentration vs. control group following chronic administration of kava or DZ either alone or in combination with kava. In conclusion, the present study suggests the possibility of combining a low dose DZ with kava to reduce harmful effects and might be recommended for clinical use in patients chronically treated with this synthetic anticonvulsant drug.

  4. Enhanced stability and antibacterial efficacy of a traditional Chinese medicine-mediated silver nanoparticle delivery system.

    Science.gov (United States)

    Sun, Wenjie; Qu, Ding; Ma, Yihua; Chen, Yan; Liu, Congyan; Zhou, Jing

    2014-01-01

    Silver nanoparticles (AgNPs) are widely used as antibacterial products in various fields. Recent studies have suggested that AgNPs need an appropriate stabilizer to improve their stability. Some antibacterial traditional Chinese medicines (TCMs) contain various reductive components, which can not only stabilize AgNPs but also enhance their antimicrobial activity. In this study, we developed a series of novel AgNPs using a TCM extract as a stabilizer, reducing agent, and antimicrobial agent (TCM-AgNPs). A storage stability investigation of the TCM-AgNPs suggested a significant improvement when compared with bare AgNPs. Further, conjugation of TCMs onto the AgNP surface resulted in stronger antimicrobial potency on antibacterial evaluation using Pseudomonas aeruginosa, Staphylococcus epidermidis, and Staphylococcus aureus with minimum inhibitory concentration 50% (MIC50) ratios (and minimum bactericidal concentration 90% [MBC90] ratios) of AgNPs to respective TCM-AgNPs as assessment indices. Among these, P. cuspidatum Sieb. et-conjugated AgNPs (P.C.-AgNPs) had the advantage of a combination of TCMs and AgNPs and was studied in detail with regard to its synthesis and characterization. The extraction time, reaction temperature, and concentrations of AgNO3 and Polygonum cuspidatum Sieb. et extract were critical factors in the preparation of P.C.-AgNPs. Further, the results of X-ray diffraction and Fourier transform infrared spectroscopy indicated successful preparation of P.C.-AgNPs. In representative studies, P.C.-AgNPs showed a well-defined spherical shape, a homogeneous small particle size (36.78 nm), a narrow polydispersity index (0.105), and a highly negative zeta potential (-23.6 mV) on transmission electron microscopy and dynamic light scattering. These results indicate that TCM-AgNPs have a potential role as antibacterial agents in the clinic setting.

  5. Enhanced antifungal efficacy of tebuconazole using gated pH-driven mesoporous nanoparticles

    Directory of Open Access Journals (Sweden)

    Mas N

    2014-05-01

    Full Text Available Núria Mas,1–3 Irene Galiana,3 Silvia Hurtado,† Laura Mondragón,1–3 Andrea Bernardos,1–3 Félix Sancenón,1–3 María D Marcos,1–3 Pedro Amorós,4 Nuria Abril-Utrillas,5 Ramón Martínez-Máñez,1–3 José Ramón Murguía1,3 1Centro de Reconocimiento Molecular y Desarrollo Tecnológico (IDM, Centro Mixto Universidad Politécnica de Valencia, Universidad de Valencia, Valencia, Spain; 2Departamento de Química, Universidad Politécnica de Valencia, Valencia, Spain; 3CIBER de Bioingeniería, Biomateriales y Nanomedicina, Madrid, Spain; 4Institut de Ciència del Materials (ICMUV, Universitat de València, Valencia, Spain; 5Servicio Ginecología y Obstetricia, Hospital de la Plana, Vila-real, Spain†Silvia Hurtado passed away in September 2013 Abstract: pH-sensitive gated mesoporous silica nanoparticles have been synthesized. Increased extracellular pH and internalization into living yeast cells triggered molecular gate aperture and cargo release. Proper performance of the system was demonstrated with nanodevices loaded with fluorescein or with the antifungal agent tebuconazole. Interestingly, nanodevices loaded with tebuconazole significantly enhanced tebuconazole cytotoxicity. As alterations of acidic external pH are a key parameter in the onset of fungal vaginitis, this nanodevice could improve the treatment for vaginal mycoses.Keywords: capped mesoporous nanoparticles, intracellular release, pH-responsive nanoparticles, Saccharomyces cerevisiae, tebuconazole loading

  6. Novel monoclonal antibody against beta 1 integrin enhances cisplatin efficacy in human lung adenocarcinoma cells.

    Science.gov (United States)

    Kim, Min-Young; Cho, Woon-Dong; Hong, Kwon Pyo; Choi, Da Bin; Hong, Jeong Won; Kim, Soseul; Moon, Yoo Ri; Son, Seung-Myoung; Lee, Ok-Jun; Lee, Ho-Chang; Song, Hyung Geun

    2016-05-01

    The use of anti-beta 1 integrin monoclonal antibody in lung cancer treatment has proven beneficial. Here, we developed a novel monoclonal antibody (mAb), called P5, by immunizing mice with human peripheral blood mononuclear cells (PBMC). Its anti-tumor effect is now being tested, in a clinical phase III trial, in combinatorial treatments with various chemical drugs. To confirm that P5 indeed binds to beta 1 integrin, cell lysates were immunoprecipitated with commercial anti-beta 1 integrin mAb (TS2/16) and immunoblotted against P5 to reveal a 140 kDa molecular weight band, as expected. Immunoprecipitation with P5 followed by LC/MS protein sequence analysis further verified P5 antigen to be beta 1 integrin. Cisplatin treatment upregulated cell surface expression of beta 1 integrin in A549 cells, while causing inhibition of cell growth. When cells were co-treated with different concentrations of P5 mAb, the cisplatin-mediated inhibitory effect was enhanced in a dose-dependent manner. Our findings show that a combinatorial treatment of P5 mAb and cisplatin in A549 cells resulted in a 30% increase in apoptosis, compared to baseline, and significantly more when compared to either the cisplatin or P5 alone group. The entire peptide sequences in CDR from variable region of Ig heavy and light chain gene for P5 mAb are also disclosed. Together, these results provide evidence of the beneficial effect of P5 mAb in combinatorial treatment of human lung adenocarcinoma.

  7. Enhanced efficacy and reduced side effects of diazepam by kava combination

    Directory of Open Access Journals (Sweden)

    Rasha A. Tawfiq

    2014-09-01

    Full Text Available The long term use of antiepileptic drugs possesses many unwanted effects; thus, new safe combinations are urgently mandated. Hence, the present study aimed to investigate the anticonvulsant effect of kava alone or in combination with a synthetic anticonvulsant drug, diazepam (DZ. To this end, female Wistar rats were divided into two subsets, each comprising 6 groups as follows: group (i received 1% Tween 80 p.o. and served as control, while groups (ii and (iii received kava at two dose levels (100 and 200 mg/kg, p.o.. The remaining three groups received (iv DZ alone (10 mg/kg p.o. or kava in combination with DZ (v (5 mg/kg, p.o. or (vi (10 mg/kg, p.o.. Results of the present study revealed that kava increased the maximal electroshock seizure threshold (MEST and enhanced the anticonvulsant effect of diazepam following both acute and chronic treatment. Moreover, neither kava nor its combination with DZ impaired motor co-ordination either acutely or chronically. Furthermore, kava ameliorated both the reduction in locomotor activity as well as changes in liver function tests induced by chronic administration of DZ. Moreover, no elevation was shown in the creatinine concentration vs. control group following chronic administration of kava or DZ either alone or in combination with kava. In conclusion, the present study suggests the possibility of combining a low dose DZ with kava to reduce harmful effects and might be recommended for clinical use in patients chronically treated with this synthetic anticonvulsant drug.

  8. Enhanced stability and antibacterial efficacy of a traditional Chinese medicine-mediated silver nanoparticle delivery system

    Directory of Open Access Journals (Sweden)

    Sun WJ

    2014-11-01

    Full Text Available Wenjie Sun,1,2,* Ding Qu,1,* Yihua Ma,1 Yan Chen,1,2 Congyan Liu,1 Jing Zhou11Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, 2Department of Pharmaceutics, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China*These authors contributed equally to this workAbstract: Silver nanoparticles (AgNPs are widely used as antibacterial products in various fields. Recent studies have suggested that AgNPs need an appropriate stabilizer to improve their stability. Some antibacterial traditional Chinese medicines (TCMs contain various reductive components, which can not only stabilize AgNPs but also enhance their antimicrobial activity. In this study, we developed a series of novel AgNPs using a TCM extract as a stabilizer, reducing agent, and antimicrobial agent (TCM-AgNPs. A storage stability investigation of the TCM-AgNPs suggested a significant improvement when compared with bare AgNPs. Further, conjugation of TCMs onto the AgNP surface resulted in stronger antimicrobial potency on antibacterial evaluation using Pseudomonas aeruginosa, Staphylococcus epidermidis, and Staphylococcus aureus with minimum inhibitory concentration 50% (MIC50 ratios (and minimum bactericidal concentration 90% [MBC90] ratios of AgNPs to respective TCM-AgNPs as assessment indices. Among these, P. cuspidatum Sieb. et-conjugated AgNPs (P.C.-AgNPs had the advantage of a combination of TCMs and AgNPs and was studied in detail with regard to its synthesis and characterization. The extraction time, reaction temperature, and concentrations of AgNO3 and Polygonum cuspidatum Sieb. et extract were critical factors in the preparation of P.C.-AgNPs. Further, the results of X-ray diffraction and Fourier transform infrared spectroscopy indicated successful preparation of P.C.-AgNPs. In representative studies, P.C.-AgNPs showed a well-defined spherical shape, a homogeneous

  9. Shikonin enhances efficacy of a gene-based cancer vaccine via induction of RANTES

    Directory of Open Access Journals (Sweden)

    Chen Hui-Ming

    2012-04-01

    effectively enhance anti-tumor potency of a gene-based cancer vaccine via the induction of RANTES expression at the skin immunization site.

  10. A Galleria mellonella infection model reveals double and triple antibiotic combination therapies with enhanced efficacy versus a multidrug-resistant strain of Pseudomonas aeruginosa.

    Science.gov (United States)

    Krezdorn, Jessica; Adams, Sophie; Coote, Peter J

    2014-07-01

    The aim of this study was to compare the inhibitory effect of antibiotic combinations in vitro with efficacy in Galleria mellonella larvae in vivo to identify efficacious combinations that target Pseudomonas aeruginosa. P. aeruginosa NCTC 13437, a multidrug-resistant strain resistant to β-lactams and aminoglycosides, was used. Susceptibility to cefotaxime, piperacillin, meropenem, amikacin, levofloxacin and colistin alone, or in dual or triple combinations, was measured in vitro via a 24 h time-kill assay. In vitro results were then compared with the efficacy of the same dual or triple antibiotic combinations versus G. mellonella larvae infected with P. aeruginosa. G. mellonella haemolymph burden of P. aeruginosa was determined over 96 h post-infection and treatment with the most potent combination therapies. Many dual and triple combinations of antibiotics displayed synergistic inhibition of multidrug-resistant P. aeruginosa in vitro. There was little correlation between combinations that were synergistic in vitro and those that showed enhanced efficacy in vivo versus infected G. mellonella larvae. The most potent dual and triple combinations in vivo were cefotaxime plus piperacillin, and meropenem plus piperacillin and amikacin, respectively. Fewer combinations were found to offer enhanced therapeutic benefit in vivo compared with in vitro. The therapeutic benefit arising from treatment with antibiotic combinations in vivo correlated with reduced larval burden of P. aeruginosa. This study has identified antibiotic combinations that merit further investigation for their clinical potential and has demonstrated the utility of using G. mellonella to screen for novel antibiotic treatments that demonstrate efficacy in vivo.

  11. Sequential co-delivery of miR-21 inhibitor followed by burst release doxorubicin using NIR-responsive hollow gold nanoparticle to enhance anticancer efficacy.

    Science.gov (United States)

    Ren, Yu; Wang, Ruirui; Gao, Lizhang; Li, Ke; Zhou, Xuan; Guo, Hua; Liu, Chaoyong; Han, Donglin; Tian, Jianguo; Ye, Qing; Hu, Ye Tony; Sun, Duxin; Yuan, Xubo; Zhang, Ning

    2016-04-28

    Previous literature and our study showed the delivery sequence of microRNA inhibitor and chemotherapeutic compounds achieve distinct therapeutic anticancer efficacy. Yet, it is challenging to use nanoparticle to achieve sequential drug delivery. In the current study, we designed sequential co-delivery system using a near-infrared-radiation (NIR) responsive hollow gold nanoparticle (HGNPs) to achieve sequential release of microRNA inhibitor (miR-21i)/doxirubicin(Dox) in order to achieve synergistic efficacy. PAMAM modified HGNPs was used to encapsulate miR-21i and Dox. Upon entering tumor cells, miRNA-21i was released first to sensitize the cancer cells, the subsequent burst release of Dox was achieved by NIR triggered collapse of HGNPs. This sequential delivery of miRNA-21i and Dox produced a synergistic apoptotic response, thereby enhancing anticancer efficacy by 8-fold and increasing anti-cancer stem cell activity by 50-fold. The sequential delivery of miR-21i and Dox using HGNPs under NIR after intravenous administration showed high tumor accumulation and significantly improved efficacy, which was 4-fold compared to free Dox group. These data suggested that the sequential co-delivery of miR-21i followed by burst release Dox using NIR-responsive HGNPs sensitized cancer cells to chemotherapeutic compound, which provided a novel concept for co-delivery miRNA inhibitors and chemotherapeutic compounds to enhance their efficacy.

  12. Effects of Self-Efficacy-Enhancing Interventions on the Math/Science Self-Efficacy and Career Interests, Goals, and Actions of Career Undecided College Students.

    Science.gov (United States)

    Luzzo, Darrell Anthony; Hasper, Patricia; Albert, Katrice A.; Bibby, Maureen A.; Martinelli, Edward A., Jr.

    1999-01-01

    Study evaluates the effects of both performance accomplishment and vicarious learning experiences on the math/science self-efficacy and career interests, goals, and actions of career-undecided college students. Undergraduate participants were assigned one of four treatment conditions for the study. Theoretical and counseling implications of the…

  13. Evaluation of the diagnostic efficacy of SPIO enhanced MRI in patients with focal hepatic lesions. Comparison with CECT and CTAP

    Energy Technology Data Exchange (ETDEWEB)

    Kasugai, Hisashi; Katayama, Nobuhito; Sakai, Shigeru; Yamakawa, Tatsuo [Teikyo Univ., Kawasaki, Kanagawa (Japan). Mizonokuchi Hospital

    2002-11-01

    The aim of this study was to compare the diagnostic efficacy of superparamagnetic iron oxide (SPIO)-enhanced MRI for the detection and diagnostic accuracy of focal liver lesions with helical contrast enhanced CT (CECT) and CT during arterial portography (CTAP). Thirty-nine patients (25 men and 14 women, mean age 63.5 years) were examined by SPIO-MRI and triple-phase CECT. Eleven of them were also examined by CTAP. There were a total of 96 confirmed focal hepatic lesions, 61 metastatic cancers in 18 patients and 35 hepatocellular carcinomas (HCCs) in 21 patients. Final diagnosis was established by operation in 25 cases, by biopsy in 7 cases, and by progression of disease on follow-up examination in the other 7 cases. The sensitivity of SPIO-MRI for HCC detection was almost equal to CECT, but that of SPIO-MRI for metastatic cancer detection, especially cancers smaller than 1 cm in size, was significantly superior to CECT. The sensitivity of SPIO-MRI for both HCC and metastatic cancer detection was almost equal to that of CTAP, but the specificity of SPIO-MRI for detection of both lesions was significantly superior to that of CTAP because CTAP produced a higher incidence of false-positive findings. In conclusion, SPIO-MRI could take the place of CTAP as a non-invasive excellent modality to determine the distribution of hepatic lesions preoperatively. SPIO-MRI could also be a useful modality to follow liver metastasis postoperatively in patients with advanced digestive cancers. (author)

  14. Pre-service teachers' knowledge of phonemic awareness: relationship to perceived knowledge, self-efficacy beliefs, and exposure to a multimedia-enhanced lecture.

    Science.gov (United States)

    Martinussen, Rhonda; Ferrari, Julia; Aitken, Madison; Willows, Dale

    2015-10-01

    This study examined the relations among perceived and actual knowledge of phonemic awareness (PA), exposure to PA instruction during practicum, and self-efficacy for teaching PA in a sample of 54 teacher candidates (TCs) enrolled in a 1-year Bachelor of Education program in a Canadian university. It also assessed the effects of a brief multimedia-enhanced lecture on TCs' actual knowledge of PA and efficacy ratings. Prior to the lecture, teacher candidates' scores on the PA assessment were relatively low with a mean percentage correct of 56.3%. Actual knowledge was not significantly correlated with perceived knowledge or self-efficacy ratings. Perceived knowledge was significantly and positively correlated with efficacy ratings and students' rating of their exposure to PA instruction during their practicum experience. A path analysis revealed that the relationship between exposure to PA instruction and self-efficacy beliefs was mediated by perceived knowledge controlling for actual knowledge and general prior experience working with young children. Analyses also revealed that TCs made significant gains in self-efficacy as well as actual knowledge when re-assessed after the lecture with a mean post-lecture score of 71.4%. Written feedback from the TCs indicated that the digital video clips included in the lecture provided clarity regarding the type of instructional practices that teachers could use to support phonemic awareness development in children. Implications for practice and future research on teacher preparation are discussed.

  15. Targeted delivery of the hydroxylase inhibitor DMOG provides enhanced efficacy with reduced systemic exposure in a murine model of colitis.

    Science.gov (United States)

    Tambuwala, Murtaza M; Manresa, Mario C; Cummins, Eoin P; Aversa, Vincenzo; Coulter, Ivan S; Taylor, Cormac T

    2015-11-10

    Targeting hypoxia-sensitive pathways has recently been proposed as a new therapeutic approach to the treatment of intestinal inflammation. HIF-hydroxylases are enzymes which confer hypoxic-sensitivity upon the hypoxia-inducible factor (HIF), a major regulator of the adaptive response to hypoxia. Previous studies have shown that systemic (intraperitoneal) administration of hydroxylase inhibitors such as dimethyloxalylglycine (DMOG) is profoundly protective in multiple models of colitis, however the therapeutic potential of this approach is limited due to potential side-effects associated with systemic drug exposure and the fact that orally delivered DMOG is ineffective (likely due to drug inactivation by gastric acid). In order to overcome these issues, we formulated DMOG in a liquid emulsion drug delivery system which, when coated with specific polymer coatings, permits oral delivery of a reduced dose which is released locally throughout the colon. This colon-targeted DMOG formulation demonstrated increased relative colonic bioactivity with reduced systemic exposure and provided a similar degree of protection to systemic (intraperitoneal) administration at a 40-fold lower dose in DSS-induced colitis. In summary, targeted delivery of DMOG to the colon provides local protection resulting in enhanced efficacy with reduced systemic exposure in the treatment of colitis. This novel approach to targeting hydroxylase inhibitors to specific diseased regions of the GI tract may improve it's potential as a new therapeutic in inflammatory bowel diseases such as ulcerative colitis.

  16. Does computerized working memory training with game elements enhance motivation and training efficacy in children with ADHD?

    Science.gov (United States)

    Prins, Pier J M; Dovis, Sebastiaan; Ponsioen, Albert; ten Brink, Esther; van der Oord, Saskia

    2011-03-01

    This study examined the benefits of adding game elements to standard computerized working memory (WM) training. Specifically, it examined whether game elements would enhance motivation and training performance of children with ADHD, and whether it would improve training efficacy. A total of 51 children with ADHD aged between 7 and 12 years were randomly assigned to WM training in a gaming format or to regular WM training that was not in a gaming format. Both groups completed three weekly sessions of WM training. Children using the game version of the WM training showed greater motivation (i.e., more time training), better training performance (i.e., more sequences reproduced and fewer errors), and better WM (i.e., higher scores on a WM task) at post-training than children using the regular WM training. Results are discussed in terms of executive functions and reinforcement models of ADHD. It is concluded that WM training with game elements significantly improves the motivation, training performance, and working memory of children with ADHD. The findings of this study are encouraging and may have wide-reaching practical implications in terms of the role of game elements in the design and implementation of new intervention efforts for children with ADHD.

  17. Gracilaria lemaneiformis polysaccharide as integrin-targeting surface decorator of selenium nanoparticles to achieve enhanced anticancer efficacy.

    Science.gov (United States)

    Jiang, Wenting; Fu, Yuanting; Yang, Fang; Yang, Yufeng; Liu, Ting; Zheng, Wenjie; Zeng, Lilan; Chen, Tianfeng

    2014-08-27

    The poor permeability of glioma parenchyma represents a major limit for antiglioblastoma drug delivery. Gracilaria lemaneiformis polysaccharide (GLP), which has a high binding affinity to αvβ3 integrin overexpressed in glioma cells, was employed in the present study to functionalize selenium nanoparticles (SeNPs) to achieve antiglioblastoma efficacy. GLP-SeNPs showed satisfactory size distribution, high stability, and selectivity between cancer and normal cells. In U87 glioma cell membrane, which has a high integrin expression level, GLP-SeNPs exhibited significantly higher cellular uptake than unmodified SeNPs. As expected, U87 cells exhibited a greater uptake of GLP-SeNPs than C6 cells with low integrin expression level. Furthermore, the internalization of GLP-SeNPs was inhibited by cyclo-(Arg-Gly-Asp-Phe-Lys) peptides, suggesting that cellular uptake into U87 cells and C6 cells occurred via αvβ3 integrin-mediated endocytosis. For U87 cells, the cytotoxicity of SeNPs decorated by GLP was enhanced significantly because of the induction of various apoptosis signaling pathways. Internalized GLP-SeNPs triggered intracellular reactive oxygen species downregulation. Therefore, p53, MAPKs, and AKT pathways were activated to advance cell apoptosis. These findings suggest that surface decoration of nanomaterials with GLP could be an efficient strategy for design and preparation of glioblastoma targeting nanodrugs.

  18. Enhanced efficacy of sequential administration of Albendazole for the clearance of Wuchereria bancrofti infection: Double blind RCT.

    Science.gov (United States)

    De Britto, R L; Vanamail, P; Sankari, T; Vijayalakshmi, G; Das, L K; Pani, S P

    2015-06-01

    Till today, there is no effective treatment protocol for the complete clearance of Wuchereria bancrofti (W.b) infection that causes secondary lymphoedema. In a double blind randomized control trial (RCT), 146 asymptomatic W. b infected individuals were randomly assigned to one of the four regimens for 12 days, DEC 300 mg + Doxycycline 100 mg coadministration or DEC 300 mg + Albendazole 400 mg co-administration or DEC 300 mg + Albendazole 400 mg sequential administration or control regimen DEC 300 mg and were followed up at 13, 26 and 52 weeks post-treatment for the clearance of infection. At intake, there was no significant variation in mf counts (F(3,137)=0.044; P=0.988) and antigen levels (F(3,137)=1.433; P=0.236) between the regimens. Primary outcome analysis showed that DEC + Albendazole sequential administration has an enhanced efficacy over DEC + Albendazole co-administration (80.6 Vs 64.7%), and this regimen is significantly different when compared to DEC + doxycycline co-administration and control (PAlbendazole sequential administration appears to be a better option for rapid clearance of W. b microfilariae in 13 weeks time. (Clinical trials.gov identifier - NCT02005653).

  19. Closing escape routes: inhibition of IL-8 signaling enhances the anti-tumor efficacy of PI3K inhibitors.

    Science.gov (United States)

    Juvekar, Ashish; Wulf, Gerburg M

    2013-04-08

    The phosphoinositide 3-kinase (PI3K) pathway serves as a relay where signals that emanate from the cell membrane are received and converted into intracellular signals that promote proliferation and survival. Inhibitors of PI3K hold promise for the treatment of breast cancer because activation of this pathway is highly prevalent. However, as is increasingly observed with inhibitors of cell signaling, there appear to be mechanisms of primary and secondary resistance. Britschgi and colleagues report that compensatory activation of the IL-8 signaling axis is a mechanism of primary resistance to PI3K inhibitors in some triple-negative breast cancers. In a set of experiments that carefully emulate the clinical scenario in a mouse model, they show that simultaneous inhibition of Janus kinase 2 enhances the efficacy of PI3K/mammalian target of rapamycin inhibition. Their paper lends further support to the concept that successful design of treatments with signal transduction inhibitors must anticipate potential escape routes - and include agents to simultaneously block them.

  20. Safety and Efficacy of Gadoxetate Disodium–Enhanced Liver MRI in Pediatric Patients Aged >2 Months to <18 Years—Results of a Retrospective, Multicenter Study

    Science.gov (United States)

    Geller, James; Kasahara, Mureo; Martinez, Mercedes; Soresina, Annarosa; Kashanian, Fran; Endrikat, Jan

    2016-01-01

    PURPOSE To assess the safety and efficacy of gadoxetate disodium–enhanced liver MR imaging in pediatric patients. MATERIAL AND METHODS Retrospective, multicenter study including pediatric patients aged >2 months to <18 years who underwent contrast-enhanced liver MRI due to focal liver lesions. A single intravenous bolus injection of 0.025 to 0.05 mmol/kg body weight of gadoxetate disodium was administered. Adverse events (AEs) up to 24 hours after injection were recorded and a one-year follow-up was conducted for all serious and unexpected AEs. Efficacy was defined based on the additional diagnostic information obtained from the combined (pre- and postcontrast) image sets as compared with the precontrast image sets by blinded reading. RESULTS A total of 52 patients for safety and 51 patients for efficacy analyses were evaluated. Twenty-two patients (42.3%) reported a total of 51 serious AEs (SAEs) and one AE after one year. No SAE or AE was related to gadoxetate disodium injection. Gadoxetate disodium–related effects on vital signs were not seen. Additional diagnostic information was obtained for 86.3% of patients. The three most improved efficacy variables were lesion-to-background contrast, lesion characterization, and improved border delineation in 78.4%, 76.5%, and 70.6% of patients, respectively. CONCLUSION Gadoxetate disodium in pediatric patients did not raise any clinically significant safety concern. Contrast enhancement provided additional clinically relevant information. PMID:27478381

  1. Enhanced efficacy and immunogenicity of 78kDa antigen formulated in various adjuvants against murine visceral leishmaniasis.

    Science.gov (United States)

    Nagill, Rajeev; Kaur, Sukhbir

    2010-05-21

    Leishmania infection causes localized cutaneous to severe visceral disease in humans and animals. Current control measures, based on antimonial compounds, are not effective because of resistance in Leishmania. Vaccination would be a feasible alternative, but as yet no vaccine to protect humans against infection has been commercialized. Parasite antigens that preferentially stimulate the induction of significant protection through Th1 response presents a rational approach for a vaccine against leishmaniasis. With this view in mind, we investigated the potential of 78kDa antigen of Leishmania donovani alone and along with different adjuvants against murine visceral leishmaniasis. Various adjuvants used along with 78kDa antigen include monophosphoryl lipid A (MPL-A), liposomal encapsulation, recombinant IL-12, autoclaved Leishmania antigen (ALD) and Freund's adjuvant (FCA). BALB/c mice were immunized subcutaneously thrice with respective vaccine formulation. Challenge infection was given intracardially after 2 weeks of second booster. A significant decrease in parasite burden was seen in vaccinees over the infected controls on all post challenge days and was found that maximum protection was provided by 78kDa+rIL-12 vaccine and it was highly immunogenic as depicted by the reduction in parasite load (71-94.8%), reduction in infection rate of peritoneal macrophages (92.9-98%), enhanced DTH response (6.5-10.5 fold), increase in IgG2a anti-leishmanial antibody production (3-3.7 fold) and up-regulation of IFN-gamma (3.7-6.5 fold) and IL-2 levels (7.7-12.3 fold), which demonstrate the generation of protective Th1 type of immune response. Comparable results were also observed in 78kDa+MPL-A and liposome-encapsulated 78kDa vaccines with 56.5-92% and 62.9-93.4% reduction in parasite load respectively. Significant results have also been obtained with 78kDa antigen+ALD, 78kDa antigen+FCA and 78kDa antigen alone group but the protective efficacy was reduced as compared to the

  2. Enhancing Writing Self-Efficacy Beliefs of Students with Learning Disabilities Improves Their Writing Processes and Products

    Science.gov (United States)

    de Caso, Ana Maria; Garcia, Jesus Nicasio; Diez, Carmen; Robledo, Patricia; Alvarez, Maria Lourdes

    2010-01-01

    Introduction: The use of self efficacy has been suggested as an effective classroom intervention procedure. The present research examined the use of self-efficacy training on the writing of Spanish elementary student with learning disabilities. Objectives: We present a research study focused on the improvement of the writing product and the…

  3. Strontium-doped calcium polyphosphate/ultrahigh molecular weight polyethylene composites: A new class of artificial joint components with enhanced biological efficacy to aseptic loosening

    Energy Technology Data Exchange (ETDEWEB)

    Gu, Zhipeng [College of Polymer Science and Engineering, Sichuan University, Chengdu 610065 (China); Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu 610041 (China); Huang, Bingxue; Li, Yiwen [College of Polymer Science and Engineering, Sichuan University, Chengdu 610065 (China); Tian, Meng [Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu 610041 (China); Li, Li [Department of Oncology, the 452 Hospital of Chinese PLA, Chengdu 610021 (China); Yu, Xixun, E-mail: yuxixun@163.com [College of Polymer Science and Engineering, Sichuan University, Chengdu 610065 (China)

    2016-04-01

    To enhance implant stability and prolong the service life of artificial joint component, a new approach was proposed to improve the wear resistance of artificial joint component and endow artificial joint component with the biological efficacy of resistance to aseptic loosening. Strontium calcium polyphosphate (SCPP) were interfused in ultrahigh molecular weight polyethylene (UHMWPE) by a combination of liquid nitrogen ball-milling and flat-panel curing process to prepare the SCPP/UHMWPE composites. The micro-structure, mechanical characterization, tribological characterization and bioactivities of various SCPP/UHMWPE composites were investigated. The results suggested that this method could statistically improve the wear resistance of UHMWPE resulting from a good SCPP particle dispersion. Moreover, it is also observed that the SCPP/UHMWPE composites-wear particles could promote the production of OPG by osteoblasts and decrease the production of RANKL by osteoblasts, and then increase the OPG/RANKL ratio. This indicated that the SCPP/UHMWPE composites had potential efficacy to prevent and treat aseptic loosening. Above all, the SCPP/UHMWPE composites with a suitable SCPP content would be the promising materials for fabricating artificial joint component with ability to resist aseptic loosening. - Highlights: • SCPP/UHMWPE composites could enhance biological efficacy of resistance to aseptic loosening. • SCPP would improve biological efficacy with a few sacrifice of wear resistance. • The results might provide a promising wear-resistant material for fabricating acetabular cup.

  4. Delivery of acetylthevetin B, an antitumor cardiac glycoside, using polymeric micelles for enhanced therapeutic efficacy against lung cancer cells

    Science.gov (United States)

    Zhu, Jing-jing; Zhang, Xin-xin; Miao, Yun-qiu; He, Shu-fang; Tian, Dan-mei; Yao, Xin-sheng; Tang, Jin-shan; Gan, Yong

    2017-01-01

    Acetylthevetin B (ATB), a cardiac glycoside from the seed of Thevetia peruviana (Pers) K Schum (yellow oleander), exhibits not only antitumor activity but also potential cardiac toxicity. In the present study, we attempted to enhance its antitumor action and decrease its adverse effects via chitosan-Pluronic P123 (CP) micelle encapsulation. Two ATB-loaded CP micelles (ATB-CP1, ATB-CP2) were prepared using an emulsion/solvent evaporation technique. They were spherical in shape with a particle size of 40–50 nm, showed a neutral zeta potential, and had acceptable encapsulation efficiency (>90%). Compared to the free ATB (IC50=2.94 μmol/L), ATB-loaded CP micelles exerted much stronger cytotoxicity against human lung cancer A549 cells with lower IC50 values (0.76 and 1.44 μmol/L for ATB-CP1 and ATB-CP2, respectively). After administration of a single dose in mice, the accumulation of ATB-loaded CP1 micelles in the tumor and lungs, respectively, was 15.31-fold and 9.49-fold as high as that of free ATB. A549 xenograft tumor mice treated with ATB-loaded CP1 micelles for 21 d showed the smallest tumor volume (one-fourth of that in the control group) and the highest inhibition rate (85.6%) among all the treatment groups. After 21-d treatment, no significant pathological changes were observed in hearts and other main tissues. In summary, ATB may serve as a promising antitumor chemotherapeutic agent for lung cancer, and its antitumor efficacy was significantly improved by CP micelles, with lower adverse effects. PMID:27917871

  5. Polyethylene glycol-modified gelatin/polylactic acid nanoparticles for enhanced photodynamic efficacy of a hypocrellin derivative in vitro.

    Science.gov (United States)

    Babu, Anish; Periasamy, Jayaprakash; Gunasekaran, Amsaveni; Kumaresan, Ganesan; Naicker, Selvaraj; Gunasekaran, Paramasamy; Murugesan, Ramachandran

    2013-02-01

    The present study focused on the development of a novel biodegradable nanoparticle system based on polyethyleneglycol-modified gelatin (PEG-GEL) and polylactic acid (PLA) biopolymers for improving the photodynamic efficacy of cyclohexane-1,2-diamino hypocrellin B (CHA2HB), a potent photodynamic therapeutic (PDT) agent. The CHA2HB-loaded PEG-GEL/PLA nanoparticles showed near-spherical morphology with an average size of 190 nm at a PLA to PEG-GEL ratio of 1:3. The drug loading was sufficient enough to produce potentially toxic reactive oxygen species (ROS) needed for photodynamic therapy (PDT). Slow and controlled drug release was observed in normal conditions, whereas enzyme assistance resulted in a relatively fast release due to partial disintegration of CHA2HB-loaded PEG-GEL/PLA nanoparticles. In vitro experiments indicated that CHA2HB-loaded PEG-GEL-PLA nanoparticles are efficiently taken up by cancer cells such as human breast adenocarcinoma (MCF-7), human gastric sarcoma (AGS) and mice specific Dalton's lymphoma (DLA) in a time dependent manner. Further, CHA2HB-loaded PEG-GEL/PLA nanoparticles evoked superior phototoxicity compared to free-CHA2HB towards all the three cell lines investigated. Interestingly, PDT effectiveness was different for the different cell type studied. CHA2HB-loaded PEG-GEL/PLA nanoparticles induced both apoptotic and necrotic cell death as a result of photoirradiation. Thus, our data suggest that PEG-GEL/PLA nanoparticles are highly effective in delivery and phototoxic enhancement of CHA2HB against model cancer cells in vitro.

  6. 1,25-Dihydroxyvitamin D3 pretreatment enhances the efficacy of allergen immunotherapy in a mouse allergic asthma model

    Institute of Scientific and Technical Information of China (English)

    MA Jian-xin; XIA Jun-bo; CHENG Xiao-ming; WANG Chang-zheng

    2010-01-01

    Background Allergen-specific immunotherapy can induce immune tolerance to specific allergens by regulating immune status of individuals. However, its clinical application is limited due to individual differences in efficacy among patients and un-confirmed safety. 1,25 Dihydroxyvitamin D3 (1,25(OH)2D3) has been shown to be involved in a variety of physiological processes, including immune response regulation. In the present study we explored the role of 1,25(OH)2D3 pretreatment for immunotherapy.Methods Seventy-five BALB/c mice were randomly divided into five groups (15 mice per group). The mouse allergic asthma model was established by intra-peritoneal injection of ovalbumin (OVA, 10 μg) and aluminium hydroxide (2 mg)as an adjuvant. Intra-peritoneal injection of 50 ng of 1,25(OH)2D3 served as a pretreatment, subcutaneous injection of OVA (100 μg) as an immunotherapy, and 1% OVA inhalation as a challenge. Histopathological analysis was performed on four mice per group. The number of cells and their classification in bronchoalvolar lavage (BAL) fluid were assayed.Levels of serum OVA-specific immunoglobulin E (slgE) and IFN-Y, IL-4, IL-5 and IL-10 in BAL fluid were measured by ELISA.Results After 1,25(OH)2D3 pretreatment, immunotherapy could significantly inhibit the infiltration of inflammatory cells into lung tissues and BAL fluid of mice with allergic asthma when compared with un-treated animals (eosinophils:(7.46±1.34)×104/ml vs. (13.41±1.67)×104/ml, P <0.05). In addition, levels of IL-4 ((36.g1±7.87) pg/ml vs. (43.70±6.42)pg/ml, P >0.05) and IL-5 ((41.97±7.93) pg/ml vs. (60.14±8.35) pg/ml, P <0.05) in BAL fluid and serum slgE ((0.42±0.05)vs. (0.75±0.06) OD units, P <0.05) were profoundly reduced. However, the IL-10 level in BAL fluid was significantly increased ((67.74±6.57) pg/ml vs. (44.62±8.81) pg/ml, P <0.05).Conclusions These results indicated that 1,25(OH)2D3 pretreatment enhanced the inhibitory effects of immunotherapy on allergic

  7. A multi-center, comparative, phase 3 study to determine the efficacy of gadofosveset-enhanced magnetic resonance angiography for evaluation of renal artery disease

    Energy Technology Data Exchange (ETDEWEB)

    McGregor, Robert [St. Boniface General Hospital, Winnipeg, Manitoba (Canada); Vymazal, Josef [Hospital Na Homolce, Prague (Czech Republic); Martinez-Lopez, Manuel [Hospital Medica Sur, Mexico City (Mexico); Neuwirth, Jiri [Faculty Hospital Motol, Prague (Czech Republic); Salgado, Perla [American British Cowdray Medical Center, Mexico City (Mexico); Beregi, Jean-Paul [Hopital Cardiologique, Lille (France); Peduto, Anthony [Westmead Hospital, Westmead New South Wales (Australia); Pena-Almaguer, Erasmo de la [Christus-Muguerza Medical Center, Monterrey, Nuevo Leon (Mexico); Slater, Greg J. [Greenslopes Private Hospital, Greenslopes, Queensland (Australia); Shamsi, Kohkan [Berlex Laboratories, Montville, NJ (United States); Parsons, Edward C. [EPIX Pharmaceuticals, Inc., Lexington, MA (United States)], E-mail: eparsons@epixpharma.com

    2008-02-15

    Purpose: To determine prospectively the safety and efficacy of the blood-pool contrast agent gadofosveset trisodium in renal artery magnetic resonance angiography (MRA). Materials and methods: Gadofosveset (0.03 mmol/kg) was administered to adult patients with known or suspected renal arterial disease in a multi-center phase 3 single dose study. The drug binds reversibly to albumin, prolonging the blood residence time, and allowing collection of images in the first-pass and steady-state phases. The combination of these images was compared to non-contrast MRA, using catheter X-ray angiography (XRA) as the standard of reference (SOR). All MRA images were collected at 1.5 T in one imaging session for direct comparison, and XRA within 30 days. Sensitivity, specificity, and accuracy for diagnosing significant disease (stenosis {>=}50%) were calculated for MRA using three independent blinded readers. Patient safety was monitored for 72-96 h. Results: A total of 145 patients at 18 centers were enrolled and received gadofosveset; the 127 with complete efficacy data entered the primary efficacy analysis. Gadofosveset-enhanced MRA led to significant improvement (p < 0.01) in sensitivity (+25%, +26%, +42%), specificity (+23%, +25%, +29%), and accuracy (+23%, +28%, +29%) over non-enhanced MRA for the three readers. The rate of uninterpretable examinations decreased from 30% to less than 2%. There were no serious adverse events, and the most common adverse events were nausea, pruritis, and headache (8% each). No significant trends in clinical chemistry parameters, nor significant changes in serum creatinine, were found following administration of gadofosveset. Conclusion: In patients with known or suspected renal arterial disease, multi-phase gadofosveset-enhanced MRA significantly improves sensitivity, specificity, and accuracy versus non-enhanced MRA. Gadofosveset was safe and well tolerated in this patient population.

  8. When does transformational leadership enhance employee proactive behavior? The role of autonomy and role breadth self-efficacy.

    Science.gov (United States)

    Den Hartog, Deanne N; Belschak, Frank D

    2012-01-01

    Two multisource studies address the interactive effects of personal and contextual variables on employees' proactive behavior. In line with previous work, we find positive main effects of transformational leadership, role breadth self-efficacy, and job autonomy on employee proactive behavior (personal initiative in Study 1 and prosocial proactive behavior in Study 2). As expected, a 3-way interaction qualifies these main effects: In situations of high autonomy, transformational leadership relates positively to proactive behavior for individuals high (but not low) on self-efficacy. Vice versa, in situations low on job autonomy, transformational leadership relates positively to proactive behavior for individuals low (but not high) on self-efficacy. This pattern is found both for self-ratings and peer-ratings of employees' proactive behavior in Study 1 and for supervisor ratings of such behavior in Study 2.

  9. A proactive classroom management model to enhance self-efficacy levels in teachers of adolescents who display disruptive behaviors.

    Science.gov (United States)

    Pace, Rolanda T; Boykins, Anita D; Davis, Sheila P

    2014-02-01

    The aims of this project were to determine teachers' self-efficacy levels at baseline and after participating in a proactive classroom management model intervention. Teachers (N = 26) were recruited from a rural middle school in a south central state. Data required for analysis were drawn from the Teachers' Sense of Efficacy Scale (long form). A statistically significant difference (t[25] = 7.68, p classroom management training for teachers as well as the need for psychiatric and mental health nurse consultants within the school system. Teacher classroom management strategies should also include appropriate response to individual student's needs, effective communication, and insight regarding the behaviors of students from diverse backgrounds.

  10. Extinction learning as a moderator of d-cycloserine efficacy for enhancing exposure therapy in posttraumatic stress disorder

    NARCIS (Netherlands)

    Kleine, R.A. de; Smits, J.A.; Hendriks, G.J.; Becker, E.S.; Minnen, A. van

    2015-01-01

    Augmentation of exposure therapy with d-cycloserine (DCS) has proven efficacious across anxiety disorders, although results in PTSD have been mixed. Work in animals and anxiety-disordered patients suggest that the potentiating effects of DCS are dependent on the level of extinction learning during e

  11. When does transformational leadership enhance employee proactive behavior? The role of autonomy and role breadth self-efficacy

    NARCIS (Netherlands)

    den Hartog, D.N.; Belschak, F.D.

    2012-01-01

    Two multisource studies address the interactive effects of personal and contextual variables on employees' proactive behavior. In line with previous work, we find positive main effects of transformational leadership, role breadth self-efficacy, and job autonomy on employee proactive behavior (person

  12. Assessing and Enhancing Pre-Service Science Teachers' Self-Efficacy to Teach Science through Argumentation: Challenges and Possible Solutions

    Science.gov (United States)

    Aydeniz, Mehmet; Ozdilek, Zehra

    2016-01-01

    The purpose of this study was to explore the impact of an intervention on pre-service science teachers' self-efficacy to teach science through argumentation and explore the challenges they experienced while implementing argumentation. Forty pre-service science teachers in their final semester of schooling participated in an intervention that…

  13. An Examination of the Efficacy of Insights in Enhancing the Academic and Behavioral Development of Children in Early Grades

    Science.gov (United States)

    O'Connor, Erin E.; Cappella, Elise; McCormick, Meghan P.; McClowry, Sandee G.

    2014-01-01

    The primary aim of this group randomized trial was to test the efficacy of INSIGHTS Into Children's Temperament (INSIGHTS) in increasing the academic achievement and sustained attention and reducing the disruptive behavior problems of low-income kindergarten and 1st grade children. Twenty-two urban elementary schools serving low-income families…

  14. Enhancing understanding, flow and self-efficacy in learners with developmental and attention difficulties through interventions with differentiated technology

    DEFF Research Database (Denmark)

    Voldborg, Hanne; Sorensen, Elsebeth Korsgaard

    2016-01-01

    The purpose of this paper is to investigate in which way technologies may be used to increase inclusion and a feeling of flow and self-efficacy in learning processes when it comes to learners with developmental and attention deficits (focus learners) in a mainstream classroom. The paper is an out...

  15. Diagnostic efficacy of gadoxetic acid (Primovist)-enhanced MRI and spiral CT for a therapeutic strategy: comparison with intraoperative and histopathologic findings in focal liver lesions

    Energy Technology Data Exchange (ETDEWEB)

    Hammerstingl, Renate; Vogl, Thomas J. [Johann Wolfgang Goethe-Univ., Inst. of Diagnostic and Interventional Radiology, Frankfurt am Main (Germany); Huppertz, Alexander [Imaging Science Inst., Charite - Siemens, Berlin (Germany); Breuer, Josy; Balzer, Thomas [Gobal Clinical Development Diagnostics, Bayer Schering Pharma AG, Berlin (Germany); Blakeborough, Anthony [Royal Hallamshire Hospital, Dept. of Radiology, Sheffield (United Kingdom); Carter, Rick [Bayer Health Care Ltd., Burgess Hill, West Sussex (United Kingdom); Castells Fuste, Lluis [Hospital Vall d' Hebron, Liver Unit, Dept. of Internal Medicine, Barcelona (Spain); Heinz-Peer, Gertraud [Universitaetsklinik fuer Radiodiagnostik, Allg. Krankenhaus der Stadt Wien, Wien (Germany); Judmaier, Werner [Univ. Hospital Innsbruck, Dept. of Magnetic Resonance Imaging and Spectroscopy, Innsbruck (Austria); Laniado, Michael [Universitaetsklinikum Carl Gustav Carus, Technische Univ. Dresden, Inst. for Diagnostic Radiology, Dresden (Germany); Manfredi, Riccardo M. [Univ. of Verona, Dept. of Radiology, Verona (Italy); Mathieu, Didier G. [Centre d' Imagerie, Aix en Provence (France); Mueller, Dieter [Georg-August Univ., Dept. of Radiology, Goettingen (Germany); Mortele, Koenraad [Brigham and Women' s Hospital, Dept. of Radiology (L1), Boston, MA (United States); Reimer, Peter [Klinikum Karlsruhe, Dept. of Radiology, Karlsruhe (Germany); Reiser, Maximilian F. [Ludwig-Maximilians-Univ. Munich - Klinikum Grosshadern, Inst. of Clinical Radiology, Munich (Germany); Robinson, Philip J. [St James' s Univ. Hospital, Dept. of Clinical Radiology, Leeds (United Kingdom); Shamsi, Kohkan [Berlex Labs. Inc., Montville, NJ (United States); Strotzer, Michael [Univ. Hospital, Dept. of Diagnostic Radiology, Regensburg (Germany); Taupitz, Matthias [Universitaetsklinikum Charite, Med. Fakultaet der Humboldt-Univ., Dept. of Radiology, Berlin (Germany); Tombach, Bernd; Valeri, Gianluca; Beers, Bernhard E. van [and others

    2008-03-15

    A multicenter study has been employed to evaluate the diagnostic efficacy of magnetic resonance imaging (MRI) using the new liver-specific contrast agent gadoxetic acid (Gd-EOB-DTPA, Primovist), as opposed to contrast-enhanced biphasic spiral computed tomography (CT), in the diagnosis of focal liver lesions, compared with a standard of reference (SOR). One hundred and sixty-nine patients with hepatic lesions eligible for surgery underwent Gd-EOB-DTPA-enhanced MRI as well as CT within 6 weeks. Pathologic evaluation of the liver specimen combined with intraoperative ultrasound established the SOR. Data sets were evaluated on-site (14 investigators) and off-site (three independent blinded readers). Gd-EOB-DTPA was well tolerated. Three hundred and two lesions were detected in 131 patients valid for analysis by SOR. The frequency of correctly detected lesions was significantly higher on Gd-EOB-DTPA-enhanced MRI compared with CT in the clinical evaluation [10.44%; 95% confidence interval (CI): 4.88, 16.0]. In the blinded reading there was a trend towards Gd-EOB-DTPA-enhanced MRI, not reaching statistical significance (2.14%; 95% CI: -4.32, 8.6). However, the highest rate of correctly detected lesions with a diameter below 1 cm was achieved by Gd-EOB-DTPA-enhanced MRI. Differential diagnosis was superior for Gd-EOB-DTPA-enhanced MRI (82.1%) versus CT (71.0%). A change in surgical therapy was documented in 19 of 131 patients (14.5%) post Gd-EOB-DTPA-enhanced MRI. Gd-EOB-DTPA-enhanced MRI was superior in the diagnosis and therapeutic management of focal liver lesions compared with CT. (orig.)

  16. Electromagnetic Modelling of Raman Enhancement from Nanoscale Structures as a Means to Predict the Efficacy of SERS Substrates

    Directory of Open Access Journals (Sweden)

    Richard J. C. Brown

    2007-01-01

    Full Text Available The requirement to optimise the balance between signal enhancement and reproducibility in surface enhanced Raman spectroscopy (SERS is stimulating the development of novel substrates for enhancing Raman signals. This paper describes the application of finite element electromagnetic modelling to predict the Raman enhancement produced from a variety of SERS substrates with differently sized, spaced and shaped morphologies with nanometre dimensions. For the first time, a theoretical comparison between four major generic types of SERS substrate (including metal nanoparticles, structured surfaces, and sharp tips has been performed and the results are presented and discussed. The results of the modelling are consistent with published experimental data from similar substrates.

  17. Enhanced in vivo antitumor efficacy of dual-functional peptide-modified docetaxel nanoparticles through tumor targeting and Hsp90 inhibition.

    Science.gov (United States)

    Jiang, Yao; Yang, Nan; Zhang, Huifeng; Sun, Bo; Hou, Chunying; Ji, Chao; Zheng, Ji; Liu, Yanyong; Zuo, Pingping

    2016-01-10

    Although conventional anticancer drugs exhibit excellent efficacy, serious adverse effects and/or even toxicity have occurred due to their nonselectivity. Moreover, active targeting approaches have not consistently led to successful outcomes. Ligands that simultaneously possess targeting capability and exert a strong influence on intracellular signaling cascades may be expected to improve the therapeutic efficacy of active targeting nanoparticulate carriers. In this study, we screened a targeting peptide, LPLTPLP, which specifically bound to non-small cell lung cancer (NSCLC) specimens in vitro. Surprisingly, this peptide inhibited the expression of Hsp90 and induced apoptosis by preventing autophagy in A549 cells treated with docetaxel. The results suggested that this peptide might be used as a promising dual-functional ligand for cancer treatment. Based on these findings, we designed and developed a novel active targeting delivery system by modifying docetaxel nanoparticles (DNP) with the dual-functional ligand LPLTPLP. We consistently demonstrated that the cellular uptake of nanoparticles (NPs) was significantly enhanced in vitro. Furthermore, the targeting NPs exhibited significantly improved antitumor efficacy and biodistribution compared with nontargeting nanodrug and free docetaxel. These findings demonstrate the feasibility of dual-functional NPs for efficient anticancer therapy.

  18. Association with amino acids does not enhance efficacy of polymerized liposomes as a system for lung gene delivery

    OpenAIRE

    Elga eBernardo Bandeira De Melo; Miquéias eLopes-Pacheco; Nadia eChiaramoni; Débora eFerreira; Maria Julieta eFernandez-Ruocco; Maria Jimena ePrieto; Tatiana eMaron-Gutierrez; Perrotta, Ramiro M.; Hugo C Castro-Faria-Neto; Patricia Rieken Macedo Rocco; Silvia del Valle Alonso; Marcelo Marcos Morales

    2016-01-01

    Development of improved drug and gene delivery systems directly into the lungs is highly desirable given the important burden of respiratory diseases. We aimed to evaluate the safety and efficacy of liposomes composed of photopolymerized lipids (1,2-bis-(tricosa-10,12-diynoyl)-sn-glycero-3-phosphocholine) associated with amino acids as vectors for gene delivery into the lungs of healthy animals. Lipopolymer vesicles, in particular, are more stable than other types of liposomes. In this study,...

  19. Enhanced Efficacy of a Facial Hydrating Serum in Subjects with Normal or Self-Perceived Dry Skin

    OpenAIRE

    2011-01-01

    Objective: To evaluate the efficacy and tolerance of a facial hydrating serum when added to a moisturizer regimen compared to a moisturizer regimen alone. Design: Evaluator-blinded, single-center, clinical study with investigator assessments at Baseline and Week 2. Treatment: After washing with a facial cleanser in the morning and evening, subjects either applied the hydrating serum to their face followed by application of the moisturizer or applied only a moisturizer. Participants: Thirty-tw...

  20. Using Robotics and Game Design to Enhance Children's Self-Efficacy, STEM Attitudes, and Computational Thinking Skills

    Science.gov (United States)

    Leonard, Jacqueline; Buss, Alan; Gamboa, Ruben; Mitchell, Monica; Fashola, Olatokunbo S.; Hubert, Tarcia; Almughyirah, Sultan

    2016-12-01

    This paper describes the findings of a pilot study that used robotics and game design to develop middle school students' computational thinking strategies. One hundred and twenty-four students engaged in LEGO® EV3 robotics and created games using Scalable Game Design software. The results of the study revealed students' pre-post self-efficacy scores on the construct of computer use declined significantly, while the constructs of videogaming and computer gaming remained unchanged. When these constructs were analyzed by type of learning environment, self-efficacy on videogaming increased significantly in the combined robotics/gaming environment compared with the gaming-only context. Student attitudes toward STEM, however, did not change significantly as a result of the study. Finally, children's computational thinking (CT) strategies varied by method of instruction as students who participated in holistic game development (i.e., Project First) had higher CT ratings. This study contributes to the STEM education literature on the use of robotics and game design to influence self-efficacy in technology and CT, while informing the research team about the adaptations needed to ensure project fidelity during the remaining years of the study.

  1. Using Robotics and Game Design to Enhance Children's Self-Efficacy, STEM Attitudes, and Computational Thinking Skills

    Science.gov (United States)

    Leonard, Jacqueline; Buss, Alan; Gamboa, Ruben; Mitchell, Monica; Fashola, Olatokunbo S.; Hubert, Tarcia; Almughyirah, Sultan

    2016-06-01

    This paper describes the findings of a pilot study that used robotics and game design to develop middle school students' computational thinking strategies. One hundred and twenty-four students engaged in LEGO® EV3 robotics and created games using Scalable Game Design software. The results of the study revealed students' pre-post self-efficacy scores on the construct of computer use declined significantly, while the constructs of videogaming and computer gaming remained unchanged. When these constructs were analyzed by type of learning environment, self-efficacy on videogaming increased significantly in the combined robotics/gaming environment compared with the gaming-only context. Student attitudes toward STEM, however, did not change significantly as a result of the study. Finally, children's computational thinking (CT) strategies varied by method of instruction as students who participated in holistic game development (i.e., Project First) had higher CT ratings. This study contributes to the STEM education literature on the use of robotics and game design to influence self-efficacy in technology and CT, while informing the research team about the adaptations needed to ensure project fidelity during the remaining years of the study.

  2. The role of intrinsic motivation in a group of low vision patients participating in a self-management programme to enhance self-efficacy and quality of life.

    Science.gov (United States)

    Tay, Kay Chai Peter; Drury, Vicki Blair; Mackey, Sandra

    2014-02-01

    Self-management programmes have previously been found to decrease health problems, enhance quality of life and increase independence. However, there is no literature that examines the influence of the participants' intrinsic motivation on the outcomes of such programmes. This study examined the role of intrinsic motivation in a pilot low vision self-management programme to enhance self-efficacy and quality of life of the programme participants. A positive association was observed between the female participants' perceived choice and perceived competence, two underlying dimensions of the Intrinsic Motivation Inventory. In addition, a positive correlation was observed between the younger participants' perceived competence and the change in their quality of life. The findings provide some support for consideration of participants' intrinsic motivation in the development of effective self-management programmes.

  3. A Randomized Trial of Comparing the Efficacy of Two Neurofeedback Protocols for Treatment of Clinical and Cognitive Symptoms of ADHD: Theta Suppression/Beta Enhancement and Theta Suppression/Alpha Enhancement

    Directory of Open Access Journals (Sweden)

    Arash Mohagheghi

    2017-01-01

    Full Text Available Introduction. Neurofeedback (NF is an adjuvant or alternative therapy for children with Attention Deficit Hyperactivity Disorder (ADHD. This study intended to compare the efficacy of two different NF protocols on clinical and cognitive symptoms of ADHD. Materials and Methods. In this clinical trial, sixty children with ADHD aged 7 to 10 years old were randomly grouped to receive two different NF treatments (theta suppression/beta enhancement protocol and theta suppression/alpha enhancement protocol. Clinical and cognitive assessments were conducted prior to and following the treatment and also after an eight-week follow-up. Results. Both protocols alleviated the symptoms of ADHD in general (p<0.001, hyperactivity (p<0.001, inattention (p<0.001, and omission errors (p<0.001; however, they did not affect the oppositional and impulsive scales nor commission errors. These effects were maintained after an eight-week intervention-free period. The only significant difference between the two NF protocols was that high-frequency alpha enhancement protocol performed better in suppressing omission errors (p<0.001. Conclusion. The two NF protocols with theta suppression/beta enhancement and theta suppression/alpha enhancement have considerable and comparable effect on clinical symptoms of ADHD. Alpha enhancement protocol was more effective in suppressing omission errors.

  4. Armored CAR T-cells: utilizing cytokines and pro-inflammatory ligands to enhance CAR T-cell anti-tumour efficacy.

    Science.gov (United States)

    Yeku, Oladapo O; Brentjens, Renier J

    2016-04-15

    Chimaeric antigen receptor (CAR) T-cells are T-cells that have been genetically modified to express an artificial construct consisting of a synthetic T-cell receptor (TCR) targeted to a predetermined antigen expressed on a tumour. Coupling the T-cell receptor to a CD3ζ signalling domain paved the way for first generation CAR T-cells that were efficacious against cluster of differentiation (CD)19-expressing B-cell malignancies. Optimization with additional signalling domains such as CD28 or 4-1BB in addition to CD3ζ provided T-cell activation signal 2 and further improved the efficacy and persistence of these second generation CAR T-cells. Third generation CAR T-cells which utilize two tandem costimulatory domains have also been reported. In this review, we discuss a different approach to optimization of CAR T-cells. Through additional genetic modifications, these resultant armored CAR T-cells are typically modified second generation CAR T-cells that have been further optimized to inducibly or constitutively secrete active cytokines or express ligands that further armor CAR T-cells to improve efficacy and persistence. The choice of the 'armor' agent is based on knowledge of the tumour microenvironment and the roles of other elements of the innate and adaptive immune system. Although there are several variants of armored CAR T-cells under investigation, here we focus on three unique approaches using interleukin-12 (IL-12), CD40L and 4-1BBL. These agents have been shown to further enhance CAR T-cell efficacy and persistence in the face of a hostile tumour microenvironment via different mechanisms.

  5. Effect of Self-Efficacy Enhancing Education Program on Family Caregivers’ Competencies in Caring for Patients with mild Traumatic Brain Injury in Yogyakarta, Indonesia

    Directory of Open Access Journals (Sweden)

    Erfin Firmawati

    2015-03-01

    Full Text Available Purpose: This study was conducted to examine the effect of a self-efficacy enhancing education program on family caregivers’ competencies regarding perceived confidence and performance in caring for patients with mild TBI in Yogyakarta, Indonesia. Methods: The quasi-experimental study, two groups pre-test and post-test design was conducted. Fifty family caregivers and patients with mild TBI who met the inclusion criteria were recruited. The first 25 control group received the routine care were, while another 25 subjects in the experimental group received a self-efficacy enhancing education program developed by the researchers. The program was constructed using Bandura’s four sources of self-efficacy. The family caregivers’ perceived confidence and performance were measured by using the Perceived Confidence Questionnaire (PCQ and the Performance Questionnaire (PQ. The data were analyzed using paired t-test, independent t-test, Wilcoxon Signed Rank test, and Mann-Whitney U test. Results: The findings showed that the family caregivers who participated in the program had a higher in perceived confidence (t = 8.30, p < .05 and performance (U = .00, p < .05 in caring for patients with mild TBI upon the completion of the program. Conclusion: This study suggests the program may have contributed in improving the family caregivers’ competencies regarding perceived confidence and also influencing their performance in caring for patients with mild TBI. Therefore, this program is recommended for nurses to extend this knowledge for nursing practices and improve family caregivers’ competencies in caring for patients with mild TBI before and after discharge.

  6. Bcl-2—Enhanced Efficacy of Microtubule-Targeting Chemotherapy through Bim Overexpression: Implications for Cancer Treatment

    Directory of Open Access Journals (Sweden)

    Amandine Savry

    2013-01-01

    Full Text Available Bcl-2 is commonly overexpressed in tumors, where it is often associated with unfavorable outcome. However, it has also been linked to a favorable sensitivity to microtubule-targeting agents (MTAs. We show that Bcl-2– overexpressing lung and breast cancer cells were more sensitive to both paclitaxel and vinorelbine. Bcl-2 overexpression also significantly potentiated in vivo efficacy of paclitaxel, in terms of tumor volume decrease and survival benefits, in models of nude mice bearing lung cancer xenografts. To further investigate this favorable effect of Bcl-2, a genomic approach was taken. It revealed that Bcl-2 overexpression induced up-regulation of the proapoptotic protein Bim in lung cancer cells and that, conversely, Bcl-2 silencing decreased Bim expression level. A gene regulation study implicated the transcription factor Forkhead box-containing protein, class O3a in Bim up-regulation. Lastly, we show that Bim was responsible for MTA-triggered lung cancer cell death through a dynamin-related protein 1–mediated mitochondrial fragmentation. The Bcl-2–governed Bim induction evidence offers for the first time an explanation for the favorable higher sensitivity to treatment shown by Bcl-2–overexpressing cells. We suggest that Bim could be a powerful predictive factor for tumor response to MTA chemotherapy. Our data also give new insight into some failures in the efficacy of therapies targeted against Bcl-2.

  7. Enhanced antitumor efficacy and reduced systemic toxicity of sulfatide-containing nanoliposomal doxorubicin in a xenograft model of colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Jia Lin

    Full Text Available Sulfatide is a glycosphingolipid known to interact with several extracellular matrix proteins, such as tenascin-C which is overexpressed in many types of cancer including that of the colon. In view of the limited success of chemotherapy in colorectal cancer and high toxicity of doxorubicin (DOX, a sulfatide-containing liposome (SCL encapsulation approach was taken to overcome these barriers. This study assessed the in vitro cytotoxicity, biodistribution, therapeutic efficacy and systemic toxicity in vivo of sulfatide-containing liposomal doxorubicin (SCL-DOX using human colonic adenocarcinoma HT-29 xenograft as the experimental model. In vitro, SCL-DOX was shown to be delivered into the nuclei and displayed prolonged retention compared with the free DOX. The use of this nanodrug delivery system to deliver DOX for treatment of tumor-bearing mice produced a much improved therapeutic efficacy in terms of tumor growth suppression and extended survival in contrast to the free drug. Furthermore, treatment of tumor-bearing mice with SCL-DOX resulted in a lower DOX uptake in the principal sites of toxicity of the free drug, namely the heart and skin, as well as reduced myelosuppression and diminished cardiotoxicity. Such natural lipid-guided nanodrug delivery systems may represent a new strategy for the development of effective anticancer chemotherapeutics targeting the tumor microenvironment for both primary tumor and micrometastases.

  8. Synergistic Enhancement of Antitumor Efficacy by PEGylated Multi-walled Carbon Nanotubes Modified with Cell-Penetrating Peptide TAT

    Science.gov (United States)

    Hu, Shanshan; Wang, Tong; Pei, Xibo; Cai, He; Chen, Junyu; Zhang, Xin; Wan, Qianbing; Wang, Jian

    2016-10-01

    In the present study, a cell-penetrating peptide, the transactivating transcriptional factor (TAT) domain from HIV, was linked to PEGylated multi-walled carbon nanotubes (MWCNTs) to develop a highly effective antitumor drug delivery system. FITC was conjugated on MWCNTs-polyethylene glycol (PEG) and MWCNTs-PEG-TAT to provide fluorescence signal for tracing the cellular uptake of the nanocarrier. After loaded with an anticancer agent, doxorubicin (DOX) via π - π stacking interaction, the physicochemical characteristics, release profile and biological evaluation of the obtained nano-sized drug carrier were investigated. The DOX loaded MWCNTs-PEG and MWCNTs-PEG-TAT drug carriers both displayed appropriate particle size, excellent stability, high drug loading, and pH-dependent drug release profile. Nevertheless, compared with DOX-MWCNTs-PEG, DOX-MWCNTs-PEG-TAT showed improved cell internalization, intracellular distribution and potentiated anticancer efficacy due to the TAT-mediated membrane translocation, endosomal escape and nuclear targeting. Furthermore, the therapeutic efficacy of DOX was not compromised after being conjugated with MWCNTs-PEG-TAT and the proposed nanocarrier was also confirmed to have a good biocompatibility. In conclusion, our results suggested that the unique combination of TAT and MWCNTs as a multifunctional drug delivery system might be a powerful tool for improved anticancer drug development.

  9. Efficacy and durability of hyaluronic acid fillers for malar enhancement: a prospective, randomized, spilt-face clinical controlled trial.

    Science.gov (United States)

    Jeong, Ki Heon; Gwak, Min Jae; Moon, Sung Kyung; Lee, Sang Jun; Shin, Min Kyung

    2017-01-31

    Various hyaluronic acid fillers can be used for facial attenuation and rejuvenation. The efficacy and durability of hyaluronic acid fillers are of major concern to dermatologists and patients. This study aimed to evaluate three dimensional morphology, tissue distribution, and changes in volume after injection of two different hyaluronic acid fillers. Ten Korean women were enrolled in this study. Each subject was injected with monophasic hyaluronic acid filler in one malar area and biphasic filler in the other. Clinical outcome was measured before and after injection, and after 2, 4, 6, 8, 12, and 24 weeks, using the Global Aesthetic Improvement Scale, photographs and Moire's topography. Facial magnetic resonance imaging (MRI) was performed twice over six months. Both products showed good results after injection and demonstrated good durability over time. MRI was a useful modality for assessing tissue distribution and volume changes. The effects and durability after injection of monophasic hyaluronic acid filler and biphasic hyaluronic acid filler are generally comparable.

  10. Coadministration of black seeds and turmeric shows enhanced efficacy in preventing metabolic syndrome in fructose-fed rats.

    Science.gov (United States)

    Amin, Faridah; Gilani, Anwarul-Hassan; Mehmood, Malik Hassan; Siddiqui, Bina S; Khatoon, Nasima

    2015-02-01

    Among noncommunicable diseases, metabolic syndrome (MS), a cluster of metabolic disorders including obesity, hyperglycemia, hyperlipidemia and hypertension, is highly prevalent in modern society. Its management requires lifestyle modifications and/or the life-long use of multiple medications, hence demanding development of safe alternative remedies. This study was aimed to establish the efficacy of combined use of black seeds and turmeric using fructose-fed rat model of MS. The high-performance liquid chromatographic fingerprints of turmeric and black seeds showed the presence of curcumin and thymoquinone, respectively, as their major constitutes. Different doses of black seeds and turmeric, individually and in combination, were administered to fructose-fed rats for up to 6 weeks representing characteristic features of MS. At 3 weeks of the treatment, black seeds and turmeric lowered (P turmeric at low doses over individually tested herbs, in improving features of MS.

  11. Enhanced antitumoral efficacy and immune response following conditionally replicative adenovirus containing constitutive HSF1 delivery to rodent tumors

    Directory of Open Access Journals (Sweden)

    Fan Rong

    2012-05-01

    Full Text Available Abstract Background Oncolytic adenoviruses are promising as anticancer agents but have limited clinical responses. Our previous study showed that heat shock transcription factor 1 (HSF1 overexpression could increase the anti-tumor efficacy of E1B55kD deleted oncolytic adenovirus through increasing the viral burst. Due to the important roles of heat shock proteins (HSPs in eliciting innate and adaptive immunity, we reasoned that besides increasing the viral burst, HSF1 may also play a role in increasing tumor specific immune response. Methods In the present study, intra-dermal murine models of melanoma (B16 and colorectal carcinoma (CT26 were treated with E1B55kD deleted oncolytic adenovirus Adel55 or Adel55 incorporated with cHSF1, HSF1i, HSP70, or HSP90 by intra-tumoral injection. Tumors were surgically excised 72 h post injection and animals were analyzed for tumor resistance and survival rate. Results Approximately 95% of animals in the Adel55-cHSF1 treated group showed sustained resistance upon re-challenge with autologous tumor cells, but not in PBS, Adel55, or Adel55-HSF1i treated groups. Only 50–65% animals in the Adel55-HSP70 and Adel55-HSP90 treated group showed tumor resistance. Tumor resistance was associated with development of tumor type specific cellular immune responses. Adel55-cHSF1 treatment also showed higher efficacy in diminishing progression of the secondary tumor focus than Adel55-HSP70 or Adel55-HSP90 treatment. Conclusions Besides by increasing its burst in tumor cells, cHSF1 could also augment the potential of E1B55kD deleted oncolytic adenovirus by increasing the tumor-specific immune response, which is beneficial to prevent tumor recurrence. cHSF1 is a better gene for neoadjuvant immunotherapy than other heat shock protein genes.

  12. Enhanced protective efficacy of nonpathogenic recombinant leishmania tarentolae expressing cysteine proteinases combined with a sand fly salivary antigen.

    Directory of Open Access Journals (Sweden)

    Farnaz Zahedifard

    2014-03-01

    Full Text Available BACKGROUND: Novel vaccination approaches are needed to prevent leishmaniasis. Live attenuated vaccines are the gold standard for protection against intracellular pathogens such as Leishmania and there have been new developments in this field. The nonpathogenic to humans lizard protozoan parasite, Leishmania (L tarentolae, has been used effectively as a vaccine platform against visceral leishmaniasis in experimental animal models. Correspondingly, pre-exposure to sand fly saliva or immunization with a salivary protein has been shown to protect mice against cutaneous leishmaniasis. METHODOLOGY/PRINCIPAL FINDINGS: Here, we tested the efficacy of a novel combination of established protective parasite antigens expressed by L. tarentolae together with a sand fly salivary antigen as a vaccine strategy against L. major infection. The immunogenicity and protective efficacy of different DNA/Live and Live/Live prime-boost vaccination modalities with live recombinant L. tarentolae stably expressing cysteine proteinases (type I and II, CPA/CPB and PpSP15, an immunogenic salivary protein from Phlebotomus papatasi, a natural vector of L. major, were tested both in susceptible BALB/c and resistant C57BL/6 mice. Both humoral and cellular immune responses were assessed before challenge and at 3 and 10 weeks after Leishmania infection. In both strains of mice, the strongest protective effect was observed when priming with PpSP15 DNA and boosting with PpSP15 DNA and live recombinant L. tarentolae stably expressing cysteine proteinase genes. CONCLUSION/SIGNIFICANCE: The present study is the first to use a combination of recombinant L. tarentolae with a sand fly salivary antigen (PpSP15 and represents a novel promising vaccination approach against leishmaniasis.

  13. Enhanced Protective Efficacy of Nonpathogenic Recombinant Leishmania tarentolae Expressing Cysteine Proteinases Combined with a Sand Fly Salivary Antigen

    Science.gov (United States)

    Taheri, Tahereh; Taslimi, Yasaman; Doustdari, Fatemeh; Seyed, Negar; Torkashvand, Fatemeh; Meneses, Claudio; Papadopoulou, Barbara; Kamhawi, Shaden; Valenzuela, Jesus G.; Rafati, Sima

    2014-01-01

    Background Novel vaccination approaches are needed to prevent leishmaniasis. Live attenuated vaccines are the gold standard for protection against intracellular pathogens such as Leishmania and there have been new developments in this field. The nonpathogenic to humans lizard protozoan parasite, Leishmania (L) tarentolae, has been used effectively as a vaccine platform against visceral leishmaniasis in experimental animal models. Correspondingly, pre-exposure to sand fly saliva or immunization with a salivary protein has been shown to protect mice against cutaneous leishmaniasis. Methodology/Principal Findings Here, we tested the efficacy of a novel combination of established protective parasite antigens expressed by L. tarentolae together with a sand fly salivary antigen as a vaccine strategy against L. major infection. The immunogenicity and protective efficacy of different DNA/Live and Live/Live prime-boost vaccination modalities with live recombinant L. tarentolae stably expressing cysteine proteinases (type I and II, CPA/CPB) and PpSP15, an immunogenic salivary protein from Phlebotomus papatasi, a natural vector of L. major, were tested both in susceptible BALB/c and resistant C57BL/6 mice. Both humoral and cellular immune responses were assessed before challenge and at 3 and 10 weeks after Leishmania infection. In both strains of mice, the strongest protective effect was observed when priming with PpSP15 DNA and boosting with PpSP15 DNA and live recombinant L. tarentolae stably expressing cysteine proteinase genes. Conclusion/Significance The present study is the first to use a combination of recombinant L. tarentolae with a sand fly salivary antigen (PpSP15) and represents a novel promising vaccination approach against leishmaniasis. PMID:24675711

  14. The Efficacy of Consulting Practicum in Enhancing Students' Readiness for Professional Career in Management Information Systems: An Empirical Analysis

    Science.gov (United States)

    Akpan, Ikpe Justice

    2016-01-01

    Consulting practicum (CP) is a form of experiential learning technique to prepare students for professional careers. While CP has become a popular way to help students acquire the essential practical skills and experience to enhance career readiness and ensure a smooth transition from college to employment, there is a lack of empirical studies…

  15. Silencing of Foxp3 enhances the antitumor efficacy of GM-CSF genetically modified tumor cell vaccine against B16 melanoma

    Science.gov (United States)

    Miguel, Antonio; Sendra, Luis; Noé, Verónica; Ciudad, Carles J; Dasí, Francisco; Hervas, David; Herrero, María José; Aliño, Salvador F

    2017-01-01

    The antitumor response after therapeutic vaccination has a limited effect and seems to be related to the presence of T regulatory cells (Treg), which express the immunoregulatory molecules CTLA4 and Foxp3. The blockage of CTLA4 using antibodies has shown an effective antitumor response conducing to the approval of the human anti-CTLA4 antibody ipilimumab by the US Food and Drug Administration. On the other hand, Foxp3 is crucial for Treg development. For this reason, it is an attractive target for cancer treatment. This study aims to evaluate whether combining therapeutic vaccination with CTLA4 or Foxp3 gene silencing enhances the antitumor response. First, the “in vitro” cell entrance and gene silencing efficacy of two tools, 2′-O-methyl phosphorotioate-modified oligonucleotides (2′-OMe-PS-ASOs) and polypurine reverse Hoogsteen hairpins (PPRHs), were evaluated in EL4 cells and cultured primary lymphocytes. Following B16 tumor transplant, C57BL6 mice were vaccinated with irradiated B16 tumor cells engineered to produce granulocyte-macrophage colony-stimulating factor (GM-CSF) and were intraperitoneally treated with CTLA4 and Foxp3 2′-OMe-PS-ASO before and after vaccination. Tumor growth, mice survival, and CTLA4 and Foxp3 expression in blood cells were measured. The following results were obtained: 1) only 2′-OMe-PS-ASO reached gene silencing efficacy “in vitro”; 2) an improved survival effect was achieved combining both therapeutic vaccine and Foxp3 antisense or CTLA4 antisense oligonucleotides (50% and 20%, respectively); 3) The blood CD4+CD25+Foxp3+ (Treg) and CD4+CTLA4+ cell counts were higher in mice that developed tumor on the day of sacrifice. Our data showed that tumor cell vaccine combined with Foxp3 or CTLA4 gene silencing can increase the efficacy of therapeutic antitumor vaccination. PMID:28176947

  16. Novel nootropic drug sunifiram enhances hippocampal synaptic efficacy via glycine-binding site of N-methyl-D-aspartate receptor.

    Science.gov (United States)

    Moriguchi, Shigeki; Tanaka, Tomoya; Narahashi, Toshio; Fukunaga, Kohji

    2013-10-01

    Sunifiram is a novel pyrrolidone nootropic drug structurally related to piracetam, which was developed for neurodegenerative disorder like Alzheimer's disease. Sunifiram is known to enhance cognitive function in some behavioral experiments such as Morris water maze task. To address question whether sunifiram affects N-methyl-D-aspartate receptor (NMDAR)-dependent synaptic function in the hippocampal CA1 region, we assessed the effects of sunifiram on NMDAR-dependent long-term potentiation (LTP) by electrophysiology and on phosphorylation of synaptic proteins by immunoblotting analysis. In mouse hippocampal slices, sunifiram at 10-100 nM significantly enhanced LTP in a bell-shaped dose-response relationship which peaked at 10 nM. The enhancement of LTP by sunifiram treatment was inhibited by 7-chloro-kynurenic acid (7-ClKN), an antagonist for glycine-binding site of NMDAR, but not by ifenprodil, an inhibitor for polyamine site of NMDAR. The enhancement of LTP by sunifilam was associated with an increase in phosphorylation of α-amino-3-hydroxy-5-methylisozazole-4-propionate receptor (AMPAR) through activation of calcium/calmodulin-dependent protein kinase II (CaMKII) and an increase in phosphorylation of NMDAR through activation of protein kinase Cα (PKCα). Sunifiram treatments at 1-1000 nM increased the slope of field excitatory postsynaptic potentials (fEPSPs) in a dose-dependent manner. The enhancement was associated with an increase in phosphorylation of AMPAR receptor through activation of CaMKII. Interestingly, under the basal condition, sunifiram treatments increased PKCα (Ser-657) and Src family (Tyr-416) activities with the same bell-shaped dose-response curve as that of LTP peaking at 10 nM. The increase in phosphorylation of PKCα (Ser-657) and Src (Tyr-416) induced by sunifiram was inhibited by 7-ClKN treatment. The LTP enhancement by sunifiram was significantly inhibited by PP2, a Src family inhibitor. Finally, when pretreated with a high

  17. The diagnostic efficacy of quantitative liver MR imaging with diffusion-weighted, SWI, and hepato-specific contrast-enhanced sequences in staging liver fibrosis - a multiparametric approach

    Energy Technology Data Exchange (ETDEWEB)

    Feier, Diana [Medical University of Vienna, General Hospital of Vienna (AKH), Department of Biomedical Imaging and Image-guided Therapy, Vienna (Austria); Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Emergency County Hospital, Department of Radiology, Cluj-Napoca (Romania); Balassy, Csilla; Bastati, Nina; Fragner, Romana; Ba-Ssalamah, Ahmed [Medical University of Vienna, General Hospital of Vienna (AKH), Department of Biomedical Imaging and Image-guided Therapy, Vienna (Austria); Wrba, Friedrich [Medical University of Vienna, General Hospital of Vienna (AKH), Department of Pathology, Vienna (Austria)

    2016-02-15

    To assess the diagnostic efficacy of multiparametric MRI using quantitative measurements of the apparent diffusion coefficient (ADC) of the liver parenchyma on diffusion-weighted imaging (DWI), signal intensity (SI) on susceptibility-weighted imaging (SWI), and gadoxetic acid-enhanced T1-weighted imaging during the hepatobiliary phase for the staging of liver fibrosis. Seventy-seven patients underwent a 3T MRI examination, including DWI/SWI sequences and gadoxetic acid-enhanced T1-weighted MRI. Liver fibrosis according to liver biopsy was staged using the Metavir fibrosis score: F0 (n = 21, 27.3 %); F1 (n = 7, 9.1 %); F2 (n = 8, 10.4 %); F3 (n = 12, 15.6 %); and F4 (n = 29, 37.7 %). SI of the liver was defined using region-of-interest measurements to calculate the ADC values, the relative enhancement (RE) in the hepatobiliary phase, and the liver-to-muscle ratio (LMR) measurements for SWI. The values of RE, LMR, and ADC measurements were statistically significantly different among the five fibrosis stages (p < 0.004). Combining the three parameters in a multiparametric approach, the AUC for detecting F1 stage or greater (≥ F1) was 94 %, for F2 or greater (≥F2) was 95 %, for F3 or greater (≥F3) was 90 %, and for stage F4 was 93 %. Multiparametric MRI is an efficient non-invasive diagnostic tool for the staging of liver fibrosis. (orig.)

  18. Efficacy of Standard Versus Enhanced Features in a Web-Based Commercial Weight-Loss Program for Obese Adults, Part 2: Randomized Controlled Trial

    Science.gov (United States)

    Morgan, Philip J; Hutchesson, Melinda J; Callister, Robin

    2013-01-01

    Background Commercial Web-based weight-loss programs are becoming more popular and increasingly refined through the addition of enhanced features, yet few randomized controlled trials (RCTs) have independently and rigorously evaluated the efficacy of these commercial programs or additional features. Objective To determine whether overweight and obese adults randomized to an online weight-loss program with additional support features (enhanced) experienced a greater reduction in body mass index (BMI) and increased usage of program features after 12 and 24 weeks compared to those randomized to a standard online version (basic). Methods An assessor-blinded RCT comparing 301 adults (male: n=125, 41.5%; mean age: 41.9 years, SD 10.2; mean BMI: 32.2 kg/m2, SD 3.9) who were recruited and enrolled offline, and randomly allocated to basic or enhanced versions of a commercially available Web-based weight-loss program for 24 weeks. Results Retention at 24 weeks was greater in the enhanced group versus the basic group (basic 68.5%, enhanced 81.0%; P=.01). In the intention-to-treat analysis of covariance with imputation using last observation carried forward, after 24 weeks both intervention groups had reductions in key outcomes with no difference between groups: BMI (basic mean –1.1 kg/m2, SD 1.5; enhanced mean –1.3 kg/m2, SD 2.0; P=.29), weight (basic mean –3.3 kg, SD 4.7; enhanced mean –4.0 kg, SD 6.2; P=.27), waist circumference (basic mean –3.1 cm, SD 4.6; enhanced mean –4.0 cm, SD 6.2; P=.15), and waist-to-height ratio (basic mean –0.02, SD 0.03; enhanced mean –0.02, SD 0.04, P=.21). The enhanced group logged in more often at both 12 and 24 weeks, respectively (enhanced 12-week mean 34.1, SD 28.1 and 24-week mean 43.1, SD 34.0 vs basic 12-week mean 24.6, SD 25.5 and 24-week mean 31.8, SD 33.9; P=.002). Conclusions The addition of personalized e-feedback in the enhanced program provided limited additional benefits compared to a standard commercial Web

  19. Bcl-xL Genetic Modification Enhanced the Therapeutic Efficacy of Mesenchymal Stem Cell Transplantation in the Treatment of Heart Infarction

    Directory of Open Access Journals (Sweden)

    Xiaodong Xue

    2015-01-01

    Full Text Available Objectives. Low survival rate of mesenchymal stem cells (MSCs severely limited the therapeutic efficacy of cell therapy in the treatment of myocardial infarction (MI. Bcl-xL genetic modification might enhance MSC survival after transplantation. Methods. Adult rat bone marrow MSCs were modified with human Bcl-xL gene (hBcl-xL-MSCs or empty vector (vector-MSCs. MSC apoptosis and paracrine secretions were characterized using flow cytometry, TUNEL, and ELISA in vitro. In vivo, randomized adult rats with MI received myocardial injections of one of the three reagents: hBcl-xL-MSCs, vector-MSCs, or culture medium. Histochemistry, TUNEL, and echocardiography were carried out to evaluate cell engraftment, apoptosis, angiogenesis, scar formation, and cardiac functional recovery. Results. In vitro, cell apoptosis decreased 43%, and vascular endothelial growth factor (VEGF, insulin-like growth factor-1 (IGF-1, and plate-derived growth factor (PDGF increased 1.5-, 0.7-, and 1.2-fold, respectively, in hBcl-xL-MSCs versus wild type and vector-MSCs. In vivo, cell apoptosis decreased 40% and 26% in hBcl-xL-MSC group versus medium and vector-MSC group, respectively. Similar results were observed in cell engraftment, angiogenesis, scar formation, and cardiac functional recovery. Conclusions. Genetic modification of MSCs with hBcl-xL gene could be an intriguing strategy to improve the therapeutic efficacy of cell therapy in the treatment of heart infarction.

  20. rIL-22 as an adjuvant enhances the immunogenicity of rGroEL in mice and its protective efficacy against S. Typhi and S. Typhimurium

    Science.gov (United States)

    Kaur, Gurpreet; Charu; Charu; Bansal, Anju

    2015-01-01

    Salmonella infection, ranging from mild, self-limiting diarrhea to severe gastrointestinal, septicemic disease and enteric fever, is a global health problem both in humans and animals. Rapid development of microbial drug resistance has led to a need for efficacious and affordable vaccines against Salmonella. Microbial heat shock proteins (HSPs), including HSP60 and HSP70, are the dominant antigens that promote the host immune response. Co-administration of these antigens with cytokines, such as IL-22, which plays an important role in antimicrobial defense, can enhance the immune response and protection against pathogens. Therefore, the aim of the present study was to determine the immunogenicity of rGroEL (Hsp60) of S. Typhi, alone or administered in combination with murine rIL-22, and its protective efficacy against lethal infection with Salmonella, in mice. There was appreciable stimulation of the humoral and cell-mediated immune responses in mice immunized with rGroEL alone. However, co-administration of rGroEL with rIL-22 further boosted the antibody titers (IgG, IgG1 and IgG2a), T-cell proliferative responses and the secretion of both Th1 and Th2 cytokines. Additionally, rGroEL alone accorded 65%–70% protection against lethal challenge with S. Typhi and S. Typhimurium, which increased to 90% when co-administered with rIL-22. PMID:24858422

  1. Strontium-doped calcium polyphosphate/ultrahigh molecular weight polyethylene composites: A new class of artificial joint components with enhanced biological efficacy to aseptic loosening.

    Science.gov (United States)

    Gu, Zhipeng; Huang, Bingxue; Li, Yiwen; Tian, Meng; Li, Li; Yu, Xixun

    2016-04-01

    To enhance implant stability and prolong the service life of artificial joint component, a new approach was proposed to improve the wear resistance of artificial joint component and endow artificial joint component with the biological efficacy of resistance to aseptic loosening. Strontium calcium polyphosphate (SCPP) were interfused in ultrahigh molecular weight polyethylene (UHMWPE) by a combination of liquid nitrogen ball-milling and flat-panel curing process to prepare the SCPP/UHMWPE composites. The micro-structure, mechanical characterization, tribological characterization and bioactivities of various SCPP/UHMWPE composites were investigated. The results suggested that this method could statistically improve the wear resistance of UHMWPE resulting from a good SCPP particle dispersion. Moreover, it is also observed that the SCPP/UHMWPE composites-wear particles could promote the production of OPG by osteoblasts and decrease the production of RANKL by osteoblasts, and then increase the OPG/RANKL ratio. This indicated that the SCPP/UHMWPE composites had potential efficacy to prevent and treat aseptic loosening. Above all, the SCPP/UHMWPE composites with a suitable SCPP content would be the promising materials for fabricating artificial joint component with ability to resist aseptic loosening.

  2. Influence of penetration enhancers and molecular weight in antifungals permeation through bovine hoof membranes and prediction of efficacy in human nails.

    Science.gov (United States)

    Miron, D; Cornelio, R; Troleis, J; Mariath, J; Zimmer, A R; Mayorga, P; Schapoval, E E S

    2014-01-23

    This work aimed to evaluate the effect of different substances on the permeation of geraniol through bovine hoof membranes. Different penetration enhancers were able to increase the permeability up to 25 times compared to control. It was demonstrated that acetilcysteine in association with ascorbic acid increased the permeation, even in acid formulations. In addition, some antifungal drugs were incorporated into a gel formulation of HPMC containing acetylcysteine 5% and ascorbic acid 0.2% and then the permeation coefficient through bovine hoof membranes was evaluated. The relationship between permeability and molecular weight was established for fluconazole, miconazole, terbinafine, butenafine, geraniol and nerol. Geraniol and nerol, the antifungals with lower molecular weight, had the better permeability results. Permeability coefficients for nail plates were estimated and geraniol demonstrated similar or even better efficacy index values against T. rubrum, T. menthagrophytes and M. canis compared with terbinafine and miconazole.

  3. Efficacy of whey protein gel networks as potential viability-enhancing scaffolds for cell immobilization of Lactobacillus rhamnosus GG.

    Science.gov (United States)

    Doherty, S B; Gee, V L; Ross, R P; Stanton, C; Fitzgerald, G F; Brodkorb, A

    2010-03-01

    This study investigated cell immobilization of Lactobacillus rhamnosus GG in three separate protein products: native, denatured and hydrolysed whey protein isolate (WPI). Treatments were assessed for their ability to enhance probiotic survival during storage, heat stress and ex vivo gastric incubation. Spatial distribution of probiotic cells within immobilized treatments was evaluated by atomic force and confocal scanning laser microscopy, while cell viability was enumerated by plate count and flow cytometry (FACS). Microscopic analysis of denatured treatments revealed an oasis of immobilized cells, phase-separated from the surrounding protein matrix; an environmental characteristic analogous to hydrolysed networks. Cell immobilization in hydrolysed and denatured WPI enhanced survival by 6.1+/-0.1 and 5.8+/-0.1 log10 cycles, respectively, following 14 day storage at 37 degrees C and both treatments generated thermal protection at 57 degrees C (7.3+/-0.1 and 6.5+/-0.1 log(10) cfu/ml). Furthermore, denatured WPI enhanced probiotic protection (8.9+/-0.2 log(10) cfu/ml) following 3h gastric incubation at 37 degrees C. In conclusion, hydrolysed or denatured WPI were the most suitable matrices for cell immobilization, while native protein provided the weakest safeguard against thermal and acid stress, thus making it possible to envision whey protein gel networks as protective substrates for cell immobilization applications.

  4. Human induced pluripotent cells resemble embryonic stem cells demonstrating enhanced levels of DNA repair and efficacy of nonhomologous end-joining

    Energy Technology Data Exchange (ETDEWEB)

    Fan Jinshui; Robert, Carine [Department of Radiation Oncology, University of Maryland School of Medicine, 655 West Baltimore Street, BRB 7-023A, Baltimore, MD 21201 (United States); Jang, Yoon-Young; Liu Hua; Sharkis, Saul; Baylin, Stephen Bruce [Johns Hopkins University School of Medicine, Department of Oncology, Baltimore, MD 21231-1000 (United States); Rassool, Feyruz Virgilia, E-mail: frassool@som.umaryland.edu [Department of Radiation Oncology, University of Maryland School of Medicine, 655 West Baltimore Street, BRB 7-023A, Baltimore, MD 21201 (United States)

    2011-08-01

    Highlights: {yields} iPSC and hESC demonstrate a similar cell cycle profile, with increased S phase cells and decreased G0/G1. {yields} iPSC and hESC increased ROS and decreased DSBs, compared with differentiated parental cells. {yields} iPSC and hESC demonstrate elevated DSB repair activity, including nonhomologous end-joining, compared with differentiated parental cells. {yields} iPSC however show a partial apoptotic response to DNA damage, compared to hESC. {yields} DNA damage responses may constitute important markers for the efficacy of iPSC reprogramming. - Abstract: To maintain the integrity of the organism, embryonic stem cells (ESC) need to maintain their genomic integrity in response to DNA damage. DNA double strand breaks (DSBs) are one of the most lethal forms of DNA damage and can have disastrous consequences if not repaired correctly, leading to cell death, genomic instability and cancer. How human ESC (hESC) maintain genomic integrity in response to agents that cause DSBs is relatively unclear. Adult somatic cells can be induced to 'dedifferentiate' into induced pluripotent stem cells (iPSC) and reprogram into cells of all three germ layers. Whether iPSC have reprogrammed the DNA damage response is a critical question in regenerative medicine. Here, we show that hESC demonstrate high levels of endogenous reactive oxygen species (ROS) which can contribute to DNA damage and may arise from high levels of metabolic activity. To potentially counter genomic instability caused by DNA damage, we find that hESC employ two strategies: First, these cells have enhanced levels of DNA repair proteins, including those involved in repair of DSBs, and they demonstrate elevated nonhomologous end-joining (NHEJ) activity and repair efficacy, one of the main pathways for repairing DSBs. Second, they are hypersensitive to DNA damaging agents, as evidenced by a high level of apoptosis upon irradiation. Importantly, iPSC, unlike the parent cells they are derived

  5. Combination of Human Fas (CD95/Apo-1) Ligand with Adriamycin Significantly Enhances the Efficacy of Antitumor Response

    Institute of Scientific and Technical Information of China (English)

    Zhongchen Liu; Ruizhen Liu; Jinhua Qiu; Ping Yin; Fanghong Luo; Jinhua SU; Wenzhu Li; Caixia Chen; Xin Fan; Jiakai Zhang; Guohong Zhuang

    2009-01-01

    The prognosis of hepatocellular carcinoma (HCC) is poor, even with the combined treatment of curative resection and adjuvant chemoradiotherapy. To solve this problem, many biologic therapies have been investigated. Fas ligand (FasL, CD95L) is mainly expressed in activated T lymphocytes and natural killer (NK) cells, and plays a central role in both cell-mediated immunity and immune downregnlation. Several studies have shown that FasL is expressed in HCC. In the present report, we prepared recombinant human pET-22b(+)/FasL protein and investigated the effect of FasL on HCC cells in vitro and on tumor growth in a murine HCC tumor model. The well-known cytotoxic chemotherapeutic reagent adriamycin (ADM) served as a control. We found that FasL effectively suppressed the viability of H22 tumor cells and significantly induced the apoptosis of H22 cells. The apoptotic levels of cells treated with FasL-ADM were significantly higher than those treated with FasL or ADM alone, and the FasL-ADM combination resulted in a more than additive effect on tumor growth delay in this model. The results suggested that combined treatment of FasL and other chemotherapeutic agents 5 be a new approach to improve the efficacy of chemotherapy for HCC. Cellular & Molecular Immunology. 2009;6(3):167-174.

  6. Targeting of cancer‑associated fibroblasts enhances the efficacy of cancer chemotherapy by regulating the tumor microenvironment.

    Science.gov (United States)

    Li, Minmin; Li, Mei; Yin, Tao; Shi, Huashan; Wen, Yuan; Zhang, Binglan; Chen, Meihua; Xu, Guangchao; Ren, Kexin; Wei, Yuquan

    2016-03-01

    Cancer‑associated fibroblasts (CAFs), key components of the tumor stroma, can regulate tumorigenesis by altering the tumor microenvironment in variety of ways to promote angiogenesis, recruit inflammatory immune cells and remodel the extracellular matrix. Using a murine xenograft model of colon carcinoma, the present study observed that oxaliplatin increased the accumulation of CAFs and stimulated the production of cytokines associated with CAFs. When oxaliplatin was combined with the small‑molecule dipeptidyl peptidase inhibitor PT‑100, which inhibits CAFs by targeting fibroblast activation protein (FAP), the accumulation of CAFs was markedly reduced, xenograft tumor growth was significantly suppressed and the survival of the mice increased, compared to those of mice treated with oxaliplatin or PT‑100 alone. Furthermore, the xenograft tumor tissues of mice treated with oxaliplatin and PT‑100 contained lower numbers of tumor‑associated macrophages and dendritic cells, expressed lower levels of cytokines associated with CAFs and had a lower density of CD31+ endothelial cells. The present study demonstrated that pharmacological inhibition of CAFs improved the response to chemotherapy, reduced the recruitment of immune tumor‑promoting cells and inhibited angiogenesis. Combining chemotherapy with agents which target CAFs may represent a novel strategy for improving the efficacy of chemotherapy and reducing chemoresistance.

  7. An MMP-2 Responsive Liposome Integrating Antifibrosis and Chemotherapeutic Drugs for Enhanced Drug Perfusion and Efficacy in Pancreatic Cancer.

    Science.gov (United States)

    Ji, Tianjiao; Li, Suping; Zhang, Yinlong; Lang, Jiayan; Ding, Yanping; Zhao, Xiao; Zhao, Ruifang; Li, Yiye; Shi, Jian; Hao, Jihui; Zhao, Ying; Nie, Guangjun

    2016-02-10

    Fibrotic stroma, a critical character of pancreatic tumor microenvironment, provides a critical barrier against the penetration and efficacy of various antitumor drugs. Therefore, new strategies are urgently needed to alleviate the fibrotic mass and increase the drug perfusion within pancreatic cancer tissue. In our current work, we developed a β-cyclodextrin (β-CD) modified matrix metalloproteinase-2 (MMP-2) responsive liposome, integrating antifibrosis and chemotherapeutic drugs for regulation of pancreatic stellate cells (PSCs), a key source of the fibrosis, and targeted delivery of cytotoxic drugs for pancreatic cancer therapy. These liposomes disassembed into two functional parts upon MMP-2 cleavage at the tumor site. One part was constituted by the β-CDs and the antifibrosis drug pirfenidone, which was kept in the stroma and inhibited the expression of collagen I and TGF-β in PSCs, down-regulating the fibrosis and decreasing the stromal barrier. The other segment, the RGD peptide-modified-liposome loading the chemotherapeutic drug gemcitabine, targeted and killed pancreatic tumor cells. This integrated nanomedicine, showing an increased drug perfusion without any overt side effects, may provide a potential strategy for improvement of the pancreatic cancer therapy.

  8. Dual-drug delivery system based on in situ gel-forming nanosuspension of forskolin to enhance antiglaucoma efficacy.

    Science.gov (United States)

    Gupta, Saurabh; Samanta, Malay K; Raichur, Ashok M

    2010-03-01

    The present study was designed to improve the bioavailability of forskolin by the influence of precorneal residence time and dissolution characteristics. Nanosizing is an advanced approach to overcome the issue of poor aqueous solubility of active pharmaceutical ingredients. Forskolin nanocrystals have been successfully manufactured and stabilized by poloxamer 407. These nanocrystals have been characterized in terms of particle size by scanning electron microscopy and dynamic light scattering. By formulating Noveon AA-1 polycarbophil/poloxamer 407 platforms, at specific concentrations, it was possible to obtain a pH and thermoreversible gel with a pH(gel)/T (gel) close to eye pH/temperature. The addition of forskolin nanocrystals did not alter the gelation properties of Noveon AA-1 polycarbophil/poloxamer 407 and nanocrystal properties of forskolin. The formulation was stable over a period of 6 months at room temperature. In vitro release experiments indicated that the optimized platform was able to prolong and control forskolin release for more than 5 h. The in vivo studies on dexamethasone-induced glaucomatous rabbits indicated that the intraocular pressure lowering efficacy for nanosuspension/hydrogel systems was 31% and lasted for 12 h, which is significantly better than the effect of traditional eye suspension (18%, 4-6 h). Hence, our investigations successfully prove that the pH and thermoreversible polymeric in situ gel-forming nanosuspension with ability of controlled drug release exhibits a greater potential for glaucoma therapy.

  9. Enhancing predicted efficacy of tumor treating fields therapy of glioblastoma using targeted surgical craniectomy: A computer modeling study

    DEFF Research Database (Denmark)

    Korshoej, Anders Rosendal; Saturnino, Guilherme Bicalho; Rasmussen, Line Kirkegaard

    2016-01-01

    Objective: The present work proposes a new clinical approach to TTFields therapy of glioblastoma. The approach combines targeted surgical skull removal (craniectomy) with TTFields therapy to enhance the induced electrical field in the underlying tumor tissue. Using computer simulations, we explore...... clinical scenarios. Results: For the superficial tumor, removal of a standard craniotomy bone flap increased the electrical field strength by 60-70% in the tumor. The percentage of tissue in expected growth arrest or regression was increased from negligible values to 30-50%. The observed effects were...

  10. Treatment of medulloblastoma using an oncolytic measles virus encoding the thyroidal sodium iodide symporter shows enhanced efficacy with radioiodine

    Directory of Open Access Journals (Sweden)

    Hutzen Brian

    2012-11-01

    Full Text Available Abstract Background Medulloblastoma is the most common malignant brain tumor of childhood. Although the clinical outcome for medulloblastoma patients has improved significantly, children afflicted with the disease frequently suffer from debilitating side effects related to the aggressive nature of currently available therapy. Alternative means for treating medulloblastoma are desperately needed. We have previously shown that oncolytic measles virus (MV can selectively target and destroy medulloblastoma tumor cells in localized and disseminated models of the disease. MV-NIS, an oncolytic measles virus that encodes the human thyroidal sodium iodide symporter (NIS, has the potential to deliver targeted radiotherapy to the tumor site and promote a localized bystander effect above and beyond that achieved by MV alone. Methods We evaluated the efficacy of MV-NIS against medulloblastoma cells in vitro and examined their ability to incorporate radioiodine at various timepoints, finding peak uptake at 48 hours post infection. The effects of MV-NIS were also evaluated in mouse xenograft models of localized and disseminated medulloblastoma. Athymic nude mice were injected with D283med-Luc medulloblastoma cells in the caudate putamen (localized disease or right lateral ventricle (disseminated disease and subsequently treated with MV-NIS. Subsets of these mice were given a dose of 131I at 24, 48 or 72 hours later. Results MV-NIS treatment, both by itself and in combination with 131I, elicited tumor stabilization and regression in the treated mice and significantly extended their survival times. Mice given 131I were found to concentrate radioiodine at the site of their tumor implantations. In addition, mice with localized tumors that were given 131I either 24 or 48 hours after MV-NIS treatment exhibited a significant survival advantage over mice given MV-NIS alone. Conclusions These data suggest MV-NIS plus radioiodine may be a potentially useful therapy for

  11. N-bromotaurine surrogates for loss of antiproliferative response and enhances cisplatin efficacy in cancer cells with impaired glucocorticoid receptor.

    Science.gov (United States)

    Logotheti, Stella; Khoury, Nikolas; Vlahopoulos, Spiros A; Skourti, Elena; Papaevangeliou, Dimitra; Liloglou, Triantafyllos; Gorgoulis, Vassilis; Budunova, Irina; Kyriakopoulos, Anthony M; Zoumpourlis, Vassilis

    2016-07-01

    Glucocorticoids (GCs) are frequently used in anticancer combination regimens; however, their continuous use adds selective pressure on cancer cells to develop GC-resistance via impairment of the glucocorticoid receptor (GR), therefore creating a need for GC-alternatives. Based on the drug repurposing approach and the commonalities between inflammation and neoplasia, drugs that are either in late-stage clinical trials and/or already marketed for GC-refractory inflammatory diseases could be evaluated as GC-substitutes in the context of cancer. Advantageously, unlike new molecular entities currently being de novo developed to restore GC-responsiveness of cancer cells, such drugs have documented safety and efficacy profile, which overall simplifies their introduction in clinical cancer trials. In this study, we estimated the potential of a well-established, multistage, cell line-based, mouse skin carcinogenesis model to be exploited as an initial screening tool for unveiling covert GC-substitutes. First, we categorized the cell lines of this model to GC-sensitive and GC-resistant, in correlation with their corresponding GR status, localization, and functionality. We found that GC-resistance starts in papilloma stages, due to a dysfunctional GR, which is overexpressed, DNA binding-competent, but transactivation-incompetent in papilloma, squamous, and spindle stages of the model. Then, aided by this tool, we evaluated the ability of N-bromotaurine, a naturally occurring, small-molecule, nonsteroid anti-inflammatory drug which is under consideration for use interchangeably/in replacement to GCs in skin inflammations, to restore antiproliferative response of GC-resistant cancer cells. Unlike GCs, N-bromotaurine inhibited cell-cycle progression in GC-resistant cancer cells and efficiently synergized with cisplatin, thus indicating a potential to be exploited instead of GCs against cancer.

  12. A Francisella tularensis live vaccine strain that improves stimulation of antigen-presenting cells does not enhance vaccine efficacy.

    Directory of Open Access Journals (Sweden)

    Deanna M Schmitt

    Full Text Available Vaccination is a proven strategy to mitigate morbidity and mortality of infectious diseases. The methodology of identifying and testing new vaccine candidates could be improved with rational design and in vitro testing prior to animal experimentation. The tularemia vaccine, Francisella tularensis live vaccine strain (LVS, does not elicit complete protection against lethal challenge with a virulent type A Francisella strain. One factor that may contribute to this poor performance is limited stimulation of antigen-presenting cells. In this study, we examined whether the interaction of genetically modified LVS strains with human antigen-presenting cells correlated with effectiveness as tularemia vaccine candidates. Human dendritic cells infected with wild-type LVS secrete low levels of proinflammatory cytokines, fail to upregulate costimulatory molecules, and activate human T cells poorly in vitro. One LVS mutant, strain 13B47, stimulated higher levels of proinflammatory cytokines from dendritic cells and macrophages and increased costimulatory molecule expression on dendritic cells compared to wild type. Additionally, 13B47-infected dendritic cells activated T cells more efficiently than LVS-infected cells. A deletion allele of the same gene in LVS displayed similar in vitro characteristics, but vaccination with this strain did not improve survival after challenge with a virulent Francisella strain. In vivo, this mutant was attenuated for growth and did not stimulate T cell responses in the lung comparable to wild type. Therefore, stimulation of antigen-presenting cells in vitro was improved by genetic modification of LVS, but did not correlate with efficacy against challenge in vivo within this model system.

  13. Targeting GRP75 improves HSP90 inhibitor efficacy by enhancing p53-mediated apoptosis in hepatocellular carcinoma.

    Science.gov (United States)

    Guo, Weiwei; Yan, Lichong; Yang, Ling; Liu, Xiaoyu; E, Qiukai; Gao, Peiye; Ye, Xiaofei; Liu, Wen; Zuo, Ji

    2014-01-01

    Heat shock protein 90 (HSP90) inhibitors are potential drugs for cancer therapy. The inhibition of HSP90 on cancer cell growth largely through degrading client proteins, like Akt and p53, therefore, triggering cancer cell apoptosis. Here, we show that the HSP90 inhibitor 17-AAG can induce the expression of GRP75, a member of heat shock protein 70 (HSP70) family, which, in turn, attenuates the anti-growth effect of HSP90 inhibition on cancer cells. Additionally, 17-AAG enhanced binding of GRP75 and p53, resulting in the retention of p53 in the cytoplasm. Blocking GRP75 with its inhibitor MKT-077 potentiated the anti-tumor effects of 17-AAG by disrupting the formation of GRP75-p53 complexes, thereby facilitating translocation of p53 into the nuclei and leading to the induction of apoptosis-related genes. Finally, dual inhibition of HSP90 and GRP75 was found to significantly inhibit tumor growth in a liver cancer xenograft model. In conclusion, the GRP75 inhibitor MKT-077 enhances 17-AAG-induced apoptosis in HCCs and increases p53-mediated inhibition of tumor growth in vivo. Dual targeting of GRP75 and HSP90 may be a useful strategy for the treatment of HCCs.

  14. Targeting GRP75 improves HSP90 inhibitor efficacy by enhancing p53-mediated apoptosis in hepatocellular carcinoma.

    Directory of Open Access Journals (Sweden)

    Weiwei Guo

    Full Text Available Heat shock protein 90 (HSP90 inhibitors are potential drugs for cancer therapy. The inhibition of HSP90 on cancer cell growth largely through degrading client proteins, like Akt and p53, therefore, triggering cancer cell apoptosis. Here, we show that the HSP90 inhibitor 17-AAG can induce the expression of GRP75, a member of heat shock protein 70 (HSP70 family, which, in turn, attenuates the anti-growth effect of HSP90 inhibition on cancer cells. Additionally, 17-AAG enhanced binding of GRP75 and p53, resulting in the retention of p53 in the cytoplasm. Blocking GRP75 with its inhibitor MKT-077 potentiated the anti-tumor effects of 17-AAG by disrupting the formation of GRP75-p53 complexes, thereby facilitating translocation of p53 into the nuclei and leading to the induction of apoptosis-related genes. Finally, dual inhibition of HSP90 and GRP75 was found to significantly inhibit tumor growth in a liver cancer xenograft model. In conclusion, the GRP75 inhibitor MKT-077 enhances 17-AAG-induced apoptosis in HCCs and increases p53-mediated inhibition of tumor growth in vivo. Dual targeting of GRP75 and HSP90 may be a useful strategy for the treatment of HCCs.

  15. The efficacy of the enhanced Aussie Optimism Positive Thinking Skills Program in improving social and emotional learning in middle childhood.

    Science.gov (United States)

    Myles-Pallister, Jacqueline D; Hassan, Sharinaz; Rooney, Rosanna M; Kane, Robert T

    2014-01-01

    The aim of the current study was to investigate the effects of the modified and enhanced Aussie Optimism Positive Thinking Skills Program (AO-PTS) on Year 4 and 5 children's social and emotional learning (SEL) skills. AO-PTS is a universal-school based program that is implemented by class teachers as part of regular school curricula and was developed for the prevention of depression and anxiety. The study comprised a total of 683 Year 4 and 5 students from 10 private primary schools in Western Australia. Students were assessed on two subscales of emotional attribution at school whilst parents reported on their children's externalizing and internalizing problems outside of school and at home. Two analyses were conducted: seven intervention schools were assessed at pre- and post-test (Analysis 1) and pre-post change in three intervention schools were compared to pre-post change in three matched control schools (Analysis 2). Results from Analysis 1 showed that the intervention children had increased in their overall emotional attribution accuracy and decreased in total difficulties and hyperactivity; Results from Analysis 2 revealed no intervention effect on emotional attribution accuracy or internalizing or externalizing problems. These findings suggest that the enhanced AO-PTS's effects on SEL were not evident in the short-term period after intervention. The non-significant findings and future directions for AO-PTS research and program modification were discussed.

  16. The Efficacy of the Enhanced Aussie Optimism Positive Thinking Skills Program in Improving Social and Emotional Learning in Middle Childhood

    Directory of Open Access Journals (Sweden)

    Jacqueline D Myles-Pallister

    2014-08-01

    Full Text Available The aim of the current study was to investigate the effects of the modified and enhanced Aussie Optimism Positive Thinking Skills Program (AO-PTS on Year 4 and 5 children’s social and emotional learning (SEL skills. AO-PTS is a universal-school based program that is implemented by class teachers as part of regular school curricula and was developed for the prevention of depression and anxiety. The study comprised a total of 683 Year 4 and 5 students from 10 private primary schools in Western Australia. Students were assessed on two subscales of emotional attribution at school whilst parents reported on their children’s externalizing and internalizing problems outside of school and at home. Two analyses were conducted: seven intervention schools were assessed at pre- and post-test (Analysis 1 and pre-post change in three intervention schools were compared to pre-post change in three matched control schools (Analysis 2. Results from Analysis 1 showed that the intervention children had increased in their overall emotional attribution accuracy and decreased in total difficulties and hyperactivity; Results from Analysis 2 revealed no intervention effect on emotional attribution accuracy or internalizing or externalizing problems. These findings suggest that the enhanced AO-PTS’s effects on SEL were not evident in the short-term period after intervention. The non-significant findings and future directions for AO-PTS research and program modification were discussed.

  17. Enhanced Protective Efficacy of H5 Subtype Influenza Vaccine with Modification of the Multibasic Cleavage Site of Hemagglutinin in Retroviral Pseudotypes

    Institute of Scientific and Technical Information of China (English)

    Ling Tao; JianJun Chen; Jin Meng; Yao Chen; Hongxia Li; Yan Liu; Zhenhua Zheng

    2013-01-01

    Traditionally,the multibasic cleavage site (MBCS) of surface protein H5-hemagglutinin (HA) is converted to a monobasic one so as to weaken the virulence of recombinant H5N1 influenza viruses and to produce inactivated and live attenuated vaccines.Whether such modification benefits new candidate vaccines has not been adequately investigated.We previously used retroviral vectors to generate wtH5N1 pseudotypes containing the wild-type HA (wtH5) from A/swine/Anhui/ca/2004 (H5N1) virus.Here,we generated mtH5N1 pseudotypes,which contained a mutant-type HA (mtH5) with a modified monobasic cleavage site.Groups of mice were subcutaneously injected with the two types of influenza pseudotypes.Compared to the group immunized with wtH5N1 pseudotypes,the inoculation of mtH5N1 pseudotypes induced significantly higher levels of HA specific IgG and IFN-γ in immunized mice,and enhanced protection against the challenge of mouse-adapted avian influenza virus A/Chicken/Henan/12/2004 (H5N1).This study suggests modification of the H5-hemagglutinin MBCS in retroviral pseudotypes enhances protection efficacy in mice and this information may be helpful for development of vaccines from mammalian cells to fight against H5N1 influenza viruses.

  18. Enhanced Efficacy of a Codon-Optimized DNA Vaccine Encoding the Glycoprotein Precursor Gene of Lassa Virus in a Guinea Pig Disease Model When Delivered by Dermal Electroporation

    Directory of Open Access Journals (Sweden)

    Niranjan Y. Sardesai

    2013-07-01

    Full Text Available Lassa virus (LASV causes a severe, often fatal, hemorrhagic fever endemic to West Africa. Presently, there are no FDA-licensed medical countermeasures for this disease. In a pilot study, we constructed a DNA vaccine (pLASV-GPC that expressed the LASV glycoprotein precursor gene (GPC. This plasmid was used to vaccinate guinea pigs (GPs using intramuscular electroporation as the delivery platform. Vaccinated GPs were protected from lethal infection (5/6 with LASV compared to the controls. However, vaccinated GPs experienced transient viremia after challenge, although lower than the mock-vaccinated controls. In a follow-on study, we developed a new device that allowed for both the vaccine and electroporation pulse to be delivered to the dermis. We also codon-optimized the GPC sequence of the vaccine to enhance expression in GPs. Together, these innovations resulted in enhanced efficacy of the vaccine. Unlike the pilot study where neutralizing titers were not detected until after virus challenge, modest neutralizing titers were detected in guinea pigs before challenge, with escalating titers detected after challenge. The vaccinated GPs were never ill and were not viremic at any timepoint. The combination of the codon-optimized vaccine and dermal electroporation delivery is a worthy candidate for further development.

  19. Enhancement of the priming efficacy of DNA vaccines encoding dendritic cell-targeted antigens by synergistic toll-like receptor ligands

    Directory of Open Access Journals (Sweden)

    Kornbluth Richard S

    2009-08-01

    Full Text Available Abstract Background Targeting of protein antigens to dendritic cells (DC via the DEC205 receptor enhances presentation of antigen-derived peptides on MHC-I and MHC-II molecules and, in the presence of costimulatory signals, antigen-specific immune responses. The immunogenicity and efficacy of DNA vaccination can also be enhanced by fusing the encoded antigen to single chain antibodies directed against DEC205. To further improve this strategy, we evaluated different toll-like receptor ligands (TLR and CD40 ligands (CD40L as adjuvants for DNA vaccines encoding a DEC205-single-chain antibody fused to the ovalbumin model antigen or HIV-1 Gag and assessed the priming efficacy of DNA in a DNA prime adenoviral vector boost immunization regimen. Results Mice were primed with the adjuvanted DEC-205 targeted DNA vaccines and boosted with adenoviral vectors encoding the same antigens. CD8+ T cell responses were determined after the adenoviral booster immunization, to determine how well the different DNA immunization regimens prime for the adenoviral boost. In the absence of adjuvants, targeting of DNA-encoded ovalbumin to DCs suppressed CD8+ T-cell responses after the adenoviral booster immunization. CD8+ T-cell responses to the DEC205 targeted DNA vaccines increased only slightly by adding either the TLR-9 ligand CpG, the TLR-3 ligand Poly I:C, or CD40 ligand expression plasmids. However, the combination of both TLR-ligands led to a strong enhancement of CD8+ T-cell responses compared to a non-targeted DNA vaccine. This finding was confirmed using HIV Gag as antigen. Conclusion Although DNA prime adenoviral vector boost immunizations belong to the strongest inducers of cytotoxic T cell responses in different animal models and humans, the CD8+ T cell responses can be further improved by targeting the DNA encoded antigen to DEC205 in the presence of synergistic TLR ligands CpG and Poly I:C.

  20. Nanodrug-enhanced radiofrequency tumor ablation: effect of micellar or liposomal carrier on drug delivery and treatment efficacy.

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    Marwan Moussa

    Full Text Available PURPOSE: To determine the effect of different drug-loaded nanocarriers (micelles and liposomes on delivery and treatment efficacy for radiofrequency ablation (RFA combined with nanodrugs. MATERIALS/METHODS: Fischer 344 rats were used (n = 196. First, single subcutaneous R3230 tumors or normal liver underwent RFA followed by immediate administration of i.v. fluorescent beads (20, 100, and 500 nm, with fluorescent intensity measured at 4-24 hr. Next, to study carrier type on drug efficiency, RFA was combined with micellar (20 nm or liposomal (100 nm preparations of doxorubicin (Dox; targeting HIF-1α or quercetin (Qu; targeting HSP70. Animals received RFA alone, RFA with Lipo-Dox or Mic-Dox (1 mg i.v., 15 min post-RFA, and RFA with Lipo-Qu or Mic-Qu given 24 hr pre- or 15 min post-RFA (0.3 mg i.v.. Tumor coagulation and HIF-1α or HSP70 expression were assessed 24 hr post-RFA. Third, the effect of RFA combined with i.v. Lipo-Dox, Mic-Dox, Lipo-Qu, or Mic-Qu (15 min post-RFA compared to RFA alone on tumor growth and animal endpoint survival was evaluated. Finally, drug uptake was compared between RFA/Lipo-Dox and RFA/Mic-Dox at 4-72 hr. RESULTS: Smaller 20 nm beads had greater deposition and deeper tissue penetration in both tumor (100 nm/500 nm and liver (100 nm (p<0.05. Mic-Dox and Mic-Qu suppressed periablational HIF-1α or HSP70 rim thickness more than liposomal preparations (p<0.05. RFA/Mic-Dox had greater early (4 hr intratumoral doxorubicin, but RFA/Lipo-Dox had progressively higher intratumoral doxorubicin at 24-72 hr post-RFA (p<0.04. No difference in tumor growth and survival was seen between RFA/Lipo-Qu and RFA/Mic-Qu. Yet, RFA/Lipo-Dox led to greater animal endpoint survival compared to RFA/Mic-Dox (p<0.03. CONCLUSION: With RF ablation, smaller particle micelles have superior penetration and more effective local molecular modulation. However, larger long-circulating liposomal carriers can result in greater intratumoral drug

  1. PLGA-PLL-PEG-Tf-based targeted nanoparticles drug delivery system enhance antitumor efficacy via intrinsic apoptosis pathway

    Directory of Open Access Journals (Sweden)

    Bao W

    2015-01-01

    the DNR-loaded NPs group than that in other ones. Interestingly, pathological assessment showed no apparent damage to the main organs. In summary, the results obtained from this study showed that the novel NPs DDS could improve the efficacy of DNR in the treatment of leukemia and induce apoptosis via intrinsic pathway. Thus, it can be inferred that the new drug delivery may be a useful clinical tool.Keywords: PLGA-PLL-PEG, daunorubicin, transferrin, K562 cells, apoptosis

  2. Lymphotactin enhances the in-vitro immune efficacy of dendritoma formed by dendritic cells and mouse hepatocellular carcinoma cells

    Institute of Scientific and Technical Information of China (English)

    张浩; 蒋国平; 郑树森; 吴丽花; 朱峰; 杨振林

    2004-01-01

    Objective: To investigate the in-vitro antitumor immune responses of dendritoma formed by mouse hepatocellular carcinoma (HCC) cells and lymphotactin (Lptn) gene modified dendritic cells (DCs). Method: DCs prepared from mouse bone marrow were genetically modified by lymphotactin adenovirus, and fused with H22 cells by polyethylene glycol (PEG). RT-PCR and ELISA were employed to identify lymphotactin expression at mRNA and protein level. Cell phenotypes and fusion efficiency was detected by FACS. The stimulatory effect of DC on T cells was detected by mixed lymphocyte reaction. The cytotoxicity activity against H22 cells was assayed by LDH method. Results: Lymphotactin could be efficiently expressed by DCLptn/H22 hybridoma. DCLptn/H22 cells could induce potent T cell proliferation effect and generate strong cytotoxic T lymphocyte (CTL) reaction against allogenic H22 cells. Conclusion: Lymphotactin genetic modification could enhance the in vitro immune activity of the dendritoma.

  3. Structure-Based Rational Design of Prodrugs To Enable Their Combination with Polymeric Nanoparticle Delivery Platforms for Enhanced Antitumor Efficacy**

    Science.gov (United States)

    Wang, Hangxiang; Xie, Haiyang; Wu, Jiaping; Wei, Xuyong; Zhou, Lin; Xu, Xiao; Zheng, Shusen

    2014-01-01

    Drug-loaded nanoparticles (NPs) are of particular interest for efficient cancer therapy due to their improved drug delivery and therapeutic index in various types of cancer. However, the encapsulation of many chemotherapeutics into delivery NPs is often hampered by their unfavorable physicochemical properties. Here, we employed a drug reform strategy to construct a small library of SN-38 (7-ethyl-10-hydroxycamptothecin)-derived prodrugs, in which the phenolate group was modified with a variety of hydrophobic moieties. This esterification fine-tuned the polarity of the SN-38 molecule and enhanced the lipophilicity of the formed prodrugs, thereby inducing their self-assembly into biodegradable poly(ethylene glycol)-block-poly(d,l-lactic acid) (PEG-PLA) nanoparticulate structures. Our strategy combining the rational engineering of prodrugs with the pre-eminent features of conventionally used polymeric materials should open new avenues for designing more potent drug delivery systems as a therapeutic modality. PMID:25196427

  4. Enhanced intracellular delivery and antibacterial efficacy of enrofloxacin-loaded docosanoic acid solid lipid nanoparticles against intracellular Salmonella

    Science.gov (United States)

    Xie, Shuyu; Yang, Fei; Tao, Yanfei; Chen, Dongmei; Qu, Wei; Huang, Lingli; Liu, Zhenli; Pan, Yuanhu; Yuan, Zonghui

    2017-01-01

    Enrofloxacin-loaded docosanoic acid solid lipid nanoparticles (SLNs) with different physicochemical properties were developed to enhance activity against intracellular Salmonella. Their cellular uptake, intracellular elimination and antibacterial activity were studied in RAW 264.7 cells. During the experimental period, SLN-encapsulated enrofloxacin accumulated in the cells approximately 27.06–37.71 times more efficiently than free drugs at the same extracellular concentration. After incubation for 0.5 h, the intracellular enrofloxacin was enhanced from 0.336 to 1.147 μg/mg of protein as the sizes of nanoparticles were increased from 150 to 605 nm, and from 0.960 to 1.147 μg/mg of protein when the charge was improved from −8.1 to −24.9 mv. The cellular uptake was more significantly influenced by the size than it was by the charge, and was not affected by whether the charge was positive or negative. The elimination of optimal SLN-encapsulated enrofloxacin from the cells was significantly slower than that of free enrofloxacin after removing extracellular drug. The inhibition effect against intracellular Salmonella CVCC541 of 0.24 and 0.06 μg/mL encapsulated enrofloxacin was stronger than 0.6 μg/mL free drug after all of the incubation periods and at 48 h, respectively. Docosanoic acid SLNs are thus considered as a promising carrier for intracellular bacterial treatment. PMID:28112240

  5. Efficacy of enhanced HIV counseling for risk reduction during pregnancy and in the postpartum period: a randomized controlled trial.

    Directory of Open Access Journals (Sweden)

    Suzanne Maman

    Full Text Available INTRODUCTION: Pregnancy and the postpartum period present important intervention opportunities. Counseling can leverage the motivation women have during this time to change behaviors that may negatively affect their health and the heath of their infants. METHODS: Pregnant women attending an antenatal clinic in South Africa were randomly allocated to treatment (n=733 and control arms (n=747. Treatment arm participants received enhanced HIV pre- and post-test counseling, legal support and access to support groups at baseline, which occurred at the first antenatal visit, and then six and ten weeks postpartum. Control arm participants received standard HIV testing and counseling (HTC and two postpartum attention control sessions. Outcomes were incidence of sexually transmitted infection (STI by 14 weeks postpartum and past 30-day inconsistent condom use at 14 weeks and 9 months postpartum. RESULTS: There were no intervention effects on incident STIs for either HIV-negative (adjusted risk ratio (aRR 1.01, 95% CI 0.71-1.44 or HIV-positive participants (aRR 0.86, 95% CI 0.61-1.23. The intervention was associated with a 28% decrease in risk of past 30-day inconsistent condom use at nine-months among HIV-negative women (aRR 0.72,95% CI 0.59-0.88, but did not affect inconsistent condom use among HIV-positive women (aRR1.08; 95% CI 0.67-1.75. DISCUSSION: An enhanced counseling intervention during pregnancy and the postpartum period can lead to reductions in inconsistent condom use among HIV-negative women. Results underscore the importance of the counseling that accompanies HIV HTC. More work is needed to understand how to promote and sustain risk reduction among HIV-positive women. TRIAL REGISTRATION: ClinicalTrials.gov NCT01683461.

  6. Omega-3 Polyunsaturated Fatty Acids Enhance Cisplatin Efficacy in Gastric Cancer Cells by Inducing Apoptosis via ADORA1.

    Science.gov (United States)

    Sheng, Hong; Chen, Xuehua; Liu, Binya; Li, Pu; Cao, Weixin

    2016-01-01

    It has been suggested that administration of the omega-3 polyunsaturated fatty acids (ω-3 PUFAs), including docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), can alter the toxicity and/or activity of several anticancer drugs in in vitro and in vivo studies. Here, we investigated the ability of ω-3 PUFAs to potentiate the antineoplastic activity of cisplatin (CDDP) in gastric cancer cells. The increase in CDDP-induced growth inhibition was measured by the IC50 values obtained when the cells were incubated with CDDP alone or with CDDP plus DHA or EPA. DHA and EPA enhanced the growth-inhibition activity of increasing concentrations of CDDP. The interactions between CDDP and DHA or EPA at the cellular level were assessed through the combination index (CI) method of Chou-Talalay. The results demonstrated synergism between CDDP and DHA or EPA in MKN45 cells. Cell cycle analysis showed that the combination treatment increased G0/G1 phase and S phase arrest, and significantly increased the number of apoptotic cells. According to our previous study, ω -3 PUFAs induce apoptosis of gastric cells via ADORA1, a subtype of adenosine receptor functionally related to cell death. The ADORA1 mRNA and protein expression was higher in the combination treatment than in the individual treatments. Notable, when GC cells were pretreated with DPCPX, a selective ADORA1 antagonist, the combination treatment effect on apoptosis was significantly reduced. Our results suggest that ω-3 PUFAs enhance the antineoplastic effects of CDDP in gastric cancer cells, and the synergistic effect between ω-3 PUFAs and CDDP is partly dependent on activating the ADORA1-mediated apoptosis pathway.

  7. Enhanced efficacy of synergistic combinations of antimicrobial peptides with caspofungin versus Candida albicans in insect and murine models of systemic infection.

    Science.gov (United States)

    MacCallum, D M; Desbois, A P; Coote, P J

    2013-08-01

    The objective of this study was to determine whether combinations of antimicrobial peptides (AMPs) with caspofungin display enhanced antifungal activity versus Candida albicans in vitro and in vivo. Three conventional AMPs that satisfied criteria favouring their potential development as novel antifungals were selected for investigation. Colistin sulphate was also included as a cyclic peptide antibiotic used in the clinic. Minimum inhibitory concentrations (MICs) were determined for each antifungal agent and checkerboard assays were used to determine fractional inhibitory concentration index (FICI) values for dual combinations of AMPs or colistin with caspofungin. Viability assays were performed for the same combinations in order to investigate fungicidal interactions. Synergistic antifungal combinations were then tested for efficacy in vivo and compared to monotherapies in wax moth larva and murine models of systemic C. albicans infection. In combination with caspofungin, each of the AMPs [hMUC7-12, DsS3(1-16), hLF(1-11)] and colistin were synergistic and candidacidal in vitro. The treatment of infected wax moth larvae with combinations of caspofungin with hMUC7-12, DsS3(1-16) or colistin resulted in significant enhancements in survival compared to treatment with monotherapies. Notably, the treatment of C. albicans-infected mice with a combination of caspofungin and DsS3(1-16) resulted in the enhancement of survival compared to groups treated with just the individual agents. This study demonstrates that combination therapies containing caspofungin and AMPs or colistin merit further development as potential novel treatments for C. albicans infections.

  8. Enhancement of HCV polytope DNA vaccine efficacy by fusion to an N-terminal fragment of heat shock protein gp96.

    Science.gov (United States)

    Pishraft-Sabet, Leila; Kosinska, Anna D; Rafati, Sima; Bolhassani, Azam; Taheri, Tahereh; Memarnejadian, Arash; Alavian, Seyed-Moayed; Roggendorf, Michael; Samimi-Rad, Katayoun

    2015-01-01

    Induction of a strong hepatitis C virus (HCV)-specific immune response plays a key role in control and clearance of the virus. A polytope (PT) DNA vaccine containing B- and T-cell epitopes could be a promising vaccination strategy against HCV, but its efficacy needs to be improved. The N-terminal domain of heat shock protein gp96 (NT(gp96)) has been shown to be a potent adjuvant for enhancing immunity. We constructed a PT DNA vaccine encoding four HCV immunodominant cytotoxic T lymphocyte epitopes (two HLA-A2- and two H2-D(d)-specific motifs) from the Core, E2, NS3 and NS5B antigens in addition to a T-helper CD4+ epitope from NS3 and a B-cell epitope from E2. The NT(gp96) was fused to the C- or N-terminal end of the PT DNA (PT-NT(gp96) or NT(gp96)-PT), and their potency was compared. Cellular and humoral immune responses against the expressed peptides were evaluated in CB6F1 mice. Our results showed that immunization of mice with PT DNA vaccine fused to NT(gp96) induced significantly stronger T-cell and antibody responses than PT DNA alone. Furthermore, the adjuvant activity of NT(gp96) was more efficient in the induction of immune responses when fused to the C-terminal end of the HCV DNA polytope. In conclusion, the NT(gp96) improved the efficacy of the DNA vaccine, and this immunomodulatory effect was dependent on the position of the fusion.

  9. Enhanced antitumor efficacy of a vascular disrupting agent combined with an antiangiogenic in a rat liver tumor model evaluated by multiparametric MRI.

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    Feng Chen

    Full Text Available A key problem in solid tumor therapy is tumor regrowth from a residual viable rim after treatment with a vascular disrupting agent (VDA. As a potential solution, we studied a combined treatment of a VDA and antiangiogenic. This study was approved by the institutional ethical committee for the use and care of laboratory animals. Rats with implanted liver tumors were randomized into four treatment groups: 1 Zd6126 (Zd; 2 Thalidomide (Tha; 3 Zd in combination with Tha (ZdTha; and 4 controls. Multiparametric MRIs were performed and quantified before and after treatment. Circulating endothelial progenitor cells (EPCs and plasma stromal cell-derived factor-1α (SDF-1α were monitored. Tumor apoptosis, necrosis, and microvessels were verified by histopathology. A single use of Zd or Tha did not significantly delay tumor growth. The combined ZdTha showed enhanced antitumor efficacy due to synergistic effects; it induced a cumulative tumor apoptosis or necrosis, which resulted in significant delay in tumor growth and reduction in the viable tumor rim; it also reduced tumor vessel permeability; and it improved tumor hemodynamic indexes, most likely via a transient normalization of tumor vasculature induced by Tha. A stepwise linear regression analysis showed that the apparent diffusion coefficient was an independent predictor of tumor growth. We found no significant increases in Zd-induced circulating EPCs or plasma SDF-1α. ZdTha showed improved therapeutic efficacy in solid tumors compared to either agent alone. The therapeutic effects were successfully tracked in vivo with multiparametric MRI.

  10. Self-compassion enhances the efficacy of explicit cognitive reappraisal as an emotion regulation strategy in individuals with major depressive disorder.

    Science.gov (United States)

    Diedrich, Alice; Hofmann, Stefan G; Cuijpers, Pim; Berking, Matthias

    2016-07-01

    Cognitive reappraisal has been shown to be an effective strategy to regulate depressed mood in healthy and remitted depressed individuals. However, individuals currently suffering from a clinical depression often experience difficulties in utilizing this strategy. Therefore, the goal of this study was to examine whether the efficacy of explicit cognitive reappraisal in major depressive disorder can be enhanced through the use of self-compassion and emotion-focused acceptance as preparatory strategies. Thereby, explicit cognitive reappraisal refers to purposefully identifying, challenging, and modifying depressiogenic cognitions to reduce depressed mood. To test our hypotheses, we induced depressed mood at four points in time in 54 participants (64.8% female; age M = 35.59, SD = 11.49 years) meeting criteria for major depressive disorder. After each mood induction, participants were instructed to either wait, or employ self-compassion, acceptance, or reappraisal to regulate their depressed mood. Depressed mood was assessed before and after each mood induction and regulation period on a visual analog scale. Results indicated that participants who had utilized self-compassion as a preparatory strategy experienced a significantly greater reduction of depressed mood during reappraisal than did those who had been instructed to wait prior to reappraisal. Participants who had used acceptance as a preparatory strategy did not experience a significantly greater reduction of depressed mood during subsequent reappraisal than those in the waiting condition. These findings provide preliminary evidence that the efficacy of explicit cognitive reappraisal is moderated by the precursory use of other emotion regulation strategies. In particular, they suggest that depressed individuals might benefit from using self-compassion to facilitate the subsequent use of explicit cognitive reappraisal.

  11. Silencing of Foxp3 enhances the antitumor efficacy of GM-CSF genetically modified tumor cell vaccine against B16 melanoma

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    Miguel A

    2017-01-01

    Full Text Available Antonio Miguel,1 Luis Sendra,1 Verónica Noé,2 Carles J Ciudad,2 Francisco Dasí,3,4 David Hervas,5 María José Herrero,1,6 Salvador F Aliño17 1Department of Pharmacology, Faculty of Medicine, University of Valencia, 2Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, University of Barcelona, 3Research University Hospital of Valencia, INCLIVA Health Research Institute, 4Department of Physiology, Faculty of Medicine, University of Valencia Foundation, 5Biostatistics Unit, 6Pharmacogenetics Unit, Instituto de Investigación Sanitaria La Fe (IIS La Fe, 7Clinical Pharmacology Unit, ACM Hospital Universitario y Politécnico La Fe, Valencia, Spain Abstract: The antitumor response after therapeutic vaccination has a limited effect and seems to be related to the presence of T regulatory cells (Treg, which express the immunoregulatory molecules CTLA4 and Foxp3. The blockage of CTLA4 using antibodies has shown an effective antitumor response conducing to the approval of the human anti-CTLA4 antibody ipilimumab by the US Food and Drug Administration. On the other hand, Foxp3 is crucial for Treg development. For this reason, it is an attractive target for cancer treatment. This study aims to evaluate whether combining therapeutic vaccination with CTLA4 or Foxp3 gene silencing enhances the antitumor response. First, the “in vitro” cell entrance and gene silencing efficacy of two tools, 2'-O-methyl phosphorotioate-modified oligonucleotides (2'-OMe-PS-ASOs and polypurine reverse Hoogsteen hairpins (PPRHs, were evaluated in EL4 cells and cultured primary lymphocytes. Following B16 tumor transplant, C57BL6 mice were vaccinated with irradiated B16 tumor cells engineered to produce granulocyte-macrophage colony-stimulating factor (GM-CSF and were intraperitoneally treated with CTLA4 and Foxp3 2'-OMe-PS-ASO before and after vaccination. Tumor growth, mice survival, and CTLA4 and Foxp3 expression in blood cells were measured. The following

  12. Enhanced oral bioavailability and anticancer efficacy of fisetin by encapsulating as inclusion complex with HPβCD in polymeric nanoparticles.

    Science.gov (United States)

    Kadari, Amrita; Gudem, Sagarika; Kulhari, Hitesh; Bhandi, Murali Mohan; Borkar, Roshan M; Kolapalli, Venkata Ramana Murthy; Sistla, Ramakrishna

    2017-11-01

    Fisetin (FST), a potent anticancer phytoconstituent, exhibits poor aqueous solubility and hence poor bioavailability. The aim of the present study is to improve the oral bioavailability of FST by encapsulating into PLGA NPs (poly-lactide-co-glycolic acid nanoparticles) as a complex of HPβCD (hydroxyl propyl beta cyclodextrin) and to assess its anti-cancer activity against breast cancer cells. FST-HPβCD inclusion complex (FHIC) was prepared and the supramolecular complex formation was characterized by FTIR, DSC, PXRD and (1)H NMR. FHIC encapsulated PLGA nanoparticles (FHIC-PNP) were prepared and were studied for in vitro anticancer activity, cellular uptake, apoptosis and reactive oxygen species generation in MCF-7 human breast cancer cells. Comparative bioavailability of FST was determined after oral administration in C57BL6 mice as pure FST and FHIC-PNP. The results revealed that FHIC-PNP not only enhanced the anti-cancer activity and apoptosis of FST against MCF-7 cells but also improved its oral bioavailability, as demonstrated by increased peak plasma concentration and total drug absorbed.

  13. Glycyrrhiza uralensis water extract enhances dendritic cell maturation and antitumor efficacy of HPV dendritic cell-based vaccine

    Science.gov (United States)

    Aipire, Adila; Li, Jinyu; Yuan, Pengfei; He, Jiang; Hu, Yelang; Liu, Lu; Feng, Xiaoli; Li, Yijie; Zhang, Fuchun; Yang, Jianhua; Li, Jinyao

    2017-01-01

    Licorice has been used as herbal medicine and natural sweetener. Here, we prepared Glycyrrhiza uralensis water extract (GUWE) and investigated the effect of GUWE on the maturation and function of dendritic cells (DCs) and its adjuvant effect on DC-based vaccine. We observed that GUWE dose-dependently promoted DC maturation and cytokine secretion through TLR4 signaling pathway. The capacity of DC to stimulate allogenic splenocyte proliferation was also enhanced by GUWE treatment. Compared with control group, GUWE treated DCs pulsed with human papillomavirus (HPV)-16 E6/E7 peptides significantly inhibited the tumor growth in both early and late therapeutic groups. In early therapeutic group, the frequencies of induced regulatory T cells (iTregs: CD4+CD25−Fopx3+) and CD4+ and CD8+ T cells were significantly decreased and increased, respectively. HPV-16-specific CD8+ T cell responses were significantly induced and negatively correlated with iTreg frequencies and tumor weight. These results indicated the immunoregulatory activities of licorice. PMID:28272545

  14. A novel curcumin analog (H-4073 enhances the therapeutic efficacy of cisplatin treatment in head and neck cancer.

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    Bhavna Kumar

    Full Text Available Chemotherapy constitutes the standard modality of treatment for localized head and neck squamous cell carcinomas (HNSCC. However, many patients fail to respond and relapse after this treatments due to the acquisition of chemo-resistance. Therefore, there is an urgent need to develop novel drugs that could reverse the resistant phenotype. Curcumin, the constituent of the spice turmeric has been shown to have anti-inflammatory, anti-oxidant and anti-proliferative properties in several tumor types. However, use of curcumin has been limited due to its poor bio-absorption. Recently, a novel class of curcumin analogs, based on diarylidenylpiperidones (DAP, has been developed by incorporating a piperidone link to the beta-diketone structure and fluoro substitutions on the phenyl groups. In this study, we evaluated the effectiveness of H-4073, a parafluorinated variant of DAP, using both in vitro and in vivo head and neck cancer models. Our results demonstrate that H-4073 is a potent anti-tumor agent and it significantly inhibited cell proliferation in all the HNSCC cell lines tested in a dose-dependent manner. In addition, pretreatment of cisplatin-resistant HNSCC cell lines with H-4073 significantly reversed the chemo-resistance as observed by cell viability assay (MTT, apoptosis assay (Annexin V binding and cleaved caspase-3 (Western blot. H-4073 mediated its anti-tumor effects by inhibiting JAK/STAT3, FAK, Akt and VEGF signaling pathways that play important roles in cell proliferation, migration, survival and angiogenesis. In the SCID mouse xenograft model, H-4073 significantly enhanced the anti-tumor and anti-angiogenesis effects of cisplatin, with no added systemic toxicity. Interestingly, H-4073 inhibited tumor angiogenesis by blocking VEGF production by tumor cells as well as directly inhibiting endothelial cell function. Taken together, our results suggest that H-4073 is a potent anti-tumor agent and it can be used to overcome chemotherapy

  15. Size Selective Green Synthesis of Silver and Gold Nanoparticles: Enhanced Antibacterial Efficacy of Resveratrol Capped Silver Sol.

    Science.gov (United States)

    Shukla, Shashi P; Roy, Mainak; Mukherjee, Poulomi; Das, Laboni; Neogy, Suman; Srivastava, Dinesh; Adhikari, Soumyakanti

    2016-03-01

    In view of potential biomedical application of the noble metal nanoparticles, we report a size controlled yet simple and green synthesis of resveratrol stabilized silver and gold nanoparticles having low polydispersity of size. Here, resveratrol plays two simultaneous roles, reducing the metal ions and providing efficient capping of the small nanoparticles. This gives rise to specific size of silver and gold nanoparticles at specific ratios of metal to resveratrol. The particles have been characterized by XRD and transmission electron microscopy. The nanoparticle sols are stable for months. The UV Visible absorption spectra of the silver sol show the plasmon peak of spherical nanoparticles, presence of which is further reflected in the TEM images. Size of the silver particles obtained is in between 11 to 21 nm depending on the ratio of resveratrol to metal ion used. Resveratrol capped silver nanoparticles exhibit high antibacterial activity against Gram negative wild type E coli BW (25113). The minimum inhibitory concentration (MIC) of nano-silver against the bacterium has been estimated to be 6.48 μg/ml, which is significantly lower than that reported in some earlier as well as recent publications. Reaction of gold ions with resveratrol, on the other hand, produces gold nanoparticles of sizes varying from 7 to 29 nm at different ratios of resveratrol to the metal ions. Particles with higher size and aspect ratio are formed at lower concentration of the capping agent whereas particles with very small size and pseudo-spherical morphology are formed at higher capping concentration. Difference in the formation kinetics of silver and gold nanoparticles has been attributed to the different growth mechanisms in the two cases. Possible modes of anchorage of resveratrol to silver nanoparticles have been investigated using surface enhanced resonance Raman spectroscopy (SERS) which shows that the silver nanoparticles are capped by resveratrol molecule primarily through O

  16. Heat shock protein 90 and calcineurin pathway inhibitors enhance the efficacy of triazoles against Scedosporium prolificans via induction of apoptosis

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    Fazal Shirazi

    2014-06-01

    Full Text Available Scedosporium prolificans is a pathogenic mold resistant to current antifungals, and infection results in high mortality. Simultaneous targeting of both ergosterol biosynthesis and heat shock protein 90 (Hsp90 or the calcineurin pathway in S. prolificans may be an important strategy for enhancing the potency of antifungal agents. We hypothesized that the inactive triazoles posaconazole (PCZ and itraconazole (ICZ acquire fungicidal activity when combined with the calcineurin inhibitor tacrolimus (TCR or Hsp90 inhibitor 17-demethoxy-17-(2-propenylamino geldanamycin (17AAG. PCZ, ICZ, TCR and 17AAG alone were inactive in vitro against S. prolificans spores (MICs > 128 μg/ml. In contrast, MICs for PCZ or ICZ in combination with TCR or 17AAG (0.125-0.50 μg/ml were much lower compared with drug alone. In addition PCZ and ICZ in combination with TCR or 17AAG became fungicidal. Because apoptosis is regulated by the calcineurin pathway in fungi and is under the control of Hsp90, we hypothesized that this synergistic fungicidal effect is mediated via apoptosis. This observed fungicidal activity was mediated by increased apoptosis of S. prolificans germlings, as evidenced by reactive oxygen species accumulation, decreased mitochondrial membrane potential, phosphatidylserine externalization, and DNA fragmentation. Furthermore, induction of caspase-like activity was correlated with TCR or 17AAG + PCZ/ICZ-induced cell death. In conclusion, we report for the first time that PCZ or ICZ in combination with TCR or 17AAG renders S. prolificans exquisitely sensitive to PCZ or ICZ via apoptosis. This finding may stimulate the development of new therapeutic strategies for patients infected with this recalcitrant fungus.

  17. Efficacy of various protein-based coating on enhancing the shelf life of fresh eggs during storage.

    Science.gov (United States)

    Caner, Cengiz; Yüceer, Muhammed

    2015-07-01

    The effectiveness of various coatings (whey protein isolate [WPI], whey protein concentrate [WPC], zein, and shellac) on functional properties, interior quality, and eggshell breaking strength of fresh eggs were evaluated during storage at 24 °: C for 6 weeks. Coatings and storage time had significant effects on Haugh unit, yolk index, albumen pH, dry matter (DMA), relative whipping capacity (RWC), and albumen viscosity. Uncoated eggs had higher albumen pH (9.56) and weight loss, and lower albumen viscosity (5.73), Haugh unit (HU), and yolk index (YI) during storage. Among the coated eggs, the shellac and zein coated eggs had the highest value of albumen viscosity (27.26 to 26.90), HU (74.10 to 73.61), and YI (44.84 to 44.63) after storage. Shellac (1.44%) was more effective in preventing weight loss than WPC (4.59%), WPI (4.60%), and zein (2.13%) coatings. Uncoated eggs had the higest value (6.71%) of weight lost. All coatings increased shell strength (5.18 to 5.73 for top and 3.58 to 4.71 for bottom) significantly (P coated. The shellac and zein coatings were more effective for maintaining the internal quality of fresh eggs during storage. Fourier transform near infrared (FT-NIR) in the 800 to 2500 nm reflection spectra were used to quantify the contents of the fresh eggs at the end of storage. Eggs coated with shellac or zein displayed a higher absorbance at 970 and 1,197 nm respectively (OH vibration of water) compared with those coated with WPI or WPC and the uncoated group at the end of storage. The coatings improved functional properties and also shell strength and could be a viable alternative technology for maintaining the internal quality of eggs during long-term storage. This study highlights the promising use of various coatings to both enhance the functional properties and to reduce the breakage of eggs.

  18. Triterpene-loaded microemulsion using Coix lacryma-jobi seed extract as oil phase for enhanced antitumor efficacy: preparation and in vivo evaluation

    Directory of Open Access Journals (Sweden)

    Qu D

    2013-12-01

    Full Text Available Ding Qu, Junjie He, Congyan Liu, Jing Zhou, Yan ChenKey Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, People’s Republic of ChinaAbstract: Ganoderma lucidum triterpene-loaded microemulsions (TMEs using Coix lacryma-jobi (adlay seed oil as oil phase were prepared, characterized, and evaluated for enhanced antitumor activity. Ternary phase diagrams for the TMEs were constructed and the optimal preparation was developed. Transmission electron microscopy and dynamic light scattering showed that this formulation had a well defined spherical shape, a homogeneous distribution, a small size, and a narrow polydispersity index. The drug-loading rate was determined to be 9.87% by ultraviolet spectrophotometry, and acceptable stability under various stimulations in vitro was confirmed. Importantly, the TME formulation showed a significantly greater antiproliferative effect towards human lung carcinoma (A549 cells and murine lung tumor (Lewis cells in comparison with suspension formulations containing triterpene and adlay seed oil as a positive control. The half-maximal inhibitory concentration of the TMEs was about 0.62 mg crude drug per mL, being 2.5-fold improved relative to that of the corresponding suspension formulation, but no significant cytotoxicity was observed for the bare microemulsion in A549 cells and Lewis cells. In vivo, the TME formulation showed markedly enhanced antitumor efficacy in a xenograft model of Lewis lung cancer after intragastric administration. Compared with cyclophosphamide, the TME formulation showed similar antitumor activity but less general toxicity. These results indicate the feasibility of using a microemulsion to increase the solubility of triterpene and adlay. TMEs hold promise as an efficient drug delivery system for the treatment of lung cancer.Keywords: microemulsion, Ganoderma lucidum, triterpene, adlay seed oil, lung cancer

  19. Integration of Artificial Photosynthesis System for Enhanced Electronic Energy-Transfer Efficacy: A Case Study for Solar-Energy Driven Bioconversion of Carbon Dioxide to Methanol.

    Science.gov (United States)

    Ji, Xiaoyuan; Su, Zhiguo; Wang, Ping; Ma, Guanghui; Zhang, Songping

    2016-09-01

    Biocatalyzed artificial photosynthesis systems provide a promising strategy to store solar energy in a great variety of chemicals. However, the lack of direct interface between the light-capturing components and the oxidoreductase generally hinders the trafficking of the chemicals and photo-excited electrons into the active center of the redox biocatalysts. To address this problem, a completely integrated artificial photosynthesis system for enhanced electronic energy-transfer efficacy is reported by combining co-axial electrospinning/electrospray and layer-by-layer (LbL) self-assembly. The biocatalysis part including multiple oxidoreductases and coenzymes NAD(H) was in situ encapsulated inside the lumen polyelectrolyte-doped hollow nanofibers or microcapsules fabricated via co-axial electrospinning/electrospray; while the precise and spatial arrangement of the photocatalysis part, including electron mediator and photosensitizer for photo-regeneration of the coenzyme, was achieved by ion-exchange interaction-driven LbL self-assembly. The feasibility and advantages of this integrated artificial photosynthesis system is fully demonstrated by the catalyzed cascade reduction of CO2 to methanol by three dehydrogenases (formate, formaldehyde, and alcohol dehydrogenases), incorporating the photo-regeneration of NADH under visible-light irradiation. Compared to solution-based systems, the methanol yield increases from 35.6% to 90.6% using the integrated artificial photosynthesis. This work provides a novel platform for the efficient and sustained production of a broad range of chemicals and fuels from sunlight.

  20. Nab-paclitaxel Efficacy in the Orthotopic Model of Human Breast Cancer Is Significantly Enhanced By Concurrent Anti–Vascular Endothelial Growth Factor A Therapy

    Directory of Open Access Journals (Sweden)

    Lisa D. Volk

    2008-06-01

    Full Text Available Nab-paclitaxel is an albumin-bound 130-nm particle form of paclitaxel that has shown an improved efficacy in experimental tumor models and clinical studies compared with solvent-based paclitaxel. Anti–vascular endothelial growth factor A (VEGF-A antibody bevacizumab is known to enhance antitumor activity of cytotoxic drugs. This study evaluated the effects of combined nab-paclitaxel and bevacizumab therapy on growth and metastatic spread of orthotopic breast tumors. Cytotoxic and clonogenic assays measured VEGF-A–dependent modulation of nabpaclitaxel toxicity on cultured tumor cells. Antitumor effects were assessed in mice with luciferase-tagged, wellestablished MDA-MB-231 tumors (250–310 mm3 treated with one, two, or three cycles of nab-paclitaxel (10 mg/ kg, daily for five consecutive days, bevacizumab (2–8 mg/kg, twice a week, or with combination of both drugs. VEGF-A protected MDA-MB-231 cells against nab-paclitaxel cytotoxicity, whereas bevacizumab sensitized cells to the effect of the drug. Combined bevacizumab and nab-paclitaxel treatment synergistically inhibited tumor growth and metastasis resulting in up to 40% of complete regressions of well-established tumors. This therapy also decreased the incidence of lymphatic and pulmonary metastases by 60% and 100%, respectively. The significant increase in the cure of tumor-bearing mice in the nab-paclitaxel/bevacizumab combined group compared with mice treated with single drugs strongly advocates for implementing such strategy in clinics.

  1. Granulocyte-macrophage colony-stimulating factor DNA prime-protein boost strategy to enhance efficacy of a recombinant pertussis DNA vaccine

    Institute of Scientific and Technical Information of China (English)

    Qing-tian LI; Yong-zhang ZHU; Jia-you CHU; Ke DONG; Ping HE; Chun-yan FENG; Bao-yu HU; Shu-min ZHANG; Xiao-kui GUO

    2006-01-01

    Aim: To investigate a new strategy to enhance the efficacy of a recombinant pertussis DNA vaccine. The strategy is co-injection with cytokine plasmids as prime, and boosted with purified homologous proteins. Method: A recombinant pertussis DNA vaccine containing the pertussis toxin subunit 1 (PTS1), fragments of the filamentous hemagglutinin (FHA) gene and pertactin (PRN) gene encoding filamentous hemagglutinin and pertactin were constructed. Balb/c mice were immunized with several DNA vaccines and antigen-specific antibodies anti-PTSl, anti-PRN, anti-FHA, cytokines interleukin (IL)-10, IL-4, IFN-γ, TNF-oc, and spleno-cyte-proliferation assay were used to describe immune responses. Results: The recombinant DNA vaccine could elicit similar immune responses in mice as that of separate plasmids encoding the 3 fragments, respectively. Mice immunized with DNA and boosted with the corresponding protein elicited more antibodies than those that received DNA as boost. In particular, when the mice were co-immunized with murine granulocyte-macrophage colony-stimulating factor plasmids and boosted with proteins, all 4 cytokines and the 3 antigen-specific antibodies were significantly increased compared to the pVAXl group. Anti-PTSl, anti-FHA, IL-4 and TNF-α elicited in the colony stimulating factor (CSF) prime-protein boost group showed significant increase compared to all the other groups. Conclusion: This prime and boost strategy has proven to be very useful in improving the immunogenicity of DNA vaccines against pertussis.

  2. Enhanced efficacy of combined {sup 213}Bi-DTPA-F3 and paclitaxel therapy of peritoneal carcinomatosis is mediated by enhanced induction of apoptosis and G2/M phase arrest

    Energy Technology Data Exchange (ETDEWEB)

    Vallon, Mario; Seidl, Christof; Blechert, Birgit; Li, Zhoulei; Gaertner, Florian C.; Senekowitsch-Schmidtke, Reingard; Essler, Markus [Technische Universitaet Muenchen, Department of Nuclear Medicine, Munich (Germany); Gilbertz, Klaus-Peter [German Armed Forces, Institute of Radiobiology, Munich (Germany); Baumgart, Anja [Technische Universitaet Muenchen, III. Medical Department, Munich (Germany); Aichler, Michaela; Feuchtinger, Annette; Walch, Axel K. [Helmholtz Zentrum Muenchen, Institute of Pathology, Neuherberg (Germany); Bruchertseifer, Frank; Morgenstern, Alfred [Institute for Transuranium Elements, European Commission, Joint Research Centre, Karlsruhe (Germany)

    2012-12-15

    Targeted therapy with {alpha}-particle emitting radionuclides is a promising new option in cancer therapy. Stable conjugates of the vascular tumour-homing peptide F3 with the {alpha}-emitter {sup 213}Bi specifically target tumour cells. The aim of our study was to determine efficacy of combined {sup 213}Bi-diethylenetriaminepentaacetic acid (DTPA)-F3 and paclitaxel treatment compared to treatment with either {sup 213}Bi-DTPA-F3 or paclitaxel both in vitro and in vivo. Cytotoxicity of treatment with {sup 213}Bi-DTPA-F3 and paclitaxel, alone or in combination, was assayed towards OVCAR-3 cells using the alamarBlue assay, the clonogenic assay and flow cytometric analyses of the mode of cell death and cell cycle arrest. Therapeutic efficacy of the different treatment options was assayed after repeated treatment of mice bearing intraperitoneal OVCAR-3 xenograft tumours. Therapy monitoring was performed by bioluminescence imaging and histopathologic analysis. Treatment of OVCAR-3 cells in vitro with combined {sup 213}Bi-DTPA-F3 and paclitaxel resulted in enhanced cytotoxicity, induction of apoptosis and G2/M phase arrest compared to treatment with either {sup 213}Bi-DTPA-F3 or paclitaxel. Accordingly, i.p. xenograft OVCAR-3 tumours showed the best response following repeated (six times) combined therapy with {sup 213}Bi-DTPA-F3 (1.85 MBq) and paclitaxel (120 {mu}g) as demonstrated by bioluminescence imaging and histopathologic investigation of tumour spread on the mesentery of the small and large intestine. Moreover, mean survival of xenograft mice that received combined therapy with {sup 213}Bi-DTPA-F3 and paclitaxel was significantly superior to mice treated with either {sup 213}Bi-DTPA-F3 or paclitaxel alone. Combined treatment with {sup 213}Bi-DTPA-F3 and paclitaxel significantly increased mean survival of mice with peritoneal carcinomatosis of ovarian origin, thus favouring future therapeutic application. (orig.)

  3. Comparative efficacy of a yeast product and bacitracin methylene disalicylate in enhancing early growth and intestinal maturation in broiler chicks from breeder hens of different ages.

    Science.gov (United States)

    Fasina, Y O; Thanissery, R R

    2011-05-01

    The intestine of the newly hatched chick is immature at hatch. Yeast contains nucleotides and β-glucans that enhance intestinal development and chick growth. Accordingly, a 14-d experiment was conducted to evaluate the efficacy of a novel yeast product and bacitracin methylene disalicylate in enhancing early growth and intestinal maturation in chicks obtained from young (26-27 wk old) and old (58 to 59 wk old) breeder hens. Chicks (384) were randomly assigned to 8 dietary treatments. Treatment 1 (YH) consisted of chicks, from young hens, fed corn-soybean meal (SBM) diet alone. Treatment 2 (YHB) consisted of chicks, from young hens, fed corn-SBM basal into which BMD was added at 0.055 g/kg. Treatment 3 (YHE) consisted of chicks, from young hens, fed corn-SBM basal into which yeast extract (YE) was added at 0.075% level. Treatment 4 (YHED) consisted of chicks, from young hens, fed corn-SBM basal into which YE was added at 0.15% level. Treatments 5 (OH), 6 (OHB), 7 (OHE), and 8 (OHED) consisted of chicks from old hens fed diets similar to those given to YH in treatments 1, 2, 3, and 4, respectively. Growth performance (body weight gain and feed conversion ratio) was evaluated on d 7 and 14. Intestinal tissue samples were also analyzed for alkaline phosphatase (ALP) activity as an indicator of intestinal maturation on d 4 and 13 of experiment. Results showed that by d 14 of experiment, only BMD treatments (YHB and OHB) improved body weight gain (P yeast-supplemented treatments (YHE, YHED, OHE, and OHED) were statistically similar (P > 0.05) to those of the BMD treatments. Ileal ALP activity was consistently enhanced by BMD and yeast product supplemented at 0.075% of the diet. It was concluded that antibiotic BMD and our novel yeast product supplemented at 0.075% of the diet improved early chick growth and maturation of the ileal segment of the small intestine.

  4. Myeloablative temozolomide enhances CD8⁺ T-cell responses to vaccine and is required for efficacy against brain tumors in mice.

    Directory of Open Access Journals (Sweden)

    Luis A Sanchez-Perez

    Full Text Available Temozolomide (TMZ is an alkylating agent shown to prolong survival in patients with high grade glioma and is routinely used to treat melanoma brain metastases. A prominent side effect of TMZ is induction of profound lymphopenia, which some suggest may be incompatible with immunotherapy. Conversely, it has been proposed that recovery from chemotherapy-induced lymphopenia may actually be exploited to potentiate T-cell responses. Here, we report the first demonstration of TMZ as an immune host-conditioning regimen in an experimental model of brain tumor and examine its impact on antitumor efficacy of a well-characterized peptide vaccine. Our results show that high-dose, myeloablative (MA TMZ resulted in markedly reduced CD4(+, CD8(+ T-cell and CD4(+Foxp3(+ TReg counts. Adoptive transfer of naïve CD8(+ T cells and vaccination in this setting led to an approximately 70-fold expansion of antigen-specific CD8(+ T cells over controls. Ex vivo analysis of effector functions revealed significantly enhanced levels of pro-inflammatory cytokine secretion from mice receiving MA TMZ when compared to those treated with a lower lymphodepletive, non-myeloablative (NMA dose. Importantly, MA TMZ, but not NMA TMZ was uniquely associated with an elevation of endogenous IL-2 serum levels, which we also show was required for optimal T-cell expansion. Accordingly, in a murine model of established intracerebral tumor, vaccination-induced immunity in the setting of MA TMZ-but not lymphodepletive, NMA TMZ-led to significantly prolonged survival. Overall, these results may be used to leverage the side-effects of a clinically-approved chemotherapy and should be considered in future study design of immune-based treatments for brain tumors.

  5. Humanized monoclonal antibody 2C9-cIgG has enhanced efficacy for yellow fever prophylaxis and therapy in an immunocompetent animal model.

    Science.gov (United States)

    Julander, Justin G; Thibodeaux, Brett A; Morrey, John D; Roehrig, John T; Blair, Carol D

    2014-03-01

    Yellow fever virus (YFV) causes significant human disease and mortality in tropical regions of South and Central America and Africa, despite the availability of an effective vaccine. No specific therapy for YF is available. We previously showed that the humanized monoclonal antibody (MAb) 2C9-cIgG provided prophylactic and therapeutic protection from mortality in interferon receptor-deficient strain AG129 mice challenged with YF 17D-204 vaccine. In this study we tested the prophylactic and therapeutic efficacy of this MAb against virulent YFV infection in an immunocompetent hamster model. Intraperitoneal (ip) administration of a single dose of MAb 2C9-cIgG 24h prior to YFV challenge resulted in significantly improved survival rates in animals treated with 380 or 38 μg of MAb compared to untreated animals. Treatment with the higher dose also resulted in significantly improved weight gain and reductions in serum alanine aminotransferase (ALT) and virus titers in serum and liver. Prophylactic treatment with 2C9-cIgG 24h prior to virus challenge prevented the development of a virus-neutralizing antibody (vnAb) response in hamsters. Administration of a single ip dose of 380 μg of 2C9-cIgG as late as 72 h post-YFV challenge also resulted in significant improvement in survival rates. Hamsters treated at 4-72 h post-virus challenge developed a robust vnAb response. Enhanced survival and improvement of various disease parameters in the hamster model when MAb 2C9-cIgG is administered up to 3 days after virus challenge demonstrate the clinical potential of specific antibody therapy for YF.

  6. Chief Joseph Kokanee Enhancement Project; Strobe Light Deterrent Efficacy Test and Fish Behavior Determination at the Grand Coulee Dam Third Powerplant Forebay, 2002-2003 Annual Report.

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, R.; McKinstry, C.; Simmons, C. (Pacific Northwest National Laboratory)

    2003-01-01

    Since 1995, the Confederated Tribes of the Colville Reservation (Colville Confederated Tribes) have managed the Chief Joseph Kokanee Enhancement Project as part of the Northwest Power Planning Council (NWPPC) Fish and Wildlife Program. Project objectives have focused on understanding natural production of kokanee (a land-locked sockeye salmon) and other fish stocks in the area above Grand Coulee and Chief Joseph Dams on the Columbia River. A 42-month investigation concluded that entrainment at Grand Coulee Dam ranged from 211,685 to 576,676 fish annually. Further analysis revealed that 85% of the total entrainment occurred at the dam's third powerplant. These numbers represent a significant loss to the tribal fisheries upstream of the dam. In response to a suggestion by the NWPPC Independent Scientific Review Panel, the scope of work for the Chief Joseph Kokanee Enhancement Project was expanded to include a multiyear pilot test of a strobe light system to help mitigate fish entrainment. This report details the work conducted during the second year of the study by researchers of the Colville Confederated Tribes in collaboration with the Pacific Northwest National Laboratory. The 2002 study period extended from May 18 through July 30. The objective of the study was to determine the efficacy of a prototype strobe light system to elicit a negative phototactic response in kokanee and rainbow trout. The prototype system consisted of six strobe lights affixed to an aluminum frame suspended vertically underwater from a barge secured in the center of the entrance to the third powerplant forebay. The lights, controlled by a computer, were aimed to illuminate a specific region directly upstream of the barge. Three light level treatments were used: 6 of 6 lights on, 3 of 6 lights on, and all lights off. These three treatment conditions were applied for an entire 24-hr day and were randomly assigned within a 3-day block throughout the study period. A seven

  7. Chief Joseph Kokanee Enhancement Project : Strobe Light Deterrent Efficacy Test and Fish Behavior Determination at Grond Coulee Dam Third Powerplant Forebay.

    Energy Technology Data Exchange (ETDEWEB)

    Simmons, M.A.; McKinstry, C.A.; Simmons, C.S.

    2002-01-01

    Since 1995, the Colville Confederated Tribes have managed the Chief Joseph Kokanee Enhancement Project as part of the Northwest Power Planning Council's (NWPPC) Fish and Wildlife Program. Project objectives have focused on understanding natural production of kokanee (a land-locked sockeye salmon) and other fish stocks in the area above Grand Coulee and Chief Joseph Dams on the Columbia River. A 42-month investigation concluded that entrainment at Grand Coulee Dam ranged from 211,685 to 576,676 fish annually. Further analysis revealed that 85% of the total entrainment occurred at the dam's third powerplant. These numbers represent a significant loss to the tribal fisheries upstream of the dam. In response to a suggestion by the NWPPC's Independent Scientific Review Panel, the scope of work for the Chief Joseph Kokanee Enhancement Project was expanded to include a multiyear pilot test of a strobe light system to help mitigate fish entrainment. This report details the work conducted during the first year of the study by researchers of the Colville Confederated Tribes in collaboration with the Pacific Northwest National Laboratory (PNNL). The objective of the study was to determine the efficacy of a prototype strobe light system to elicit a negative phototactic response in kokanee and rainbow trout. Analysis of the effect of strobe lights on the distribution (numbers) and behavior of kokanee and rainbow trout was based on 51, 683 fish targets detected during the study period (June 30 through August 1, 2001). Study findings include the following: (1) Analysis of the count data indicated that significantly more fish were present when the lights were on compared to off. This was true for both the 24-hr tests as well as the 1-hr tests. Powerplant discharge, distance from lights, and date were significant factors in the analysis. (2) Behavioral results indicated that fish within 14 m of the lights were trying to avoid the lights by swimming across the lighted

  8. Quenching of singlet oxygen by natural and synthetic antioxidants and assessment of electronic UV/Visible absorption spectra for alleviating or enhancing the efficacy of photodynamic therapy

    Directory of Open Access Journals (Sweden)

    Kaneez Fatima

    2016-02-01

    Full Text Available Photodynamic therapy (PDT is one of the methods involved in cancer therapy exploiting singlet oxygen as a weapon to kill cancer cells. Singlet oxygen, a bizarre reactive oxygen species as it is not related to electron transfer to O2 but it is one of the most active intermediate involved in biochemical reactions as it directly reacts with all the major macromolecules like DNA, protein, lipids etc, various photosensitized oxidations and in the photodegradation of dyes and polymers. Recent studies about the usage of antioxidant along with the photo-sensitizer involved in photodynamic therapy have shown concentration- dependent dual behavior like usually it retards the efficacy of PDT but at a higher dose mostly, it actually enhances the damaging effect of PDT. The natural and synthetic antioxidants are being used in our day to day life in order to increase the shelf life of various food ingredients and processed foods. In this paper, we have compared natural and synthetic antioxidants along with the known singlet oxygen quencher (DABCO in order to understand the quenching potential of singlet oxygen (1O2 which is lowest electronically excited state of molecular oxygen. The singlet oxygen can be artificially generated through various methods such as sunlight, phosphate, ozonides, NaOCl and H2O2 etc. We have studied the mechanisms of the few antioxidant effects on the bleaching of RNO linked with the energy decay of 1O2 produced by the Mallet reaction (H2O2+HOCl and #8200; and #8594; and #8200;HCl+H2O+1O2. beta-Carotene, and #945;-Tocopherol, Ascorbic acid and Quercetin exhibited best dose-dependent singlet quenching ranging from 92.3 to 56.5 % at 100 and #956;M among others. Overall singlet oxygen is a major concern of light-related properties so we have analyzed the theoretical aspect of electronic UV/visible absorption spectra of the antioxidants studied through ZINDO CI semi-empirical Hamiltonian method. We have compared only the first singlet

  9. Analysis on the Ways to Enhance Independent College Students' Self-efficacy%提升独立学院学生自我效能感的路径分析

    Institute of Scientific and Technical Information of China (English)

    史娜

    2012-01-01

    Enhance independent college students' self-efficacy, can help students to actively and effectively complete their assignments at the university level tasks and to enhance the self-comprehensive quality, rapid integration into the community to lay a solid foundation for the future. Upgrade path of self-efficacy in independent colleges from three aspects exploration: reasonable set of the students professional learning to promote student's accumulated experience and vicarious experience success in school, the use of reinforced rules to enhance students' self-awareness, the use of the theory of positive emotions enhance ability students emotionality.%提升独立学院学生的自我效能感,能够帮助学生在大学阶段积极有效地完成课业任务并全面提升自我综合素质,为今后快速融入社会夯实基础。自我效能感在独立学院的提升路径可从三个方面探析:合理设置学生专业学习方式以促进学生在校成功经验及替代经验的积累、运用补强法则提升学生自我感知能力、运用积极情绪理论提升对学生的情绪唤醒能力。

  10. Chief Joseph Kokanee Enhancement Project; Strobe Light Deterrent Efficacy Test and Fish Behavior Determination at the Grand Coulee Dam Third Powerplant Forebay, 2003-2004 Annual Report.

    Energy Technology Data Exchange (ETDEWEB)

    Simmons, M.; McKinstry, C.; Cook, C.

    2004-01-01

    Since 1995, the Confederated Tribes of the Colville Reservation (Colville Confederated Tribes) have managed the Chief Joseph Kokanee Enhancement Project as part of the Northwest Power Planning Council (NWPPC) Fish and Wildlife Program. Project objectives have focused on understanding natural production of kokanee (a land-locked sockeye salmon) and other fish stocks in the area above Grand Coulee and Chief Joseph Dams on the Columbia River. A 42-month investigation from 1996 to 1999 determined that from 211,685 to 576,676 fish were entrained annually at Grand Coulee Dam. Analysis of the entrainment data found that 85% of the total entrainment occurred at the dam's third powerplant. These numbers represent a significant loss to the tribal fisheries upstream of the dam. In response to a suggestion by the NWPPC Independent Scientific Review Panel, the scope of work for the Chief Joseph Kokanee Enhancement Project was expanded to include a multiyear pilot test of a strobe light system to help mitigate fish entrainment. This report details the work conducted during the third year of the strobe light study by researchers of the Colville Confederated Tribes in collaboration with the Pacific Northwest National Laboratory. The objective of the study is to determine the efficacy of a prototype strobe light system to elicit a negative phototactic response in kokanee and rainbow trout under field conditions. The prototype system consists of six strobe lights affixed to an aluminum frame suspended 15 m vertically underwater from a barge secured in the center of the entrance to the third powerplant forebay. The lights, controlled by a computer, illuminate a region directly upstream of the barge. The 2003 study period extended from June 16 through August 1. Three light treatments were used: all six lights on for 24 hours, all lights off for 24 hours, and three of six lights cycled on and off every hour for 24 hours. These three treatment conditions were assigned randomly

  11. Path to Enhance Private College Counselors' Self-efficacy%民办高校辅导员自我效能提升路径研究

    Institute of Scientific and Technical Information of China (English)

    王库; 查宇驰

    2014-01-01

    民办高校的自身发展的现状和特点,使得民办高校辅导员自我效能现状问题较多,其辅导员自我效能的提升应成为民办高校迫切关注的问题加以重视。根据Bandura自我效能研究的理论,本文将从民办高校的现状和特点针对民办高校辅导员自我效能提升进行研究,试探提出辅导员自我、系部组织、高校三位一体的自我效能提升路径。%With regards to the current development status and characteristics of private colleges, the problem of counselors' self-efficacy is increasing. And promote of private college counselors self-efficacy should be gain more concern. According to the theory of Bandura self-efficacy research, this article will make research from the status and characteristics of private colleges on the promotion of self-efficacy of the colleges counselors. In this paper a trinity of self-efficacy (which includes the counselor, schools and college) path was put forward.

  12. Toothbrushing efficacy

    NARCIS (Netherlands)

    Rosema, N.A.M.

    2015-01-01

    This thesis will explore the most meaningful aspects which are considered to be of interest regarding the efficacy of toothbrushes. One could discuss efficacy by means of plaque removal as well as by means of the effect on gingival inflammation. Plaque removal may be considered as a surrogate effect

  13. Enhanced antitumor efficacy and counterfeited cardiotoxicity of combinatorial oral therapy using Doxorubicin- and Coenzyme Q10-liquid crystalline nanoparticles in comparison with intravenous Adriamycin

    DEFF Research Database (Denmark)

    Swarnakar, Nitin K; Thanki, Kaushik; Jain, Sanyog

    2014-01-01

    and strong synergism for combination at 1:10 dose ratio owing to higher cellular uptake, nuclear colocalization, higher apoptotic index and 8-OHdG levels. The prophylactic antitumor efficacy of the CoQ10-LCNPs was also established using tumor induction and progression studies. Finally, therapeutic antitumor...... efficacy was found to be significantly higher (~1.76- and ~4.5-fold) for the combination as compared to Dox-LCNPs (per oral) and Adriamycin (i.v.) respectively. Notably, level of residual tumor burden was insignificant (P>0.05) after 30days in case of combination and LipoDox® (i.v.). Interestingly......, with Dox-induced-cardiotoxicity was completely counterfeited in combination. In nutshell, LCNPs pose great potential in improving the therapeutic efficacy of drugs by oral route of administration. FROM THE CLINICAL EDITOR: This study describes the use of liquid crystalline nanoparticles containing coenzyme...

  14. Impact of the enhanced education of"eight kinds of consciousness"on the self-efficacy and creative efficacy of nursing students before clinical practice%实习前实训课教学中强化"八种意识"教育对护生自我效能和创新效能的影响

    Institute of Scientific and Technical Information of China (English)

    李小苑

    2012-01-01

    目的:探讨护生实习前实训课教学过程中强化"八种意识"教育对其自我效能、创新效能及实训成绩的影响.方法:将我院统招录取的三年制护理专科层次2个班的学生100名作为研究对象,并设为研究班和对照班各50名;对照班按照学院教务科安排进行实习前实训课教学,研究班在进行实习前实训课教学的同时,强化"八种意识"教育.两班同时开始实习前的实训课教学,实训课开始、结束时分别采用自我效能感量表、大学生创新效能感量表评定护生自我效能、创新效能状况,比较实训课前后两班学生自我效能感、创新效能感及实训成绩.结果:实训课后研究班学生自我效能感、创新效能感及实训考核成绩均优于对照班(P<0.01).结论:护生实习前进行实训课教学,同时强化"八种意识"教育,对护生自我效能、创新效能及实训成绩均有良好的影响和促进改善作用.%Objective: To investigate the impact of the enhanced education of" eight kinds of consciousness" on the self -efficacy and creative efficacy of nursing students before clinical practice. Methods: 100 3 - year college students of 2 classes enrolled by national entrance examination were taken as the object of study and were divided into the study group and the control group( 50 students in each group ). The students in the control group were arranged to have internship training course before clinical practice and the students in the study group were additionally given the enhanced education of " eight kinds of consciousness" . The self - efficacy and creative efficacy of nursing students were assessed by self - efficacy scale and creative efficacy scale and compared between the two groups before and after training course. Residts:The self - efficacy,creative efficacy and examination results of nursing students were better in the study group than the control group( P <0. 01 ). Conclusion:The enhanced

  15. The Development and Evaluation of an Achievement Test for Measuring the Efficacy of Task-Based Writing Activities to Enhance Iranian EFL Learners' Reading Comprehension

    Science.gov (United States)

    Nejad, Ferdows Mohsen; Khosravian, Fereshteh

    2014-01-01

    The present study examined the reliability of an achievement test to measure the efficacy of task-based writing activities to improve Iranian EFL learners' reading comprehension at the intermediate level in a private language institute in Ilam, Iran, namely Alefba language institute. To achieve the goal, the techniques for evaluating reliability…

  16. Enhanced antifungal efficacy in experimental invasive pulmonary aspergillosis by combination of AmBisome with Fungizone as assessed by several parameters of antifungal response

    NARCIS (Netherlands)

    M.J. Becker (Martin); S. de Marie (Siem); M.H.A.M. Fens (Marcel); W.C.J. Hop (Wim); H.A. Verbrugh (Henri); I.A.J.M. Bakker-Woudenberg (Irma)

    2002-01-01

    textabstractIn common with a proportion of patients with invasive pulmonary aspergillosis (IPA), the efficacy of AmBisome treatment regimens in our rat model remains suboptimal. To investigate whether this might be the result of initially low antifungal activity of amphotericin B a

  17. Enhancing the Efficacy of Prostate Cancer Immunotherapy by Manipulating T-Cell Receptor Signaling in Order to Alter Peripheral Regulatory T-Cell Activity

    Science.gov (United States)

    2009-07-01

    27] Ross S, Spencer SD, Holcomb I, Tan C, Hongo J, Devaux B, et al. Prostate stem cell antigen as therapy target: tissue expression and in vivo...Holcomb I, Tan C, Hongo J, Devaux B, et al. Prostate stem cell antigen as therapy target: tissue expression and in vivo efficacy of an immunoconjugate

  18. Enhancing Physical Education and Sport Science Students' Self-Efficacy and Attitudes regarding Information and Communication Technologies through a Computer Literacy Course

    Science.gov (United States)

    Papastergiou, Marina

    2010-01-01

    Information and Communication Technologies (ICT) have become an integral component of Physical Education (PE) and Sport Science (SS) curricula and professions. It is thus imperative that PE and SS students develop ICT skills, self-efficacy in ICT and positive attitudes towards ICT. This study was aimed at designing a computer literacy course…

  19. Lipid nanocarriers of a lipid-conjugated estrogenic derivative inhibit tumor growth and enhance cisplatin activity against triple-negative breast cancer: pharmacokinetic and efficacy evaluation.

    Science.gov (United States)

    Andey, Terrick; Sudhakar, Godeshala; Marepally, Srujan; Patel, Apurva; Banerjee, Rajkumar; Singh, Mandip

    2015-04-06

    Breast cancer is the leading cause of malignancies among women globally. The triple negative breast cancer (TNBC) subtype is the most difficult to treat and accounts for 15% of all cases. Targeted therapies have been developed for TNBC but come short of clinical translation due to acquired tumor resistance. An effective therapy against TNBC must combine properties of target specificity, efficient tumor killing, and translational relevance. The objective of this study was to formulate a nontoxic, cationic, lipid-conjugated estrogenic derivative (ESC8), with demonstrated anticancer activity, for oral delivery in mice bearing triple negative breast cancer (TNBC) as xenograft tumors. The in vitro cell viability, Caco-2 permeability, and cell cycle dynamics of ESC8-treated TNBC cells were investigated. ESC8 was formulated as liposomes, solid lipid nanoparticles (SLNs), and nanostructured lipid carriers (NLCs) and characterized for size, zeta potential, entrapment efficiency, size stability, and tumor biodistribution. Pharmacokinetic modeling of plasma concentration-time course data was carried out following intravenous and oral administration in Sprague-Dawley rats. In vivo efficacy investigation of ESC8-SLNC was carried out in Nu/Nu mice bearing MDA-MB-231 TNBC as xenograft tumors, and the molecular dynamics modulating tumor growth inhibition was analyzed by Western blot. In vitro ESC8 inhibited TNBC and non-TNBC cell viability with IC50 ranging from 1.81 to 3.33 μM. ESC8 was superior to tamoxifen and Cisplatin in inhibiting MDA-MB-231 cell viability; and at 2.0 μM ESC8 enhanced Cisplatin cytotoxicity 16-fold. Intravenous ESC8 (2.0 mg/kg) was eliminated at a rate of 0.048 ± 0.01 h(-1) with a half-life of 14.63 ± 2.95 h in rats. ESC8 was orally bioavailable (47.03%) as solid lipid nanoparticles (ESC8-SLN). ESC8-SLN (10 mg/kg/day, ×14 days, p.o.) inhibited breast tumor growth by 74% (P < 0.0001 vs control) in mice bearing MDA-MB-231 cells as xenografts; and when

  20. 路径化健康教育改善肠造口病人自我效能%Health education path enhances self-efficacy of stoma patients

    Institute of Scientific and Technical Information of China (English)

    郑蕾; 金艳; 施晓群; 张慧; 徐菁

    2016-01-01

    Objective To assess health education path in improving the self-efficacy of stoma patients. Methods A total of 80 cases, who underwent enterostomy in the department of surgery Ruijin Hospital from May to December 2012, were divided into intervention group and control group 40 cases each. The patients in intervention group adopted health education path and the patients in control group adopted routine health education. Self-efficacy of the patients was com-pared between 2 groups with the test using stoma self-efficacy scale before surgery, 1 week after surgery and discharge. A follow-up of postoperative self-efficacy was done by telephone in 2015. Results The score of self-efficacy of patients in in-tervention group (74.35 ±27.90) were higher than that in control group (51.30 ±22.58) (P0.05). Sixty-two cases were followed and 18 cases lost (22.5%). The follow-up showed that the score of intervention group (108.27±12.29) were higher than that of control group (93.93±13.23), P0.05)。术后随访病人62例,失访18例,失访率为22.5%。术后随访干预组病人自我效能评分(108.27±12.29)高于对照组病人自我效能评分(93.93±13.23),P<0.05。结论:应用路径化健康教育能改善肠造口病人术后自我效能。

  1. Cilengitide in Treating Children With Refractory Primary Brain Tumors

    Science.gov (United States)

    2013-09-27

    Childhood Central Nervous System Germ Cell Tumor; Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Ependymoblastoma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood High-grade Cerebellar Astrocytoma; Childhood High-grade Cerebral Astrocytoma; Childhood Infratentorial Ependymoma; Childhood Low-grade Cerebellar Astrocytoma; Childhood Low-grade Cerebral Astrocytoma; Childhood Medulloepithelioma; Childhood Mixed Glioma; Childhood Oligodendroglioma; Childhood Supratentorial Ependymoma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Brain Tumor; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma

  2. Protein-pacing caloric-restriction enhances body composition similarly in obese men and women during weight loss and sustains efficacy during long-term weight maintenance

    DEFF Research Database (Denmark)

    Arciero, Paul J; Edmonds, Rohan; He, Feng

    2016-01-01

    /day) in obese adults. Less is known whether obese men and women respond similarly to P-CR during weight loss (WL) and whether a modified P-CR (mP-CR) is more efficacious than a HH diet during long-term (52 week) weight maintenance (WM). The purposes of this study were to evaluate the efficacy of: (1) P......-CR on TBF, ABF, resting metabolic rate (RMR), and biomarkers between obese men and women during WL (weeks 0-12); and (2) mP-CR compared to a HH diet during WM (weeks 13-64). During WL, men (n = 21) and women (n = 19) were assessed for TBF, ABF, VAT, RMR, and biomarkers at weeks 0 (pre) and 12 (post). Men......) completed WM. mP-CR regained significantly less body weight (6%), TBF (12%), and ABF (17%) compared to HH (p diet....

  3. The Influence of An Enhanced Night Guard Vital Bleaching Therapy on Treatment Efficacy and Stability%活髓牙夜间脱色后巩固治疗对美白效果稳定性的影响

    Institute of Scientific and Technical Information of China (English)

    杜森; 王旭东; 纪虹利; 高玉光

    2014-01-01

    Objective To evaluate the clinical efficacy of an enhanced therapy after night guard vital bleaching to maintain a longer whitening effect .Methods Fifty pre-selected patients with discolored teeth were randomly and evenly divided into 2 groups .The treatment group received one enhanced therapy every month after night guard vital bleaching,a total of 12 times.The control group was treated with NGVB only .Vitalescence Esthetic Restorative Masters Shade Guide was used to record the change of color and help evaluate the lightening efficacy .Two groups were followed up for two years and the lightening efficacy was evaluated again by then .Results Two years later ,the treatment group's bleaching efficacy stayed the same as two years ago ,while that of control group dropped greatly .Conclusion The en-hanced therapy could greatly reduce the rebounce of discoloration .It is economical and practical ,easy to operate ,and is highly recommended to be used along with NGVB .%目的:评价巩固治疗在活髓牙夜间脱色( NGVB)中维持美白效果的影响。方法经过筛选的50位变色牙患者被随机均分为两组接受16%过氧化脲NGVB治疗。实验组在常规NGVB治疗后每个月巩固治疗1次,巩固12次,对照组则仅接受常规的NGVB漂白治疗。用VITALESCENCE美学修复比色板比较牙齿漂白前后的色阶变化,追踪2年后,再次评价漂白临床效果。结果实验组美白有效率与2年前相比无明显差异而对照组则下降明显。结论巩固治疗能够减少美白后效果反弹,经济实惠,操作简单,值得在NGVB治疗后推广。

  4. Oral lipid-based nanoformulation of tafenoquine enhanced bioavailability and blood stage antimalarial efficacy and led to a reduction in human red blood cell loss in mice

    Directory of Open Access Journals (Sweden)

    Melariri P

    2015-02-01

    Full Text Available Paula Melariri,1 Lonji Kalombo,2 Patric Nkuna,2 Admire Dube,2,3 Rose Hayeshi,2 Benhards Ogutu,4,5 Liezl Gibhard,6 Carmen deKock,6 Peter Smith,6 Lubbe Wiesner,6 Hulda Swai2 1Polymers and Composites, Material Science and Manufacturing, Council for Scientific and Industrial Research, Port Elizabeth, South Africa; 2Polymer and Composites, Material Science and Manufacturing, Council for Scientific and Industrial Research, Pretoria, South Africa; 3School of Pharmacy, University of the Western Cape, Bellville, South Africa; 4Centre for Research in Therapeutic Sciences, Strathmore University, Nairobi, Kenya; 5Centre for Clinical Research, Kenya Medical Research Institute, Nairobi, Kenya; 6Division of Pharmacology, University of Cape Town Medical School, Groote Schuur Hospital, Cape Town, South Africa Abstract: Tafenoquine (TQ, a new synthetic analog of primaquine, has relatively poor bioavailability and associated toxicity in glucose-6-phosphate dehydrogenase (G6PD-deficient individuals. A microemulsion formulation of TQ (MTQ with sizes <20 nm improved the solubility of TQ and enhanced the oral bioavailability from 55% to 99% in healthy mice (area under the curve 0 to infinity: 11,368±1,232 and 23,842±872 min·µmol/L for reference TQ and MTQ, respectively. Average parasitemia in Plasmodium berghei-infected mice was four- to tenfold lower in the MTQ-treated group. In vitro antiplasmodial activities against chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum indicated no change in half maximal inhibitory concentration, suggesting that the microemulsion did not affect the inherent activity of TQ. In a humanized mouse model of G6PD deficiency, we observed reduction in toxicity of TQ as delivered by MTQ at low but efficacious concentrations of TQ. We hereby report an enhancement in the solubility, bioavailibility, and efficacy of TQ against blood stages of Plasmodium parasites without a corresponding increase in toxicity

  5. Protein-pacing caloric-restriction enhances body composition similarly in obese men and women during weight loss and sustains efficacy during long-term weight maintenance

    DEFF Research Database (Denmark)

    Arciero, Paul J; Edmonds, Rohan; He, Feng;

    2016-01-01

    Short-Term protein-pacing (P; ~6 meals/day, >30% protein/day) and caloric restriction (CR, ~25% energy deficit) improves total (TBF), abdominal (ABF) and visceral (VAT) fat loss, energy expenditure, and biomarkers compared to heart healthy (HH) recommendations (3 meals/day, 15% protein/day) in ob......Short-Term protein-pacing (P; ~6 meals/day, >30% protein/day) and caloric restriction (CR, ~25% energy deficit) improves total (TBF), abdominal (ABF) and visceral (VAT) fat loss, energy expenditure, and biomarkers compared to heart healthy (HH) recommendations (3 meals/day, 15% protein....../day) in obese adults. Less is known whether obese men and women respond similarly to P-CR during weight loss (WL) and whether a modified P-CR (mP-CR) is more efficacious than a HH diet during long-term (52 week) weight maintenance (WM). The purposes of this study were to evaluate the efficacy of: (1) P...... and women had similar reductions (p weight (10%), TBF (19%), ABF (25%), VAT (33%), glucose (7%-12%), insulin (40%), leptin (>50%) and increase in % lean body mass (9%). RMR (kcals/kg bodyweight) was unchanged and respiratory quotient decreased 9%. Twenty-four subjects (mP-CR, n = 10; HH, n = 14...

  6. Metronomic paclitaxel-loaded mPEG-PLA nanoparticles show enhanced anti-tumor efficacy compared to maximum tolerated dose administration

    Science.gov (United States)

    Fei, Tan; Yang, Lian-juan; Mo, Xiao-hui; Wang, Xiu-li; Jun, Gu

    2014-11-01

    Low-dose metronomic (LDM) chemotherapy with cytotoxic agents, aimed at disrupting tumor endothelial cells, is an alternative method to maximum tolerated dose chemotherapy targeting proliferating tumor cells in clinical practice. However, even in the LDM schedule, cytotoxic agents still exhibit serious side effects due to non-distribution and high accumulated doses in the body. Nanocarriers can maximize the efficacy of the encapsulated drug by adjusting the pharmacokinetics and bio-distribution pattern, and minimize excessive toxic side effects. In the present study, we prepared polyethylene glycol (PEG)-coated stealth nanoparticles containing paclitaxel (PTX-NP) in order to evaluate their accumulation in tumor and their anti-tumor activity following LDM administration. PTX-NPs were prepared by a modified emulsification/solvent diffusion method with methoxy PEG-poly(lactide). The in vitro viability, migration, and tube formation of primary human umbilical vein endothelial cells, in addition to thrombospondin-1 positive expression and microvessel density in vivo, confirmed the anti-angiogenic activity of PTX-NP. The cellular uptake and retention study, in addition to pharmacokinetics in Sprague-Dawley rats demonstrated sustained circulation of PTX-NP. The in vivo tumor accumulation of PTX-NP was monitored using the Xenogen IVIS 200 non-invasive optical imaging system. The anti-tumor activity of LDM PTX-NP was studied in B16 melanoma cancer-bearing mice in vivo. In conclusion, PTX-NP improved tumor accumulation and anti-tumor efficacy following LDM administration.

  7. Non-RVD mutations that enhance the dynamics of the TAL repeat array along the superhelical axis improve TALEN genome editing efficacy

    Science.gov (United States)

    Tochio, Naoya; Umehara, Kohei; Uewaki, Jun-ichi; Flechsig, Holger; Kondo, Masaharu; Dewa, Takehisa; Sakuma, Tetsushi; Yamamoto, Takashi; Saitoh, Takashi; Togashi, Yuichi; Tate, Shin-ichi

    2016-01-01

    Transcription activator-like effector (TALE) nuclease (TALEN) is widely used as a tool in genome editing. The DNA binding part of TALEN consists of a tandem array of TAL-repeats that form a right-handed superhelix. Each TAL-repeat recognises a specific base by the repeat variable diresidue (RVD) at positions 12 and 13. TALEN comprising the TAL-repeats with periodic mutations to residues at positions 4 and 32 (non-RVD sites) in each repeat (VT-TALE) exhibits increased efficacy in genome editing compared with a counterpart without the mutations (CT-TALE). The molecular basis for the elevated efficacy is unknown. In this report, comparison of the physicochemical properties between CT- and VT-TALEs revealed that VT-TALE has a larger amplitude motion along the superhelical axis (superhelical motion) compared with CT-TALE. The greater superhelical motion in VT-TALE enabled more TAL-repeats to engage in the target sequence recognition compared with CT-TALE. The extended sequence recognition by the TAL-repeats improves site specificity with limiting the spatial distribution of FokI domains to facilitate their dimerization at the desired site. Molecular dynamics simulations revealed that the non-RVD mutations alter inter-repeat hydrogen bonding to amplify the superhelical motion of VT-TALE. The TALEN activity is associated with the inter-repeat hydrogen bonding among the TAL repeats. PMID:27883072

  8. Assessing the efficacy of the healthy eating and lifestyle programme (HELP compared with enhanced standard care of the obese adolescent in the community: study protocol for a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Christie Deborah

    2011-11-01

    Full Text Available Abstract Background The childhood obesity epidemic is one of the foremost UK health priorities. Childhood obesity tracks into adult life and places individuals at considerable risk for diabetes, cardiovascular disease, liver disease and other morbidities. There is widespread need for paediatric lifestyle programmes as change may be easier to accomplish in childhood than later in life. Study Design/Method The study will evaluate the management of adolescent obesity by conducting a Medical Research Council complex intervention phase III efficacy randomised clinical trial of the Healthy Eating Lifestyle Programme within primary care. The study tests a community delivered multi-component intervention designed for adolescents developed from best practice as identified by National Institute for Health and Clinical Excellence. The hospital based pilot reduced body mass index and improved health-related quality of life. Subjects will be individually randomised to receiving either the Healthy Eating Lifestyle Programme (12 fortnightly family sessions or enhanced standard care. Baseline and follow up assessments will be undertaken blind to allocation status. A health economic evaluation is also being conducted. 200 obese young people (13-17 years, body mass index > 98th centile for age and sex will be recruited from primary care within the greater London area. The primary hypothesis is that a motivational and solution-focused family-based weight management programme delivered over 6 months is more efficacious in reducing body mass index in obese adolescents identified in the community than enhanced standard care. The primary outcome will be body mass index at the end of the intervention, adjusted for baseline body mass index, age and sex. The secondary hypothesis is that the Healthy Eating Lifestyle Programme is more efficacious in improving quality of life and psychological function and reducing waist circumference and cardiovascular risk factors in

  9. A Pilot Study of the Feasibility and Efficacy of the Strategies to Enhance Positive Parenting (STEPP) Program for Single Mothers of Children with ADHD

    Science.gov (United States)

    Chacko, Anil; Wymbs, Brian T.; Flammer-Rivera, Lizette M.; Pelham, William E.; Walker, Kathryn S.; Arnold, Fran W.; Visweswaraiah, Hema; Swanger-Gagne, Michelle; Girio, Erin L.; Pirvics, Lauma L.; Herbst, Laura

    2008-01-01

    Objective: The Strategies to Enhance Positive Parenting (STEPP) program was developed to address putative factors related to poor engagement in and outcomes following traditional behavioral parent training (BPT) for single mothers of children diagnosed with ADHD. Method: Twelve single mothers of children with ADHD were enrolled in an initial…

  10. Efficacy of single dose pegfilgrastim in enhancing the mobilization of CD34+ peripheral blood stem cells in aggressive lymphoma patients treated with cisplatin-aracytin-containing regimens.

    Science.gov (United States)

    Nosari, A; Cairoli, R; Ciapanna, D; Gargantini, L; Intropido, L; Baraté, C; Scarpati, B; Santoleri, L; Nador, G; Pezzetti, L; Morra, E

    2006-09-01

    Systematic data on the ability of pegfilgrastim to mobilize stem cells after chemotherapy are scarce. We evaluated the efficacy of a single 6 mg dose of pegfilgrastim for mobilizing peripheral blood stem cells (PBSC) in aggressive lymphoma patients. Between July 2004 and October 2005, 17 aggressive non-Hodgkin's lymphoma and 11 poor-risk Hodgkin's lymphoma were treated with cycles containing cisplatin-aracytin. At the end of chemotherapy, the patients received 6 mg of pegfilgrastim. Duration of grade 4 neutropenia, adverse events, time to neutrophil recovery, peak and harvest of CD34+ cells were recorded. Twenty-seven out of 28 patients harvested a median of 17.3 x 10(6)/CD34+ cells (range 2.5-28.9) after a median of 9 days (range 8-12 days), with a single apheresis procedure in 25 cases. All patients had grade 3-4 neutropenia, median duration 3 days. The only adverse event was mild bone pain. To date, 13 patients have been autografted with a median of 15.4 x 10(6) CD34+ pegfilgrastim-mobilized cells per kg (range 2.5-28.9) with rapid and sustained engraftment. Mobilization, harvesting and autografting of pegfilgrastim-mobilized PBC can be successfully achieved in pretreated patients with aggressive lymphoma.

  11. Scientific Opinion on the safety and efficacy of Suilectin? (Phaseolus vulgaris lectins as a zootechnical additive for suckling piglets (performance enhancer

    Directory of Open Access Journals (Sweden)

    EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP

    2015-01-01

    Full Text Available The active substance of Suilectin™ is a mixture of five phytohaemagglutinin (PHA isoforms. The Panel on Additives and Products or Substances used in Animal Feed (FEEDAP considers that the haemagglutination activity (measured by haemagglutinating units (HAUs does not reflect the biological activity of the additive in a comprehensive way. The additive is intended only for aqueous suspension in water for drinking or in liquid complementary feed for suckling piglets. The FEEDAP Panel concludes that the additive is safe for suckling piglets when used under the proposed conditions of use of 220 HAU/piglet for three days. The Panel also considers that there are no reasons to expect that the dose of 660 HAU/piglet in a single administration would not be safe. The use of Suilectin in accordance with the conditions of use proposed by the applicant is considered to be of no concern for the health of the consumer. Suilectin is not an irritant to skin or eyes and is not a skin sensitiser. However, considering its physical and toxicological properties, there is a potential hazard by inhalation exposure. Considering that PHAs are immunogenic substances, the additive should be considered to be a respiratory sensitiser. The additive is a natural plant substance and its use will not result in a substantial increase in concentration in the environment. Therefore there are no safety concerns for the environment. The FEEDAP Panel cannot conclude on the efficacy of the additive in suckling piglets.

  12. A fusogenic dengue virus-derived peptide enhances antitumor efficacy of an antibody-ribonuclease fusion protein targeting the EGF receptor.

    Science.gov (United States)

    Kiesgen, Stefan; Liebers, Nora; Cremer, Martin; Arnold, Ulrich; Weber, Tobias; Keller, Armin; Herold-Mende, Christel; Dyckhoff, Gerhard; Jäger, Dirk; Kontermann, Roland E; Arndt, Michaela A E; Krauss, Jürgen

    2014-10-01

    Due to its frequent overexpression in a variety of solid tumors the epidermal growth factor receptor (EGFR) is a well-established target for therapeutic interventions in epithelial cancers. In order to target EGFR in head and neck cancer, we have generated a ribonuclease (RNase) fusion protein comprising a humanized anti-EGFR antibody single-chain Fv fragment (scFv) and Ranpirnase, an RNase from Rana pipiens. Fusion of Ranpirnase to the N-terminus of the scFv via a flexible glycine-serine linker (G4S)3 resulted in very poor cytotoxicity of the fusion protein. As endosomal accumulation and lysosomal degradation have been reported to diminish the antitumor efficacy of ribonuclease or toxin-based immunoagents, we explored a fusion peptide from dengue virus that has been reported to be involved in the endosomal escape of the virus. This peptide was introduced as a linker between Ranpirnase and the scFv moiety. The modified immunoRNase exhibited exceptionally high cytotoxicity toward EGFR-expressing head and neck cell lines without affecting specificity. These results indicate that endosomal entrapment needs to be considered for Ranpirnase-based immunoagents and might be overcome by the use of tailored transduction domains from viral proteins.

  13. Enhanced immunogenicity of multiple-epitopes of foot-and-mouth disease virus fused with porcine interferon alpha in mice and protective efficacy in guinea pigs and swine.

    Science.gov (United States)

    Du, Yijun; Li, Yufeng; He, Hairong; Qi, Jing; Jiang, Wenming; Wang, Xinglong; Tang, Bo; Cao, Jun; Wang, Xianwei; Jiang, Ping

    2008-04-01

    Foot-and-mouth disease (FMD) is a highly contagious and economically devastating vesicular disease of cloven-hoofed animals. In this study, three amino acid residues 21-60, 141-160 and 200-213 from VP1 protein of FMDV were selected as multiple-epitopes (VPe), and a recombinant adenovirus expressing the multiple-epitopes fused with porcine interferon alpha (rAd-pIFN alpha-VPe) was constructed. Six groups of female BALB/c mice (18 mice per group) were inoculated subcutaneously (s.c.) twice at 2-week intervals with the recombinant adenoviruses and the immune responses were examined. Following this the protective efficacy of rAd-pIFN alpha-VPe was examined in guinea pigs and swine. The results showed that both FMDV-specific humoral and cell-mediated immune responses could be induced by rAd-VPe and increased when rAd-pIFN alpha is included in this regime in mice model. Moreover, the levels of the immune responses in the group inoculated with rAd-pIFN alpha-VPe were significantly higher than the group inoculated with rAd-VPe plus rAd-pIFN alpha. All guinea pigs and swine vaccinated with rAd-pIFN alpha-VPe were completely protected from viral challenge. It demonstrated that recombinant adenovirus rAd-pIFN alpha-VPe might be an attractive candidate vaccine for preventing FMDV infection.

  14. Enhancing the efficacy of delivering reperfusion therapy: a European and North American experience with ST-segment elevation myocardial infarction networks.

    Science.gov (United States)

    Huber, Kurt; Goldstein, Patrick; Danchin, Nicolas; Fox, Keith A A; Welsh, Robert; Granger, Christopher B; Henry, Timothy; Gersh, Bernard J

    2013-02-01

    Advances in technique and adjunctive medication have improved outcome of ST-segment elevation myocardial infarction (STEMI) patients. However, the timely delivery and administration of reperfusion strategies to all eligible patients remain challenging. Currently, up to one-third of eligible STEMI patients in industrialized countries worldwide receive no specific reperfusion treatment, a problem that is rectified by the development and implementation of STEMI networks, as also recommended by the latest European Society of Cardiology and American College of Cardiology/American Heart Association guidelines. Indeed, over the last 5 years, published figures demonstrate that STEMI networks increase the percentage of patients treated by any reperfusion strategy, and the percentage of patients receiving treatment within the recommended time frames has also improved, thereby reducing in-hospital and long-term mortality to very low levels. This manuscript demonstrates how STEMI networks can be adapted to local needs and circumstances against pre-existing barriers and despite the heterogeneity in local situations, patient's characteristics, treatment delays, and distances for transfer. Modern and efficacious networks must be prepared to offer both primary percutaneous coronary intervention and thrombolytic therapy, preferably prehospital, as long as primary percutaneous coronary intervention cannot be guaranteed to all individuals within the recommended timeline.

  15. Study of the enhanced anticancer efficacy of gambogic acid on Capan-1 pancreatic cancer cells when mediated via magnetic Fe3O4 nanoparticles

    Directory of Open Access Journals (Sweden)

    Wang C

    2011-09-01

    Full Text Available Cailian Wang1,*, Haijun Zhang1,*, Baoan Chen2, Haitao Yin1, Wenwen Wang11Department of Oncology, Zhongda Hospital, Medical School, Southeast University, Nanjing, People's Republic of China; 2Department of Hematology, Zhongda Hospital, Medical School, Southeast University, Nanjing, People's Republic of China *These authors contributed equally to this workBackground: Gambogic acid (GA, a potent anticancer agent, is limited in clinical administration due to its poor water solubility. The aim of this study was to explore a drug delivery system based on magnetic Fe3O4 nanoparticles (MNP- Fe3O4 conjugated with GA to increase water solubility of the drug and enhance its chemotherapeutic efficiency for pancreatic cancer.Methods: GA was conjugated with the MNP- Fe3O4 colloidal suspension by mechanical absorption polymerization to construct GA-loaded MNP- Fe3O4, which acted as a drug delivery system.Results: Combination therapy with GA and MNP- Fe3O4 induced remarkable improvement in anticancer activity, which was demonstrated by optical microscopic observations, MTT assay, and nuclear DAPI staining. Furthermore, the possible signaling pathway was explored by Western blot. In Capan-1 pancreatic cancer cells, our observations demonstrated that this strategy could enhance potential anticancer efficiency by inducing apoptosis. The mechanisms of the synergistic effect may be due to reducing protein expression of Bcl-2 and enhancing that of Bax, caspase 9, and caspase 3.Conclusion: These findings demonstrate that a combination of GA and MNPs- Fe3O4 represents a promising approach to the treatment of pancreatic cancer.Keywords: gambogic acid, pancreatic cancer, magnetic nanoparticles, drug delivery system, apoptosis

  16. Combination photodynamic therapy using 5-fluorouracil and aminolevulinate enhances tumor-selective production of protoporphyrin IX and improves treatment efficacy of squamous skin cancers and precancers

    Science.gov (United States)

    Maytin, Edward V.; Anand, Sanjay

    2016-03-01

    In combination photodynamic therapy (cPDT), a small-molecule drug is used to modulate the physiological state of tumor cells prior to giving aminolevulinate (ALA; a precursor for protoporphyrin IX, PpIX). In our laboratory we have identified three agents (methotrexate, 5-fluorouracil, and vitamin D) that can enhance therapeutic effectiveness of ALAbased photodynamic therapy for cutaneous squamous cell carcinoma (SCC). However, only one (5-fluorouracil; 5-FU) is FDA-approved for skin cancer management. Here, we describe animal and human studies on 5-FU mechanisms of action, in terms of how 5-FU pretreatment leads to enhanced PpIX accumulation and improves selectivity of ALA-PDT treatment. In A431 subcutaneous tumors in mice, 5-FU changed expression of heme enzyme (upregulating coproporphyrinogen oxidase, and down-regulating ferrochelatase), inhibited tumor cell proliferation (Ki-67), enhanced differentiation (E-cadherin), and led to strong, tumor-selective increases in apoptosis. Interestingly, enhancement of apoptosis by 5-FU correlated strongly with an increased accumulation of p53 in tumor cells that persisted for 24 h post- PDT. In a clinical trial using a split-body, bilaterally controlled study design, human subjects with actinic keratoses (AK; preneoplastic precursors of SCC) were pretreated on one side of the face, scalp, or forearms with 5-FU cream for 6 days, while the control side received no 5-FU. On the seventh day, the levels of PpIX in 4 test lesions were measured by noninvasive fluorescence dosimetry, and then all lesions were treated with PDT using methyl-aminolevulinate (MAL) and red light (635 nm). Relative amounts of PpIX were found to be increased ~2-fold in 5-FU pretreated lesions relative to controls. At 3 months after PDT, the overall clinical response to PDT (reduction in lesion counts) was 2- to 3-fold better for the 5-FU pretreated lesions, a clinically important result. In summary, 5-FU is a useful adjuvant to aminolevulinate-based PDT

  17. Co-delivery of IL17RB siRNA and doxorubicin by chitosan-based nanoparticles for enhanced anticancer efficacy in breast cancer cells.

    Science.gov (United States)

    Alinejad, Vahideh; Hossein Somi, Mohammad; Baradaran, Behzad; Akbarzadeh, Parvin; Atyabi, Fatemeh; Kazerooni, Hanif; Samadi Kafil, Hosein; Aghebati Maleki, Leili; Siah Mansouri, Homayoon; Yousefi, Mehdi

    2016-10-01

    Overexpression of IL17RB is associated with poor prognosis and short survival of the breast cancer patients.IL17RB/IL17B signaling triggers a substantial increase in the cell growth, proliferation and migration through the activation of NF-κB as well as the up-regulation of the Bcl-2. In this study we designed carboxymethyl dextran (CMD) Chitosan nanoparticles (ChNPs) to encapsulated IL17RB siRNA and doxorubicin (DOX) as an anticancer drug. Then we investigated the efficiency of the simultaneous delivery of drug/siRNA on viability and gene expression of MDA-MB361 cell lines. Furthermore the efficacy of dual agent nanoparticles to induce apoptosis and inhibit migration of breast cancer cells was assessed by Annexin-V and wound healing assays respectively. Our results showed that DOX-siRNA-CMD-ChNPs had about 114nm size; with polydispersity index and zeta potential about 0.3 and 10.1mV respectively. Fourier transform infrared spectroscopy (FTIR) confirmed the formation of DOX-siRNA-CMD-ChNPs complex. In addition IL17RB siRNA had significant effect on DOX-induced cytotoxicity in MDA-MB361 cells. Furthermore treatment with dual agent nanoparticles resulted in a significant silencing of NF-κB and Bcl-2 relative gene expression, apoptosis induction and migration inhibition in MDA-MB361 cells. In conclusion, co-delivery of IL17RB siRNA and DOX can be considered as an effective system for the treatment of breast cancer.

  18. Enhanced anti-tumor efficacy by co-delivery of doxorubicin and paclitaxel with amphiphilic methoxy PEG-PLGA copolymer nanoparticles.

    Science.gov (United States)

    Wang, Hai; Zhao, Ying; Wu, Yan; Hu, Yu-lin; Nan, Kaihui; Nie, Guangjun; Chen, Hao

    2011-11-01

    The use of single chemotherapeutic drug has shown some limitations in anti-tumor treatment, such as development of drug resistance, high toxicity and limited regime of clinical uses. The combination of two or more therapeutic drugs is feasible means to overcome the limitations. Co-delivery strategy has been proposed to minimize the amount of each drug and to achieve the synergistic effect for cancer therapies. Attempts have been made to deliver chemotherapeutic drugs simultaneously using drug carriers, such as micelles, liposomes, and inorganic nanoparticles (NPs). Here we reported core-shell NPs that were doubly emulsified from an amphiphilic copolymer methoxy poly(ethylene glycol)-poly(lactide-co-glycolide) (mPEG-PLGA). These NPs offered advantages over other nanocarriers, as they were easy to fabricate by improved double emulsion method, biocompatible, and showed high loading efficacy. More importantly, these NPs could co-deliver hydrophilic doxorubicin (DOX) and hydrophobic paclitaxel (TAX). The drug-loaded NPs possessed a better polydispersity, indicating that they are more readily subject to controlled size distribution. Studies on drug release and cellular uptake of the co-delivery system demonstrated that both drugs were effectively taken up by the cells and released simultaneously. Furthermore, the co-delivery nanocarrier suppressed tumor cells growth more efficiently than the delivery of either DOX or TAX at the same concentrations, indicating a synergistic effect. Moreover, the NPs loading drugs with a DOX/TAX concentration ratio of 2:1 showed the highest anti-tumor activity to three different types of tumor cells. This nanocarrier might have important potential in clinical implications for co-delivery of multiple anti-tumor drugs with different properties.

  19. Efficacy of FurosapTM, a novel Trigonella foenum-graecum seed extract, in Enhancing Testosterone Level and Improving Sperm Profile in Male Volunteers

    Science.gov (United States)

    Maheshwari, Anuj; Verma, Narsingh; Swaroop, Anand; Bagchi, Manashi; Preuss, Harry G.; Tiwari, Kiran; Bagchi, Debasis

    2017-01-01

    Background: Dietary fiber rich fenugreek (Trigonella foenum-graecum) seeds have exhibited cardioprotective, hypolipidemic and other health benefits. Furosap (FS), an innovative, patented, 20% protodioscin-enriched extract was developed in our laboratory from fenugreek seeds. This study examined the free and total testosterone levels, sperm profile and morphology, sexual health, mood and mental alertness, and broad spectrum safety parameters of FS in 50 male volunteers following supplementation over a period of 12 weeks. Methods: Institutional Review Board (IRB) and other regulatory approvals were obtained for our study. This one-arm, open-labelled, multi-center study was conducted in 50 male volunteers (age: 35 to 65 years) over a period of 12 weeks to determine the efficacy of FS (500 mg/day/subject) on free and total testosterone levels, sperm profile, sperm morphology, libido and sexual health, mood and mental alertness, and broad spectrum safety parameters. Results: Free testosterone levels were improved up to 46% in 90% of the study population. 85.4% of the study population showed improvements in sperm counts. Sperm morphology improved in 14.6% of volunteers. Majority of the subjects enrolled in the study demonstrated improvements in mental alertness and mood. Furthermore, cardiovascular health and libido were significantly improved. Extensive safety parameters were evaluated which included blood chemistry data. No significant changes were observed in serum lipid function, cholesterol, triglyceride, HDL and LDL levels, hemogram (CBC), hepatotoxicity and nephrotoxicity. Conclusion: Overall, the results demonstrate that FS, enriched in 20% protodioscin, is safe and effective in attenuating testosterone levels, healthy sperm profile, mental alertness, cardiovascular health and overall performance in human subjects. PMID:28138310

  20. MAPK pathway inhibition enhances the efficacy of an anti-endothelin B receptor drug conjugate by inducing target expression in melanoma.

    Science.gov (United States)

    Asundi, Jyoti; Lacap, Jennifer A; Clark, Suzanna; Nannini, Michelle; Roth, Leslie; Polakis, Paul

    2014-06-01

    Therapies targeting the mitogen-activated protein (MAP) kinase pathway in melanoma have produced significant clinical responses; however, duration of response is limited by acquisition of drug resistance. Rational drug combinations may improve outcomes in this setting. We assessed the therapeutic combination of an antibody-drug conjugate (ADC) targeting the endothelin B receptor (EDNRB) with small-molecule inhibitors of the MAP kinase signaling pathway in melanoma. Cell lines and tumor models containing either mutant BRAF or NRAS, or wild-type for both, were exposed to small-molecule inhibitors of BRAF and MEK. Expression of EDNRB was analyzed and the therapeutic impact of combining the anti-EDNRB ADC with the BRAF and MEK inhibitors was assessed. Increased expression of EDNRB in response to inhibition of BRAF and/or MEK was observed and augmented the antitumor activity of the ADC. Enhanced target expression and ADC antitumor activity were realized irrespective of the response of the tumor model to the BRAF or MEK inhibitors alone and could be achieved in melanoma with mutant NRAS, BRAF, or neither mutation. Cells that acquired resistance to BRAF inhibition through long-term culture retained drug-induced elevated levels of EDNRB expression. Expression of EDNRB was not enhanced in normal human melanocytes by inhibition of BRAF and the combination of the ADC with MAPK inhibitors was well-tolerated in mice. The anti-EDNRB ADC combines well with BRAF and MEK inhibitors and could have therapeutic use in the majority of human melanoma cases.

  1. PEGylated dendritic diaminocyclohexyl-platinum (II) conjugates as pH-responsive drug delivery vehicles with enhanced tumor accumulation and antitumor efficacy.

    Science.gov (United States)

    Pan, Dayi; She, Wenchuan; Guo, Chunhua; Luo, Kui; Yi, Qiangying; Gu, Zhongwei

    2014-12-01

    Environmentally responsive peptide dendrimers loaded with drugs are suitable candidates for cancer therapy. In this study, we report the preparation and characterization of mPEGylated peptide dendrimer-linked diaminocyclohexyl platinum (II) (dendrimer-DACHPt) conjugates as pH-responsive drug delivery vehicles for tumor suppression in mice. The DACHPt has a molecular structure, is and activity closely related to oxaliplatin and was linked to dendrimer via N,O-chelate coordination. The products were pH-responsive and released drug significantly faster in acidic environments (pH 5.0) than pH 7.4. Consequently, the conjugates suppressed tumor growth better than clinical oxaliplatin(®) without inducing toxicity in an SKOV-3 human ovarian cancer xenograft. Through the systemic delivery of conjugates, 25-fold higher tumor platinum uptake at 36 h post-injection was seen observed due to the enhanced permeability and retention (EPR) effect thereby remarkably enhancing the therapeutic indexes of this small-molecule drug. Thus, the mPEGylated peptide dendrimer-linked DACH-platinum conjugates are novel potential drug delivery systems with implications in future ovarian cancer therapy.

  2. Enhancing anti-tumor efficacy of Doxorubicin by non-covalent conjugation to gold nanoparticles - in vitro studies on feline fibrosarcoma cell lines.

    Directory of Open Access Journals (Sweden)

    Michał Wójcik

    Full Text Available BACKGROUND: Feline injection-site sarcomas are malignant skin tumors of mesenchymal origin, the treatment of which is a challenge for veterinary practitioners. Methods of treatment include radical surgery, radiotherapy and chemotherapy. The most commonly used cytostatic drugs are cyclophosphamide, doxorubicin and vincristine. However, the use of cytostatics as adjunctive treatment is limited due to their adverse side-effects, low biodistribution after intravenous administration and multidrug resistance. Colloid gold nanoparticles are promising drug delivery systems to overcome multidrug resistance, which is a main cause of ineffective chemotherapy treatment. The use of colloid gold nanoparticles as building blocks for drug delivery systems is preferred due to ease of surface functionalization with various molecules, chemical stability and their low toxicity. METHODS: Stability and structure of the glutathione-stabilized gold nanoparticles non-covalently modified with doxorubicin (Au-GSH-Dox was confirmed using XPS, TEM, FT-IR, SAXRD and SAXS analyses. MTT assay, Annexin V and Propidium Iodide Apoptosis assay and Rhodamine 123 and Verapamil assay were performed on 4 feline fibrosarcoma cell lines (FFS1WAW, FFS1, FFS3, FFS5. Statistical analyses were performed using Graph Pad Prism 5.0 (USA. RESULTS: A novel approach, glutathione-stabilized gold nanoparticles (4.3 +/- 1.1 nm in diameter non-covalently modified with doxorubicin (Au-GSH-Dox was designed and synthesized. A higher cytotoxic effect (p<0.01 of Au-GSH-Dox than that of free doxorubicin has been observed in 3 (FFS1, FFS3, FFS1WAW out of 4 feline fibrosarcoma cell lines. The effect has been correlated to the activity of glycoprotein P (main efflux pump responsible for multidrug resistance. CONCLUSIONS: The results indicate that Au-GSH-Dox may be a potent new therapeutic agent to increase the efficacy of the drug by overcoming the resistance to doxorubicin in feline fibrosarcoma cell lines

  3. Clarithromycin highly-loaded gastro-floating fine granules prepared by high-shear melt granulation can enhance the efficacy of Helicobacter pylori eradication.

    Science.gov (United States)

    Aoki, Hajime; Iwao, Yasunori; Mizoguchi, Midori; Noguchi, Shuji; Itai, Shigeru

    2015-05-01

    In an effort to develop a new gastro-retentive drug delivery system (GRDDS) without a large amount of additives, 75% clarithromycin (CAM) loaded fine granules were prepared with three different hydrophobic binders by high-shear melt granulation and their properties were evaluated. Granules containing the higher hydrophobic binder showed sustained drug release and were able to float over 24h. The synchrotron X-ray CT measurement indicated that both the high hydrophobicity of the binder and the void space inside the granules might be involved in their buoyancy. In an in vivo experiment, the floating granules more effectively eradicated Helicobacter pylori than a CAM suspension by remaining in the stomach for a longer period. In short, CAM highly-loaded gastro-floating fine granules can enhance the eradication efficiency of H. pylori compared with CAM alone.

  4. A TLR7 agonist enhances the antitumor efficacy of obinutuzumab in murine lymphoma models via NK cells and CD4 T cells.

    Science.gov (United States)

    Cheadle, E J; Lipowska-Bhalla, G; Dovedi, S J; Fagnano, E; Klein, C; Honeychurch, J; Illidge, T M

    2017-01-03

    Anti-CD20 monoclonal antibodies (mAb) such as rituximab have been proven to be highly effective at improving outcome in B-cell malignancies. However, many patients ultimately relapse and become refractory to treatment. The glycoengineered anti-CD20 mAb obinutuzumab was developed to induce enhanced antibody-dependent cellular cytotoxicity, antibody-dependent phagocytosis and direct cell death and was shown to lead to improved outcomes in a randomized study in B-CLL. We hypothesized that immune stimulation through Toll-like receptor 7 (TLR7) agonism in combination with obinutuzumab would further enhance lymphoma clearance and the generation of long-term antitumor immune responses. Here we demonstrate, in syngeneic human CD20 (hCD20)-expressing models of lymphoma, that systemic administration of a TLR7 agonist (R848) increases responses when administered in combination with obinutuzumab and protects against disease recurrence. Depletion studies demonstrate that primary antitumor activity is dependent on both NK cells and CD4(+) T cells but not on CD8(+) T cells. However, both CD4(+) and CD8(+) T cells appear necessary for the generation of protective immunological memory. Importantly, increased tumor-free survival post obinutuzumab and R848 combination therapy was seen in hCD20 transgenic mice, which express hCD20 on normal B cells. These findings provide a rationale for clinical testing of obinutuzumab in combination with systemically administered TLR7 agonists to further improve outcome.Leukemia advance online publication, 3 January 2017; doi:10.1038/leu.2016.352.

  5. The Efficacy of Internet-Based Mindfulness Training and Cognitive-Behavioral Training With Telephone Support in the Enhancement of Mental Health Among College Students and Young Working Adults: Randomized Controlled Trial

    Science.gov (United States)

    Chio, Floria HN; Chan, Amy TY; Lui, Wacy WS; Wu, Ellery KY

    2017-01-01

    Background College students and working adults are particularly vulnerable to stress and other mental health problems, and mental health promotion and prevention are needed to promote their mental health. In recent decades, mindfulness-based training has demonstrated to be efficacious in treating physical and psychological conditions. Objective The aim of our study was to examine the efficacy of an Internet-based mindfulness training program (iMIND) in comparison with the well-established Internet-based cognitive-behavioral training program (iCBT) in promoting mental health among college students and young working adults. Methods This study was a 2-arm, unblinded, randomized controlled trial comparing iMIND with iCBT. Participants were recruited online and offline via mass emails, advertisements in newspapers and magazines, announcement and leaflets in primary care clinics, and social networking sites. Eligible participants were randomized into either the iMIND (n=604) or the iCBT (n=651) condition. Participants received 8 Web-based sessions with information and exercises related to mindfulness or cognitive-behavioral principles. Telephone or email support was provided by trained first tier supporters who were supervised by the study’s research team. Primary outcomes included mental and physical health-related measures, which were self-assessed online at preprogram, postprogram, and 3-month follow-up. Results Among the 1255 study participants, 213 and 127 completed the post- and 3-month follow-up assessment, respectively. Missing data were treated using restricted maximum likelihood estimation. Both iMIND (n=604) and iCBT (n=651) were efficacious in improving mental health, psychological distress, life satisfaction, sleep disturbance, and energy level. Conclusions Both Internet-based mental health programs showed potential in improving the mental health from pre- to postassessment, and such improvement was sustained at the 3-month follow-up. The high attrition

  6. Anti-BlyS antibody reduces the immune reaction against enzyme and enhances the efficacy of enzyme replacement therapy in Fabry disease model mice.

    Science.gov (United States)

    Sato, Yohei; Ida, Hiroyuki; Ohashi, Toya

    2017-02-02

    Formation of antibodies against a therapeutic enzyme is an important complication during enzyme replacement therapy (ERT) for lysosomal storage diseases. Fabry disease (FD) is caused by a deficiency of alpha-galactosidase (GLA), which results in the accumulation of globotriaosylceramide (GL-3). We have shown immune tolerance induction (ITI) during ERT in FD model mice by using an anti-B lymphocyte stimulator (anti-BlyS) antibody (belimumab). A single dose of the anti-BlyS antibody temporarily lowered the percentage of B cells and IgG antibody titer against recombinant human GLA. Administration of a low maintenance dose of the anti-BlyS antibody suppressed the B cell population and immunotolerance was induced in 20% of mice, but antibody formation could not be prevented. We then increased the maintenance dose of the anti-BlyS antibody and immunotolerance was induced in 50% of mice. Therapeutic enzyme distribution and clearance of GL-3 were also enhanced by a high maintenance dose of the anti-BlyS antibody.

  7. Strategy to enhance the anticancer efficacy of X-ray radiotherapy in melanoma cells by platinum complexes, the role of ROS-mediated signaling pathways.

    Science.gov (United States)

    Xie, Qiang; Lan, Guoqiang; Zhou, Yangliang; Huang, Jiamin; Liang, Yuanwei; Zheng, Wenjie; Fu, Xiaoyan; Fan, Cundong; Chen, Tianfeng

    2014-11-01

    Radiotherapy plays an important role in treatment of cancers with low toxicity to the surrounding normal tissues. However, it still fails to eradicate hypoxic tumors due to the occurrence of radioresistance. Therefore, the search for new radiation sensitizers is of great significance. Platinum (Pt) complexes have been identified as potential radiation sensitizers to increase the sensitivity of cancer cells to radiotherapy. In the present study, we have synthesized four Pt complexes containing (2 - benzimidazole [4, 5-f] - [1, 10] phenanthroline) ligand and found that they could effectively enhance the X-ray-induced growth inhibition against A375 human melanoma cells through induction of G2/M cell cycle arrest. In contrast, they showed much lower cytotoxicity toward human normal cells. The complexes also dramatically inhibited the TrxR activity and caused intracellular ROS overproduction, due to the Auger electron effect of heavy metal element under X-ray radiation. Excessive ROS triggered DNA damage and activated downstream signaling pathways, including the phosphorylation of p53 and p38MAPK, and down-regulation of phosphorylated AKT and ERK, finally resulted in increase of radiosensitivity and inhibition of tumor reproduction. Taken together, our results suggest that the synthetic Pt complexes could be further developed as sensitizers of X-ray radiotherapy.

  8. Co-expression of the C-terminal domain of Yersinia enterocolitica invasin enhances the efficacy of classical swine-fever-vectored vaccine based on human adenovirus

    Indian Academy of Sciences (India)

    Helin Li; Pengbo Ning; Zhi Lin; Wulong Liang; Kai Kang; Lei He; Yanming Zhang

    2015-03-01

    The use of adenovirus vector-based vaccines is a promising approach for generating antigen-specific immune responses. Improving vaccine potency is necessary in other approaches to address their inadequate protection for the majority of infectious diseases. This study is the first to reconstruct a recombinant replication-defective human adenovirus co-expressing E2 and invasin C-terminal (InvC) glycoproteins (rAd-E2-InvC). rAd-E2-InvC with 2×106 TCID50 was intramuscularly administered two times to CSFV-free pigs at 14 day intervals. No adverse clinical reactions were observed in any of the pigs after the vaccination. The CSFV E2-specific antibody titer was significantly higher in the rAd-E2-InvC group than that in the rAdV-E2 group as measured by NPLA and blocking ELISA. Pigs immunized with rAd-E2-InvC were completely protected against lethal challenge. Neither CSFV RNA nor pathological changes were detected in the tissues after CSFV challenge. These results demonstrate that rAd-E2-InvC could be an alternative to the existing CSF vaccine. Moreover, InvC that acts as an adjuvant could enhance the immunogenicity of rAdV-E2 and induce high CSFV E2-specific antibody titer and protection level.

  9. Enhanced protective efficacy against tuberculosis provided by a recombinant urease deficient BCG expressing heat shock protein 70-major membrane protein-II having PEST sequence.

    Science.gov (United States)

    Tsukamoto, Yumiko; Maeda, Yumi; Tamura, Toshiki; Mukai, Tetsu; Mitarai, Satoshi; Yamamoto, Saburo; Makino, Masahiko

    2016-12-07

    Enhancement of the T cell-stimulating ability of Mycobacterium bovis BCG (BCG) is necessary to develop an effective tuberculosis vaccine. For this purpose, we introduced the PEST-HSP70-major membrane protein-II (MMPII)-PEST fusion gene into ureC-gene depleted recombinant (r) BCG to produce BCG-PEST. The PEST sequence is involved in the proteasomal processing of antigens. BCG-PEST secreted the PEST-HSP70-MMPII-PEST fusion protein and more efficiently activated human monocyte-derived dendritic cells (DCs) in terms of phenotypic changes and cytokine productions than an empty-vector-introduced BCG or HSP70-MMPII gene-introduced ureC gene-depleted BCG (BCG-DHTM). Autologous human naïve CD8(+) T cells and naïve CD4(+) T cells were effectively activated by BCG-PEST and produced IFN-γ in an antigen-specific manner through DCs. These T cell activations were closely associated with phagosomal maturation and intraproteasomal protein degradation in antigen-presenting cells. Furthermore, BCG-PEST produced long-lasting memory-type T cells in C57BL/6 mice more efficiently than control rBCGs. Moreover, a single subcutaneous injection of BCG-PEST more effectively reduced the multiplication of subsequent aerosol-challenged Mycobacterium tuberculosis of the standard H37Rv strain and clinically isolated Beijing strain in the lungs than control rBCGs. The vaccination effect of BCG-PEST lasted for at least 6months. These results indicate that BCG-PEST may be able to efficiently control the spread of tuberculosis in human.

  10. Diagnostic Efficacy of All Series of Dynamic Contrast Enhanced Breast MR Images Using Gradient Vector Flow (GVF Segmentation and Novel Border Feature Extraction for Differentiation Between Malignant

    Directory of Open Access Journals (Sweden)

    L. Bahreini

    2010-12-01

    Full Text Available Background/Objective: To discriminate between malignant and benign breast lesions;"nconventionally, the first series of Breast Subtraction Dynamic Contrast-Enhanced Magnetic"nResonance Imaging (BS DCE-MRI images are used for quantitative analysis. In this study, we"ninvestigated whether using all series of these images could provide us with more diagnostic"ninformation."nPatients and Methods: This study included 60 histopathologically proven lesions. The steps of"nthis study were as follows: selecting the regions of interest (ROI, segmentation using Gradient"nVector Flow (GVF snake for the first time, defining new feature sets, using artificial neural network"n(ANN for optimal feature set selection, evaluation using receiver operating characteristic (ROC"nanalysis."nResults: The results showed GVF snake method correctly segmented 95.3% of breast lesion"nborders at the overlap threshold of 0.4. The first classifier which used the optimal feature set"nextracted only from the first series of BS DCE-MRI images achieved an area under the curve"n(AUC of 0.82, specificity of 60% at sensitivity of 81%. The second classifier which used the same"noptimal feature set but was extracted from all five series of these images achieved an AUC of"n0.90, specificity of 79% at sensitivity of 81%."nConclusion: The result of GVF snake segmentation showed that it could make an accurate"nsegmentation in the borders of breast lesions. According to this study, using all five series of BS"nDCE-MRI images could provide us with more diagnostic information about the breast lesion and"ncould improve the performance of breast lesion classifiers in comparison with using the first"nseries alone.

  11. Entrapment of H1N1 Influenza Virus Derived Conserved Peptides in PLGA Nanoparticles Enhances T Cell Response and Vaccine Efficacy in Pigs.

    Directory of Open Access Journals (Sweden)

    Jagadish Hiremath

    Full Text Available Pigs are believed to be one of the important sources of emerging human and swine influenza viruses (SwIV. Influenza virus conserved peptides have the potential to elicit cross-protective immune response, but without the help of potent adjuvant and delivery system they are poorly immunogenic. Biodegradable polylactic-co-glycolic acid (PLGA nanoparticle (PLGA-NP based vaccine delivery system enhances cross-presentation of antigens by the professional antigen presenting cells. In this study, Norovirus P particle containing SwIV M2e (extracellular domain of the matrix protein 2 chimera and highly conserved two each of H1N1 peptides of pandemic 2009 and classical human influenza viruses were entrapped in PLGA-NPs. Influenza antibody-free pigs were vaccinated with PLGA-NPs peptides cocktail vaccine twice with or without an adjuvant, Mycobacterium vaccae whole cell lysate, intranasally as mist. Vaccinated pigs were challenged with a virulent heterologous zoonotic SwIV H1N1, and one week later euthanized and the lung samples were analyzed for the specific immune response and viral load. Clinically, pigs vaccinated with PLGA-NP peptides vaccine had no fever and flu symptoms, and the replicating challenged SwIV was undetectable in the bronchoalveolar lavage fluid. Immunologically, PLGA-NP peptides vaccination (without adjuvant significantly increased the frequency of antigen-specific IFNγ secreting CD4 and CD8 T cells response in the lung lymphocytes, despite not boosting the antibody response both at pre- and post-challenge. In summary, our data indicated that nanoparticle-mediated delivery of conserved H1N1 influenza peptides induced the virus specific T cell response in the lungs and reduced the challenged heterologous virus load in the airways of pigs.

  12. Polymorphism in the Plasmodium falciparum chloroquine-resistance transporter protein links verapamil enhancement of chloroquine sensitivity with the clinical efficacy of amodiaquine

    Directory of Open Access Journals (Sweden)

    Warhurst David C

    2003-09-01

    Full Text Available Abstract Background Chloroquine accumulates in the acidic digestive vacuole of the intraerythrocytic malaria parasite, and prevents the detoxication of haematin released during haemoglobin digestion. Changes in protein PfCRT in the digestive vacuole membrane of growing intra-erythrocytic stages of Plasmodium falciparum are crucial for resistance. Expressed in yeast, PfCRT resembles an anion channel. Depressed anion channel function could increase intralysosomal pH to reduce entry of basic drug, or enhanced function could reduce drug interaction with target haematin. The most important resistance-associated change is from positively-charged lysine-76 to neutral threonine which could facilitate drug efflux through a putative channel. It has been proposed that the resistance-reversing effect of verapamil is due to hydrophobic binding to the mutated PfCRT protein, and replacement of the lost positive charge, which repels the access of 4-aminoquinoline cations, thus partially restoring sensitivity. Desethylamodiaquine, the active metabolite of amodiaquine, which has significant activity in chloroquine-resistance, may also act similarly on its own. Methods Changes in physicochemical parameters in different CQ-resistant PfCRT sequences are analysed, and correlations with drug activity on lines transfected with different alleles of the pfcrt gene are examined. Results and conclusions The results support the idea that PfCRT is a channel which, in resistant parasites, can allow efflux of chloroquine from the digestive vacuole. Activity of the chloroquine/verapamil combination and of desethylamodiaquine both correlate with the mean hydrophobicity of PfCRT residues 72-76. This may partly explain clinical-resistance to amodiaquine found in the first chloroquine-resistant malaria cases from South America and enables tentative prediction of amodiaquine's clinical activity against novel haplotypes of PfCRT.

  13. Local radiative treatment of hepatocellular cancer with phosphorus-32 glassmicrospheres to enhance the efficacy of hepatic artery chemoembolism andpossibly related with MDR expressed P-glycoprotein

    Institute of Scientific and Technical Information of China (English)

    Zao Jiang; Lu Liu; Wen Fang; Wei Zhang Shou; Dong Sheng Zhang; Mei Mei Dai

    2000-01-01

    .05, Chi-squaur test). The median survival period ofthe patients were 532 and 564 d in group Ⅰ and Ⅱ respectivcey (Kaplan-Meire method).CONCLUSION The enhanced effectiveness of the local treatment of 32 P-GMS conjugated withchemotherapeutics may be related to the local action on the MDR expressed p-glycoprotein.

  14. Thidiazuron-enhanced biosynthesis and antimicrobial efficacy of silver nanoparticles via improving phytochemical reducing potential in callus culture of Linum usitatissimum L.

    Directory of Open Access Journals (Sweden)

    Anjum S

    2016-02-01

    Full Text Available Sumaira Anjum, Bilal Haider AbbasiDepartment of Biotechnology, Quaid-i-Azam University, Islamabad, PakistanAbstract: Green synthesis of silver nanoparticles (AgNPs by using plants is an emerging class of nanobiotechnology. It revolutionizes all domains of medical sciences by synthesizing chemical-free AgNPs for various biomedical applications. In this report, AgNPs were successfully synthesized by using whole plant extract (WPE and thidiazuron-induced callus extract (CE of Linum usitatissimum. The phytochemical analysis revealed that the total phenolic and flavonoid contents were higher in CE than that in WPE. Ultraviolet-visible spectroscopy of synthesized AgNPs showed a characteristic surface plasmon band in the range of 410–426 nm. Bioreduction of CE-mediated AgNPs was completed in a shorter time than that of WPE-mediated AgNPs. Scanning electron microscopy showed that both types of synthesized AgNPs were spherical in shape, but CE-mediated AgNPs were smaller in size (19–24 nm and more scattered in distribution than that of WPE-mediated AgNPs (49–54 nm. X-ray diffraction analysis confirmed crystalline nature (face-centered cubic of both types of AgNPs. Fourier-transform infrared spectroscopy revealed that the polyphenols and flavonoids were mainly responsible for reduction and capping of synthesized AgNPs. Energy dispersive X-ray analysis further confirmed the successful synthesis of AgNPs. Moreover, the synthesized AgNPs were found to be stable over months with no change in the surface plasmon bands. More importantly, CE-mediated AgNPs displayed significantly higher bactericidal activity against multiple drug-resistant human pathogens than WPE-mediated AgNPs. The present work highlighted the potent role of thidiazuron in in vitro-derived cultures for enhanced biosynthesis of chemical-free AgNPs, which can be used as nanomedicines in many biomedical applications.Keywords: silver nanoparticles, Linum usitatissimum L., in vitro

  15. Enhancement of radiotherapy efficacy by miR-200c-loaded gelatinase-stimuli PEG-Pep-PCL nanoparticles in gastric cancer cells

    Directory of Open Access Journals (Sweden)

    Cui FB

    2014-05-01

    Full Text Available Fang-bo Cui,1,* Qin Liu,1,* Ru-Tian Li,1 Jie Shen,1 Pu-yuan Wu,1 Li-Xia Yu,1 Wen-jing Hu,1 Feng-lei Wu,2 Chun-Ping Jiang,1 Guo-feng Yue,2 Xiao-Ping Qian,1 Xi-Qun Jiang,3 Bao-Rui Liu11The Comprehensive Cancer Center of Drum-Tower Hospital, Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University, Nanjing, 2Nanjing Medical University, 3Laboratory of Mesoscopic Chemistry and Department of Polymer Science and Engineering, College of Chemistry and Chemical Engineering, Nanjing University, Nanjing, People's Republic of China*These authors contributed equally to this workAbstract: Radiotherapy is the main locoregional control modality for many types of unresectable tumors, including gastric cancer. However, many patients fail radiotherapy due to intrinsic radioresistance of cancer cells, which has been found to be strongly associated with cancer stem cell (CSC-like properties. In this study, we developed a nanoparticle formulation to deliver miR-200c, which is reported to inhibit CSC-like properties, and then evaluated its potential activity as a radiosensitizer. miR-200c nanoparticles significantly augmented radiosensitivity in three gastric cancer cell lines (sensitization enhancement ratio 1.13–1.25, but only slightly in GES-1 cells (1.06. In addition to radioenhancement, miR-200c nanoparticles reduced the expression of CD44, a putative CSC marker, and the percentage of CD44+ BGC823 cells. Meanwhile, other CSC-like properties, including invasiveness and resistance to apoptosis, could be suppressed by miR-200c nanoparticles. CSC-associated radioresistance mechanisms, involving reactive oxygen species levels and DNA repair capacity, were also attenuated. We have demonstrated that miR-200c nanoparticles are an effective radiosensitizer in gastric cancer cells and induce little radiosensitization in normal cells, which suggests that they are as a promising candidate for further preclinical and clinical evaluation

  16. Principals' transformational leadership and teachers' collective efficacy.

    Science.gov (United States)

    Dussault, Marc; Payette, Daniel; Leroux, Mathieu

    2008-04-01

    The study was designed to test the relationship of principals' transformational, transactional, and laissez-faire leadership with teachers' collective efficacy. Bandura's theory of efficacy applied to the group and Bass's transformational leadership theory were used as the theoretical framework. Participants included 487 French Canadian teachers from 40 public high schools. As expected, there were positive and significant correlations between principals' transformational and transactional leadership and teachers' collective efficacy. Also, there was a negative and significant correlation between laissez-faire leadership and teachers' collective efficacy. Moreover, regression analysis showed transformational leadership significantly enhanced the predictive capabilities of transactional leadership on teachers' collective efficacy. These results confirm the importance of leadership to predict collective efficacy and, by doing so, strengthen Bass's theory of leadership.

  17. Chief Joseph Kokanee Enhancement Project; Strobe Light Deterrent Efficacy Test and Fish Behavior Determination at Grand Coulee Dam Third Powerplant Forebay, 2005-2006 Annual Report.

    Energy Technology Data Exchange (ETDEWEB)

    Simmons, M.; Johnson, Robert; McKinstry, C. [Pacific Northwest National Laboratory

    2006-03-01

    The construction of Grand Coulee and Chief Joseph dams on the Columbia River resulted in the complete extirpation of the anadromous fishery upstream of these structures. Today, this area is totally dependent upon resident fish resources to support local fisheries. The resident fishing is enhanced by an extensive stocking program for target species in the existing fishery, including kokanee (Oncorhynchus nerka kennerlyi) and rainbow trout (O. mykiss). The kokanee fishery in Lake Roosevelt has not been meeting the return goals set by fisheries managers despite the stocking program. Investigations of physical and biological factors that could affect the kokanee population found predation and entrainment had a significant impact on the fish population. In 1999 and 2000, walleye (Sander vitreum) consumed between 15% and 9%, respectively, of the hatchery kokanee within 41 days of their release, while results from a study in the late 1990s estimated that entrainment at Grand Coulee Dam could account for up to 30% of the total mortality of the stocked fish. To address the entrainment loss, the Bonneville Power Administration commissioned a study to determine if fish would avoid areas illuminated by strobe lights in the forebay of the third powerplant. This work was conducted by Pacific Northwest National Laboratory (PNNL) in conjunction with the Confederated Tribes of the Colville Reservation (Colville Confederated Tribes). From 2002 through 2004, six strobe lights were suspended in the center of the opening to the third powerplant forebay during summer months. Results from those studies indicated that fish appeared to be attracted to the illuminated area but only at night and when flow conditions within the third powerplant forebay were minimal. However, small but consistent results from these studies indicated that under high flow conditions, fish might be avoiding the lights. The 2005 study was designed to examine whether, under high flow conditions near the penstock

  18. Examining the influence of other-efficacy and self-efficacy on personal performance.

    Science.gov (United States)

    Dunlop, William L; Beatty, Daniel J; Beauchamp, Mark R

    2011-08-01

    This research examined the relative effects of other-efficacy and self-efficacy beliefs in relation to individual performance within a cooperative dyadic setting. Pairs of female participants (M(age) = 20.08, SD = 1.93) performed three practice trials on a dyadic dance-based videogame. Other-efficacy and self-efficacy beliefs were then manipulated through the provision of bogus feedback regarding each pair member's coordination abilities. Following the administration of this feedback, pairs performed a final trial on this dance-based task. The results revealed a main effect for other-efficacy, such that participants in the enhanced other-efficacy conditions outperformed those in the inhibited other-efficacy conditions on this task. A main effect for self-efficacy was not observed. Furthermore, there was no evidence of an interaction between other-efficacy and self-efficacy. The results of this study suggest that other-efficacy may supersede the effects of self-efficacy in supporting personal performance within cooperative relational contexts.

  19. Hydrostatic Compress Force Enhances the Viability and Decreases the Apoptosis of Condylar Chondrocytes through Integrin-FAK-ERK/PI3K Pathway

    Science.gov (United States)

    Ma, Dandan; Kou, Xiaoxing; Jin, Jing; Xu, Taotao; Wu, Mengjie; Deng, Liquan; Fu, Lusi; Liu, Yi; Wu, Gang; Lu, Haiping

    2016-01-01

    Reduced mechanical stimuli in many pathological cases, such as hemimastication and limited masticatory movements, can significantly affect the metabolic activity of mandibular condylar chondrocytes and the growth of mandibles. However, the molecular mechanisms for these phenomena remain unclear. In this study, we hypothesized that integrin-focal adhesion kinase (FAK)-ERK (extracellular signal–regulated kinase)/PI3K (phosphatidylinositol-3-kinase) signaling pathway mediated the cellular response of condylar chondrocytes to mechanical loading. Primary condylar chondrocytes were exposed to hydrostatic compressive forces (HCFs) of different magnitudes (0, 50, 100, 150, 200, and 250 kPa) for 2 h. We measured the viability, morphology, and apoptosis of the chondrocytes with different treatments as well as the gene, protein expression, and phosphorylation of mechanosensitivity-related molecules, such as integrin α2, integrin α5, integrin β1, FAK, ERK, and PI3K. HCFs could significantly increase the viability and surface area of condylar chondrocytes and decrease their apoptosis in a dose-dependent manner. HCF of 250 kPa resulted in a 1.51 ± 0.02-fold increase of cell viability and reduced the ratio of apoptotic cells from 18.10% ± 0.56% to 7.30% ± 1.43%. HCFs could significantly enhance the mRNA and protein expression of integrin α2, integrin α5, and integrin β1 in a dose-dependent manner, but not ERK1, ERK2, or PI3K. Instead, HCF could significantly increase phosphorylation levels of FAK, ERK1/2, and PI3K in a dose-dependent manner. Cilengitide, the potent integrin inhibitor, could dose-dependently block such effects of HCFs. HCFs enhances the viability and decreases the apoptosis of condylar chondrocytes through the integrin-FAK-ERK/PI3K pathway. PMID:27827993

  20. Rational design of a comprehensive cancer therapy platform using temperature-sensitive polymer grafted hollow gold nanospheres: simultaneous chemo/photothermal/photodynamic therapy triggered by a 650 nm laser with enhanced anti-tumor efficacy

    Science.gov (United States)

    Deng, Xiaoran; Chen, Yinyin; Cheng, Ziyong; Deng, Kerong; Ma, Ping'an; Hou, Zhiyao; Liu, Bei; Huang, Shanshan; Jin, Dayong; Lin, Jun

    2016-03-01

    Combining multi-model treatments within one single system has attracted great interest for the purpose of synergistic therapy. In this paper, hollow gold nanospheres (HAuNs) coated with a temperature-sensitive polymer, poly(oligo(ethylene oxide) methacrylate-co-2-(2-methoxyethoxy)ethyl methacrylate) (p(OEGMA-co-MEMA)), co-loaded with DOX and a photosensitizer Chlorin e6 (Ce6) were successfully synthesized. As high as 58% DOX and 6% Ce6 by weight could be loaded onto the HAuNs-p(OEGMA-co-MEMA) nanocomposites. The grafting polymer brushes outside the HAuNs play the role of ``gate molecules'' for controlled drug release by 650 nm laser radiation owing to the temperature-sensitive property of the polymer and the photothermal effect of HAuNs. The HAuNs-p(OEGMA-co-MEMA)-Ce6-DOX nanocomposites with 650 nm laser radiation show effective inhibition of cancer cells in vitro and enhanced anti-tumor efficacy in vivo. In contrast, control groups without laser radiation show little cytotoxicity. The nanocomposite demonstrates a way of ``killing three birds with one stone'', that is, chemotherapy, photothermal and photodynamic therapy are triggered simultaneously by the 650 nm laser stimulation. Therefore, the nanocomposites show the great advantages of multi-modal synergistic effects for cancer therapy by a remote-controlled laser stimulus.Combining multi-model treatments within one single system has attracted great interest for the purpose of synergistic therapy. In this paper, hollow gold nanospheres (HAuNs) coated with a temperature-sensitive polymer, poly(oligo(ethylene oxide) methacrylate-co-2-(2-methoxyethoxy)ethyl methacrylate) (p(OEGMA-co-MEMA)), co-loaded with DOX and a photosensitizer Chlorin e6 (Ce6) were successfully synthesized. As high as 58% DOX and 6% Ce6 by weight could be loaded onto the HAuNs-p(OEGMA-co-MEMA) nanocomposites. The grafting polymer brushes outside the HAuNs play the role of ``gate molecules'' for controlled drug release by 650 nm laser radiation

  1. Microbiota Influences Vaccine and Mucosal Adjuvant Efficacy

    Science.gov (United States)

    2017-01-01

    A symbiotic relationship between humans and the microbiota is critical for the maintenance of our health, including development of the immune system, enhancement of the epithelial barrier, and acquisition of nutrients. Recent research has shown that the microbiota impacts immune cell development and differentiation. These findings suggest that the microbiota may also influence adjuvant and vaccine efficacy. Indeed, several factors such as malnutrition and poor sanitation, which affect gut microbiota composition, impair the efficacy of vaccines. Although there is little evidence that microbiota alters vaccine efficacy, further understanding of human immune system-microbiota interactions may lead to the effective development of adjuvants and vaccines for the treatment of diseases. PMID:28261017

  2. Changes in Science Teaching Self-Efficacy among Primary Teacher Education Students

    Science.gov (United States)

    Palmer, David; Dixon, Jeanette; Archer, Jennifer

    2015-01-01

    Many preservice primary teachers have low self-efficacy for science teaching. Although science methods courses have often been shown to enhance self-efficacy, science content courses have been relatively ineffective in this respect. This study investigated whether a tailored science content course would enhance self-efficacy. The participants were…

  3. Adolescent Work Experience and Self-efficacy.

    Science.gov (United States)

    Cunnien, Keith A; Martinrogers, Nicole; Mortimer, Jeylan T

    2009-01-01

    PURPOSE OF THIS PAPER: To assess the relationship between high school work experiences and self-efficacy. DESIGN/METHODOLOGY/APPROACH: OLS regressions are applied to longitudinal data from the Youth Development Study to examine work experiences and self-efficacy. FINDINGS: The analyses indicate that employment fosters self-efficacy in multiple realms, Occasional and sporadic workers exhibit less self-efficacy than steady workers. Supervisory support may be especially important in enhancing adolescents' confidence as they anticipate their future family lives, community participation, personal health, and economic achievements. RESEARCH LIMITATIONS/IMPLICATIONS: This research includes only a small set of the work dimensions that may be important for adolescents. Ethnography and in-depth interviews are recommended to further explore the subjective and emotional dimensions of youth work experiences. PRACTICAL IMPLICATIONS: In developing policies and guidance, educators, parents, and employers should be aware that steady employment and supervisory support enhance the development of adolescent self-efficacy. ORIGINAL VALUE OF PAPER: This paper finds evidence that adolescent work experiences spill over to influence youth's developing confidence in the realms of family life, community and personal health. It also suggests that sporadic and occasional work patterns can impair the development of self-efficacy in adolescence.

  4. Efficacy of ibandronate: a long term confirmation.

    Science.gov (United States)

    Di Munno, Ombretta; Delle Sedie, Andrea

    2010-01-01

    Data deriving from randomized clinical trials, observational studies and meta-analyses, including treatment regimens unlicensed for use in clinical practice, clearly support that 150 mg once-monthly oral and 3 mg quarterly i.v. doses of ibandronate are associated with efficacy, safety and tolerability; notably both these marketed regimens, which largely correspond to ACE ≥10.8 mg, may in addition provide a significant efficacy on non-vertebral and clinical fracture (Fx) efficacy. The MOBILE and the DIVA LTE studies confirmed a sustained efficacy of monthly oral and quarterly i.v. regimens respectively, over 5 years. Furthermore, improved adherence rates with monthly ibandronate, deriving from studies evaluating large prescription databases, promise to enhance fracture protection and decrease the social and economic burden of postmenopausal osteoporosis.

  5. Self-Efficacy and Computers.

    Science.gov (United States)

    Olivier, Terry A.; Shapiro, Faye

    1993-01-01

    Presents a conceptual analysis of self-efficacy and reviews the literature on self-efficacy in the microcomputer environment. Topics addressed include self-efficacy versus other theories; efficacy versus outcome expectations; and sources of efficacy information, including performance accomplishments, vicarious experiences, verbal persuasion, and…

  6. The anxioselective agent 7-(2-chloropyridin-4-yl)pyrazolo-[1,5-a]-pyrimidin-3-yl](pyridin-2-yl)methanone (DOV 51892) is more efficacious than diazepam at enhancing GABA-gated currents at alpha1 subunit-containing GABAA receptors.

    Science.gov (United States)

    Popik, Piotr; Kostakis, Emmanuel; Krawczyk, Martyna; Nowak, Gabriel; Szewczyk, Bernadeta; Krieter, Philip; Chen, Zhengming; Russek, Shelley J; Gibbs, Terrell T; Farb, David H; Skolnick, Phil; Lippa, Arnold S; Basile, Anthony S

    2006-12-01

    Studies using mice with point mutations of GABA(A) receptor alpha subunits suggest that the sedative and anxiolytic properties of 1,4-benzodiazepines are mediated, respectively, by GABA(A) receptors bearing the alpha(1) and alpha(2) subunits. This hypothesis predicts that a compound with high efficacy at GABA(A) receptors containing the alpha(1) subunit would produce sedation, whereas an agonist acting at alpha(2) subunit-containing receptors (with low or null efficacy at alpha(1)-containing receptors) would be anxioselective. Electrophysiological studies using recombinant GABA(A) receptors expressed in Xenopus oocytes indicate that maximal potentiation of GABA-stimulated currents by the pyrazolo-[1,5-a]-pyrimidine, DOV 51892, at alpha(1)beta(2)gamma(2S) constructs of the GABA(A) receptor was significantly higher (148%) than diazepam. In contrast, DOV 51892 was considerably less efficacious and/or potent than diazepam in enhancing GABA-stimulated currents mediated by constructs containing alpha(2), alpha(3), or alpha(5) subunits. In vivo, DOV 51892 increased punished responding in the Vogel conflict test, an effect blocked by flumazenil, and increased the percentage of time spent in the open arms of the elevated plus-maze. However, DOV 51892 had no consistent effects on motor function or muscle relaxation at doses more than 1 order of magnitude greater than the minimal effective anxiolytic dose. Although the mutant mouse data predict that the high-efficacy potentiation of GABA(A1a) receptor-mediated currents by DOV 51892 would be sedating, behavioral studies demonstrate that DOV 51892 is anxioselective, indicating that GABA potentiation mediated by alpha(1) subunit-containing GABA(A) receptors may be neither the sole mechanism nor highly predictive of the sedative properties of benzodiazepine recognition site modulators.

  7. Application of self-efficacy theory in dental clinical practice.

    Science.gov (United States)

    Kakudate, N; Morita, M; Fukuhara, S; Sugai, M; Nagayama, M; Kawanami, M; Chiba, I

    2010-11-01

    In clinical practice, self-efficacy refers to how certain a patient feels about his or her ability to take the necessary action to improve the indicators and maintenance of health. It is assumed that the prognosis for patient behaviour can be improved by assessing the proficiency of their self-efficacy through providing psychoeducational instructions adapted for individual patients, and promoting behavioural change for self-care. Therefore, accurate assessment of self-efficacy is an important key in daily clinical preventive care. The previous research showed that the self-efficacy scale scores predicted patient behaviour in periodontal patients and mother's behaviour in paediatric dental practice. Self-efficacy belief is constructed from four principal sources of information: enactive mastery experience, vicarious experience, verbal persuasion, and physiological and affective states. Thus, self-efficacy can be enhanced by the intervention exploiting these sources. The previous studies revealed that behavioural interventions to enhance self-efficacy improved oral-care behaviour of patients. Therefore, assessment and enhancement of oral-care specific self-efficacy is important to promote behaviour modification in clinical dental practice. However, more researches are needed to evaluate the suitability of the intervention method.

  8. DMPP-enhanced control efficacy of chili pepper Phytophthora blight using ammonium bicarbonate:Action effects and mechanisms%DMPP 增强碳酸氢铵防控辣椒疫病的效果与机制

    Institute of Scientific and Technical Information of China (English)

    曹云; 王光飞; 郭德杰; 马艳; 罗德旭; 孙玉东; 汪国莲

    2016-01-01

    Phytophthora blight of chili pepper, caused by oomycetes of Phytophthora capsici, has been reported to be a key limiting factor of chili pepper production worldwide. Increased public interest in protecting the environment and human health has prompted research in agronomic strategies that reduce the use of fungicides. Alternative control methods with high efficacy, low cost and limited environmental effect are high-priority research areas for sustainable agriculture. Under the same incubation conditions (soil moisture of 60% of field capacity, temperature of 25 ℃ and inoculation concentration of P. capsici of 500 CFU·g-1), DMPP (1% applied pure N) and ammonium bicarbonate (AB) [100 mg(N)·kg-1] were added tofluvo-aquic soil and incubated for 15 d. Soil without any addition of DMPP and/or AB was set as the control. After incubation, DMPP or AB-treated soil was used to grow chili pepper in a pot experiment for 28 d. The effect of DMPP and AB application on disease incidence of Phytophthora blight of chili pepper was then compared. The soil physio-chemical and microbial responses (soil pH, electric conductivity, concentrations of different forms of nitrogen; numbers of total bacteria, fungi, P. capsici and ammonia-oxidizing bacteria) to the addition of DMPP and AB were determined. The relationship between Phytophthora blight disease incidence and soil phyiso-chemical and microbial characteristics was evaluated. The aim of the study was to investigate the control effects of DMPP-enhanced ammonium biocarbonate on Phytophthora blight of chili pepper and correlation with soil physio-chemical properties, and provided technological support for control of Phytophthora blight of chili pepper of greenhouse. The results suggested that compared with the control, the contents of soil ammonium nitrogen in DMPP and DMPP+AB treatments were higher, and the contents of nitrate and nitrite nitrogen significantly lower. The application of DMPP for 15 d decreased copied gene numbers

  9. How to enhance the self-efficacy of journal editors of higher vocational colleges%如何提升高职学报编辑的自我效能感

    Institute of Scientific and Technical Information of China (English)

    王丽婷

    2012-01-01

    Self-efficacy is the driving force of stimulating editors' work motivation to achieve the supposed target.Only if the journals of higher vocational colleges improve their social influence,evaluate editors' capability objectively,strengthen the occupation development management of editors,and improve the importance of editing work,can the editors' self-efficacy be promoted and developed and ultimately reflected in the high quality of editing practice.%自我效能感是激发编辑的工作动机、实现编辑目标的原动力。高职学报只有努力提升自身的社会影响力,客观评价编辑的编辑水平,加强对编辑的职业成长管理,提高编辑工作声望,才有助于编辑自我效能感的提升和发展,并最终体现于高质量的编辑实践中。

  10. Co-administration of rIpaB domain of Shigella with rGroEL of S. Typhi enhances the immune responses and protective efficacy against Shigella infection.

    Science.gov (United States)

    Chitradevi, Sekar Tamil Selvi; Kaur, Gurpreet; Uppalapati, Sivaramakrishna; Yadav, Anandprakash; Singh, Dependrapratap; Bansal, Anju

    2015-11-01

    Shigella species cause severe bacillary dysentery in humans and are associated with high morbidity and mortality. The Invasion plasmid antigen (IpaB) protein, which is conserved across all Shigella spp., induces macrophage cell death and is required to invade host cells. The present study evaluates the immunogenicity and protective efficacy of the recombinant (r) domain region of IpaB (rIpaB) of S. flexneri. rIpaB was administered either alone or was co-administered with the rGroEL (heat shock protein 60) protein from S. Typhi as an adjuvant in a mouse model of intranasal immunization. The IpaB domain region (37 kDa) of S. flexneri was amplified from an invasion plasmid, cloned, expressed in BL21 Escherichia coli cells and purified. Immunization with the rIpaB domain alone stimulated both humoral and cell-mediated immune responses. Furthermore, robust antibody (IgG, IgA) and T-cell responses were induced when the rIpaB domain was co-administered with rGroEL. Antibody isotyping revealed higher IgG1 and IgG2a antibody titers and increased interferon-gamma (IFN-γ) secretion in the co-administered group. Immunization of mice with the rIpaB domain alone protected 60%-70% of the mice from lethal infection by S. flexneri, S. boydii and S. sonnei, whereas co-administration with rGroEL increased the protective efficacy to 80%-85%. Organ burden and histopathological studies also revealed a significant reduction in lung infection in the co-immunized mice compared with mice immunized with the rIpaB domain alone. This study emphasizes that the co-administration of the rIpaB domain and rGroEL protein improves immune responses in mice and increases protective efficacy against Shigella infection. This is also the first report to evaluate the potential of the GroEL (Hsp 60) protein of S. Typhi as an adjuvant molecule, thereby overcoming the need for commercial adjuvants.

  11. Co-administration of rIpaB domain of Shigella with rGroEL of S. Typhi enhances the immune responses and protective efficacy against Shigella infection

    Science.gov (United States)

    Chitradevi, Sekar Tamil Selvi; Kaur, Gurpreet; Uppalapati, Sivaramakrishna; Yadav, Anandprakash; Singh, Dependrapratap; Bansal, Anju

    2015-01-01

    Shigella species cause severe bacillary dysentery in humans and are associated with high morbidity and mortality. The Invasion plasmid antigen (IpaB) protein, which is conserved across all Shigella spp., induces macrophage cell death and is required to invade host cells. The present study evaluates the immunogenicity and protective efficacy of the recombinant (r) domain region of IpaB (rIpaB) of S. flexneri. rIpaB was administered either alone or was co-administered with the rGroEL (heat shock protein 60) protein from S. Typhi as an adjuvant in a mouse model of intranasal immunization. The IpaB domain region (37 kDa) of S. flexneri was amplified from an invasion plasmid, cloned, expressed in BL21 Escherichia coli cells and purified. Immunization with the rIpaB domain alone stimulated both humoral and cell-mediated immune responses. Furthermore, robust antibody (IgG, IgA) and T-cell responses were induced when the rIpaB domain was co-administered with rGroEL. Antibody isotyping revealed higher IgG1 and IgG2a antibody titers and increased interferon-gamma (IFN-γ) secretion in the co-administered group. Immunization of mice with the rIpaB domain alone protected 60%–70% of the mice from lethal infection by S. flexneri, S. boydii and S. sonnei, whereas co-administration with rGroEL increased the protective efficacy to 80%–85%. Organ burden and histopathological studies also revealed a significant reduction in lung infection in the co-immunized mice compared with mice immunized with the rIpaB domain alone. This study emphasizes that the co-administration of the rIpaB domain and rGroEL protein improves immune responses in mice and increases protective efficacy against Shigella infection. This is also the first report to evaluate the potential of the GroEL (Hsp 60) protein of S. Typhi as an adjuvant molecule, thereby overcoming the need for commercial adjuvants. PMID:25640657

  12. The Combined Effects of Classroom Teaching and Learning Strategy Use on Students' Chemistry Self-Efficacy

    Science.gov (United States)

    Cheung, Derek

    2015-02-01

    For students to be successful in school chemistry, a strong sense of self-efficacy is essential. Chemistry self-efficacy can be defined as students' beliefs about the extent to which they are capable of performing specific chemistry tasks. According to Bandura (Psychol. Rev. 84:191-215, 1977), students acquire information about their level of self-efficacy from four sources: performance accomplishments, vicarious experiences, verbal persuasion, and physiological states. No published studies have investigated how instructional strategies in chemistry lessons can provide students with positive experiences with these four sources of self-efficacy information and how the instructional strategies promote students' chemistry self-efficacy. In this study, questionnaire items were constructed to measure student perceptions about instructional strategies, termed efficacy-enhancing teaching, which can provide positive experiences with the four sources of self-efficacy information. Structural equation modeling was then applied to test a hypothesized mediation model, positing that efficacy-enhancing teaching positively affects students' chemistry self-efficacy through their use of deep learning strategies such as metacognitive control strategies. A total of 590 chemistry students at nine secondary schools in Hong Kong participated in the survey. The mediation model provided a good fit to the student data. Efficacy-enhancing teaching had a direct effect on students' chemistry self-efficacy. Efficacy-enhancing teaching also directly affected students' use of deep learning strategies, which in turn affected students' chemistry self-efficacy. The implications of these findings for developing secondary school students' chemistry self-efficacy are discussed.

  13. Personal, social, and cultural correlates of self-efficacy beliefs among South Korean college smokers.

    Science.gov (United States)

    Cho, Hyunyi; So, Jiyeon; Lee, Jinro

    2009-06-01

    Much research has documented the significant influence of self-efficacy on smoking cessation, but considerably less is known as to what health communicators can do to promote or address barriers to self-efficacy. This study investigated personal, social, and cultural correlates of smoking self-efficacy. A survey of college smokers was done in South Korea, where the current smoking rate among males is over 56%. At the personal level, the perceived success-fullness of the last quit trial positively predicted self-efficacy. At the social level, interpersonal communication with friends was positively associated with self-efficacy. The cultural orientation of independent self-construal was positively associated with self-efficacy. These results indicate that factors affecting smokers' self-efficacy are operative in multiple domains and levels. Future communication programs should promote positive perceptions about prior quit trials, and segment the audience in terms of their self-construal to effectively enhance self-efficacy.

  14. 24-h Efficacy of Glaucoma Treatment Options.

    Science.gov (United States)

    Konstas, Anastasios G P; Quaranta, Luciano; Bozkurt, Banu; Katsanos, Andreas; Garcia-Feijoo, Julian; Rossetti, Luca; Shaarawy, Tarek; Pfeiffer, Norbert; Miglior, Stefano

    2016-04-01

    Current management of glaucoma entails the medical, laser, or surgical reduction of intraocular pressure (IOP) to a predetermined level of target IOP, which is commensurate with either stability or delayed progression of visual loss. In the published literature, the hypothesis is often made that IOP control implies a single IOP measurement over time. Although the follow-up of glaucoma patients with single IOP measurements is quick and convenient, such measurements often do not adequately reflect the untreated IOP characteristics, or indeed the quality of treated IOP control during the 24-h cycle. Since glaucoma is a 24-h disease and the damaging effect of elevated IOP is continuous, it is logical that we should aim to understand the efficacy of all treatment options throughout the 24-h period. This article first reviews the concept and value of diurnal and 24-h IOP monitoring. It then critically evaluates selected available evidence on the 24-h efficacy of medical, laser and surgical therapy options. During the past decade several controlled trials have significantly enhanced our understanding on the 24-h efficacy of all glaucoma therapy options. Nevertheless, more long-term evidence is needed to better evaluate the 24-h efficacy of glaucoma therapy and the precise impact of IOP characteristics on glaucomatous progression and visual prognosis.

  15. 增强自我效能干预对癫痫患者自尊、总体幸福感及应对方式的影响%The effect of enhancing self-efficacy intervention on self-esteem, overall well-being and coping Styles of patients With epilepsy

    Institute of Scientific and Technical Information of China (English)

    刘桂苓; 楚平华

    2010-01-01

    Objective To explore the effect of enhancing self-efficacy intervention on self-esteem, overall well-being and coping styles of patients with epilepsy. Methods A total of 112 patients with epilepsy were randomly divided into the study group and control group, the control group was given the general health education, and the study groups was given the enhancing self-efficacy intervention, including incentives, social suppor, behavioral approach. Use of The self-esteem scale (SES) and the feelings of inadequacy scale (F1S) , the overall well-being scale (GWB) , and coping style questionnaires was used to evaluate the therapeutic effect before and after training in patients with self-control and two sets of cross-referencing, when the patient was discharged a year impact Results After intervention the SES, FIS, and GWB scores of study group were significantly higher than those of control group , and the immature coping styles scores of study group (self-blame, fantasy, retreat) were significantly lower than those of the control group (P < 0. 01) . Conclusions To enhance self-efficacy intervention, eliminate low self-esteem, enhance their self-confidence and self-esteem and cope with a positive approach to solve the problem can significantly improve the overall well-being in patients with epilepsy.%目的 探讨增强自我效能干预对癫痫患者自尊、总体幸福感及应对方式的影响.方法 将112例癫痫患者随机均分为研究组和对照组,对照组实施一般健康教育,研究组进行增强自我效能干预,内容包括:激励、社会支持、行为方法.学习采用集体授课和个别教育相结合的形式.采用自尊量表(SES)和缺陷感量表(FIS)、总体幸福感量表(GWB)及应付方式问卷对患者进行训练前后自身对照和两组相互对照,在患者出院1年时进行效果评价.结果 研究组经干预治疗后SES、FIS及GWB评分均明显高于对照组,不成熟的应付方式(自责、幻想、

  16. Phosphodiesterase 4 inhibitors augment the ability of formoterol to enhance glucocorticoid-dependent gene transcription in human airway epithelial cells: a novel mechanism for the clinical efficacy of roflumilast in severe chronic obstructive pulmonary disease.

    Science.gov (United States)

    Moodley, Thunicia; Wilson, Sylvia M; Joshi, Taruna; Rider, Christopher F; Sharma, Pawan; Yan, Dong; Newton, Robert; Giembycz, Mark A

    2013-04-01

    Post-hoc analysis of two phase III clinical studies found that the phosphodiesterase 4 (PDE4) inhibitor, roflumilast, reduced exacerbation frequency in patients with severe chronic obstructive pulmonary disease (COPD) who were taking inhaled corticosteroids (ICS) concomitantly, whereas patients not taking ICS derived no such benefit. In contrast, in two different trials also performed in patients with severe COPD, roflumilast reduced exacerbation rates in the absence of ICS, indicating that PDE4 inhibition alone is sufficient for therapeutic activity to be realized. Given that roflumilast is recommended as an "add-on" medication to patients with severe disease who will inevitably be taking a long-acting β2-adrenoceptor agonist (LABA)/ICS combination therapy, we tested the hypothesis that roflumilast augments the ability of glucocorticoids to induce genes with anti-inflammatory activity. Using a glucocorticoid response element (GRE) luciferase reporter transfected into human airway epithelial cells [both bronchial epithelium + adenovirus 12 - SV40 hybrid (BEAS-2B) cells and primary cultures], roflumilast enhanced fluticasone propionate-induced GRE-dependent transcription. Roflumilast also produced a sinistral displacement of the concentration-response curves that described the augmentation of GRE-dependent transcription by the LABA formoterol. In BEAS-2B cells and primary airway epithelia, roflumilast interacted with formoterol in a positive cooperative manner to enhance the expression of several glucocorticoid-inducible genes that have anti-inflammatory potential. We suggest that the ability of roflumilast and formoterol to interact in this way supports the concept that these drugs together may impart clinical benefit beyond that achievable by an ICS alone, a PDE4 inhibitor alone, or an ICS/LABA combination therapy. Roflumilast may, therefore, be especially effective in patients with severe COPD.

  17. Superior efficacy of new medicines?

    NARCIS (Netherlands)

    Luijn, J.C.F. van; Gribnau, F.W.J.; Leufkens, H.G.M.

    2010-01-01

    PURPOSE: To provide an overview of and discuss newly authorised medicines with an improved efficacy. METHODS: This analysis focussed on new medicines with an improved efficacy based on the results of randomised active control trials. Information on comparative efficacy was obtained from the European

  18. Pre-irradiation with low-dose 12C6+ beam significantly enhances the efficacy of AdCMV-p53 gene therapy in human non-small lung cancer

    Institute of Scientific and Technical Information of China (English)

    LIU Bing; DUAN Xin; ZHANG Hong; LI WenJian; LI Qiang; ZHOU GuangMing; XIE Yi; HAO JiFang; MIN FengLing; ZHOU QingMing

    2007-01-01

    The combination of ionizing radiation and gene therapy has been investigated. However, there are very few reports about the combination of heavy-ion irradiation and gene therapy. To determine if the pre-exposure to low-dose heavy ion beam enhances the suppression of AdCMV-p53 on non-small lung cancer (NSLC), the cells pre-irradiated or non-irradiated were infected with 20, 40 MOl of AdCMV-p53. Survival fraction and the relative biology effect (RBE) were determined by clonogenic assay. The results showed that the proportions of p53 positive cells in 12C6+ beam induced AdCMV-p53 infected cells were more than 90%, which were significantly more than those in γ-ray induced AdCMV-p53 infected cells. The pre-exposure to low-dose 12C6+ beam significantly prevented the G0/G1 arrest and activated G2/M checkpoints. The pre-exposure to 12C6+ beam significantly improved cell to apoptosis. RBEs for the 12C6+ + AdCMV-p53 infection groups were 30%-60%, 20% -130% and 30%-70% more than those for the 12C6+-irradiated only, AdCMV-p53 infected only, and γ-irradiation induced AdCMVp53 infected groups, respectively. The data suggested that the pre-exposure to low-dose 12C6+ beam significantly promotes exogenous p53 expression in NSLC, and the suppression of AdCMV-p53 gene therapy on NSLC.

  19. Pre-irradiation with low-dose 12C6+ beam significantly enhances the efficacy of AdCMV-p53 gene therapy in human non-small lung cancer

    Science.gov (United States)

    Liu, Bing; Zhang, Hong; Li, Wenjian; Li, Qiang; Zhou, Guangming; Xie, Yi; Hao, Jifang; Min, Fengling; Zhou, Qingming; Duan, Xin

    2007-04-01

    The combination of ionizing radiation and gene therapy has been investigated. However, there are very few reports about the combination of heavy-ion irradiation and gene therapy. To determine if the pre-exposure to low-dose heavy ion beam enhances the suppression of AdCMV-p53 on non-small lung cancer (NSLC), the cells pre-irradiated or non-irradiated were infected with 20, 40 MOI of AdCMV-p53. Survival fraction and the relative biology effect (RBE) were determined by clonogenic assay. The results showed that the proportions of p53 positive cells in 12C6+ beam induced AdCMV-p53 infected cells were more than 90%, which were significantly more than those in γ-ray induced AdCMV-p53 infected cells. The pre-exposure to low-dose 12C6+ beam significantly prevented the G0/G1 arrest and activated G2/M checkpoints. The pre-exposure to 12C6+ beam significantly improved cell to apoptosis. RBEs for the 12C6+ + AdCMV-p53 infection groups were 30% 60%, 20% 130% and 30% 70% more than those for the 12C6+-irradiated only, AdCMV-p53 infected only, and γ-irradiation induced AdCMVp53 infected groups, respectively. The data suggested that the pre-exposure to low-dose 12C6+ beam significantly promotes exogenous p53 expression in NSLC, and the suppression of AdCMV-p53 gene therapy on NSLC.

  20. Pre-irradiation with low-dose 12C6+beam significantly enhances the efficacy of AdCMV-p53 gene therapy in human non-small lung cancer

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The combination of ionizing radiation and gene therapy has been investigated. However, there are very few reports about the combination of heavy-ion irradiation and gene therapy. To determine if the pre-exposure to low-dose heavy ion beam enhances the suppression of AdCMV-p53 on non-small lung cancer (NSLC), the cells pre-irradiated or non-irradiated were infected with 20, 40 MOI of AdCMV-p53. Survival fraction and the relative biology effect (RBE) were determined by clonogenic assay. The results showed that the proportions of p53 positive cells in 12C6+ beam induced AdCMV-p53 infected cells were more than 90%, which were signifi-cantly more than those in γ-ray induced AdCMV-p53 infected cells. The pre-exposure to low-dose 12C6+ beam significantly prevented the G0/G1 arrest and activated G2/M checkpoints. The pre-exposure to 12C6+ beam significantly improved cell to apoptosis. RBEs for the 12C6+ + AdCMV-p53 infection groups were 30%-60%, 20%-130% and 30%-70% more than those for the 12C6+-irradiated only, AdCMV-p53 infected only, and γ-irradiation induced AdCMVp53 infected groups, respectively. The data suggested that the pre-exposure to low-dose 12C6+ beam significantly promotes exogenous p53 expression in NSLC, and the suppression of AdCMV-p53 gene therapy on NSLC.

  1. Doubling Down on the PI3K-AKT-mTOR Pathway Enhances the Antitumor Efficacy of PARP Inhibitor in Triple Negative Breast Cancer Model beyond BRCA-ness

    Directory of Open Access Journals (Sweden)

    Pradip De

    2014-01-01

    Full Text Available Phosphoinositide 3-kinase (PI3K pathway, in addition to its pro-proliferative and antiapoptotic effects on tumor cells, contributes to DNA damage repair (DDR. We hypothesized that GDC-0980, a dual PI3K-mammalian target of rapamycin (mTOR inhibitor, would induce an efficient antitumor effect in BRCA-competent triple negative breast cancer (TNBC model when combined with ABT888 and carboplatin. Mechanism-based in vitro studies demonstrated that GDC-0980 treatment alone or in combination led to DNA damage (increased pγH2AXS139; Western blot, immunofluorescence, gain in poly ADP-ribose (PAR, and a subsequent sensitization of BRCA-competent TNBC cells to ABT888 plus carboplatin with a time-dependent 1 decrease in proliferation signals (pAKTT308/S473, pP70S6KT421/S424, pS6RPS235/236, PAR/poly(ADP-ribose polymerase (PARP ratios, PAR/pγH2AX ratios, live/dead cell ratios, cell cycle progression, and three-dimensional clonogenic growths and 2 increase in apoptosis markers (cleaved caspases 3 and 9, a pro-apoptotic BH3-only of Bcl-2 family (BIM, cleaved PARP, annexin V. The combination was effective in vitro in BRCA-wild-type PIK3CA-H1047R-mutated BT20 and PTEN-null HCC70 cells. The combination blocked the growth of established xenograft tumors by 80% to 90% with a concomitant decrease in tumor Ki67, CD31, phosphorylated vascular endothelial growth factor receptor, pS6RPS235/236, and p4EBP1T37/46 as well as an increase in cleaved caspase 3 immunohistochemistry (IHC levels. Interestingly, a combination with GDC-0941, a pan-PI3K inhibitor, failed to block the tumor growth in MDA-MB231. Results demonstrate that the dual inhibition of PI3K and mTOR regulates DDR. In a BRCA-competent model, GDC-0980 enhanced the antitumor activity of ABT888 plus carboplatin by inhibiting both tumor cell proliferation and tumor-induced angiogenesis along with an increase in the tumor cell apoptosis. This is the first mechanism-based study to demonstrate the integral role of the

  2. The efficacy of pivmecillinam

    DEFF Research Database (Denmark)

    Jansåker, Filip; Frimodt-Møller, Niels; Bjerrum, Lars

    2016-01-01

    regimen is superior to a 3-day regimen. With this study we aim to identify and to compare the efficacy of pivmecillinam 400 mg t.i.d in a 3-day respectively 5-day regimen, against community acquired uncomplicated LUTI, i.e., in women at the age of 18-70 year old. METHOD/DESIGN: The general practitioner....... DISCUSSION: Pivmecillinam is an excellent choice against urinary tract infections and we believe this study will fill in the gaps and strengthen the evidence on the treatment against one of the most common infections in our society. Thus, aiming to provide a more rational and ecological beneficial...

  3. Negative self-efficacy and goal effects revisited.

    Science.gov (United States)

    Bandura, Albert; Locke, Edwin A

    2003-02-01

    The authors address the verification of the functional properties of self-efficacy beliefs and document how self-efficacy beliefs operate in concert with goal systems within a sociocognitive theory of self-regulation in contrast to the focus of control theory on discrepancy reduction. Social cognitive theory posits proactive discrepancy production by adoption of goal challenges working in concert with reactive discrepancy reduction in realizing them. Converging evidence from diverse methodological and analytic strategies verifies that perceived self-efficacy and personal goals enhance motivation and performance attainments. The large body of evidence, as evaluated by 9 meta-analyses for the effect sizes of self-efficacy beliefs and by the vast body of research on goal setting, contradicts findings (J. B. Vancouver, C. M. Thompson, & A. A. Williams, 2001; J. B. Vancouver, C. M. Thompson, E. C. Tischner, & D. J. Putka 2002) that belief in one's capabilities and personal goals is self-debilitating.

  4. Approaching Environmental Sustainability: Perceptions of Self-Efficacy and Changeability.

    Science.gov (United States)

    Schutte, Nicola S; Bhullar, Navjot

    2017-04-03

    This paper describes a model focused on the role of self-efficacy and belief in changeability of behavior in motivating environmentally sustainable behavior. The model was tested in two studies. The first study found that participants who had greater self-efficacy for sustainability behavior and a greater belief in their changeability of sustainability behavior had a higher level of approach motivation toward sustainability behavior and reported more such actual behavior. The second study investigated the effect of brief interventions intended to increase perception of self-efficacy for sustainability-related purchasing and changeability of sustainability-related purchasing. The intervention that focused on enhancing self-efficacy for making sustainability-related purchases had the strongest impact on intention to purchase. These findings have implications for interventions intended to change behavior related to environmental sustainability.

  5. Self-efficacy strategies to improve exercise in patients with heart failure: A systematic review

    OpenAIRE

    Rajati, Fatemeh; Sadeghi, Masoumeh; Feizi, Awat; Sharifirad, Gholamreza; Hasandokht, Tolu; Mostafavi, Firoozeh

    2014-01-01

    BACKGROUND Despite exercise is recommended as an adjunct to medication therapy in patients with heart failure (HF), non-adherence to exercise is a major problem. While improving self-efficacy is an effective way to increase physical activity, the evidence concerning the relationship between strategies to enhance self-efficacy and exercise among HF has not been systematically reviewed. The objective of this systematic review is to assess the effect of interventions to change the self-efficacy ...

  6. Understanding Teaching Assistant Self-Efficacy in Role and in Training: Its Susceptibility to Influence

    Science.gov (United States)

    Higgins, Helen; Gulliford, Anthea

    2014-01-01

    There has been a noted growth in the number of teaching assistants (TAs) in mainstream schools. Research is inconclusive about their efficacy at changing outcomes for children and has proposed more training for TAs. Generic training models have suggested that enhancing self-efficacy in turn improves performance. This exploratory study investigated…

  7. Self-efficacy and its influence on recovery of patients with stroke : a systematic review

    NARCIS (Netherlands)

    Korpershoek, Corrie; van der Bijl, Jaap; Hafsteinsdottir, Thora B.

    2011-01-01

    Aims. To provide an overview of the literature focusing on the influence of self-efficacy and self-efficacy enhancing interventions on mobility, activities of daily living, depression and quality of life of patients with stroke. Background. There is growing evidence for the importance of self-effica

  8. Midazolam-sirupus, formulation and pharmacodynamic efficacy

    Directory of Open Access Journals (Sweden)

    K. Goracinova

    2002-04-01

    Full Text Available Due to its pharmacokinetic and pharmacodynamic properties (sedation, amnesia and relief of anxiety Midazolam has become a comm only used agent for conscious sedation of children before diagnostic or therapeutic procedure or before induction of anesthesia. Con sidering the advantage of oral administration to avoid the additional trauma of starting an IV in the child, and the fact that there is no ad equate dosage form (Midazolam - Syrupus on the drug market in our country, the aim of the presented work was to formulate syrupus using syrupus b ase/aqueous solution of viscosity enhancer - HPMC, in combination with suitable sweetener, flavor, and preservatives, and to evaluate its q uality and stability. The pharmacodynamic efficacy/sedative effect of Midazolam HCl - Syrupus formulation was evaluated in 33 pediatric patients comp aring this with the efficacy of intramuscularly administered Midazolam HCl (35 pediatric patients in accordance with the Ramsay scale for analgosedation. The formulation manifested good quality in respect to physical properties, physico-chemical parameters (pH value, relative dens ity, drug content, ingredients content antimicrobial efficacy and microbiological quality according to Ph Eur 3. In the conditions chara cteristic of the second (II climate zone, the dosage form was stable for four months. The sedative effect of orally administered Midazolam was manifested in a period necessary for surgical premedication (30 - 45 min. The majority of patients (71% entered the second phase on the Ramsa y scale, when Midazolam was administered in a dose of 0.40 mg/kg.

  9. Efficacy of antihypertensive drugs.

    Science.gov (United States)

    Dixon, G T; Johnson, E S

    1976-03-01

    The magnitude of the fall in blood-pressure in response to an antihypertensive drug depends on the level of the pretreatment pressure, and there is a direct relationship between the two in that the higher the pretreatment pressure the greater the fall in pressure in response to treatment. This simple relationship is inherent in the practical situation of titrating the diastolic blood-pressures of a group of hypertensive patients to a predetermined level. It is assumed that notionally the dose of an antihypertensive drug can be increased in all patients until the diastolic pressure is reduced to the predetermined level. When the fall in diastolic pressure (deltaD.P.) is plotted against pretreatment diastolic pressure (P.T.D.P.), the points for all patients lie on a straight line of slope unity and negative deltaD.P.-intercept numerically equal to the predetermined diastolic-pressure level. This straight-line relationship is termed the predetermined ideal response line. Analysis of data from clinical trials shows that, despite the variability inherent in the practical situation, the data appear to conform to this straight-line relationship. The method of assessing the efficacy of antihypertensive agents is essentially a comparison of each experimental point with the theoretical predetermined response line. In its simplest form the method consists in constructing a scatter diagram of deltaD.P. against P.T.D.P. for all patients. Patients can then be classified as responders or non-responders according to their position on the diagram relative to the predetermined response line. This method of assessing the efficacy of antihypertensive agents has several advantages, the most important of which is that it provides a simple method for displaying all the relevant information in a readily comparable form.

  10. EFFECT OF MUSIC THERAPY ON INTRINSIC MOTIVATION, PHYSICAL SELF EFFICACY AND PERFORMANCE OF FEMALE FOOTBALL PLAYERS

    OpenAIRE

    Mamta Sharma; Gagandeep Kaur

    2015-01-01

    Music therapy is increasingly used in sports for enhancing sport performance. It provides a mean of improving mental strength among sportspersons. The purpose of this study is to enhance intrinsic motivation, physical self-efficacy and performance of female football players through music therapy. For this purpose, twenty two female football players, in the age group of 21-26 were screened on the basis of their scores on Sport Motivation Scale and Physical Self-Efficacy Scale. Then, they were ...

  11. Targeted CNx Nanowire-Drug Complexes for Enhanced Chemotherapeutic Efficacy

    Science.gov (United States)

    2009-09-01

    Zhongrui Li‡ and Alexandru S. Biris‡ (2008). Temperature Measurement of Carbon Nanotubes Using Infrared Thermography Chemistry of Materials 20, 4011...The relative efficiency of conversion of nIR irradiation into heat for DNA-encased MWNTs relative to non-DNA-encased MWNTs and other materials is...successful, the use of aptamers. Details of the successful approach to building N-MWNTs with targeting molecule: Raw, carbon vapor deposition (CVD) MWNTs

  12. Enhancing the Efficacy of Antihypertensive Treatrnent with Pharmacogenomics

    Institute of Scientific and Technical Information of China (English)

    陈慧

    2004-01-01

    In 2003, two new guidelines for hypertensive prevention and management have beenprovided by American JNC7 and European Society of Hypertension. They advocated that the physician should choose drugs following individualized treatment , which should also be followed by integrative traditional and western medicine. The emerging field of pharmaeogenomies has the potential to fundamentally change the management of essential hypertension (EH), a common polygenic syndrome characterized by substantial inter-individual variability in drug responsiveness.

  13. Enhancing the Efficacy of Antihypertensive Treatment with Pharmacogenomics

    Institute of Scientific and Technical Information of China (English)

    陈慧

    2004-01-01

    @@ In 2003, two newguidelines for hypertensive prevention and management have been provided by American JNC7 and European Society of Hypertension.They advocated that the physician should choose drugs following individualized treatment,which should also be followed by integrative traditional and western medicine.

  14. Reticence, Accuracy and Efficacy

    Science.gov (United States)

    Oreskes, N.; Lewandowsky, S.

    2015-12-01

    James Hansen has cautioned the scientific community against "reticence," by which he means a reluctance to speak in public about the threat of climate change. This may contribute to social inaction, with the result that society fails to respond appropriately to threats that are well understood scientifically. Against this, others have warned against the dangers of "crying wolf," suggesting that reticence protects scientific credibility. We argue that both these positions are missing an important point: that reticence is not only a matter of style but also of substance. In previous work, Bysse et al. (2013) showed that scientific projections of key indicators of climate change have been skewed towards the low end of actual events, suggesting a bias in scientific work. More recently, we have shown that scientific efforts to be responsive to contrarian challenges have led scientists to adopt the terminology of a "pause" or "hiatus" in climate warming, despite the lack of evidence to support such a conclusion (Lewandowsky et al., 2015a. 2015b). In the former case, scientific conservatism has led to under-estimation of climate related changes. In the latter case, the use of misleading terminology has perpetuated scientific misunderstanding and hindered effective communication. Scientific communication should embody two equally important goals: 1) accuracy in communicating scientific information and 2) efficacy in expressing what that information means. Scientists should strive to be neither conservative nor adventurous but to be accurate, and to communicate that accurate information effectively.

  15. The Role of Interactions between Student and Classroom Context in Developing Adaptive Self-Efficacy in One Sixth-Grade Mathematics Classroom

    Science.gov (United States)

    Yetkin Ozdemir, I. Elif; Pape, Stephen J.

    2013-01-01

    Research and theory suggest several instructional practices that could enhance student self-efficacy. However, little is known about the ways these instructional practices interact with individual students to create opportunities or challenges for developing adaptive self-efficacy. In this study, we focused on two sources of efficacy, mastery…

  16. Emdogain: evidence of efficacy.

    Science.gov (United States)

    Greenstein, G

    2000-04-01

    This article addresses the use of enamel matrix proteins (Emdogain) to enhance regeneration of the periodontium. Information regarding the role of Emdogain to induce cementogenesis and histologic evidence in animals and humans that it can initiate regeneration of diseased sites are discussed. Several clinical trials have indicated that Emdogain plus modified Widman flap surgery provide a better result than the surgery alone. Several other investigations have indicated that flap surgery plus Emdogain or a bioabsorbable membrane achieve similar results. However, this latter finding needs further validation. Clinical examples of successful therapy with Emdogain are presented.

  17. Obesity and hormonal contraceptive efficacy.

    Science.gov (United States)

    Robinson, Jennifer A; Burke, Anne E

    2013-09-01

    Obesity is a major public health concern affecting an increasing proportion of reproductive-aged women. Avoiding unintended pregnancy is of major importance, given the increased risks associated with pregnancy, but obesity may affect the efficacy of hormonal contraceptives by altering how these drugs are absorbed, distributed, metabolized or eliminated. Limited data suggest that long-acting, reversible contraceptives maintain excellent efficacy in obese women. Some studies demonstrating altered pharmacokinetic parameters and increased failure rates with combined oral contraceptives, the contraceptive patch and emergency contraceptive pills suggest decreased efficacy of these methods. It is unclear whether bariatric surgery affects hormonal contraceptive efficacy. Obese women should be offered the full range of contraceptive options, with counseling that balances the risks and benefits of each method, including the risk of unintended pregnancy.

  18. Paromomycin-loaded albumin microspheres: efficacy and stability studies.

    Science.gov (United States)

    Khan, Wahid; Kumar, Rajendra; Singh, Sukhvinder; Arora, Sunil Kumar; Kumar, Neeraj

    2013-06-01

    In the present work, paromomycin-loaded albumin microspheres (PM-MS) have been formulated for passive targeting of paromomycin (PM) to macrophages, for the treatment of visceral leishmaniasis (VL). PM-MS were prepared by spray-drying method with a mean particle size of ≈ 3 µm. Thermal and chemical cross-linking methods were used for controlling drug release from the prepared microspheres (MS). PM-MS were then tested for efficacy and stability studies. In efficacy study, in vitro promastigote assay was carried out to assess the susceptibility of promastigote to PM in the concentration range of 5.0-150 µg/ml; cytotoxicity assay was performed to determine possible toxicity of PM for the host cells (peritoneal macrophages) and intracellular amastigote assay was carried out to determine the efficacy of free PM (PM solution) and encapsulated PM (PM-MS). Results obtained indicated a significant increase in efficacy of PM-MS in comparison to PM solution at equivalent concentration. Subsequently, stability studies of prepared formulation was carried out at various temperature and humidity conditions, these studies provided stability of formulation at all tested conditions including accelerated conditions. Thus, it can be concluded that present work provides an optimized formulation with stability and enhanced efficacy.

  19. Self-efficacy as a mediator of the relationship between perceived union barriers and women's participation in union activities.

    Science.gov (United States)

    Bulger, C A; Mellor, S

    1997-12-01

    This study investigated the influence of union self-efficacy (expectations of success in pursuit of union activities) as a mediator of the relationship between perceptions of barriers to union participation and women's participation in union activities (N = 89). Perceived barriers were defined in 4 domains (community, family, union, work), and self-efficacy was operationalized based on C. Lee and P. Bobko's (1994) analysis of self-efficacy measures (self-efficacy magnitude, self-efficacy strength). Union self-efficacy was found to mediate the relationship between the magnitude of perceived union barriers and the magnitude of union participation, although mediation was limited to women with weak union self-efficacy. Implications for designing training and intervention programs to enhance women's participation in the face of perceived barriers are discussed.

  20. 心理干预对中国高血压病患者治疗效果影响的系统评价和Meta分析%Psychological interventions enhance the efficacy of drug therapy in patients undergoing primary hypertension: systematic review of observational RCT with meta-analysis

    Institute of Scientific and Technical Information of China (English)

    龙淑芳; 史潇; 谢妮

    2012-01-01

    目的 明确心理干预对中国高血压病患者收缩压及舒张压的降压效果的影响,为高血压病的治疗开辟新思路.方法 全面检索国内相关文献,并对符合要求的文献进行质量评价.采用Meta分析法对以往研究报道的心理干预对高血压病患者收缩压及舒张压的降压效果的影响进行合并分析,采用敏感性分析结果的稳定性,采用Begg's和Egger's法分析纳入研究的发表偏倚.结果 共纳入6篇符合要求的文献进行合并分析.收缩压和舒张压合并效应量和95%CI分别为-13.72(-21.07,-6.37)和-8.33(-13.57,-3.09).经敏感性分析明确系统稳定.Begg's和Egger's检测未测及发表偏倚.结论 对高血压病患者进行心理干预能够提高药物治疗的效果.%Objective To investigate whether psychological interventions have effects on hypertention therapy.Methods We searched on the intemet for eligible articles.The quality of the eligible articles was assessed.Meta-analysis was conducted to investigate the effect of psychological interventions on patients with primary hypertension.Sensitivity analysis was conducted to reanalyze the uncertain results.Begg' s and Egger' s tests were conducted to evaluate the presence of publication bias.Results A total of six controlled studies were included.The findings from our metaanalysis indicated an evidence of positive impact of psychological interventions on systolic pressure and diastolic pressure (systolic pressure:WMD-13.72,95% CI:-21.07,-6.37; diastolic pressure:WMD-8.33,95% CI:-13.57,-3.09).The results of sensitivity analysis confirmed the reliability of the results.The statistical results did not show publication bias.Conclusion In summary,psychological interventions enhance the efficacy of drug therapy in patients undergoing primary hypertension.

  1. Formulation Optimization of a Composite Preservative for Enhanced Efficacy to Inhibit Spoilage Bacteria in Low Temperature Smoked and Cooked Sausages%复合防腐剂对低温熏煮香肠中腐败菌的抑制效果

    Institute of Scientific and Technical Information of China (English)

    岳喜庆; 刘娜

    2012-01-01

    低温熏煮香肠中的腐败菌(乳酸杆菌、假单胞菌、肠杆菌、芽孢杆菌)是导致香肠货架期较短的根本原因。根据单因素试验选出脱氢醋酸钠、双乙酸钠、ε-聚赖氨酸3种效果较好的防腐剂。利用响应面方法对3种复合防腐剂的抑菌效果进行优化。应用Box-Behnken试验设计,建立3种防腐剂的二次多项式回归方程模型进行分析。结果表明:在双乙酸钠0.024g/L、脱氢醋酸钠0.017g/L、ε-聚赖氨酸0.029g/L的条件下复合防腐剂对引起低温熏煮香肠腐败的微生物的生长有很好的抑制作用。%The presence of spoilage bacteria(Lactobacillus,Pseudomonas,Enterobacter and Bacillus) is the fundamental cause of the short shelf-life of low temperature smoked and cooked sausages.In this study,one-factor-at-a-time experiments were carried out to identify sodium diacetate,sodium dehydroacetate and ε-poly-L-lysine as better preservatives for low temperature smoked and cooked sausages.The formulation of the three preservatives for enhanced efficacy to inhibit spoilage bacteria in low temperature smoked and cooked sausages was optimized by response surface methodology.A quadratic polynomial regression model was built using Box-Behnken design and analyzed.The results showed that a composite preservative comprising 0.024 g/L sodium diacetate,0.017 g/L sodium dehydroacetate and 0.029 g/Lε-poly-L-lysine had good inhibitory effect on the growth of spoilage microorganisms in low temperature smoked and cooked sausages.

  2. Effects of the Badge Mechanism on Self-Efficacy and Learning Performance in a Game-Based English Learning Environment

    Science.gov (United States)

    Yang, Jie Chi; Quadir, Benazir; Chen, Nian-Shing

    2016-01-01

    A growing number of studies have been conducted on digital game-based learning (DGBL). However, there has been a lack of attention paid to individuals' self-efficacy and learning performance in the implementation of DGBL. This study therefore investigated how the badge mechanism in DGBL enhanced users' self-efficacy in the subject domain of…

  3. Folic acid conjugated self-assembled layered double hydroxide nanoparticles for high-efficacy-targeted drug delivery.

    Science.gov (United States)

    Yan, Li; Chen, Wei; Zhu, Xiaoyue; Huang, Longbiao; Wang, Zhigang; Zhu, Guangyu; Roy, V A L; Yu, K N; Chen, Xianfeng

    2013-12-04

    Enhanced selectivity and efficacy is important for advanced drug delivery. Herein, a novel type of folic acid conjugated self-assembled layered double hydroxide nanoparticles is reported. These nanoparticles have a drug loading capacity of 27 wt% and are able to enter cell nuclei and dramatically improve the efficacy of MTX.

  4. Microwave ablation of liver metastases guided by contrast-enhanced ultrasound

    DEFF Research Database (Denmark)

    Lorentzen, T; Skjoldbye, B O; Nolsoe, C P

    2011-01-01

    The aim of our study was to evaluate the efficacy of microwave (MW) ablation of liver metastases guided by B-mode ultrasound (US) and contrast-enhanced US (CEUS).......The aim of our study was to evaluate the efficacy of microwave (MW) ablation of liver metastases guided by B-mode ultrasound (US) and contrast-enhanced US (CEUS)....

  5. Exploring the Effects of Self-efficacy on Vocabulary Learning Strategies

    Directory of Open Access Journals (Sweden)

    Atsushi Mizumoto

    2012-12-01

    Full Text Available This study examined the effects of self-efficacy on language learning strategies by focusing on vocabulary learning strategies (VLSs. A group of 281 EFL learners from two universities participated in the study. They completed the Vocabulary Size Test (Nation & Beglar, 2007, questionnaires on self-efficacy, and an open-ended question about their use of VLSs. The learners were divided into three groups based on their responses to the self-efficacy questionnaire. The effect of self-efficacy was then examined by utilizing text mining. The results show that the effects of self-efficacy were observed in the participants’ open-ended responses. It also became clear that those with high self-efficacy were active users of VLSs, they employed deep strategies, and they were metacognitively superior to participants with medium and low efficiency. Those with medium self-efficacy were also active users of VLSs, but they used shallow strategies compared with the high self-efficiency group. Those with low self-efficacy tended to be passive users of VLSs. The pedagogical implications of the current study are discussed mainly in terms of incorporating self-efficacy and self-regulation enhancing instructions into vocabulary teaching.

  6. Tip enhancement

    CERN Document Server

    Kawata, Satoshi

    2007-01-01

    This book discusses the recent advances in the area of near-field Raman scattering, mainly focusing on tip-enhanced and surface-enhanced Raman scattering. Some of the key features covered here are the optical structuring and manipulations, single molecule sensitivity, analysis of single-walled carbon nanotubes, and analytic applications in chemistry, biology and material sciences. This book also discusses the plasmonic materials for better enhancement, and optical antennas. Further, near-field microscopy based on second harmonic generation is also discussed. Chapters have been written by some of the leading scientists in this field, who present some of their recent work in this field.·Near-field Raman scattering·Tip-enhanced Raman spectroscopy·Surface-enhanced Raman spectroscopy·Nano-photonics·Nanoanalysis of Physical, chemical and biological materials beyond the diffraction limits·Single molecule detection

  7. Expressing and responding to self-efficacy in client–social worker interactions

    DEFF Research Database (Denmark)

    Danneris, Sophie; Dall, Tanja

    2017-01-01

    and that social work professionals responses to clients’ expressions can range from supporting to transferring to challenging. Insight into the detailed ways in which self-efficacy is managed in the institutional framework of employment services, we argue, provides a starting point for reflexive consideration......Self-efficacy is a pivotal element when the long-term unemployed are to increase their chances of labour market participation, making the ways in which clients’ beliefs in their capabilities are reflected in the delivery of public employment services particularly relevant. While existing research...... has pointed to the importance of both meetings with social services and self-efficacy for return to work, little knowledge exists on how self-efficacy is managed in these meetings. However, if social work professionals are to effectively enhance clients’ self-efficacy, knowing that self...

  8. Learning to fit in: an exploratory study of general perceived self efficacy in selected refugee groups.

    Science.gov (United States)

    Sulaiman-Hill, Cheryl M R; Thompson, Sandra C

    2013-02-01

    As self efficacy beliefs help determine an individual's response to challenging situations, we explored the impact of the refugee experience on efficacy beliefs and their contribution to resettlement. General self efficacy (GSE) was assessed in 186 resettled Afghan and Kurdish refugees against a range of personal and temporal variables. Although no differences in GSE in relation to temporal factors were noted, significant relationships between self efficacy, lower psychological distress and higher subjective well being were evident. The findings suggest that GSE, because of its positive association with mental health and well being, is a variable worthy of further examination in refugees. In addition to ensuring a supportive environment for learning English, proactive employment strategies should be encouraged. Further research examining the use of successful refugee role models to promote self efficacy, enhance motivation for learning and ensure newly arrived refugees view resettlement as a challenge, rather than a threat, is recommended.

  9. Synergistic effect of enhancers for transdermal drug delivery.

    Science.gov (United States)

    Mitragotri, S

    2000-11-01

    Transdermal drug delivery offers a non-invasive route of drug administration, although its applications are limited by low skin permeability. Various enhancers including iontophoresis, chemicals, ultrasound, and electroporation have been shown to enhance transdermal drug transport. Although all these methods have been individually shown to enhance transdermal drug transport, their combinations have often been found to enhance transdermal transport more effectively than each of them alone. This paper summarizes literature studies on these combinations with respect to their efficacy and mechanisms.

  10. A conceptual model of referee efficacy

    Directory of Open Access Journals (Sweden)

    Félix eGuillén

    2011-02-01

    Full Text Available This paper presents a conceptual model of referee efficacy, defines the concept, proposes sources of referee specific efficacy information, and suggests consequences of having high or low referee efficacy. Referee efficacy is defined as the extent to which referees believe they have the capacity to perform successfully in their job. Referee efficacy beliefs are hypothesized to be influenced by mastery experiences, referee knowledge/education, support from significant others, physical/mental preparedness, environmental comfort, and perceived anxiety. In turn, referee efficacy beliefs are hypothesized to influence referee performance, referee stress, athlete rule violations, athlete satisfaction, and co-referee satisfaction.

  11. Broken Windows and Collective Efficacy

    Directory of Open Access Journals (Sweden)

    Aldrin Abdullah

    2015-01-01

    Full Text Available The broken windows thesis posits that signs of disorder increase crime and fear, both directly and indirectly. Although considerable theoretical evidence exists to support the idea that disorder is positively related to fear of crime, the empirical literature on examining the indirect effect of the individual’s perception of incivilities on fear of crime is limited, especially in developing countries. This research was conducted to assess the indirect relationship between perceived disorder and fear of crime through collective efficacy. A total of 235 households from Penang, Malaysia, participated in this study. Results reveal that high perception of disorder is negatively associated with collective efficacy. High collective efficacy is associated with low fear of crime. Moreover, a significant and indirect effect of disorder on fear of crime exists through collective efficacy. The results provide empirical support for the broken windows theory in the Malaysian context and suggest that both environmental conditions and interactions of residents play a role in the perceived fear of crime.

  12. The "Efficacy-Effectiveness Gap"

    DEFF Research Database (Denmark)

    Nordon, Clementine; Karcher, Helene; Groenwold, Rolf H H;

    2016-01-01

    BACKGROUND: The concept of the "efficacy-effectiveness gap" (EEG) has started to challenge confidence in decisions made for drugs when based on randomized controlled trials alone. Launched by the Innovative Medicines Initiative, the GetReal project aims to improve understanding of how to reconcil...

  13. Control efficacy of complex networks

    Science.gov (United States)

    Gao, Xin-Dong; Wang, Wen-Xu; Lai, Ying-Cheng

    2016-06-01

    Controlling complex networks has become a forefront research area in network science and engineering. Recent efforts have led to theoretical frameworks of controllability to fully control a network through steering a minimum set of driver nodes. However, in realistic situations not every node is accessible or can be externally driven, raising the fundamental issue of control efficacy: if driving signals are applied to an arbitrary subset of nodes, how many other nodes can be controlled? We develop a framework to determine the control efficacy for undirected networks of arbitrary topology. Mathematically, based on non-singular transformation, we prove a theorem to determine rigorously the control efficacy of the network and to identify the nodes that can be controlled for any given driver nodes. Physically, we develop the picture of diffusion that views the control process as a signal diffused from input signals to the set of controllable nodes. The combination of mathematical theory and physical reasoning allows us not only to determine the control efficacy for model complex networks and a large number of empirical networks, but also to uncover phenomena in network control, e.g., hub nodes in general possess lower control centrality than an average node in undirected networks.

  14. Self Efficacy: Operationalizing Challenge Education.

    Science.gov (United States)

    McGowan, Michael L.

    1986-01-01

    Examines self-efficacy theory and how it can be utilized in describing participant change in adventure/challenge programs. Explores connection between personal experience and how people view ability to function in world around them. Discusses Bandura's theory and interaction of sources of information: performance accomplishment, vicarious…

  15. 远程磁导航指导下加强肺静脉前庭消融策略治疗心房纤颤有效性研究%Efficacy of enhanced ablation on pulmonary vein antrum isolation under remote magnetic navigation in patients with atrial fibrillation

    Institute of Scientific and Technical Information of China (English)

    郭文杰; 徐伟豪; 兰凯; 彭利; 张玉霄; 卢才义

    2016-01-01

    目的:探讨在远程磁导航系统( RMN)辅助下应用加强消融策略行心房纤颤( AF)射频消融治疗对AF远期成功率的影响。方法连续选取2013年1月至2015年6月在解放军总医院住院行导管射频消融治疗且自愿参加该临床研究的患者49例非瓣膜性AF患者随机分成两组,传统消融组(CAG, n=24)和加强消融组(EAG, n=25)。 CAG组对左右肺静脉行单环线性消融,EAG组在CAG消融基础上,靠近原有消融径线,在心房侧再次行线性消融,形成双环线性消融。术中应用磁导航消融导管,RMN系统、CARTO 3系统和Lasso环状标测电极,术后常规使用24 h动态心电图随访。结果所有患者均消融成功,EAG组较CAG组消融时间明显延长[(45.66±6.59)vs (40.10±3.48)min,P<0.01],而在曝光时间、手术时间和静脉血测定脑利钠肽前体上差异无统计学意义( P>0.05)。术后随访(19.3±5.6)个月,应用动态心电图随访发现EAG组复发率较CAG组明显降低(33.33%vs 8.00%,P<0.05)。二次手术时发现复发患者均存在电传导恢复情况,8例再次手术均成功。结论加强消融策略能有效改善AF患者的远期成功率,降低复发率。%Objective To assess the long-term efficacy of enhanced ablation in pulmonary vein antrum ( PVA) guided by remote magnetic navigation ( RMN) in the patients with atrial fibrillation ( AF) .Methods From January 2013 to June 2015, 49 consecutive patients with refractory non-valvular AF who undergoing radiofrequency catheter ablation and voluntarily taking part in this study in our hospital were recruited in this study .They were randomized into a conventional ablation group ( CAG, n =24 ) and an enhanced ablation group ( EAG, n=25) .PVA isolation was achieved by creating a single ablation circle in the patients of CAG group , and was double ablation circles at PVA in those of EAG group .An irrigated

  16. Reporter nanoparticle that monitors its anticancer efficacy in real time.

    Science.gov (United States)

    Kulkarni, Ashish; Rao, Poornima; Natarajan, Siva; Goldman, Aaron; Sabbisetti, Venkata S; Khater, Yashika; Korimerla, Navya; Chandrasekar, Vineethkrishna; Mashelkar, Raghunath A; Sengupta, Shiladitya

    2016-04-12

    The ability to monitor the efficacy of an anticancer treatment in real time can have a critical effect on the outcome. Currently, clinical readouts of efficacy rely on indirect or anatomic measurements, which occur over prolonged time scales postchemotherapy or postimmunotherapy and may not be concordant with the actual effect. Here we describe the biology-inspired engineering of a simple 2-in-1 reporter nanoparticle that not only delivers a cytotoxic or an immunotherapy payload to the tumor but also reports back on the efficacy in real time. The reporter nanoparticles are engineered from a novel two-staged stimuli-responsive polymeric material with an optimal ratio of an enzyme-cleavable drug or immunotherapy (effector elements) and a drug function-activatable reporter element. The spatiotemporally constrained delivery of the effector and the reporter elements in a single nanoparticle produces maximum signal enhancement due to the availability of the reporter element in the same cell as the drug, thereby effectively capturing the temporal apoptosis process. Using chemotherapy-sensitive and chemotherapy-resistant tumors in vivo, we show that the reporter nanoparticles can provide a real-time noninvasive readout of tumor response to chemotherapy. The reporter nanoparticle can also monitor the efficacy of immune checkpoint inhibition in melanoma. The self-reporting capability, for the first time to our knowledge, captures an anticancer nanoparticle in action in vivo.

  17. INTEGRATING ENTREPRENEURIAL SELF-EFFICACY INTO EDUCATION AT UNIVERSITIES

    Directory of Open Access Journals (Sweden)

    Ljerka Sedlan-König

    2016-12-01

    Full Text Available Educational institutions are urged to provide more enterprising individuals who will either act as entrepreneurs, or will be able to manage their careers and lives in an entrepreneurial way. The purpose of this study is to address the role of teaching at universities in maximizing entrepreneurial self-efficacy, and to examine the possibility to maximize the likelihood of entrepreneurial behavior by enhancing entrepreneurial self-efficacy with university students. The study investigates the impact that entrepreneurial self-efficacy has on the development of entrepreneurial motivation and behavior using a sample of 324 students of Josip Juraj Strossmayer University of Osijek in Croatia. The results of the research indicate that students demonstrate a higher propensity for entrepreneurial behavior and a higher probability of starting their own business if they feel more self-efficient. The research has also highlighted that teaching at universities does not significantly improve the perception of entrepreneurial self-efficacy in students and that firsthand experience has a more important role in that. An important conclusion to emerge from this research is that in order to influence entrepreneurial behavior, it is necessary to make better use of experience-based learning and supplement university courses with components of informal and/or non-formal education.

  18. Effects of an educational intervention on female biomedical scientists' research self-efficacy.

    Science.gov (United States)

    Bakken, Lori L; Byars-Winston, Angela; Gundermann, Dawn M; Ward, Earlise C; Slattery, Angela; King, Andrea; Scott, Denise; Taylor, Robert E

    2010-05-01

    Women and people of color continue to be underrepresented among biomedical researchers to an alarming degree. Research interest and subsequent productivity have been shown to be affected by the research training environment through the mediating effects of research self-efficacy. This article presents the findings of a study to determine whether a short-term research training program coupled with an efficacy enhancing intervention for novice female biomedical scientists of diverse racial backgrounds would increase their research self-efficacy beliefs. Forty-three female biomedical scientists were randomized into a control or intervention group and 15 men participated as a control group. Research self-efficacy significantly increased for women who participated in the self-efficacy intervention workshop. Research self-efficacy within each group also significantly increased following the short-term research training program, but cross-group comparisons were not significant. These findings suggest that educational interventions that target sources of self-efficacy and provide domain-specific learning experiences are effective at increasing research self-efficacy for women and men. Further studies are needed to determine the longitudinal outcomes of this effort.

  19. Regulatory focus, self-efficacy and outcome expectations as drivers of motivation to consume healthy food products.

    Science.gov (United States)

    Tudoran, Ana Alina; Scholderer, Joachim; Brunsø, Karen

    2012-10-01

    In this paper we apply the principle of Regulatory Focus Theory to investigate the interaction between self-efficacy and outcome expectations on individuals' intentions to adopt health behaviors. The participants, 959 individuals (Survey 1) and 2400 individuals (Survey 2), reported self-efficacy beliefs and outcome expectations with regard to the consumption of omega-3 supplements and omega-3-enriched food products. We found that the relationship prevention outcome expectations-intention was significantly attenuated at low levels of self-efficacy and strengthened at high levels of self-efficacy, respectively; whereas, the relationship promotion outcome expectations-intention was unaffected by the perceived levels of self-efficacy. The implications suggest that consumers' motivation to adopt healthy food products, such as omega-3 supplements and omega-3 enriched products, should be encouraged by stimulating promotion outcome expectations. However, when a prevention frame is used, the individuals' motivation should be significantly enhanced by self-efficacy beliefs.

  20. Pre-Service Teachers' Mathematics Self-Efficacy and Mathematics Teaching Self-Efficacy

    Science.gov (United States)

    Zuya, Habila Elisha; Kwalat, Simon Kevin; Attah, Bala Galle

    2016-01-01

    Pre-service mathematics teachers' mathematics self-efficacy and mathematics teaching self-efficacy were investigated in this study. The purpose was to determine the confidence levels of their self-efficacy in mathematics and mathematics teaching. Also, the study was aimed at finding whether their mathematics self-efficacy and teaching…

  1. Relationship between Counseling Self-Efficacy and Multicultural Counseling Self-Efficacy among School Counselors

    Science.gov (United States)

    Crook, Tylon

    2010-01-01

    The purpose of this dissertation was to examine the relationship between school counselors' counseling self-efficacy and multicultural counseling self-efficacy. In addition, this study measured school counselors' levels of general school counseling self-efficacy, multicultural counseling self-efficacy, and the relationship between school counselor…

  2. Speech enhancement

    CERN Document Server

    Benesty, Jacob; Chen, Jingdong

    2006-01-01

    We live in a noisy world! In all applications (telecommunications, hands-free communications, recording, human-machine interfaces, etc.) that require at least one microphone, the signal of interest is usually contaminated by noise and reverberation. As a result, the microphone signal has to be ""cleaned"" with digital signal processing tools before it is played out, transmitted, or stored.This book is about speech enhancement. Different well-known and state-of-the-art methods for noise reduction, with one or multiple microphones, are discussed. By speech enhancement, we mean not only noise red

  3. Safety and efficacy of tenecteplase in acute myocardial infarction.

    Science.gov (United States)

    Guerra, Daniel R; Karha, Juhana; Gibson, C Michael

    2003-05-01

    The use of intravenous thrombolytic agents has revolutionised the treatment of acute myocardial infarction. However, the improved mortality achieved with these drugs is tempered by the risk of serious bleeding complications, especially intracranial haemorrhage (ICH). Tenecteplase (TNKase, Genetech Inc.) is an engineered variant of alteplase (Activase, Genentech Inc.) designed to have increased fibrin specificity, greater efficacy and a longer half-life. The longer half-life of tenecteplase compared to alteplase allows for convenient single bolus administration of the drug. In addition, tenecteplase dosing is based on actual or estimated patient weight, which enhances both the safety and efficacy outcomes. Large clinical trials have demonstrated equivalence in mortality and ICH between tenecteplase and alteplase. Compared to alteplase, tenecteplase use leads to lower rates of bleeding complications and a decreased risk of ICH among low weight, elderly women.

  4. Self-Efficacy: Conditioning the Entrepreneurial Mindset

    DEFF Research Database (Denmark)

    Neergaard, Helle; Mauer, René; Kirketerp Linstad, Anne

    2009-01-01

    Research that has sought to identify the underlying determinants of self-efficacy is sparse. This chapter seeks to identify antecedents of entrepreneurial self-efficacy and the processes that produce and reinforce self-efficacy. It seeks to broaden our understanding of the self-efficacy concept t...... through an exploration of its origins and via a journey to its impact in the field of entrepreneurship. Finally, it suggests pedagogical initiatives needed to promote entrepreneurial self-efficacy in the different social arenas of life....

  5. Self-efficacy strategies to improve exercise in patients with heart failure: A systematic review

    Science.gov (United States)

    Rajati, Fatemeh; Sadeghi, Masoumeh; Feizi, Awat; Sharifirad, Gholamreza; Hasandokht, Tolu; Mostafavi, Firoozeh

    2014-01-01

    BACKGROUND Despite exercise is recommended as an adjunct to medication therapy in patients with heart failure (HF), non-adherence to exercise is a major problem. While improving self-efficacy is an effective way to increase physical activity, the evidence concerning the relationship between strategies to enhance self-efficacy and exercise among HF has not been systematically reviewed. The objective of this systematic review is to assess the effect of interventions to change the self-efficacy on exercise in patients with HF. METHODS A systematic database search was conducted for articles reporting exercise self-efficacy interventions. Databases such as PubMed, ProQuest, CINAHL, Scopus, and PsycINFO, and the Cochrane Library were searched with restrictions to the years 2000-June 2014. A search of relevant databases identified 10 studies. Published randomized controlled intervention studies focusing strategies to change self-efficacy to exercise adherence in HF were eligible for inclusion. In addition, studies that have applied self-efficacy-based interventions to improve exercise are discussed. RESULTS Limited published data exist evaluating the self-efficacy strategies to improve exercise in HF. Dominant strategies to improve patients’ self-efficacy were performance accomplishments, vicarious experience, verbal persuasion, emotional arousal. CONCLUSION Evidence from some trials supports the view that incorporating the theory of self-efficacy into the design of an exercise intervention is beneficial. Moreover, exercise interventions aimed at integrating the four strategies of exercise self-efficacy can have positive effects on confidence and the ability to initiate exercise and recover HF symptoms. Findings of this study suggest that a positive relationship exists between self-efficacy and initiating and maintaining exercise in HF, especially in the short-term period. PMID:25815022

  6. Optimizing Liposomal Cisplatin Efficacy through Membrane Composition Manipulations

    Directory of Open Access Journals (Sweden)

    Natalia Zisman

    2011-01-01

    Full Text Available The first liposomal formulation of cisplatin to be evaluated clinically was SPI-077. Although the formulation demonstrated enhanced cisplatin tumor accumulation in preclinical models it did not enhance clinical efficacy, possibly due to limited cisplatin release from the formulation localized within the tumor. We have examined a series of liposomal formulations to address the in vivo relationship between cisplatin release rate and formulation efficacy in the P388 murine leukemia model. The base formulation of phosphatidylcholine: phosphatidylglycerol: cholesterol was altered in the C18 and C16 phospholipid content to influence membrane fluidity and thereby impacting drug circulation lifetime and drug retention. Phase transition temperatures (Tm ranged from 42–55°C. The high Tm formulations demonstrated enhanced drug retention properties accompanied by low antitumor activity while the lowest Tm formulations released the drug too rapidly in the plasma, limiting drug delivery to the tumor which also resulted in low antitumor activity. A formulation composed of DSPC : DPPC : DSPG : Chol; (35 : 35 : 20 : 10 with an intermediate drug release rate and a cisplatin plasma half-life of 8.3 hours showed the greatest antitumor activity. This manuscript highlights the critical role that drug release rates play in the design of an optimized drug delivery vehicle.

  7. Optimizing Liposomal Cisplatin Efficacy through Membrane Composition Manipulations.

    Science.gov (United States)

    Zisman, Natalia; Dos Santos, Nancy; Johnstone, Sharon; Tsang, Alan; Bermudes, David; Mayer, Lawrence; Tardi, Paul

    2011-01-01

    The first liposomal formulation of cisplatin to be evaluated clinically was SPI-077. Although the formulation demonstrated enhanced cisplatin tumor accumulation in preclinical models it did not enhance clinical efficacy, possibly due to limited cisplatin release from the formulation localized within the tumor. We have examined a series of liposomal formulations to address the in vivo relationship between cisplatin release rate and formulation efficacy in the P388 murine leukemia model. The base formulation of phosphatidylcholine: phosphatidylglycerol: cholesterol was altered in the C18 and C16 phospholipid content to influence membrane fluidity and thereby impacting drug circulation lifetime and drug retention. Phase transition temperatures (T(m)) ranged from 42-55°C. The high T(m) formulations demonstrated enhanced drug retention properties accompanied by low antitumor activity while the lowest T(m) formulations released the drug too rapidly in the plasma, limiting drug delivery to the tumor which also resulted in low antitumor activity. A formulation composed of DSPC : DPPC : DSPG : Chol; (35 : 35 : 20 : 10) with an intermediate drug release rate and a cisplatin plasma half-life of 8.3 hours showed the greatest antitumor activity. This manuscript highlights the critical role that drug release rates play in the design of an optimized drug delivery vehicle.

  8. Aid Efficacy: An Institutional Approach

    Directory of Open Access Journals (Sweden)

    José Antonio Alonso Rodríguez

    2006-01-01

    Full Text Available This work aims to explore some of the weaknesses that the international aid system presents for efficaciously operating in promoting development. For this, it adopts an institutionalapproach, attempting to investigate the problems of asymmetry in information that occur both in relationships between donor and receiver and within aid organisations. The analysis of these aspects leads the author to underscore the importance that learning processes have in enriching interventions in development; he also underscores the importance of the attitudes and aptitudes of the agents in fostering these processes of improvement in aid quality.

  9. Speech Enhancement

    DEFF Research Database (Denmark)

    Benesty, Jacob; Jensen, Jesper Rindom; Christensen, Mads Græsbøll;

    of methods and have been introduced in somewhat different contexts. Linear filtering methods originate in stochastic processes, while subspace methods have largely been based on developments in numerical linear algebra and matrix approximation theory. This book bridges the gap between these two classes......Speech enhancement is a classical problem in signal processing, yet still largely unsolved. Two of the conventional approaches for solving this problem are linear filtering, like the classical Wiener filter, and subspace methods. These approaches have traditionally been treated as different classes...... of methods by showing how the ideas behind subspace methods can be incorporated into traditional linear filtering. In the context of subspace methods, the enhancement problem can then be seen as a classical linear filter design problem. This means that various solutions can more easily be compared...

  10. ICTs, Openness and Citizen Perceptions of Government: How Civic Technologies Can Facilitate External Citizen Efficacy

    Directory of Open Access Journals (Sweden)

    Rebecca Rumbul

    2016-12-01

    Full Text Available This article examines whether civic technologies deliver an effective technique for developing the political efficacy of citizens and altering their perceived accountability of governments. Employing a survey-based methodology, a quantitative analysis was performed on the users of civic technology sites in the USA, UK, Kenya and South Africa. The primary question posed is whether the specific citizen monitoring actions facilitated by these sites cause a related effect in altering the extent to which citizens believe that governments are responsive to citizen-audit. The results indicate an enhancement in citizen efficacy and perceptions of government accountability. Notable differences detected in the user demographics between the countries studied demonstrate a wide spectrum of citizen usage; however, with common confidence displayed by respondents in the efficacy of the ICT. The findings indicate that the publication and citizen-audit of government information through civic technologies in developed and developing countries increases feelings of external efficacy and perceived government accountability.

  11. The Effect of Mathematics Self-Efficacy on Anxiety of Teaching Mathematics

    Directory of Open Access Journals (Sweden)

    Alattin URAL

    2015-04-01

    Full Text Available The aim of the study is to investigate the effect of mathematics self-efficacy belief on anxiety of teaching mathematics. The participants of the study consist of 42 mathematics teacher candidates in the Department of Mathematics Education, Faculty of Education. The scale of mathematics self-efficacy, developed by Umay (2001, and the scale of mathematics teaching anxiety, developed by Peker (2006, was enrolled as measurement tools. Pearson correlation was used for the correlation between teacher candidates’ average points from the both scales. The results revealed that there was a significant and negative correlation mathematics self-efficacy beliefs and anxiety of teaching mathematics. This result means that the students’ mathematics teaching anxiety decreases as their mathematics self-efficacy beliefs increase. On the other hand, it was seen that mathematics self-efficacy belief explains 35% of the variance in teaching mathematics anxiety. Besides, it was determined that mathematics teacher candidates’ mathematics teaching anxiety was at low level, and mathematics efficacy beliefs are at high level. Mathematics self-efficacy refers to the belief or perception that one is capable of organizing and executing the actions necessary to succeed at a given mathematical task. For this aim, their knowledge and abilities relating mathematical concepts and also their confidences about their mathematical abilities must be enhanced.

  12. Physical activity intervention effects on perceived stress in working mothers: the role of self-efficacy.

    Science.gov (United States)

    Mailey, Emily L; McAuley, Edward

    2014-01-01

    Working mothers often report elevated stress, and efforts to improve their coping resources are needed to buffer the detrimental effects of stress on health. This study examined the impact of changes in physical activity, self-efficacy, and self-regulation across the course of a brief intervention on subsequent levels of stress in working mothers. Participants (N = 141) were randomly assigned to an intervention or control condition (2:1 ratio). The intervention was conducted in Illinois between March 2011 and January 2012 and consisted of two group-mediated workshop sessions with content based on social cognitive theory. Participants completed measures of physical activity, self-efficacy, self-regulation, and perceived stress at baseline, immediately postintervention, and 6-month follow-up. Stress levels declined across the 6-month period in both groups. Changes in stress were negatively associated with changes in self-efficacy and self-regulation among intervention participants only. Regression analyses revealed the intervention elicited short-term increases in physical activity, self-efficacy, and self-regulation, but only changes in self-efficacy predicted perceived stress at 6-month follow-up. These results suggest that enhancing self-efficacy is likely to improve working mothers' perceived capabilities to cope with stressors in their lives. Future interventions should continue to focus on increasing self-efficacy to promote improvements in physical activity and psychological well-being in this population.

  13. Self-Efficacy as a Positive Youth Development Construct: A Conceptual Review

    Directory of Open Access Journals (Sweden)

    Sandra K. M. Tsang

    2012-01-01

    Full Text Available Self-efficacy denotes people's beliefs about their ability to perform in different situations. It functions as a multilevel and multifaceted set of beliefs that influence how people feel, think, motivate themselves, and behave during various tasks. Self-efficacy beliefs are informed by enactive attainment, vicarious experience, imaginal experiences, and social persuasion as well as physical and emotional states. These beliefs are mediated by cognitive, motivational, affective, and selection processes to generate actual performance. Self-efficacy development is closely intertwined with a person's experiences, competencies, and developmental tasks in different domains at different stages in life. This paper reviews the literature to outline the definition and theoretical conceptualizations of the construct originally devised by Bandura that have flourished since the 1990s. Drawing from the studies of the construct to assess self-efficacy, and to inform positive youth development, the paper will present the determinants of the development of self-efficacy beliefs and identify the connection between self-efficacy and adolescent developmental outcomes. The paper will conclude with strategies to enhance youth self-efficacy and proposals for future research directions.

  14. Improved therapy for neuroblastoma using a combination approach: superior efficacy with vismodegib and topotecan.

    Science.gov (United States)

    Chaturvedi, Nagendra K; McGuire, Timothy R; Coulter, Don W; Shukla, Ashima; McIntyre, Erin M; Sharp, John Graham; Joshi, Shantaram S

    2016-03-22

    Aberrant activation/expression of pathways/molecules including NF-kB, mTOR, hedgehog and polo-like-kinase-1 (PLK1) are correlated with poor-prognosis neuroblastoma. Therefore, to identify a most efficacious treatment for neuroblastoma, we investigated the efficacy of NF-kB/mTOR dual-inhibitor 13-197, hedgehog inhibitor vismodegib and PLK1 inhibitor BI2536 alone or combined with topotecan against high-risk neuroblastoma. The in vitro efficacy of the inhibitors alone or combined with topotecan on cell growth/apoptosis and molecular mechanism(s) were investigated. Results showed that as single agents 13-197, BI2536 and vismodegib significantly decreased neuroblastoma cell growth and induced apoptosis by targeting associated pathways/molecules. In combination with topotecan, 13-197 did not show significant additive/synergistic effects against neuroblastoma. However, BI2536 or vismodegib further significantly decreased neuroblastoma cell growth/survival. These results clearly showed that vismodegib combination with topotecan was synergistic and more efficacious compared with BI2536 in combination. Together, in vitro data demonstrated that vismodegib was most efficacious in potentiating topotecan-induced antineuroblastoma effects. Therefore, we tested the combined efficacy of vismodegib and topotecan against neuroblastoma in vivo using NSG mice. This resulted in significantly (pvismodegib and topotecan showed a significant enhanced antineuroblastoma efficacy by targeting associated pathways/molecules which warrants further preclinical evaluation for translation to the clinic.

  15. Anticancer Efficacy of Polyphenols and Their Combinations

    Directory of Open Access Journals (Sweden)

    Aleksandra Niedzwiecki

    2016-09-01

    Full Text Available Polyphenols, found abundantly in plants, display many anticarcinogenic properties including their inhibitory effects on cancer cell proliferation, tumor growth, angiogenesis, metastasis, and inflammation as well as inducing apoptosis. In addition, they can modulate immune system response and protect normal cells against free radicals damage. Most investigations on anticancer mechanisms of polyphenols were conducted with individual compounds. However, several studies, including ours, have indicated that anti-cancer efficacy and scope of action can be further enhanced by combining them synergistically with chemically similar or different compounds. While most studies investigated the anti-cancer effects of combinations of two or three compounds, we used more comprehensive mixtures of specific polyphenols and mixtures of polyphenols with vitamins, amino acids and other micronutrients. The mixture containing quercetin, curcumin, green tea, cruciferex, and resveratrol (PB demonstrated significant inhibition of the growth of Fanconi anemia head and neck squamous cell carcinoma and dose-dependent inhibition of cell proliferation, matrix metalloproteinase (MMP-2 and -9 secretion, cell migration and invasion through Matrigel. PB was found effective in inhibition of fibrosarcoma HT-1080 and melanoma A2058 cell proliferation, MMP-2 and -9 expression, invasion through Matrigel and inducing apoptosis, important parameters for cancer prevention. A combination of polyphenols (quercetin and green tea extract with vitamin C, amino acids and other micronutrients (EPQ demonstrated significant suppression of ovarian cancer ES-2 xenograft tumor growth and suppression of ovarian tumor growth and lung metastasis from IP injection of ovarian cancer A-2780 cells. The EPQ mixture without quercetin (NM also has shown potent anticancer activity in vivo and in vitro in a few dozen cancer cell lines by inhibiting tumor growth and metastasis, MMP-2 and -9 secretion, invasion

  16. Teaching Efficacy in the Classroom: Skill Based Training for Teachers' Empowerment

    Science.gov (United States)

    Karimzadeh, Mansoureh; Salehi, Hadi; Embi, Mohamed Amin; Nasiri, Mehdi; Shojaee, Mohammad

    2014-01-01

    This study aims to use an experimental research design to enhance teaching efficacy by social-emotional skills training in teachers. The statistical sample comprised of 68 elementary teachers (grades 4 and 5) with at least 10 years teaching experience and a bachelor's degree who were randomly assigned into control (18 female, 16 male) and…

  17. The Effects of Professional Development Initiatives on EFL Teachers' Degree of Self Efficacy

    Science.gov (United States)

    Karimi, Mohammad Nabi

    2011-01-01

    Despite the importance of teacher efficacy, there has been little research on the effects of interventions intended to increase it. Thus, the present study considered the potential of Professional Development (PD) in enhancing teachers' beliefs about their teaching ability. The study was quantitative in nature and utilized the reliable survey…

  18. Efficacy of dimethylglycine as a feed additive to improve broiler production

    NARCIS (Netherlands)

    Kalmar, I.D.; Verstegen, M.W.A.; Vanrompay, D.; Maenner, K.; Zentek, J.; Iben, C.; Leitgeb, R.; Schiavone, A.; Prola, L.; Janssens, G.

    2014-01-01

    Dimethylglycine (DMG) is a naturally occurring glycine derivative, which is useful as additive to broiler diets as it improves nutrient digestibility and reduces the development of broiler ascites syndrome. This study evaluated the efficacy of dietary DMG to enhance performance of broiler chickens.

  19. Testing the Efficacy of Theoretically Derived Improvements in the Treatment of Social Phobia

    Science.gov (United States)

    Rapee, Ronald M.; Gaston, Jonathan E.; Abbott, Maree J.

    2009-01-01

    Recent theoretical models of social phobia suggest that targeting several specific cognitive factors in treatment should enhance treatment efficacy over that of more traditional skills-based treatment programs. In the current study, 195 people with social phobia were randomly allocated to 1 of 3 treatments: standard cognitive restructuring plus in…

  20. The Influence of the Ultrasonic Intensity on the Cleaning Efficacy of Passive Ultrasonic Irrigation

    NARCIS (Netherlands)

    Jiang, Lei-Meng; Verhaagen, Bram; Versluis, Michel; Langedijk, Jelmer; Wesselink, Paul; van der Sluis, Lucas W. M.

    2011-01-01

    Introduction: It is not clear whether increasing the ultrasonic intensity would enhance the cleaning efficacy of passive ultrasonic irrigation (PUI) inside a root canal. The aim of this study was to evaluate the effect of the ultrasonic intensity on PUI to remove dentin debris and whether there is a

  1. Effects of dietary sodium and hydrochlorothiazide on the antiproteinuric efficacy of losartan

    NARCIS (Netherlands)

    L. Vogt (Liffert); F. Waanders (Femke); F. Boomsma (Frans); D. de Zeeuw (Dick); G. Navis (Gerjan)

    2008-01-01

    textabstractThere is large interindividual variability in the antiproteinuric response to blockade of the renin-angiotensin-aldosterone system (RAAS). A low-sodium diet or addition of diuretics enhances the effects of RAAS blockade on proteinuria and BP, but the efficacy of the combination of these

  2. Effects of dietary sodium and hydrochlorothiazide on the antiproteinuric efficacy of losartan

    NARCIS (Netherlands)

    Vogt, Liffert; Waanders, Fernke; Boornsma, Frans; de Zeeuw, Dick; Navis, Gerjan

    2008-01-01

    There is large interindividual variability in the antiproteinuric response to blockade of the renin-angiotensin-aldosterone system (RAAS). A low-sodium diet or addition of diuretics enhances the effects of RAAS blockade on proteinuria and BP, but the efficacy of the combination of these intervention

  3. The effect of blood brain barrier modulation on oxime efficacy in nerve agent poisoning (Abstract)

    NARCIS (Netherlands)

    Joosen, M.; Schans, M.J. van der; Dijk, C.G.M. van; Kuijpers, WC.; Wortelboer, H.M.; Helden, H.P.M. van

    2012-01-01

    One of the shortcomings of current treatment of nerve agent poisoning is that oximes hardly penetrate the blood brain barrier (BBB), whereas nerve agents easily do. Enhancing the efficacy of current oximes in the brain, would therefore provide an attractive approach to improve medical countermeasure

  4. In vitro thrombolytic efficacy of echogenic liposomes loaded with tissue plasminogen activator and octafluoropropane gas

    Science.gov (United States)

    Shekhar, Himanshu; Bader, Kenneth B.; Huang, Shenwen; Peng, Tao; Huang, Shaoling; McPherson, David D.; Holland, Christy K.

    2017-01-01

    Echogenic liposomes loaded with the thrombolytic recombinant tissue-type plasminogen activator (rt-PA) are under development for the treatment of ischemic stroke. These agents are designed to co-encapsulate cavitation nuclei to promote bubble activity in response to ultrasound exposure, and to enable localized delivery of thrombolytic. Stable cavitation improves the efficacy of the thrombolytic through enhanced fluid mixing. Echogenic liposomes that encapsulate air-filled microbubbles nucleate scant stable cavitation activity in response to 120 kHz intermittent ultrasound exposure, and have demonstrated thrombolytic efficacy equivalent to rt-PA alone. It was hypothesized that encapsulating octafluoropropane (OFP) gas within rt-PA-loaded liposomes instead of air will enhance ultrasound-mediated stable cavitation activity and increase thrombolytic efficacy compared to previous studies. The thrombolytic efficacy and cavitation activity nucleated from liposomes that encapsulate OFP microbubbles and rt-PA (OFP t-ELIP) was evaluated in vitro. Human whole blood clots were exposed to human fresh-frozen plasma alone, rt-PA (0, 0.32, 1.58, and 3.15 µg ml-1), or OFP t-ELIP at equivalent enzymatic activity, with and without exposure to intermittent ultrasound. Further, numerical simulations were performed to gain insight into the mechanisms of cavitation nucleation. Sustained ultraharmonic activity was nucleated from OFP t-ELIP when exposed to ultrasound. Furthermore, the thrombolytic efficacy was enhanced compared to rt-PA alone at concentrations of 1.58 µg ml-1 and 3.15 µg ml-1 (p  cavitation activity and enhance the efficacy of thrombolysis.

  5. Antioxidants and the skin: understanding formulation and efficacy.

    Science.gov (United States)

    Oresajo, Christian; Pillai, Sreekumar; Manco, Megan; Yatskayer, Margarita; McDaniel, David

    2012-01-01

    Antioxidants are molecules capable of inhibiting the oxidation of other molecules. Although oxidation reactions are essential for life, they can also be damaging. All living organisms maintain complex systems of multiple types of antioxidants to protect their cells from oxidative damage. Antioxidants can also act as pro-oxidants, under certain circumstances. The efficacy and benefit of an antioxidant is, therefore, very much dependent on the delivery of the antioxidant to the organism. Topically applied antioxidants constitute an important group of pharmacologically active agents capable of preventing the occurrence and reducing the severity of UV-induced skin damage and skin aging. Antioxidants protect skin cells against the damaging effects of reactive oxygen species (ROS), such as singlet oxygen, superoxide, peroxyl radicals, hydroxyl radicals, and peroxynitrite. ROS induced oxidative stress in the skin has been linked to cancer, aging, inflammation, and photodamage. This review focuses on antioxidants used in the cosmetic industry for protection of skin, formulation methods used to enhance their efficacy, and methods used to test the efficacy of antioxidants in topical formulations.

  6. Anticancer efficacy of unique pyridine-based tetraindoles.

    Science.gov (United States)

    Fu, Chih-Wei; Hsieh, Yun-Jung; Chang, Tzu Ting; Chen, Chia-Ling; Yang, Cheng-Yu; Liao, Anne; Hsiao, Pei-Wen; Li, Wen-Shan

    2015-11-02

    Results of previous studies demonstrated that the tetraindole, SK228, which has a high lipid but low water solubility, displayed moderate anticancer efficacy in a xenograft model of breast cancer. This finding led to the proposal that new, pyridine based tetraindole (PBT) analogs of SK228, containing tetraindole moieties distributed about central protonated pyridine cores, would have enhanced bioavailabilities and anticancer efficacies. Among the PBTs prepared and subjected to biological studies, 3f (FCW81) was observed to display the highest antiproliferative activity against the two triple negative breast cancer (TNBCs) cell lines, MDA-MB-231 and BT549. In addition, its mode of action was shown to involve G2/M arrest of the cell cycle along with the promotion of increased levels of cyclin B1 and p-chk2 and a decreased level of p-cdc2. DNA damage and induction of apoptosis caused by FCW81 was found to be associated with a decrease in DNA repair. Significantly, FCW81 displays therapeutic efficacy in a xenograft model of human breast cancer by not only serving to inhibit markedly the growth of cancer cells but also to block effectively cancer cell metastasis. Collectively, the results of these studies have led to the identification of novel pyridine-tetraindole based anticancer agents with potential use in TNBC therapy.

  7. EDITORIAL: Enhancing nanolithography Enhancing nanolithography

    Science.gov (United States)

    Demming, Anna

    2012-01-01

    Lithography was invented in late 18th century Bavaria by an ambitious young playwright named Alois Senefelder. Senefelder experimented with stone, wax, water and ink in the hope of finding a way of reproducing text so that he might financially gain from a wider distribution of his already successful scripts. His discovery not only facilitated the profitability of his plays, but also provided the world with an affordable printing press that would ultimately democratize the dissemination of art, knowledge and literature. Since Senefelder, experiments in lithography have continued with a range of innovations including the use of electron beams and UV that allow increasingly higher-resolution features [1, 2]. Applications for this have now breached the limits of paper printing into the realms of semiconductor and microelectronic mechanical systems technology. In this issue, researchers demonstrate a technique for fabricating periodic features in poly(3,4-ethylene dioxythiophene)-poly(styrenesulfonate) (PEDOT-PSS) [3]. Their method combines field enhancements from silica nanospheres with laser-interference lithography to provide a means of patterning a polymer that has the potential to open the market of low-end, high-volume microelectronics. Laser-interference lithography has already been used successfully in patterning. Researchers in Korea used laser-interference lithography to generate stamps for imprinting a two-dimensional photonic crystal structure into green light emitting diodes (LEDs) [4]. The imprinted patterns comprised depressions 100 nm deep and 180 nm wide with a periodicity of 295 nm. In comparison with unpatterned LEDs, the intensity of photoluminescence was enhanced by a factor of seven in the LEDs that had the photonic crystal structures imprinted in them. The potential of exploiting field enhancements around nanostructures for new technologies has also attracted a great deal of attention. Researchers in the USA and Australia have used the field

  8. Effects of cognitive and experiential group therapy on self-efficacy and perceptions of employability of chemically dependent women.

    Science.gov (United States)

    Washington, O

    1999-01-01

    This quasi-experimental study assessed effects of cognitive and experiential group therapy on self-efficacy and perceptions of employability for 52 chemically dependent adult women. The sample was 98% African American. Therapy consisted of six 90-min group sessions held twice weekly. The participants were pre- and posttested with the Self-Efficacy Scale (M. Sherer et al., 1982) and the Ghiselli Self-Description Inventory (E. E. Ghiselli, 1975). After the intervention, the cognitive group had significantly higher levels than the experiential group of social self-efficacy and need for self-actualization, an indicator of aspiration for employment. General self-efficacy and decisiveness, indicators of employability, significantly increased over time for both groups. Interventions to enhance people's belief in their ability to successfully perform tasks and control outcomes, promote personal growth, teach responsibility, and enhance self-awareness could be used to develop employability skills that reduce recidivism.

  9. Smoking cessation in cardiac patients: the influence of action plans, coping plans and self-efficacy on quitting smoking.

    Science.gov (United States)

    de Hoog, Natascha; Bolman, Catherine; Berndt, Nadine; Kers, Esther; Mudde, Aart; de Vries, Hein; Lechner, Lilian

    2016-06-01

    Smoking cessation is the most effective action for cardiac patients who smoke to improve their prognosis, yet more than one-half of cardiac patients continue to smoke after hospital admission. This study examined the influence of action plans, coping plans and self-efficacy on intention to quit and smoking cessation in cardiac patients. Cardiac patients completed a baseline questionnaire (N = 245) assessing demographic characteristics, smoking behavior, intention, self-efficacy, relapse self-efficacy and action and coping plans. Six months later (N = 184) continued abstinence from smoking was assessed. Self-efficacy predicted intention to quit smoking and was an indirect predictor of continued abstinence, through intention. Intention to quit smoking and making action plans both directly influenced continued abstinence. Future interventions to facilitate smoking cessation in cardiac patients should put strong emphasis on enhancing self-efficacy and on making specific action plans to increase the likelihood of smoking cessation.

  10. Teachers' Sense of Efficacy: Examining the Relationship of Teacher Efficacy and Student Achievement

    Science.gov (United States)

    Alrefaei, Nouf

    The purpose of this study was to investigate which teachers' characteristics have an impact on teachers' sense of efficacy. In addition, the relationship between mathematics and science fifth grade teachers' sense of efficacy and student achievement was examined. Two characteristics related to teachers were examined: teachers' years of teaching experience and teachers' highest degree. Participants included 62 mathematics and science teachers from three school districts in Northwest Arkansas. When comparing fifth grade mathematics and science teachers' efficacy beliefs based on their highest degree, a significant difference in teachers' efficacy beliefs was found based on their degrees. Teachers with a Bachelor degree have higher total efficacy than teachers who hold Master's degrees. Moreover, an investigation to determine if there is a difference in mathematics and science teachers' efficacy beliefs in the three subscale of teachers' efficacy (for classroom management, for student engagement, and for instructional strategies) revealed a significant difference in teachers' efficacy for two of the three constructs. However, when examining teachers' sense of efficacy based on their teaching experience, no differences in teachers' efficacy were found. A correlation was conducted and the results indicated that there was no significant relationship between fifth grade teachers' sense of efficacy and students' achievement in the benchmark test in mathematics and science. The recommendations from this study should be used to inform other scholars and administrators of the importance of teachers' sense of efficacy in order to improve students' achievement gains.

  11. Examining Relationships among Elementary Mathematics Teachers' Efficacy and Their Students' Mathematics Self-Efficacy and Achievement

    Science.gov (United States)

    Chang, Yu-Liang

    2015-01-01

    The purpose of this study was to examine the effects of fifth-grade mathematics teachers' efficacy (MTE) on their students' mathematics self-efficacy (SMSE) and mathematical achievement (SMA) in classrooms. Two mathematics efficacy instruments were administered to 58 classes (i.e. 58 teachers and 1244 fifth-graders respectively) to gather data…

  12. Principal Self-Efficacy and Work Engagement: Assessing a Norwegian Principal Self-Efficacy Scale

    Science.gov (United States)

    Federici, Roger A.; Skaalvik, Einar M.

    2011-01-01

    One purpose of the present study was to develop and test the factor structure of a multidimensional and hierarchical Norwegian Principal Self-Efficacy Scale (NPSES). Another purpose of the study was to investigate the relationship between principal self-efficacy and work engagement. Principal self-efficacy was measured by the 22-item NPSES. Work…

  13. The Relative Importance of Specific Self-Efficacy Sources in Pretraining Self-Efficacy Beliefs

    Science.gov (United States)

    Howardson, Garett N.; Behrend, Tara S.

    2015-01-01

    Self-efficacy is clearly important for learning. Research identifying the most important sources of self-efficacy beliefs, however, has been somewhat limited to date in that different disciplines focus largely on different sources of self-efficacy. Whereas education researchers focus on Bandura's original sources of "enactive mastery,"…

  14. Examining Elementary Teachers' Engineering Self-Efficacy and Engineering Teacher Efficacy

    Science.gov (United States)

    Hammack, Rebekah; Ivey, Toni

    2017-01-01

    Research indicates that teacher efficacy influences student achievement and is situation specific. With the Next Generation Science Standards calling for the incorporation of engineering practices into K-12 classrooms, it is important to identify teachers' engineering teaching efficacy. A study of K-5 teachers' engineering self-efficacy and…

  15. Impact of Teacher Preparation upon Teacher Efficacy

    Science.gov (United States)

    Redmon, Robert J.

    2007-01-01

    A cohort of students in a teacher preparation program completed questionnaires measuring their feelings of teacher self efficacy at three points in the program. Results suggest that pre-service teachers' feelings of self efficacy do improve as a result of their participation in such programs. (Contains 1 figure and 1 table. Teacher Efficacy…

  16. Novice teachers’ classroom management self efficacy beliefs

    Directory of Open Access Journals (Sweden)

    Türkay Nuri Tok

    2016-12-01

    Full Text Available This study aims to determine novice teachers’ classrom management self efficacy beliefs as well as the extent to which these beliefs change according to independent variables. This research which aims to determine novice teachers’ classroom management self efficacy beliefs is a survey type research. The participants of the study are 85 novice teachers on duty in their first year in Hatay Province in Turkey. Classroom Management Self-Efficacy Convictions Scale that is internally consistent and valid in measuring classroom management self-efficacy beliefs of prospective teachers devised by Çetin (2013 was used in the study. There is not any statistically significant difference in terms of school of graduation and classroom management efficacy belief and result expectation sub-dimension. There is not any statistically significant difference in classroom management efficacy belief and result expectation sub-dimension. In terms of gender, there is not any statistically significant difference in the result expectation sub-dimension but there is a statistically significant difference in classroom management efficacy belief. Male novice teachers have higher level of classroom management efficacy beliefs than female novice teachers.

  17. Development of Physics Self-Efficacy Scale

    Science.gov (United States)

    Çalişkan, Serap; Selçuk, Gamze S.; Erol, Mustafa

    2007-04-01

    In this article, we describe development of a Physics Self-Efficacy Scale (PSES) that is a self-administered measure to assess physics self-efficacy beliefs regarding one's ability to successfully perform physics tasks in physics classroom. The scale is initially composed of 56 items prepared following a brief scrutiny of relating literature on self-efficacy. It was initially administered 30 physics teacher candidates and was also examined by 6 experts of physics education, then ambiguous or incomprehensible 6 items were dismissed. This PSES was tested on 558 undergraduate students all completed fundamental physics courses. Cronbach's Alpha reliability coefficient of the PSES was calculated as 0.94. The final version of the PSES contained 30 items with 5 dimensions namely, 1. Self-efficacy towards solving physics problems, 2. Self-efficacy towards physics laboratory, 3. Self-efficacy towards learning physics, 4. Self-efficacy towards application of physics knowledge and 5. Self-efficacy towards memorizing physics knowledge.

  18. Self-Efficacy for Creative Productivity.

    Science.gov (United States)

    Schack, Gina

    The Efficacy Scale for Creative Productivity (ESCreP) was developed to measure students' convictions that they could be creative producers. Self-efficacy, an individual's estimation of ability to perform a behavior, is based upon performance accomplishments, vicarious experiences, verbal persuasion, and emotional or physiological arousal. Three…

  19. The impact of clinical simulation on learner self-efficacy in pre-registration nursing education.

    Science.gov (United States)

    Pike, Tamsin; O'Donnell, Victoria

    2010-07-01

    Clinical simulation is becoming increasingly popular in pre-registration nursing education. Incorporating teaching and learning strategies that enhance learner self-efficacy will theoretically improve clinical competence (Bandura, 1986, 1997). This paper presents the findings of a study that aimed to explore the impact of clinical simulation on self-efficacy beliefs amongst pre-registration nurses. A preliminary study (Pike, 2008) used a pre- and post-test design to measure learner self-efficacy before and after a clinical simulation session. Qualitative responses to questions on the post-test questionnaire provided themes to explore in a focus group interview with a convenience sample of nine participants. Thematic content analysis of the interview highlighted two principal findings. Firstly, students described low levels of self-efficacy with regards to communication skills, an area identified as a priority within pre-registration nursing education (NMC, 2007a). Second, students highlighted the need for learning experiences within clinical simulation to be more authentic, to improve the theory to practice gap. It is argued by incorporating strategies within clinical simulation that enhance learner self-efficacy, overall clinical competence will be improved. Suggestions for how pedagogical approaches may be developed within clinical simulation are discussed, whilst acknowledging the limitations of the small scale nature of the study.

  20. The effects of tailoring knowledge acquisition on colorectal cancer screening self-efficacy.

    Science.gov (United States)

    Jerant, Anthony; To, Patricia; Franks, Peter

    2015-01-01

    Interventions tailored to psychological factors such as personal and vicarious behavioral experiences can enhance behavioral self-efficacy but are complex to develop and implement. Information seeking theory suggests tailoring acquisition of health knowledge (without concurrent psychological factor tailoring) could enhance self-efficacy, simplifying the design of tailored behavior change interventions. To begin to examine this issue, the authors conducted exploratory analyses of data from a randomized controlled trial, comparing the effects of an experimental colorectal cancer screening intervention tailoring knowledge acquisition with the effects of a nontailored control on colorectal cancer screening knowledge and self-efficacy in 1159 patients comprising three ethnicity/language strata (Hispanic/Spanish, 23.4%, Hispanic/English, 27.2%, non-Hispanic/English, 49.3%) and 5 recruitment center strata. Adjusted for study strata, the mean postintervention knowledge score was significantly higher in the experimental group than in the control group. Adjusted experimental intervention exposure (B = 0.22, 95% CI [0.14, 0.30]), preintervention knowledge (B = 0.11, 95% CI [0.05, 0.16]), and postintervention knowledge (B = 0.03, 95% CI [0.01, 0.05]) were independently associated with subsequent colorectal cancer screening self-efficacy (p self-efficacy, with potential implications for tailored intervention design, but this implication requires confirmation in studies specifically designed to examine this issue.

  1. The Influence of Oxytocin on the Blood Perfusion of Uterine Fibroids: Contrast-enhanced Ultrasonography Evaluation

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    Yang Wang

    2016-03-01

    Conclusion: This CEUS study demonstrated that the use of parenteral oxytocin can significantly reduce the blood perfusion of the uterine fibroids, which may help to enhance the therapeutic efficacy for high intensity focused ultrasound ablation of uterine fibroids.

  2. Influence of an Intensive, Field-Based Life Science Course on Preservice Teachers' Self-Efficacy for Environmental Science Teaching

    Science.gov (United States)

    Trauth-Nare, Amy

    2015-08-01

    Personal and professional experiences influence teachers' perceptions of their ability to implement environmental science curricula and to positively impact students' learning. The purpose of this study was twofold: to determine what influence, if any, an intensive field-based life science course and service learning had on preservice teachers' self-efficacy for teaching about the environment and to determine which aspects of the combined field-based course/service learning preservice teachers perceived as effective for enhancing their self-efficacy. Data were collected from class documents and written teaching reflections of 38 middle-level preservice teachers. Some participants ( n = 18) also completed the Environmental Education Efficacy Belief Instrument at the beginning and end of the semester. Both qualitative and quantitative data analyses indicated a significant increase in PSTs' personal efficacies for environmental teaching, t(17) = 4.50, p = .000, d = 1.30, 95 % CI (.33, .90), but not outcome expectancy, t(17) = 1.15, p = .268, d = .220, 95 % CI (-.06, .20). Preservice teachers reported three aspects of the course as important for enhancing their self-efficacies: learning about ecological concepts through place-based issues, service learning with K-5 students and EE curriculum development. Data from this study extend prior work by indicating that practical experiences with students were not the sole factor in shaping PSTs' self-efficacy; learning ecological concepts and theories in field-based activities grounded in the local landscape also influenced PSTs' self-efficacy.

  3. Maximum Spectral Luminous Efficacy of White Light

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    Murphy, T W

    2013-01-01

    As lighting efficiency improves, it is useful to understand the theoretical limits to luminous efficacy for light that we perceive as white. Independent of the efficiency with which photons are generated, there exists a spectrally-imposed limit to the luminous efficacy of any source of photons. We find that, depending on the acceptable bandpass and---to a lesser extent---the color temperature of the light, the ideal white light source achieves a spectral luminous efficacy of 250--370 lm/W. This is consistent with previous calculations, but here we explore the maximum luminous efficacy as a function of photopic sensitivity threshold, color temperature, and color rendering index; deriving peak performance as a function of all three parameters. We also present example experimental spectra from a variety of light sources, quantifying the intrinsic efficacy of their spectral distributions.

  4. Life satisfaction and self-efficacy in patients affected by a first stroke living in Kuwait: a two-phase study.

    Science.gov (United States)

    Omu, Onutobor; Reynolds, Frances

    2013-08-01

    Life satisfaction and self-efficacy are important aspects of stroke rehabilitation. Previous research focuses on Western stroke survivors, neglecting the stroke experience in the Middle East. This research was conducted in Kuwait and entailed both quantitative and qualitative phases to obtain a more comprehensive, clinically relevant understanding of self-efficacy and life satisfaction during stroke rehabilitation in this culture. The aims were to: 1) investigate the relationships between self-efficacy and life satisfaction in female patients affected by stroke (Phase 1); and 2) explore health professionals' views regarding the importance of self-efficacy and possible strategies for enhancing self-efficacy during rehabilitation, through semi-structured interviews (Phase 2). Significant correlations were found between patients' general self-efficacy, and psychosocial adaptation self-efficacy following stroke. Self-efficacy (both general and psychosocial adaptation) showed significant correlations with life satisfaction post-stroke. Health professionals (more than half of whom were physiotherapists) recognised the importance of self-efficacy within stroke rehabilitation and identified five main ways to increase self-efficacy during stroke rehabilitation. These were to: 1) motivate and encourage patients; 2) provide more education about stroke and rehabilitation; 3) identify change; 4) offer a high-quality environment and therapy; and 5) set goals. In conclusion, psychosocial self-efficacy was identified as having a stronger relationship to life satisfaction compared with general self-efficacy within this sample of Kuwaiti female patients. Health professionals suggested various strategies for enhancing self-efficacy and thereby life satisfaction post-stroke during the rehabilitation process in Kuwait. Despite the collectivist culture of Kuwait, the findings indicate that the patient's own confidence and sense of responsibility for progress may be relevant to

  5. Anti-cancer efficacy of silybin derivatives -- a structure-activity relationship.

    Directory of Open Access Journals (Sweden)

    Chapla Agarwal

    Full Text Available Silybin or silibinin, a flavonolignan isolated from Milk thistle seeds, is one of the popular dietary supplements and has been extensively studied for its antioxidant, hepatoprotective and anti-cancer properties. We have envisioned that potency of silybin could be further enhanced through suitable modification/s in its chemical structure. Accordingly, here, we synthesized and characterized a series of silybin derivatives namely 2,3-dehydrosilybin (DHS, 7-O-methylsilybin (7OM, 7-O-galloylsilybin (7OG, 7,23-disulphatesilybin (DSS, 7-O-palmitoylsilybin (7OP, and 23-O-palmitoylsilybin (23OP; and compared their anti-cancer efficacy using human bladder cancer HTB9, colon cancer HCT116 and prostate carcinoma PC3 cells. In all the 3 cell lines, DHS, 7OM and 7OG demonstrated better growth inhibitory effects and compared to silybin, while other silybin derivatives showed lesser or no efficacy. Next, we prepared the optical isomers (A and B of silybin, DHS, 7OM and 7OG, and compared their anti-cancer efficacy. Isomers of these three silybin derivatives also showed better efficacy compared with respective silybin isomers, but in each, there was no clear cut silybin A versus B isomer activity preference. Further studies in HTB cells found that DHS, 7OM and 7OG exert better apoptotic activity than silibinin. Clonogenic assays in HTB9 cells further confirmed that both the racemic mixtures as well as pure optical isomers of DHS, 7OM and 7OG were more effective than silybin. Overall, these results clearly suggest that the anti-cancer efficacy of silybin could be significantly enhanced through structural modifications, and identify strong anti-cancer efficacy of silybin derivatives, namely DHS, 7OM, and 7OG, signifying that their efficacy and toxicity should be evaluated in relevant pre-clinical cancer models in rodents.

  6. Analysis of cohesion and collective efficacy profiles for the performance of soccer players.

    Science.gov (United States)

    Leo, Francisco M; Sánchez-Miguel, Pedro A; Sánchez-Oliva, David; Amado, Diana; García-Calvo, Tomás

    2013-12-18

    The principal aims of the study were to define different profiles of cohesion and perceived efficacy in soccer players and to measure their differences in performance. The subjects were 235 soccer players in the under-18 category who played in the National League in Spain and 15 coaches whose ages ranged from 29 to 45 years. Diverse instruments to assess cohesion, perceived efficacy, and expectations of success were used in the study. Moreover, we measured playing time and performance. The results of the study proved the existence of four cohesion and efficacy profiles that presented significant differences in expectations of success, playing time, and performance. Furthermore, significant differences were found in the distribution of players in the teams as a function of performance. The main conclusion of this study is that soccer players with higher cohesion and collective efficacy levels belonged to teams that completed the season at the top-level classification. In contrast, athletes with low cohesion and collective efficacy usually played in unsuccessful teams. Coaches and sports psychologists are encouraged to promote both social and task cohesion and collective efficacy to enhance team performance.

  7. Registered nurses' self-efficacy for assessing and responding to woman abuse in emergency department settings.

    Science.gov (United States)

    Hollingsworth, Erin; Ford-Gilboe, Marilyn

    2006-12-01

    Enhanced knowledge regarding the factors that influence and support the self-efficacy of emergency department (ED) registered nurses and their provision of care to women who have experienced abuse is necessary for the promotion of optimal health care. The purpose of this study was to examine the self-efficacy of registered nurses with respect to assessing and responding to woman abuse in the ED. Study hypotheses and research questions were derived from Bandura's theory of self-efficacy. A secondary analysis (N = 158) of data from the Violence against Women: Health Care Provider Survey was completed. Originally, survey questions were not developed to operationalize the concepts outlined by Bandura. However, they were found to be good indicators. Four scales were developed from the item pool, validated through factor analysis and used to operationalize study variables. Positive relationships were found between self-efficacy information available to ED registered nurses and their self-efficacy for assessing and responding to woman abuse (r= .73, p Bandura's theory and demonstrate that the clinical responses of ED registered nurses are complex and must be understood in terms of self-efficacy and the factors that support its development.

  8. Relations between Breastfeeding Self-efficacy and Maternal Health Literacy among Pregnant Women

    Directory of Open Access Journals (Sweden)

    Elham Charoghchian Khorasani

    2017-01-01

    Full Text Available Introduction: Breastfeeding self-efficacy show self-confidence and the ability of mothers to perform breastfeeding and maternal health literacy, ability of women to gain access to, understand, and use information in ways that promote and maintain their health and their children. Aim: this study was Measuring Associations between self-efficacy breastfeeding and maternal health literacy. Methods: This descriptive study was carried out in Mashhad health center in 2015. 185 pregnant women with first experience were selected randomly. Data were collected through health literacy maternal questionnaire and self-efficacy breastfeeding Fox & Dennis questionnaire and analyzed by descriptive and statistical tests in the SPSS/18. Results: The mean score of women's self-efficacy breastfeeding and standard deviation were 120.5 and 11.7 respectively and the mean maternal health literacy was 42.7±5.6. The results regression showed that the only variable that significantly associated with breastfeeding self-efficacy was maternal health literacy. Implications for practice: According to the results of this study, maternal health literacy must be raised to enhance breastfeeding self-efficacy, which could lead to an improvement in maternal breastfeeding in the society.

  9. Evaluating Self-Efficacy Expected of Polytechnic Engineering Students as a Measure of Employability

    Directory of Open Access Journals (Sweden)

    Oguche Innocent Ojonugwa

    2015-07-01

    Full Text Available In the face of increasing unemployment partly due to decreasing employability skills of Nigeria polytechnic students, many graduates of Nigeria polytechnic have a dwindle self-efficacy. 420 HND 2 polytechnic engineering students in north central states of Nigeria were surveyed. Data were collected using questionnaire consisting of 4 Likert-type statements. Student’s self-efficacy was measured by asking students to rate themselves  from 1 (“No confidence” to 4 (“Complete confidence”.The self-efficacy of engineering students in Nigeria polytechnic were examined using mean and standard deviation. The mean score for Self-appraisal, Occupational Information, Goal selection, Planning and Problem solving are as follow (3.32, (2.97, (3.28, (3.082 and (3.012 respectively with self-appraisal scoring higher than the others. These findings enhance our understanding of the importance of self-efficacy in the development of employability skills of polytechnic engineering students in Nigeria, more importantly self-appraisal had the highest mean score. The practical implication is that the teaching style will have to shift from being teacher-centred leaning to student-centred learning in order to address and accommodate the need of student’s self-efficacy.Key words: Self-efficacy; Employability; Employability skills; Nigerian polytechnics; Engineering students

  10. Psychometric evaluation of dietary self-efficacy and outcome expectation scales in female college freshmen.

    Science.gov (United States)

    Kedem, Leia E; Evans, Ellen M; Chapman-Novakofski, Karen

    2014-11-01

    Lifestyle interventions commonly measure psychosocial beliefs as precursors to positive behavior change, but often overlook questionnaire validation. This can affect measurement accuracy if the survey has been developed for a different population, as differing behavioral influences may affect instrument validity. The present study aimed to explore psychometric properties of self-efficacy and outcome expectation scales-originally developed for younger children-in a population of female college freshmen (N = 268). Exploratory principal component analysis was used to investigate underlying data patterns and assess validity of previously published subscales. Composite scores for reliable subscales (Cronbach's α ≥ .70) were calculated to help characterize self-efficacy and outcome expectation beliefs in this population. The outcome expectation factor structure clearly comprised of positive (α = .81-.90) and negative outcomes (α = .63-.67). The self-efficacy factor structure included themes of motivation and effort (α = .75-.94), but items pertaining to hunger and availability cross-loaded often. Based on cross-loading patterns and low Cronbach's alpha values, respectively, self-efficacy items regarding barriers to healthy eating and negative outcome expectation items should be refined to improve reliability. Composite scores suggested that eating healthfully was associated with positive outcomes, but self-efficacy to do so was lower. Thus, dietary interventions for college students may be more successful by including skill-building activities to enhance self-efficacy and increase the likelihood of behavior change.

  11. Examining Elementary School-Aged Children's Self-Efficacy and Proxy Efficacy for Fruit and Vegetable Consumption

    Science.gov (United States)

    Geller, Karly S.; Dzewaltowski, David A.

    2010-01-01

    Children's self-efficacy for fruit and vegetable consumption (FVC) and proxy efficacy to influence others to make fruit and vegetables (FV) available may influence their FVC. A previous investigation has demonstrated that self-efficacy for fruit consumption, self-efficacy for vegetable consumption, proxy efficacy to influence parents to make FV…

  12. At-Risk Boys' Social Self-Efficacy and Physical Activity Self-Efficacy in a Summer Sports Camp

    Science.gov (United States)

    Su, Xiaoxia; Xiang, Ping; McBride, Ron E.; Liu, Jiling; Thornton, Michael A.

    2016-01-01

    This study examined at-risk boys' social self-efficacy and physical activity self-efficacy within Bandura's self-efficacy framework. A total of 97 boys, aged between 10 and 13 years, attending a summer sports camp completed questionnaires assessing their social self-efficacy, physical activity self- efficacy, prosocial behaviors, and effort.…

  13. The application of Bandura's self-efficacy theory to abstinence-oriented alcoholism treatment.

    Science.gov (United States)

    Rollnick, S; Heather, N

    1982-01-01

    This paper explores the relevance of self-efficacy theory (Bandura, 1977b) to the process of abstinence treatment and the phenomenon of relapse. By distinguishing between the particular efficacy and outcome expectations created in treatment it is possible to clarify some of the problems encountered between clinicians and alcoholics. Bandura's theory also explains why some treatment methods might be more effective than others. Analysis of relapse suggests that while some of the expectations created in treatment might serve to promote abstinence, others might unwittingly precipitate relapse. The understanding of abstinence treatment could be enhanced by the testing of hypotheses which emerge from this analysis.

  14. Cancer survivors’ self-efficacy to self-manage in the year following primary treatment

    OpenAIRE

    Foster, Claire; Breckons, Matthew; Cotterell, P.; Barbosa, D.; Calman, Lynn; Corner, Jessica; Fenlon, Deborah; Foster, R.; Grimmett, Chloe; Richardson, Alison; Smith, P.W.

    2014-01-01

    PURPOSE\\ud Cancer survivors are increasingly expected to manage the consequences of cancer and its treatment for themselves. There is evidence that self-efficacy is important for successful self-management and that this can be enhanced with support. The purpose of this study was to assess self-efficacy to manage problems in the year following primary treatment.\\ud \\ud METHODS\\ud \\ud This cross-sectional online survey included cancer survivors who had completed their treatment within the past ...

  15. Efficacy of intraoperative neurophysiological monitoring.

    Science.gov (United States)

    Fisher, R S; Raudzens, P; Nunemacher, M

    1995-01-01

    Intraoperative neurophysiological monitoring is of benefit in protecting tissue at risk for trauma or ischemia during surgical procedures. Monitoring modalities include EEG, computer processed EEG, somatosensory (SEP), auditory (BAEP), and visual evoked potentials (VEP), and cranial nerve monitoring. The efficacy of monitoring is controversial, because no properly controlled prospective study of outcome with and without monitoring has been done. The weight of evidence suggests that loss of spontaneous EEG and SEP correlate well with critical reductions of cerebral blood flow. Meta-analysis of series comprising 3,028 patients undergoing carotid endarterectomies shows that SEP deteriorated in 5.6% of cases, with 20% of these having postoperative deficits, but more might have had deficits if they had not been shunted. SEP monitoring can be useful in surgery affecting brain and cord vasculature. Monitoring is not indicated for routine lumbosacral spine surgery. BAEPs have predictive value for preservation of hearing after acoustic neuroma surgery, and other surgery near the brainstem. VEPs have been too variable to be of major use in the operating room. For neurophysiologic monitoring to be useful, it must be performed by an experienced team, and the surgeon must be willing to act on the findings. Under these circumstances, monitoring can reduce surgical complications in selected cases.

  16. Teachers' self-efficacy, motivation adn teaching strategies - Auto-eficacia Docente, Motivación del Profesor y Estrategias de Enseñanza

    Directory of Open Access Journals (Sweden)

    Pedro Rosario

    2009-12-01

    Full Text Available According to previous research, teachers’ efficacy relating to teaching practices is highly dependent on the extent to which they are confident about their own capabilities to manage the new demands on their professional role. The present work aimed at: a gathering information about the way teachers manage different aspects of self-efficacy (i.e., enhancing their instructional process in order to optimize their lessons and engage the students in the learning process, in order to identify homogeneous self-efficacy profiles, b investigating the way these profiles relate to different levels and types of motivation, teaching strategies and teachers’ self-esteem. Ninety-five teachers from five Spanish public Universities participated in this study. Three different profiles of teachers’ efficacy have been identified: 1 high self-efficacy in the three dimensions; 2 medium self-efficacy in the enhancement of the teaching process and of lessons management, and medium-high efficacy in the engagement of students, and 3 low self-efficacy in the three dimensions. ANOVA results supported previous findings since teachers’ self-efficacy beliefs played a crucial role on teachers’ motivation and professional engagement.

  17. An Analysis on the Effect of Computer Self-Efficacy over Scientific Research Self-Efficacy and Information Literacy Self-Efficacy

    Science.gov (United States)

    Tuncer, Murat

    2013-01-01

    Present research investigates reciprocal relations amidst computer self-efficacy, scientific research and information literacy self-efficacy. Research findings have demonstrated that according to standardized regression coefficients, computer self-efficacy has a positive effect on information literacy self-efficacy. Likewise it has been detected…

  18. Self-Efficacy Mediates the Effects of Topiramate and GRIK1 Genotype on Drinking

    Science.gov (United States)

    Kranzler, Henry R.; Armeli, Stephen; Wetherill, Reagan; Feinn, Richard; Tennen, Howard; Gelernter, Joel; Covault, Jonathan; Pond, Timothy

    2014-01-01

    Previous studies indicate that topiramate reduces alcohol use among problem drinkers, with one study showing that the effect was moderated by a polymorphism (rs2832407) in GRIK1, the gene encoding the GluK1 kainate subunit. We examined whether the interactive effect of medication and genotype (a) altered the association between daily self-efficacy and later day drinking and (b) had an indirect effect on drinking via self-efficacy. Methods In a 12-week, placebo-controlled trial of topiramate, we used daily interactive voice response technology to measure self-efficacy (i.e., confidence in avoiding heavy drinking later in the day) and drinking behavior in 122 European-American heavy drinkers. Results Topiramate’s effects on both self-efficacy and drinking level were moderated by rs2832407. C-allele homozygotes treated with topiramate showed higher levels of self-efficacy and lower levels of nighttime drinking across the 12-week trial. Further, the interactive effect of topiramate and genotype on mean nighttime drinking levels was mediated by mean levels of self-efficacy. Conclusion By modeling topiramate’s effects on nighttime drinking across multiple levels of analysis, we found that self-efficacy, a key psychological construct, mediated the effect of topiramate, which was moderated by rs2832407 genotype. Thus, it may be possible to use an individualized assessment (i.e., genotype) to select treatment (i.e., topiramate or psychotherapy aimed at enhancing self-efficacy) to optimize the reduction in heavy drinking to provide a personalized treatment approach. PMID:25496338

  19. Leadership, self-efficacy, and student achievement

    Science.gov (United States)

    Grayson, Kristin

    This study examined the relationships between teacher leadership, science teacher self-efficacy, and fifth-grade science student achievement in diverse schools in a San Antonio, Texas, metropolitan school district. Teachers completed a modified version of the Leadership Behavior Description Question (LBDQ) Form XII by Stogdill (1969), the Science Efficacy and Belief Expectations for Science Teaching (SEBEST) by Ritter, Boone, and Rubba (2001, January). Students' scores on the Texas Assessment of Knowledge and Skills (TAKS) measured fifth-grade science achievement. At the teacher level of analysis multiple regressions showed the following relationships between teachers' science self-efficacy and teacher classroom leadership behaviors and the various teacher and school demographic variables. Predictors of teacher self efficacy beliefs included teacher's level of education, gender, and leadership initiating structure. The only significant predictor of teacher self-efficacy outcome expectancy was gender. Higher teacher self-efficacy beliefs predicted higher leadership initiating structure. At the school level of analysis, higher school levels of percentage of students from low socio-economic backgrounds and higher percentage of limited English proficient students predicted lower school student mean science achievement. These findings suggest a need for continued research to clarify relationships between teacher classroom leadership, science teacher self-efficacy, and student achievement especially at the teacher level of analysis. Findings also indicate the importance of developing instructional methods to address student demographics and their needs so that all students, despite their backgrounds, will achieve in science.

  20. Thermal styling: efficacy, convenience, damage tradeoffs.

    Science.gov (United States)

    Harper, Don; Qi, Jia Catherine; Kaplan, Peter

    2011-01-01

    We introduce a simple method to explore the efficacy of thermal styling, By using a temperature gradient curling iron we rapidly explore a range of thermal treatment conditions. The thermodynamic literature on the glass transition in keratin fibers explains the surprisingly limited role of elevated temperature in improvements in the efficacy of holding the styled curvature of the fibers. The onset of damage, however, is strongly temperature dependent. This combination of measurements of damage and efficacy shows the range of conditions over which thermal protection products must be functional.

  1. Clinical efficacy of photodynamic therapy

    Science.gov (United States)

    Park, Ye-Kyu

    2016-01-01

    Objective The management of cervical intraepithelial neoplasia (CIN) and early invasive cancer of the uterine cervix is very difficult to approach, especially in case of young woman who wants to preserve her fertility. Conization of the cervix may have various kinds of disadvantage. The objective of this clinical retrospective study is to investigate the therapeutic effects and clinical efficacy of photodynamic therapy (PDT) including combined chemo-photodynamic therapy in patients with pre-malignant CIN and malignant invasive cervical cancer. Methods Total number of PDT trial case was 50 cases and total number of patient was 22 patients who registered to PDT clinic. We used photogem sensitizer and 632 nm diode laser in early two cases. After then we performed PDT using photofrin sensitizer and 630 nm diode laser in other cases. We used flat-cut, microlens, cylindrical diffuser, and interstitial type optic fibers in order to irradiate the lesions. 240 J/cm2 energy was irradiated to the lesions. Results CIN 2 were 4 cases (18.2%) and CIN 3 were 15 (68.2%) and invasive cervical cancer were 3 (13.6%). Complete remission (CR) was found in 20 patients (91%). One case of 19 patients with CIN lesion recurred at 18 months after PDT treatment. CR was found in 18 cases in the patients with CIN lesions (95%). CR was found in 2 cases in the patients with invasive cervical cancer (67%). Conclusion Our data showed that CR rate was fantastic in CIN group (95%). This study suggests that PDT can be recommended as new optimistic management modality on the patients with pre-malignant CIN lesions including carcinoma in situ and relatively early invasive cancer of the uterine cervix. Combined chemo-photodynamic therapy is essential in case of invasive cervical cancer. For the young age group who desperately want to preserve their fertility and have a healthy baby, PDT can be a beacon of hope. PMID:27896250

  2. Pharmacological enhancement of behavioral therapy: focus on posttraumatic stress disorder.

    Science.gov (United States)

    Choi, Dennis C; Rothbaum, Barbara O; Gerardi, Maryrose; Ressler, Kerry J

    2010-01-01

    Improved efficacy in the treatment of posttraumatic stress disorder (PTSD) and other anxiety disorders is urgently needed. Traditional anxiety treatments of hypnosis and psychodynamic therapy may be of some help, but uncontrolled studies lead to inconclusive results on the efficacy of these treatment techniques. There is a larger literature supporting the efficacy of cognitive-behavioral procedures with PTSD, including prolonged exposure therapy, eye movement desensitization and reprocessing, and anxiety management techniques. The cutting-edge technology of virtual reality-based exposure therapy for PTSD is particularly exciting. To further build on effective psychosocial treatments, current pharmacological augmentation approaches to emotional learning are being combined with psychotherapy. In particular, D-cycloserine, a partial NMDA agonist, has shown to be effective in facilitating the exposure/extinction therapy to improve the efficacy of treating anxiety disorders, and may guide the way for new pharmacological enhancements of behavioral therapy.

  3. Concurrent Anticonvulsant/Ketogenic Diet Efficacy

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2009-09-01

    Full Text Available Researchers at the Johns Hopkins Hospital, Baltimore, studied retrospectively the comparative efficacy of six most frequently used anticonvulsants when employed in combination with the ketogenic diet (KD for treatment of 115 children with epilepsy.

  4. A fluorinated dendrimer achieves excellent gene transfection efficacy at extremely low nitrogen to phosphorus ratios

    Science.gov (United States)

    Wang, Mingming; Liu, Hongmei; Li, Lei; Cheng, Yiyun

    2014-01-01

    Polymers have shown great promise in the design of high efficient and low cytotoxic gene vectors. Here we synthesize fluorinated dendrimers for use as gene vectors. Fluorinated dendrimers achieve excellent gene transfection efficacy in several cell lines (higher than 90% in HEK293 and HeLa cells) at extremely low N/P ratios. These polymers show superior efficacy and biocompatibility compared with several commercial transfection reagents such as Lipofectamine 2000 and SuperFect. Fluorination enhances the cellular uptake of the dendrimer/DNA polyplexes and facilitates their endosomal escape. In addition, the fluorinated dendrimer shows excellent serum resistance and exhibits high gene transfection efficacy even in medium containing 50% FBS. The results suggest that fluorinated dendrimers are a new class of highly efficient gene vectors and fluorination is a promising strategy to design gene vectors without involving sophisticated syntheses.

  5. Interprofessional clinical training improves self-efficacy of health care students

    DEFF Research Database (Denmark)

    Nørgaard, Birgitte; Draborg, Eva; Vestergaard, Poul Erik;

    2013-01-01

    Background: Interprofessional collaboration potentially enhances patient safety and satisfaction, and reduces tensions and conflicts among health professionals. However, health professionals often lack sufficient knowledge of other professional roles and competences to engage in interprofessional...... teamwork. The aim of this study was to assess the impact of an interprofessional training programme on students' perceived self-efficacy. Methods: A quasi-experimental study with an intervention group (239 students) and a control group (405 students). The intervention was an interprofessional clinical...... study (ICS) unit including students from nursing, medicine, physiotherapy, occupational therapy, laboratory technology and radiography. Data on students' perceived self-efficacy were collected through web-based questionnaires. Aspects of self-efficacy measured were: (1) collaboration with other...

  6. Nanoparticle Drug Loading as a Design Parameter to Improve Docetaxel Pharmacokinetics and Efficacy

    Science.gov (United States)

    Chu, Kevin S.; Schorzman, Allison N.; Finniss, Mathew C.; Bowerman, Charles J.; Peng, Lei; Luft, J. Christopher; Madden, Andrew; Wang, Andrew Z.; Zamboni, William C.; DeSimone, Joseph M.

    2013-01-01

    Nanoparticle (NP) drug loading is one of the key defining characteristics of a NP formulation. However, the effect of NP drug loading on therapeutic efficacy and pharmacokinetics has not been thoroughly evaluated. Herein, we characterized the efficacy, toxicity and pharmacokinetic properties of NP docetaxel formulations that have differential drug loading but are otherwise identical. Particle Replication in Non-wetting Templates (PRINT®), a soft-lithography fabrication technique, was used to formulate NPs with identical size, shape and surface chemistry, but with variable docetaxel loading. The lower weight loading (9%-NP) of docetaxel was found to have a superior pharmacokinetic profile and enhanced efficacy in a murine cancer model when compared to that of a higher docetaxel loading (20%-NP). The 9%-NP docetaxel increased plasma and tumor docetaxel exposure and reduced liver, spleen and lung exposure when compared to that of 20%-NP docetaxel. PMID:23899444

  7. Examining teacher self-efficacy about best practices in science during a professional development series

    Science.gov (United States)

    Menez, Jessica L.

    Using extant data that were collected as part of a larger project, the current study examined teacher self-efficacy and the teachers' intentions to implement workshop content throughout the course of a six-week professional development workshop focused on enhancing science motivation for students through the adoption of specific instructional strategies. There were a total of 20 middle and high school teacher participants. Results indicated teacher self-efficacy changed significantly from pre to post. Teachers showed higher teacher self-efficacy after the professional development, in particular for influencing student engagement. In addition, we found a moderate correlation between the level of confidence after the implementation of a strategy and teachers intention of trying the strategy again. Finally, new direction for future research topics made possible by this study are presented.

  8. Enhancement in Sport, and Enhancement outside Sport.

    Science.gov (United States)

    Douglas, Thomas

    2007-12-01

    Sport is one of the first areas in which enhancement has become commonplace. It is also one of the first areas in which the use of enhancement technologies has been heavily regulated. Some have thus seen sport as a testing ground for arguments about whether to permit enhancement. However, I argue that there are fairness-based objections to enhancement in sport that do not apply as strongly in some other areas of human activity. Thus, I claim that there will often be a stronger case for permitting enhancement outside of sport than for permitting enhancement in sport. I end by considering some methodological implications of this conclusion.

  9. Acceptance-Enhanced Behavior Therapy for Trichotillomania in Adolescents

    Science.gov (United States)

    Fine, Kathi M.; Walther, Michael R.; Joseph, Jessica M.; Robinson, Jordan; Ricketts, Emily J.; Bowe, William E.; Woods, Douglas W.

    2012-01-01

    Although several studies have examined the efficacy of Acceptance Enhanced Behavior Therapy (AEBT) for the treatment of trichotillomania (TTM) in adults, data are limited with respect to the treatment of adolescents. Our case series illustrates the use of AEBT for TTM in the treatment of two adolescents. The AEBT protocol (Woods & Twohig, 2008) is…

  10. The Influence of Delivery Vectors on HIV Vaccine Efficacy

    Directory of Open Access Journals (Sweden)

    Beatrice Omusiro Ondondo

    2014-08-01

    Full Text Available Development of an effective HIV/AIDS vaccine remains a big challenge, largely due to the enormous HIV diversity which propels immune escape. Thus novel vaccine strategies are targeting multiple variants of conserved antibody and T cell epitopic regions which would incur a huge fitness cost to the virus in the event of mutational escape. Besides immunogen design, the delivery modality is critical for vaccine potency and efficacy, and should be carefully selected in order to not only maximise transgene expression, but to also enhance the immuno-stimulatory potential to activate innate and adaptive immune systems. To date, five HIV vaccine candidates have been evaluated for efficacy and protection from acquisition was only achieved in a small proportion of vaccinees in the RV144 study which used a canarypox vector for delivery. Conversely, in the STEP study (HVTN 502 where human adenovirus serotype 5 (Ad5 was used, strong immune responses were induced but vaccination was more associated with increased risk of HIV acquisition than protection in vaccinees with pre-existing Ad5 immunity. The possibility that pre-existing immunity to a highly promising delivery vector may alter the natural course of HIV to increase acquisition risk is quite worrisome and a huge setback for HIV vaccine development. Thus, HIV vaccine development efforts are now geared towards delivery platforms which attain superior immunogenicity while concurrently limiting potential catastrophic effects likely to arise from pre-existing immunity or vector-related immuno-modulation. However, it still remains unclear whether it is poor immunogenicity of HIV antigens or substandard immunological potency of the safer delivery vectors that has limited the success of HIV vaccines. This article discusses some of the promising delivery vectors to be harnessed for improved HIV vaccine efficacy.

  11. Toxicity Reducing and Efficacy Enhancing Effect of Sodium Cantharidinate Vitamin B6 Injection on GP Chemotherapy Regimen in Treatment of Advanced Non-Small Cell Lung Carcinoma%斑蝥酸钠维生素B6注射液对GP方案治疗晚期非小细胞肺癌减毒增效作用观察

    Institute of Scientific and Technical Information of China (English)

    曹晶杰; 宋一雪; 蒋潮涌

    2013-01-01

    Objective To observe the efficacy and the influence on the immune function and analgesic effect of Sodium Cantharidinate and Vitamin B6 Injection in treating advanced non-small cell lung carcinoma (NSCLC) patients combined with GP chemotherapy. Methods Totally 79 patients with advanced NSCLC were randomly divided into the observation group and the control group. The observation group accepted GP chemotherapy plus Sodium Cantharidinate and Vitamin B6 Injection, and the control group was treated with GP chemotherapy. After 2 cycles of chemotherapy, the efficacy was evaluated, cellular immune function index and analgesic effect were observed. Results The objective response rate (RR) of the treatment group was 72.50%(29/40), and the control group was 48.72%(19/39). There was no significant difference between the two groups (P>0.05). After 2 cycles of treatment, the ratio of CD3+, CD4+, CD8+, CD4+/CD8+ and NK in the observation group were higher than the control group, with significant differences (P<0.05). The pain relief rate in the observation group was 75.00%(30/40), and it was 51.28%(20/39) in the control group, the difference was significant between the two groups (P<0.05). Conclusion Sodium Cantharidinate and Vitamin B6 Injection combined with GP chemotherapy can improve the short-term effect rate and the cellular immune function. It can also relieve the pain and improve the guality of life of patients with advanced NSCLC.%目的观察斑蝥酸钠维生素B6注射液对接受GP方案(吉西他滨+顺铂)治疗的晚期非小细胞肺癌(NSCLC)患者临床疗效、免疫功能及止痛效果的影响。方法将79例晚期NSCLC患者分为观察组和对照组,2组患者均给予GP方案化疗,同时观察组予斑蝥酸钠维生素B6注射液治疗,疗程为2个周期。评价2组近期疗效,对比免疫功能,并评估止痛效果。结果观察组的客观缓解率为72.50%(29/40),对照组为48.72%(19/39),差异有统计学意义(P<0.05)

  12. Self-efficacy and depression in late life: a primary prevention proposal.

    Science.gov (United States)

    Blazer, D G

    2002-11-01

    Feelings of sadness and loneliness are ubiquitous in late life and a risk factor for depression and perhaps other mental illnesses in late life. Targeting sadness and loneliness for an intervention addresses both primary risk reduction for depressive disorders and promotion of overall mental health in the elderly. Nevertheless, few studies document the efficacy of primary prevention efforts in preventing depressive disorders in the elderly. The author argues that the attainment of positive mental health depends in considerable part upon an individual's self-efficacy--the belief that one can organize and execute the courses of action required to develop and enhance a person's belief that he or she can act in ways that lead to a desired goal. Self-efficacy is strengthened, not by some general or abstract instruction, but rather by the experience of successfully dealing with and thus overcoming specific problems. The extant literature suggests that many potential approaches may be available to develop and enhance self-efficacy in the elderly--approaches that potentially could be broadly applicable in community settings.

  13. Rational Design of Biobetters with Enhanced Stability.

    Science.gov (United States)

    Courtois, Fabienne; Schneider, Curtiss P; Agrawal, Neeraj J; Trout, Bernhardt L

    2015-08-01

    Biotherapeutics are the fastest growing class of pharmaceutical with a rapidly evolving market facing the rise of biosimilar and biobetter products. In contrast to a biosimilar, which is derived from the same gene sequence as the innovator product, a biobetter has enhanced properties, such as enhanced efficacy or reduced immunogenicity. Little work has been carried out so far to increase the intrinsic stability of biotherapeutics via sequence changes, even though, aggregation, the primary degradation pathway of proteins, leads to issues ranging from manufacturing failure to immunological response and to loss of therapeutic activity. Using our spatial aggregation propensity tool as a first step to a rational design approach to identify aggregation-prone regions, biobetters of rituximab have been produced with enhanced stability by introducing site-specific mutations. Significant stabilization against aggregation was achieved for rituximab with no decrease in its binding affinity to the antigen.

  14. Multifaceted Impact of Self-Efficacy Beliefs on Academic Functioning.

    Science.gov (United States)

    Bandura, Albert; And Others

    1996-01-01

    Analyzed the psychosocial influences through which efficacy beliefs affect academic achievement. Found that parents' sense of academic efficacy and aspirations for their children, children's beliefs in their efficacy to regulate their own learning and academic attainments, children's perceived social efficacy and ability to manage peer pressure,…

  15. Examining Preservice Teachers' Culturally Responsive Teaching Self-Efficacy Doubts

    Science.gov (United States)

    Siwatu, Kamau Oginga; Chesnut, Steven Randall; Alejandro, Angela Ybarra; Young, Haeni Alecia

    2016-01-01

    This study was designed to add to the research on teachers' self-efficacy beliefs by examining preservice teachers' culturally responsive teaching self-efficacy doubts. We examined the tasks that preservice teachers felt least efficacious to successfully execute and explored the reasoning behind these self-efficacy doubts. Consequently, we were…

  16. Academic service partnerships: organizational efficiency and efficacy between organizations.

    Science.gov (United States)

    Fetsch, Susan H; DeBasio, Nancy O

    2011-01-01

    Two leading nursing organizations, the Greater Kansas City Area Collegiate Nurse Educators and the Kansas City Area Nurse Executives, represent the Kansas City metropolitan area nursing programs and area employers. These two organizations have been engaged in collaborative workforce planning and strategy development around key nursing issues for over 25 years. This model of collaboration is unique in that the partnership is between organizations representing 17 nursing programs and 28 hospitals. The collaborative partnership has enhanced organizational efficiency and efficacy between the groups, which has directly benefited the organizational members. Most importantly, it has had a transformative impact on both nursing education and professional practice in the Kansas City metropolitan area. This article describes the evolution of the partnership and the collaborative work that has led to the accomplishment of mutual goals.

  17. Safety and efficacy of quadrapeutics versus chemoradiation in head and neck carcinoma xenograft model.

    Science.gov (United States)

    Lukianova-Hleb, Ekaterina Y; Kim, Yoo-Shin; Aryasomayajula, Bhawani; Boulikas, Teni; Phan, Jack; Hung, Mien-Chie; Torchilin, Vladimir P; O'Neill, Brian E; Lapotko, Dmitri O

    2015-01-01

    Chemoradiation is the strongest anti-tumor therapy but in resistant unresectable cancers it often lacks safety and efficacy. We compared our recently developed cell-level combination approach, quadrapeutics, to chemoradiation therapy to establish pre-clinical data for its biodistribution, safety and efficacy in head and neck squamous cell carcinoma (HNSCC), as a clinically challenging aggressive and resistant cancer. In vitro and in vivo models of four carcinomas were treated with standard chemoradiation and quadrapeutics using identical drug and radiation doses. We applied liposomal cisplatin or doxorubicin, colloidal gold, near-infrared laser pulses and radiation, all at low safe doses. The final evaluation used a xenograft model of HNSCC. Quadrapeutics enhanced standard chemoradiation in vitro by reducing head and neck cancer cell proliferation by 1000-fold, inhibiting tumor growth in vivo by 34-fold and improving animal survival by 5-fold, and reducing the side effects to a negligible level. In quadrapeutics, we observed an "inversion" of the drug efficacy of two standard drugs: doxorubicin, a low efficacy drug for the cancers studied, was two times more efficient than cisplatin, the first choice drug in clinic for HNSCC. The radical therapeutic gain of quadrapeutics resulted from the intracellular synergy of the four components employed which we administered in a specific sequence, while the reduction in the toxicity was due to the low doses of all four components. The biodistribution, safety and efficacy data for quadrapeutics in HNSCC ensure its high translational potential and justify the possibility of clinical trials.

  18. Association of Self-Efficacy and Outcome Expectations with Physical Activity in Adults with Arthritis

    Directory of Open Access Journals (Sweden)

    Thelma J. Mielenz

    2013-01-01

    Full Text Available Background and Purpose. The purpose of this study is to determine whether higher baseline levels of (a self-efficacy for physical activity, (b self-efficacy for arthritis self-management, and (c outcome expectations for exercise are associated with higher physical activity levels following an exercise intervention for adults with arthritis. Methods. A secondary analysis of the intervention cohort (n=130 within a randomized controlled trial of the People with Arthritis Can Exercise program was performed. Multiple linear regression evaluated the relationship between physical activity at a time point three months after the completion of an exercise intervention and three main explanatory variables. Results. After controlling for baseline physical activity, neither self-efficacy for arthritis self-management nor outcome expectations for exercise related to three-month physical activity levels. There was a relationship between three-month physical activity and self-efficacy for physical activity. Conclusions. Future research is needed to evaluate the ability of self-efficacy-enhancing programs to increase physical activity in adults with arthritis.

  19. Effect of Robotics on Elementary Preservice Teachers' Self-Efficacy, Science Learning, and Computational Thinking

    Science.gov (United States)

    Jaipal-Jamani, Kamini; Angeli, Charoula

    2016-12-01

    The current impetus for increasing STEM in K-12 education calls for an examination of how preservice teachers are being prepared to teach STEM. This paper reports on a study that examined elementary preservice teachers' (n = 21) self-efficacy, understanding of science concepts, and computational thinking as they engaged with robotics in a science methods course. Data collection methods included pretests and posttests on science content, prequestionnaires and postquestionnaires for interest and self-efficacy, and four programming assignments. Statistical results showed that preservice teachers' interest and self-efficacy with robotics increased. There was a statistically significant difference between preknowledge and postknowledge scores, and preservice teachers did show gains in learning how to write algorithms and debug programs over repeated programming tasks. The findings suggest that the robotics activity was an effective instructional strategy to enhance interest in robotics, increase self-efficacy to teach with robotics, develop understandings of science concepts, and promote the development of computational thinking skills. Study findings contribute quantitative evidence to the STEM literature on how robotics develops preservice teachers' self-efficacy, science knowledge, and computational thinking skills in higher education science classroom contexts.

  20. Effect of Robotics on Elementary Preservice Teachers' Self-Efficacy, Science Learning, and Computational Thinking

    Science.gov (United States)

    Jaipal-Jamani, Kamini; Angeli, Charoula

    2017-04-01

    The current impetus for increasing STEM in K-12 education calls for an examination of how preservice teachers are being prepared to teach STEM. This paper reports on a study that examined elementary preservice teachers' ( n = 21) self-efficacy, understanding of science concepts, and computational thinking as they engaged with robotics in a science methods course. Data collection methods included pretests and posttests on science content, prequestionnaires and postquestionnaires for interest and self-efficacy, and four programming assignments. Statistical results showed that preservice teachers' interest and self-efficacy with robotics increased. There was a statistically significant difference between preknowledge and postknowledge scores, and preservice teachers did show gains in learning how to write algorithms and debug programs over repeated programming tasks. The findings suggest that the robotics activity was an effective instructional strategy to enhance interest in robotics, increase self-efficacy to teach with robotics, develop understandings of science concepts, and promote the development of computational thinking skills. Study findings contribute quantitative evidence to the STEM literature on how robotics develops preservice teachers' self-efficacy, science knowledge, and computational thinking skills in higher education science classroom contexts.

  1. Hypoglycemic efficacy of chitosan-coated insulin liposomes after oral administration in mice

    Institute of Scientific and Technical Information of China (English)

    Zheng-hong WU; Qi-neng PING; Yi WEI; Jia-ming LAI

    2004-01-01

    AIM: To evaluate the hypoglycemic efficacy of insulin liposomes coated by chitosan with different molecular weights and concentrations after oral administration in mice. METHODS: Insulin-liposomes were prepared by reversed-phase evaporation. Chitosan coating was carried out by incubation of the liposomal suspensions with the chitosan solution. The hypoglycemic efficacies of chitosan-coated insulin liposomes were investigated by monitoring the blood glucose level using the glucose oxidase method after oral administration to healthy mice. RESULTS:In all the insulin liposomes, the insulin liposomes coated by 0.2 % chitosan (M. 1000 kDa) showed a better hypoglycemic efficacy as compared with the other liposomes coated by chitosan. The minimum blood glucose level was 15.1%±6.0 % of the initial (n=6). The hypoglycemic efficacy lasted for 4 h after oral administration to mice.CONCLUSION: Chitosan-coated liposomes could reduce tryptic digestion on insulin, and enhance enteral absorption of insulin. The molecular weights and concentrations of chitosan had significant effects on hypoglycemic efficacy of chitosan-coated insulin liposomes after oral administration to healthy mice.

  2. Heterogeneous reallocation of presynaptic efficacy in recurrent excitatory circuits adapting to inactivity.

    Science.gov (United States)

    Mitra, Ananya; Mitra, Siddhartha S; Tsien, Richard W

    2011-12-18

    Recurrent excitatory circuits face extreme challenges in balancing efficacy and stability. We recorded from CA3 pyramidal neuron pairs in rat hippocampal slice cultures to characterize synaptic and circuit-level changes in recurrent synapses resulting from long-term inactivity. Chronic tetrodotoxin treatment greatly reduced the percentage of connected CA3-CA3 neurons, but enhanced the strength of the remaining connections; presynaptic release probability sharply increased, whereas quantal size was unaltered. Connectivity was decreased in activity-deprived circuits by functional silencing of synapses, whereas three-dimensional anatomical analysis revealed no change in spine or bouton density or aggregate dendrite length. The silencing arose from enhanced Cdk5 activity and could be reverted by acute Cdk5 inhibition with roscovitine. Our results suggest that recurrent circuits adapt to chronic inactivity by reallocating presynaptic weights heterogeneously, strengthening certain connections while silencing others. This restricts synaptic output and input, preserving signaling efficacy among a subset of neuronal ensembles while protecting network stability.

  3. Personal definitions of science and the self-efficacy and classroom practice of elementary school teachers

    Science.gov (United States)

    Hanson, Deborah L.

    Science is a subject that many elementary teachers struggle to teach. One of the reasons documented in the literature is the low science teaching self-efficacy of many elementary teachers. This study investigated possible connections between how a teacher defines science (her personal definition of science) and her science teaching self-efficacy. Thirteen teachers participating in Science EDUCATES, a professional development program that emphasized NOS, scientific inquiry and physical science content knowledge, were investigated to see how their science teaching self-efficacy was impacted as changes to their personal definition of science occurred. Two of these teachers were selected for further study; in addition, two teachers, outside the professional development, were also studied. Personal definitions of science were gathered using the VNOS-D2 and VOSI-E survey instruments while science teaching self-efficacy was measured by the STEBI survey. Interviews and classroom observations were conducted to see the patterns that emerged between the teachers' personal definition of science, their science self-efficacy and their classroom practices. The teachers in the professional development did increase their science teaching self-efficacy and contributed this increase to their enhanced knowledge about NOS and how scientific knowledge is generated. This increased science content knowledge led to a statistically significant difference in the PSTE scores of the teachers. Teachers with low to mid science teaching self-efficacy levels seem to have various elements embedded within their personal definition of science that prevents them from engaging fully in science. Their science practices seem to pattern those subjects, like social studies or language arts, they are more comfortable teaching. Understanding NOS helped the teachers to change their personal definitions of science and place their classroom practices more in line with the recommendations in the national reform

  4. Design and validation of a standards-based science teacher efficacy instrument

    Science.gov (United States)

    Kerr, Patricia Reda

    subscales. Correlations were computed for BAT, BASA, and demographic variables to identify relationships between teacher efficacy, teacher characteristics, and school characteristics. Further research is recommended to refine the instrument and apply its use to a larger sample of science teachers. Its further development also has significance for the enhancement of science teacher education programs.

  5. Ascorbic acid in cancer chemoprevention: translational perspectives and efficacy.

    Science.gov (United States)

    Ullah, Mohammad F; Bhat, Showket H; Hussain, Eram; Abu-Duhier, Faisel; Ahmad, Aamir; Hadi, S M

    2012-12-01

    Chemoprevention, which is referred to as the use of nontoxic natural or synthetic chemicals to intervene in multistage carcinogenesis has since decades attracted a considerable interest in plant-derived chemical constituents often termed as "phytochemicals" or sometimes as "Nutraceuticals" in case they are derived from dietary sources. A comprehensive search of the literature show that such an interest in natural product pharmacology has surged in the last 25 years and particularly risen at exponential rates since the last one decade. Phytochemicals such as curcumin (from spice turmeric), resveratrol (from red wine) and genistein (from soy) share the major efforts as indicated by overwhelming publications, despite skepticism concerning their bioavailability. Ascorbic acid (AA), the popular anti-oxidant in fruits and vegetables, has even a longer historical perspective than these dietary agents as for more than 35 years; there had been lingering questions about the efficacy of AA in cancer therapy. The footprints of AA from "scurvy" to "cancer" though complex seems to carry potential provided the puzzle could be set right. The use of AA in cancer treatment has been debated extensively as evident from the literature but surprisingly the complementing early phase bench work on the mechanistic studies for anticancer action was rather retarded. Proposed mechanisms of action for AA in the prevention and treatment of cancer includes antioxidant as well as pro-oxidant properties, stimulation of the immune system, altering carcinogen metabolism, enhancement of collagen synthesis necessary for tumor encapsulation and interference with cancer cell signaling. The observation that the intravenous administration of AA enhances its bioavailability to the extent of deriving pharmacological benefits against cancer has in recent years partially supported the clinical plausibility (efficacy) of AA towards realizing its translational advantage. Here, we provide an overview of AA with

  6. Bandura's theory of self-efficacy: applications to oncology.

    Science.gov (United States)

    Lev, E L

    1997-01-01

    Self-efficacy (Bandura, 1986) has been shown to impact on health practices as well as adaptation to illness and treatment. The purposes of this paper are to describe self-efficacy theory and review literature using self-efficacy theory to investigate prevention of cancer and adaptation to cancer. Measurement of self-efficacy is also discussed. Evidence from research examining applications of Bandura's theory of self-efficacy in oncology suggests relationships between self-efficacy and cancer prevention and self-efficacy and adaptation to cancer. Strong percepts of self-efficacy predict intention to quit smoking, increased participation in screening programs, and adjustment to cancer diagnosis. Increased self-efficacy is associated with increased adherence to treatment, increased self-care behaviors, and decreased physical and psychological symptoms. The advanced practice nurse is in an excellent position to give feedback that may help support patients' self-efficacy.

  7. Meta-analysis of clinical and preclinical studies comparing the anticancer efficacy of liposomal versus conventional non-liposomal doxorubicin.

    Science.gov (United States)

    Petersen, Grant H; Alzghari, Saeed K; Chee, Wayne; Sankari, Sana S; La-Beck, Ninh M

    2016-06-28

    While liposome-mediated delivery of cytotoxic chemotherapy has been shown to significantly enhance drug tolerability in patients as compared to the conventional formulation, the fundamental question remains whether they also improve anticancer efficacy. Thus, we performed a systematic literature search for randomized clinical trials directly comparing efficacy of liposomal cytotoxic chemotherapy versus their equivalent conventional formulation. The search yielded 14 clinical trials (8 anthracycline, 4 cisplatin, 1 paclitaxel, 1 irinotecan) that meet inclusion criteria, with a total of 2589 patients. We found that efficacy in patients was not different between liposomal and conventional chemotherapy as assessed by objective response (odds ratio 1.03; 95% confidence interval [CI] 0.82-1.30), overall survival (hazard ratio [HR] 1.05; 95% CI 0.95-1.17), and progression free survival rates (HR 1.01; 95% CI, 0.92-1.11). Subgroup analyses of only the anthracycline trials also did not show any efficacy advantage for the liposomal formulation. Since pegylated liposomal doxorubicin (PLD) was the most prevalent formulation in these clinical trials, we also performed a meta-analysis of 11 preclinical studies comparing efficacy of PLD and conventional doxorubicin in tumor-bearing mice. In contrast with clinical results, animal studies showed significantly increased survival in mice treated with PLD compared to conventional doxorubicin (HR 0.39; 95% CI 0.27-0.56). We discuss the possible reasons why the pharmacological advantages of carrier-mediated chemotherapy did not translate into enhanced clinical efficacy including the role of the enhanced permeability and retention (EPR) effect and the tumor microenvironment, the optimal dosing regimen for carrier-mediated agents, and the lack of standardization in the conduct and reporting of preclinical studies evaluating anticancer efficacy of these agents. Our study shows that the full clinical potential of carrier-mediated drugs

  8. Covariates of Self-Efficacy: Caregiver Characteristics Related to Mental Health Services Self-Efficacy

    Science.gov (United States)

    Reich, S.; Bickman, L.; Heflinger, C. A.

    2004-01-01

    Increasingly, professionals are recognizing the need to involve parents and other caregivers in the mental health treatment of children. However, parents and caregivers may not feel efficacious when participating in mental health care. Self-efficacy is a mechanism of human agency that describes people's beliefs about their capabilities to exercise…

  9. An Exploration of the Relationship among Teacher Efficacy, Collective Teacher Efficacy, and Goal Consensus

    Science.gov (United States)

    Kurz, Terri Barber; Knight, Stephanie L.

    2004-01-01

    This study explored the relationships among individual teacher efficacy, collective teacher efficacy, and goal consensus/vision. Participants included 113 teachers of a high school located in the southwestern USA. During a teacher inservice meeting, teachers completed three surveys that measured the variables under study. Correlational and…

  10. Does Emotional Self-Efficacy Predict Teachers' Self-Efficacy and Empathy?

    Science.gov (United States)

    Goroshit, Mariana; Hen, Meirav

    2014-01-01

    Research has shown that teachers' self-efficacy and empathy are two of the most important variables consistently related to outcomes of positive teaching and student learning. Emotional self-efficacy refers to peoples' judgment regarding their own capacity to process emotional information accurately and effectively. It is considered a powerful…

  11. Co-constructing Efficacy: A "Communities of Practice" Perspective on Teachers' Efficacy Beliefs

    Science.gov (United States)

    Takahashi, Sola

    2011-01-01

    Teachers' efficacy beliefs are critical to improving student learning, but we have yet to fully understand how these beliefs develop. The prevailing model of teachers' efficacy development emerges from cognitive theories, but sociocultural theories may add insights to modeling the impact of teachers' school contexts. This case study takes a…

  12. Arsenic trioxide enhances the therapeutic efficacy of adjuvant post-operative chemotherapy of gastric carcinoma while protecting bone marrow%三氧化二砷改善胃癌患者术后辅助化疗疗效同时减轻骨髓抑制

    Institute of Scientific and Technical Information of China (English)

    Hong Sui; Yuxian Bai; Yu Han; Kaibing Wang

    2009-01-01

    Objective: The aim of the study was to investigate the prospective study if treatment with arsenic trioxide (As2O3) could enhance disease-free survival as adjuvant post-operative chemotherapy for gastric cancer patients and protect bone marrow from the negative effects of chemotherapy. Methods: 84 adults were randomized into two groups. Patients in treat- ment group were treated with As203 and FOLFOX regimen, the other were administered with FOLFOX regimen only. Results: Four patients were withdrawn in treatment group after 3-4 cycles and the reasons were headache and fidgety (n = 2), ar- rhythmia (n = 1) and AST/ALT elevation (n = 1), while 1 patient in control group after 4 cycles for neutropenia. In the treatment group, the median DFS was 28.34 months (95% CI, 25-33 months). While in control group, the median DFS was 24.50 months (95% CI, 20-30 months). This difference was not statistically significant (chi-square: 2.8885; P value: 0.0892). Pa- tients in the same subgroup of node-positive was 29 in the treatment group and 32 in control group, respectively. The median DFS was 27.87 months (95% CI, 25-31 months) in the treatment group and 24.18 months (95% CI, 19-31 months) in the control group with promising statistical significance (HR 1.89; chi-square: 4.78; P value: 0.0287). The most common grades 3-4 toxicity was leucopenia (n = 11) in control group and the difference was significant (chi-square: 3.9768, P value: 0.046) compared with that in treatment group (n = 4). Conclusion: The combination of arsenic trioxide and FOLFOX regimen has a potential advantage of enhancing disease-free survival in patients with gastric cancer in nodal-positive status as post-opera- tive chemotherapy, and protect bone marrow from the negative effects of chemotherapy.

  13. Antimicrobial efficacy of silver ions in combination with tea tree oil against ; and

    OpenAIRE

    Low, W.L.; Martin, C.; Hill, D J; Kenward, M A

    2011-01-01

    International audience; Tea tree oil (TTO) and silver ions (Ag), either alone or in combination with other antimicrobial compounds, have been used in the treatment of topical infections. However, there appears to be little data on the efficacy of TTO combined with silver in the absence of any other agents. TTO and Ag were added, alone and in combination, to suspension cultures of , and . Treatment of these cultures with TTO and Ag at sub-minimal lethal concentrations resulted in an enhanced l...

  14. Efficacy of Osteoporosis Therapies in Diabetic Patients.

    Science.gov (United States)

    Schwartz, Ann V

    2017-02-01

    Diabetes is characterized by increased fracture risk and by reduced bone strength for a given density. Contributing factors may include lower bone turnover and accumulation of advanced glycation endproducts. There are concerns that the pharmacological therapies for osteoporosis, particularly anti-resorptive therapies that suppress bone turnover, may not be as effective in the setting of diabetes. This review considers clinical trials and observational studies that have assessed the efficacy of anti-resorptive and anabolic therapies in diabetic patients. Post hoc analyses of randomized trials indicate that raloxifene has similar efficacy for prevention of vertebral fractures in diabetic compared with non-diabetic patients. Evidence from randomized clinical trials is lacking for anti-fracture efficacy of other osteoporosis therapies in diabetes. However, observational studies suggest that bisphosphonates are effective in preventing fractures in diabetic patients. The great majority of diabetic patients in studies to date have been type 2, and efficacy of osteoporosis therapies in type 1 diabetic patients remains to be addressed. Further evaluation of the efficacy of osteoporosis therapies in the setting of diabetes is needed to provide optimal fracture prevention for this population.

  15. Efficacy of OptiphosTM phytase on mineral digestibility in diets for breeding sows: effect during pregnancy an lactation

    NARCIS (Netherlands)

    Jongbloed, A.W.; Diepen, van J.T.M.; Binnendijk, G.P.; Bikker, P.; Vereecken, M.; Bierman, K.

    2013-01-01

    Phosphorus in most diets for breeding sows is digested for 20 to 40%, thus leading to a relatively high amount of P in the manure. To enhance the P digestibility in diets for both lactating and gestating sows, two separate experiments were carried out to study the efficacy of OptiphosTM phytase deri

  16. The Efficacy of Positive Psychology Interventions to Increase Well-Being and the Role of Mental Imagery Ability

    Science.gov (United States)

    Odou, Natasha; Vella-Brodrick, Dianne A.

    2013-01-01

    This study examined the effects of mental imagery ability (MIA) on the efficacy of two positive psychology interventions (PPIs) to enhance well-being. Participants (N = 210) were randomly assigned to either: Three Good Things (TGT), Best Possible Selves (BPS), or a control group and completed well-being questionnaires pre and post intervention.…

  17. Relationship between Student's Self-Directed-Learning Readiness and Academic Self-Efficacy and Achievement Motivation in Students

    Science.gov (United States)

    Saeid, Nasim; Eslaminejad, Tahere

    2017-01-01

    Self-directed learning readiness to expand and enhance learning, This is an important goal of higher education, Besides his academic self-efficacy can be improved efficiency and Achievement Motivation, so understanding how to use these strategies by students is very important. Because the purpose this study is determination of relationship between…

  18. The Predict of academic self-efficacy through social Well-Being of Students at University of Medical Sciences

    Directory of Open Access Journals (Sweden)

    Ali akbar Ajam

    2016-04-01

    Conclusion: The findings showed that some social health components (namely social flourishing, social cohesion, social solidarity and social acceptance are predictive of students’ self-efficacy. Therefore, holding workshops and training courses are recommended in order to enhance the social health status of university students.

  19. The Effect of Wilderness Therapy on Adolescents' Cognitive Autonomy and Self-Efficacy: Results of a Non-Randomized Trial

    Science.gov (United States)

    Margalit, Daniella; Ben-Ari, Amichai

    2014-01-01

    Background: Adolescents participate in decision-making processes involving risky behaviors. Management of these important decisions may be promoted by enhancing adolescents' self-efficacy beliefs and cognitive autonomy. Objective: In order to elucidate the value of wilderness therapy to the successful management of decision making processes among…

  20. Testing the Efficacy of "INSIGHTS" on Student Disruptive Behavior, Classroom Management, and Student Competence in Inner City Primary Grades

    Science.gov (United States)

    McClowry, Sandra Graham; Snow, David L.; Tamis-LeMonda, Catherine S.; Rodriguez, Eileen T.

    2010-01-01

    A prevention trial tested the efficacy of "INSIGHTS into Children's Temperament" as compared to a Read Aloud attention control condition in reducing student disruptive behavior and enhancing student competence and teacher classroom management. Participants included 116 first and second grade students, their parents, and their 42 teachers…

  1. Self-efficacy analysis among HIV positive patients in Jimma University Specialized Hospital: a cross-sectional study

    Directory of Open Access Journals (Sweden)

    Netsanet Fentahun

    2014-07-01

    Conclusions: The HIV patients had high self-efficacy on disclosure, safe sex and treatment adherence. This good practice should be promoted and enhanced in different part of Ethiopia. The HIV patients had low awareness about their parents' HIV status. Future effort should be made on awareness level about their parents' HIV status.

  2. Mesenchymal stem cells and cutaneous wound healing: novel methods to increase cell delivery and therapeutic efficacy.

    Science.gov (United States)

    Lee, Dylan E; Ayoub, Nagi; Agrawal, Devendra K

    2016-03-09

    Mesenchymal stem cells (MSCs) (also known as multipotent mesenchymal stromal cells) possess the capacity for self-renewal and multi-lineage differentiation, and their ability to enhance cutaneous wound healing has been well characterized. Acting via paracrine interactions, MSCs accelerate wound closure, increase angiogenesis, promote resolution of wound inflammation, favorably regulate extracellular matrix remodeling, and encourage regeneration of skin with normal architecture and function. A number of studies have employed novel methods to amplify the delivery and efficacy of MSCs. Non-traditional sources of MSCs, including Wharton's jelly and medical waste material, have shown efficacy comparable to that of traditional sources, such as bone marrow and adipose tissue. The potential of alternative methods to both introduce MSCs into wounds and increase migration of MSCs into wound areas has also been demonstrated. Taking advantage of the associations between MSCs with M2 macrophages and microRNA, methods to enhance the immunomodulatory capacity of MSCs have shown success. New measures to enhance angiogenic capabilities have also exhibited effectiveness, often demonstrated by increased levels of proangiogenic vascular endothelial growth factor. Finally, hypoxia has been shown to have strong wound-healing potential in terms of increasing MSC efficacy. We have critically reviewed the results of the novel studies that show promise for the continued development of MSC-based wound-healing therapies and provide direction for continued research in this field.

  3. Developing the Reader Self-Efficacy Scale

    Directory of Open Access Journals (Sweden)

    Hakan ÜLPER

    2013-04-01

    Full Text Available Reading comprehension has affective and social dimensions as well as its cognitive dimension. Thus, to understand and improve reading instruction, affective and social dimensions should be well understood. Perceived self-efficacy is one of affective issues influencing learning and it should be taken into consideration in reading instruction. With this in mind, this study aims at developing the Reader Self-Efficacy Scale with a group of 518 students as participants. Exploratory and confirmatory factor analyses revealed a 6-item scale with one factor. The Cronbach Alpha coefficient was determined to be 0.948. This new Reader Self-Efficacy Scale could easily be used for training and research purposes depending on its high validity and reliability.

  4. Field efficacy of acaricides against Varroa destructor

    Science.gov (United States)

    Gracia, María Jesús; Moreno, Carlos; Ferrer, Montserrat; Sanz, Alfredo; Peribáñez, Miguel Ángel; Estrada, Rosa

    2017-01-01

    Field trials were conducted in Northeast Spain (Aragón) to evaluate the effectiveness of two acaricides against Varroa destructor. These experiments took into account the season of the year, apiary, colony, and developmental state and strength of the colony. The acaricides used were a synthetic (amitraz, Apivar®) and a natural (formulated from Api Life Var®, thymol oil and thymol alcohol) product. The treatments used in the present study reduce high infestations of V. destructor, although they do not eliminate the infestation. Similar efficacies between treatments were found. Nevertheless, the efficacy of a treatment depends on the apiary where applied. Moreover, the detected variability in the apiary and hive poses a challenge to the identification of the significant factors. Therefore, more field studies to assess efficacies in several apiaries are needed to obtain a better understanding of the effects of the applied treatments. PMID:28158303

  5. Contrast-enhanced endoscopic ultrasonography

    Institute of Scientific and Technical Information of China (English)

    Nischita K Reddy; Ana Maria Ioncic(a); Adrian S(a)ftoiu; Peter Vilmann; Manoop S Bhutani

    2011-01-01

    Contrast agents are increasingly being used to characterize the vasculature in an organ of interest,to better delineate benign from malignant pathology and to aid in staging and directing therapeutic procedures.We review the mechanisms of action of first,second and third generation contrast agents and their use in various endoscopic procedures in the gastrointestinal tract.Various applications of contrast-enhanced endoscopic ultrasonography include differentiating benign from malignant mediastinal lymphadenopathy,assessment of depth of invasion of esophageal,gastric and gall bladder cancers and visualization of the portal venous system and esophageal varices.In addition,contrast agents can be used to differentiate pancreatic lesions.The use of color Doppler further increases the ability to diagnose and differentiate various pancreatic malignancies.The sensitivity of power Doppler sonography to depict tumor neovascularization can be increased by contrast agents.Contrast-enhanced harmonic imaging is a useful aid in identifying the tumor vasculature and studying pancreatic microperfusion.In the future,these techniques could potentially be used to quantify tumor perfusion,to assess and monitor the efficacy of antiangiogenic agents,to assist targeted drug delivery and allow molecular imaging.

  6. Self-Efficacy and green entrepreneurship

    Science.gov (United States)

    Tan, K. L.; Suhaida, S.; Leong, Y. P.

    2013-06-01

    The objective of this study is to investigate empirically the extent to which self-efficacy contributes to the development of green entrepreneurial intention. The measurement constructs of self-efficacy were classified into market opportunities, innovative environment, initiating relationships, defining purpose, coping with challenges, and developing human resources. The study comprises 252 usable convenient samples through structured questionnaires. The coefficient of determination R2 shows that the variance of intention to entrepreneurship is explained by the variance of the independent variables. It was also found that the model is fit for prediction.

  7. Enhancement in Sport, and Enhancement outside Sport

    OpenAIRE

    Douglas, Thomas

    2007-01-01

    Sport is one of the first areas in which enhancement has become commonplace. It is also one of the first areas in which the use of enhancement technologies has been heavily regulated. Some have thus seen sport as a testing ground for arguments about whether to permit enhancement. However, I argue that there are fairness-based objections to enhancement in sport that do not apply as strongly in some other areas of human activity. Thus, I claim that there will often be a stronger case for permit...

  8. Development of preservice elementary teachers' science self- efficacy beliefs and its relation to science conceptual understanding

    Science.gov (United States)

    Menon, Deepika

    beliefs included: (1) enhanced science conceptual understandings, (2) active learning experiences, (3) teaching strategies, and (4) instructor as a role-model. Findings suggest that despite of the nature of prior science experiences preservice elementary teachers previously had, an exposure to a course that integrates relevant science content along with modeled instructional strategies can positively impact science self-efficacy beliefs. While some course elements such as active learning experiences and teaching models seemed to impact all groups positively, the low group participants were particularly influenced by the multiple representations of the content and the course instructor as a role model. These findings have important implications for preservice science teacher preparation programs.

  9. Cognitive Behavioral Therapy and Motivational Enhancement Therapy.

    Science.gov (United States)

    Wu, Sarah S; Schoenfelder, Erin; Hsiao, Ray Chih-Jui

    2016-10-01

    Although cognitive behavioral therapy (CBT) is widely recognized as the preferred treatment of psychiatric disorders, less is known about the application of CBT to substance use disorders, particularly in adolescence. This article discusses how CBT conceptualizes substance use and how it is implemented as a treatment of adolescent substance abuse. The article draws on several manuals for CBT that implement it as a standalone treatment or in combination with motivational enhancement therapies. Also reviewed are several studies that examined the efficacy of CBT. Finally, the implications are discussed. Numerous starting resources are provided to help a clinician implement CBT.

  10. Middle school science teachers' teaching self-efficacy and students' science self-efficacy

    Science.gov (United States)

    Pisa, Danielle

    Project 2061, initiated by the American Association for the Advancement of Science (AAAS), developed recommendations for what is essential in education to produce scientifically literate citizens. Furthermore, they suggest that teachers teach effectively. There is an abundance of literature that focuses on the effects of a teacher's science teaching self-efficacy and a student's science self-efficacy. However, there is no literature on the relationship between the two self-efficacies. This study investigated if there is a differential change in students' science self-efficacy over an academic term after instruction from a teacher with high science teaching self-efficacy. Quantitative analysis of STEBI scores for teachers showed that mean STEBI scores did not change over one academic term. A t test indicated that there was no statistically significant difference in mean SMTSL scores for students' science self-efficacy over the course of one academic term for a) the entire sample, b) each science class, and c) each grade level. In addition, ANOVA indicated that there was no statistically significant difference in mean gain factor of students rated as low, medium, and high on science self-efficacy as measured by the SMTSL, when students received instruction from a teacher with a high science teaching self-efficacy value as measured by the STEBI. Finally, there was no statistically significant association between the pre- and post-instructional rankings of SMTSL by grade level when students received instruction from a teacher with a high science teaching self-efficacy value as measured by the STEBI. This is the first study of its kind. Studies indicated that teaching strategies typically practiced by teachers with high science teaching were beneficial to physics self-efficacy (Fencl & Scheel, 2005). Although it was unsuccessful at determining whether or not a teacher with high science teaching self-efficacy has a differential affect on students' science self-efficacy

  11. Self-efficacy, foreign language anxiety as predictors of academic performance among professional program students in a general English proficiency writing test.

    Science.gov (United States)

    Chen, M C; Lin, Huey-Ju

    2009-10-01

    Questionnaires were administered to 120 students. Cluster analysis was used to examine whether specific groups could be described by a writing self-efficacy scale, English writing anxiety scale, and a written General English Proficiency Test. Three clusters were observed. Demographic variables were compared for each cluster, including age, sex, program of study, years of English instruction, native language, and number of English speaking acquaintances. Efforts to reduce writing anxiety and promote writing self-efficacy could enhance writing scores of participants.

  12. Linalool Affects the Antimicrobial Efficacy of Essential Oils.

    Science.gov (United States)

    Herman, Anna; Tambor, Krzysztof; Herman, Andrzej

    2016-02-01

    The high concentrations of essential oils are generally required to receive microbial purity of the products (cosmetics, medicine). On the other hand, their application due to the high concentration of essential oils may be limited by changes in organoleptic and textural quality of the products, as well as they cause irritation and allergies in users. Addition of linalool to essential oil may significantly enhance its antimicrobial effectiveness and reduce their concentrations in products, taking advantage of their synergistic and additive effects. The aim of the study was to compare antimicrobial activity of essential oil alone and in combination with linalool. The antimicrobial activity of the essential oil of Thymus vulgaris, Juniperus communis, Pelargonium graveolens, Citrus bergamia, Citrus grandis, Lavandula angustifolia, Cinnamomum zeylanicum, Melaleuca alternifolia, Syzygium aromaticum, linalool and their combination was investigated against bacteria and fungi using the disc diffusion method. The addition of linalool to S. aromaticum oil in a synergistic manner enhanced its antimicrobial efficacy against P. aeruginosa and A. brasiliensis. Moreover, the additive interaction between this oil and linalool was observed against S. aureus, E. coli and C. albicans. It was also found that linalool in an additive manner increased the antimicrobial effectiveness of T. vulgaris oil against P. aeruginosa. The antimicrobial properties of mixture of essential oils with their active constituents may be used for creating new strategies to maintain microbiological purity of products.

  13. MOTOR IMAGERY AND TENNIS SERVE PERFORMANCE: THE EXTERNAL FOCUS EFFICACY

    Directory of Open Access Journals (Sweden)

    Aymeric Guillot

    2013-06-01

    Full Text Available There is now ample evidence that motor imagery (MI contributes to enhance motor performance. Previous research also demonstrated that directing athletes' attention to the effects of their movements on the environment is more effective than focusing on the action per se. The present study aimed therefore at evaluating whether adopting an external focus during MI contributes to enhance tennis serve performance. Twelve high-level young tennis players were included in a test-retest procedure. The effects of regular training were first evaluated. Then, players were subjected to a MI intervention during which they mentally focused on ball trajectory and specifically visualized the space above the net where the serve can be successfully hit. Serve performance was evaluated during both a validated serve test and a real match. The main results showed a significant increase in accuracy and velocity during the ecological serve test after MI practice, as well as a significant improvement in successful first serves and won points during the match. Present data therefore confirmed the efficacy of MI in combination of physical practice to improve tennis serve performance, and further provided evidence that it is feasible to adopt external attentional focus during MI. Practical applications are discussed

  14. Virucidal efficacy of hydrogen peroxide vapour disinfection

    NARCIS (Netherlands)

    Tuladhar, E.; Terpstra, P.; Koopmans, M.; Duizer, E.

    2012-01-01

    Background: Viral contamination of surfaces is thought to be important in transmission. Chemical disinfection can be an effective means of intervention, but little is known about the virucidal efficacy of hydrogen peroxide vapour (HPV) against enteric and respiratory viruses. Aim: To measure the vir

  15. Efficacy of coughing in tetraplegic patients

    NARCIS (Netherlands)

    van der Schans, CP; Piers, DA; Mulder, GA

    2000-01-01

    Study Design. A randomized cross-over design study in six tetraplegic patients. Objectives. To investigate the efficacy of coughing in tetraplegic patients. Summary of Background Data. In tetraplegic patients, pulmonary complications due to insufficient clearance of bronchial mucus frequently are de

  16. Self-Efficacy, Taiwan Elementary Teachers Perspective

    Science.gov (United States)

    Jack, Brady M.; Liu, Chia-Ju; Chiu, Hoan-Lin

    2005-01-01

    This paper presents the results of a case study involving Taiwanese elementary teachers who teach science at the elementary grade school level. It advocates the position that a teacher's personal science efficacy belief influences his or her science teaching outcome expectations. It promotes the position that the success Taiwan has experienced in…

  17. Self-Efficacy and Academic Listening

    Science.gov (United States)

    Graham, Suzanne

    2011-01-01

    This paper takes as its starting point the difficulties inherent in listening in a second language. It argues that self-efficacy, broadly defined as the belief in one's ability to carry out specific tasks successfully, is crucial to the development of effective listening skills, and that listening strategy instruction has the potential to boost…

  18. Evaluating Ritual Efficacy: Evidence from the Supernatural

    Science.gov (United States)

    Legare, Cristine H.; Souza, Andre L.

    2012-01-01

    Rituals pose a cognitive paradox: although widely used to treat problems, rituals are causally opaque (i.e., they lack a causal explanation for their effects). How is the efficacy of ritual action evaluated in the absence of causal information? To examine this question using ecologically valid content, three studies (N=162) were conducted in…

  19. Sweat Therapy Theory, Practice, and Efficacy

    Science.gov (United States)

    Eason, Allen; Colmant, Stephen; Winterowd, Carrie

    2009-01-01

    The purpose of this article is to examine the potential application of sweat rituals to group counseling, adventure therapy, and other forms of group work by describing a theoretical model for how sweat rituals work and presenting the results of a randomized comparative outcome study on the efficacy of sweat therapy. The theoretical model proposes…

  20. Self-Efficacy and Music Performance

    Science.gov (United States)

    McPherson, Gary E.; McCormick, John

    2006-01-01

    This study is the second in a series of investigations attempting to clarify relationships between variables that impact on a young musician's ability to perform music (as assessed on a graded music examination). Consistent with studies on school academic subjects, our previous investigation demonstrated the importance of self-efficacy in…

  1. Promoting Efficacy Research on Functional Analytic Psychotherapy

    Science.gov (United States)

    Maitland, Daniel W. M.; Gaynor, Scott T.

    2012-01-01

    Functional Analytic Psychotherapy (FAP) is a form of therapy grounded in behavioral principles that utilizes therapist reactions to shape target behavior. Despite a growing literature base, there is a paucity of research to establish the efficacy of FAP. As a general approach to psychotherapy, and how the therapeutic relationship produces change,…

  2. Disrupted Cl(-) homeostasis contributes to reductions in the inhibitory efficacy of diazepam during hyperexcited states.

    Science.gov (United States)

    Deeb, Tarek Z; Nakamura, Yasuko; Frost, Greg D; Davies, Paul A; Moss, Stephen J

    2013-08-01

    The K(+) -Cl(-) cotransporter type 2 is the major Cl(-) extrusion mechanism in most adult neurons. This process in turn leads to Cl(-) influx upon activation of γ-aminobutyric acid type A (GABAA ) receptors and the canonical hyperpolarising inhibitory postsynaptic potential. Several neurological disorders are treated with drugs that target and enhance GABAA receptor signaling, including the commonly used benzodiazepine diazepam and the anesthetic propofol. Some of these disorders are also associated with deficits in GABAA signaling and become less sensitive to therapeutic drugs that target GABAA receptors. To date, it is unknown if alterations in the neuronal Cl(-) gradient affect the efficacies of diazepam and propofol. We therefore used the in vitro model of glutamate-induced hyperexcitability to test if alterations in the Cl(-) gradient affect the efficacy of GABAA modulators. We exclusively utilised the gramicidin perforated-patch-clamp configuration to preserve the endogenous Cl(-) gradient in rat neurons. Brief exposure to glutamate reduced the inhibitory efficacy of diazepam within 5 min, which was caused by the collapse of the Cl(-) gradient, and not due to reductions in GABAA receptor number. Unlike diazepam, propofol retained its efficacy by shunting the membrane conductance despite the glutamate-induced appearance of depolarising GABAA -mediated currents. Similarly, pharmacological inhibition of K(+) -Cl(-) cotransporter type 2 by furosemide disrupted Cl(-) homeostasis and reduced the efficacy of diazepam but not propofol. Collectively our results suggest that pathological hyperexcitable conditions could cause the rapid accumulation of intracellular Cl(-) and the appearance of depolarising GABAA -mediated currents that would decrease the efficacy of diazepam.

  3. Hemoaction game: an educational step to improve hemophilia children and nurses self-efficacy

    Directory of Open Access Journals (Sweden)

    NOOASHIN BEHESHTIPOOR

    2016-10-01

    Full Text Available As hemophilia is a chronic bleeding disease and can interfere with daily performance of children, these children require continuous training to prevent bleeding and take timely action (1. Since children nurses play an important role in the education of involved children and their Selfefficacy and also due to today’s approach which is using educational computer games, the use of educational games in respect to teach hemophilia children how to have self-efficacy can be effective (2. Hemoaction game is a computerized educational game designed by the World Federation of Hemophilia to educate hemophilia disease and related procedures to the care of children with hemophilia. By the use of this game children with hemophilia (aged 8-12 and also nursing experts were educated how to increase self efficacy. Nursing School of Shiraz University of Medical Sciences has used this game for the first time after its publishing, in the world (3. The results of the mentioned study demonstrates that after the Hemophilia disease and its related procedures were instructed to children with hemophilia and nursing experts in order to know how to increase patients’ self efficacy by modern approaches, self efficacy of hemophilia children and nurses were both improved. This educational method is a novel way to enhance both Hemophilia children and nursing staff, as major participants in routine and lifelong education process, self-efficacy. Due to nurses’ important role in improving children with hemophilia self-efficacy by different instructions and world leading educational approaches towards use of modern technology in education, using Hemoaction educational game, published by World Federation of Hemophilia and used by Nursing and Midwifery College of Shiraz University of Medical Sciences for the first time, can fulfill hemophilia children needs of care.

  4. The role of self-efficacy, emotional intelligence and leadership style as attributes of leadership effectiveness

    Directory of Open Access Journals (Sweden)

    Yvette Ramchunder

    2014-02-01

    Full Text Available Orientation: Researching the impact of psychological constructs on police leadership may add value when appointing people in leadership positions or developing people for leadership roles in the police environment.Research purpose: The purpose of this study is to explore the relationship between three constructs, namely emotional intelligence, self-efficacy and leadership effectiveness in a policing context.Motivation for this study: In the police sector, there are difficulties in linking leadership to organisational outcomes since common police-leadership measures are affected by multiple contributory factors. This study explores the psychological constructs of emotional intelligence and self-efficacy on the leadership effectiveness of the police.Research design, approach and method: This research adopted a quantitative approach to assess the relationship between emotional intelligence and self-efficacy as attributes of leadership effectiveness. A total of 107 police personnel in commanding positions made up the sample. The measuring instruments used were the Assessing Emotions Scale, the Self-efficacy Scale and the Multifactor Leadership Questionnaire (MLQ Form 5X.Main findings: The results confirmed a positive relationship between emotional intelligence and self-efficacy and leadership effectiveness. The correlations were significant at the 0.01 level (2-tailed.Practical/managerial implications: Emotional intelligence and self-efficacy should be considered as attributes during the selection of leaders in police organisations or used for developmental purposes to enhance these attributes in police leaders.Contribution/value-add: The insights gained from the findings may be used to guide the selection of future leaders in the policing environment, and they could also be used to establish future developmental programmes and research initiatives.

  5. 分组合作学习法:提高大学公共英语课堂效率的有效策略%Cooperative Learning in Groups: An Effective Way of Enhancing Classroom Efficacy in College English Teaching

    Institute of Scientific and Technical Information of China (English)

    刘亚竞

    2012-01-01

    As a kind of teaching strategy, cooperative learning has been widely acclaimed as an effective means of teaching. It is found that cooperative learning is more often applied to English majors than non - English majors. Given the large number of non - English major students in universities, the application of cooperative learning in groups is faced with many practical difficulties. This paper presents an empirical research on the possibility of applying cooperative learning in groups to college English teaching. It turns out that college English teaching effects will be greatly enhanced in terms of learning content, learning manner, learner participation, learner recognition, and learner initiative with the adoption of cooperative learning in groups.%分组合作学习法是一种近年来被广泛应用的教学策略和有效的教学手段。在教学实践中,英语专业的教学对分组合作学习法的应用由来已久。但对于公共英语教学,该教学策略的实施面临着学者众,多难以操作等诸多难题。笔者结合自身的公共英语教学经历,对分组合作学习法是否可以成功地运用于公共英语的教学做了大胆地尝试。使得大学公共英语教学从上课形式到学习内容、学习方式等各方面都有了质的飞跃。学生对于该学习法使用的认可度、对大学英语课堂学习效果的满意率的提高均充分显示了分组合作学习法的使用极大地调动了学生学习的主观能动性、提高了大学公共英语教学的课堂效率。

  6. Efficacy of clinical gait analysis: A systematic review.

    Science.gov (United States)

    Wren, Tishya A L; Gorton, George E; Ounpuu, Sylvia; Tucker, Carole A

    2011-06-01

    The aim of this systematic review was to evaluate and summarize the current evidence base related to the clinical efficacy of gait analysis. A literature review was conducted to identify references related to human gait analysis published between January 2000 and September 2009 plus relevant older references. The references were assessed independently by four reviewers using a hierarchical model of efficacy adapted for gait analysis, and final scores were agreed upon by at least three of the four reviewers. 1528 references were identified relating to human instrumented gait analysis. Of these, 116 original articles addressed technical accuracy efficacy, 89 addressed diagnostic accuracy efficacy, 11 addressed diagnostic thinking and treatment efficacy, seven addressed patient outcomes efficacy, and one addressed societal efficacy, with some of the articles addressing multiple levels of efficacy. This body of literature provides strong evidence for the technical, diagnostic accuracy, diagnostic thinking and treatment efficacy of gait analysis. The existing evidence also indicates efficacy at the higher levels of patient outcomes and societal cost-effectiveness, but this evidence is more sparse and does not include any randomized controlled trials. Thus, the current evidence supports the clinical efficacy of gait analysis, particularly at the lower levels of efficacy, but additional research is needed to strengthen the evidence base at the higher levels of efficacy.

  7. [Self-efficacy among health learners/self-efficacy among health educators].

    Science.gov (United States)

    Chikamoto, Y

    1998-01-01

    The Social Cognitive Theory has helped health educators develop effective health education programs that target self-efficacy among participants in changing their health behavior. Bandura has identified four resources on which individuals determine their levels of self-efficacy: (1) performance accomplishment, (2) vicarious reinforcement, (3) verbal persuasion, and (4) emotional arousal. Examples of health education strategies that utilize each of the four resources to increase participants' self-efficacy are described. Health education professionals in Japan have attempted to use programs based on the Social Cognitive Theory for Japanese populations. It is criticized that health educators that use such programs are not well trained in effective use, and that those programs have not been utilized at their maximum potentials. Using the frame-work of the Social Cognitive Theory, the importance of incorporating ways to increase self-efficacy of health educators in providing health education services into education and training of health educators is discussed.

  8. Non Pharmacological Cognitive Enhancers - Current Perspectives.

    Science.gov (United States)

    Sachdeva, Ankur; Kumar, Kuldip; Anand, Kuljeet Singh

    2015-07-01

    Cognition refers to the mental processes involved in thinking, knowing, remembering, judging, and problem solving. Cognitive dysfunctions are an integral part of neuropsychiatric disorders as well as in healthy ageing. Cognitive Enhancers are molecules that help improve aspects of cognition like memory, intelligence, motivation, attention and concentration. Recently, Non Pharmacological Cognitive Enhancers have gained popularity as effective and safe alternative to various established drugs. Many of these Non Pharmacological Cognitive Enhancers seem to be more efficacious compared to currently available Pharmacological Cognitive Enhancers. This review describes and summarizes evidence on various Non Pharmacological Cognitive Enhancers such as physical exercise, sleep, meditation and yoga, spirituality, nutrients, computer training, brain stimulation, and music. We also discuss their role in ageing and different neuro-psychiatric disorders, and current status of Cochrane database recommendations. We searched the Pubmed database for the articles and reviews having the terms 'non pharmacological and cognitive' in the title, published from 2000 till 2014. A total of 11 results displayed, out of which 10 were relevant to the review. These were selected and reviewed. Appropriate cross-references within the articles along with Cochrane reviews were also considered and studied.

  9. What Differentiates Employees' Job Performance Under Stressful Situations: The Role of General Self-Efficacy.

    Science.gov (United States)

    Lu, Chang-Qin; Du, Dan-Yang; Xu, Xiao-Min

    2016-10-02

    The aim of this research is to verify the two-dimensional challenge-hindrance stressor framework in the Chinese context, and investigate the moderating effect of general self-efficacy in the stress process. Data were collected from 164 Chinese employee-supervisor dyads. The results demonstrated that challenge stressors were positively related to job performance while hindrance stressors were negatively related to job performance. Furthermore, general self-efficacy strengthened the positive relationship between challenge stressors and job performance, whereas the attenuating effect of general self-efficacy on the negative relationship between hindrance stressors and job performance was nonsignificant. These findings qualify the two-dimensional challenge-hindrance stressor framework, and support the notion that employees with high self-efficacy benefit more from the positive effect of challenge stressors in the workplace. By investigating the role of an individual difference variable in the challenge-hindrance stressor framework, this research provides a more accurate picture of the nature of job stress, and enhances our understanding of the job stressor-job performance relationship.

  10. Synergistic Antitumor Efficacy of Oncolytic Adenovirus Combined with Chemotherapy

    Institute of Scientific and Technical Information of China (English)

    LI Yue-min; QIAN Qi-jun; SONG San-tai; JIANG Ze-fei; ZHANG Qi; QU Yi-mei; SU Chang-qing; ZHAO Chuan-hua; LI Zhi-qiang; GE Fei-jiao

    2007-01-01

    Objective: Chemotherapy is an effective means of treating breast cancer, and cancer-specific replicative adenovirus is also a promising antitumor agent in recent years. Our investigation aims to demonstrate that CNHK300 can mediate selective antitumor efficacy and produce synergistic cytotoxicity with chemotherapy on HER-2 over-expressing breast cancer. Methods: We engineered the telomerase-dependent replicative adenovirus CNHK300 by placing the E1A gene under the control of the human hTERT promoter. By analysis of E1A expression, we proved the fidelity of hTERT promoter in adenovirus genome and the selective expression of E1A in telomerase-positive breast cancer cells but not in normal fibroblast cells. By proliferation test, we further showed efficient replication of CNHK300 in breast cancer cells with apparently attenuated proliferation in normal fibroblast cells. Finally, we demonstrated by MTT methods that CNHK300 virus caused potent cytolysis and produced synergistic cytotoxicity with chemotherapy in breast cancer cells with attenuated cytotoxicity on normal cells. Results: In this virus, the E1A gene is successfully placed under the control of the human hTERT promoter. CNHK300 virus replicated as efficiently as the wild-type adenovirus and caused intensive cell killing in HER-2 over-expressing breast cancer cells in vitro. In contrast, telomerase-negative normal fibroblast cells, which expressed no hTERT activity, were not able to support CNHK300 replication. Combined treatment of CNHK300 with paclitaxel improved cytotoxicity on cancer cells. Conclusion: We conclude that CNHK300 can produce selective antitumor efficacy and enhance the in vitro response of chemotherapy on HER-2 overexpressing breast cancer.

  11. Mild hyperthermia enhances transport of liposomal gemcitabine and improves in vivo therapeutic response.

    Science.gov (United States)

    Kirui, Dickson K; Celia, Christian; Molinaro, Roberto; Bansal, Shyam S; Cosco, Donato; Fresta, Massimo; Shen, Haifa; Ferrari, Mauro

    2015-05-01

    Obstructive biological barriers limit the transport and efficacy of cancer nanotherapeutics. Creative manipulation of tumor microenvironment provides promising avenues towards improving chemotherapeutic response. Such strategies include the use of mechanical stimuli to overcome barriers, and increase drug delivery and therapeutic efficacy. The rational use of gold nanorod-mediated mild hyperthermia treatment (MHT) alters tumor transport properties, increases liposomal gemcitabine (Gem Lip) delivery, and antitumor efficacy in pancreatic cancer CAPAN-1 tumor model. MHT treatment leads to a threefold increase in accumulation of 80-nm liposomes and enhances spatial interstitial distribution. I.v. injection of Gem Lip and MHT treatment lead to a threefold increase in intratumor gemcitabine concentration compared to chemotherapeutic infusion alone. Furthermore, combination of MHT treatment with infusion of 12 mg kg(-1) Gem Lip leads to a twofold increase in therapeutic efficacy and inhibition of CAPAN-1 tumor growth when compared to equimolar chemotherapeutic treatment alone. Enhanced therapeutic effect is confirmed by reduction in tumor size and increase in apoptotic index where MHT treatment combined with 12 mg kg(-1) Gem Lip achieves similar therapeutic efficacy as the use of 60 mg kg(-1) free gemcitabine. In conclusion, improvements in vivo efficacy are demonstrated resulting from MHT treatment that overcome transport barriers, promote delivery, improve efficacy of nanomedicines.

  12. Preservice Teachers: Investigations in Early Fieldwork and Mathematics Efficacy Beliefs

    Science.gov (United States)

    Hunt-Ruiz, Heidi

    2011-01-01

    In this quasi-experimental study, 127 preservice teachers from two community colleges enrolled in a mathematics for teachers two-course sequence. Control and experimental groups were used to investigate the effect that fieldwork had on efficacy beliefs. The Mathematics for Teaching Efficacy Beliefs Instrument (MATHEMATICS TEACHING EF