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Sample records for therapies provide enhanced

  1. Therapy Provider Phase Information

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Therapy Provider Phase Information dataset is a tool for providers to search by their National Provider Identifier (NPI) number to determine their phase for...

  2. A treatment schedule of conventional physical therapy provided to enhance upper limb sensorimotor recovery after stroke: expert criterion validity and intra-rater reliability.

    Science.gov (United States)

    Donaldson, Catherine; Tallis, Raymond C; Pomeroy, Valerie M

    2009-06-01

    Inadequate description of treatment hampers progress in stroke rehabilitation. To develop a valid, reliable, standardised treatment schedule of conventional physical therapy provided for the paretic upper limb after stroke. Eleven neurophysiotherapists participated in the established methodology: semi-structured interviews, focus groups and piloting a draft treatment schedule in clinical practice. Different physiotherapists (n=13) used the treatment schedule to record treatment given to stroke patients with mild, moderate and severe upper limb paresis. Rating of adequacy of the treatment schedule was made using a visual analogue scale (0 to 100mm). Mean (95% confidence interval) visual analogue scores were calculated (expert criterion validity). For intra-rater reliability, each physiotherapist observed a video tape of their treatment and immediately completed a treatment schedule recording form on two separate occasions, 4 to 6 weeks apart. The Kappa statistic was calculated for intra-rater reliability. The treatment schedule consists of a one-page A4 recording form and a user booklet, detailing 50 treatment activities. Expert criterion validity was 79 (95% confidence interval 74 to 84). Intra-rater Kappa was 0.81 (P<0.001). This treatment schedule can be used to document conventional physical therapy in subsequent clinical trials in the geographical area of its development. Further work is needed to investigate generalisability beyond this geographical area.

  3. Provider confidence in opioid prescribing and chronic pain management: results of the Opioid Therapy Provider Survey.

    Science.gov (United States)

    Pearson, Amy Cs; Moman, Rajat N; Moeschler, Susan M; Eldrige, Jason S; Hooten, W Michael

    2017-01-01

    Many providers report lack of confidence in managing patients with chronic pain. Thus, the primary aim of this study was to investigate the associations of provider confidence in managing chronic pain with their practice behaviors and demographics. The primary outcome measure was the results of the Opioid Therapy Provider Survey, which was administered to clinicians attending a pain-focused continuing medical education conference. Nonparametric correlations were assessed using Spearman's rho. Of the respondents, 55.0% were women, 92.8% were white, and 56.5% were physicians. Primary care providers accounted for 56.5% of the total respondents. The majority of respondents (60.8%) did not feel confident managing patients with chronic pain. Provider confidence in managing chronic pain was positively correlated with 1) following an opioid therapy protocol (P=0.001), 2) the perceived ability to identify patients at risk for opioid misuse (P=0.006), and 3) using a consistent practice-based approach to improve their comfort level with prescribing opioids (Pconfidence was negatively correlated with the perception that treating pain patients was a "problem in my practice" (P=0.005). In this study, the majority of providers did not feel confident managing chronic pain. However, provider confidence was associated with a protocolized and consistent practice-based approach toward managing opioids and the perceived ability to identify patients at risk for opioid misuse. Future studies should investigate whether provider confidence is associated with measurable competence in managing chronic pain and explore approaches to enhance appropriate levels of confidence in caring for patients with chronic pain.

  4. Relationship Enhancement Therapy: A Case Study for Treating Vaginismus.

    Science.gov (United States)

    Harman, Marsha J.; And Others

    1994-01-01

    A case study of Relationship Enhancement (RE) therapy with a couple, in which the woman was identified as having vaginismus, is presented including excerpts of transcripts from the therapy sessions. RE's effectiveness at improving communication skills and providing structure in which the couple could discuss the intimate issues affecting the…

  5. Provider confidence in opioid prescribing and chronic pain management: results of the Opioid Therapy Provider Survey

    Directory of Open Access Journals (Sweden)

    Pearson AC

    2017-06-01

    Full Text Available Amy CS Pearson,1 Rajat N Moman,2 Susan M Moeschler,3 Jason S Eldrige,3 W Michael Hooten3 1Department of Anesthesiology & Perioperative Medicine, Mayo School of Graduate Medical Education, Mayo Clinic, 2Mayo Clinic School of Medicine, 3Department of Anesthesiology & Perioperative Medicine, Mayo College of Medicine, Rochester, MN, USA Introduction: Many providers report lack of confidence in managing patients with chronic pain. Thus, the primary aim of this study was to investigate the associations of provider confidence in managing chronic pain with their practice behaviors and demographics.Materials and methods: The primary outcome measure was the results of the Opioid Therapy Provider Survey, which was administered to clinicians attending a pain-focused continuing medical education conference. Nonparametric correlations were assessed using Spearman’s rho.Results: Of the respondents, 55.0% were women, 92.8% were white, and 56.5% were physicians. Primary care providers accounted for 56.5% of the total respondents. The majority of respondents (60.8% did not feel confident managing patients with chronic pain. Provider confidence in managing chronic pain was positively correlated with 1 following an opioid therapy protocol (P=0.001, 2 the perceived ability to identify patients at risk for opioid misuse (P=0.006, and 3 using a consistent practice-based approach to improve their comfort level with prescribing opioids (P<0.001. Provider confidence was negatively correlated with the perception that treating pain patients was a “problem in my practice” (P=0.005.Conclusion: In this study, the majority of providers did not feel confident managing chronic pain. However, provider confidence was associated with a protocolized and consistent practice-based approach toward managing opioids and the perceived ability to identify patients at risk for opioid misuse. Future studies should investigate whether provider confidence is associated with measurable

  6. Behavioral Therapy, Incentives Enhance Addiction Treatment

    Science.gov (United States)

    ... Research News From NIH Behavioral Therapy, Incentives Enhance Addiction Treatment Past Issues / Summer 2006 Table of Contents ... that people who are trying to end their addiction to marijuana can benefit from a treatment program ...

  7. Enhancing Targeted Therapy for Myeloproliferative Neoplasms

    Science.gov (United States)

    2013-10-01

    Myeloproliferative Neoplasms PRINCIPAL INVESTIGATOR: Gary W. Reuther CONTRACTING...2. REPORT TYPE Annual 3. DATES COVERED 30 2012-2 2013 4. TITLE AND SUBTITLE Enhancing Targeted Therapy for Myeloproliferative Neoplasms ...AVAILABILITY STATEMENT Approved for Public Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Myeloproliferative neoplasms

  8. Predictors of Adopting Motivational Enhancement Therapy

    Science.gov (United States)

    Ager, Richard; Roahen-Harrison, Stephanie; Toriello, Paul J.; Kissinger, Patricia; Morse, Patricia; Morse, Edward; Carney, Linton; Rice, Janet

    2011-01-01

    Substance abuse counselors have shown limited success in adopting evidence-based practices (EBPs). The purpose of this paper is to identify the barriers and facilitators of adopting an EBP called motivational enhancement therapy (MET). One hundred thirty-six predominantly female (60%) African American (68%) addiction counselors representing over…

  9. Providing Educationally Relevant Occupational and Physical Therapy Services

    Science.gov (United States)

    Laverdure, Patricia A.; Rose, Deborah S.

    2012-01-01

    As defined in the Individuals with Disabilities Education Improvement Act, occupational and physical therapists provide services to support students to access, participate, and progress in their educational program within the least restrictive educational environment. Educationally relevant occupational and physical therapy services in school…

  10. Dynamic contrast enhanced ultrasound for therapy monitoring

    Energy Technology Data Exchange (ETDEWEB)

    Hudson, John M. [Department of Medical Biophysics, University of Toronto, Toronto, ON (Canada); Williams, Ross [Imaging Research, Sunnybrook Research Institute, Toronto, ON (Canada); Tremblay-Darveau, Charles; Sheeran, Paul S. [Department of Medical Biophysics, University of Toronto, Toronto, ON (Canada); Milot, Laurent [Department of Medical Imaging, University of Toronto, Toronto, ON (Canada); Bjarnason, Georg A. [Department of Medical Oncology, University of Toronto, and Sunnybrook Odette Cancer Centre, Toronto, ON (Canada); Burns, Peter N., E-mail: burns@sri.utoronto.ca [Department of Medical Biophysics, University of Toronto, Toronto, ON (Canada); Imaging Research, Sunnybrook Research Institute, Toronto, ON (Canada); Department of Medical Imaging, University of Toronto, Toronto, ON (Canada)

    2015-09-15

    Quantitative imaging is a crucial component of the assessment of therapies that target the vasculature of angiogenic or inflamed tissue. Dynamic contrast-enhanced ultrasound (DCE-US) using microbubble contrast offers the advantages of being sensitive to perfusion, non-invasive, cost effective and well suited to repeated use at the bedside. Uniquely, it employs an agent that is truly intravascular. This papers reviews the principles and methodology of DCE-US, especially as applied to anti-angiogenic cancer therapies. Reproducibility is an important attribute of such a monitoring method: results are discussed. More recent technical advances in parametric and 3D DCE-US imaging are also summarised and illustrated.

  11. Provider perspectives on patient-provider communication for adjuvant endocrine therapy symptom management.

    Science.gov (United States)

    Turner, Kea; Samuel, Cleo A; Donovan, Heidi As; Beckjord, Ellen; Cardy, Alexandra; Dew, Mary Amanda; van Londen, G J

    2017-04-01

    Providers' communication skills play a key role in encouraging breast cancer survivors to report symptoms and adhere to long-term treatments such as adjuvant endocrine therapy (AET). The purpose of this study was to examine provider perspectives on patient-provider communication regarding AET symptom management and to explore whether provider perspectives vary across the multi-disciplinary team of providers involved in survivorship care. We conducted three one-hour focus groups with a multi-disciplinary group of health care providers including oncology specialists, primary care physicians, and non-physician providers experienced in caring for breast cancer survivors undergoing AET (n = 13). Themes were organized using Epstein and Street's (2007) Framework for Patient-Centered Communication in Cancer Care. The findings of this study suggest providers' communication behaviors including managing survivors' uncertainty, responding to survivors' emotions, exchanging information, and enabling self-management influences the quality of patient-provider communication about AET symptoms. Additionally, lack of systematic symptom assessment tools for AET requires providers to use discretion in determining which symptoms to discuss with survivors resulting in approaches that vary based on providers' discipline. There may be AET-specific provider communication skills and behaviors that promote effective patient-provider communication but additional research is needed to identify practices and policies that encourage these skills and behaviors among the many providers involved in survivorship care. Efforts are also needed to coordinate AET symptom assessment across providers, clarify providers' roles in symptom assessment, and determine best practices for AET symptom communication.

  12. Accuracy of marketing claims by providers of stereotactic radiation therapy.

    Science.gov (United States)

    Narang, Amol K; Lam, Edwin; Makary, Martin A; Deweese, Theodore L; Pawlik, Timothy M; Pronovost, Peter J; Herman, Joseph M

    2013-01-01

    Direct-to-consumer advertising by industry has been criticized for encouraging overuse of unproven therapies, but advertising by health care providers has not been as carefully scrutinized. Stereotactic radiation therapy is an emerging technology that has sparked controversy regarding the marketing campaigns of some manufacturers. Given that this technology is also being heavily advertised on the Web sites of health care providers, the accuracy of providers' marketing claims should be rigorously evaluated. We reviewed the Web sites of all U.S. hospitals and private practices that provide stereotactic radiation using two leading brands of stereotactic radiosurgery technology. Centers were identified by using data from the manufacturers. Centers without Web sites were excluded. The final study population consisted of 212 centers with online advertisements for stereotactic radiation. Web sites were evaluated for advertisements that were inconsistent with advertising guidelines provided by the American Medical Association. Most centers (76%) had individual pages dedicated to the marketing of their brand of stereotactic technology that frequently contained manufacturer-authored images (50%) or text (55%). Advertising for the treatment of tumors that have not been endorsed by professional societies was present on 66% of Web sites. Centers commonly claimed improved survival (22%), disease control (20%), quality of life (17%), and toxicity (43%) with stereotactic radiation. Although 40% of Web sites championed the center's regional expertise in delivering stereotactic treatments, only 15% of Web sites provided data to support their claims. Provider advertisements for stereotactic radiation were prominent and aggressive. Further investigation of provider advertising, its effects on quality of care, and potential oversight mechanisms is needed.

  13. Accuracy of Marketing Claims by Providers of Stereotactic Radiation Therapy

    Science.gov (United States)

    Narang, Amol K.; Lam, Edwin; Makary, Martin A.; DeWeese, Theodore L.; Pawlik, Timothy M.; Pronovost, Peter J.; Herman, Joseph M.

    2013-01-01

    Purpose: Direct-to-consumer advertising by industry has been criticized for encouraging overuse of unproven therapies, but advertising by health care providers has not been as carefully scrutinized. Stereotactic radiation therapy is an emerging technology that has sparked controversy regarding the marketing campaigns of some manufacturers. Given that this technology is also being heavily advertised on the Web sites of health care providers, the accuracy of providers' marketing claims should be rigorously evaluated. Methods: We reviewed the Web sites of all US hospitals and private practices that provide stereotactic radiation using two leading brands of stereotactic radiosurgery technology. Centers were identified by using data from the manufacturers. Centers without Web sites were excluded. The final study population consisted of 212 centers with online advertisements for stereotactic radiation. Web sites were evaluated for advertisements that were inconsistent with advertising guidelines provided by the American Medical Association. Results: Most centers (76%) had individual pages dedicated to the marketing of their brand of stereotactic technology that frequently contained manufacturer-authored images (50%) or text (55%). Advertising for the treatment of tumors that have not been endorsed by professional societies was present on 66% of Web sites. Centers commonly claimed improved survival (22%), disease control (20%), quality of life (17%), and toxicity (43%) with stereotactic radiation. Although 40% of Web sites championed the center's regional expertise in delivering stereotactic treatments, only 15% of Web sites provided data to support their claims. Conclusion: Provider advertisements for stereotactic radiation were prominent and aggressive. Further investigation of provider advertising, its effects on quality of care, and potential oversight mechanisms is needed. PMID:23633973

  14. Challenges in providing services in methadone maintenance therapy clinics in China: service providers' perceptions.

    Science.gov (United States)

    Lin, Chunqing; Wu, Zunyou; Rou, Keming; Pang, Lin; Cao, Xiaobin; Shoptaw, Steven; Detels, Roger

    2010-05-01

    The Methadone Maintenance Therapy (MMT) program has been initiated in China since 2004. As of the end of November, 2008, 558 MMT clinics had been established countrywide. The objective of this study was to elucidate the difficulties and challenges as perceived by service providers working in MMT clinics. One service provider from each of the 28 MMT study clinics in Zhejiang and Jiangxi Provinces of China participated in a face-to-face in-depth interview for about 1-2h to describe their perceptions of working in MMT clinics. Qualitative data were analysed using ATLAS.ti. The grounded theory was used to guide the data analysis. Participants identified major problems in providing services in MMT clinics including lack of resources, professional training, and institutional support. Difficulties in pursuit of career, concern for personal safety, low income, heavy working load, and poor opinion of MMT by Chinese society often contributed to greater stress and burnout among the service providers. The MMT programs in China desperately need additional resource allocation and institutional support for the current and perhaps future expansion of the programs. The service providers are in urgent need of professional training to improve the quality of care they can offer MMT clients. Copyright 2009 Elsevier B.V. All rights reserved.

  15. Providers' roles in enhancing patients' adherence to pain self management.

    Science.gov (United States)

    Dorflinger, Lindsey; Kerns, Robert D; Auerbach, Stephen M

    2013-03-01

    Practice guidelines and empirical research related to pain management encourage clinicians to take active roles in providing education about self management and promoting adoption of a self-management approach. The purpose of the study was to review the relevant literature, summarize aspects of the patient-provider interaction that influence patient engagement in self management for chronic pain, and outline practice recommendations in this area. Review of the literature on aspects of the patient-provider interaction that promote engagement in pain self-management was used. Findings are synthesized into recommendations for providers. Patients benefit from a biopsychosocial and patient-centered approach. Patients are more likely to fully disclose when providers respond empathically, which can improve conceptualization and treatment. Patient education and motivation play important roles in engaging patients in self management. Self management is influenced in part by the patient-provider communication process. Suggestions for communication strategies to facilitate patient engagement in self-management techniques, including empathic discussion of barriers and motivation enhancement, are provided.

  16. Photocatalyzing CO2 to CO for Enhanced Cancer Therapy.

    Science.gov (United States)

    Zheng, Di-Wei; Li, Bin; Li, Chu-Xin; Xu, Lu; Fan, Jin-Xuan; Lei, Qi; Zhang, Xian-Zheng

    2017-11-01

    Continuous exposure to carbon monoxide (CO) can sensitize cancer cells to chemotherapy while protect normal cells from apoptosis. The Janus face of CO thus provides an ideal strategy for cancer therapy. Here, a photocatalytic nanomaterial (HisAgCCN) is introduced to transform endogenous CO2 to CO for improving cancer therapy in vivo. The CO production rate of HisAgCCN reaches to 65 µmol h-1 gmat-1 , which can significantly increase the cytotoxicity of anticancer drug (doxorubicin, DOX) by 70%. Interestingly, this study finds that HisAgCCN can enhance mitochondria biogenesis and aggravate oxidative stress in cancer cells, whereas protect normal cells from chemotherapy-induced apoptosis as well. Proteomics and metabolomics studies reveal that HisAgCCN can enhance mitochondria biogenesis and aggravate oxidative stress in cancer cells specifically. In vivo studies indicate that HisAgCCN/DOX combination therapy presents a synergetic tumor inhibition, which might provide a new direction for clinical cancer therapy. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Using Art in Narrative Therapy: Enhancing Therapeutic Possibilities.

    Science.gov (United States)

    Carlson, Thomas D.

    1997-01-01

    Shows how applying art-therapy techniques to the basic principles of narrative therapy enhances the potential for therapists and families to open the door to externalizing conversations that lead to a new life. (Author/MKA)

  18. Ethical Dilemmas of Providing Pro Bono Art Therapy

    Science.gov (United States)

    Moon, Bruce L.

    2011-01-01

    This viewpoint addresses ethical questions regarding the provision of art therapy as a pro bono service, a term from Latin roots that mean "for the public good." Approaches to ethical reasoning are discussed using the case of pro bono art therapy in a residential treatment program for adolescents.

  19. Collaborative business processes for enhancing partnerships among software services providers

    Science.gov (United States)

    Heil Cancian, Maiara; Rabelo, Ricardo; Gresse von Wangenheim, Christiane

    2015-08-01

    Software services have represented a powerful view to support the realisation of the service-oriented architecture (SOA) paradigm. Using open standards and facilitating systems projects, they have increasingly been used as a corporate architectural approach to create interoperable services-based software solutions that can more easily be reused and shared across disparate applications. In the context of software companies, most of them are small firms having enormous difficulties to keep competitive. One strategy to enhance their sustainability is to enlarge partnerships among them at a more valuable level by jointly offering (web) services-based solutions. However, their culture of collaboration is low, and partnerships are usually done with the same companies and sporadically. This article presents an approach to support a more intense collaboration among software companies to attend business opportunities in a more agile way, joining capacities and capabilities which they would not have if they worked alone. This requires, however, some preparedness. From the perspective of business processes, they should understand how to carry out a collaboration more properly. This is essentially what this article is about. It presents a comprehensive list of collaborative business processes and base practices that can also act as a guide for service providers' managers to implement and manage the collaboration along its lifecycle. Processes have been validated and results are discussed.

  20. Immune Depletion to Enhance Immunotoxin Therapy

    Science.gov (United States)

    Patients with advanced mesothelioma who have not benefited from previous chemotherapy will receive pentostatin and cyclophosphamide to prevent an anti-immunotoxin immune response prior to and in conjunction with SS1P immunotoxin therapy.

  1. Enhancing Immune Checkpoint Inhibitor Therapy In Kidney Cancer

    Science.gov (United States)

    2016-10-01

    AWARD NUMBER: W81XWH-15-1-0141 TITLE: Enhancing Immune Checkpoint Inhibitor therapy in Kidney Cancer PRINCIPAL INVESTIGATOR: Hans-Joerg Hammers...Immune Checkpoint Inhibitor therapy in Kidney Cancer 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH- 15-1-0141 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S...to develop strategies to enhance immune checkpoint inhibition in kidney cancer . The work is designed to test different strategies to induce or

  2. Image processing and enhancement provided by commercial dental software programs

    National Research Council Canada - National Science Library

    Lehmann, T M; Troeltsch, E; Spitzer, K

    2002-01-01

    To identify and analyse methods/algorithms for image processing provided by various commercial software programs used in direct digital dental imaging and to map them onto a standardized nomenclature...

  3. Therapy Caps and Variation in Cost of Outpatient Occupational Therapy by Provider, Insurance Status, and Geographic Region.

    Science.gov (United States)

    Pergolotti, Mackenzi; Lavery, Jessica; Reeve, Bryce B; Dusetzina, Stacie B

    This article describes the cost of occupational therapy by provider, insurance status, and geographic region and the number of visits allowed and out-of-pocket costs under proposed therapy caps. This retrospective, population-based study used Medicare Provider Utilization and Payment Data for occupational therapists billing in 2012 and 2013 (Ns = 3,662 and 3,820, respectively). We examined variations in outpatient occupational therapy services with descriptive statistics and the impact of therapy caps on occupational therapy visits and patient out-of-pocket costs. Differences in cost between occupational and physical therapists were minimal. The most frequently billed service was therapeutic exercises. Wisconsin had the most inflated outpatient costs in both years. Under the proposed therapy cap, patients could receive an evaluation plus 12-14 visits. . Wide variation exists in potential patient out-of-pocket costs for occupational therapy services on the basis of insurance coverage and state. Patients without insurance pay a premium.

  4. Enhancing Healthcare Provider Feedback and Personal Health Literacy

    DEFF Research Database (Denmark)

    Kaltoft, Mette Kjer; Nielsen, Jesper Bo; Salkeld, Glenn

    2015-01-01

    In this protocol for a pilot study we seek to establish the feasibility of using a web-based survey to simultaneously supply healthcare organisations and agencies with feedback on a key aspect of the care experience they provide and increase the generic health decision literacy of the individuals...

  5. Enhanced methanol production in plants provides broad spectrum insect resistance.

    Science.gov (United States)

    Dixit, Sameer; Upadhyay, Santosh Kumar; Singh, Harpal; Sidhu, Om Prakash; Verma, Praveen Chandra; K, Chandrashekar

    2013-01-01

    Plants naturally emit methanol as volatile organic compound. Methanol is toxic to insect pests; but the quantity produced by most of the plants is not enough to protect them against invading insect pests. In the present study, we demonstrated that the over-expression of pectin methylesterase, derived from Arabidopsis thaliana and Aspergillus niger, in transgenic tobacco plants enhances methanol production and resistance to polyphagous insect pests. Methanol content in the leaves of transgenic plants was measured using proton nuclear spectroscopy (1H NMR) and spectra showed up to 16 fold higher methanol as compared to control wild type (WT) plants. A maximum of 100 and 85% mortality in chewing insects Helicoverpa armigera and Spodoptera litura larvae was observed, respectively when fed on transgenic plants leaves. The surviving larvae showed less feeding, severe growth retardation and could not develop into pupae. In-planta bioassay on transgenic lines showed up to 99 and 75% reduction in the population multiplication of plant sap sucking pests Myzus persicae (aphid) and Bemisia tabaci (whitefly), respectively. Most of the phenotypic characters of transgenic plants were similar to WT plants. Confocal microscopy showed no deformities in cellular integrity, structure and density of stomata and trichomes of transgenic plants compared to WT. Pollen germination and tube formation was also not affected in transgenic plants. Cell wall enzyme transcript levels were comparable with WT. This study demonstrated for the first time that methanol emission can be utilized for imparting broad range insect resistance in plants.

  6. Enhanced Methanol Production in Plants Provides Broad Spectrum Insect Resistance

    Science.gov (United States)

    Dixit, Sameer; Upadhyay, Santosh Kumar; Singh, Harpal; Sidhu, Om Prakash; Verma, Praveen Chandra; K, Chandrashekar

    2013-01-01

    Plants naturally emit methanol as volatile organic compound. Methanol is toxic to insect pests; but the quantity produced by most of the plants is not enough to protect them against invading insect pests. In the present study, we demonstrated that the over-expression of pectin methylesterase, derived from Arabidopsis thaliana and Aspergillus niger, in transgenic tobacco plants enhances methanol production and resistance to polyphagous insect pests. Methanol content in the leaves of transgenic plants was measured using proton nuclear spectroscopy (1H NMR) and spectra showed up to 16 fold higher methanol as compared to control wild type (WT) plants. A maximum of 100 and 85% mortality in chewing insects Helicoverpa armigera and Spodoptera litura larvae was observed, respectively when fed on transgenic plants leaves. The surviving larvae showed less feeding, severe growth retardation and could not develop into pupae. In-planta bioassay on transgenic lines showed up to 99 and 75% reduction in the population multiplication of plant sap sucking pests Myzus persicae (aphid) and Bemisia tabaci (whitefly), respectively. Most of the phenotypic characters of transgenic plants were similar to WT plants. Confocal microscopy showed no deformities in cellular integrity, structure and density of stomata and trichomes of transgenic plants compared to WT. Pollen germination and tube formation was also not affected in transgenic plants. Cell wall enzyme transcript levels were comparable with WT. This study demonstrated for the first time that methanol emission can be utilized for imparting broad range insect resistance in plants. PMID:24223989

  7. Enhanced methanol production in plants provides broad spectrum insect resistance.

    Directory of Open Access Journals (Sweden)

    Sameer Dixit

    Full Text Available Plants naturally emit methanol as volatile organic compound. Methanol is toxic to insect pests; but the quantity produced by most of the plants is not enough to protect them against invading insect pests. In the present study, we demonstrated that the over-expression of pectin methylesterase, derived from Arabidopsis thaliana and Aspergillus niger, in transgenic tobacco plants enhances methanol production and resistance to polyphagous insect pests. Methanol content in the leaves of transgenic plants was measured using proton nuclear spectroscopy (1H NMR and spectra showed up to 16 fold higher methanol as compared to control wild type (WT plants. A maximum of 100 and 85% mortality in chewing insects Helicoverpa armigera and Spodoptera litura larvae was observed, respectively when fed on transgenic plants leaves. The surviving larvae showed less feeding, severe growth retardation and could not develop into pupae. In-planta bioassay on transgenic lines showed up to 99 and 75% reduction in the population multiplication of plant sap sucking pests Myzus persicae (aphid and Bemisia tabaci (whitefly, respectively. Most of the phenotypic characters of transgenic plants were similar to WT plants. Confocal microscopy showed no deformities in cellular integrity, structure and density of stomata and trichomes of transgenic plants compared to WT. Pollen germination and tube formation was also not affected in transgenic plants. Cell wall enzyme transcript levels were comparable with WT. This study demonstrated for the first time that methanol emission can be utilized for imparting broad range insect resistance in plants.

  8. Enhancing photodynamic therapy of refractory solid cancers

    NARCIS (Netherlands)

    Weijer, R.

    2017-01-01

    Photodynamic therapy (PDT) is based on the activation of a photosensitizer by (laser) light to locally produce highly destructive reactive oxygen species. When employed for cancer treatment, PDT is able to induce tumor cell death, microvascular damage, and an anti-tumor immune response. All these

  9. Behaviors of providers of traditional korean medicine therapy and complementary and alternative medicine therapy for the treatment of cancer patients.

    Science.gov (United States)

    Yu, Jun-Sang; Kim, Chun-Bae; Kim, Ki-Kyong; Lee, Ji-Eun; Kim, Min-Young

    2015-03-01

    In Korea, cancer is one of the most important causes of death. Cancer patients have sought alternative methods, like complementary and alternative medicine (CAM) together with Western medicine, to treat cancer. Also, there are many kinds of providers of CAM therapy, including providers of Korean oriental medicine therapy. The purpose of this study is to identify the behaviors of Korean oriental medicine therapy and CAM therapy providers who treat cancer patients and to provide background knowledge for establishing a new policy with the management and quality control of CAM. Structured and well organized questionnaires were made, and 350 persons were surveyed concerning the providers of CAM or Korean oriental medicine. The questionnaires were collected and analyzed. The questionnaires (182) were collected. The questionnaires identified a total of 73 known providers, such as medicinal professionals or other providers of CAM suppliers, 35.6% of whom had had experience with treating cancer patients (52.6% vs. 29.6%). The treatment methods were a little different: alternative therapy and nutritional therapy being preferred by medicinal professionals and mind body modulation therapy and alternative therapy being preferred by other CAM providers. Four patients (7.4%) experienced side effects, and 6 patients (12.5%) experienced legal problems. As the method for managing the therapy, CAM providers, medicinal professionals, and other CAM providers had different viewpoints. For example, some CAM providers stated that both legislation and an official education on CAM or a national examination were needed as a first step to establish the provider's qualifications and that as a second step, a license test was needed for quality control. To the contrary, medicinal professionals stated that a license test was needed before legislation. Adequate management and quality control of CAM providers is thought to involve both education and legislation.

  10. Behaviors of Providers of Traditional Korean Medicine Therapy and Complementary and Alternative Medicine Therapy for the Treatment of Cancer Patients

    Directory of Open Access Journals (Sweden)

    Jun-Sang Yu

    2015-03-01

    Full Text Available Objectives: In Korea, cancer is one of the most important causes of death. Cancer patients have sought alternative methods, like complementary and alternative medicine (CAM together with Western medicine, to treat cancer. Also, there are many kinds of providers of CAM therapy, including providers of Korean oriental medicine therapy. The purpose of this study is to identify the behaviors of Korean oriental medicine therapy and CAM therapy providers who treat cancer patients and to provide background knowledge for establishing a new policy with the management and quality control of CAM. Methods: Structured and well organized questionnaires were made, and 350 persons were surveyed concerning the providers of CAM or Korean oriental medicine. The questionnaires were collected and analyzed. Results: The questionnaires (182 were collected. The questionnaires identified a total of 73 known providers, such as medicinal professionals or other providers of CAM suppliers, 35.6% of whom had had experience with treating cancer patients (52.6% vs. 29.6%. The treatment methods were a little different: alternative therapy and nutritional therapy being preferred by medicinal professionals and mind body modulation therapy and alternative therapy being preferred by other CAM providers. Four patients (7.4% experienced side effects, and 6 patients (12.5% experienced legal problems. As the method for managing the therapy, CAM providers, medicinal professionals, and other CAM providers had different viewpoints. For example, some CAM providers stated that both legislation and an official education on CAM or a national examination were needed as a first step to establish the provider’s qualifications and that as a second step, a license test was needed for quality control. To the contrary, medicinal professionals stated that a license test was needed before legislation. Conclusion: Adequate management and quality control of CAM providers is thought to involve both

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  12. Caregiver-Provided Physical Therapy Home Programs for Children with Motor Delay: A Scoping Review.

    Science.gov (United States)

    Gorgon, Edward James R

    2018-01-17

    Caregiver-provided physical therapy home programs (PTHP) play an important role in enhancing motor outcomes in pediatric patient populations. This scoping review systematically mapped clinical trials of caregiver-provided PTHP that were aimed at enhancing motor outcomes in children who have or who are at risk for motor delay, with the purpose of (1) describing trial characteristics; (2) assessing methodologic quality, and (3) examining the reporting of caregiver-related components. Physiotherapy Evidence Database (PEDro), Cochrane CENTRAL, PubMed, Scopus, ScienceDirect, ProQuest Central, CINAHL, LILACS, and OTseeker were searched up to July 31, 2017. Two reviewers independently assessed study eligibility. Randomized or quasi-randomized controlled trials on PTHP administered by parents, other family members, friends, or informal caregivers to children who had or who were at risk for motor delay were included. Two reviewers independently appraised trial quality on the PEDro scale and extracted data. Twenty-four articles representing 17 individual trials were identified. Populations and interventions investigated were heterogeneous. Most of the trials had important research design limitations and methodological issues that could limit usefulness in ascertaining the effectiveness of caregiver-provided PTHP. Few (4 of 17) trials indicated involvement of caregivers in the PTHP planning, assessed how the caregivers learned from the training or instructions provided, or carried out both. Included studies were heterogeneous, and unpublished data were excluded. Although caregiver-provided PTHP are important in addressing motor outcomes in this population, there is a lack of evidence at the level of clinical trials to guide practice. More research is urgently needed to determine the effectiveness of caregiver-provided PTHP. Future studies should address the many important issues identified in this scoping review to improve the usefulness of the trial results.

  13. The Loss and Recovery of Erotic Intimacy in Primary Relationships: Narrative Therapy and Relationship Enhancement Therapy.

    Science.gov (United States)

    Snyder, Maryhelen

    2000-01-01

    Therapists working with intimate relationships are frequently confronted with issues regarding the loss of erotic intimacy, differences in levels of sexual desire, and the existence of intimate relationships outside the primary. Proposes that an approach derived from an integration of narrative therapy and relationship enhancement therapy can be…

  14. Physicians' Preferences for Communication of Pharmacist-Provided Medication Therapy Management in Community Pharmacy.

    Science.gov (United States)

    Guthrie, Kendall D; Stoner, Steven C; Hartwig, D Matthew; May, Justin R; Nicolaus, Sara E; Schramm, Andrew M; DiDonato, Kristen L

    2017-02-01

    (1) To identify physicians' preferences in regard to pharmacist-provided medication therapy management (MTM) communication in the community pharmacy setting; (2) to identify physicians' perceived barriers to communicating with a pharmacist regarding MTM; and (3) to determine whether Missouri physicians feel MTM is beneficial for their patients. A cross-sectional prospective survey study of 2021 family and general practice physicians registered with MO HealthNet, Missouri's Medicaid program. The majority (52.8%) of physicians preferred MTM data to be communicated via fax. Most physicians who provided care to patients in long-term care (LTC) facilities (81.0%) preferred to be contacted at their practice location as opposed to the LTC facility. The greatest barriers to communication were lack of time and inefficient communication practices. Improved/enhanced communication was the most common suggestion for improvement in the MTM process. Approximately 67% of respondents reported MTM as beneficial or somewhat beneficial for their patients. Survey respondents saw value in the MTM services offered by pharmacists. However, pharmacists should use the identified preferences and barriers to improve their currently utilized communication practices in hopes of increasing acceptance of recommendations. Ultimately, this may assist MTM providers in working collaboratively with patients' physicians.

  15. Generating demand for pharmacist-provided medication therapy management: identifying patient-preferred marketing strategies.

    Science.gov (United States)

    Garcia, Gladys M; Snyder, Margie E; McGrath, Stephanie Harriman; Smith, Randall B; McGivney, Melissa Somma

    2009-01-01

    To identify effective strategies for marketing pharmacist-provided medication therapy management (MTM) services to patients in a self-insured employer setting. Qualitative study. University of Pittsburgh during March through May 2008. 26 university employees taking at least one chronic medication. Three focus group sessions were conducted using a semistructured topic guide to facilitate the discussion. Employees' perceived medication-related needs, perceived benefits of pharmacist-provided MTM, potential barriers for employee participation in MTM, and effective strategies for marketing MTM. Participants reported concerns with timing of doses, medication costs, access, and ensuring adherence. Participants generally felt positively toward pharmacists; however, the level of reported patient contact with pharmacists varied among participants. Some participants questioned pharmacists' education and qualifications for this enhanced role in patient care. Perceived benefits of MTM noted by participants included the opportunity to obtain personalized information about their medications and the potential for improved communication among their health providers. Barriers to patient participation were out-of-pocket costs and lack of time for MTM visits. Participants suggested use of alternative words to describe MTM and marketing approaches that involve personal contact. Pharmacists should emphasize parts of MTM that patients feel are most beneficial (i.e., provision of a personal medication record) and use patient-friendly language to describe MTM when marketing their practice. Patients will need greater exposure to the concept of MTM and the pharmacists' role in order to correctly describe and assign value to this type of pharmacist patient care practice.

  16. How nanotechnology can enhance docetaxel therapy

    OpenAIRE

    Zhang, Li; Zhang, Na

    2013-01-01

    Li Zhang, Na ZhangSchool of Pharmaceutical Science, Shandong University, Shandong Province, People's Republic of ChinaAbstract: Docetaxel has been recognized as one of the most efficient anticancer drugs over the past decade; however, its poor water solubility and systemic toxicity have greatly limited its clinical application. In recent decades, the emergence of nanotechnology has provided new drug delivery systems for docetaxel, which can improve its water solubility, minimize the s...

  17. Training in Integrative Therapies Increases Self-Efficacy in Providing Nondrug Therapies and Self-Confidence in Offering Compassionate Care.

    Science.gov (United States)

    Kemper, Kathi J; Hill, Ellie

    2017-10-01

    Patient demand and clinician interest have driven professional training in integrative therapies, but few rigorous evaluations have been published. This project evaluated the proof of concept of training in acupressure, guided imagery, massage, and Reiki on clinicians' sense of self-efficacy in providing nondrug therapies, self-confidence in providing compassionate care, and engagement with work. Three out of 4 topics met minimum enrollment numbers; 22 of 24 participants completed follow-up as well as pretraining surveys. All would recommend the training to others and planned changes in personal and professional care. There were significant improvements in self-efficacy in using nondrug therapies, confidence in providing compassionate care, and unplanned absenteeism ( P self-efficacy, confidence in providing compassionate care, and engagement with work. Additional studies are needed to determine the impact on quality of care and long-term workforce engagement.

  18. Parent-Child Interaction Therapy: Enhancing Parent-Child Relationships

    Directory of Open Access Journals (Sweden)

    Anthony J. Urquiza

    2012-07-01

    Full Text Available Disruptive child behavior problems are common problems for parents and can be associated with serious delinquent behaviors and aggressive/violent behaviors in adolescence and adulthood. Parenting interventions to address disruptive child behavior problems has gained widespread acceptance. One of these parenting interventions is Parent-Child Interaction Therapy (PCIT. PCIT is a 14- to 20-week, founded on social learning and attachment theories, designed for children between 2 and 7 years of age with disruptive, or externalizing, behavior problems. This article will provide a brief review of the history of PCIT, a description of the basic components of PCIT, and an overview of recent developments that highlight the promise of PCIT with maltreating parent-child relationships, traumatized children, and in developing resilience in young children. In addressing the three basic treatment objectives for PCIT (i.e., reduction in child behavior problems, improving parenting skills, enhancing the quality of parent-child relationships, there is an abundance of research demonstrating very strong treatment effects and therefore, its value to the field. Recent research has also demonstrated the value of PCIT in reducing trauma symptoms in young children.

  19. Biliary complications following orthotopic liver transplantation: May contrast-enhanced MR Cholangiography provide additional information?

    Directory of Open Access Journals (Sweden)

    Piero Boraschi

    2016-01-01

    Conclusions: Contrast-enhanced T1-weighted MR Cholangiography may improve the level of diagnostic confidence provided by conventional T2-weighted MR Cholangiography in the evaluation of biliary complications after orthotopic liver transplantation.

  20. Agency over Phantom Limb Enhanced by Short-Term Mirror Therapy.

    Science.gov (United States)

    Imaizumi, Shu; Asai, Tomohisa; Koyama, Shinichi

    2017-01-01

    Most amputees experience phantom limb, whereby they feel that the amputated limb is still present. In some cases, these experiences include pain that can be alleviated by "mirror therapy." Mirror therapy consists of superimposing a mirrored image of the moving intact limb onto the phantom limb. This therapy provides a closed loop between the motor command to the amputated limb and its predicted visual feedback. This loop is also involved in the sense of agency, a feeling of controlling one's own body. However, it is unclear how mirror therapy is related to the sense of agency over a phantom limb. Using mirror therapy, we investigated phantom limb pain and the senses of agency and ownership (i.e., a feeling of having one's own body) of the phantom limb. Nine upper-limb amputees, five of whom reported recent phantom limb pain, underwent a single 15-min trial of mirror therapy. Before and after the trial, the participants completed a questionnaire regarding agency, ownership, and pain related to their phantom limb. They reported that the sense of agency over the phantom limb increased following the mirror therapy trial, while the ownership slightly increased but not as much as did the agency. The reported pain did not change; that is, it was comparably mild before and after the trial. These results suggest that short-term mirror therapy can, at least transiently, selectively enhance the sense of agency over a phantom limb, but may not alleviate phantom limb pain.

  1. Occupational Therapy in Primary Care: Determining Receptiveness of Occupational Therapists and Primary Care Providers

    Directory of Open Access Journals (Sweden)

    Sue Dahl-Popolizio

    2017-07-01

    Full Text Available Background: Primary care (PC is an emerging practice setting for occupational therapy; however, few occupational therapists currently practice in this setting due to barriers, including uncertainty about reimbursement and the role of occupational therapists. This pilot study aimed to determine if PC providers and occupational therapists are receptive to occupational therapists as integrated interprofessional PC team members if barriers to inclusion are addressed. Method: After a brief educational paragraph explaining potential occupational therapy contributions to PC teams, the participants accessed a link to survey questions regarding their personal level of receptiveness to occupational therapy in PC. The questions comprised Likert scale and open-ended answers. Results: Of the Likert scale responses, 94%-99% provided by occupational therapists and 82%-97% provided by PC providers indicated possibly or yes to the inclusion of occupational therapists on the PC team. The descriptive responses were primarily supportive. Discussion: The majority of the occupational therapists and PC providers surveyed indicated support for including occupational therapists in primary care. This indicates that when barriers are addressed, occupational therapists and PC providers are receptive to the inclusion of occupational therapists as members of the interprofessional PC team.

  2. Electroporation enhances antimicrobial photodynamic therapy mediated by the hydrophobic photosensitizer, hypericin, Electroporation enhances antimicrobial photodynamic inactivation

    OpenAIRE

    de Melo, Wanessa de Cássia Martins Antunes; Lee, Alexander N; Perussi, Janice Rodrigues; Hamblin, Michael R.

    2013-01-01

    The effective transport of photosensitizers (PS) across the membrane and the intracellular accumulation of PS are the most crucial elements in antimicrobial photodynamic therapy (aPDT). However, due to the morphological complexity of Gram-negative bacteria the penetration of PS is limited, especially hydrophobic PS. Electroporation (EP) could increase the effectiveness of aPDT, by promoting the formation of transient pores that enhance the permeability of the bacterial membrane to PS. In this...

  3. Enhanced Radiation Therapy of Gold Nanoparticles in Liver Cancer

    Directory of Open Access Journals (Sweden)

    Meili Guo

    2017-03-01

    Full Text Available Gold nanoparticles (GNPs were widely used in X-ray imaging and radiation therapy due to strong photoelectric effects and secondary electrons under high energy irradiation. As liver cancer is one of the most common forms of cancer, the use of GNPs could enhance liver cancer radiotherapy. We synthesized polyethylene glycol (PEG-coated GNPs of two different sizes by chemical reduction reaction. Blood stability, cellular uptake, cytotoxicity and radiation therapy were investigated. A 3–5 nm red shift of SPR caused by interactions between PEG-coated GNPs and plasma indicated their good stability. Cellular uptake assay showed that PEG-coated GNPs would enhance an appreciable uptake. GNPs preferred to combine with blood proteins, and thus induced the formation of 30–50 nm Au-protein corona. GNPs were endocytosed by cytoplasmic vesicles, localized in intracellular region, and presented concentration dependent cell viability. Clonogenic assay illustrated that the PEG-coated GNPs could sensitize two liver cancer cell lines to irradiation.

  4. Inhibiting tryptophan metabolism enhances interferon therapy in kidney cancer.

    Science.gov (United States)

    Trott, Josephine F; Kim, Jeffrey; Abu Aboud, Omran; Wettersten, Hiromi; Stewart, Benjamin; Berryhill, Grace; Uzal, Francisco; Hovey, Russell C; Chen, Ching-Hsien; Anderson, Katie; Graef, Ashley; Sarver, Aaron L; Modiano, Jaime F; Weiss, Robert H

    2016-10-11

    Renal cell carcinoma (RCC) is increasing in incidence, and a complete cure remains elusive. While immune-checkpoint antibodies are promising, interferon-based immunotherapy has been disappointing. Tryptophan metabolism, which produces immunosuppressive metabolites, is enhanced in RCC. Here we show indolamine-2,3-dioxygenase-1 (IDO1) expression, a kynurenine pathway enzyme, is increased not only in tumor cells but also in the microenvironment of human RCC compared to normal kidney tissues. Neither kynurenine metabolites nor IDO inhibitors affected the survival or proliferation of human RCC or murine renal cell adenocarcinoma (RENCA) cells in vitro. However, interferon-gamma (IFNγ) induced high levels of IDO1 in both RCC and RENCA cells, concomitant with enhanced kynurenine levels in conditioned media. Induction of IDO1 by IFNα was weaker than by IFNγ. Neither the IDO1 inhibitor methyl-thiohydantoin-DL-tryptophan (MTH-trp) nor IFNα alone inhibited RENCA tumor growth, however the combination of MTH-trp and IFNα reduced tumor growth compared to IFNα. Thus, the failure of IFNα therapy for human RCC is likely due to its inability to overcome the immunosuppressive environment created by increased IDO1. Based on our data, and given that IDO inhibitors are already in clinical trials for other malignancies, IFNα therapy with an IDO inhibitor should be revisited for RCC.

  5. Macrophage mediated PCI enhanced gene-directed enzyme prodrug therapy

    Science.gov (United States)

    Christie, Catherine E.; Zamora, Genesis; Kwon, Young J.; Berg, Kristian; Madsen, Steen J.; Hirschberg, Henry

    2015-03-01

    Photochemical internalization (PCI) is a photodynamic therapy-based approach for improving the delivery of macromolecules and genes into the cell cytosol. Prodrug activating gene therapy (suicide gene therapy) employing the transduction of the E. coli cytosine deaminase (CD) gene into tumor cells, is a promising method. Expression of this gene within the target cell produces an enzyme that converts the nontoxic prodrug, 5-FC, to the toxic metabolite, 5-fluorouracil (5-FU). 5-FC may be particularly suitable for brain tumors, because it can readily cross the bloodbrain barrier (BBB). In addition the bystander effect, where activated drug is exported from the transfected cancer cells into the tumor microenvironment, plays an important role by inhibiting growth of adjacent tumor cells. Tumor-associated macrophages (TAMs) are frequently found in and around glioblastomas. Monocytes or macrophages (Ma) loaded with drugs, nanoparticles or photosensitizers could therefore be used to target tumors by local synthesis of chemo attractive factors. The basic concept is to combine PCI, to enhance the ex vivo transfection of a suicide gene into Ma, employing specially designed core/shell NP as gene carrier.

  6. The use of genes for performance enhancement: doping or therapy?

    Directory of Open Access Journals (Sweden)

    R.S. Oliveira

    2011-12-01

    Full Text Available Recent biotechnological advances have permitted the manipulation of genetic sequences to treat several diseases in a process called gene therapy. However, the advance of gene therapy has opened the door to the possibility of using genetic manipulation (GM to enhance athletic performance. In such ‘gene doping’, exogenous genetic sequences are inserted into a specific tissue, altering cellular gene activity or leading to the expression of a protein product. The exogenous genes most likely to be utilized for gene doping include erythropoietin (EPO, vascular endothelial growth factor (VEGF, insulin-like growth factor type 1 (IGF-1, myostatin antagonists, and endorphin. However, many other genes could also be used, such as those involved in glucose metabolic pathways. Because gene doping would be very difficult to detect, it is inherently very attractive for those involved in sports who are prepared to cheat. Moreover, the field of gene therapy is constantly and rapidly progressing, and this is likely to generate many new possibilities for gene doping. Thus, as part of the general fight against all forms of doping, it will be necessary to develop and continually improve means of detecting exogenous gene sequences (or their products in athletes. Nevertheless, some bioethicists have argued for a liberal approach to gene doping.

  7. Spinal Manipulative Therapy and Sports Performance Enhancement: A Systematic Review.

    Science.gov (United States)

    Botelho, Marcelo B; Alvarenga, Bruno A P; Molina, Nícolly; Ribas, Marcos; Baptista, Abrahão F

    2017-09-01

    The purpose of this study was to review the literature regarding the relationship between spinal manipulative therapy (SMT) and sports performance. PubMed and Embase databases were searched for original studies published up to July 2016. Inclusion criteria were if SMT has been applied to athletes and if any sports performance-related outcome was measured. Of the 581 potential studies, 7 clinical trials were selected. Most studies had adequate quality (≥6/11) when assessed by the PEDro scale. None of those studies assessed performance at an event or competition. Four studies revealed improvement in a sports performance test after SMT. Meta-analysis could not be performed because of the wide differences in methodologies, design, and outcomes measured. Spinal manipulative therapy influences a wide range of neurophysiological parameters that could be associated with sports performance. Of the 3 studies where SMT did not improve test performance, 2 used SMT not for therapeutic correction of a dysfunctional vertebral joint but to an arbitrary previously set joint. Although 4 of 7 studies showed that SMT improved sports performance tests, the evidence is still weak to support its use. Spinal manipulative therapy may be a promising approach for performance enhancement that should be investigated with more consistent methodologic designs. Copyright © 2017. Published by Elsevier Inc.

  8. Gold Nanoparticles and Their Alternatives for Radiation Therapy Enhancement

    Directory of Open Access Journals (Sweden)

    Daniel R. Cooper

    2014-10-01

    Full Text Available Radiation therapy is one of the most commonly used treatments for cancer. The dose of delivered ionizing radiation can be amplified by the presence of high-Z materials via an enhancement of the photoelectric effect; the most widely studied material is gold (atomic number 79. However, a large amount is needed to obtain a significant dose enhancement, presenting a challenge for delivery. In order to make this technique of broader applicability, the gold must be targeted, or alternative formulations developed that do not rely solely on the photoelectric effect. One possible approach is to excite scintillating nanoparticles with ionizing radiation, and then exploit energy transfer between these particles and attached dyes in a manner analogous to photodynamic therapy. Doped rare-earth halides and semiconductor quantum dots have been investigated for this purpose. However, although the spectrum of emitted light after radiation excitation is usually similar to that seen with light excitation, the yield is not. Measurement of scintillation yields is challenging, and in many cases has been done only for bulk materials, with little understanding of how the principles translate to the nanoscale. Another alternative is to use local heating using gold or iron, followed by application of ionizing radiation. Hyperthermia pre-sensitizes the tumors, leading to an improved response. Another approach is to use chemotherapeutic drugs that can radiosensitize tumors. Drugs may be attached to high-Z nanoparticles or encapsulated. This article discusses each of these techniques, giving an overview of the current state of nanoparticle-assisted radiation therapy and future directions.

  9. Neuroprotective dimethyl fumarate synergizes with immunomodulatory interferon beta to provide enhanced axon protection in autoimmune neuroinflammation.

    Science.gov (United States)

    Reick, Christiane; Ellrichmann, Gisa; Thöne, Jan; Scannevin, Robert H; Saft, Carsten; Linker, Ralf A; Gold, Ralf

    2014-07-01

    Despite recent advances in development of treatments for multiple sclerosis, there is still an unmet need for more effective and also safe therapies. Based on the modes of action of interferon-beta (IFN-β) and dimethyl fumarate (DMF), we hypothesized that anti-inflammatory and neuroprotective effects may synergize in experimental autoimmune encephalomyelitis (EAE). EAE was induced in C57BL/6 mice by immunization with MOG35-55-peptide. Murine IFN-β was injected s.c. every other day at 10.000IU, and DMF was provided at 15mg/kg by oral gavage twice daily. Control mice received PBS injections and were treated by oral gavage with the vehicle methylcellulose. Mice were scored daily by blinded observers and histological, FACS and cytokine studies were performed to further elucidate the underlying mechanism of action. Combination therapy significantly ameliorated EAE disease course in comparison to controls and monotherapy with IFN-β. Histological analyses showed a significant effect on axon preservation with almost twice as much axons present in inflamed lesions as compared to control. Remarkably, the effect on axonal preservation was more pronounced under combination therapy than with both monotherapies. Neither monotherapy nor combination therapy demonstrated modulation of cytokines and frequency of antigen presenting cells. Combination of IFN-β and DMF resulted in greater beneficial effects with improved tissue protection as compared to the respective monotherapies. Further combination studies of these safe therapies in human disease are warranted. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. MTFeedback: Providing Notifications to Enhance Teacher Awareness of Small Group Work in the Classroom

    Science.gov (United States)

    Martinez-Maldonado, Roberto; Clayphan, Andrew; Yacef, Kalina; Kay, Judy

    2015-01-01

    The teacher has very important roles in the classroom, particularly as manager of most resources for learning activities and in providing timely feedback that can enhance learning. But teachers need to be aware of students' achievements and weaknesses to decide how to time feedback. We present MTFeedback, a system that harnesses the new…

  11. Training School Mental Health Providers to Deliver Cognitive-Behavioral Therapy.

    Science.gov (United States)

    Beidas, Rinad S; Mychailyszyn, Matthew P; Edmunds, Julie M; Khanna, Muniya S; Downey, Margaret Mary; Kendall, Philip C

    2012-12-01

    Anxiety disorders are among the most prevalent mental health difficulties experienced by youth. A well-established literature has identified cognitive-behavior therapy (CBT) as the gold-standard psychosocial treatment for youth anxiety disorders. Access to CBT in community clinics is limited, but a potential venue for the provision of CBT for child anxiety disorders is the school setting. The present study examined a subset of data from a larger study in which therapists from a variety of settings, including schools, were trained in CBT for child anxiety (N = 17). The study investigated the relationship between provider- and organizational-level variables associated with training and implementation among school mental health providers. The present findings indicate a positive relationship between provider attitudes and adherence to CBT. Self-reported barriers to implementation were also identified. Integrating CBT into school mental health providers' repertoires through training and consultation is a critical step for dissemination and implementation of empirically supported psychosocial treatments.

  12. Providing therapy to children and families in foster care: a systemic-relational approach.

    Science.gov (United States)

    Lewis, Catherine

    2011-12-01

    Foster care is a system created to protect children from an unsafe home environment yet multiple foster home placements, conflictual or nonexistent relationships between foster parents and birth parents, long, drawn out court battles, and living in an on-going state of not knowing when or if they will be going home are just some of the challenges many children in care are expected to manage. This paper presents a guide for therapists working with families involved in foster care. Utilizing ideas from the postmodern therapies and structural family therapy, suggestions will be provided about who needs to talk to whom about what, when to have these necessary conversations, and how to talk to people in a way that mobilizes adults to take action for the children, with the goal of minimizing postplacement trauma, strengthening and repairing relational bonds, and moving children out of foster care and into permanent homes as quickly as possible.

  13. Music provided through a portable media player (iPod) blunts pain during physical therapy.

    Science.gov (United States)

    Bellieni, Carlo Valerio; Cioncoloni, David; Mazzanti, Sandra; Bianchi, Maria Elena; Morrone, Ilenia; Becattelli, Rossana; Perrone, Serafina; Buonocore, Giuseppe

    2013-12-01

    This research studied, 25 adult patients who underwent physical therapy to assess the analgesic effect of distraction with the use of music during physical therapy. Patients randomly underwent physical therapy once with music provided by an iPod and once without music. In both sessions patients underwent identical physical procedures. At end of both sessions patients filled in 5-item questionnaire where they scored pain and other parameters, such as stress, enjoyment, interaction, and satisfaction, on 10-cm visual analog scale. The mean scores (range, 0-10) of the two sessions were statistically compared. Mean pain scores were significantly lower (p = .031) during the session in which patients received music (4.8 ± 2.5) than during the session without music (5.8 ± 2.3). The other items of the questionnaire did not disclose any statistically significant difference when the sessions with versus without music were compared. Enjoyment (8.5 ± 1.6), interaction (8.3 ± 1.9), and satisfaction (8.6 ± 1.7) scores with music did not significantly differ in the sessions without music (8.5 ± 2.1, 8.5 ± 1.9, and, 8.5 ± 1.5, respectively); mean stress score was, 3.9 in both sessions. The conclusion of the study is that music provided through a portable media player has an analgesic effect. This can be an effective analgesic strategy during painful physical therapy. Copyright © 2013 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.

  14. Acoustic Droplet Vaporization for the Enhancement of Ultrasound Thermal Therapy

    Science.gov (United States)

    Zhang, Man; Fabiilli, Mario; Carson, Paul; Padilla, Frederic; Swanson, Scott; Kripfgans, Oliver; Fowlkes, Brian

    2011-01-01

    Acoustic droplet vaporization (ADV) is an ultrasound method for converting biocompatible microdroplets into microbubbles. The objective is to demonstrate that ADV bubbles can enhance high intensity focused ultrasound (HIFU) therapy by controlling and increasing energy absorption at the focus. Thermal phantoms were made with or without droplets. Compound lesions were formed in the phantoms by 5-second exposures with 5-second delays. Center to center spacing of individual lesions was 5.5 mm in either a linear pattern or a spiral pattern. Prior to the HIFU, 10 cycle tone bursts with 0.25% duty cycle were used to vaporize the droplets, forming an “acoustic trench” within 30 seconds. The transducer was then focused in the middle of the back bubble wall to form thermal lesions in the trench. All lesions were imaged optically and with 2T MRI. With the use of ADV and the acoustic trench, a uniform thermal ablation volume of 15 cm3 was achieved in 4 minutes; without ADV only less than 15% of this volume was filled. The commonly seen tadpole shape characteristic of bubble-enhanced HIFU lesions was not evident with the acoustic trench. In conclusion, ADV shows promise for the spatial control and dramatic acceleration of thermal lesion production by HIFU. PMID:21804749

  15. Provider perspectives on barriers and facilitators to adjuvant endocrine therapy-related symptom management.

    Science.gov (United States)

    Samuel, Cleo A; Turner, Kea; Donovan, Heidi A S; Beckjord, Ellen; Cardy, Alexandra; Dew, Mary Amanda; van Londen, G J

    2017-07-06

    Adjuvant endocrine therapy (AET) utilization is linked to improved clinical outcomes among breast cancer survivors (BCS); yet, AET adherence rates remain suboptimal. Little is known about provider perspectives regarding barriers and facilitators to AET-related symptom management (SM). In this study, we examined provider perspectives on the barriers and facilitators to AET-related SM among BCS and opportunities for improvement. We conducted three focus groups (FGs) with a multidisciplinary group of healthcare providers (n = 13) experienced in caring for BCS undergoing AET. We utilized semi-structured discussion guides to elicit provider perspectives on AET-related SM. FGs were audiotaped, transcribed, and analyzed using qualitative software to identify key themes. Providers described patient-, provider-, and system-level barriers and facilitators to AET-related SM. At the patient-level, barriers included competing demands, limited time/resources, and possible misattribution of some symptoms to AET, while family/social relationships and insurance emerged as important facilitators. Discomfort with SM, limited time, and challenges distinguishing AET-related symptoms from other conditions were key provider-level barriers. Provider-level facilitators included routine symptom documentation and strong provider relationships. Care fragmentation and complexity of the cancer care delivery system were described as system-level barriers; however, survivor clinics were endorsed by providers. Provider perspectives on AET-related SM can shed light on SM barriers and facilitators spanning multiple levels of the cancer care delivery system. Strategies for improving AET-related SM in BCS include increasing patients' knowledge and engagement in SM, equipping providers with efficient SM strategies, and improving coordination of symptom-related services through survivorship programs.

  16. Analysis of pharmacist-provided medication therapy management (MTM) services in community pharmacies over 7 years.

    Science.gov (United States)

    Barnett, Mitchell J; Frank, Jessica; Wehring, Heidi; Newland, Brand; VonMuenster, Shannon; Kumbera, Patty; Halterman, Tom; Perry, Paul J

    2009-01-01

    Although community pharmacists have historically been paid primarily for drug distribution and dispensing services, medication therapy management (MTM) services evolved in the 1990s as a means for pharmacists and other providers to assist physicians and patients in managing clinical, service, and cost outcomes of drug therapy. The Medicare Prescription Drug, Improvement, and Modernization Act of 2003 (MMA 2003) and the subsequent implementation of Medicare Part D in January 2006 for the more than 20 million Medicare beneficiaries enrolled in the Part D benefit formalized MTM services for a subset of high-cost patients. Although Medicare Part D has provided a new opportunity for defining the value of pharmacist-provided MTM services in the health care system, few publications exist which quantify changes in the provision of pharmacist-provided MTM services over time. To (a) describe the changes over a 7-year period in the primary types of MTM services provided by community pharmacies that have contracted with drug plan sponsors through an MTM administrative services company, and (b) quantify potential MTM-related cost savings based on pharmacists' self-assessments of the likely effects of their interventions on health care utilization. Medication therapy management claims from a multistate MTM administrative services company were analyzed over the 7-year period from January 1, 2000, through December 31, 2006. Data extracted from each MTM claim included patient demographics (e.g., age and gender), the drug and type that triggered the intervention (e.g., drug therapeutic class and therapy type as either acute, intermittent, or chronic), and specific information about the service provided (e.g., Reason, Action, Result, and Estimated Cost Avoidance [ECA]). ECA values are derived from average national health care utilization costs, which are applied to pharmacist self-assessment of the "reasonable and foreseeable" outcome of the intervention. ECA values are updated

  17. Challenging obesity: Patient, provider, and expert perspectives on the roles of available and emerging nonsurgical therapies.

    Science.gov (United States)

    Apovian, Caroline M; Garvey, W Timothy; Ryan, Donna H

    2015-07-01

    Adult obesity is recognized as a chronic disease. According to principles of chronic disease management, healthcare professionals should work collaboratively with patients to determine appropriate therapeutic strategies that address overweight and obesity, specifically considering a patient's disease status in addition to their individual needs, preferences, and attitudes regarding treatment. A central role and responsibility of healthcare professionals in this process is to inform and educate patients about their treatment options. Although current recommendations for the management of adult obesity provide general guidance regarding safe and proper implementation of lifestyle, pharmacological, and surgical interventions, healthcare professionals need awareness of specific evidence-based information that supports individualized clinical application of these therapies. More specifically, healthcare professionals should be up-to-date on approaches that promote successful lifestyle management and be knowledgeable about newer weight loss pharmacotherapies, so they can offer patients with obesity a wide range of options to personalize their treatment. Accordingly, this educational activity has been developed to provide participants with the latest information on treatment recommendations and therapeutic advances in lifestyle intervention and pharmacotherapy for adult obesity management. This supplement is based on the content presented at a live CME symposium held in conjunction with ObesityWeek 2014. This supplement provides an expert summary of current treatment recommendations and recent advances in nonsurgical therapies for the management of adult obesity. Patient and provider perspectives on obesity management are highlighted in embedded video clips available via QR codes, and new evidence will be applied using clinically relevant case studies. This supplement provides a topical update of obesity management, including clinical practice examples, for healthcare

  18. Challenging Obesity: Patient, Provider, and Expert Perspectives on the Roles of Available and Emerging Nonsurgical Therapies

    Science.gov (United States)

    Apovian, Caroline M.; Garvey, W. Timothy; Ryan, Donna H.

    2015-01-01

    Objective Adult obesity is recognized as a chronic disease. According to principles of chronic disease management, healthcare professionals should work collaboratively with patients to determine appropriate therapeutic strategies that address overweight and obesity, specifically considering a patient’s disease status in addition to their individual needs, preferences, and attitudes regarding treatment. A central role and responsibility of healthcare professionals in this process is to inform and educate patients about their treatment options. Although current recommendations for the management of adult obesity provide general guidance regarding safe and proper implementation of lifestyle, pharmacological, and surgical interventions, healthcare professionals need awareness of specific evidence-based information that supports individualized clinical application of these therapies. More specifically, healthcare professionals should be up-to-date on approaches that promote successful lifestyle management and be knowledgeable about newer weight loss pharmacotherapies, so they can offer patients with obesity a wide range of options to personalize their treatment. Accordingly, this educational activity has been developed to provide participants with the latest information on treatment recommendations and therapeutic advances in lifestyle intervention and pharmacotherapy for adult obesity management. Design and Methods This supplement is based on the content presented at a live CME symposium held in conjunction with ObesityWeek 2014. Results This supplement provides an expert summary of current treatment recommendations and recent advances in nonsurgical therapies for the management of adult obesity. Patient and provider perspectives on obesity management are highlighted in embedded video clips available via QR codes, and new evidence will be applied using clinically relevant case studies. Conclusions This supplement provides a topical update of obesity management

  19. Agency over Phantom Limb Enhanced by Short-Term Mirror Therapy

    Directory of Open Access Journals (Sweden)

    Shu Imaizumi

    2017-10-01

    Full Text Available Most amputees experience phantom limb, whereby they feel that the amputated limb is still present. In some cases, these experiences include pain that can be alleviated by “mirror therapy.” Mirror therapy consists of superimposing a mirrored image of the moving intact limb onto the phantom limb. This therapy provides a closed loop between the motor command to the amputated limb and its predicted visual feedback. This loop is also involved in the sense of agency, a feeling of controlling one’s own body. However, it is unclear how mirror therapy is related to the sense of agency over a phantom limb. Using mirror therapy, we investigated phantom limb pain and the senses of agency and ownership (i.e., a feeling of having one’s own body of the phantom limb. Nine upper-limb amputees, five of whom reported recent phantom limb pain, underwent a single 15-min trial of mirror therapy. Before and after the trial, the participants completed a questionnaire regarding agency, ownership, and pain related to their phantom limb. They reported that the sense of agency over the phantom limb increased following the mirror therapy trial, while the ownership slightly increased but not as much as did the agency. The reported pain did not change; that is, it was comparably mild before and after the trial. These results suggest that short-term mirror therapy can, at least transiently, selectively enhance the sense of agency over a phantom limb, but may not alleviate phantom limb pain.

  20. Attitudes of patients and care providers to enhanced recovery after surgery programs after major abdominal surgery.

    Science.gov (United States)

    Hughes, Michael; Coolsen, Marielle M E; Aahlin, Eirik K; Harrison, Ewen M; McNally, Stephen J; Dejong, C H C; Lassen, Kristoffer; Wigmore, Stephen J

    2015-01-01

    Enhanced recovery after surgery (ERAS) is a well-established pathway of perioperative care in surgery in an increasing number of specialties. To implement protocols and maintain high levels of compliance, continued support from care providers and patients is vital. This survey aimed to assess the perceptions of care providers and patients of the relevance and importance of the ERAS targets and strategies. Pre- and post-operative surveys were completed by patients who underwent major hepatic, colorectal, or oesophagogastric surgery in three major centers in Scotland, Norway, and The Netherlands. Anonymous web-based and article surveys were also sent to surgeons, anesthetists, and nurses experienced in delivering enhanced recovery protocols. Each questionnaire asked the responder to rate a selection of enhanced recovery targets and strategies in terms of perceived importance. One hundred nine patients and 57 care providers completed the preoperative survey. Overall, both patients and care providers rated the majority of items as important and supported ERAS principles. Freedom from nausea (median, 10; interquartile range [IQR], 8-10) and pain at rest (median, 10; IQR, 8-10) were the care components rated the highest by both patients and care providers. Early return of bowel function (median, 7; IQR, 5-8) and avoiding preanesthetic sedation (median, 6; IQR, 3.75-8) were scored the lowest by care providers. ERAS principles are supported by both patients and care providers. This is important when attempting to implement and maintain an ERAS program. Controversies still remain regarding the relative importance of individual ERAS components. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Evaluation of the local dose enhancement in the combination of proton therapy and nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Martínez-Rovira, I., E-mail: immamartinez@gmail.com; Prezado, Y. [Laboratoire d’Imagerie et Modélisation en Neurobiologie et Cancérologie (IMNC), Centre National de la Recherche Scientifique (CNRS), Université Paris 7 and 11, Campus Universitaire, Bât. 440, 1er étage, 15 rue Georges Clemenceau, Orsay Cedex 91406 (France)

    2015-11-15

    Purpose: The outcome of radiotherapy can be further improved by combining irradiation with dose enhancers such as high-Z nanoparticles. Since 2004, spectacular results have been obtained when low-energy x-ray irradiations have been combined with nanoparticles. Recently, the same combination has been explored in hadron therapy. In vitro studies have shown a significant amplification of the biological damage in tumor cells charged with nanoparticles and irradiated with fast ions. This has been attributed to the increase in the ionizations and electron emissions induced by the incident ions or the electrons in the secondary tracks on the high-Z atoms, resulting in a local energy deposition enhancement. However, this subject is still a matter of controversy. Within this context, the main goal of the authors’ work was to provide new insights into the dose enhancement effects of nanoparticles in proton therapy. Methods: For this purpose, Monte Carlo calculations (GATE/GEANT4 code) were performed. In particular, the GEANT4-DNA toolkit, which allows the modeling of early biological damages induced by ionizing radiation at the DNA scale, was used. The nanometric radial energy distributions around the nanoparticle were studied, and the processes (such as Auger deexcitation or dissociative electron attachment) participating in the dose deposition of proton therapy treatments in the presence of nanoparticles were evaluated. It has been reported that the architecture of Monte Carlo calculations plays a crucial role in the assessment of nanoparticle dose enhancement and that it may introduce a bias in the results or amplify the possible final dose enhancement. Thus, a dosimetric study of different cases was performed, considering Au and Gd nanoparticles, several nanoparticle sizes (from 4 to 50 nm), and several beam configurations (source-nanoparticle distances and source sizes). Results: This Monte Carlo study shows the influence of the simulations’ parameters on the local

  2. Health care provider education as a tool to enhance antibiotic stewardship practices.

    Science.gov (United States)

    Ohl, Christopher A; Luther, Vera P

    2014-06-01

    Antibiotic stewardship education for health care providers provides a foundation of knowledge and an environment that facilitates and supports optimal antibiotic prescribing. There is a need to extend this education to medical students and health care trainees. Education using passive techniques is modestly effective for increasing prescriber knowledge, whereas education using active techniques is more effective for changing prescribing behavior. Such education has been shown to enhance other antibiotic stewardship interventions. In this review, the need and suggested audience for antibiotic stewardship education are highlighted, and effective education techniques are recommended for increasing knowledge of antibiotics and improving their use. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Enhancing the Therapy Experience Using Principles of Video Game Design.

    Science.gov (United States)

    Folkins, John Wm; Brackenbury, Tim; Krause, Miriam; Haviland, Allison

    2016-02-01

    This article considers the potential benefits that applying design principles from contemporary video games may have on enhancing therapy experiences. Six principles of video game design are presented, and their relevance for enriching clinical experiences is discussed. The motivational and learning benefits of each design principle have been discussed in the education literature as having positive impacts on student motivation and learning and are related here to aspects of clinical practice. The essential experience principle suggests connecting all aspects of the experience around a central emotion or cognitive connection. The discovery principle promotes indirect learning in focused environments. The risk-taking principle addresses the uncertainties clients face when attempting newly learned skills in novel situations. The generalization principle encourages multiple opportunities for skill transfer. The reward system principle directly relates to the scaffolding of frequent and varied feedback in treatment. Last, the identity principle can assist clients in using their newly learned communication skills to redefine self-perceptions. These principles highlight areas for research and interventions that may be used to reinforce or advance current practice.

  4. Initiation of antiretroviral therapy in youth with HIV: a U.S.-based provider survey.

    Science.gov (United States)

    Gagliardo, Christina; Murray, Meghan; Saiman, Lisa; Neu, Natalie

    2013-09-01

    In 2009, the Department of Health and Human Services (DHHS) recommended initiating antiretroviral therapy (ART) for youth with HIV at higher CD4 counts (≤500 cells/mm³) than previously recommended (≤350 cells/mm³). Barriers experienced by providers regarding ART initiation in this population have not been assessed. From 12/2011-01/2012, we asked providers from the American Academy of HIV Medicine (AAHIVM) [corrected] listserv who prescribed ART to youth (ages 13-25 years) with behaviorally-acquired HIV to complete a web-based survey. We presented a clinical vignette to explore potential barriers for initiating ART. Overall, 274/290 (94%) respondents completed the survey. Most felt confident that evidence supported initiating ART at higher CD4 counts (94%), and that benefits outweighed the risks of long-term toxicity (98%) or developing resistance (88%). Most (96%) initiated ART in the patient vignette (age 19 years, CD4 count ~400). Patient characteristics (e.g., unstable housing or drug use) were perceived as large barriers to ART initiation. Low response rate (13%) was a limitation. Respondents were knowledgeable about relevant DHHS guidelines, believed sufficient evidence supported ART initiation at higher CD4 counts, and would provide treatment to those with CD4 counts ≤500cells/mm³. Understanding and overcoming barriers to initiation of ART perceived by providers is important to ensure implementation of ART treatment guidelines.

  5. Treatment as prevention: are Argentinean HIV care providers willing to adopt earlier antiretroviral therapy?

    Science.gov (United States)

    Socías, María Eugenia; Sued, Omar; Pryluka, Daniel; Patterson, Patricia; Fink, Valeria; Cesar, Carina; Cahn, Pedro

    2014-01-01

    HIV guidelines increasingly recommend antiretroviral therapy (ART) initiation at a higher CD4 levels. The extent to which these evolving standards are translated into routine clinical care has not been evaluated in Argentina. During October 2012, we conducted an online survey among Argentinean HIV clinicians to assess their attitudes and practices toward ART initiation and its potential use for HIV prevention. Of the 280 physicians included, 61% would prescribe ART at CD4 ≤ 500 cells/µL for asymptomatic patients. Although, only 11% would recommend ART irrespective of CD4 cell count, 72% would do it for serodiscordant couples, and 75% for sex workers. Most participants agreed that they would consider earlier initiation of ART if transmission risk exists, and that expansion of ART could help decrease HIV incidence. These results suggest that a large proportion of Argentinean HIV care providers are willing to adopt the recently updated Argentinean guidelines recommending earlier ART, especially when high HIV transmission risk exists.

  6. Robotic therapy provides a stimulus for upper limb motor recovery after stroke that is complementary to and distinct from conventional therapy.

    Science.gov (United States)

    Brokaw, Elizabeth B; Nichols, Diane; Holley, Rahsaan J; Lum, Peter S

    2014-05-01

    Individuals with chronic stroke often have long-lasting upper extremity impairments that impede function during activities of daily living. Rehabilitation robotics have shown promise in improving arm function, but current systems do not allow realistic training of activities of daily living. We have incorporated the ARMin III and HandSOME device into a novel robotic therapy modality that provides functional training of reach and grasp tasks. To compare the effects of equal doses of robotic and conventional therapy in individuals with chronic stroke. Subjects were randomized to 12 hours of robotic or conventional therapy and then crossed over to the other therapy type after a 1-month washout period. Twelve moderate to severely impaired individuals with chronic stroke were enrolled, and 10 completed the study. Across the 3-month study period, subjects showed significant improvements in the Fugl-Meyer (P = .013) and Box and Blocks tests (P = .028). The robotic intervention produced significantly greater improvements in the Action Research Arm Test than conventional therapy (P = .033). Gains in the Box and Blocks test from conventional therapy were larger than from robotic therapy in subjects who received conventional therapy after robotic therapy (P = .044). Data suggest that robotic therapy can elicit improvements in arm function that are distinct from conventional therapy and supplements conventional methods to improve outcomes. Results from this pilot study should be confirmed in a larger study.

  7. TH-E-BRD-01: Innovation in (gold) Nanoparticle-Enhanced Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Krishnan, S; Chithrani, B; Berbeco, R [Brigham and Women' s Hospital, Boston, MA (United States)

    2014-06-15

    spans across multiple specialties (clinical radiation oncology, radiation physics, radiation biology, nanotechnology, material science, biomedical engineering, pharmacology, chemistry, and tumor biology) and numerous specialty journals, there is no single compilation of extant research in this arena or forum for merging analogous concepts and paradigms. This symposium will provide such a venue — my presentation will start with familiarizing the audience with the potential applications of metallic nanoparticles in radiation therapy using specific illustrative examples and begin to explore ways to understand the underlying mechanisms of the effects observed. Biological effects of Gold nanoparticles in radiation therapy Gold nanoparticles (GNP) have been investigated as platforms to carry drugs or radio-sensitizing agents to tumors due to the biocompatibility of gold and relative ease of conjugation with therapeutic and targeting moieties. Recently, there has been interest in exploiting the physical properties of gold, specifically the high atomic number, to enhance radiation therapy. When irradiated, gold atoms will produce low energy electrons, depositing energy within a short distance. The ratio of dose deposited in the presence of the GNP to the dose deposited in the absence of GNP is referred to as the dose enhancement factor (DEF). This factor has been shown to depend on the concentration of GNP and the energy of the incident photons. The physics of this process, preliminary in vitro and in vivo experiments and future directions for this nascent field are described in this presentation. Gold Nanoparticles for improved therapeutic outcome in radiation therapy The application of nanoparticles (NPs) for improved therapeutics is at the forefront of cancer nanotechnology. Among other NP systems, gold nanoparticles (GNPs) are extensively used due to its impressive ability to act as both an anticancer drug carrier in chemotherapy and as a dose enhancer in radiotherapy

  8. Technology-Enhanced Peer Review: Benefits and Implications of Providing Multiple Reviews

    DEFF Research Database (Denmark)

    Papadopoulos, Pantelis M.; Lagkas, Thomas D.; Demetriadis, Stavros N.

    2016-01-01

    This study analyses the impact of self and peer feedback in technology-enhanced peer review settings. The impact of receiving peer comments (“receiver” perspective) is compared to that of reaching own insights by reviewing others’ work (“giver” perspective). In this study, 38 sophomore students...... were randomly assigned in two conditions and engaged in peer review activity facilitated by a web-based learning environment asking them to provide multiple reviews. In the Peer Reviewed (PR) condition students both reviewed peer work and received peer comments for their own work. By contrast......, in the Self Reviewed (SR) condition students provided peer reviews, but did not receive any. Instead, they were asked to perform self reviewing, before proceeding to any revisions of their work. Result showed that the two groups were comparable in all aspects, suggesting that the lack of getting peer reviews...

  9. A modified transmission tip-enhanced Raman scattering (TERS) setup provides access to opaque samples.

    Science.gov (United States)

    Deckert-Gaudig, Tanja; Richter, Marc; Knebel, Detlef; Jähnke, Torsten; Jankowski, Tilo; Stock, Erik; Deckert, Volker

    2014-01-01

    The combination of scanning probe microscopy and Raman spectroscopy enables chemical characterization of surfaces at highest spatial resolution. This so-called tip-enhanced Raman scattering (TERS) can be employed for a variety of samples where a label-free characterization or identification of constituents on the nanometer scale is pursued. Present TERS setup geometries are always a compromise for specific dedicated applications and show different advantages and disadvantages: Transmission back-reflection setups, when using immersion objectives with a high numerical aperture, intrinsically provide the highest collection efficiency but cannot be applied for opaque samples. Those samples demand upright setups, at the cost of lower collection efficiency, even though very efficient systems using a parabolic mirror for illumination and collection have been demonstrated. In this contribution it is demonstrated that the incorporation of a dichroic mirror to a transmission TERS setup provides easy access to opaque samples without further modification of the setup.

  10. Technology-Enhanced Peer Review: Benefits and Implications of Providing Multiple Reviews

    DEFF Research Database (Denmark)

    Papadopoulos, Pantelis M.; Lagkas, Thomas D.; Demetriadis, Stavros N.

    2017-01-01

    This study analyses the impact of self and peer feedback in technology-enhanced peer review settings. The impact of receiving peer comments (“receiver” perspective) is compared to that of reaching own insights by reviewing others’ work (“giver” perspective). In this study, 38 sophomore students...... were randomly assigned in two conditions and engaged in peer review activity facilitated by a web-based learning environment asking them to provide multiple reviews. In the Peer Reviewed (PR) condition students both reviewed peer work and received peer comments for their own work. By contrast......, in the Self Reviewed (SR) condition students provided peer reviews, but did not receive any. Instead, they were asked to perform self reviewing, before proceeding to any revisions of their work. Result showed that the two groups were comparable in all aspects, suggesting that the lack of getting peer reviews...

  11. The Status of Home Intravenous Therapy Instruction Provided by U.S. Schools and Colleges of Pharmacy.

    Science.gov (United States)

    Monk, Mary R.; And Others

    1991-01-01

    A survey of 74 pharmacy schools found under half offered home intravenous (IV) therapy instruction. About 13 percent offered a course primarily devoted to home IV therapy; only two schools required it. Clinical departments were the primary providers, and various instructional resources were used. Additional home health care coursework is…

  12. GENE THERAPY APPROACHES TO ENHANCING PLASTICITY AND REGENERATION AFTER SPINAL CORD INJURY

    Science.gov (United States)

    Franz, Steffen; Weidner, Norbert; Blesch, Armin

    2011-01-01

    During the past decades, new insights into mechanisms that limit plasticity and functional recovery after spinal cord injury have spurred the development of novel approaches to enhance axonal regeneration and rearrangement of spared circuitry. Gene therapy may provide one means to address mechanisms that underlie the insufficient regenerative response of injured neurons and can also be used to identify factors important for axonal growth. Several genetic approaches aimed to modulate the environment of injured axons, for example by localized expression of growth factors, to enhance axonal sprouting and regeneration and to guide regenerating axons towards their target have been described. In addition, genetic modification of injured neurons via intraparenchymal injection, or via retrograde transport of viral vectors has been used to manipulate the intrinsic growth capacity of injured neurons. In this review we will summarize some of the progress and limitations of cell transplantation and gene therapy to enhance axonal bridging and regeneration across a lesion site, and to maximize the function, collateral sprouting and connectivity of spared axonal systems. PMID:21281633

  13. Integrative analysis of kinase networks in TRAIL-induced apoptosis provides a source of potential targets for combination therapy

    DEFF Research Database (Denmark)

    So, Jonathan; Pasculescu, Adrian; Dai, Anna Y.

    2015-01-01

    /threonine kinase (PXK) and AP2-associated kinase 1 (AAK1), which promote receptor endocytosis and may enable cells to resist TRAIL-induced apoptosis by enhancing endocytosis of the TRAIL receptors. We assembled protein interaction maps using mass spectrometry-based protein interaction analysis and quantitative...... combination therapies to selectively kill cancer cells....

  14. The Motivational Enhancement Therapy and Cognitive Behavioral Therapy Supplement: 7 Sessions of Cognitive Behavioral Therapy for Adolescent Cannabis Users, Cannabis Youth Treatment (CYT) Series, Volume 2.

    Science.gov (United States)

    Webb, Charles; Scudder, Meleney; Kaminer, Yifrah; Kaden, Ron

    This manual, a supplement to "Motivational Enhancement Therapy and Cognitive Behavioral Therapy for Adolescent Cannabis Users: 5 Sessions, Cannabis Youth Treatment (CYT) Series, Volume 1", presents a seven-session cognitive behavioral treatment (CBT7) approach designed especially for adolescent cannabis users. It addresses the implementation and…

  15. Photodynamic therapy: occupational hazards and preventative recommendations for clinical administration by healthcare providers.

    Science.gov (United States)

    Breskey, John D; Lacey, Steven E; Vesper, Benjamin J; Paradise, William A; Radosevich, James A; Colvard, Michael D

    2013-08-01

    Photodynamic therapy (PDT) as a medical treatment for cancers is an increasing practice in clinical settings, as new photosensitizing chemicals and light source technologies are developed and applied. PDT involves dosing patients with photosensitizing drugs, and then exposing them to light using a directed energy device in order to manifest a therapeutic effect. Healthcare professionals providing PDT should be aware of potential occupational health and safety hazards posed by these treatment devices and photosensitizing agents administered to patients. Here we outline and identify pertinent health and safety considerations to be taken by healthcare staff during PDT procedures. Physical hazards (for example, non-ionizing radiation generated by the light-emitting device, with potential for skin and eye exposure) and chemical hazards (including the photosensitizing agents administered to patients that have the potential for exposure via skin, subcutaneous, ingestion, or inhalation routes) must be considered for safe use of PDT by the healthcare professional. Engineering, administrative, and personal protective equipment controls are recommendations for the safe use and handling of PDT agents and light-emitting technologies.

  16. Sodium oxybate therapy provides multidimensional improvement in fibromyalgia: results of an international phase 3 trial

    Science.gov (United States)

    Spaeth, Michael; Bennett, Robert M; Benson, Beverly A; Wang, Y Grace; Lai, Chinglin; Choy, Ernest H

    2012-01-01

    Background Fibromyalgia is characterised by chronic musculoskeletal pain and multiple symptoms including fatigue, multidimensional function impairment, sleep disturbance and tenderness. Along with pain and fatigue, non-restorative sleep is a core symptom of fibromyalgia. Sodium oxybate (SXB) is thought to reduce non-restorative sleep abnormalities. This study evaluated effects of SXB on fibromyalgia-related pain and other symptoms. Methods 573 patients with fibromyalgia according to 1990 American College of Rheumatology criteria were enrolled at 108 centres in eight countries. Subjects were randomly assigned to placebo, SXB 4.5 g/night or SXB 6 g/night. The primary efficacy endpoint was the proportion of subjects with ≥30% reduction in pain visual analogue scale from baseline to treatment end. Other efficacy assessments included function, sleep quality, effect of sleep on function, fatigue, tenderness, health-related quality of life and subject's impression of change in overall wellbeing. Results Significant improvements in pain, sleep and other symptoms associated with fibromyalgia were seen in SXB treated subjects compared with placebo. The proportion of subjects with ≥30% pain reduction was 42.0% for SXB4.5 g/night (p=0.002) and 51.4% for SXB6 g/night (panxiety, somnolence, fatigue, muscle spasms and peripheral oedema. Conclusion These results, combined with findings from previous phase 2 and 3 studies, provide supportive evidence that SXB therapy affordsimportant benefits across multiple symptoms in subjects with fibromyalgia. PMID:22294641

  17. Researching the acceptability of using Skype to provide Speech and Language Therapy

    Science.gov (United States)

    Matthews, Rebecca Alison; Woll, Bencie; Clarke, Mike

    2012-01-01

    In the current economic climate, whilst the demand for health services, including Speech and Language Therapy (SLT) continues to rise, there is pressure to reduce health service budgets, Tele-technology—the use of tele-communication technology to link patient and clinician remotely—could potentially provide a solution to meeting the demand for SLT with reduced resources. However, only a few SLT services in the United Kingdom (UK) have reported on using tele-technology to provide their service (Howell, Tripoliti and Pring, 2009; Styles, 2008; McCullough, 2001; Katsavarus, 2001). In 2002 the American Speech and Hearing Association (ASHA) surveyed its members on their experience and views of using tele-technology and specifically video-conferencing to provide an SLT service. The analysis of the responses identified five areas of concern—lack of professional guidelines, limited evidence of clinical efficacy, disruption and problems managing the technology, change in the interaction and loss of rapport as well as anticipated, additional costs to provide the service. The study reported here set up an SLT service using the desktop videoconferencing system, Skype, in an independent SLT practice based in the UK. Data were collected to evaluate the acceptability of the clinical sessions, the technology, the quality of interaction and costs of an SLT service using Skype. Eleven participants aged between 7 and 14 years with varying therapy needs took part. Each received a mix of face-to-face (F2F) and Skype SLT over the ten session trial period. Data were collected for every session using a report card; adults supporting the children were asked for their views using a questionnaire at the beginning and end of the trial; the child participants were interviewed after the trial period was over; one F2F and one Skype session was video recorded for each participant; work activity was recorded along with identifiable costs of F2F and Skype SLT sessions. A total of 110 session

  18. Pharmacist-provided medication therapy management (MTM) program impacts outcomes for employees with diabetes.

    Science.gov (United States)

    Pinto, Sharrel L; Kumar, Jinender; Partha, Gautam; Bechtol, Robert A

    2014-02-01

    The objective of this prospective, pre-post longitudinal study was to assess the impact of pharmacist-provided medication therapy management (MTM) services on employees' health and well-being by evaluating their clinical and humanistic outcomes. City of Toledo employees and/or their spouses and dependents with diabetes with or without comorbid conditions were enrolled in the pharmacist-conducted MTM program. Participants scheduled consultations with the pharmacist at predetermined intervals. Overall health outcomes, such as clinical markers, health-related quality of life (HRQoL), disease knowledge, and social and process measures, were documented at these visits and assessed for improvement. Changes in patient outcomes over time were analyzed using Wilcoxon signed rank and Friedman test at an a priori level of 0.05. Spearman correlation was used to measure the relationship between clinical and humanistic outcomes. A total of 101 patients enrolled in the program. At the end of 1 year, patients' A1c levels decreased on average by 0.27 from their baseline values. Systolic and diastolic blood pressure also decreased on average by 6.0 and 4.2 mmHg, respectively. Patient knowledge of disease conditions and certain aspects or components of HRQoL also improved. Improvements in social and process measures also were also observed. Improved clinical outcomes and quality of life can affect employee productivity and help reduce costs for employers by reducing disease-related missed days of work. Employers seeking to save costs and impact productivity can utilize the services provided by pharmacists.

  19. Costs of Providing Infusion Therapy for Rheumatoid Arthritis in a Hospital-based Infusion Center Setting.

    Science.gov (United States)

    Schmier, Jordana; Ogden, Kristine; Nickman, Nancy; Halpern, Michael T; Cifaldi, Mary; Ganguli, Arijit; Bao, Yanjun; Garg, Vishvas

    2017-08-01

    Many hospital-based infusion centers treat patients with rheumatoid arthritis (RA) with intravenous biologic agents, yet may have a limited understanding of the overall costs of infusion in this setting. The purposes of this study were to conduct a microcosting analysis from a hospital perspective and to develop a model using an activity-based costing approach for estimating costs associated with the provision of hospital-based infusion services (preparation, administration, and follow-up) in the United States for maintenance treatment of moderate to severe RA. A spreadsheet-based model was developed. Inputs included hourly wages, time spent providing care, supply/overhead costs, laboratory testing, infusion center size, and practice pattern information. Base-case values were derived from data from surveys, published studies, standard cost sources, and expert opinion. Costs are presented in year-2017 US dollars. The base case modeled a hospital infusion center serving patients with RA treated with abatacept, tocilizumab, infliximab, or rituximab. Estimated overall costs of infusions per patient per year were $36,663 (rituximab), $36,821 (tocilizumab), $44,973 (infliximab), and $46,532 (abatacept). Of all therapies, the biologic agents represented the greatest share of overall costs, ranging from 87% to $91% of overall costs per year. Excluding infusion drug costs, labor accounted for 53% to 57% of infusion costs. Biologic agents represented the highest single cost associated with RA infusion care; however, personnel, supplies, and overhead costs also contributed substantially to overall costs (8%-16%). This model may provide a helpful and adaptable framework for use by hospitals in informing decision making about services offered and their associated financial implications. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  20. Costs of a motivational enhancement therapy coupled with cognitive behavioral therapy versus brief advice for pregnant substance users.

    Directory of Open Access Journals (Sweden)

    Xiao Xu

    Full Text Available To determine and compare costs of a nurse-administered behavioral intervention for pregnant substance users that integrated motivational enhancement therapy with cognitive behavioral therapy (MET-CBT to brief advice (BA administered by an obstetrical provider. Both interventions were provided concurrent with prenatal care.We conducted a micro-costing study that prospectively collected detailed resource utilization and unit cost data for each of the two intervention arms (MET-CBT and BA within the context of a randomized controlled trial. A three-step approach for identifying, measuring and valuing resource utilization was used. All cost estimates were inflation adjusted to 2011 U.S. dollars.A total of 82 participants received the MET-CBT intervention and 86 participants received BA. From the societal perspective, the total cost (including participants' time cost of the MET-CBT intervention was $120,483 or $1,469 per participant. In contrast, the total cost of the BA intervention was $27,199 or $316 per participant. Personnel costs (nurse therapists and obstetric providers for delivering the intervention sessions and supervising the program composed the largest share of the MET-CBT intervention costs. Program set up costs, especially intervention material design and training costs, also contributed substantially to the overall cost.Implementation of an MET-CBT program to promote drug abstinence in pregnant women is associated with modest costs. Future cost effectiveness and cost benefit analyses integrating costs with outcomes and benefits data will enable a more comprehensive understanding of the intervention in improving the care of substance abusing pregnant women.

  1. Effects of Improvisational Music Therapy vs Enhanced Standard Care on Symptom Severity Among Children With Autism Spectrum Disorder

    Science.gov (United States)

    Bieleninik, Łucja; Geretsegger, Monika; Mössler, Karin; Assmus, Jörg; Thompson, Grace; Gattino, Gustavo; Elefant, Cochavit; Gottfried, Tali; Igliozzi, Roberta; Muratori, Filippo; Suvini, Ferdinando; Kim, Jinah; Crawford, Mike J.; Odell-Miller, Helen; Oldfield, Amelia; Casey, Órla; Finnemann, Johanna; Carpente, John; Park, A-La; Grossi, Enzo

    2017-01-01

    Importance Music therapy may facilitate skills in areas affected by autism spectrum disorder (ASD), such as social interaction and communication. Objective To evaluate effects of improvisational music therapy on generalized social communication skills of children with ASD. Design, Setting, and Participants Assessor-blinded, randomized clinical trial, conducted in 9 countries and enrolling children aged 4 to 7 years with ASD. Children were recruited from November 2011 to November 2015, with follow-up between January 2012 and November 2016. Interventions Enhanced standard care (n = 182) vs enhanced standard care plus improvisational music therapy (n = 182), allocated in a 1:1 ratio. Enhanced standard care consisted of usual care as locally available plus parent counseling to discuss parents’ concerns and provide information about ASD. In improvisational music therapy, trained music therapists sang or played music with each child, attuned and adapted to the child’s focus of attention, to help children develop affect sharing and joint attention. Main Outcomes and Measures The primary outcome was symptom severity over 5 months, based on the Autism Diagnostic Observation Schedule (ADOS), social affect domain (range, 0-27; higher scores indicate greater severity; minimal clinically important difference, 1). Prespecified secondary outcomes included parent-rated social responsiveness. All outcomes were also assessed at 2 and 12 months. Results Among 364 participants randomized (mean age, 5.4 years; 83% boys), 314 (86%) completed the primary end point and 290 (80%) completed the last end point. Over 5 months, participants assigned to music therapy received a median of 19 music therapy, 3 parent counseling, and 36 other therapy sessions, compared with 3 parent counseling and 45 other therapy sessions for those assigned to enhanced standard care. From baseline to 5 months, mean ADOS social affect scores estimated by linear mixed-effects models decreased from 14

  2. [A web information system for enhancing management and improving special care services provided to dependent persons].

    Science.gov (United States)

    Alvarez-Bermejo, J A; Hernández-Capel, D M; Belmonte-Ureña, L J; Roca-Piera, J

    2009-01-01

    Ensuring the quality of services provided in centres where dependent persons are seen by specialist services, by improving and enhancing how information -salary, control of tasks, patients' records, etc.- is shared between staff and carers. A web information system has been developed and experimentally deployed to accomplish this. The accuracy of the system was evaluated by assessing how confident the employees were with it rather than relying on statistical data. It was experimentally deployed since January 2009 in Asociación de Personas con Discapacidad "El Saliente" that manages several day centres in Almeria, for dependent persons over 65 years old, particularly those affected by Alzheimer' disease. Incidence data was collected during the experimental period. A total of 84% of the employees thought that the system helped to manage documents, administrative duties, etc., and 92.4% said they could attend to really important tasks because the system was responsible for alerting them of every task, such as medication timetables, checking all patients were present (to prevent an Alzheimer affected person leaving the centre) etc. During this period the incidences reported were reduced by about a 30%, although data is still partially representative. As the life expectancy of the population gets longer, these centres will increase. Providing systems such as the one presented here would be of great help for administrative duties (sensitive data protection...) as well as ensuring high quality care and attention.

  3. Dental Providers' Perspectives on Diagnosis-Driven Dentistry: Strategies to Enhance Adoption of Dental Diagnostic Terminology.

    Science.gov (United States)

    Obadan-Udoh, Enihomo; Simon, Lisa; Etolue, Jini; Tokede, Oluwabunmi; White, Joel; Spallek, Heiko; Walji, Muhammad; Kalenderian, Elsbeth

    2017-07-13

    The routine use of standardized diagnostic terminologies (DxTMs) in dentistry has long been the subject of academic debate. This paper discusses the strategies suggested by a group of dental stakeholders to enhance the uptake of DxTMs. Through unstructured interviewing at the 'Toward a Diagnosis-Driven Profession' National Conference held on 19 March 2016 in Los Angeles, CA, USA participants were asked how enthusiastic they were about implementing and consistently using DxTMs at their work. They also brainstormed on strategies to improve the widespread use of DxTMs. Their responses are summarized by recursive abstraction and presented in themes. Conference participants were very enthusiastic about using a DxTM in their place of work. Participants enumerated several strategies to make DxTMs more appealing including: the use of mandates, a value proposition for providers, communication and education, and integration with EHRs and existing systems. All groups across the dental healthcare delivery spectrum will need to work together for the success of the widespread and consistent use of DxTMs. Understanding the provider perspective is however the most critical step in achieving this goal, as they are the group who will ultimately be saddled with the critical task of ensuring DxTM use at the point of care.

  4. Enhanced jump performance when providing augmented feedback compared to an external or internal focus of attention.

    Science.gov (United States)

    Keller, Martin; Lauber, Benedikt; Gottschalk, Marius; Taube, Wolfgang

    2015-01-01

    Factors such as an external focus of attention (EF) and augmented feedback (AF) have been shown to improve performance. However, the efficacy of providing AF to enhance motor performance has never been compared with the effects of an EF or an internal focus of attention (IF). Therefore, the aim of the present study was to identify which of the three conditions (AF, EF or IF) leads to the highest performance in a countermovement jump (CMJ). Nineteen volunteers performed 12 series of 8 maximum CMJs. Changes in jump height between conditions and within the series were analysed. Jump heights differed between conditions (P jump heights at the end of the series in AF (+1.60%) and lower jump heights at the end of the series in EF (-1.79%) and IF (-1.68%) were observed. Muscle activity did not differ between conditions. The differences between conditions and within the series provide evidence that AF leads to higher performance and better progression within one series than EF and IF. Consequently, AF seems to outperform EF and IF when maximising jump height.

  5. Omega-3 polyunsaturated fatty acids enhance cerebral angiogenesis and provide long-term protection after stroke

    Science.gov (United States)

    Wang, Jiayin; Shi, Yejie; Zhang, Lili; Zhang, Feng; Hu, Xiaoming; Zhang, Wengting; Leak, Rehana K.; Gao, Yanqin; Chen, Ling; Chen, Jun

    2014-01-01

    Stroke is a devastating neurological disorder and one of the leading causes of death and serious disability. After cerebral ischemia, revascularization in the ischemic boundary zone provides nutritive blood flow as well as various growth factors to promote the survival and activity of neurons and neural progenitor cells. Enhancement of angiogenesis and the resulting improvement of cerebral microcirculation are key restorative mechanisms and represent an important therapeutic strategy for ischemic stroke. In the present study, we tested the hypothesis that post-stroke angiogenesis would be enhanced by omega-3 polyunsaturated fatty acids (n-3 PUFAs), a major component of dietary fish oil. To this end, we found that transgenic fat-1 mice that overproduce n-3 PUFAs exhibited long-term behavioral and histological protection against transient focal cerebral ischemia (tFCI). Importantly, fat-1 transgenic mice also exhibited robust improvements in revascularization and angiogenesis compared to wild type littermates, suggesting a potential role for n-3 fatty acids in post-stroke cerebrovascular remodeling. Mechanistically, n-3 PUFAs induced upregulation of angiopoietin 2 (Ang 2) in astrocytes after tFCI and stimulated extracellular Ang 2 release from cultured astrocytes after oxygen and glucose deprivation. Ang 2 facilitated endothelial proliferation and barrier formation in vitro by potentiating the effects of VEGF on phospholipase Cγ1 and Src signaling. Consistent with these findings, blockade of Src activity in post-stroke fat-1 mice impaired n-3 PUFA-induced angiogenesis and exacerbated long-term neurological outcomes. Taken together, our findings strongly suggest that n-3 PUFA supplementation is a potential angiogenic treatment capable of augmenting brain repair and improving long-term functional recovery after cerebral ischemia. PMID:24794156

  6. Enhanced Exercise Therapy in Parkinson?s disease: A comparative effectiveness trial

    OpenAIRE

    Ridgel, Angela L.; Walter, Benjamin L.; Tatsuoka, Curtis; Walter, Ellen M.; Col?n-Zimmermann, Kari; Welter, Elisabeth; Sajatovic, Martha

    2015-01-01

    Objectives Exercise can improve motor function in people with Parkinson?s disease but depression reduces the motivation to participate in regular exercise. The aim of this study was to develop a novel Enhanced Exercise Therapy program that uses manual-driven guided exercise and peer-facilitated psychoeducation for individuals with Parkinson?s disease and depression. Design 24 week randomized controlled design. Methods Thirty individuals were randomized to Enhanced Exercise Therapy or self-gui...

  7. Enhancing Behavioral Couple Therapy: Addressing the Therapeutic Alliance, Hope, and Diversity

    Science.gov (United States)

    Kelly, Shalonda; Iwamasa, Gayle Y.

    2005-01-01

    The strengths and weaknesses of behavioral couple therapy (BCT) are well documented and disseminated, and this couple therapy approach continues to evolve. Newer behaviorally based approaches share an openness to integration and can enhance the ability of BCT to address three key process-related variables: the therapeutic alliance, hope, and…

  8. Autologous Immune Enhancement Therapy for Cancer - Our experience since 2004

    Directory of Open Access Journals (Sweden)

    Hiroshi Terunuma

    2012-01-01

    Full Text Available Cancer, the major killer disease of the century requires a multi-pronged approach and among the latest modalities of treatments, Immunotherapy occupies a promising role. Immunotherapy for cancer was first started to be practised in the NIH and cell based immunotherapy for cancer is in practice for the past three decades. [1, 2] There are several literatures from various countries on the successful application of cell based Immunotherapies for various solid tumours and haematological malignancies. [3-8] Our team’s association with immune cells started when I was working on RNA transcriptome analysis to understand the immune system in HIV carriers which in turn required in vitro expansion of human Natural Killer (NK cells. [9] This led to the customization of protocols which has resulted in successful in vitro expansion, activation of NK cells and T cells for Immunotherapy. The purpose of Biotherapy institute of Japan (BIJ is to support research and clinical application of immune cells like NK cells, γδT cells, αβT cells, Cytotoxic T lymphocytes (CTL and Dendritic cells (DC for application as Autologous Immune Enhancement Therapy (AIET to fight against cancer. AIET using NK cells, CTLs, DCs etc have been administered for more than 5000 patients since 2004 till date by BIJ. Principle of AIET: For AIET using NK cells, the process involves separation of lymphocytes from the peripheral blood of the patient followed by selective NK cell expansion using the expansion kit (BINKIT, BIJ, JAPAN without feeder layers and then infusion of the expanded-activated NK cells. [10,11] As reports suggest that the activity of peripheral blood NK cells are lower in cancer patients compared to normal individuals [12] and as in vitro expansion of NK cells increases the cytotoxic ability 5 to 10 fold, [13] the NK cells are expanded in vivo and then infused to the patient in AIET. We are also working on combination immunotherapy using NK cells and CTLs and also NK

  9. Multifunctional liposomes for enhanced anti-cancer therapy

    Science.gov (United States)

    Falcao, Claudio Borges

    2011-12-01

    with half of the concentration needed for G3139 alone in CL to reduce the cell viability by 40%. Also, it was found greater apoptotic signal in cells treated with CLs containing D-(KLAKLAK)2/G3139 complexes than CLs with G3139 only. In vivo, D-(KLAKLAK) 2/G3139 complexes in CL significantly inhibited tumor growth compared to the saline treated group, through apoptosis induction. However, the mechanism involved in cell death by apoptosis seems to be independent of reduction of bcl-2 protein levels. PEG2000 at 1% mol could significantly reduce activity of PCL formulation towards B16(F10) cells compared to CLs. After pre-incubation at pH 7.4, PCL and pH-PCL had decreased activity compared to CL towards B16(F10) cells. After pre-incubation at pH 5.0, while CL and PCL had the same activity with the cells as in neutral pH, pH-PCL formulation had its PEG cleaved and its cytotoxicity was restored against the melanoma cells. Thus, D-(KLAKLAK)2/G3139 complexes in CL had enhanced anti-cancer therapy, through apoptosis, than G3139 alone in CL in vitro and in vivo. In vitro, PCL and pH-PCL particles obtained can have a prolonged blood residence time, and, once a tumor tissue is reached, pH-PCL can have its cytotoxicity restored because of hydrolysis of cleavable PEG at a lowered pH.

  10. Mirror therapy enhances upper extremity motor recovery in stroke patients.

    Science.gov (United States)

    Mirela Cristina, Luca; Matei, Daniela; Ignat, Bogdan; Popescu, Cristian Dinu

    2015-12-01

    The purpose of this study was to evaluate the effects of mirror therapy program in addition with physical therapy methods on upper limb recovery in patients with subacute ischemic stroke. 15 subjects followed a comprehensive rehabilitative treatment, 8 subjects received only control therapy (CT) and 7 subjects received mirror therapy (MT) for 30 min every day, five times a week, for 6 weeks in addition to the conventional therapy. Brunnstrom stages, Fugl-Meyer Assessment (upper extremity), the Ashworth Scale, and Bhakta Test (finger flexion scale) were used to assess changes in upper limb motor recovery and motor function after intervention. After 6 weeks of treatment, patients in both groups showed significant improvements in the variables measured. Patients who received MT showed greater improvements compared to the CT group. The MT treatment results included: improvement of motor functions, manual skills and activities of daily living. The best results were obtained when the treatment was started soon after the stroke. MT is an easy and low-cost method to improve motor recovery of the upper limb.

  11. Comparison of gadolinium nanoparticles and molecular contrast agents for radiation therapy-enhancement.

    Science.gov (United States)

    Delorme, Rachel; Taupin, Florence; Flaender, Mélanie; Ravanat, Jean-Luc; Champion, Christophe; Agelou, Mathieu; Elleaume, Hélène

    2017-11-01

    . In vitro, radiosensitization was observed with GdNPs incubated 5 h with the cells (2.1 mg Gd/mL) at all energies. Experimental DEFs were found to be greater than computational DEFs but follow a similar trend with irradiation energy. However, an important radiosensitivity was observed experimentally with GdNPs at high energy (1.25 MeV), whereas no effect was expected from modeling. This effect was correlated with GdNPs incubation time. In vitro, GdCA provided no dose enhancement at 1.25 MeV energies, in agreement with computed data. These results provide a foundation on which to base optimizations of the physical parameters in Gd radiation-enhanced therapy. Strong evidence was provided that GdCA or GdNPs could both be used for radiation dose-enhancement therapy. There in vivo biological distribution, in the tumor volume and at the cellular scale, will be the key factor for providing large dose enhancements and determine their therapeutic efficacy. © 2017 American Association of Physicists in Medicine.

  12. Comparison of Family and Therapist Perceptions of Physical and Occupational Therapy Services Provided to Young Children with Cerebral Palsy

    Science.gov (United States)

    LaForme Fiss, Alyssa C.; McCoy, Sarah Westcott; Chiarello, Lisa A.

    2012-01-01

    The purpose of this study was to determine whether parents and therapists have similar perceptions of therapy services provided to young children with cerebral palsy (CP), reflecting collaboration and provision of family-centered care. Forty-six parents of young children with CP and 40 therapists providing services for those children participated.…

  13. AWG, Enhancing Professional Skills, Providing Resources and Assistance for Women in the Geosciences

    Science.gov (United States)

    Sundermann, C.; Cruse, A. M.; AssociationWomen Geoscientists

    2011-12-01

    The Association for Women Geoscientists (AWG) was founded in 1977. AWG is an international organization, with ten chapters, devoted to enhancing the quality and level of participation of women in geosciences, and introducing women and girls to geoscience careers. Our diverse interests and expertise cover the entire spectrum of geoscience disciplines and career paths, providing unexcelled networking and mentoring opportunities to develop leadership skills. Our membership is brought together by a common love of earth, atmospheric and ocean sciences, and the desire to ensure rewarding opportunities for women in the geosciences. AWG offers a variety of scholarships, including the Chrysalis scholarship for women who are returning to school after a life-changing interruption, and the Sands and Takken awards for students to make presentations at professional meetings. AWG promotes professional development through workshops, an online bi-monthly newsletter, more timely e-mailed newsletters, field trips, and opportunities to serve in an established professional organization. AWG recognizes the work of outstanding women geoscientists and of outstanding men supporters of women in the geosciences. The AWG Foundation funds ten scholarships, a Distinguished Lecture Program, the Geologist-in-the-Parks program, Science Fair awards, and numerous Girl Scout programs. Each year, AWG sends a contingent to Congressional Visits Day, to help educate lawmakers about the unique challenges that women scientists face in the geoscience workforce.

  14. Enhancing patient-provider communication for long-term post-stroke spasticity management.

    Science.gov (United States)

    Sunnerhagen, K S; Francisco, G E

    2013-11-01

    Stroke is a major public health concern, with estimated 16 million people worldwide experiencing first-time strokes each year, a number that is expected to rise. Two-thirds of those experiencing a stroke are younger than 70 years of age. Stroke is a leading cause of disability in adults as a result of major sequelae that include spasticity, cognitive impairment, paresis, and depression. Disabling spasticity, defined as spasticity severe enough to require intervention, occurs in 4% of stroke survivors within 1 year of first-time stroke. The aim of this report is to focus instead on a discussion of patient-provider communication, and its role in post-stroke spasticity (PSS) rehabilitation within the context of patient-centered health care. A discussion based on a review of the literature, mainly since 2000. Problems within communication are identified and suggestion to enhance communication are proposed thus improving patient-centered goal setting/goal achievement for the effective management of spasticity rehabilitation. These are as follows: (i) involving family members, (ii) educating patients and family members on stroke and rehabilitation, and (iii) establishing a common definition for long-term goals. Increased communication among physicians, patients, and payers may bridge some of the gaps and increase the effectiveness of PSS rehabilitation and management. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Epidemiology of tuberculosis in a high HIV prevalence population provided with enhanced diagnosis of symptomatic disease.

    Directory of Open Access Journals (Sweden)

    Elizabeth L Corbett

    2007-01-01

    Full Text Available Directly observed treatment short course (DOTS, the global control strategy aimed at controlling tuberculosis (TB transmission through prompt diagnosis of symptomatic smear-positive disease, has failed to prevent rising tuberculosis incidence rates in Africa brought about by the HIV epidemic. However, rising incidence does not necessarily imply failure to control tuberculosis transmission, which is primarily driven by prevalent infectious disease. We investigated the epidemiology of prevalent and incident TB in a high HIV prevalence population provided with enhanced primary health care.Twenty-two businesses in Harare, Zimbabwe, were provided with free smear- and culture-based investigation of TB symptoms through occupational clinics. Anonymised HIV tests were requested from all employees. After 2 y of follow-up for incident TB, a culture-based survey for undiagnosed prevalent TB was conducted. A total of 6,440 of 7,478 eligible employees participated. HIV prevalence was 19%. For HIV-positive and -negative participants, the incidence of culture-positive tuberculosis was 25.3 and 1.3 per 1,000 person-years, respectively (adjusted incidence rate ratio = 18.8; 95% confidence interval [CI] = 10.3 to 34.5: population attributable fraction = 78%, and point prevalence after 2 y was 5.7 and 2.6 per 1,000 population (adjusted odds ratio = 1.7; 95% CI = 0.5 to 6.8: population attributable fraction = 14%. Most patients with prevalent culture-positive TB had subclinical disease when first detected.Strategies based on prompt investigation of TB symptoms, such as DOTS, may be an effective way of controlling prevalent TB in high HIV prevalence populations. This may translate into effective control of TB transmission despite high TB incidence rates and a period of subclinical infectiousness in some patients.

  16. The use of genes for performance enhancement: doping or therapy?

    National Research Council Canada - National Science Library

    Oliveira, R S; Collares, T F; Smith, K R; Collares, T V; Seixas, F K

    2011-01-01

    ...) to enhance athletic performance. In such 'gene doping', exogenous genetic sequences are inserted into a specific tissue, altering cellular gene activity or leading to the expression of a protein product...

  17. Comparison of Physical Pretreatment Regimens to Enhance Protoporphyrin IX Uptake in Photodynamic Therapy

    DEFF Research Database (Denmark)

    Bay, Christiane; Lerche, Catharina Margrethe; Ferrick, Bradford

    2017-01-01

    Importance: Skin pretreatment is recommended for adequate penetration of topical photosensitizing agents and subsequent protoporphyrin IX (PPIX) accumulation in photodynamic therapy (PDT). Objective: To compare the relative potential of different physical pretreatments to enhance PPIX fluorescence...... indicate relatively enhanced PDT response by AFXL pretreatment in diseased skin. Trial Registration: clinicaltrials.gov Identifier: NCT02372370....

  18. Education Affects Attitudes of Physical Therapy Providers toward People with Dementia

    Science.gov (United States)

    Staples, William H.; Killian, Clyde B.

    2012-01-01

    A survey was sent to every skilled nursing home (N = 495) in Indiana regarding the demographics, education, and whether the severity of dementia impacts the attitudes of people in physical therapy practice. Physical therapists (PTs) and physical therapist assistants (PTAs) practicing in nursing homes spend considerable time (44.0%) working with…

  19. Provider-patient in-office discussions of response to hepatitis C antiviral therapy and impact on patient comprehension.

    Science.gov (United States)

    Hamilton, Heidi E; Nelson, Meaghan; Martin, Paul; Cotler, Scott J

    2006-04-01

    Providers need to communicate projected response rates effectively to enable patients with hepatitis C virus to make informed decisions about therapy. This study used interactional sociolinguistics (1) to evaluate how gastroenterologists and allied health professionals communicate information regarding response rates to antiviral therapy, (2) to determine how these discussions relate to where the patient is in the continuum of evaluation and treatment, (3) to assess whether patients were aligned with providers in their perceptions of response rates after office visits, and (4) to identify factors that improve provider-patient alignment. Gastroenterologists, allied health professionals, and patients with hepatitis C virus were videotaped and audiotaped during regularly scheduled visits. Postvisit interviews were conducted separately with patients and providers. Visits and postvisits were transcribed and analyzed using validated sociolinguistic techniques. The phase of hepatitis C virus treatment shaped the benchmarks of response talk, although across the treatment continuum providers overwhelmingly made strategic use of positive statistics, providing motivation. In postvisit interviews, 55% of providers and patients were aligned on response rates. Patients with a favorable outcome and patients who asked response-related questions in the visit were more likely to be aligned with providers. Areas identified for improvement included the tendency to discuss response rates before an individualized assessment could be made, balancing motivation and accuracy, and assessing the patient's perspective before delivering any bad news, if necessary. Sociolinguistic analysis provides a powerful tool to evaluate provider-patient interactions and to identify ways to improve in-office communication regarding antiviral therapy.

  20. Continuous Renal Replacement Therapy: Reviewing Current Best Practice to Provide High-Quality Extracorporeal Therapy to Critically Ill Patients.

    Science.gov (United States)

    Connor, Michael J; Karakala, Nithin

    2017-07-01

    Continuous renal replacement therapy (CRRT) use continues to expand globally. Despite improving technology, CRRT remains a complex intervention. Delivery of high-quality CRRT requires close collaboration of a multidisciplinary team including members of the critical care medicine, nephrology, nursing, pharmacy, and nutrition support teams. While significant gaps in medical evidence regarding CRRT persist, the growing evidence base supports evolving best practice and consensus to define high-quality CRRT. Unfortunately, there is wide variability in CRRT operating characteristics and limited uptake of these best practices. This article will briefly review the current best practice on important aspects of CRRT delivery including CRRT dose, anticoagulation, dialysis vascular access, fluid management, and drug dosing in CRRT. Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  1. Glucocorticoids enhance in vivo exposure-based therapy of spider phobia.

    Science.gov (United States)

    Soravia, Leila M; Heinrichs, Markus; Winzeler, Livia; Fisler, Melanie; Schmitt, Wolfgang; Horn, Helge; Dierks, Thomas; Strik, Werner; Hofmann, Stefan G; de Quervain, Dominique J-F

    2014-05-01

    Preclinical and clinical studies indicate that the administration of glucocorticoids may promote fear extinction processes. In particular, it has been shown that glucocorticoids enhance virtual reality based exposure therapy of fear of heights. Here, we investigate whether glucocorticoids enhance the outcome of in vivo exposure-based group therapy of spider phobia. In a double blind, block-randomized, placebo-controlled, between-subject study design, 22 patients with specific phobia of spiders were treated with two sessions of in vivo exposure-based group therapy. Cortisol (20 mg) or placebo was orally administered 1 hr before each therapy session. Patients returned for a follow-up assessment one month after therapy. Exposure-based group therapy led to a significant decrease in phobic symptoms as assessed with the Fear of Spiders Questionnaire (FSQ) from pretreatment to immediate posttreatment and to follow-up. The administration of cortisol to exposure therapy resulted in increased salivary cortisol concentrations and a significantly greater reduction in fear of spiders (FSQ) as compared to placebo at follow-up, but not immediately posttreatment. Furthermore, cortisol-treated patients reported significantly less anxiety during standardized exposure to living spiders at follow-up than placebo-treated subjects. Notably, groups did not differ in phobia-unrelated state-anxiety before and after the exposure sessions and at follow-up. These findings indicate that adding cortisol to in vivo exposure-based group therapy of spider phobia enhances treatment outcome. © 2013 Wiley Periodicals, Inc.

  2. Narrative enhancement and cognitive therapy (NECT) effectiveness: a quasi-experimental study.

    Science.gov (United States)

    Roe, David; Hasson-Ohayon, Ilanit; Mashiach-Eizenberg, Michal; Derhy, Oren; Lysaker, Paul H; Yanos, Philip T

    2014-04-01

    Accumulated evidence suggests that approximately one third of people with a serious mental illness (SMI) experience elevated self-stigma. Narrative enhancement and cognitive therapy (NECT) is a structured group-based intervention aimed to reduce self-stigma. The current study aims to examine the effectiveness of NECT. A quasi-experimental design. Baseline and follow-up data were collected and outcomes were compared between 63 persons with SMI who participated in NECT and 56 persons who received treatment as usual. The NECT treatment group showed significant (p < .05) reductions in self-stigma and increases in self-esteem, quality of life, and Hope-Agency scores between pre- and posttreatment assessments, compared with the control group. The current results provide preliminary support for the use of NECT as an effective treatment to reduce self-stigma and its implications for treatment and practice are discussed. © 2013 Wiley Periodicals, Inc.

  3. Gene manipulation to enhance MIBG-targeted radionuclide therapy

    Energy Technology Data Exchange (ETDEWEB)

    Mairs, Robert J. [Targeted Therapy Group, Centre for Oncology and Applied Pharmacology, Cancer Research UK Beatson Laboratories, University of Glasgow, G61 1BD Glasgow (United Kingdom)]. E-mail: r.mairs@beatson.gla.ac.uk; Fullerton, Natasha E. [Targeted Therapy Group, Centre for Oncology and Applied Pharmacology, Cancer Research UK Beatson Laboratories, University of Glasgow, G61 1BD Glasgow (United Kingdom); Department of Urology, Gartnavel General Hospital, Glasgow G12 0NY (United Kingdom); Cosimo, Emilio [Targeted Therapy Group, Centre for Oncology and Applied Pharmacology, Cancer Research UK Beatson Laboratories, University of Glasgow, G61 1BD Glasgow (United Kingdom); Boyd, Marie [Targeted Therapy Group, Centre for Oncology and Applied Pharmacology, Cancer Research UK Beatson Laboratories, University of Glasgow, G61 1BD Glasgow (United Kingdom)

    2005-10-01

    The goal of targeted radionuclide therapy is the deposition in malignant cells of sterilizing doses of radiation without damaging normal tissue. The radiopharmaceutical [{sup 131}I]meta-iodobenzylguanidine ([{sup 131}I]MIBG) is an effective single agent for the treatment of neuroblastoma. However, uptake of the drug in malignant sites is insufficient to cure disease. A growing body of experimental evidence indicates exciting possibilities for the integration of gene transfer with [{sup 131}I]MIBG-targeted radiotherapy.

  4. Antioxidant therapy enhances pulpal healing in bleached teeth.

    Science.gov (United States)

    Lima, Adriano Fonseca; Marques, Marcelo Rocha; Soares, Diana Gabriela; Hebling, Josimeri; Marchi, Giselle Maria; de Souza Costa, Carlos Alberto

    2016-02-01

    The purpose of this study was to evaluate the histopathological effects of an antioxidant therapy on the pulp tissue of rat teeth exposed to a bleaching gel with 35% hydrogen peroxide. Forty rats were subjected to oral ingestion by gavage of distilled water (DW) or ascorbic acid (AA) 90 min before the bleaching therapy. For the bleaching treatment, the agent was applied twice for 5 min each to buccal surfaces of the first right mandibular molars. Then, the animals were sacrificed at 6 hr, 24 hr, 3 day, or 7 day post-bleaching, and the teeth were processed for microscopic evaluation of the pulp tissue. At 6 hr, the pulp tissue showed moderate inflammatory reactions in all teeth of both groups. In the DW and AA groups, 100% and 80% of teeth exhibited pulp tissue with significant necrosis and intense tissue disorganization, respectively. At 24 hr, the AA-treated group demonstrated a greater regenerative capability than the DW group, with less intense inflammatory reaction and new odontoblast layer formation in 60% of the teeth. For up to the 7 day period, the areas of pulpal necrosis were replaced by viable connective tissue, and the dentin was underlined by differentiated odontoblast-like cells in most teeth of both groups. A slight reduction in initial pulpal damage during post-bleaching was promoted by AA therapy. However, the pulp tissue of AA-treated animals featured faster regenerative potential over time.

  5. Antioxidant therapy enhances pulpal healing in bleached teeth

    Directory of Open Access Journals (Sweden)

    Adriano Fonseca Lima

    2016-02-01

    Full Text Available Objectives The purpose of this study was to evaluate the histopathological effects of an antioxidant therapy on the pulp tissue of rat teeth exposed to a bleaching gel with 35% hydrogen peroxide. Materials and Methods Forty rats were subjected to oral ingestion by gavage of distilled water (DW or ascorbic acid (AA 90 min before the bleaching therapy. For the bleaching treatment, the agent was applied twice for 5 min each to buccal surfaces of the first right mandibular molars. Then, the animals were sacrificed at 6 hr, 24 hr, 3 day, or 7 day post-bleaching, and the teeth were processed for microscopic evaluation of the pulp tissue. Results At 6 hr, the pulp tissue showed moderate inflammatory reactions in all teeth of both groups. In the DW and AA groups, 100% and 80% of teeth exhibited pulp tissue with significant necrosis and intense tissue disorganization, respectively. At 24 hr, the AA-treated group demonstrated a greater regenerative capability than the DW group, with less intense inflammatory reaction and new odontoblast layer formation in 60% of the teeth. For up to the 7 day period, the areas of pulpal necrosis were replaced by viable connective tissue, and the dentin was underlined by differentiated odontoblast-like cells in most teeth of both groups. Conclusions A slight reduction in initial pulpal damage during post-bleaching was promoted by AA therapy. However, the pulp tissue of AA-treated animals featured faster regenerative potential over time

  6. Candesartan and amlodipine combination therapy provides powerful vascular protection in stroke-prone spontaneously hypertensive rats.

    Science.gov (United States)

    Takai, Shinji; Jin, Denan; Shimosato, Takashi; Sakonjo, Hiroshi; Miyazaki, Mizuo

    2011-02-01

    The vascular protective effects of placebo, candesartan (1 mg kg(-1) per day) monotherapy, candesartan (1 mg kg(-1) per day) and amlodipine (1 mg kg(-1) per day) combination therapy, and candesartan (1 mg kg(-1) per day) and hydrochlorothiazide (HCTZ) (10 mg kg(-1) per day) combination therapy for 2 weeks were compared in stroke-prone, spontaneously hypertensive rats. Candesartan monotherapy significantly reduced blood pressure, and both combination therapies were equally and significantly lower than the monotherapy. Acetylcholine-induced vascular relaxation was significantly stronger in all therapeutic groups than in the placebo-treated group. Furthermore, the relaxation was significantly stronger in the candesartan plus amlodipine-treated group than in the candesartan-treated group; however, there was no significant difference between the candesartan- and candesartan plus HCTZ-treated groups. Vascular gene expressions of the NADPH oxidase subunits p22(phox), gp91(phox), NOX1 and NOX4 were significantly attenuated in all therapeutic groups compared with the placebo-treated group, and there were no significant differences among those groups. However, a significant augmentation of vascular superoxide dismutase activity was observed in the candesartan plus amlodipine-treated group, but not in other groups. Malondialdehyde levels in the vascular tissues were significantly attenuated in all therapeutic groups. Compared with the candesartan-treated group, significant attenuation was observed in the candesartan plus amlodipine-treated group, but not in the candesartan plus HCTZ-treated group. Immunohistological analysis showed that areas positive for 4-hydroxy-2-nonenal were significantly reduced in all therapeutic groups, but this reduction was significantly greater for the candesartan plus amlodipine-treated group than for the candesartan-treated group. Thus, candesartan and amlodipine combination therapy could have a powerful protective effect in vascular tissues via

  7. The effects of enhanced access to antiretroviral therapy: a qualitative ...

    African Journals Online (AJOL)

    Results: Most participants felt that enhanced access to ART would increase risky sexual behaviour; namely promiscuity, lack of faithfulness among couples, multiple partners, prostitution, unprotected sexual practices, rape and lack of abstinence as the risky sexual behaviours. A few FGDs, however, indicated that increased ...

  8. Cilostazol Improves Proangiogenesis Functions in Human Early Endothelial Progenitor Cells through the Stromal Cell-Derived Factor System and Hybrid Therapy Provides a Synergistic Effect In Vivo.

    Science.gov (United States)

    Tseng, Shih-Ya; Chao, Ting-Hsing; Li, Yi-Heng; Cho, Chung-Lung

    2016-01-01

    This study investigated the effect of cilostazol on proangiogenesis functions in human early endothelial progenitor cells (EPCs) in vitro and the therapeutic implication of hybrid therapy with cilostazol and human early EPCs in vivo. Cilostazol significantly increased colony-forming units and enhanced differentiation of EPCs toward endothelial lineage. Treatments resulted in antiapoptotic effects and stimulated proliferation and migration and in vitro vascular tube formation through activation of stromal cell-derived factor-1 (SDF-1)/C-X-C chemokine receptor type 4 (CXCR4)/phosphatidylinositol-3 kinase (PI3K)/Akt signaling pathway. Blood flow recovery and capillary density in murine ischemic hindlimbs were significantly improved in cilostazol-treated, human early EPCs-treated, and cotreatment groups. The effects were attenuated with SDF-1α inhibition. Plasma SDF-1α levels were significantly higher in 3 active treatment groups after surgery, with greatest effects observed in hybrid therapy. The angiogenic effects of transplanted EPCs pretreated with cilostazol ex vivo were superior to untreated EPCs using in vivo Matrigel assay. Implanted EPCs were incorporated into the capillary, with pretreatment or cotreatment with cilostazol resulting in enhanced effects. Taken together, cilostazol promotes a large number of proangiogenic functions in human early EPCs through activation of SDF-1/CXCR4/PI3K/Akt signaling, and hybrid therapy provides a synergistic effect in vivo. Cotreatment may be beneficial in ischemic disease.

  9. Enhanced Exercise Therapy in Parkinson’s disease: A comparative effectiveness trial

    Science.gov (United States)

    Ridgel, Angela L.; Walter, Benjamin L.; Tatsuoka, Curtis; Walter, Ellen M.; Colón-Zimmermann, Kari; Welter, Elisabeth; Sajatovic, Martha

    2015-01-01

    Objectives Exercise can improve motor function in people with Parkinson’s disease but depression reduces the motivation to participate in regular exercise. The aim of this study was to develop a novel Enhanced Exercise Therapy program that uses manual-driven guided exercise and peer-facilitated psychoeducation for individuals with Parkinson’s disease and depression. Design 24 week randomized controlled design. Methods Thirty individuals were randomized to Enhanced Exercise Therapy or self-guided therapy, and evaluated at baseline, 12-weeks and at 24-weeks. Enhanced Exercise Therapy included group exercise and group psychoeducation for 12 weeks. Between 13–24 weeks, individuals had access to the fitness facility but group sessions were not held. Self-guided therapy included written guidelines for a self-paced exercise program and psychoeducation. Primary outcome measures included the number of exercise sessions and International Physical Activity Questionnaire score. Secondary measures included resting heart rate, supine blood pressure, estimated VO2max and incidence of orthostatic hypotension. Results Twenty four individuals completed the study (80% retention) and both groups attended similar number of exercise sessions. There were no significant changes in cardiovascular fitness measures but there was a significant increase in the amount of physical activity in the Enhanced Exercise Therapy group and a decrease in the self-guided therapy group during the post-intervention period. Conclusions Enhanced exercise therapy appears to promote engagement in an exercise program and more physical activity, even after group sessions were concluded in individuals with Parkinson’s disease and depression. PMID:25709055

  10. The Integration of Speech Therapy Techniques with Those of Movement, Music, and Sensory Integrative Therapies in Order to Provide Communication Systems for Severely Emotionally Disturbed Children.

    Science.gov (United States)

    LeShay, Debra N.

    Project LINK at the Developmental Center for Autistic Children in Philadelphia provides therapy to emotionally disturbed children and training and consultation for teachers and mental health professionals. Each child is evaluated by treatment team members through repeated observations and informal assessments. The primary goal of treatment is the…

  11. Management of pain induced by exercise and mobilization during physical therapy programs: views of patients and care providers

    Directory of Open Access Journals (Sweden)

    Rannou François

    2011-07-01

    Full Text Available Abstract Background The expectations of patients for managing pain induced by exercise and mobilization (PIEM have seldom been investigated. We identified the views of patients and care providers regarding pain management induced by exercise and mobilization during physical therapy programs. Methods We performed a qualitative study based on semi-structured interviews with a stratified sample of 12 patients (7 women and 14 care providers (6 women: 4 general practitioners [GPs], 1 rheumatologist, 1 physical medicine physician, 1 geriatrician, 2 orthopedic surgeons, and 5 physical therapists. Results Patients and care providers have differing views on PIEM in the overall management of the state of disease. Patients' descriptions of PIEM were polymorphic, and they experienced it as decreased health-related quality of life. The impact of PIEM was complex, and patient views were sometimes ambivalent, ranging from denial of symptoms to discontinuation of therapy. Care providers agreed that PIEM is generally not integrated in management strategies. Care providers more often emphasized the positive and less often the negative dimensions of PIEM than did patients. However, the consequences of PIEM cited included worsened patient clinical condition, fears about physical therapy, rejection of the physical therapist and refusal of care. PIEM follow-up is not optimal and is characterized by poor transmission of information. Patients expected education on how better to prevent stress and anxiety generated by pain, education on mobilization, and adaptations of physical therapy programs according to pain intensity. Conclusion PIEM management could be optimized by alerting care providers to the situation, improving communication among care providers, and providing education to patients and care providers.

  12. Fractionated aminolevulinic acid-photodynamic therapy provides additional evidence for the use of PDT for non-melanoma skin cancer

    NARCIS (Netherlands)

    de Haas, E. R. M.; de Vijlder, H. C.; Sterenborg, H. J. C. M.; Neumann, H. A. M.; Robinson, D. J.

    2008-01-01

    ?Background Photodynamic therapy (PDT) is an accepted treatment for superficial basal cel carcinoma (sBCC) and Bowens disease. In Rotterdam, extensive preclinical research has lead to an optimized twofold illumination scheme for aminolevulinic acid-PDT (ALA-PDT). Objective To provide additional

  13. Metazoan Nuclear Pores Provide a Scaffold for Poised Genes and Mediate Induced Enhancer-Promoter Contacts.

    Science.gov (United States)

    Pascual-Garcia, Pau; Debo, Brian; Aleman, Jennifer R; Talamas, Jessica A; Lan, Yemin; Nguyen, Nha H; Won, Kyoung J; Capelson, Maya

    2017-04-06

    Nuclear pore complex components (Nups) have been implicated in transcriptional regulation, yet what regulatory steps are controlled by metazoan Nups remains unclear. We identified the presence of multiple Nups at promoters, enhancers, and insulators in the Drosophila genome. In line with this binding, we uncovered a functional role for Nup98 in mediating enhancer-promoter looping at ecdysone-inducible genes. These genes were found to be stably associated with nuclear pores before and after activation. Although changing levels of Nup98 disrupted enhancer-promoter contacts, it did not affect ongoing transcription but instead compromised subsequent transcriptional activation or transcriptional memory. In support of the enhancer-looping role, we found Nup98 to gain and retain physical interactions with architectural proteins upon stimulation with ecdysone. Together, our data identify Nups as a class of architectural proteins for enhancers and supports a model in which animal genomes use the nuclear pore as an organizing scaffold for inducible poised genes. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Providing effective trauma care: the potential for service provider views to enhance the quality of care (qualitative study nested within a multicentre longitudinal quantitative study).

    Science.gov (United States)

    Beckett, Kate; Earthy, Sarah; Sleney, Jude; Barnes, Jo; Kellezi, Blerina; Barker, Marcus; Clarkson, Julie; Coffey, Frank; Elder, Georgina; Kendrick, Denise

    2014-07-08

    To explore views of service providers caring for injured people on: the extent to which services meet patients' needs and their perspectives on factors contributing to any identified gaps in service provision. Qualitative study nested within a quantitative multicentre longitudinal study assessing longer term impact of unintentional injuries in working age adults. Sampling frame for service providers was based on patient-reported service use in the quantitative study, patient interviews and advice of previously injured lay research advisers. Service providers' views were elicited through semistructured interviews. Data were analysed using thematic analysis. Participants were recruited from a range of settings and services in acute hospital trusts in four study centres (Bristol, Leicester, Nottingham and Surrey) and surrounding areas. 40 service providers from a range of disciplines. Service providers described two distinct models of trauma care: an 'ideal' model, informed by professional knowledge of the impact of injury and awareness of best models of care, and a 'real' model based on the realities of National Health Service (NHS) practice. Participants' 'ideal' model was consistent with standards of high-quality effective trauma care and while there were examples of services meeting the ideal model, 'real' care could also be fragmented and inequitable with major gaps in provision. Service provider accounts provide evidence of comprehensive understanding of patients' needs, awareness of best practice, compassion and research but reveal significant organisational and resource barriers limiting implementation of knowledge in practice. Service providers envisage an 'ideal' model of trauma care which is timely, equitable, effective and holistic, but this can differ from the care currently provided. Their experiences provide many suggestions for service improvements to bridge the gap between 'real' and 'ideal' care. Using service provider views to inform service design

  15. Patterns of Substance Use During Cognitive Enhancement Therapy: An 18-Month Randomized Feasibility Study.

    Science.gov (United States)

    Eack, Shaun M; Hogarty, Susan S; Bangalore, Srihari S; Keshavan, Matcheri S; Cornelius, Jack R

    2016-01-01

    Substance use problems are common among people with schizophrenia, as are significant cognitive impairments. Because of potential shared neurobiological pathways, it is possible that cognitive remediation interventions may be associated with improvements in both substance use and cognition. This study examined the impact of cognitive remediation on alcohol and cannabis use and the cognitive correlates of changes in substance use among outpatients with schizophrenia. Individuals with schizophrenia who were receiving outpatient services at a psychiatric clinic and had moderate or higher addiction severity scores (N = 31) were randomized to 18 months of cognitive enhancement therapy (n = 22) or usual care (n = 9). Cognitive enhancement therapy is a cognitive remediation approach that integrates computer-based training in attention, memory, and problem solving with a group-based social cognition curriculum. Usual care was provided to all participants and consisted of routine psychiatric care. Primary outcomes included days of alcohol and cannabis use, assessed with the Timeline Followback method every six months and modeled using penalized quasi-likelihood growth curves. Participants were on average 38.23 (SD = 13.44) years of age, had been ill for 14.19 (SD = 11.28) years, and were mostly male (n = 22, 71%), and about half were Caucasian (n = 16, 52%). Temporal patterns of substance use days were highly variable and followed nonlinear trajectories. Intent-to-treat analyses indicated that, compared to patients only receiving usual care, those receiving cognitive enhancement therapy were significantly less likely to use alcohol (OR = .22; 95% CI: .05, .90; p = .036), but not cannabis (OR = 1.89; 95% CI: .02, 142.99; p = .774) over time, and they reduced their alcohol use at significantly accelerated rates (OR = 1.02; 95% CI: 1.01, 1.03; p = .003). Changes in cognition were variably associated with substance use outcomes, although improvements in visual learning and

  16. Cognitive-behavioral therapy: How medical providers can increase patient and family openness and access to evidence-based multimodal therapy for pediatric migraine

    Science.gov (United States)

    Ernst, Michelle M.; O’Brien, Hope; Powers, Scott W.

    2015-01-01

    While evidence supports the recommendation for cognitive behavioral therapy (CBT) for pediatric migraine, few children actually receive this evidence-based intervention. In this article we briefly review the most recent empirical evidence supporting CBT. We then identify both provider/system-related barriers as well as patient-related barriers. Finally, we provide practical solutions to addressing these barriers in the service of facilitating children receiving optimal comprehensive management of their headaches. PMID:26198185

  17. Enhancing CBT for Chronic Insomnia: A Randomised Clinical Trial of Additive Components of Mindfulness or Cognitive Therapy.

    Science.gov (United States)

    Wong, Mei Yin; Ree, Melissa J; Lee, Christopher W

    2016-09-01

    Although cognitive behavioural therapy (CBT) for insomnia has resulted in significant reductions in symptoms, most patients are not classified as good sleepers after treatment. The present study investigated whether additional sessions of cognitive therapy (CT) or mindfulness-based therapy (MBT) could enhance CBT in 64 participants with primary insomnia. All participants were given four sessions of standard CBT as previous research had identified this number of sessions as an optimal balance between therapist guidance and patient independence. Participants were then allocated to further active treatment (four sessions of CT or MBT) or a no further treatment control. The additional treatments resulted in significant improvements beyond CBT on self-report and objective measures of sleep and were well tolerated as evidenced by no dropouts from either treatment. The effect sizes for each of these additional treatments were large and clinically significant. The mean scores on the primary outcome measure, the Insomnia Severity Index, were 5.74 for CT and 6.69 for MBT, which are within the good-sleeper range. Treatment effects were maintained at follow-up. There were no significant differences between CT and MBT on any outcome measure. These results provide encouraging data on how to enhance CBT for treatment of insomnia. Copyright © 2015 John Wiley & Sons, Ltd. CBT treatments for insomnia can be enhanced using recent developments in cognitive therapy. CBT treatments for insomnia can be enhanced using mindfulness-based treatments. Both cognitive therapy and mindfulness produce additional clinically significant change. Copyright © 2015 John Wiley & Sons, Ltd.

  18. Enhanced 5-aminolevulinic acid-gold nanoparticle conjugate-based photodynamic therapy using pulse laser

    Science.gov (United States)

    Xu, Hao; Yao, Cuiping; Wang, Jing; Chang, Zhennan; Zhang, Zhenxi

    2016-02-01

    The low bioavailability is a crucial limitation for the application of 5-aminolevulinic acid (ALA) in theranostics. In this research, 5-aminolevulinic acid and gold nanoparticle conjugates (ALA-GNPs) were synthesized to improve the bioavailability of ALA and to investigate the impact of ALA photodynamic therapy (ALA-PDT) in Hela cells. A 532 nm pulse laser and light-emitting diode (central wavelengths 502 nm) were jointly used as light sources in PDT research. The results show a 532 nm pulse laser can control ALA release from ALA-GNPs by adjusting the pulse laser dose. This laser control release may be attributed to the heat generation from GNPs under pulse laser irradiation, which indicates accurately adjusting the pulse laser dose to control the drug release in the cell interior can be considered as a new cellular surgery modality. Furthermore, the PDT results in Hela cells indicate the enhancement of ALA release by pulse laser before PDT can promote the efficacy of cell eradication in the light-emitting diode PDT (LED-PDT). This laser mediated drug release system can provide a new online therapy approach in PDT and it can be utilized in the optical monitor technologies based individual theranostics.

  19. A New Green Titania with Enhanced NIR Absorption for Mitochondria-Targeted Cancer Therapy

    Science.gov (United States)

    Mou, Juan; Lin, Tianquan; Huang, Fuqiang; Shi, Jianlin; Chen, Hangrong

    2017-01-01

    A new kind of green titania (G-TiO2-x) with obvious green color was facilely synthesized from black titania (B-TiO2-x) through subsequently strong ultrasonication. Comparatively, this stable G-TiO2-x shows much enhanced near infrared (NIR) absorption, especially around 920 nm, which can be ascribed to the obvious change of TiO2-x lattice order owing to the effect of ultrasonication. This feature enables G-TiO2-x to be stimulated with 980 nm laser in the combined photodynamic therapy (PDT) and photothermal therapy (PTT), which is greatly beneficial for improving tissue penetration depth. Furthermore, since mitochondria are preferred subcellular organelles for PDT/PTT, G-TiO2-x was further designed to conjugate with triphenylphosphonium (TPP) ligand for mitochondria-targeted PDT/PTT to obtain precise cancer treatment. Attributing to the high mitochondria-targeting efficiency and simultaneously synergistic PDT/PTT, high phototherapeutic efficacy and safety with a much lower laser power density (980 nm, 0.72 W cm-2) and low materials dosage were achieved both in vitro and in vivo. In addition, negligible toxicity was found, indicating high biocompatibility. This novel G-TiO2-x could provide new strategies for future precise minimal/non-invasive tumor treatment. PMID:28529636

  20. Leadership qualities when providing therapy for women who suffer from eating difficulties.

    Science.gov (United States)

    Rørtveit, Kristine; Severinsson, Elisabeth

    2012-07-01

    The aim of this study was to reflect on aspects of mental health nursing leadership qualities with special focus on the therapeutic process for women who suffer from eating difficulties (ED). Therapy for patients with ED involves motivating them to make meaningful changes. Leadership qualities in MHN should focus on the relationship with the patient and positive empowerment processes. In-depth interviews were conducted with six women suffering from ED who had participated in art therapy. The interviews were analysed by means of an interpretative hermeneutic approach. A main theme 'The mental health nurse as a formative and mindful leader in a group therapeutic relationship' and two themes 'Leading sensitively towards awakening the patients' awareness of their pre-understanding' and 'Leading dialectically towards solving patients' existential dilemmas' were developed and comprised two aspects of leadership. The nurse-patient relationship is influenced by the patients' pre-understanding and existential dilemmas. Leadership qualities associated with being formative and mindful represent important aspects of this relationship and should be investigated and thematically described in greater detail in future research. The nurse-patient relationship should focus on clinical supervision, in order to strengthen the nurses' leadership qualities in terms of being aware and dialectical. © 2011 Blackwell Publishing Ltd.

  1. Technology-Enhanced Peer Review: Benefits and Implications of Providing Multiple Reviews

    Science.gov (United States)

    Papadopoulos, Pantelis M.; Lagkas, Thomas D.; Demetriadis, Stavros N.

    2017-01-01

    This study analyses the impact of self and peer feedback in technology-enhanced peer review settings. The impact of receiving peer comments ("receiver" perspective) is compared to that of reaching own insights by reviewing others' work ("giver" perspective). In this study, 38 sophomore students were randomly assigned in two…

  2. Coal-oxygen process provides CO/sub 2/ for enhanced recovery

    Energy Technology Data Exchange (ETDEWEB)

    Abraham, B.M.

    1982-03-15

    Carbon dioxide for use in enhanced oil recovery could be produced by electric power plants which burn coal in an O/SUB/2/CO/SUB/2 mixture. The process appears to be competitive with the monoethanol amine and hot potassium carbonate methods of CO/SUB/2 recovery from flue gases.

  3. Providing Training Enhances the Biomechanical Improvements of an Alternative Computer Mouse Design

    NARCIS (Netherlands)

    Houwink, A.; Oude Hengel, K.M.; Odell, D.; Dennerlein, J.T.

    2009-01-01

    Objective: The purpose of this study is to determine if an alternative mouse promotes more neutral postures and decreases forearm muscle activity and if training enhances these biomechanical benefits. Background: Computer mouse use is a risk factor for developing musculoskeletal disorders;

  4. Nanoparticles for Radiation Therapy Enhancement: the Key Parameters.

    Science.gov (United States)

    Retif, Paul; Pinel, Sophie; Toussaint, Magali; Frochot, Céline; Chouikrat, Rima; Bastogne, Thierry; Barberi-Heyob, Muriel

    2015-01-01

    This review focuses on the radiosensitization strategies that use high-Z nanoparticles. It does not establish an exhaustive list of the works in this field but rather propose constructive criticisms pointing out critical factors that could improve the nano-radiation therapy. Whereas most reviews show the chemists and/or biologists points of view, the present analysis is also seen through the prism of the medical physicist. In particular, we described and evaluated the influence of X-rays energy spectra using a numerical analysis. We observed a lack of standardization in preclinical studies that could partially explain the low number of translation to clinical applications for this innovative therapeutic strategy. Pointing out the critical parameters of high-Z nanoparticles radiosensitization, this review is expected to contribute to a larger preclinical and clinical development.

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

    Science.gov (United States)

    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.

  6. Genetic engineering of stem cells for enhanced therapy.

    Science.gov (United States)

    Nowakowski, Adam; Andrzejewska, Anna; Janowski, Miroslaw; Walczak, Piotr; Lukomska, Barbara

    2013-01-01

    Stem cell therapy is a promising strategy for overcoming the limitations of current treatment methods. The modification of stem cell properties may be necessary to fully exploit their potential. Genetic engineering, with an abundance of methodology to induce gene expression in a precise and well-controllable manner, is particularly attractive for this purpose. There are virus-based and non-viral methods of genetic manipulation. Genome-integrating viral vectors are usually characterized by highly efficient and long-term transgene expression, at a cost of safety. Non-integrating viruses are also highly efficient in transduction, and, while safer, offer only a limited duration of transgene expression. There is a great diversity of transfectable forms of nucleic acids; however, for efficient shuttling across cell membranes, additional manipulation is required. Both physical and chemical methods have been employed for this purpose. Stem cell engineering for clinical applications is still in its infancy and requires further research. There are two main strategies for inducing transgene expression in therapeutic cells: transient and permanent expression. In many cases, including stem cell trafficking and using cell therapy for the treatment of rapid-onset disease with a short healing process, transient transgene expression may be a sufficient and optimal approach. For that purpose, mRNA-based methods seem ideally suited, as they are characterized by a rapid, highly efficient transfection, with outstanding safety. Permanent transgene expression is primarily based on the application of viral vectors, and, due to safety concerns, these methods are more challenging. There is active, ongoing research toward the development of non-viral methods that would induce permanent expression, such as transposons and mammalian artificial chromosomes.

  7. Stimulation of dendritic cells enhances immune response after photodynamic therapy

    Science.gov (United States)

    Mroz, Pawel; Castano, Ana P.; Hamblin, Michael R.

    2009-02-01

    Photodynamic therapy (PDT) involves the administration of photosensitizers followed by illumination of the primary tumor with red light producing reactive oxygen species that cause vascular shutdown and tumor cell necrosis and apoptosis. Anti-tumor immunity is stimulated after PDT due to the acute inflammatory response, priming of the immune system to recognize tumor-associated antigens (TAA). The induction of specific CD8+ Tlymphocyte cells that recognize major histocompatibility complex class I (MHC-I) restricted epitopes of TAAs is a highly desirable goal in cancer therapy. The PDT killed tumor cells may be phagocytosed by dendritic cells (DC) that then migrate to draining lymph nodes and prime naÃve T-cells that recognize TAA epitopes. This process is however, often sub-optimal, in part due to tumor-induced DC dysfunction. Instead of DC that can become mature and activated and have a potent antigen-presenting and immune stimulating phenotype, immature dendritic cells (iDC) are often found in tumors and are part of an immunosuppressive milieu including regulatory T-cells and immunosuppressive cytokines such as TGF-beta and IL10. We here report on the use of a potent DC activating agent, an oligonucleotide (ODN) that contains a non-methylated CpG motif and acts as an agonist of toll like receptor (TLR) 9. TLR activation is a danger signal to notify the immune system of the presence of invading pathogens. CpG-ODN (but not scrambled non-CpG ODN) increased bone-marrow DC activation after exposure to PDT-killed tumor cells, and significantly increased tumor response to PDT and mouse survival after peri-tumoral administration. CpG may be a valuable immunoadjuvant to PDT especially for tumors that produce DC dysfunction.

  8. Linagliptin provides effective, well-tolerated add-on therapy to pre-existing oral antidiabetic therapy over 1 year in Japanese patients with type 2 diabetes.

    Science.gov (United States)

    Inagaki, N; Watada, H; Murai, M; Kagimura, T; Gong, Y; Patel, S; Woerle, H-J

    2013-09-01

    To evaluate the long-term safety and efficacy of linagliptin as add-on therapy to one approved oral antidiabetic drug (OAD) in Japanese patients with type 2 diabetes mellitus and insufficient glycaemic control. This 52-week, multicentre, open-label, parallel-group study evaluated once-daily linagliptin 5 mg as add-on therapy to one OAD [biguanide, glinide, glitazone, sulphonylurea (SU) or α-glucosidase inhibitors (A-GI)] in 618 patients. After a 2-week run-in, patients on SU or A-GI were randomized to either linagliptin (once daily, 5 mg) or metformin (twice or thrice daily, up to 2250 mg/day) as add-on therapy. Patients receiving the other OADs received linagliptin add-on therapy (non-randomized). Adverse events were mostly mild or moderate, and rates were similar across all groups. Hypoglycaemic events were rare, except in the SU group. Overall, 26 (5.8%) hypoglycaemic events were reported in patients receiving linagliptin (non-randomized). Hypoglycaemic events were similar for linagliptin and metformin added to A-GI (1/61 vs. 2/61, respectively) or SU (17/124 vs. 10/63, respectively). Significant reductions in glycated haemoglobin (HbA1c) levels (between -0.7 and -0.9%) occurred throughout the study period for the background therapy groups that received linagliptin (baseline HbA1c 7.9-8.1%). The decline in HbA1c levels was indistinguishable between linagliptin and metformin groups when administered as add-on therapy to A-GI or SU. Once-daily linagliptin showed safety and tolerability over 1 year and provided effective add-on therapy leading to significant HbA1c reductions, similar to metformin, over 52 weeks in Japanese patients. © 2013 Blackwell Publishing Ltd.

  9. Integrated opioid substitution therapy and HIV care: a qualitative systematic review and synthesis of client and provider experiences.

    Science.gov (United States)

    Guise, Andy; Seguin, Maureen; Mburu, Gitau; McLean, Susie; Grenfell, Pippa; Islam, Zahed; Filippovych, Sergii; Assan, Happy; Low, Andrea; Vickerman, Peter; Rhodes, Tim

    2017-09-01

    People who use drugs in many contexts have limited access to opioid substitution therapy and HIV care. Service integration is one strategy identified to support increased access. We reviewed and synthesized literature exploring client and provider experiences of integrated opioid substitution therapy and HIV care to identify acceptable approaches to care delivery. We systematically reviewed qualitative literature. We searched nine bibliographic databases, supplemented by manual searches of reference lists of articles from the database search, relevant journals, conferences, key organizations and consultation with experts. Thematic synthesis was used to develop descriptive themes in client and provider experiences. The search yielded 11 articles for inclusion, along with 8 expert and policy reports. We identify five descriptive themes: the convenience and comprehensive nature of co-located care, contrasting care philosophies and their role in shaping integration, the limits to disclosure and communication between clients and providers, opioid substitution therapy enabling HIV care access and engagement, and health system challenges to delivering integrated services. The discussion explores how integrated opioid substitution therapy and HIV care needs to adapt to specific social conditions, rather than following universal approaches. We identify priorities for future research. Acceptable integrated opioid substitution therapy and HIV care for people who use drugs and providers is most likely through co-located care and relies upon attention to stigma, supportive relationships and client centred cultures of delivery. Further research is needed to understand experiences of integrated care, particularly delivery in low and middle income settings and models of care focused on community and non-clinic based delivery.

  10. Enhancing legacy in palliative care: study protocol for a randomized controlled trial of Dignity Therapy focused on positive outcomes.

    Science.gov (United States)

    Montross-Thomas, Lori P; Irwin, Scott A; Meier, Emily A; Gallegos, Jarred V; Golshan, Shahrokh; Roeland, Eric; McNeal, Helen; Munson, Diane; Rodseth, Laura

    2015-09-21

    Dignity Therapy is a brief psychotherapy that can enhance a sense of legacy while addressing the emotional and existential needs of patients receiving hospice or palliative care. In Dignity Therapy, patients create a formalized "legacy" document that records their most cherished memories, their lessons learned in life, as well as their hopes and dreams for loved ones in the future. To date, this treatment has been studied for its impact on mitigating distress within hospice and palliative care populations and has provided mixed results. This study will instead focus on whether Dignity Therapy enhances positive outcomes in this population. In this study, 90 patients with cancer receiving hospice or palliative care will complete a mixed-methods randomized controlled trial of Dignity Therapy (n = 45) versus Supportive Attention (n = 45). The patients will be enrolled in the study for 3 weeks, receiving a total of six study visits. The primary outcomes examine whether the treatment will quantitatively increase levels of positive affect and a sense of life closure. Secondary outcomes focus on gratitude, hope, life satisfaction, meaning in life, resilience, and self-efficacy. Using a fixed, embedded dataset design, this study will additionally use qualitative interviews to explore patients' perceptions regarding the use of positive outcome measures and whether these outcomes are appropriately matched to their experiences in therapy. Dignity Therapy has shown mixed results when evaluating its impact on distress, although no other study to date has solely focused on the potential positive aspects of this treatment. This study is novel in its use of mixed methods assessments to focus on positive outcomes, and will provide valuable information about patients' direct experiences in this area. ISRCTN91389194.

  11. Continuity in the provider of home-based physical therapy services and its implications for outcomes of patients.

    Science.gov (United States)

    Russell, David; Rosati, Robert J; Andreopoulos, Evie

    2012-02-01

    A growing body of research suggests that greater continuity of health care is positively associated with improved outcomes of patients. However, few studies have examined this issue in the context of physical therapy. The purpose of this study was to evaluate whether the level of continuity in the provider (provider continuity) of physical therapy services was related to outcomes in a population of patients receiving home health care. This was a retrospective observational study. Clinical and administrative records were retrieved for a population of adult patients receiving physical therapy services from a large, urban, not-for-profit certified home health care agency in 2009. Descriptive and multivariable analyses were used to examine how the level of provider continuity, calculated by use of a formula that models dispersion in contact between the patient and the providers of physical therapy services, varied across characteristics and outcomes of patients. Logistic regression analyses indicated that patients with lower levels of provider continuity had significantly higher odds of hospitalization (odds ratio [OR]=2.06, 95% confidence interval [CI]=1.90-2.23) and lower odds of improvements in the number of activity limitations (OR=0.85, 95% CI=0.80-0.92) and in the severity of activity limitations (OR=0.85, 95% CI=0.78-0.93) between the beginning and the end of the home health care episode. Baseline clinical characteristics associated with continuity of care suggest some level of indication bias. Outcome measures for activities of daily living were limited to patients who were not hospitalized during their home health stay. These findings build upon research suggesting that continuity in the patient-provider relationship is an important determinant of outcomes of patients.

  12. Dual-targeting nanosystem for enhancing photodynamic therapy efficiency.

    Science.gov (United States)

    Xu, Jiangsheng; Zeng, Fang; Wu, Hao; Yu, Changmin; Wu, Shuizhu

    2015-05-06

    Photodynamic therapy (PDT) has been recognized as a valuable treatment option for localized cancers. Herein, we demonstrate a cellular and subcellular targeted strategy to facilitate PDT efficacy. The PDT system was fabricated by incorporating a cationic porphyrin derivative (MitoTPP) onto the polyethylene glycol (PEG)-functionalized and folic acid-modified nanographene oxide (NGO). For this PDT system, NGO serves as the carrier for MitoTPP as well as the quencher for MitoTPP's fluorescence and singlet oxygen ((1)O2) generation. Attaching a hydrophobic cation to the photosensitizer ensures its release from NGO at lower pH values as well as its mitochondria-targeting capability. Laser confocal microscope experiments demonstrate that this dual-targeted nanosystem could preferably enter the cancer cells overexpressed with folate receptor, and release its cargo MitoTPP, which subsequently accumulates in mitochondria. Upon light irradiation, the released MitoTPP molecules generate singlet oxygen and cause oxidant damage to the mitochondria. Cell viability assays suggest that the dual-targeted nanohybrids exhibit much higher cytotoxicity toward the FR-positive cells.

  13. A Randomized Clinical Trial of Cognitive Enhancement Therapy for Adults with Autism Spectrum Disorders

    Science.gov (United States)

    2015-10-01

    of the neuroplastic effects of CET on brain function in support of cognitive enhancement in adult autism . Analyses of treatment effects to date...the need and potential for CET to be a significant treatment advance for verbal adults with autism . Importantly, improvements were found in daily life function and in brain circuitry supporting core abilities....This project is focused on conducting the first randomized-controlled trial of Cognitive Enhancement Therapy (CET) in 54 verbal adults with autism

  14. THE USE OF PERFORMANCE ENHANCING SWIMWEAR DURING AQUA THERAPY FOR CEREBRAL PALSY – A CASE STUDY

    OpenAIRE

    Kangas, Emmi-Sofia

    2016-01-01

    The purpose of the thesis was to study the effects of the use of performance enhancing swimwear on a client with Cerebral Palsy (CP). This was done by interviewing a client with Spastic Diplegic CP who uses performance enhancing swimwear during aqua therapy sessions with her physiotherapist. For additional insight about the use of the swimwear the physiotherapist was also interviewed. CP is the most common motor disability in childhood, primarily affecting motor control and movement coord...

  15. Community mental health provider modifications to cognitive therapy: implications for sustainability.

    Science.gov (United States)

    Wiltsey Stirman, Shannon; Calloway, Amber; Toder, Katherine; Miller, Christopher J; Devito, Andrea K; Meisel, Samuel N; Xhezo, Regina; Evans, Arthur C; Beck, Aaron T; Crits-Christoph, Paul

    2013-10-01

    This study identified modifications to an evidence-based psychosocial treatment (cognitive therapy) within a community mental health system after clinicians had received intensive training and consultation. A coding system, consisting of four types of contextual modifications, 12 types of content-related modifications, seven levels at which modifications can occur, and a code for changes to training or evaluation processes, was applied to data from interviews with 27 clinicians who treat adult consumers within a mental health system. Nine of 12 content modifications were endorsed, and four (tailoring, integration into other therapeutic approaches, loosening structure, and drift) accounted for 65% of all modifications identified. Contextual modifications were rarely endorsed by clinicians in this sample. Modifications typically occurred at the client or clinician level. Clinicians in community mental health settings made several modifications to an evidence-based practice (EBP), often in an effort to improve the fit of the intervention to the client's needs or to the clinician's therapeutic style. These findings have implications for implementation and sustainability of EBPs in community settings, client-level outcomes, and training and consultation.

  16. Enhancing attention in neurodegenerative diseases: current therapies and future directions

    Directory of Open Access Journals (Sweden)

    Sharma Kanchan

    2016-01-01

    Full Text Available We all experience at least occasional lapses in attention but in some neurological conditions, loss of attention is pervasive and debilitating. Treating deficits in attention first requires an understanding of the neurobiology of attention, which we now understand to be a set of different cognitive processes. Cholinesterase inhibitors are already established as effective attentional enhancers used in the treatment of certain dementias. Other stimulant agents such as modafanil, amphetamine and methylphenidate have demonstrated limited success in healthy individuals where attention is already optimal and clinical trials in patients with neurological disease are sparse. Dietary and lifestyle changes are gaining increasing prominence, as are experimental treatments such as deep brain stimulation and transcranial magnetic stimulation. As the therapeutic arsenal widens, clinicians will be able to match specific treatments to selective deficits in attention, giving patients a tailored management plan. Here we review common diseases that impair attention and emphasise how an understanding of attentional processing within the brain might lead to improved therapeutic strategies.

  17. Supportive accountability: a model for providing human support to enhance adherence to eHealth interventions.

    Science.gov (United States)

    Mohr, David C; Cuijpers, Pim; Lehman, Kenneth

    2011-03-10

    The effectiveness of and adherence to eHealth interventions is enhanced by human support. However, human support has largely not been manualized and has usually not been guided by clear models. The objective of this paper is to develop a clear theoretical model, based on relevant empirical literature, that can guide research into human support components of eHealth interventions. A review of the literature revealed little relevant information from clinical sciences. Applicable literature was drawn primarily from organizational psychology, motivation theory, and computer-mediated communication (CMC) research. We have developed a model, referred to as "Supportive Accountability." We argue that human support increases adherence through accountability to a coach who is seen as trustworthy, benevolent, and having expertise. Accountability should involve clear, process-oriented expectations that the patient is involved in determining. Reciprocity in the relationship, through which the patient derives clear benefits, should be explicit. The effect of accountability may be moderated by patient motivation. The more intrinsically motivated patients are, the less support they likely require. The process of support is also mediated by the communications medium (eg, telephone, instant messaging, email). Different communications media each have their own potential benefits and disadvantages. We discuss the specific components of accountability, motivation, and CMC medium in detail. The proposed model is a first step toward understanding how human support enhances adherence to eHealth interventions. Each component of the proposed model is a testable hypothesis. As we develop viable human support models, these should be manualized to facilitate dissemination.

  18. Chinese newspaper coverage of (unproven) stem cell therapies and their providers.

    Science.gov (United States)

    Ogbogu, Ubaka; Du, Li; Rachul, Christen; Bélanger, Lisa; Caulfield, Timothy

    2013-04-01

    China is a primary destination for stem cell tourism, the phenomenon whereby patients travel abroad to receive unproven stem cell-based treatments that have not been approved in their home countries. Yet, much remains unknown about the state of the stem cell treatment industry in China and about how the Chinese view treatments and providers. Given the media's crucial role in science/health communication and in framing public dialogue, this study sought to examine Chinese newspaper portrayal and perceptions of stem cell treatments and their providers. Based on a content analysis of over 300 newspaper articles, the study revealed that while Chinese newspaper reporting is generally neutral in tone, it is also inaccurate, overly positive, heavily influenced by "interested" treatment providers and focused on the therapeutic uses of stem cells to address the health needs of the local population. The study findings suggest a need to counterbalance providers' influence on media reporting through strategies that encourage media uptake of accurate information about stem cell research and treatments.

  19. Open communication: Recommendations for enhancing communication among primary care and mental health providers, services, and systems.

    Science.gov (United States)

    Wong, Shale L; Talmi, Ayelet

    2015-06-01

    Comments on the article "Please break the silence: Parents' views on communication between pediatric primary care and mental health providers" by Greene et al. (see record 2015-14521-001). The article highlights the need to improve communication between primary care and mental health care providers to better serve children and families. The report reaffirms that parents understand the value and necessity of collaborative care, as evidenced by the identification of gaps in consistency of bidirectional communication between providers in traditional and separate practice settings and the desire for improved care coordination. (c) 2015 APA, all rights reserved).

  20. Potential for Enhanced Therapeutic Activity of Biological Cancer Therapies with Doxycycline Combination

    Science.gov (United States)

    Tang, Hui; Sampath, Padma; Yan, Xinmin; Thorne, Stephen H

    2012-01-01

    Despite significant strides made in the clinical translation of adoptive immune cell therapies, it is apparent that many tumors incorporate strategies to avoid recognition by receptors expressed on the immune cells, such as NKG2D. Strategies that stabilize the expression of ligands for these receptors may enhance the therapeutic potential of these and related therapies. Doxycycline inhibits matrix metalloproteinases (MMPs) that act to cleave the extracellular domain of MICA/B, ligands for the NKG2D receptor. Doxycycline treatment blocked shedding of MICA/B from a panel of human tumor cells, but also acted to increase their expression and cell surface translocation, possibly through its action on ATM. This meant that many tumor cells displayed increased MICA/B expression and enhanced susceptibility to CIK cells. Interestingly, doxycycline also selectively enhanced the replication of oncolytic vaccinia in many tumor cell lines, leading to increased sensitivity to these therapies. Combination (CIK-oncolytic vaccinia) therapies used in conjunction with doxycyline led to increased anti-tumor effects. The unexpected and pleiotropic beneficial anti-tumor effects of doxycycline on both immune cell and oncolytic viral therapies make it an excellent candidate for rapid clinical testing. PMID:23282955

  1. Enhancing human regulatory T cells in vitro for cell therapy applications.

    Science.gov (United States)

    Milward, Kate F; Wood, Kathryn J; Hester, Joanna

    2017-10-01

    Adoptive cellular therapies are gaining popularity as a means to treat clinical conditions, with potentially fewer risks and greater efficacy than traditional pharmacological strategies. Regulatory T cells (Tregs) are currently undergoing clinical trials in various immune-mediated pathologies, including transplant rejection and autoimmune conditions. In general, cell therapy relies upon ex vivo expansion of the cell product, in order to administer more cells than can be isolated from one person. In vitro manipulation of cell therapy products, prior to administration to patients, offers the opportunity to enhance the efficacy of the final cell therapy product in other ways. For example, cells can be exposed to reagents that enhance their longevity or functional potency after transfer into the patient. Genetic modification strategies can even permit the design of cells with bespoke functionality. Crucially, in vitro manipulation of therapeutic cells in isolation can exert these influences upon the biology of the therapeutic cells, without systemic exposure of the patient to the reagents being used. Quality control assessments can be integrated into the procedure prior to administration, to protect the patient from the risk of adverse events, should the procedure produce undesirable results. With a particular focus on Tregs, this review surveys the diverse strategies that are being employed to enhance the efficacy of cell therapy via in vitro manipulation of cells, and highlights some emerging technologies that may propel this endeavour in the future. Copyright © 2017 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

  2. A Spirulina-Enhanced Diet Provides Neuroprotection in an α-Synuclein Model of Parkinson's Disease

    Science.gov (United States)

    Pabon, Mibel M.; Jernberg, Jennifer N.; Morganti, Josh; Contreras, Jessika; Hudson, Charles E.; Klein, Ronald L.; Bickford, Paula C.

    2012-01-01

    Inflammation in the brain plays a major role in neurodegenerative diseases. In particular, microglial cell activation is believed to be associated with the pathogenesis of neurodegenerative diseases, including Parkinson’s disease (PD). An increase in microglia activation has been shown in the substantia nigra pars compacta (SNpc) of PD models when there has been a decrease in tyrosine hydroxylase (TH) positive cells. This may be a sign of neurotoxicity due to prolonged activation of microglia in both early and late stages of disease progression. Natural products, such as spirulina, derived from blue green algae, are believed to help reverse this effect due to its anti-inflammatory/anti-oxidant properties. An adeno-associated virus vector (AAV9) for α-synuclein was injected in the substantia nigra of rats to model Parkinson's disease and to study the effects of spirulina on the inflammatory response. One month prior to surgeries, rats were fed either a diet enhanced with spirulina or a control diet. Immunohistochemistry was analyzed with unbiased stereological methods to quantify lesion size and microglial activation. As hypothesized, spirulina was neuroprotective in this α-synuclein model of PD as more TH+ and NeuN+ cells were observed; spirulina concomitantly decreased the numbers of activated microglial cells as determined by MHCII expression. This decrease in microglia activation may have been due, in part, to the effect of spirulina to increase expression of the fractalkine receptor (CX3CR1) on microglia. With this study we hypothesize that α-synuclein neurotoxicity is mediated, at least in part, via an interaction with microglia. We observed a decrease in activated microglia in the rats that received a spirulina- enhanced diet concomitant to neuroprotection. The increase in CX3CR1 in the groups that received spirulina, suggests a potential mechanism of action. PMID:23028885

  3. A spirulina-enhanced diet provides neuroprotection in an α-synuclein model of Parkinson's disease.

    Science.gov (United States)

    Pabon, Mibel M; Jernberg, Jennifer N; Morganti, Josh; Contreras, Jessika; Hudson, Charles E; Klein, Ronald L; Bickford, Paula C

    2012-01-01

    Inflammation in the brain plays a major role in neurodegenerative diseases. In particular, microglial cell activation is believed to be associated with the pathogenesis of neurodegenerative diseases, including Parkinson's disease (PD). An increase in microglia activation has been shown in the substantia nigra pars compacta (SNpc) of PD models when there has been a decrease in tyrosine hydroxylase (TH) positive cells. This may be a sign of neurotoxicity due to prolonged activation of microglia in both early and late stages of disease progression. Natural products, such as spirulina, derived from blue green algae, are believed to help reverse this effect due to its anti-inflammatory/anti-oxidant properties. An adeno-associated virus vector (AAV9) for α-synuclein was injected in the substantia nigra of rats to model Parkinson's disease and to study the effects of spirulina on the inflammatory response. One month prior to surgeries, rats were fed either a diet enhanced with spirulina or a control diet. Immunohistochemistry was analyzed with unbiased stereological methods to quantify lesion size and microglial activation. As hypothesized, spirulina was neuroprotective in this α-synuclein model of PD as more TH+ and NeuN+ cells were observed; spirulina concomitantly decreased the numbers of activated microglial cells as determined by MHCII expression. This decrease in microglia activation may have been due, in part, to the effect of spirulina to increase expression of the fractalkine receptor (CX3CR1) on microglia. With this study we hypothesize that α-synuclein neurotoxicity is mediated, at least in part, via an interaction with microglia. We observed a decrease in activated microglia in the rats that received a spirulina- enhanced diet concomitant to neuroprotection. The increase in CX3CR1 in the groups that received spirulina, suggests a potential mechanism of action.

  4. A spirulina-enhanced diet provides neuroprotection in an α-synuclein model of Parkinson's disease.

    Directory of Open Access Journals (Sweden)

    Mibel M Pabon

    Full Text Available Inflammation in the brain plays a major role in neurodegenerative diseases. In particular, microglial cell activation is believed to be associated with the pathogenesis of neurodegenerative diseases, including Parkinson's disease (PD. An increase in microglia activation has been shown in the substantia nigra pars compacta (SNpc of PD models when there has been a decrease in tyrosine hydroxylase (TH positive cells. This may be a sign of neurotoxicity due to prolonged activation of microglia in both early and late stages of disease progression. Natural products, such as spirulina, derived from blue green algae, are believed to help reverse this effect due to its anti-inflammatory/anti-oxidant properties. An adeno-associated virus vector (AAV9 for α-synuclein was injected in the substantia nigra of rats to model Parkinson's disease and to study the effects of spirulina on the inflammatory response. One month prior to surgeries, rats were fed either a diet enhanced with spirulina or a control diet. Immunohistochemistry was analyzed with unbiased stereological methods to quantify lesion size and microglial activation. As hypothesized, spirulina was neuroprotective in this α-synuclein model of PD as more TH+ and NeuN+ cells were observed; spirulina concomitantly decreased the numbers of activated microglial cells as determined by MHCII expression. This decrease in microglia activation may have been due, in part, to the effect of spirulina to increase expression of the fractalkine receptor (CX3CR1 on microglia. With this study we hypothesize that α-synuclein neurotoxicity is mediated, at least in part, via an interaction with microglia. We observed a decrease in activated microglia in the rats that received a spirulina- enhanced diet concomitant to neuroprotection. The increase in CX3CR1 in the groups that received spirulina, suggests a potential mechanism of action.

  5. Alcohol Treatment and Cognitive-Behavioral Therapy: Enhancing Effectiveness by Incorporating Spirituality and Religion

    Science.gov (United States)

    Hodge, David R.

    2011-01-01

    Cognitive-behavioral therapy (CBT) is an effective modality for the treatment of alcoholism. Given widespread interest in incorporating spirituality into professional treatment, this article orients practitioners to spiritually modified CBT, an approach that may enhance outcomes with some spiritually motivated clients. More specifically, by…

  6. Cognitive Enhancement Therapy for Adults with Autism Spectrum Disorder: Results of an 18-Month Feasibility Study

    Science.gov (United States)

    Eack, Shaun M.; Greenwald, Deborah P.; Hogarty, Susan S.; Bahorik, Amber L.; Litschge, Maralee Y.; Mazefsky, Carla A.; Minshew, Nancy J.

    2013-01-01

    Adults with autism experience significant impairments in social and non-social information processing for which few treatments have been developed. This study conducted an 18-month uncontrolled trial of Cognitive Enhancement Therapy (CET), a comprehensive cognitive rehabilitation intervention, in 14 verbal adults with autism spectrum disorder to…

  7. Evaluating an Adjunctive Mobile App to Enhance Psychological Flexibility in Acceptance and Commitment Therapy.

    Science.gov (United States)

    Levin, Michael E; Haeger, Jack; Pierce, Benjamin; Cruz, Rick A

    2017-11-01

    The primary aims of this study were to evaluate the feasibility and potential efficacy of a novel adjunctive mobile app designed to enhance the acquisition, strengthening, and generalization of acceptance and commitment therapy (ACT) skills being taught in therapy. A sample of 14 depressed/anxious clients receiving ACT used the ACT Daily app for 2 weeks in a pre-post, open trial design. Participants reported a high degree of program satisfaction. Clients significantly improved over the 2-week period on depression and anxiety symptoms as well as a range of psychological inflexibility measures. Analyses of mobile app data indicated effects of ACT Daily skill coaching on in-the-moment measures of inflexibility and symptoms, with unique effects found for acceptance and mindfulness. Adjunctive ACT mobile apps appear promising in enhancing therapy effects on psychological inflexibility and outcomes. A tailored skill coaching approach like ACT Daily based on randomly prompted assessments may be especially promising.

  8. Mitochondria-targeted cationic porphyrin-triphenylamine hybrids for enhanced two-photon photodynamic therapy.

    Science.gov (United States)

    Hammerer, Fabien; Poyer, Florent; Fourmois, Laura; Chen, Su; Garcia, Guillaume; Teulade-Fichou, Marie-Paule; Maillard, Philippe; Mahuteau-Betzer, Florence

    2018-01-01

    The proof of concept for two-photon activated photodynamic therapy has already been achieved for cancer treatment but the efficiency of this approach still heavily relies on the availability of photosensitizers combining high two-photon absorption and biocompatibility. In this line we recently reported on a series of porphyrin-triphenylamine hybrids which exhibit high singlet oxygen production quantum yield as well as high two-photon absorption cross-sections but with a very poor cellular internalization. We present herein new photosensitizers of the same porphyrin-triphenylamine hybrid series but bearing cationic charges which led to strongly enhanced water solubility and thus cellular penetration. In addition the new compounds have been found localized in mitochondria that are preferential target organelles for photodynamic therapy. Altogether the strongly improved properties of the new series combined with their specific mitochondrial localization lead to a significantly enhanced two-photon activated photodynamic therapy efficiency. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Natural products as potential cancer therapy enhancers: A preclinical update

    Directory of Open Access Journals (Sweden)

    Abed Agbarya

    2014-09-01

    Full Text Available Cancer is a multifactorial disease that arises as a consequence of alterations in many physiological processes. Recently, hallmarks of cancer were suggested that include sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and metastasis, along with two emerging hallmarks including reprogramming energy metabolism and escaping immune destruction. Treating multifactorial diseases, such as cancer with agents targeting a single target, might provide partial treatment and, in many cases, disappointing cure rates. Epidemiological studies have consistently shown that the regular consumption of fruits and vegetables is strongly associated with a reduced risk of developing chronic diseases, such as cardiovascular diseases and cancer. Since ancient times, plants, herbs, and other natural products have been used as healing agents. Moreover, the majority of the medicinal substances available today have their origin in natural compounds. Traditionally, pharmaceuticals are used to cure diseases, and nutrition and herbs are used to prevent disease and to provide an optimal balance of macro- and micro-nutrients needed for good health. We explored the combination of natural products, dietary nutrition, and cancer chemotherapeutics for improving the efficacy of cancer chemotherapeutics and negating side effects.

  10. Costs of providing infusion therapy for patients with inflammatory bowel disease in a hospital-based infusion center setting.

    Science.gov (United States)

    Afzali, Anita; Ogden, Kristine; Friedman, Michael L; Chao, Jingdong; Wang, Anthony

    2017-04-01

    Inflammatory bowel disease (IBD) (e.g. ulcerative colitis [UC] and Crohn's disease [CD]) severely impacts patient quality-of-life. Moderate-to-severe disease is often treated with biologics requiring infusion therapy, adding incremental costs beyond drug costs. This study evaluates US hospital-based infusion services costs for treatment of UC or CD patients receiving infliximab or vedolizumab therapy. A model was developed, estimating annual costs of providing monitored infusions using an activity-based costing framework approach. Multiple sources (published literature, treatment product inserts) informed base-case model input estimates. The total modeled per patient infusion therapy costs in Year 1 with infliximab and vedolizumab was $38,782 and $41,320, respectively, and Year 2+, $49,897 and $36,197, respectively. Drug acquisition cost was the largest total costs driver (90-93%), followed by costs associated with hospital-based infusion provision: labor (53-56%, non-drug costs), allocated overhead (23%, non-drug costs), non-labor (23%, non-drug costs), and laboratory (7-10%, non-drug costs). Limitations included reliance on published estimates, base-case cost estimates infusion drug, and supplies, not accounting for volume pricing, assumption of a small hospital infusion center, and that, given the model adopts the hospital perspective, costs to the patient were not included in infusion administration cost base-case estimates. This model is an early step towards a framework to fully analyze infusion therapies' associated costs. Given the lack of published data, it would be beneficial for hospital administrators to assess total costs and trade-offs with alternative means of providing biologic therapies. This analysis highlights the value to hospital administrators of assessing cost associated with infusion patient mix to make more informed resource allocation decisions. As the landscape for reimbursement changes, tools for evaluating the costs of infusion therapy

  11. Through the Looking Glass: Real-Time Video Using 'Smart' Technology Provides Enhanced Intraoperative Logistics.

    Science.gov (United States)

    Baldwin, Andrew C W; Mallidi, Hari R; Baldwin, John C; Sandoval, Elena; Cohn, William E; Frazier, O H; Singh, Steve K

    2016-01-01

    In the setting of increasingly complex medical therapies and limited physician resources, the recent emergence of 'smart' technology offers tremendous potential for improved logistics, efficiency, and communication between medical team members. In an effort to harness these capabilities, we sought to evaluate the utility of this technology in surgical practice through the employment of a wearable camera device during cardiothoracic organ recovery. A single procurement surgeon was trained for use of an Explorer Edition Google Glass (Google Inc., Mountain View, CA) during the recovery process. Live video feed of each procedure was securely broadcast to allow for members of the home transplant team to remotely participate in organ assessment. Primary outcomes involved demonstration of technological feasibility and validation of quality assurance through group assessment. The device was employed for the recovery of four organs: a right single lung, a left single lung, and two bilateral lung harvests. Live video of the visualization process was remotely accessed by the home transplant team, and supplemented final verification of organ quality. In each case, the organs were accepted for transplant without disruption of standard procurement protocols. Media files generated during the procedures were stored in a secure drive for future documentation, evaluation, and education purposes without preservation of patient identifiers. Live video streaming can improve quality assurance measures by allowing off-site members of the transplant team to participate in the final assessment of donor organ quality. While further studies are needed, this project suggests that the application of mobile 'smart' technology offers not just immediate value, but the potential to transform our approach to the practice of medicine.

  12. Enhancing Shared Decision Making Through Carefully Designed Interventions That Target Patient And Provider Behavior

    NARCIS (Netherlands)

    Tai-Seale, M.; Elwyn, G.; Wilson, C.J.; Stults, C.; Dillon, E.C.; Li, M.; Chuang, J.; Meehan, A.; Frosch, D.L.

    2016-01-01

    Patient-provider communication and shared decision making are essential for primary care delivery and are vital contributors to patient experience and health outcomes. To alleviate communication shortfalls, we designed a novel, multidimensional intervention aimed at nudging both patients and primary

  13. Amide I'-II' 2D IR spectroscopy provides enhanced protein secondary structural sensitivity.

    Science.gov (United States)

    Deflores, Lauren P; Ganim, Ziad; Nicodemus, Rebecca A; Tokmakoff, Andrei

    2009-03-11

    We demonstrate how multimode 2D IR spectroscopy of the protein amide I' and II' vibrations can be used to distinguish protein secondary structure. Polarization-dependent amide I'-II' 2D IR experiments on poly-l-lysine in the beta-sheet, alpha-helix, and random coil conformations show that a combination of amide I' and II' diagonal and cross peaks can effectively distinguish between secondary structural content, where amide I' infrared spectroscopy alone cannot. The enhanced sensitivity arises from frequency and amplitude correlations between amide II' and amide I' spectra that reflect the symmetry of secondary structures. 2D IR surfaces are used to parametrize an excitonic model for the amide I'-II' manifold suitable to predict protein amide I'-II' spectra. This model reveals that the dominant vibrational interaction contributing to this sensitivity is a combination of negative amide II'-II' through-bond coupling and amide I'-II' coupling within the peptide unit. The empirically determined amide II'-II' couplings do not significantly vary with secondary structure: -8.5 cm(-1) for the beta sheet, -8.7 cm(-1) for the alpha helix, and -5 cm(-1) for the coil.

  14. Enhanced tumor contrast during breast lumpectomy provided by independent component analysis of localized reflectance measures

    Science.gov (United States)

    Eguizabal, Alma; Laughney, Ashley M.; Garcia Allende, Pilar Beatriz; Krishnaswamy, Venkataramanan; Wells, Wendy A.; Paulsen, Keith D.; Pogue, Brian W.; Lopez-Higuera, Jose M.; Conde, Olga M.

    2012-03-01

    A spectral analysis technique to enhance tumor contrast during breast conserving surgery is proposed. A set of 29 surgically-excised breast tissues have been imaged in local reflectance geometry. Measures of broadband reflectance are directly analyzed using Principle Component Analysis (PCA), on a per sample basis, to extract areas of maximal spectral variation. A dynamic selection threshold has been applied to obtain the final number of principal components, accounting for inter-patient variability. A blind separation technique based on Independent Component Analysis (ICA) is then applied to extract diagnostically powerful results. ICA application reveals that the behavior of one independent component highly correlates with the pathologic diagnosis and it surpasses the contrast obtained using empirical models. Moreover, blind detection characteristics (no training, no comparisons with training reference data) and no need for parameterization makes the automated diagnosis simple and time efficient, favoring its translation to the clinical practice. Correlation coefficient with model-based results up to 0.91 has been achieved.

  15. An oral multi-particulate, modified release, hydrocortisone replacement therapy that provides physiological cortisol exposure

    Science.gov (United States)

    Huatan, Hiep; Merke, Deborah; Arlt, Wiebke; Ross, Richard J.

    2013-01-01

    Objective It is not possible with current hydrocortisone replacement to mimic the diurnal cortisol profile in patients with adrenal insufficiency. Previous attempts with modified release technology were unsuccessful. Our objective was to develop hydrocortisone formulations that recreate the diurnal cortisol profile using multi-particulate technology. Design and Measurements Screening by in-vitro dissolution profiles, pharmacokinetic testing in dexamethasone suppressed dogs and humans, and comparison to a reference population. Setting Field laboratories and clinical research facility. Results Formulations were generated using an enteric (delayed-release) design configuration with an extended (sustained-release) dissolution profile. In-vitro dissolution confirmed delayed and sustained hydrocortisone release. However, in dogs and humans, sustained release resulted in reduced bioavailability. A formulation, DIURF-006, was developed that maintained delayed release but omitted the sustained release functionality. Pharmacokinetic characterisation of DIURF-006 showed that, despite absence of a sustained release component, absorption was sufficiently sustained to deliver extended hydrocortisone absorption. In dexamethasone-suppressed volunteers (n=16) receiving a twice daily ‘toothbrush’ regimen (20mg at 23:00h and 10mg at 07:00h), DIURF-006 gave a similar cortisol profile to physiological cortisol levels: DIURF-006 vs physiological, Geomean AUC 5610 vs 4706 hr*nmol/l, Geomean Cmax 665 vs 594 nmol/l and Median Tmax 8.5h vs clock time 08:12 hours for peak cortisol. The relative bioavailability of DIURF-006 vs hydrocortisone was 89% and cortisol levels increased linearly with doses between 5 and 30mg. Conclusion A multi-particulate oral hydrocortisone formulation with only an enteric coat provides delayed and sustained absorption and when given in a ‘toothbrush’ regimen provides physiological cortisol exposure. PMID:23980724

  16. An oral multiparticulate, modified-release, hydrocortisone replacement therapy that provides physiological cortisol exposure.

    Science.gov (United States)

    Whitaker, Martin; Debono, Miguel; Huatan, Hiep; Merke, Deborah; Arlt, Wiebke; Ross, Richard J

    2014-04-01

    It is not possible with current hydrocortisone replacement to mimic the diurnal cortisol profile in patients with adrenal insufficiency. Previous attempts with modified-release technology were unsuccessful. Our objective was to develop hydrocortisone formulations that recreate the diurnal cortisol profile using multiparticulate technology. Screening by in vitro dissolution profiles, pharmacokinetic (PK) testing in dexamethasone-suppressed dogs and humans, and comparison with a reference population. Field laboratories and clinical research facility. Formulations were generated using an enteric (delayed release) design configuration with an extended (sustained release) dissolution profile. In vitro dissolution confirmed delayed and sustained hydrocortisone release. However, in dogs and humans, sustained release resulted in reduced bioavailability. A formulation, DIURF-006, was developed that maintained delayed release but omitted the sustained-release functionality. PK characterization of DIURF-006 showed that, despite absence of a sustained-release component, absorption was sufficiently sustained to deliver extended hydrocortisone absorption. In dexamethasone-suppressed volunteers (n = 16) receiving a twice-daily 'toothbrush' regimen (20 mg at 23:00 h and 10 mg at 07:00 h), DIURF-006 gave a similar cortisol profile to physiological cortisol levels: DIURF-006 vs physiological, Geomean AUC 5610 vs 4706 h * nmol/l, Geomean Cmax 665 vs 594 nmol/l and Median Tmax 8·5 h vs clock time 08:12 h for peak cortisol. The relative bioavailability of DIURF-006 vs hydrocortisone was 89%, and cortisol levels increased linearly with doses between 5 and 30 mg. A multiparticulate oral hydrocortisone formulation with only an enteric coat provides delayed and sustained absorption and when given in a 'toothbrush' regimen provides physiological cortisol exposure. © 2013 John Wiley & Sons Ltd.

  17. Enhancing client welfare through better communication of private mental health data between rural service providers

    Directory of Open Access Journals (Sweden)

    Oliver Kisalay Burmeister

    2015-11-01

    Full Text Available Client welfare is detrimentally affected by poor communication of data between rural service providers, which in part is complicated by privacy legislation. A study of service provision involving interviews with mental health professionals, found challenges in communicative processes between agencies were exacerbated by the heavy workloads. Dependence on individual interpretations of legislation, and on manual handling, led to delays that detrimentally affected client welfare. The main recommendation arising from this article is the creation of an ehealth system that is able to negotiate differing levels of access to client data through centralised controls, where the administration of that system ensures that it stays current with changing legislative requirements. The main contribution of the proposed model is to combine two well-known concepts: data integration and generalisation. People with mental illness are amongst the most vulnerable members of society, and current ehealth systems that provide access to medical records inadequately cater to their needs.

  18. Enhancing Pediatric Trainees' and Students' Knowledge in Providing Care to Transgender Youth.

    Science.gov (United States)

    Vance, Stanley R; Deutsch, Madeline B; Rosenthal, Stephen M; Buckelew, Sara M

    2017-04-01

    To enhance pediatric trainees' and students' knowledge of the psychosocial and medical issues facing transgender youth through a comprehensive curriculum. During the 2015-2016 academic year, we administered a transgender youth curriculum to fourth-year medical students, pediatric interns, psychiatry interns, and nurse practitioner students on their 1-month adolescent and young adult medicine rotation. The curriculum included six interactive, online modules and an observational experience in a multidisciplinary pediatric gender clinic. The online modules had a primary care focus with topics of general transgender terminology, taking a gender history, taking a psychosocial history, performing a sensitive physical examination, and formulating an assessment, psychosocial plan, and medical plan. At the completion of the curriculum, learners completed an evaluation that assessed change in perceived awareness and knowledge of transgender-related issues and learner satisfaction with the curriculum. Twenty learners participated in the curriculum with 100% completing the curriculum evaluations, 100% reporting completing all six online modules, and 90% attending the gender clinic. Learners demonstrated a statistically significant improvement in all pre-post knowledge/awareness measures. On a Likert scale where 5 indicated very satisfied, learners' mean rating of the quality of the curriculum was 4.5 ± .7; quality of the modules was 4.4 ± .7; and satisfaction with the observational experience was 4.5 ± .8. A comprehensive curriculum comprised interactive online modules and an observational experience in a pediatric gender clinic was effective at improving pediatric learners' perceived knowledge of the medical and psychosocial issues facing transgender youth. Learners also highly valued the curriculum. Copyright © 2016 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

  19. Myocyte enhancer factor 2D provides a cross-talk between chronic inflammation and lung cancer.

    Science.gov (United States)

    Zhu, Hai-Xing; Shi, Lin; Zhang, Yong; Zhu, Yi-Chun; Bai, Chun-Xue; Wang, Xiang-Dong; Zhou, Jie-Bai

    2017-03-24

    Lung cancer is the leading cause of cancer-related morbidity and mortality worldwide. Patients with chronic respiratory diseases, such as chronic obstructive pulmonary disease (COPD), are exposed to a higher risk of developing lung cancer. Chronic inflammation may play an important role in the lung carcinogenesis among those patients. The present study aimed at identifying candidate biomarker predicting lung cancer risk among patients with chronic respiratory diseases. We applied clinical bioinformatics tools to analyze different gene profile datasets with a special focus on screening the potential biomarker during chronic inflammation-lung cancer transition. Then we adopted an in vitro model based on LPS-challenged A549 cells to validate the biomarker through RNA-sequencing, quantitative real time polymerase chain reaction, and western blot analysis. Bioinformatics analyses of the 16 enrolled GSE datasets from Gene Expression Omnibus online database showed myocyte enhancer factor 2D (MEF2D) level significantly increased in COPD patients coexisting non-small-cell lung carcinoma (NSCLC). Inflammation challenge increased MEF2D expression in NSCLC cell line A549, associated with the severity of inflammation. Extracellular signal-regulated protein kinase inhibition could reverse the up-regulation of MEF2D in inflammation-activated A549. MEF2D played a critical role in NSCLC cell bio-behaviors, including proliferation, differentiation, and movement. Inflammatory conditions led to increased MEF2D expression, which might further contribute to the development of lung cancer through influencing cancer microenvironment and cell bio-behaviors. MEF2D might be a potential biomarker during chronic inflammation-lung cancer transition, predicting the risk of lung cancer among patients with chronic respiratory diseases.

  20. Development of a Boron Neutron Capture Enhanced Fast Neutron Therapy Beam

    Energy Technology Data Exchange (ETDEWEB)

    Sweezy, Jeremy Ed [Georgia Tech

    2002-01-01

    The combination of fast neutron therapy and boron neutron capture therapy is currently under investigation at several fast neutron therapy centers worldwide. This treatment method, termed boron neutron capture enhanced fast neutron therapy (BNCEFNT) utilizes a boron containing drug to selectively increase the dose to the target tumor. BNCEFNT may be useful in the treatment of some radioresistant brain tumors, such as glioblastoma multiforme. A neutron therapy beam for boron neutron capture enhanced fast neutron therapy has been developed for the existing Fermilab Neutron Therapy Facility. This beam produces a significant dose enhancement due to the the boron neutron capture reaction. The beam was developed by designing a filter and collimator system using the Monte Carlo radiation transport code, MCNPX. The MCNPX code was benchmarked against depth-dose measurements of the standard treatment beam. The new BNCEFNT beam is filtered with 18.3-cm of low carbon steel and is collimated with steel. Measurements of the dose enhancement of the new BNCEFNT beam were performed with paired tissue equivalent ion chambers. One of the ion chambers has boron incorporated in the wall of the chamber to measure the dose due to boron neutron capture. The measured boron dose enhancement of the BNCEFNT beam is (16.3 ± 2.6)% per 100-ppm 10B for a 20-cm diameter beam and (10.0 ± 1.6)% per 100-ppm 10B for a 10-cm diameter beam. The dose rate of the new beam is reduced to 4.4% of the dose rate of the standard treatment beam. xxi A conceptual design that overcomes the reduced dose rate is also presented. This design uses a tungsten collimator placed near the patient, with a 1.5-cm tungsten filter just upstream of the collimator. Using graphite moderation of neutrons around the patient a percent dose enhancement of 15% can be attained with good collimation, for field sizes as small as 5 × 5 cm2 , and without a reduction in dose rate.

  1. Pulmonary rehabilitation and COPD: providing patients a good environment for optimizing therapy

    Directory of Open Access Journals (Sweden)

    Corhay JL

    2013-12-01

    Full Text Available Jean-Louis Corhay, Delphine Nguyen Dang, Hélène Van Cauwenberge, Renaud Louis Department of Pneumology, Centre Hospitalier Universitaire du Sart-Tilman Liège, Liège, Belgium Abstract: Chronic obstructive pulmonary disease (COPD is an obstructive and progressive airway disease associated with an important reduction in daily physical activity and psychological problems that contribute to the patient's disability and poor health-related quality of life (HRQoL. Nowadays, pulmonary rehabilitation (PR plays an essential role in the management of symptomatic patients with COPD, by breaking the vicious circle of dyspnea–decreased activity–deconditioning–isolation. Indeed the main benefits of comprehensive PR programs for patients with COPD include a decrease in symptoms (dyspnea and fatigue, improvements in exercise tolerance and HRQoL, reduction of health care utilization (particularly bed-days, as well as an increase in physical activity. Several randomized studies and meta-analyses greatly established the benefits of PR, which additionally, is recommended in a number of influential guidelines. This review aimed to highlight the impact of PR on COPD patients, focusing on the clinical usefulness of PR, which provides patients a good support for change. Keywords: chronic obstructive pulmonary disease, exercise training, physical activity, quality of life

  2. Anti-TNF-alpha therapy enhances the effects of enzyme replacement therapy in rats with mucopolysaccharidosis type VI.

    Directory of Open Access Journals (Sweden)

    Efrat Eliyahu

    Full Text Available Although enzyme replacement therapy (ERT is available for several lysosomal storage disorders, the benefit of this treatment to the skeletal system is very limited. Our previous work has shown the importance of the Toll-like receptor 4/TNF-alpha inflammatory pathway in the skeletal pathology of the mucopolysaccharidoses (MPS, and we therefore undertook a study to examine the additive benefit of combining anti-TNF-alpha therapy with ERT in a rat model of MPS type VI.MPS VI rats were treated for 8 months with Naglazyme® (recombinant human N-acetyl-galactosamine-4-sulfatase, or by a combined protocol using Naglazyme® and the rat-specific anti-TNF-alpha drug, CNTO1081. Both protocols led to markedly reduced serum levels of TNF-alpha and RANKL, although only the combined treatment reduced TNF-alpha in the articular cartilage. Analysis of cultured articular chondrocytes showed that the combination therapy also restored collagen IIA1 expression, and reduced expression of the apoptotic marker, PARP. Motor activity and mobility were improved by ERT, and these were significantly enhanced by combination treatment. Tracheal deformities in the MPS VI animals were only improved by combination therapy, and there was a modest improvement in bone length. Ceramide levels in the trachea also were markedly reduced. MicroCT analysis did not demonstrate any significant positive effects on bone microarchitecture from either treatment, nor was there histological improvement in the bone growth plates.The results demonstrate that combining ERT with anti-TNF-alpha therapy improved the treatment outcome and led to significant clinical benefit. They also further validate the usefulness of TNF-alpha, RANKL and other inflammatory molecules as biomarkers for the MPS disorders. Further evaluation of this combination approach in other MPS animal models and patients is warranted.

  3. Providing Sources of Self-Efficacy Through Technology Enhanced Post-Stroke Rehabilitation in the Home.

    Science.gov (United States)

    Parker, Jack; Mawson, Susan

    2017-01-01

    This research explores the impact of receiving feedback through a Personalised Self-Managed Rehabilitation System (PSMrS) for home-based post-stroke rehabilitation on the users' self-efficacy; more specifically, mastery experiences and the interpretation of biomechanical data. Embedded within a realistic evaluation methodological approach, exploring the promotion of self-efficacy from the utilisation of computer-based technology to facilitate post-stroke upper-limb rehabilitation in the home included; semi-structured interviews, quantitative user data (activity and usage), observations and field notes. Data revealed that self-efficacy was linked with obtaining positive knowledge of results feedback. Encouragingly, this also transferred to functional activities such as, confidence to carry out kitchen tasks and bathroom personal activities. Findings suggest the PSMrS was able to provide key sources of self-efficacy by providing feedback which translated key biomechanical data to the users. Users could interpret and understand their performance, gain a sense of mastery and build their confidence which in some instances led to increased confidence to carry out functional activities. However, outcome expectations and socio-structural factors impacted on the self-efficacy associated with the use of the system. Increasing the understanding of how these factors promote or inhibit self-management and self-efficacy is therefore crucial to the successful adoption of technology solutions and promotion of self-efficacy.

  4. Local dose enhancement of proton therapy by ceramic oxide nanoparticles investigated with Geant4 simulations.

    Science.gov (United States)

    McKinnon, Sally; Guatelli, Susanna; Incerti, Sebastien; Ivanchenko, Vladimir; Konstantinov, Konstantin; Corde, Stéphanie; Lerch, Michael; Tehei, Moeava; Rosenfeld, Anatoly

    2016-12-01

    Nanoparticles (NPs) have been shown to enhance X-ray radiotherapy and proton therapy of cancer. The effectiveness of radiation damage is enhanced in the presence of high atomic number (high-Z) NPs due to increased production of low energy, higher linear energy transfer (LET) secondary electrons when NPs are selectively internalized by tumour cells. This work quantifies the local dose enhancement produced by the high-Z ceramic oxide NPs Ta2O5 and CeO2, in the target tumour, for the first time in proton therapy, by means of Geant4 simulations. The dose enhancement produced by the ceramic oxides is compared against gold NPs. The energy deposition on a nanoscale around a single nanoparticle of 100nm diameter is investigated using the Geant4-DNA extension to model particle interactions in the water medium. Enhancement of energy deposition in nano-sized shells of water, local to the NP boundary, ranging between 14% and 27% was observed for proton energies of 5MeV and 50MeV, depending on the NP material. Enhancement of electron production and energy deposition can be correlated to the direct DNA damage mechanism if the NP is in close proximity to the nucleus. Copyright © 2016 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

  5. SU-E-T-56: Brain Metastasis Treatment Plans for Contrast-Enhanced Synchrotron Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Obeid, L; Adam, J [Grenoble Institut des Neurosciences, La Tronche, Rhone-Alpes (France); Tessier, A [Centre Hospitalier Universitaire, La Tronche, Rhone-Alpes (France); Vautrin, M; Benkebil, M [DOSIsoft, Cachan, Ile de France (France); Sihanath, R [Centre Hospitalier Universitaire, La Tronche, Rhone- Alpes (France)

    2014-06-01

    Purpose: Iodine-enhanced radiotherapy is an innovative treatment combining the selective accumulation of an iodinated contrast agent in brain tumors with irradiations using monochromatic medium energy x-rays. The aim of this study is to compare dynamic stereotactic arc-therapy and iodineenhanced SSRT. Methods: Five patients bearing brain metastasis received a standard helical 3D-scan without iodine. A second scan was acquired 13 min after an 80 g iodine infusion. Two SSRT treatment plans (with/without iodine) were performed for each patient using a dedicated Monte Carlo (MC) treatment planning system (TPS) based on the ISOgray TPS. Ten coplanar beams (6×6 cm2, shaped with collimator) were simulated. MC statistical error objective was less than 5% in the 50% isodose. The dynamic arc-therapy plan was achieved on the Iplan Brainlab TPS. The treatment plan validation criteria were fixed such that 100% of the prescribed dose is delivered at the beam isocentre and the 70% isodose contains the whole target volume. The comparison elements were the 70% isodose volume, the average and maximum doses delivered to organs at risk (OAR): brainstem, optical nerves, chiasma, eyes, skull bone and healthy brain parenchyma. Results: The stereotactic dynamic arc-therapy remains the best technique in terms of dose conformation. Iodine-enhanced SSRT presents similar performances to dynamic arc-therapy with increased brainstem and brain parenchyma sparing. One disadvantage of SSRT is the high dose to the skull bone. Iodine accumulation in metastasis may increase the dose by 20–30%, allowing a normal tissue sparing effect at constant prescribed dose. Treatment without any iodine enhancement (medium-energy stereotactic radiotherapy) is not relevant with degraded HDVs (brain, parenchyma and skull bone) comparing to stereotactic dynamic arc-therapy. Conclusion: Iodine-enhanced SSRT exhibits a good potential for brain metastasis treatment regarding the dose distribution and OAR criteria.

  6. Synergistic GABA-Enhancing Therapy against Seizures in a Mouse Model of Dravet Syndrome

    Science.gov (United States)

    Oakley, John C.; Cho, Alvin R.; Cheah, Christine S.; Scheuer, Todd

    2013-01-01

    Seizures remain uncontrolled in 30% of patients with epilepsy, even with concurrent use of multiple drugs, and uncontrolled seizures result in increased morbidity and mortality. An extreme example is Dravet syndrome (DS), an infantile-onset severe epilepsy caused by heterozygous loss of function mutations in SCN1A, the gene encoding the brain type-I voltage-gated sodium channel NaV1.1. Studies in Scn1a heterozygous knockout mice demonstrate reduced excitability of GABAergic interneurons, suggesting that enhancement of GABA signaling may improve seizure control and comorbidities. We studied the efficacy of two GABA-enhancing drugs, clonazepam and tiagabine, alone and in combination, against thermally evoked myoclonic and generalized tonic-clonic seizures. Clonazepam, a positive allosteric modulator of GABA-A receptors, protected against myoclonic and generalized tonic-clonic seizures. Tiagabine, a presynaptic GABA reuptake inhibitor, was protective against generalized tonic-clonic seizures but only minimally protective against myoclonic seizures and enhanced myoclonic seizure susceptibility at high doses. Combined therapy with clonazepam and tiagabine was synergistic against generalized tonic-clonic seizures but was additive against myoclonic seizures. Toxicity determined by rotorod testing was additive for combination therapy. The synergistic actions of clonazepam and tiagabine gave enhanced seizure protection and reduced toxicity, suggesting that combination therapy may be well tolerated and effective for seizures in DS. PMID:23424217

  7. Crosstalk between immune cell and oncolytic vaccinia therapy enhances tumor trafficking and antitumor effects.

    Science.gov (United States)

    Sampath, Padma; Li, Jun; Hou, Weizhou; Chen, Hannah; Bartlett, David L; Thorne, Steve H

    2013-03-01

    The combination of an oncolytic virus, that directly destroys tumor cells and mediates an acute immune response, with an immune cell therapy, capable of further enlisting and enhancing the host immune response, has the potential to create a potent therapeutic effect. We have previously developed several strategies for optimizing the delivery of oncolytic vaccinia virus vectors to their tumor targets, including the use of immune cell-based carrier vehicles and the incorporation of mutations that increase production of the enveloped form of vaccinia (extracellular enveloped viral (EEV)) that is better adapted to spread within a host. Here, we initially combine these approaches to create a novel therapeutic, consisting of an immune cell (cytokine-induced killer, CIK) preloaded with an oncolytic virus that is EEV enhanced. This resulted in direct interaction between the viral and immune cell components with each assisting the other in directing the therapy to the tumor and so enhancing the antitumor effects. This effect could be further improved through CCL5 expression from the virus. The resulting multicomponent therapy displays the ability for synergistic crosstalk between components, so significantly enhancing tumor trafficking and antitumor effects.

  8. Therapeutic alliance in Enhanced Cognitive Behavioural Therapy for bulimia nervosa: probably necessary but definitely insufficient.

    Science.gov (United States)

    Raykos, Bronwyn C; McEvoy, Peter M; Erceg-Hurn, David; Byrne, Susan M; Fursland, Anthea; Nathan, Paula

    2014-06-01

    The present paper assessed therapeutic alliance over the course of Enhanced Cognitive Behavioural Therapy (CBT-E) in a community-based sample of 112 patients with a diagnosis of bulimia nervosa (BN) or atypical BN. Temporal assessment of alliance was conducted at three time points (the start, middle and end of treatment) and the relationship between alliance and treatment retention and outcome was explored. Results indicated that the alliance between patient and therapist was strong at all stages of CBT-E, and even improved in the early stages of treatment when behaviour change was initiated (weekly in-session weighing, establishing regular eating, and ceasing binge-eating and compensatory behaviours). The present study found no evidence that alliance was related to treatment retention or outcomes, or that symptom severity or problematic interpersonal styles interacted with alliance to influence outcomes. Alliance was also unrelated to baseline emotional or interpersonal difficulties. The study provides no evidence that alliance has clinical utility for the prediction of treatment retention or outcome in CBT-E for BN, even for individuals with severe symptoms or problematic interpersonal styles. Early symptom change was the best predictor of outcome in CBT-E. Further research is needed to determine whether these results are generalizable to patients with anorexia nervosa. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

  9. Evaluating motivational enhancement therapy adherence and competence among Spanish-speaking therapists.

    Science.gov (United States)

    Santa Ana, Elizabeth J; Carroll, Kathleen M; Añez, Luis; Paris, Manuel; Ball, Samuel A; Nich, Charla; Frankforter, Tami L; Suarez-Morales, Lourdes; Szapocznik, José; Martino, Steve

    2009-07-01

    Despite the fact that the number of Hispanic individuals in need of treatment for substance use problems is increasing internationally, no studies have investigated the extent to which therapists can provide empirically supported treatments to Spanish-speaking clients with adequate fidelity. Twenty-three bilingual Hispanic therapists from five community outpatient treatment programs in the United States were randomly assigned to deliver either three sessions of motivational enhancement therapy (MET) or an equivalent number of drug counseling-as-usual (CAU) sessions in Spanish to 405 Spanish-speaking clients randomly assigned to these conditions. Independent ratings of 325 sessions indicated the adherence/competence rating system had good to excellent interrater reliability and indicated strong support for an a priori defined fundamental MET skill factor. Support for an advanced MET skill factor was relatively weaker. The rating scale indicated significant differences in therapists' MET adherence and competence across conditions. These findings indicate that the rating system has promise for assessing the performance of therapists who deliver MET in Spanish and suggest that bilingual Spanish-speaking therapists from the community can be trained to implement MET with adequate fidelity and skill using an intensive multisite training and supervision model.

  10. Increased extracellular pressure provides a novel adjuvant stimulus for enhancement of conventional dendritic cell maturation strategies

    Energy Technology Data Exchange (ETDEWEB)

    Craig, David H.; Shiratsuchi, Hiroe [Department of Surgery, Michigan State University, Lansing, MI (United States); John D. Dingell VA Medical Center, Detroit, MI (United States); Basson, Marc D., E-mail: marc.basson@hc.msu.edu [Department of Surgery, Michigan State University, Lansing, MI (United States); John D. Dingell VA Medical Center, Detroit, MI (United States)

    2009-09-11

    Dendritic cell (DC)-based vaccine strategies have gained increasing popularity in recent years. Methods for ex vivo generation of immunocompetent mature DCs still require optimization. DCs have been shown to phenotypically mature under elevated pressure. We compared the effects of pressure on DC maturation with LPS- and cytokine-stimulation. Human monocyte-derived immature or LPS- and cytokine-matured DCs were exposed to ambient or 40 mmHg increased pressure for 12 h, then assessed for expression of CD80, CD86, CD40, MHC-I/II, and inflammatory cytokine production. DCs were also evaluated for capacity to stimulate T-cell proliferation by co-culture with allogeneic lymphocytes. Pressure significantly increased cytokine production and expression of all surface molecules on immature DC other than MHC-I and CD40. Pressure/LPS-treated DCs displayed further upregulation of MHC-I, CD40, and IL-12p70. Cytokine-matured DCs appeared less responsive to pressure. T-cell proliferation correlated with MHC expression. Results suggest mechanical stimulation of DCs may provide a useful adjuvant to TLR-agonist maturation strategies.

  11. A compensatory mutation provides resistance to disparate HIV fusion inhibitor peptides and enhances membrane fusion.

    Directory of Open Access Journals (Sweden)

    Matthew P Wood

    Full Text Available Fusion inhibitors are a class of antiretroviral drugs used to prevent entry of HIV into host cells. Many of the fusion inhibitors being developed, including the drug enfuvirtide, are peptides designed to competitively inhibit the viral fusion protein gp41. With the emergence of drug resistance, there is an increased need for effective and unique alternatives within this class of antivirals. One such alternative is a class of cyclic, cationic, antimicrobial peptides known as θ-defensins, which are produced by many non-human primates and exhibit broad-spectrum antiviral and antibacterial activity. Currently, the θ-defensin analog RC-101 is being developed as a microbicide due to its specific antiviral activity, lack of toxicity to cells and tissues, and safety in animals. Understanding potential RC-101 resistance, and how resistance to other fusion inhibitors affects RC-101 susceptibility, is critical for future development. In previous studies, we identified a mutant, R5-tropic virus that had evolved partial resistance to RC-101 during in vitro selection. Here, we report that a secondary mutation in gp41 was found to restore replicative fitness, membrane fusion, and the rate of viral entry, which were compromised by an initial mutation providing partial RC-101 resistance. Interestingly, we show that RC-101 is effective against two enfuvirtide-resistant mutants, demonstrating the clinical importance of RC-101 as a unique fusion inhibitor. These findings both expand our understanding of HIV drug-resistance to diverse peptide fusion inhibitors and emphasize the significance of compensatory gp41 mutations.

  12. Effectiveness of enhanced communication therapy in the first four months after stroke for aphasia and dysarthria: a randomised controlled trial

    Science.gov (United States)

    Hesketh, Anne; Patchick, Emma; Young, Alys; Davies, Linda; Vail, Andy; Long, Andrew F; Watkins, Caroline; Wilkinson, Mo; Pearl, Gill; Ralph, Matthew A Lambon; Tyrrell, Pippa

    2012-01-01

    Objective To assess the effectiveness of enhanced communication therapy in the first four months after stroke compared with an attention control (unstructured social contact). Design Externally randomised, pragmatic, parallel, superiority trial with blinded outcome assessment. Setting Twelve UK hospital and community stroke services. Participants 170 adults (mean age 70 years) randomised within two weeks of admission to hospital with stroke (December 2006 to January 2010) whom speech and language therapists deemed eligible, and 135 carers. Interventions Enhanced, agreed best practice, communication therapy specific to aphasia or dysarthria, offered by speech and language therapists according to participants’ needs for up to four months, with continuity from hospital to community. Comparison was with similarly resourced social contact (without communication therapy) from employed visitors. Outcome measures Primary outcome was blinded, functional communicative ability at six months on the Therapy Outcome Measure (TOM) activity subscale. Secondary outcomes (unblinded, six months): participants’ perceptions on the Communication Outcomes After Stroke scale (COAST); carers’ perceptions of participants from part of the Carer COAST; carers’ wellbeing on Carers of Older People in Europe Index and quality of life items from Carer COAST; and serious adverse events. Results Therapist and visitor contact both had good uptake from service users. An average 22 contacts (intervention or control) over 13 weeks were accepted by users. Impairment focused therapy was the approach most often used by the speech and language therapists. Visitors most often provided general conversation. In total, 81/85 of the intervention group and 72/85 of the control group completed the primary outcome measure. Both groups improved on the TOM activity subscale. The estimated six months group difference was not statistically significant, with 0.25 (95% CI –0.19 to 0.69) points in favour of

  13. Reduction of infectivity in chronic hepatitis B virus carriers among healthcare providers and pregnant women by antiviral therapy.

    Science.gov (United States)

    Gerlich, Wolfram H

    2014-01-01

    The main purpose of therapy for infectious diseases is restoration or protection of the patient's health, but suppression or elimination of infectious agents is also important. In two well-defined situations, reduction of potential infectivity may be the main reason for therapy in hepatitis B virus (HBV) carriers who do not suffer from significant disease: (1) healthcare providers who perform exposure-prone procedures to prevent transmission of HBV to individuals, and (2) pregnant women in the third trimester to prevent transmission to the fetus. This article describes the necessity to recognize highly viremic HBV-infected individuals in these situations, the methods to estimate the risk of transmission, and the therapeutic possibilities to prevent transmission. With today's methods of monitoring HBV DNA, it is possible to reliably estimate the risk of transmission. The drugs entecavir or tenofovir are able to suppress infectivity of HBV carriers to levels acceptable for healthcare providers performing exposure-prone procedures. According to the CDC, 'chronic HBV infection in itself should not preclude the practice or study of medicine, surgery, dentistry, or allied health professions.' Treatment of pregnant women with very high levels of HBV DNA prevents the transmission to the fetus and further if the newborn receives immediate active/passive immunization against HBV. © 2014 S. Karger AG, Basel.

  14. New graduates’ perceptions of preparedness to provide speech-language therapy services in general and dysphagia services in particular

    Directory of Open Access Journals (Sweden)

    Shajila Singh

    2015-06-01

    Methods: New graduates of six South African universities were recruited to participate in a survey by completing an electronic questionnaire exploring their perceptions of the dysphagia curricula and their preparedness to practise across the scope of the profession of speechlanguage therapy. Results: Eighty graduates participated in the study yielding a response rate of 63.49%. Participants perceived themselves to be well prepared in some areas (e.g. child language: 100%; articulation and phonology: 97.26%, but less prepared in other areas (e.g. adult dysphagia: 50.70%; paediatric dysarthria: 46.58%; paediatric dysphagia: 38.36% and most unprepared to provide services requiring sign language (23.61% and African languages (20.55%. There was a significant relationship between perceptions of adequate theory and clinical learning opportunities with assessment and management of dysphagia and perceptions of preparedness to provide dysphagia services. Conclusion: There is a need for review of existing curricula and consideration of developing a standard speech-language therapy curriculum across universities, particularly in service provision to a multilingual population, and in both the theory and clinical learning of the assessment and management of adult and paediatric dysphagia, to better equip graduates for practice.

  15. Gold nanorods as photothermal agents and autofluorescence enhancer to track cell death during plasmonic photothermal therapy

    Science.gov (United States)

    Kannadorai, Ravi Kumar; Chiew, Geraldine Giap Ying; Luo, Kathy Qian; Liu, Quan

    2015-07-01

    The transverse and longitudinal plasmon resonance in gold nanorods can be exploited to localize the photothermal therapy and influence the fluorescence to monitor the treatment outcome at the same time. While the longitudinal plasmon peak contributes to the photothermal effect, the transverse peak can enhance fluorescence. After cells take in PEGylated nanorods through endocytosis, autofluorescence from endogenous fluorophores such as nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD) in the mitochondria is enhanced two times, which is a good indicator of the respiratory status of the cell. When cells are illuminated continuously with near infrared laser, the temperature reaches the hyperthermic region within the first four minutes, which demonstrates the efficiency of gold nanorods in photothermal therapy. The cell viability test and autofluorescence intensity show good correlation indicating the progress of cell death over time.

  16. Dengue virus specific IgY provides protection following lethal dengue virus challenge and is neutralizing in the absence of inducing antibody dependent enhancement.

    Science.gov (United States)

    Fink, Ashley L; Williams, Katherine L; Harris, Eva; Alvine, Travis D; Henderson, Thomas; Schiltz, James; Nilles, Matthew L; Bradley, David S

    2017-07-01

    Dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) are severe disease manifestations that can occur following sequential infection with different dengue virus serotypes (DENV1-4). At present, there are no licensed therapies to treat DENV-induced disease. DHF and DSS are thought to be mediated by serotype cross-reactive antibodies that facilitate antibody-dependent enhancement (ADE) by binding to viral antigens and then Fcγ receptors (FcγR) on target myeloid cells. Using genetically engineered DENV-specific antibodies, it has been shown that the interaction between the Fc portion of serotype cross-reactive antibodies and FcγR is required to induce ADE. Additionally, it was demonstrated that these antibodies were as neutralizing as their non-modified variants, were incapable of inducing ADE, and were therapeutic following a lethal, antibody-enhanced infection. Therefore, we hypothesized that avian IgY, which do not interact with mammalian FcγR, would provide a novel therapy for DENV-induced disease. We demonstrate here that goose-derived anti-DENV2 IgY neutralized DENV2 and did not induce ADE in vitro. Anti-DENV2 IgY was also protective in vivo when administered 24 hours following a lethal DENV2 infection. We were also able to demonstrate via epitope mapping that both full-length and alternatively spliced anti-DENV2 IgY recognized different epitopes, including epitopes that have not been previously identified. These observations provide evidence for the potential therapeutic applications of goose-derived anti-DENV2 IgY.

  17. A Randomized Clinical Trial of Cognitive Enhancement Therapy for Adults with Autism Spectrum Disorders

    Science.gov (United States)

    2013-10-01

    Mayer-Salovey-Caruso Emotional Intelligence Test, and the Penn Emotion Recognition Test, both performance-based measures of social cognition that... Autism Spectrum Disorders PRINCIPAL INVESTIGATOR: Nancy J. Minshew, M.D. CONTRACTING ORGANIZATION: University of Pittsburgh...Enhancement Therapy for Adults with Autism Spectrum Disorders 5a. CONTRACT NUMBER W81XWH-11-1-0665 5b. GRANT NUMBER W81XWH-11-1-0665 5c. PROGRAM

  18. New graduates’ perceptions of preparedness to provide speech-language therapy services in general and dysphagia services in particular

    Directory of Open Access Journals (Sweden)

    Shajila Singh

    2015-02-01

    Full Text Available Background: Upon graduation, newly qualified speech-language therapists are expected to provide services independently. This study describes new graduates’ perceptions of their preparedness to provide services across the scope of the profession and explores associations between perceptions of dysphagia theory and clinical learning curricula with preparedness for adult and paediatric dysphagia service delivery.Methods: New graduates of six South African universities were recruited to participate in a survey by completing an electronic questionnaire exploring their perceptions of the dysphagia curricula and their preparedness to practise across the scope of the profession of speechlanguage therapy. Results: Eighty graduates participated in the study yielding a response rate of 63.49%. Participants perceived themselves to be well prepared in some areas (e.g. child language: 100%; articulation and phonology: 97.26%, but less prepared in other areas (e.g. adult dysphagia: 50.70%; paediatric dysarthria: 46.58%; paediatric dysphagia: 38.36% and most unprepared to provide services requiring sign language (23.61% and African languages (20.55%. There was a significant relationship between perceptions of adequate theory and clinical learning opportunities with assessment and management of dysphagia and perceptions of preparedness to provide dysphagia services. Conclusion: There is a need for review of existing curricula and consideration of developing a standard speech-language therapy curriculum across universities, particularly in service provision to a multilingual population, and in both the theory and clinical learning of the assessment and management of adult and paediatric dysphagia, to better equip graduates for practice.

  19. Combined gene/cell therapies provide long-term and pervasive rescue of multiple pathological symptoms in a murine model of globoid cell leukodystrophy

    Science.gov (United States)

    Ricca, Alessandra; Rufo, Nicole; Ungari, Silvia; Morena, Francesco; Martino, Sabata; Kulik, Wilem; Alberizzi, Valeria; Bolino, Alessandra; Bianchi, Francesca; Del Carro, Ubaldo; Biffi, Alessandra; Gritti, Angela

    2015-01-01

    Globoid cell leukodystrophy (GLD) is a lysosomal storage disease caused by deficient activity of β-galactocerebrosidase (GALC). The infantile forms manifest with rapid and progressive central and peripheral demyelination, which represent a major hurdle for any treatment approach. We demonstrate here that neonatal lentiviral vector-mediated intracerebral gene therapy (IC GT) or transplantation of GALC-overexpressing neural stem cells (NSC) synergize with bone marrow transplant (BMT) providing dramatic extension of lifespan and global clinical–pathological rescue in a relevant GLD murine model. We show that timely and long-lasting delivery of functional GALC in affected tissues ensured by the exclusive complementary mode of action of the treatments underlies the outstanding benefit. In particular, the contribution of neural stem cell transplantation and IC GT during the early asymptomatic stage of the disease is instrumental to enhance long-term advantage upon BMT. We clarify the input of central nervous system, peripheral nervous system and periphery to the disease, and the relative contribution of treatments to the final therapeutic outcome, with important implications for treatment strategies to be tried in human patients. This study gives proof-of-concept of efficacy, tolerability and clinical relevance of the combined gene/cell therapies proposed here, which may constitute a feasible and effective therapeutic opportunity for children affected by GLD. PMID:25749991

  20. Nintedanib, a triple angiokinase inhibitor, enhances cytotoxic therapy response in pancreatic cancer.

    Science.gov (United States)

    Awasthi, Niranjan; Hinz, Stefan; Brekken, Rolf A; Schwarz, Margaret A; Schwarz, Roderich E

    2015-03-01

    Angiogenesis remains a sensible target for pancreatic ductal adenocarcinoma (PDAC) therapy. VEGF, PDGF, FGF and their receptors are expressed at high levels and correlate with poor prognosis in human PDAC. Nintedanib is a triple angiokinase inhibitor that targets VEGFR1/2/3, FGFR1/2/3 and PDGFRα/β signaling. We investigated the antitumor activity of nintedanib alone or in combination with the cytotoxic agent gemcitabine in experimental PDAC. Nintedanib inhibited proliferation of cells from multiple lineages found in PDAC, with gemcitabine enhancing inhibitory effects. Nintedanib blocked PI3K/MAPK activity and induced apoptosis in vitro and in vivo. In a heterotopic model, net local tumor growth compared to controls (100%) was 60.8 ± 10.5% in the gemcitabine group, -2.1 ± 9.9% after nintedanib therapy and -12.4 ± 16% after gemcitabine plus nintedanib therapy. Effects of therapy on intratumoral proliferation, microvessel density and apoptosis corresponded with tumor growth inhibition data. In a PDAC survival model, median animal survival after gemcitabine, nintedanib and gemcitabine plus nintedanib was 25, 31 and 38 days, respectively, compared to 16 days in controls. The strong antitumor activity of nintedanib in experimental PDAC supports the potential of nintedanib-controlled mechanisms as targets for improved clinical PDAC therapy. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  1. HIF-1α- Targeting Acriflavine Provides Long Term Survival and Radiological Tumor Response in Brain Cancer Therapy.

    Science.gov (United States)

    Mangraviti, Antonella; Raghavan, Tula; Volpin, Francesco; Skuli, Nicolas; Gullotti, David; Zhou, Jinyuan; Asnaghi, Laura; Sankey, Eric; Liu, Ann; Wang, Yuan; Lee, Dong-Hoon; Gorelick, Noah; Serra, Riccardo; Peters, Michael; Schriefer, Destiny; Delaspre, Fabien; Rodriguez, Fausto J; Eberhart, Charles G; Brem, Henry; Olivi, Alessandro; Tyler, Betty

    2017-11-02

    Tumor progression, limited efficacy of current standard treatments, and the rise in patient mortality are associated with gene expression caused by the synergistic action of intratumoral hypoxia and HIF-1α activation. For this reason, recent investigations have focused on HIF-targeting therapeutic agents, with encouraging preclinical and clinical results in solid tumors. Here we describe the efficacy of a HIF-1α inhibitor, Acriflavine, and demonstrate its potency against brain cancer. This safe antibacterial dye induces cell death and apoptosis in several glioma cell lines, targets HIF-1α-mediated pathways, and decreases the level of PGK1, VEGF and HIF-1α in vitro and in vivo. Administered locally via biodegradable polymers, Acriflavine provides significant benefits in survival resulting in nearly 100% long term survival, confirmed by MRI and histological analyses. This study reports preclinical evidence that this safe, small molecule can contribute to brain tumor therapy and highlights the significance of HIF-1α-targeting molecules.

  2. Glycogen metabolism has a key role in the cancer microenvironment and provides new targets for cancer therapy.

    Science.gov (United States)

    Zois, Christos E; Harris, Adrian L

    2016-02-01

    Metabolic reprogramming is a hallmark of cancer cells and contributes to their adaption within the tumour microenvironment and resistance to anticancer therapies. Recently, glycogen metabolism has become a recognised feature of cancer cells since it is upregulated in many tumour types, suggesting that it is an important aspect of cancer cell pathophysiology. Here, we provide an overview of glycogen metabolism and its regulation, with a focus on its role in metabolic reprogramming of cancer cells under stress conditions such as hypoxia, glucose deprivation and anticancer treatment. The various methods to detect glycogen in tumours in vivo as well as pharmacological modulators of glycogen metabolism are also reviewed. Finally, we discuss the therapeutic value of targeting glycogen metabolism as a strategy for combinational approaches in cancer treatment.

  3. Factors informing HIV providers' decisions to start antiretroviral therapy for young people living with behaviorally acquired HIV.

    Science.gov (United States)

    Lee, Lana; Rand, Cynthia S; Ellen, Jonathan M; Agwu, Allison L

    2014-09-01

    Young people with behaviorally acquired HIV (BHIV) are less likely than adults to initiate antiretroviral therapy (ART) despite meeting treatment criteria. We explored critical factors involved in healthcare providers' decision making regarding ART initiation for young people with BHIV (aged 12-24 years). Semistructured interviews were conducted with 23 HIV providers from diverse training backgrounds caring for youth with BHIV at four adult clinics and one pediatric clinic in a high prevalence urban city. Interview domains probed clinical and nonclinical patient characteristics, the role of adherence, and provider attitudes working with youth to establish decision-making priorities for ART initiation. The constant comparative approach was used to develop grounded theory on providers' decision making on ART initiation. Clinical criteria, particularly the CD4 count, and the public health implications of HIV transmission determined the urgency for ART initiation. However, patient-related concerns regarding treatment readiness and adherence hampered the decision to initiate, especially at higher CD4 counts. Providers who acknowledged developmental characteristics of youth (e.g., evolving adult identity and self-efficacy around health management) appeared more cautious in assessing future ART adherence and responded with intensive clinical support. Extensive involvement of multidisciplinary teams was identified as an important strategy to retain youth in care, whereas strengthening youth-targeted approaches may be an unmet need in adult clinics. Evaluation of providers' awareness of the developmental features of youth and characteristics of youth-targeted approaches in clinics caring for youth with BHIV may inform interventions to increase youth engagement in care and subsequent decisions to successfully initiate ART. Copyright © 2014 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

  4. Does manual therapy provide additional benefit to breathing retraining in the management of dysfunctional breathing? A randomised controlled trial.

    Science.gov (United States)

    Jones, Mandy; Troup, Fiona; Nugus, John; Roughton, Michael; Hodson, Margaret; Rayner, Charlotte; Bowen, Frances; Pryor, Jennifer

    2015-01-01

    Dysfunctional breathing (DB) is associated with an abnormal breathing pattern, unexplained breathlessness and significant patient morbidity. Treatment involves breathing retraining through respiratory physiotherapy. Recently, manual therapy (MT) has also been used, but no evidence exists to validate its use. This study sought to investigate whether MT produces additional benefit when compared with breathing retraining alone in patients with DB. Sixty subjects with primary DB were randomised into either breathing retraining (standard treatment; n = 30) or breathing retraining plus MT (intervention; n = 30) group. Both the groups received standardised respiratory physiotherapy, which included: DB education, breathing retraining, home regimen, and audio disc. Intervention group subjects additionally received MT following further assessment. Data from 57 subjects were analysed. At baseline, standard treatment group subjects were statistically younger (41.7 + 13.5 versus 50.8 + 13.0 years; p = 0.001) with higher Nijmegen scores (38.6 + 9.5 versus 31.5 + 6.9; p = 0.001). However, no significant difference was found between the groups for primary outcome Nijmegen score (95% CI (-1.1, 6.6) p = 0.162), or any secondary outcomes (Hospital Anxiety & Depression Score, spirometry or exercise tolerance). Breathing retraining is currently the mainstay of treatment for patients with DB. The results of this study suggest MT provides no additional benefit in this patient group. Dysfunctional breathing (DB) is associated with significant patient morbidity but often goes unrecognised, leading to prolonged investigation and significant use of health care resources. Breathing retraining remains the primary management of this condition. However, physiotherapists are also using manual therapy (MT) as an adjunctive treatment for patients with DB. However, the results of this study suggest that MT provides no further benefit and cannot be recommended in

  5. Effects of Improvisational Music Therapy vs Enhanced Standard Care on Symptom Severity Among Children With Autism Spectrum Disorder: The TIME-A Randomized Clinical Trial.

    Science.gov (United States)

    Bieleninik, Lucja; Geretsegger, Monika; Mössler, Karin; Assmus, Jörg; Thompson, Grace; Gattino, Gustavo; Elefant, Cochavit; Gottfried, Tali; Igliozzi, Roberta; Muratori, Filippo; Suvini, Ferdinando; Kim, Jinah; Crawford, Mike J; Odell-Miller, Helen; Oldfield, Amelia; Casey, Órla; Finnemann, Johanna; Carpente, John; Park, A-La; Grossi, Enzo; Gold, Christian

    2017-08-08

    Music therapy may facilitate skills in areas affected by autism spectrum disorder (ASD), such as social interaction and communication. To evaluate effects of improvisational music therapy on generalized social communication skills of children with ASD. Assessor-blinded, randomized clinical trial, conducted in 9 countries and enrolling children aged 4 to 7 years with ASD. Children were recruited from November 2011 to November 2015, with follow-up between January 2012 and November 2016. Enhanced standard care (n = 182) vs enhanced standard care plus improvisational music therapy (n = 182), allocated in a 1:1 ratio. Enhanced standard care consisted of usual care as locally available plus parent counseling to discuss parents' concerns and provide information about ASD. In improvisational music therapy, trained music therapists sang or played music with each child, attuned and adapted to the child's focus of attention, to help children develop affect sharing and joint attention. The primary outcome was symptom severity over 5 months, based on the Autism Diagnostic Observation Schedule (ADOS), social affect domain (range, 0-27; higher scores indicate greater severity; minimal clinically important difference, 1). Prespecified secondary outcomes included parent-rated social responsiveness. All outcomes were also assessed at 2 and 12 months. Among 364 participants randomized (mean age, 5.4 years; 83% boys), 314 (86%) completed the primary end point and 290 (80%) completed the last end point. Over 5 months, participants assigned to music therapy received a median of 19 music therapy, 3 parent counseling, and 36 other therapy sessions, compared with 3 parent counseling and 45 other therapy sessions for those assigned to enhanced standard care. From baseline to 5 months, mean ADOS social affect scores estimated by linear mixed-effects models decreased from 14.08 to 13.23 in the music therapy group and from 13.49 to 12.58 in the standard care group (mean difference, 0

  6. Cognitive behavioural therapy attenuates the enhanced early facial stimuli processing in social anxiety disorders: an ERP investigation.

    Science.gov (United States)

    Cao, Jianqin; Liu, Quanying; Li, Yang; Yang, Jun; Gu, Ruolei; Liang, Jin; Qi, Yanyan; Wu, Haiyan; Liu, Xun

    2017-07-28

    Previous studies of patients with social anxiety have demonstrated abnormal early processing of facial stimuli in social contexts. In other words, patients with social anxiety disorder (SAD) tend to exhibit enhanced early facial processing when compared to healthy controls. Few studies have examined the temporal electrophysiological event-related potential (ERP)-indexed profiles when an individual with SAD compares faces to objects in SAD. Systematic comparisons of ERPs to facial/object stimuli before and after therapy are also lacking. We used a passive visual detection paradigm with upright and inverted faces/objects, which are known to elicit early P1 and N170 components, to study abnormal early face processing and subsequent improvements in this measure in patients with SAD. Seventeen patients with SAD and 17 matched control participants performed a passive visual detection paradigm task while undergoing EEG. The healthy controls were compared to patients with SAD pre-therapy to test the hypothesis that patients with SAD have early hypervigilance to facial cues. We compared patients with SAD before and after therapy to test the hypothesis that the early hypervigilance to facial cues in patients with SAD can be alleviated. Compared to healthy control (HC) participants, patients with SAD had more robust P1-N170 slope but no amplitude effects in response to both upright and inverted faces and objects. Interestingly, we found that patients with SAD had reduced P1 responses to all objects and faces after therapy, but had selectively reduced N170 responses to faces, and especially inverted faces. Interestingly, the slope from P1 to N170 in patients with SAD was flatter post-therapy than pre-therapy. Furthermore, the amplitude of N170 evoked by the facial stimuli was correlated with scores on the interaction anxiousness scale (IAS) after therapy. Our results did not provide electrophysiological support for the early hypervigilance hypothesis in SAD to faces, but

  7. Design of a boron neutron capture enhanced fast neutron therapy assembly

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Zhonglu [Georgia Inst. of Technology, Atlanta, GA (United States)

    2006-12-01

    The use of boron neutron capture to boost tumor dose in fast neutron therapy has been investigated at several fast neutron therapy centers worldwide. This treatment is termed boron neutron capture enhanced fast neutron therapy (BNCEFNT). It is a combination of boron neutron capture therapy (BNCT) and fast neutron therapy (FNT). It is believed that BNCEFNT may be useful in the treatment of some radioresistant brain tumors, such as glioblastoma multiform (GBM). A boron neutron capture enhanced fast neutron therapy assembly has been designed for the Fermilab Neutron Therapy Facility (NTF). This assembly uses a tungsten filter and collimator near the patient's head, with a graphite reflector surrounding the head to significantly increase the dose due to boron neutron capture reactions. The assembly was designed using Monte Carlo radiation transport code MCNP version 5 for a standard 20x20 cm2 treatment beam. The calculated boron dose enhancement at 5.7-cm depth in a water-filled head phantom in the assembly with a 5x5 cm2 collimation was 21.9% per 100-ppm 10B for a 5.0-cm tungsten filter and 29.8% for a 8.5-cm tungsten filter. The corresponding dose rate for the 5.0-cm and 8.5-cm thick filters were 0.221 and 0.127 Gy/min, respectively; about 48.5% and 27.9% of the dose rate of the standard 10x10 cm2 fast neutron treatment beam. To validate the design calculations, a simplified BNCEFNT assembly was built using four lead bricks to form a 5x5 cm2 collimator. Five 1.0-cm thick 20x20 cm2 tungsten plates were used to obtain different filter thicknesses and graphite bricks/blocks were used to form a reflector. Measurements of the dose enhancement of the simplified assembly in a water-filled head phantom were performed using a pair of tissue-equivalent ion chambers. One of the ion chambers is loaded with 1000-ppm natural boron (184-ppm 10B) to measure dose due to boron neutron capture. The

  8. A systematic review of randomized controlled trials on curative and health enhancement effects of forest therapy

    Directory of Open Access Journals (Sweden)

    Kamioka H

    2012-07-01

    Full Text Available Hiroharu Kamioka,1 Kiichiro Tsutani,2 Yoshiteru Mutoh,3 Takuya Honda,4 Nobuyoshi Shiozawa,5 Shinpei Okada,6 Sang-Jun Park,6 Jun Kitayuguchi,7 Masamitsu Kamada,8 Hiroyasu Okuizumi,9 Shuichi Handa91Faculty of Regional Environment Science, Tokyo University of Agriculture, Tokyo, 2Department of Drug Policy and Management, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, 3Todai Policy Alternatives Research Institute, The University of Tokyo, Tokyo, 4Japanese Society for the Promotion of Science, Tokyo, 5Food Labeling Division, Consumer Affairs Agency, Cabinet Office, Government of Japan, Tokyo, 6Physical Education and Medicine Research Foundation, Nagano, 7Physical Education and Medicine Research Center Unnan, Shimane, 8Department of Environmental and Preventive Medicine, Shimane University School of Medicine, Shimane, 9Mimaki Onsen (Spa Clinic, Tomi City, Nagano, JapanObjective: To summarize the evidence for curative and health enhancement effects through forest therapy and to assess the quality of studies based on a review of randomized controlled trials (RCTs.Study design: A systematic review based on RCTs.Methods: Studies were eligible if they were RCTs. Studies included one treatment group in which forest therapy was applied. The following databases – from 1990 to November 9, 2010 – were searched: MEDLINE via PubMed, CINAHL, Web of Science, and Ichushi-Web. All Cochrane databases and Campbell Systematic Reviews were also searched up to November 9, 2010.Results: Two trials met all inclusion criteria. No specific diseases were evaluated, and both studies reported significant effectiveness in one or more outcomes for health enhancement. However, the results of evaluations with the CONSORT (Consolidated Standards of Reporting Trials 2010 and CLEAR NPT (A Checklist to Evaluate a Report of a Nonpharmacological Trial checklists generally showed a remarkable lack of description in the studies. Furthermore, there was a

  9. Does Extracorporeal Shock Wave Therapy Enhance Healing of Osteochondritis Dissecans of the Rabbit Knee?: A Pilot Study

    National Research Council Canada - National Science Library

    Lyon, Roger; Liu, Xue Cheng; Kubin, Martin; Schwab, Joseph

    2013-01-01

    ... (ie, drilling, excision, or débridement). Since extracorporeal shock wave therapy (ESWT) enhances healing of long-bone nonunion fractures, we speculated ESWT would reactivate the healing process in OCD...

  10. Piracetam therapy does not enhance cognitive functioning in children with down syndrome.

    Science.gov (United States)

    Lobaugh, N J; Karaskov, V; Rombough, V; Rovet, J; Bryson, S; Greenbaum, R; Haslam, R H; Koren, G

    2001-04-01

    Piracetam is widely used as a purported means of improving cognitive function in children with Down syndrome. Its efficacy, however, has not been rigorously assessed. To determine whether 4 months of piracetam therapy (80-100 mg/kg per day) enhances cognitive function in children with Down syndrome. A randomized, double-blind, placebo-controlled crossover study. Twenty-five children with Down syndrome (aged 6.5-13 years) and their caregivers participated. After undergoing a baseline cognitive assessment, children were randomly assigned to 1 of 2 treatment groups: piracetam-placebo or placebo-piracetam. The difference in performance while taking piracetam vs while taking placebo on tests assessing a wide range of cognitive functions, including attention, learning, and memory. Eighteen children completed the study, 4 withdrew, and 3 were excluded at baseline. Piracetam therapy did not significantly improve cognitive performance over placebo use but was associated with central nervous system stimulatory effects in 7 children: aggressiveness (n = 4), agitation or irritability (n = 2), sexual arousal (n = 2), poor sleep (n = 1), and decreased appetite (n = 1). Piracetam therapy did not enhance cognition or behavior but was associated with adverse effects.

  11. Targeted Multifunctional Nanoparticles cure and image Brain Tumors: Selective MRI Contrast Enhancement and Photodynamic Therapy

    Science.gov (United States)

    Kopelman, Raoul

    2008-03-01

    Aimed at targeted therapy and imaging of brain tumors, our approach uses targeted, multi-functional nano-particles (NP). A typical nano-particle contains a biologically inert, non-toxic matrix, biodegradable and bio-eliminable over a long time period. It also contains active components, such as fluorescent chemical indicators, photo-sensitizers, MRI contrast enhancement agents and optical imaging dyes. In addition, its surface contains molecular targeting units, e.g. peptides or antibodies, as well as a cloaking agent, to prevent uptake by the immune system, i.e. enabling control of the plasma residence time. These dynamic nano-platforms (DNP) contain contrast enhancement agents for the imaging (MRI, optical, photo-acoustic) of targeted locations, i.e. tumors. Added to this are targeted therapy agents, such as photosensitizers for photodynamic therapy (PDT). A simple protocol, for rats implanted with human brain cancer, consists of tail injection with DNPs, followed by 5 min red light illumination of the tumor region. It resulted in excellent cure statistics for 9L glioblastoma.

  12. Enhancing provider knowledge and patient screening for palliative care needs in chronic multimorbid patients receiving home-based primary care.

    Science.gov (United States)

    Wharton, Tracy; Manu, Erika; Vitale, Caroline A

    2015-02-01

    This article describes a pilot model to increase palliative care (PC) knowledge and collaboration among providers and to systematically identify chronic multimorbid home care patients who would benefit from focused discussion of potential PC needs. Thirty health care providers from a home-based primary care team attended interdisciplinary trainings. The Palliative Performance Scale (PPS) tool was used to trigger discussions of potential palliative needs at team rounds for patients who scored below a cutoff point on the tool. Palliative Performance Scale implementation added little burden on nurses and triggered a discussion in 51 flagged patients. The tool successfully identified 75% of patients who died or were discharged. Screening was systematic and consistent and resulted in targeted discussions about PC needs without generating additional burden on our PC consult service. This model shows promise for enhancing collaborative patient care and access to PC. © The Author(s) 2013.

  13. Can tDCS enhance item-specific effects and generalizion after linguistically motivated aphasia therapy for verbs?

    Directory of Open Access Journals (Sweden)

    Vânia ede Aguiar

    2015-07-01

    Full Text Available Background. Aphasia therapy focusing on abstract properties of language promotes both item-specific effects and generalization to untreated materials. Neuromodulation with transcranial Direct Current Stimulation (tDCS has been shown to enhance item-specific improvement, but its potential to enhance generalization has not been systematically investigated. Here, we test the efficacy of ACTION (a linguistically motivated protocol and tDCS in producing item-specific and generalized improvement in aphasia.Method. Nine individuals with post-stroke aphasia participated in this study. Participants were pre-tested with a diagnostic language battery and a cognitive screening. Experimental tasks were administered over multiple baselines. Production of infinitives, of finite verbs and of full sentences were assessed before and after each treatment phase. Nonword repetition was used as a control measure. Each subject was treated in two phases. Ten daily 1-hour treatment sessions were provided per phase, in a double-blind, cross-over design. Linguistically-motivated language therapy focusing on verb inflection and sentence construction was provided in both phases. Each session began with 20 minutes of real or sham tDCS. Stimulation site was determined individually, based on MRI scans.Results. Group data showed improved production of treated and untreated verbs, attesting the efficacy of behavioral treatment, and its potential to yield generalization. Each individual showed significant item-specific improvement. Generalization occurred in the first phase of treatment for all subjects, and in the second phase for two subjects. Stimulation effects at the group level were significant for treated and untreated verbs altogether, but a ceiling effect for Sham cannot be excluded, as scores between real tDCS and Sham differed only before treatment.Conclusion. Our data demonstrate the efficacy of ACTION and suggest that tDCS may enhance both item-specific effects and

  14. Can tDCS enhance item-specific effects and generalization after linguistically motivated aphasia therapy for verbs?

    Science.gov (United States)

    de Aguiar, Vânia; Bastiaanse, Roelien; Capasso, Rita; Gandolfi, Marialuisa; Smania, Nicola; Rossi, Giorgio; Miceli, Gabriele

    2015-01-01

    Aphasia therapy focusing on abstract properties of language promotes both item-specific effects and generalization to untreated materials. Neuromodulation with transcranial Direct Current Stimulation (tDCS) has been shown to enhance item-specific improvement, but its potential to enhance generalization has not been systematically investigated. Here, we test the efficacy of ACTION (a linguistically motivated protocol) and tDCS in producing item-specific and generalized improvement in aphasia. Nine individuals with post-stroke aphasia participated in this study. Participants were pre-tested with a diagnostic language battery and a cognitive screening. Experimental tasks were administered over multiple baselines. Production of infinitives, of finite verbs and of full sentences were assessed before and after each treatment phase. Nonword repetition was used as a control measure. Each subject was treated in two phases. Ten daily 1-h treatment sessions were provided per phase, in a double-blind, cross-over design. Linguistically-motivated language therapy focusing on verb inflection and sentence construction was provided in both phases. Each session began with 20 min of real or sham tDCS. Stimulation site was determined individually, based on MRI scans. Group data showed improved production of treated and untreated verbs, attesting the efficacy of behavioral treatment, and its potential to yield generalization. Each individual showed significant item-specific improvement. Generalization occurred in the first phase of treatment for all subjects, and in the second phase for two subjects. Stimulation effects at the group level were significant for treated and untreated verbs altogether, but a ceiling effect for Sham cannot be excluded, as scores between real tDCS and Sham differed only before treatment. Our data demonstrate the efficacy of ACTION and suggest that tDCS may enhance both item-specific effects and generalization.

  15. Low intensity laser therapy speeds wound healing in hemophilia by enhancing platelet procoagulant activity.

    Science.gov (United States)

    Hoffman, Maureane; Monroe, Dougald M

    2012-01-01

    Our group has previously shown that cutaneous wound healing is delayed and histologically abnormal in a mouse model of hemophilia. Hemostasis is not only required to stop bleeding at the time of wounding, but also produces bioactive substances that promote appropriate inflammatory and proliferative responses during healing. Low intensity laser therapy (LILT) has been reported to enhance impaired wound healing in a variety of animal and human studies. The current studies were conducted to test the hypothesis that LILT can improve healing in a hemophilia B mouse model. Three daily treatments with 12 J/sq cm of 650 nm laser illumination reduced the time to closure of a 3-mm cutaneous punch biopsy wound in the hemophilic mice. All wounds were closed at 13 days in the sham-treated hemophilic mice, compared with 10 days in the LILT-treated hemophilic mice, and 9 days in wild-type mice. While LILT can speed healing by enhancing proliferation of cutaneous cells, we found that an additional mechanism likely contributes to the efficacy of LILT in the hemophilic mice. LILT enhanced the mechanical rigidity and platelet activity of clots formed from human platelet-rich plasma. Illumination of isolated platelets increased the mitochondrial membrane potential and enhanced binding of coagulation factors to the surface of activated platelets. Thus, while LILT can directly promote proliferative responses during healing, it also appears to enhance hemostasis in an animal model with impaired coagulation. These data suggest that trials of LILT as an adjunct to the usual hemostatic therapies in hemophilia are warranted. © 2012 by the Wound Healing Society.

  16. Polydopamine-coated gold nanostars for CT imaging and enhanced photothermal therapy of tumors

    Science.gov (United States)

    Li, Du; Shi, Xiangyang; Jin, Dayong

    2016-12-01

    The advancement of biocompatible nanoplatforms with dual functionalities of diagnosis and therapeutics is strongly demanded in biomedicine in recent years. In this work, we report the synthesis and characterization of polydopamine (pD)-coated gold nanostars (Au NSs) for computed tomography (CT) imaging and enhanced photothermal therapy (PTT) of tumors. Au NSs were firstly formed via a seed-mediated growth method and then stabilized with thiolated polyethyleneimine (PEI-SH), followed by deposition of pD on their surface. The formed pD-coated Au NSs (Au-PEI@pD NSs) were well characterized. We show that the Au-PEI@pD NSs are able to convert the absorbed near-infrared laser light into heat, and have strong X-ray attenuation property. Due to the co-existence of Au NSs and the pD, the light to heat conversion efficiency of the NSs can be significantly enhanced. These very interesting properties allow their uses as a powerful theranostic nanoplatform for efficient CT imaging and enhanced phtotothermal therapy of cancer cells in vitro and the xenografted tumor model in vivo. With the easy functionalization nature enabled by the coated pD shell, the developed pD-coated Au NSs may be developed as a versatile nanoplatform for targeted CT imaging and PTT of different types of cancer.

  17. Maize benefits the predatory beetle, Propylea japonica (Thunberg, to provide potential to enhance biological control for aphids in cotton.

    Directory of Open Access Journals (Sweden)

    Fang Ouyang

    Full Text Available BACKGROUND: Biological control provided by natural enemies play an important role in integrated pest management. Generalist insect predators provide an important biological service in the regulation of agricultural insect pests. Our goal is to understand the explicit process of oviposition preference, habitat selection and feeding behavior of predators in farmland ecosystem consisting of multiple crops, which is central to devising and delivering an integrated pest management program. METHODOLOGY: The hypotheses was that maize can serve as habitat for natural enemies and benefits predators to provide potential to enhance biological control for pest insects in cotton. This explicit process of a predatory beetle, Propylea japonica, in agricultural ecosystem composed of cotton and maize were examined by field investigation and stable carbon isotope analysis during 2008-2010. PRINCIPAL FINDING: Field investigation showed that P. japonica adults will search host plants for high prey abundance before laying eggs, indicating indirectly that P. japonica adults prefer to inhabit maize plants and travel to cotton plants to actively prey on aphids. The δ(13C values of adult P. japonica in a dietary shift experiment found that individual beetles were shifting from a C(3- to a C(4-based diet of aphids reared on maize or cotton, respectively, and began to reflect the isotope ratio of their new C(4 resources within one week. Approximately 80-100% of the diet of P. japonica adults in maize originated from a C(3-based resource in June, July and August, while approximately 80% of the diet originated from a C(4-based resource in September. CONCLUSION/SIGNIFICANCE: Results suggest that maize can serve as a habitat or refuge source for the predatory beetle, P. japonica, and benefits predators to provide potential to enhance biological control for insect pests in cotton.

  18. Maize benefits the predatory beetle, Propylea japonica (Thunberg), to provide potential to enhance biological control for aphids in cotton.

    Science.gov (United States)

    Ouyang, Fang; Men, Xingyuan; Yang, Bing; Su, Jianwei; Zhang, Yongsheng; Zhao, Zihua; Ge, Feng

    2012-01-01

    Biological control provided by natural enemies play an important role in integrated pest management. Generalist insect predators provide an important biological service in the regulation of agricultural insect pests. Our goal is to understand the explicit process of oviposition preference, habitat selection and feeding behavior of predators in farmland ecosystem consisting of multiple crops, which is central to devising and delivering an integrated pest management program. The hypotheses was that maize can serve as habitat for natural enemies and benefits predators to provide potential to enhance biological control for pest insects in cotton. This explicit process of a predatory beetle, Propylea japonica, in agricultural ecosystem composed of cotton and maize were examined by field investigation and stable carbon isotope analysis during 2008-2010. Field investigation showed that P. japonica adults will search host plants for high prey abundance before laying eggs, indicating indirectly that P. japonica adults prefer to inhabit maize plants and travel to cotton plants to actively prey on aphids. The δ(13)C values of adult P. japonica in a dietary shift experiment found that individual beetles were shifting from a C(3)- to a C(4)-based diet of aphids reared on maize or cotton, respectively, and began to reflect the isotope ratio of their new C(4) resources within one week. Approximately 80-100% of the diet of P. japonica adults in maize originated from a C(3)-based resource in June, July and August, while approximately 80% of the diet originated from a C(4)-based resource in September. Results suggest that maize can serve as a habitat or refuge source for the predatory beetle, P. japonica, and benefits predators to provide potential to enhance biological control for insect pests in cotton.

  19. Effects of Cognitive Enhancement Therapy on Employment Outcomes in Early Schizophrenia: Results from a 2-Year Randomized Trial

    Science.gov (United States)

    Eack, Shaun M.; Hogarty, Gerard E.; Greenwald, Deborah P.; Hogarty, Susan S.; Keshavan, Matcheri S.

    2011-01-01

    Objective: To examine the effects of psychosocial cognitive rehabilitation on employment outcomes in a randomized controlled trial for individuals with early course schizophrenia. Method: Early course schizophrenia outpatients (N = 58) were randomly assigned to cognitive enhancement therapy (CET) or an enriched supportive therapy (EST) control and…

  20. Undergraduate medical textbooks do not provide adequate information on intravenous fluid therapy: a systematic survey and suggestions for improvement.

    Science.gov (United States)

    Powell, Arfon G M T; Paterson-Brown, Simon; Drummond, Gordon B

    2014-02-20

    Inappropriate prescribing of intravenous (IV) fluid, particularly 0.9% sodium chloride, causes post-operative complications. Fluid prescription is often left to junior medical staff and is frequently poorly managed. One reason for poor intravenous fluid prescribing practices could be inadequate coverage of this topic in the textbooks that are used. We formulated a comprehensive set of topics, related to important common clinical situations involving IV fluid therapy, (routine fluid replacement, fluid loss, fluids overload) to assess the adequacy of textbooks in common use. We assessed 29 medical textbooks widely available to students in the UK, scoring the presence of information provided by each book on each of the topics. The scores indicated how fully the topics were considered: not at all, partly, and adequately. No attempt was made to judge the quality of the information, because there is no consensus on these topics. The maximum score that a book could achieve was 52. Three of the topics we chose were not considered by any of the books. Discounting these topics as "too esoteric", the maximum possible score became 46. One textbook gained a score of 45, but the general score was poor (median 11, quartiles 4, 21). In particular, coverage of routine postoperative management was inadequate. Textbooks for undergraduates cover the topic of intravenous therapy badly, which may partly explain the poor knowledge and performance of junior doctors in this important field. Systematic revision of current textbooks might improve knowledge and practice by junior doctors. Careful definition of the remit and content of textbooks should be applied more widely to ensure quality and "fitness for purpose", and avoid omission of vital knowledge.

  1. Integrating Medication Therapy Management (MTM) Services Provided by Community Pharmacists into a Community-Based Accountable Care Organization (ACO).

    Science.gov (United States)

    Isetts, Brian

    2017-10-16

    (1) Background: As the U.S. healthcare system evolves from fee-for-service financing to global population-based payments designed to be accountable for both quality and total cost of care, the effective and safe use of medications is gaining increased importance. The purpose of this project was to determine the feasibility of integrating medication therapy management (MTM) services provided by community pharmacists into the clinical care teams and the health information technology (HIT) infrastructure for Minnesota Medicaid recipients of a 12-county community-based accountable care organization (ACO). (2) Methods: The continuous quality improvement evaluation methodology employed in this project was the context + mechanism = outcome (CMO) model to account for the fact that programs only work insofar as they introduce promising ideas, solutions and opportunities in the appropriate social and cultural contexts. Collaborations between a 12-county ACO and 15 community pharmacies in Southwest Minnesota served as the social context for this feasibility study of MTM referrals to community pharmacists. (3) Results: All 15 community pharmacy sites were integrated into the HIT infrastructure through Direct Secure Messaging, and there were 32 recipients who received MTM services subsequent to referrals from the ACO at 5 of the 15 community pharmacies over a 1-year implementation phase. (4) Conclusion: At the conclusion of this project, an effective electronic communication and MTM referral system was activated, and consideration was given to community pharmacists providing MTM in future ACO shared savings agreements.

  2. Health care provider communication training in rural Tanzania empowers HIV-infected patients on antiretroviral therapy to discuss adherence problems.

    Science.gov (United States)

    Erb, S; Letang, E; Glass, T R; Natamatungiro, A; Mnzava, D; Mapesi, H; Haschke, M; Duthaler, U; Berger, B; Muri, L; Bader, J; Marzolini, C; Elzi, L; Klimkait, T; Langewitz, W; Battegay, M

    2017-10-01

    Self-reported adherence assessment in HIV-infected patients on antiretroviral therapy (ART) is challenging and may overestimate adherence. The aim of this study was to improve the ability of health care providers to elicit patients' reports of nonadherence using a "patient-centred" approach in a rural sub-Saharan African setting. A prospective interventional cohort study of HIV-infected patients on ART for ≥ 6 months attending an HIV clinic in rural Tanzania was carried out. The intervention consisted of a 2-day workshop for health care providers on patient-centred communication and the provision of an adherence assessment checklist for use in the consultations. Patients' self-reports of nonadherence (≥ 1 missed ART dose/4 weeks), subtherapeutic plasma ART concentrations (communication can successfully be implemented with a simple intervention in rural Africa. It increases the likelihood of HIV-infected patients reporting problems with adherence to ART; however, sustainability remains a challenge. © 2017 The Authors HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.

  3. Effects of an immuno-enhanced diet containing antioxidants in esophageal cancer surgery following neoadjuvant therapy.

    Science.gov (United States)

    Aiko, S; Kumano, I; Yamanaka, N; Tsujimoto, H; Takahata, R; Maehara, T

    2012-02-01

    Neoadjuvant therapy-induced immunological deterioration may be a key factor in postoperative morbidity in patients with esophageal cancer. This study aimed to determine the effects of perioperative feeding with an immuno-enhanced diet on immune competence in patients treated with neoadjuvant therapy followed by surgery. Because an immuno-enhanced diet that contained several antioxidants was used, perioperative oxidative stress and the effects of the immuno-enhanced diet on this stress were also investigated. Of 39 patients with esophageal cancer who underwent similar surgical procedures, 26 patients who received chemotherapy or chemoradiation therapy before surgery were randomly divided into two groups: group 1 (n= 14) was given an immuno-enhanced diet for 5 days before surgery, and group 2 (n= 12) received no enteral feeding products before surgery. Group 3 (n= 13) consisted of patients that did not receive neoadjuvant therapy and received no enteral feeding products before surgery. Several markers for coagulation and fibrinolysis were determined and immunological assessments were performed for each patient. To measure reactive oxygen metabolites and the total antioxidant capacity, diacron-reactive oxygen metabolites (d-ROMs) and OXY-adsorbent tests were performed using a free radical elective evaluator. Significant depression in lymphocyte numbers was observed in groups 1 and 2 before and early after surgery as compared to group 3. Numbers of B cells, CD4/CD8 ratio, and phytohemagglutinin-induced lymphocyte transformation tests were also significantly decreased in groups 1 and 2 on postoperative day 1. Fibrin and fibrinogen degradation products were significantly elevated in group 2 compared to group 1. d-ROMs and OXY-adsorbent test values were elevated before surgery and were decreased transiently early after surgery. Compared to groups 2 and 3, d-ROMs values were significantly lower in group 1 patients throughout the postoperative period, while OXY

  4. A Randomized Controlled Comparison of Integrative Cognitive-Affective Therapy and Cognitive-Behavioral Therapy-Enhanced for Bulimia Nervosa

    Science.gov (United States)

    Wonderlich, Stephen A.; Peterson, Carol B.; Crosby, Ross D.; Smith, Tracey L.; Klein, Marjorie H.; Mitchell, James E.; Crow, Scott J.

    2016-01-01

    Background The purpose of this investigation was to compare a new psychotherapy for bulimia nervosa, Integrative Cognitive-Affective Therapy (ICAT), with an established treatment, Cognitive-Behavioral Therapy-Enhanced (CBT-E). Method Eighty adults with symptoms of bulimia nervosa were randomized to ICAT or CBT-E for 21 sessions over 19 weeks. Bulimic symptoms, measured by the Eating Disorder Examination, were assessed at baseline, end of treatment, and 4-month follow-up. Treatment outcome, as measured by binge eating frequency, purging frequency, global eating disorder severity, emotion regulation, self-oriented cognition, depression, anxiety, and self-esteem, was determined using generalized estimating equations, logistic regression, and a general linear model (intent-to-treat). Results Both treatments were associated with significant improvement in bulimic symptoms as well as all measures of outcome, and no statistically significant differences were observed between the two conditions at end of treatment or follow-up. Intent-to-treat abstinence rates for ICAT (37.5% at end of treatment, 32.5% at follow-up) and CBT-E (22.5% at both end of treatment and follow-up) were not significantly different. Conclusions ICAT was associated with significant improvements in bulimic and associated symptoms that did not differ from those obtained with CBT-E. This initial randomized controlled trial of a new individual psychotherapy for bulimia nervosa suggests that targeting emotion and self-oriented cognition in the context of nutritional rehabilitation may be efficacious and worthy of further study. PMID:23701891

  5. Pulmonary Physical Therapy Techniques to Enhance Survival in Amyotrophic Lateral Sclerosis: A Systematic Review.

    Science.gov (United States)

    Macpherson, Chelsea E; Bassile, Clare C

    2016-07-01

    Respiratory insufficiency is the primary cause of morbidity and mortality in individuals with amyotrophic lateral sclerosis (ALS). Although mechanical interventions are effective in prolonging survival through respiratory support, pulmonary physical therapy interventions are being investigated. The purpose of this systematic review was to examine the effectiveness of pulmonary physical therapy interventions across the progressive stages of ALS. Six databases were searched for articles from inception to December 2014 investigating pulmonary physical therapy interventions in the ALS population. The search strategy followed Cochrane Collaboration guidelines with replication per database. Effect sizes (ES) were calculated for primary outcome measures: forced vital capacity (FVC) and peak cough expiratory flow (PCEF). Seven studies met inclusion criteria. Four studies used control groups whereas the remainder used repeated measures. With the exception of diaphragmatic breathing, pulmonary physical therapy interventions were effective in improving multiple respiratory outcome measures in this population. Inspiratory muscle training (IMT) was shown to prolong respiratory muscle strength with a strong effect size (ES = 1.48) for FVC. In addition, mean length of survival increased by 12 months. Lung volume recruitment training (LVRT) strongly enhanced immediate cough efficacy with improved FVC (ES = 1.02) and PCEF (ES = 1.82). Manually assisted cough (MAC) only improved PCEF by a small amount (ES = 0.15, bulbar ALS; ES = 0.16, classical ALS groups). Specific pulmonary physical therapy interventions (IMT, LVRT, and MAC) have effectiveness in improving respiratory outcome measures and increasing survival. These should be routinely incorporated into the comprehensive management of individuals with ALS. More rigorous methodological investigations should be performed to replicate these findings.Video abstract available with brief technique demonstration of IMT and LVRT (see

  6. Music therapy in pediatric palliative care: family-centered care to enhance quality of life.

    Science.gov (United States)

    Lindenfelser, Kathryn J; Hense, Cherry; McFerran, Katrina

    2012-05-01

    Research into the value of music therapy in pediatric palliative care (PPC) has identified quality of life as one area of improvement for families caring for a child in the terminal stages of a life-threatening illness. This small-scale investigation collected data in a multisite, international study including Minnesota, USA, and Melbourne, Australia. An exploratory mixed method design used the qualitative data collected through interviews with parents to interpret results from the PedsQL Family Impact Module of overall parental quality of life. Parents described music therapy as resulting in physical improvements of their child by providing comfort and stimulation. They also valued the positive experiences shared by the family in music therapy sessions that were strength oriented and family centered. This highlighted the physical and communication scales within the PedsQL Family Impact Module, where minimal improvements were achieved in contrast to some strong results suggesting diminished quality of life in cognitive and daily activity domains. Despite the significant challenges faced by parents during this difficult time, parents described many positive experiences in music therapy, and the overall score for half of the parents in the study did not diminish. The value of music therapy as a service that addresses the family-centered agenda of PPC is endorsed by this study.

  7. Providing guidance for genomics-based cancer treatment decisions: insights from stakeholder engagement for post-prostatectomy radiation therapy.

    Science.gov (United States)

    Abe, James; Lobo, Jennifer M; Trifiletti, Daniel M; Showalter, Timothy N

    2017-08-24

    Despite the emergence of genomics-based risk prediction tools in oncology, there is not yet an established framework for communication of test results to cancer patients to support shared decision-making. We report findings from a stakeholder engagement program that aimed to develop a framework for using Markov models with individualized model inputs, including genomics-based estimates of cancer recurrence probability, to generate personalized decision aids for prostate cancer patients faced with radiation therapy treatment decisions after prostatectomy. We engaged a total of 22 stakeholders, including: prostate cancer patients, urological surgeons, radiation oncologists, genomic testing industry representatives, and biomedical informatics faculty. Slides were at each meeting to provide background information regarding the analytical framework. Participants were invited to provide feedback during the meeting, including revising the overall project aims. Stakeholder meeting content was reviewed and summarized by stakeholder group and by theme. The majority of stakeholder suggestions focused on aspects of decision aid design and formatting. Stakeholders were enthusiastic about the potential value of using decision analysis modeling with personalized model inputs for cancer recurrence risk, as well as competing risks from age and comorbidities, to generate a patient-centered tool to assist decision-making. Stakeholders did not view privacy considerations as a major barrier to the proposed decision aid program. A common theme was that decision aids should be portable across multiple platforms (electronic and paper), should allow for interaction by the user to adjust model inputs iteratively, and available to patients both before and during consult appointments. Emphasis was placed on the challenge of explaining the model's composite result of quality-adjusted life years. A range of stakeholders provided valuable insights regarding the design of a personalized decision

  8. Surgical innovation-enhanced quality and the processes that assure patient/provider safety: A surgical conundrum.

    Science.gov (United States)

    Bruny, Jennifer; Ziegler, Moritz

    2015-12-01

    Innovation is a crucial part of surgical history that has led to enhancements in the quality of surgical care. This comprises both changes which are incremental and those which are frankly disruptive in nature. There are situations where innovation is absolutely required in order to achieve quality improvement or process improvement. Alternatively, there are innovations that do not necessarily arise from some need, but simply are a new idea that might be better. All change must assure a significant commitment to patient safety and beneficence. Innovation would ideally enhance patient care quality and disease outcomes, as well stimulate and facilitate further innovation. The tensions between innovative advancement and patient safety, risk and reward, and demonstrated effectiveness versus speculative added value have created a contemporary "surgical conundrum" that must be resolved by a delicate balance assuring optimal patient/provider outcomes. This article will explore this delicate balance and the rules that govern it. Recommendations are made to facilitate surgical innovation through clinical research. In addition, we propose options that investigators and institutions may use to address competing priorities. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Can tDCS enhance item-specific effects and generalization after linguistically motivated aphasia therapy for verbs?

    NARCIS (Netherlands)

    de Aguiar, Vania; Bastiaanse, Roelien; Capasso, Rita; Gandolfi, Marialuisa; Smania, Nicola; Rossi, Giorgio; Miceli, Gabriele

    2015-01-01

    Background: Aphasia therapy focusing on abstract properties of language promotes both item-specific effects and generalization to untreated materials. Neuromodulation with transcranial Direct Current Stimulation (tDCS) has been shown to enhance item-specific improvement, but its potential to enhance

  10. Sensitivity enhancement and contrasting information provided by free radicals in oriented-sample NMR of bicelle-reconstituted membrane proteins

    Science.gov (United States)

    Tesch, Deanna M.; Nevzorov, Alexander A.

    2014-02-01

    Elucidating structure and topology of membrane proteins (MPs) is essential for unveiling functionality of these important biological constituents. Oriented-sample solid-state NMR (OS-NMR) is capable of providing such information on MPs under nearly physiological conditions. However, two dimensional OS-NMR experiments can take several days to complete due to long longitudinal relaxation times combined with the large number of scans to achieve sufficient signal sensitivity in biological samples. Here, free radicals 5-DOXYL stearic acid, TEMPOL, and CAT-1 were added to uniformly 15N-labeled Pf1 coat protein reconstituted in DMPC/DHPC bicelles, and their effect on the longitudinal relaxation times (T1Z) was investigated. The dramatically shortened T1Z's allowed for the signal gain per unit time to be used for either: (i) up to a threefold reduction of the total experimental time at 99% magnetization recovery or (ii) obtaining up to 74% signal enhancement between the control and radical samples during constant experimental time at “optimal” relaxation delays. In addition, through OS-NMR and high-field EPR studies, free radicals were able to provide positional constraints in the bicelle system, which provide a description of the location of each residue in Pf1 coat protein within the bicellar membranes. This information can be useful in the determination of oligomerization states and immersion depths of larger membrane proteins.

  11. Sensitivity enhancement and contrasting information provided by free radicals in oriented-sample NMR of bicelle-reconstituted membrane proteins.

    Science.gov (United States)

    Tesch, Deanna M; Nevzorov, Alexander A

    2014-02-01

    Elucidating structure and topology of membrane proteins (MPs) is essential for unveiling functionality of these important biological constituents. Oriented-sample solid-state NMR (OS-NMR) is capable of providing such information on MPs under nearly physiological conditions. However, two dimensional OS-NMR experiments can take several days to complete due to long longitudinal relaxation times combined with the large number of scans to achieve sufficient signal sensitivity in biological samples. Here, free radicals 5-DOXYL stearic acid, TEMPOL, and CAT-1 were added to uniformly (15)N-labeled Pf1 coat protein reconstituted in DMPC/DHPC bicelles, and their effect on the longitudinal relaxation times (T1Z) was investigated. The dramatically shortened T1Z's allowed for the signal gain per unit time to be used for either: (i) up to a threefold reduction of the total experimental time at 99% magnetization recovery or (ii) obtaining up to 74% signal enhancement between the control and radical samples during constant experimental time at "optimal" relaxation delays. In addition, through OS-NMR and high-field EPR studies, free radicals were able to provide positional constraints in the bicelle system, which provide a description of the location of each residue in Pf1 coat protein within the bicellar membranes. This information can be useful in the determination of oligomerization states and immersion depths of larger membrane proteins. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. All-trans retinoic acid enhances bystander effect of suicide gene therapy in the treatment of breast cancer.

    Science.gov (United States)

    Kong, Heng; Liu, Xia; Yang, Liucheng; Qi, Ke; Zhang, Haoyun; Zhang, Jingwen; Huang, Zonghai; Wang, Hongxian

    2016-03-01

    All-trans retinoic acid (ATRA) has been shown to enhance the expression of connexin 43 (Cx43) and the bystander effect (BSE) in suicide gene therapy. These in turn improve effects of suicide gene therapies for several tumor types. However, whether ATRA can improve BSE remains unclear in suicide gene therapy for breast cancer. In the present study, MCF-7, human breast cancer cells were treated with ATRA in combination with a VEGFP-TK/CD gene suicide system developed by our group. We found that this combination enhances the efficiency of cell killing and apoptosis of breast cancer by strengthening the BSE in vitro. ATRA also promotes gap junction intercellular communication (GJIC) in MCF-7 cells by upregulation of the connexin 43 mRNA and protein in MCF-7 cells. These results indicate that enhancement of GJIC by ATRA in suicide gene system might serve as an attractive and cost-effective strategy of therapy for breast cancer cells.

  13. Medical School Anatomy and Pathology Workshops for High School Students Enhance Learning and Provide Inspiration for Careers in Medicine

    Science.gov (United States)

    Fenderson, Bruce A.; Veloski, J. Jon; Livesey, Michael; Wojdon-Smith, Tracey

    2016-01-01

    “Anatomy and Pathology Workshop” is a cadaver-based outreach program that models medical education to large groups of high school students. This study was designed to evaluate the impact of this program on students’ knowledge of anatomy and interest in biomedical science. A total of 144 high school students participated in the workshop in 2015. Preworkshop and postworkshop assessments were administered to assess students’ learning. A postworkshop survey was conducted to solicit students’ reflections and feedback. It was found that student performance in the postworkshop examination (mean 78%) had significantly improved when compared to the performance in the preexamination (mean 54%), indicating that this program enhances learning. Students were also inspired to consider opportunities in medicine and allied health professions—97% indicated that they had a better understanding of medical education; 95% agreed that they had better understanding of the human body; 84% thought anatomy was interesting and exciting; and 62% of the students indicated that they looked forward to studying medicine or another health profession. Students rated the instructors highly—95% agreed that the instructors were professional and served as role models. Medical/graduate student instructors were also highly regarded by the high school students—96% thought it was valuable to have student instructors and 94% thought that student instructors were caring and enthusiastic about teaching. In summary, this study demonstrates that outreach programs provided by medical schools help young adults during their formative years by modeling professionalism, providing role models, enhancing learning, and encouraging many to consider opportunities in the health professions. PMID:28725784

  14. Porphyrin lipid nanoparticles for enhanced photothermal therapy in a patient-derived orthotopic pancreas xenograft cancer model

    Science.gov (United States)

    MacLaughlin, Christina M.; Ding, Lili; Jin, Cheng; Cao, Pingjiang; Siddiqui, Iram; Hwang, David M.; Chen, Juan; Wilson, Brian C.; Zheng, Gang; Hedley, David W.

    2016-03-01

    Local disease control is a major problem in the treatment of pancreatic cancer, because curative-intent surgery is only possible in a minority of patients, and radiotherapy cannot be delivered in curative doses. Despite the promise of photothermal therapy (PTT) for ablation of pancreatic tumors, this approach remains under investigated. Using photothermal sensitizers in combination with laser light for PTT can result in more efficient conversion of light energy to heat, and confinement of thermal destruction to the tumor, thus sparing adjacent organs and vasculature. Porphyrins have been previously employed as photosensitizers for PDT and PTT, however their incorporation in to "porphysomes", lipid-based nanoparticles each containing ~80,000 porphyrins through conjugation of pyropheophorbide to phospholipids, carries two distinct advantages: 1) high-density porphyrin packing imparts the nanoparticles with enhanced photonic properties for imaging and phototherapy; 2) the enhanced permeability and retention effect may be exploited for optimal delivery of porphysomes to the tumor region thus high payload porphyrin delivery. The feasibility of porphysome-enhanced PTT for pancreatic cancer treatment was investigated using a patient-derived orthotopic pancreas xenograft tumor model. Uptake of porphysomes at the orthotopic tumor site was validated using ex vivo fluorescence imaging of intact organs of interest. The accumulation of porphysomes in orthotopic tumor microstructure was also confirmed by fluorescence imaging of excised tissue slices. PTT progress was monitored as changes in tumor surface temperature using IR optical imaging. Histological analyses were conducted to examine microstructure changes in tissue morphology, and the viability of remaining tumor tissues following exposure to heat. These studies may also provide insight as to the contribution of heat sink in application of thermal therapies to highly vascularized pancreatic tumors.

  15. Enhancing organizational capacity to provide cancer control programs among Latino churches: design and baseline findings of the CRUZA Study.

    Science.gov (United States)

    Allen, Jennifer D; Torres, Maria Idali; Tom, Laura S; Rustan, Sarah; Leyva, Bryan; Negron, Rosalyn; Linnan, Laura A; Jandorf, Lina; Ospino, Hosffman

    2015-04-09

    Faith-based organizations (FBOs) have been successful in delivering health promotion programs for African Americans, though few studies have been conducted among Latinos. Even fewer have focused on organizational change, which is required to sustain community-based initiatives. We hypothesized that FBOs serving Latinos would be more likely to offer evidence-based strategies (EBS) for cancer control after receiving a capacity enhancement intervention to implement health programs, and designed the CRUZA trial to test this hypothesis. This paper describes the CRUZA design and baseline findings. We identified Catholic parishes in Massachusetts that provided Spanish-language mass (n = 65). A baseline survey assessed organizational characteristics relevant to adoption of health programs, including readiness for adoption, "fit" between innovation and organizational mission, implementation climate, and organizational culture. In the next study phase, parishes that completed the baseline assessment will be recruited to a randomized cluster trial, with the parish as the unit of analysis. Both groups will receive a Program Manual and Toolkit. Capacity Enhancement parishes will also be offered technical support, assistance forming health committees and building inter-institutional partnerships, and skills-based training. Of the 49 parishes surveyed at baseline (75%), one-third (33%) reported having provided at least one health program in the prior year. However, only two program offerings were cancer-specific. Nearly one-fifth (18%) had an active health ministry. There was a high level of organizational readiness to adopt cancer control programs, high congruence between parish missions and CRUZA objectives, moderately conducive implementation climates, and organizational cultures supportive of CRUZA programming. Having an existing health ministry was significantly associated with having offered health programs within the past year. Relationships between health program

  16. Motivational enhancement therapy in addition to physical therapy improves motivational factors and treatment outcomes in people with low back pain: a randomized controlled trial.

    Science.gov (United States)

    Vong, Sinfia K; Cheing, Gladys L; Chan, Fong; So, Eric M; Chan, Chetwyn C

    2011-02-01

    To examine whether the addition of motivational enhancement treatment (MET) to conventional physical therapy (PT) produces better outcomes than PT alone in people with chronic low back pain (LBP). A double-blinded, prospective, randomized, controlled trial. PT outpatient department. Participants (N=76) with chronic LBP were randomly assigned to receive 10 sessions of either MET plus PT or PT alone. MET included motivational interviewing strategies and motivation-enhancing factors. The PT program consisted of interferential therapy and back exercises. Motivational-enhancing factors, pain intensity, physical functions, and exercise compliance. The MET-plus-PT group produced significantly greater improvements than the PT group in 3 motivation-enhancing factors; proxy efficacy (Pmotivation and exercise compliance and show better improvement in physical function in patients with chronic LBP compared with PT alone. Copyright © 2011 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  17. Chemotherapy-Induced Macrophage Infiltration into Tumors Enhances Nanographene-Based Photodynamic Therapy.

    Science.gov (United States)

    Zhao, Yang; Zhang, Chenran; Gao, Liquan; Yu, Xinhe; Lai, Jianhao; Lu, Dehua; Bao, Rui; Wang, Yanpu; Jia, Bing; Wang, Fan; Liu, Zhaofei

    2017-11-01

    Increased recruitment of tumor-associated macrophages (TAM) to tumors following chemotherapy promotes tumor resistance and recurrence and correlates with poor prognosis. TAM depletion suppresses tumor growth, but is not highly effective due to the effects of tumorigenic mediators from other stromal sources. Here, we report that adoptive macrophage transfer led to a dramatically enhanced photodynamic therapy (PDT) effect of 2-(1-hexyloxyethyl)-2-devinyl pyropheophor-bide-alpha (HPPH)-coated polyethylene glycosylated nanographene oxide [GO(HPPH)-PEG] by increasing its tumor accumulation. Moreover, tumor treatment with commonly used chemotherapeutic drugs induced an increase in macrophage infiltration into tumors, which also enhanced tumor uptake and the PDT effects of GO(HPPH)-PEG, resulting in tumor eradication. Macrophage recruitment to tumors after chemotherapy was visualized noninvasively by near-infrared fluorescence and single-photon emission CT imaging using F4/80-specific imaging probes. Our results demonstrate that chemotherapy combined with GO(HPPH)-PEG PDT is a promising strategy for the treatment of tumors, especially those resistant to chemotherapy. Furthermore, TAM-targeted molecular imaging could potentially be used to predict the efficacy of combination therapy and select patients who would most benefit from this treatment approach. Cancer Res; 77(21); 6021-32. ©2017 AACR. ©2017 American Association for Cancer Research.

  18. Myxoma virus combined with rapamycin treatment enhances adoptive T cell therapy for murine melanoma brain tumors.

    Science.gov (United States)

    Thomas, Diana L; Doty, Rosalinda; Tosic, Vesna; Liu, Jia; Kranz, David M; McFadden, Grant; Macneill, Amy L; Roy, Edward J

    2011-10-01

    Adoptive transfer of tumor-specific T cells has shown some success for treating metastatic melanoma. We evaluated a novel strategy to improve adoptive therapy by administering both T cells and oncolytic myxoma virus to mice with syngeneic B16.SIY melanoma brain tumors. Adoptive transfer of activated CD8(+) 2C T cells that recognize SIY peptide doubled survival time, but SIY-negative tumors recurred. Myxoma virus killed B16.SIY cells in vitro, and intratumoral injection of virus led to selective and transient infection of the tumor. Virus treatment recruited innate immune cells to the tumor and induced IFNβ production in the brain, resulting in limited oncolytic effects in vivo. To counter this, we evaluated the safety and efficacy of co-administering 2C T cells, myxoma virus, and either rapamycin or neutralizing antibodies against IFNβ. Mice that received either triple combination therapy survived significantly longer with no apparent side effects, but eventually relapsed. Importantly, rapamycin treatment did not impair T cell-mediated tumor destruction, supporting the feasibility of combining adoptive immunotherapy and rapamycin-enhanced virotherapy. Myxoma virus may be a useful vector for transient delivery of therapeutic genes to a tumor to enhance T cell responses.

  19. Potential of microneedles in enhancing delivery of photosensitising agents for photodynamic therapy.

    Science.gov (United States)

    Kearney, Mary-Carmel; Brown, Sarah; McCrudden, Maelíosa T C; Brady, Aaron J; Donnelly, Ryan F

    2014-12-01

    Photodynamic therapy can be used in the treatment of pre-malignant and malignant diseases. It offers advantages over other therapies currently used in the treatment of skin lesions including avoidance of damage to surrounding tissue and minimal or no scarring. Unfortunately, systemic delivery of photosensitising agents can result in adverse effects, such as prolonged cutaneous photosensitivity; while topical administration lacks efficacy in the clearance of deeper skin lesions and those with a thick overlying keratotic layer. Therefore, enhancement of conventional photosensitiser delivery is desired. However, the physicochemical properties of photosensitising agents, such as extreme hydrophilicity or lipophilicity and large molecular weights make this challenging. This paper reviews the potential of microneedles as a viable method to overcome these delivery-limiting physicochemical characteristics and discusses the current benefits and limitations of solid, dissolving and hydrogel-forming microneedles. Clinical studies in which microneedles have successfully improved photodynamic therapy are also discussed, along with benefits which microneedles offer, such as precise photosensitiser localisation, painless application and reduction in waiting times between photosensitiser administration and irradiation highlighted. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Cognitive enhancement therapy for adult autism spectrum disorder: Results of an 18-month randomized clinical trial.

    Science.gov (United States)

    Eack, Shaun M; Hogarty, Susan S; Greenwald, Deborah P; Litschge, Maralee Y; Porton, Shannondora A; Mazefsky, Carla A; Minshew, Nancy J

    2017-12-29

    Cognitive remediation is a promising approach to treating core cognitive deficits in adults with autism, but rigorously controlled trials of comprehensive interventions that target both social and non-social cognition over a sufficient period of time to impact functioning are lacking. This study examined the efficacy of cognitive enhancement therapy (CET) for improving core cognitive and employment outcomes in adult autism. Verbal adult outpatients with autism spectrum disorder (N = 54) were randomized to an 18-month, single-blind trial of CET, a cognitive remediation approach that integrates computer-based neurocognitive training with group-based training in social cognition, or an active enriched supportive therapy (EST) comparison focused on psychoeducation and condition management. Primary outcomes were composite indexes of neurocognitive and social-cognitive change. Competitive employment was a secondary outcome. Intent-to-treat analyses indicated that CET produced significant differential increases in neurocognitive function relative to EST (d = .46, P = .013). Both CET and EST were associated with large social-cognitive improvements, with CET demonstrating an advantage at 9 (d = .58, P = 0.020), but not 18 months (d = .27, P = 0.298). Effects on employment indicated that participants treated with CET were significantly more likely to gain competitive employment than those in EST, OR = 6.21, P = 0.023, which was mediated by cognitive improvement. CET is a feasible and potentially effective treatment for core cognitive deficits in adult autism spectrum disorder. The treatment of cognitive impairments in this population can contribute to meaningful improvements in adult outcomes. Autism Res 2017. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Cognitive enhancement therapy (CET), an 18-month cognitive remediation intervention designed to improve thinking and social understanding, was found to be

  1. Results of ENHANCED Implantable Cardioverter Defibrillator Programming to Reduce Therapies and Improve Quality of Life (from the ENHANCED-ICD Study)

    DEFF Research Database (Denmark)

    Mastenbroek, Mirjam H.; Pedersen, Susanne S.; van der Tweel, Ingeborg

    2016-01-01

    -reported outcomes. The "ENHANCED Implantable Cardioverter Defibrillator programming to reduce therapies and improve quality of life" study (ENHANCED-ICD study) was a prospective, safety-monitoring study enrolling 60 primary and secondary prevention patients at the University Medical Center Utrecht. Patients...... programming strategy, unnecessary ICD therapy was prevented in 10% of ENHANCED-ICD patients during a median follow-up period of 1.3 years. With respect to patient-reported outcomes, levels of distress were highest and perceived health status lowest at the time of implantation, which both gradually improved...... during follow-up. In conclusion, the ENHANCED-ICD study demonstrates that programming a NID 60/80 for VT/VF detection is safe for ICD patients and does not negatively impact their quality of life....

  2. Circulating primers enhance platelet function and induce resistance to antiplatelet therapy

    Science.gov (United States)

    Blair, T A; Moore, S F; Hers, I

    2015-01-01

    Background Aspirin and P2Y12 antagonists are antiplatelet compounds that are used clinically in patients with thrombosis. However, some patients are ‘resistant’ to antiplatelet therapy, which increases their risk of developing acute coronary syndromes. These patients often present with an underlying condition that is associated with altered levels of circulating platelet primers and platelet hyperactivity. Platelet primers cannot stimulate platelet activation, but, in combination with physiologic stimuli, significantly enhance platelet function. Objectives To explore the role of platelet primers in resistance to antiplatelet therapy, and to evaluate whether phosphoinositide 3-kinase (PI3K) contributes to this process. Methods and Results We used platelet aggregation, thromboxane A2 production and ex vivo thrombus formation as functional readouts of platelet activity. Platelets were treated with the potent P2Y12 inhibitor AR-C66096, aspirin, or a combination of both, in the presence or absence of the platelet primers insulin-like growth factor-1 (IGF-1) and thrombopoietin (TPO), or the Gz-coupled receptor ligand epinephrine. We found that platelet primers largely overcame the inhibitory effects of antiplatelet compounds on platelet functional responses. IGF-1-mediated and TPO-mediated, but not epinephrine-mediated, enhancements in the presence of antiplatelet drugs were blocked by the PI3K inhibitors wortmannin and LY294002. Conclusions These results demonstrate that platelet primers can contribute to antiplatelet resistance. Furthermore, our data demonstrate that there are PI3K-dependent and PI3K-independent mechanisms driving primer-mediated resistance to antiplatelet therapy. PMID:26039631

  3. Ketogenic diets enhance oxidative stress and radio-chemo-therapy responses in lung cancer xenografts.

    Science.gov (United States)

    Allen, Bryan G; Bhatia, Sudershan K; Buatti, John M; Brandt, Kristin E; Lindholm, Kaleigh E; Button, Anna M; Szweda, Luke I; Smith, Brian J; Spitz, Douglas R; Fath, Melissa A

    2013-07-15

    Ketogenic diets are high in fat and low in carbohydrates as well as protein which forces cells to rely on lipid oxidation and mitochondrial respiration rather than glycolysis for energy metabolism. Cancer cells (relative to normal cells) are believed to exist in a state of chronic oxidative stress mediated by mitochondrial metabolism. The current study tests the hypothesis that ketogenic diets enhance radio-chemo-therapy responses in lung cancer xenografts by enhancing oxidative stress. Mice bearing NCI-H292 and A549 lung cancer xenografts were fed a ketogenic diet (KetoCal 4:1 fats: proteins+carbohydrates) and treated with either conventionally fractionated (1.8-2 Gy) or hypofractionated (6 Gy) radiation as well as conventionally fractionated radiation combined with carboplatin. Mice weights and tumor size were monitored. Tumors were assessed for immunoreactive 4-hydroxy-2-nonenal-(4HNE)-modified proteins as a marker of oxidative stress as well as proliferating cell nuclear antigen (PCNA) and γH2AX as indices of proliferation and DNA damage, respectively. The ketogenic diets combined with radiation resulted in slower tumor growth in both NCI-H292 and A549 xenografts (P ketogenic diet also slowed tumor growth when combined with carboplatin and radiation, relative to control. Tumors from animals fed a ketogenic diet in combination with radiation showed increases in oxidative damage mediated by lipid peroxidation as determined by 4HNE-modified proteins as well as decreased proliferation as assessed by decreased immunoreactive PCNA. These results show that a ketogenic diet enhances radio-chemo-therapy responses in lung cancer xenografts by a mechanism that may involve increased oxidative stress.

  4. Stem cell therapy and curcumin synergistically enhance recovery from spinal cord injury.

    Directory of Open Access Journals (Sweden)

    D Ryan Ormond

    Full Text Available Acute traumatic spinal cord injury (SCI is marked by the enhanced production of local cytokines and pro-inflammatory substances that induce gliosis and prevent reinnervation. The transplantation of stem cells is a promising treatment strategy for SCI. In order to facilitate functional recovery, we employed stem cell therapy alone or in combination with curcumin, a naturally-occurring anti-inflammatory component of turmeric (Curcuma longa, which potently inhibits NF-κB. Spinal cord contusion following laminectomy (T9-10 was performed using a weight drop apparatus (10 g over a 12.5 or 25 mm distance, representing moderate or severe SCI, respectively in Sprague-Dawley rats. Neural stem cells (NSC were isolated from subventricular zone (SVZ and transplanted at the site of injury with or without curcumin treatment. Functional recovery was assessed by BBB score and body weight gain measured up to 6 weeks following SCI. At the conclusion of the study, the mass of soleus muscle was correlated with BBB score and body weight. Stem cell therapy improved recovery from moderate SCI, however, it had a limited effect on recovery after severe SCI. Curcumin stimulated NSC proliferation in vitro, and in combination with stem cell therapy, induced profound recovery from severe SCI as evidenced by improved functional locomotor recovery, increased body weight, and soleus muscle mass. These findings demonstrate that curcumin in conjunction with stem cell therapy synergistically improves recovery from severe SCI. Furthermore, our results indicate that the effect of curcumin extends beyond its known anti-inflammatory properties to the regulation of stem cell proliferation.

  5. HDAC inhibitors as cognitive enhancers in fear, anxiety and trauma therapy: where do we stand?

    Science.gov (United States)

    Whittle, Nigel; Singewald, Nicolas

    2014-04-01

    A novel strategy to treat anxiety and fear-related disorders such as phobias, panic and PTSD (post-traumatic stress disorder) is combining CBT (cognitive behavioural therapy), including extinction-based exposure therapy, with cognitive enhancers. By targeting and boosting mechanisms underlying learning, drug development in this field aims at designing CBT-augmenting compounds that help to overcome extinction learning deficits, promote long-term fear inhibition and thus support relapse prevention. Progress in revealing the role of epigenetic regulation of specific genes associated with extinction memory generation has opened new avenues in this direction. The present review examines recent evidence from pre-clinical studies showing that increasing histone acetylation, either via genetic or pharmacological inhibition of HDACs (histone deacetylases) by e.g. vorinostat/SAHA (suberoylanilide hydroxamic acid), entinostat/MS-275, sodium butyrate, TSA (trichostatin A) or VPA (valproic acid), or by targeting HATs (histone acetyltransferases), augments fear extinction and, importantly, generates a long-term extinction memory that can protect from return of fear phenomena. The molecular mechanisms and pathways involved including BDNF (brain-derived neurotrophic factor) and NMDA (N-methyl-D-aspartate) receptor signalling are just beginning to be revealed. First studies in healthy humans are in support of extinction-facilitating effects of HDAC inhibitors. Very recent evidence that HDAC inhibitors can rescue deficits in extinction-memory-impaired rodents indicates a potential clinical utility of this approach also for exposure therapy-resistant patients. Important future work includes investigation of the long-term safety aspects of HDAC inhibitor treatment, as well as design of isotype(s)-specific inhibitors. Taken together, HDAC inhibitors display promising potential as pharmacological adjuncts to augment the efficacy of exposure-based approaches in anxiety and trauma therapy.

  6. BEMER Electromagnetic Field Therapy Reduces Cancer Cell Radioresistance by Enhanced ROS Formation and Induced DNA Damage.

    Directory of Open Access Journals (Sweden)

    Katja Storch

    Full Text Available Each year more than 450,000 Germans are expected to be diagnosed with cancer subsequently receiving standard multimodal therapies including surgery, chemotherapy and radiotherapy. On top, molecular-targeted agents are increasingly administered. Owing to intrinsic and acquired resistance to these therapeutic approaches, both the better molecular understanding of tumor biology and the consideration of alternative and complementary therapeutic support are warranted and open up broader and novel possibilities for therapy personalization. Particularly the latter is underpinned by the increasing utilization of non-invasive complementary and alternative medicine by the population. One investigated approach is the application of low-dose electromagnetic fields (EMF to modulate cellular processes. A particular system is the BEMER therapy as a Physical Vascular Therapy for which a normalization of the microcirculation has been demonstrated by a low-frequency, pulsed EMF pattern. Open remains whether this EMF pattern impacts on cancer cell survival upon treatment with radiotherapy, chemotherapy and the molecular-targeted agent Cetuximab inhibiting the epidermal growth factor receptor. Using more physiological, three-dimensional, matrix-based cell culture models and cancer cell lines originating from lung, head and neck, colorectal and pancreas, we show significant changes in distinct intermediates of the glycolysis and tricarboxylic acid cycle pathways and enhanced cancer cell radiosensitization associated with increased DNA double strand break numbers and higher levels of reactive oxygen species upon BEMER treatment relative to controls. Intriguingly, exposure of cells to the BEMER EMF pattern failed to result in sensitization to chemotherapy and Cetuximab. Further studies are necessary to better understand the mechanisms underlying the cellular alterations induced by the BEMER EMF pattern and to clarify the application areas for human disease.

  7. BEMER Electromagnetic Field Therapy Reduces Cancer Cell Radioresistance by Enhanced ROS Formation and Induced DNA Damage.

    Science.gov (United States)

    Storch, Katja; Dickreuter, Ellen; Artati, Anna; Adamski, Jerzy; Cordes, Nils

    2016-01-01

    Each year more than 450,000 Germans are expected to be diagnosed with cancer subsequently receiving standard multimodal therapies including surgery, chemotherapy and radiotherapy. On top, molecular-targeted agents are increasingly administered. Owing to intrinsic and acquired resistance to these therapeutic approaches, both the better molecular understanding of tumor biology and the consideration of alternative and complementary therapeutic support are warranted and open up broader and novel possibilities for therapy personalization. Particularly the latter is underpinned by the increasing utilization of non-invasive complementary and alternative medicine by the population. One investigated approach is the application of low-dose electromagnetic fields (EMF) to modulate cellular processes. A particular system is the BEMER therapy as a Physical Vascular Therapy for which a normalization of the microcirculation has been demonstrated by a low-frequency, pulsed EMF pattern. Open remains whether this EMF pattern impacts on cancer cell survival upon treatment with radiotherapy, chemotherapy and the molecular-targeted agent Cetuximab inhibiting the epidermal growth factor receptor. Using more physiological, three-dimensional, matrix-based cell culture models and cancer cell lines originating from lung, head and neck, colorectal and pancreas, we show significant changes in distinct intermediates of the glycolysis and tricarboxylic acid cycle pathways and enhanced cancer cell radiosensitization associated with increased DNA double strand break numbers and higher levels of reactive oxygen species upon BEMER treatment relative to controls. Intriguingly, exposure of cells to the BEMER EMF pattern failed to result in sensitization to chemotherapy and Cetuximab. Further studies are necessary to better understand the mechanisms underlying the cellular alterations induced by the BEMER EMF pattern and to clarify the application areas for human disease.

  8. Low-level laser therapy: a useful technique for enhancing the proliferation of various cultured cells.

    Science.gov (United States)

    AlGhamdi, Khalid M; Kumar, Ashok; Moussa, Noura A

    2012-01-01

    The aim of this work is to review the available literature on the details of low-level laser therapy (LLLT) use for the enhancement of the proliferation of various cultured cell lines including stem cells. A cell culture is one of the most useful techniques in science, particularly in the production of viral vaccines and hybrid cell lines. However, the growth rate of some of the much-needed mammalian cells is slow. LLLT can enhance the proliferation rate of various cell lines. Literature review from 1923 to 2010. By investigating the outcome of LLLT on cell cultures, many articles report that it produces higher rates of ATP, RNA, and DNA synthesis in stem cells and other cell lines. Thus, LLLT improves the proliferation of the cells without causing any cytotoxic effects. Mainly, helium neon and gallium-aluminum-arsenide (Ga-Al-As) lasers are used for LLLT on cultured cells. The results of LLLT also vary according to the applied energy density and wavelengths to which the target cells are subjected. This review suggests that an energy density value of 0.5 to 4.0 J/cm(2) and a visible spectrum ranging from 600 to 700 nm of LLLT are very helpful in enhancing the proliferation rate of various cell lines. With the appropriate use of LLLT, the proliferation rate of cultured cells, including stem cells, can be increased, which would be very useful in tissue engineering and regenerative medicine.

  9. Carbon Nanoparticle Enhance Photoacoustic Imaging and Therapy for Bone Tissue Engineering

    Science.gov (United States)

    Talukdar, Yahfi

    , compared to non-stimulated controls. The results taken together indicate that carbon nanoparticle enhanced PA stimulation serves as an anabolic stimulus for bone regeneration. The results suggest opportunities towards the development of implant device combination therapies for bone loss due to disease or trauma.

  10. Resistance to insulin therapy among patients and providers: results of the cross-national Diabetes Attitudes, Wishes, and Needs (DAWN) study

    NARCIS (Netherlands)

    Peyrot, M.; Rubin, R.R.; Lauritzen, T.; Skovlund, S.E.; Snoek, F.J.; Matthews, D.R.; Landgraf, R.; Kleinebreil, L.

    2005-01-01

    OBJECTIVE - To examine the correlates of patient and provider attitudes toward insulin therapy. RESEARCH DESIGN AND METHODS - Data are from surveys of patients with type 2 diabetes not taking insulin (n = 2,061) and diabetes care providers (nurses = 1,109; physicians = 2,681) in 13 countries in

  11. Control group design: enhancing rigor in research of mind-body therapies for depression.

    Science.gov (United States)

    Kinser, Patricia Anne; Robins, Jo Lynne

    2013-01-01

    Although a growing body of research suggests that mind-body therapies may be appropriate to integrate into the treatment of depression, studies consistently lack methodological sophistication particularly in the area of control groups. In order to better understand the relationship between control group selection and methodological rigor, we provide a brief review of the literature on control group design in yoga and tai chi studies for depression, and we discuss challenges we have faced in the design of control groups for our recent clinical trials of these mind-body complementary therapies for women with depression. To address the multiple challenges of research about mind-body therapies, we suggest that researchers should consider 4 key questions: whether the study design matches the research question; whether the control group addresses performance, expectation, and detection bias; whether the control group is ethical, feasible, and attractive; and whether the control group is designed to adequately control for nonspecific intervention effects. Based on these questions, we provide specific recommendations about control group design with the goal of minimizing bias and maximizing validity in future research.

  12. New oral targeted therapies for metastatic breast cancer disrupt the traditional patients' management-A healthcare providers' view.

    Science.gov (United States)

    Martin, E; Pourtau, L; Di Palma, M; Delaloge, S

    2017-11-01

    Although a cure still cannot be expected for metastatic breast cancer, thanks to progressive advances in treatments, life expectancy has been increasing over the past 15 years. This study aims to present the impact on the organisation of patients' management of newly released oral targeted therapies dedicated to metastatic breast cancer and the obstacles to their diffusion. Our work is based on the analysis of 40 semi-structured interviews, conducted with oncology healthcare professionals in three regions of France (2015-2016). It shows three main results. First, the prescription of an oral targeted therapy requires greater collaboration between healthcare professionals than traditional intravenous oncology drugs, which may be challenging. Second, there remain many barriers to the dissemination of oral targeted therapies. Third, taking an oral targeted therapy keeps the patient away from the hospital facility and asks for a strong therapeutic alliance. The management of oral targeted therapies is time-consuming for medical oncologists and disrupts the traditional care pathway. The multiplication of actors involved in patients' management reinforces the slowdown in the deployment and acceptance of therapeutic innovations. More players equal a higher risk of slowdown. Questioning and re-designing hospital organisation and management modalities towards this type of care are critical. © 2016 John Wiley & Sons Ltd.

  13. Human platelet lysate gel provides a novel three dimensional-matrix for enhanced culture expansion of mesenchymal stromal cells.

    Science.gov (United States)

    Walenda, Gudrun; Hemeda, Hatim; Schneider, Rebekka K; Merkel, Rudolf; Hoffmann, Bernd; Wagner, Wolfgang

    2012-12-01

    Cell culture in regenerative medicine needs to facilitate efficient expansion according to good manufacturing practice requirements. Human platelet lysate (HPL) can be used as a substitute for fetal calf serum without the risk of xenogeneic immune reactions or transmission of bovine pathogens. Heparin needs to be added as anticoagulant before addition of HPL to culture medium; otherwise, HPL-medium forms a gel within 1 h. Here, we demonstrated that such HPL-gels provide a suitable 3D-matrix for cell culture that-apart from heparin-consists of the same components as the over-layered culture medium. Mesenchymal stromal cells (MSCs) grew in several layers at the interface between HPL-gel and HPL-medium without contact with any artificial biomaterials. Notably, proliferation of MSCs was much higher on HPL-gel compared with tissue culture plastic. Further, the frequency of initial fibroblastoid colony forming units (CFU-f) increased on HPL-gel. The viscous consistency of HPL-gel enabled passaging with a convenient harvesting and reseeding procedure by pipetting cells together with their HPL-matrix-this method does not require washing steps and can easily be automated. The immunophenotype and in vitro differentiation potential toward adipogenic, osteogenic, and chondrogenic lineage were not affected by culture-isolation on HPL-gel. Taken together, HPL-gel has many advantages over conventional plastic surfaces: it facilitates enhanced CFU-f outgrowth, increased proliferation rates, higher cell densities, and nonenzymatic passaging procedures for culture expansion of MSCs.

  14. CD36 Provides Host Protection Against Klebsiella pneumoniae Intrapulmonary Infection by Enhancing Lipopolysaccharide Responsiveness and Macrophage Phagocytosis.

    Science.gov (United States)

    Olonisakin, Tolani F; Li, Huihua; Xiong, Zeyu; Kochman, Elizabeth J K; Yu, Minting; Qu, Yanyan; Hulver, Mei; Kolls, Jay K; St Croix, Claudette; Doi, Yohei; Nguyen, Minh-Hong; Shanks, Robert M Q; Mallampalli, Rama K; Kagan, Valerian E; Ray, Anuradha; Silverstein, Roy L; Ray, Prabir; Lee, Janet S

    2016-12-15

    Klebsiella pneumoniae remains an important cause of intrapulmonary infection and invasive disease worldwide. K. pneumoniae can evade serum killing and phagocytosis primarily through the expression of a polysaccharide capsule, but its pathogenicity is also influenced by host factors. We examined whether CD36, a scavenger receptor that recognizes pathogen and modified self ligands, is a host determinant of K. pneumoniae pathogenicity. Despite differences in serum sensitivity and virulence of 3 distinct K. pneumoniae (hypermucoviscous K1, research K2, and carbapenemase-producing ST258) strains, the absence of CD36 significantly increased host susceptibility to acute intrapulmonary infection by K. pneumoniae, regardless of strain. We demonstrate that CD36 enhances LPS responsiveness to K. pneumoniae to increase downstream cytokine production and macrophage phagocytosis that is independent of polysaccharide capsular antigen. Our study provides new insights into host determinants of K. pneumoniae pathogenicity and raises the possibility that functional mutations in CD36 may predispose individuals to K. pneumoniae syndromes. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  15. Enhancement of a 252Cf-based neutron beam via subcritical multiplication for neutron capture therapy.

    Science.gov (United States)

    Wang, C K; Zino, J F; Kessler, G

    2000-01-01

    Previous studies indicated that an epithermal-neutron beam based on bare 252Cf is not feasible for neutron capture therapy (NCT). It was reported that a clinically useful epithermal-neutron beam requires a minimum of 1.0 g of 252Cf, which is more than twice the US current annual supply. However, it was reasoned that the required quantity of 252Cf could be dramatically reduced when used with a subcritical multiplying assembly (SMA). This reasoning is based on the assumption that the epithermal-neutron beam intensity for NCT is directly proportional to the fission neutron population, and that the neutron multiplying factor of the SMA can be estimated by 1/(1 - k(eff)). We have performed detailed Monte Carlo calculations to investigate the validity of the above reasoning. Our results show that 1/(1 - k(eff)) grossly overestimates the beam enhancement factor for NCT. For example, Monte Carlo calculations predict a beam enhancement factor of 6.0 for an optimized SMA geometry with k(eff) = 0.968. This factor is much less than 31 predicted by 1/(1 - k(eff)). The overestimation is due to the fact that most of the neutrons produced in the SMA are self-shielded, whereas self-shielding is negligible in a bare 252Cf source. Since the beam intensity of a 0.1 g 252Cf with the optimized SMA enhancement is still more than an order of magnitude too low compared to the existing reactor beams, we conclude that the enhancement via an SMA for a 252Cf-based epithermal-neutron beam is inadequate for NCT.

  16. Structure of the physical therapy benefit in a typical Blue Cross Blue Shield preferred provider organization plan available in the individual insurance market in 2011.

    Science.gov (United States)

    Sandstrom, Robert W; Lehman, Jedd; Hahn, Lee; Ballard, Andrew

    2013-10-01

    The Affordable Care Act of 2010 establishes American Health Benefit Exchanges. The benefit design of insurance plans in state health insurance exchanges will be based on the structure of existing small-employer-sponsored plans. The purpose of this study was to describe the structure of the physical therapy benefit in a typical Blue Cross Blue Shield (BCBS) preferred provider organization (PPO) health insurance plan available in the individual insurance market in 2011. A cross-sectional survey design was used. The physical therapy benefit within 39 BCBS PPO plans in 2011 was studied for a standard consumer with a standard budget. First, whether physical therapy was a benefit in the plan was determined. If so, then the structure of the benefit was described in terms of whether the physical therapy benefit was a stand-alone benefit or part of a combined-discipline benefit and whether a visit or financial limit was placed on the physical therapy benefit. Physical therapy was included in all BCBS plans that were studied. Ninety-three percent of plans combined physical therapy with other disciplines. Two thirds of plans placed a limit on the number of visits covered. The results of the study are limited to 1 standard consumer, 1 association of insurance companies, 1 form of insurance (a PPO), and 1 PPO plan in each of the 39 states that were studied. Physical therapy is a covered benefit in a typical BCBS PPO health insurance plan. Physical therapy most often is combined with other therapy disciplines, and the number of covered visits is limited in two thirds of plans.

  17. Involvement of reactive oxygen species in the enhancement of membrane lipid peroxidation by sonodynamic therapy with functionalized fullerenes.

    Science.gov (United States)

    Yumita, Nagahiko; Iwase, Yumiko; Watanabe, Takahiro; Nishi, Koji; Kuwahara, Hiroyuki; Shigeyama, Masato; Sadamoto, Kiyomi; Ikeda, Toshihiko; Umemura, Shin-Ichiro

    2014-11-01

    Sonodynamic cancer therapy is based on the preferential uptake and/or retention of a sonosensitizing drug (sonosensitizer) in tumor tissues and subsequent activation of the drug by ultrasound irradiation. In the present study, we investigated the participation of lipid peroxidation in the mechanism of the sonodynamically-induced antitumor effect with functionalized fullerenes, such as polyhydroxy fullerene (PHF. Ultrasonically-induced cell damage and lipid peroxidation with PHF were compared in the same in vitro insonation setup. Sarcoma 180 cells suspended in PBS were exposed to 2 MHz ultrasound in the presence and absence of PHF. Cell viability was determined by the Trypan Blue exclusion test. Lipid peroxidation in cell membranes was estimated by measuring the amount of malondialdehyde as the thiobarbituric acid-reactive-substances. Significant enhancement of the rates of both ultrasonically-induced cell damage and lipid peroxidation was observed in the presence of PHF, both of which were positively correlated with PHF. The enhancement of cell damage and lipid peroxidation with PHF was suppressed by reactive oxygen scavengers such as histidine and tryptophan. The good correlation observed in the presence of PHF suggests that membrane lipid peroxidation is one of the important intermediary events in sonodynamically-induced cellular damage. The inhibitory effects of histidine and tryptophan also provide evidence that singlet oxygen plays an important role in PHF-mediated sonosensitization of membranes and that this moiety may be an important mediator of cell destruction in sonodynamic therapy associated with PHF and ultrasound. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  18. Ozone therapy as an adjunct to vancomycin enhances bacterial elimination in methicillin resistant Staphylococcus aureus mediastinitis.

    Science.gov (United States)

    Gulmen, Senol; Kurtoglu, Tunay; Meteoglu, Ibrahim; Kaya, Selcuk; Okutan, Huseyin

    2013-11-01

    We aimed to investigate the influence of intraperitoneal ozone therapy on bacterial elimination and mediastinal inflammation in experimental Staphylococcus aureus mediastinitis. Forty Wistar-Albino rats were randomized into five groups (eight per group) as follows: uncontaminated group, untreated contaminated group, ozone group, vancomycin group, and vancomycin + ozone group. Uncontaminated group underwent upper median sternotomy. The remaining four groups were inoculated with 0.5 mL 10(8) colony-forming units/mL methicillin-resistant Staphylococcus aureus in the mediastinal and sternal layers. Untreated contaminated group had no treatment. Rats in the vancomycin group received intramuscular vancomycin (40 mg/kg/d), and ozone was administered intraperitoneally (70 μg/mL, 1 mg/kg/d) in the ozone group for the treatment of mediastinitis. Vancomycin + ozone group rats were treated by the combination of both methods. At the end of 10 d, quantitative bacterial cultures and sternal tissue samples were obtained for determination of bacterial counts and histologic degree of inflammation. Both the vancomycin and the ozone treatments caused significant reduction of bacterial counts in quantitative bacterial cultures. Combination of vancomycin and ozone treatments resulted in further reduction of bacterial counts in mediastinum and sternum. Histologic examination of tissue samples revealed significant reduction in severity of mediastinitis related inflammation in vancomycin and vancomycin + ozone groups compared with untreated contaminated group. Ozone therapy as an adjunct to vancomycin leads to enhanced bacterial elimination in infected sternal and mediastinal tissues in experimental methicillin-resistant Staphylococcus aureus mediastinitis. The benefit of adjuvant ozone therapy is suggested to be related to its bactericidal effect. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. Attitudes Toward Combining Psychological, Mind-Body Therapies and Nutritional Approaches for the Enhancement of Mood.

    Science.gov (United States)

    Lores, Taryn Jade; Henke, Miriam; Chur-Hansen, Anna

    2016-01-01

    Context • Interest has been rising in the use of complementary and alternative medicine (CAM) for the promotion of health and treatment of disease. To date, the majority of CAM research has focused on exploring the demographic characteristics, attitudes, and motivations of CAM users and on the efficacy of different therapies and products. Less is known with respect to the psychological characteristics of people who use CAM. Previous research has not investigated the usefulness of integrating mind-body therapies with natural products in a combined mood intervention. Objective • The study intended to investigate attitudes toward a proposed new approach to the treatment of mood, one that integrates psychological mind-body therapies and natural nutritional products. Design • Participants completed an online survey covering demographics, personality traits, locus of control, use of CAM, attitudes toward the proposed psychonutritional approach, and mood. Setting • This study was conducted at the University of Adelaide School of Psychology (Adelaide, SA, Australia). Participants • Participants were 333 members of the Australian general public, who were recruited online via the social-media platform Facebook. The majority were women (83.2%), aged between 18 and 81 y. Outcome Measures • Measures included the Multidimensional Health Locus of Control Scale Form B, the Ten-Item Personality Inventory, and the Depression, Anxiety and Stress Scale. Results • Participants were positive about the proposed approach and were likely to try it to enhance their moods. The likeliness of use of the combined approach was significantly higher in the female participants and was associated with higher levels of the personality trait openness and an internal health locus of control, after controlling for all other variables. Conclusions • Interest exists for an intervention for mood that incorporates both psychological and nutritional approaches. Further research into the

  20. The targeting mechanism of DHA ligand and its conjugate with Gemcitabine for the enhanced tumor therapy

    Science.gov (United States)

    Li, Siwen; Qin, Jingyi; Tian, Caiping; Cao, Jie; Fida, Guissi; Wang, Zhaohui; Chen, Haiyan; Qian, Zhiyu; Chen, Wei R; Gu, Yueqing

    2014-01-01

    Docosahexaenoic acid (DHA), an omega-3 C22 natural fatty acid serving as a precursor for metabolic and biochemical pathways, was reported as a targeting ligand of anticancer drugs. However, its tumor targeting ability and mechanism has not been claimed. Here we hypothesized that the uptake of DHA by tumor cells is related to the phosphatidylethanolamine (PE) contents in cell membranes. Thus, in this manuscript, the tumor-targeting ability of DHA was initially demonstrated in vitro and in vivo on different tumor cell lines by labeling DHA with fluorescence dyes. Subsequently, the tumor targeting ability was then correlated with the contents of PE in cell membranes to study the uptake mechanism. Further, DHA was conjugated with anticancer drug gemcitabine (DHA-GEM) for targeted tumor therapy. Our results demonstrated that DHA exhibited high tumor targeting ability and PE is the main mediator, which confirmed our hypothesis. The DHA-GEM displayed enhanced therapeutic efficacy than that of GEM itself, indicating that DHA is a promising ligand for tumor targeted therapy. PMID:25004114

  1. Providing Opportunities for Student Self-Assessment: The Impact on the Acquisition of Psychomotor Skills in Occupational Therapy Students

    Science.gov (United States)

    Jay, Julie; Owen, Antonette

    2016-01-01

    The Occupational Therapy department at the University of the Witwatersrand in South Africa is responsible for ensuring students achieve psychomotor skill proficiency, as it is an essential component of health care practice. The aim of this study was to determine whether the introduction of opportunities to afford self-evaluation better prepared…

  2. A mass merchandiser's role in enhancing pharmacy students' business plan development skills for medication therapy management services.

    Science.gov (United States)

    Moultry, Aisha Morris

    2011-09-10

    To develop a relationship between a pharmacy management course and a mass merchandiser and to determine whether involving pharmacy managers from the mass merchandiser in the course would enhance student skills in developing a business plan for medication therapy management services. The pharmacy managers from the mass merchandiser participated in lectures, provided panel discussions, and conducted a business plan competition. Learning was assessed by means of 4 examinations and 1 project (ie, the business plan). At the conclusion of the semester, surveys were administered to solicit student input and gain insight from pharmacy managers on the perceived value of this portion of the course. Students' average grade on the business plan assignment, which included the oral presentation, the peer assessment, and the written proposal, was 92.2%. Approximately 60% (n=53) of surveyed students agreed or strongly agreed that their management skills had improved because of the participation of pharmacy managers from the mass merchandiser. All of the managers enjoyed participating in the experience. The involvement of pharmacy managers from a mass merchandiser enhanced student learning in the classroom, and managers felt that their participation was an important contribution to the development of future pharmacists.

  3. A Mass Merchandiser's Role in Enhancing Pharmacy Students’ Business Plan Development Skills for Medication Therapy Management Services

    Science.gov (United States)

    2011-01-01

    Objectives. To develop a relationship between a pharmacy management course and a mass merchandiser and to determine whether involving pharmacy managers from the mass merchandiser in the course would enhance student skills in developing a business plan for medication therapy management services. Design. The pharmacy managers from the mass merchandiser participated in lectures, provided panel discussions, and conducted a business plan competition. Learning was assessed by means of 4 examinations and 1 project (ie, the business plan). At the conclusion of the semester, surveys were administered to solicit student input and gain insight from pharmacy managers on the perceived value of this portion of the course. Assessment. Students’ average grade on the business plan assignment, which included the oral presentation, the peer assessment, and the written proposal, was 92.2%. Approximately 60% (n = 53) of surveyed students agreed or strongly agreed that their management skills had improved because of the participation of pharmacy managers from the mass merchandiser. All of the managers enjoyed participating in the experience. Conclusions. The involvement of pharmacy managers from a mass merchandiser enhanced student learning in the classroom, and managers felt that their participation was an important contribution to the development of future pharmacists. PMID:21969719

  4. The Influence of Patient Choice of First Provider on Costs and Outcomes: Analysis From a Physical Therapy Patient Registry.

    Science.gov (United States)

    Denninger, Thomas R; Cook, Chad E; Chapman, Cole G; McHenry, Timothy; Thigpen, Charles A

    2018-02-01

    Study Design Retrospective study. Background Alternative models of care that allow patients to choose direct access to physical therapy have shown promise in terms of cost reduction for neck and back pain. However, real-world exploration within the US health care system is notably limited. Objectives To compare total claims paid and patient outcomes for patients with neck and back pain who received physical therapy intervention via direct access versus medical referral. Methods Data were accessed for patients seeking care for neck or back pain (n = 603) between 2012 and 2014, who chose to begin care either through traditional medical referral or direct access to a physical therapy- led spine management program. All patients received a standardized, pragmatic physical therapy approach, with patient-reported measures of pain and disability assessed before and after treatment. Patient demographics and outcomes data were obtained from the medical center patient registry and combined with total claims paid calculated for the year after the index claim. Linear mixed-effects modeling was used to analyze group differences in pain and disability, visits/time, and annualized costs. Results Patients who chose to enter care via the direct-access physical therapy-led spine management program displayed significantly lower total costs (mean difference, $1543; 95% confidence interval: $51, $3028; P = .04) than those who chose traditional medical referral. Patients in both groups showed clinically important improvements in pain and disability, which were similar between groups (P>.05). Conclusion The initial patient choice to begin care with a physical therapist for back or neck pain resulted in lower cost of care over the next year, while resulting in similar improvements in patient outcomes at discharge from physical therapy. These findings add to the emerging literature suggesting that patients' choice to access physical therapy through direct access may be associated with lower

  5. Noncontact, low-frequency ultrasound therapy enhances neovascularization and wound healing in diabetic mice.

    Science.gov (United States)

    Maan, Zeshaan N; Januszyk, Michael; Rennert, Robert C; Duscher, Dominik; Rodrigues, Melanie; Fujiwara, Toshihiro; Ho, Natalie; Whitmore, Arnetha; Hu, Michael S; Longaker, Michael T; Gurtner, Geoffrey C

    2014-09-01

    Chronic wounds are a major source of morbidity for patients and represent a significant health burden. Implementing noninvasive techniques that accelerate healing of these wounds would provide great benefit. Ultrasound appears to be an effective modality for the treatment of chronic wounds in humans. MIST Therapy is a noncontact, low-frequency ultrasound treatment delivered through a saline mist. A variety of mechanisms have been proposed to explain the efficacy of ultrasound therapy, but the underlying molecular and cellular pathways impacted by this technique remain unclear. The in vivo effect of noncontact, low-frequency ultrasound was therefore examined in a humanized excisional wound model. The treatment group received noncontact, low-frequency ultrasound therapy three times per week, whereas the control group received a standard dressing change. Wounds were photographed at regular intervals to calculate healing kinetics. Wound tissue was harvested and processed for histology, quantitative polymerase chain reaction, and enzyme-linked immunosorbent assay. The MIST group demonstrated significantly accelerated wound healing, with 17.3 days to wound closure compared with 24 days in the controls (p healing evidenced by significantly decreased mean wound area relative to original size (68 percent versus 80 percent; p frequency ultrasound-treated mice compared with controls. Noncontact, low-frequency ultrasound treatment improves neovascularization and wound closure rates in excisional wounds for diabetic mice, likely because of the stimulated release of angiogenic factors.

  6. A Biomimic Reconstituted High Density Lipoprotein Nanosystem for Enhanced VEGF Gene Therapy of Myocardial Ischemia

    Directory of Open Access Journals (Sweden)

    Xiaotian Sun

    2015-01-01

    Full Text Available A biomimic reconstituted high density lipoprotein (rHDL based system, rHDL/Stearic-PEI/VEGF complexes, was fabricated as an advanced nanovector for delivering VEGF plasmid. Here, Stearic-PEI was utilized to effectively condense VEGF plasmid and to incorporate the plasmid into rHDL. The rHDL/Stearic-PEI/VEGF complexes with diameter under 100 nm and neutral surface charge demonstrated enhanced stability under the presence of bovine serum albumin. Moreover, in vitro cytotoxicity and transfection assays on H9C2 cells further revealed their superiority, as they displayed lower cytotoxicity with much higher transfection efficiency when compared to PEI 10K/VEGF and Lipos/Stearic-PEI/VEGF complexes. In addition, in vivo investigation on ischemia/reperfusion rat model implied that rHDL/Stearic-PEI/VEGF complexes possessed high transgene capacity and strong therapeutic activity. These findings indicated that rHDL/Stearic-PEI/VEGF complexes could be an ideal gene delivery system for enhanced VEGF gene therapy of myocardial ischemia, which might be a new promising strategy for effective myocardial ischemia treatment.

  7. Transferrin-Modified Nanoparticles for Photodynamic Therapy Enhance the Antitumor Efficacy of Hypocrellin A

    Directory of Open Access Journals (Sweden)

    Xi Lin

    2017-11-01

    Full Text Available Photodynamic therapy (PDT has emerged as a potent novel therapeutic modality that induces cell death through light-induced activation of photosensitizer. But some photosensitizers have characteristics of poor water-solubility and non-specific tissue distribution. These characteristics become main obstacles of PDT. In this paper, we synthesized a targeting drug delivery system (TDDS to improve the water-solubility of photosensitizer and enhance the ability of targeted TFR positive tumor cells. TDDS is a transferrin-modified Poly(D,L-Lactide-co-glycolide (PLGA and carboxymethyl chitosan (CMC nanoparticle loaded with a photosensitizer hypocrellin A (HA, named TF-HA-CMC-PLGA NPs. Morphology, size distribution, Fourier transform infrared (FT-IR spectra, encapsulation efficiency, and loading capacity of TF-HA-CMC-PLGA NPs were characterized. In vitro TF-HA-CMC-PLGA NPs presented weak dark cytotoxicity and significant photo-cytotoxicity with strong reactive oxygen species (ROS generation and apoptotic cancer cell death. In vivo photodynamic antitumor efficacy of TF-HA-CMC-PLGA NPs was investigated with an A549 (TFR positive tumor-bearing model in male athymic nude mice. TF-HA-CMC-PLGA NPs caused tumor delay with a remarkable tumor inhibition rate of 63% for 15 days. Extensive cell apoptosis in tumor tissue and slight side effects in normal organs were observed. The results indicated that TDDS has great potential to enhance PDT therapeutic efficacy.

  8. Enhancement of photodynamic therapy effect by temporally inhibiting infarction with anticoagulant heparin

    Science.gov (United States)

    Yang, Liyong; Zhao, Hongyou

    2008-12-01

    Photodynamic Therapy (PDT) is one of the tumor-targeting therapeutics, and has been an established medical practice in recent years. PDT mediates tumor destruction mainly by killing tumor cells directly and damaging the tumor-associated vasculature, also inducing an immune response against tumor cells. For the Photofrin-mediated PDT, Vascular system injury is the predominant destruction that results in vascular collapse and blood plasma leakage, then leading to tumor infarction. However, thrombus formation during PDT may influence the light transmission and oxygen supply. Also some tumor cells not killed by PDT may irritate angiogenesis, causing the tumor recurrence under the condition of hypoxia after PDT. In our work, to prolong coagulation and formation of thrombus, an anticoagulant heparin was employed before the Photofrin-mediated PDT. After being administrated both Photofrin and anticoagulant heparin, the BALB/c mice with the subcutaneous EMT6 mammary carcinomas model were exposed to laser (635nm). And then an enhanced effect was received. Our experiments indicated that its antitumor effect may be attributed to the improvement of the light delivery to the deep part of tumor and oxygen supply for PDT. The results suggested that heparin can be used to enhance the effect of PDT in a solid tumor treatment.

  9. Evaluating Motivational Enhancement Therapy Adherence and Competence Among Spanish-speaking Therapists

    OpenAIRE

    Santa Ana, Elizabeth J.; Carroll, Kathleen M.; Añez, Luis; Paris, Manuel; Ball, Samuel A.; Nich, Charla; Frankforter, Tami L.; Suarez-Morales, Lourdes; Szapocznik, José; Martino, Steve

    2009-01-01

    Despite the fact that the number of Hispanic individuals in need of treatment for substance use problems is increasing internationally, no studies have investigated the extent to which therapists can provide empirically supported treatments to Spanish-speaking clients with adequate fidelity. Twenty-three bilingual Hispanic therapists from five community outpatient treatment programs in the United States were randomly assigned to deliver either three sessions of motivational enhancement therap...

  10. Video games and rehabilitation: using design principles to enhance engagement in physical therapy.

    Science.gov (United States)

    Lohse, Keith; Shirzad, Navid; Verster, Alida; Hodges, Nicola; Van der Loos, H F Machiel

    2013-12-01

    Patient nonadherence with therapy is a major barrier to rehabilitation. Recovery is often limited and requires prolonged, intensive rehabilitation that is time-consuming, expensive, and difficult. We review evidence for the potential use of video games in rehabilitation with respect to the behavioral, physiological, and motivational effects of gameplay. In this Special Interest article, we offer a method to evaluate effects of video game play on motor learning and their potential to increase patient engagement with therapy, particularly commercial games that can be interfaced with adapted control systems. We take the novel approach of integrating research across game design, motor learning, neurophysiology changes, and rehabilitation science to provide criteria by which therapists can assist patients in choosing games appropriate for rehabilitation. Research suggests that video games are beneficial for cognitive and motor skill learning in both rehabilitation science and experimental studies with healthy subjects. Physiological data suggest that gameplay can induce neuroplastic reorganization that leads to long-term retention and transfer of skill; however, more clinical research in this area is needed. There is interdisciplinary evidence suggesting that key factors in game design, including choice, reward, and goals, lead to increased motivation and engagement. We maintain that video game play could be an effective supplement to traditional therapy. Motion controllers can be used to practice rehabilitation-relevant movements, and well-designed game mechanics can augment patient engagement and motivation in rehabilitation. We recommend future research and development exploring rehabilitation-relevant motions to control games and increase time in therapy through gameplay.Video Abstract available (see Video, Supplemental Digital Content 1, http://links.lww.com/JNPT/A61) for more insights from the authors.

  11. Monitoring ankylosing spondylitis therapy by dynamic contrast-enhanced and diffusion-weighted magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Gaspersic, Natasa [University Medical Centre, Department of Rheumatology, Ljubljana (Slovenia); Sersa, Igor [Jozef Stefan Institute, Ljubljana (Slovenia); Jevtic, Vladimir [Medical Faculty, Department of Radiology, Ljubljana (Slovenia); Tomsic, Matija; Praprotnik, Sonja [University Medical Centre, Department of Rheumatology, Ljubljana (Slovenia)

    2008-02-15

    The effects of different therapies on enthesitis/osteitis in active ankylosing spondylitis (AS) were evaluated by magnetic resonance imaging (MRI). The aim was to assess the role of quantitative MRI in the evaluation of AS treatment efficacy. Thirty patients with active spondylitis or bilateral sacroilitis were selected and followed up for 1 year. Ten of the patients were treated only with non-steroidal anti-inflammatory drugs, 10 patients additionally received at baseline an intravenous pulse of glucocorticoids and 10 patients were treated with regular infusions of infliximab. Disease activity was measured according to clinical instruments and laboratory tests. For each patient, one selected inflamed lesion was followed from baseline through control visits quantitatively by diffusion-weighted imaging (DWI) measuring the apparent diffusion coefficient (ADC) and by dynamic contrast-enhanced imaging (DCEI) with evaluation of the enhancement factor (f{sub enh}) and enhancement gradient (g{sub enh}). Clinical and quantitative MRI parameters diminished significantly with regression of the inflammatory activity. The improvement in AS was most pronounced in patients treated with infliximab; after 12 months the ADC diminished from an average of 1.31 to 0.88 x 10{sup -3} mm{sup 2}/s, f{sub enh} from 1.85 to 0.60, and g{sub enh} from 3.09 to 1.40 %/s. Diffusion-weighted imaging and DCEI were shown to be effective in quantifying changes in inflammation in skeletal lesions during the treatment of AS, and could therefore be convenient for assessing treatment efficacy. To the best of our knowledge this is the first time DWI was used to evaluate the activity of skeletal inflammation in rheumatic diseases such as AS. (orig.)

  12. The Use of Corticosteroids as Adjuvant Therapy for Painful Bone Metastases: A Large Cross-Sectional Survey of Palliative Care Providers.

    Science.gov (United States)

    White, Patrick; Arnold, Robert; Bull, Janet; Cicero, Brandon

    2018-01-01

    Bone metastases are a common complication in patients with advanced cancer but little is known regarding current practice patterns of palliative care providers when prescribing corticosteroids as adjuvant therapy for painful bone metastases. To identify current practice patterns among palliative care providers when prescribing corticosteroids for the treatment of painful bone metastases. A cross-sectional, online survey of the membership of the American Academy of Hospice and Palliative Medicine. Providers were asked to report how frequently they prescribed corticosteroids as adjuvant therapy in patients with painful bone metastases, and to specify the corticosteroid, dosage, treatment duration, and the gastroprotective strategy most frequently utilized. Seven hundred sixty-five participants responded to the survey and 600 (78%) of respondents completed the survey. Ninety-eight percent of respondents completing the survey reported having prescribed corticosteroids as adjuvant pain therapy, and 66% ordered corticosteroids for the majority of their patients with painful bone metastases. Dexamethasone was the most widely prescribed corticosteroid. Eight milligrams divided twice daily was the most common dosage selected and once started, it was usually continued indefinitely. Corticosteroids are commonly prescribed as adjuvant therapy in the treatment of painful bone metastases in patients with limited life expectancy. Dexamethasone is the most commonly selected corticosteroid by American palliative care providers with variation existing among providers regarding dosing schedule, treatment duration, and gastroprotective strategies. Clinical trials comparing a total daily dose of four versus eight milligrams of dexamethasone would be clinically useful to inform evidence-based practice.

  13. Does Manual Therapy Provide Additional Benefit To Breathing Retraining In The Management Of Dysfunctional Breathing? A Randomised Controlled Trial

    OpenAIRE

    Jones, MO; Troup, F; Nugus, J; Roughton, M; Hodson, ME; Rayner, C.; Bowen, F; Pryor, J

    2015-01-01

    Purpose: Dysfunctional breathing (DB) is associated with an abnormal breathing pattern, unexplained breathlessness and significant patient morbidity. Treatment involves breathing retraining through respiratory physiotherapy. Recently, manual therapy (MT) has also been used, but no evidence exists to validate its use. This study sought to investigate whether MT produces additional benefit when compared with breathing retraining alone in patients with DB. Methods: Sixty subjects with primary...

  14. Combined passive acoustic mapping and magnetic resonance thermometry for monitoring phase-shift nanoemulsion enhanced focused ultrasound therapy

    Science.gov (United States)

    Crake, Calum; Meral, F. Can; Burgess, Mark T.; Papademetriou, Iason T.; McDannold, Nathan J.; Porter, Tyrone M.

    2017-08-01

    Focused ultrasound (FUS) has the potential to enable precise, image-guided noninvasive surgery for the treatment of cancer in which tumors are identified and destroyed in a single integrated procedure. However, success of the method in highly vascular organs has been limited due to heat losses to perfusion, requiring development of techniques to locally enhance energy absorption and heating. In addition, FUS procedures are conventionally monitored using MRI, which provides excellent anatomical images and can map temperature, but is not capable of capturing the full gamut of available data such as the acoustic emissions generated during this inherently acoustically-driven procedure. Here, we employed phase-shift nanoemulsions (PSNE) embedded in tissue phantoms to promote cavitation and hence temperature rise induced by FUS. In addition, we incorporated passive acoustic mapping (PAM) alongside simultaneous MR thermometry in order to visualize both acoustic emissions and temperature rise, within the bore of a full scale clinical MRI scanner. Focal cavitation of PSNE could be resolved using PAM and resulted in accelerated heating and increased the maximum elevated temperature measured via MR thermometry compared to experiments without nanoemulsions. Over time, the simultaneously acquired acoustic and temperature maps show translation of the focus of activity towards the FUS transducer, and the magnitude of the increase in cavitation and focal shift both increased with nanoemulsion concentration. PAM results were well correlated with MRI thermometry and demonstrated greater sensitivity, with the ability to detect cavitation before enhanced heating was observed. The results suggest that PSNE could be beneficial for enhancement of thermal focused ultrasound therapies and that PAM could be a critical tool for monitoring this process.

  15. Studying the effect of photodynamic therapy (PDT) to enhance healing of femur fractures using polarimetric second-harmonic generation microscopy

    Science.gov (United States)

    Golaraei, Ahmad; Raja, Vaishnavi; Akens, Margarete K.; Wilson, Brian C.; Barzda, Virginijus

    2017-07-01

    Linear polarization-in, polarization-out second-harmonic generation microscopy was used to study the effect of Photodynamic therapy treatment on enhancing the healing of femur fracture by investigating the ultrastructure of collagen as a major component of bone matrix.

  16. 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)

  17. Emotion Regulation Enhancement of Cognitive Behavior Therapy for College Student Problem Drinkers: A Pilot Randomized Controlled Trial

    Science.gov (United States)

    Ford, Julian D.; Grasso, Damion J.; Levine, Joan; Tennen, Howard

    2018-01-01

    This pilot randomized clinical trial tested an emotion regulation enhancement to cognitive behavior therapy (CBT) with 29 college student problem drinkers with histories of complex trauma and current clinically significant traumatic stress symptoms. Participants received eight face-to-face sessions of manualized Internet-supported CBT for problem…

  18. Effectiveness of enhanced cognitive behavioral therapy (CBT-E) for eating disorders : study protocol for a randomized controlled trial

    NARCIS (Netherlands)

    de Jong, Martie; Korrelboom, Kees; van der Meer, Iris; Deen, Mathijs; Hoek, Hans W.; Spinhoven, Philip

    2016-01-01

    Background: While eating disorder not otherwise specified (EDNOS) is the most common eating disorder (ED) diagnosis in routine clinical practice, no specific treatment methods for this diagnosis have yet been developed and studied. Enhanced cognitive behavioral therapy (CBT-E) has been described and

  19. Effectiveness of enhanced cognitive behavioral therapy (CBT-E) for eating disorders : Study protocol for a randomized controlled trial

    NARCIS (Netherlands)

    de Jong, M.; Korrelboom, C.W.; van der Meer, I.; Deen, M.; Hoek, H.W.; Spinhoven, P.

    2016-01-01

    Background While eating disorder not otherwise specified (EDNOS) is the most common eating disorder (ED) diagnosis in routine clinical practice, no specific treatment methods for this diagnosis have yet been developed and studied. Enhanced cognitive behavioral therapy (CBT-E) has been described and

  20. Generation and modelling of megavoltage photon beams for contrast-enhanced radiation therapy

    Science.gov (United States)

    Robar, J. L.

    2006-11-01

    Contrast-enhanced radiation therapy (CERT) is a treatment approach involving the irradiation of tumours containing high atomic number (Z) contrast media, using low-quality x-ray beams. This work describes the experimental generation of x-ray beams using a linear accelerator with low-Z target materials (beryllium and aluminium), in order to produce photon energy spectra appropriate for CERT. Measurements were made to compare the experimental beams to conventional linear accelerator photon beams in terms of per cent depth dose. Monte Carlo simulation was used to model the generation of each beam, and models were validated against experimental measurement. Validated models were used to demonstrate changes in photon spectra as well as to quantify the variation of tumour dose enhancement with iodinated contrast medium concentration in a simulated tumour volume. Finally, the ratio of the linear attenuation coefficient for iodinated contrast medium relative to water was determined experimentally as a function of iodine concentration. Beams created with low-Z targets show significant changes in energy spectra compared to conventional beams. For the 4 MeV/Be beam, for example, 33% of photons have energies below 60 keV. Measurements and calculation show that both the linear attenuation coefficient ratio and dose enhancement factor (DEF) increase most rapidly at concentrations below 46 mg I ml-1. There is a significant dependence of DEF on electron energy and a lesser dependence on target material. The 4 MeV/Be beam is the most promising in terms of magnitude of DEF—for example, DEF values of 1.16 and 1.29 are obtained for concentrations of 20 mg I ml-1 and 50 mg I ml-1, respectively. DEF will increase or decrease, respectively, for shallower or deeper tumours at a rate of approximately 1.1% cm-1. In summary, we show that significant dose enhancement is possible by altering the linear accelerator target and filtration, but the magnitude is highly dependent on contrast

  1. Biventricular apical thrombi demonstrated by contrast-enhanced cardiac MRI following anteroapical STEMI and unsuccessful reperfusion therapy.

    Science.gov (United States)

    Keeble, William; Vondermuhll, Isabelle; Paterson, Ian

    2008-08-01

    Contrast-enhanced cardiac magnetic resonance imaging can define the territory and extent of myocardial infarction from patterns of late gadolinium enhancement. Following failure to reperfuse with thrombolytic therapy, a case of myocardial infarction is described in which ongoing symptoms and an electrocardiogram change led to a diagnostic dilemma. Cardiac magnetic resonance imaging confirmed an apical infarction, an aneurysm and acute pericarditis. In addition, late gadolinium enhancement unexpectedly revealed the presence of biventricular apical thrombi. The prevalence of cardiac thrombi and pulmonary emboli may be greater than generally appreciated.

  2. Impediments to Enhancement of CPT-11 Anticancer Activity by E. coli Directed Beta-Glucuronidase Therapy

    Science.gov (United States)

    Hsieh, Yuan-Ting; Chen, Kai-Chuan; Cheng, Chiu-Min; Cheng, Tian-Lu; Tao, Mi-Hua; Roffler, Steve R.

    2015-01-01

    CPT-11 is a camptothecin analog used for the clinical treatment of colorectal adenocarcinoma. CPT-11 is converted into the therapeutic anti-cancer agent SN-38 by liver enzymes and can be further metabolized to a non-toxic glucuronide SN-38G, resulting in low SN-38 but high SN-38G concentrations in the circulation. We previously demonstrated that adenoviral expression of membrane-anchored beta-glucuronidase could promote conversion of SN-38G to SN-38 in tumors and increase the anticancer activity of CPT-11. Here, we identified impediments to effective tumor therapy with E. coli that were engineered to constitutively express highly active E. coli beta-glucuronidase intracellularly to enhance the anticancer activity of CPT-11. The engineered bacteria, E. coli (lux/βG), could hydrolyze SN-38G to SN-38, increased the sensitivity of cultured tumor cells to SN-38G by about 100 fold and selectively accumulated in tumors. However, E. coli (lux/βG) did not more effectively increase CPT-11 anticancer activity in human tumor xenografts as compared to non-engineered E. coli. SN-38G conversion to SN-38 by E. coli (lux/βG) appeared to be limited by slow uptake into bacteria as well as by segregation of E. coli in necrotic regions of tumors that may be relatively inaccessible to systemically-administered drug molecules. Studies using a fluorescent glucuronide probe showed that significantly greater glucuronide hydrolysis could be achieved in mice pretreated with E. coli (lux/βG) by direct intratumoral injection of the glucuronide probe or by intratumoral lysis of bacteria to release intracellular beta-glucuronidase. Our study suggests that the distribution of beta-glucuronidase, and possibly other therapeutic proteins, in the tumor microenvironment might be an important barrier for effective bacterial-based tumor therapy. Expression of secreted therapeutic proteins or induction of therapeutic protein release from bacteria might therefore be a promising strategy to enhance anti

  3. Orthodontic widening of the palate may provide a cure for selected children with therapy-resistant enuresis.

    Science.gov (United States)

    Nevéus, Tryggve; Leissner, Lena; Rudblad, Stig; Bazargani, Farhan

    2014-11-01

    According to a number of small case series, orthodontic treatment may have anti-enuretic effects. Thus, we evaluated whether widening of the palate can alleviate enuresis and whether prognostic information can be gained from examining children's nocturnal respiration and nasal airway dimensions. Children with therapy-resistant enuresis underwent polysomnography, focusing on nocturnal respiration, and had their nasal airways examined. Rapid maxillary expansion was performed, widening the maxilla by approximately 0.5 cm. The dental appliance was removed after 6 months. Enuresis frequency was evaluated four times: at baseline, with the orthodontic apparatus in situ, after completed maxillary expansion and 1 year post-treatment. Of the 34 children recruited, one dropped out due to oral discomfort. The numbers of wet nights per week on the four assessment occasions were 5.48 ± 1.48, 5.12 ± 1.73, 3.09 ± 2.49 and 2.63 ± 2.81; p enuresis frequency at baseline (p = 0.001) and to have larger nasal airway dimensions (p = 0.01). Orthodontic widening of the palate may be curative in a subgroup of children with therapy-resistant enuresis. ©2014 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  4. Enhancing photodynamic therapy of a metastatic mouse breast cancer by immune stimulation

    Science.gov (United States)

    Castano, Ana P.; Hamblin, Michael R.

    2006-02-01

    One in 8 women in the United States will develop breast cancer during her lifetime and 40,000 die each year. Deaths are due to tumors that have metastasized despite local control. Photodynamic therapy (PDT) is a promising cancer treatment in which a photosensitizer (PS) accumulates in tumors and is subsequently activated by visible light of an appropriate wavelength. The energy of the light is transferred to molecular oxygen to produce reactive oxygen species that produce cell death and tumor ablation. Mechanisms include cytotoxicity to tumor cells, shutting down of the tumor vasculature, and the induction of a host immune response. The precise mechanisms involved in the PDT-mediated induction of anti-tumor immunity are not yet understood. Potential contributing factors are alterations in the tumor microenvironment via stimulation of proinflammatory cytokines and direct effects of PDT on the tumor that increase immunogenicity. We have studied PDT of 410.4 variant 4T1 tumors growing in the mammary fat pad (orthotopic) in Balb/c mice and which produce metastasis. We have shown that a PDT regimen that produces vascular shutdown and tumor necrosis leads to initial tumor ablation but the tumors recur at the periphery. We studied the combination of PDT with immunostimulating therapies. Low dose cyclophosphamide (CY) is a specific mechanism to deplete the regulatory T cells (CD4+CD25+), these cells play an important role in the immunosuppression activity of tumors. In combination with PDT that produces release of tumor specific antigens, this immunostimulation may lead to generation of cytotoxic CD8 T-lymphocytes that recognize and destroy the tumor. The second alternative therapy is the use of a novel combination of the immunostimulant CpG oligodeoxynucleotides (CpG-ODN) and PDT. CpG-ODN is recognized by Toll-like receptor 9 and directly or indirectly triggers B cells, NK cells, monocyte-macrophages and dendritic cells to proliferate, mature and secrete cytokines

  5. Enhanced factor VIII heavy chain for gene therapy of hemophilia A.

    Science.gov (United States)

    Chen, Lingxia; Lu, Hui; Wang, Jinhui; Sarkar, Rita; Yang, Xiao; Wang, Hongli; High, Katherine A; Xiao, Weidong

    2009-03-01

    Hemophilia A gene therapy using recombinant adenovirus-associated virus (AAV) vectors has been hampered by the size of the factor VIII (FVIII) cDNA. Previously, splitting the FVIII coding sequence into a heavy-chain (HC) fragment and a light-chain (LC) fragment for dual recombinant AAV vector delivery has been successfully explored. However, the main disadvantage of this approach is a "chain imbalance" problem in which LC secretion is approximately 1-2 logs higher than that of HC, and therefore, the majority of protein synthesized is nonfunctional. To improve HC secretion, we constructed alternate FVIII HCs based on our observation that LC facilitates HC secretion. To our surprise, most of the new HC molecules exhibited enhanced expression over the traditional HC molecule (HC(745)). The optimized HC mutein, HC(HL), including additional acidic-region-3 (ar3) sequences, exhibited three- to fivefold higher activity in both enzyme-linked immunosorbent assay (ELISA) and activated partial thromboplastin time (aPTT) assay in in vitro testing. Further characterization suggested ar3 sequences increased HC secretion, rather than promoting HC synthesis. Intravenous delivery of AAV8-HC(HL)+AAV8-LC or AAV8-HC(745)+AAV8-LC achieved phenotypic correction in hemophilia A mice. Mice receiving AAV8-HC(HL)+AAV8-LC achieved three- to fourfold higher HC expression than AAV8-HC(745)+AAV8-LC, consistent with the FVIII functional assays. HC(HL) should be substituted for HC(745) in a dual AAV vector strategy due to its enhanced expression.

  6. Enhanced effects of combined cognitive bias modification and computerised cognitive behaviour therapy on social anxiety

    Directory of Open Access Journals (Sweden)

    Emma Butler

    2015-12-01

    Full Text Available This study examines whether combined cognitive bias modification for interpretative biases (CBM-I and computerised cognitive behaviour therapy (C-CBT can produce enhanced positive effects on interpretation biases and social anxiety. Forty socially anxious students were randomly assigned into two conditions, an intervention group (positive CBM-I + C-CBT or an active control (neutral CBM-I + C-CBT. At pre-test, participants completed measures of social anxiety, interpretative bias, cognitive distortions, and social and work adjustment. They were exposed to 6 × 30 min sessions of web-based interventions including three sessions of either positive or neutral CBM-I and three sessions of C-CBT, one session per day. At post-test and two-week follow-up, participants completed the baseline measures. A combined positive CBM-I + C-CBT produced less negative interpretations of ambiguous situations than neutral CBM-I + C-CBT. The results also showed that both positive CBM-I + C-CBT and neutral CBM-I + C-CBT reduced social anxiety and cognitive distortions as well as improving work and social adjustment. However, greater effect sizes were observed in the positive CBM-I + C-CBT condition than the control. This indicates that adding positive CBM-I to C-CBT enhanced the training effects on social anxiety, cognitive distortions, and social and work adjustment compared to the neutral CBM-I + C-CBT condition.

  7. Anti-angiogenic therapy with contrast-enhanced ultrasound in colorectal cancer patients with liver metastasis.

    Science.gov (United States)

    Wu, Zhiyong; Yang, Xiaowei; Chen, Li; Wang, Zhikuan; Shi, Yan; Mao, Hui; Dai, Guanghai; Yu, Xiaoling

    2017-05-01

    The aim of the study was to evaluate the efficacy of anti-angiogenic therapy with dynamic contrast-enhanced ultrasound (DCE-US) in colorectal cancer (CRC) patients with liver metastasis.A total of 50 CRC patients with liver metastasis who received bevacizumab (BEV)-based chemotherapy (BEV + FOLFOX6 protocol) were recruited into the present study. Before the study (d0), and 3, 7, 14, and 42 days (d3, d7, d14, and d42) after chemotherapy, DCE-US was performed, and tumor perfusion was evaluated quantitatively by retention time (RT), peak enhancement (PE), and wash-in area under the curve (WiAUC) on the basis of a contrast-uptake curve determined with original linear data.Routine ultrasonography was used to evaluate metastatic foci in the liver at baseline. A metastatic focus was selected for dynamic monitoring with ultrasound. The metastatic foci were 1.5 to 8 cm (median: 2.5 cm). The results of hemodynamics monitored at different time points, including RT, PE, and WiAUC, showed that RT at baseline was significantly different between groups (P liver as standard RT-quotient, a similar trend was observed, and no marked difference was noted in the standard RT-quotient between the 2 groups. The median progression-free survival was significantly higher in the increased-RT group (10.8 months) than the decreased-RT group (2.5 months) (P = .002). There were no significant differences in peak intensity and WiAUC between the 2 groups.DCE-US can be used to quantitatively evaluate the hemodynamics of liver metastasis in CRC patients who received bevacizumab-based chemotherapy.

  8. Outcomes of implementation of enhanced goal directed therapy in high-risk patients undergoing abdominal surgery

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    Lakshmi Kumar

    2015-01-01

    Full Text Available Background and Aims: Advanced monitoring targeting haemodynamic and oxygenation variables can improve outcomes of surgery in high-risk patients. We aimed to assess the impact of goal directed therapy (GDT targeting cardiac index (CI and oxygen extraction ratio (O 2 ER on outcomes of high-risk patients undergoing abdominal surgery. Methods: In a prospective randomised trial, forty patients (American Society of Anaesthesiologists II and III undergoing major abdominal surgeries were randomised into two groups. In-Group A mean arterial pressure ≥ 65 mmHg, central venous pressure ≥ 8-10 mmHg, urine output ≥ 0.5 mL/kg/h and central venous oxygen saturation ≥ 70% were targeted intra-operatively and 12 h postoperatively. In-Group-B (enhanced GDT, in addition to the monitoring in-Group-A, CI ≥ 2.5 L/min/m 2 and O 2 ER ≤ 27% were targeted. The end-points were lactate levels and base deficit during and after surgery. The secondary end points were length of Intensive Care Unit (ICU and hospital stay and postoperative complications. Wilcoxon Mann Whitney and Chi-square tests were used for statistical assessment. Results: Lactate levels postoperatively at 4 and 8 h were lower in-Group-B (P < 0.05. The mean base deficit at 3, 4, 5 and 6 h intra-operatively and postoperatively after 4, 8 and 12 h were lower in-Group-B (P < 0.05. There were no significant differences in ICU stay (2.10 ± 1.52 vs. 2.90 ± 2.51 days or hospital stay (10.85 + 4.39 vs. 13.35 + 6.77 days between Group A and B. Conclusions: Implementation of enhanced GDT targeting CI and OER was associated with improved tissue oxygenation.

  9. Internet-provided cognitive behaviour therapy of posttraumatic stress symptoms following childbirth-a randomized controlled trial.

    Science.gov (United States)

    Nieminen, Katri; Berg, Ida; Frankenstein, Katri; Viita, Lina; Larsson, Kamilla; Persson, Ulrika; Spånberger, Loviisa; Wretman, Anna; Silfvernagel, Kristin; Andersson, Gerhard; Wijma, Klaas

    2016-06-01

    The aim of this study was to analyse the effects of trauma-focused guided Internet-based cognitive behaviour therapy for relieving posttraumatic stress disorder (PTSD) symptoms following childbirth, a problem that about 3% women encounter postpartum. Following inclusion, 56 traumatized women were randomized to either treatment or to a waiting list control group. Primary outcome measures were the Traumatic Event Scale (TES) and Impact of Event Scale-Reversed (IES-R). Secondary measures were Beck depression inventory II, Patient Health Questionnaire (PHQ-9), Beck Anxiety Inventory, Quality Of Life Inventory and the EuroQol 5 Dimensions. The treatment was guided by a clinician and lasted eight weeks and comprised eight modules of written text. The between-group effect size (ES) was d = .82 (p quality of life. The results need to be verified in larger trials. Further studies are also needed to examine long-term effects.

  10. Red blood cell membrane-camouflaged melanin nanoparticles for enhanced photothermal therapy.

    Science.gov (United States)

    Jiang, Qin; Luo, Zimiao; Men, Yongzhi; Yang, Peng; Peng, Haibao; Guo, Ranran; Tian, Ye; Pang, Zhiqing; Yang, Wuli

    2017-10-01

    Photothermal therapy (PTT) has represented a promising noninvasive approach for cancer treatment in recent years. However, there still remain challenges in developing non-toxic and biodegradable biomaterials with high photothermal efficiency in vivo. Herein, we explored natural melanin nanoparticles extracted from living cuttlefish as effective photothermal agents and developed red blood cell (RBC) membrane-camouflaged melanin (Melanin@RBC) nanoparticles as a platform for in vivo antitumor PTT. The as-obtained natural melanin nanoparticles demonstrated strong absorption at NIR region, higher photothermal conversion efficiency (∼40%) than synthesized melanin-like polydopamine nanoparticles (∼29%), as well as favorable biocompatibility and biodegradability. It was shown that RBC membrane coating on melanin nanoparticles retained their excellent photothermal property, enhanced their blood retention and effectively improved their accumulation at tumor sites. With the guidance of their inherited photoacoustic imaging capability, optimal accumulation of Melanin@RBC at tumors was achieved around 4 h post intravenous injection. Upon irradiation by an 808-nm laser, the developed Melanin@RBC nanoparticles exhibited significantly higher PTT efficacy than that of bare melanin nanoparticles in A549 tumor-bearing mice. Given that both melanin nanoparticles and RBC membrane are native biomaterials, the developed Melanin@RBC platform could have great potential in clinics for anticancer PTT. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. A Platinum(IV) Pro-drug Preferentially Targets IDO Providing Enhanced Ovarian Cancer Immuno-Chemotherapy

    OpenAIRE

    Awuah, Samuel G.; Zheng, Yao-Rong; Bruno, Peter M.; Hemann, Michael T.; Lippard, Stephen J.

    2015-01-01

    Expression of indoleamine-2,3-dioxygenase (IDO), an immunosuppressive enzyme in human tumors, leads to immune evasion and tumor tolerance. IDO is therefore a tumor immunotherapeutic target, and several IDO inhibitors are currently undergoing clinical trials. IDO inhibitors can enhance the efficacy of common cancer chemotherapeutics. Here we investigated Pt(IV) – (D)-1-methyltryptophan conjugates 1 and 2 for combined immunomodulation and DNA cross-link-triggered apoptosis for cancer ‘immuno-ch...

  12. Perception of risk and communication among conventional and complementary health care providers involving cancer patients' use of complementary therapies: a literature review.

    Science.gov (United States)

    Stub, Trine; Quandt, Sara A; Arcury, Thomas A; Sandberg, Joanne C; Kristoffersen, Agnete E; Musial, Frauke; Salamonsen, Anita

    2016-09-08

    Communication between different health care providers (conventional and complementary) and cancer patients about their use of complementary therapies affects the health and safety of the patients. The aim of this study was to examine the qualitative research literature on the perception of and communication about the risk of complementary therapies between different health care providers and cancer patients. Systematic searches in six medical databases covering literature from 2000 to 2015 were performed. The studies were accessed according to the level of evidence and summarized into different risk situations. Qualitative content analysis was used to analyze the text data, and the codes were defined before and during the data analysis. Twenty-nine papers were included in the primary analysis and five main themes were identified and discussed. The main risk situations identified were 1. Differences in treatment concepts and philosophical values among complementary and conventional health care providers. 2. Adverse effects from complementary products and herbs due to their contamination/toxicity and interactions with conventional cancer treatment. 3. Health care physicians and oncologists find it difficult to recommend many complementary modalities due to the lack of scientific evidence for their effect. 4. Lack of knowledge and information about complementary and conventional cancer treatments among different health care providers. The risk of consuming herbs and products containing high level of toxins is a considerable threat to patient safety (direct risk). At the same time, the lack of scientific evidence of effect for many complementary therapies and differences in treatment philosophy among complementary and conventional health care providers potentially hinder effective communication about these threats with mutual patients (indirect risk). As such, indirect risk may pose an additional risk to patients who want to combine complementary therapies with

  13. Plasmonic enhancement of cyanine dyes for near-infrared light-triggered photodynamic/photothermal therapy and fluorescent imaging

    Science.gov (United States)

    Lu, Mindan; Kang, Ning; Chen, Chuan; Yang, Liuqing; Li, Yang; Hong, Minghui; Luo, Xiangang; Ren, Lei; Wang, Xiumin

    2017-11-01

    Near-infrared (NIR) triggered cyanine dyes have attracted considerable attention in multimodal tumor theranostics. However, NIR cyanine dyes used in tumor treatment often suffer from low fluorescence intensity and weak singlet oxygen generation efficiency, resulting in inadequate diagnostic and therapy efficacy for tumors. It is still a great challenge to improve both the photodynamic therapy (PDT) and fluorescent imaging (FLI) efficacy of cyanine dyes in tumor applications. Herein, a novel multifunctional nanoagent AuNRs@SiO2-IR795 was developed to realize the integrated photothermal/photodynamic therapy (PTT/PDT) and FLI at a very low dosage of IR795 (0.4 μM) based on metal-enhanced fluorescence (MEF) effects. In our design, both the fluorescence intensity and reactive oxygen species of AuNRs@SiO2-IR795 nanocomposites were significantly enhanced up to 51.7 and 6.3 folds compared with free IR795, owing to the localized surface plasmon resonance band of AuNRs overlapping with the absorption or fluorescence emission band of the IR795 dye. Under NIR laser irradiation, the cancer cell inhibition efficiency in vitro with synergetic PDT/PTT was up to 82.3%, compared with 10.3% for free IR795. Moreover, the enhanced fluorescence intensity of our designed nanocomposites was helpful to track their behavior in tumor cells. Therefore, our designed nanoagents highlight the applications of multimodal diagnostics and therapy in tumors based on MEF.

  14. A tool to enhance occupational therapy reasoning from ICF perspective: The Hasselt Occupational Performance Profile (H-OPP).

    Science.gov (United States)

    Ghysels, R; Vanroye, E; Westhovens, M; Spooren, A

    2017-03-01

    In order to enhance occupational therapy reasoning in clinical practice, different elements such as client-centred approach, evidence-based care and interdisciplinary work should be taken into account, but is a challenge. To describe the development of the digital Hasselt Occupational Performance Profile (H-OPP © ) that enhances occupational therapy reasoning from ICF perspective. A participative qualitative design was used to create the H-OPP © in an iterative way in which occupational therapy lectures, ICF experts, students and occupational therapists in the field were involved. After linking occupational therapy terminology to the ICF, different stages of the H-OPP were identified and elaborated with main features: generating an occupational performance profile based on inventarization of problems and possibilities, formulating an occupational performance diagnosis and enabling to create an intervention plan. In all stages, both the perspectives of the client and the occupational therapist were taken into account. To increase practical use, the tool was further elaborated and digitalized. The H-OPP © is a digital coach that guides and facilitates professional reasoning in (novice) occupational therapists. It augments involvement of the client system. Furthermore, it enhances interdisciplinary communication and evidence-based care.

  15. Gene Therapy Vectors with Enhanced Transfection Based on Hydrogels Modified with Affinity Peptides

    Science.gov (United States)

    Shepard, Jaclyn A.; Wesson, Paul J.; Wang, Christine E.; Stevans, Alyson C.; Holland, Samantha J.; Shikanov, Ariella; Grzybowski, Bartosz A.; Shea, Lonnie D.

    2011-01-01

    Regenerative strategies for damaged tissue aim to present biochemical cues that recruit and direct progenitor cell migration and differentiation. Hydrogels capable of localized gene delivery are being developed to provide a support for tissue growth, and as a versatile method to induce the expression of inductive proteins; however, the duration, level, and localization of expression isoften insufficient for regeneration. We thus investigated the modification of hydrogels with affinity peptides to enhance vector retention and increase transfection within the matrix. PEG hydrogels were modified with lysine-based repeats (K4, K8), which retained approximately 25% more vector than control peptides. Transfection increased 5- to 15-fold with K8 and K4 respectively, over the RDG control peptide. K8- and K4-modified hydrogels bound similar quantities of vector, yet the vector dissociation rate was reduced for K8, suggesting excessive binding that limited transfection. These hydrogels were subsequently applied to an in vitro co-culture model to induce NGF expression and promote neurite outgrowth. K4-modified hydrogels promoted maximal neurite outgrowth, likely due to retention of both the vector and the NGF. Thus, hydrogels modified with affinity peptides enhanced vector retention and increased gene delivery, and these hydrogels may provide a versatile scaffold for numerous regenerative medicine applications. PMID:21514659

  16. Manipulating the tumor microenvironment ex vivo for enhanced expansion of tumor-infiltrating lymphocytes for adoptive cell therapy.

    Science.gov (United States)

    Chacon, Jessica Ann; Sarnaik, Amod A; Chen, Jie Qing; Creasy, Caitlin; Kale, Charuta; Robinson, John; Weber, Jeffrey; Hwu, Patrick; Pilon-Thomas, Shari; Radvanyi, Laszlo

    2015-02-01

    Cultured tumor fragments from melanoma metastases have been used for years as a source of tumor-infiltrating lymphocytes (TIL) for adoptive cell therapy (ACT). The expansion of tumor-reactive CD8(+) T cells with interleukin-2 (IL2) in these early cultures is critical in generating clinically active TIL infusion products, with a population of activated 4-1BB CD8(+) T cells recently found to constitute the majority of tumor-specific T cells. We used an agonistic anti-4-1BB antibody added during the initial tumor fragment cultures to provide in situ 4-1BB costimulation. We found that addition of an agonistic anti-4-1BB antibody could activate 4-1BB signaling within early cultured tumor fragments and accelerated the rate of memory CD8(+) TIL outgrowth that were highly enriched for melanoma antigen specificity. This was associated with NFκB activation and the induction of T-cell survival and memory genes, as well as enhanced IL2 responsiveness, in the CD8(+) T cells in the fragments and emerging from the fragments. Early provision of 4-1BB costimulation also affected the dendritic cells (DC) by activating NFκB in DC and promoting their maturation inside the tumor fragments. Blocking HLA class I prevented the enhanced outgrowth of CD8(+) T cells with anti-4-1BB, suggesting that an ongoing HLA class I-mediated antigen presentation in early tumor fragment cultures plays a role in mediating tumor-specific CD8(+) TIL outgrowth. Our results highlight a previously unrecognized concept in TIL ACT that the tumor microenvironment can be dynamically regulated in the initial tumor fragment cultures to regulate the types of T cells expanded and their functional characteristics. ©2014 American Association for Cancer Research.

  17. Enhanced radiation sensitivity and radiation recall dermatitis (RRD after hypericin therapy – case report and review of literature

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    Schäfer Christof

    2006-09-01

    Full Text Available Abstract Background Modern radiotherapy (RT reduces the side effects at organ at risk. However, skin toxicity is still a major problem in many entities, especially head and neck cancer. Some substances like chemotherapy provide a risk of increased side effects or can induce a "recall phenomenon" imitating acute RT-reactions months after RT. Moreover, some phototoxic drugs seem to enhance side effects of radiotherapy while others do not. We report a case of "radiation recall dermatitis" (RRD one year after RT as a result of taking hypericin (St. John's wort. Case report A 65 year old man with completely resected squamous cell carcinoma of the epiglottis received an adjuvant locoregional RT up to a dose of 64.8 Gy. The patient took hypericin during and months after RT without informing the physician. During radiotherapy the patient developed unusual intensive skin reactions. Five months after RT the skin was completely bland at the first follow up. However, half a year later the patient presented erythema, but only within the area of previously irradiated skin. After local application of a steroid cream the symptoms diminished but returned after the end of steroid therapy. The anamnesis disclosed that the patient took hypericin because of depressive mood. We recommended to discontinue hypericin and the symptoms disappeared afterward. Conclusion Several drugs are able to enhance skin toxicity of RT. Furthermore, the effect of RRD is well known especially for chemotherapy agents such as taxans. However, the underlying mechanisms are not known in detail so far. Moreover, it is unknown whether photosensitising drugs can also be considered to increase radiation sensitivity and whether a recall phenomenon is possible. The first report of a hypericin induced RRD and review of the literature are presented. In clinical practise many interactions between drugs and radiotherapy were not noticed and if registered not published. We recommend to ask especially

  18. Patient age is related to the types of physical therapy interventions provided for chronic low back pain: an observational study.

    Science.gov (United States)

    Greenberger, Hilary B; Beissner, Katherine; Jewell, Dianne V

    2012-11-01

    Retrospective analysis of a longitudinal cohort of patients treated for chronic low back pain (CLBP). To determine whether patient age is associated with types of physical therapy interventions received for CLBP. Advancing age is associated with less positive treatment outcomes in patients with CLBP. If patient age influences a therapist's choice of interventions, it may partially explain the difference in treatment outcomes. Data were examined in a sample of 7392 patients (62% women, 38% men; mean ± SD age, 56.7 ± 16.5 years) with CLBP. We used a generalized estimating equation to examine the probability of each subject receiving each of the individual intervention categories in the presence of the other intervention categories. A significant interaction between intervention category and age existed after controlling for gender, duration of symptoms, comorbidities, payer source, and functional status at initial intake (χ(2) = 130.27, df = 8, Ppain modalities, joint mobility techniques, ice, or McKenzie exercises decreased with advancing age. The probability of receiving augmented soft tissue mobilization and balance/mobility training increased as age increased. The impact of age on physical therapist treatment choices varies depending on the type of intervention. Other variables in addition to age may have an impact on treatment choice. Further research is needed to determine how therapists incorporate age into their clinical decision making.

  19. Habituation to thaxtomin A in hybrid poplar cell suspensions provides enhanced and durable resistance to inhibitors of cellulose synthesis

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    Beaulieu Carole

    2010-12-01

    Full Text Available Abstract Background Thaxtomin A (TA, a phytotoxin produced by the phytopathogen Streptomyces scabies, is essential for the development of potato common scab disease. TA inhibits cellulose synthesis but its actual mode of action is unknown. Addition of TA to hybrid poplar (Populus trichocarpa x Populus deltoides cell suspensions can activate a cellular program leading to cell death. In contrast, it is possible to habituate hybrid poplar cell cultures to grow in the presence of TA levels that would normally induce cell death. The purpose of this study is to characterize TA-habituated cells and the mechanisms that may be involved in enhancing resistance to TA. Results Habituation to TA was performed by adding increasing levels of TA to cell cultures at the time of subculture over a period of 12 months. TA-habituated cells were then cultured in the absence of TA for more than three years. These cells displayed a reduced size and growth compared to control cells and had fragmented vacuoles filled with electron-dense material. Habituation to TA was associated with changes in the cell wall composition, with a reduction in cellulose and an increase in pectin levels. Remarkably, high level of resistance to TA was maintained in TA-habituated cells even after being cultured in the absence of TA. Moreover, these cells exhibited enhanced resistance to two other inhibitors of cellulose biosynthesis, dichlobenil and isoxaben. Analysis of gene expression in TA-habituated cells using an Affymetrix GeneChip Poplar Genome Array revealed that durable resistance to TA is associated with a major and complex reprogramming of gene expression implicating processes such as cell wall synthesis and modification, lignin and flavonoid synthesis, as well as DNA and chromatin modifications. Conclusions We have shown that habituation to TA induced durable resistance to the bacterial toxin in poplar cells. TA-habituation also enhanced resistance to two other structurally

  20. Heidelberg Neuro-Music Therapy Enhances Task-Negative Activity in Tinnitus Patients

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    Christoph M. Krick

    2017-07-01

    Full Text Available Background: Suffering from tinnitus causes mental distress in most patients. Recent findings point toward a diminished activity of the brain's default-mode network (DMN in subjects with mental disorders including depression or anxiety and also recently in subjects with tinnitus-related distress. We recently developed a therapeutic intervention, namely the Heidelberg Neuro-Music Therapy (HNMT, which shows an effective reduction of tinnitus-related distress following a 1-week short-term treatment. This approach offers the possibility to evaluate the neural changes associated with the improvements in tinnitus distress. We previously reported gray matter (GM reorganization in DMN regions and in primary auditory areas following HNMT in cases of recent-onset tinnitus. Here we evaluate on the same patient group, using functional MRI (fMRI, the activity of the DMN following the improvements tinnitus-related distress related to the HNMT intervention.Methods: The DMN activity was estimated by the task-negative activation (TNA during long inter-trial intervals in a word recognition task. The level of TNA was evaluated twice, before and after the 1-week study period, in 18 treated tinnitus patients (“treatment group,” TG, 21 passive tinnitus controls (PTC, and 22 active healthy controls (AC. During the study, the participants in TG and AC groups were treated with HNMT, whereas PTC patients did not receive any tinnitus-specific treatment. Therapy-related effects on DMN activity were assessed by comparing the pairs of fMRI records from the TG and PTC groups.Results: Treatment of the TG group with HNMT resulted in an augmented DMN activity in the PCC by 2.5% whereas no change was found in AC and PTC groups. This enhancement of PCC activity correlated with a reduction in tinnitus distress (Spearman Rho: −0.5; p < 0.005.Conclusion: Our findings show that an increased DMN activity, especially in the PCC, underlies the improvements in tinnitus

  1. Heidelberg Neuro-Music Therapy Enhances Task-Negative Activity in Tinnitus Patients

    Science.gov (United States)

    Krick, Christoph M.; Argstatter, Heike; Grapp, Miriam; Plinkert, Peter K.; Reith, Wolfgang

    2017-01-01

    Background: Suffering from tinnitus causes mental distress in most patients. Recent findings point toward a diminished activity of the brain's default-mode network (DMN) in subjects with mental disorders including depression or anxiety and also recently in subjects with tinnitus-related distress. We recently developed a therapeutic intervention, namely the Heidelberg Neuro-Music Therapy (HNMT), which shows an effective reduction of tinnitus-related distress following a 1-week short-term treatment. This approach offers the possibility to evaluate the neural changes associated with the improvements in tinnitus distress. We previously reported gray matter (GM) reorganization in DMN regions and in primary auditory areas following HNMT in cases of recent-onset tinnitus. Here we evaluate on the same patient group, using functional MRI (fMRI), the activity of the DMN following the improvements tinnitus-related distress related to the HNMT intervention. Methods: The DMN activity was estimated by the task-negative activation (TNA) during long inter-trial intervals in a word recognition task. The level of TNA was evaluated twice, before and after the 1-week study period, in 18 treated tinnitus patients (“treatment group,” TG), 21 passive tinnitus controls (PTC), and 22 active healthy controls (AC). During the study, the participants in TG and AC groups were treated with HNMT, whereas PTC patients did not receive any tinnitus-specific treatment. Therapy-related effects on DMN activity were assessed by comparing the pairs of fMRI records from the TG and PTC groups. Results: Treatment of the TG group with HNMT resulted in an augmented DMN activity in the PCC by 2.5% whereas no change was found in AC and PTC groups. This enhancement of PCC activity correlated with a reduction in tinnitus distress (Spearman Rho: −0.5; p < 0.005). Conclusion: Our findings show that an increased DMN activity, especially in the PCC, underlies the improvements in tinnitus-related distress

  2. Comparison of three-dimensional, assist-as-needed robotic arm/hand movement training provided with Pneu-WREX to conventional tabletop therapy after chronic stroke.

    Science.gov (United States)

    Reinkensmeyer, David J; Wolbrecht, Eric T; Chan, Vicky; Chou, Cathy; Cramer, Steven C; Bobrow, James E

    2012-11-01

    Robot-assisted movement training can help individuals with stroke reduce arm and hand impairment, but robot therapy is typically only about as effective as conventional therapy. Refining the way that robots assist during training may make them more effective than conventional therapy. Here, the authors measured the therapeutic effect of a robot that required individuals with a stroke to achieve virtual tasks in three dimensions against gravity. The robot continuously estimated how much assistance patients needed to perform the tasks and provided slightly less assistance than needed to reduce patient slacking. Individuals with a chronic stroke (n = 26; baseline upper limb Fugl-Meyer score, 23 ± 8) were randomized into two groups and underwent 24 one-hour training sessions over 2 mos. One group received the assist-as-needed robot training and the other received conventional tabletop therapy with the supervision of a physical therapist. Training helped both groups significantly reduce their motor impairment, as measured by the primary outcome measure, the Fugl-Meyer score, but the improvement was small (3.0 ± 4.9 points for robot therapy vs. 0.9 ± 1.7 for conventional therapy). There was a trend for greater reduction for the robot-trained group (P = 0.07). The robot group largely sustained this gain at the 3-mo follow-up. The robot-trained group also experienced significant improvements in Box and Blocks score and hand grip strength, whereas the control group did not, but these improvements were not sustained at follow-up. In addition, the robot-trained group showed a trend toward greater improvement in sensory function, as measured by the Nottingham Sensory Test (P = 0.06). These results suggest that in patients with chronic stroke and moderate-severe deficits, assisting in three-dimensional virtual tasks with an assist-as-needed controller may make robotic training more effective than conventional tabletop training.

  3. Sonic hedgehog signaling inhibition provides opportunities for targeted therapy by sulforaphane in regulating pancreatic cancer stem cell self-renewal.

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    Mariana Rodova

    Full Text Available Dysregulation of the sonic hedgehog (Shh signaling pathway has been associated with cancer stem cells (CSC and implicated in the initiation of pancreatic cancer. Pancreatic CSCs are rare tumor cells characterized by their ability to self-renew, and are responsible for tumor recurrence accompanied by resistance to current therapies. The lethality of these incurable, aggressive and invasive pancreatic tumors remains a daunting clinical challenge. Thus, the objective of this study was to investigate the role of Shh pathway in pancreatic cancer and to examine the molecular mechanisms by which sulforaphane (SFN, an active compound in cruciferous vegetables, inhibits self-renewal capacity of human pancreatic CSCs. Interestingly, we demonstrate here that Shh pathway is highly activated in pancreatic CSCs and plays important role in maintaining stemness by regulating the expression of stemness genes. Given the requirement for Hedgehog in pancreatic cancer, we investigated whether hedgehog blockade by SFN could target the stem cell population in pancreatic cancer. In an in vitro model, human pancreatic CSCs derived spheres were significantly inhibited on treatment with SFN, suggesting the clonogenic depletion of the CSCs. Interestingly, SFN inhibited the components of Shh pathway and Gli transcriptional activity. Interference of Shh-Gli signaling significantly blocked SFN-induced inhibitory effects demonstrating the requirement of an active pathway for the growth of pancreatic CSCs. SFN also inhibited downstream targets of Gli transcription by suppressing the expression of pluripotency maintaining factors (Nanog and Oct-4 as well as PDGFRα and Cyclin D1. Furthermore, SFN induced apoptosis by inhibition of BCL-2 and activation of caspases. Our data reveal the essential role of Shh-Gli signaling in controlling the characteristics of pancreatic CSCs. We propose that pancreatic cancer preventative effects of SFN may result from inhibition of the Shh pathway

  4. Is more intensive better? Client and service provider outcomes for intensive versus standard therapy schedules for functional voice disorders.

    Science.gov (United States)

    Wenke, Rachel J; Stabler, Penny; Walton, Chloe; Coman, Leah; Lawrie, Melissa; O'Neill, John; Theodoros, Deborah; Cardell, Elizabeth

    2014-09-01

    Functional dysphonias are commonly associated with reduced treatment attendance leading to variable treatment outcomes. Preliminary research has proposed that intensive treatment may improve client adherence and outcomes; however, further research into the application of intensive models in functional dysphonia in comparison with standard intensity models is warranted. The present study evaluated the impact of intensive and standard treatments on functional, well-being, and service outcome measures in clients with functional dysphonia. Participants with a functional dysphonia were randomly allocated to one of two treatment groups: (1) intensive treatment (n = 7) or (2) standard treatment (n = 9). Participants completed the voice handicap index (VHI) and the Australian therapy outcome measures voice assessment (conducted by a blinded assessor) before and after treatment and 4 weeks after treatment. Satisfaction questionnaires were completed after treatment and data pertaining to attendance and duration of intervention were collected throughout treatment. In addition to a vocal hygiene education session, all participants received a total of 8 hours of treatment; intensive treatment consisted of four 1-hour treatment sessions per week over 2 weeks, whereas the standard group received one 1-hour treatment session per week over 8 weeks. High satisfaction and statistically significant improvements on the VHI ratings were found after treatment in the intensive group. Significantly greater attendance rates were found in the intensive group. Intensive treatment is a potentially viable service delivery option for functional dysphonia and warrants further larger scale investigation. Copyright © 2014 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

  5. Growth factor-based therapies provide additional benefit beyond physical therapy in resistant elbow tendinopathy: a prospective, single-blind, randomised trial of autologous blood injections versus platelet-rich plasma injections.

    Science.gov (United States)

    Creaney, Leon; Wallace, Andrew; Curtis, Mark; Connell, David

    2011-09-01

    Growth factor technologies are increasingly used to enhance healing in musculoskeletal injuries, particularly in sports medicine. Two such products; platelet-rich plasma (PRP) and autologous blood, have a growing body of supporting evidence. No previous trial has directly compared the efficacy of these two methods. Growth factor administration improves tissue regeneration in patients who have failed to respond to conservative therapy. A prospective, double-blind, randomised trial. Elbow tendinopathy patients who had failed conservative physical therapy were divided into two patient groups: PRP injection (N=80) and autologous blood injection (ABI) (N=70). Each patient received two injections at 0 and 1 month. Patient-related tennis elbow evaluation (PRTEE) was recorded by a blinded investigator at 0, 1, 3 and 6 months. The main outcome measure was PRTEE, a validated composite outcome for pain, activities of daily living and physical function, utilising a 0-100 scale. At 6 months the authors observed a 66% success rate in the PRP group versus 72% in the ABI group, p=NS. There was a higher rate of conversion to surgery in the ABI group (20%) versus the PRP group (10%). In patients who are resistant to first-line physical therapy such as eccentric loading, ABI or PRP injections are useful second-line therapies to improve clinical outcomes. In this study, up to seven out of 10 additional patients in this difficult to treat cohort benefit from a surgery-sparing intervention.

  6. A novel double-enhanced suicide gene therapy in a colon cancer cell line mediated by gef and apoptin.

    Science.gov (United States)

    Boulaiz, Houria; Aránega, Antonia; Cáceres, Blanca; Blanca, Cáceres; Alvarez, Pablo; Pablo, Alvarez; Serrano-Rodríguez, Fernando; Fernando, Rodríguez-Serrano; Carrillo, Esmeralda; Esmeralda, Carrillo; Melguizo, Consolación; Consolación, Melguizo; Prados, Jose; Jose, Prados

    2014-02-01

    Double-suicide gene therapy is a promising strategy for the treatment of advanced cancer. It has become an important research line in the development of gene therapy to overcome the drawbacks of single-gene therapy. The aim of this study was to investigate the usefulness of double-suicide gene therapy with the two suicide genes, gef and apoptin, in colon carcinoma. gef and apoptin genes were cloned into a doxycycline-regulated retrovirus-mediated gene expression system. Expression of both genes in the DLD-1 cell line was confirmed by reverse transcriptase polymerase chain reaction (RT-PCR). Cell viability was determined with the sulforhodamine B colorimetric assay, and the cell cycle was studied by propidium iodide (PI) staining. Annexin V-FITC and PI assays were used to evaluate apoptosis, and the results were confirmed by electron microscopy. The mitochondrial membrane potential was measured by JC-1 assay. Our results showed that the combined expression of gef and apoptin genes was strikingly more effective than the expression of either gene alone. Co-expression of gef and apoptin synergistically enhanced the decrease in cell viability, increasing necrosis and inducing apoptosis in colon cancer cells via the mitochondrial pathway, which can be deficient in advanced or metastatic colon cancer. Double-suicide gene therapy based on gef and apoptin genes may be a candidate for the development of new colon cancer strategies, and further studies are warranted to establish the usefulness of double-suicide gene therapy in vivo.

  7. Yohimbine enhancement of exposure therapy for social anxiety disorder: a randomized controlled trial.

    Science.gov (United States)

    Smits, Jasper A J; Rosenfield, David; Davis, Michelle L; Julian, Kristin; Handelsman, Pamela R; Otto, Michael W; Tuerk, Peter; Shiekh, Michael; Rosenfield, Ben; Hofmann, Stefan G; Powers, Mark B

    2014-06-01

    Preclinical and clinical trials suggest that yohimbine may augment extinction learning without significant side effects. However, previous clinical trials have only examined adults with specific phobias. Yohimbine has not yet been investigated in the augmentation of exposure therapy for other anxiety disorders. Adults (n = 40) with a DSM-IV diagnosis of social anxiety disorder were randomized to placebo or yohimbine HCl (10.8 mg) 1 hour before each of four exposure sessions. Outcome measures were collected at baseline, each treatment session, posttreatment, and 1-month follow-up. Yohimbine was well tolerated. Yohimbine augmentation, relative to placebo augmentation, resulted in faster improvement and better outcomes on self-report measures of social anxiety disorder severity (Liebowitz Social Anxiety Scale, d = .53) and depressed mood severity (Beck Depression Inventory, d = .37) but not on the clinician-rated measures (Clinical Global Impressions-Severity Scale, d = .09; Clinical Global Impressions-Improvement Scale, d = .25). Between-group differences on the Liebowitz Social Anxiety Scale were moderated by the level of fear reported at the end of an exposure exercise (end fear), such that the advantage of yohimbine over placebo was only evident among patients who reported low end fear. The results provide moderate support for yohimbine as a therapeutic augmentation strategy for exposure therapy in social anxiety disorder, one that may be especially effective when coupled with successful exposure experiences. Beneficial effects for yohimbine were readily evident for self-report measures but not for clinician-rated outcomes of social anxiety severity and improvement. © 2013 Society of Biological Psychiatry Published by Society of Biological Psychiatry All rights reserved.

  8. Dual-therapeutic reporter genes fusion for enhanced cancer gene therapy and imaging.

    Science.gov (United States)

    Sekar, T V; Foygel, K; Willmann, J K; Paulmurugan, R

    2013-05-01

    Two of the successful gene-directed enzyme prodrug therapies include herpes simplex virus-thymidine kinase (HSV1-TK) enzyme-ganciclovir prodrug and the Escherichia coli nitroreductase (NTR) enzyme-CB1954 prodrug strategies; these enzyme-prodrug combinations produce activated cytotoxic metabolites of the prodrugs capable of tumor cell death by inhibiting DNA synthesis and killing quiescent cells, respectively. Both these strategies also affect significant bystander cell killing of neighboring tumor cells that do not express these enzymes. We have developed a dual-combination gene strategy, where we identified HSV1-TK and NTR fused in a particular orientation can effectively kill tumor cells when the tumor cells are treated with a fusion HSV1-TK-NTR gene- along with a prodrug combination of GCV and CB1954. In order to determine whether the dual-system demonstrate superior therapeutic efficacy than either HSV1-TK or NTR systems alone, we conducted both in vitro and in vivo tumor xenograft studies using triple negative SUM159 breast cancer cells, by evaluating the efficacy of cell death by apoptosis and necrosis upon treatment with the dual HSV1-TK genes-GCV-CB1954 prodrugs system, and compared the efficiency to HSV1-TK-GCV and NTR-CB1954. Our cell-based studies, tumor regression studies in xenograft mice, histological analyses of treated tumors and bystander studies indicate that the dual HSV1-TK-NTR-prodrug system is two times more efficient even with half the doses of both prodrugs than the respective single gene-prodrug system, as evidenced by enhanced apoptosis and necrosis of tumor cells in vitro in culture and xenograft of tumor tissues in animals.

  9. Enhanced Optical Head Tracking for Cranial Radiation Therapy: Supporting Surface Registration by Cutaneous Structures

    Energy Technology Data Exchange (ETDEWEB)

    Wissel, Tobias, E-mail: wissel@rob.uni-luebeck.de [Institute for Robotics and Cognitive Systems, University of Lübeck, Lübeck (Germany); Graduate School for Computing in Medicine and Life Science, University of Lübeck, Lübeck (Germany); Stüber, Patrick; Wagner, Benjamin [Institute for Robotics and Cognitive Systems, University of Lübeck, Lübeck (Germany); Graduate School for Computing in Medicine and Life Science, University of Lübeck, Lübeck (Germany); Bruder, Ralf [Institute for Robotics and Cognitive Systems, University of Lübeck, Lübeck (Germany); Erdmann, Christian [Institute for Neuroradiology, Universitätsklinikum Schleswig-Hostein, Campus Lübeck, Lübeck (Germany); Deutz, Christin-Sophie [Clinic for Oral and Maxillo-Facial Surgery, Universitätsklinikum Schleswig-Hostein, Campus Lübeck, Lübeck (Germany); Sack, Benjamin [Department of Neurology, Universitätsklinikum Schleswig-Hostein, Campus Lübeck, Lübeck (Germany); Manit, Jirapong [Institute for Robotics and Cognitive Systems, University of Lübeck, Lübeck (Germany); Graduate School for Computing in Medicine and Life Science, University of Lübeck, Lübeck (Germany); and others

    2016-06-01

    Purpose: To support surface registration in cranial radiation therapy by structural information. The risk for spatial ambiguities is minimized by using tissue thickness variations predicted from backscattered near-infrared (NIR) light from the forehead. Methods and Materials: In a pilot study we recorded NIR surface scans by laser triangulation from 30 volunteers of different skin type. A ground truth for the soft-tissue thickness was segmented from MR scans. After initially matching the NIR scans to the MR reference, Gaussian processes were trained to predict tissue thicknesses from NIR backscatter. Moreover, motion starting from this initial registration was simulated by 5000 random transformations of the NIR scan away from the MR reference. Re-registration to the MR scan was compared with and without tissue thickness support. Results: By adding prior knowledge to the backscatter features, such as incident angle and neighborhood information in the scanning grid, we showed that tissue thickness can be predicted with mean errors of <0.2 mm, irrespective of the skin type. With this additional information, the average registration error improved from 3.4 mm to 0.48 mm by a factor of 7. Misalignments of more than 1 mm were almost thoroughly (98.9%) pushed below 1 mm. Conclusions: For almost all cases tissue-enhanced matching achieved better results than purely spatial registration. Ambiguities can be minimized if the cutaneous structures do not agree. This valuable support for surface registration increases tracking robustness and avoids misalignment of tumor targets far from the registration site.

  10. Simplifying ART cohort monitoring: Can pharmacy stocks provide accurate estimates of patients retained on antiretroviral therapy in Malawi?

    Directory of Open Access Journals (Sweden)

    Tweya Hannock

    2012-07-01

    Full Text Available Abstract Background Routine monitoring of patients on antiretroviral therapy (ART is crucial for measuring program success and accurate drug forecasting. However, compiling data from patient registers to measure retention in ART is labour-intensive. To address this challenge, we conducted a pilot study in Malawi to assess whether patient ART retention could be determined using pharmacy records as compared to estimates of retention based on standardized paper- or electronic based cohort reports. Methods Twelve ART facilities were included in the study: six used paper-based registers and six used electronic data systems. One ART facility implemented an electronic data system in quarter three and was included as a paper-based system facility in quarter two only. Routine patient retention cohort reports, paper or electronic, were collected from facilities for both quarter two [April–June] and quarter three [July–September], 2010. Pharmacy stock data were also collected from the 12 ART facilities over the same period. Numbers of ART continuation bottles recorded on pharmacy stock cards at the beginning and end of each quarter were documented. These pharmacy data were used to calculate the total bottles dispensed to patients in each quarter with intent to estimate the number of patients retained on ART. Information for time required to determine ART retention was gathered through interviews with clinicians tasked with compiling the data. Results Among ART clinics with paper-based systems, three of six facilities in quarter two and four of five facilities in quarter three had similar numbers of patients retained on ART comparing cohort reports to pharmacy stock records. In ART clinics with electronic systems, five of six facilities in quarter two and five of seven facilities in quarter three had similar numbers of patients retained on ART when comparing retention numbers from electronically generated cohort reports to pharmacy stock records. Among

  11. Induced Pluripotent Stem Cell-Derived Neural Stem Cell Therapy Enhances Recovery in an Ischemic Stroke Pig Model.

    Science.gov (United States)

    Baker, Emily W; Platt, Simon R; Lau, Vivian W; Grace, Harrison E; Holmes, Shannon P; Wang, Liya; Duberstein, Kylee Jo; Howerth, Elizabeth W; Kinder, Holly A; Stice, Steve L; Hess, David C; Mao, Hui; West, Franklin D

    2017-08-30

    Induced pluripotent stem cell-derived neural stem cells (iNSCs) have significant potential as an autologous, multifunctional cell therapy for stroke, which is the primary cause of long term disability in the United States and the second leading cause of death worldwide. Here we show that iNSC transplantation improves recovery through neuroprotective, regenerative, and cell replacement mechanisms in a novel ischemic pig stroke model. Longitudinal multiparametric magnetic resonance imaging (MRI) following iNSC therapy demonstrated reduced changes in white matter integrity, cerebral blood perfusion, and brain metabolism in the infarcted tissue. The observed tissue level recovery strongly correlated with decreased immune response, enhanced neuronal protection, and increased neurogenesis. iNSCs differentiated into neurons and oligodendrocytes with indication of long term integration. The robust recovery response to iNSC therapy in a translational pig stroke model with increased predictive potential strongly supports that iNSCs may be the critically needed therapeutic for human stroke patients.

  12. Cell Based Autologous Immune Enhancement Therapy (AIET after Radiotherapy in a Locally Advanced Carcinoma of the Cervix

    Directory of Open Access Journals (Sweden)

    Sumana Premkumar

    2013-01-01

    Full Text Available Radiotherapy is the primary form of treatment in patients with locally advanced cervical carcinoma. However for residual disease in the form of the persistent lymph nodes, surgery or chemotherapy is recommended. As surgery is not acceptable by every patient and chemotherapy has associated side effects, we hereby report the positive outcome of in vitro expanded natural killer cell and activated T lymphocyte based autologous immune enhancement therapy (AIET for the residual lymphadenopathy in a patient with locally advanced cervical cancer after radiation. After six transfusions of AIET, there was complete resolution of residual lymph nodes and there was no evidence of local lesion. The patient also reported improvement in quality of life. As AIET has been reported as the least toxic among the available therapies for cancer, combining AIET with conventional forms of therapy in similar patients might not only improve the outcome but may also help the patients achieve a good quality of life.

  13. Effectiveness of enhanced cognitive behavioral therapy (CBT-E) in the treatment of anorexia nervosa: a prospective multidisciplinary study

    OpenAIRE

    Danielsen, Yngvild S.; Guro Årdal Rekkedal; Stein Frostad; Ute Kessler

    2016-01-01

    Abstract Background Anorexia nervosa (AN) is a debilitating psychiatric disorder associated with a wide array of negative health complications and psychiatric comorbidity. Existing evidence for AN treatment in adults is weak, and no empirically supported treatment has been reliably established. The primary objective of this study is to gain knowledge about the effectiveness of enhanced cognitive behavioral therapy (CBT-E) for anorexia nervosa delivered in a public hospital setting. Baseline p...

  14. In vitro combination therapy using low dose clotrimazole and photodynamic therapy leads to enhanced killing of the dermatophyte Trichophyton rubrum.

    Science.gov (United States)

    Morton, C Oliver; Chau, Mousawi; Stack, Colin

    2014-10-15

    Superficial infections of the skin and mucous membranes caused by dermatophyte fungi are amongst the most common and challenging infections to treat. Previously we demonstrated the phototoxic effects of photodynamic therapy (PDT) towards Trichophyton rubrum, using a green laser to photoactivate Rose Bengal (RB). The aim of this study was to evaluate whether we could; (1) achieve a similar effect using an inexpensive light-emitting diode (LED) to photoactivate RB and (2) to evaluate whether our PDT regime could be combined with standard antifungal drug therapy and increase its effectiveness. We designed and built our own inexpensive green (530 nm) LED source and tested its efficacy as part our RB-PDT regime in vitro against T. rubrum. We also examined the potential benefits of incorporating PDT as part of combination therapy and whether the order in which this was done had an impact. First we subjected spore suspensions to sub-inhibitory concentrations of a number of antifungal agents (CLT, MCZ and TRB) for 72 hours followed by RB-PDT. Secondly we subjected spore suspensions to sub-inhibitory PDT followed by drug treatment and evaluated if there were any changes to the minimum inhibitory concentrations (MICs) of the drugs tested. The optimal conditions for photoinactivation of T. rubrum using RB-PDT alone were 140 μM of RB and 24 J/cm2 of LED (equating to a 30-minute exposure). These parameters also caused a 100% reduction in the viability of the pathogenic yeast Candida albicans and the model fungus Saccharomyces cerevisiae. By combining our RB-PDT regime as an adjunct to antifungal drugs we were able to dramatically reduce the exposure times. Treatment of spore suspensions using a sub-inhibitory dose of clotrimazole (CLT) followed by RB-PDT, this order was critical, significantly reduced the exposure times required to achieve 100% inhibition of T. rubrum to 15 minutes as compared to RB-PDT alone. The combination of antifungal drug and RB-PDT represents an

  15. How can technology enhance cognitive behavioral therapy: the case of pediatric obsessive compulsive disorder

    National Research Council Canada - National Science Library

    Lidewij H Wolters; Vivian op de Beek; Bernhard Weidle; Norbert Skokauskas

    2017-01-01

    .... This debate paper focuses on new technologies as a potential vehicle to address the challenges faced by traditional treatment, with special reference to cognitive behavioral therapy for pediatric...

  16. Creative art therapy to enhance rehabilitation for stroke patients: a randomized controlled trial.

    Science.gov (United States)

    Kongkasuwan, Ratcharin; Voraakhom, Kotchakorn; Pisolayabutra, Prim; Maneechai, Pichai; Boonin, Jiraporn; Kuptniratsaikul, Vilai

    2016-10-01

    To examine the efficacy of creative art therapy plus conventional physical therapy, compared with physical therapy only, in increasing cognitive ability, physical functions, psychological status and quality of life of stroke patients. Randomized controlled trial with blinded assessor. An in-patient setting PARTICIPANTS: One hundred and eighteen stroke patients aged ⩾50 years who could communicate verbally. All participants received conventional physical therapy five days per week. An intervention group received additional creative art therapy, twice a week for four weeks, in a rehabilitation ward. Cognitive function, anxiety and depression, physical performance and quality of life were measured with the Abbreviated Mental Test, the Hospital Anxiety and Depression Scale, the modified Barthel Index scale and the pictorial Thai Quality of Life questionnaire, respectively. Mean differences for the intervention group were significantly greater than the control group for depression (-4.5, 95% CI -6.5, -2.5, part therapy and most reported improved concentration (68.5%), emotion (79.6%), self-confidence (72.2%) and motivation (74.1%). Creative art therapy combined with conventional physical therapy can significantly decrease depression, improve physical functions and increase quality of life compared with physical therapy alone. © The Author(s) 2015.

  17. Enhancement of Intermittent Androgen Ablation Therapy by Finasteride Administration in Animal Models

    National Research Council Canada - National Science Library

    Wang, Zhou

    2003-01-01

    .... Intermittent androgen ablation therapy may slow down the development of androgen refractory tumors because intermittent recovery of androgens can induce differentiation of prostatic epithelial cells...

  18. Nectar-providing plants enhance the energetic state of herbivores as well as their parasitoids under field conditions

    NARCIS (Netherlands)

    Winkler, K.; Wäckers, F.L.; Pinto, D.M.

    2009-01-01

    1. The use of flowering vegetation has been widely advocated as a strategy for providing parasitoids and predators with nectar and pollen. However, their herbivorous hosts and prey may exploit floral food sources as well. 2. Previous laboratory studies have shown that not all flower species are

  19. A High School Counselor's Leadership in Providing School-Wide Screenings for Depression and Enhancing Suicide Awareness

    Science.gov (United States)

    Erickson, Anne; Abel, Nicholas R.

    2013-01-01

    The prevalence of mental health issues and suicidal thoughts and actions among school-aged children and adolescents is a serious issue. This article examines the scope of the problem nationwide and provides a brief overview of the literature regarding the effectiveness of school-wide screening programs for depression and suicide risk. The authors…

  20. Enhancing Context Analysis with Intelligence in Providing e-Health Services: Less Infrastructure Dependency in Supporting Cardio-Vascular Patients

    NARCIS (Netherlands)

    Verbraeck, A.; Widya, I.A.; Shishkov, Boris; Cordeiro, J.; Ranchordas, A.

    2009-01-01

    In Europe, we observe an increasing number of people with health problems, who could theoretically receive care outside of a hospital when their condition could be properly monitored. Not being able to provide this monitoring leads to an increasing pressure on an already overcrowded hospital system

  1. [The impact of the sonotherapy and compression therapy on enhancement of healing venous leg ulcers after surgical treatment].

    Science.gov (United States)

    Taradaj, Jakub; Franek, Andrzej; Dolibog, Patrycja; Cierpka, Lech; Błaszczak, Edward

    2007-12-01

    The aim of this paper was to describe the impact of the sonotherapy and compression therapy on enhancement of healing venous leg ulcers after surgical treatment. Three comparative groups of patients--A, B and C were made at random from patients with venous leg ulcers, which had been earlier operated by modified Babcock' method. The 24 patients were included (in use of software Monte Carlo) to the group A, 25 patients to the group B and 24 patients to the group C (control group). The patients in all comparative groups were treated pharmacologically. Ulcerations at patients in group A were additionally treated in use of ultrasound. And ulcerations at patients in group B were additionally treated in use of compression therapy. The evaluated factors were to estimate the sonotherapy and compression therapy causes any changes of the surface, longest and widest dimensions, and volume of tissue defect. For all comparative groups calculated the Gilman parameter. The weekly speed of changes of surface and volume were estimated too. After therapy there was statistically significant decrease of whole surface and pus-covered and granulation area, longest and widest dimensions, and volume of ulcers in all groups while there was no statistically significant difference--except pus-covered areas--between the groups observed. Comparison in terms of pus-covered area indicated a significant difference between all groups, in favor groups A and B than C. There are no special reasons for application of ultrasound and compression therapy in enhancement of healing process--however the following results must be verified on bigger population and longer patient observation. The sonotherapy and compression therapy promote only decontamination process compared with control group.

  2. Development and Validation of a Training Program Using a Cognitive Behavioral Therapy Approach with the Purpose of Enabling Community Pharmacists to Provide Empathic Patient Counseling.

    Science.gov (United States)

    Tanuma, Kazunori; Watanabe, Fumiyuki; Maeda, Hatsuyo; Shiina, Miki; Hara, Kazuo; Kamei, Miwako

    2017-01-01

    To enable community pharmacists to provide empathic patient counseling, we developed and validated a training program based on cognitive reframing, which is one of the cognitive behavioral therapies. We divided 24 community pharmacists into two groups, providing training to the intervention group. The duration of the training program was two hours per session, with a total of eight hours. We conducted a survey of the intervention group to evaluate their training experience. In addition, we performed two role-play scenarios on patient counseling using simulated patients, evaluating the patient counseling alliance scores and the degrees of the psychological distance between the patients and pharmacists. The degree of satisfaction correlated with four training items, including "explanation by comics". When pharmacists felt that the cognitive behavioral therapy approach was successful, no significant differences were found in the patient counseling alliance grades. However, the psychological distance between the patients and pharmacists was smaller. We were able to infer that a cognitive behavioral therapy approach could decrease the psychological distance between patients and pharmacists, thereby enabling empathic patient counseling.

  3. Synergistic Effect of Anti-Angiogenic and Radiation Therapy: Quantitative Evaluation with Dynamic Contrast Enhanced MR Imaging.

    Directory of Open Access Journals (Sweden)

    Hyun Jung Koo

    Full Text Available We assessed the effects of anti-angiogenic therapy (AAT on radiation therapy (RT, evaluating the tumor growth and perfusion patterns on dynamic contrast enhanced MR (DCE-MR images.Thirteen nude mice with heterotopic xenograft cancer of human lung cancer cell line were used. To observe the interval change of the tumor size and demonstrate the time-signal intensity enhancement curve of the tumor, the mice were subdivided into four groups: control (n = 2, AAT (n = 2, RT (n = 5, and combined therapy (AART, n = 4. DCE-MR images were taken four weeks after treatment. Perfusion parameters were obtained based on the Brix model. To compare the interval size changes in the RT group with those in the AART group, repeated measures ANOVA was used. Perfusion parameters in both the RT and AART groups were compared using a Mann-Whitney U test.Tumor growth was more suppressed in AART group than in the other groups. Control group showed the rapid wash-in and wash-out pattern on DCE-MR images. In contrast to RT group with delayed and prolonged enhancement, both AAT and AART groups showed the rapid wash-in and plateau pattern. The signal intensity in the plateau/time to peak enhancement (P<0.016 and the maximum enhancement ratio (P<0.016 of AART group were higher than those of RT group.AART showed synergistic effects in anticancer treatment. The pattern of the time-intensity curve on the DCE-MR images in each group implies that AAT might help maintain the perfusion in the cancer of AART group.

  4. Bidirectional functions of thrombin on fibrinolysis: Evidence of thrombin-dependent enhancement of fibrinolysis provided by spontaneous plasma clot lysis.

    Science.gov (United States)

    Tomczyk, Martyna; Suzuki, Yuko; Sano, Hideto; Brzoska, Tomasz; Tanaka, Hiroki; Urano, Tetsumei

    2016-07-01

    Besides procoagulant activity, thrombin exhibits anticoagulant and profibrinolytic activities. We demonstrated that the euglobulin clot lysis time (ECLT) was shortened by endogenously generated thrombin as a result of the inactivation of plasminogen activator inhibitor type 1 (PAI-1). In contrast, thrombin suppressed fibrinolytic activity through the activation of thrombin activatable fibrinolysis inhibitor (TAFI). Here, using three different clot lysis assays of the ECLT, the tissue plasminogen activator supplemented plasma clot lysis time (tPA-PCLT) and the spontaneous plasma clot lysis time (s-PCLT), we analyzed how the coagulation process modifies fibrinolysis. The ECLT was shortened by exogenously supplemented thrombin in a dose-dependent manner in the absence of calcium ion (Ca(++)), whereas this shortening was not observed in the presence of Ca(++) where endogenous prothrombin was effectively activated to thrombin. This shortening was also not observed for the tPA-PCLT, in which tPA is supplemented in excess and PAI-1 activity is mostly lost. On the contrary, thrombin dose-dependently prolonged the tPA-PCLT, which was mostly abolished by inhibitors of carboxypeptidase and activated FXIII, suggesting that the prolongation is TAFI- and Factor XIII-dependent. The s-PCLT was shortened when thrombin generation was boosted by supplementing tissue factor and phosphatidylserine together with Ca(++), which was more apparent in the presence of inhibitors of activated FXIII and activated TAFI. Thus, thrombin appeared to express its enhancing effect on fibrinolysis even in plasma, in addition to its inhibiting effect. These bidirectional functions of thrombin on fibrinolysis seem to take place on demand under different environments to maintain adequate vascular blood flow. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Contrast-enhanced spectral mammography: Does mammography provide additional clinical benefits or can some radiation exposure be avoided?

    Science.gov (United States)

    Fallenberg, Eva Maria; Dromain, Clarisse; Diekmann, Felix; Renz, Diane M; Amer, Heba; Ingold-Heppner, Barbara; Neumann, Avidan U; Winzer, Klaus J; Bick, Ulrich; Hamm, Bernd; Engelken, Florian

    2014-07-01

    The purpose of this study was to compare contrast-enhanced spectral mammography (CESM) with mammography (MG) and combined CESM + MG in terms of detection and size estimation of histologically proven breast cancers in order to assess the potential to reduce radiation exposure. A total of 118 patients underwent MG and CESM and had final histological results. CESM was performed as a bilateral examination starting 2 min after injection of iodinated contrast medium. Three independent blinded radiologists read the CESM, MG, and CESM + MG images with an interval of at least 4 weeks to avoid case memorization. Sensitivity and size measurement correlation and differences were calculated, average glandular dose (AGD) levels were compared, and breast densities were reported. Fisher's exact and Wilcoxon tests were performed. A total of 107 imaging pairs were available for analysis. Densities were ACR1: 2, ACR2: 45, ACR3: 42, and ACR4: 18. Mean AGD was 1.89 mGy for CESM alone, 1.78 mGy for MG, and 3.67 mGy for the combination. In very dense breasts, AGD of CESM was significantly lower than MG. Sensitivity across readers was 77.9 % for MG alone, 94.7 % for CESM, and 95 % for CESM + MG. Average tumor size measurement error compared to postsurgical pathology was -0.6 mm for MG, +0.6 mm for CESM, and +4.5 mm for CESM + MG (p < 0.001 for CESM + MG vs. both modalities). CESM alone has the same sensitivity and better size assessment as CESM + MG and was significantly better than MG with only 6.2 % increase in AGD. The combination of CESM + MG led to systematic size overestimation. When a CESM examination is planned, additional MG can be avoided, with the possibility of saving up to 61 % of radiation dose, especially in patients with dense breasts.

  6. Gold Nano-Popcorn Based Targeted Diagonosis, Nanotherapy Treatment and In-Situ Monitoring of Photothermal Therapy Response of Prostate Cancer Cells Using Surface Enhanced Raman Spectroscopy

    Science.gov (United States)

    Lu, Wentong; Singh, Anant Kumar; Khan, Sadia Afrin; Senapati, Dulal; Yu, Hongtao; Ray, Paresh Chandra

    2010-01-01

    Prostate cancer is the second leading cause of cancer-related death among the American male population and the cost of treating prostate cancer patients is about $10 billion/year in the US. Current treatments are mostly ineffective against advanced stage prostate cancer disease and are often associated with severe side effects. Driven by the need, in this manuscript, we report multifunctional nanotechnology-driven gold nano-popcorn based surface enhanced Raman scattering (SERS) assay for targeted sensing, nanotherapy treatment and in-situ monitoring of photothermal nanotherapy response during the therapy process. Our experimental data show that in the presence of LNCaP human prostate cancer cell, multifunctional popcorn shape gold nanoparticle forms several hot spots and provides a significant enhancement of the Raman signal intensity by several orders of magnitude (2.5 × 109). As a result, it can recognize human prostate cancer cell in 50 cells level. Our results indicate that the localized heating that occurs during NIR irradiation is able to cause irreparable cellular damage of the prostate cancer cell. Our in-situ time dependent results demonstrates for the first time that by monitoring SERS intensity change, one can monitor photo thermal nanotherapy response during therapy process. Possible mechanisms and operating principle of our SERS assay have been discussed. Ultimately, this nanotechnology driven assay could have enormous potential applications in rapid, on-site targeted sensing, nanotherapy treatment and monitoring of nanotherapy process which is critical to providing effective treatment of cancer disease. PMID:21128627

  7. Gold nano-popcorn-based targeted diagnosis, nanotherapy treatment, and in situ monitoring of photothermal therapy response of prostate cancer cells using surface-enhanced Raman spectroscopy.

    Science.gov (United States)

    Lu, Wentong; Singh, Anant Kumar; Khan, Sadia Afrin; Senapati, Dulal; Yu, Hongtao; Ray, Paresh Chandra

    2010-12-29

    Prostate cancer is the second leading cause of cancer-related death among the American male population, and the cost of treating prostate cancer patients is about $10 billion/year in the United States. Current treatments are mostly ineffective against advanced-stage prostate cancer and are often associated with severe side effects. Driven by these factors, we report a multifunctional, nanotechnology-driven, gold nano-popcorn-based surface-enhanced Raman scattering (SERS) assay for targeted sensing, nanotherapy treatment, and in situ monitoring of photothermal nanotherapy response during the therapy process. Our experimental data show that, in the presence of LNCaP human prostate cancer cells, multifunctional popcorn-shaped gold nanoparticles form several hot spots and provide a significant enhancement of the Raman signal intensity by several orders of magnitude (2.5 × 10(9)). As a result, it can recognize human prostate cancer cells at the 50-cells level. Our results indicate that the localized heating that occurs during near-infrared irradiation can cause irreparable cellular damage to the prostate cancer cells. Our in situ time-dependent results demonstrate for the first time that, by monitoring SERS intensity changes, one can monitor photothermal nanotherapy response during the therapy process. Possible mechanisms and operating principles of our SERS assay are discussed. Ultimately, this nanotechnology-driven assay could have enormous potential applications in rapid, on-site targeted sensing, nanotherapy treatment, and monitoring of the nanotherapy process, which are critical to providing effective treatment of cancer.

  8. Experiential Learning in Occupational Therapy: Can It Enhance Readiness for Clinical Practice?

    Science.gov (United States)

    Knecht-Sabres, Lisa Jean

    2013-01-01

    This mixed method study examined the effectiveness of experiential learning opportunities near the end of the occupational therapy students' didactic education. A pretest/posttest design with a gain score approach was used to determine whether there was a significant improvement in the occupational therapy students' self-perception of their…

  9. Facilitating Occupational Therapy Student Learning to Enhance Cross-Cultural Effectiveness

    Science.gov (United States)

    Gilbertson, Barbara Carol Hooper

    2012-01-01

    Developing cultural awareness and effectiveness is critical to meaningful and successful occupational therapy practice and of concern to occupational therapists worldwide (World Federation of Occupational Therapists, 2010). Occupational therapy graduates, not fully representative of the demographics of the populations they will meet clinically,…

  10. TU-H-CAMPUS-TeP3-05: Evaluation of the Microscopic Dose Enhancement in the Nanoparticle-Enhanced Auger Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Sung, W; Jung, S [Program in Biomedical Radiation Sciences, Department of Transdisciplinary Studies, Seoul National University, Seoul (Korea, Republic of); Ye, S [Program in Biomedical Radiation Sciences, Department of Transdisciplinary Studies, Seoul National University, Seoul (Korea, Republic of); Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2016-06-15

    Purpose: The aim of this study is to apply Monte Carlo simulations to investigate the nanoparticle dose enhancement for Auger therapy. Methods: Two nanoparticle fabrications were considered: nanoshell and nanosphere. In the first step, a single nanoparticle was irradiated with Auger emitters. The electrons were scored in a phase space at the outer surface of the nanoparticle with Geant4-Penelope. In the second step, the previously recorded phase space was used as a source and placed at the center of a cell-size water phantom. The nanoscale dose was evaluated in water around the nanoparticle with Geant4-DNA. The dose enhancement factor (DEF) is defined as the ratio of doses with and without nanoparticles. The nanoparticles were replaced by corresponding water nanoparticle with the same size and volume source which represents typical situation of Auger emitters without nanoparticle. Various sizes/materials of nanoparticles and isotopes were considered. Results: Nanoshell - Microscopic dose was increased up to 130% at 20 – 100 nm distances from the surface of Au-{sup 125}I nanoshell. However, dose at less than 20 nm distance was reduced due to absorbed low energy electrons in gold nanoshell. The amounts and regions of the dose enhancement were dependent on nanoshell size, materials, and isotopes. Nanosphere - The increased amounts of electrons up to 300% and reduced average energy with nanosphere were observed compared with water nanoparticle. We observed localized dose enhancement (up to a factor 3.6) in the immediate vicinity (< 50 nm) of Au-{sup 125} I nanosphere. The dose enhancement patterns vary according to nanosphere sizes and isotopes. Conclusion: We conclude that Auger therapy with nanoparticles can lead to change of electron energy spectrum and dose enhancements at certain range. The dose enhancement patterns vary according to nanoparticle sizes, materials, and isotopes. This work was supported by the National Research Foundation of Korea (NRF) grant

  11. MRI active guidewire with an embedded temperature probe and providing a distinct tip signal to enhance clinical safety

    Directory of Open Access Journals (Sweden)

    Sonmez Merdim

    2012-06-01

    Full Text Available Abstract Background The field of interventional cardiovascular MRI is hampered by the unavailability of active guidewires that are both safe and conspicuous. Heating of conductive guidewires is difficult to predict in vivo and disruptive to measure using external probes. We describe a clinical-grade 0.035” (0.89 mm guidewire for MRI right and left heart catheterization at 1.5 T that has an internal probe to monitor temperature in real-time, and that has both tip and shaft visibility as well as suitable flexibility. Methods The design has an internal fiberoptic temperature probe, as well as a distal solenoid to enhance tip visibility on a loopless antenna. We tested different tip-solenoid configurations to balance heating and signal profiles. We tested mechanical performance in vitro and in vivo in comparison with a popular clinical nitinol guidewire. Results The solenoid displaced the point of maximal heating (“hot spot” from the tip to a more proximal location where it can be measured without impairing guidewire flexion. Probe pullback allowed creation of lengthwise guidewire temperature maps that allowed rapid evaluation of design prototypes. Distal-only solenoid attachment offered the best compromise between tip visibility and heating among design candidates. When fixed at the hot spot, the internal probe consistently reflected the maximum temperature compared external probes. Real-time temperature monitoring was performed during porcine left heart catheterization. Heating was negligible using normal operating parameters (flip angle, 45°; SAR, 1.01 W/kg; the temperature increased by 4.2°C only during high RF power mode (flip angle, 90°; SAR, 3.96 W/kg and only when the guidewire was isolated from blood cooling effects by an introducer sheath. The tip flexibility and in vivo performance of the final guidewire design were similar to a popular commercial guidewire. Conclusions We integrated a fiberoptic temperature probe inside

  12. MRI active guidewire with an embedded temperature probe and providing a distinct tip signal to enhance clinical safety.

    Science.gov (United States)

    Sonmez, Merdim; Saikus, Christina E; Bell, Jamie A; Franson, Dominique N; Halabi, Majdi; Faranesh, Anthony Z; Ozturk, Cengizhan; Lederman, Robert J; Kocaturk, Ozgur

    2012-06-21

    The field of interventional cardiovascular MRI is hampered by the unavailability of active guidewires that are both safe and conspicuous. Heating of conductive guidewires is difficult to predict in vivo and disruptive to measure using external probes. We describe a clinical-grade 0.035" (0.89 mm) guidewire for MRI right and left heart catheterization at 1.5 T that has an internal probe to monitor temperature in real-time, and that has both tip and shaft visibility as well as suitable flexibility. The design has an internal fiberoptic temperature probe, as well as a distal solenoid to enhance tip visibility on a loopless antenna. We tested different tip-solenoid configurations to balance heating and signal profiles. We tested mechanical performance in vitro and in vivo in comparison with a popular clinical nitinol guidewire. The solenoid displaced the point of maximal heating ("hot spot") from the tip to a more proximal location where it can be measured without impairing guidewire flexion. Probe pullback allowed creation of lengthwise guidewire temperature maps that allowed rapid evaluation of design prototypes. Distal-only solenoid attachment offered the best compromise between tip visibility and heating among design candidates. When fixed at the hot spot, the internal probe consistently reflected the maximum temperature compared external probes.Real-time temperature monitoring was performed during porcine left heart catheterization. Heating was negligible using normal operating parameters (flip angle, 45°; SAR, 1.01 W/kg); the temperature increased by 4.2°C only during high RF power mode (flip angle, 90°; SAR, 3.96 W/kg) and only when the guidewire was isolated from blood cooling effects by an introducer sheath. The tip flexibility and in vivo performance of the final guidewire design were similar to a popular commercial guidewire. We integrated a fiberoptic temperature probe inside a 0.035" MRI guidewire. Real-time monitoring helps detect deleterious

  13. Adjunctive therapy with statins reduces residual albuminuria/proteinuria and provides further renoprotection by downregulating the angiotensin II-AT1 pathway in hypertensive nephropathy.

    Science.gov (United States)

    Zhang, Zhi; Li, Ziqiang; Cao, Kaijin; Fang, Dailong; Wang, Fazhan; Bi, Gang; Yang, Jian; He, Yingju; Wu, Jinhui; Wei, Yuquan; Song, Xiangrong

    2017-07-01

    Blockade of the renin-angiotensin II (Ang II) system by AT1 blockers (ARBs) and angiotensin-converting enzyme inhibitors retards the progression of chronic kidney disease (CKD) by reducing albuminuria/proteinuria. However, many patients with CKD suffer from residual albuminuria/proteinuria, which is an independent risk factor for CKD progression. The aim of the current study is to investigate the effect of pitavastatin, one of the adjunctive agents to ARBs, on the reduction of albuminuria/proteinuria and further renoprotection mediated by telmisartan in spontaneously hypertensive rats. Forty-two-week-old spontaneously hypertensive rats were grouped randomly and received 8 weeks of treatments with vehicle, telmisartan, pitavastatin or a combination of telmisartan and pitavastatin. Both albuminuria and proteinuria were inhibited significantly in the telmisartan-treated group, but an obviously residual albuminuria was maintained. The combination treatment with telmisartan and pitavastatin displayed a more effective decrease in albuminuria and proteinuria, even to the normal level. Enhanced nephroprotection was also observed in this combination group, which was independent of the cholesterol-lowering effects. Further mechanistic studies revealed that the combination therapy greatly attenuated the expression of intrarenal Ang II and AT1, thereby decreasing the activation of TGF-β-Smad and NF-κB and inhibiting fibrosis and inflammation. Adjunctive therapy with pitavastatin dramatically reduced residual albuminuria/proteinuria and enhanced nephroprotection, likely by downregulating the expression of intrarenal Ang II and AT1. It could be concluded that statins might be a promising adjunctive therapeutic agent to conventional ARB treatment in hypertensive renal damage.

  14. Do frontline health care providers know enough about artemisinin-based combination therapy to rationally treat malaria? A cross-sectional survey in Gezira State, Sudan.

    Science.gov (United States)

    Mannan, Abeer A; Elmardi, Khalid A; Idris, Yassir A; Spector, Jonathan M; Ali, Nahid A; Malik, Elfatih M

    2015-03-26

    In 2004, artemisinin-based combination therapy (ACT) was introduced in Sudan for the treatment of malaria. The role of health care providers working in first-level health care facilities is central for the effective implementation of this revised malaria treatment policy. However, information about their level of ACT knowledge is inadequate. This study sought to describe frontline health care providers' knowledge about the formulations and dose regimens of nationally recommended ACT in Sudan. This cross-sectional study took place in Gezira State, Sudan. Data were gathered from five localities comprising forty primary health care facilities. A total of 119 health care providers participated in the study (72 prescribers and 47 dispensers). The primary outcome was the proportion of health care providers who were ACT knowledgeable, a composite indicator of health care providers' ability to (1) define what combination therapy is; (2) identify the recommended first- and second-line treatments; and (3) correctly state the dose regimens for each. All prescribers and 95.7% (46/47) of dispensers were aware of the new national malaria treatment policy. However, 93.1% (67/72) of prescribers compared to 87.2% (41/47) of dispensers recognized artesunate-sulphadoxine/pyrimethamine as the recommended first-line treatment in Sudan. Only a small number of prescribers and dispensers (9.4% and 13.6%, respectively) were able to correctly define the meaning of a combination therapy. Overall, only 22% (26/119, 95% CI 14.6-29.4) of health care providers were found to be ACT knowledgeable with no statistically significant difference between prescribers and dispensers. Overall, ACT knowledge among frontline health care providers is very poor. This finding suggests that efforts are needed to improve knowledge of prescribers and dispensers working in first-level health care facilities, perhaps through implementing focused, provider-oriented training programmes. Additionally, a system for

  15. SU-E-T-571: Newly Emerging Integrated Transmission Detector Systems Provide Online Quality Assurance of External Beam Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Hoffman, D; Chung, E; Hess, C; Stern, R; Benedict, S [UC Davis Cancer Center, Sacramento, CA (United States)

    2015-06-15

    Purpose: Two newly emerging transmission detectors positioned upstream from the patient have been evaluated for online quality assurance of external beam radiotherapy. The prototype for the Integral Quality Monitor (IQM), developed by iRT Systems GmbH (Koblenz, Germany) is a large-area ion chamber mounted on the linac accessory tray to monitor photon fluence, energy, beam shape, and gantry position during treatment. The ion chamber utilizes a thickness gradient which records variable response dependent on beam position. The prototype of Delta4 Discover™, developed by ScandiDos (Uppsala, Sweden) is a linac accessory tray mounted 4040 diode array that measures photon fluence during patient treatment. Both systems are employable for patient specific QA prior to treatment delivery. Methods: Our institution evaluated the reproducibility of measurements using various beam types, including VMAT treatment plans with both the IQM ion chamber and the Delta4 Discover diode array. Additionally, the IQM’s effect on photon fluence, dose response, simulated beam error detection, and the accuracy of the integrated barometer, thermometer, and inclinometer were characterized. The evaluated photon beam errors are based on the annual tolerances specified in AAPM TG-142. Results: Repeated VMAT treatments were measured with 0.16% reproducibility by the IQM and 0.55% reproducibility by the Delta4 Discover. The IQM attenuated 6, 10, and 15 MV photon beams by 5.43±0.02%, 4.60±0.02%, and 4.21±0.03% respectively. Photon beam profiles were affected <1.5% in the non-penumbra regions. The IQM’s ion chamber’s dose response was linear and the thermometer, barometer, and inclinometer agreed with other calibrated devices. The device detected variations in monitor units delivered (1%), field position (3mm), single MLC leaf positions (13mm), and photon energy. Conclusion: We have characterized two new transmissions detector systems designed to provide in-vivo like measurements upstream

  16. The Role of Business Education Provided Through Lifelong Learning in Enhancing Profesional Competencies. Evidence from the Eu-27 Dataset

    Directory of Open Access Journals (Sweden)

    Vlad Dumitrache

    2014-08-01

    Full Text Available This paper examines the macroeconomic implications of business education provided by the process of lifelong learning, based on a panel dataset comprising the EU-27 countries. Business education is a valuable component of adult education, and the lifelong learning represents the main channel facilitating the transfer of this knowledge. A number of three panel regression models are conducted separately for the New Member States (NMS and Old Member States (OMS. The positive effects of business education on economic growth and duration of working life are found to be more significant and powerful in the NMS than in the OMS. The empirical analysis also shows that business education is a determinant of the subjective poverty reduction only in the OMS, while the third-level education attainment contributes to the poverty reduction in the NMS, only when been accompanied by business education.

  17. IEEE 802.15.4 Frame Aggregation Enhancement to Provide High Performance in Life-Critical Patient Monitoring Systems.

    Science.gov (United States)

    Akbar, Muhammad Sajjad; Yu, Hongnian; Cang, Shuang

    2017-01-28

    In wireless body area sensor networks (WBASNs), Quality of Service (QoS) provision for patient monitoring systems in terms of time-critical deadlines, high throughput and energy efficiency is a challenging task. The periodic data from these systems generates a large number of small packets in a short time period which needs an efficient channel access mechanism. The IEEE 802.15.4 standard is recommended for low power devices and widely used for many wireless sensor networks applications. It provides a hybrid channel access mechanism at the Media Access Control (MAC) layer which plays a key role in overall successful transmission in WBASNs. There are many WBASN's MAC protocols that use this hybrid channel access mechanism in variety of sensor applications. However, these protocols are less efficient for patient monitoring systems where life critical data requires limited delay, high throughput and energy efficient communication simultaneously. To address these issues, this paper proposes a frame aggregation scheme by using the aggregated-MAC protocol data unit (A-MPDU) which works with the IEEE 802.15.4 MAC layer. To implement the scheme accurately, we develop a traffic patterns analysis mechanism to understand the requirements of the sensor nodes in patient monitoring systems, then model the channel access to find the performance gap on the basis of obtained requirements, finally propose the design based on the needs of patient monitoring systems. The mechanism is initially verified using numerical modelling and then simulation is conducted using NS2.29, Castalia 3.2 and OMNeT++. The proposed scheme provides the optimal performance considering the required QoS.

  18. Distribution patterns of Gd-DTPA-enhanced magnetic resonance imaging after intravenous tissue plasminogen activator therapy for acute myocardial infarction

    Energy Technology Data Exchange (ETDEWEB)

    Fukuzawa, Shigeru; Watanabe, Hiroyuki; Shimada, Kazuhiro; Katagiri, Nakoto; Ozawa, Shun (Funabashi Municipal Medical Center, Chiba (Japan))

    1994-03-01

    In patients who received thrombolytic therapy for acute myocardial infarction (AMI), we observed 3 distinct patterns in gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA)-enhanced magnetic resonance (MR) imaging. To clarify the significance of these distribution patterns of Gd-DTPA, 20 consecutive patients underwent Gd-DTPA-enhanced MR imaging 7-10 days after AMI. All of the patients received intravenous recombinant tissue plasminogen activator (IVTPA) within 6 h of onset. Echocardiograms were obtained prior to and serially over 10 days, and interpreted for regional wall motion. Coronary angiograms were obtained the day before discharge. None of the 6 patients with a closed infarct-related artery, and 9 of the 14 patients with an open artery, demonstrated subendocardial enhancement (p<0.05). All of these latter 9 patients demonstrated a significant improvement in wall motion between days 1 and 10 after AMI. In contrast, only 1 of the 7 patients with transmural enhancement and none of the 4 patients with non-homogeneous enhancement demonstrated improvement of wall motion on day 10 (p<0.05). We concluded that subendocardial enhancement was a fair prognostic sign for restoration of regional cardiac function in patients who received IVTPA during AMI. (author).

  19. The roles of macrophages and nitric oxide in interleukin-3-enhanced HSV-Sr39tk-mediated prodrug therapy.

    Directory of Open Access Journals (Sweden)

    Ching-Fang Yu

    Full Text Available The herpes simplex virus thymidine kinase/ganciclovir (HSV-sr39tk/GCV system is a well-established prodrug system used in cancer gene therapy. However, this system is currently not effective enough to eradicate malignant tumors completely. This study aimed to evaluate whether co-expression of interleukin-3 (IL-3 could enhance the anti-tumor activity of HSV-sr39tk/GCV prodrug gene therapy using a murine TRAMP-C1 prostate tumor model. In vitro results demonstrated that HSV-sr39tk-transfected cells exhibited enhanced sensitivity to the GCV prodrug, which was not affected by co-expression of the mIL-3 gene. However, in vivo studies showed that co-expression of the mIL-3 gene significantly increased the HSV-sr39tk/GCV-induced tumor growth delay and even cured the tumor. The TRAMP-C1-specific immune response of spleen lymphocytes from mice bearing HSV-sr39tk- and IL-3-expressing TRAMP-C1 tumors was measured by ELISA. Results showed that IL-3-activated IL-4-dominant lymphocytes became IFN-γ- dominant lymphocytes after combined HSV-sr39tk/GCV therapy. The efficacy of combined therapies on tumor regression was reduced when macrophages populations were depleted by carrageenan or NO production was inhibited by administration of the iNOS inhibitor, L-NAME. These results suggest that utilizing a bicistronic vector to express HSV-sr39tk and the IL-3 gene induced an enhanced macrophage- or NO-dependent anti-tumor effect.

  20. Analgesia Is Enhanced by Providing Information regarding Good Outcomes Associated with an Odor: Placebo Effects in Aromatherapy?

    Directory of Open Access Journals (Sweden)

    Yuri Masaoka

    2013-01-01

    Full Text Available No previous report has described whether information regarding an odor used in aromatherapy has placebo effects. We investigated whether placebo analgesia was engendered by verbal information regarding the analgesic effects of an odor. Twelve of 24 subjects were provided with the information that a lavender odor would reduce pain (informed, whereas the other 12 subjects were not (not-informed. Concurrent with respiration recording, the subjects were administered a lavender-odor or no-odor treatment during application of painful stimulation to the forefinger. The subjects reported their experience of pain and its unpleasantness on a visual analogue scale after the painful stimulation. The lavender-odor treatment significantly alleviated pain and unpleasantness compared with the no-odor treatment in the informed (P<0.01 and not-informed groups (P<0.05. The no-odor treatment in the informed group significantly alleviated pain and unpleasantness compared with both the no-odor and lavender-odor treatments in the not-informed group (P<0.05. Rapid and shallow breathing induced by the painful stimulation became slow and deep during the lavender-odor and no-odor treatments in both groups. Information regarding a lavender odor, the lavender odor itself, and slower breathing contributed to reduced perceptions of pain and unpleasantness during painful stimulation, suggesting that placebo effects significantly contribute to analgesia in aromatherapy.

  1. Enhancing pediatric workforce diversity and providing culturally effective pediatric care: implications for practice, education, and policy making.

    Science.gov (United States)

    2013-10-01

    This policy statement serves to combine and update 2 previously independent but overlapping statements from the American Academy of Pediatrics (AAP) on culturally effective health care (CEHC) and workforce diversity. The AAP has long recognized that with the ever-increasing diversity of the pediatric population in the United States, the health of all children depends on the ability of all pediatricians to practice culturally effective care. CEHC can be defined as the delivery of care within the context of appropriate physician knowledge, understanding, and appreciation of all cultural distinctions, leading to optimal health outcomes. The AAP believes that CEHC is a critical social value and that the knowledge and skills necessary for providing CEHC can be taught and acquired through focused curricula across the spectrum of lifelong learning. This statement also addresses workforce diversity, health disparities, and affirmative action. The discussion of diversity is broadened to include not only race, ethnicity, and language but also cultural attributes such as gender, religious beliefs, sexual orientation, and disability, which may affect the quality of health care. The AAP believes that efforts must be supported through health policy and advocacy initiatives to promote the delivery of CEHC and to overcome educational, organizational, and other barriers to improving workforce diversity.

  2. Communication architecture for AAL. Supporting patient care by health care providers in AAL-enhanced living quarters.

    Science.gov (United States)

    Nitzsche, T; Thiele, S; Häber, A; Winter, A

    2014-01-01

    This article is part of the Focus Theme of Methods of Information in Medicine on "Using Data from Ambient Assisted Living and Smart Homes in Electronic Health Records". Concepts of Ambient Assisted Living (AAL) support a long-term health monitoring and further medical and other services for multi-morbid patients with chronic diseases. In Germany many AAL and telemedical applications exist. Synergy effects by common agreements for essential application components and standards are not achieved. It is necessary to define a communication architecture which is based on common definitions of communication scenarios, application components and communication standards. The development of a communication architecture requires different steps. To gain a reference model for the problem area different AAL and telemedicine projects were compared and relevant data elements were generalized. The derived reference model defines standardized communication links. As a result the authors present an approach towards a reference architecture for AAL-communication. The focus of the architecture lays on the communication layer. The necessary application components are identified and a communication based on standards and their extensions is highlighted. The exchange of patient individual events supported by an event classification model, raw and aggregated data from the personal home area over a telemedicine center to health care providers is possible.

  3. No Ifs, No Butts: Compliance with Smoking Cessation in Secondary Care Guidance (NICE PH48) by Providers of Cancer Therapies (Radiotherapy and Chemotherapy) in the UK

    Science.gov (United States)

    Hutton, Daniel; Gee, Ivan; McGee, Ciara E.; Mellor, Rebecca

    2016-01-01

    Background: Legislation preventing smoking in public places was introduced in England in July 2007. Since then, smoke-free policies have been extended to the majority of hospitals including those providing cancer therapies. Whilst studies have been conducted on the impact and effectiveness of hospital smoke-free policy in the UK and other countries, there have not been any studies with a focus on cancer care providers. Cancer patients are a priority group for smoking cessation and support and this study aimed to examine implementation of the National Institute Clinical Excellence (NICE) guidance (PH48) in acute cancer care trusts in the UK. Methods: Participants were recruited from UK radiotherapy and chemotherapy departments (total 80 sites, 65 organisations) and asked to complete a 15 min online questionnaire exploring the implementation of NICE guidance at their hospital site. Results: Considerable variability in implementation of the NICE guidance was observed. A total of 79.1% trusts were smoke-free in theory; however, only 18.6% were described as smoke-free in practice. Areas of improvement were identified in information and support for patients and staff including in Nicotine Replacement Therapy (NRT) provision, staff training and clarity on e-cigarette policies. Conclusions: While some trusts have effective smoke-free policies and provide valuable cessation support services for patients, improvements are required to ensure that all sites fully adopt the NICE guidance. PMID:27983709

  4. No Ifs, No Butts: Compliance with Smoking Cessation in Secondary Care Guidance (NICE PH48 by Providers of Cancer Therapies (Radiotherapy and Chemotherapy in the UK

    Directory of Open Access Journals (Sweden)

    Daniel Hutton

    2016-12-01

    Full Text Available Background: Legislation preventing smoking in public places was introduced in England in July 2007. Since then, smoke-free policies have been extended to the majority of hospitals including those providing cancer therapies. Whilst studies have been conducted on the impact and effectiveness of hospital smoke-free policy in the UK and other countries, there have not been any studies with a focus on cancer care providers. Cancer patients are a priority group for smoking cessation and support and this study aimed to examine implementation of the National Institute Clinical Excellence (NICE guidance (PH48 in acute cancer care trusts in the UK. Methods: Participants were recruited from UK radiotherapy and chemotherapy departments (total 80 sites, 65 organisations and asked to complete a 15 min online questionnaire exploring the implementation of NICE guidance at their hospital site. Results: Considerable variability in implementation of the NICE guidance was observed. A total of 79.1% trusts were smoke-free in theory; however, only 18.6% were described as smoke-free in practice. Areas of improvement were identified in information and support for patients and staff including in Nicotine Replacement Therapy (NRT provision, staff training and clarity on e-cigarette policies. Conclusions: While some trusts have effective smoke-free policies and provide valuable cessation support services for patients, improvements are required to ensure that all sites fully adopt the NICE guidance.

  5. The providing resources to enhance African American patients' readiness to make decisions about kidney disease (PREPARED) study: protocol of a randomized controlled trial.

    Science.gov (United States)

    Ephraim, Patti L; Powe, Neil R; Rabb, Hamid; Ameling, Jessica; Auguste, Priscilla; Lewis-Boyer, LaPricia; Greer, Raquel C; Crews, Deidra C; Purnell, Tanjala S; Jaar, Bernard G; DePasquale, Nicole; Boulware, L Ebony

    2012-10-12

    Living related kidney transplantation (LRT) is underutilized, particularly among African Americans. The effectiveness of informational and financial interventions to enhance informed decision-making among African Americans with end stage renal disease (ESRD) and improve rates of LRT is unknown. We report the protocol of the Providing Resources to Enhance African American Patients' Readiness to Make Decisions about Kidney Disease (PREPARED) Study, a two-phase study utilizing qualitative and quantitative research methods to design and test the effectiveness of informational (focused on shared decision-making) and financial interventions to overcome barriers to pursuit of LRT among African American patients and their families. Study Phase I involved the evidence-based development of informational materials as well as a financial intervention to enhance African American patients' and families' proficiency in shared decision-making regarding LRT. In Study Phase 2, we are currently conducting a randomized controlled trial in which patients with new-onset ESRD receive 1) usual dialysis care by their nephrologists, 2) the informational intervention (educational video and handbook), or 3) the informational intervention in addition to the option of participating in a live kidney donor financial assistance program. The primary outcome of the randomized controlled trial will include patients' self-reported rates of consideration of LRT (including family discussions of LRT, patient-physician discussions of LRT, and identification of a LRT donor). Results from the PREPARED study will provide needed evidence on ways to enhance the decision to pursue LRT among African American patients with ESRD.

  6. Massage Therapy for Reducing Stress Hormones and Enhancing Immune Function in Breast Cancer Survivors

    National Research Council Canada - National Science Library

    Ironson, Gail

    2001-01-01

    The objectives and specific aims of the ongoing study are to evaluate massage and relaxation therapies for an ethnically diverse group of women with early stages of breast cancer (Stages 1 and 2) for 1...

  7. Massage Therapy for Reducing Stress Hormones and Enhancing Immune Function in Breast Cancer Survivors

    National Research Council Canada - National Science Library

    Tronson, Gail

    2000-01-01

    The objectives and specific aims of the ongoing study are to evaluate massage and relaxation therapies for an ethnically diverse group of women with early stages of breast cancer (Stages 1 and 2) for (1...

  8. Yohimbine Enhancement of Exposure Therapy for Social Anxiety Disorder: A Randomized Controlled Trial

    NARCIS (Netherlands)

    Smits, J.A.J.; Rosenfield, D.; Davis, M.L.; Julian, K.; Handelsman, P.R.; Otto, M.W.; Tuerk, P.; Shiekh, M.; Rosenfield, B.; Hofmann, S.G.; Powers, M.B.

    2014-01-01

    Background Preclinical and clinical trials suggest that yohimbine may augment extinction learning without significant side effects. However, previous clinical trials have only examined adults with specific phobias. Yohimbine has not yet been investigated in the augmentation of exposure therapy for

  9. Use of case-based reasoning to enhance intensive management of patients on insulin pump therapy.

    Science.gov (United States)

    Schwartz, Frank L; Shubrook, Jay H; Marling, Cynthia R

    2008-07-01

    This study was conducted to develop case-based decision support software to improve glucose control in patients with type 1 diabetes mellitus (T1DM) on insulin pump therapy. While the benefits of good glucose control are well known, achieving and maintaining good glucose control remains a difficult task. Case-based decision support software may assist by recalling past problems in glucose control and their associated therapeutic adjustments. Twenty patients with T1DM on insulin pumps were enrolled in a 6-week study. Subjects performed self-glucose monitoring and provided daily logs via the Internet, tracking insulin dosages, work, sleep, exercise, meals, stress, illness, menstrual cycles, infusion set changes, pump problems, hypoglycemic episodes, and other events. Subjects wore a continuous glucose monitoring system at weeks 1, 3, and 6. Clinical data were interpreted by physicians, who explained the relationship between life events and observed glucose patterns as well as treatment rationales to knowledge engineers. Knowledge engineers built a prototypical system that contained cases of problems in glucose control together with their associated solutions. Twelve patients completed the study. Fifty cases of clinical problems and solutions were developed and stored in a case base. The prototypical system detected 12 distinct types of clinical problems. It displayed the stored problems that are most similar to the problems detected, and offered learned solutions as decision support to the physician. This software can screen large volumes of clinical data and glucose levels from patients with T1DM, identify clinical problems, and offer solutions. It has potential application in managing all forms of diabetes.

  10. Oxygen-generating hybrid nanoparticles to enhance fluorescent/photoacoustic/ultrasound imaging guided tumor photodynamic therapy.

    Science.gov (United States)

    Gao, Shi; Wang, Guohao; Qin, Zainen; Wang, Xiangyu; Zhao, Guoqing; Ma, Qingjie; Zhu, Lei

    2017-01-01

    Photodynamic therapy (PDT) is a promising tumor treatment modality that can convert oxygen into cytotoxic singlet oxygen (SO) via photosensitizer to ablate tumor growth. However, the uncontrolled cancer cell proliferation during tumor development and the oxygen consumption during PDT always result in an insufficient oxygen level in tumors, which can adversely affect the PDT efficiency in turn. We designed an oxygen-generating PDT nanocomplex by encapsulating a manganese dioxide nanoparticle (MnO 2 NP) in an indocyanine green (ICG) modified hyaluronic acid nanoparticle (HANP) to overcome this limitation. Because of the excellent fluorescent and photoacoustic properties, the tumor accumulation of the ICG-HANP/MnO 2 (IHM) nanocomplex was monitored by fluorescent imaging and photoacoustic imaging after intravenous administration into the SCC7 tumor-bearing mouse model. Both high fluorescent and photoacoustic signals were detected and found peak at 6 h post-injection (tumor-muscle ratio: 4.03 ± 0.36 for fluorescent imaging and 2.93 ± 0.13 for photoacoustic imaging). In addition, due to the high reactivity of MnO 2 NP to H 2 O 2 , an unfavorable tumor cell metabolic, the oxygen content in the tumor is elevated 2.25 ± 0.07 times compared to that without IHM treatment as ultrasound imaging confirmed. After laser irradiation, significant tumor growth inhibition was observed in the IHM-treated group compared to the ICG-HANP-treated group, attributed to the beneficial oxygen-generating property of IHM for PDT. It is expected that the design of IHM will provide an alternative way of improving clinical PDT efficacy and will be widely applied in cancer theranostics. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Effects of a music therapy group intervention on enhancing social skills in children with autism.

    Science.gov (United States)

    LaGasse, A Blythe

    2014-01-01

    Research indicates that music therapy can improve social behaviors and joint attention in children with Autism Spectrum Disorder (ASD); however, more research on the use of music therapy interventions for social skills is needed to determine the impact of group music therapy. To examine the effects of a music therapy group intervention on eye gaze, joint attention, and communication in children with ASD. Seventeen children, ages 6 to 9, with a diagnosis of ASD were randomly assigned to the music therapy group (MTG) or the no-music social skills group (SSG). Children participated in ten 50-minute group sessions over a period of 5 weeks. All group sessions were designed to target social skills. The Social Responsiveness Scale (SRS), the Autism Treatment Evaluation Checklist (ATEC), and video analysis of sessions were used to evaluate changes in social behavior. There were significant between-group differences for joint attention with peers and eye gaze towards persons, with participants in the MTG demonstrating greater gains. There were no significant between-group differences for initiation of communication, response to communication, or social withdraw/behaviors. There was a significant interaction between time and group for SRS scores, with improvements for the MTG but not the SSG. Scores on the ATEC did not differ over time between the MTG and SSG. The results of this study support further research on the use of music therapy group interventions for social skills in children with ASD. Statistical results demonstrate initial support for the use of music therapy social groups to develop joint attention. © the American Music Therapy Association 2014. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  12. Enhancing recovery rates: lessons from year one of the English 'Improving access to psychological therapies' programme

    OpenAIRE

    Clark, David M.; Alex Gyani; Richard Layard; Roz Shafran

    2013-01-01

    Background: The English Improving Access to Psychological Therapies (IAPT) initiative aims to make evidence-based psychological therapies for depression and anxiety disorder more widely available in the National Health Service (NHS). 32 IAPT services based on a stepped care model were established in the first year of the programme. We report on the reliable recovery rates achieved by patients treated in the services and identify predictors of recovery at patient level, service level, and as a...

  13. Treatment response evaluation with three-dimensional contrast-enhanced ultrasound for liver cancer after local therapies

    Energy Technology Data Exchange (ETDEWEB)

    Xu Huixiong, E-mail: xuhuixiong@hotmail.co [Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, First Affiliated Hospital, Sun Yat-Sen University, 58th Zhongshan Road 2, Guangzhou 510080 (China); Lu Mingde, E-mail: lumd@21cn.co [Department of Hepatobiliary Surgery, First Affiliated Hospital, Sun Yat-Sen University, 58th Zhongshan Road 2, Guangzhou 510080 (China); Xie Xiaohua; Xie Xiaoyan [Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, First Affiliated Hospital, Sun Yat-Sen University, 58th Zhongshan Road 2, Guangzhou 510080 (China); Kuang Ming [Department of Hepatobiliary Surgery, First Affiliated Hospital, Sun Yat-Sen University, 58th Zhongshan Road 2, Guangzhou 510080 (China); Xu Zuofeng; Liu Guangjian; Wang Zhu; Chen Lida; Lin Manxia [Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, First Affiliated Hospital, Sun Yat-Sen University, 58th Zhongshan Road 2, Guangzhou 510080 (China)

    2010-10-15

    Objective: To investigate the potential usefulness of three-dimensional contrast-enhanced ultrasound (3D-CEUS) in evaluating the treatment response for liver cancer after local therapies. Methods: A total of 107 lesions in 95 consecutive patients with liver cancer underwent local therapies and thereafter received low acoustic power 3D-CEUS examination. The LOGIQ 9 ultrasound scanner and a volume transducer were used and the ultrasound contrast agent was SonoVue. The image quality of 3D-CEUS images was evaluated and the influence of 3D-CEUS to clinical outcome was investigated. Results: The image quality of 3D-CEUS was defined as high in 102 (102/107, 95.3%) lesions and common in 5 (5/107, 4.7%) lesions. 3D-CEUS did not change the diagnosis in any patient compared with 2D-CEUS. However, 3D-CEUS changed the management in 3 (2.8%) of 107 lesions, increased confidence but made no change in diagnosis in 85 (79.5%) lesions, added some information but did not change management or diagnosis in 15 (14.0%), and made no change in 4 (3.7%), respectively, in comparison with 2D-CEUS. Conclusion: 3D-CEUS enhances the diagnostic confidence in the majority of the patients and even changes the management in some patients. 3D-CEUS has potential usefulness in evaluating treatment response for liver cancer after local therapies.

  14. Use of Individual Feedback during Human Gross Anatomy Course for Enhancing Professional Behaviors in Doctor of Physical Therapy Students

    Science.gov (United States)

    Youdas, James W.; Krause, David A.; Hellyer, Nathan J.; Rindflesch, Aaron B.; Hollman, John H.

    2013-01-01

    Medical professionals and public consumers expect that new physical therapy graduates possess cognitive, technical, and behavioral skills required to provide safe and high-quality care to patients. The purpose of this study was to determine if a repertoire of ten professional behaviors assessed at the beginning of doctorate of physical therapy…

  15. Dexamethasone enhances programmed cell death 1 (PD-1) expression during T cell activation: an insight into the optimum application of glucocorticoids in anti-cancer therapy.

    Science.gov (United States)

    Xing, Kailin; Gu, Bingxin; Zhang, Ping; Wu, Xianghua

    2015-06-26

    Programmed cell death 1 (PD-1) is a key cell-surface receptor of CD28 superfamily that triggers inhibitory pathways to attenuate T-cell responses and promote T-cell tolerance. As a crucial role in tumor immunity, PD-1 has been a focus of studies in anti-cancer therapy. It has been approved that tumors could exploit PD-1-dependent immune suppression for immune evasion. Considering the wide use of glucocorticoids (GCs) in anti-cancer therapy and their immunosuppressive effects, we explored whether GCs could influence the expression of PD-1. In our study, we used dexamethasone (DEX) as a model glucocorticoid and demonstrated that DEX could enhance PD-1 expression in a dose-dependent manner. The effects were completely inhibited by the glucocorticoid receptor (GR) antagonist mifepristone (RU486), indicating that the effect of DEX on PD-1 is mediated through GR. We further found the sensitivity to DEX-induced upregulation of PD-1 expression had a significant difference between different T cell subsets, with memory T cells more susceptible to this effect. We also showed that DEX could suppress T cell functions via inhibition of cytokines production such as IL-2, IFN-γ, TNF-α and induction of apoptosis of T cells. Our findings suggest a novel way by which DEX suppress the function of activated T lymphocytes by enhancing expression of PD-1 and provide an insight into the optimum clinical application of GCs.

  16. 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. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Gold nanoparticle nucleated cavitation for enhanced high intensity focused ultrasound therapy

    Science.gov (United States)

    McLaughlan, J. R.; Cowell, D. M. J.; Freear, S.

    2018-01-01

    High intensity focused ultrasound (HIFU) or focused ultrasound surgery is a non-invasive technique for the treatment of cancerous tissue, which is limited by difficulties in getting real-time feedback on treatment progress and long treatment durations. The formation and activity of acoustic cavitation, specifically inertial cavitation, during HIFU exposures has been demonstrated to enhance heating rates. However, without the introduction of external nuclei its formation an activity can be unpredictable, and potentially counter-productive. In this study, a combination of pulse laser illumination (839 nm), HIFU exposures (3.3 MHz) and plasmonic gold nanorods (AuNR) was demonstrated as a new approach for the guidance and enhancement of HIFU treatments. For imaging, short duration HIFU pulses (10 μs) demonstrated broadband acoustic emissions from AuNR nucleated cavitation with a signal-to-noise ranging from 5–35 dB for peak negative pressures between 1.19–3.19  ±  0.01 MPa. In the absence of either AuNR or laser illumination these emissions were either not present or lower in magnitude (e.g. 5 dB for 3.19 MPa). Continuous wave (CW) HIFU exposures for 15 s, were then used to generate thermal lesions for peak negative pressures from 0.2–2.71  ±  0.01 MPa at a fluence of 3.4 mJ cm-2 . Inertial cavitation dose (ICD) was monitored during all CW exposures, where exposures combined with both laser illumination and AuNRs resulted in the highest level of detectable emissions. This parameter was integrated over the entire exposure to give a metric to compare with measured thermal lesion area, where it was found that a minimum total ICD of 1.5 × 103 a.u. was correlated with the formation of thermal lesions in gel phantoms. Furthermore, lesion area (mm2) was increased for equivalent exposures without either AuNRs or laser illumination. Once combined with cancer targeting AuNRs this approach could allow for the future theranostic use of HIFU

  18. Exposure therapy leads to enhanced late frontal positivity in 8- to 13-year-old spider phobic girls

    Science.gov (United States)

    Leutgeb, Verena; Schäfer, Axel; Köchel, Angelika; Schienle, Anne

    2012-01-01

    Neurobiological studies have demonstrated that psychotherapy is able to alter brain function in adults, however little exists on this topic with respect to children. This waiting-list controlled investigation focused on therapy-related changes of the P300 and the late positive potential (LPP) in 8- to 13-year-old spider phobic girls. Thirty-two patients were presented with phobia-relevant, generally disgust-inducing, fear-inducing, and affectively neutral pictures while an electroencephalogram was recorded. Participants received one session of up to 4 h of cognitive-behavioral exposure therapy. Treated children showed enhanced amplitudes of the LPP at frontal sites in response to spider pictures. This result is interpreted to reflect an improvement in controlled attentional engagement and is in line with already existing data for adult females. Moreover, the girls showed a therapy-specific reduction in overall disgust proneness, as well as in experienced arousal and disgust when viewing disgust pictures. Thus, exposure therapy seems to have broad effects in children. PMID:22388043

  19. Enhancing Exposure Therapy for Anxiety Disorders, Obsessive Compulsive Disorder, and Posttraumatic Stress Disorder

    Science.gov (United States)

    McGuire, Joseph F.; Lewin, Adam B.; Storch, Eric A.

    2014-01-01

    Translating findings from basic science, several compounds have been identified that may enhance therapeutic outcomes and/or expedite treatment gains when administered alongside exposure-based treatments. Four of these compounds (referred to as cognitive enhancers) have been evaluated in the context of randomized controlled trials for anxiety disorders (e.g., specific phobias, panic disorder, social anxiety disorder), obsessive compulsive disorder (OCD), and posttraumatic stress disorder (PTSD). These cognitive enhancers include D-cycloserine, yohimbine hydrochloride, glucocorticoids and cortisol, and brain derived neurotrophic factor. There is consistent evidence that cognitive enhancers can enhance therapeutic outcomes and/or expedite treatment gains across anxiety disorders, OCD, and PTSD. Emerging evidence has highlighted the importance of within-session fear habituation and between-session fear learning, which can either enhance fear extinction or reconsolidate of fear responses. Although findings from these trials are promising, there are several considerations that warrant further evaluation prior to wide-spread use of cognitive enhancers in exposure-based treatments. Consistent trial design and large sample sizes are important in future studies of cognitive enhancers. PMID:24972729

  20. Radiation dose enhancement in skin therapy with nanoparticle addition: A Monte Carlo study on kilovoltage photon and megavoltage electron beams.

    Science.gov (United States)

    Zheng, Xiao J; Chow, James C L

    2017-02-28

    To investigated the dose enhancement due to the incorporation of nanoparticles in skin therapy using the kilovoltage (kV) photon and megavoltage (MV) electron beams. Monte Carlo simulations were used to predict the dose enhancement when different types and concentrations of nanoparticles were added to skin target layers of varying thickness. Clinical kV photon beams (105 and 220 kVp) and MV electron beams (4 and 6 MeV), produced by a Gulmay D3225 orthovoltage unit and a Varian 21 EX linear accelerator, were simulated using the EGSnrc Monte Carlo code. Doses at skin target layers with thicknesses ranging from 0.5 to 5 mm for the photon beams and 0.5 to 10 mm for the electron beams were determined. The skin target layer was added with the Au, Pt, I, Ag and Fe 2 O 3 nanoparticles with concentrations ranging from 3 to 40 mg/mL. The dose enhancement ratio (DER), defined as the dose at the target layer with nanoparticle addition divided by the dose at the layer without nanoparticle addition, was calculated for each nanoparticle type, nanoparticle concentration and target layer thickness. It was found that among all nanoparticles, Au had the highest DER (5.2-6.3) when irradiated with kV photon beams. Dependence of the DER on the target layer thickness was not significant for the 220 kVp photon beam but it was for 105 kVp beam for Au nanoparticle concentrations higher than 18 mg/mL. For other nanoparticles, the DER was dependent on the atomic number of the nanoparticle and energy spectrum of the photon beams. All nanoparticles showed an increase of DER with nanoparticle concentration during the photon beam irradiations regardless of thickness. For electron beams, the Au nanoparticles were found to have the highest DER (1.01-1.08) when the beam energy was equal to 4 MeV, but this was drastically lower than the DER values found using photon beams. The DER was also found affected by the depth of maximum dose of the electron beam and target thickness. For other nanoparticles

  1. Enhanced normalisation of CD4/CD8 ratio with early antiretroviral therapy in primary HIV infection

    Directory of Open Access Journals (Sweden)

    John Thornhill

    2014-11-01

    Full Text Available Introduction: Despite normalization of total CD4 counts, ongoing immune dysfunction is noted amongst those on antiretroviral therapy (ART. Low CD4/CD8 ratio is associated with a high risk of AIDS and non-AIDS events and may act as a marker of immune senescence [1]. This ratio is improved by ART although normalization is uncommon (~7% [2]. The probability of normalization of CD4 count is improved with immediate ART initiation in primary HIV infection (PHI [3]. We examined whether CD4/CD8 ratio similarly normalized in immediate vs. deferred ART at PHI. Material and Methods: Using data from the SPARTAC trial and the UK Register of HIV Seroconverters, we examined the effect of ART with time (continuous from HIV seroconversion (SC on CD4/CD8 ratio (≥1 adjusted for sex, risk group, ethnicity, enrolment from an African site and both CD4 count and age at ART initiation. We also examined that effect by dichotomizing HIV duration at ART initiation (ART started within six months of SC: early ART; ART initiated>six months after SC: deferred. We also considered time to CD4 count normalization (≥900 cells/mm3. Results: In total, 353 initiated ART with median (IQR 97.9 (60.5, 384.5 days from estimated seroconversion; 253/353 early ART, 100 deferred ART. At one year after starting ART, 114/253 (45% early ART had normalized CD4/8 ratio, compared with 11/99 (11% in the deferred group, whilst 83/253 (33% of early ART had normalized CD4 counts, compared with 3/99 (3% in the deferred group. Individuals initiating within six months of PHI were significantly more likely to reach normal ratio than those initiating later (HR, 95% CI 2.96, 1.75 – 5.01, p<0.001. The longer after SC ART was initiated, the reduced likelihood of achieving normalization of CD4/CD8 ratio (HR 0.98, 95% CI 0.96 – 0.99 for each 30-day increase. CD4 count at ART initiation was also associated with normalization, as expected (HR 1.002, 95% CI 1.001 – 1.002, p<0.001. There was an

  2. Combined regimen of photodynamic therapy mediated by Gallium phthalocyanine chloride and Metformin enhances anti-melanoma efficacy.

    Science.gov (United States)

    Tudor, Diana; Nenu, Iuliana; Filip, Gabriela Adriana; Olteanu, Diana; Cenariu, Mihai; Tabaran, Flaviu; Ion, Rodica Mariana; Gligor, Lucian; Baldea, Ioana

    2017-01-01

    Melanoma therapy is challenging, especially in advanced cases, due to multiple developed tumor defense mechanisms. Photodynamic therapy (PDT) might represent an adjuvant treatment, because of its bimodal action: tumor destruction and immune system awakening. In this study, a combination of PDT mediated by a metal substituted phthalocyanine-Gallium phthalocyanine chloride (GaPc) and Metformin was used against melanoma. The study aimed to: (1) find the anti-melanoma efficacy of GaPc-PDT, (2) assess possible beneficial effects of Metformin addition to PDT, (3) uncover some of the mechanisms underlining cell killing and anti-angiogenic effects. Two human lightly pigmented melanoma cell lines: WM35 and M1/15 subjected to previous Metformin exposure were treated by GaPc-PDT. Cell viability, death mechanism, cytoskeleton alterations, oxidative damage, were assessed by means of colorimetry, flowcytometry, confocal microscopy, spectrophotometry, ELISA, Western Blotting. GaPc proved an efficient photosensitizer. Metformin addition enhanced cell killing by mechanisms dependent on the cell line, namely apoptosis in the metastatic M1/15 and necrosis in the radial growth phase, WM35. Cell death mechanism relied on the inhibition of nuclear transcription factor (NF)-κB activation and tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) sensitization, leading to TRAIL and TNF-α induced apoptosis. Metformin diminished the anti-angiogenic effect of PDT. Metformin addition to GaPc-PDT increased tumor cell killing through enhanced oxidative damage and induction of proapoptotic mechanisms, but altered PDT anti-angiogenic effects. Combination of Metformin and PDT might represent a solution to enhance the efficacy, leading to a potential adjuvant role of PDT in melanoma therapy.

  3. Combined regimen of photodynamic therapy mediated by Gallium phthalocyanine chloride and Metformin enhances anti-melanoma efficacy.

    Directory of Open Access Journals (Sweden)

    Diana Tudor

    Full Text Available Melanoma therapy is challenging, especially in advanced cases, due to multiple developed tumor defense mechanisms. Photodynamic therapy (PDT might represent an adjuvant treatment, because of its bimodal action: tumor destruction and immune system awakening. In this study, a combination of PDT mediated by a metal substituted phthalocyanine-Gallium phthalocyanine chloride (GaPc and Metformin was used against melanoma. The study aimed to: (1 find the anti-melanoma efficacy of GaPc-PDT, (2 assess possible beneficial effects of Metformin addition to PDT, (3 uncover some of the mechanisms underlining cell killing and anti-angiogenic effects.Two human lightly pigmented melanoma cell lines: WM35 and M1/15 subjected to previous Metformin exposure were treated by GaPc-PDT. Cell viability, death mechanism, cytoskeleton alterations, oxidative damage, were assessed by means of colorimetry, flowcytometry, confocal microscopy, spectrophotometry, ELISA, Western Blotting.GaPc proved an efficient photosensitizer. Metformin addition enhanced cell killing by mechanisms dependent on the cell line, namely apoptosis in the metastatic M1/15 and necrosis in the radial growth phase, WM35. Cell death mechanism relied on the inhibition of nuclear transcription factor (NF-κB activation and tumor necrosis factor (TNF-related apoptosis-inducing ligand (TRAIL sensitization, leading to TRAIL and TNF-α induced apoptosis. Metformin diminished the anti-angiogenic effect of PDT.Metformin addition to GaPc-PDT increased tumor cell killing through enhanced oxidative damage and induction of proapoptotic mechanisms, but altered PDT anti-angiogenic effects.Combination of Metformin and PDT might represent a solution to enhance the efficacy, leading to a potential adjuvant role of PDT in melanoma therapy.

  4. Vitamin D as a potential enhancer of aminolevulinate-based photodynamic therapy for nonmelanoma skin cancer

    Science.gov (United States)

    Maytin, Edward V.; Anand, Sanjay; Atanaskova, Natasha; Wilson, Clara

    2010-02-01

    Vitamin D3 (Vit D3) is a hormone essential for normal bone and cardiovascular health, and may participate in preventing nonmelanoma skin cancers (NMSC). Calcitriol (1,25 dihydroxyD3) is the active form of the hormone. We showed previously that calcitriol is a potent inducer of protoporphyrin IX (PpIX) in skin keratinocytes grown in organotypic cultures. Here, we investigated the ability of Vit D3 to enhance PpIX levels within skin tumors in vivo. Squamous tumors, generated by chemical carcinogenesis in mice, were pretreated for 3 days with topical calcitriol. Then 5-aminolevulinic acid (5-ALA) was applied topically, and PpIX levels were measured by noninvasive fluorimetry and in biopsied tissue. Calcitriol pretreatment resulted in a 3 to 4-fold elevation of PpIX in tumors, relative to no pretreatmen, providing significantly more photosensitizer available for tumor destruction. For deep tumors, topical calcitriol may not penetrate sufficiently. Therefore we explored whether systemic Vit D3, given short-term (3 days), might elevate PpIX within NMSC in a deep tumor model (subcutaneously-implanted A431 human squamous carcinoma cells). Defined amounts of calcitriol were injected into the mice for 3 d, followed by systemic 5-ALA, tissue biopsy, and confocal microscopic measurement of PpIX in frozen tissues. PpIX was clearly elevated after systemically delivered calcitriol. More work is needed, but if the amount of calcitriol required to elevate PpIX levels proves to be small, then the approach may ultimately prove attractive. Since most Americans are currently Vitamin D deficient, a small increase in calcitriol might be possible without risk of hypercalcemia.

  5. Enhanced cognitive behavioral therapy for eating disorders adapted for a group setting.

    Science.gov (United States)

    Wade, Stephanie; Byrne, Sue; Allen, Karina

    2017-08-01

    This randomized control trial is an evaluation of the effectiveness of enhanced cognitive behavioral treatment (CBT-E) for eating disorders adapted for a group setting. The study aimed to examine the effects of group CBT-E on eating disorder psychopathology and additional maintaining pathology. A transdiagnostic sample of individuals with eating disorders with a BMI ≥ 18 kg/m2 (N = 40) were randomized to an immediate-start or delayed-start condition so as to compare therapeutic effects of group CBT-E with a waitlist control. Global Eating Disorder Examination Questionnaire (EDE-Q) scores, BMI, and measures of Clinical Perfectionism, Self-Esteem, Interpersonal Difficulties, and Mood Intolerance were measured across the 8-week control period, throughout the group treatment and at 3-months post-treatment. Over 70% of those who entered the trial completed treatment. The first eight weeks of group CBT-E were more effective at reducing Global EDE-Q scores than no treatment (waitlist control). By post-treatment, good outcome (a Global EDE-Q within 1 SD of Australian community norms plus BMI ≥ 18.5) was achieved by 67.9% of treatment completers and 66.7% of the total sample. Symptom abstinence within the previous month was reported by 14.3% of treatment completers and 10.3% of the total sample. Significant reductions in Clinical Perfectionism, Self-Esteem, Interpersonal Difficulties, and Mood Intolerance were also observed. This study demonstrated that a group version of CBT-E can be effective at reducing eating disorder psychopathology in a transdiagnostic sample of individuals with eating disorders. Group CBT-E could provide a means of increasing availability of evidence-based treatment for eating disorders. © 2017 Wiley Periodicals, Inc.

  6. Error-enhancing robot therapy to induce motor control improvement in childhood onset primary dystonia

    Directory of Open Access Journals (Sweden)

    Casellato Claudia

    2012-07-01

    Full Text Available Abstract Background Robot-generated deviating forces during multijoint reaching movements have been applied to investigate motor control and to tune neuromotor adaptation. Can the application of force to limbs improve motor learning? In this framework, the response to altered dynamic environments of children affected by primary dystonia has never been studied. Methods As preliminary pilot study, eleven children with primary dystonia and eleven age-matched healthy control subjects were asked to perform upper limb movements, triangle-reaching (three directions and circle-writing, using a haptic robot interacting with ad-hoc developed task-specific visual interfaces. Three dynamic conditions were provided, null additive external force (A, constant disturbing force (B and deactivation of the additive external force again (C. The path length for each trial was computed, from the recorded position data and interaction events. Results The results show that the disturbing force affects significantly the movement outcomes in healthy but not in dystonic subjects, already compromised in the reference condition: the external alteration uncalibrates the healthy sensorimotor system, while the dystonic one is already strongly uncalibrated. The lack of systematic compensation for perturbation effects during B condition is reflected into the absence of after-effects in C condition, which would be the evidence that CNS generates a prediction of the perturbing forces using an internal model of the environment. The most promising finding is that in dystonic population the altered dynamic exposure seems to induce a subsequent improvement, i.e. a beneficial after-effect in terms of optimal path control, compared with the correspondent reference movement outcome. Conclusions The short-time error-enhancing training in dystonia could represent an effective approach for motor performance improvement, since the exposure to controlled dynamic alterations induces a refining

  7. Efforts to enhance the effect of radiation therapy. Mechanism of action and clinical application of radiation sensitizers

    Energy Technology Data Exchange (ETDEWEB)

    Tamamoto, Tetsuro; Takahashi, Akihisa; Ohnishi, Takeo [Nara Medical Univ., Kashihara (Japan)

    2000-06-01

    Efforts have been made to enhance the effect of radiation therapy by means of reducing the radiation sensitivity in normal tissues and of increasing the sensitivity in tumors. Since the target of radiation is DNA, direct sensitizing can be expected for DNA-injuring chemicals like bleomycin, pepleomycin, alkylating agents, mitomycin and platinum complexes. Sensitization can be also possible by inhibiting the nucleic acid synthesis: inhibitors like ribonucleotide reductase, pyrimidine and purine analogs and folate analogs. Angiogenesis inhibitors and oxygenating agents, by altering the circumstances in the tumor tissues, can be a sensitizer. Cytocidal effect of radiation is enhanced by inhibiting the DNA repair: inhibitors of poly(ADP-ribose) polymerase and topoisomerases. Biological response modifiers are used to reduce the adverse effects. Inhibitors of protein kinase C and A are also the sensitizer inhibiting the intracellular signal transduction. Development of a better sensitizer is expected. (K.H.)

  8. Efficacy of Play Therapy on Self-Healing and Enhancing Life-skills of ...

    African Journals Online (AJOL)

    The objectives of the study are to know whether play therapy can facilitate the selfhealing process, to improve the academic performance, increase the attentive level, and to ensure self-confidence and esteem of children under difficult circumstances. Data for this study were the case works of the researcher (for about two ...

  9. The Evolution of "Enhanced" Cognitive Behavior Therapy for Eating Disorders: Learning from Treatment Nonresponse

    Science.gov (United States)

    Cooper, Zafra; Fairburn, Christopher G.

    2011-01-01

    In recent years there has been widespread acceptance that cognitive behavior therapy (CBT) is the treatment of choice for bulimia nervosa. The cognitive behavioral treatment of bulimia nervosa (CBT-BN) was first described in 1981. Over the past decades the theory and treatment have evolved in response to a variety of challenges. The treatment has…

  10. High dose simvastatin exhibits enhanced lipid lowering effects relative to simvastatin/ezetimibe combination therapy

    Science.gov (United States)

    Technical Abstract: Background: Statins are the frontline in cholesterol reduction therapies; however use in combination with agents that possess complimentary mechanisms of action may achieve further reduce in LDL-C. Methods and Results: Thirty-nine patients were treated with either 80mg simvasta...

  11. Epidermal growth factor receptor targeting enhances adenoviral vector based suicide gene therapy of osteosarcoma

    NARCIS (Netherlands)

    Witlox, M.A.; van Beusechem, V.W.; Grill, J.; Haisma, H.J.; Schaap, G.; Bras, J.; Van Diest, P.; De Gast, A.; Curiel, D.T.; Pinedo, H.M.; Gerritsen, W.R.; Wuisman, P.I.

    2002-01-01

    Background Despite improvements in the treatment of osteosarcoma (OS) there are still too many patients who cannot benefit from current treatment modalities. Therefore, new therapeutic approaches are warranted. Here we explore the efficacy of targeted adenoviral based suicide gene therapy. Methods

  12. Detection of Treatment Success after Photodynamic Therapy Using Dynamic Contrast-Enhanced Magnetic Resonance Imaging

    NARCIS (Netherlands)

    Schreurs, Tom J. L.; Jacobs, Igor; Nicolay, Klaas; Prompers, Jeanine J.; Strijkers, Gustav J.

    2017-01-01

    Early evaluation of response to therapy is crucial for selecting the optimal therapeutic follow-up strategy for cancer patients. PDT is a photochemistry-based treatment modality that induces tumor tissue damage by cytotoxic oxygen radicals, generated by a pre-injected photosensitive drug upon light

  13. Detection of treatment success after photodynamic therapy using Dynamic Contrast-Enhanced Magnetic Resonance Imaging

    NARCIS (Netherlands)

    Schreurs, Tom J.L.; Jacobs, Igor; Nicolay, Klaas; Prompers, Jeanine J.; Strijkers, Gustav J.

    2017-01-01

    Early evaluation of response to therapy is crucial for selecting the optimal therapeutic follow-up strategy for cancer patients. PDT is a photochemistry-based treatment modality that induces tumor tissue damage by cytotoxic oxygen radicals, generated by a pre-injected photosensitive drug upon light

  14. Enhancement of liver regeneration by the association of Hyptis pectinata with laser therapy.

    Science.gov (United States)

    Melo, Gustavo B; Silva, Renata L; Melo, Valdinaldo A; Lima, Sônia O; Antoniolli, Angelo R; Castro-E-silva, Tiago; Marcassa, Luis G; Bagnato, Vanderlei S; Zucoloto, Sérgio; Ramalho, Leandra N Z; Ramalho, Fernando S; Castro-E-silva, Orlando

    2005-05-01

    Since new molecules that normally would accelerate regeneration can also be potentialized by light, the use of new substances combined with laser therapy seems to be a natural type of experiment. Therefore, the purpose of this study was to assess the effects of Hyptis pectinata leaves on liver regeneration after partial hepatectomy (PH) associated with laser therapy. Twenty-four rats were divided into four groups--PH(control), PHL (laser therapy), PH200 (200 mg/kg of Hyptispectinata), and PHL200 (200 mg/kg of the plant and laser)--which were submitted to 67% hepatectomy. Laser treatment consisted of focusing the light on the remaining liver after hepatectomy. The data analyzed were serum levels of aminotransferases, liver regeneration, and mitochondrial function. Group PH200 showed a statistically significant decrease in AST levels, and PHL200 disclosed an augmentation in ALT levels. The liver regeneration index was significantly increased in group PHL200. Concerning liver mitochondrial respiratory assay, groups PH200 and PHL200 showed lower state 3 levels than groups PH and PHL. Group PHL showed an increase in state 4 levels and a reduction in membrane potential and RCR. The present study shows that the association of the aqueous extract of Hyptis pectinata leaves at 200 mg/kg with intraoperative laser therapy can stimulate liver regeneration and cause a reduction in liver mitochondrial respiratory function without altering its phosphorylative activity.

  15. Effect of enhanced iron chelation therapy on glucose metabolism in patients with beta-thalassaemia major.

    Science.gov (United States)

    Farmaki, Kalistheni; Angelopoulos, Nicholas; Anagnostopoulos, George; Gotsis, Efstathios; Rombopoulos, Grigorios; Tolis, George

    2006-08-01

    Recently introduced chelation regimens that combine deferoxamine (DFO) and deferiprone have been shown to have greater efficacy in promoting iron excretion than either chelator alone and have been associated with rapid reduction of the iron load in the heart and liver, and with reversal of cardiac dysfunction. It is unclear whether this combined therapy could be associated with a reduction in iron load or decline in the severity of iron-induced endocrinopathies. Starting in January 2001, 42 patients with beta-thalassaemia major, previously maintained on subcutaneous DFO only, were switched to combined treatment with DFO and deferiprone. The primary endpoint was to investigate the effects of this therapy on the glucose metabolism characteristics of this population. Combination therapy markedly decreased ferritin levels (638 +/- 1345 vs. 2991 +/- 2093 microg/l, P < 0.001). Glucose responses were improved at all times during an oral glucose tolerance test, particularly in patients in early stages of glucose intolerance. Glucose quantitative secretion also decreased significantly with combined therapy, while no significant change occurred in insulin levels in any group. Insulin secretion, according to the homeostasis assessment model, markedly increased in all groups, while overall reduction in insulin sensitivity did not reach statistical significance. This study showed that the combination of DFO and deferiprone was associated with an improvement in liver iron deposition and glucose intolerance.

  16. A randomized controlled comparison of integrative cognitive-affective therapy (ICAT) and enhanced cognitive-behavioral therapy (CBT-E) for bulimia nervosa.

    Science.gov (United States)

    Wonderlich, S A; Peterson, C B; Crosby, R D; Smith, T L; Klein, M H; Mitchell, J E; Crow, S J

    2014-02-01

    The purpose of this investigation was to compare a new psychotherapy for bulimia nervosa (BN), integrative cognitive-affective therapy (ICAT), with an established treatment, 'enhanced' cognitive-behavioral therapy (CBT-E). Eighty adults with symptoms of BN were randomized to ICAT or CBT-E for 21 sessions over 19 weeks. Bulimic symptoms, measured by the Eating Disorder Examination (EDE), were assessed at baseline, at the end of treatment (EOT) and at the 4-month follow-up. Treatment outcome, measured by binge eating frequency, purging frequency, global eating disorder severity, emotion regulation, self-oriented cognition, depression, anxiety and self-esteem, was determined using generalized estimating equations (GEEs), logistic regression and a general linear model (intent-to-treat). Both treatments were associated with significant improvement in bulimic symptoms and in all measures of outcome, and no statistically significant differences were observed between the two conditions at EOT or follow-up. Intent-to-treat abstinence rates for ICAT (37.5% at EOT, 32.5% at follow-up) and CBT-E (22.5% at both EOT and follow-up) were not significantly different. ICAT was associated with significant improvements in bulimic and associated symptoms that did not differ from those obtained with CBT-E. This initial randomized controlled trial of a new individual psychotherapy for BN suggests that targeting emotion and self-oriented cognition in the context of nutritional rehabilitation may be efficacious and worthy of further study.

  17. The providing resources to enhance African American patients’ readiness to make decisions about kidney disease (PREPARED study: protocol of a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Ephraim Patti L

    2012-10-01

    Full Text Available Abstract Background Living related kidney transplantation (LRT is underutilized, particularly among African Americans. The effectiveness of informational and financial interventions to enhance informed decision-making among African Americans with end stage renal disease (ESRD and improve rates of LRT is unknown. Methods/design We report the protocol of the Providing Resources to Enhance African American Patients’ Readiness to Make Decisions about Kidney Disease (PREPARED Study, a two-phase study utilizing qualitative and quantitative research methods to design and test the effectiveness of informational (focused on shared decision-making and financial interventions to overcome barriers to pursuit of LRT among African American patients and their families. Study Phase I involved the evidence-based development of informational materials as well as a financial intervention to enhance African American patients’ and families’ proficiency in shared decision-making regarding LRT. In Study Phase 2, we are currently conducting a randomized controlled trial in which patients with new-onset ESRD receive 1 usual dialysis care by their nephrologists, 2 the informational intervention (educational video and handbook, or 3 the informational intervention in addition to the option of participating in a live kidney donor financial assistance program. The primary outcome of the randomized controlled trial will include patients’ self-reported rates of consideration of LRT (including family discussions of LRT, patient-physician discussions of LRT, and identification of a LRT donor. Discussion Results from the PREPARED study will provide needed evidence on ways to enhance the decision to pursue LRT among African American patients with ESRD. Trial registration ClinicalTrials.gov NCT01439516

  18. Adaptive auto-regulation of androgen receptor provides a paradigm shifting rationale for bipolar androgen therapy (BAT) for castrate resistant human prostate cancer.

    Science.gov (United States)

    Isaacs, John T; D'Antonio, Jason M; Chen, Shuangling; Antony, Lizamma; Dalrymple, Susan P; Ndikuyeze, Georges H; Luo, Jun; Denmeade, Samuel R

    2012-10-01

    Cell culture/xenograft and gene arrays of clinical material document that development of castration resistant prostate cancer (CRPC) cells involves acquisition of adaptive auto-regulation resulting in >25-fold increase in Androgen Receptor (AR) protein expression in a low androgen environment. Such adaptive AR increase paradoxically is a liability in castrated hosts, however, when supraphysiologic androgen is acutely replaced. Cell synchronization/anti-androgen response is due to AR binding to replication complexes (RC) at origin of replication sites (ORS) in early G1 associated with licensing/restricting DNA for single round of duplication during S-phase. When CRPC cells are acutely exposed to supraphysiologic androgen, adaptively increased nuclear AR is over-stabilized, preventing sufficient degradation in mitosis, inhibiting DNA re-licensing, and thus death in the subsequent cell cycle. These mechanistic results and the fact that AR/RC binding occurs in metastatic CRPCs directly from patients provides a paradigm shifting rationale for bipolar androgen therapy (BAT) in patient progressing on chronic androgen ablation. BAT involves giving sequential cycles alternating between periods of acute supraphysiologic androgen followed by acute ablation to take advantage of vulnerability produced by adaptive auto-regulation and binding of AR to RC in CRPC cells. BAT therapy is effective in xenografts and based upon positive results has entered clinical testing. Copyright © 2012 Wiley Periodicals, Inc.

  19. Using multimedia information and communication technology (ICT) to provide added value to reminiscence therapy for people with dementia : Lessons learned from three field studies.

    Science.gov (United States)

    Bejan, Alexander; Gündogdu, Ramazan; Butz, Katherina; Müller, Nadine; Kunze, Christophe; König, Peter

    2018-01-01

    In the care of people with dementia (PwD), occupational therapies and activities aiming at maintaining the quality of life of PwD, such as reminiscence therapy (RT), are taking on a more and more important role. Information and communication technology (ICT) has the potential to improve and to facilitate RT by facilitating access to and selection of biographical information and related contents or by providing novel multimodal interaction forms to trigger memories; however, interactive multimedia technology is barely used in practice. This article presents three exploratory field studies that evaluated different aspects of RT technology use for PwD in care homes, including the utilization of online movie databases, interactive surface touch computers as well as natural user interfaces allowing gestures and haptic interaction. In these studies, the usage of prototype systems was observed in occupational sessions by 5, 12 and 16 PwD. The results indicate positive effects of technology use, e. g. in the form of verbally elicited reminiscence statements, expressed joy and playful interaction. Lessons learned for the design of technology-based RT interventions are presented and discussed.

  20. Comparing cognitive behavioural therapy for eating disorders integrated with behavioural weight loss therapy to cognitive behavioural therapy-enhanced alone in overweight or obese people with bulimia nervosa or binge eating disorder: study protocol for a randomised controlled trial.

    Science.gov (United States)

    Palavras, Marly Amorim; Hay, Phillipa; Touyz, Stephen; Sainsbury, Amanda; da Luz, Felipe; Swinbourne, Jessica; Estella, Nara Mendes; Claudino, Angélica

    2015-12-18

    Around 40 % of individuals with eating disorders of recurrent binge eating, namely bulimia nervosa and binge eating disorder, are obese. In contrast to binge eating disorder, currently there is no evidence base for weight management or weight loss psychological therapies in the treatment of bulimia nervosa despite their efficacy in binge eating disorder. Thus, a manualised therapy called HAPIFED (Healthy APproach to weIght management and Food in Eating Disorders) has been developed. HAPIFED integrates the leading evidence-based psychological therapies, cognitive behavioural therapy-enhanced (CBT-E) and behavioural weight loss treatment (BWLT) for binge eating disorder and obesity respectively. The aim of the present study is to detail the protocol for a randomised controlled trial (RCT) of HAPIFED versus CBT-E for people with bulimia nervosa and binge eating disorder who are overweight/obese. A single-blind superiority RCT is proposed. One hundred Brazilian participants aged ≥ 18 years, with a diagnosis of bulimia nervosa or binge eating disorder, BMI > 27 to < 40 kg/m(2), will be recruited from both community and clinics and individually randomised to a therapy arm. Five groups of ten participants will receive the experimental intervention (HAPIFED) and the other five groups of ten the control intervention (CBT-E). Both therapies are manualised, and in this RCT will comprise 1 individual session and 29 office-based group sessions over 6 months. Assessment points will be at baseline, end of therapy, and 6 and 12 months after end of therapy. The primary outcome of this intervention will be reduced weight. Secondary outcomes will be improved metabolic indicators of weight management, reduction in eating disorder symptoms including improved control over eating, improved adaptive function, physical and mental health-related quality of life, and reduced levels of depression and anxiety. This study will be the first to investigate a psychological therapy

  1. Early biomarkers from dynamic contrast-enhanced magnetic resonance imaging to predict the response to antiangiogenic therapy in high-grade gliomas

    Energy Technology Data Exchange (ETDEWEB)

    Piludu, Francesca; Vidiri, Antonello [Regina Elena National Cancer Institute, Radiology and Diagnostic Imaging Department, Rome (Italy); Marzi, Simona [Regina Elena National Cancer Institute, Medical Physics Laboratory, Rome (Italy); Pace, Andrea; Villani, Veronica [Regina Elena National Cancer Institute, Neurology Division, Rome (Italy); Fabi, Alessandra [Regina Elena National Cancer Institute, Oncology Department, Rome (Italy); Carapella, Carmine Maria [Regina Elena National Cancer Institute, Oncologic Surgery Department, Rome (Italy); Terrenato, Irene [Regina Elena National Cancer Institute, Biostatistics-Scientific Direction, Rome (Italy); Antenucci, Anna [Regina Elena National Cancer Institute, Clinical Pathology, Rome (Italy)

    2015-12-15

    The aim of this study is to investigate whether early changes in tumor volume and perfusion measurements derived from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) may predict response to antiangiogenic therapy in recurrent high-grade gliomas. Twenty-seven patients who received bevacizumab every 3 weeks were enrolled in the study. For each patient, three MRI scans were performed: at baseline, after the first dose, and after the fourth dose of bevacizumab. The entire tumor volume (V{sub tot}), as well as contrast-enhanced and noncontrast-enhanced tumor subvolumes (V{sub CE-T1} and V{sub NON-CE-T1}, respectively) were outlined using post-contrast T1-weighted images as a guide for the tumor location. Histogram analysis of normalized IAUGC (nIAUGC) and transfer constant K{sup trans} maps were performed. Each patient was classified as a responder patient if he/she had a partial response or a stable disease or as a nonresponder patient if he/she had progressive disease. Responding patients showed a larger reduction in V{sub NON-CE-T1} after a single dose, compared to nonresponding patients. Tumor subvolumes with increased values of nIAUGC and K{sup trans}, after a single dose, significantly differed between responders and nonresponders. The radiological response was found to be significantly associated to the clinical outcome. After a single dose, V{sub tot} was predictive of overall survival (OS), while V{sub CE-T1} showed a tendency of correlation with OS. Tumor subvolumes with increased nIAUGC and K{sup trans} showed the potential for improving the diagnostic accuracy of DCE. Early assessments of the entire tumor volume, including necrotic areas, may provide complementary information of tumor behavior in response to anti-VEGF therapies and is worth further investigation. (orig.)

  2. Optimal gadolinium dose level for magnetic resonance imaging (MRI) contrast enhancement of U87-derived tumors in athymic nude rats for the assessment of photodynamic therapy

    Science.gov (United States)

    Cross, Nathan; Varghai, Davood; Flask, Chris A.; Feyes, Denise K.; Oleinick, Nancy L.; Dean, David

    2009-02-01

    This study aims to determine the effect of varying gadopentetate dimeglumine (Gd-DTPA) dose on Dynamic Contrast Enhanced-Magnetic Resonance Imaging (DCE-MRI) tracking of brain tumor photodynamic therapy (PDT) outcome. Methods: We injected 2.5 x 105 U87 cells (derived from human malignant glioma) into the brains of six athymic nude rats. After 9, 12, and 13 days DCE-MRI images were acquired on a 9.4 T micro-MRI scanner before and after administration of 100, 150, or 200 μL of Gd-DTPA. Results: Tumor region normalized DCE-MRI scan enhancement at peak was: 1.217 over baseline (0.018 Standard Error [SE]) at the 100 μL dose, 1.339 (0.013 SE) at the 150 μL dose, and 1.287 (0.014 SE) at the 200 μL dose. DCE-MRI peak tumor enhancement at the 150 μL dose was significantly greater than both the 100 μL dose (p < 3.323E-08) and 200 μL dose (p < 0.0007396). Discussion: In this preliminary study, the 150 μL Gd-DTPA dose provided the greatest T1 weighted contrast enhancement, while minimizing negative T2* effects, in DCE-MRI scans of U87-derived tumors. Maximizing Gd-DTPA enhancement in DCE-MRI scans may assist development of a clinically robust (i.e., unambiguous) technique for PDT outcome assessment.

  3. Robust aptamer–polydopamine-functionalized M-PLGA–TPGS nanoparticles for targeted delivery of docetaxel and enhanced cervical cancer therapy

    Science.gov (United States)

    Xu, Guojun; Yu, Xinghua; Zhang, Jinxie; Sheng, Yingchao; Liu, Gan; Tao, Wei; Mei, Lin

    2016-01-01

    One limitation of current biodegradable polymeric nanoparticles (NPs) is the contradiction between functional modification and maintaining formerly excellent bioproperties with simple procedures. Here, we reported a robust aptamer–polydopamine-functionalized mannitol-functionalized poly(lactide-co-glycolide) (M-PLGA)–D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) nanoformulation (Apt-pD-NPs) for the delivery of docetaxel (DTX) with enhanced cervical cancer therapy effects. The novel DTX-loaded Apt-pD-NPs possess satisfactory advantages: 1) increased drug loading content and encapsulation efficiency induced by star-shaped copolymer M-PLGA–TPGS; 2) significant active targeting effect caused by conjugated AS1411 aptamers; and 3) excellent long-term compatibility by incorporation of TPGS. Therefore, with simple preparation procedures and excellent bioproperties, the new functionalized Apt-pD-NPs could maximally increase the local effective drug concentration on tumor sites, achieving enhanced treatment effectiveness and minimizing side effects. In a word, the robust DTX-loaded Apt-pD-NPs could be used as potential nanotherapeutics for cervical cancer treatment, and the aptamer–polydopamine modification strategy could be a promising method for active targeting of cancer therapy with simple procedures. PMID:27382282

  4. Robust aptamer-polydopamine-functionalized M-PLGA-TPGS nanoparticles for targeted delivery of docetaxel and enhanced cervical cancer therapy.

    Science.gov (United States)

    Xu, Guojun; Yu, Xinghua; Zhang, Jinxie; Sheng, Yingchao; Liu, Gan; Tao, Wei; Mei, Lin

    2016-01-01

    One limitation of current biodegradable polymeric nanoparticles (NPs) is the contradiction between functional modification and maintaining formerly excellent bioproperties with simple procedures. Here, we reported a robust aptamer-polydopamine-functionalized mannitol-functionalized poly(lactide-co-glycolide) (M-PLGA)-D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) nanoformulation (Apt-pD-NPs) for the delivery of docetaxel (DTX) with enhanced cervical cancer therapy effects. The novel DTX-loaded Apt-pD-NPs possess satisfactory advantages: 1) increased drug loading content and encapsulation efficiency induced by star-shaped copolymer M-PLGA-TPGS; 2) significant active targeting effect caused by conjugated AS1411 aptamers; and 3) excellent long-term compatibility by incorporation of TPGS. Therefore, with simple preparation procedures and excellent bioproperties, the new functionalized Apt-pD-NPs could maximally increase the local effective drug concentration on tumor sites, achieving enhanced treatment effectiveness and minimizing side effects. In a word, the robust DTX-loaded Apt-pD-NPs could be used as potential nanotherapeutics for cervical cancer treatment, and the aptamer-polydopamine modification strategy could be a promising method for active targeting of cancer therapy with simple procedures.

  5. Centers for Medicare and Medicaid Services Support for Medication Therapy Management (Enhanced Medication Therapy Management): Testing Strategies for Improving Medication Use Among Beneficiaries Enrolled in Medicare Part D.

    Science.gov (United States)

    Brandt, Nicole J; Cooke, Catherine E

    2017-05-01

    In 2006, Medicare beneficiaries began receiving prescription coverage benefits through Part D of the Medicare benefit. Medicare Part D plans must provide medication therapy (MTM) services. MTM services aim to improve medication use and are targeted toward eligible beneficiaries, determined by morbidity, prescription use, and anticipated cost of prescription use. Now, 10 years after the start of Medicare Part D, several changes have been made to the program's design. This article focuses on changes related to MTM and the impact that these changes have and will continue to have on Medicare beneficiaries and medication use. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Enhancing the Collection, Discussion and Use of Family Health History by Consumers, Nurses and Other Health Care Providers: Because Family Health History Matters.

    Science.gov (United States)

    Underwood, Sandra Millon; Kelber, Sheryl

    2015-09-01

    The family health history (FHH) has long been used by nurses and other health care providers in clinical practice to determine if an individual, their family members, or their future generations are at an increased risk of heritable disease development. Information gleaned from the FHH can be used to better integrate preventive strategies into the plan of care. This report presents a summary of an exploratory pilot study that focused on the collection and use of FHH among a targeted group of Midwestern men and women. Findings suggest a need for efforts to further enhance the public's awareness of the importance of FHH. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Heavy Charged Particle Radiobiology: Using Enhanced Biological Effectiveness and Improved Beam Focusing to Advance Cancer Therapy

    Science.gov (United States)

    Allen, Christopher; Borak, Thomas B.; Tsujii, Hirohiko; Nickoloff, Jac A.

    2011-01-01

    Ionizing radiation causes many types of DNA damage, including base damage and single- and double-strand breaks. Photons, including X-rays and γ-rays, are the most widely used type of ionizing radiation in radiobiology experiments, and in radiation cancer therapy. Charged particles, including protons and carbon ions, are seeing increased use as an alternative therapeutic modality. Although the facilities needed to produce high energy charged particle beams are more costly than photon facilities, particle therapy has shown improved cancer survival rates, reflecting more highly focused dose distributions and more severe DNA damage to tumor cells. Despite early successes of charged particle radiotherapy, there is room for further improvement, and much remains to be learned about normal and cancer cell responses to charged particle radiation. PMID:21376738

  8. Heavy charged particle radiobiology: using enhanced biological effectiveness and improved beam focusing to advance cancer therapy.

    Science.gov (United States)

    Allen, Christopher; Borak, Thomas B; Tsujii, Hirohiko; Nickoloff, Jac A

    2011-06-03

    Ionizing radiation causes many types of DNA damage, including base damage and single- and double-strand breaks. Photons, including X-rays and γ-rays, are the most widely used type of ionizing radiation in radiobiology experiments, and in radiation cancer therapy. Charged particles, including protons and carbon ions, are seeing increased use as an alternative therapeutic modality. Although the facilities needed to produce high energy charged particle beams are more costly than photon facilities, particle therapy has shown improved cancer survival rates, reflecting more highly focused dose distributions and more severe DNA damage to tumor cells. Despite early successes of charged particle radiotherapy, there is room for further improvement, and much remains to be learned about normal and cancer cell responses to charged particle radiation. 2011 Elsevier B.V. All rights reserved.

  9. Dietary calcium supplementation enhances efficacy but also toxicity of EGFR inhibitor therapy for colon cancer.

    Science.gov (United States)

    Rinella, Erica S; Bankaitis, Eric D; Threadgill, David W

    2012-02-01

    The inverse correlation between levels of dietary calcium and colorectal cancer (CRC) incidence has been extensively investigated. However, the impact of supplemental calcium on cancer therapy remains unknown. We used four models of CRC, Caco-2 and HCT116 human cancer cell lines and Apc (Min/+) and azoxymethane carcinogen-induced mouse models, to investigate the impact of a western-style diet low in calcium (0.05%) vs. a similar diet but supplemented with calcium (5%) on therapeutic targeting of the epidermal growth factor receptor (EGFR). We found that calcium supplementation combined with pharmacologic blockade of EGFR results in an additive effect on tumor growth inhibition in all models. Unexpectedly, the combined use of dietary calcium supplementation and EGFR inhibitors also resulted in elevated toxicity suggesting that careful consideration be given when combining dietary supplements with prescribed cancer therapies.

  10. BEMER Electromagnetic Field Therapy Reduces Cancer Cell Radioresistance by Enhanced ROS Formation and Induced DNA Damage

    OpenAIRE

    Storch, Katja; Dickreuter, Ellen; Artati, Anna; Adamski, Jerzy; Cordes, Nils

    2016-01-01

    Each year more than 450,000 Germans are expected to be diagnosed with cancer subsequently receiving standard multimodal therapies including surgery, chemotherapy and radiotherapy. On top, molecular-targeted agents are increasingly administered. Owing to intrinsic and acquired resistance to these therapeutic approaches, both the better molecular understanding of tumor biology and the consideration of alternative and complementary therapeutic support are warranted and open up broader and novel ...

  11. Nintedanib, a triple angiokinase inhibitor, enhances cytotoxic therapy response in pancreatic cancer

    OpenAIRE

    Awasthi, Niranjan; Hinz, Stefan; Brekken, Rolf A.; Schwarz, Margaret A; Schwarz, Roderich E.

    2014-01-01

    Angiogenesis remains a sensible target for pancreatic ductal adenocarcinoma (PDAC) therapy. VEGF, PDGF, FGF and their receptors are expressed at high levels and correlate with poor prognosis in human PDAC. Nintedanib is a triple angiokinase inhibitor that targets VEGFR1/2/3, FGFR1/2/3 and PDGFRα/β signaling. We investigated the antitumor activity of nintedanib alone or in combination with the cytotoxic agent gemcitabine in experimental PDAC. Nintedanib inhibited proliferation of cells from mu...

  12. PSES-a Novel Prostate Specific Chimeric Enhancer for Prostate Cancer Gene Therapy

    Science.gov (United States)

    2007-02-01

    most new cancer diagnoses, aside from skin cancer, at 234,460 men in the United States and will be the second most common cause of cancer deaths at...that prostate cancer will account for the most new cancer diagnoses, aside from skin cancer, at 234,460 men in the United States and will be the second...prostatectomy, cryoablation therapy, external beam radiation and brachytherapy ; however, 25% of these men will experience biochemical disease recurrence

  13. Determination of breast cancer response to bevacizumab therapy using contrast-enhanced ultrasound and artificial neural networks.

    Science.gov (United States)

    Hoyt, Kenneth; Warram, Jason M; Umphrey, Heidi; Belt, Lin; Lockhart, Mark E; Robbin, Michelle L; Zinn, Kurt R

    2010-04-01

    The purpose of this study was to evaluate contrast-enhanced ultrasound and neural network data classification for determining the breast cancer response to bevacizumab therapy in a murine model. An ultrasound scanner operating in the harmonic mode was used to measure ultrasound contrast agent (UCA) time-intensity curves in vivo. Twenty-five nude athymic mice with orthotopic breast cancers received a 30-microL tail vein bolus of a perflutren microsphere UCA, and baseline tumor imaging was performed using microbubble destruction-replenishment techniques. Subsequently, 15 animals received a 0.2-mg injection of bevacizumab, whereas 10 control animals received an equivalent dose of saline. Animals were reimaged on days 1, 2, 3, and 6 before euthanasia. Histologic assessment of excised tumor sections was performed. Time-intensity curve analysis for a given region of interest was conducted using customized software. Tumor perfusion metrics on days 1, 2, 3, and 6 were modeled using neural network data classification schemes (60% learning and 40% testing) to predict the breast cancer response to therapy. The breast cancer response to a single dose of bevacizumab in a murine model was immediate and transient. Permutations of input to the neural network data classification scheme revealed that tumor perfusion data within 3 days of bevacizumab dosing was sufficient to minimize the prediction error to 10%, whereas measurements of physical tumor size alone did not appear adequate to assess the therapeutic response. Contrast-enhanced ultrasound may be a useful tool for determining the response to bevacizumab therapy and monitoring the subsequent restoration of blood flow to breast cancer.

  14. STAT3 silencing enhances the efficacy of the HSV.tk suicide gene in gastrointestinal cancer therapy.

    Science.gov (United States)

    Ahn, Ye-Hyeon; Yi, Hwajung; Shin, Ji-Young; Lee, Kang-Duck; Shin, Seung-Pil; Lee, Sang-Jin; Song, Jaewhan; Chun, Kyung-Hee

    2012-04-01

    Aberrant activation of Signal Transducer and Activator of Transcription 3 (STAT3) signaling has been shown to be associated with uncontrolled cell proliferation and suppression of host-immune surveillance. Conversely, silencing STAT3 can have the dual effects of inhibiting cancer cell proliferation and inducing anti-tumor immune responses. Here, we report on the effects of STAT3 silencing on suicide gene therapy with thymidine kinase (tk). STAT3 silencing by siRNA inhibited the proliferation of AGS human gastric cancer cells through G1 cell cycle arrest, decreased levels of immune-suppressive cytokines, and increased levels of immune-activating cytokines. CT26 mouse colon adenocarcinoma cells, in which STAT3 expression was knocked-down by a STAT3 shRNA-containing lentivirus, grew more slowly in syngenic model Balb/c mice than control CT26 cells. Moreover, we found that STAT3 silencing augmented the efficacy of suicide gene therapy in CT26 cell xenografted mice. When we administrated adenoviruses harboring the herpes simplex virus thymidine kinase gene (Ad5.CMV.HSV.tk) into STAT3-silenced CT26 cell tumors, extensive apoptosis was observed and there was a significant reduction in the size of CT26 cell tumors. STAT3 silencing also enhanced the recruitment and cytotoxic activity of CD3(+)CD8(+) T-cells, and changed the cytokine expression pattern of CT26 cell tumors, reflecting augmentation of anti-cancer immune responses. We conclude that combining suicide gene therapy with STAT3 silencing can result in enhanced anti-cancer effects.

  15. Quantitative investigation of the edge enhancement in in-line phase contrast projections and tomosynthesis provided by distributing microbubbles on the interface between two tissues: a phantom study

    Science.gov (United States)

    Wu, Di; Donovan Wong, Molly; Li, Yuhua; Fajardo, Laurie; Zheng, Bin; Wu, Xizeng; Liu, Hong

    2017-12-01

    The objective of this study was to quantitatively investigate the ability to distribute microbubbles along the interface between two tissues, in an effort to improve the edge and/or boundary features in phase contrast imaging. The experiments were conducted by employing a custom designed tissue simulating phantom, which also simulated a clinical condition where the ligand-targeted microbubbles are self-aggregated on the endothelium of blood vessels surrounding malignant cells. Four different concentrations of microbubble suspensions were injected into the phantom: 0%, 0.1%, 0.2%, and 0.4%. A time delay of 5 min was implemented before image acquisition to allow the microbubbles to become distributed at the interface between the acrylic and the cavity simulating a blood vessel segment. For comparison purposes, images were acquired using three system configurations for both projection and tomosynthesis imaging with a fixed radiation dose delivery: conventional low-energy contact mode, low-energy in-line phase contrast and high-energy in-line phase contrast. The resultant images illustrate the edge feature enhancements in the in-line phase contrast imaging mode when the microbubble concentration is extremely low. The quantitative edge-enhancement-to-noise ratio calculations not only agree with the direct image observations, but also indicate that the edge feature enhancement can be improved by increasing the microbubble concentration. In addition, high-energy in-line phase contrast imaging provided better performance in detecting low-concentration microbubble distributions.

  16. Enhancing cell and gene therapy manufacture through the application of advanced fluorescent optical sensors (Review).

    Science.gov (United States)

    Harrison, Richard P; Chauhan, Veeren M

    2017-12-15

    Cell and gene therapies (CGTs) are examples of future therapeutics that can be used to cure or alleviate the symptoms of disease, by repairing damaged tissue or reprogramming defective genetic information. However, despite the recent advancements in clinical trial outcomes, the path to wide-scale adoption of CGTs remains challenging, such that the emergence of a "blockbuster" therapy has so far proved elusive. Manufacturing solutions for these therapies require the application of scalable and replicable cell manufacturing techniques, which differ markedly from the existing pharmaceutical incumbent. Attempts to adopt this pharmaceutical model for CGT manufacture have largely proved unsuccessful. The most significant challenges facing CGT manufacturing are process analytical testing and quality control. These procedures would greatly benefit from improved sensory technologies that allow direct measurement of critical quality attributes, such as pH, oxygen, lactate and glucose. In turn, this would make manufacturing more robust, replicable and standardized. In this review, the present-day state and prospects of CGT manufacturing are discussed. In particular, the authors highlight the role of fluorescent optical sensors, focusing on their strengths and weaknesses, for CGT manufacture. The review concludes by discussing how the integration of CGT manufacture and fluorescent optical sensors could augment future bioprocessing approaches.

  17. Hypocrellin B and nano silver loaded polymeric nanoparticles: Enhanced generation of singlet oxygen for improved photodynamic therapy.

    Science.gov (United States)

    Natesan, Subramanian; Krishnaswami, Venkateshwaran; Ponnusamy, Chandrasekar; Madiyalakan, Madi; Woo, Thomas; Palanisamy, Rajaguru

    2017-08-01

    A nanoparticulate photodynamic approach was employed with an objective to achieve enhanced production of singlet oxygen ((1)O2), for the management of posterior segment eye diseases like age related macular degeneration. The hypocrellin B (HB) loaded poly lactide-co-glycolide nanoparticle formulations were incorporated with nano silver (HBS-NPs). The optimized HBS-NPs contained 2.60±0.06mg/mL of HB and showed (i) 135.6 to 828.2nm size range, and (ii) negative zeta potential with a narrow polydispersity index. The DSC thermograms suggested the amorphous nature of HB inside the HBS-NPs. With the average encapsulation efficiency of 92.9±1.79%, the drug release from the HBS-NPs followed a biphasic pattern with an initial burst of 3.50% during first 8h followed by a sustained release of 47.82% within 3days. The interaction between nano silver and HB as assessed by the increase in spectral intensity of Raman spectrum demonstrates that HB may be attached over the nano silver. Generation of reactive oxygen species (ROS) by HBS-NPs was significantly higher than that of HB/HB-NPs. The singlet oxygen generating efficiency assessed using EPR spectrometer follows the order of nano silver>HB-NPs>pure HB drug solution>HBS-NPs. The HBS-NPs had a concentration and time dependent phototoxicity on A549 (human adeno lung carcinoma) cells in the presence of light providing a superior phototoxic effect (82.2% at 50μM) at 2h irradiation. The CAM treated with HBS-NPs showed a significant anti-angiogenic effect compared to a blank formulation. In vivo biodistribution studies revealed that intravenous administration of HBS-NPs lead into significant exposure to the posterior segment of the eye. This proof of principle study demonstrates that HB based nanoparticles may be a valuable new tool for application in ocular photodynamic therapy for the treatment of AMD in future. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Development of a gene therapy strategy to target hepatocellular carcinoma based inhibition of protein phosphatase 2A using the α-fetoprotein promoter enhancer and pgk promoter: an in vitro and in vivo study

    Directory of Open Access Journals (Sweden)

    Li Wei

    2012-11-01

    Full Text Available Abstract Background Hepatocellular carcinoma (HCC is one of the leading causes of cancer-related deaths worldwide. Current therapies are insufficient, making HCC an intractable disease. Our previous studies confirmed that inhibition of protein phosphatase 2A (PP2A may provide a promising therapeutic strategy for cancer. Unfortunately, constitutive expression of PP2A in normal tissues limits the application of PP2A inhibition. Thus, a HCC-specific gene delivery system should be developed. The α-fetoprotein (AFP promoter is commonly used in HCC-specific gene therapy strategies; however, the utility of this approach is limited due to the weak activity of the AFP promoter. It has been shown that linking the AFP enhancer with the promoter of the non-tissue-specific, human housekeeping phosphoglycerate kinase (pgk gene can generate a strong and HCC-selective promoter. Methods We constructed a HCC-specific gene therapy system to target PP2A using the AFP enhancer/pgk promoter, and evaluated the efficiency and specificity of this system both in vitro and in vivo. Results AFP enhancer/pgk promoter-driven expression of the dominant negative form of the PP2A catalytic subunit α (DN-PP2Acα exerted cytotoxic effects against an AFP-positive human hepatoma cell lines (HepG2 and Hep3B, but did not affect AFP-negative human hepatoma cells (SK-HEP-1 or normal human liver cells (L-02. Moreover, AFP enhancer/pgk promoter driven expression of DN-PP2Acα inhibited the growth of AFP-positive HepG2 tumors in nude mice bearing solid tumor xenografts, but did not affect AFP-negative SK-HEP-1 tumors. Conclusions The novel approach of AFP enhancer/pgk promoter-driven expression of DN-PP2Acα may provide a useful cancer gene therapy strategy to selectively target HCC.

  19. Provider recommendations for patient-reported muscle symptoms on statin therapy: Insights from the Understanding Statin Use in America and Gaps in Patient Education survey.

    Science.gov (United States)

    Jacobson, Terry A; Khan, Abdullah; Maki, Kevin C; Brinton, Eliot A; Cohen, Jerome D

    Statin-associated muscle symptoms are reported by 10% to 29% of patients in clinical practice and are a major determinant of statin nonadherence, discontinuation, and switching. Little is known about what advice patients receive from their providers when dealing with these symptoms. The objective of the study was to assess patient's reports of provider advice when experiencing new or worsened muscle symptoms while taking a statin. Data were analyzed from the Understanding Statin Use in America and Gaps in Education survey, a self-administered internet-based survey of 10,138 adults with a reported history of high cholesterol and statin use. Of the respondents, 60% of former statin users (n = 1220) reported ever experiencing new or worsened muscle pain on a statin, in contrast to 25% of current users (n = 8918; P < .001). Former statin users reported stopping more statins because of muscle symptoms (mean ± standard deviation, 2.2 ± 1.7) compared with current users (mean 1.6 ± 1.5, P < .0001). For those with muscle-related symptoms while on a statin, participants reported that providers most often suggested switching to another statin (33.8%), stopping the statin (15.9%), continuing the statin with further monitoring of muscle symptoms (12.2%), reducing the statin dose (9.8%), or getting a blood test for signs of muscle damage (9.2%). A lower percentage were advised to add either vitamin D (7.0%) or coenzyme Q10 (5.8%), or to switch to nonstatin therapy (6.1%) or red yeast rice (2.6%). This study highlights patient experience with statin-associated muscle symptoms and the strategies recommended by providers in managing these symptoms. More research is needed to develop patient-centric and evidence-based approaches to managing statin-associated muscle symptoms, which is especially important in light of recent data showing increased cardiovascular risk among those who discontinue statin therapy. Copyright © 2017 National Lipid Association. Published by

  20. Pharmacology of cognitive enhancers for exposure-based therapy of fear, anxiety and trauma-related disorders

    Science.gov (United States)

    Singewald, N.; Schmuckermair, C.; Whittle, N.; Holmes, A.; Ressler, K.J.

    2015-01-01

    Pathological fear and anxiety are highly debilitating and, despite considerable advances in psychotherapy and pharmacotherapy they remain insufficiently treated in many patients with PTSD, phobias, panic and other anxiety disorders. Increasing preclinical and clinical evidence indicates that pharmacological treatments including cognitive enhancers, when given as adjuncts to psychotherapeutic approaches [cognitive behavioral therapy including extinction-based exposure therapy] enhance treatment efficacy, while using anxiolytics such as benzodiazepines as adjuncts can undermine long-term treatment success. The purpose of this review is to outline the literature showing how pharmacological interventions targeting neurotransmitter systems including serotonin, dopamine, noradrenaline, histamine, glutamate, GABA, cannabinoids, neuropeptides (oxytocin, neuropeptides Y and S, opioids) and other targets (neurotrophins BDNF and FGF2, glucocorticoids, L-type-calcium channels, epigenetic modifications) as well as their downstream signaling pathways, can augment fear extinction and strengthen extinction memory persistently in preclinical models. Particularly promising approaches are discussed in regard to their effects on specific aspects of fear extinction namely, acquisition, consolidation and retrieval, including long-term protection from return of fear (relapse) phenomena like spontaneous recovery, reinstatement and renewal of fear. We also highlight the promising translational value of the preclinial research and the clinical potential of targeting certain neurochemical systems with, for example d-cycloserine, yohimbine, cortisol, and L-DOPA. The current body of research reveals important new insights into the neurobiology and neurochemistry of fear extinction and holds significant promise for pharmacologically-augmented psychotherapy as an improved approach to treat trauma and anxiety-related disorders in a more efficient and persistent way promoting enhanced symptom

  1. Low Z target switching to increase tumor endothelial cell dose enhancement during gold nanoparticle-aided radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Berbeco, Ross I., E-mail: rberbeco@partners.org; Detappe, Alexandre [Department of Radiation Oncology, Brigham and Women’s Hospital, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts 02115 (United States); Tsiamas, Panogiotis [Department of Radiation Oncology, St. Jude Children’s Hospital, Memphis, Tennessee 38105 (United States); Parsons, David; Yewondwossen, Mammo; Robar, James [Department of Radiation Oncology and Department of Physics and Atmospheric Science, Dalhousie University, Halifax, Nova Scotia B3H 1V7 (Canada)

    2016-01-15

    Purpose: Previous studies have introduced gold nanoparticles as vascular-disrupting agents during radiation therapy. Crucial to this concept is the low energy photon content of the therapy radiation beam. The authors introduce a new mode of delivery including a linear accelerator target that can toggle between low Z and high Z targets during beam delivery. In this study, the authors examine the potential increase in tumor blood vessel endothelial cell radiation dose enhancement with the low Z target. Methods: The authors use Monte Carlo methods to simulate delivery of three different clinical photon beams: (1) a 6 MV standard (Cu/W) beam, (2) a 6 MV flattening filter free (Cu/W), and (3) a 6 MV (carbon) beam. The photon energy spectra for each scenario are generated for depths in tissue-equivalent material: 2, 10, and 20 cm. The endothelial dose enhancement for each target and depth is calculated using a previously published analytic method. Results: It is found that the carbon target increases the proportion of low energy (<150 keV) photons at 10 cm depth to 28% from 8% for the 6 MV standard (Cu/W) beam. This nearly quadrupling of the low energy photon content incident on a gold nanoparticle results in 7.7 times the endothelial dose enhancement as a 6 MV standard (Cu/W) beam at this depth. Increased surface dose from the low Z target can be mitigated by well-spaced beam arrangements. Conclusions: By using the fast-switching target, one can modulate the photon beam during delivery, producing a customized photon energy spectrum for each specific situation.

  2. Gene therapy with IL-12 induced enhanced anti-tumor activity in fibrosarcoma mouse model.

    Science.gov (United States)

    Razi Soofiyani, Saiedeh; Kazemi, Tohid; Lotfipour, Farzaneh; Mohammad Hosseini, Akbar; Shanehbandi, Dariush; Hallaj-Nezhadi, Somayeh; Baradaran, Behzad

    2016-12-01

    Context Immunotherapy is among the most promising modalities for treatment of cancer. Recently, interleukin 12 (IL-12) has been used as an immunotherapeutic agent in cancer gene therapy. IL-12 can activate dendritic cells (DCs) and boost anti-tumor immune responses. Objective In the current study, we have investigated if IL-12 gene therapy can lead to the regression of tumor mass in a mouse model of fibrosarcoma. Material and methods To investigate the therapeutic efficacy of IL-12, WEHI-164 tumor cells were transfected with murine-IL12 plasmids using Lipofectamine. Enzyme linked immunosorbent assay (ELISA) was used to confirm IL-12 expression in transfected cells. The fibrosarcoma mouse model was established by subcutaneous injection of transfected cells to Balb/C mice. Mice were sacrificed and the tumors were extracted. Tumor sizes were measured by caliper. The expression of IL-12 and IFN-γ was studied with real-time PCR and western blotting. The expression of Ki-67(a tumor proliferation marker) in tumor mass was studied by immunohistochemistry staining. Results and discussion The group treated with IL-12 showed a significant decrease in tumor mass volume (P: 0.000). The results of real-time PCR and western blotting showed that IL-12 and IFN-γ expression increased in the group treated with IL-12 (relative expression of IL-12: 1.9 and relative expression of IFN-γ: 1.766). Immunohistochemistry staining showed that Ki-67 expression was reduced in the group treated with IL-12. Conclusion IL-12 gene therapy successfully led to regress of tumor mass in the fibrosarcoma mouse model. This may serve as a candidate therapeutic approach for treatment of cancer.

  3. Adjunctive albuterol enhances the response to enzyme replacement therapy in late-onset Pompe disease.

    Science.gov (United States)

    Koeberl, Dwight D; Austin, Stephanie; Case, Laura E; Smith, Edward C; Buckley, Anne F; Young, Sarah P; Bali, Deeksha; Kishnani, Priya S

    2014-05-01

    Effective dosages for enzyme replacement therapy (ERT) in Pompe disease are much higher than for other lysosomal storage disorders, which has been attributed to low cation-independent mannose-6-phosphate receptor (CI-MPR) in skeletal muscle. We have previously demonstrated the benefit of increased CI-MPR-mediated uptake of recombinant human acid-α-glucosidase during ERT in mice with Pompe disease following addition of albuterol therapy. Currently we have completed a pilot study of albuterol in patients with late-onset Pompe disease already on ERT for >2 yr, who were not improving further. The 6-min walk test (6MWT) distance increased in all 7 subjects at wk 6 (30±13 m; P=0.002), wk 12 (34±14 m; P=0.004), and wk 24 (42±37 m; P=0.02), in comparison with baseline. Grip strength was improved significantly for both hands at wk 12. Furthermore, individual subjects reported benefits; e.g., a female patient could stand up from sitting on the floor much more easily (time for supine to standing position decreased from 30 to 11 s), and a male patient could readily swing his legs out of his van seat (hip abduction increased from 1 to 2+ on manual muscle testing). Finally, analysis of the quadriceps biopsies suggested increased CI-MPR at wk 12 (P=0.08), compared with baseline. With the exception of 1 patient who succumbed to respiratory complications of Pompe disease in the first week, only mild adverse events have been reported, including tremor, transient difficulty falling asleep, and mild urinary retention (requiring early morning voiding). Therefore, this pilot study revealed initial safety and efficacy in an open label study of adjunctive albuterol therapy in patients with late-onset Pompe disease who had been stable on ERT with no improvements noted over the previous several years.

  4. SnWO4-based nanohybrids with full energy transfer for largely enhanced photodynamic therapy and radiotherapy.

    Science.gov (United States)

    Zhang, Meng; Cui, Zhaowen; Song, Ruixue; Lv, Bin; Tang, Zhongmin; Meng, Xianfu; Chen, Xiaoyan; Zheng, Xiangpeng; Zhang, Jiawen; Yao, Zhenwei; Bu, Wenbo

    2018-02-01

    The "partial matching" between upconversion nanoparticle (UCNP) emission and absorption by photosensitizers (PSs) often leads to a theoretically reduced therapeutic efficiency in UC-based photodynamic therapy (PDT) strategies in which the chosen PSs have limited capabilities and are unable to utilize all the near-infrared-upconverted light. In this study, needle-like SnWO 4 nanocrystals (SWs) with a broad UV-vis absorption region were synthesized to solve the problem. After covalent conjugation with UCNPs, all the UCNP-emitted light was effectively absorbed by SWs, triggering the type-I PDT process to activate ROS maxima. The unique nanostructure of the as-formed UCNP-SnWO 4 nanohybrids (USWs) also enhanced the receiving light intensities of SW, which further boosted the antitumor efficacy. Meanwhile, the strong X-ray attenuation capacity of both tungsten and tin elements qualified the USWs as excellent radio-sensitizers for radiotherapy (RT) enhancement, which played a complementary role with PDT treatment because PDT-mediated induction arrested the cells in the G0-G1 cell cycle phase, and RT was more damaging toward cells in the G2/M phase. The remarkably enhanced UC-PDT/RT efficiency of USWs was next validated in vitro and in vivo, and the combined NIR light and ionizing irradiation treatment completely suppressed tumor growth, revealing its great potential as an efficient anticancer therapeutic agent against solid tumors. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Functional and physical competition between phospholamban and its mutants provides insight into the molecular mechanism of gene therapy for heart failure.

    Science.gov (United States)

    Lockamy, Elizabeth L; Cornea, Razvan L; Karim, Christine B; Thomas, David D

    2011-05-13

    We have used functional co-reconstitution of purified sarcoplasmic reticulum (SR) Ca(2+)-ATPase (SERCA) with phospholamban (PLB), its inhibitor in the heart, to test the hypothesis that loss-of-function (LOF) PLB mutants (PLB(M)) can compete with wild-type PLB (PLB(W)) to relieve SERCA inhibition. Co-reconstitution at varying PLB-to-SERCA ratios was conducted using synthetic PLB(W), gain-of-function mutant I40A, or LOF mutants S16E (phosphorylation mimic) or L31A. Inhibitory potency was defined as the fractional increase in K(Ca), measured from the Ca(2+)-dependence of ATPase activity. At saturating PLB, the inhibitory potency of I40A was about three times that of PLB(W), while the potency of each of the LOF PLB(M) was about one third that of PLB(W). However, there was no significant variation in the apparent SERCA affinity for these four PLB variants. When SERCA was co-reconstituted with mixtures of PLB(W) and LOF PLB(M), inhibitory potency was reduced relative to that of PLB(W) alone. Furthermore, FRET between donor-labeled SERCA and acceptor-labeled PLB(W) was decreased by both (unlabeled) LOF PLB(M). These results show that LOF PLB(M) can compete both physically and functionally with PLB(W), provide a rational explanation for the partial success of S16E-based gene therapy in animal models of heart failure, and establish a powerful platform for designing and testing more effective PLB(M) targeted for gene therapy of heart failure in humans. Copyright © 2011 Elsevier Inc. All rights reserved.

  6. Treatment Outcomes and Costs of Providing Antiretroviral Therapy at a Primary Health Clinic versus a Hospital-Based HIV Clinic in South Africa.

    Directory of Open Access Journals (Sweden)

    Lawrence C Long

    Full Text Available In 2010 South Africa revised its HIV treatment guidelines to allow the initiation and management of patients on antiretroviral therapy (ART by nurses, rather than solely doctors, under a program called NIMART (Nurse Initiated and Managed Antiretroviral Therapy. We compared the outcomes and costs of NIMART between the two major public sector HIV treatment delivery models in use in South Africa today, primary health clinics and hospital-based HIV clinics.The study was conducted at one hospital-based outpatient HIV clinic and one primary health clinic (PHC in Gauteng Province. A retrospective cohort of adult patients initiated on ART at the PHC was propensity-score matched to patients initiated at the hospital outpatient clinic. Each patient was assigned a 12-month outcome of alive and in care or died/lost to follow up. Costs were estimated from the provider perspective for the 12 months after ART initiation. The proportion of patients alive and in care at 12 months did not differ between the PHC (76.5% and the hospital-based site (74.2%. The average annual cost per patient alive and in care at 12 months after ART initiation was significantly lower at the PHC (US$238 than at the hospital outpatient clinic (US$428.Initiating and managing ART patients at PHCs under NIMART is producing equally good outcomes as hospital-based HIV clinic care at much lower cost. Evolution of hospital-based clinics into referral facilities that serve complicated patients, while investing most program expansion resources into PHCs, may be a preferred strategy for achieving treatment coverage targets.

  7. Postoperative intensity-modulated radiation therapy provides favorable local control and low toxicities in patients with soft tissue sarcomas in the extremities and trunk wall

    Directory of Open Access Journals (Sweden)

    Wang JY

    2015-10-01

    Full Text Available Jianyang Wang, Shulian Wang, Yongwen Song, Xinfan Liu, Jing Jin, Weihu Wang, Zihao Yu, Yueping Liu, Yexiong Li Department of Radiation Oncology, Cancer Hospital and Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China Purpose: To investigate the efficacy and toxicity of postoperative intensity-modulated radiation therapy (IMRT for patients with soft tissue sarcomas (STSs in the extremities and trunk wall. Patients and methods: Eighty patients with localized STSs in the extremities and trunk wall treated with function-conserving surgery and postoperative IMRT were analyzed. The primary locations were in the extremities in 51 patients and in the trunk wall in 29 patients. The margins were positive in nine patients and negative in 71 patients. The median dose of IMRT was 64 Gy. Results: At a median follow-up time of 38 months, eight patients developed local recurrences. The 5-year local control (LC rate was 88.1%. The patients with negative margins exhibited much better LC than did those with positive margins (90% vs 64.8%, P=0.023. Multivariate analysis revealed that positive margin was an independent risk factor for LC. The 5-year distant metastasis-free survival, disease-free survival, and overall survival rates were 75.2%, 72.6%, and 83.6%, respectively. Large tumor size (>5 cm was significantly associated with poor overall survival. Edema and joint stiffness were observed in 17.6% and 9.8% of patients with extremity STSs, respectively. Conclusion: IMRT provides excellent LC and low toxicity for patients with STSs in the extremities and trunk wall. Keywords: soft tissue sarcoma, extremities and trunk wall, intensity-modulated radiation therapy, local control, toxicitiess

  8. Patients' and Health Care Providers' Evaluation of Quality of Life Issues in Advanced Cancer Using Functional Assessment of Chronic Illness Therapy - Palliative Care Module (FACIT-Pal) Scale.

    Science.gov (United States)

    Khan, Luluel; Zeng, Liang; Cella, David; Thavarajah, Nemica; Chen, Emily; Zhang, Liying; Bennett, Margaret; Peckham, Kenneth; De Costa, Sandra; Beaumont, Jennifer L; Tsao, May; Danjoux, Cyril; Barnes, Elizabeth; Sahgal, Arjun; Chow, Edward

    2012-10-01

    To examine the agreement of Health Care Providers (HCPs) and patients' evaluation of quality of life on the Functional Assessment of Chronic Illness therapy - Palliative care module (FACIT-Pal) scale. Sixty advanced cancer patients and fifty-six health care providers involved in their care at Sunnybrook Health Sciences Centre completed a modified version of the FACIT- Pal. In the survey, patients and HCPs indicated the 10 top issues affecting the quality of life of patients with advanced cancer most profoundly. The percentage of participants selecting each item as one of their 10 most relevant items was calculated in HCPs and patients. There were differences in relative rankings of QOL issues among patients and HCPs. Among the top 10 items which were identified from both patients and HCPs, there were differences in the rankings. Patients ranked emotional support from family (40.9%) as most important followed by pain (38.6%), lack of energy (31.8%) and able to enjoy life (29.6%). HCPs ranked in the following order: pain (73.2%), lack of energy (63.4%), nausea (51.2%) and dyspnea (51.2%) whereas patients rated nausea at 18.2 % and dyspnea at 9.09%. There is a discrepancy between scores of patients and HCPs as they may prioritize differently. HCPs tended to put more emphasis on physical symptoms, whereas patients had emotional and global issues as priorities.

  9. ET-17TRANSIENT FASTING ENHANCES REPLICATION AND THERAPEUTIC ACTIVITY OF ONCOLYTIC HSV IN GLIOBLASTOMA THERAPY

    OpenAIRE

    Esaki, Shinichi; Rabkin, Samuel D; Martuza, Robert L; Wakimoto, Hiroaki

    2014-01-01

    BACKGROUND AND OBJECTIVE: Short term fasting has been shown to enhance efficacy of chemotherapy by sensitizing tumor cells and protecting normal cells in a variety of cancer models including glioblastoma (GBM). Malignant cells, unlike normal cells, respond to fasting by promoting oncogenic signaling and protein synthesis, which could in turn sensitize them to anti-cancer agents, broadening therapeutic window. We hypothesize that fasting increases replication of oncolytic herpes simplex virus ...

  10. Enhancement of Radiation Therapy in Prostate Cancer by DNA-PKcs Inhibitor

    Science.gov (United States)

    2014-09-01

    EZH2 in- tensity levels.Reprint requests to: D. W. Nathan Kim, MD Southwestern Medical Center, Department of Forest Park Rd, Dallas, TX 75390. Tel: (214... Biomed Mater Res A 2012;100(8):1998-2005. 23. Jia Y, Yuan M, Yuan H, Huang X, Sui X, Cui X, Tang F, Peng J, Chen J, Lu S and others. Co...Multifunctionality of indocyanine green-loaded biodegradable nanoparticles for enhanced optical imaging and hyperthermia intervention of cancer. J Biomed Opt

  11. A Novel Solubility-Enhanced Rubusoside-Based Micelles for Increased Cancer Therapy

    OpenAIRE

    Zhang, Meiying; Dai, Tongcheng; Feng, Nianping

    2017-01-01

    Many anti-cancer drugs have a common problem of poor solubility. Increasing the solubility of the drugs is very important for its clinical applications. In the present study, we revealed that the solubility of insoluble drugs was significantly enhanced by adding rubusoside (RUB). Further, it was demonstrated that RUB could form micelles, which was well characterized by Langmuir monolayer investigation, transmission electron microscopy, atomic-force microscopy, and cryogenic transmission elect...

  12. Respiratory Challenges in Breast Cancer: Potential for Enhanced Diagnostics and Therapy

    Science.gov (United States)

    2009-07-31

    and Briers J D 1981 Flow Visualization by Means of Single-Exposure Speckle Photography Optics Communications 37 326-30 Ferguson R D, Hammer D X...their selective toxicities toward oxygenated and hypoxic tumor cells Cancer Res 41 73-81 Vaupel P, Hockel, M. 2002 Tumor hypoxia and therapeutic ...multi- site EPR oximetry as a prognostic marker for enhanced therapeutic efficacy of fractionated radiotherapy,” Radiotherapy and Oncology (2008

  13. Low-level laser therapy (LLLT) reduces inflammatory infiltrate and enhances skeletal muscle repair: Histomorphometric parameters

    Science.gov (United States)

    Paiva-Oliveira, E. L.; Lima, N. C.; Silva, P. H.; Sousa, N. T. A.; Barbosa, F. S.; Orsini, M.; Silva, J. G.

    2012-09-01

    Low level laser therapy (LLLT) has been suggested as an effective therapeutics in inflammatory processes modulation and tissue repairing. However, there is a lack of studies that analyze the anti-inflammatory effects of the infrared lasers in muscular skeletal injury. The aim of this study was to investigate the effects of low-level laser therapy 904 nm in the repair process of skeletal muscle tissue. Swiss mice were submitted to cryoinjury and divided in test (LLLT-treated) and control groups. Histological sections were stained with hematoxylin-eosin to assess general morphology and inflammatory influx, and Picrossirus to quantify collagen fibers deposition. Our results showed significant reduction in inflammatory infiltrated in irradiated mice after 4 days of treatment compared to control ( p = 0.01). After 8 days, the irradiated group showed high levels at regenerating myofibers with significant statistically differences in relation at control group ( p test group, when compared with control group ( p = 0.05). Our data suggests that LLLT reduces the inflammatory response in the initial stages of injury and accelerates the process of muscular tissue repair.

  14. A Novel Solubility-Enhanced Rubusoside-Based Micelles for Increased Cancer Therapy

    Science.gov (United States)

    Zhang, Meiying; Dai, Tongcheng; Feng, Nianping

    2017-04-01

    Many anti-cancer drugs have a common problem of poor solubility. Increasing the solubility of the drugs is very important for its clinical applications. In the present study, we revealed that the solubility of insoluble drugs was significantly enhanced by adding rubusoside (RUB). Further, it was demonstrated that RUB could form micelles, which was well characterized by Langmuir monolayer investigation, transmission electron microscopy, atomic-force microscopy, and cryogenic transmission electron microscopy. The RUB micelles were ellipsoid with the horizontal distance of 25 nm and vertical distance of 1.2 nm. Insoluble synergistic anti-cancer drugs including curcumin and resveratrol were loaded in RUB to form anti-cancer micelles RUB/CUR + RES. MTT assay showed that RUB/CUR + RES micelles had more significant toxicity on MCF-7 cells compared to RUB/CUR micelles + RUB/RES micelles. More importantly, it was confirmed that RUB could load other two insoluble drugs together for remarkably enhanced anti-cancer effect compared to that of RUB/one drug + RUB/another drug. Overall, we concluded that RUB-based micelles could efficiently load insoluble drugs for enhanced anti-cancer effect.

  15. Different arms of the adaptive immune system induced by a combination vaccine work in concert to provide enhanced clearance of influenza.

    Science.gov (United States)

    Cobbin, Joanna C A; Zeng, Weiguang; Jackson, David C; Brown, Lorena E

    2014-01-01

    Current split influenza virus vaccines that induce strain-specific neutralising antibodies provide some degree of protection against influenza infection but there is a clear need to improve their effectiveness. The constant antigenic drift of influenza viruses means that vaccines are often not an exact match to the circulating strain and so levels of relevant antibodies may not be sufficiently high to afford protection. In the situation where the emergent influenza virus is completely novel, as is the case with pandemic strains, existing vaccines may provide no benefit. In this study we tested the concept of a combination vaccine consisting of sub-optimal doses of split influenza virus vaccine mixed with a cross-protective T-cell inducing lipopeptide containing the TLR2 ligand Pam2Cys. Mice immunised with combination vaccines showed superior levels of lung viral clearance after challenge compared to either split virus or lipopeptide alone, mediated through activation of enhanced humoral and/or additional cellular responses. The mechanism of action of these vaccines was dependent on the route of administration, with intranasal administration being superior to subcutaneous and intramuscular routes, potentially through the induction of memory CD8+ T cells in the lungs. This immunisation strategy not only provides a mechanism for minimising the dose of split virus antigen but also, through the induction of cross-protective CD8+ T cells, proves a breadth of immunity to provide potential benefit upon encounter with serologically diverse influenza isolates.

  16. Different arms of the adaptive immune system induced by a combination vaccine work in concert to provide enhanced clearance of influenza.

    Directory of Open Access Journals (Sweden)

    Joanna C A Cobbin

    Full Text Available Current split influenza virus vaccines that induce strain-specific neutralising antibodies provide some degree of protection against influenza infection but there is a clear need to improve their effectiveness. The constant antigenic drift of influenza viruses means that vaccines are often not an exact match to the circulating strain and so levels of relevant antibodies may not be sufficiently high to afford protection. In the situation where the emergent influenza virus is completely novel, as is the case with pandemic strains, existing vaccines may provide no benefit. In this study we tested the concept of a combination vaccine consisting of sub-optimal doses of split influenza virus vaccine mixed with a cross-protective T-cell inducing lipopeptide containing the TLR2 ligand Pam2Cys. Mice immunised with combination vaccines showed superior levels of lung viral clearance after challenge compared to either split virus or lipopeptide alone, mediated through activation of enhanced humoral and/or additional cellular responses. The mechanism of action of these vaccines was dependent on the route of administration, with intranasal administration being superior to subcutaneous and intramuscular routes, potentially through the induction of memory CD8+ T cells in the lungs. This immunisation strategy not only provides a mechanism for minimising the dose of split virus antigen but also, through the induction of cross-protective CD8+ T cells, proves a breadth of immunity to provide potential benefit upon encounter with serologically diverse influenza isolates.

  17. Trial participants' experiences of early enhanced speech and language therapy after stroke compared with employed visitor support: a qualitative study nested within a randomized controlled trial.

    Science.gov (United States)

    Young, Alys; Gomersall, Timothy; Bowen, Audrey

    2013-02-01

    To explore trial participants' experiences of the process and outcomes of early, enhanced speech and language therapy after stroke with support from an employed visitor. Qualitative study nested within a randomized controlled trial. Twney-two people who, after stroke, had a diagnosis of aphasia (12), dysarthria (5) or both (5) and who participated in the ACT NoW study. Eight English NHS usual care settings. Individual interviews. Thematic content analysis assisted by a bespoke data transformation protocol for incorporating non-verbal and semantically ambiguous data. Participants highly regarded regular and sustained contact with someone outside of immediate family/friends who engaged them in deliberate activities/communication in the early months after stroke. Participants identified differences in the process of intervention between speech and language therapists and employed visitors. But no major discriminations were made between the impact or value of this contact according to whether provided by a speech and language therapist or employed visitor. Participant-defined criteria for effectiveness of contact included: impact on mood and confidence, self-recognition of progress and the meeting of individual needs. As in the randomized controlled trial, participants reported no evidence of added benefit of early communication therapy beyond that from attention control. The findings do not imply that regular contact with any non-professional can have beneficial effects for someone with aphasia or dysarthria in the early weeks following a stroke. The study points to specific conditions that would have to be met for contact to have a positive effect.

  18. Ruthenium(II) Complex Incorporated UiO-67 Metal-Organic Framework Nanoparticles for Enhanced Two-Photon Fluorescence Imaging and Photodynamic Cancer Therapy.

    Science.gov (United States)

    Chen, Rui; Zhang, Jinfeng; Chelora, Jipsa; Xiong, Yuan; Kershaw, Stephen V; Li, King Fai; Lo, Pik-Kwan; Cheah, Kok Wai; Rogach, Andrey L; Zapien, Juan Antonio; Lee, Chun-Sing

    2017-02-22

    Ruthenium(II) tris(bipyridyl) cationic complex (Ru(bpy) 3 2+ ) incorporated UiO-67 (Universitetet i Oslo) nanoscale metal-organic frameworks (NMOFs) with an average diameter of ∼92 nm were developed as theranostic nanoplatform for in vitro two-photon fluorescence imaging and photodynamic therapy. After incorporation into porous UiO-67 nanoparticles, the quantum yield, luminescence lifetime, and two-photon fluorescence intensity of Ru(bpy) 3 2+ guest molecules were much improved owing to the steric confinement effect of MOF pores. Benefiting from these merits, the as-synthesized nanoparticles managed to be internalized by A549 cells while providing excellent red fluorescence in cytoplasm upon excitation with 880 nm irradiation. Photodynamic therapeutic application of the Ru(bpy) 3 2+ -incorporated UiO-67 NMOFs was investigated in vitro. The Ru(bpy) 3 2+ -incorporated UiO-67 NMOFs exhibited good biocompatibility without irradiation while having good cell-killing rates upon irradiation. In view of these facts, the developed Ru(bpy) 3 2+ -incorporated NMOFs give a new potential pathway to achieve enhanced two-photon fluorescence imaging and photodynamic therapy.

  19. Preparing to provide MTM services.

    Science.gov (United States)

    Glenn, Zandra M; Mahdavian, Soheyla L; Woodard, Todd J

    2015-02-01

    Medication Therapy Management (MTM) has been a way for pharmacist to enhance their position as an integral member of the health care team as the need for improved clinical and economic outcomes in relation to the US health care system became apparent. MTM Certificate training programs are provided by numerous organizations. Collaboration Practice Agreements (CPA) are gaining significance as the role of the pharmacist is expanding in the care of patients as part of a multidisciplinary health care team. One major hurdle that many pharmacists are faced with is receiving reimbursement for the services provided. The Medicare Modernization Act of 2003 recognized that pharmacists play an important role in the management of patient care and that pharmacists bring an expertise and knowledge that will help to identify and resolve patient medication therapy problems. © The Author(s) 2014.

  20. Awareness of nicotine replacement therapy among South African smokers and their interest in using it for smoking cessation when provided for free.

    Science.gov (United States)

    Agaku, Israel T; Ayo-Yusuf, Olalekan A

    2014-04-01

    This study assessed knowledge of South African smokers about nicotine replacement therapy (NRT) and their interest in using it for smoking cessation if it is provided free. The 2007 South African Social Attitudes Survey was analyzed for 689 smokers aged ≥ 16 years. Prevalence of receipt of tobacco cessation counseling from a health care professional as well as self-reported knowledge about NRT was calculated. Multivariable logistic regression was used to assess factors associated with interest in using NRT if provided for free. About 26.1% of current smokers reported ever receiving tobacco cessation counselling from a health care professional. Although 67.7% of smokers were aware of NRT, only 3.9% had ever used NRT. However, 77.6% of those aware of NRT were interested in using it for smoking cessation if offered for free. After adjusting for potential confounders, smokers' interest in using NRT was inversely associated with interest in harm-reduction switching to snuff (adjusted odds ratio [AOR] = 0.34; 95% confidence interval [CI] = 0.14-0.80) and also reduced with each unit increase in lifetime duration of smoking (AOR = 0.93; 95% CI = 0.88-0.99). Interest in NRT use was higher among polytobacco users compared with exclusive cigarette smokers (AOR = 10.21; 95% CI = 1.08-96.15) and generally increased with increasing age of smoker. About two-thirds of smokers knew about NRT, and the majority were interested in using NRT for smoking cessation if provided free. These findings underscore the need to increase awareness of smokers about NRT through mass-media campaigns as well as include tobacco dependence treatment as part of the national health insurance programs of low- and middle-income countries.

  1. Versatile molybdenum disulfide based antibacterial composites for in vitro enhanced sterilization and in vivo focal infection therapy

    Science.gov (United States)

    Zhang, Wentao; Shi, Shuo; Wang, Yanru; Yu, Shaoxuan; Zhu, Wenxin; Zhang, Xu; Zhang, Daohong; Yang, Baowei; Wang, Xin; Wang, Jianlong

    2016-06-01

    Biologically, MoS2-based nanostructures have been intensely applied for the photothermal therapy of cancer, but rarely for antibacterial uses. In this contribution, a multifunctional chitosan (CS) functionalized magnetic MoS2 (abbreviated to CFM) was constructed to nonspecifically combat bacterial infection by integrating bacterial conjugation and enrichment, and NIR-triggered photothermal sterilization. Owing to the abundant introduced amino groups, the CFM complex offers a significantly enhanced conjugation efficiency without obvious specificity towards both Gram-positive and -negative bacteria compared to amino-free magnetic MoS2. The magnetic properties of CFM obtained from iron oxide facilitate the enrichment of a CFM-bacteria conjugate, improving the photothermal efficiency of CFM as a photothermal antibacterial agent. Specifically, after being trapped together with bacteria cells, CFM shows an enhanced in vitro photothermal sterilization ability. In vivo S. aureus-induced abscess treatment studies show faster healing when CFM is used as subcutaneous nano-localized heating sources with the assistance of an external magnet to concentrate the CFM-bacteria conjugate. This work establishes an innovative solution and a novel antimicrobial agent for combating bacterial infections without the use of antibiotics, which may open a new area of application and research for MoS2-based nanostructures.Biologically, MoS2-based nanostructures have been intensely applied for the photothermal therapy of cancer, but rarely for antibacterial uses. In this contribution, a multifunctional chitosan (CS) functionalized magnetic MoS2 (abbreviated to CFM) was constructed to nonspecifically combat bacterial infection by integrating bacterial conjugation and enrichment, and NIR-triggered photothermal sterilization. Owing to the abundant introduced amino groups, the CFM complex offers a significantly enhanced conjugation efficiency without obvious specificity towards both Gram

  2. Neurofeedback Therapy for Enhancing Visual Attention: State-of-the-Art and Challenges

    DEFF Research Database (Denmark)

    Ordikhani-Seyedlar, Mehdi; Lebedev, Mikhail A; Sørensen, Helge Bjarup Dissing

    2016-01-01

    We have witnessed a rapid development of brain-computer interfaces (BCIs) linking the brain to external devices. BCIs can be utilized to treat neurological conditions and even to augment brain functions. BCIs offer a promising treatment for mental disorders, including disorders of attention. Here...... of attentional neural signals remains a fundamental challenge for the development of efficient therapies for disorders of attention....... function. Although progress has been made in the studies of neural mechanisms of attention, extraction of attention-related neural signals needed for BCI operations is a difficult problem. To attain good BCI performance, it is important to select the features of neural activity that represent attentional...... signals. BCI decoding of attention-related activity may be hindered by the presence of different neural signals. Therefore, BCI accuracy can be improved by signal processing algorithms that dissociate signals of interest from irrelevant activities. Notwithstanding recent progress, optimal processing...

  3. Invasion-promoting extracellular matrix composition enhances photodynamic therapy response in 3D pancreatic cancer models

    Science.gov (United States)

    Cramer, Gwendolyn M.; El-Hamidi, Hamid; Celli, Jonathan P.

    2017-02-01

    Pancreatic ductal adenocarcinoma (PDAC) is characterized by extracellular matrix-rich stromal involvement, but it is not clear how ECM properties that affect invasiveness and chemotherapy response influence efficacy of photodynamic therapy (PDT). To disentangle the mechanical and biochemical effects of ECM composition, we measured the effects of various combinations of ECM proteins on growth behavior, invasive potential, and therapeutic response of multicellular 3D pancreatic tumor models. These spheroids were grown in attachment-free conditions before embedding in combinations of rheologically characterized collagen 1 and Matrigel combinations and treated with oxaliplatin chemotherapy and PDT. We find that cells invading from collagen-embedded tumor spheroids, the least rigid ECM substrate described here, displayed better response to PDT than to oxaliplatin chemotherapy. Overall, our results support that ECM-mediated invading PDAC populations remain responsive to PDT in conditions that induce chemoresistance.

  4. Enhancing gingival biotype through chorion membrane with innovative step in periodontal pocket therapy.

    Science.gov (United States)

    Kothiwale, Shaila; Rathore, Amrita; Panjwani, Vishal

    2016-03-01

    A thick gingival biotype is a requisite for good periodontal health. It has important role in resisting trauma and subsequent gingival recession. The gingival thickness is a significant predictor of clinical outcome of periodontal surgeries. Various surgical procedures are used to increase the gingival thickness. The present study incorporated the innovative step of placement of chorion membrane to objectively evaluate the increase in thickness of gingival biotype during periodontal pocket therapy. The patients in age group between 25 and 45 years with chronic periodontitis, indicated for flap surgery were selected for the study. The sites with pocket depth of 6-8 mm in the mandibular anterior teeth were divided into test and control sites. Periodontal flap surgery was carried at both the sites and chorion membrane was placed at the test sites. The gingival thickness measurement was assessed using a markings marked on injection needle, these markings were read using digital vernier caliper, pre and post operatively. The baseline values of gingival thickness at test site (1.04 ± 0.19 at mid buccal region, 1.24 ± 0.20 at mid papillary) and control site (0.94 ± 0.11 at mid buccal region, 1.14 ± 0.11 at mid papillary region) showed no statistically significant difference. At test sites, 6 weeks post treatment (1.36 ± 0.16 at mid buccal region and 1.48 ± 0.17 at mid papillary region) as compared to control sites (1.06 ± 0.11 at mid buccal region, 1.24 ± 0.11 at mid papillary) showed statistically significant increase in gingival thickness (p ≤ 0.05*). The innovative step of placement of chorion membrane during periodontal pocket therapy facilitated increase in the gingival thickness in the areas with thin gingival biotype.

  5. Nanoparticle-enhanced synergistic HIFU ablation and transarterial chemoembolization for efficient cancer therapy

    Science.gov (United States)

    You, Yufeng; Wang, Zhigang; Ran, Haitao; Zheng, Yuanyi; Wang, Dong; Xu, Jinshun; Wang, Zhibiao; Chen, Yu; Li, Pan

    2016-02-01

    High-intensity focused ultrasound (HIFU) is being generally explored as a non-invasive therapeutic modality to treat solid tumors. However, the clinical use of HIFU for large and deep tumor-ablation applications such as hepatocellular carcinoma (HCC) is currently entangled with long treatment duration and high operating energy. This critical issue can be potentially resolved by the introduction of HIFU synergistic agents (SAs). Traditional SAs such as microbubbles and microparticles face the problem of large size, short cycle time, damage to mononuclear phagocytic system and unsatisfactory targeting efficiency. In this work, we have developed a facile and versatile nanoparticle-based HIFU synergistic cancer surgery enhanced by transarterial chemoembolization for high-efficiency HCC treatment based on elaborately designed Fe3O4-PFH/PLGA nanocapsules. Multifunctional Fe3O4-PFH/PLGA nanocapsules were administrated into tumor tissues via transarterial injection combined with Lipiodol to achieve high tumor accumulation because transarterial chemoembolization by Lipiodol could block the blood vessels. The high synergistic HIFU ablation effect was successfully achieved against HCC tumors based on the phase-transformation performance of the perfluorohexane (PFH) inner core in the composite nanocapsules, as systematically demonstrated in VX2 liver tumor xenograft in rabbits. Multifunctional Fe3O4-PFH/PLGA nanocapsules were also demonstrated as efficient contrast agents for ultrasound, magnetic resonance and photoacoustic tri-modality imagings, potentially applicable for imaging-guided HIFU synergistic surgery. Therefore, the elaborate integration of traditional transarterial chemoembolization with recently developed nanoparticle-enhanced HIFU cancer surgery could efficiently enhance the HCC cancer treatment outcome, initiating a new and efficient therapeutic protocol/modality for clinic cancer treatment.

  6. Enhanced Tumor Accumulation of Sub-2 nm Gold Nanoclusters for Cancer Radiation Therapy

    CERN Document Server

    Zhang, Xiao-Dong; Luo, Zhentao; Wu, Di; Shen, Xiu; Song, Sha-Sha; Sun, Yuan-Ming; Liu, Pei-Xun; Zhao, Jing; Huo, Shuaidong; Fan, Saijun; Fan, Feiyue; Liang, Xing-Jie; Xie, Jianping

    2013-01-01

    A new type of metabolizable and efficient radiosensitizer for cancer radiotherapy is presented in this study by combining ultrasmall Au nanoclusters (NCs, <2 nm) with biocompatible coating ligands (glutathione, GSH). The new nano-construct (GSH-coated Au25 NCs) inherits attractive features of both the Au core (strong radiosensitizing effect) and GSH shell (good biocompatibility). It can preferentially accumulate in tumor via the improved EPR effect, which leads to strong enhancement for cancer radiotherapy. After the treatment, the small-sized GSH-Au25 NCs can be efficiently cleared by the kidney, minimizing any potential side effects due to the accumulation of Au25 NCs in the body.

  7. Enhancer of zeste homolog 2: A potential target for tumor therapy.

    Science.gov (United States)

    Xiao, Yongtao

    2011-04-01

    Enhancer of zeste homolog 2 (EZH2) is a subunit of the Polycomb-Repressive Complex 2 (PRC2), which catalyses the trimethylation of histone H3 on Lys 27 (H3K27) and involves in genes repression. EZH2 is amplified and overexpressed in a variety of cancers, including prostate and breast cancer. Overexpression of EZH2 has been associated with the invasion and progression of malignant cancers, especially with the progression of prostate cancer. Here, we review the structure and biological function of EZH2, especially focused on its activities in the tumorigenesis. Copyright © 2011 Elsevier Ltd. All rights reserved.

  8. 5-Fluorouracil as an enhancer of aminolevulinate-based photodynamic therapy for skin cancer: New use for a venerable agent?

    Science.gov (United States)

    Maytin, Edward V.; Anand, Sanjay; Wilson, Clara; Iyer, Karthik

    2011-02-01

    5-Fluorouracil (5-FU) was developed in the 1950s as an anticancer drug and is now widely used to treat many cancers, including colon and breast carcinoma. 5-FU causes fluoronucleotide misincorporation into RNA and DNA, inhibits thymidylate synthase, and leads to growth arrest and apoptosis. For skin precancers (actinic keratoses; AK), 5-FU is prescribed as a topical agent and was essentially the only option for treating widespread AK of the skin prior to FDA approval of photodynamic therapy (PDT) in 1999. PDT is now gradually replacing 5-FU as a preferred treatment for AK, but neither PDT nor 5-FU are effective for true skin cancers (basal or squamous cell), particularly for tumors >1 mm in depth. In our ongoing work to improve the efficacy of PDT for skin cancer, we previously showed that PDT efficacy can be significantly enhanced by preconditioning tumors with methotrexate (MTX), which leads to increased production of protoporphyrin IX (PpIX) in target cells. However, because MTX must be given orally or intravenously, it is considered unacceptable for widespread human use due to potential toxicity. MTX and 5-FU exert similar effects on the thymidylate synthesis pathway, so we reasoned that topical 5-FU could be a potential alternative to MTX. In this paper, exploratory studies that test 5-FU as a preconditioning agent for PDT are presented. In a cutaneous model of squamous cell carcinoma (chemically-induced papillomatous tumors in mice), 5-FU significantly enhances PpIX accumulation and therefore emerges as a new candidate agent for combination therapy with PDT.

  9. DNA-Mutation Inventory to Refine and Enhance Cancer Treatment (DIRECT): a catalog of clinically relevant cancer mutations to enable genome-directed anticancer therapy.

    Science.gov (United States)

    Yeh, Paul; Chen, Heidi; Andrews, Jenny; Naser, Riyad; Pao, William; Horn, Leora

    2013-04-01

    Tumor gene mutation status is becoming increasingly important in the treatment of patients with cancer. A comprehensive catalog of tumor gene-response outcomes from individual patients is needed, especially for actionable mutations and rare variants. We created a proof-of-principle database [DNA-mutation Inventory to Refine and Enhance Cancer Treatment (DIRECT)], starting with lung cancer-associated EGF receptor (EGFR) mutations, to provide a resource for clinicians to prioritize treatment decisions based on a patient's tumor mutations at the point of care. A systematic search of literature published between June 2005 and May 2011 was conducted through PubMed to identify patient-level, mutation-drug response in patients with non-small cell lung cancer (NSCLC) with EGFR mutant tumors. Minimum inclusion criteria included patient's EGFR mutation, corresponding treatment, and an associated radiographic outcome. A total of 1,021 patients with 1,070 separate EGFR tyrosine kinase inhibitor therapy responses from 116 different publications were included. About 188 unique EGFR mutations occurring in 207 different combinations were identified: 149 different mutation combinations were associated with disease control and 42 were associated with disease progression. Four secondary mutations, in 16 different combinations, were associated with acquired resistance. As tumor sequencing becomes more common in oncology, this comprehensive electronic catalog can enable genome-directed anticancer therapy. DIRECT will eventually encompass all tumor mutations associated with clinical outcomes on targeted therapies. Users can make specific queries at http://www.mycancergenome.org/about/direct to obtain clinically relevant data associated with various mutations. ©2013 AACR.

  10. Double-targeted and double-enhanced suicide gene therapy mediated by generation 5 polyamidoamine dendrimers for prostate cancer.

    Science.gov (United States)

    Chen, Yue; Wang, Gang; Kong, Deling; Zhang, Zhihong; Yang, Kuo; Liu, Ranlu; Zhao, Weiming; Xu, Yong

    2013-03-01

    Herpes simplex virus (HSV)-thymidine kinase (TK)/ganciclovir (GCV) system is one of the most widely used and efficient suicide gene therapy for prostate cancer, but the lack of favorable gene vector and target limits its application. In this study, we established a novel system using nonviral gene vector G5-PAMAM-D to express HSV-TK and connexin43 (Cx43) gene driven by prostate-specific membrane antigen (PSMA) promoter, and evaluated the anti-tumor effect of this system. G5-PAMAM-D delivered PSMAe/p-TK-Cx43 showed expression of TK and Cx43 only in LNCaP cells, but not in PC-3 and other cells. The transfection efficiency of this system was comparable to lipofectamine 2000 by propidium iodide staining assay. With gemcitabine, folate-G5-PAMAM-D delivered PSMAe/p-TK-Cx43 (folate-G5-PAMAM-D/PSMAe/p-TK-Cx43) significantly decreased prostate cancer LNCaP cell proliferation and promoted apoptosis in vitro. With gemcitabine, the systemic deliver of folate-G5-PAMAM-D/PSMAe/p-TK-Cx43 significantly inhibited tumor growth in the LNCaP xenograft animal model. Our study demonstrates that this double-targeted and double-enhanced system is effective in inducing cell growth inhibition and apoptosis in vitro and suppressing tumor growth in vivo. In conclusion, Cx43 and gemcitabine combined with HSV-TK/GCV gene therapy using nonviral vector G5-PAMAM-D hold great potential as a novel approach for the gene therapy of prostate cancer. Copyright © 2011 Wiley Periodicals, Inc.

  11. Chaperone therapy for neuronopathic lysosomal diseases: competitive inhibitors as chemical chaperones for enhancement of mutant enzyme activities.

    Science.gov (United States)

    Suzuki, Yoshiyuki; Ogawa, Seiichiro; Sakakibara, Yasubumi

    2009-05-26

    Chaperone therapy is a newly developed molecular approach to lysosomal diseases, a group of human genetic diseases causing severe brain damage. We found two valienamine derivatives, N-octyl-4-epi-beta-valienamine (NOEV) and N-octyl-beta-valienamine (NOV), as promising therapeutic agents for human beta-galactosidase deficiency disorders (mainly G(M1)-gangliosidosis) and beta-glucosidase deficiency disorders (Gaucher disease), respectively. We briefly reviewed the historical background of research in carbasugar glycosidase inhibitors. Originally NOEV and NOV had been discovered as competitive inhibitors, and then their paradoxical bioactivities as chaperones were confirmed in cultured fibroblasts from patients with these disorders. Subsequently G(M1)-gangliosidosis model mice were developed and useful for experimental studies. Orally administered NOEV entered the brain through the blood-brain barrier, enhanced beta-galactosidase activity, reduced substrate storage, and improved neurological deterioration clinically. Furthermore, we executed computational analysis for prediction of molecular interactions between beta-galactosidase and NOEV. Some preliminary results of computational analysis of molecular interaction mechanism are presented in this article. NOV also showed the chaperone effect toward several beta-glucosidase gene mutations in Gaucher disease. We hope chaperone therapy will become available for some patients with G(M1)-gangliosidosis, Gaucher disease, and potentially other lysosomal storage diseases with central nervous system involvement.

  12. Mechanisms of Functional Improvement in a Two-Year Trial of Cognitive Enhancement Therapy for Early Schizophrenia

    Science.gov (United States)

    Eack, Shaun M.; Pogue-Geile, Michael F.; Greenwald, Deborah P.; Hogarty, Susan S.; Keshavan, Matcheri S.

    2013-01-01

    Background Cognitive rehabilitation has emerged as an effective treatment for addressing cognitive impairments and functional disability in schizophrenia; however, the degree to which changes in various social and non-social cognitive processes translate into improved functioning during treatment remains unclear. This research sought to identify the neurocognitive and social-cognitive mechanisms of functional improvement during a two-year trial of Cognitive Enhancement Therapy (CET) for early course schizophrenia. Method Patients in the early course of schizophrenia were randomly assigned to CET (n = 31) or an Enriched Supportive Therapy control (n = 27) and treated for up to two years. A comprehensive neurocognitive assessment battery and the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT) were completed annually, along with measures of functioning. Mediator analyses using mixed-effects growth models were conducted to examine the effects of neurocognitive and social-cognitive improvement on functional change. Results Two-year improvement in neurocognition and the emotion management branch of the MSCEIT were found to be significantly related to improved functional outcome in early course schizophrenia patients. Neurocognitive improvement, primarily in executive functioning, and social-cognitive change in emotion management also mediated the robust effects of CET on functioning. Conclusions Improvements in neurocognition and social cognition that result from cognitive rehabilitation are both significant mediators of functional improvement in early course schizophrenia. Cognitive rehabilitation programs for schizophrenia may need to target deficits in both social and non-social cognition to achieve an optimal functional response. PMID:20860867

  13. Focused ultrasound enhanced molecular imaging and gene therapy for multifusion reporter gene in glioma-bearing rat model.

    Science.gov (United States)

    Yang, Feng-Yi; Chang, Wen-Yuan; Lin, Wei-Ting; Hwang, Jeng-Jong; Chien, Yi-Chun; Wang, Hsin-Ell; Tsai, Min-Lan

    2015-11-03

    The ability to monitor the responses of and inhibit the growth of brain tumors during gene therapy has been severely limited due to the blood-brain barrier (BBB). A previous study has demonstrated the feasibility of noninvasive in vivo imaging with 123I-2'-fluoro-2'-deoxy-5-iodo-1-β-D-arabinofuranosyluracil (123I-FIAU) for monitoring herpes simplex virus type 1 thymidine kinase (HSV1-tk) cancer gene expression in an experimental animal model. Here, we tested the enhancement of SPECT with 123I-FIAU and ganciclovir (GCV) treatment in brain tumors after BBB disruption induced by focused ultrasound (FUS) in the presence of microbubbles. We established an orthotopic F98 glioma-bearing rat model with trifusion reporter genes. The results of this study showed that the rat model of HSV1-tk-expressing glioma cells could be successfully detected by SPECT imaging after FUS-induced BBB disruption on day 10 after implantation. Compared to the control group, animals receiving the GCV with or without sonication exhibited a significant antitumor activity (P therapy in brain diseases.

  14. Immediate Anti-tumor Necrosis Factor-α (Etanercept) Therapy Enhances Axonal Regeneration After Sciatic Nerve Crush

    Science.gov (United States)

    Kato, Kinshi; Liu, Huaqing; Kikuchi, Shin-ichi; Myers, Robert R.; Shubayev, Veronica I.

    2015-01-01

    Peripheral nerve regeneration begins immediately after injury. Understanding the mechanisms by which early modulators of axonal degeneration regulate neurite outgrowth may affect the development of new strategies to promote nerve repair. Tumor necrosis factor-α (TNF-α) plays a crucial role in the initiation of degenerative cascades after peripheral nerve injury. Here we demonstrate using real-time Taqman quantitative RT-PCR that, during the time course (days 1–60) of sciatic nerve crush, TNF-α mRNA expression is induced at 1 day and returned to baseline at 5 days after injury in nerve and the corresponding dorsal root ganglia (DRG). Immediate therapy with the TNF-α antagonist etanercept (fusion protein of TNFRII and human IgG), administered systemically (i.p.) and locally (epineurially) after nerve crush injury, enhanced the rate of axonal regeneration, as determined by nerve pinch test and increased number of characteristic clusters of regenerating nerve fibers distal to nerve crush segments. These fibers were immunoreactive for growth associated protein-43 (GAP-43) and etanercept, detected by anti-human IgG immunofluorescence. Increased GAP-43 expression was found in the injured nerve and in the corresponding DRG and ventral spinal cord after systemic etanercept compared with vehicle treatments. This study established that immediate therapy with TNF-α antagonist supports axonal regeneration after peripheral nerve injury. PMID:19746434

  15. Enhanced delivery of gold nanoparticles by acoustic cavitation for photoacoustic imaging and photothermal therapy

    Science.gov (United States)

    Wang, Yu-Hsin; Liao, Ai-Ho; Lin, Jia-Yu; Lee, Cheng-Ru; Wu, Cheng-Ham; Liu, Tzu-Min; Wang, Churng-Ren; Li, Pai-Chi

    2013-03-01

    Gold-nanorods incorporated with microbubbles (AuMBs) were introduced as a photoacoustic/ultrasound dual- modality contrast agent in our previous study. The application can be extended to theragnosis purpose. With the unique physical characteristics of AuMBs, we propose an enhanced delivery method for the encapsulated particles. For example, laser thermotherapy mediated by plasmonic nanoparticles can be made more effective by using microbubbles as a targeted carrier and acoustic cavitation for enhanced sonoporation. The hypothesis was experimentally tested. Firts, these AuMBs first act as molecular probes with binding to specific ligands. The improved targeting efficacy was macroscopically observed by an ultrasound system. The extended retention of targeted AuMB was observed and recorded for 30 minutes in a CT-26 tumor bearing mouse. Secondly, cavitation induced by time-varying acoustic field was also applied to disrupt the microbubbles and cause increased transient cellular permeability (a.k.a., sonoporation). Multimodal optical microscope based on a Cr:forsterite laser was used to directly observe these effects. The microscope can acquired third-harmonic generation (THG) and two-photon fluorescent (2PF) signals produced by the AuMBs. In vitro examination shows approximately a 60% improvement in terms of fluorescence signals from the cellular uptake of gold nanoparticles after sonoporation treatment. Therefore, we conclude that the controlled release is feasible and can further improve the therapeutic effects of the nanoparticles.

  16. Examining the effects of enhanced provider-patient communication on postoperative tonsillectomy pain: protocol of a randomised controlled trial performed by nurses in daily clinical care.

    Science.gov (United States)

    van Vliet, Liesbeth M; van Dulmen, Sandra; Thiel, Bram; van Deelen, Gerard W; Immerzeel, Stephanie; Godfried, Marc B; Bensing, Jozien M

    2017-11-03

    Placebo effects (true biopsychological effects not attributable to the active ingredients of medical technical interventions) can be attributed to several mechanisms, such as expectancy manipulation and empathy manipulation elicited by a provider's communication. So far, effects have primarily been shown in laboratory settings. The aim of this study is to determine the separate and combined effects of expectancy manipulation and empathy manipulation during preoperative and postoperative tonsillectomy analgesia care on clinical adult patients' outcomes. Using a two-by-two randomised controlled trial, 128 adult tonsillectomy patients will be randomly assigned to one out of four conditions differing in the level of expectancy manipulation (standard vs enhanced) and empathy manipulation (standard vs enhanced). Day care ward nurses are trained to deliver the intervention, while patients are treated via the standard analgesia protocol and hospital routines. The primary outcome, perceived pain, is measured via hospital routine by a Numeric Rating Scale, and additional prehospitalisation, perihospitalisation and posthospitalisation questionnaires are completed (until day 3, ie, 2 days after the operation). The manipulation is checked using audio recordings of nurse-patient interactions. Although communication is manipulated, the manipulations do not cross norms or values of acceptable behaviour. Standard medical care is provided. The ethical committee of the UMC Utrecht and the local OLVG hospital committee approved the study. Results will be published via (inter)national peer-reviewed journals and a lay publication. NTR5994; Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  17. An online virtual-patient program to teach pharmacists and pharmacy students how to provide diabetes-specific medication therapy management.

    Science.gov (United States)

    Battaglia, Jessica N; Kieser, Mara A; Bruskiewitz, Ruth H; Pitterle, Michael E; Thorpe, Joshua M

    2012-09-10

    To develop, implement, and assess the effectiveness of an online medication therapy management (MTM) program to train pharmacists and pharmacy students in providing MTM services for patients with diabetes and to increase their intent to perform these services. An online program was created using an Internet-based learning platform to simulate 4 MTM meetings between a pharmacist and a virtual patient diagnosed with diabetes. Eighty students and 42 pharmacists completed the program. After completing the program, scores on post-intervention assessments showed significant improvement in 2 areas: control over performing MTM, and knowledge of how to perform MTM. Students had a significantly less-positive attitude about MTM and a decline in their perception of the social expectation that MTM is part of the practice of pharmacy, while pharmacists' attitudes did not change significantly in these areas. This online program using a virtual patient improved both participants' belief that they have control over performing MTM, and their knowledge of how to perform MTM for diabetic patients, which may increase the likelihood that pharmacists and pharmacy students will perform MTM in the future.

  18. Bitargeted microemulsions based on coix seed ingredients for enhanced hepatic tumor delivery and synergistic therapy.

    Science.gov (United States)

    Qu, Ding; Sun, Wenjie; Liu, Mingjian; Liu, Yuping; Zhou, Jing; Chen, Yan

    2016-04-30

    A hepatic tumor bitargeted microemulsions drug delivery system using coix seed oil and coix seed polysaccharide (CP) acting as anticancer components, as well as functional excipients, was developed for enhanced tumor-specific accumulation by CP-mediated enhancement on passive tumor targeting and modification of galactose stearate (tumor-targeted ligand). In the physicochemical characteristics studies, galactose stearate-modified coix seed multicomponent microemulsions containing 30% CP (w%) (Gal-C-MEs) had a well-defined spherical shape with a small size (47.63 ± 1.41 nm), a narrow polydispersity index (PDI, 0.101 ± 0.002), and a nearly neutral surface charge (-4.37 ± 1.76 mV). The half-maximal inhibitory concentration (IC50) of Gal-C-MEs against HepG2 cells was 70.2 μg/mL, which decreased by 1.8-fold in comparison with that of coix seed multicomponent microemulsions (C-MEs). The fluorescence intensity of fluorescein isothiocyanate (FITC)-loaded Gal-C-MEs (FITC-Gal-C-MEs) internalized by HepG2 cells was 1.8-fold higher than that of FITC-loaded C-MEs (FIT C-C-MEs), but the cellular uptake of the latter became reduce by 1.6-fold when the weight ratio of CP decreased up to 10%. In the cell apoptosis studies, C-MEs (containing 30% CP) did not show a significant difference with Gal-C-MEs, but exhibited 3.3-fold and 1.5-fold increase relative to C-MEs containing 10% CP and 20% CP, respectively. In the in vivo tumor targeting studies, Cy5-loaded Gal-C-MEs (Cy5-Gal-C-MEs), notably distributed in the tumor sites and still found even at 48 h post-administration, displayed the strongest capability of tumor tissue accumulation and retention among all the test groups. Most importantly, Gal-C-MEs had stronger inhibition of tumor growth, prolonged survival time and more effectively tumor cell apoptosis induction in comparison with C-MEs containing different amounts of CP, which further confirmed that a certain amount of CP and tumor-targeted ligand were of great importance to

  19. Heme Oxygenase-1 Gene Therapy Provides Cardioprotection Via Control of Post-Ischemic Inflammation: An Experimental Study in a Pre-Clinical Pig Model.

    Science.gov (United States)

    Hinkel, Rabea; Lange, Philipp; Petersen, Björn; Gottlieb, Elena; Ng, Judy King Man; Finger, Stefanie; Horstkotte, Jan; Lee, Seungmin; Thormann, Michael; Knorr, Maike; El-Aouni, Chiraz; Boekstegers, Peter; Reichart, Bruno; Wenzel, Philip; Niemann, Heiner; Kupatt, Christian

    2015-07-14

    Heme oxygenase-1 (HO-1) is an inducible stress-responsive enzyme converting heme to bilirubin, carbon monoxide, and free iron, which exerts anti-inflammatory and antiapoptotic effects. Although efficient cardioprotection after HO-1 overexpression has been reported in rodents, its role in attenuating post-ischemic inflammation is unclear. This study assessed the efficacy of recombinant adenoassociated virus (rAAV)-encoding human heme oxygenase-1 (hHO-1) in attenuating post-ischemic inflammation in a murine and a porcine ischemia/reperfusion model. Murine ischemia was induced by 45 min of left anterior descending occlusion, followed by 24 h of reperfusion and functional as well as fluorescent-activated cell sorting analysis. Porcine hearts were subjected to 60 min of ischemia and 24h of reperfusion before hemodynamic and histologic analyses were performed. Human microvascular endothelial cells transfected with hHO-1 displayed an attenuated interleukin-6 and intercellular adhesion molecule 1 expression, resulting in reduced monocytic THP-1 cell recruitment in vitro. In murine left anterior descending occlusion and reperfusion, the post-ischemic influx of CD45(+) leukocytes, Ly-6G(+) neutrophils, and Ly-6C(high) monocytes was further exacerbated in HO-1-deficient hearts and reversed by rAAV.hHO-1 treatment. Conversely, in our porcine model of ischemia, the post-ischemic influx of myeloperoxidase-positive neutrophils and CD14(+) monocytes was reduced by 49% and 87% after rAAV.hHO-1 transduction, similar to hHO-1 transgenic pigs. Functionally, rAAV.hHO-1 and hHO-1 transgenic left ventricles displayed a smaller loss of ejection fraction than control animals. Whereas HO-1 deficiency exacerbates post-ischemic cardiac inflammation in mice, hHO-1 gene therapy attenuates inflammation after ischemia and reperfusion in murine and porcine hearts. Regional hHO-1 gene therapy provides cardioprotection in a pre-clinical porcine ischemia/reperfusion model. Copyright © 2015 American

  20. Family Therapy

    Science.gov (United States)

    Family therapy Overview By Mayo Clinic Staff Family therapy is a type of psychological counseling (psychotherapy) that can help family members improve communication and resolve conflicts. Family therapy is usually provided ...

  1. Assessing lung function using contrast-enhanced dual-energy computed tomography for potential applications in radiation therapy.

    Science.gov (United States)

    Lapointe, Andréanne; Bahig, Houda; Blais, Danis; Bouchard, Hugo; Filion, Édith; Carrier, Jean-François; Bedwani, Stéphane

    2017-10-01

    There is an increasing interest in the evaluation of lung function from physiological images in radiation therapy treatment planning to reduce the extent of postradiation toxicities. The purpose of this work was to retrieve reliable functional information from contrast-enhanced dual-energy computed tomography (DECT) for new applications in radiation therapy. The functional information obtained by DECT is also compared with other methods using single-energy CT (SECT) and single-photon emission computed tomography (SPECT) with CT. The differential function between left and right lung, as well as between lobes is computed for all methods. Five lung cancer patients were retrospectively selected for this study; each underwent a SPECT/CT scan and a contrast-injected DECT scan, using 100 and 140 Sn kVp. The DECT images are postprocessed into iodine concentration maps, which are further used to determine the perfused blood volume. These maps are calculated in two steps: (a) a DECT stoichiometric calibration adapted to the presence of iodine and followed by (b) a two-material decomposition technique. The functional information from SECT is assumed proportional to the HU numbers from a mixed CT image. The functional data from SPECT/CT are considered proportional to the number of counts. A radiation oncologist segmented the entire lung volume into five lobes on both mixed CT images and low-dose CT images from SPECT/CT to allow a regional comparison. The differential function for each subvolume is computed relative to the entire lung volume. The differential function per lobe derived from SPECT/CT correlates strongly with DECT (Pearson's coefficient r = 0.91) and moderately with SECT (r = 0.46). The differential function for the left lung shows a mean difference of 7% between SPECT/CT and DECT; and 17% between SPECT/CT and SECT. The presence of nonfunctional areas, such as localized emphysema or a lung tumor, is reflected by an intensity drop in the iodine concentration maps

  2. Cognitive behavioral therapy for insomnia enhances depression outcome in patients with comorbid major depressive disorder and insomnia.

    Science.gov (United States)

    Manber, Rachel; Edinger, Jack D; Gress, Jenna L; San Pedro-Salcedo, Melanie G; Kuo, Tracy F; Kalista, Tasha

    2008-04-01

    Insomnia impacts the course of major depressive disorder (MDD), hinders response to treatment, and increases risk for depressive relapse. This study is an initial evaluation of adding cognitive behavioral therapy for insomnia (CBTI) to the antidepressant medication escitalopram (EsCIT) in individuals with both disorders. A randomized, controlled, pilot study in a single academic medical center. 30 individuals (61% female, mean age 35 +/- 18) with MDD and insomnia. EsCIT and 7 individual therapy sessions of CBTI or CTRL (quasi-desensitization). Depression was assessed with the HRSD17 and the depression portion of the SCID, administered by raters masked to treatment assignment, at baseline and after 2, 4, 6, 8, and 12 weeks of treatment. The primary outcome was remission of MDD at study exit, which required both an HRSD17 score depression (61.5%) than EsCIT + CTRL (33.3%). EsCIT + CBTI was also associated with a greater remission from insomnia (50.0%) than EsCIT + CTRL (7.7%) and larger improvement in all diary and actigraphy measures of sleep, except for total sleep time. This pilot study provides evidence that augmenting an antidepressant medication with a brief, symptom focused, cognitive-behavioral therapy for insomnia is promising for individuals with MDD and comorbid insomnia in terms of alleviating both depression and insomnia.

  3. Prompt gamma ray diagnostics and enhanced hadron-therapy using neutron-free nuclear reactions

    Directory of Open Access Journals (Sweden)

    L. Giuffrida

    2016-10-01

    Full Text Available We propose a series of simulations about the potential use of Boron isotopes to trigger neutron-free (aneutronic nuclear reactions in cancer cells through the interaction with an incoming energetic proton beam, thus resulting in the emission of characteristic prompt gamma radiation (429 keV, 718 keV and 1435 keV. Furthermore assuming that the Boron isotopes are absorbed in cancer cells, the three alpha-particles produced in each p-11B aneutronic nuclear fusion reactions can potentially result in the enhancement of the biological dose absorbed in the tumor region since these multi-MeV alpha-particles are stopped inside the single cancer cell, thus allowing to spare the surrounding tissues. Although a similar approach based on the use of 11B nuclei has been proposed in [Yoon et al. Applied Physics Letters 105, 223507 (2014], our work demonstrate, using Monte Carlo simulations, the crucial importance of the use of 10B nuclei (in a solution containing also 11B for the generation of prompt gamma-rays, which can be applied to medical imaging. In fact, we demonstrate that the use of 10B nuclei can enhance the intensity of the 718 keV gamma-ray peak more than 30 times compared to the solution containing only 11B nuclei. A detailed explanation of the origin of the different prompt gamma-rays, as well as of their application as real-time diagnostics during a potential cancer treatment, is here discussed.

  4. Neurofeedback therapy for enhancing visual attention: state-of-the-art and challenges

    Directory of Open Access Journals (Sweden)

    Mehdi Ordikhani-Seyedlar

    2016-08-01

    Full Text Available We have witnessed a rapid development of brain-computer interfaces (BCIs linking the brain to external devices. BCIs can be utilized to treat neurological conditions and even to augment brain functions. BCIs offer a promising treatment for mental disorders, including disorders of attention. Here we review the current state of the art and challenges of attention-based BCIs, with a focus on visual attention. Attention-based BCIs utilize electroencephalograms (EEGs or other recording techniques to generate neurofeedback, which patients use to improve their attention, a complex cognitive function. Although progress has been made in the studies of neural mechanisms of attention, extraction of attention-related neural signals needed for BCI operations is a difficult problem. To attain good BCI performance, it is important to select the features of neural activity that represent attentional signals. BCI decoding of attention-related activity may be hindered by the presence of different neural signals. Therefore, BCI accuracy can be improved by signal processing algorithms that dissociate signals of interest from irrelevant activities. Notwithstanding recent progress, optimal processing of attentional neural signals remains a fundamental challenge for the development of efficient therapies for disorders of attention.

  5. Coming Together to Move Apart: Family Therapy for Enhancing Adolescent Development.

    Science.gov (United States)

    Abrams, Madeleine Seifter

    2015-01-01

    An important goal of adolescent development is emotional separation from the family of origin. Differing views on how to accomplish this task exist, and these are reflected in the choice of treatment modality. It has been common practice in the treatment of adolescents for work with parents to be done separately from the adolescent. Since social, cultural, and economic factors have an impact on development, as society changes it is important to think creatively about effective ways to accomplish the process of becoming a functioning adult. It is in this context that authors have focused recently on the need for young adults to have a positive connection with their parents. This paper will address the role of involvement of family in the psychotherapy of adolescents either by inviting them to participate in some of the individual sessions or through conjoint family therapy to facilitate forward development. Clinical illustrations will demonstrate the issues of an adolescent with unresolved early traumatic separation, an adolescent who is fulfilling parental needs, an adolescent with too much power in the family, the importance of beginning treatment after assessing where everyone is emotionally, and the problem of premature disconnection by parents.

  6. A Simulation Study on the Feasibility of Radio Enhancement Therapy with Calcium Tungstate and Hafnium Oxide Nanoparticles

    CERN Document Server

    Sherck, Nicholas J

    2016-01-01

    Herein is a simulation study on the radio enhancement potential of calcium tungstate (CaWO4) and hafnium oxide (HfO2) nanoparticles (NPs) relative to gold (Au) NPs. The work utilizes the extensively studied Au NP as the "gold standard" to which the novel materials can be compared. All three materials were investigated in-silico with the software Penetration and Energy Loss of Positrons and Electrons (PENELOPE) developed by Francesc Salvat and distributed in the United States by the Radiation Safety Information Computational Center (RSICC) at Oak Ridge National Laboratory. The aims are: (1) Do CaWO4 and HfO2 NPs function like Au?, and (2) if not, how else might they function to enhance radio therapy? Our investigations have found that HfO2 likely functions as Au, but not as effectively. CaWO4 likely does not function as Au, and we propose that CaWO4 may exhibit cancer killing traits through its intrinsic UV luminescence property.

  7. Enhanced angiogenic effect of adipose-derived stromal cell spheroid with low-level light therapy in hindlimb ischemia mice

    Science.gov (United States)

    Park, In-Su; Ahn, Jin-Chul; Chung, Phil-Sang

    2014-02-01

    Adipose-derived stromal cells (ASCs) are attractive cell source for tissue engineering. However, one obstacle to this approach is that the transplanted ASC population can decline rapidly in the recipient tissue. The aim of this study was to investigate the effects of low-level laser therapy (LLLT) on transplanted human ASCs (hASCs) spheroid in a hindlimb ischemia animal model. LLLT, hASCs spheroid and hASCs spheroid transplantation with LLLT (spheroid + LLLT) were applied to the ischemic hindlimbs in athymic mice. The survival, differentiation and secretion of vascular endothelial growth (VEGF) of spheroid ASCs were evaluated by immunohistochemistry. The spheroid + LLLT group enhanced the tissue regeneration, including angiogenesis, compared with other groups. The spheroid contributed tissue regeneration via differentiation and secretion of growth factors. In the spheroid + LLLT group, the survival of spheroid hASCs was increased by the decreased apoptosis of spheroid hASCs in the ischemic hindlimb. The secretion of growth factors was stimulated in the spheroid + LLLT group compared with the ASCs group and spheroid group. These data suggest that LLLT is an effective biostimulator of spheroid hASCs in tissue regeneration that enhances the survival of ASCs and stimulates the secretion of growth factors in the ischemic hindlimb.

  8. Cooperative Strategies for Enhancing Performance of Photothermal Therapy (PTT) Agent: Optimizing Its Photothermal Conversion and Cell Internalization Ability.

    Science.gov (United States)

    Du, Baoji; Ma, Chongbo; Ding, Guanyu; Han, Xu; Li, Dan; Wang, Erkang; Wang, Jin

    2017-04-01

    Photothermal conversion ability (PCA) and cell internalization ability (CIA) are two key factors for determining the performance of photothermal agents. The previous studies mostly focus on improving the PCA by exploring new photothermal nanomaterials. Herein, the authors take the hybrids of graphene and gold nanostar (GGN) as an example to investigate the gradually enhanced phototherapy effect by changing the PCA and CIA of photothermal therapy (PTT) agent simultaneously. Based on the GGN, the GGN and the reduced GGN protected by bovine serum albumin (BSA) or BSA-FA (folic acid) are prepared, which are named as GGNB, rGGNB, and rGGNB-FA, respectively. The rGGNB showed an enhanced PCA compared to GGNB, leading to strong cell ablation. On the other hand, the 1,2-dioleoyl-3-trimethylammoniumpropan (DOTAP) can activate the endocytosis and promote the CIA of rGGNB, further help rGGNB to be more internalized into the cells. Finally, rGGNB-FA with the target ability can make itself further internalized into the cells with the aid of DOTAP, which can significantly destroy the cancer cells even at the low laser density of 0.3 W cm-2 . Therefore, a new angle of view is brought out for researching the PTT agents of high performance. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Effects of hyperbaric oxygen therapy in enhancing expressions of e-NOS, TNF-α and VEGF in wound healing

    Science.gov (United States)

    Susilo, Imam; Devi, Anita; Purwandhono, Azham; Hadi Warsito, Sunaryo

    2017-05-01

    Wound healing is a physiological process that occurs progressively through overlapping phases. Tissue oxygenation is an important part of the complex regulation for wound healing. Hyperbaric Oxygen (HBO) therapy is a method of increasing oxygen delivery to tissues. The therapy improves tissue oxygenation and stimulates the formation of H2O2 as a secondary messenger for Tumour Necrosis Factor alpha (TNF α), e-NOS, VEGF and Nuclear Factor Kappa Beta phosphorylation (NF-Kb) which play an important role in the rapid transcription of a wide variety of genes in response to extracellular stimuli. This study aims to determine the effects of Hyperbaric Oxygen therapy in enhancing the expressions of e-NOS, TNF-α, VEGF and wound healing. This study is an animal study with a ‘randomized control group of pre-test and post test design’ on 28 Wistar rats. Randomly, the rats were divided into 4 groups with 7 rats in each group. The HBO treatment group 1 received 5 sessions of HBO 2.4 ATA in 3 × 30 minutes; the HBO treatment group 2 received 10 sessions of HBO 2.4 ATA in 3 × 30 minutes; and each of the control groups were without HBO. Each of the 28 male rats were given a full thickness excisional wound of 1 × 1cm. Examinations of e-NOS, TNF-α, VEGF expressions and wound healing were performed on day-0 (pre-HBO) and day-5 HBO or on day-0 (pre-HBO) and day-10 HBO. The resultsshowthat the Hyperbaric Oxygen therapy can improve e-NOS (p=0.02), TNF-α (p= 0.02), VEGF expression (p=0.02) and wound healing (p=0.002) significantly in the provision of HBO 2.4 ATA for 3 × 30 minutes in 5 sessions over 5 consecutive days. While the 10 sessions of HBO 2.4 ATA for 3 × 30 minutes over 10 consecutive days only increase e-NOS (p=0.02), TNF-α (p=0.04), VEGF expression significantly (p=0.03) but do not improve wound healing significantly (p=0.3) compared with no HBO. The study concludes that HBO can improve the expressions of e-NOS, TNF-α, VEGF and wound healing in the provision of HBO

  10. Enhanced

    Directory of Open Access Journals (Sweden)

    Martin I. Bayala

    2014-06-01

    Full Text Available Land Surface Temperature (LST is a key parameter in the energy balance model. However, the spatial resolution of the retrieved LST from sensors with high temporal resolution is not accurate enough to be used in local-scale studies. To explore the LST–Normalised Difference Vegetation Index relationship potential and obtain thermal images with high spatial resolution, six enhanced image sharpening techniques were assessed: the disaggregation procedure for radiometric surface temperatures (TsHARP, the Dry Edge Quadratic Function, the Difference of Edges (Ts∗DL and three models supported by the relationship of surface temperature and water stress of vegetation (Normalised Difference Water Index, Normalised Difference Infrared Index and Soil wetness index. Energy Balance Station data and in situ measurements were used to validate the enhanced LST images over a mixed agricultural landscape in the sub-humid Pampean Region of Argentina (PRA, during 2006–2010. Landsat Thematic Mapper (TM and Moderate Resolution Imaging Spectroradiometer (EOS-MODIS thermal datasets were assessed for different spatial resolutions (e.g., 960, 720 and 240 m and the performances were compared with global and local TsHARP procedures. Results suggest that the Ts∗DL technique is the most adequate for simulating LST to high spatial resolution over the heterogeneous landscape of a sub-humid region, showing an average root mean square error of less than 1 K.

  11. Enhancing the Reach of Cognitive-Behavioral Therapy Targeting Posttraumatic Stress in Acute Care Medical Settings.

    Science.gov (United States)

    Darnell, Doyanne; O'Connor, Stephen; Wagner, Amy; Russo, Joan; Wang, Jin; Ingraham, Leah; Sandgren, Kirsten; Zatzick, Douglas

    2017-03-01

    Injured patients presenting to acute care medical settings have high rates of posttraumatic stress disorder (PTSD) and comorbidities, such as depression and substance use disorders. Integrating behavioral interventions that target symptoms of PTSD and comorbidities into the acute care setting can overcome common barriers to obtaining mental health care. This study examined the feasibility and acceptability of embedding elements of cognitive-behavioral therapy (CBT) in the delivery of routine postinjury care management. The investigation also explored the potential effectiveness of completion of CBT element homework that targeted PTSD symptom reduction. This study was a secondary analysis of data from a U.S. clinical trial of the effectiveness of a stepped collaborative care intervention versus usual care for injured inpatients. The investigation examined patients' willingness at baseline (prerandomization) to engage in CBT and pre- and postrandomization mental health service utilization among 115 patients enrolled in the clinical trial. Among intervention patients (N=56), the investigation examined acceptability of the intervention and used multiple linear regression to examine the association between homework completion as reported by the care manager and six-month PTSD symptom reduction as assessed by the PTSD Checklist-Civilian DSM-IV Version. Patients in the intervention condition reported obtaining significantly more psychotherapy or counseling than patients in the control group during the six-month follow-up, as well as a high degree of intervention acceptability. Completion of CBT element homework assignments was associated with improvement in PTSD symptoms. Integrating behavioral interventions into routine acute care service delivery may improve the reach of evidence-based mental health care targeting PTSD.

  12. Prompt gamma ray diagnostics and enhanced hadron-therapy using neutron-free nuclear reactions

    CERN Document Server

    Giuffrida, L; Cirrone, G A P; Picciotto, A; Korn, G

    2016-01-01

    We propose a series of simulations about the potential use of Boron isotopes to trigger neutron-free (aneutronic) nuclear reactions in cancer cells through the interaction with an incoming energetic proton beam, thus resulting in the emission of characteristic prompt gamma radiation (429 keV, 718 keV and 1435 keV). Furthermore assuming that the Boron isotopes are absorbed in cancer cells, the three alpha-particles produced in each p-11B aneutronic nuclear fusion reactions can potentially result in the enhancement of the biological dose absorbed in the tumor region since these multi-MeV alpha-particles are stopped inside the single cancer cell, thus allowing to spare the surrounding tissues. Although a similar approach based on the use of 11B nuclei has been proposed in [1], our work demonstrate, using Monte Carlo simulations, the crucial importance of the use of 10B nuclei (in a solution containing also 11B) for the generation of prompt gamma-rays, which can be applied to medical imaging. In fact, we demonstr...

  13. Antiplatelet effects of clopidogrel compared with aspirin after myocardial infarction: enhanced inhibitory effects of combination therapy.

    Science.gov (United States)

    Moshfegh, K; Redondo, M; Julmy, F; Wuillemin, W A; Gebauer, M U; Haeberli, A; Meyer, B J

    2000-09-01

    We sought to compare the inhibitory effects of the combination of two doses of aspirin plus clopidogrel with either drug alone on platelet aggregation and activation. Enhanced platelet inhibitory effects of clopidogrel by aspirin on platelet aggregation and activation are suggested by experimental studies but have not been shown in humans. The effects of clopidogrel 75 mg or aspirin 100 (300) mg on platelet aggregation and activation by flow cytometry after stimulation with various agonists were determined in 30 patients with a past history of myocardial infarction. Clopidogrel alone or in combination with aspirin markedly inhibited adenosine diphosphate (ADP)-mediated platelet aggregation compared with monotherapy with aspirin (24.6 +/- 3.3% or 26.6 +/- 2.7% vs. 44.7 +/- 2.9%; p after stimulation with ADP or thrombin (p after activation with low dose thrombin (p after stimulation with collagen and thrombin compared with monotherapies. Thus, this dual antiplatelet treatment strategy deserves further evaluation in clinical trials for secondary prevention of acute myocardial infarction or unstable angina.

  14. Enhancing RPE Cell-Based Therapy Outcomes for AMD: The Role of Bruch's Membrane.

    Science.gov (United States)

    Heller, Janosch P; Martin, Keith R

    2014-06-01

    Age-related macular degeneration (AMD) is the leading cause of legal blindness in older people in the developed world. The disease involves damage to the part of the retina responsible for central vision. Degeneration of retinal pigment epithelial (RPE) cells, photoreceptors, and choriocapillaris may contribute to visual loss. Over the past decades, scientists and clinicians have tried to replace lost RPE cells in patients with AMD using cells from different sources. In recent years, advances in generating RPE cells from stem cells have been made and clinical trials are currently evaluating the safety and efficiency of replacing the degenerated RPE cell layer with stem cell-derived RPE cells. However, the therapeutic success of transplantation of stem cell-derived RPE cells may be limited unless the transplanted cells can adhere and survive in the long term in the diseased eye. One hallmark of AMD is the altered extracellular environment of Bruch's membrane to which the grafted cells have to adhere. Here, we discuss recent approaches to overcome the inhibitory environment of the diseased eye and to enhance the survival rate of transplanted RPE cells. Our aim is to highlight novel approaches that may have the potential to improve the efficacy of RPE transplantation for AMD in the future.

  15. Selective transfection with osmotically active sorbitol modified PEI nanoparticles for enhanced anti-cancer gene therapy.

    Science.gov (United States)

    Nguyen, Kim Cuc Thi; Muthiah, Muthunarayanan; Islam, Mohammad Ariful; Kalash, R Santhosh; Cho, Chong-Su; Park, Hansoo; Lee, Il-Kwon; Kim, Hyeoung-Joon; Park, In-Kyu; Cho, Kyung A

    2014-07-01

    Polysorbitol-mediated transporter (PSMT) has been previously shown to achieve high transfection efficiency with minimal cytotoxicity. Polysorbitol backbone possesses osmotic properties and leads to enhanced cellular uptake. The PSMT/pDNA nanoparticles were prepared and the particle size, surface charge of the nanoparticles was determined for the study. PSMT delivers genes into cells by the caveolae mediated endocytic pathway. Caveolae expression is usually altered in transformed cancer cells. Transfection through the caveolae may help PSMT to selectively transfect cancer cells rather than normal cells. Transfection of the luciferase gene by PSMT was tested in various cell types including cancer cell lines, primary cells, and immortalized cells. Luciferase transgene expression mediated by PSMT was remarkably increased in HeLa cells compared to expression using the control carrier Lipofectamine. Moreover, the toxicity of PSMT was comparable to the control carrier (Lipofectamine) in the same cells. Selective transfection of cancer cells using PSMT was further confirmed by co-culture of cancer and normal cells, which showed that transgene expression was pre-dominantly achieved in cancer cells. A functional p53 gene was also delivered into HeLa cells using PSMT and the selective transgene expression of p53 protein in cancer cells was analyzed through western blotting and confocal microscopy. HeLa cells transfected with PSMT/p53 plasmid nanoparticles showed cellular damage and apoptosis, which was confirmed through propidium iodide staining. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Enhanced Lung Recovery after Surgery, Is It A Necessary for Precision Therapy?

    Directory of Open Access Journals (Sweden)

    Guowei CHE

    2017-08-01

    Full Text Available The concept of enhanced recovery after surgery (ERAS has already been accepted by almost all the clinicians and nurses, the practice of which is based on interdisciplinary cooperation. The reason is still unclear why the effect of ERAS varies a lot though the same ERAS scheme is used. The main cause may be the same ERAS scheme can not be suitable for different patients. In other words, does ERAS also need to conform to Precision Medicine Theory? This study is focused on the necessity and clinical efficacy of “Precision ERAS” performed in lung cancer patients. The conclusions are the following: first of all, an accurate judgment of patients who need ERAS should be done properly before surgery, which means that the high risks assessment should be done accurately. Secondly, a specific ERAS scheme should be carried out in each independent patient who has obvious clinical symptoms in order to alleviate clinical symptoms and improve the ptients’ quality of life (QOL. Thirdly, for the asymptomatic patitents who also don’t have severe concomitant diseases, process-optimized ERAS should be selected to make patients feel more comfortable and shorten the average length of stay (ALOS. To summary, “subtraction” instead of “addition” should be considered when performing ERAS.

  17. A Multicomponent Intervention to Improve Primary Care Provider Adherence to Chronic Opioid Therapy Guidelines and Reduce Opioid Misuse: A Cluster Randomized Controlled Trial Protocol.

    Science.gov (United States)

    Lasser, Karen E; Shanahan, Christopher; Parker, Victoria; Beers, Donna; Xuan, Ziming; Heymann, Orlaith; Lange, Allison; Liebschutz, Jane M

    2016-01-01

    Prescription opioid misuse is a significant public health problem as well as a patient safety concern. Primary care providers (PCPs) are the leading prescribers of opioids for chronic pain, yet few PCPs follow standard practice guidelines regarding assessment and monitoring. This cluster randomized controlled trial will determine whether four implementation strategies; nurse care management, use of a patient registry, academic detailing, and electronic tools, will increase PCP adherence to chronic opioid therapy guidelines and reduce opioid misuse among patients, relative to electronic tools alone. The implementation strategies and intervention content are based on the chronic care model. We include 53 PCPs from three Boston-area community health centers and one urban safety-net hospital-based primary care practice who have at least four patients meeting the following inclusion criteria: 1) age≥18; 2) one or more completed visits to the primary care practice in the past year; 3) long-term opioid treatment defined as three or more opioid prescriptions written at least 21days apart within 6months and 4) an inpatient or outpatient ICD-9-CM diagnosis for musculoskeletal or neuropathic pain. We consider PCPs to be study subjects, and obtained a waiver of informed consent for patients because the study is promoting an established standard of care. We enrolled participants (PCPs) from December 2012 through March 2015. PCPs were randomized to receive the intervention, which includes four components: 1) nurse care management, 2) use of a patient registry, 3) academic detailing, and 4) electronic tools, or a control condition, which includes only the use of the electronic tools. The intervention PCPs receive the services of a nurse-managed registry for planning individual patient care and conducting population-based care for patients receiving opioids for chronic pain. In academic detailing visits, trained co-investigators provide intervention PCPs with individualized

  18. A qualitative systematic review of service user and service provider perspectives on the acceptability, relative benefits, and potential harms of art therapy for people with non-psychotic mental health disorders.

    Science.gov (United States)

    Scope, Alison; Uttley, Lesley; Sutton, Anthea

    2017-03-01

    This systematic review aimed to synthesize qualitative evidence relating to user and service provider perspective on the acceptability and relative benefits and potential harms of art therapy for people with non-psychotic mental disorders. A comprehensive literature search was conducted in 13 major bibliographic databases from May to July 2013. A qualitative evidence synthesis was conducted using thematic framework synthesis. The searches identified 10,270 citations from which 12 studies were included. Ten studies included data from 183 service users, and two studies included data from 16 service providers. The evidence demonstrated that art therapy was an acceptable treatment. The benefits associated with art therapy included the following: the development of relationships with the therapist and other group members; understanding the self/own illness/the future; gaining perspective; distraction; personal achievement; expression; relaxation; and empowerment. Small numbers of patients reported varying reasons for not wanting to take part, and some highlighted potentially negative effects of art therapy which included the evoking of feelings which could not be resolved. The findings suggest that for the majority of respondents art therapy was an acceptable intervention, although this was not the case for all respondents. Therefore, attention should be focussed on both identifying those who are most likely to benefit from art therapy and ensuring any potential harms are minimized. The findings provide evidence to commissioners and providers of mental health services about the value of future art therapy services. Art therapy was reported to be an acceptable treatment for the majority of respondents. Art therapy may not be a preferred treatment option for a small number of patients, emphasizing the importance of considering patient preference in choice of treatment, and selection of the most suitable patients for art therapy. Consideration should be made of adjustments

  19. Dilemmas in providing resilience-enhancing social services to long-term social assistance clients. A qualitative study of Swedish social workers

    Science.gov (United States)

    2012-01-01

    Background Long-term recipients of social assistance face barriers to social and economic inclusion, and have poorer health and more limited opportunities for improving their health than many other groups in the population. During recent decades there have been changes in Swedish social policy, with cutbacks in public benefits and a re-emphasis on means-tested policies. In this context, it is important to investigate the necessary conditions for social workers to offer social assistance and services, as well as the mediating role of social workers between public policies and their clients. Swedish social services aim to promote social inclusion by strengthening the individual´s own resources. We investigated the issues that arise when providing social services to long-term social assistance clients within the framework of resilience, which focuses on the processes leading to positive functioning in adverse conditions. Methods Interviews were conducted with 23 social workers in Stockholm and analysed by qualitative content analysis. Results The main theme to emerge from the interviews concerned the constraints that the social workers faced in providing social services to social assistance clients. The first subtheme focused on dilemmas in the interaction between social workers and clients resulting from the dual role of exercising authority and supporting and building trust with clients. Working conditions of social workers also played a crucial role. The second subtheme addressed the impact of the societal context, such as labour market opportunities and coordination between authorities. Conclusions Overall, we found that social workers to a great extent tried to find individual solutions to structural problems. To provide resilience-enhancing social services to long-term social assistance clients with varying obstacles and needs requires a constructive working environment, supportive societal structures and inter-sectoral cooperation between different authorities

  20. People with stroke spend more time in active task practice, but similar time in walking practice, when physiotherapy rehabilitation is provided in circuit classes compared to individual therapy sessions: an observational study.

    Science.gov (United States)

    English, Coralie; Hillier, Susan; Kaur, Gurpreet; Hundertmark, Laura

    2014-03-01

    Do people with stroke spend more time in active task practice during circuit class therapy sessions versus individual physiotherapy sessions? Do people with stroke practise different tasks during circuit class therapy sessions versus individual physiotherapy sessions? Prospective, observational study. Twenty-nine people with stroke in inpatient rehabilitation settings. Individual therapy sessions and circuit class therapy sessions provided within a larger randomised controlled trial. Seventy-nine therapy sessions were video-recorded and the footage was analysed for time spent engaged in various categories of activity. In a subsample of 28 videos, the number of steps taken by people with stroke per therapy session was counted. Circuit class therapy sessions were of a longer duration (mean difference 38.0minutes, 95% CI 29.9 to 46.1), and participants spent more time engaged in active task practice (mean difference 23.8minutes, 95% CI 16.1 to 31.4) compared with individual sessions. A greater percentage of time in circuit class therapy sessions was spent practising tasks in sitting (mean difference 5.3%, 95% CI 2.4 to 8.2) and in sit-to-stand practice (mean difference 2.7%, 95% CI 1.4 to 4.1), and a lower percentage of time in walking practice (mean difference 19.1%, 95% CI 10.0 to 28.1) compared with individual sessions. PARTICIPANTS took an average of 371 steps (SD 418) during therapy sessions and this did not differ significantly between group and individual sessions. People with stroke spent more time in active task practice, but a similar amount of time in walking practice when physiotherapy was offered in circuit class therapy sessions versus individual therapy sessions. There is a need for effective strategies to increase the amount of walking practice during physiotherapy sessions for people after stroke. Copyright © 2014 Australian Physiotherapy Association. Published by Elsevier B.V. All rights reserved.

  1. Clinical characteristics predict benefits from eptifibatide therapy during coronary stenting: insights from the Enhanced Suppression of the Platelet IIb/IIIa Receptor With Integrilin Therapy (ESPRIT) trial.

    Science.gov (United States)

    Puma, Joseph A; Banko, Lesan T; Pieper, Karen S; Sacchi, Terrence J; O'Shea, J Conor; Dery, Jean Pierre; Tcheng, James E

    2006-02-21

    In order to determine a differential benefit from treatment, we compared the long-term outcome of high-risk versus low-risk patients and evaluated survival free from death or myocardial infarction at one year. Newer anticoagulant strategies during percutaneous coronary intervention have necessitated a reanalysis of the role of intravenous GP IIb/IIIa inhibitors. The Enhanced Suppression of the Platelet IIb/IIIa Receptor with Integrilin Therapy trial randomized 2,064 patients undergoing nonurgent coronary stent implantation to eptifibatide or placebo. High-risk characteristics were defined as age >75 years, diabetes, elevated cardiac markers, ST-segment elevation myocardial infarction within 7 days, or unstable angina within 48 h of randomization. Age <5 years, absence of diabetes, and any other reason for admission were considered low risk characterstics. There were 1,018 patients in the high-risk group (50.8% eptifibatide, 49.2% placebo) and 1,045 patients in the low-risk group (50.0% eptifibatide, 50.0% placebo). Baseline demographics were similar in both groups except for more hypertension (63% vs. 55%, respectively), peripheral vascular disease (8.2% vs. 5.2%, respectively), prior stroke (5.5% vs. 3.2%, respectively), and female gender (33% vs. 22%, respectively) in the high-risk than the low-risk group. At one year, the composite end point of death or myocardial infarction occurred in 15.89% of placebo patients and 7.99% of eptifibatide patients in the high-risk group and 9.02% of the placebo and 8.11% of eptifibatide patients in the low-risk group. Although eptifibatide treatment improved outcomes for all patients, preprocedural clinical characteristics can define a subgroup of patients who may derive greatest benefit from its use during coronary stent placement.

  2. Minimally toxic approach for treatment of cutaneous breast cancer metastases: capecitabine-enhanced photodynamic therapy

    Science.gov (United States)

    Anand, Sanjay; Bullock, Taylor; Maytin, Edward V.

    2017-02-01

    Cutaneous metastasis (CM) occurs in 20% of patients with breast carcinoma (BCA), and is extremely difficult to treat. These CM are relatively resistant to chemotherapy, generally responding only to ionizing radiation (IR). Multiple rounds of IR, however, lead to debilitating fibrosis and radiation dermatitis. An alternative to IR is needed for better management of BCA/CM. In our laboratory, we have developed differentiation-enhanced combination PDT (cPDT), a concept in which a pro-differentiating agent (methotrexate; vitamin D; or 5-fluorouracil, 5FU) is used as a neoadjuvant prior to PDT. After using these neoadjuvants, levels of protoporphyrin IX (PpIX) were elevated in animal tumor models of skin, prostate, and BCA, leading to better PDT efficacy. However, all the agents have toxicity issues. Here, we use a nontoxic 5FU precursor called Capecitabine (CPBN) for cPDT. CBPN is a standard chemotherapeutic for metastatic BCA, and is metabolized to 5FU specifically within tumor tissue. Murine (4T1) and human (MCF-7) BCA cell lines were injected into breast fat pads of nude mice. After tumor nodules appeared, CPBN (400-600 mg/kg/day) was administered by oral gavage for five days followed by intraperitoneal ALA administration on day 6. Mice were sacrificed and tumors harvested. CPBN pretreatment led to a 4-fold elevation of PpIX levels in tumors, relative to vehicle control. Not only did PpIX levels increase, but also PpIX distribution became more homogeneous after CPBN pretreatment. In summary, the use of non-toxic CPBN as a neoadjuvant prior to PDT is a combination approach with significant potential for translation into the clinic.

  3. Non-invasive brain stimulation enhances the effects of Melodic Intonation Therapy

    Directory of Open Access Journals (Sweden)

    Bradley W. Vines

    2011-09-01

    Full Text Available Research has suggested that a fronto-temporal network in the right hemisphere may be responsible for mediating Melodic Intonation Therapy’s positive effects on speech recovery. We investigated the potential for a non-invasive brain stimulation technique, transcranial direct current stimulation (tDCS, to augment the benefits of MIT in patients with non-fluent aphasia by modulating neural activity in the brain during treatment with MIT. The polarity of the current applied to the scalp determines the effects of tDCS on the underlying tissue: anodal tDCS increases excitability, whereas cathodal tDCS decreases excitability. We applied anodal tDCS to the posterior inferior frontal gyrus (IFG of the right hemisphere, an area that has been shown to both contribute to singing through the mapping of sounds to ariculatory actions and serve as a key region in the process of recovery from aphasia, particularly in patients with large left hemispheric lesions. The stimulation was applied while patients were treated with MIT by a trained therapist. Six patients with moderate to severe non-fluent aphasia underwent three consecutive days of anodal-tDCS+MIT, and an equivalent series of sham-tDCS+MIT. The two treatment series were separated by one week, and the order in which the treatments were administered was randomized. Compared to the effects of sham-tDCS+MIT, anodal-tDCS+MIT led to significant improvements in fluency of speech. These results support the hypothesis that, as the brain seeks to reorganize and compensate for damage to left-hemisphere language centers, combining anodal-tDCS with MIT may further recovery from post-stroke aphasia by enhancing activity in a right-hemisphere sensorimotor network for articulation.

  4. Variations of dynamic contrast-enhanced magnetic resonance imaging in evaluation of breast cancer therapy response: a multicenter data analysis challenge.

    Science.gov (United States)

    Huang, Wei; Li, Xin; Chen, Yiyi; Li, Xia; Chang, Ming-Ching; Oborski, Matthew J; Malyarenko, Dariya I; Muzi, Mark; Jajamovich, Guido H; Fedorov, Andriy; Tudorica, Alina; Gupta, Sandeep N; Laymon, Charles M; Marro, Kenneth I; Dyvorne, Hadrien A; Miller, James V; Barbodiak, Daniel P; Chenevert, Thomas L; Yankeelov, Thomas E; Mountz, James M; Kinahan, Paul E; Kikinis, Ron; Taouli, Bachir; Fennessy, Fiona; Kalpathy-Cramer, Jayashree

    2014-02-01

    Pharmacokinetic analysis of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) time-course data allows estimation of quantitative parameters such as K (trans) (rate constant for plasma/interstitium contrast agent transfer), v e (extravascular extracellular volume fraction), and v p (plasma volume fraction). A plethora of factors in DCE-MRI data acquisition and analysis can affect accuracy and precision of these parameters and, consequently, the utility of quantitative DCE-MRI for assessing therapy response. In this multicenter data analysis challenge, DCE-MRI data acquired at one center from 10 patients with breast cancer before and after the first cycle of neoadjuvant chemotherapy were shared and processed with 12 software tools based on the Tofts model (TM), extended TM, and Shutter-Speed model. Inputs of tumor region of interest definition, pre-contrast T1, and arterial input function were controlled to focus on the variations in parameter value and response prediction capability caused by differences in models and associated algorithms. Considerable parameter variations were observed with the within-subject coefficient of variation (wCV) values for K (trans) and v p being as high as 0.59 and 0.82, respectively. Parameter agreement improved when only algorithms based on the same model were compared, e.g., the K (trans) intraclass correlation coefficient increased to as high as 0.84. Agreement in parameter percentage change was much better than that in absolute parameter value, e.g., the pairwise concordance correlation coefficient improved from 0.047 (for K (trans)) to 0.92 (for K (trans) percentage change) in comparing two TM algorithms. Nearly all algorithms provided good to excellent (univariate logistic regression c-statistic value ranging from 0.8 to 1.0) early prediction of therapy response using the metrics of mean tumor K (trans) and k ep (=K (trans)/v e, intravasation rate constant) after the first therapy cycle and the corresponding

  5. Variations of Dynamic Contrast-Enhanced Magnetic Resonance Imaging in Evaluation of Breast Cancer Therapy Response: A Multicenter Data Analysis Challenge1

    Science.gov (United States)

    Huang, Wei; Li, Xin; Chen, Yiyi; Li, Xia; Chang, Ming-Ching; Oborski, Matthew J; Malyarenko, Dariya I; Muzi, Mark; Jajamovich, Guido H; Fedorov, Andriy; Tudorica, Alina; Gupta, Sandeep N; Laymon, Charles M; Marro, Kenneth I; Dyvorne, Hadrien A; Miller, James V; Barbodiak, Daniel P; Chenevert, Thomas L; Yankeelov, Thomas E; Mountz, James M; Kinahan, Paul E; Kikinis, Ron; Taouli, Bachir; Fennessy, Fiona; Kalpathy-Cramer, Jayashree

    2014-01-01

    Pharmacokinetic analysis of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) time-course data allows estimation of quantitative parameters such as Ktrans (rate constant for plasma/interstitium contrast agent transfer), ve (extravascular extracellular volume fraction), and vp (plasma volume fraction). A plethora of factors in DCE-MRI data acquisition and analysis can affect accuracy and precision of these parameters and, consequently, the utility of quantitative DCE-MRI for assessing therapy response. In this multicenter data analysis challenge, DCE-MRI data acquired at one center from 10 patients with breast cancer before and after the first cycle of neoadjuvant chemotherapy were shared and processed with 12 software tools based on the Tofts model (TM), extended TM, and Shutter-Speed model. Inputs of tumor region of interest definition, pre-contrast T1, and arterial input function were controlled to focus on the variations in parameter value and response prediction capability caused by differences in models and associated algorithms. Considerable parameter variations were observed with the within-subject coefficient of variation (wCV) values for Ktrans and vp being as high as 0.59 and 0.82, respectively. Parameter agreement improved when only algorithms based on the same model were compared, e.g., the Ktrans intraclass correlation coefficient increased to as high as 0.84. Agreement in parameter percentage change was much better than that in absolute parameter value, e.g., the pairwise concordance correlation coefficient improved from 0.047 (for Ktrans) to 0.92 (for Ktrans percentage change) in comparing two TM algorithms. Nearly all algorithms provided good to excellent (univariate logistic regression c-statistic value ranging from 0.8 to 1.0) early prediction of therapy response using the metrics of mean tumor Ktrans and kep (=Ktrans/ve, intravasation rate constant) after the first therapy cycle and the corresponding percentage changes. The results

  6. Improved evaluation of antivascular cancer therapy using constrained tracer-kinetic modeling for multi-agent dynamic contrast-enhanced MRI

    NARCIS (Netherlands)

    Hectors, Stefanie; Jacobs, Igor; Lok, Jasper; Peters, Johannes; Bussink, Johan; Hoeben, Freek J. M.; Keizer, Henk; Janssen, Henk M.; Nicolay, Klaas; Schabel, Matthias; Strijkers, Gustav

    2018-01-01

    Dynamic contrast-enhanced MRI (DCE-MRI) is a promising technique for assessing the response of tumor vasculature to anti-vascular therapies. Multi-agent DCE-MRI employs a combination of low and high molecular weight contrast agents, which potentially improves the accuracy of estimation of tumor

  7. Has the degree of contrast enhancement with MR imaging in laryngeal carcinoma added value to Anatomic parameters regarding prediction of response to radiation therapy?

    NARCIS (Netherlands)

    Ljumanovic, R.; Pouwels, P. J. W.; Langendijk, J. A.; Knol, D. L.; Van der Valk, P.; Leemans, C. R.; Castelijns, J. A.

    BACKGROUND AND PURPOSE: Our aim was to retrospectively investigate the prognostic significance of the degree of contrast enhancement in tumors and its additional value in previously considered MR imaging parameters with regard to local control of laryngeal cancer treated with radiation therapy (RT)

  8. Mannan-conjugated adenovirus enhanced gene therapy effects on murine hepatocellular carcinoma cells in vitro and in vivo.

    Science.gov (United States)

    Liu, Zhongbing; Ke, Famin; Duan, Chenggang; Lan, Huan; Li, Juan; Gao, Cen; Li, Jinwei; Zhong, Zhirong

    2013-08-21

    The incidence of advanced hepatocellular carcinoma (HCC) is increasing worldwide, and its prognosis is extremely poor. For some patients for whom surgical treatments are not appropriate, one can only rely on chemotherapy. In the conventional chemotherapy, side effects usually occurred in most cases due to high toxicity levels. Moreover, the development of drug resistance toward chemotherapeutic agents often prevents the successful long-term use of chemotherapy for HCC. Gene therapy represents the exciting biotechnological advance that may revolutionize the conventional fashion of cancer treatment. Overexpression of phosphatase and tensin homologue (PTEN) in cancer cells carrying deletion/mutant type of it can induce the apoptosis of cancer cells and inhibit cell proliferation. In this work, in order to make full use of the high transfectivity of adenovirus, we managed to conjugate the polysaccharide mannan (polymannose) to the surface of the adenovirus chemically under appropriate oxidizing conditions to prepare the mannan-modified adenovirus (Man-Ad5-PTEN). The cytotoxicity and anticancer activity of Man-Ad5-PTEN were assessed in vitro. Reporter gene expression of LacZ transferred by Man-Ad5-LacZ was verified on mannose receptor-deficient NIH/3T3 cells versus mannose receptor-efficient macrophages. Hepatocellular carcinoma cell lines transduced by mannan-modified adenovirus were assayed for cell cycle, apoptosis, invasion, and migration. Further, we detected the antitumor effect on intraperitoneal H22 tumor-bearing mice treated by Man-Ad5-PTEN alone or combined with chemotherapeutic agent of doxorubicin. The results demonstrated that cell growth suppression was not observed in Chang normal hepatocyte cells and the cell killing by Man-Ad5-PTEN is tumor selective. Further, the results showed that the strategy of mannan conjugation could enhance adenovirus-mediated PTEN gene therapy effects on murine hepatocellular carcinoma cells in vitro and in vivo.

  9. Nabiximols combined with motivational enhancement/cognitive behavioral therapy for the treatment of cannabis dependence: A pilot randomized clinical trial.

    Directory of Open Access Journals (Sweden)

    Jose M Trigo

    Full Text Available The current lack of pharmacological treatments for cannabis use disorder (CUD warrants novel approaches and further investigation of promising pharmacotherapy. We previously showed that nabiximols (27 mg/ml Δ9-tetrahydrocannabinol (THC/ 25 mg/ml cannabidiol (CBD, Sativex® can decrease cannabis withdrawal symptoms. Here, we assessed in a pilot study the tolerability and safety of self-titrated nabiximols vs. placebo among 40 treatment-seeking cannabis-dependent participants.Subjects participated in a double blind randomized clinical trial, with as-needed nabiximols up to 113.4 mg THC/105 mg CBD or placebo daily for 12 weeks, concurrently with Motivational Enhancement Therapy and Cognitive Behavioral Therapy (MET/CBT. Primary outcome measures were tolerability and abstinence, secondary outcome measures were days and amount of cannabis use, withdrawal, and craving scores. Participants received up to CDN$ 855 in compensation for their time.Medication was well tolerated and no serious adverse events (SAEs were observed. Rates of adverse events did not differ between treatment arms (F1,39 = 0.205, NS. There was no significant change in abstinence rates at trial end. Participants were not able to differentiate between subjective effects associated with nabiximols or placebo treatments (F1,40 = 0.585, NS. Cannabis use was reduced in the nabiximols (70.5% and placebo groups (42.6%. Nabiximols reduced cannabis craving but no significant differences between the nabiximols and placebo groups were observed on withdrawal scores.Nabiximols in combination with MET/CBT was well tolerated and allowed for reduction of cannabis use. Future clinical trials should explore the potential of high doses of nabiximols for cannabis dependence.

  10. Patient-specific determinants of responsiveness to robot-enhanced treadmill therapy in children and adolescents with cerebral palsy.

    Science.gov (United States)

    Schroeder, Andreas Sebastian; Von Kries, Rüdiger; Riedel, Christina; Homburg, Maria; Auffermann, Helene; Blaschek, Astrid; Jahn, Klaus; Heinen, Florian; Borggraefe, Ingo; Berweck, Steffen

    2014-12-01

    The aim of the study was to evaluate patient-specific determinants of responsiveness to robot-enhanced repetitive treadmill therapy (ROBERT) in patients with early-developed movement disorders. Patients were treated over 12 sessions during a 3-week period. Gross Motor Function Measure-66 (GMFM-66) scores 1 day before ROBERT were compared with scores recorded 1 day after ROBERT. The association of GMFM-66 baseline score, age, sex, aetiology, and add-on botulinum toxin therapy to response to treatment was assessed. Eighty-three patients aged between 4 and 18 years (48 males, 35 females; mean age 10y 8mo, SD 6y 1mo; Gross Motor Function Classification System level I [n=12], II [n=21], III [n=35], IV [n=10], and V [n=1]) were each treated for a total of 7.2 (SD 1.9) treadmill walking hours. Aetiology was bilateral spastic cerebral palsy (BS-CP; n=69), unilateral CP (n=3), ataxic CP (n=3), hereditary spastic paraparesis (n=6), and genetic syndrome including spasticity (n=2). Meaningful improvements were observed in GMFM-66 (+2.5; 95% CI 2.0-3.0), GMFM-D (+5.2; 95% CI 3.6-6.8), and GMFM-E (+4.0; 95% CI 2.8-5.3). There was a high inter-individual variability in treatment response. After multivariable adjustment, the improvements in GMFM-66 and GMFM-E scores were positively associated with the GMFM-66 baseline score. The effect on GMFM-D improvement was inversely associated with age. Gross motor abilities at baseline and age were identified as relevant determinants for the high degree of interpersonal variability in response to ROBERT. © 2014 Mac Keith Press.

  11. TrkB gene therapy by adeno-associated virus enhances recovery after cervical spinal cord injury.

    Science.gov (United States)

    Martínez-Gálvez, Gabriel; Zambrano, Juan M; Diaz Soto, Juan C; Zhan, Wen-Zhi; Gransee, Heather M; Sieck, Gary C; Mantilla, Carlos B

    2016-02-01

    Unilateral cervical spinal cord hemisection at C2 (C2SH) interrupts descending bulbospinal inputs to phrenic motoneurons, paralyzing the diaphragm muscle. Recovery after C2SH is enhanced by brain derived neurotrophic factor (BDNF) signaling via the tropomyosin-related kinase subtype B (TrkB) receptor in phrenic motoneurons. The role for gene therapy using adeno-associated virus (AAV)-mediated delivery of TrkB to phrenic motoneurons is not known. The present study determined the therapeutic efficacy of intrapleural delivery of AAV7 encoding for full-length TrkB (AAV-TrkB) to phrenic motoneurons 3 days post-C2SH. Diaphragm EMG was recorded chronically in male rats (n=26) up to 21 days post-C2SH. Absent ipsilateral diaphragm EMG activity was verified 3 days post-C2SH. A greater proportion of animals displayed recovery of ipsilateral diaphragm EMG activity during eupnea by 14 and 21 days post-SH after AAV-TrkB (10/15) compared to AAV-GFP treatment (2/11; p=0.031). Diaphragm EMG amplitude increased over time post-C2SH (pAAV-TrkB treated animals displaying recovery achieved 48% of the pre-injury values compared to 27% in AAV-GFP treated animals. Phrenic motoneuron mRNA expression of glutamatergic AMPA and NMDA receptors revealed a significant, positive correlation (r(2)=0.82), with increased motoneuron NMDA expression evident in animals treated with AAV-TrkB and that displayed recovery after C2SH. Overall, gene therapy using intrapleural delivery of AAV-TrkB to phrenic motoneurons is sufficient to promote recovery of diaphragm activity, adding a novel potential intervention that can be administered after upper cervical spinal cord injury to improve impaired respiratory function. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Sample Stacking Provides Three Orders of Magnitude Sensitivity Enhancement in SDS Capillary Gel Electrophoresis of Adeno-Associated Virus Capsid Proteins.

    Science.gov (United States)

    Zhang, Chao-Xuan; Meagher, Michael M

    2017-03-21

    Size-based protein analysis utilizing only 25 ng of total proteins has been realized by sodium dodecyl sulfate capillary gel electrophoresis (SDS CGE) with head-column field-amplified sample stacking as an online sample preconcentration technique. This method has been used as a replacement of SDS-PAGE for purity analysis of adeno-associated virus (AAV) therapeutic products of different serotypes and transgenes. A limit of detection of 0.2 ng/mL (3.3 pM) capsid proteins was achieved with convenient UV absorbance detection at 214 nm, equivalent to 20 pg of protein (330 attomole) loaded in the autosampler vial. For purity analysis, only 25 ng of total AAV capsid proteins (4.3 femtomole virus particles) were loaded to the autosampler vial. The sensitivity is comparable to silver-stained SDS-PAGE. The RSD of purity measurement was 0.0-0.8%, comparable to conventional SDS CGE utilizing 0.1-0.5 mg proteins. The new method provided 3 orders of magnitude sensitivity enhancement as compared to conventional SDS CGE. It shares all the advantages of conventional SDS CGE (labor-saving, easy automation, and convenient quantitation) and also the high sensitivity of silver stained SDS-PAGE. The sample stacking SDS CGE technique can be adopted for size-based analysis of other types of proteins. It is especially useful when protein quantity or concentration is not sufficient for regular SDS CGE or SDS-PAGE assay.

  13. A virosomal respiratory syncytial virus vaccine adjuvanted with monophosphoryl lipid A provides protection against viral challenge without priming for enhanced disease in cotton rats.

    Science.gov (United States)

    Kamphuis, Tobias; Stegmann, Toon; Meijerhof, Tjarko; Wilschut, Jan; de Haan, Aalzen

    2013-11-01

    Non-replicating respiratory syncytial virus (RSV) vaccine candidates could potentially prime for enhanced respiratory disease (ERD) due to a T-cell-mediated immunopathology, following RSV infection. Vaccines with built-in immune response modifiers, such as Toll-like receptor (TLR) ligands, may avoid such aberrant imprinting of the immune system. We developed reconstituted RSV envelopes (virosomes) with incorporated TLR4 ligand, monophosphoryl lipid A (RSV-MPLA virosomes). Immune responses and lung pathology after vaccination and challenge were investigated in ERD-prone cotton rats and compared with responses induced by live virus and formaldehyde-inactivated vaccine (FI-RSV), a known cause of ERD upon RSV challenge. Vaccination with RSV-MPLA virosomes induced higher levels of virus-neutralizing antibodies than FI-RSV or live virus infection and provided protection against infection. FI-RSV, but not RSV-MPLA virosomes, primed for increases in expression of Th2 cytokines IL-4, IL-5, IL-13, and Th1 cytokine IL-1b, 6 hour-5 days after infection. By contrast, RSV-MPLA virosomes induced IFN-γ transcripts to similar levels as induced by live virus. Animals vaccinated with FI-RSV, but not RSV-MPLA virosomes showed alveolitis, with prominent neutrophil influx and peribronchiolar and perivascular infiltrates. These results show that RSV-MPLA virosomes represent a safe and immunogenic vaccine candidate that warrants evaluation in a clinical setting. © 2013 John Wiley & Sons Ltd.