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  1. Bioactive glasses potential biomaterials for future therapy

    CERN Document Server

    Kaur, Gurbinder

    2017-01-01

    This book describes the history, origin and basic characteristics of bioactive materials. It includes a chapter dedicated to hydroxyapatite mineral, its formation and its bioactive properties. The authors address how cytotoxicity is a determining step for bioactivity. Applications of bioactive materials in the contexts of tissue regeneration, bone regeneration and cancer therapy are also covered. Silicate, metallic and mesoporous glasses are described, as well as the challenges and future prospects of research in this field.

  2. Bioactive Polymeric Nanoparticles for Periodontal Therapy.

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    Raquel Osorio

    Full Text Available to design calcium and zinc-loaded bioactive and cytocompatible nanoparticles for the treatment of periodontal disease.PolymP-nActive nanoparticles were zinc or calcium loaded. Biomimetic calcium phosphate precipitation on polymeric particles was assessed after 7 days immersion in simulated body fluid, by scanning electron microscopy attached to an energy dispersive analysis system. Amorphous mineral deposition was probed by X-ray diffraction. Cell viability analysis was performed using oral mucosa fibroblasts by: 1 quantifying the liberated deoxyribonucleic acid from dead cells, 2 detecting the amount of lactate dehydrogenase enzyme released by cells with damaged membranes, and 3 by examining the cytoplasmic esterase function and cell membranes integrity with a fluorescence-based method using the Live/Dead commercial kit. Data were analyzed by Kruskal-Wallis and Mann-Whitney tests.Precipitation of calcium and phosphate on the nanoparticles surfaces was observed in calcium-loaded nanoparticles. Non-loaded nanoparticles were found to be non-toxic in all the assays, calcium and zinc-loaded particles presented a dose dependent but very low cytotoxic effect.The ability of calcium-loaded nanoparticles to promote precipitation of calcium phosphate deposits, together with their observed non-toxicity may offer new strategies for periodontal disease treatment.

  3. Bioactive Polymeric Nanoparticles for Periodontal Therapy.

    Science.gov (United States)

    Osorio, Raquel; Alfonso-Rodríguez, Camilo Andrés; Medina-Castillo, Antonio L; Alaminos, Miguel; Toledano, Manuel

    2016-01-01

    to design calcium and zinc-loaded bioactive and cytocompatible nanoparticles for the treatment of periodontal disease. PolymP-nActive nanoparticles were zinc or calcium loaded. Biomimetic calcium phosphate precipitation on polymeric particles was assessed after 7 days immersion in simulated body fluid, by scanning electron microscopy attached to an energy dispersive analysis system. Amorphous mineral deposition was probed by X-ray diffraction. Cell viability analysis was performed using oral mucosa fibroblasts by: 1) quantifying the liberated deoxyribonucleic acid from dead cells, 2) detecting the amount of lactate dehydrogenase enzyme released by cells with damaged membranes, and 3) by examining the cytoplasmic esterase function and cell membranes integrity with a fluorescence-based method using the Live/Dead commercial kit. Data were analyzed by Kruskal-Wallis and Mann-Whitney tests. Precipitation of calcium and phosphate on the nanoparticles surfaces was observed in calcium-loaded nanoparticles. Non-loaded nanoparticles were found to be non-toxic in all the assays, calcium and zinc-loaded particles presented a dose dependent but very low cytotoxic effect. The ability of calcium-loaded nanoparticles to promote precipitation of calcium phosphate deposits, together with their observed non-toxicity may offer new strategies for periodontal disease treatment.

  4. Sustained low-dose growth hormone therapy optimizes bioactive insulin-like growth factor-I level and may enhance CD4 T-cell number in HIV infection

    DEFF Research Database (Denmark)

    Andersen, Ove; Hansen, Birgitte Rønde; Troensegaard, William

    2010-01-01

    High-dose recombinant human growth hormone (rhGH) (2-6 mg/day) regimes may facilitate T-cell restoration in patients infected with human immunodeficiency virus (HIV) on highly active antiretroviral therapy (HAART). However, high-dose rhGH regimens increase insulin-like growth factor-I (IGF......-I) to supra-physiological levels associated with severe side effects. The present study investigated whether lower doses of rhGH may improve T-cell restoration in patients infected with HIV following an expedient response of total and bioactive (i.e., free) IGF-I. A previous 16-week pilot-study included six...... levels. These data support the notion that low-dose rhGH regimens may increase expediently total and bioactive IGF-I and improve T-cell restoration in patients infected with HIV on HAART....

  5. Optimization of Bioactive Polyphenols Extraction from Picea Mariana Bark

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    Nellie Francezon

    2017-12-01

    Full Text Available Reported for its antioxidant, anti-inflammatory and non-toxicity properties, the hot water extract of Picea mariana bark was demonstrated to contain highly valuable bioactive polyphenols. In order to improve the recovery of these molecules, an optimization of the extraction was performed using water. Several extraction parameters were tested and extracts obtained analyzed both in terms of relative amounts of different phytochemical families and of individual molecules concentrations. As a result, low temperature (80 °C and low ratio of bark/water (50 mg/mL were determined to be the best parameters for an efficient polyphenol extraction and that especially for low molecular mass polyphenols. These were identified as stilbene monomers and derivatives, mainly stilbene glucoside isorhapontin (up to 12.0% of the dry extract, astringin (up to 4.6%, resveratrol (up to 0.3%, isorhapontigenin (up to 3.7% and resveratrol glucoside piceid (up to 3.1% which is here reported for the first time for Picea mariana. New stilbene derivatives, piceasides O and P were also characterized herein as new isorhapontin dimers. This study provides novel information about the optimal extraction of polyphenols from black spruce bark, especially for highly bioactive stilbenes including the trans-resveratrol.

  6. Optimizing intraoperative fluid therapy.

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    Stephens, Robert; Mythen, Monty

    2003-08-01

    Correcting the fluid status of the surgical patient is an integral part of good anaesthetic practice. There have been few areas in anaesthesia and perioperative medicine as controversial as fluid resuscitation. Uncertainties still exist as to what the best solution to give is, whether it be a colloid or a crystalloid, and how and when to give it. As well as increasing awareness of the different properties of various colloids, there has been interest in the nature of the carrier solutions, essentially a choice between saline or Ringer's lactate (compound sodium lactate or Hartmann's solution). In this article we review recent studies involving crystalloids, the 'new colloids', and on the amount and timing of fluid therapy. Saline based fluids (including most colloids) are associated with a hyperchloremic metabolic acidosis, and a hypocoagulable state, although these may not necessarily harm the patient. Saline may have deleterious effects on renal function. Colloids in solutions similar to Ringer's lactate ('balanced solutions') may avoid these effects although few are currently available. Several studies that have used fluids (along with other therapies) to improve organ perfusion around the time of surgery have been associated with a better outcome. Compared with Ringer's lactate, saline, and saline-based colloids are associated with a hyperchloremic metabolic acidosis, and a hypocoagulable state although they may not be associated with adverse patient outcomes. Increasing awareness of the 'Stewart hypothesis' has led to new ways of managing hyperchloremic metabolic acidosis. The 'crystalloid-colloid debate' continues, and has led to an awareness that these different fluids, along with their carrier solutions are drugs with different effects. Several studies, in which patients have received more fluid in the protocol group, have found better clinical outcomes in the 'optimized' patients.

  7. Optimization of media for production of bioactive compounds by ...

    African Journals Online (AJOL)

    Streptomyces are economically and biotechnologically valuable prokaryotes responsible for production of bioactive secondary metabolites, notably antibiotics, ... create a great potential for upscaling secondary metabolites such as antibiotics and might remain an area of research interest in the future antibiotic discovery.

  8. Algorithms for optimizing drug therapy

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    Martin Lene

    2004-07-01

    Full Text Available Abstract Background Drug therapy has become increasingly efficient, with more drugs available for treatment of an ever-growing number of conditions. Yet, drug use is reported to be sub optimal in several aspects, such as dosage, patient's adherence and outcome of therapy. The aim of the current study was to investigate the possibility to optimize drug therapy using computer programs, available on the Internet. Methods One hundred and ten officially endorsed text documents, published between 1996 and 2004, containing guidelines for drug therapy in 246 disorders, were analyzed with regard to information about patient-, disease- and drug-related factors and relationships between these factors. This information was used to construct algorithms for identifying optimum treatment in each of the studied disorders. These algorithms were categorized in order to define as few models as possible that still could accommodate the identified factors and the relationships between them. The resulting program prototypes were implemented in HTML (user interface and JavaScript (program logic. Results Three types of algorithms were sufficient for the intended purpose. The simplest type is a list of factors, each of which implies that the particular patient should or should not receive treatment. This is adequate in situations where only one treatment exists. The second type, a more elaborate model, is required when treatment can by provided using drugs from different pharmacological classes and the selection of drug class is dependent on patient characteristics. An easily implemented set of if-then statements was able to manage the identified information in such instances. The third type was needed in the few situations where the selection and dosage of drugs were depending on the degree to which one or more patient-specific factors were present. In these cases the implementation of an established decision model based on fuzzy sets was required. Computer programs

  9. Optimization of liquid culture conditions of Philippine wild edible mushrooms as potential source of bioactive lipids

    Science.gov (United States)

    With remarkable bioactivities and delightful taste, mushrooms have been a commercial nutraceutical around the world. Mushrooms are cultivated on solid materials. Here we report the successful cultivation of four Philippine edible mushrooms in liquid medium. This work highlights the optimal liquid cu...

  10. Robust optimization of SVM hyperparameters in the classification of bioactive compounds.

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    Czarnecki, Wojciech M; Podlewska, Sabina; Bojarski, Andrzej J

    2015-01-01

    Support Vector Machine has become one of the most popular machine learning tools used in virtual screening campaigns aimed at finding new drug candidates. Although it can be extremely effective in finding new potentially active compounds, its application requires the optimization of the hyperparameters with which the assessment is being run, particularly the C and [Formula: see text] values. The optimization requirement in turn, establishes the need to develop fast and effective approaches to the optimization procedure, providing the best predictive power of the constructed model. In this study, we investigated the Bayesian and random search optimization of Support Vector Machine hyperparameters for classifying bioactive compounds. The effectiveness of these strategies was compared with the most popular optimization procedures-grid search and heuristic choice. We demonstrated that Bayesian optimization not only provides better, more efficient classification but is also much faster-the number of iterations it required for reaching optimal predictive performance was the lowest out of the all tested optimization methods. Moreover, for the Bayesian approach, the choice of parameters in subsequent iterations is directed and justified; therefore, the results obtained by using it are constantly improved and the range of hyperparameters tested provides the best overall performance of Support Vector Machine. Additionally, we showed that a random search optimization of hyperparameters leads to significantly better performance than grid search and heuristic-based approaches. The Bayesian approach to the optimization of Support Vector Machine parameters was demonstrated to outperform other optimization methods for tasks concerned with the bioactivity assessment of chemical compounds. This strategy not only provides a higher accuracy of classification, but is also much faster and more directed than other approaches for optimization. It appears that, despite its simplicity

  11. Optimization on Extraction Engineering of the Anti - inflammatory Bioactive Materials from Ainsliaea Fragrans Champ

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    Yang Jie

    2016-01-01

    Full Text Available Ainsliaea fragrans Champ.(A.fragrans is a traditional Chinese herbal, phenolic compounds was the major anti - inflammatory bioactive constituents. To improve the bioavailability and enhanced the curative effect of A.fragrans, the anti - inflammatory effect of phenolic acids and the “non-active” group of control vectors constitute a new biomedical material, which is of great significance to the treatment of diseases inflammation. Hence, in this thesis, regarding the total phenolic acid transfer rate as the indicator, L9(34 orthogonal design was used to optimize the extraction process of total Phenolic acid from A.fragrans by reflux extraction method on solvent dosage, extraction times and extraction time.The optimal extraction technology was as follows: 15 times of water volume, reflux extraction 3 times, extraction time 60 min. The result of pharmacological activity indicated anti-inflammatory effect: 95% ethanol extraction > water extraction > 30% ethanol extraction > 60% ethanol extraction.

  12. Optimizing adherence to antiretroviral therapy.

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    Sahay, Seema; Reddy, K Srikanth; Dhayarkar, Sampada

    2011-12-01

    HIV has now become a manageable chronic disease. However, the treatment outcomes may get hampered by suboptimal adherence to ART. Adherence optimization is a concrete reality in the wake of 'universal access' and it is imperative to learn lessons from various studies and programmes. This review examines current literature on ART scale up, treatment outcomes of the large scale programmes and the role of adherence therein. Social, behavioural, biological and programme related factors arise in the context of ART adherence optimization. While emphasis is laid on adherence, retention of patients under the care umbrella emerges as a major challenge. An in-depth understanding of patients' health seeking behaviour and health care delivery system may be useful in improving adherence and retention of patients in care continuum and programme. A theoretical framework to address the barriers and facilitators has been articulated to identify problematic areas in order to intervene with specific strategies. Empirically tested objective adherence measurement tools and approaches to assess adherence in clinical/ programme settings are required. Strengthening of ART programmes would include appropriate policies for manpower and task sharing, integrating traditional health sector, innovations in counselling and community support. Implications for the use of theoretical model to guide research, clinical practice, community involvement and policy as part of a human rights approach to HIV disease is suggested.

  13. Mineral trioxide aggregate and other bioactive endodontic cements: an updated overview - part I: vital pulp therapy.

    Science.gov (United States)

    Parirokh, M; Torabinejad, M; Dummer, P M H

    2018-02-01

    Mineral trioxide aggregate (MTA) is a bioactive endodontic cement (BEC) mainly comprised of calcium and silicate elements. The cement was introduced by Torabinejad in the 1990s and has been approved by the Food and Drug Administration to be used in the United States in 1997. A number of new BECs have also been introduced to the market, including BioAggregate, Biodentine, BioRoot RCS, calcium-enriched mixture cement, Endo-CPM, Endocem, EndoSequence, EndoBinder, EndoSeal MTA, iRoot, MicroMega MTA, MTA Bio, MTA Fillapex, MTA Plus, NeoMTA Plus, OrthoMTA, Quick-Set, RetroMTA, Tech Biosealer and TheraCal LC. It has been claimed that these materials have properties similar to those of MTA without its drawbacks. In this article, the chemical composition and the application of MTA and other BECs for vital pulp therapy (VPT), including indirect pulp cap, direct pulp cap, partial pulpotomy, pulpotomy and partial pulpectomy, have been reviewed and compared. Based on selected keywords, all papers regarding chemical composition and VPT applications of BECs had been reviewed. Most of the materials had calcium and silicate in their composition. Instead of referring to the cements based on their chemical compositions, we suggest the term 'bioactive endodontic cements (BECs)', which seems more appropriate for these materials because, in spite of differences in their chemical compositions, bioactivity is a common property for all of them. Numerous articles were found regarding use of BECs as VPT agents for indirect and direct pulp capping, partial pulpotomy and cervical pulpotomy. Most of these investigations used MTA for VPT. In most studies, newly introduced materials have been compared to MTA. Some of the BECs have shown promising results; however, the number of their studies compared to investigations on MTA is limited. Most studies had several methodological shortcomings. Future investigations with rigorous methods and materials are needed. © 2017 International Endodontic

  14. Charge-selective fractions of naturally occurring nanoparticles as bioactive nanocarriers for cancer therapy.

    Science.gov (United States)

    Wang, Yongzhong; Yi, Sijia; Sun, Leming; Huang, Yujian; Zhang, Mingjun

    2014-10-01

    A carnivorous fungus, Arthrobotrys oligospora, has been shown to secrete nanoparticles. In the present work, the potential of two charge-selective fractions of fungal nanoparticles (FNPs) as bioactive nanocarriers in cancer therapy is explored by investigating their immunostimulatory activities, cytotoxic mechanisms and in vitro immunochemotherapeutic effects. A surface charge-selective fractionation procedure to purify crude FNPs has been established, and two FNP fractions (i.e. FNP1 and FNP2), with different surface charges and similarly reduced diameters of 100-200nm, are obtained. Both FNP fractions enhance the secretion of multiple proinflammatory cytokines and chemokines from macrophages and splenocytes. However, FNP2 has stronger cytotoxicity than FNP1. It is FNP2 not FNP1 that could clearly inhibit cell proliferation by inducing apoptosis and arresting cells at the sub G0/G1 phase. Both the FNP fractions can form pH-responsive nanocomplexes with doxorubicin (DOX) via electrostatic interactions. For direct cytotoxicity, DOX-FNP2 complexes demonstrate higher activity than DOX against multiple tumor cells, while DOX-FNP1 complexes show weaker activity than DOX. Interestingly, in a co-culture experiment where splenocytes are co-cultured with tumor cells, both DOX-FNP complexes demonstrate higher cytotoxicity than DOX. In conclusion, this work proposes a combined therapeutics for cancer treatment using charge-selective fractions of FNPs as bioactive nanocarriers. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  15. Optimal primary therapy of ovarian cancer.

    Science.gov (United States)

    Bookman, M A

    2016-04-01

    Epithelial ovarian cancer continues to have the highest case-fatality ratio of all gynecologic cancers, in spite of ongoing advances in risk-assessment, genomics, tumor biology, cytoreductive surgery, chemotherapy, and molecular-targeted interventions. Primary treatment options for advanced-stage disease not only should reflect current best standards, but also need to be tailored for individual patients, with consideration of local resources. Formulation of recommendations for optimal primary therapy based on a selective review of data from completed randomized trials, analysis of ongoing trials, and integration with current tumor biology, within the context of individualized clinical care. Recommendations were presented for discussion during an international meeting of experts in ovarian cancer treatment. Key recommendations include full adjuvant therapy for early-stage high-grade serous cancer; tailored utilization of neoadjuvant chemotherapy based on patient comorbidities, extent of disease, and likelihood of achieving optimal surgical cytoreduction; preferred utilization of carboplatin with weekly paclitaxel as primary therapy; consideration of intraperitoneal cisplatin-based therapy in appropriate patients; avoidance of maintenance chemotherapy; lack of necessity for bevacizumab during primary chemotherapy and primary maintenance; acknowledgement of research opportunities and priorities. Integrated multidisciplinary care, including cytoreductive surgery and platinum-based chemotherapy, remain central to the optimal management of women with advanced-stage ovarian cancer. However, even with recent technical advances, the impact on disease-related mortality is limited, and more attention will be focused on the early integration of research, particularly with neoadjuvant chemotherapy and interval cytoreductive surgery. © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For

  16. Extraction Optimization, Preliminary Characterization and Bioactivities in Vitro of Ligularia hodgsonii Polysaccharides

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    Xueping Song

    2016-05-01

    Full Text Available The optimization extraction, preliminary characterization and bioactivities of Ligularia hodgsonii polysaccharides were investigated. Based on single-factor experiments and orthogonal array test, the optimum extraction conditions were obtained as follows: extraction time 3 h, temperature 85 °C, water/raw material ratio 36. Further Sevag deproteinization and dialysis yielded the dialyzed Ligularia hodgsonii polysaccharides (DLHP, 19.2 ± 1.4 mg/g crude herb. Compositional analysis, size-exclusion chromatography connected with multi-angle laser light-scattering and refractive index (SEC-MALLS-RI, Fourier transform infrared (FT-IR and 1H nuclear magnetic resonance (NMR spectroscopy were employed for characterization of the polysaccharides. DLHP was found to have a major component with a weight-average molecular weight of 1.17 × 105 Da, mainly comprising of glucose, galactose, arabinose, mannose, rhamnose, glucuronic acid and galacturonic acid. By in vitro antioxidant activity assays, DLHP presented remarkable scavenging capacities towards 1,1-diphenyl-2-picrylhydrazyl (DPPH, 2,2′-azinobis (3-ethylbenzothiazoline-6-sulfonic acid (ABTS and hydroxyl radicals, and ferrous ions chelating ability. Moreover, it exhibited appreciable anti-hyperglycemic activity as demonstrated by differential inhibition of α-glucosidase and α-amylase. The results indicated that DLHP could potentially be a resource for antioxidant and hypoglycemic agents.

  17. Bioactive Peptides

    Directory of Open Access Journals (Sweden)

    Eric Banan-Mwine Daliri

    2017-04-01

    Full Text Available The increased consumer awareness of the health promoting effects of functional foods and nutraceuticals is the driving force of the functional food and nutraceutical market. Bioactive peptides are known for their high tissue affinity, specificity and efficiency in promoting health. For this reason, the search for food-derived bioactive peptides has increased exponentially. Over the years, many potential bioactive peptides from food have been documented; yet, obstacles such as the need to establish optimal conditions for industrial scale production and the absence of well-designed clinical trials to provide robust evidence for proving health claims continue to exist. Other important factors such as the possibility of allergenicity, cytotoxicity and the stability of the peptides during gastrointestinal digestion would need to be addressed. This review discusses our current knowledge on the health effects of food-derived bioactive peptides, their processing methods and challenges in their development.

  18. Bioactive Peptides.

    Science.gov (United States)

    Daliri, Eric Banan-Mwine; Oh, Deog H; Lee, Byong H

    2017-04-26

    The increased consumer awareness of the health promoting effects of functional foods and nutraceuticals is the driving force of the functional food and nutraceutical market. Bioactive peptides are known for their high tissue affinity, specificity and efficiency in promoting health. For this reason, the search for food-derived bioactive peptides has increased exponentially. Over the years, many potential bioactive peptides from food have been documented; yet, obstacles such as the need to establish optimal conditions for industrial scale production and the absence of well-designed clinical trials to provide robust evidence for proving health claims continue to exist. Other important factors such as the possibility of allergenicity, cytotoxicity and the stability of the peptides during gastrointestinal digestion would need to be addressed. This review discusses our current knowledge on the health effects of food-derived bioactive peptides, their processing methods and challenges in their development.

  19. Optimization of ultrasound assisted extraction of bioactive components from brown seaweed Ascophyllum nodosum using response surface methodology.

    Science.gov (United States)

    Kadam, Shekhar U; Tiwari, Brijesh K; Smyth, Thomas J; O'Donnell, Colm P

    2015-03-01

    The objective of this study was to investigate the effect of key extraction parameters of extraction time (5-25 min), acid concentration (0-0.06 M HCl) and ultrasound amplitude (22.8-114 μm) on yields of bioactive compounds (total phenolics, fucose and uronic acid) from Ascophyllumnodosum. Response surface methodology was employed to optimize the extraction variables for bioactive compounds' yield. A second order polynomial model was fitted well to the extraction experimental data with (R(2)>0.79). Extraction yields of 143.12 mgGAE/gdb, 87.06 mg/gdb and 128.54 mg/gdb were obtained for total phenolics, fucose and uronic acid respectively at optimized extraction conditions of extraction time (25 min), acid concentration (0.03 M HCl) and ultrasonic amplitude (114 μm). Mass spectroscopy analysis of extracts show that ultrasound enhances the extraction of high molecular weight phenolic compounds from A. nodosum. This study demonstrates that ultrasound assisted extraction (UAE) can be employed to enhance extraction of bioactive compounds from seaweed. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Cardiac resynchronization therapy optimization by finger plethysmography.

    Science.gov (United States)

    Butter, Christian; Stellbrink, Christoph; Belalcazar, Andres; Villalta, Don; Schlegl, Michael; Sinha, Anil; Cuesta, Francisca; Reister, Craig

    2004-11-01

    We tested a simple noninvasive method for cardiac resynchronization therapy (CRT) optimization using standard finger photoplethysmography (FPPG). CRT can increase left ventricular cardiac output in patients with heart failure and ventricular conduction delay. Optimal therapy delivery depends on an appropriate AV delay. Multiple invasive and noninvasive methods have been attempted to identify patients and the best AV delay for CRT, but all suffer from a combination of high patient risk, cost, complexity, and low reproducibility. FPPG and invasive aortic pressure data were simultaneously collected from 57 heart failure patients during intrinsic rhythm alternating with very brief periods of pacing at 4 to 5 AV delays. After correcting data for artifacts, the median percentage responses for each AV delay were classified as positive, negative, or neutral compared to baseline (Wilcoxon rank test). FPPG correctly identified positive aortic pulse pressure responses with 71% sensitivity (95% CI: 60-80%) and 90% specificity (95% CI: 84-94%) and negative aortic pulse pressure responses with 57% sensitivity (95% CI: 44-69%) and 96% specificity (95% CI: 91-98%). The magnitude of FPPG changes were strongly correlated with positive aortic pulse pressure changes (R(2) = 0.73, P < .0001) but less well correlated with negative aortic pulse pressure changes (R(2) = 0.43, P < .0001). FPPG selected 78% of the patients having positive aortic pulse pressure changes to CRT and identified the AV delay giving maximum aortic pulse pressure change in all selected patients. FPPG can provide a simple noninvasive method for identifying significant changes in aortic pulse pressure with high specificity, including identifying patients in whom aortic pulse pressure increases with CRT and the AV delay giving the maximum aortic pulse pressure.

  1. Alternatives for optimal hormone replacement therapy.

    Science.gov (United States)

    Sitruk-Ware, R

    2003-08-01

    To satisfy the needs of women with a wide variety of different medical histories and preferences, a wide choice of various forms of hormone replacement therapy (HRT) is desirable. The potential long-term benefits of HRT, in terms of osteoporosis, cardiovascular disease and dementia, require good compliance, which in turn requires an HRT formulation that is highly acceptable. An absence of weight gain and lack of androgenic effects are of great importance, as are predictable bleeding and positive effects on postmenopausal symptoms and quality of life. HRT should be tailored to each woman's needs by the choice of appropriate estrogens and particularly a progestogen with a suitable pharmacological profile. An ideal progestogen should be targeted at preventing endometrial hyperplasia without opposing the effects of estrogen on the vessels. Several new progestogens have been synthesized in recent years. Dienogest, the progestogenic component of a new hormone replacement therapy with estradiol valerate, has many desirable features, including antiandrogenic properties; in this respect, it is unique amongst progestogens derived from testosterone. Tailored HRT should treat symptoms, minimize risk factors, meet personal preferences and lifestyle needs, and not be contraindicated for concomitant diseases. During the next decade, optimal HRT must match a number of trends, including an aging population, and is likely to be influenced by the outcome of major trials such as the Women's Health Initiative trial whose negative results will impact the prescriptions, the advent of new compounds--particularly the selective estrogen receptor modulators and progestogen receptor modulators--and the introduction of new methods of delivery, including vaginal rings and medicated intrauterine systems.

  2. Antigastric Cancer Bioactive Aurantiochytrium Oil Rich in Docosahexaenoic Acid: From Media Optimization to Cancer Cells Cytotoxicity Assessment.

    Science.gov (United States)

    Shakeri, Shahryar; Amoozyan, Neda; Fekrat, Farzaneh; Maleki, Mahmood

    2017-11-01

    Dietary eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) may have a role in contributing to the prevention or inhibition of some malignancies. DHA, the most important polyunsaturated fatty acid (PUFA) in fish and thraustochytrid oils, is known for its anticancer activity. However, antigastric cancer activity of thraustochytrid microbial oil is still unclear. In this investigation, 45 thraustochytrid strains were screened for the production of antigastric cancer oil. Cytotoxicity of 12 thraustochytrid oils was assessed by 3-(4,5-dimethythiazol- 2-yl)-2,5-diphenyl tetrazolium bromide (MTT) on gastric cancer AGS cells. The most cytotoxic effect was related to the oil extracted from the qe-4 strain with 45% cell cytotoxicity. Therefore, the Taguchi methodology was used to optimize this bioactive microbial oil. The amounts of biomass, oil, and DHA were increased to 10.32 g/L, 3.86 g/L, and 1390 mg/L, respectively. Furthermore, the use of glycerol in low saline medium enhanced the yield of DHA. Then, the cytotoxicity of thraustochytrids oil rich in DHA or C16 (0.5 to 10 mg/mL), was assessed on AGS cells. Only the oil that was rich in DHA showed an inhibitory effect (IC50 ) on AGS cells (same as the standard DHA at 1.26 mg/mL). These new findings revealed that thraustochytrid derived oil rich in DHA, has an inhibitory effect on gastric cancer cells. Phylogenetic analysis showed that qe-4 is related to the genus Aurantiochytrium (AN: KR091914) as a potential candidate for the production of bioactive oil. In conclusion, these results certainly support further investigations on this bioactive microbial oil as an additive for the fortification of food and dairy products. Thraustochytrid microbial oil rich in DHA, showed antigastric cancer activity comparable to that of pure DHA; indicating that this microbial bioactive omega-3 oil rich in the very important PUFA (DHA), can be applied as an additive for the fortification of food and dairy products. Also

  3. Risk-optimized proton therapy to minimize radiogenic second cancers

    DEFF Research Database (Denmark)

    Rechner, Laura A; Eley, John G; Howell, Rebecca M

    2015-01-01

    Proton therapy confers substantially lower predicted risk of second cancer compared with photon therapy. However, no previous studies have used an algorithmic approach to optimize beam angle or fluence-modulation for proton therapy to minimize those risks. The objectives of this study were...... to demonstrate the feasibility of risk-optimized proton therapy and to determine the combination of beam angles and fluence weights that minimizes the risk of second cancer in the bladder and rectum for a prostate cancer patient. We used 6 risk models to predict excess relative risk of second cancer. Treatment...

  4. Optimization of fluoride-containing bioactive glasses as a novel scolicidal agent adjunct to hydatid surgery.

    Science.gov (United States)

    Rostami, Ali; Mozafari, Masoud; Gholipourmalekabadi, Mazaher; Caicedo, Hector Hugo; Lasjerdi, Zohreh; Sameni, Marzieh; Samadikuchaksaraei, Ali

    2015-08-01

    We have presented a novel scolicidal agent made from fluoride-containing bioactive glass (FBG). The samples were characterized by XRD and the ion release behavior of the samples was evaluated at 37°C. The scolicidal activity, cellular response and antibacterial activity and biocompatibility of the different concentrations of the FBG (ranging from 0.5 to 2 mg ml(-1)) were evaluated in vitro and in vivo. The results showed an easy diffusion of the fluoride through the glass matrix in an F concentration-dependent manner. The FBG showed an intensive scolicidal property, so that toxicity effect begun from 5 min and the samples with 20, 10, 5 and 0% fluoride showed 98±2, 93±5.8, 76.2±6 and 5.8±1.7% scolicidal activity, respectively, after 8h exposing time. Our data revealed that scolicidal activity of the FBG increased with the increase of F ratio and concentrations of the bioactive glass. On the other hand, all the synthesized FBG samples found to be cyto-biocompatible when tested in vitro (MTT and LDH assays) and in vivo (no significant infiltration of inflammatory cells compared with control, p>0.05), and antibacterial against Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa. The results demonstrated that the synthesized FBG might have a potential application in prevention of post-surgery infections, especially hydatidosis. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Optimization of Polysaccharide Ultrasonic Extraction Conditions Using Purple Sweet Potato Tubers Based on Free Radical Scavenging and Glycosylation Inhibitory Bioactivities.

    Science.gov (United States)

    Guo, Haihua; Kong, Fansheng; Yan, Chunyan

    2017-01-01

    The purple sweet potato, Ipomoea batatas, belongs to the family Convolvulaceae. It is one of the most widely consumed tubers in Asia and is found in many dishes. Many people with diabetes eat purple sweet potato tubers to help reduce blood glucose in China. To predict the ultrasonic conditions for getting the optimal in vitro antioxidant and antiglycated activity of ultrasonic extracted polysaccharides from purple sweet potato (I. batatas) tubers, the artificial neural network (ANN) regression models was used in this study. The antioxidant activity of polysaccharides was quantified by evaluating the hydroxyl radical scavenging effect after ultrasonic extraction, and the data were used in conjunction with optimized extraction conditions to train the predictive ANN models. The following conditions were predicted to yield optimal hydroxyl scavenging activity: 200 W, 22°C, and 40 min. In contrast, conditions of 230 W, 22°C, and 50 min yielded the greatest inhibitory effect on albumin nonenzymatic glycosylation. The accuracy and predictive ability of the models ranged from good to excellent, as indicated by R(2) values ranging from 0.953 to 0.998. The results of the present study showed that ANN predictive models are useful in ultrasonic processing, which can rapidly and accurately predict the optimum extraction conditions for polysaccharides based on their antioxidant and antiglycated activities. In addition, the results of the present study suggest that the consumption of sweet potatoes may help reduce free radicals in the body and prevent or treat diabetes. Ultrasonic extraction conditions were simulated and optimized using artificial neural networkBioactivities showed nonlinear relationship with ultrasonic conditionsThe optimal extraction conditions were 200 W, 22°C, and 40 min for the highest antioxidant capacityThe optimal extraction conditions were 230 W, 22°C, and 50 min for the highest antiglycated effect. Abbreviations used: IBP: Polysaccharide of Ipomoea

  6. Estimating the wound healing ability of bioactive milk proteins using an optimized cell based assay

    DEFF Research Database (Denmark)

    Nyegaard, Steffen; Andreasen, Trine; Rasmussen, Jan Trige

    pure milk proteins and isolates are added and migration quantified. This is done by performing a nuclei count and by measuring the migrated distance. The high reproducibility and gentle nature of the inserts makes this approach a good alternative to the traditional scratch assay. In perspective......Milk contains many different proteins of which the larger constituents like the caseins and major whey constituents are well characterized. We have for some time been studying the structure and function of proteins associated with the milk fat globule membrane like lactadherin, MUC1/15, xanthine...... healing assay to determine the bioactive effects of various milk proteins using human small intestine cells grown on extracellular matrix. Silicone inserts are placed in a 96-well plate and enterocytes seeded around it, creating a monolayer with a cell free area. In current ongoing experiments, various...

  7. Determinants of Optimal Adherence to Antiretroviral Therapy among ...

    African Journals Online (AJOL)

    SITWALA COMPUTERS

    Determinants of Optimal Adherence to Antiretroviral. Therapy among People Living With HIV/AIDS. Registered for Antiretroviral Therapy in Zimbabwe. 1. 2. L Gonah , A Mukwirimba .... and Shona (native language in Masvingo province) language speakers trained on quantitative research methodology participated in data ...

  8. Two Effective Heuristics for Beam Angle Optimization in Radiation Therapy

    CERN Document Server

    Yarmand, Hamed

    2013-01-01

    In radiation therapy, mathematical methods have been used for optimizing treatment planning for delivery of sufficient dose to the cancerous cells while keeping the dose to critical surrounding structures minimal. This optimization problem can be modeled using mixed integer programming (MIP) whose solution gives the optimal beam orientation as well as optimal beam intensity. The challenge, however, is the computation time for this large scale MIP. We propose and investigate two novel heuristic approaches to reduce the computation time considerably while attaining high-quality solutions. We introduce a family of heuristic cuts based on the concept of 'adjacent beams' and a beam elimination scheme based on the contribution of each beam to deliver the dose to the tumor in the ideal plan in which all potential beams can be used simultaneously. We show the effectiveness of these heuristics for intensity modulated radiation therapy (IMRT) and stereotactic body radiation therapy (SBRT) on a clinical liver case.

  9. The quest for optimal antimicrobial therapy

    NARCIS (Netherlands)

    Mol, Petrus Gerardus Maria

    2005-01-01

    Since the discovery of sulphonam ides and penicillin in the 1930's, and their widespread use in clinical practice during World War II a plethora of new antimicrobial agents have entered the market. Initial optim ism has faded that these new drugs would eliminate infectious diseases as killer

  10. Optimal Furosemide Therapy in Critically Ill infants

    NARCIS (Netherlands)

    M.M.J. van der Vorst

    2007-01-01

    textabstractFurosemide as continuous infusion is used in infants after cardiopulmonary bypass (CPB) surgery and during extracorporeal membrane oxygenation (ECMO). The currently used regimens which start with low dose (0.05 - 0.1 mg/kg.hr) may not be optimal in this group of patients with

  11. Extraction Optimization, Characterization, and Bioactivities of Polysaccharides from Pinelliae Rhizoma Praeparatum Cum Alumine Employing Ultrasound-Assisted Extraction.

    Science.gov (United States)

    Liu, Yu-Jie; Mo, Xue-Lin; Tang, Xiao-Zhang; Li, Jiang-Hua; Hu, Mei-Bian; Yan, Dan; Peng, Wei; Wu, Chun-Jie

    2017-06-09

    In this study, the ultrasound-assisted extraction of polysaccharides (PSA) from Pinelliae Rhizoma Praeparatum Cum Alumine (PRPCA) was optimized by response surface methodology (RSM). The structural characteristics of PSA were analyzed by UV-vis spectroscopy, infrared spectroscopy, scanning electron microscopy, high performance gel permeation chromatography and high performance liquid chromatography, respectively. In addition, antioxidant and antimicrobial activities of PSA were studied by different in vitro assays. Results indicated that the optimal extraction conditions were as follows: the ratio of water to raw of 30 mL/g, extraction time of 46.50 min, ultrasonic temperature of 72.00 °C, and ultrasonic power of 230 W. Under these conditions, the obtained PSA yield (13.21 ± 0.37%) was closely agreed with the predicted yield by the model. The average molecular weights of the PSA were estimated to be 5.34 × 10³ and 6.27 × 10⁵ Da. Monosaccharide composition analysis indicated that PSA consisted of mannose, galactose uronic acid, glucose, galactose, arabinose with a molar ratio of 1.83:0.55:75.75:1.94:0.45. Furthermore, PSA exhibited moderate antioxidant and antibacterial activities in vitro. Collectively, this study provides a promising strategy to obtain bioactive polysaccharides from processed products of herbal medicines.

  12. Extraction Optimization, Characterization, and Bioactivities of Polysaccharides from Pinelliae Rhizoma Praeparatum Cum Alumine Employing Ultrasound-Assisted Extraction

    Directory of Open Access Journals (Sweden)

    Yu-Jie Liu

    2017-06-01

    Full Text Available In this study, the ultrasound-assisted extraction of polysaccharides (PSA from Pinelliae Rhizoma Praeparatum Cum Alumine (PRPCA was optimized by response surface methodology (RSM. The structural characteristics of PSA were analyzed by UV-vis spectroscopy, infrared spectroscopy, scanning electron microscopy, high performance gel permeation chromatography and high performance liquid chromatography, respectively. In addition, antioxidant and antimicrobial activities of PSA were studied by different in vitro assays. Results indicated that the optimal extraction conditions were as follows: the ratio of water to raw of 30 mL/g, extraction time of 46.50 min, ultrasonic temperature of 72.00 °C, and ultrasonic power of 230 W. Under these conditions, the obtained PSA yield (13.21 ± 0.37% was closely agreed with the predicted yield by the model. The average molecular weights of the PSA were estimated to be 5.34 × 103 and 6.27 × 105 Da. Monosaccharide composition analysis indicated that PSA consisted of mannose, galactose uronic acid, glucose, galactose, arabinose with a molar ratio of 1.83:0.55:75.75:1.94:0.45. Furthermore, PSA exhibited moderate antioxidant and antibacterial activities in vitro. Collectively, this study provides a promising strategy to obtain bioactive polysaccharides from processed products of herbal medicines.

  13. Optimization approaches to volumetric modulated arc therapy planning

    Energy Technology Data Exchange (ETDEWEB)

    Unkelbach, Jan, E-mail: junkelbach@mgh.harvard.edu; Bortfeld, Thomas; Craft, David [Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114 (United States); Alber, Markus [Department of Medical Physics and Department of Radiation Oncology, Aarhus University Hospital, Aarhus C DK-8000 (Denmark); Bangert, Mark [Department of Medical Physics in Radiation Oncology, German Cancer Research Center, Heidelberg D-69120 (Germany); Bokrantz, Rasmus [RaySearch Laboratories, Stockholm SE-111 34 (Sweden); Chen, Danny [Department of Computer Science and Engineering, University of Notre Dame, Notre Dame, Indiana 46556 (United States); Li, Ruijiang; Xing, Lei [Department of Radiation Oncology, Stanford University, Stanford, California 94305 (United States); Men, Chunhua [Department of Research, Elekta, Maryland Heights, Missouri 63043 (United States); Nill, Simeon [Joint Department of Physics at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, London SM2 5NG (United Kingdom); Papp, Dávid [Department of Mathematics, North Carolina State University, Raleigh, North Carolina 27695 (United States); Romeijn, Edwin [H. Milton Stewart School of Industrial and Systems Engineering, Georgia Institute of Technology, Atlanta, Georgia 30332 (United States); Salari, Ehsan [Department of Industrial and Manufacturing Engineering, Wichita State University, Wichita, Kansas 67260 (United States)

    2015-03-15

    Volumetric modulated arc therapy (VMAT) has found widespread clinical application in recent years. A large number of treatment planning studies have evaluated the potential for VMAT for different disease sites based on the currently available commercial implementations of VMAT planning. In contrast, literature on the underlying mathematical optimization methods used in treatment planning is scarce. VMAT planning represents a challenging large scale optimization problem. In contrast to fluence map optimization in intensity-modulated radiotherapy planning for static beams, VMAT planning represents a nonconvex optimization problem. In this paper, the authors review the state-of-the-art in VMAT planning from an algorithmic perspective. Different approaches to VMAT optimization, including arc sequencing methods, extensions of direct aperture optimization, and direct optimization of leaf trajectories are reviewed. Their advantages and limitations are outlined and recommendations for improvements are discussed.

  14. Optimization of PEG-based extraction of polysaccharides from Dendrobium nobile Lindl. and bioactivity study.

    Science.gov (United States)

    Zhang, Yi; Wang, Hongxin; Wang, Peng; Ma, ChaoYang; He, GuoHua; Rahman, Md Ramim Tanver

    2016-11-01

    Polyethylene glycol (PEG) as a green solvent was employed to extract polysaccharide. The optimal conditions for PEG-based ultrasonic extraction of Dendrobium nobile Lindl. polysaccharide (JCP) were determined by response surface methodology. Under the optimal conditions: extraction temperature of 58.5°C; ultrasound power of 193W, and the concentration of polyethylene glycol-200 (PEG-200) solution of 45%, the highest JCP yield was obtained as 15.23±0.57%, which was close to the predicted yield, 15.57%. UV and FT-IR analysis revealed the general characteristic absorption peaks of both JCP with water extraction (JCPw) and PEG-200 solvent extraction (JCPp). Thermal analysis of both JCPs was performed with Thermal Gravimetric Analyzer (TGA) and Differential Scanning Calorimeter (DSC). Antioxidant activities of two polysaccharides were also compared and no significant difference in vitro was obtained. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Optimization of a bioactive exopolysaccharide production from endophytic Fusarium solani SD5.

    Science.gov (United States)

    Mahapatra, Subhadip; Banerjee, Debdulal

    2013-09-12

    Endophytic fungi were less investigated for exopolysaccharide production. In this study endophytic Fusarium solani SD5 was used for optimization of exopolysaccharide production. One variable at a time method and response surface methodology were employed to explore the optimum medium compositions and fermentation conditions. The organism produced maximum exopolysaccharide after 13.68 days of incubation at 28 °C in potato dextrose broth supplemented with (g%/l) glucose, 9.8; yeast extract, 0.69; KCl, 0.05; KH₂PO₄, 0.05 with medium pH 6.46. Use of 50 ml medium in 250 ml Erlenmeyer flask gives highest exopolysaccharide production. The organism produced more than two times higher exopolysaccharide (2.276 ± 0.032 g/l EPS) at optimized condition compared to pre-optimized condition (0.96 ± 0.021). In vivo toxicity test established nontoxic nature of the EPS (≤400 mg EPS/Kg of body weight). The EPS slightly altered intestinal indigenous bacteria and influenced the growth of beneficial Lactobacillus spp. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Optimization of culture conditions by response surface methodology and unstructured kinetic modeling for bioactive metabolite production by Nocardiopsis litoralis VSM-8.

    Science.gov (United States)

    Managamuri, Ushakiranmayi; Vijayalakshmi, Muvva; Poda, Sudhakar; Ganduri, V S Rama Krishna; Babu, R Satish

    2016-12-01

    Response surface methodology-based central composite design on five variables incubation time, pH, temperature, sucrose concentration, and soya peptone concentration was employed for optimization of the production of bioactive compounds by Nocardiopsis litoralis strain VSM 8. The main quadratic effects and interactions of the five variables on the production of bioactive metabolites were investigated. A second-order polynomial model produced a satisfied fit for experimental data with regard to the production of the bioactive metabolites. Regression analysis showed that high R 2 values of all the five responses are significant and adjusted R 2 values showed good agreement with the experimental and predicted values. The present model was used to evaluate the direct interaction and quadratic effects to optimize the physico-chemical parameters for the production of bioactive metabolites that inhibit the pathogenic microorganisms measured in terms of zones of inhibition (responses). Mathematical kinetic model development and estimation of kinetic parameters also showed good approximation in terms of model fitting and regression analysis.

  17. Extraction of bioactives from Orthosiphon stamineus using microwave and ultrasound-assisted techniques: Process optimization and scale up.

    Science.gov (United States)

    Chan, Chung-Hung; See, Tiam-You; Yusoff, Rozita; Ngoh, Gek-Cheng; Kow, Kien-Woh

    2017-04-15

    This work demonstrated the optimization and scale up of microwave-assisted extraction (MAE) and ultrasonic-assisted extraction (UAE) of bioactive compounds from Orthosiphon stamineus using energy-based parameters such as absorbed power density and absorbed energy density (APD-AED) and response surface methodology (RSM). The intensive optimum conditions of MAE obtained at 80% EtOH, 50mL/g, APD of 0.35W/mL, AED of 250J/mL can be used to determine the optimum conditions of the scale-dependent parameters i.e. microwave power and treatment time at various extraction scales (100-300mL solvent loading). The yields of the up scaled conditions were consistent with less than 8% discrepancy and they were about 91-98% of the Soxhlet extraction yield. By adapting APD-AED method in the case of UAE, the intensive optimum conditions of the extraction, i.e. 70% EtOH, 30mL/g, APD of 0.22W/mL, AED of 450J/mL are able to achieve similar scale up results. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Optimization of conditions to achieve high content of gamma amino butyric acid in germinated black rice, and changes in bioactivities

    Directory of Open Access Journals (Sweden)

    Chaiyavat CHAIYASUT

    Full Text Available Abstract The present study estimated the optimum germination conditions to achieve high content of Gamma-amino butyric acid (GABA and other phytochemicals in Thai black rice cultivar Kum Payao (BR. The Box–Behnken design of response surface methodology was employed to optimize the germination conditions. The changes in the GABA, phytochemical content, impact of salt, and temperature stress variation on phytochemical content, and stability of GABA were studied. The results showed that 12 h of soaking at pH 7, followed by 36 h of germination was the optimum condition to achieve maximum GABA content (0.2029 mg/g of germinated BR (GBR. The temperature (8 and 30 °C, and salt (50-200 mM NaCl content affected the phytochemicals of GBR, especially GABA, and anthocyanins. Obviously, the antioxidant capability, and enzyme (α-amylase and α-glucosidase inhibiting nature of BR was significantly (P < 0.001 increased after germination. The storage of GBR at 4 °C significantly, preserved the GABA content (∼80% for 45 days. Primarily, the current study revealed the changes in phytochemical content, and bioactivity of Thai black rice cr. Kum Payao during germination. More studies should be carried out on pharmacological benefits of GABA-rich GBR.

  19. EUD-based biological optimization for carbon ion therapy

    Energy Technology Data Exchange (ETDEWEB)

    Brüningk, Sarah C., E-mail: sarah.brueningk@icr.ac.uk; Kamp, Florian; Wilkens, Jan J. [Department of Radiation Oncology, Technische Universität München, Klinikum rechts der Isar, Ismaninger Str. 22, München 81675, Germany and Physik-Department, Technische Universität München, James-Franck-Str. 1, Garching 85748 (Germany)

    2015-11-15

    Purpose: Treatment planning for carbon ion therapy requires an accurate modeling of the biological response of each tissue to estimate the clinical outcome of a treatment. The relative biological effectiveness (RBE) accounts for this biological response on a cellular level but does not refer to the actual impact on the organ as a whole. For photon therapy, the concept of equivalent uniform dose (EUD) represents a simple model to take the organ response into account, yet so far no formulation of EUD has been reported that is suitable to carbon ion therapy. The authors introduce the concept of an equivalent uniform effect (EUE) that is directly applicable to both ion and photon therapies and exemplarily implemented it as a basis for biological treatment plan optimization for carbon ion therapy. Methods: In addition to a classical EUD concept, which calculates a generalized mean over the RBE-weighted dose distribution, the authors propose the EUE to simplify the optimization process of carbon ion therapy plans. The EUE is defined as the biologically equivalent uniform effect that yields the same probability of injury as the inhomogeneous effect distribution in an organ. Its mathematical formulation is based on the generalized mean effect using an effect-volume parameter to account for different organ architectures and is thus independent of a reference radiation. For both EUD concepts, quadratic and logistic objective functions are implemented into a research treatment planning system. A flexible implementation allows choosing for each structure between biological effect constraints per voxel and EUD constraints per structure. Exemplary treatment plans are calculated for a head-and-neck patient for multiple combinations of objective functions and optimization parameters. Results: Treatment plans optimized using an EUE-based objective function were comparable to those optimized with an RBE-weighted EUD-based approach. In agreement with previous results from photon

  20. Marine Polysaccharides: A Source of Bioactive Molecules for Cell Therapy and Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Anne-Marie Fischer

    2011-09-01

    Full Text Available The therapeutic potential of natural bioactive compounds such as polysaccharides, especially glycosaminoglycans, is now well documented, and this activity combined with natural biodiversity will allow the development of a new generation of therapeutics. Advances in our understanding of the biosynthesis, structure and function of complex glycans from mammalian origin have shown the crucial role of this class of molecules to modulate disease processes and the importance of a deeper knowledge of structure-activity relationships. Marine environment offers a tremendous biodiversity and original polysaccharides have been discovered presenting a great chemical diversity that is largely species specific. The study of the biological properties of the polysaccharides from marine eukaryotes and marine prokaryotes revealed that the polysaccharides from the marine environment could provide a valid alternative to traditional polysaccharides such as glycosaminoglycans. Marine polysaccharides present a real potential for natural product drug discovery and for the delivery of new marine derived products for therapeutic applications.

  1. Optimization of adaptive radiation therapy in cervical cancer: Solutions for photon and proton therapy

    NARCIS (Netherlands)

    van de Schoot, A.J.A.J.

    2016-01-01

    In cervical cancer radiation therapy, an adaptive strategy is required to compensate for interfraction anatomical variations in order to achieve adequate dose delivery. In this thesis, we have aimed at optimizing adaptive radiation therapy in cervical cancer to improve treatment efficiency and

  2. Evaluation of antimicrobial properties of bioactive glass used in regenerative periodontal therapy

    Directory of Open Access Journals (Sweden)

    Ram Sabarish Chandrasekar

    2015-01-01

    Full Text Available Context: Bone grafting materials which have an inherent anti-microbial property against initial colonizers of plaque bacteria would be useful in regenerative periodontal surgical procedures. Aims: This study was performed to analyze the antibacterial property of a Perioglas™ against a common oral commensal Streptococcus salivarius (early colonizer. Settings and Design: In vitro observational study. Materials and Methods: Perioglas™ (in various concentrations was assessed for its antibacterial property against the ATCC 13419 strain of S. salivarius. The anti-microbial activity was analyzed in terms of reduction in colony-forming units in culture plates and smear following a 24 h incubation at 37°C. Statistical Analysis Used: Observational study - No statistical analysis applicable. Results: The bioactive glass (BAG exerted an antibacterial effect against the S. salivarius in the suspending media and smear. The antibacterial activity of BAG increased in proportion with its concentration. Conclusions: Perioglas™ demonstrated a considerable antibacterial effect against S. salivarius at 50 mg/mL concentration.

  3. Linear energy transfer incorporated intensity modulated proton therapy optimization

    Science.gov (United States)

    Cao, Wenhua; Khabazian, Azin; Yepes, Pablo P.; Lim, Gino; Poenisch, Falk; Grosshans, David R.; Mohan, Radhe

    2018-01-01

    The purpose of this study was to investigate the feasibility of incorporating linear energy transfer (LET) into the optimization of intensity modulated proton therapy (IMPT) plans. Because increased LET correlates with increased biological effectiveness of protons, high LETs in target volumes and low LETs in critical structures and normal tissues are preferred in an IMPT plan. However, if not explicitly incorporated into the optimization criteria, different IMPT plans may yield similar physical dose distributions but greatly different LET, specifically dose-averaged LET, distributions. Conventionally, the IMPT optimization criteria (or cost function) only includes dose-based objectives in which the relative biological effectiveness (RBE) is assumed to have a constant value of 1.1. In this study, we added LET-based objectives for maximizing LET in target volumes and minimizing LET in critical structures and normal tissues. Due to the fractional programming nature of the resulting model, we used a variable reformulation approach so that the optimization process is computationally equivalent to conventional IMPT optimization. In this study, five brain tumor patients who had been treated with proton therapy at our institution were selected. Two plans were created for each patient based on the proposed LET-incorporated optimization (LETOpt) and the conventional dose-based optimization (DoseOpt). The optimized plans were compared in terms of both dose (assuming a constant RBE of 1.1 as adopted in clinical practice) and LET. Both optimization approaches were able to generate comparable dose distributions. The LET-incorporated optimization achieved not only pronounced reduction of LET values in critical organs, such as brainstem and optic chiasm, but also increased LET in target volumes, compared to the conventional dose-based optimization. However, on occasion, there was a need to tradeoff the acceptability of dose and LET distributions. Our conclusion is that the

  4. Linear energy transfer incorporated intensity modulated proton therapy optimization.

    Science.gov (United States)

    Cao, Wenhua; Khabazian, Azin; Yepes, Pablo P; Lim, Gino J; Poenisch, Falk; Grosshans, David R; Mohan, Radhe

    2017-11-13

    The purpose of this study was to investigate the feasibility of incorporating linear energy transfer (LET) into the optimization of intensity modulated proton therapy (IMPT) plans. Because increased LET correlates with increased biological effectiveness of protons, high LETs in target volumes and low LETs in critical structures and normal tissues are preferred in an IMPT plan. However, if not explicitly incorporated into the optimization criteria, different IMPT plans may yield similar physical dose distributions but greatly different LET, specifically dose-averaged LET, distributions. Conventionally, the IMPT optimization criteria (or cost function) only includes dose-based objectives in which the relative biological effectiveness (RBE) is assumed to have a constant value of 1.1. In this study, we added LET-based objectives for maximizing LET in target volumes and minimizing LET in critical structures and normal tissues. Due to the fractional programming nature of the resulting model, we used a variable reformulation approach so that the optimization process is computationally equivalent to conventional IMPT optimization. In this study, five brain tumor patients who had been treated with proton therapy at our institution were selected. Two plans were created for each patient based on the proposed LET-incorporated optimization (LETOpt) and the conventional dose-based optimization (DoseOpt). The optimized plans were compared in terms of both dose (assuming a constant RBE of 1.1 as adopted in clinical practice) and LET. Both optimization approaches were able to generate comparable dose distributions. The LET-incorporated optimization achieved not only pronounced reduction of LET values in critical organs, such as brainstem and optic chiasm, but also increased LET in the target volumes, compared to the conventional dose-based optimization. However, on occasion, there was a need to tradeoff the acceptability of dose and LET distributions. Our conclusion is that the

  5. Percutaneous coronary intervention with optimal medical therapy vs. optimal medical therapy alone for patients with stable angina pectoris

    Directory of Open Access Journals (Sweden)

    Gorenoi, Vitali

    2011-01-01

    Full Text Available Scientific background: Stable Angina Pectoris (AP is a main syndrome of chronic coronary artery disease (CAD, a disease with enormous epidemiological and health economic relevance. Medical therapy and percutaneous coronary interventions (PCI are the most important methods used in the treatment of chronic CAD. Research questions: The evaluation addresses questions on medical efficacy, incremental cost-effectiveness as well as ethic, social and legal aspects in the use of PCI in CAD patients in comparison to optimal medical therapy alone. Methods: A systematic literature search was conducted in June 2010 in the electronic databases (MEDLINE, EMBASE etc. and was completed by a hand search. The medical analysis was initially based on systematic reviews of randomized controlled trials (RCT and was followed by the evaluation of RCT with use of current optimal medical therapy. The results of the RCT were combined using meta-analysis. The strength and the applicability of the determined evidence were appraised. The health economic analysis was initially focused on the published studies. Additionally, a health economic modelling was performed with clinical assumptions derived from the conducted meta-analysis and economic assumptions derived from the German Diagnosis Related Groups 2011. Results: Seven systematic reviews (applicability of the evidence low and three RCT with use of optimal medical therapy (applicability of the evidence for the endpoints AP and revascularisations moderate, for further endpoints high were included in the medical analysis. The results from RCT are used as a base of the evaluation. The routine use of the PCI reduces the proportion of patients with AP attacks in the follow-up after one and after three years in comparison with optimal medical therapy alone (evidence strength moderate; however, this effect was not demonstrated in the follow-up after five years (evidence strength low. The difference in effect in the follow

  6. Percutaneous coronary intervention with optimal medical therapy vs. optimal medical therapy alone for patients with stable angina pectoris.

    Science.gov (United States)

    Gorenoi, Vitali; Schönermark, Matthias P; Hagen, Anja

    2011-01-01

    Stable Angina Pectoris (AP) is a main syndrome of chronic coronary artery disease (CAD), a disease with enormous epidemiological and health economic relevance. Medical therapy and percutaneous coronary interventions (PCI) are the most important methods used in the treatment of chronic CAD. The evaluation addresses questions on medical efficacy, incremental cost-effectiveness as well as ethic, social and legal aspects in the use of PCI in CAD patients in comparison to optimal medical therapy alone. A systematic literature search was conducted in June 2010 in the electronic databases (MEDLINE, EMBASE etc.) and was completed by a hand search. The medical analysis was initially based on systematic reviews of randomized controlled trials (RCT) and was followed by the evaluation of RCT with use of current optimal medical therapy. The results of the RCT were combined using meta-analysis. The strength and the applicability of the determined evidence were appraised. The health economic analysis was initially focused on the published studies. Additionally, a health economic modelling was performed with clinical assumptions derived from the conducted meta-analysis and economic assumptions derived from the German Diagnosis Related Groups 2011. Seven systematic reviews (applicability of the evidence low) and three RCT with use of optimal medical therapy (applicability of the evidence for the endpoints AP and revascularisations moderate, for further endpoints high) were included in the medical analysis. The results from RCT are used as a base of the evaluation. The routine use of the PCI reduces the proportion of patients with AP attacks in the follow-up after one and after three years in comparison with optimal medical therapy alone (evidence strength moderate); however, this effect was not demonstrated in the follow-up after five years (evidence strength low). The difference in effect in the follow-up after four to five years was not found for the further investigated clinical

  7. Prioritized efficiency optimization for intensity modulated proton therapy.

    Science.gov (United States)

    Müller, Birgit S; Wilkens, Jan J

    2016-12-07

    A high dosimetric quality and short treatment time are major goals in radiotherapy planning. Intensity modulated proton therapy (IMPT) plans obtain dose distributions of great conformity but often result in long delivery times which are typically not incorporated into the optimization process. We present an algorithm to optimize delivery efficiency of IMPT plans while maintaining plan quality, and study the potential trade-offs of these interdependent objectives. The algorithm is based on prioritized optimization, a stepwise approach to implemented objectives. First the quality of the plan is optimized. The second step of the prioritized efficiency optimization (PrEfOpt) routine offers four alternatives for reducing delivery time: minimization of the total spot weight sum (A), maximization of the lowest spot intensity of each energy layer (B), elimination of low-weighted spots (C) or energy layers (D). The trade-off between dosimetric quality (step I) and treatment time (step II) is controlled during the optimization by option-dependent parameters. PrEfOpt was applied to a clinical patient case, and plans for different trade-offs were calculated. Delivery times were simulated for two virtual facilities with constant and variable proton current, i.e. independent and dependent on the optimized spot weight distributions. Delivery times decreased without major degradation of plan quality; absolute time reductions varied with the applied method and facility type. Minimizing the total spot weight sum (A) reduced times by 28% for a similar plan quality at a constant current (changes of minimum dose in the target  optimization step into the optimization process can yield reduced delivery times with similar plan qualities. A potential clinical application of PrEfOpt is the generation of multiple plans with different trade-offs for a multicriteria optimization setting. Then, the planner can select the preferred compromise between treatment time and quality for each

  8. Heuristic optimization of the scanning path of particle therapy beams

    Energy Technology Data Exchange (ETDEWEB)

    Pardo, J.; Donetti, M.; Bourhaleb, F.; Ansarinejad, A.; Attili, A.; Cirio, R.; Garella, M. A.; Giordanengo, S.; Givehchi, N.; La Rosa, A.; Marchetto, F.; Monaco, V.; Pecka, A.; Peroni, C.; Russo, G.; Sacchi, R. [Istituto Nazionale di Fisica Nucleare, Sezione di Torino, Via P. Giuria 1, I-10125 Torino (Italy); Istituto Nazionale di Fisica Nucleare, Sezione di Torino, Via P. Giuria 1, I-10125 Torino (Italy) and Fondazione CNAO, Via Caminadella 16, I-20123, Milano (Italy); Dipartimento di Fisica Sperimentale, Universita di Torino, Via P. Giuria 1, I-10125 Torino (Italy); Istituto Nazionale di Fisica Nucleare, Sezione di Torino, Via P. Giuria 1, I-10125 Torino (Italy) and Dipartimento di Fisica Sperimentale, Universita di Torino, Via P. Giuria 1, I-10125 Torino (Italy); Istituto Nazionale di Fisica Nucleare, Sezione di Torino, Via P. Giuria 1, I-10125 Torino (Italy); Istituto Nazionale di Fisica Nucleare, Sezione di Torino, Via P. Giuria 1, I-10125 Torino (Italy) and Dipartimento di Fisica Sperimentale, Universita di Torino, Via P. Giuria 1, I-10125 Torino (Italy); Istituto Nazionale di Fisica Nucleare, Sezione di Torino, Via P. Giuria 1, I-10125 Torino (Italy); Istituto Nazionale di Fisica Nucleare, Sezione di Torino, Via P. Giuria 1, I-10125 Torino (Italy) and Dipartimento di Fisica Sperimentale, Universita di Torino, Via P. Giuria 1, I-10125 Torino (Italy); Istituto Nazionale di Fisica Nucleare, Sezione di Torino, Via P. Giuria 1, I-10125 Torino (Italy); Istituto Nazionale di Fisica Nucleare, Sezione di Torino, Via P. Giuria 1, I-10125 Torino (Italy) and Dipartimento di Fisica Sperimentale, Universita di Torino, Via P. Giuria 1, I-10125 Torino (Italy)

    2009-06-15

    Quasidiscrete scanning is a delivery strategy for proton and ion beam therapy in which the beam is turned off when a slice is finished and a new energy must be set but not during the scanning between consecutive spots. Different scanning paths lead to different dose distributions due to the contribution of the unintended transit dose between spots. In this work an algorithm to optimize the scanning path for quasidiscrete scanned beams is presented. The classical simulated annealing algorithm is used. It is a heuristic algorithm frequently used in combinatorial optimization problems, which allows us to obtain nearly optimal solutions in acceptable running times. A study focused on the best choice of operational parameters on which the algorithm performance depends is presented. The convergence properties of the algorithm have been further improved by using the next-neighbor algorithm to generate the starting paths. Scanning paths for two clinical treatments have been optimized. The optimized paths are found to be shorter than the back-and-forth, top-to-bottom (zigzag) paths generally provided by the treatment planning systems. The gamma method has been applied to quantify the improvement achieved on the dose distribution. Results show a reduction of the transit dose when the optimized paths are used. The benefit is clear especially when the fluence per spot is low, as in the case of repainting. The minimization of the transit dose can potentially allow the use of higher beam intensities, thus decreasing the treatment time. The algorithm implemented for this work can optimize efficiently the scanning path of quasidiscrete scanned particle beams. Optimized scanning paths decrease the transit dose and lead to better dose distributions.

  9. FINITE ELEMENT ANALYSIS FOR OPTIMIZING ANTENNA FOR MICROWAVE COAGULATION THERAPY

    Directory of Open Access Journals (Sweden)

    MARWAHA S.

    2012-08-01

    Full Text Available Microwave coagulation therapy (MCT is emerging as an attractive modality for thermal therapy of soft tissues targeted in short periods of time, making it particularly suitable for ablation of hepatic and other tumors. In this field of microwave coagulation therapy, the use of minimally invasive antenna is recognized as a very promising technique for the treatment of small tumors because a very thin antenna can be easily inserted inside the body and precisely localized using the advanced 3D imaging techniques and surgical robots. The authors investigated the microwave coaxial antenna operating at 2.45 GHz by varying the slots size for the removal of liver tumor. The analysis was done using 2D finite element modeling. By several optimization steps the antenna is simulated and optimized by comparing the values of specific absorption rate (SAR, mesh statistics and temperature distributions in tissue generated by the antenna with the variations of dimensions of slot from 1 mm to 1.7 mm.

  10. Prioritized efficiency optimization for intensity modulated proton therapy

    Science.gov (United States)

    Müller, Birgit S.; Wilkens, Jan J.

    2016-12-01

    A high dosimetric quality and short treatment time are major goals in radiotherapy planning. Intensity modulated proton therapy (IMPT) plans obtain dose distributions of great conformity but often result in long delivery times which are typically not incorporated into the optimization process. We present an algorithm to optimize delivery efficiency of IMPT plans while maintaining plan quality, and study the potential trade-offs of these interdependent objectives. The algorithm is based on prioritized optimization, a stepwise approach to implemented objectives. First the quality of the plan is optimized. The second step of the prioritized efficiency optimization (PrEfOpt) routine offers four alternatives for reducing delivery time: minimization of the total spot weight sum (A), maximization of the lowest spot intensity of each energy layer (B), elimination of low-weighted spots (C) or energy layers (D). The trade-off between dosimetric quality (step I) and treatment time (step II) is controlled during the optimization by option-dependent parameters. PrEfOpt was applied to a clinical patient case, and plans for different trade-offs were calculated. Delivery times were simulated for two virtual facilities with constant and variable proton current, i.e. independent and dependent on the optimized spot weight distributions. Delivery times decreased without major degradation of plan quality; absolute time reductions varied with the applied method and facility type. Minimizing the total spot weight sum (A) reduced times by 28% for a similar plan quality at a constant current (changes of minimum dose in the target  <1%). For a variable proton current, eliminating low-weighted spots (C) led to remarkably faster delivery (16%). The implementation of an efficiency-optimization step into the optimization process can yield reduced delivery times with similar plan qualities. A potential clinical application of PrEfOpt is the generation of multiple plans with different trade

  11. Natural products from aquatic eukaryotic microorganisms for cancer therapy: Perspectives on anti-tumour properties of ciliate bioactive molecules.

    Science.gov (United States)

    Catalani, Elisabetta; Proietti Serafini, Francesca; Zecchini, Silvia; Picchietti, Simona; Fausto, Anna Maria; Marcantoni, Enrico; Buonanno, Federico; Ortenzi, Claudio; Perrotta, Cristiana; Cervia, Davide

    2016-11-01

    Several modern drugs, including those for cancer therapy, have been isolated from natural sources, are based on natural products and its derivatives, or mime natural products. Some of them are in clinical use, others in clinical trials. The success of natural products in drug discovery is related to their biochemical characteristics and to the technologic methods used to study their feature. Natural compounds may acts as chemo-preventive agents and as factors that increase therapeutic efficacy of existing drugs, thus overcoming cancer cell drug resistance that is the main factor determining the failure in conventional chemotherapy. Water environment, because of its physical and chemical conditions, shows an extraordinary collection of natural biological substances with an extensive structural and functional diversity. The isolation of bioactive molecules has been reported from a great variety of aquatic organisms; however, the therapeutic application of molecules from eukaryotic microorganisms remains inadequately investigated and underexploited on a systematic basis. Herein we describe the biological activities in mammalian cells of selected substances isolated from ciliates, free-living protozoa common almost everywhere there is water, focusing on their anti-tumour actions and their possible therapeutic activity. In particular, we unveil the cellular and molecular machine mediating the effects of cell type-specific signalling protein pheromone Er-1 and secondary metabolites, i.e. euplotin C and climacostol, in cancer cells. To support the feasibility of climacostol-based approaches, we also present novel findings and report additional mechanisms of action using both in vitro and in vivo models of mouse melanomas, with the scope of highlighting new frontiers that can be explored also in a therapeutic perspective. The high skeletal chemical difference of ciliate compounds, their sustainability and availability, also through the use of new organic synthesis

  12. Optimization and simplification of antiretroviral therapy for adults and children.

    Science.gov (United States)

    Ford, Nathan; Flexner, Charles; Vella, Stefano; Ripin, David; Vitoria, Marco

    2013-11-01

    The review reflects on opportunities and challenges for HIV treatment optimization for the next 5 years. Considering all currently available options, the fixed-dose combination of tenofovir + lamivudine (or emtricitabine) + efavirenz is considered as the best option for first-line treatment for the short to medium term. Second-line therapy will likely continue to be comprised of a boosted protease inhibitor in combination with two nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), with potential for combining with integrase inhibitors. For children, there is potential for simplification and harmonization with adult antiretroviral regimens. First-line therapy for children younger than 3 years of age may be best delivered using two nucleoside reverse transcriptase inhibitors (NRTIs) and a boosted protease inhibitor; above 3 years of age, the standard of care is two NRTIs and a non-nucleoside reverse transcriptase inhibitor (NNRTI) as recommended for adults. Important research questions include the dosing and safety of new antiretroviral agents and formulations, particularly once-daily fixed-dose combinations, the role of integrase inhibitors and the optimal second-line regimen for NNRTI-exposed children who fail protease inhibitor-containing first-line regimens. Treatment simplification is critical to further antiretroviral therapy scaling-up and support long-term retention in care. Future guidance should consider the broader benefits of earlier antiretroviral therapy initiation beyond potential AIDS mortality reduction, notably mitigation of short- and long-term HIV-associated comorbidities, reduction of HIV transmission, increased retention in care, and enhancing programme simplification.

  13. Optimization of cell disruption methods for efficient recovery of bioactive metabolites via NMR of three freshwater microalgae (chlorophyta).

    Science.gov (United States)

    Ma, Nyuk Ling; Teh, Kit Yinn; Lam, Su Shiung; Kaben, Anne Marie; Cha, Thye San

    2015-08-01

    This study demonstrates the use of NMR techniques coupled with chemometric analysis as a high throughput data mining method to identify and examine the efficiency of different disruption techniques tested on microalgae (Chlorella variabilis, Scenedesmus regularis and Ankistrodesmus gracilis). The yield and chemical diversity from the disruptions together with the effects of pre-oven and pre-freeze drying prior to disruption techniques were discussed. HCl extraction showed the highest recovery of oil compounds from the disrupted microalgae (up to 90%). In contrast, NMR analysis showed the highest intensity of bioactive metabolites obtained for homogenized extracts pre-treated with freeze-drying, indicating that homogenizing is a more favorable approach to recover bioactive substances from the disrupted microalgae. The results show the potential of NMR as a useful metabolic fingerprinting tool for assessing compound diversity in complex microalgae extracts. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Optimized Solid Phase-Assisted Synthesis of Dendrons Applicable as Scaffolds for Radiolabeled Bioactive Multivalent Compounds Intended for Molecular Imaging

    Directory of Open Access Journals (Sweden)

    Gabriel Fischer

    2014-05-01

    Full Text Available Dendritic structures, being highly homogeneous and symmetric, represent ideal scaffolds for the multimerization of bioactive molecules and thus enable the synthesis of compounds of high valency which are e.g., applicable in radiolabeled form as multivalent radiotracers for in vivo imaging. As the commonly applied solution phase synthesis of dendritic scaffolds is cumbersome and time-consuming, a synthesis strategy was developed that allows for the efficient assembly of acid amide bond-based highly modular dendrons on solid support via standard Fmoc solid phase peptide synthesis protocols. The obtained dendritic structures comprised up to 16 maleimide functionalities and were derivatized on solid support with the chelating agent DOTA. The functionalized dendrons furthermore could be efficiently reacted with structurally variable model thiol-bearing bioactive molecules via click chemistry and finally radiolabeled with 68Ga. Thus, this solid phase-assisted dendron synthesis approach enables the fast and straightforward assembly of bioactive multivalent constructs for example applicable as radiotracers for in vivo imaging with Positron Emission Tomography (PET.

  15. Perspective in optimization of stem cell therapies for heart regeneration.

    Science.gov (United States)

    Gapska, Paulina; Kurpisz, Maciej

    2017-12-07

    There is a variety of mechanisms(s) factor(s) that may influence stem cell therapies for heart regeneration. Among the best candidates for stem cell source are: mesenchymal stem cells (also those isolated from adipose tissue), cardiac cell progenitors (CPC) and descendants of iPSC cells. iPSC/s can be potentially beneficial although their pluripotent induction has been still in question due to: low propagation efficacy, danger of genomic integration/instability, biological risk of current vector system teratoma formation etc. which have been discussed in this review. Optimization protocols are required in order to enhance stem cells resistance to pathological conditions that they may encounter in pathological organ and to increase their retention. Combination between gene transfer and stem cell therapy is now more often used in pre-clinical studies with the prospect of subsequent clinical trials. Complementary substances have been contemplated to support stem cell viability (mainly anti-inflammatory and anti- apoptotic agents), which have been tested in animal models with promising results. Integration of nanotechnology both for efficient stem cell imaging as well as with the aim to provide cell supporting scaffolds seem to be inevitable for further development of cellular therapies. The whole organ (heart) reconstruction as well as biodegradable scaffolds and scaffold-free cell sheets have been also outlined.

  16. [Uveitis associated with juvenile idiopathic arthritis : Optimization of immunomodulatory therapy].

    Science.gov (United States)

    Heiligenhaus, A; Tappeiner, C; Walscheid, K; Heinz, C

    2016-05-01

    Uveitis associated with juvenile idiopathic arthritis (JIA-associated uveitis) is a vision-threatening disorder with a high complication rate. Besides early diagnosis within screening programs an adequate therapy is essential for improvement of the long-term prognosis. Corticosteroid therapy is often insufficient. In addition to conventional immunosuppression, immunomodulatory drugs, so-called biologicals, are novel highly effective treatment modalities. A systematic search of the literature was carried out for biologicals currently used in the treatment of JIA-associated uveitis. Review of current publications, summary of treatment guidelines and discussion of treatment options for therapy refractive patients. In accordance with the current recommendations tumor necrosis factor (TNF) inhibitors are administered if uveitis inactivity cannot be achieved with topical corticosteroids and in the next stage with immunosuppressants (methotrexate preferred). According to the currently available data adalimumab is then preferred. When the effectiveness of TNF inhibitors ceases during long-term administration and/or recurrences, other biological response modifiers are attractive treatment options (e. g. lymphocyte inhibitors or specific receptor antagonists). The TNF inhibitors are of major importance for the treatment of JIA-associated uveitis. Prospective studies and registries would be desirable in order to be able to compare the value of TNF inhibitors and other biologicals and for optimization of treatment recommendations.

  17. Perspective in optimization of stem cell therapies for heart regeneration

    Directory of Open Access Journals (Sweden)

    Paulina Gapska

    2017-12-01

    Full Text Available There is a variety of mechanisms(s factor(s that may influence stem cell therapies for heart regeneration. Among the best candidates for stem cell source are: mesenchymal stem cells (also those isolated from adipose tissue, cardiac cell progenitors (CPC and descendants of iPSC cells. iPSC/s can be potentially beneficial although their pluripotent induction has been still in question due to: low propagation efficacy, danger of genomic integration/instability, biological risk of current vector system teratoma formation etc. which have been discussed in this review. Optimization protocols are required in order to enhance stem cells resistance to pathological conditions that they may encounter in pathological organ and to increase their retention. Combination between gene transfer and stem cell therapy is now more often used in pre-clinical studies with the prospect of subsequent clinical trials. Complementary substances have been contemplated to support stem cell viability (mainly anti-inflammatory and anti- apoptotic agents, which have been tested in animal models with promising results. Integration of nanotechnology both for efficient stem cell imaging as well as with the aim to provide cell supporting scaffolds seem to be inevitable for further development of cellular therapies. The whole organ (heart reconstruction as well as biodegradable scaffolds and scaffold-free cell sheets have been also outlined.

  18. A challenge for theranostics: is the optimal particle for therapy also optimal for diagnostics?

    Science.gov (United States)

    Dreifuss, Tamar; Betzer, Oshra; Shilo, Malka; Popovtzer, Aron; Motiei, Menachem; Popovtzer, Rachela

    2015-09-01

    Theranostics is defined as the combination of therapeutic and diagnostic capabilities in the same agent. Nanotechnology is emerging as an efficient platform for theranostics, since nanoparticle-based contrast agents are powerful tools for enhancing in vivo imaging, while therapeutic nanoparticles may overcome several limitations of conventional drug delivery systems. Theranostic nanoparticles have drawn particular interest in cancer treatment, as they offer significant advantages over both common imaging contrast agents and chemotherapeutic drugs. However, the development of platforms for theranostic applications raises critical questions; is the optimal particle for therapy also the optimal particle for diagnostics? Are the specific characteristics needed to optimize diagnostic imaging parallel to those required for treatment applications? This issue is examined in the present study, by investigating the effect of the gold nanoparticle (GNP) size on tumor uptake and tumor imaging. A series of anti-epidermal growth factor receptor conjugated GNPs of different sizes (diameter range: 20-120 nm) was synthesized, and then their uptake by human squamous cell carcinoma head and neck cancer cells, in vitro and in vivo, as well as their tumor visualization capabilities were evaluated using CT. The results showed that the size of the nanoparticle plays an instrumental role in determining its potential activity in vivo. Interestingly, we found that although the highest tumor uptake was obtained with 20 nm C225-GNPs, the highest contrast enhancement in the tumor was obtained with 50 nm C225-GNPs, thus leading to the conclusion that the optimal particle size for drug delivery is not necessarily optimal for imaging. These findings stress the importance of the investigation and design of optimal nanoparticles for theranostic applications.Theranostics is defined as the combination of therapeutic and diagnostic capabilities in the same agent. Nanotechnology is emerging as an

  19. Optimization in Radiation Therapy: Applications in Brachytherapy and Intensity Modulated Radiation Therapy

    Science.gov (United States)

    McGeachy, Philip David

    Over 50% of cancer patients require radiation therapy (RT). RT is an optimization problem requiring maximization of the radiation damage to the tumor while minimizing the harm to the healthy tissues. This dissertation focuses on two main RT optimization problems: 1) brachytherapy and 2) intensity modulated radiation therapy (IMRT). The brachytherapy research involved solving a non-convex optimization problem by creating an open-source genetic algorithm optimizer to determine the optimal radioactive seed distribution for a given set of patient volumes and constraints, both dosimetric- and implant-based. The optimizer was tested for a set of 45 prostate brachytherapy patients. While all solutions met the clinical standards, they also benchmarked favorably with those generated by a standard commercial solver. Compared to its compatriot, the salient features of the generated solutions were: slightly reduced prostate coverage, lower dose to the urethra and rectum, and a smaller number of needles required for an implant. Historically, IMRT requires modulation of fluence while keeping the photon beam energy fixed. The IMRT-related investigation in this thesis aimed at broadening the solution space by varying photon energy. The problem therefore involved simultaneous optimization of photon beamlet energy and fluence, denoted by XMRT. Formulating the problem as convex, linear programming was applied to obtain solutions for optimal energy-dependent fluences, while achieving all clinical objectives and constraints imposed. Dosimetric advantages of XMRT over single-energy IMRT in the improved sparing of organs at risk (OARs) was demonstrated in simplified phantom studies. The XMRT algorithm was improved to include clinical dose-volume constraints and clinical studies for prostate and head and neck cancer patients were investigated. Compared to IMRT, XMRT provided improved dosimetric benefit in the prostate case, particularly within intermediate- to low-dose regions (≤ 40 Gy

  20. Optimal antiviral switching to minimize resistance risk in HIV therapy.

    Directory of Open Access Journals (Sweden)

    Rutao Luo

    Full Text Available The development of resistant strains of HIV is the most significant barrier to effective long-term treatment of HIV infection. The most common causes of resistance development are patient noncompliance and pre-existence of resistant strains. In this paper, methods of antiviral regimen switching are developed that minimize the risk of pre-existing resistant virus emerging during therapy switches necessitated by virological failure. Two distinct cases are considered; a single previous virological failure and multiple virological failures. These methods use optimal control approaches on experimentally verified mathematical models of HIV strain competition and statistical models of resistance risk. It is shown that, theoretically, order-of-magnitude reduction in risk can be achieved, and multiple previous virological failures enable greater success of these methods in reducing the risk of subsequent treatment failures.

  1. Allogeneic cell therapy bioprocess economics and optimization: downstream processing decisions.

    Science.gov (United States)

    Hassan, Sally; Simaria, Ana S; Varadaraju, Hemanthram; Gupta, Siddharth; Warren, Kim; Farid, Suzanne S

    2015-01-01

    To develop a decisional tool to identify the most cost effective process flowsheets for allogeneic cell therapies across a range of production scales. A bioprocess economics and optimization tool was built to assess competing cell expansion and downstream processing (DSP) technologies. Tangential flow filtration was generally more cost-effective for the lower cells/lot achieved in planar technologies and fluidized bed centrifugation became the only feasible option for handling large bioreactor outputs. DSP bottlenecks were observed at large commercial lot sizes requiring multiple large bioreactors. The DSP contribution to the cost of goods/dose ranged between 20-55%, and 50-80% for planar and bioreactor flowsheets, respectively. This analysis can facilitate early decision-making during process development.

  2. Projections onto the Pareto surface in multicriteria radiation therapy optimization.

    Science.gov (United States)

    Bokrantz, Rasmus; Miettinen, Kaisa

    2015-10-01

    To eliminate or reduce the error to Pareto optimality that arises in Pareto surface navigation when the Pareto surface is approximated by a small number of plans. The authors propose to project the navigated plan onto the Pareto surface as a postprocessing step to the navigation. The projection attempts to find a Pareto optimal plan that is at least as good as or better than the initial navigated plan with respect to all objective functions. An augmented form of projection is also suggested where dose-volume histogram constraints are used to prevent that the projection causes a violation of some clinical goal. The projections were evaluated with respect to planning for intensity modulated radiation therapy delivered by step-and-shoot and sliding window and spot-scanned intensity modulated proton therapy. Retrospective plans were generated for a prostate and a head and neck case. The projections led to improved dose conformity and better sparing of organs at risk (OARs) for all three delivery techniques and both patient cases. The mean dose to OARs decreased by 3.1 Gy on average for the unconstrained form of the projection and by 2.0 Gy on average when dose-volume histogram constraints were used. No consistent improvements in target homogeneity were observed. There are situations when Pareto navigation leaves room for improvement in OAR sparing and dose conformity, for example, if the approximation of the Pareto surface is coarse or the problem formulation has too permissive constraints. A projection onto the Pareto surface can identify an inaccurate Pareto surface representation and, if necessary, improve the quality of the navigated plan.

  3. [Optimization of modern conservative therapy of micropenis in hypogonadal men].

    Science.gov (United States)

    Petrovich, R Iu; Sokoll'shchik, M M; Tiuzikov, I A; Konstantinova, I V; Astakhova, M A

    2014-01-01

    The study was aimed to the optimization of conservative therapy of micropenis in hypogonadal men using combination of traction therapy and androgen replacment therapy (ART) with injections of prolonged testosterone undecanoate (Nebido) and to evaluatiom of the safety of ART in terms of the risk of prostate cancer against the background of combined treatment of micropenis by both methods within 12 months. The study included 16 men aged 22-62 years with micropenis and hypogonadism. 10 men were diagnosed with primary hypogonadism, 6 men were diagnosed with secondary hypogonadism without reserve gonadal function; therefore, all 16 patients were treated with testosterone undecanoate 1000 mg intramuscularly according to the scheme: the second injection 6 weeks after the first injection, then each injection once a 12 weeks, the course of 12 months. During the first 3 months of ART, hypogonadism in all men was eliminated, but only at 6 month of ART, the length of the penis in the flaccid state at maximum extension increased from 5.8±1.2 to 8.3±1.2 cm (ppenis - from 6.8±1.1 to 11.8±0.9 (ppenis in the flaccid state at maximum extension increased by 58% of the original length, and in a state of erection - by 114% (p<0.05). During the 12 months of treatment, prostate volume in all men increased from 3.4±1.2 to 16.3±1.2 (p<0.05), which corresponds to the size of the prostate in healthy men. Total blood PSA level increased from 0.72±0.03 to 1.4±0.05 ng/ml (p<0.05), but it was in the acceptable range of reference values for healthy men during whole period of ART in all patients. Start therapy with prolonged testosterone undecanoate for 6 months significantly increases the efficiency of traction therapy in men with hypogonadism and micropenis, but for maintenance of the effect, ART should be continued during all period of treatment.

  4. Optimal duration of dual antiplatelet therapy after coronary stent implantation.

    Science.gov (United States)

    Witberg, Guy; Lev, Eli; Kornowski, Ran

    2015-11-15

    Dual antiplatelet pharmacotherapy reduces ischemic events at the cost of excess bleeding in patients who underwent coronary stenting. The currently recommended treatment period is based on trials held some 20 years ago and not relevant to current clinical practice. In recent years, numerous clinical trials have tried to answer the question of what is the optimal duration of therapy to maximize clinical benefit. These trials showed 2 seemingly conflicting answers-on one hand, shorter treatment duration seems to be safer in reducing bleeding while not increasing ischemic events, and on the other hand, longer duration is superior in terms of preventing ischemic events albeit at the cost of increased bleeding rates. In this review, we summarize the evidence favoring each approach, highlight the limitations of the various pivotal clinical trials in this field, review future directions of research and changes in practice that may influence the duration of antiplatelet therapy, and attempt to propose a personalized approach to achieve maximal benefit for the individual patient. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. The Advantages of Collimator Optimization for Intensity Modulated Radiation Therapy

    Science.gov (United States)

    Doozan, Brian

    The goal of this study was to improve dosimetry for pelvic, lung, head and neck, and other cancers sites with aspherical planning target volumes (PTV) using a new algorithm for collimator optimization for intensity modulated radiation therapy (IMRT) that minimizes the x-jaw gap (CAX) and the area of the jaws (CAA) for each treatment field. A retroactive study on the effects of collimator optimization of 20 patients was performed by comparing metric results for new collimator optimization techniques in Eclipse version 11.0. Keeping all other parameters equal, multiple plans are created using four collimator techniques: CA 0, all fields have collimators set to 0°, CAE, using the Eclipse collimator optimization, CAA, minimizing the area of the jaws around the PTV, and CAX, minimizing the x-jaw gap. The minimum area and the minimum x-jaw angles are found by evaluating each field beam's eye view of the PTV with ImageJ and finding the desired parameters with a custom script. The evaluation of the plans included the monitor units (MU), the maximum dose of the plan, the maximum dose to organs at risk (OAR), the conformity index (CI) and the number of fields that are calculated to split. Compared to the CA0 plans, the monitor units decreased on average by 6% for the CAX method with a p-value of 0.01 from an ANOVA test. The average maximum dose remained within 1.1% difference between all four methods with the lowest given by CAX. The maximum dose to the most at risk organ was best spared by the CAA method, which decreased by 0.62% compared to the CA0. Minimizing the x-jaws significantly reduced the number of split fields from 61 to 37. In every metric tested the CAX optimization produced comparable or superior results compared to the other three techniques. For aspherical PTVs, CAX on average reduced the number of split fields, lowered the maximum dose, minimized the dose to the surrounding OAR, and decreased the monitor units. This is achieved while maintaining the same

  6. Optimizing global liver function in radiation therapy treatment planning.

    Science.gov (United States)

    Wu, Victor W; Epelman, Marina A; Wang, Hesheng; Edwin Romeijn, H; Feng, Mary; Cao, Yue; Ten Haken, Randall K; Matuszak, Martha M

    2016-09-07

    Liver stereotactic body radiation therapy (SBRT) patients differ in both pre-treatment liver function (e.g. due to degree of cirrhosis and/or prior treatment) and radiosensitivity, leading to high variability in potential liver toxicity with similar doses. This work investigates three treatment planning optimization models that minimize risk of toxicity: two consider both voxel-based pre-treatment liver function and local-function-based radiosensitivity with dose; one considers only dose. Each model optimizes different objective functions (varying in complexity of capturing the influence of dose on liver function) subject to the same dose constraints and are tested on 2D synthesized and 3D clinical cases. The normal-liver-based objective functions are the linearized equivalent uniform dose ([Formula: see text]) (conventional '[Formula: see text] model'), the so-called perfusion-weighted [Formula: see text] ([Formula: see text]) (proposed 'fEUD model'), and post-treatment global liver function (GLF) (proposed 'GLF model'), predicted by a new liver-perfusion-based dose-response model. The resulting [Formula: see text], fEUD, and GLF plans delivering the same target [Formula: see text] are compared with respect to their post-treatment function and various dose-based metrics. Voxel-based portal venous liver perfusion, used as a measure of local function, is computed using DCE-MRI. In cases used in our experiments, the GLF plan preserves up to [Formula: see text] more liver function than the fEUD ([Formula: see text]) plan does in 2D cases, and up to [Formula: see text] in 3D cases. The GLF and fEUD plans worsen in [Formula: see text] of functional liver on average by 1.0 Gy and 0.5 Gy in 2D and 3D cases, respectively. Liver perfusion information can be used during treatment planning to minimize the risk of toxicity by improving expected GLF; the degree of benefit varies with perfusion pattern. Although fEUD model optimization is computationally inexpensive and often

  7. Optimized Photodynamic Therapy with Multifunctional Cobalt Magnetic Nanoparticles

    Directory of Open Access Journals (Sweden)

    Kyong-Hoon Choi

    2017-06-01

    Full Text Available Photodynamic therapy (PDT has been adopted as a minimally invasive approach for the localized treatment of superficial tumors, representing an improvement in the care of cancer patients. To improve the efficacy of PDT, it is important to first select an optimized nanocarrier and determine the influence of light parameters on the photosensitizing agent. In particular, much more knowledge concerning the importance of fluence and exposure time is required to gain a better understanding of the photodynamic efficacy. In the present study, we synthesized novel folic acid-(FA and hematoporphyrin (HP-conjugated multifunctional magnetic nanoparticles (CoFe2O4-HPs-FAs, which were characterized as effective anticancer reagents for PDT, and evaluated the influence of incubation time and light exposure time on the photodynamic anticancer activities of CoFe2O4-HPs-FAs in prostate cancer cells (PC-3 cells. The results indicated that the same fluence at different exposure times resulted in changes in the anticancer activities on PC-3 cells as well as in reactive oxygen species formation. In addition, an increase of the fluence showed an improvement for cell photo-inactivation. Therefore, we have established optimized conditions for new multifunctional magnetic nanoparticles with direct application for improving PDT for cancer patients.

  8. Particle swarm optimizer for weighting factor selection in intensity-modulated radiation therapy optimization algorithms.

    Science.gov (United States)

    Yang, Jie; Zhang, Pengcheng; Zhang, Liyuan; Shu, Huazhong; Li, Baosheng; Gui, Zhiguo

    2017-01-01

    In inverse treatment planning of intensity-modulated radiation therapy (IMRT), the objective function is typically the sum of the weighted sub-scores, where the weights indicate the importance of the sub-scores. To obtain a high-quality treatment plan, the planner manually adjusts the objective weights using a trial-and-error procedure until an acceptable plan is reached. In this work, a new particle swarm optimization (PSO) method which can adjust the weighting factors automatically was investigated to overcome the requirement of manual adjustment, thereby reducing the workload of the human planner and contributing to the development of a fully automated planning process. The proposed optimization method consists of three steps. (i) First, a swarm of weighting factors (i.e., particles) is initialized randomly in the search space, where each particle corresponds to a global objective function. (ii) Then, a plan optimization solver is employed to obtain the optimal solution for each particle, and the values of the evaluation functions used to determine the particle's location and the population global location for the PSO are calculated based on these results. (iii) Next, the weighting factors are updated based on the particle's location and the population global location. Step (ii) is performed alternately with step (iii) until the termination condition is reached. In this method, the evaluation function is a combination of several key points on the dose volume histograms. Furthermore, a perturbation strategy - the crossover and mutation operator hybrid approach - is employed to enhance the population diversity, and two arguments are applied to the evaluation function to improve the flexibility of the algorithm. In this study, the proposed method was used to develop IMRT treatment plans involving five unequally spaced 6MV photon beams for 10 prostate cancer cases. The proposed optimization algorithm yielded high-quality plans for all of the cases, without human

  9. Optimizing electrode placement for hemodynamic benefit in cardiac resynchronization therapy.

    Science.gov (United States)

    Babbs, Charles F

    2012-09-01

    Research is needed to explore the relative benefits of alternative electrode placements in biventricular and left ventricular (LV) pacing for heart failure with left bundle branch block (LBBB). A fast computational model of the left ventricle, running on an ordinary laptop computer, was created to simulate the spread of electrical activation over the myocardial surface, together with the resulting electrocardiogram, segmental wall motion, stroke volume, and ejection fraction in the presence of varying degrees of mitral regurgitation. Arbitrary zones of scar and blocked electrical conduction could be modeled. Simulations showed there are both sweet spots and poor spots for LV electrode placement, sometimes separated by only a few centimeters. In heart failure with LBBB, pacing at poor spots can produce little benefit or even reduce pumping effectiveness. Pacing at sweet spots can produce up to 35% improvement in ejection fraction. Relatively larger benefit occurs in dilated hearts, in keeping with the greater disparity between early and late activated muscle. Sweet spots are typically located on the basal to midlevel, inferolateral wall. Poor spots are located on or near the interventricular septum. Anteroapical scar with conduction block causes little shift in locations for optimal pacing. Hearts with increased passive ventricular compliance and absence of preejection mitral regurgitation exhibit greater therapeutic gain. The durations and wave shapes of QRS complexes in the electrocardiogram can help predict optimum electrode placement in real time. Differences between poor responders and hyperresponders to cardiac resynchronization therapy can be understood in terms of basic anatomy, physiology, and pathophysiology. Computational modeling suggests general strategies for optimal electrode placement. In a given patient heart size, regional pathology and regional dynamics allow individual pretreatment planning to target optimal electrode placement. ©2012, The

  10. Tumor Necrosis Factor (TNF Bioactivity at the Site of an Acute Cell-Mediated Immune Response Is Preserved in Rheumatoid Arthritis Patients Responding to Anti-TNF Therapy

    Directory of Open Access Journals (Sweden)

    Rachel Byng-Maddick

    2017-08-01

    Full Text Available The impact of anti-tumor necrosis factor (TNF therapies on inducible TNF-dependent activity in humans has never been evaluated in vivo. We aimed to test the hypothesis that patients responding to anti-TNF treatments exhibit attenuated TNF-dependent immune responses at the site of an immune challenge. We developed and validated four context-specific TNF-inducible transcriptional signatures to quantify TNF bioactivity in transcriptomic data. In anti-TNF treated rheumatoid arthritis (RA patients, we measured the expression of these biosignatures in blood, and in skin biopsies from the site of tuberculin skin tests (TSTs as a human experimental model of multivariate cell-mediated immune responses. In blood, anti-TNF therapies attenuated TNF bioactivity following ex vivo stimulation. However, at the site of the TST, TNF-inducible gene expression and genome-wide transcriptional changes associated with cell-mediated immune responses were comparable to that of RA patients receiving methotrexate only. These data demonstrate that anti-TNF agents in RA patients do not inhibit inducible TNF activity at the site of an acute inflammatory challenge in vivo, as modeled by the TST. We hypothesize instead that their therapeutic effects are limited to regulating TNF activity in chronic inflammation or by alternative non-canonical pathways.

  11. Tumor Necrosis Factor (TNF) Bioactivity at the Site of an Acute Cell-Mediated Immune Response Is Preserved in Rheumatoid Arthritis Patients Responding to Anti-TNF Therapy.

    Science.gov (United States)

    Byng-Maddick, Rachel; Turner, Carolin T; Pollara, Gabriele; Ellis, Matthew; Guppy, Naomi J; Bell, Lucy C K; Ehrenstein, Michael R; Noursadeghi, Mahdad

    2017-01-01

    The impact of anti-tumor necrosis factor (TNF) therapies on inducible TNF-dependent activity in humans has never been evaluated in vivo. We aimed to test the hypothesis that patients responding to anti-TNF treatments exhibit attenuated TNF-dependent immune responses at the site of an immune challenge. We developed and validated four context-specific TNF-inducible transcriptional signatures to quantify TNF bioactivity in transcriptomic data. In anti-TNF treated rheumatoid arthritis (RA) patients, we measured the expression of these biosignatures in blood, and in skin biopsies from the site of tuberculin skin tests (TSTs) as a human experimental model of multivariate cell-mediated immune responses. In blood, anti-TNF therapies attenuated TNF bioactivity following ex vivo stimulation. However, at the site of the TST, TNF-inducible gene expression and genome-wide transcriptional changes associated with cell-mediated immune responses were comparable to that of RA patients receiving methotrexate only. These data demonstrate that anti-TNF agents in RA patients do not inhibit inducible TNF activity at the site of an acute inflammatory challenge in vivo, as modeled by the TST. We hypothesize instead that their therapeutic effects are limited to regulating TNF activity in chronic inflammation or by alternative non-canonical pathways.

  12. Optimal therapy of type 2 diabetes: a controversial challenge

    Science.gov (United States)

    Dardano, Angela; Penno, Giuseppe; Del Prato, Stefano; Miccoli, Roberto

    2014-01-01

    Type 2 diabetes mellitus (T2DM) is one of the most common chronic disorders in older adults and the number of elderly diabetic subjects is growing worldwide. Nonetheless, the diagnosis of T2DM in elderly population is often missed or delayed until an acute metabolic emergency occurs. Accumulating evidence suggests that both aging and environmental factors contribute to the high prevalence of diabetes in the elderly. Clinical management of T2DM in elderly subjects presents unique challenges because of the multifaceted geriatric scenario. Diabetes significantly lowers the chances of “successful” aging, notably it increases functional limitations and impairs quality of life. In this regard, older diabetic patients have a high burden of comorbidities, diabetes-related complications, physical disability, cognitive impairment and malnutrition, and they are more susceptible to the complications of dysglycemia and polypharmacy. Several national and international organizations have delivered guidelines to implement optimal therapy in older diabetic patients based on individualized treatment goals. This means appreciation of the heterogeneity of the disease as generated by life expectancy, functional reserve, social support, as well as personal preference. This paper will review current treatments for achieving glycemic targets in elderly diabetic patients, and discuss the potential role of emerging treatments in this patient population. PMID:24753144

  13. Integrative medicine on optimizing clopidogrel and aspirin therapy.

    Science.gov (United States)

    Chen, Hui

    2018-01-15

    This article reviews the available published data on optimizing clopidogrel and aspirin therapy using translational and integrative medicine. Translational and evidence-based medical studies show that the CYP2C19 gene mutation (CYP2C19*2 and CYP2C19*3) could affect > 50% of the Chinese population, and that this mutation is closely associated with clopidogrel resistance and an increased risk of major adverse cardiovascular events, particularly stent thrombosis in patients following percutaneous coronary intervention (PCI). Adjusted-dose warfarin and aspirin reduce stroke in patients with atrial fibrillation (AF), and warfarin is substantially more efficacious than aspirin. However, a poor compliance is a big problem in warfarin use especially in China. The genetic variants of vitamin K expoxide reductase might account for the universally lower warfarin dosage used in Chinese population. The available evidence indicates that the integrating mainstream treatments (e.g., clopidogrel, CYP2C19 genotyping) and non-mainstream medicines [e.g., Chinese medicines, Naoxintong Capsule (, NXT)] to treat CYP2C19 gene mutation patients following PCI can be effective. Aspirin combined NXT and the adjusted-dose warfarin was equally effective in elderly patients with non-valvular AF in prevention of ischemic stroke.

  14. Therapy Optimization in Multiple Sclerosis: a cohort study of therapy adherence and risk of relapse.

    Science.gov (United States)

    Cohen, B A; Coyle, P K; Leist, T; Oleen-Burkey, M A; Schwartz, M; Zwibel, H

    2015-01-01

    The objective of the Therapy Optimization in MS (TOP MS) Study was to prospectively assess the relationship between MS disease-modifying therapy (DMT) adherence and MS relapse risk over 2 years. Potential participants were recruited for TOP MS by specialty pharmacies who dispensed glatiramer acetate and beta interferons for MS nationwide. Signed IRB-approved informed consents were returned to the pharmacies. TOP MS used electronic data capture with monthly patient entries. Adherence, measured by medication possession ratio (MPR), was derived from pharmacy shipment records. Logistic regression examined the association between protocol-defined relapses and DMT MPR (0.5-0.9). TOP MS enrolled 3151 persons with MS, and 2410 completed the full 2 years. Across all therapies, the mean MPR for the 2-year completer cohort of 2049 who maintained the same DMT was 0.9+0.2 (range: 0.1-1.0), with 63.8% reaching a 2-year MPR >0.9. Evaluated by categories of MPR, the proportion of participants remaining relapse-free for 24 months increased with increasing MPR, and the proportion with >1 relapses declined with increasing levels of MPR (p0.9 MPR group was 64% that of a patient in the MPR 1 DMT prior to the current one was an independent predictor of relapse. The study provides class III evidence that improvement in adherence to DMT for MS is associated with improved clinical outcomes as measured by relapse reduction. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Nutrient Optimization Using Response Surface Methodology for Simultaneous Biomass and Bioactive Compound Production by Lion's Mane Medicinal Mushroom, Hericium erinaceus (Agaricomycetes).

    Science.gov (United States)

    Ofosu, Fred K; Yu, Xiaobin; Wang, Qiang; Li, Hanguang

    2016-01-01

    Due to the unpleasant side effects of long-term use of commercially available drugs, the discovery and development of natural therapeutic agents to prevent life-debilitating diseases is urgently needed. In the present study, the optimization of medium composition for maximum mycelial biomass and bioactive compounds production by Hericium erinaceus was studied using response surface methodology based on a central composite design. Under the optimal conditions and at a pH of 5.41 ± 0.28, the maximum mycelial biomass and exopolysaccharide production reached 25.0 ± 1.38 g/L and 1.73 ± 0.06 g/L, respectively, compared with 22.65 ± 0.10 g/L and 1.56 ± 0.23 g/L in the basal medium, after 7 days of cultivation. Furthermore, we report for the first time the production of adenosine, both intra- and extracellularly in submerged cultures of H. erinaceus. Although most of the adenosine detected existed in the culture medium, the highest intracellular and extracellular adenosine concentrations of 150.84 ± 1.87 mg/L and 142.48 ± 3.78 mg/L were achieved after 7 and 6 days of cultivation, respectively.

  16. Optimization and pharmacological validation of a leukocyte migration assay in zebrafish larvae for the rapid in vivo bioactivity analysis of anti-inflammatory secondary metabolites.

    Directory of Open Access Journals (Sweden)

    María Lorena Cordero-Maldonado

    Full Text Available Over the past decade, zebrafish (Danio rerio have emerged as an attractive model for in vivo drug discovery. In this study, we explore the suitability of zebrafish larvae to rapidly evaluate the anti-inflammatory activity of natural products (NPs and medicinal plants used in traditional medicine for the treatment of inflammatory disorders. First, we optimized a zebrafish assay for leukocyte migration. Inflammation was induced in four days post-fertilization (dpf zebrafish larvae by tail transection and co-incubation with bacterial lipopolysaccharides (LPS, resulting in a robust recruitment of leukocytes to the zone of injury. Migrating zebrafish leukocytes were detected in situ by myeloperoxidase (MPO staining, and anti-inflammatory activity was semi-quantitatively scored using a standardized scale of relative leukocyte migration (RLM. Pharmacological validation of this optimized assay was performed with a panel of anti-inflammatory drugs, demonstrating a concentration-responsive inhibition of leukocyte migration for both steroidal and non-steroidal anti-inflammatory drugs (SAIDs and NSAIDs. Subsequently, we evaluated the bioactivity of structurally diverse NPs with well-documented anti-inflammatory properties. Finally, we further used this zebrafish-based assay to quantify the anti-inflammatory activity in the aqueous and methanolic extracts of several medicinal plants. Our results indicate the suitability of this LPS-enhanced leukocyte migration assay in zebrafish larvae as a front-line screening platform in NP discovery, including for the bioassay-guided isolation of anti-inflammatory secondary metabolites from complex NP extracts.

  17. Bioactive Core-Shell Nanofiber Hybrid Scaffold for Efficient Suicide Gene Transfection and Subsequent Time Resolved Delivery of Prodrug for Anticancer Therapy.

    Science.gov (United States)

    Sukumar, Uday Kumar; Packirisamy, Gopinath

    2015-08-26

    Nanofiber scaffold's ability to foster seemingly nonexistent interface with the cells enables them to effectively deliver various bioactive molecules to cells in the vicinity. Among such bioactive molecules, therapeutically active nucleic acid has been the most common candidate. In spite of such magnanimous efforts in this field, it remains a paradox that suicide gene delivery by nanofibers has never been sought for anticancer application. To investigate such a possibility, in the present work, a composite core-shell nanofiberous scaffold has been realized which could efficiently transfect suicide gene into cancer cells and simultaneously deliver prodrug, 5-Fluorocytosine (5-FC) in a controlled and sustained manner. The scaffold's ability to instigate apoptosis by suicide gene therapy in nonsmall lung cancer cells (A549) was ascertained at both phenotypic and genotypic levels. A cascade of events starting from suicide gene polyplex release from nanofibers, transfection, and expression of cytosine deaminase-uracil phosphoribosyltransferase (CD::UPRT) suicide gene by A549; subsequent prodrug release; and its metabolic conversion into toxic intermediates which finally culminates in host cells apoptosis has been monitored in a time-dependent manner. This work opens up new application avenues for nanofiber-based scaffolds which can effectively manage cancer prognosis.

  18. Optimization of Micellar Electrokinetic Chromatography Method for the Simultaneous Determination of Seven Hydrophilic and Four Lipophilic Bioactive Components in Three Salvia Species.

    Science.gov (United States)

    Cao, Jiliang; Hu, Ji; Wei, Jinchao; Li, Baocai; Zhang, Mi; Xiang, Cheng; Li, Peng

    2015-08-21

    A micellar electrokinetic chromatography (MEKC) method was developed for the simultaneous determination of seven hydrophilic phenolic acids and four lipophilic tanshinones in three Salvia species. In normal MEKC mode using SDS as surfactant, the investigated 11 compounds could not be well separated. Therefore, several buffer modifiers including β-cyclodextrins (β-CD), ionic liquid 1-butyl-3-methylimidazolium tetrafluoroborate ([bmim]BF4) and organic solvents have been added to the buffer solution to improve the separation selectivity. Under the optimized conditions (BGE, 15 mM sodium tetraborate with 10 mM SDS, 5 mM β-CD, 10 mM [bmim]BF4 and 15% ACN (v/v) as additives; buffer pH, 9.8; voltage, 20 kV; temperature, 25 °C), the 11 investigated analytes could achieve baseline separation in 34 min. The proposed MEKC was additionally validated by evaluating the linearity (R(2) ≥ 0.9965), LODs (0.27-1.39 μg·mL(-1)), and recovery (94.26%-105.17%), demonstrating this method was reproducible, accurate and reliable. Moreover, the contents of the 11 compounds in three Salvia species, including S. miltiorrhiza, S. przewalskii and S. castanea were analyzed. The result showed that the established MEKC method was simple and practical for the simultaneous determination of the hydrophilic and lipophilic bioactive components in Salvia species, which could be used to effectively evaluate the quality of these valued medicinal plants.

  19. Data to establish the optimal standard regimen and predicting the response to docetaxel therapy

    Directory of Open Access Journals (Sweden)

    Emad Y. Moawad

    2015-12-01

    Full Text Available This paper contains data to establish the optimal standard regimen and predicting the response to docetaxel therapy (Moawad, 2014 [1]. Docetaxel has been in use for over a decade without demonstrating data indicates a predictable response in the treatment of cancer. Data of puzzling response to docetaxel therapy was due to its cell cycle specific effect. Although several administered schedules were investigated, the relative therapeutic advantage of high versus low doses has not been identified yet. Also the antitumor target of docetaxel has not yet been identified to optimize therapy by predicting the response of patients prior to therapy to provide a protection against treatment failure. In the present paper, we demonstrate the data used to optimize docetaxel therapy and investigate the possibility of predicting for the first time the antitumor target of docetaxel.

  20. Optimizing proton therapy at the LBL medical accelerator

    Energy Technology Data Exchange (ETDEWEB)

    Alonso, J.

    1992-03-01

    This Grant has marked the beginning of a multi-year study process expected to lead to design and construction of at least one, possibly several hospital-based proton therapy facilities in the United States.

  1. Optimizing proton therapy at the LBL medical accelerator. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Alonso, J.

    1992-03-01

    This Grant has marked the beginning of a multi-year study process expected to lead to design and construction of at least one, possibly several hospital-based proton therapy facilities in the United States.

  2. Optimization of pressurized liquid extraction by response surface methodology of Goji berry (Lycium barbarum L.) phenolic bioactive compounds.

    Science.gov (United States)

    Tripodo, Giusy; Ibáñez, Elena; Cifuentes, Alejandro; Gilbert-López, Bienvenida; Fanali, Chiara

    2018-01-03

    Pressurized liquid extraction (PLE) has been used for the first time in this work to extract phenolic compounds from Goji berries according to a multilevel factorial design using response surface methodology. The global yield (% w/dw, weight/dry-weight), total phenolic content (TPC), total flavonoid (TF) and antioxidant activity (determined via ABTS assay, expressed as TEAC value) were used as response variables to study the effects of temperature (50-180°C) and green solvent composition (mixtures of ethanol/water). Phenolic compounds characterization was performed by high performance liquid chromatography-diode array detector-tandem mass spectrometry (HPLC-DAD-MS/MS). The optimum PLE conditions predicted by the model were as follows: 180°C and 86% ethanol in water with a good desirability value of 0.815. The predicted conditions were confirmed experimentally and once the experimental design was validated for commercial fruit samples, the PLE extraction of phenolic compounds from three different varieties of fruit samples (Selvatico mongolo, Bigol, and Polonia) was performed. Nine phenolic compounds were tentatively identified in these extracts, including phenolic acids and their derivatives, and flavonols. The optimized PLE conditions were compared to a conventional solid-liquid extraction, demonstrating that PLE is a useful alternative to extract phenolic compounds from Goji berry. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Brachytherapy optimal planning with application to intravascular radiation therapy.

    Science.gov (United States)

    Sadegh, P; Mourtada, F A; Taylor, R H; Anderson, J H

    1999-09-01

    We have been studying brachytherapy planning with the objective of minimizing the maximum deviation of the delivered dose from prescribed dose bounds for treatment volumes. A general framework for optimal treatment planning is presented and the minmax optimization is formulated as a linear program. Dose rate calculations are based on the dosimetry formulation of the American Association of Physicists in Medicine, Task Group 43. We apply the technique to optimal planning for intravascular brachytherapy of intimal hyperplasia using ultrasound data and 192Ir seeds. The planning includes determination of an optimal dwell-time sequence for a train of seeds that deliver radiation while stepping through the vessel lesion. The results illustrate the advantage of this strategy over the common approach of delivering radiation by positioning a single train of seeds along the whole lesion.

  4. Optimal control of multiplicative control systems arising from cancer therapy

    Science.gov (United States)

    Bahrami, K.; Kim, M.

    1975-01-01

    This study deals with ways of curtailing the rapid growth of cancer cell populations. The performance functional that measures the size of the population at the terminal time as well as the control effort is devised. With use of the discrete maximum principle, the Hamiltonian for this problem is determined and the condition for optimal solutions are developed. The optimal strategy is shown to be a bang-bang control. It is shown that the optimal control for this problem must be on the vertices of an N-dimensional cube contained in the N-dimensional Euclidean space. An algorithm for obtaining a local minimum of the performance function in an orderly fashion is developed. Application of the algorithm to the design of antitumor drug and X-irradiation schedule is discussed.

  5. Optimization of Micellar Electrokinetic Chromatography Method for the Simultaneous Determination of Seven Hydrophilic and Four Lipophilic Bioactive Components in Three Salvia Species

    Directory of Open Access Journals (Sweden)

    Jiliang Cao

    2015-08-01

    Full Text Available A micellar electrokinetic chromatography (MEKC method was developed for the simultaneous determination of seven hydrophilic phenolic acids and four lipophilic tanshinones in three Salvia species. In normal MEKC mode using SDS as surfactant, the investigated 11 compounds could not be well separated. Therefore, several buffer modifiers including β-cyclodextrins (β-CD, ionic liquid 1-butyl-3-methylimidazolium tetrafluoroborate ([bmim]BF4 and organic solvents have been added to the buffer solution to improve the separation selectivity. Under the optimized conditions (BGE, 15 mM sodium tetraborate with 10 mM SDS, 5 mM β-CD, 10 mM [bmim]BF4 and 15% ACN (v/v as additives; buffer pH, 9.8; voltage, 20 kV; temperature, 25 °C, the 11 investigated analytes could achieve baseline separation in 34 min. The proposed MEKC was additionally validated by evaluating the linearity (R2 ≥ 0.9965, LODs (0.27–1.39 μg·mL–1, and recovery (94.26%–105.17%, demonstrating this method was reproducible, accurate and reliable. Moreover, the contents of the 11 compounds in three Salvia species, including S. miltiorrhiza, S. przewalskii and S. castanea were analyzed. The result showed that the established MEKC method was simple and practical for the simultaneous determination of the hydrophilic and lipophilic bioactive components in Salvia species, which could be used to effectively evaluate the quality of these valued medicinal plants.

  6. Optimizing Cognitive-Behavioral Therapy for Childhood Psychiatric Disorders

    Science.gov (United States)

    Piacentini, John

    2008-01-01

    Reports that expand the understanding of the treatment of childhood obsessive-compulsive disorder by using exposure-based cognitive-behavioral therapy in the age group of 5 to 8-year-olds are presented. A model for collecting the common core elements of evidence-based psychosocial treatments for childhood disorders is also presented.

  7. Optimal Levels of Emotional Arousal in Experiential Therapy of Depression

    Science.gov (United States)

    Carryer, Jonathan R.; Greenberg, Leslie S.

    2010-01-01

    Objective: To determine the relationship between length of time spent expressing highly aroused emotion and therapeutic outcome. Method: Thirty-eight clients (14 male, 24 female) between the ages of 22 and 60 years (M = 39.5, SD = 9.71), treated for depression with experiential therapy, were rated on working alliance and expressed emotional…

  8. Optimizing anti-TNF therapy in inflammatory bowel disease

    NARCIS (Netherlands)

    Brandse, J.F.

    2015-01-01

    Anti-TNF, zoals infliximab en adalimumab, zijn effectief voor de behandeling van chronische ontstekingsziekten van de darm (IBD): de ziekte van Crohn en colitis ulcerosa. Deze middelen zijn echter kostbaar en niet alle patiënten hebben baat bij de therapie. Dit proefschrift beschrijft hoe de mate

  9. Determinants of optimal adherence to antiretroviral therapy among ...

    African Journals Online (AJOL)

    Background: Successful Antiretroviral therapy (ART) was shown to rely on high levels of medication adherence to enable maximum and durable viral suppression for the prolongation of life among people living with HIV/AIDS. Objective: The study sought to determine individual and environmental factors that influence ...

  10. Optimizing supervised exercise therapy for patients with intermittent claudication

    NARCIS (Netherlands)

    Nicolaï, Saskia P A; Hendriks, Erik J M; Prins, Martin H; Teijink, Joep A W; van Asselt, Thea

    2010-01-01

    BACKGROUND: The first-line intervention for intermittent claudication is usually supervised exercise therapy (SET). The literature describes a range of exercise programs varying in setting, duration, and content. The purpose of the present study was to examine the exercise protocols offered and to

  11. Brachytherapy optimal planning with application to intravascular radiation therapy

    DEFF Research Database (Denmark)

    Sadegh, Payman; Mourtada, Firas A.; Taylor, Russell H.

    1999-01-01

    . Dose rate calculations are based on the sosimetry formulation of the American Association of Physicists in Medicine, Task Group 43. We apply the technique to optimal planning for intravascular brachytherapy of intimal hyperplasia using ultrasound data and 192Ir seeds. The planning includes...

  12. Ways to Optimize Therapy of Prolonged Conjugation Jaundice in Infants

    Directory of Open Access Journals (Sweden)

    O.G. Shadrin

    2015-10-01

    Full Text Available The article is devoted to the optimization of the treatment of prolonged conjugation jaundice. Inclusion of ursodeoxycholic acid in the treatment of neonatal prolonged conjugation jaundice in a dose of 15–20 mg/kg of body mass per day increases the terms of regression of clinical and paraclinical signs of jaundice as much as 2 times and leads to cytolysis normalization. The preparation has a sufficient level of safety, there were not revealed side effects whilst its application.

  13. SU-E-T-295: Simultaneous Beam Sampling and Aperture Shape Optimization for Station Parameter Optimized Radiation Therapy (SPORT)

    Energy Technology Data Exchange (ETDEWEB)

    Zarepisheh, M; Li, R; Xing, L [Stanford UniversitySchool of Medicine, Stanford, CA (United States); Ye, Y [Stanford Univ, Management Science and Engineering, Stanford, Ca (United States); Boyd, S [Stanford University, Electrical Engineering, Stanford, CA (United States)

    2014-06-01

    Purpose: Station Parameter Optimized Radiation Therapy (SPORT) was recently proposed to fully utilize the technical capability of emerging digital LINACs, in which the station parameters of a delivery system, (such as aperture shape and weight, couch position/angle, gantry/collimator angle) are optimized altogether. SPORT promises to deliver unprecedented radiation dose distributions efficiently, yet there does not exist any optimization algorithm to implement it. The purpose of this work is to propose an optimization algorithm to simultaneously optimize the beam sampling and aperture shapes. Methods: We build a mathematical model whose variables are beam angles (including non-coplanar and/or even nonisocentric beams) and aperture shapes. To solve the resulting large scale optimization problem, we devise an exact, convergent and fast optimization algorithm by integrating three advanced optimization techniques named column generation, gradient method, and pattern search. Column generation is used to find a good set of aperture shapes as an initial solution by adding apertures sequentially. Then we apply the gradient method to iteratively improve the current solution by reshaping the aperture shapes and updating the beam angles toward the gradient. Algorithm continues by pattern search method to explore the part of the search space that cannot be reached by the gradient method. Results: The proposed technique is applied to a series of patient cases and significantly improves the plan quality. In a head-and-neck case, for example, the left parotid gland mean-dose, brainstem max-dose, spinal cord max-dose, and mandible mean-dose are reduced by 10%, 7%, 24% and 12% respectively, compared to the conventional VMAT plan while maintaining the same PTV coverage. Conclusion: Combined use of column generation, gradient search and pattern search algorithms provide an effective way to optimize simultaneously the large collection of station parameters and significantly improves

  14. Psychogenic urticaria: The issues of diagnosis and optimization of therapy

    Directory of Open Access Journals (Sweden)

    A. A. Pribytkov

    2014-01-01

    Full Text Available Objective: to reveal clinical and immunological criteria for psychogenic urticaria (PU and to determine the therapeutic efficacy of alimemazine in this abnormality.Patients and methods. Ninety-three patients with PU, 46 apparently healthy individuals, and 90 patients with chronic autoimmune urticaria (CAU were examined. The methods included clinical examination; use of the Goldberg anxiety rating scale; enzyme immunoassay of serum substance P levels. The efficacy of alimemazine was evaluated in an open-label comparative randomized trial for 4 weeks.Results and discussion. Patients with PU significantly more frequently showed a predominance of manifestations of itching over skin rashes and higher levels of anxiety disorders than those with CAU. The mean serum concentration of substance P was 0.006±0.005 ng/ml in the patients with CAU, 0.026±0.02 ng/ml in healthy individuals, and 8.46±0.95 ng/ml in the patients with PU (p<0.0001. Addition of standard therapy (second-generation antihistamines, disintoxication with alimemazine 15–30 mg/day ensured statistically significant advantages over the control (standard therapy in the following indicators: reductions in the severity of the disease, the degree of anxiety disorders, and the serum levels of substance P. Alimemazine was noted to be satisfactorily tolerated. Thus, the authors established the following diagnostic criteria for PU: a psychotraumatic situation; dermal manifestations after psychogeny; high anxiety; a predominance of the manifestations of itching over the dermal symptoms of urticaria; and elevated serum substance P concentrations. Standard therapy added by alimemazine versus that without the drug was found to be effective. There were reductions in the symptoms of urticaria, the degree of anxiety disorders, and the levels of substance P.

  15. New Insights in the Design of Bioactive Peptides and Chelating Agents for Imaging and Therapy in Oncology

    Directory of Open Access Journals (Sweden)

    Anna Lucia Tornesello

    2017-08-01

    Full Text Available Many synthetic peptides have been developed for diagnosis and therapy of human cancers based on their ability to target specific receptors on cancer cell surface or to penetrate the cell membrane. Chemical modifications of amino acid chains have significantly improved the biological activity, the stability and efficacy of peptide analogues currently employed as anticancer drugs or as molecular imaging tracers. The stability of somatostatin, integrins and bombesin analogues in the human body have been significantly increased by cyclization and/or insertion of non-natural amino acids in the peptide sequences. Moreover, the overall pharmacokinetic properties of such analogues and others (including cholecystokinin, vasoactive intestinal peptide and neurotensin analogues have been improved by PEGylation and glycosylation. Furthermore, conjugation of those peptide analogues to new linkers and bifunctional chelators (such as AAZTA, TETA, TRAP, NOPO etc., produced radiolabeled moieties with increased half life and higher binding affinity to the cognate receptors. This review describes the most important and recent chemical modifications introduced in the amino acid sequences as well as linkers and new bifunctional chelators which have significantly improved the specificity and sensitivity of peptides used in oncologic diagnosis and therapy.

  16. [Optimizing epilepsy therapy in children and adolescents with lamotrigine].

    Science.gov (United States)

    Siemes, H; Brandl, U; Helmstädter, C; Kurlemann, G; Rating, D; Sälke-Kellermann, R A; Stephani, U; Uberall, M; Wiemer-Kruel, A; Bergmann, L

    2005-01-01

    Lamotrigine is a broadly effective antiepileptic drug in mono- and add-on therapy for children and adolescents with focal and generalized epilepsies. Some epileptologists consider lamotrigine as the drug of primary choice in older school children and adolescents because of its good tolerability (no increase of body weight, no impairment of cognitive functions, due to new data probably no teratogenic properties). Lamotrigine can be used with good efficacy in numerable epilepsy diseases, such as tuberous sclerosis, juvenile neuronal lipofuscinosis and Rett syndrome. The first studies show that lamotrigine is also effective in children under 2 years of age. For therapy of difficult-to-treat epilepsies the combination of lamotrigine with valproate has proved as especially useful. This clinical observation is supported by new results of animal experiments. The dose-dependant and typical CNS side effects vertigo, ataxia, nausea, tremor and diplopia are found most frequently. The rate of allergic skin rashes which was very high before 1998 has decreased markedly by new dosage guidelines and is now as low as in older antiepileptic drugs. Lamotrigine does not impair cognitive functions, especially not memory and language. It has mood-stabilizing features and may improve quality of life. In animal experiments lamotrigine shows antiepileptogenic and neuroprotective effects.

  17. [Optimizing therapy of arterial hypertension in a health cure].

    Science.gov (United States)

    Schreiber, J; Biermann, J

    1986-08-01

    On 514 male and female patients (average age 51.9 years) with arterial hypertension I and II according to WHO who had been admitted to cure a check-up of the efficacy of the current antihypertensive therapy and the compliance of the patients was carried out. At the beginning of the cure 15.5% of the hypertensives were normotonic, 30.2% with limiting value and 52.3% hypertonic. The analysis of the habit of intake of antihypertensive drugs revealed that only 48.4% of the patients before the cure had taken their medicaments according to the prescription of the physician. The main cause for unsatisfying results of the therapy is the bad compliance of the hypertensives, in our opinion a sequela of the often existing freedom from symptoms. Further causes we see in the irregularities of the intake of medicaments, particularly during shift-work, in wrong habits of nutrition and in a too passive way of life. At the end of the cure in 64.5% of all patients a normotonic stabilisation of the blood pressure was to be stated, 27.8% had limiting values, in 7.4% no stabilisation of the blood pressure into the normal or borderline region could be achieved. Under cure conditions modes of behaviour furthering the disease and wrong habits of life and eating can be changed. The cure gives good conditions by means of health-educational measures and using the motivation for an active way of life which is present in the patient at the end of the cure better to carry the aims of the medical treatment.

  18. Comparing immune-tumor growth models with drug therapy using optimal control

    Science.gov (United States)

    Martins, Marisa C.; Rocha, Ana Maria A. C.; Costa, M. Fernanda P.; Fernandes, Edite M. G. P.

    2016-06-01

    In this paper we compare the dynamics of three tumor growth models that include an immune system and a drug administration therapy using optimal control. The objective is to minimize a combined function of the total of tumor cells over time and a chemotherapeutic drug administration.

  19. A fast optimization algorithm for multicriteria intensity modulated proton therapy planning.

    Science.gov (United States)

    Chen, Wei; Craft, David; Madden, Thomas M; Zhang, Kewu; Kooy, Hanne M; Herman, Gabor T

    2010-09-01

    To describe a fast projection algorithm for optimizing intensity modulated proton therapy (IMPT) plans and to describe and demonstrate the use of this algorithm in multicriteria IMPT planning. The authors develop a projection-based solver for a class of convex optimization problems and apply it to IMPT treatment planning. The speed of the solver permits its use in multicriteria optimization, where several optimizations are performed which span the space of possible treatment plans. The authors describe a plan database generation procedure which is customized to the requirements of the solver. The optimality precision of the solver can be specified by the user. The authors apply the algorithm to three clinical cases: A pancreas case, an esophagus case, and a tumor along the rib cage case. Detailed analysis of the pancreas case shows that the algorithm is orders of magnitude faster than industry-standard general purpose algorithms (MOSEK'S interior point optimizer, primal simplex optimizer, and dual simplex optimizer). Additionally, the projection solver has almost no memory overhead. The speed and guaranteed accuracy of the algorithm make it suitable for use in multicriteria treatment planning, which requires the computation of several diverse treatment plans. Additionally, given the low memory overhead of the algorithm, the method can be extended to include multiple geometric instances and proton range possibilities, for robust optimization.

  20. Optimizing clarithromycin-containing therapy for Helicobacter pylori in the era of antibiotic resistance.

    Science.gov (United States)

    Molina-Infante, Javier; Gisbert, Javier P

    2014-08-14

    The efficacy of triple therapy for Helicobacter pylori infection has dramatically declined over the last decade, largely related to increasing clarithromycin resistance rates. From a microbiological standpoint, bismuth quadruple therapy is the ideal replacement since it combines drugs for which resistance does not impair its efficacy. Nonetheless, several obstacles such as availability, complexity or tolerance prevent a general implementation of bismuth quadruple therapy, so non-bismuth quadruple regimens remain the best first-line treatment in clinical practice in many geographical areas. We review the rationale and efficacy of several optimization tools (increasing the length of duration, high-dose acid suppression, probiotics), which have been largely evaluated over the last 5 years to increase the effectiveness of standard triple therapy. Then, we update available evidence on the effectiveness of several non-bismuth quadruple therapies (sequential, concomitant, hybrid, miscellaneous therapy), which have gained interest lately. We also revise evidence on the efficacy of the aforementioned optimization tools for non-bismuth quadruples schemes and, finally we provide a novel regionalized therapeutic algorithm, based on novel formulas recently developed for predicting the outcome of non-bismuth quadruple regimens, upon local antibiotic resistance rates.

  1. Optimal Endpoint of Therapy in IBD: An Update on Factors Determining a Successful Drug Withdrawal

    Directory of Open Access Journals (Sweden)

    Anita Annaházi

    2015-01-01

    Full Text Available Ulcerative colitis (UC and Crohn’s disease (CD are chronic inflammatory disorders, which require long term treatment to achieve remission and to prevent relapses and cancer. While current therapies are effective in most cases, they can have rare but serious side effects and are often associated with high costs. On the other hand, early discontinuation of an effective treatment may lead to a quick relapse and to complications at the restart of therapy. Therefore it is essential to determine the optimal duration of maintenance therapy, but clear guidelines are missing. The most important questions when deciding whether to continue or withdraw therapy in quiescent UC and CD patients are the efficacy of the continuous treatment to maintain remission in the long term, the frequency and severity of side effects, and the chance of relapse after discontinuation of therapy. This review summarizes the current knowledge on these topics with respect to 5-aminosalicylates, thiopurines, methotrexate, and biological therapies and collects information regarding when and in which specific patient groups, in the absence of risk factors, can withdrawal of therapy be considered without a high risk of relapse. Additionally, the particular aspect of colorectal cancer prevention by current therapies will also be discussed.

  2. Direct-aperture optimization applied to selection of beam orientations in intensity-modulated radiation therapy

    Science.gov (United States)

    Bedford, J. L.; Webb, S.

    2007-01-01

    Direct-aperture optimization (DAO) was applied to iterative beam-orientation selection in intensity-modulated radiation therapy (IMRT), so as to ensure a realistic segmental treatment plan at each iteration. Nested optimization engines dealt separately with gantry angles, couch angles, collimator angles, segment shapes, segment weights and wedge angles. Each optimization engine performed a random search with successively narrowing step sizes. For optimization of segment shapes, the filtered backprojection (FBP) method was first used to determine desired fluence, the fluence map was segmented, and then constrained direct-aperture optimization was used thereafter. Segment shapes were fully optimized when a beam angle was perturbed, and minimally re-optimized otherwise. The algorithm was compared with a previously reported method using FBP alone at each orientation iteration. An example case consisting of a cylindrical phantom with a hemi-annular planning target volume (PTV) showed that for three-field plans, the method performed better than when using FBP alone, but for five or more fields, neither method provided much benefit over equally spaced beams. For a prostate case, improved bladder sparing was achieved through the use of the new algorithm. A plan for partial scalp treatment showed slightly improved PTV coverage and lower irradiated volume of brain with the new method compared to FBP alone. It is concluded that, although the method is computationally intensive and not suitable for searching large unconstrained regions of beam space, it can be used effectively in conjunction with prior class solutions to provide individually optimized IMRT treatment plans.

  3. Direct leaf trajectory optimization for volumetric modulated arc therapy planning with sliding window delivery

    CERN Document Server

    Papp, Dávid

    2013-01-01

    We propose a novel optimization model for volumetric modulated arc therapy (VMAT) planning that directly optimizes deliverable leaf trajectories in the treatment plan optimization problem, and eliminates the need for a separate arc-sequencing step. In this model, a 360-degree arc is divided into a given number of arc segments in which the leaves move unidirectionally. This facilitates an algorithm that determines the optimal piecewise linear leaf trajectories for each arc segment, which are deliverable in a given treatment time. Multi-leaf collimator (MLC) constraints, including maximum leaf speed and interdigitation, are accounted for explicitly. The algorithm is customized to allow for VMAT delivery using constant gantry speed and dose rate, however, the algorithm generalizes to variable gantry speed if beneficial. We demonstrate the method for three different tumor sites: a head-and-neck case, a prostate case, and a paraspinal case. For that purpose, we first obtain a reference plan for intensity modulated...

  4. Primary prevention with a defibrillator: are therapies always really optimized before implantation?

    Science.gov (United States)

    Foucault, Anthony; Amelot, Mathieu; Gomes, Sophie; Champ-Rigot, Laure; Saloux, Eric; Pellissier, Arnaud; Labombarda, Fabien; Scanu, Patrice; Milliez, Paul

    2012-11-01

    Left ventricle ejection fraction (LVEF) ≤ 30-35% is widely accepted as a cut-off for primary prevention with an implantable cardiac defibrillator (ICD) in patients with both ischaemic and non-ischaemic cardiomyopathy supposedly on optimal medical therapy. This study reports evolutions of LVEF and treatments of patients implanted in our institution with an ICD for primary prevention of sudden death, after 2 years of follow-up. Among 84 patients with LVEF under 35% implanted between 2005 and 2007, 28 (33%) had improved their LVEF >35% after the 2 years of follow-up. During this period, even if Beta-blockers (98%) and renin-angiotensin system (RAS) blockers (95%) were already initially prescribed, treatments were significantly optimized with improvement of maximal doses of beta-blockers and RAS blockers at 2 year follow-up compared with initial prescription (62 vs. 37% and 68 vs. 45%, respectively). In patients with improved LVEF, a trend toward a better treatment optimization and revascularization procedures (in the sub-group of ischaemic patients) were observed compared with non-improved LVEF patients. In our study of patients with prophylactic ICD, one-third of them have improved their LVEF after a 2 year follow-up. Despite an optimal medical therapy at the time of implantation, we were able to further improve the maximal treatment doses after implantation. This study highlights the issue of what should be considered as 'optimal' therapy and the possibility of improvement of LVEF related to a real optimized treatment before implantation.

  5. Computational Modeling of Medical Images of Brain Tumor Patients for Optimized Radiation Therapy Planning

    DEFF Research Database (Denmark)

    Agn, Mikael

    In brain tumor radiation therapy, the aim is to maximize the delivered radiation dose to the targeted tumor and at the same time minimize the dose to sensitive healthy structures – so-called organs-at-risk (OARs). When planning a radiation therapy session, the tumor and the OARs therefore need...... to be delineated on medical images of the patient’s head, to be able to optimize a radiation dose plan. In clinical practice, the delineation is performed manually with limited assistance from automatic procedures, which is both time-consuming and typically suffers from poor reproducibility. There is, therefore...

  6. Optimization of Proton CT Detector System and Image Reconstruction Algorithm for On-Line Proton Therapy.

    Directory of Open Access Journals (Sweden)

    Chae Young Lee

    Full Text Available The purposes of this study were to optimize a proton computed tomography system (pCT for proton range verification and to confirm the pCT image reconstruction algorithm based on projection images generated with optimized parameters. For this purpose, we developed a new pCT scanner using the Geometry and Tracking (GEANT 4.9.6 simulation toolkit. GEANT4 simulations were performed to optimize the geometric parameters representing the detector thickness and the distance between the detectors for pCT. The system consisted of four silicon strip detectors for particle tracking and a calorimeter to measure the residual energies of the individual protons. The optimized pCT system design was then adjusted to ensure that the solution to a CS-based convex optimization problem would converge to yield the desired pCT images after a reasonable number of iterative corrections. In particular, we used a total variation-based formulation that has been useful in exploiting prior knowledge about the minimal variations of proton attenuation characteristics in the human body. Examinations performed using our CS algorithm showed that high-quality pCT images could be reconstructed using sets of 72 projections within 20 iterations and without any streaks or noise, which can be caused by under-sampling and proton starvation. Moreover, the images yielded by this CS algorithm were found to be of higher quality than those obtained using other reconstruction algorithms. The optimized pCT scanner system demonstrated the potential to perform high-quality pCT during on-line image-guided proton therapy, without increasing the imaging dose, by applying our CS based proton CT reconstruction algorithm. Further, we make our optimized detector system and CS-based proton CT reconstruction algorithm potentially useful in on-line proton therapy.

  7. Loco-regional therapies for patients with hepatocellular carcinoma awaiting liver transplantation: Selecting an optimal therapy.

    Science.gov (United States)

    Byrne, Thomas J; Rakela, Jorge

    2016-06-24

    Hepatocellular carcinoma (HCC) is a common, increasingly prevalent malignancy. For all but the smallest lesions, surgical removal of cancer via resection or liver transplantation (LT) is considered the most feasible pathway to cure. Resection - even with favorable survival - is associated with a fairly high rate of recurrence, perhaps since most HCCs occur in the setting of cirrhosis. LT offers the advantage of removing not only the cancer but the diseased liver from which the cancer has arisen, and LT outperforms resection for survival with selected patients. Since time waiting for LT is time during which HCC can progress, loco-regional therapy (LRT) is widely employed by transplant centers. The purpose of LRT is either to bridge patients to LT by preventing progression and waitlist dropout, or to downstage patients who slightly exceed standard eligibility criteria initially but can fall within it after treatment. Transarterial chemoembolization and radiofrequency ablation have been the most widely utilized LRTs to date, with favorable efficacy and safety as a bridge to LT (and for the former, as a downstaging modality). The list of potentially effective LRTs has expanded in recent years, and includes transarterial chemoembolization with drug-eluting beads, radioembolization and novel forms of extracorporal therapy. Herein we appraise the various LRT modalities for HCC, and their potential roles in specific clinical scenarios in patients awaiting LT.

  8. The cost of a combination Anti-Retroviral Therapy (cART optimization pathway as maintenance therapy in HIV-1 infected patients

    Directory of Open Access Journals (Sweden)

    Roberto Ravasio

    2017-11-01

    CONCLUSIONS: From the Italian NHS’s perspective, the adoption of a specific cART optimization pathway represents a cost-saving option as maintenance antiretroviral therapy in HIV-1 infected patients.

  9. Interaction between vestibular compensation mechanisms and vestibular rehabilitation therapy: ten recommendations for optimal functional recovery

    Directory of Open Access Journals (Sweden)

    LACOUR eMichel

    2015-01-01

    Full Text Available This review questions the relationships between the plastic events responsible for the recovery of vestibular function after a unilateral vestibular loss (vestibular compensation, which has been well described in animal models in the last decades, and the vestibular rehabilitation (VR therapy elaborated on a more empirical basis for vestibular loss patients. The main objective is not to propose a catalogue of results but to provide clinicians with an understandable view on when and how to perform VR therapy, and why VR may benefit from basic knowledge and may influence the recovery process. With this perspective, 10 major recommendations are proposed as ways to identify an optimal functional recovery. Among them are the crucial role of active and early VR therapy, coincidental with a post-lesion sensitive period for neuronal network remodelling, the instructive role that VR therapy may play in this functional reorganisation, the need for progression in the VR therapy protocol, which is based mainly on adaptation processes, the necessity to take into account the sensorimotor, cognitive and emotional profile of the patient to propose individual or à la carte VR therapies, and the importance of motivational and ecologic contexts. More than 10 general principles are very likely, but these principles seem crucial for the fast recovery of vestibular loss patients to ensure good quality of life.

  10. Interaction between Vestibular Compensation Mechanisms and Vestibular Rehabilitation Therapy: 10 Recommendations for Optimal Functional Recovery.

    Science.gov (United States)

    Lacour, Michel; Bernard-Demanze, Laurence

    2014-01-01

    This review questions the relationships between the plastic events responsible for the recovery of vestibular function after a unilateral vestibular loss (vestibular compensation), which has been well described in animal models in the last decades, and the vestibular rehabilitation (VR) therapy elaborated on a more empirical basis for vestibular loss patients. The main objective is not to propose a catalog of results but to provide clinicians with an understandable view on when and how to perform VR therapy, and why VR may benefit from basic knowledge and may influence the recovery process. With this perspective, 10 major recommendations are proposed as ways to identify an optimal functional recovery. Among them are the crucial role of active and early VR therapy, coincidental with a post-lesion sensitive period for neuronal network remodeling, the instructive role that VR therapy may play in this functional reorganization, the need for progression in the VR therapy protocol, which is based mainly on adaptation processes, the necessity to take into account the sensorimotor, cognitive, and emotional profile of the patient to propose individual or "à la carte" VR therapies, and the importance of motivational and ecologic contexts. More than 10 general principles are very likely, but these principles seem crucial for the fast recovery of vestibular loss patients to ensure good quality of life.

  11. Analysis of endocardial acceleration during intraoperative optimization of cardiac resynchronization therapy.

    Science.gov (United States)

    Hernandez, Alfredo I; Ziglio, Filippo; Amblard, Amel; Senhadji, Lotfi; Leclercq, Christophe

    2013-01-01

    Cardiac resynchronization therapy (CRT) is the therapy of choice for selected patients suffering from drug-refractory congestive heart failure and presenting an interventricular desynchronization. CRT is delivered by an implantable biventricular pacemaker, which stimulates the right atrium and both ventricles at specific timings. The optimization and personalization of this therapy requires to quantify both the electrical and the mechanical cardiac functions during the intraoperative and postoperative phases. The objective of this paper is to evaluate the feasibility of the calculation of features extracted from endocardial acceleration (EA) signals and the potential utility of these features for the intraoperative optimization of CRT. Endocardial intraoperative data from one patient are analyzed for 33 different pacing configurations, including changes in the atrio-ventricular and inter-ventricular delays and different ventricular stimulation sites. The main EA features are extracted for each pacing configuration and analyzed so as to estimate the intra-configuration and inter-configuration variability. Results show the feasibility of the proposed approach and suggest the potential utility of EA for intraoperative monitoring of the cardiac function and defining optimal, adaptive pacing configurations.

  12. Bare Bones of Bioactive Glass

    Science.gov (United States)

    2000-01-01

    Paul Ducheyne, a principal investigator in the microgravity materials science program and head of the University of Pernsylvania's Center for Bioactive Materials and Tissue Engineering, is leading the trio as they use simulated microgravity to determine the optimal characteristics of tiny glass particles for growing bone tissue. The result could make possible a much broader range of synthetic bone-grafting applications. Even in normal gravity, bioactive glass particles enhance bone growth in laboratory tests with flat tissue cultures. Ducheyne and his team believe that using the bioactive microcarriers in a rotating bioreactor in microgravity will produce improved, three-dimensional tissue cultures. The work is sponsored by NASA's Office of Biological and Physical Research. The bioreactor is managed by the Biotechnology Cell Science Program at NASA's Johnson Space Center (JSC). NASA-sponsored bioreactor research has been instrumental in helping scientists to better understand normal and cancerous tissue development. In cooperation with the medical community, the bioreactor design is being used to prepare better models of human colon, prostate, breast and ovarian tumors. Cartilage, bone marrow, heart muscle, skeletal muscle, pancreatic islet cells, liver and kidney are just a few of the normal tissues being cultured in rotating bioreactors by investigators. Credit: NASA and University of Pennsylvania Center for Bioactive Materials and Tissue Engineering.

  13. Systems Pharmacology Approaches for Optimization of Antiangiogenic Therapies: Challenges and Opportunities

    Directory of Open Access Journals (Sweden)

    Satish eSharan

    2015-02-01

    Full Text Available Targeted therapies have become an important therapeutic paradigm for multiple malignancies. The rapid development of resistance to these therapies impedes the successful management of advanced cancer. Due to the redundancy in angiogenic signaling, alternative proangiogenic factors are activated upon treatment with anti-VEGF agents. Higher doses of the agents lead to greater stimulation of compensatory proangiogenic pathways that limit the therapeutic efficacy of VEGF-targeted drugs and produce escape mechanisms for tumor. Evidence suggests that dose intensity and schedules affect the dynamics of the development of this resistance. Thus, an optimal dosing regimen is crucial to maximizing the therapeutic benefit of antiangiogenic agents and limiting treatment resistance. A systems pharmacology approach using multiscale computational modeling can facilitate a mechanistic understanding of these dynamics of angiogenic biomarkers and their impacts on tumor reduction and resistance. Herein, we discuss a systems pharmacology approach integrating the biology of VEGF-targeted therapy resistance, including circulating biomarkers, and pharmacodynamics to enable the optimization of antiangiogenic therapy for therapeutic gains.

  14. A nested partitions framework for beam angle optimization in intensity-modulated radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    D' Souza, Warren D; Nazareth, Daryl P [Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD (United States); Zhang, Hao H; Shi Leyuan [Department of Industrial and Systems Engineering, University of Wisconsin, Madison, WI (United States); Meyer, Robert R [Computer Sciences Department, University of Wisconsin, Madison, WI (United States)], E-mail: dsouzaw@ohsu.edu

    2008-06-21

    Coupling beam angle optimization with dose optimization in intensity-modulated radiation therapy (IMRT) increases the size and complexity of an already large-scale combinatorial optimization problem. We have developed a novel algorithm, nested partitions (NP), that is capable of finding suitable beam angle sets by guiding the dose optimization process. NP is a metaheuristic that is flexible enough to guide the search of a heuristic or deterministic dose optimization algorithm. The NP method adaptively samples from the entire feasible region, or search space, and coordinates the sampling effort with a systematic partitioning of the feasible region at successive iterations, concentrating the search in promising subsets. We used a 'warm-start' approach by initiating NP with beam angle samples derived from an integer programming (IP) model. In this study, we describe our implementation of the NP framework with a commercial optimization algorithm. We compared the NP framework with equi-spaced beam angle selection, the IP method, greedy heuristic and random sampling heuristic methods. The results of the NP approach were evaluated using two clinical cases (head and neck and whole pelvis) involving the primary tumor and nodal volumes. Our results show that NP produces better quality solutions than the alternative considered methods.

  15. Spherical cluster analysis for beam angle optimization in intensity-modulated radiation therapy treatment planning

    Science.gov (United States)

    Bangert, Mark; Oelfke, Uwe

    2010-10-01

    An intuitive heuristic to establish beam configurations for intensity-modulated radiation therapy is introduced as an extension of beam ensemble selection strategies applying scalar scoring functions. It is validated by treatment plan comparisons for three intra-cranial, pancreas, and prostate cases each. Based on a patient specific matrix listing the radiological quality of candidate beam directions individually for every target voxel, a set of locally ideal beam angles is generated. The spherical distribution of locally ideal beam angles is characteristic for every treatment site and patient: ideal beam angles typically cluster around distinct orientations. We interpret the cluster centroids, which are identified with a spherical K-means algorithm, as irradiation angles of an intensity-modulated radiation therapy treatment plan. The fluence profiles are subsequently optimized during a conventional inverse planning process. The average computation time for the pre-optimization of a beam ensemble is six minutes on a state-of-the-art work station. The treatment planning study demonstrates the potential benefit of the proposed beam angle optimization strategy. For the three prostate cases under investigation, the standard treatment plans applying nine coplanar equi-spaced beams and treatment plans applying an optimized non-coplanar nine-beam ensemble yield clinically comparable dose distributions. For symmetric patient geometries, the dose distribution formed by nine equi-spaced coplanar beams cannot be improved significantly. For the three pancreas and intra-cranial cases under investigation, the optimized non-coplanar beam ensembles enable better sparing of organs at risk while guaranteeing equivalent target coverage. Beam angle optimization by spherical cluster analysis shows the biggest impact for target volumes located asymmetrically within the patient and close to organs at risk.

  16. Spherical cluster analysis for beam angle optimization in intensity-modulated radiation therapy treatment planning.

    Science.gov (United States)

    Bangert, Mark; Oelfke, Uwe

    2010-10-07

    An intuitive heuristic to establish beam configurations for intensity-modulated radiation therapy is introduced as an extension of beam ensemble selection strategies applying scalar scoring functions. It is validated by treatment plan comparisons for three intra-cranial, pancreas, and prostate cases each. Based on a patient specific matrix listing the radiological quality of candidate beam directions individually for every target voxel, a set of locally ideal beam angles is generated. The spherical distribution of locally ideal beam angles is characteristic for every treatment site and patient: ideal beam angles typically cluster around distinct orientations. We interpret the cluster centroids, which are identified with a spherical K-means algorithm, as irradiation angles of an intensity-modulated radiation therapy treatment plan. The fluence profiles are subsequently optimized during a conventional inverse planning process. The average computation time for the pre-optimization of a beam ensemble is six minutes on a state-of-the-art work station. The treatment planning study demonstrates the potential benefit of the proposed beam angle optimization strategy. For the three prostate cases under investigation, the standard treatment plans applying nine coplanar equi-spaced beams and treatment plans applying an optimized non-coplanar nine-beam ensemble yield clinically comparable dose distributions. For symmetric patient geometries, the dose distribution formed by nine equi-spaced coplanar beams cannot be improved significantly. For the three pancreas and intra-cranial cases under investigation, the optimized non-coplanar beam ensembles enable better sparing of organs at risk while guaranteeing equivalent target coverage. Beam angle optimization by spherical cluster analysis shows the biggest impact for target volumes located asymmetrically within the patient and close to organs at risk.

  17. Contractility sensor-guided optimization of cardiac resynchronization therapy: results from the RESPOND-CRT trial.

    Science.gov (United States)

    Brugada, Josep; Delnoy, Peter Paul; Brachmann, Johannes; Reynolds, Dwight; Padeletti, Luigi; Noelker, Georg; Kantipudi, Charan; Rubin Lopez, José Manuel; Dichtl, Wolfgang; Borri-Brunetto, Alberto; Verhees, Luc; Ritter, Philippe; Singh, Jagmeet P

    2017-03-07

    Although cardiac resynchronization therapy (CRT) is effective in patients with systolic heart failure (HF) and a wide QRS interval, a substantial proportion of patients remain non-responsive. The SonR contractility sensor embedded in the right atrial lead enables individualized automatic optimization of the atrioventricular (AV) and interventricular (VV) timings. The RESPOND-CRT study investigated the safety and efficacy of the contractility sensor system in HF patients undergoing CRT. RESPOND-CRT was a prospective, randomized, double-blinded, multicentre, non-inferiority trial. Patients were randomized (2:1, respectively) to receive weekly, automatic CRT optimization with SonR vs. an Echo-guided optimization of AV and VV timings. The primary efficacy endpoint was the rate of clinical responders (patients alive, without adjudicated HF-related events, with improvement in New York Heart Association class or quality of life), at 12 months. The study randomized 998 patients. Responder rates were 75.0% in the SonR arm and 70.4% in the Echo arm (mean difference, 4.6%; 95% CI, -1.4% to 10.6%; P optimization using the contractility sensor was safe and as effective as Echo-guided AV and VV optimization in increasing response to CRT. NCT01534234.

  18. Effect of amiodarone and sotalol on ventricular defibrillation threshold: the optimal pharmacological therapy in cardioverter defibrillator patients (OPTIC) trial

    National Research Council Canada - National Science Library

    Hohnloser, Stefan H; Dorian, Paul; Roberts, Robin; Gent, Michael; Israel, Carsten W; Fain, Eric; Champagne, Jean; Connolly, Stuart J

    2006-01-01

    .... The Optimal Pharmacological Therapy in Cardioverter Defibrillator Patients (OPTIC) trial was a randomized clinical trial evaluating the efficacy of amiodarone plus beta-blocker and sotalol versus beta-blocker alone for reduction of ICD shocks...

  19. SU-F-T-209: Multicriteria Optimization Algorithm for Intensity Modulated Radiation Therapy Using Pencil Proton Beam Scanning

    Energy Technology Data Exchange (ETDEWEB)

    Beltran, C; Kamal, H [Mayo Clinic, Rochester, MN (United States)

    2016-06-15

    Purpose: To provide a multicriteria optimization algorithm for intensity modulated radiation therapy using pencil proton beam scanning. Methods: Intensity modulated radiation therapy using pencil proton beam scanning requires efficient optimization algorithms to overcome the uncertainties in the Bragg peaks locations. This work is focused on optimization algorithms that are based on Monte Carlo simulation of the treatment planning and use the weights and the dose volume histogram (DVH) control points to steer toward desired plans. The proton beam treatment planning process based on single objective optimization (representing a weighted sum of multiple objectives) usually leads to time-consuming iterations involving treatment planning team members. We proved a time efficient multicriteria optimization algorithm that is developed to run on NVIDIA GPU (Graphical Processing Units) cluster. The multicriteria optimization algorithm running time benefits from up-sampling of the CT voxel size of the calculations without loss of fidelity. Results: We will present preliminary results of Multicriteria optimization for intensity modulated proton therapy based on DVH control points. The results will show optimization results of a phantom case and a brain tumor case. Conclusion: The multicriteria optimization of the intensity modulated radiation therapy using pencil proton beam scanning provides a novel tool for treatment planning. Work support by a grant from Varian Inc.

  20. Beam angle optimization for intensity-modulated radiation therapy using a guided pattern search method

    Science.gov (United States)

    Rocha, Humberto; Dias, Joana M.; Ferreira, Brígida C.; Lopes, Maria C.

    2013-05-01

    Generally, the inverse planning of radiation therapy consists mainly of the fluence optimization. The beam angle optimization (BAO) in intensity-modulated radiation therapy (IMRT) consists of selecting appropriate radiation incidence directions and may influence the quality of the IMRT plans, both to enhance better organ sparing and to improve tumor coverage. However, in clinical practice, most of the time, beam directions continue to be manually selected by the treatment planner without objective and rigorous criteria. The goal of this paper is to introduce a novel approach that uses beam’s-eye-view dose ray tracing metrics within a pattern search method framework in the optimization of the highly non-convex BAO problem. Pattern search methods are derivative-free optimization methods that require a few function evaluations to progress and converge and have the ability to better avoid local entrapment. The pattern search method framework is composed of a search step and a poll step at each iteration. The poll step performs a local search in a mesh neighborhood and ensures the convergence to a local minimizer or stationary point. The search step provides the flexibility for a global search since it allows searches away from the neighborhood of the current iterate. Beam’s-eye-view dose metrics assign a score to each radiation beam direction and can be used within the pattern search framework furnishing a priori knowledge of the problem so that directions with larger dosimetric scores are tested first. A set of clinical cases of head-and-neck tumors treated at the Portuguese Institute of Oncology of Coimbra is used to discuss the potential of this approach in the optimization of the BAO problem.

  1. Direct leaf trajectory optimization for volumetric modulated arc therapy planning with sliding window delivery

    Energy Technology Data Exchange (ETDEWEB)

    Papp, Dávid, E-mail: Papp.David@mgh.harvard.edu; Unkelbach, Jan [Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, 30 Fruit Street, Boston, Massachusetts 02114 (United States)

    2014-01-15

    Purpose: The authors propose a novel optimization model for volumetric modulated arc therapy (VMAT) planning that directly optimizes deliverable leaf trajectories in the treatment plan optimization problem, and eliminates the need for a separate arc-sequencing step. Methods: In this model, a 360° arc is divided into a given number of arc segments in which the leaves move unidirectionally. This facilitates an algorithm that determines the optimal piecewise linear leaf trajectories for each arc segment, which are deliverable in a given treatment time. Multileaf collimator constraints, including maximum leaf speed and interdigitation, are accounted for explicitly. The algorithm is customized to allow for VMAT delivery using constant gantry speed and dose rate, however, the algorithm generalizes to variable gantry speed if beneficial. Results: The authors demonstrate the method for three different tumor sites: a head-and-neck case, a prostate case, and a paraspinal case. The authors first obtain a reference plan for intensity modulated radiotherapy (IMRT) using fluence map optimization and 20 intensity-modulated fields in equally spaced beam directions, which is beyond the standard of care. Modeling the typical clinical setup for the treatment sites considered, IMRT plans using seven or nine beams are also computed. Subsequently, VMAT plans are optimized by dividing the 360° arc into 20 corresponding arc segments. Assuming typical machine parameters (a dose rate of 600 MU/min, and a maximum leaf speed of 3 cm/s), it is demonstrated that the optimized VMAT plans with 2–3 min delivery time are of noticeably better quality than the 7–9 beam IMRT plans. The VMAT plan quality approaches the quality of the 20-beam IMRT benchmark plan for delivery times between 3 and 4 min. Conclusions: The results indicate that high quality treatments can be delivered in a single arc with 20 arc segments if sufficient time is allowed for modulation in each segment.

  2. Multi-GPU configuration of 4D intensity modulated radiation therapy inverse planning using global optimization

    Science.gov (United States)

    Hagan, Aaron; Sawant, Amit; Folkerts, Michael; Modiri, Arezoo

    2018-01-01

    We report on the design, implementation and characterization of a multi-graphic processing unit (GPU) computational platform for higher-order optimization in radiotherapy treatment planning. In collaboration with a commercial vendor (Varian Medical Systems, Palo Alto, CA), a research prototype GPU-enabled Eclipse (V13.6) workstation was configured. The hardware consisted of dual 8-core Xeon processors, 256 GB RAM and four NVIDIA Tesla K80 general purpose GPUs. We demonstrate the utility of this platform for large radiotherapy optimization problems through the development and characterization of a parallelized particle swarm optimization (PSO) four dimensional (4D) intensity modulated radiation therapy (IMRT) technique. The PSO engine was coupled to the Eclipse treatment planning system via a vendor-provided scripting interface. Specific challenges addressed in this implementation were (i) data management and (ii) non-uniform memory access (NUMA). For the former, we alternated between parameters over which the computation process was parallelized. For the latter, we reduced the amount of data required to be transferred over the NUMA bridge. The datasets examined in this study were approximately 300 GB in size, including 4D computed tomography images, anatomical structure contours and dose deposition matrices. For evaluation, we created a 4D-IMRT treatment plan for one lung cancer patient and analyzed computation speed while varying several parameters (number of respiratory phases, GPUs, PSO particles, and data matrix sizes). The optimized 4D-IMRT plan enhanced sparing of organs at risk by an average reduction of 26% in maximum dose, compared to the clinical optimized IMRT plan, where the internal target volume was used. We validated our computation time analyses in two additional cases. The computation speed in our implementation did not monotonically increase with the number of GPUs. The optimal number of GPUs (five, in our study) is directly related to the

  3. Optimizing insulin pump therapy: the potential advantages of using a structured diabetes management program.

    Science.gov (United States)

    Lange, Karin; Ziegler, Ralph; Neu, Andreas; Reinehr, Thomas; Daab, Iris; Walz, Marion; Maraun, Michael; Schnell, Oliver; Kulzer, Bernhard; Reichel, Andreas; Heinemann, Lutz; Parkin, Christopher G; Haak, Thomas

    2015-03-01

    Use of continuous subcutaneous insulin infusion (CSII) therapy improves glycemic control, reduces hypoglycemia and increases treatment satisfaction in individuals with diabetes. As a number of patient- and clinician-related factors can hinder the effectiveness and optimal usage of CSII therapy, new approaches are needed to address these obstacles. Ceriello and colleagues recently proposed a model of care that incorporates the collaborative use of structured SMBG into a formal approach to personalized diabetes management within all diabetes populations. We adapted this model for use in CSII-treated patients in order to enable the implementation of a workflow structure that enhances patient-physician communication and supports patients' diabetes self-management skills. We recognize that time constraints and current reimbursement policies pose significant challenges to healthcare providers integrating the Personalised Diabetes Management (PDM) process into clinical practice. We believe, however, that the time invested in modifying practice workflow and learning to apply the various steps of the PDM process will be offset by improved workflow and more effective patient consultations. This article describes how to implement PDM into clinical practice as a systematic, standardized process that can optimize CSII therapy.

  4. Eddy current analysis and optimization of fast scanning magnet for a proton therapy system

    Science.gov (United States)

    Liu, Xu; Qin, Bin; Liu, Kaifeng; Chen, Wei; Liang, Zhikai; Chen, Qushan; Chen, Dezhi; Fan, Mingwu

    2017-08-01

    Proton therapy is now recognized as one of the most effective radiation therapy methods for cancers. A proton therapy facility with multiple gantry treatment rooms is under development in HUST (Huazhong University of Science and Technology), which is based on isochronous superconducting cyclotron scheme. In the beam line, the scanning system spreads out the proton beam on the target according to the complex tumour shape by two scanning magnets for horizontal and vertical scanning independently. Since these two magnets are excited by alternating currents and the maximum repetition frequency is up to 100 Hz, eddy currents and losses are expected to be significant. Slits are proven to be an effective way to reduce the eddy currents. To evaluate the heat distribution due to eddy losses in the pole end of the scanning magnet, the transient electromagnetic analysis and steady-state thermal analysis are performed. This paper describes design considerations of the scanning system and mainly analyses the eddy current effect of the scanning magnets. Different coil shapes and slit arrangements are simulated and compared to obtain the optimal configuration. The maximum temperatures of two magnets are optimized below 70 °C. In addition, the lag effect due to eddy currents is also discussed.

  5. Optimal dosage and dwell time of ethanol lock therapy on catheters infected with Candida species.

    Science.gov (United States)

    Öncü, Serkan

    2014-04-01

    Anti-infective lock therapy is a treatment strategy in conjunction with systemic antifungal agents for the treatment of intravascular catheter infections caused by fungi. In this study, the optimal dosage and dwell time of ethanol lock solution (ELS) effective against catheters infected by Candida species were assessed. Biofilm forming isolates of Candida albicans, Candida parapsilosis and Candida tropicalis was used as the study isolates. Infected catheters were exposed to ELS at 20%, 30%, 40%, 60% and 80% strength for a variety dwell times (15 min, 30 min, 1 h, 2 h, 4 h, 8 h, 12 h and 24 h). Fungal eradication was evaluated by the quantitative culture techniques. ELS's with 40% and greater strength sterilized the catheters within 30 min. Lower strength of ELS's (20% and 30%) sterilized the catheters in 24 h and 2 h, respectively. According to the study, lock therapy with ≥40% ethanol for 30 min appear to be the optimal schedule in sterilizing Candida infected catheters. Ethanol lock therapy with such concentrations and dwell time may be a useful adjunct to systemic anti-fungal antibiotics in sterilizing (and cleaning) and eradicating fungal catheter related infections in the hope of preserving crucial central venous access. Copyright © 2013 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  6. Clinico-psychological analysis of systematic (vestibular and nonsystematic (psychogenic vertigo, therapy optimization

    Directory of Open Access Journals (Sweden)

    Elena Mikhailovna Illarionova

    2011-01-01

    Full Text Available Objective: to study the clinical and psychoemotional characteristics in patients with systematic and nonsystematic vertigo and to optimize therapy. Patients and methods. The clinical features were analyzed in 25 patients with systematic vertigo and 25 patients with psychogenic vertigo. Their psychoemotional sphere was studied using the Beck depression inventory, the Spielberger-hanin personality- and situation-related anxiety inventory, and the vestibular inventory. Results. There were statistically significant clinical differences and a higher degree of anxiety-depressive disorders in the patients with psychogenic vertigo. Drug therapy in combination with stabilometric platform exercises based on the biological feedback principle was stated to be effective in patients with different types of vertigo, in those with psychogenic dizziness in particular.

  7. Optimal timing of speech and language therapy for aphasia after stroke: more evidence needed.

    Science.gov (United States)

    Nouwens, Femke; Visch-Brink, Evy G; Van de Sandt-Koenderman, Mieke M E; Dippel, Diederik W J; Koudstaal, Peter J; de Lau, Lonneke M L

    2015-01-01

    Aphasia due to stroke affects communication and quality of life. Most stroke survivors with aphasia receive speech and language therapy. Although an early start of treatment is advocated in clinical practice, evidence for "The earlier, the better" in aphasia rehabilitation is weak. Hence, clinicians are faced with the dilemma of when to initiate intensive treatment: as early as possible, when most of the spontaneous recovery occurs but when patients are often ill, or later, when the patients' condition is more stabilized. Here we discuss whether aphasia outcome is affected by timing of treatment in relation to stroke onset and whether there is evidence for an optimal window of time during which language therapy should be provided. Findings from various rehabilitation research fields are discussed and combined to provide principles for future research.

  8. Optimal Neutron Source & Beam Shaping Assembly for Boron Neutron Capture Therapy

    Energy Technology Data Exchange (ETDEWEB)

    J. Vujic; E. Greenspan; W.E. Kastenber; Y. Karni; D. Regev; J.M. Verbeke, K.N. Leung; D. Chivers; S. Guess; L. Kim; W. Waldron; Y. Zhu

    2003-04-30

    There were three objectives to this project: (1) The development of the 2-D Swan code for the optimization of the nuclear design of facilities for medical applications of radiation, radiation shields, blankets of accelerator-driven systems, fusion facilities, etc. (2) Identification of the maximum beam quality that can be obtained for Boron Neutron Capture Therapy (BNCT) from different reactor-, and accelerator-based neutron sources. The optimal beam-shaping assembly (BSA) design for each neutron source was also to e obtained. (3) Feasibility assessment of a new neutron source for NCT and other medical and industrial applications. This source consists of a state-of-the-art proton or deuteron accelerator driving and inherently safe, proliferation resistant, small subcritical fission assembly.

  9. Optimal Neutron Source and Beam Shaping Assembly for Boron Neutron Capture Therapy

    CERN Document Server

    Vujic, J L; Greenspan, E; Guess, S; Karni, Y; Kastenber, W E; Kim, L; Leung, K N; Regev, D; Verbeke, J M; Waldron, W L; Zhu, Y

    2003-01-01

    There were three objectives to this project: (1) The development of the 2-D Swan code for the optimization of the nuclear design of facilities for medical applications of radiation, radiation shields, blankets of accelerator-driven systems, fusion facilities, etc. (2) Identification of the maximum beam quality that can be obtained for Boron Neutron Capture Therapy (BNCT) from different reactor-, and accelerator-based neutron sources. The optimal beam-shaping assembly (BSA) design for each neutron source was also to e obtained. (3) Feasibility assessment of a new neutron source for NCT and other medical and industrial applications. This source consists of a state-of-the-art proton or deuteron accelerator driving and inherently safe, proliferation resistant, small subcritical fission assembly.

  10. Optimization of levofloxacin-loaded crosslinked chitosan microspheres for inhaled aerosol therapy.

    Science.gov (United States)

    Gaspar, Marisa C; Sousa, João J S; Pais, Alberto A C C; Cardoso, Olga; Murtinho, Dina; Serra, M Elisa S; Tewes, Frédéric; Olivier, Jean-Christophe

    2015-10-01

    The aim of this work was the development of innovative levofloxacin-loaded swellable microspheres (MS) for the dry aerosol therapy of pulmonary chronicPseudomonas aeruginosainfections in Cystic Fibrosis patients. In a first step, a factorial design was applied to optimize formulations of chitosan-based MS with glutaraldehyde as crosslinker. After optimization, other crosslinkers (genipin, glutaric acid and glyceraldehyde) were tested. Analyses of MS included aerodynamic and swelling properties, morphology, drug loading, thermal and chemical characteristics,in vitroantibacterial activity and drug release studies. The prepared MS presented a drug content ranging from 39.8% to 50.8% of levofloxacin in an amorphous or dispersed state, antibacterial activity and fast release profiles. The highest degree of swelling was obtained for MS crosslinked with glutaric acid and genipin. These formulations also presented satisfactory aerodynamic properties, making them a promising alternative, in dry-powder inhalers, to levofloxacin solution for inhalation. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Optimal Cardiac Resynchronization Therapy Pacing Rate in Non-Ischemic Heart Failure Patients

    DEFF Research Database (Denmark)

    Ghotbi, Adam Ali; Sander, Mikael; Køber, Lars

    2015-01-01

    BACKGROUND: The optimal pacing rate during cardiac resynchronization therapy (CRT) is unknown. Therefore, we investigated the impact of changing basal pacing frequencies on autonomic nerve function, cardiopulmonary exercise capacity and self-perceived quality of life (QoL). METHODS: Twelve CRT...... by microneurography (MSNA), peak oxygen consumption (pVO2), N-terminal pro-brain natriuretic peptide (p-NT-proBNP), echocardiography and QoL. RESULTS: DDD-80 pacing for 3 months increased the mean heart rate from 77.3 to 86.1 (p = 0.001) and reduced sympathetic activity compared to DDD-60 (51±14 bursts/100 cardiac...

  12. Acquiring the optimal time for hyperbaric therapy in the rat model of CFA induced arthritis.

    Science.gov (United States)

    Koo, Sung Tae; Lee, Chang-Hyung; Shin, Yong Il; Ko, Hyun Yoon; Lee, Da Gyo; Jeong, Han-Sol

    2014-01-01

    We previously published an article about the pressure effect using a rheumatoid animal model. Hyperbaric therapy appears to be beneficial in treating rheumatoid arthritis (RA) by reducing the inflammatory process in an animal model. In this sense, acquiring the optimal pressure-treatment time parameter for RA is important and no optimal hyperbaric therapy time has been suggested up to now. The purpose of our study was to acquire the optimal time for hyperbaric therapy in the RA rat model. Controlled animal study. Following injection of complete Freund's adjuvant (CFA) into one side of the knee joint, 32 rats were randomly assigned to 3 different time groups (1, 3, 5 hours a day) under 1.5 atmospheres absolute (ATA) hyperbaric chamber for 12 days. The pain levels were assessed daily for 2 weeks by weight bearing force (WBF) of the affected limb. In addition, the levels of gelatinase, MMP-2, and MMP-9 expression in the synovial fluids of the knees were analyzed. The reduction of WBF was high at 2 days after injection and then it was spontaneously increased up to 14 days in all 3 groups. There were significant differences of WBF between 5 hours and control during the third through twelfth days, between 3 hours and control during the third through fifth and tenth through twelfth days, and between 3 hours and 5 hours during the third through seventh days (P CFA injection in all groups compared to the initial findings, however, the 3 hour group showed a smaller MMP-9/MMP-2 ratio than the control group. Although enough samples were used for the study to support our hypothesis, more samples will be needed to raise the validity and reliability. The effect of hyperbaric treatment appears to be dependent upon the elevated therapy time under 1.5 ATA pressure for a short period of time; however, the long-term effects were similar in all pressure groups. Further study will be needed to acquire the optimal pressure-treatment parameter relationship in various conditions for

  13. CANCER IMMUNOLOGY AND IMMUNOTHERAPY – UNDERSTANDING AND ADAPTATION THE CURRENT EVIDENCE TO OPTIMIZE PATIENT THERAPY OUTCOMES.

    Directory of Open Access Journals (Sweden)

    Orlin Savov

    2015-11-01

    Full Text Available The aim of this publication includes the try to act as intermediary to the readers, which should be able to understand: - The description of the cancer immunotherapy mechanisms in the context of current therapy decisions for the treatment of cancer - The including criteria for those patients with cancer who could be appropriate candidates for immunotherapy - And to optimize patient outcomes by using best practices to manage the adverse events associated with immunotherapy treatment More than 15 promising immunotherapy approaches being tested in clinical trials with appropriate patients and colleagues for enrollment and peer-to-peer education purposes, respectively.

  14. Application of Monte Carlo Simulation of Total Skin Electron Therapy for Treatment Optimization.

    Science.gov (United States)

    Shokrani, Parvaneh

    A technique for treatment of total skin irradiation was simulated using the Monte Carlo method. By application of this simulation, optimization of the Total Skin Electron Therapy (TSET) technique was accomplished. The purpose of the optimization process was to select the properties of the optimal TSET secondary scatterer. The optimization process was divided into four steps. First, the geometry of the treatment head of a Phillips SL-20 linear accelerator and the geometry of the TSET technique were simulated. Using a combination of the EGS4 Monte Carlo code system, geometry routines, and a package of variance reduction techniques, spectrum of the electron beam, at the exit window of the treatment head and at the treatment plane (located at 300 cm), was calculated. Second, to confirm the accuracy of calculations, the calculated depth dose curves, field uniformity and bremsstrahlung contamination for a control scatterer were compared to the measurement values. Third, a group of materials were selected to perform as a candidate for the optimal TSET scatterer. The treatment field characteristics produced by these materials were calculated and the optimal scatterer was selected. Forth, selection of the optimal scatterer was confirmed by way of physical measurements. Physical measurements showed that the EGS4 Monte Carlo code system, together with the TSET user code, developed in this research, simulated the TSET technique accurately. However there were some problem areas. The central axis surface dose was underestimated by simulations and there was inconsistency associated with radial distribution of bremsstrahlung contamination. Monte Carlo simulation of the TSET technique predicted a 0.059 mm thickness of lead as the optimal scatterer. This scatterer was predicted to produce a minimum uniformity of 73%, a d_{80%} of between 1.8-2.1 cm and a 30% increase in dose rate (as compared to the control scatterer). Moreover, the Monte Carlo simulations TSET technique and

  15. Ultraviolet spectroscopic evaluation of bioactive saponin fraction ...

    African Journals Online (AJOL)

    The use of herbal therapy is a common practice in Africa. One of the commonly used herbs is Vernonia amygdalina. Processing of the plant for use leads to the loss of phytochemical principles like saponin which has been shown to possess bioactivity. This study was to evaluate and characterize the saponin principles, ...

  16. SU-F-T-79: Monte Carlo Investigation of Optimizing Parameters for Modulated Electron Arc Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Al Ashkar, E; Eraba, K; Imam, M [Azhar university, Nasr City, Cairo (Egypt); Eldib, A; Ma, C [Fox Chase Cancer Center, Philadelphia, PA (United States)

    2016-06-15

    Purpose: Electron arc therapy provides excellent dose distributions for treating superficial tumors along curved surfaces. However this modality has not received widespread application due to the lack of needed advancement in electron beam delivery, accurate electron dose calculation and treatment plan optimization. The aim of the current work is to investigate possible parameters that can be optimized for electron arc (eARC) therapy. Methods: The MCBEAM code was used to generate phase space files for 6 and 12MeV electron beam energies from a Varian trilogy machine. An Electron Multi-leaf collimator eMLC of 2cm thickness positioned at 82 cm source collimated distance was used in the study. Dose distributions for electron arcs were calculated inside a cylindrical phantom using the MCSIM code. The Cylindrical phantom was constructed with 0.2cm voxels and a 15cm diameter. Electron arcs were delivered with two different approaches. The first approach was to deliver the arc as segments of very small field widths. In this approach we also tested the impact of the segment size and the arc increment angle. The second approach is to deliver the arc as a sum of large fields each covering the whole target as seen from the beam eye view. Results: In considering 90 % as the prescription isodose line, the first approach showed a region of buildup proceeding before the prescription zone. This build up is minimizing with the second approach neglecting need for bolus. The second approach also showed less x-ray contamination. In both approaches the variation of the segment size changed the size and location of the prescription isodose line. The optimization process for eARC could involve interplay between small and large segments to achieve desired coverage. Conclusion: An advanced modulation of eARCs will allow for tailored dose distribution for superficial curved target as with challenging scalp cases.

  17. Markov model for characterizing neuropsychologic impairment and Monte Carlo simulation for optimizing efavirenz therapy.

    Science.gov (United States)

    Bisaso, Kuteesa R; Mukonzo, Jackson K; Ette, Ene I

    2015-11-01

    The study was undertaken to develop a pharmacokinetic-pharmacodynamic model to characterize efavirenz-induced neuropsychologic impairment, given preexistent impairment, which can be used for the optimization of efavirenz therapy via Monte Carlo simulations. The modeling was performed with NONMEM 7.2. A 1-compartment pharmacokinetic model was fitted to efavirenz concentration data from 196 Ugandan patients treated with a 600-mg daily efavirenz dose. Pharmacokinetic parameters and area under the curve (AUC) were derived. Neuropsychologic evaluation of the patients was done at baseline and in week 2 of antiretroviral therapy. A discrete-time 2-state first-order Markov model was developed to describe neuropsychologic impairment. Efavirenz AUC, day 3 efavirenz trough concentration, and female sex increased the probability (P01) of neuropsychologic impairment. Efavirenz oral clearance (CL/F) increased the probability (P10) of resolution of preexistent neuropsychologic impairment. The predictive performance of the reduced (final) model, given the data, incorporating AUC on P01and CL /F on P10, showed that the model adequately characterized the neuropsychologic impairment observed with efavirenz therapy. Simulations with the developed model predicted a 7% overall reduction in neuropsychologic impairment probability at 450 mg of efavirenz. We recommend a reduction in efavirenz dose from 600 to 450 mg, because the 450-mg dose has been shown to produce sustained antiretroviral efficacy. © 2015, The American College of Clinical Pharmacology.

  18. Range optimization for mono- and bi-energetic proton modulated arc therapy with pencil beam scanning

    Science.gov (United States)

    Sanchez-Parcerisa, Daniel; Kirk, Maura; Fager, Marcus; Burgdorf, Brendan; Stowe, Malorie; Solberg, Tim; Carabe, Alejandro

    2016-11-01

    The development of rotational proton therapy plans based on a pencil-beam-scanning (PBS) system has been limited, among several other factors, by the energy-switching time between layers, a system-dependent parameter that ranges between a fraction of a second and several seconds. We are investigating mono- and bi-energetic rotational proton modulated arc therapy (PMAT) solutions that would not be affected by long energy switching times. In this context, a systematic selection of the optimal proton energy for each arc is vital. We present a treatment planning comparison of four different range selection methods, analyzing the dosimetric outcomes of the resulting treatment plans created with the ranges obtained. Given the patient geometry and arc definition (gantry and couch trajectories, snout elevation) our in-house treatment planning system (TPS) FoCa was used to find the maximum, medial and minimum water-equivalent thicknesses (WETs) of the target viewed from all possible field orientations. Optimal ranges were subsequently determined using four methods: (1) by dividing the max/min WET interval into equal steps, (2) by taking the average target midpoints from each field, (3) by taking the average WET of all voxels from all field orientations, and (4) by minimizing the fraction of the target which cannot be reached from any of the available angles. After the range (for mono-energetic plans) or ranges (for bi-energetic plans) were selected, the commercial clinical TPS in use in our institution (Varian Eclipse™) was used to produce the PMAT plans using multifield optimization. Linear energy transfer (LET) distributions of all plans were also calculated using FoCa and compared among the different methods. Mono- and bi-energetic PMAT plans, composed of a single 180° arc, were created for two patient geometries: a C-shaped target located in the mediastinal area of a thoracic tissue-equivalent phantom and a small brain tumor located directly above the brainstem. All

  19. Development and optimization of SPE-HPLC-UV/ELSD for simultaneous determination of nine bioactive components in Shenqi Fuzheng Injection based on Quality by Design principles.

    Science.gov (United States)

    Wang, Lu; Qu, Haibin

    2016-03-01

    A method combining solid phase extraction, high performance liquid chromatography, and ultraviolet/evaporative light scattering detection (SPE-HPLC-UV/ELSD) was developed according to Quality by Design (QbD) principles and used to assay nine bioactive compounds within a botanical drug, Shenqi Fuzheng Injection. Risk assessment and a Plackett-Burman design were utilized to evaluate the impact of 11 factors on the resolutions and signal-to-noise of chromatographic peaks. Multiple regression and Pareto ranking analysis indicated that the sorbent mass, sample volume, flow rate, column temperature, evaporator temperature, and gas flow rate were statistically significant (p design combined with response surface analysis was employed to study the relationships between the quality of SPE-HPLC-UV/ELSD analysis and four significant factors, i.e., flow rate, column temperature, evaporator temperature, and gas flow rate. An analytical design space of SPE-HPLC-UV/ELSD was then constructed by calculated Monte Carlo probability. In the presented approach, the operating parameters of sample preparation, chromatographic separation, and compound detection were investigated simultaneously. Eight terms of method validation, i.e., system-suitability tests, method robustness/ruggedness, sensitivity, precision, repeatability, linearity, accuracy, and stability, were accomplished at a selected working point. These results revealed that the QbD principles were suitable in the development of analytical procedures for samples in complex matrices. Meanwhile, the analytical quality and method robustness were validated by the analytical design space. The presented strategy provides a tutorial on the development of a robust QbD-compliant quantitative method for samples in complex matrices.

  20. Comparison of optimization algorithms in intensity-modulated radiation therapy planning

    Science.gov (United States)

    Kendrick, Rachel

    Intensity-modulated radiation therapy is used to better conform the radiation dose to the target, which includes avoiding healthy tissue. Planning programs employ optimization methods to search for the best fluence of each photon beam, and therefore to create the best treatment plan. The Computational Environment for Radiotherapy Research (CERR), a program written in MATLAB, was used to examine some commonly-used algorithms for one 5-beam plan. Algorithms include the genetic algorithm, quadratic programming, pattern search, constrained nonlinear optimization, simulated annealing, the optimization method used in Varian EclipseTM, and some hybrids of these. Quadratic programing, simulated annealing, and a quadratic/simulated annealing hybrid were also separately compared using different prescription doses. The results of each dose-volume histogram as well as the visual dose color wash were used to compare the plans. CERR's built-in quadratic programming provided the best overall plan, but avoidance of the organ-at-risk was rivaled by other programs. Hybrids of quadratic programming with some of these algorithms seems to suggest the possibility of better planning programs, as shown by the improved quadratic/simulated annealing plan when compared to the simulated annealing algorithm alone. Further experimentation will be done to improve cost functions and computational time.

  1. First clinical evaluation of an atrial haemodynamic sensor lead for automatic optimization of cardiac resynchronization therapy.

    Science.gov (United States)

    Duncker, David; Delnoy, Peter Paul; Nägele, Herbert; Mansourati, Jacques; Mont, Lluís; Anselme, Frédéric; Stengel, Petra; Anselmi, Francesca; Oswald, Hanno; Leclercq, Christophe

    2016-05-01

    One option to improve cardiac resynchronization therapy (CRT) responder rates lies in the optimization of pacing intervals. A haemodynamic sensor embedded in the SonRtip atrial lead measures cardiac contractility and provides a systematic automatic atrioventricular and interventricular delays optimization. This multi-centre study evaluated the safety and performance of the lead, up to 1 year. A total of 99 patients were implanted with the system composed of the lead and a CRT-Defibrillator device. Patients were followed at 1, 3, 6, and 12 months post-implant. The primary safety objective was to demonstrate that the atrial lead complication free rate was superior to 90% at 3-months follow-up visit. A lead handling questionnaire was filled by implanting investigators. Lead electrical performances and the performance of the system to compute AV and VV delays were evaluated at each study visit over 1 year. The complication free rate at 3 months post-implant was 99.0% [95%CI 94.5-100.0%], P 75% of the weeks. The atrial lead is safe to implant and shows stable electrical performance over time. It therefore offers a promising tool for automatic CRT optimization to further improve responder rates to CRT. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Cardiology.

  2. Beam neutron energy optimization for boron neutron capture therapy using Monte Carlo method

    Directory of Open Access Journals (Sweden)

    Ali Pazirandeh

    2006-06-01

    Full Text Available  In last two decades the optimal neutron energy for the treatment of deep seated tumors in boron neutron capture therapy in view of neutron physics and chemical compounds of boron carrier has been under thorough study. Although neutron absorption cross section of boron is high (3836b, the treatment of deep seated tumors such as gliobelastoma multiform (GBM requires beam of neutrons of higher energy that can penetrate deeply into the brain and thermalize in the proximity of the tumor. Dosage from recoil proton associated with fast neutrons however poses some constraints on maximum neutron energy that can be used in the treatment. For this reason neutrons in the epithermal energy range of 10eV-10keV are generally to be the most appropriate. The simulation carried out by Monte Carlo methods using MCBNCT and MCNP4C codes along with the cross section library in 290 groups extracted from ENDF/B6 main library. The optimal neutron energy for deep seated tumors depends on the size and depth of tumor. Our estimated optimized energy for the tumor of 5cm wide and 1-2cm thick stands at 5cm depth is in the range of 3-5keV

  3. A GPU-accelerated and Monte Carlo-based intensity modulated proton therapy optimization system.

    Science.gov (United States)

    Ma, Jiasen; Beltran, Chris; Seum Wan Chan Tseung, Hok; Herman, Michael G

    2014-12-01

    Conventional spot scanning intensity modulated proton therapy (IMPT) treatment planning systems (TPSs) optimize proton spot weights based on analytical dose calculations. These analytical dose calculations have been shown to have severe limitations in heterogeneous materials. Monte Carlo (MC) methods do not have these limitations; however, MC-based systems have been of limited clinical use due to the large number of beam spots in IMPT and the extremely long calculation time of traditional MC techniques. In this work, the authors present a clinically applicable IMPT TPS that utilizes a very fast MC calculation. An in-house graphics processing unit (GPU)-based MC dose calculation engine was employed to generate the dose influence map for each proton spot. With the MC generated influence map, a modified least-squares optimization method was used to achieve the desired dose volume histograms (DVHs). The intrinsic CT image resolution was adopted for voxelization in simulation and optimization to preserve spatial resolution. The optimizations were computed on a multi-GPU framework to mitigate the memory limitation issues for the large dose influence maps that resulted from maintaining the intrinsic CT resolution. The effects of tail cutoff and starting condition were studied and minimized in this work. For relatively large and complex three-field head and neck cases, i.e., >100,000 spots with a target volume of ∼ 1000 cm(3) and multiple surrounding critical structures, the optimization together with the initial MC dose influence map calculation was done in a clinically viable time frame (less than 30 min) on a GPU cluster consisting of 24 Nvidia GeForce GTX Titan cards. The in-house MC TPS plans were comparable to a commercial TPS plans based on DVH comparisons. A MC-based treatment planning system was developed. The treatment planning can be performed in a clinically viable time frame on a hardware system costing around 45,000 dollars. The fast calculation and

  4. Including robustness in multi-criteria optimization for intensity-modulated proton therapy.

    Science.gov (United States)

    Chen, Wei; Unkelbach, Jan; Trofimov, Alexei; Madden, Thomas; Kooy, Hanne; Bortfeld, Thomas; Craft, David

    2012-02-07

    We present a method to include robustness in a multi-criteria optimization (MCO) framework for intensity-modulated proton therapy (IMPT). The approach allows one to simultaneously explore the trade-off between different objectives as well as the trade-off between robustness and nominal plan quality. In MCO, a database of plans each emphasizing different treatment planning objectives, is pre-computed to approximate the Pareto surface. An IMPT treatment plan that strikes the best balance between the different objectives can be selected by navigating on the Pareto surface. In our approach, robustness is integrated into MCO by adding robustified objectives and constraints to the MCO problem. Uncertainties (or errors) of the robust problem are modeled by pre-calculated dose-influence matrices for a nominal scenario and a number of pre-defined error scenarios (shifted patient positions, proton beam undershoot and overshoot). Objectives and constraints can be defined for the nominal scenario, thus characterizing nominal plan quality. A robustified objective represents the worst objective function value that can be realized for any of the error scenarios and thus provides a measure of plan robustness. The optimization method is based on a linear projection solver and is capable of handling large problem sizes resulting from a fine dose grid resolution, many scenarios, and a large number of proton pencil beams. A base-of-skull case is used to demonstrate the robust optimization method. It is demonstrated that the robust optimization method reduces the sensitivity of the treatment plan to setup and range errors to a degree that is not achieved by a safety margin approach. A chordoma case is analyzed in more detail to demonstrate the involved trade-offs between target underdose and brainstem sparing as well as robustness and nominal plan quality. The latter illustrates the advantage of MCO in the context of robust planning. For all cases examined, the robust optimization for

  5. Proton energy optimization and reduction for intensity-modulated proton therapy

    Science.gov (United States)

    Cao, Wenhua; Lim, Gino; Liao, Li; Li, Yupeng; Jiang, Shengpeng; Li, Xiaoqiang; Li, Heng; Suzuki, Kazumichi; Zhu, X. Ronald; Gomez, Daniel; Zhang, Xiaodong

    2014-10-01

    Intensity-modulated proton therapy (IMPT) is commonly delivered via the spot-scanning technique. To ‘scan’ the target volume, the proton beam is controlled by varying its energy to penetrate the patient’s body at different depths. Although scanning the proton beamlets or spots with the same energy can be as fast as 10-20 m s-1, changing from one proton energy to another requires approximately two additional seconds. The total IMPT delivery time thus depends mainly on the number of proton energies used in a treatment. Current treatment planning systems typically use all proton energies that are required for the proton beam to penetrate in a range from the distal edge to the proximal edge of the target. The optimal selection of proton energies has not been well studied. In this study, we sought to determine the feasibility of optimizing and reducing the number of proton energies in IMPT planning. We proposed an iterative mixed-integer programming optimization method to select a subset of all available proton energies while satisfying dosimetric criteria. We applied our proposed method to six patient datasets: four cases of prostate cancer, one case of lung cancer, and one case of mesothelioma. The numbers of energies were reduced by 14.3%-18.9% for the prostate cancer cases, 11.0% for the lung cancer cases and 26.5% for the mesothelioma case. The results indicate that the number of proton energies used in conventionally designed IMPT plans can be reduced without degrading dosimetric performance. The IMPT delivery efficiency could be improved by energy layer optimization leading to increased throughput for a busy proton center in which a delivery system with slow energy switch is employed.

  6. Support vector machine based training of multilayer feedforward neural networks as optimized by particle swarm algorithm: application in QSAR studies of bioactivity of organic compounds.

    Science.gov (United States)

    Lin, Wei-Qi; Jiang, Jian-Hui; Zhou, Yan-Ping; Wu, Hai-Long; Shen, Guo-Li; Yu, Ru-Qin

    2007-01-30

    Multilayer feedforward neural networks (MLFNNs) are important modeling techniques widely used in QSAR studies for their ability to represent nonlinear relationships between descriptors and activity. However, the problems of overfitting and premature convergence to local optima still pose great challenges in the practice of MLFNNs. To circumvent these problems, a support vector machine (SVM) based training algorithm for MLFNNs has been developed with the incorporation of particle swarm optimization (PSO). The introduction of the SVM based training mechanism imparts the developed algorithm with inherent capacity for combating the overfitting problem. Moreover, with the implementation of PSO for searching the optimal network weights, the SVM based learning algorithm shows relatively high efficiency in converging to the optima. The proposed algorithm has been evaluated using the Hansch data set. Application to QSAR studies of the activity of COX-2 inhibitors is also demonstrated. The results reveal that this technique provides superior performance to backpropagation (BP) and PSO training neural networks.

  7. Explicit and convex optimization of plan quality measures in intensity-modulated radiation therapy treatment planning

    CERN Document Server

    Engberg, Lovisa; Forsgren, Anders; Hårdemark, Björn

    2016-01-01

    Given the widespread agreement that doses-at-volume play important roles in quality assessment of radiation therapy treatment plans, planning objectives that correlate well with explicit dose-at-volume optimization are likely to correlate well with plan quality. In this study, planning objectives are formulated to explicitly either minimize or maximize convex approximations of dose-at-volume, namely, mean-tail-doses. This is in contrast to the conventionally used planning objectives, which are used to maximize clinical goal fulfilment by relating to deviations from dose-at-volume thresholds. Advantages of the proposed planning objectives are investigated through juxtaposition with conventional objectives in a computational study of two patient cases, each with three doses-at-volume to be minimized subject to PTV coverage. With proposed planning objectives, this is translated into minimizing three mean-tail-doses. Comparison with conventional objectives is carried out in the dose-at-volume domain and in the no...

  8. Optimization of the HA-1-specific T-cell receptor for gene therapy of hematologic malignancies

    Science.gov (United States)

    van Loenen, Marleen M.; de Boer, Renate; Hagedoorn, Renate S.; van Egmond, Esther H.M.; Falkenburg, J.H. Frederik; Heemskerk, Mirjam H.M.

    2011-01-01

    To broaden the applicability of adoptive T-cell therapy for the treatment of hematologic malignancies, we aim to start a clinical trial using HA-1-TCR transferred virus-specific T cells. TCRs directed against the minor histocompatibility antigen (MiHA) HA-1 are good candidates for TCR gene transfer to treat hematologic malignancies because of the hematopoiesis-restricted expression and favorable frequency of HA-1. For optimal anti-leukemic reactivity, high cell-surface expression of the introduced TCR is important. Previously, however, we have demonstrated that gene transferred HA-1-TCRs are poorly expressed at the cell-surface. In this study several strategies were explored to improve expression of transferred HA-1-TCRs. PMID:21109688

  9. The Use of Optimism in Narrative Therapy with Sexual Abuse Survivors

    Directory of Open Access Journals (Sweden)

    Z. Seda Sahin

    2009-12-01

    Full Text Available Examining the victim’s causal attributions and attribution style associated with sexual abuse may add to the understanding of how survivors make meaning of such experiences and create the related narratives. Through the use of optimism in narrative therapy, the survivor is encouraged to deconstruct the dominant story of being a victim and making new, personal meanings in order to broaden the possibility for other plot-lines and preferred stories with the problems related to sexual abuse being attributed to external, unstable and specific factors. By using the questions that the authors of this paper propose, the therapist can help to deconstruct their dominant stories and create a more optimistic subjugated story.

  10. Group purchasing organizations: optimizing cardiac device selection, therapy delivery, and fiscal responsibility.

    Science.gov (United States)

    Sweesy, Mark W; Wilkoff, Bruce L; Smith, Kerry W; Holland, James L

    2006-12-01

    Group purchasing organizations (GPOs) have played a major role in supporting health care delivery in recent years as the healthcare industry has faced stronger economic pressures. Consequently, a position statement was drafted to act as a guideline for a GPO in creating a fiscally responsible, yet unrestricted environment for physicians to select the most appropriate cardiac device for their patients. This cardiac device selection guideline is to be implemented in hundreds of member hospitals but may be of use in non-member hospitals as well. The guideline will only be effective when the physicians or cardiac device caregivers have the knowledge and skills to optimally program and match device therapies and algorithms to individual patient needs.

  11. Multifield Optimization Intensity Modulated Proton Therapy for Head and Neck Tumors: A Translation to Practice

    Energy Technology Data Exchange (ETDEWEB)

    Frank, Steven J., E-mail: sjfrank@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Cox, James D. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Gillin, Michael; Mohan, Radhe [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Garden, Adam S.; Rosenthal, David I.; Gunn, G. Brandon [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Weber, Randal S. [Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Kies, Merrill S. [Department of Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Lewin, Jan S. [Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Munsell, Mark F. [Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Palmer, Matthew B. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Sahoo, Narayan; Zhang, Xiaodong; Liu, Wei; Zhu, X. Ronald [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2014-07-15

    Background: We report the first clinical experience and toxicity of multifield optimization (MFO) intensity modulated proton therapy (IMPT) for patients with head and neck tumors. Methods and Materials: Fifteen consecutive patients with head and neck cancer underwent MFO-IMPT with active scanning beam proton therapy. Patients with squamous cell carcinoma (SCC) had comprehensive treatment extending from the base of the skull to the clavicle. The doses for chemoradiation therapy and radiation therapy alone were 70 Gy and 66 Gy, respectively. The robustness of each treatment plan was also analyzed to evaluate sensitivity to uncertainties associated with variations in patient setup and the effect of uncertainties with proton beam range in patients. Proton beam energies during treatment ranged from 72.5 to 221.8 MeV. Spot sizes varied depending on the beam energy and depth of the target, and the scanning nozzle delivered the spot scanning treatment “spot by spot” and “layer by layer.” Results: Ten patients presented with SCC and 5 with adenoid cystic carcinoma. All 15 patients were able to complete treatment with MFO-IMPT, with no need for treatment breaks and no hospitalizations. There were no treatment-related deaths, and with a median follow-up time of 28 months (range, 20-35 months), the overall clinical complete response rate was 93.3% (95% confidence interval, 68.1%-99.8%). Xerostomia occurred in all 15 patients as follows: grade 1 in 10 patients, grade 2 in 4 patients, and grade 3 in 1 patient. Mucositis within the planning target volumes was seen during the treatment of all patients: grade 1 in 1 patient, grade 2 in 8 patients, and grade 3 in 6 patients. No patient experienced grade 2 or higher anterior oral mucositis. Conclusions: To our knowledge, this is the first clinical report of MFO-IMPT for head and neck tumors. Early clinical outcomes are encouraging and warrant further investigation of proton therapy in prospective clinical trials.

  12. GPU-based ultra-fast direct aperture optimization for online adaptive radiation therapy

    CERN Document Server

    Men, Chunhua; Jiang, Steve B

    2010-01-01

    Online adaptive radiation therapy (ART) has great promise to significantly reduce normal tissue toxicity and/or improve tumor control through real-time treatment adaptations based on the current patient anatomy. However, the major technical obstacle for clinical realization of online ART, namely the inability to achieve real-time efficiency in treatment re-planning, has yet to be solved. To overcome this challenge, this paper presents our work on the implementation of an intensity modulated radiation therapy (IMRT) direct aperture optimization (DAO) algorithm on graphics processing unit (GPU) based on our previous work on CPU. We formulate the DAO problem as a large-scale convex programming problem, and use an exact method called column generation approach to deal with its extremely large dimensionality on GPU. Five 9-field prostate and five 5-field head-and-neck IMRT clinical cases with 5\\times5 mm2 beamlet size and 2.5\\times2.5\\times2.5 mm3 voxel size were used to evaluate our algorithm on GPU. It takes onl...

  13. GPU-based ultra-fast direct aperture optimization for online adaptive radiation therapy.

    Science.gov (United States)

    Men, Chunhua; Jia, Xun; Jiang, Steve B

    2010-08-07

    Online adaptive radiation therapy (ART) has great promise to significantly reduce normal tissue toxicity and/or improve tumor control through real-time treatment adaptations based on the current patient anatomy. However, the major technical obstacle for clinical realization of online ART, namely the inability to achieve real-time efficiency in treatment re-planning, has yet to be solved. To overcome this challenge, this paper presents our work on the implementation of an intensity-modulated radiation therapy (IMRT) direct aperture optimization (DAO) algorithm on the graphics processing unit (GPU) based on our previous work on the CPU. We formulate the DAO problem as a large-scale convex programming problem, and use an exact method called the column generation approach to deal with its extremely large dimensionality on the GPU. Five 9-field prostate and five 5-field head-and-neck IMRT clinical cases with 5 x 5 mm(2) beamlet size and 2.5 x 2.5 x 2.5 mm(3) voxel size were tested to evaluate our algorithm on the GPU. It takes only 0.7-3.8 s for our implementation to generate high-quality treatment plans on an NVIDIA Tesla C1060 GPU card. Our work has therefore solved a major problem in developing ultra-fast (re-)planning technologies for online ART.

  14. OPTIMAL REGIMENS OF THE BASAL-BOLUS INSULIN THERAPY IN ADOLESCENTS WITH TYPE 1 DIABETES MELLITUS

    Directory of Open Access Journals (Sweden)

    G. A. Galkina

    2015-01-01

    Full Text Available This study was aimed to determine peculiarities in regimens of the pump insulin therapy and to reveal the optimal basal-to-bolus insulin ratio that are necessary for achieving optimal glycemic control in adoles-cents with type 1 diabetes mellitus (T1DM.  82 adolescents at the age of 14–18 with T1DM, using continuous subcutaneous insulin infusion (CSII from 5 months to 7.5 years were monitored with continuous glucose monitoring (CGM system «Guar-dian Real Time» or CGM system, built in MiniMed Paradigm Revel System 722 (Medtronic Minimed, USA. Assessing the quality of glycaemic control was based on the level of glycated haemoglobin (HbA1c. The results of CGM were reviewed and average for 3 days performances: total daily dose of insulin, dose of basal and bolus insulin, basal-to-bolus insulin ratio, carbohydrate content of the meal, expressed in BE, carbohydrate ratio, insulin sensitivity factor were determined. The patients were subdivided into 2 groups: group 1 – adolescents with the optimal/suboptimal glycemic control (n = 55, 2 – adolescents with long-standing poorly controlled T1DM (n = 27. Average total daily dose of basal insulin (U in a day, U per kg in a day in adolescents group 1 was significantly higher, com-pared with patients in group 2 (р = 0.043; р = 0.038 respectively. Patients in group 2 received more car-bohydrates with a meal intake and had higher doses of average total daily bolus insulin. The average ba-sal-to-bolus ratio from group 1 patients was 51/49%, compared with group 2 patients – 45/55% (р = 0.026.  An important condition for achieving optimal glycemic control is a high level of compliance and skills of adolescents. Optimal well-balanced basal-to-bolus insulin ratio in adolescents with T1DM on CSII, which can provide improvements in blood glucose management and reducing the risk of complications of the disease, is 51/49%. 

  15. Towards reducing thrombogenicity of LVAD therapy: optimizing surgical and patient management strategies

    Science.gov (United States)

    Chivukula, Venkat Keshav; Lafzi, Ali; Mokadam, Nahush; Beckman, Jennifer; Mahr, Claudius; Aliseda, Alberto

    2017-11-01

    Unfavourable hemodynamics in heart failure patients implanted with left ventricular assist devices (LVAD), due to non-optimal surgical configurations and patient management, strongly influence thrombogenicity. This is consistent with the increase in devastating thromboembolic complications (specifically thrombosis and stroke) in patients, even as the risk of thrombosis inside the device decreases with modern designs. Inflow cannula and outflow graft surgical configurations have been optimized via patient-specific modeling that computes the thrombogenic potential with a combination of Eulerian (endothelial) wall shear stress and Lagrangian (platelet shear history) tracking. Using this view of hemodynamics, the benefits of intermittent aortic valve opening (promoting washout and reducing stagnant flow in the aortic valve region) have been assessed in managing the patient's residual native cardiac output. The use of this methodology to understand the contribution of the hemodynamics in the flow surrounding the LVAD itself to thrombogenesis show promise in developing holistic patient-specific management strategies to minimize stroke risk and enhance efficacy of LVAD therapy. Funded in part by an AHA postdoctoral fellowship 16POST30520004.

  16. Open source machine-learning algorithms for the prediction of optimal cancer drug therapies.

    Science.gov (United States)

    Huang, Cai; Mezencev, Roman; McDonald, John F; Vannberg, Fredrik

    2017-01-01

    Precision medicine is a rapidly growing area of modern medical science and open source machine-learning codes promise to be a critical component for the successful development of standardized and automated analysis of patient data. One important goal of precision cancer medicine is the accurate prediction of optimal drug therapies from the genomic profiles of individual patient tumors. We introduce here an open source software platform that employs a highly versatile support vector machine (SVM) algorithm combined with a standard recursive feature elimination (RFE) approach to predict personalized drug responses from gene expression profiles. Drug specific models were built using gene expression and drug response data from the National Cancer Institute panel of 60 human cancer cell lines (NCI-60). The models are highly accurate in predicting the drug responsiveness of a variety of cancer cell lines including those comprising the recent NCI-DREAM Challenge. We demonstrate that predictive accuracy is optimized when the learning dataset utilizes all probe-set expression values from a diversity of cancer cell types without pre-filtering for genes generally considered to be "drivers" of cancer onset/progression. Application of our models to publically available ovarian cancer (OC) patient gene expression datasets generated predictions consistent with observed responses previously reported in the literature. By making our algorithm "open source", we hope to facilitate its testing in a variety of cancer types and contexts leading to community-driven improvements and refinements in subsequent applications.

  17. Including robustness in multi-criteria optimization for intensity-modulated proton therapy

    CERN Document Server

    Chen, Wei; Trofimov, Alexei; Madden, Thomas; Kooy, Hanne; Bortfeld, Thomas; Craft, David

    2011-01-01

    We present a method to include robustness into a multi-criteria optimization (MCO) framework for intensity-modulated proton therapy (IMPT). The approach allows one to simultaneously explore the trade-off between different objectives as well as the trade-off between robustness and nominal plan quality. In MCO, a database of plans each emphasizing different treatment planning objectives, is pre-computed to approximate the Pareto surface. An IMPT treatment plan that strikes the best balance between the different objectives can be selected by navigating on the Pareto surface. In our approach, robustness is integrated into MCO by adding robustified objectives and constraints to the MCO problem. Uncertainties of the robust problem are modeled by pre-calculated dose-influence matrices for a nominal scenario and a number of pre-defined error scenarios. A robustified objective represents the worst objective function value that can be realized for any of the error scenarios. The optimization method is based on a linear...

  18. Machine Learning Approach to Optimizing Combined Stimulation and Medication Therapies for Parkinson's Disease.

    Science.gov (United States)

    Shamir, Reuben R; Dolber, Trygve; Noecker, Angela M; Walter, Benjamin L; McIntyre, Cameron C

    2015-01-01

    Deep brain stimulation (DBS) of the subthalamic region is an established therapy for advanced Parkinson's disease (PD). However, patients often require time-intensive post-operative management to balance their coupled stimulation and medication treatments. Given the large and complex parameter space associated with this task, we propose that clinical decision support systems (CDSS) based on machine learning algorithms could assist in treatment optimization. Develop a proof-of-concept implementation of a CDSS that incorporates patient-specific details on both stimulation and medication. Clinical data from 10 patients, and 89 post-DBS surgery visits, were used to create a prototype CDSS. The system was designed to provide three key functions: (1) information retrieval; (2) visualization of treatment, and; (3) recommendation on expected effective stimulation and drug dosages, based on three machine learning methods that included support vector machines, Naïve Bayes, and random forest. Measures of medication dosages, time factors, and symptom-specific pre-operative response to levodopa were significantly correlated with post-operative outcomes (P learning algorithms were able to accurately predict 86% (12/14) of the motor improvement scores at one year after surgery. Using patient-specific details, an appropriately parameterized CDSS could help select theoretically optimal DBS parameter settings and medication dosages that have potential to improve the clinical management of PD patients. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Application of Max-SAT-based ATPG to optimal cancer therapy design.

    Science.gov (United States)

    Lin, Pey-Chang Kent; Khatri, Sunil P

    2012-01-01

    Cancer and other gene related diseases are usually caused by a failure in the signaling pathway between genes and cells. These failures can occur in different areas of the gene regulatory network, but can be abstracted as faults in the regulatory function. For effective cancer treatment, it is imperative to identify faults and select appropriate drugs to treat the faults. In this paper, we present an extensible Max-SAT based automatic test pattern generation (ATPG) algorithm for cancer therapy. This ATPG algorithm is based on Boolean Satisfiability (SAT) and utilizes the stuck-at fault model for representing signaling faults. A weighted partial Max-SAT formulation is used to enable efficient selection of the most effective drug. Several usage cases are presented for fault identification and drug selection. These cases include the identification of testable faults, optimal drug selection for single/multiple known faults, and optimal drug selection for overall fault coverage. Experimental results on growth factor (GF) signaling pathways demonstrate that our algorithm is flexible, and can yield an exact solution for each feature in much less than 1 second.

  20. Optimizing catecholaminergic polymorphic ventricular tachycardia therapy in calsequestrin-mutant mice

    Science.gov (United States)

    Katz, Guy; Khoury, Assad; Kurtzwald, Efrat; Hochhauser, Edith; Porat, Eyal; Shainberg, Asher; Seidman, Jonathan G.; Seidman, Christine E.; Lorber, Abraham; Eldar, Michael; Arad, Michael

    2014-01-01

    BACKGROUND Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a lethal arrhythmia provoked by physical or emotional stress and mediated by spontaneous Ca2+ release and delayed after-depolarizations. Beta-adrenergic blockers are the therapy of choice but fail to control arrhythmia in up to 50% of patients. OBJECTIVE To optimize antiarrhythmic therapy in recessively inherited CPVT caused by calsequestrin (CASQ2) mutations. METHODS Murine heart rhythm telemetry was obtained at rest, during treadmill exercise, and after injection of epinephrine. The protocol was repeated after injection of different antiarrhythmic drugs. Results were then validated in human patients. RESULTS Adult CASQ2 mutant mice had complex ventricular arrhythmia at rest and developed bidirectional and polymorphic ventricular tachycardia on exertion. Class I antiarrhythmic agents (procainamide, lidocaine, flecainide) were ineffective in controlling arrhythmia. Propranolol and sotalol attenuated arrhythmia at rest but failed to prevent VT during sympathetic stimulation. The calcium channel blocker verapamil showed a dose-dependent protection against CPVT. Verapamil was more effective than the dihydropyridine L-type Ca2+ channel blocker nifedipine, and its activity was markedly enhanced when combined with propranolol. Human patients homozygous for CASQ2D307H mutation, remaining symptomatic despite chronic β-blocker therapy, underwent exercise testing according to the Bruce protocol with continuous electrocardiogram recording. Verapamil was combined with propranolol at maximum tolerated doses. Adding verapamil attenuated ventricular arrhythmia and prolonged exercise duration in five of 11 patients. CONCLUSION Verapamil is highly effective against catecholamine-induced arrhythmia in mice with CASQ2 mutations and may potentiate the antiarrhythmic activity of β-blockers in humans with CPVT2. PMID:20620233

  1. Allogeneic Cell Therapy Bioprocess Economics and Optimization: Single-Use Cell Expansion Technologies

    Science.gov (United States)

    Simaria, Ana S; Hassan, Sally; Varadaraju, Hemanthram; Rowley, Jon; Warren, Kim; Vanek, Philip; Farid, Suzanne S

    2014-01-01

    For allogeneic cell therapies to reach their therapeutic potential, challenges related to achieving scalable and robust manufacturing processes will need to be addressed. A particular challenge is producing lot-sizes capable of meeting commercial demands of up to 109 cells/dose for large patient numbers due to the current limitations of expansion technologies. This article describes the application of a decisional tool to identify the most cost-effective expansion technologies for different scales of production as well as current gaps in the technology capabilities for allogeneic cell therapy manufacture. The tool integrates bioprocess economics with optimization to assess the economic competitiveness of planar and microcarrier-based cell expansion technologies. Visualization methods were used to identify the production scales where planar technologies will cease to be cost-effective and where microcarrier-based bioreactors become the only option. The tool outputs also predict that for the industry to be sustainable for high demand scenarios, significant increases will likely be needed in the performance capabilities of microcarrier-based systems. These data are presented using a technology S-curve as well as windows of operation to identify the combination of cell productivities and scale of single-use bioreactors required to meet future lot sizes. The modeling insights can be used to identify where future R&D investment should be focused to improve the performance of the most promising technologies so that they become a robust and scalable option that enables the cell therapy industry reach commercially relevant lot sizes. The tool outputs can facilitate decision-making very early on in development and be used to predict, and better manage, the risk of process changes needed as products proceed through the development pathway. Biotechnol. Bioeng. 2014;111: 69–83. © 2013 Wiley Periodicals, Inc. PMID:23893544

  2. Allogeneic cell therapy bioprocess economics and optimization: single-use cell expansion technologies.

    Science.gov (United States)

    Simaria, Ana S; Hassan, Sally; Varadaraju, Hemanthram; Rowley, Jon; Warren, Kim; Vanek, Philip; Farid, Suzanne S

    2014-01-01

    For allogeneic cell therapies to reach their therapeutic potential, challenges related to achieving scalable and robust manufacturing processes will need to be addressed. A particular challenge is producing lot-sizes capable of meeting commercial demands of up to 10(9) cells/dose for large patient numbers due to the current limitations of expansion technologies. This article describes the application of a decisional tool to identify the most cost-effective expansion technologies for different scales of production as well as current gaps in the technology capabilities for allogeneic cell therapy manufacture. The tool integrates bioprocess economics with optimization to assess the economic competitiveness of planar and microcarrier-based cell expansion technologies. Visualization methods were used to identify the production scales where planar technologies will cease to be cost-effective and where microcarrier-based bioreactors become the only option. The tool outputs also predict that for the industry to be sustainable for high demand scenarios, significant increases will likely be needed in the performance capabilities of microcarrier-based systems. These data are presented using a technology S-curve as well as windows of operation to identify the combination of cell productivities and scale of single-use bioreactors required to meet future lot sizes. The modeling insights can be used to identify where future R&D investment should be focused to improve the performance of the most promising technologies so that they become a robust and scalable option that enables the cell therapy industry reach commercially relevant lot sizes. The tool outputs can facilitate decision-making very early on in development and be used to predict, and better manage, the risk of process changes needed as products proceed through the development pathway. © 2013 Wiley Periodicals, Inc.

  3. Clinical decision tool for optimal delivery of liver stereotactic body radiation therapy: Photons versus protons.

    Science.gov (United States)

    Gandhi, Saumil J; Liang, Xing; Ding, Xuanfeng; Zhu, Timothy C; Ben-Josef, Edgar; Plastaras, John P; Metz, James M; Both, Stefan; Apisarnthanarax, Smith

    2015-01-01

    Stereotactic body radiation therapy (SBRT) for treatment of liver tumors is often limited by liver dose constraints. Protons offer potential for more liver sparing, but clinical situations in which protons may be superior to photons are not well described. We developed and validated a treatment decision model to determine whether liver tumors of certain sizes and locations are more suited for photon versus proton SBRT. Six spherical mock tumors from 1 to 6 cm in diameter were contoured on computed tomography images of 1 patient at 4 locations: dome, caudal, left medial, and central. Photon and proton plans were generated to deliver 50 Gy in 5 fractions to each tumor and optimized to deliver equivalent target coverage and maximal liver sparing. Using these plans, we developed a hypothesis-generating model to predict the optimal modality for maximal liver sparing based on tumor size and location. We then validated this model in 10 patients with liver tumors. Protons spared significantly more liver than photons for dome or central tumors ≥3 cm (dome: 134 ± 21 cm(3), P = .03; central: 108 ± 4 cm(3), P = .01). Our model correctly predicted the optimal SBRT modality for all 10 patients. For patients with dome or central tumors ≥3 cm, protons significantly increased the volume of liver spared (176 ± 21 cm(3), P = .01) and decreased the mean liver dose (8.4 vs 12.2 Gy, P = .01) while offering no significant advantage for tumors protons should be considered as the radiation modality of choice for dome and central tumors >3 cm to allow maximal liver sparing and potentially reduce radiation toxicity. Protons should also be considered for any tumor >5 cm if photon plans fail to achieve adequate coverage or exceed the mean liver threshold. Copyright © 2015 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

  4. Optimal laser parameters for port wine stain therapy: a theoretical approach.

    Science.gov (United States)

    Lahaye, C T; van Gemert, M J

    1985-06-01

    The optimal parameters for laser therapy of port wine stains (PWS) have been deduced from temperature calculations on two models: (i) the four-layer model; and (ii) the tube model in which two plane parallel layers, representing the epidermis and dermis, and a dermal rectangular blood vessel are considered. The calculations were performed with a vessel of average cross section 0.06 mm X 0.08 mm located in the centre of the laser beam. The numerical calculations were performed by an alternate direction-implicit finite difference method. The optimal parameters were: wavelengths lambda = 415, 577 and 540 nm; pulse time, 1 ms less than t1 less than or equal to 10 ms; and beam radius W1 greater than 0.1 mm. The energy densities E1 (for t1 = 1 ms) required to coagulate blood vessels down to a depth of 0.65 mm in order to establish bleaching of the PWS were 0.5, 1.6 and 2 J cm-2 for the different lambda respectively. The value for the argon laser (lambda = 488 and 514.5 nm) was E1 = 6.5 J cm-2 (t1 = 1 ms). Because, for this pulse time, heat summation effects at the boundary of the laser beam cause no drastic increase in local temperature at optimal wavelengths, the stripe technique was again considered and compared with the separated spot technique. The Nd-YAG and CO2 lasers prove even less selective than the argon laser. The influence of cooling the skin with water shows that only for lambda = 577 nm and t1 = 0.1 s is there an increase in E1 from 2.5 to 6 J cm-2 for which dermal damage occurs.

  5. Poster - Thur Eve - 65: Optimization of an automatic image contouring system for radiation therapy.

    Science.gov (United States)

    Hamilton, T; Nedialkov, N; Wierzbicki, M

    2012-07-01

    Intensity modulated radiation therapy (IMRT) is an advanced technique used to concentrate the prescribed dose in the tumour while minimizing exposure to healthy tissues. Success in IMRT is greatly dependent upon the localization of the target volume and normal tissue, thus accurate contouring is crucial. In this paper, we describe an automated atlas-based image contouring system and our approach for improving the system by performing a full-scale optimization of registration parameters using high-performance computing. To achieve this, we use manually pre-contoured CT images of ten head and neck patients. For any parameter set, each patient data is registered with the remaining patients. Accuracy of the resulting contours is determined automatically by comparing their overlap with manually defined targets using Dice's similarity coefficient (DSC). This allows us to compare all permutations of the image registration parameter sets and input data to investigate their impact on final contour accuracy. Investigating the parameter space required 27,000 image registrations and 216,000 DSC computations. To perform these registrations we introduced a large cluster of high-performance computers and developed a parallel testing harness. The metrics collected from the tests show a wide range of performance, indicating that parameter selection is crucial in our contouring system. By selecting an optimized parameter set, we increased the mean overlap of the automatically contoured regions of interest by 50% and reduced registration time by 50% compared to the original parameters. Our findings illustrate that full-scale optimization is an effective method for improving the performance of the automated image contouring system. © 2012 American Association of Physicists in Medicine.

  6. A new approach to integrate GPU-based Monte Carlo simulation into inverse treatment plan optimization for proton therapy.

    Science.gov (United States)

    Li, Yongbao; Tian, Zhen; Song, Ting; Wu, Zhaoxia; Liu, Yaqiang; Jiang, Steve; Jia, Xun

    2017-01-07

    Monte Carlo (MC)-based spot dose calculation is highly desired for inverse treatment planning in proton therapy because of its accuracy. Recent studies on biological optimization have also indicated the use of MC methods to compute relevant quantities of interest, e.g. linear energy transfer. Although GPU-based MC engines have been developed to address inverse optimization problems, their efficiency still needs to be improved. Also, the use of a large number of GPUs in MC calculation is not favorable for clinical applications. The previously proposed adaptive particle sampling (APS) method can improve the efficiency of MC-based inverse optimization by using the computationally expensive MC simulation more effectively. This method is more efficient than the conventional approach that performs spot dose calculation and optimization in two sequential steps. In this paper, we propose a computational library to perform MC-based spot dose calculation on GPU with the APS scheme. The implemented APS method performs a non-uniform sampling of the particles from pencil beam spots during the optimization process, favoring those from the high intensity spots. The library also conducts two computationally intensive matrix-vector operations frequently used when solving an optimization problem. This library design allows a streamlined integration of the MC-based spot dose calculation into an existing proton therapy inverse planning process. We tested the developed library in a typical inverse optimization system with four patient cases. The library achieved the targeted functions by supporting inverse planning in various proton therapy schemes, e.g. single field uniform dose, 3D intensity modulated proton therapy, and distal edge tracking. The efficiency was 41.6  ±  15.3% higher than the use of a GPU-based MC package in a conventional calculation scheme. The total computation time ranged between 2 and 50 min on a single GPU card depending on the problem size.

  7. Optimal duration of dual antiplatelet therapy following percutaneous coronary intervention: protocol for an umbrella review.

    Science.gov (United States)

    Elliott, Jesse; Kelly, Shannon E; Bai, Zemin; Liu, Wenfei; Skidmore, Becky; Boucher, Michel; So, Derek Y F; Wells, George A

    2017-04-04

    Although dual antiplatelet therapy (DAPT) is routinely given to patients after percutaneous coronary intervention (PCI) with stenting, the optimal duration is unknown. Recent evidence indicates there may be benefits in extending the duration beyond 12 months but such decisions may increase the risk of bleeding. Our objective is to provide a comprehensive overview of the literature for clinicians and policymakers via an umbrella review assessing the optimal duration of DAPT. We will perform a comprehensive search of the published and grey literature for systematic reviews involving randomised controlled trials (RCTs) assessing the optimal duration of DAPT following PCI with stenting. The intervention of interest is extended DAPT (beyond 12 months) compared with short-term DAPT (6-12 months). Studies will be selected for inclusion by two reviewers, and the quality will be assessed. The primary outcomes of interest are all-cause mortality and cardiovascular mortality. Secondary outcomes will be bleeding (major, minor and gastrointestinal), urgent target vessel revascularisation, major adverse cardiovascular events, myocardial infarction, stroke and stent thrombosis. Outcomes will be assessed while on DAPT and after withdrawal of DAPT. Data will be summarised with respect to the number of included RCTs, number of participants, effect estimates and heterogeneity. Data will be reported separately based on patient demographics, procedural parameters (eg, stent types, lesion complexity and concurrent disease) and clinical presentation (eg, acute coronary syndromes, infarct type). Our umbrella review aims to provide a comprehensive overview of the benefits and harms associated with extending DAPT beyond 12 months following PCI with stenting. The results of this review will inform clinical and policy decisions regarding the optimal treatment duration and reimbursement of DAPT following PCI with stenting. Results will be disseminated through a peer

  8. Porous bioactive materials

    Science.gov (United States)

    Zhang, Kai

    Bioactive materials chemically bond to tissues through the development of biologically active apatite. Porous structures in biomaterials are designed to enhance bioactivity, grow artificial tissues and achieve better integration with host tissues in the body. The goal of this research is to design, fabricate and characterize novel porous bioactive materials. 3D ordered macroporous bioactive glasses (3DOM-BGs, pore size: 200--1000 nm) were prepared using a sol-gel process and colloidal crystal templates. 3DOM-BGs are more bioactive and degradable than mesoporous (pore size periodontal fillers, and drugs and biological factors delivery agents. Anchoring artificial soft tissues (e.g., cartilage) to native bone presents a challenge. Porous polymer/bioactive glass composites are candidate materials for engineering artificial soft tissue/bone interfaces. Porous composites consisting of polymer matrices (e.g., polysulfone, polylactide, and polyurethane) and bioactive glass particles were prepared by polymer phase separation techniques adapted to include ceramic particles. Composites (thickness: 200--500 mum) have asymmetric structures with dense top layers and porous structures beneath. Porous structures consist of large pores (>100 mum) in a network of smaller (<10 mum) interconnected pores. Dense layers can be removed and large pores exposed by abrasion or salt leaching techniques. Composite modulus was enhanced with the increase of glass content, due to the change in composition and pore content. The growth of bone-like apatite on and inside composites after soaking in SBF demonstrated their potential for integration with bone. Cell culture studies revealed that composite surfaces were suitable for attachment, spreading and proliferation of chondrocytes.

  9. Optimization of construct design and fermentation strategy for the production of bioactive ATF-SAP, a saporin based anti-tumoral uPAR-targeted chimera.

    Science.gov (United States)

    Errico Provenzano, Alfredo; Posteri, Riccardo; Giansanti, Francesco; Angelucci, Francesco; Flavell, Sopsamorn U; Flavell, David J; Fabbrini, Maria Serena; Porro, Danilo; Ippoliti, Rodolfo; Ceriotti, Aldo; Branduardi, Paola; Vago, Riccardo

    2016-11-14

    The big challenge in any anti-tumor therapeutic approach is represented by the development of drugs selectively acting on the target with limited side effects, that exploit the unique characteristics of malignant cells. The urokinase (urokinase-type plasminogen activator, uPA) and its receptor uPAR have been identified as preferential target candidates since they play a key role in the evolution of neoplasms and are associated with neoplasm aggressiveness and poor clinical outcome in several different tumor types. To selectively target uPAR over-expressing cancer cells, we prepared a set of chimeric proteins (ATF-SAP) formed by the human amino terminal fragments (ATF) of uPA and the plant ribosome inactivating protein saporin (SAP). Codon-usage optimization was used to increase the expression levels of the chimera in the methylotrophic yeast Pichia pastoris. We then moved the bioprocess to bioreactors and demonstrated that the fed-batch production of the recombinant protein can be successfully achieved, obtaining homogeneous discrete batches of the desired constructs. We also determined the cytotoxic activity of the obtained batch of ATF-SAP which was specifically cytotoxic for U937 leukemia cells, while another construct containing a catalytically inactive mutant form of SAP showed no activity. Our results demonstrate that the uPAR-targeted, saporin-based recombinant fusion ATF-SAP can be produced in a fed-batch fermentation with full retention of the molecules selective cytotoxicity and hence therapeutic potential.

  10. Bioactive polymeric scaffolds for tissue engineering

    Science.gov (United States)

    Stratton, Scott; Shelke, Namdev B.; Hoshino, Kazunori; Rudraiah, Swetha; Kumbar, Sangamesh G.

    2016-01-01

    A variety of engineered scaffolds have been created for tissue engineering using polymers, ceramics and their composites. Biomimicry has been adopted for majority of the three-dimensional (3D) scaffold design both in terms of physicochemical properties, as well as bioactivity for superior tissue regeneration. Scaffolds fabricated via salt leaching, particle sintering, hydrogels and lithography have been successful in promoting cell growth in vitro and tissue regeneration in vivo. Scaffold systems derived from decellularization of whole organs or tissues has been popular due to their assured biocompatibility and bioactivity. Traditional scaffold fabrication techniques often failed to create intricate structures with greater resolution, not reproducible and involved multiple steps. The 3D printing technology overcome several limitations of the traditional techniques and made it easier to adopt several thermoplastics and hydrogels to create micro-nanostructured scaffolds and devices for tissue engineering and drug delivery. This review highlights scaffold fabrication methodologies with a focus on optimizing scaffold performance through the matrix pores, bioactivity and degradation rate to enable tissue regeneration. Review highlights few examples of bioactive scaffold mediated nerve, muscle, tendon/ligament and bone regeneration. Regardless of the efforts required for optimization, a shift in 3D scaffold uses from the laboratory into everyday life is expected in the near future as some of the methods discussed in this review become more streamlined. PMID:28653043

  11. Bioactive polymeric scaffolds for tissue engineering

    Directory of Open Access Journals (Sweden)

    Scott Stratton

    2016-12-01

    Full Text Available A variety of engineered scaffolds have been created for tissue engineering using polymers, ceramics and their composites. Biomimicry has been adopted for majority of the three-dimensional (3D scaffold design both in terms of physicochemical properties, as well as bioactivity for superior tissue regeneration. Scaffolds fabricated via salt leaching, particle sintering, hydrogels and lithography have been successful in promoting cell growth in vitro and tissue regeneration in vivo. Scaffold systems derived from decellularization of whole organs or tissues has been popular due to their assured biocompatibility and bioactivity. Traditional scaffold fabrication techniques often failed to create intricate structures with greater resolution, not reproducible and involved multiple steps. The 3D printing technology overcome several limitations of the traditional techniques and made it easier to adopt several thermoplastics and hydrogels to create micro-nanostructured scaffolds and devices for tissue engineering and drug delivery. This review highlights scaffold fabrication methodologies with a focus on optimizing scaffold performance through the matrix pores, bioactivity and degradation rate to enable tissue regeneration. Review highlights few examples of bioactive scaffold mediated nerve, muscle, tendon/ligament and bone regeneration. Regardless of the efforts required for optimization, a shift in 3D scaffold uses from the laboratory into everyday life is expected in the near future as some of the methods discussed in this review become more streamlined.

  12. Optimization of dual-energy CT acquisitions for proton therapy using projection-based decomposition.

    Science.gov (United States)

    Vilches-Freixas, Gloria; Létang, Jean Michel; Ducros, Nicolas; Rit, Simon

    2017-09-01

    Dual-energy computed tomography (DECT) has been presented as a valid alternative to single-energy CT to reduce the uncertainty of the conversion of patient CT numbers to proton stopping power ratio (SPR) of tissues relative to water. The aim of this work was to optimize DECT acquisition protocols from simulations of X-ray images for the treatment planning of proton therapy using a projection-based dual-energy decomposition algorithm. We have investigated the effect of various voltages and tin filtration combinations on the SPR map accuracy and precision, and the influence of the dose allocation between the low-energy (LE) and the high-energy (HE) acquisitions. For all spectra combinations, virtual CT projections of the Gammex phantom were simulated with a realistic energy-integrating detector response model. Two situations were simulated: an ideal case without noise (infinite dose) and a realistic situation with Poisson noise corresponding to a 20 mGy total central dose. To determine the optimal dose balance, the proportion of LE-dose with respect to the total dose was varied from 10% to 90% while keeping the central dose constant, for four dual-energy spectra. SPR images were derived using a two-step projection-based decomposition approach. The ranges of 70 MeV, 90 MeV, and 100 MeV proton beams onto the adult female (AF) reference computational phantom of the ICRP were analytically determined from the reconstructed SPR maps. The energy separation between the incident spectra had a strong impact on the SPR precision. Maximizing the incident energy gap reduced image noise. However, the energy gap was not a good metric to evaluate the accuracy of the SPR. In terms of SPR accuracy, a large variability of the optimal spectra was observed when studying each phantom material separately. The SPR accuracy was almost flat in the 30-70% LE-dose range, while the precision showed a minimum slightly shifted in favor of lower LE-dose. Photon noise in the SPR images (20 mGy dose

  13. Optimization

    CERN Document Server

    Pearce, Charles

    2009-01-01

    Focuses on mathematical structure, and on real-world applications. This book includes developments in several optimization-related topics such as decision theory, linear programming, turnpike theory, duality theory, convex analysis, and queuing theory.

  14. Optimal Duration of Imatinib Mesylate Therapy in Metastatic Gastrointestinal Stromal Tumours

    Directory of Open Access Journals (Sweden)

    Ruth Gauden

    2011-04-01

    Full Text Available While current literature provides evidence that imatinib mesylate has significant activity in patients with advanced and metastatic gastrointestinal stromal tumour (GIST, and highlights the potential for the development of anticancer drugs based on specific molecular abnormalities present in cancers, specific recommendations concerning the optimal duration of therapy remain controversial. This case presents the favourable outcome of a patient who originally presented almost 9 years ago with widespread, bulky, metastatic GIST involving the abdomen and pelvis. A sustained, complete response was achieved with imatinib and prompted an interruption in treatment 7 years after initial presentation. The disease reoccurred extensively within 9 months of treatment interruption, but once again rapidly completely responded to the recommencement of imatinib, with that response being now maintained for over 9 months. This report suggests that dramatic and durable responses to imatinib can be achieved in individual cases despite the lack of specific guidelines in the literature with respect to defining how long treatment with imatinib should be continued in the absence of evidence of tumour progression.

  15. Establishing an optimized patient-specific verification program for volumetric modulated arc therapy

    Energy Technology Data Exchange (ETDEWEB)

    Serna, Alfredo, E-mail: alfredo.serna@carm.es [Department of Medical Physics, Hospital Universitario Santa Lucía, Cartagena (Spain); Mata, Fernando; Puchades, Vicente [Department of Medical Physics, Hospital Universitario Santa Lucía, Cartagena (Spain)

    2013-10-01

    Quality assurance (QA) of volumetric modulated arc therapy (VMAT) increases the workload significantly. We compared the results from 4 verification methods to establish an efficient VMAT QA. Planning for VMAT treatments was carried out for 40 consecutive patients. Pretreatment verifications were carried out with ion chamber array Physikalish-Technische Werkstätten (PTW729), electronic portal dosimetry (EPID), ion chamber measurements, and independent dose calculation with Diamond program. 2D analyses were made using the gamma analysis (3 mm distance to agreement and 3% dose difference relative to maximum, 10% dose threshold). Average point dose difference calculated by Eclipse relative to ion chamber measurements and Diamond were 0.1%±0.9% and 0.6%±2.2%, respectively. Average pass rate for PTW729 was 99.2%±1.9% and 98.3%±1.3% for EPID. The total required time (linac occupancy time given in parentheses) for each QA method was: PTW729 43.5 minutes (26.5 minutes), EPID 14.5 minutes (2.5 minutes), ion chamber 34.5 minutes (26.5 minutes), and Diamond 12.0 minutes (0 minute). The results were consistent and allowed us to establish an optimized protocol, considering safety and accuracy as well as workload, consisting of 2 verification methods: EPID 2D analysis and independent dose calculation.

  16. Physical Therapy Adjuvants to Promote Optimization of Walking Recovery after Stroke

    Directory of Open Access Journals (Sweden)

    Mark G. Bowden

    2011-01-01

    Full Text Available Stroke commonly results in substantial and persistent deficits in locomotor function. The majority of scientific inquiries have focused on singular intervention approaches, with recent attention given to task specific therapies. We propose that measurement should indicate the most critical limiting factor(s to be addressed and that a combination of adjuvant treatments individualized to target accompanying impairment(s will result in the greatest improvements in locomotor function. We explore training to improve walking performance by addressing a combination of: (1 walking specific motor control; (2 dynamic balance; (3 cardiorespiratory fitness and (4 muscle strength and put forward a theoretical framework to maximize the functional benefits of these strategies as physical adjuvants. The extent to which any of these impairments contribute to locomotor dysfunction is dependent on the individual and will undoubtedly change throughout the rehabilitation intervention. Thus, the ability to identify and measure the relative contributions of these elements will allow for identification of a primary intervention as well as prescription of additional adjuvant approaches. Importantly, we highlight the need for future studies as appropriate dosing of each of these elements is contingent on improving the capacity to measure each element and to titrate the contribution of each to optimal walking performance.

  17. Acceptance and Commitment Therapy and Selective Optimization with Compensation for Institutionalized Older People with Chronic Pain.

    Science.gov (United States)

    Alonso-Fernández, Miriam; López-López, Almudena; Losada, Andres; González, José Luis; Wetherell, Julie Loebach

    2016-02-01

    Recent studies support the efficacy of Acceptance and Commitment Therapy (ACT) with people with chronic pain. In addition, Selective Optimization with Compensation strategies (SOC) can help the elderly with chronic pain to accept their chronic condition and increase functional autonomy. Our aim was to analyze the efficacy of an ACT treatment program combined with training in SOC strategies for elderly people with chronic pain living in nursing homes. 101 participants (mean age = 82.26; SD = 10.00; 78.6% female) were randomized to the intervention condition (ACT-SOC) or to a minimal support group (MS). Complete data are available for 53 participants (ACT-SOC: n = 27; MS: n = 26). Assessments of functional performance, pain intensity, pain acceptance, SOC strategies, emotional well being and catastrophizing beliefs were done preintervention and postintervention. Significant time by intervention changes (P = 0.05) were found in acceptance, pain related anxiety, compensation strategies, and pain interference in walking ability. Simple effects changes were found in acceptance (P = 0.01), selection strategies (P = 0.05), catastrophizing beliefs (P = 0.03), depressive symptoms (P = 0.05), pain anxiety (P = 0.01) and pain interference in mood and walking ability (P = 0.03) in the ACT-SOC group. No significant changes were found in the MS group. These results suggest that an ACT intervention combined with training in SOC strategies could help older people with pain to improve their emotional well being and their functional capability.

  18. 'Ins' and 'outs' of triple therapy: Optimal antiplatelet therapy in patients on chronic oral anticoagulation who need coronary stenting.

    Science.gov (United States)

    Dewilde, W; Verheugt, F W A; Breet, N; Koolen, J J; Ten Berg, J M

    2010-09-01

    Chronic oral anticoagulant treatment is obligatory in patients (class I) with mechanical heart valves and in patients with atrial fibrillation with CHADS2 score >1. When these patients undergo percutaneous coronary intervention with placement of a stent, there is also an indication for treatment with aspirin and clopidogrel. Unfortunately, triple therapy is known to increase the bleeding risk. For this group of patients, the bottom line is to find the ideal therapy in patients with indications for both chronic anticoagulation therapy and percutaneous intervention to prevent thromboembolic complications such as stent thrombosis without increasing the risk of bleeding. (Neth Heart J 2010;18:444-50.).

  19. Acute beneficial hemodynamic effects of a novel 3D-echocardiographic optimization protocol in cardiac resynchronization therapy.

    Directory of Open Access Journals (Sweden)

    Carolin Sonne

    Full Text Available BACKGROUND: Post-implantation therapies to optimize cardiac resynchronization therapy (CRT focus on adjustments of the atrio-ventricular (AV delay and ventricular-to-ventricular (VV interval. However, there is little consensus on how to achieve best resynchronization with these parameters. The aim of this study was to examine a novel combination of doppler echocardiography (DE and three-dimensional echocardiography (3DE for individualized optimization of device based AV delays and VV intervals compared to empiric programming. METHODS: 25 recipients of CRT (male: 56%, mean age: 67 years were included in this study. Ejection fraction (EF, the primary outcome parameter, and left ventricular (LV dimensions were evaluated by 3DE before CRT (baseline, after AV delay optimization while pacing the ventricles simultaneously (empiric VV interval programming and after individualized VV interval optimization. For AV delay optimization aortic velocity time integral (AoVTI was examined in eight different AV delays, and the AV delay with the highest AoVTI was programmed. For individualized VV interval optimization 3DE full-volume datasets of the left ventricle were obtained and analyzed to derive a systolic dyssynchrony index (SDI, calculated from the dispersion of time to minimal regional volume for all 16 LV segments. Consecutively, SDI was evaluated in six different VV intervals (including LV or right ventricular preactivation, and the VV interval with the lowest SDI was programmed (individualized optimization. RESULTS: EF increased from baseline 23±7% to 30±8 (p<0.001 after AV delay optimization and to 32±8% (p<0.05 after individualized optimization with an associated decrease of end-systolic volume from a baseline of 138±60 ml to 115±42 ml (p<0.001. Moreover, individualized optimization significantly reduced SDI from a baseline of 14.3±5.5% to 6.1±2.6% (p<0.001. CONCLUSIONS: Compared with empiric programming of biventricular pacemakers

  20. Individually optimized hemodynamic therapy reduces complications and length of stay in the intensive care unit: a prospective, randomized controlled trial.

    Science.gov (United States)

    Goepfert, Matthias S; Richter, Hans Peter; Zu Eulenburg, Christine; Gruetzmacher, Janna; Rafflenbeul, Erik; Roeher, Katharina; von Sandersleben, Alexandra; Diedrichs, Stefan; Reichenspurner, Herrmann; Goetz, Alwin E; Reuter, Daniel A

    2013-10-01

    The authors hypothesized that goal-directed hemodynamic therapy, based on the combination of functional and volumetric hemodynamic parameters, improves outcome in patients with cardiac surgery. Therefore, a therapy guided by stroke volume variation, individually optimized global end-diastolic volume index, cardiac index, and mean arterial pressure was compared with an algorithm based on mean arterial pressure and central venous pressure. This prospective, controlled, parallel-arm, open-label trial randomized 100 coronary artery bypass grafting and/or aortic valve replacement patients to a study group (SG; n = 50) or a control group (CG; n = 50). In the SG, hemodynamic therapy was guided by stroke volume variation, optimized global end-diastolic volume index, mean arterial pressure, and cardiac index. Optimized global end-diastolic volume index was defined before and after weaning from cardiopulmonary bypass and at intensive care unit (ICU) admission. Mean arterial pressure and central venous pressure served as hemodynamic goals in the CG. Therapy was started immediately after induction of anesthesia and continued until ICU discharge criteria, serving as primary outcome parameter, were fulfilled. Intraoperative need for norepinephrine was decreased in the SG with a mean (±SD) of 9.0 ± 7.6 versus 14.9 ± 11.1 µg/kg (P = 0.002). Postoperative complications (SG, 40 vs. CG, 63; P = 0.004), time to reach ICU discharge criteria (SG, 15 ± 6 h; CG, 24 ± 29 h; P therapy based on cardiac index, stroke volume variation, and optimized global end-diastolic volume index reduces complications and length of ICU stay after cardiac surgery.

  1. Impact of optimal anticoagulation therapy on chronic venous ulcer healing in thrombophilic patients with post-thrombotic syndrome.

    Science.gov (United States)

    Hinojosa, C A; Olivares-Cruz, S; Laparra-Escareno, H; Sanchez-Castro, S; Tamayo-Garcia, B; Anaya-Ayala, J E

    2016-12-02

    Post-thrombotic syndrome (PTS) is the long-term sequelae of deep venous thrombosis (DVT). PTS clinical manifestations include chronic leg pain, oedema, lipodermatosclerosis and ulcers. The objective of this study is to determine in patients with documented history of thrombophilias and DVT whether the number of previous thrombotic events and optimal anticoagulation therapy are associated with the time to venous ulcer healing following the start of compression therapy. Retrospective analysis performed in thrombophilic patients under the age of 50 years old with chronic venous ulcers secondary to DVT at the wound clinic in the National Institute of Medical Sciences and Nutrition 'Salvador Zubirán ' in Mexico City. Variables such as the number or episodes of thrombotic events, type of hypercoagulable disorder, optimal anticoagulation therapy with Warfarin monitored by therapeutic International Normalised Ratio (INR) (2-3) and compliance to compression therapy were examined. Patients that underwent superficial or perforator vein interruption or endovascular recanalisation of deep veins were excluded from the study. From a database of 29 patients with chronic venous ulcers followed in our clinic from January 1992 to September 2012, only 13 patients (61% female) met the inclusion criteria. Mean age±standard deviation (SD) was 32±12 years old. Of these, seven (54%) patients with suboptimal INR presented with an average of two previous thrombotic events and the remaining six (46%) patients with optimal INR only one event (p=0.28), the mean time to the clinical manifestation of a venous ulcer after the first episode of DVT was 39 months (range: 12-72) for patients with suboptimal INR and 82 months (range: 12-216) for those with optimal anticoagulation therapy (p=0.11). During the mean follow-up period of 52 months, all patients in optimal anticoagulation healed their ulcer; their mean time for wound healing was 44 months (range: 4-102). In the suboptimal INR group, only

  2. Second-line biologic therapy optimization in rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis.

    Science.gov (United States)

    Cantini, Fabrizio; Niccoli, Laura; Nannini, Carlotta; Cassarà, Emanuele; Kaloudi, Olga; Giulio Favalli, Ennio; Becciolini, Andrea; Benucci, Maurizio; Gobbi, Francesca Li; Guiducci, Serena; Foti, Rosario; Mosca, Marta; Goletti, Delia

    2017-10-01

    , second-line biologic therapy may be reasonably optimized in patients with RA, SpA, and PsA. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Optimizing Cone Beam Computed Tomography (CBCT) System for Image Guided Radiation Therapy

    Science.gov (United States)

    Park, Chun Joo

    Cone Beam Computed Tomography (CBCT) system is the most widely used imaging device in image guided radiation therapy (IGRT), where set of 3D volumetric image of patient can be reconstructed to identify and correct position setup errors prior to the radiation treatment. This CBCT system can significantly improve precision of on-line setup errors of patient position and tumor target localization prior to the treatment. However, there are still a number of issues that needs to be investigated with CBCT system such as 1) progressively increasing defective pixels in imaging detectors by its frequent usage, 2) hazardous radiation exposure to patients during the CBCT imaging, 3) degradation of image quality due to patients' respiratory motion when CBCT is acquired and 4) unknown knowledge of certain anatomical features such as liver, due to lack of soft-tissue contrast which makes tumor motion verification challenging. In this dissertation, we explore on optimizing the use of cone beam computed tomography (CBCT) system under such circumstances. We begin by introducing general concept of IGRT. We then present the development of automated defective pixel detection algorithm for X-ray imagers that is used for CBCT imaging using wavelet analysis. We next investigate on developing fast and efficient low-dose volumetric reconstruction techniques which includes 1) fast digital tomosynthesis reconstruction using general-purpose graphics processing unit (GPGPU) programming and 2) fast low-dose CBCT image reconstruction based on the Gradient-Projection-Barzilai-Borwein formulation (GP-BB). We further developed two efficient approaches that could reduce the degradation of CBCT images from respiratory motion. First, we propose reconstructing four dimensional (4D) CBCT and DTS using respiratory signal extracted from fiducial markers implanted in liver. Second, novel motion-map constrained image reconstruction (MCIR) is proposed that allows reconstruction of high quality and high phase

  4. Microcurrent therapy in the management of chronic tennis elbow: pilot studies to optimize parameters.

    Science.gov (United States)

    Poltawski, Leon; Johnson, Mark; Watson, Tim

    2012-09-01

    In microcurrent therapy (MCT), low-intensity electric current is applied to promote tissue healing and relieve symptoms. MCT is used with recalcitrant skin and bone lesions, but little is known about its effects on tendinopathy, and optimal treatment parameters are uncertain. Two studies were conducted to ascertain whether varying (i) current intensity and (ii) waveform and treatment duration affect outcomes of MCT for chronic tennis elbow. Two trials compared the effects of different MCT parameters on pain and function, grip strength, and sonographically graded tendon structure and hyperaemia. Trial 1 compared monophasic MCT of intensity 50 and 500 μA applied for 35 h; trial 2 compared devices delivering approximately 25 μA but with different waveforms and durations of 15 and 189 h, respectively. Treatment was applied over 3 weeks. Assessments were at baseline and 3, 6 and 15 weeks. For each trial, n = 31. In trial 1, 50 μA was more effective than 500 μA, with 93% of participants 'much better' or 'fully recovered' at 15 weeks, compared with 47% in the 500 μA group. Tendon structural normalization was superior at 50 μA, but no significant differences were found in other outcomes. In trial 2, success rates for the two groups at 15 weeks were 75% and 73%, respectively, but group improvements did not differ significantly on any measure. Pooled analysis of data from both trials showed that, immediately following treatment, blood flow had fallen in the subgroup with high baseline scores and risen in the subgroup with low scores. Low baseline score correlated significantly with treatment success. Monophasic MCT of peak current intensity 50 μA applied for tens of hours may be effective in reducing symptoms and promoting tendon normalization in chronic tennis elbow. Hyperaemia may help predict treatment outcome. A full-scale trial of the therapy is warranted. Copyright © 2011 John Wiley & Sons, Ltd.

  5. Optimization of heart failure medication after cardiac resynchronization therapy and the impact on long-term survival

    DEFF Research Database (Denmark)

    Witt, Christoffer Tobias; Kronborg, Mads Brix; Nohr, Ellen Aagaard

    2015-01-01

    AIMS: Treatment with evidence-based heart failure (HF) medication reduces morbidity and mortality, yet they remain underused and underdosed. Cardiac resynchronization therapy (CRT) improves haemodynamics, and might allow for optimization of HF medication. We analysed treatment with HF medication......HR 0.55 (0.38-0.80); P = 0.002). CONCLUSION: After CRT implantation, optimization of HF treatment is possible, and long-term adherence to HF medication remains high. Higher doses of BB and ACEi/ARB were associated with prolonged survival....

  6. New bioactive fatty acids

    Science.gov (United States)

    Many oxygenated fatty acids are bioactive compounds. Nocardia cholesterolicum and Flavobacterium DS5 convert oleic acid to 10 hydroxy stearic acid and linoleic acid to 10-hydroxy-12(Z)-octadecanoic acid. Pseudomonas aeruginosa PR3 converts oleic acid to the new compounds, 7,10-dihydroxy-8(E)-octad...

  7. Transient B cell depletion or improved transgene expression by codon optimization promote tolerance to factor VIII in gene therapy.

    Directory of Open Access Journals (Sweden)

    Brandon K Sack

    Full Text Available The major complication in the treatment of hemophilia A is the development of neutralizing antibodies (inhibitors against factor VIII (FVIII. The current method for eradicating inhibitors, termed immune tolerance induction (ITI, is costly and protracted. Clinical protocols that prevent rather than treat inhibitors are not yet established. Liver-directed gene therapy hopes to achieve long-term correction of the disease while also inducing immune tolerance. We sought to investigate the use of adeno-associated viral (serotype 8 gene transfer to induce tolerance to human B domain deleted FVIII in hemophilia A mice. We administered an AAV8 vector with either human B domain deleted FVIII or a codon-optimized transgene, both under a liver-specific promoter to two strains of hemophilia A mice. Protein therapy or gene therapy was given either alone or in conjunction with anti-CD20 antibody-mediated B cell depletion. Gene therapy with a low-expressing vector resulted in sustained near-therapeutic expression. However, supplementary protein therapy revealed that gene transfer had sensitized mice to hFVIII in a high-responder strain but not in mice of a low-responding strain. This heightened response was ameliorated when gene therapy was delivered with anti-murine CD20 treatment. Transient B cell depletion prevented inhibitor formation in protein therapy, but failed to achieve a sustained hypo-responsiveness. Importantly, use of a codon-optimized hFVIII transgene resulted in sustained therapeutic expression and tolerance without a need for B cell depletion. Therefore, anti-CD20 may be beneficial in preventing vector-induced immune priming to FVIII, but higher levels of liver-restricted expression are preferred for tolerance.

  8. Treatment planning of intensity modulated composite particle therapy with dose and linear energy transfer optimization

    Science.gov (United States)

    Inaniwa, Taku; Kanematsu, Nobuyuki; Noda, Koji; Kamada, Tadashi

    2017-06-01

    The biological effect of charged-particle beams depends on both dose and particle spectrum. As one of the physical quantities describing the particle spectrum of charged-particle beams, we considered the linear energy transfer (LET) throughout this study. We investigated a new therapeutic technique using two or more ion species in one treatment session, which we call an intensity modulated composite particle therapy (IMPACT), for optimizing the physical dose and dose-averaged LET distributions in a patient as its proof of principle. Protons and helium, carbon, and oxygen ions were considered as ion species for IMPACT. For three cubic targets of 4  ×  4  ×  4, 8  ×  8  ×  8, and 12  ×  12  ×  12 cm3, defined at the center of the water phantom of 20  ×  20  ×  20 cm3, we made IMPACT plans of two composite fields with opposing and orthogonal geometries. The prescribed dose to the target was fixed at 1 Gy, while the prescribed LET to the target was varied from 1 keV µm-1 to 120 keV µm-1 to investigate the range of LET valid for prescription. The minimum and maximum prescribed LETs, (L T_min, L T_max), by the opposing-field geometry, were (3 keV µm-1, 115 keV µm-1), (2 keV µm-1, 84 keV µm-1),and (2 keV µm-1, 66 keV µm-1), while those by the orthogonal-field geometry were (8 keV µm-1, 98 keV µm-1), (7 keV µm-1, 72 keV µm-1), and (8 keV µm-1, 57 keV µm-1) for the three targets, respectively. To show the proof of principle of IMPACT in a clinical situation, we made IMPACT plans for a prostate case. In accordance with the prescriptions, the LETs in prostate, planning target volume (PTV), and rectum could be adjusted at 80 keV µm-1, at 50 keV µm-1, and below 30 keV µm-1, respectively, while keeping the dose to the PTV at 2 Gy uniformly. IMPACT enables the optimization of the dose and the LET distributions in a patient, which will maximize the

  9. An approach to multiobjective optimization of rotational therapy. II. Pareto optimal surfaces and linear combinations of modulated blocked arcs for a prostate geometry.

    Science.gov (United States)

    Pardo-Montero, Juan; Fenwick, John D

    2010-06-01

    The purpose of this work is twofold: To further develop an approach to multiobjective optimization of rotational therapy treatments recently introduced by the authors [J. Pardo-Montero and J. D. Fenwick, "An approach to multiobjective optimization of rotational therapy," Med. Phys. 36, 3292-3303 (2009)], especially regarding its application to realistic geometries, and to study the quality (Pareto optimality) of plans obtained using such an approach by comparing them with Pareto optimal plans obtained through inverse planning. In the previous work of the authors, a methodology is proposed for constructing a large number of plans, with different compromises between the objectives involved, from a small number of geometrically based arcs, each arc prioritizing different objectives. Here, this method has been further developed and studied. Two different techniques for constructing these arcs are investigated, one based on image-reconstruction algorithms and the other based on more common gradient-descent algorithms. The difficulty of dealing with organs abutting the target, briefly reported in previous work of the authors, has been investigated using partial OAR unblocking. Optimality of the solutions has been investigated by comparison with a Pareto front obtained from inverse planning. A relative Euclidean distance has been used to measure the distance of these plans to the Pareto front, and dose volume histogram comparisons have been used to gauge the clinical impact of these distances. A prostate geometry has been used for the study. For geometries where a blocked OAR abuts the target, moderate OAR unblocking can substantially improve target dose distribution and minimize hot spots while not overly compromising dose sparing of the organ. Image-reconstruction type and gradient-descent blocked-arc computations generate similar results. The Pareto front for the prostate geometry, reconstructed using a large number of inverse plans, presents a hockey-stick shape

  10. Effect of tricalcium aluminate on the physicochemical properties, bioactivity, and biocompatibility of partially stabilized cements.

    Science.gov (United States)

    Chang, Kai-Chun; Chang, Chia-Chieh; Huang, Ying-Chieh; Chen, Min-Hua; Lin, Feng-Huei; Lin, Chun-Pin

    2014-01-01

    Mineral Trioxide Aggregate (MTA) was widely used as a root-end filling material and for vital pulp therapy. A significant disadvantage to MTA is the prolonged setting time has limited the application in endodontic treatments. This study examined the physicochemical properties and biological performance of novel partially stabilized cements (PSCs) prepared to address some of the drawbacks of MTA, without causing any change in biological properties. PSC has a great potential as the vital pulp therapy material in dentistry. This study examined three experimental groups consisting of samples that were fabricated using sol-gel processes in C3S/C3A molar ratios of 9/1, 7/3, and 5/5 (denoted as PSC-91, PSC-73, and PSC-55, respectively). The comparison group consisted of MTA samples. The setting times, pH variation, compressive strength, morphology, and phase composition of hydration products and ex vivo bioactivity were evaluated. Moreover, biocompatibility was assessed by using lactate dehydrogenase to determine the cytotoxicity and a cell proliferation (WST-1) assay kit to determine cell viability. Mineralization was evaluated using Alizarin Red S staining. Crystalline phases, which were determined using X-ray diffraction analysis, confirmed that the C3A contents of the material powder differed. The initial setting times of PSC-73 and PSC-55 ranged between 15 and 25 min; these values are significantly (pmaterial for vital pulp therapy because it exhibits optimal compressive strength, a short setting time, and high biocompatibility and bioactivity.

  11. Optimized treatment parameters to account for interfractional variability in scanned ion beam therapy of lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Brevet, Romain

    2015-02-04

    Scanned ion beam therapy of lung tumors is severely limited in its clinical applicability by intrafractional organ motion, interference effects between beam and tumor motion (interplay) as well as interfractional anatomic changes. To compensate for dose deterioration by intrafractional motion, motion mitigation techniques, such as gating have been developed. The latter confines the irradiation to a predetermined breathing state, usually the stable end-exhale phase. However, optimization of the treatment parameters is needed to further improve target dose coverage and normal tissue sparing. The aim of the study presented in this dissertation was to determine treatment planning parameters that permit to recover good target coverage and homogeneity during a full course of lung tumor treatments. For 9 lung tumor patients from MD Anderson Cancer Center (MDACC), a total of 70 weekly time-resolved computed tomography (4DCT) datasets were available, which depict the evolution of the patient anatomy over the several fractions of the treatment. Using the GSI in-house treatment planning system (TPS) TRiP4D, 4D simulations were performed on each weekly 4DCT for each patient using gating and optimization of a single treatment plan based on a planning CT acquired prior to treatment. It was found that using a large beam spot size, a short gating window (GW), additional margins and multiple fields permitted to obtain the best results, yielding an average target coverage (V95) of 96.5%. Two motion mitigation techniques, one approximating the rescanning process (multiple irradiations of the target with a fraction of the planned dose) and one combining the latter and gating, were then compared to gating. Both did neither show an improvement in target dose coverage nor in normal tissue sparing. Finally, the total dose delivered to each patient in a simulation of a fractioned treatment was calculated and clinical requirements in terms of target coverage and normal tissue sparing were

  12. Full Monte Carlo-Based Biologic Treatment Plan Optimization System for Intensity Modulated Carbon Ion Therapy on Graphics Processing Unit.

    Science.gov (United States)

    Qin, Nan; Shen, Chenyang; Tsai, Min-Yu; Pinto, Marco; Tian, Zhen; Dedes, Georgios; Pompos, Arnold; Jiang, Steve B; Parodi, Katia; Jia, Xun

    2018-01-01

    One of the major benefits of carbon ion therapy is enhanced biological effectiveness at the Bragg peak region. For intensity modulated carbon ion therapy (IMCT), it is desirable to use Monte Carlo (MC) methods to compute the properties of each pencil beam spot for treatment planning, because of their accuracy in modeling physics processes and estimating biological effects. We previously developed goCMC, a graphics processing unit (GPU)-oriented MC engine for carbon ion therapy. The purpose of the present study was to build a biological treatment plan optimization system using goCMC. The repair-misrepair-fixation model was implemented to compute the spatial distribution of linear-quadratic model parameters for each spot. A treatment plan optimization module was developed to minimize the difference between the prescribed and actual biological effect. We used a gradient-based algorithm to solve the optimization problem. The system was embedded in the Varian Eclipse treatment planning system under a client-server architecture to achieve a user-friendly planning environment. We tested the system with a 1-dimensional homogeneous water case and 3 3-dimensional patient cases. Our system generated treatment plans with biological spread-out Bragg peaks covering the targeted regions and sparing critical structures. Using 4 NVidia GTX 1080 GPUs, the total computation time, including spot simulation, optimization, and final dose calculation, was 0.6 hour for the prostate case (8282 spots), 0.2 hour for the pancreas case (3795 spots), and 0.3 hour for the brain case (6724 spots). The computation time was dominated by MC spot simulation. We built a biological treatment plan optimization system for IMCT that performs simulations using a fast MC engine, goCMC. To the best of our knowledge, this is the first time that full MC-based IMCT inverse planning has been achieved in a clinically viable time frame. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Optimal nutrition therapy in paediatric critical care in the Asia-Pacific and Middle East: a consensus.

    Science.gov (United States)

    Lee, Jan Hau; Rogers, Elizabeth; Chor, Yek Kee; Samransamruajkit, Rujipat; Koh, Pei Lin; Miqdady, Mohamad; Al-Mehaidib, Ali Ibrahim; Pudjiadi, Antonius; Singhi, Sunit; Mehta, Nilesh M

    2016-12-01

    Current practices and available resources for nutrition therapy in paediatric intensive care units (PICUs) in the Asia Pacific-Middle East region are expected to differ from western countries. Existing guidelines for nutrition management in critically ill children may not be directly applicable in this region. This paper outlines consensus statements developed by the Asia Pacific-Middle East Consensus Working Group on Nutrition Therapy in the Paediatric Critical Care Environment. Challenges and recommendations unique to the region are described. Following a systematic literature search from 2004-2014, consensus statements were developed for key areas of nutrient delivery in the PICU. This review focused on evidence applicable to the Asia Pacific-Middle East region. Quality of evidence and strength of recommendations were rated according to the Grading of Recommendation Assessment, Development and Evaluation approach. Enteral nutrition (EN) is the preferred mode of nutritional support. Feeding algorithms that optimize EN should be encouraged and must include: assessment and monitoring of nutritional status, selection of feeding route, time to initiate and advance EN, management strategies for EN intolerance and indications for using parenteral nutrition (PN). Despite heterogeneity in nutritional status of patients, availability of resources and diversity of cultures, PICUs in the region should consider involvement of dieticians and/or nutritional support teams. Robust evidence for several aspects of optimal nutrition therapy in PICUs is lacking. Nutritional assessment must be implemented to document prevalence and impact of malnutrition. Nutritional support must be given greater priority in PICUs, with particular emphasis in optimizing EN delivery.

  14. SU-F-T-193: Evaluation of a GPU-Based Fast Monte Carlo Code for Proton Therapy Biological Optimization

    Energy Technology Data Exchange (ETDEWEB)

    Taleei, R; Qin, N; Jiang, S [UT Southwestern Medical Center, Dallas, TX (United States); Peeler, C [UT MD Anderson Cancer Center, Houston, TX (United States); Jia, X [The University of Texas Southwestern Medical Ctr, Dallas, TX (United States)

    2016-06-15

    Purpose: Biological treatment plan optimization is of great interest for proton therapy. It requires extensive Monte Carlo (MC) simulations to compute physical dose and biological quantities. Recently, a gPMC package was developed for rapid MC dose calculations on a GPU platform. This work investigated its suitability for proton therapy biological optimization in terms of accuracy and efficiency. Methods: We performed simulations of a proton pencil beam with energies of 75, 150 and 225 MeV in a homogeneous water phantom using gPMC and FLUKA. Physical dose and energy spectra for each ion type on the central beam axis were scored. Relative Biological Effectiveness (RBE) was calculated using repair-misrepair-fixation model. Microdosimetry calculations were performed using Monte Carlo Damage Simulation (MCDS). Results: Ranges computed by the two codes agreed within 1 mm. Physical dose difference was less than 2.5 % at the Bragg peak. RBE-weighted dose agreed within 5 % at the Bragg peak. Differences in microdosimetric quantities such as dose average lineal energy transfer and specific energy were < 10%. The simulation time per source particle with FLUKA was 0.0018 sec, while gPMC was ∼ 600 times faster. Conclusion: Physical dose computed by FLUKA and gPMC were in a good agreement. The RBE differences along the central axis were small, and RBE-weighted dose difference was found to be acceptable. The combined accuracy and efficiency makes gPMC suitable for proton therapy biological optimization.

  15. Beam Orientation Optimization for Intensity Modulated Radiation Therapy using Adaptive l1 Minimization

    CERN Document Server

    Jia, Xun; Lou, Yifei; Jiang, Steve B

    2011-01-01

    Beam orientation optimization (BOO) is a key component in the process of IMRT treatment planning. It determines to what degree one can achieve a good treatment plan quality in the subsequent plan optimization process. In this paper, we have developed a BOO algorithm via adaptive l_1 minimization. Specifically, we introduce a sparsity energy function term into our model which contains weighting factors for each beam angle adaptively adjusted during the optimization process. Such an energy term favors small number of beam angles. By optimizing a total energy function containing a dosimetric term and the sparsity term, we are able to identify the unimportant beam angles and gradually remove them without largely sacrificing the dosimetric objective. In one typical prostate case, the convergence property of our algorithm, as well as the how the beam angles are selected during the optimization process, is demonstrated. Fluence map optimization (FMO) is then performed based on the optimized beam angles. The resulted...

  16. Effect of tricalcium aluminate on the physicochemical properties, bioactivity, and biocompatibility of partially stabilized cements.

    Directory of Open Access Journals (Sweden)

    Kai-Chun Chang

    Full Text Available BACKGROUND/PURPOSE: Mineral Trioxide Aggregate (MTA was widely used as a root-end filling material and for vital pulp therapy. A significant disadvantage to MTA is the prolonged setting time has limited the application in endodontic treatments. This study examined the physicochemical properties and biological performance of novel partially stabilized cements (PSCs prepared to address some of the drawbacks of MTA, without causing any change in biological properties. PSC has a great potential as the vital pulp therapy material in dentistry. METHODS: This study examined three experimental groups consisting of samples that were fabricated using sol-gel processes in C3S/C3A molar ratios of 9/1, 7/3, and 5/5 (denoted as PSC-91, PSC-73, and PSC-55, respectively. The comparison group consisted of MTA samples. The setting times, pH variation, compressive strength, morphology, and phase composition of hydration products and ex vivo bioactivity were evaluated. Moreover, biocompatibility was assessed by using lactate dehydrogenase to determine the cytotoxicity and a cell proliferation (WST-1 assay kit to determine cell viability. Mineralization was evaluated using Alizarin Red S staining. RESULTS: Crystalline phases, which were determined using X-ray diffraction analysis, confirmed that the C3A contents of the material powder differed. The initial setting times of PSC-73 and PSC-55 ranged between 15 and 25 min; these values are significantly (p<0.05, ANOVA and post-hoc test lower than those obtained for MTA (165 min and PSC-91 (80.5 min. All of the PSCs exhibited ex vivo bioactivity when immersed in simulated body fluid. The biocompatibility results for all of the tested cements were as favorable as those of the negative control, except for PSC-55, which exhibited mild cytotoxicity. CONCLUSION: PSC-91 is a favorable material for vital pulp therapy because it exhibits optimal compressive strength, a short setting time, and high biocompatibility and

  17. Applied bioactive polymeric materials

    CERN Document Server

    Carraher, Charles; Foster, Van

    1988-01-01

    The biological and biomedical applications of polymeric materials have increased greatly in the past few years. This book will detail some, but not all, of these recent developments. There would not be enough space in this book to cover, even lightly, all of the major advances that have occurred. Some earlier books and summaries are available by two of this book's Editors (Gebelein & Carraher) and these should be consul ted for additional information. The books are: "Bioactive Polymeric Systems" (Plenum, 1985); "Polymeric Materials In Medication" (Plenum, 1985); "Biological Acti vi ties of Polymers" (American Chemical Society, 1982). Of these three, "Bioacti ve Polymeric Systems" should be the most useful to a person who is new to this field because it only contains review articles written at an introductory level. The present book primarily consists of recent research results and applications, with only a few review or summary articles. Bioactive polymeric materials have existed from the creation of life...

  18. Efficacy of robust optimization plan with partial-arc VMAT for photon volumetric-modulated arc therapy: A phantom study.

    Science.gov (United States)

    Miura, Hideharu; Ozawa, Shuichi; Nagata, Yasushi

    2017-09-01

    This study investigated position dependence in planning target volume (PTV)-based and robust optimization plans using full-arc and partial-arc volumetric modulated arc therapy (VMAT). The gantry angles at the periphery, intermediate, and center CTV positions were 181°-180° (full-arc VMAT) and 181°-360° (partial-arc VMAT). A PTV-based optimization plan was defined by 5 mm margin expansion of the CTV to a PTV volume, on which the dose constraints were applied. The robust optimization plan consisted of a directly optimized dose to the CTV under a maximum-uncertainties setup of 5 mm. The prescription dose was normalized to the CTV D99% (the minimum relative dose that covers 99% of the volume of the CTV) as an original plan. The isocenter was rigidly shifted at 1 mm intervals in the anterior-posterior (A-P), superior-inferior (S-I), and right-left (R-L) directions from the original position to the maximum-uncertainties setup of 5 mm in the original plan, yielding recalculated dose distributions. It was found that for the intermediate and center positions, the uncertainties in the D99% doses to the CTV for all directions did not significantly differ when comparing the PTV-based and robust optimization plans (P > 0.05). For the periphery position, uncertainties in the D99% doses to the CTV in the R-L direction for the robust optimization plan were found to be lower than those in the PTV-based optimization plan (P optimization plan's efficacy using partial-arc VMAT depends on the periphery CTV position. © 2017 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

  19. Pittsburgh Response to Endovascular therapy (PRE) score: optimizing patient selection for endovascular therapy for large vessel occlusion strokes.

    Science.gov (United States)

    Rangaraju, Srikant; Aghaebrahim, Amin; Streib, Christopher; Sun, Chung-Huan; Ribo, Marc; Muchada, Marion; Nogueira, Raul; Frankel, Michael; Gupta, Rishi; Jadhav, Ashutosh; Jovin, Tudor G

    2015-11-01

    Endovascular therapy seems to benefit a subset of patients with large vessel occlusion strokes. We aimed to develop a clinically useful tool to identify patients who are likely to benefit from endovascular therapy. In a derivation cohort of consecutively treated patients with anterior circulation large vessel occlusion (Grady Memorial Hospital, N=247), independent predictors (pPittsburgh Response to Endovascular therapy (PRE) score as a predictor of good outcome. The PRE score was validated in two institutional cohorts (University of Pittsburgh Medical Center (UPMC): N=393; Unitat d'Ictus Vall d'Hebron: N=204) and its discriminative power for good outcome was compared with other validated tools. Benefit of successful recanalization was assessed in PRE score groups. Independent predictors of good outcome in the derivation cohort (age, baseline National Institute of Health Stroke Scale (NIHSS) score and Alberta Stroke Program Early CT Score (ASPECTS)) were used in the model: PRE score=age (years)+2×NIHSS-10 × ASPECTS. PRE score was highly predictive of good outcome in the derivation cohort (area under the curve (AUC)=0.79) and validation cohorts (UPMC: AUC=0.79; UIVH: AUC=0.72) with comparable rates of good outcome in all PRE risk quartiles. PRE was superior to Totaled Health Risks In Vascular Events (THRIVE) (p=0.03) and Stroke Prognostication using Age and NIHSS (SPAN) (p=0.007), with a trend towards superiority to Houston Intra-Arterial Therapy 2 (HIAT2) (p=0.06) and iSCORE (p=0.051) in predicting good outcomes. Better outcomes were associated with successful recanalization in patients with PRE scores -24 to +49 but not in patients with PRE scores <-24 or ≥ 50. The PRE score is a validated tool that predicts outcomes and may facilitate patient selection for endovascular therapy in anterior circulation large vessel occlusions. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  20. Collimator optimization for small animal radiation therapy at a micro-CT

    Energy Technology Data Exchange (ETDEWEB)

    Felix, Manuela C. [Heidelberg Univ., Mannheim (Germany). Medical Radiation Physics/Radiation Protection; Heidelberg Univ., Mannheim (Germany). Dept. of Radiation Oncology; Glatting, Gerhard [Heidelberg Univ., Mannheim (Germany). Medical Radiation Physics/Radiation Protection; Giordano, Frank A.; Wenz, Frederik; Fleckenstein, Jens [Heidelberg Univ., Mannheim (Germany). Dept. of Radiation Oncology; Brockmann, Marc A. [Heidelberg Univ., Mannheim (Germany). Dept. of Neuroradiology; University Medical Center Mainz (Germany). Dept. of Neuroradiology

    2017-05-01

    In radiation therapy of small animals treatment depths range from a few millimetres to several centimetres. In order to spare surrounding organs at risk steep dose gradients are necessary. To minimize the treatment time, and therefore the strain to the animals, a high dose rate is required. A description how these parameters can be optimized through an appropriate choice of collimators with different source surface distances (SSD) as well as different materials and geometries is presented. An industrial micro-CT unit (Y.Fox, YXLON GmbH, Hamburg, Germany) was converted into a precision irradiator for small animals. Different collimators of either stainless steel (Fe) with cylindrical bores (SSD = 42 mm) or tungsten (W) with conical bores (SSD = 14 mm) were evaluated. The dosimetry of very small radiation fields presents a challenge and was performed with GafChromic EBT3 films (Ashland, Vayne, KY, USA) in a water phantom. The films were calibrated with an ionization chamber in the uncollimated field. Treatments were performed via a rotation of the objects with a fixed radiation source. As expected, the shorter SSD of the W-collimators resulted in a (4.5 ± 1.6)-fold increase of the dose rates compared to the corresponding Fe-collimators. The ratios of the dose rates at 1 mm and 10 mm depth in the water phantom was (2.6 ± 0.2) for the Fe- and (4.5 ± 0.1) for the W-collimators. For rotational treatments in a cylindrical plastic phantom maximum dose rates of up to 1.2 Gy/min for Fe- and 5.1 Gy/min for W-collimators were measured. Choosing the smallest possible SSD leads to a high dose rate and a high surface dose, which is of advantage for the treatment of superficial target volumes. For larger SSD the dose rate is lower and the depth dose curve is shallower. This leads to a reduction of the surface dose and is best suited for treatments of deeper seated target volumes. Divergent collimator bores have, due to the reduced scatter within the collimators, a steeper

  1. Bioactive glass in tissue engineering

    Science.gov (United States)

    Rahaman, Mohamed N.; Day, Delbert E.; Bal, B. Sonny; Fu, Qiang; Jung, Steven B.; Bonewald, Lynda F.; Tomsia, Antoni P.

    2011-01-01

    This review focuses on recent advances in the development and use of bioactive glass for tissue engineering applications. Despite its inherent brittleness, bioactive glass has several appealing characteristics as a scaffold material for bone tissue engineering. New bioactive glasses based on borate and borosilicate compositions have shown the ability to enhance new bone formation when compared to silicate bioactive glass. Borate-based bioactive glasses also have controllable degradation rates, so the degradation of the bioactive glass implant can be more closely matched to the rate of new bone formation. Bioactive glasses can be doped with trace quantities of elements such as Cu, Zn and Sr, which are known to be beneficial for healthy bone growth. In addition to the new bioactive glasses, recent advances in biomaterials processing have resulted in the creation of scaffold architectures with a range of mechanical properties suitable for the substitution of loaded as well as non-loaded bone. While bioactive glass has been extensively investigated for bone repair, there has been relatively little research on the application of bioactive glass to the repair of soft tissues. However, recent work has shown the ability of bioactive glass to promote angiogenesis, which is critical to numerous applications in tissue regeneration, such as neovascularization for bone regeneration and the healing of soft tissue wounds. Bioactive glass has also been shown to enhance neocartilage formation during in vitro culture of chondrocyte-seeded hydrogels, and to serve as a subchondral substrate for tissue-engineered osteochondral constructs. Methods used to manipulate the structure and performance of bioactive glass in these tissue engineering applications are analyzed. PMID:21421084

  2. Infidelity and Behavioral Couple Therapy: Optimism in the Face of Betrayal

    Science.gov (United States)

    Atkins, David C.; Eldridge, Kathleen A.; Baucom, Donald H.; Christensen, Andrew

    2005-01-01

    Infidelity is a common issue with which distressed couples and their therapists grapple. However, there are no data on the efficacy of commonly used therapies to treat couples in which there has been an affair. In the present exploratory study, the authors examined the therapy outcomes of a sample of infidelity couples (n=19) who had participated…

  3. Infidelity and behavioral couple therapy: optimism in the face of betrayal.

    Science.gov (United States)

    Atkins, David C; Eldridge, Kathleen A; Baucom, Donald H; Christensen, Andrew

    2005-02-01

    Infidelity is a common issue with which distressed couples and their therapists grapple. However, there are no data on the efficacy of commonly used therapies to treat couples in which there has been an affair. In the present exploratory study, the authors examined the therapy outcomes of a sample of infidelity couples (n=19) who had participated in a randomized clinical trial of marital therapy (N=134). Results show that infidelity couples began treatment more distressed than noninfidelity couples; however, evidence suggests that couples who had an affair and who revealed this affair prior to or during therapy showed greater improvement in satisfaction than noninfidelity couples. Implications for therapy with infidelity couples are discussed. Copyright 2005 APA.

  4. Optimal monitoring of bypass therapy in hemophilia A patients with inhibitors by the use of clot waveform analysis.

    Science.gov (United States)

    Haku, J; Nogami, K; Matsumoto, T; Ogiwara, K; Shima, M

    2014-01-01

    Assays to determine the optimal hemostatic effects of bypass therapy in hemophilia A (HA) patients with inhibitors are difficult to compare. Clot waveform analysis (CWA), based on the continuous monitoring of routine coagulation parameters (prothrombin time/activated partial thromboplastin time), offers a useful method for assessing global clotting function. To investigate the technique of CWA for the hemostatic monitoring of bypass therapy in HA patients with inhibitors. Ellagic acid (Elg), tissue factor (TF) or both (Elg/TF) were used as trigger reagents in CWA. The standard parameters - clot time (CT), maximum coagulation velocity (|min1|), and acceleration (|min2|) - were recorded. Optimal monitoring was defined as: (i) a significant difference in these parameters between plasma from HA patients with inhibitors and normal plasmas; and (ii) a significant improvement in these indices in HA patients with inhibitors after bypass therapy. Experiments in vitro demonstrated that there were significant differences between plasma from HA patients with inhibitors and normal plasma with various triggers, in the order Elg > Elg/TF > TF. Addition of therapeutically achievable concentrations of bypassing agents, however, showed significant improvements in the different parameters only with Elg/TF, suggesting that this reagent provided the most appropriate assay. A total of 20 plasmas from HA patients with inhibitors in which bypassing agents were infused were evaluated ex vivo by Elg/TF CWA. The postinfusion parameters CT and |min2| reflected clinical effects, and were close to normal levels. Furthermore, Elg/TF CWA facilitated quantitative evaluation of perioperative hemostatic management of bypass therapy in HA patients with inhibitors. CWA is a promising method for the quantitative monitoring of bypass therapy during routine automated clotting assays with a modified trigger reagent comprising a well-balanced mixture of Elg and TF. © 2013 International Society on

  5. Optimal control for mathematical models of cancer therapies an application of geometric methods

    CERN Document Server

    Schättler, Heinz

    2015-01-01

    This book presents applications of geometric optimal control to real life biomedical problems with an emphasis on cancer treatments. A number of mathematical models for both classical and novel cancer treatments are presented as optimal control problems with the goal of constructing optimal protocols. The power of geometric methods is illustrated with fully worked out complete global solutions to these mathematically challenging problems. Elaborate constructions of optimal controls and corresponding system responses provide great examples of applications of the tools of geometric optimal control and the outcomes aid the design of simpler, practically realizable suboptimal protocols. The book blends mathematical rigor with practically important topics in an easily readable tutorial style. Graduate students and researchers in science and engineering, particularly biomathematics and more mathematical aspects of biomedical engineering, would find this book particularly useful.

  6. EFFECTS OF RELIGIOUS VERSUS STANDARD COGNITIVE-BEHAVIORAL THERAPY ON OPTIMISM IN PERSONS WITH MAJOR DEPRESSION AND CHRONIC MEDICAL ILLNESS.

    Science.gov (United States)

    Koenig, Harold G; Pearce, Michelle J; Nelson, Bruce; Daher, Noha

    2015-11-01

    We compared the effectiveness of religiously integrated cognitive behavioral therapy (RCBT) versus standard CBT (SCBT) on increasing optimism in persons with major depressive disorder (MDD) and chronic medical illness. Participants aged 18-85 were randomized to either RCBT (n = 65) or SCBT (n = 67) to receive ten 50-min sessions remotely (94% by telephone) over 12 weeks. Optimism was assessed at baseline, 12 and 24 weeks by the Life Orientation Test-Revised. Religiosity was assessed at baseline using a 29-item scale composed of religious importance, individual religious practices, intrinsic religiosity, and daily spiritual experiences. Mixed effects growth curve models were used to compare the effects of treatment group on trajectory of change in optimism. In the intention-to-treat analysis, both RCBT and SCBT increased optimism over time, although there was no significant difference between treatment groups (B = -0.75, SE = 0.57, t = -1.33, P = .185). Analyses in the highly religious and in the per protocol analysis indicated similar results. Higher baseline religiosity predicted an increase in optimism over time (B = 0.07, SE = 0.02, t = 4.12, P decline in depressive symptoms over time (B = -0.61, SE = 0.10, t = -6.30, P < .0001), both independent of treatment group. RCBT and SCBT are equally effective in increasing optimism in persons with MDD and chronic medical illness. While baseline religiosity does not moderate this effect, religiosity predicts increases in optimism over time independent of treatment group. © 2015 Wiley Periodicals, Inc.

  7. Optimization of beam angles for intensity modulated radiation therapy treatment planning using genetic algorithm on a distributed computing platform.

    Science.gov (United States)

    Nazareth, Daryl P; Brunner, Stephen; Jones, Matthew D; Malhotra, Harish K; Bakhtiari, Mohammad

    2009-07-01

    Planning intensity modulated radiation therapy (IMRT) treatment involves selection of several angle parameters as well as specification of structures and constraints employed in the optimization process. Including these parameters in the combinatorial search space vastly increases the computational burden, and therefore the parameter selection is normally performed manually by a clinician, based on clinical experience. We have investigated the use of a genetic algorithm (GA) and distributed-computing platform to optimize the gantry angle parameters and provide insight into additional structures, which may be necessary, in the dose optimization process to produce optimal IMRT treatment plans. For an IMRT prostate patient, we produced the first generation of 40 samples, each of five gantry angles, by selecting from a uniform random distribution, subject to certain adjacency and opposition constraints. Dose optimization was performed by distributing the 40-plan workload over several machines running a commercial treatment planning system. A score was assigned to each resulting plan, based on how well it satisfied clinically-relevant constraints. The second generation of 40 samples was produced by combining the highest-scoring samples using techniques of crossover and mutation. The process was repeated until the sixth generation, and the results compared with a clinical (equally-spaced) gantry angle configuration. In the sixth generation, 34 of the 40 GA samples achieved better scores than the clinical plan, with the best plan showing an improvement of 84%. Moreover, the resulting configuration of beam angles tended to cluster toward the patient's sides, indicating where the inclusion of additional structures in the dose optimization process may avoid dose hot spots. Additional parameter selection in IMRT leads to a large-scale computational problem. We have demonstrated that the GA combined with a distributed-computing platform can be applied to optimize gantry angle

  8. Bioactive glass coupling with natural polyphenols: Surface modification, bioactivity and anti-oxidant ability

    Energy Technology Data Exchange (ETDEWEB)

    Cazzola, Martina [Politecnico di Torino, Department of Applied Science and Technology, Institute of Materials Physics and Engineering, C.so Duca degli Abruzzi 24, Torino 10129 (Italy); Corazzari, Ingrid [Università degli Studi di Torino, Department of Chemistry, Via Pietro Giuria 7, Torino 10125 (Italy); Centro Interdipartimentale “G. Scansetti” per lo studio degli amianti e di altri particolati nocivi, Via Pietro Giuria 9, 10125 Torino (Italy); Prenesti, Enrico [Università degli Studi di Torino, Department of Chemistry, Via Pietro Giuria 7, Torino 10125 (Italy); Bertone, Elisa [Politecnico di Torino, Department of Applied Science and Technology, Institute of Materials Physics and Engineering, C.so Duca degli Abruzzi 24, Torino 10129 (Italy); Vernè, Enrica, E-mail: enrica.verne@polito.it [Politecnico di Torino, Department of Applied Science and Technology, Institute of Materials Physics and Engineering, C.so Duca degli Abruzzi 24, Torino 10129 (Italy); Ferraris, Sara [Politecnico di Torino, Department of Applied Science and Technology, Institute of Materials Physics and Engineering, C.so Duca degli Abruzzi 24, Torino 10129 (Italy)

    2016-03-30

    Graphical abstract: - Highlights: • Surface functionalization of bioactive glass with biomolecules has been optimized. • Biomolecules are present and active on the glass surface after functionalization. • Biomolecules affect deposition kinetics and morphology of hydroxyapatite. • Free radical scavenging activity is seen for the first time on bioactive glasses. - Abstract: Polyphenols are actually achieving an increasing interest due to their potential health benefits, such as antioxidant, anticancer, antibacterial and bone stimulation abilities. However their poor bioavailability and stability hamper an effective clinical application as therapeutic principles. The opportunity to couple these biomolecules with synthetic biomaterials, in order to obtain local delivery at the site of interest, improve their bioavailability and stability and combine their properties with the ones of the substrate, is a challenging opportunity for the biomedical research. A silica based bioactive glass, CEL2, has been successfully coupled with gallic acid and natural polyphenols extracted from red grape skins and green tea leaves. The effectiveness of grafting has been verified by means of XPS analyses and the Folin&Ciocalteu tests. In vitro bioactivity has been investigated by soaking in simulated body fluid (SBF). Surface modification after functionalization and early stage reactivity in SBF have been studied by means of zeta potential electrokinetic measurements in KCl and SBF. Finally the antioxidant properties of bare and modified bioactive glasses has been investigated by means of the evaluation of free radical scavenging activity by Electron Paramagnetic Resonance (EPR)/spin trapping technique after UV photolysis of H{sub 2}O{sub 2} highlighting scavenging activity of the bioactive glass.

  9. Optimizing targeted cancer therapy : Towards clinical application of systems biology approaches

    NARCIS (Netherlands)

    Sikkema, Arend H.; den Dunnen, Wilfred F. A.; Diks, Sander H.; Peppelenbosch, Maikel P.; de Bont, Eveline S. J. M.

    In cancer, genetic and epigenetic alterations ultimately culminate in discordant activation of signal transduction pathways driving the malignant process. Pharmacological or biological inhibition of such pathways holds significant promise with respect to devising rational therapy for cancer. Thus,

  10. Multi-field Optimization Intensity-Modulated Proton Therapy for Head and Neck Tumors – A Translation to Practice

    Science.gov (United States)

    Frank, Steven J.; Cox, James D.; Gillin, Michael; Mohan, Radhe; Garden, Adam S.; Rosenthal, David I.; Gunn, G. Brandon; Weber, Randal S.; Kies, Merrill S.; Lewin, Jan S.; Munsell, Mark F.; Palmer, Matthew B.; Sahoo, Narayan; Zhang, Xiaodong; Liu, Wei; Zhu, X. Ronald

    2014-01-01

    Summary The first fifteen consecutive patients treated with multi-field optimization intensity modulated proton therapy (MFO-IMPT) were able to complete treatment with no need for treatment breaks and no hospitalizations. Ten patients presented with SCC and 5 with ACC. There were no treatment-related deaths and with a median follow-up of 28 months, the overall clinical complete response rate was 93.3%. Early clinical outcomes warrant further investigation of proton therapy in the management of head and neck malignancies. Background We report the first clinical experience and toxicity of multi-field optimization (MFO) intensity-modulated proton therapy (IMPT) for patients with head and neck tumors. Methods Fifteen consecutive patients with head and neck cancer underwent MFO-IMPT with active scanning beam proton therapy. Patients with SCC had comprehensive treatment extending from the base of the skull to the clavicle. The dose for chemoradiation therapy and radiation therapy alone was 70 Gy and 66 Gy, respectively. The robustness of each treatment plan was also analyzed to evaluate sensitivity to uncertainties associated with variations in patient setup and the effect of uncertainties with proton beam range in patients. Proton beam energies during treatment ranged from 72.5 to 221.8 MeV. Spot sizes varied depending on the beam energy and depth of the target, and the scanning nozzle delivered the spot scanning treatment “spot-by-spot” and “layer-by-layer” Results Ten patients presented with squamous cell carcinoma (SCC) and 5 with adenoid cystic carcinoma (ACC). All 15 patients were able to complete treatment with MFO-IMPT with no need for treatment breaks and no hospitalizations. There were no treatment-related deaths and with a median follow-up of 28 months (range: 20-35), the overall clinical complete response rate was 93.3% (95%, confidence interval 68.1% to 99.8%). Xerostomia occurred in all 15 patients as follows; Grade 1 - ten patients, Grade 2 - four

  11. Is there an Optimal Neoadjuvant Therapy for Locally Advanced Pancreatic Cancer?

    OpenAIRE

    Richard Kim; Muhammad Wasif Saif

    2008-01-01

    ASCO: American Society of Clinical Oncology; CALGB: Cancer and Leukemia Group B; CBR: clinical benefit response; CDHP: 5-chloro-2,4- dihydroxypyridine; CIV: continuous infusional; EBRT: external beam radiation therapy; ECOG: Eastern Cooperative Oncology Group; FFCD-SFRO: Federation Francophone de Cancerologie Digestive and Societe Francaise de Radiotherapie Oncologique (GITSG: Gastrointestinal Tumor Study Group; OXO: potassium oxonate; RTOG: Radiation Therapy Oncology Group; SMF: streptozocin...

  12. Good Manufacturing Practices (GMP) manufacturing of advanced therapy medicinal products: a novel tailored model for optimizing performance and estimating costs.

    Science.gov (United States)

    Abou-El-Enein, Mohamed; Römhild, Andy; Kaiser, Daniel; Beier, Carola; Bauer, Gerhard; Volk, Hans-Dieter; Reinke, Petra

    2013-03-01

    Advanced therapy medicinal products (ATMP) have gained considerable attention in academia due to their therapeutic potential. Good Manufacturing Practice (GMP) principles ensure the quality and sterility of manufacturing these products. We developed a model for estimating the manufacturing costs of cell therapy products and optimizing the performance of academic GMP-facilities. The "Clean-Room Technology Assessment Technique" (CTAT) was tested prospectively in the GMP facility of BCRT, Berlin, Germany, then retrospectively in the GMP facility of the University of California-Davis, California, USA. CTAT is a two-level model: level one identifies operational (core) processes and measures their fixed costs; level two identifies production (supporting) processes and measures their variable costs. The model comprises several tools to measure and optimize performance of these processes. Manufacturing costs were itemized using adjusted micro-costing system. CTAT identified GMP activities with strong correlation to the manufacturing process of cell-based products. Building best practice standards allowed for performance improvement and elimination of human errors. The model also demonstrated the unidirectional dependencies that may exist among the core GMP activities. When compared to traditional business models, the CTAT assessment resulted in a more accurate allocation of annual expenses. The estimated expenses were used to set a fee structure for both GMP facilities. A mathematical equation was also developed to provide the final product cost. CTAT can be a useful tool in estimating accurate costs for the ATMPs manufactured in an optimized GMP process. These estimates are useful when analyzing the cost-effectiveness of these novel interventions. Copyright © 2013 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  13. Marine algae-derived bioactive peptides for human nutrition and health.

    Science.gov (United States)

    Fan, Xiaodan; Bai, Lu; Zhu, Liang; Yang, Li; Zhang, Xuewu

    2014-09-24

    Within the parent protein molecule, most peptides are inactive, and they are released with biofunctionalities after enzymatic hydrolysis. Marine algae have high protein content, up to 47% of the dry weight, depending on the season and the species. Recently, there is an increasing interest in using marine algae protein as a source of bioactive peptides due to their health promotion and disease therapy potentials. This review presents an overview of marine algae-derived bioactive peptides and especially highlights some key issues, such as in silico proteolysis and quantitative structure-activity relationship studies, in vivo fate of bioactive peptides, and novel technologies in bioactive peptides studies and production.

  14. Explicit optimization of plan quality measures in intensity-modulated radiation therapy treatment planning.

    Science.gov (United States)

    Engberg, Lovisa; Forsgren, Anders; Eriksson, Kjell; Hårdemark, Björn

    2017-06-01

    To formulate convex planning objectives of treatment plan multicriteria optimization with explicit relationships to the dose-volume histogram (DVH) statistics used in plan quality evaluation. Conventional planning objectives are designed to minimize the violation of DVH statistics thresholds using penalty functions. Although successful in guiding the DVH curve towards these thresholds, conventional planning objectives offer limited control of the individual points on the DVH curve (doses-at-volume) used to evaluate plan quality. In this study, we abandon the usual penalty-function framework and propose planning objectives that more closely relate to DVH statistics. The proposed planning objectives are based on mean-tail-dose, resulting in convex optimization. We also demonstrate how to adapt a standard optimization method to the proposed formulation in order to obtain a substantial reduction in computational cost. We investigated the potential of the proposed planning objectives as tools for optimizing DVH statistics through juxtaposition with the conventional planning objectives on two patient cases. Sets of treatment plans with differently balanced planning objectives were generated using either the proposed or the conventional approach. Dominance in the sense of better distributed doses-at-volume was observed in plans optimized within the proposed framework. The initial computational study indicates that the DVH statistics are better optimized and more efficiently balanced using the proposed planning objectives than using the conventional approach. © 2017 American Association of Physicists in Medicine.

  15. Optimal therapies of a virus replication model with pharmacological delays based on reverse transcriptase inhibitors and protease inhibitors

    Science.gov (United States)

    Pei, Yongzhen; Li, Changguo; Liang, Xiyin

    2017-11-01

    A short delay in the pharmacological effect on account of the time required for drug absorption, distribution, and penetration into target cells after application of any anti-viral drug, is defined by the pharmacological delay (Herz et al 1996 Proc. Natl Acad. Sci. USA 93 7247-51). In this paper, a virus replication model with Beddington-DeAngelis incidence rate and the pharmacological and intracellular delays is presented to describe the treatment to cure the virus infection. The optimal controls represent the efficiency of reverse transcriptase inhibitors and protease inhibitors in suppressing viral production and prohibiting new infections. Due to the fact that both the control and state variables contain delays, we derive a necessary conditions for our optimal problem. Based on these results, numerical simulations are implemented not only to show the optimal therapeutic schedules for different infection and release rates, but also to compare the effective of three treatment programs. Furthermore, comparison of therapeutic effects under different maximum tolerable dosages is shown. Our research indicates that (1) the proper and specific treatment program should be determined according to the infection rates of different virus particles; (2) the optimal combined drug treatment is the most efficient; (3) the appropriate proportion of medicament must be formulated during the therapy due to the non-monotonic relationship between maximum tolerable dosages and therapeutic effects; (4) the therapeutic effect is advantageous when the pharmacological delay is considered.

  16. Exploratory Study of 4D versus 3D Robust Optimization in Intensity Modulated Proton Therapy for Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Wei, E-mail: Liu.Wei@mayo.edu [Department of Radiation Oncology, Mayo Clinic Arizona, Phoenix, Arizona (United States); Schild, Steven E. [Department of Radiation Oncology, Mayo Clinic Arizona, Phoenix, Arizona (United States); Chang, Joe Y.; Liao, Zhongxing [Department of Radiation Oncology, the University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Chang, Yu-Hui [Division of Health Sciences Research, Mayo Clinic Arizona, Phoenix, Arizona (United States); Wen, Zhifei [Department of Radiation Physics, the University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Shen, Jiajian; Stoker, Joshua B.; Ding, Xiaoning; Hu, Yanle [Department of Radiation Oncology, Mayo Clinic Arizona, Phoenix, Arizona (United States); Sahoo, Narayan [Department of Radiation Physics, the University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Herman, Michael G. [Department of Radiation Oncology, Mayo Clinic Rochester, Rochester, Minnesota (United States); Vargas, Carlos; Keole, Sameer; Wong, William; Bues, Martin [Department of Radiation Oncology, Mayo Clinic Arizona, Phoenix, Arizona (United States)

    2016-05-01

    Purpose: The purpose of this study was to compare the impact of uncertainties and interplay on 3-dimensional (3D) and 4D robustly optimized intensity modulated proton therapy (IMPT) plans for lung cancer in an exploratory methodology study. Methods and Materials: IMPT plans were created for 11 nonrandomly selected non-small cell lung cancer (NSCLC) cases: 3D robustly optimized plans on average CTs with internal gross tumor volume density overridden to irradiate internal target volume, and 4D robustly optimized plans on 4D computed tomography (CT) to irradiate clinical target volume (CTV). Regular fractionation (66 Gy [relative biological effectiveness; RBE] in 33 fractions) was considered. In 4D optimization, the CTV of individual phases received nonuniform doses to achieve a uniform cumulative dose. The root-mean-square dose-volume histograms (RVH) measured the sensitivity of the dose to uncertainties, and the areas under the RVH curve (AUCs) were used to evaluate plan robustness. Dose evaluation software modeled time-dependent spot delivery to incorporate interplay effect with randomized starting phases of each field per fraction. Dose-volume histogram (DVH) indices comparing CTV coverage, homogeneity, and normal tissue sparing were evaluated using Wilcoxon signed rank test. Results: 4D robust optimization plans led to smaller AUC for CTV (14.26 vs 18.61, respectively; P=.001), better CTV coverage (Gy [RBE]) (D{sub 95%} CTV: 60.6 vs 55.2, respectively; P=.001), and better CTV homogeneity (D{sub 5%}-D{sub 95%} CTV: 10.3 vs 17.7, resspectively; P=.002) in the face of uncertainties. With interplay effect considered, 4D robust optimization produced plans with better target coverage (D{sub 95%} CTV: 64.5 vs 63.8, respectively; P=.0068), comparable target homogeneity, and comparable normal tissue protection. The benefits from 4D robust optimization were most obvious for the 2 typical stage III lung cancer patients. Conclusions: Our exploratory methodology study showed

  17. Feasibility and robustness of dose painting by numbers in proton therapy with contour-driven plan optimization

    Energy Technology Data Exchange (ETDEWEB)

    Barragán, A. M., E-mail: ana.barragan@uclouvain.be; Differding, S.; Lee, J. A.; Sterpin, E. [Center of Molecular Imaging, Radiotherapy and Oncology, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Brussels B-1200 (Belgium); Janssens, G. [Ion Beam Applications S.A., Louvain-la-Neuve 1348 (Belgium)

    2015-04-15

    above 5% of DPBN prescription for robust-optimized plans, while they were more than 50% for PTV plans. Low dose to organs at risk (OARs) could be achieved for both PTV and robust-optimized plans. Conclusions: DPBN in proton therapy is feasible with the use of a sufficient number subcontours, automatically generated scanning patterns, and no more than three beams are needed. Robust optimization ensured the required target coverage and minimal overdosing, while PTV-approach led to nonrobust plans with excessive overdose. Low dose to OARs can be achieved even in the presence of a high-dose escalation as in DPBN.

  18. Evaluation of the optimal combinations of modulation factor and pitch for Helical TomoTherapy plans made with TomoEdge using Pareto optimal fronts.

    Science.gov (United States)

    De Kerf, Geert; Van Gestel, Dirk; Mommaerts, Lobke; Van den Weyngaert, Danielle; Verellen, Dirk

    2015-09-17

    Modulation factor (MF) and pitch have an impact on Helical TomoTherapy (HT) plan quality and HT users mostly use vendor-recommended settings. This study analyses the effect of these two parameters on both plan quality and treatment time for plans made with TomoEdge planning software by using the concept of Pareto optimal fronts. More than 450 plans with different combinations of pitch [0.10-0.50] and MF [1.2-3.0] were produced. These HT plans, with a field width (FW) of 5 cm, were created for five head and neck patients and homogeneity index, conformity index, dose-near-maximum (D2), and dose-near-minimum (D98) were analysed for the planning target volumes, as well as the mean dose and D2 for most critical organs at risk. For every dose metric the median value will be plotted against treatment time. A Pareto-like method is used in the analysis which will show how pitch and MF influence both treatment time and plan quality. For small pitches (≤0.20), MF does not influence treatment time. The contrary is true for larger pitches (≥0.25) as lowering MF will both decrease treatment time and plan quality until maximum gantry speed is reached. At this moment, treatment time is saturated and only plan quality will further decrease. The Pareto front analysis showed optimal combinations of pitch [0.23-0.45] and MF > 2.0 for a FW of 5 cm. Outside this range, plans will become less optimal. As the vendor-recommended settings fall within this range, the use of these settings is validated.

  19. Nanogel-based scaffolds fabricated for bone regeneration with mesoporous bioactive glass and strontium: In vitro and in vivo characterization.

    Science.gov (United States)

    Zhang, Qiao; Chen, Xiaohui; Geng, Shinan; Wei, Lingfei; Miron, Richard J; Zhao, Yanbing; Zhang, Yufeng

    2017-04-01

    The delivery of novel bioactive scaffolds for the repair of bone defects remains a prominent challenge worldwide. Currently osteoporosis, a disease caused by low bone mineral density affects over 200 million people worldwide with up to half of this population experiencing at least one fracture within their lifetime. Recently temperature-sensitive p(N-isopropylacrylamide-co-butyl methylacrylate) nanogel (PIB nanogel) scaffolds have emerged as biomaterial candidate for regenerative therapies. It has the advantage of being injected from syringes as a soluble gel form (capable of delivering growth and/or living progenitor cells) yet hardens once it reaches body temperatures. Although this material demonstrates optimal clinical delivery of scaffolds, its main drawback is its low osteoconductivity and bioactivity. Recently we have demonstrated that mesoporous bioactive glass (MBG) loaded with strontium was able to regenerate osteoporotic defects in vivo and enhance osteoblast differentiation in vitro. The aim of this study was to combine the advantages of these two therapies and prepare PIB-nanogel scaffolds containing Sr-MBG and investigate their ability to regenerate femur defects created in ovarectamized rats. The results demonstrate that groups containing Sr-MBG within the nanogel formulation had significantly higher new bone formation when compared with other modalities. We further demonstrate that although nanogel demonstrated poor osteogenic ability, the addition of osteoblasts worked synergistically with Sr-MBG particles to enhance the regeneration of the created femur defects in osteoporotic animals. In conclusion, PIB nanogel scaffolds are a viable treatment modality for bone tissue engineering and may serve as a carrier-scaffold for osteogenic cells and/or bioactive scaffolds such as Sr-MBG. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1175-1183, 2017. © 2017 Wiley Periodicals, Inc.

  20. Prospective randomized study for optimal insulin therapy in type 2 diabetic patients with secondary failure

    Directory of Open Access Journals (Sweden)

    Tojo Katsuyoshi

    2008-05-01

    Full Text Available Abstract Background The large clinical trials proved that Basal-Bolus (BB insulin therapy was effective in the prevention of diabetic complications and their progression. However, BB therapy needs multiple insulin injections per a day. In this regard, a biphasic insulin analogue needs only twice-daily injections, and is able to correct postprandial hyperglycemia. Therefore it may achieve the blood glucose control as same as that of BB therapy and prevent the diabetic complications including macroangiopathy. Methods In PROBE (Prospective, Randomized, Open, Blinded-Endpoint design, forty-two type 2 diabetic patients (male: 73.8%, median(inter quartile range age: 64.5(56.8~71.0years with secondary failure of sulfonylurea (SU were randomly assigned to BB therapy with a thrice-daily insulin aspart and once-daily basal insulin (BB group or to conventional therapy with a twice-daily biphasic insulin analogue (30 Mix group, and were followed up for 6 months to compare changes in HbA1c, daily glycemic profile, intima-media thickness (IMT of carotid artery, adiponectin levels, amounts of insulin used, and QOL between the two groups. Results After 6 months, HbA1c was significantly reduced in both groups compared to baseline (30 Mix; 9.3(8.1~11.3 → 7.4(6.9~8.7%, p Conclusion Both BB and 30 mix group produced comparable reductions in HbA1c in type 2 diabetic patients with secondary failure. There was no significant change in IMT as an indicator of early atherosclerotic changes between the two groups. The basal-bolus insulin therapy may not be necessarily needed if the type 2 diabetic patients have become secondary failure. Trial registration Current Controlled Trials number, NCT00348231

  1. Accelerated bone ingrowth by local delivery of Zinc from bioactive ...

    African Journals Online (AJOL)

    Background: Synthetic bone graft substitutes such as bioactive glass (BG) material are developed in order to achieve successful bone regeneration. Zn plays an important role in the proper bone growth, development, and maintenance of healthy bones. Aims: This study aims to evaluate in vivo the performance therapy of ...

  2. Bone marrow mesenchymal stem cell therapy in ischemic stroke: mechanisms of action and treatment optimization strategies

    Directory of Open Access Journals (Sweden)

    Guihong Li

    2016-01-01

    Full Text Available Animal and clinical studies have confirmed the therapeutic effect of bone marrow mesenchymal stem cells on cerebral ischemia, but their mechanisms of action remain poorly understood. Here, we summarize the transplantation approaches, directional migration, differentiation, replacement, neural circuit reconstruction, angiogenesis, neurotrophic factor secretion, apoptosis, immunomodulation, multiple mechanisms of action, and optimization strategies for bone marrow mesenchymal stem cells in the treatment of ischemic stroke. We also explore the safety of bone marrow mesenchymal stem cell transplantation and conclude that bone marrow mesenchymal stem cell transplantation is an important direction for future treatment of cerebral ischemia. Determining the optimal timing and dose for the transplantation are important directions for future research.

  3. The Canadian Optimal Therapy of COPD Trial: Design, Organization and Patient Recruitment

    Directory of Open Access Journals (Sweden)

    Shawn D Aaron

    2004-01-01

    Full Text Available BACKGROUND: There are no published studies that have assessed whether adding long-acting beta 2-agonist bronchodilators and/or inhaled steroids to chronic therapy with tiotropium would provide additional clinical benefit to patients with moderate to severe chronic obstructive pulmonary disease (COPD.

  4. Improving the quality, efficiency and robustness of radiation therapy planning and delivery through mathematical optimization

    NARCIS (Netherlands)

    Balvert, Marleen

    2017-01-01

    Radiation therapy is an established cancer treatment which exploits ionizing radiation to harm tumourous cells. As radiation can pass through healthy tissue to reach the tumour, this treatment is particularly useful in the case of deep-seated tumours. However, it inevitably yields exposure of the

  5. Mesenchymal stem cells for regenerative therapy: optimization of cell preparation protocols.

    Science.gov (United States)

    Ikebe, Chiho; Suzuki, Ken

    2014-01-01

    Administration of bone marrow-derived mesenchymal stem cells (MSCs) is an innovative approach for the treatment of a range of diseases that are not curable by current therapies including heart failure. A number of clinical trials have been completed and many others are ongoing; more than 2,000 patients worldwide have been administered with culture-expanded allogeneic or autologous MSCs for the treatment of various diseases, showing feasibility and safety (and some efficacy) of this approach. However, protocols for isolation and expansion of donor MSCs vary widely between these trials, which could affect the efficacy of the therapy. It is therefore important to develop international standards of MSC production, which should be evidence-based, regulatory authority-compliant, of good medical practice grade, cost-effective, and clinically practical, so that this innovative approach becomes an established widely adopted treatment. This review article summarizes protocols to isolate and expand bone marrow-derived MSCs in 47 recent clinical trials of MSC-based therapy, which were published after 2007 onwards and provided sufficient methodological information. Identified issues and possible solutions associated with the MSC production methods, including materials and protocols for isolation and expansion, are discussed with reference to relevant experimental evidence with aim of future clinical success of MSC-based therapy.

  6. Navigating the road towards optimal initial therapy for chronic myeloid leukemia

    Science.gov (United States)

    Okimoto, Ross A.; Van Etten, Richard A.

    2012-01-01

    Purpose of review Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of chronic myeloid leukemia (CML) and are now widely accepted as the initial therapy of choice in this disease, supplanting interferon and allogeneic stem cell transplantation. There are currently three drugs approved by the Food and Drug Administration (FDA) for front-line treatment of CML: imatinib, nilotinib, and dasatinib. A fourth drug, bosutinib, is expected to win FDA approval in 2011. The goal of this review is to summarize the most recent information on initial treatment of CML and to aid clinicians in managing newly diagnosed CML patients. Recent findings Phase III studies comparing imatinib with nilotinib or dasatinib in newly diagnosed CML were published in July 2010, leading to accelerated FDA approval for both of these “second-generation” TKIs for initial therapy of CML. There are significant differences between the agents in terms of frequency and rate of responses, progression-free survival, and side effects. However, the follow-up period on these trials is short, and there are as yet no significant differences in overall survival. Guidelines for monitoring CML patients on TKI therapy have been recently revised. Summary Management of newly diagnosed CML patients in the coming decade will begin to resemble antibiotic treatment of infection, with therapy individualized based on patient risk factors, co-morbidities, and tolerability. In addition, the cost of therapy will emerge as an important consideration as generic imatinib becomes available in 2015. In this context, clinical trials to guide decision-making in newly diagnosed CML patients are needed. PMID:21252655

  7. Navigating the road toward optimal initial therapy for chronic myeloid leukemia.

    Science.gov (United States)

    Okimoto, Ross A; Van Etten, Richard A

    2011-03-01

    Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of chronic myeloid leukemia (CML) and are now widely accepted as the initial therapy of choice in this disease, supplanting interferon and allogeneic stem cell transplantation. There are currently three drugs approved by the US Food and Drug Administration (FDA) for front-line treatment of CML: imatinib, nilotinib, and dasatinib. A fourth drug, bosutinib, may also win FDA approval in 2011. The goal of this review is to summarize the most recent information on initial treatment of CML and to aid clinicians in managing newly diagnosed CML patients. Phase III studies comparing imatinib with nilotinib or dasatinib in newly diagnosed CML were published in June 2010, leading to accelerated FDA approval for both of these 'second-generation' TKIs for initial therapy of CML. There are significant differences between the agents in terms of frequency and rate of responses, progression-free survival, and side-effects. However, the follow-up period on these trials is short, and there are as yet no significant differences in overall survival. Guidelines for monitoring CML patients on TKI therapy have been recently revised. Management of newly diagnosed CML patients in the coming decade will begin to resemble antibiotic treatment of infection, with therapy individualized based on patient risk factors, co-morbidities, and tolerability. In addition, the cost of therapy will emerge as an important consideration as generic imatinib becomes available in 2015. In this context, clinical trials to guide decision-making in newly diagnosed CML patients are needed.

  8. Optimal therapy for patients with hepatocellular carcinoma and resistance or intolerance to sorafenib: challenges and solutions

    Directory of Open Access Journals (Sweden)

    Ray EM

    2017-11-01

    Full Text Available Emily M Ray, Hanna K Sanoff Division of Hematology/Oncology, University of North Carolina, Chapel Hill, NC, USA Abstract: The only US Food and Drug Administration (FDA-approved first-line systemic therapy for hepatocellular carcinoma (HCC is sorafenib; however, resistance or intolerance to sorafenib is unfortunately common. In this review, we briefly describe systemic therapies that can be considered for patients with HCC who show resistance or intolerance to sorafenib. For all patients with HCC who need systemic therapy, we strongly advocate for participation in clinical trials. Cytotoxic chemotherapy plays a minor role in the treatment of advanced HCC, with some data supporting the use of FOLFOX (infusional fluorouracil, leucovorin, and oxaliplatin and GEMOX (gemcitabine-oxaliplatin. Multi-target kinase inhibitors such as lenvantinib and regorafenib have recently met their primary endpoints as first- and second-line therapy, respectively, with regorafenib now representing the only FDA-approved drug for second-line treatment of HCC. Other targeted therapies remain under investigation, but results so far have not significantly changed clinical practice. Immunotherapy is an interesting area of research in the treatment of HCC with preclinical and early clinical data demonstrating exciting results; thus numerous investigational studies are currently focusing on immunotherapy in the treatment of HCC. While systemic treatment options in HCC remain a challenge for providers, in this review, we summarize the current literature and highlight areas of progress with respect to the treatment of patients with HCC and resistance or intolerance to sorafenib. Keywords: liver cancer, chemotherapy, immunotherapy

  9. Optimal structure of particles-based superparamagnetic microrobots: application to MRI guided targeted drug therapy

    Energy Technology Data Exchange (ETDEWEB)

    Mellal, Lyès [INSA Centre Val de Loire, Université d’Orléans, PRISME EA 4229 (France); Belharet, Karim [Hautes Études d’Ingénieur campus Centre, PRISME EA 4229 (France); Folio, David; Ferreira, Antoine, E-mail: antoine.ferreira@insa-cvl.fr, E-mail: antoine.ferreira@ensi-bourges.fr [INSA Centre Val de Loire, Université d’Orléans, PRISME EA 4229 (France)

    2015-02-15

    This paper presents an optimal design strategy for therapeutic magnetic micro carriers (TMMC) guided in real time by a magnetic resonance imaging (MRI) system. As aggregates of TMMCs must be formed to carry the most amount of drug and magnetic actuation capability, different clustering agglomerations could be arranged. Nevertheless, its difficult to predict the hydrodynamic behavior of any arbitrary-shaped object due to the nonlinear hydrodynamic effects. Indeed, the drag effect is related not only to the properties of the bolus but also to its interaction with the fluid viscosity, the free-stream velocity and the container geometry. In this work, we propose a mathematical framework to optimize the TMMC aggregates to improve the steering efficiency in experimental endovascular conditions. The proposed analysis is carried out on various sizes and geometries of microcarrier: spherical, ellipsoid-like, and chain-like of microsphere structures. We analyze the magnetophoretic behavior of such designs to exhibit the optimal configuration. Based on the optimal design of the boluses, experimental investigations were carried out in mm-sized fluidic artery phantoms to demonstrate the steerability of the magnetic bolus using a proof-of-concept setup. The experiments demonstrate the steerability of the magnetic bolus under different velocity, shear-stress, and trajectory constraints with a laminar viscous fluidic environment. Preliminary experiments with a MRI system confirm the feasibility of the steering of these TMMCs in hepatic artery microchannel phantom.

  10. RT-13OPTIMIZING RADIATION THERAPY FOR GLIOBLASTOMA PATIENTS: A COMPARATIVE STUDY OF USING DIFFERENT MRI MODALITIES TO MINIMIZE RADIATION INJURY

    Science.gov (United States)

    Kim, Arin; Lee, Albert Weilin; Lee, Anna; Yanagihara, Theodore; Jani, Ashish; Isaacson, Steven R.; Cheng, Simon K.; Bruce, Jeffrey N.; Sisti, Michael B.; McKhann, Guy M.; Iwamoto, Fabio; Lassman, Andrew; Wang, Tony J.C.

    2014-01-01

    Glioblastoma multiforme is the most common and lethal primary malignant brain tumor and radiation therapy is considered the standard of care in the adjuvant setting. Current radiation treatment planning guidelines recommend FLAIR MRI sequence with a 2 cm margin to encompass the subclinical tumor spread. However, the FLAIR modality extensively visualizes the surrounding edema, possibly leading to unnecessary radiation toxicity to healthy brain tissue. We hypothesize that we can optimize radiation therapy by using alternative MRI modalities or by decreasing clinical tumor volume margins to minimize toxicity without compromising accurate tumor targeting. We retrospectively collected data for 21 patients with pathology confirmed recurrence and created radiation treatment plans using ADC, ADC without FLAIR shine-through (ADCst), DWI, T1, and FLAIR. For the FLAIR both a 1 cm and 2 cm margin was used (FLAIR1 and FLAIR2). Boolean operators were used to calculate the accuracy of targeting tumor recurrence and excessive radiation volume compared to the standard FLAIR2 treatment plan. All MRI modalities had complete coverage of the recurrent tumor and the mean differences in accuracy between the different MRI modalities and FLAIR2 was not significant. However, there was a significant reduction in the excessive radiation volume compared to FLAIR2. ADCst had a 51.3% reduction, DWI 42.3%, T1 42.6%, and FLAIR1 44.6% reduction of excessive radiation volume compared to FLAIR2 (p < 0.05). ADC did not have a significant reduction of excessive radiation volume compared to FLAIR2. Our data support the hypothesis that using MRI modalities other than the standard FLAIR or decreasing the margin by 1cm may optimize radiation therapy for GBM patients by reducing unnecessary radiation dose to healthy brain tissue without compromising accuracy. By using new MRI modalities in radiation treatment planning or modifying clinical tumor volume margins we can decrease radiation toxicity to patients

  11. Inverse planning in the age of digital LINACs: station parameter optimized radiation therapy (SPORT)

    Science.gov (United States)

    Xing, Lei; Li, Ruijiang

    2014-03-01

    The last few years have seen a number of technical and clinical advances which give rise to a need for innovations in dose optimization and delivery strategies. Technically, a new generation of digital linac has become available which offers features such as programmable motion between station parameters and high dose-rate Flattening Filter Free (FFF) beams. Current inverse planning methods are designed for traditional machines and cannot accommodate these features of new generation linacs without compromising either dose conformality and/or delivery efficiency. Furthermore, SBRT is becoming increasingly important, which elevates the need for more efficient delivery, improved dose distribution. Here we will give an overview of our recent work in SPORT designed to harness the digital linacs and highlight the essential components of SPORT. We will summarize the pros and cons of traditional beamlet-based optimization (BBO) and direct aperture optimization (DAO) and introduce a new type of algorithm, compressed sensing (CS)-based inverse planning, that is capable of automatically removing the redundant segments during optimization and providing a plan with high deliverability in the presence of a large number of station control points (potentially non-coplanar, non-isocentric, and even multi-isocenters). We show that CS-approach takes the interplay between planning and delivery into account and allows us to balance the dose optimality and delivery efficiency in a controlled way and, providing a viable framework to address various unmet demands of the new generation linacs. A few specific implementation strategies of SPORT in the forms of fixed-gantry and rotational arc delivery are also presented.

  12. SU-E-T-589: Optimization of Patient Head Angle Position to Spare Hippocampus During the Brain Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Cheon, G; Kang, Y [Radiation Oncology, Seoul St. Mary’s Hospital, Seoul (Korea, Republic of); Kang, S; Kim, T; Kim, D; Suh, T [The Catholic University of Korea, Seoul (Korea, Republic of)

    2015-06-15

    Purpose: Hippocampus is one of the important organs which controls emotions, behaviors, movements the memorizing and learning ability. In the conventional head & neck therapy position, it is difficult to perform the hippocampal-sparing brain radiation therapy. The purpose of this study is to investigate optimal head angle which can save the hippocampal-sparing and organ at risk (OAR) in conformal radiation therapy (CRT), Intensity modulation radiation therapy (IMRT) and helical tomotherapy (HT). Methods: Three types of radiation treatment plans, CRT, IMRT and Tomotherapy plans, were performed for 10 brain tumor patients. The image fusion between CT and MRI data were used in the contour due to the limited delineation of the target and OAR in the CT scan. The optimal condition plan was determined by comparing the dosimetric performance of the each plan with the use of various parameters which include three different techniques (CRT, IMRT, HT) and 4 angle (0, 15, 30, 40 degree). The each treatment plans of three different techniques were compared with the following parameters: conformity index (CI), homogeneity index (HI), target coverage, dose in the OARs, monitor units (MU), beam on time and the normal tissue complication probability (NTCP). Results: HI, CI and target coverage was most excellent in head angle 30 degree among all angle. When compared by modality, target coverage and CI showed good results in IMRT and TOMO than compared to the CRT. HI at the head angle 0 degrees is 1.137±0.17 (CRT), 1.085±0.09 (IMRT) and 1.077±0.06 (HT). HI at the head angle 30 degrees is 1.056±0.08 (CRT), 1.020±0.05 (IMRT) and 1.022±0.07 (HT). Conclusion: The results of our study show that when head angle tilted at 30 degree, target coverage, HI, CI were improved, and the dose delivered to OAR was reduced compared with conventional supine position in brain radiation therapy. This work was supported by the Radiation Technology R&D program (No. 2013M2A2A7043498) and the Mid

  13. An optimized clarithromycin-free 14-day triple therapy for Helicobacter pylori eradication achieves high cure rates in Uruguay.

    Science.gov (United States)

    Dacoll, Cristina; Sánchez-Delgado, Jordi; Balter, Henia; Pazos, Ximena; Di Pace, María; Sandoya, Gabriela; Cohen, Henry; Calvet, Xavier

    Strong acid inhibition increases cure rates with triple therapy and 14-day are more effective than 7-day treatments. The combination of amoxicillin plus metronidazole at full doses has been shown to overcome metronidazole resistance and to achieve good eradication rates even in patients harboring resistant strains. No previous studies have been reported in Latin-America with this optimized triple-therapy scheme. The aim of the present study was to assess the eradication rate and tolerance of a new first-line treatment regimen associating strong acid inhibition, amoxicillin and metronidazole. Patients from the Clínica de Gastroenterología of the Hospital de Clínicas (Montevideo, Uruguay) were included. Hp status was mainly assessed by at least one of the following: histologyor urea breath test (UBT). A 14-day treatment was prescribed comprising esomeprazole 40mg twice a day plus amoxicillin 1g and metronidazole 500mg, both three times a day. H. pylori cure was assessed by UBT. Forty-one patients were enrolled. Mean age was 53.3±13 years and 17.1% of patients were male. Main indications for treatment were: functional dyspepsia (27.5%), gastritis (45%), gastric or duodenal erosions (20%), gastric ulcer (5%) and intestinal metaplasia (2.5%). H. pylori eradication was achieved in 33 of the 37 patients who returned for follow-up. Eradication rates were 80.5% (95% CI: 68.4-92.6) by intention-to-treat (ITT) analysis and 89.2% (95% CI; 79.2-99.2) per protocol (PP). No major side effects were reported; 26 patients (65.8%) complained of mild side effects (nausea, diarrhea and headache). Cure rates of this triple therapy including esomeprazole, amoxicillin and metronidazole were 81% per ITT and the treatment was well tolerated. These optimal results with a simple clarithromycin-free triple therapy are better than described for standard triple therapy but there is still room for improvement to reach the desired target of 90% per ITT. Copyright © 2017 Elsevier España, S

  14. [How to optimize lipid-lowering therapy: do not forget patient's non-compliance].

    Science.gov (United States)

    Radermecker, R P; Scheen, A J

    2010-01-01

    The pharmacological treatment of dyslipidaemia, essentially by statins, should take place in a global strategy of prevention of cardiovascular diseases. Treating a risk factor, asymptomatic by definition, which imposes an early constraint for a potential late benefit, exposes to patient's noncompliance. Besides physician's clinical inertia to initiate and adjust the lipid-lowering therapy in at risk patients, such lack of patient's compliance is one of the key elements that may explain the failure to reach or maintain therapeutic targets, and represents a major pharmacoeconomical concern. This article analyses first the main reasons explaining the poor compliance to lipid-lowering therapy and, then, describes some approaches to improve patient's adherence to medications in order to better prevent cardiovascular diseases.

  15. Optimizing antiemetic therapy in multiple-day and multiple cycles of chemotherapy

    DEFF Research Database (Denmark)

    Ellebaek, E.; Herrstedt, J.

    2008-01-01

    PURPOSE OF REVIEW: Only a few studies have investigated the effect of antiemetic therapy in patients treated with multiple-day or multiple cycles of chemotherapy. The present review will assess the available data, highlight the current recommendations and draw attention towards the remaining...... problems in this field of antiemetic treatment. RECENT FINDINGS: Evidence-based guidelines recommend a combination of a 5-HT3-receptor antagonist and dexamethasone in the prophylaxis of nausea and vomiting in multiple-day cisplatin-based chemotherapy. In patients treated with multiple cycles...... of chemotherapy the addition of a NK1-receptor antagonist aprepitant to standard antiemetic therapy has increased the antiemetic effect, and multiple cycle extension studies have demonstrated that this increment in effect is sustained during multiple cycles of chemotherapy. A recent study indicated...

  16. Seeking optimal management for radioactive iodine therapy-induced adverse effects

    Directory of Open Access Journals (Sweden)

    Andreas Charalambous

    2017-01-01

    Full Text Available Radioactive iodine therapy (RAIT is one of the important treatment modalities in the management of differentiated thyroid cancer (DTC. RAIT with iodine-131 has long been used in the management of DTC for the ablation of residual thyroid or treatment of its metastases. Despite being reasonably safe, radioiodine therapy is not always without side effects. Even relatively low administered activities of RAIT used for remnant ablation have been associated with the more clinically significant side effects of sialadenitis, xerostomia, salivary gland pain and swelling, dry eyes, excessive tearing, or alterations in taste in as many as 25% of patients. Given that there is a lack of comprehensive management of these RAIT-induced adverse effects, this paper explores the use of other nonpharmacological measures and their effectiveness as interventions to minimize salivary gland damage.

  17. Optimal Photosensitizers for Photodynamic Therapy of Infections Should Kill Bacteria but Spare Neutrophils

    OpenAIRE

    Tanaka, Masamitsu; Kinoshita, Manabu; Yoshihara, Yasuo; Shinomiya, Nariyoshi; Seki, Shuhji; Nemoto, Koichi; Hirayama, Takahiro; Dai, Tianhong; Huang, Liyi; Hamblin, Michael R.; Morimoto, Yuji

    2011-01-01

    Photodynamic therapy (PDT) for localized microbial infections exerts its therapeutic effect both by direct bacterial killing and also by the bactericidal effects of host neutrophils stimulated by PDT. Therefore, PDT-induced damage to neutrophils must be minimized, while direct photoinactivation of bacteria is maintained to maximize the therapeutic efficacy of antimicrobial PDT in vivo. However, there has been no study in which the cytocidal effect of PDT on neutrophils was investigated. In th...

  18. Quantitative comparison of optimized nanorods, nanoshells and hollow nanospheres for photothermal therapy

    OpenAIRE

    Kessentini, Sameh; Barchiesi, Dominique

    2012-01-01

    The purpose of this study is to get more efficient gold nanoparticles, for necrosis of cancer cells, in photothermal therapy. Therefore a numerical maximization of the absorption efficiency of a set of nanoparticles (nanorod, nanoshell and hollow nanosphere) is proposed, assuming that all the absorbed light is converted to heat. Two therapeutic cases (shallow and deep cancer) are considered. The numerical tools used in this study are the full Mie theory, the discrete dipole approximation and ...

  19. Interaction between Vestibular Compensation Mechanisms and Vestibular Rehabilitation Therapy: 10 Recommendations for Optimal Functional Recovery

    OpenAIRE

    Lacour, Michel; Bernard-Demanze, Laurence

    2015-01-01

    This review questions the relationships between the plastic events responsible for the recovery of vestibular function after a unilateral vestibular loss (vestibular compensation), which has been well described in animal models in the last decades, and the vestibular rehabilitation (VR) therapy elaborated on a more empirical basis for vestibular loss patients. The main objective is not to propose a catalog of results but to provide clinicians with an understandable view on when and how to per...

  20. Interaction between vestibular compensation mechanisms and vestibular rehabilitation therapy: ten recommendations for optimal functional recovery

    OpenAIRE

    LACOUR eMichel; BERNARD DEMANZE eLaurence

    2015-01-01

    This review questions the relationships between the plastic events responsible for the recovery of vestibular function after a unilateral vestibular loss (vestibular compensation), which has been well described in animal models in the last decades, and the vestibular rehabilitation (VR) therapy elaborated on a more empirical basis for vestibular loss patients. The main objective is not to propose a catalogue of results but to provide clinicians with an understandable view on when and how to p...

  1. Understanding positional cues in salamander limb regeneration: implications for optimizing cell-based regenerative therapies

    Directory of Open Access Journals (Sweden)

    Catherine D. McCusker

    2014-06-01

    Full Text Available Regenerative medicine has reached the point where we are performing clinical trials with stem-cell-derived cell populations in an effort to treat numerous human pathologies. However, many of these efforts have been challenged by the inability of the engrafted populations to properly integrate into the host environment to make a functional biological unit. It is apparent that we must understand the basic biology of tissue integration in order to apply these principles to the development of regenerative therapies in humans. Studying tissue integration in model organisms, where the process of integration between the newly regenerated tissues and the ‘old’ existing structures can be observed and manipulated, can provide valuable insights. Embryonic and adult cells have a memory of their original position, and this positional information can modify surrounding tissues and drive the formation of new structures. In this Review, we discuss the positional interactions that control the ability of grafted cells to integrate into existing tissues during the process of salamander limb regeneration, and discuss how these insights could explain the integration defects observed in current cell-based regenerative therapies. Additionally, we describe potential molecular tools that can be used to manipulate the positional information in grafted cell populations, and to promote the communication of positional cues in the host environment to facilitate the integration of engrafted cells. Lastly, we explain how studying positional information in current cell-based therapies and in regenerating limbs could provide key insights to improve the integration of cell-based regenerative therapies in the future.

  2. Optimizing antiplatelet therapy in acute coronary syndrome and percutaneous coronary intervention.

    Science.gov (United States)

    Faxon, David P

    2012-02-01

    Dual antiplatelet therapy with aspirin and clopidogrel is the standard of care for patients with acute coronary syndrome (ACS) and those undergoing percutaneous coronary intervention (PCI). It is well established that inhibition of platelet aggregation reduces the risk of recurrent thrombotic events and stent thrombosis. However, some patients show a reduced antiplatelet response to standard clopidogrel loading (300 mg) and maintenance (75 mg day(-1)) doses, which has been associated with poorer patient outcomes. Pharmacodynamic and pharmacokinetic studies show that higher-than-standard clopidogrel dosing strategies facilitate more rapid platelet inhibition of a greater intensity as a result of greater plasma concentrations of the clopidogrel active metabolite. Recently completed studies suggest that in patients with ACS undergoing PCI, higher-than-standard clopidogrel dosing regimens provide greater inhibition of platelet function and improved clinical outcomes with a small but significant increase in major bleeding. Newer, more potent antiplatelet agents such as prasugrel and ticagrelor are other alternative strategies that result in more rapid, greater inhibition of platelet function and better outcomes than standard-dose clopidogrel. Whether platelet reactivity-guided therapy or genotyping for cytochrome P450 polymorphisms is useful in managing patients needs to be further defined. Most importantly, early and effective antiplatelet therapy results in the best short- and long-term outcomes for patients with ACS or those undergoing PCI. Copyright © 2011 Wiley-Liss, Inc.

  3. Optimizing physical therapy for ankylosing spondylitis: a case study in a young football player

    Science.gov (United States)

    Tricás-Moreno, José Miguel; Lucha-López, María Orosia; Lucha-López, Ana Carmen; Salavera-Bordás, Carlos; Vidal-Peracho, Concepción

    2016-01-01

    [Purpose] Ankylosing spondylitis is prevalent in men. Modern and expert consensus documents include physical therapy among the strategies for the treatment of ankylosing spondylitis. This study aimed to describe the physical therapy approach in an athlete with ankylosing spondylitis. [Subject and Methods] The patient, refractory to treatment with anti-inflammatory medication, showed pelvic and lumbar pain and joint, muscle, and functional disorders, which were treated with orthopedic joint mobilization, dry needling, exercise, and whole-body hyperthermia. [Results] After the treatment, pain relief, normal joint mobility, improved muscle function, and return to activities of daily living and competitive sporting activities were recorded. [Conclusion] The literature provides evidence for the use of joint mobilization techniques; however, no previous studies have used the same techniques and methods. There is no previous evidence for the use of dry needling in this pathology. Exercise therapy has a higher level of evidence, and guidelines with scientific support were followed. This research confirms the effectiveness of hyperthermia for arthritis. The early stage of ankylosing spondylitis, and the young age, good overall condition, and cooperative attitude of the patient led to positive outcomes. In conclusion, a favorable response that promoted the remission of the disease was observed. PMID:27190490

  4. A systematic approach to determine optimal composition of gel used in radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Yuan-Jen [Department of Management Information Systems, Central Taiwan University of Science and Technology, Taichung, Taiwan (China); Institute of Biomedical Engineering and Material Science, Central Taiwan University of Science and Technology, Taichung, Taiwan (China); Hsieh, Bor-Tsung, E-mail: bthsieh@ctust.edu.tw [Department of Biomedical Imaging and Radiological Sciences, Central Taiwan University of Science and Technology, Taichung, Taiwan (China); Liang, Ji-An [Department of Radiation Oncology, China Medical University Hospital, Taichung, Taiwan (China)

    2011-10-01

    The design of experiment was used to find the optimal composition of N-isopropyl acrylamide (NIPAM) gel. Optical computed tomography was used to scan the polymer gel dosimeter, which was irradiated from 0 to 20 Gy. The study was conducted following a statistical method using a two-level fractional factorial plan involving four variables (gelatin-5% and 6%, NIPAM-3% and 5%, Bis-2.5% and 3%, and THPC-5 and 10 mM). We produced three batches of gels of the same composition to replicate the experiments. Based on the statistical analysis, a regression model was built. The optimal gel composition for the dose range 0-15 Gy with linearity up to 1.000 is as follows: gelatin (5.67%), NIPAM (5%), Bis (2.56%), and THPC (10 mM). The dose response of the NIPAM polymer gel attains stability about 24 h after irradiation and remains stable up to 3 months.

  5. Influence of the atrio-ventricular delay optimization on the intra left ventricular delay in cardiac resynchronization therapy

    Directory of Open Access Journals (Sweden)

    Nienaber Christoph A

    2006-01-01

    Full Text Available Abstract Background Cardiac Resynchronization Therapy (CRT leads to a reduction of left-ventricular dyssynchrony and an acute and sustained hemodynamic improvement in patients with chronic heart failure. Furthermore, an optimized AV-delay leads to an improved myocardial performance in pacemaker patients. The focus of this study is to investigate the acute effect of an optimized AV-delay on parameters of dyssynchrony in CRT patients. Method 11 chronic heart failure patients with CRT who were on stable medication were included in this study. The optimal AV-delay was defined according to the method of Ismer (mitral inflow and trans-oesophageal lead. Dyssynchrony was assessed echocardiographically at three different settings: AVDOPT; AVDOPT-50 ms and AVDOPT+50 ms. Echocardiographic assessment included 2D- and M-mode echo for the assessment of volumes and hemodynamic parameters (CI, SV and LVEF and tissue Doppler echo (strain, strain rate, Tissue Synchronisation Imaging (TSI and myocardial velocities in the basal segments Results The AVDOPT in the VDD mode (atrially triggered was 105.5 ± 38.1 ms and the AVDOPT in the DDD mode (atrially paced was 186.9 ± 52.9 ms. Intra-individually, the highest LVEF was measured at AVDOPT. The LVEF at AVDOPT was significantly higher than in the AVDOPT-50setting (p = 0.03. However, none of the parameters of dyssynchrony changed significantly in the three settings. Conclusion An optimized AV delay in CRT patients acutely leads to an improved systolic left ventricular ejection fraction without improving dyssynchrony.

  6. Convex reformulation of biologically-based multi-criteria intensity-modulated radiation therapy optimization including fractionation effects

    Science.gov (United States)

    Hoffmann, Aswin L.; den Hertog, Dick; Siem, Alex Y. D.; Kaanders, Johannes H. A. M.; Huizenga, Henk

    2008-11-01

    Finding fluence maps for intensity-modulated radiation therapy (IMRT) can be formulated as a multi-criteria optimization problem for which Pareto optimal treatment plans exist. To account for the dose-per-fraction effect of fractionated IMRT, it is desirable to exploit radiobiological treatment plan evaluation criteria based on the linear-quadratic (LQ) cell survival model as a means to balance the radiation benefits and risks in terms of biologic response. Unfortunately, the LQ-model-based radiobiological criteria are nonconvex functions, which make the optimization problem hard to solve. We apply the framework proposed by Romeijn et al (2004 Phys. Med. Biol. 49 1991-2013) to find transformations of LQ-model-based radiobiological functions and establish conditions under which transformed functions result in equivalent convex criteria that do not change the set of Pareto optimal treatment plans. The functions analysed are: the LQ-Poisson-based model for tumour control probability (TCP) with and without inter-patient heterogeneity in radiation sensitivity, the LQ-Poisson-based relative seriality s-model for normal tissue complication probability (NTCP), the equivalent uniform dose (EUD) under the LQ-Poisson model and the fractionation-corrected Probit-based model for NTCP according to Lyman, Kutcher and Burman. These functions differ from those analysed before in that they cannot be decomposed into elementary EUD or generalized-EUD functions. In addition, we show that applying increasing and concave transformations to the convexified functions is beneficial for the piecewise approximation of the Pareto efficient frontier.

  7. Convex reformulation of biologically-based multi-criteria intensity-modulated radiation therapy optimization including fractionation effects.

    Science.gov (United States)

    Hoffmann, Aswin L; den Hertog, Dick; Siem, Alex Y D; Kaanders, Johannes H A M; Huizenga, Henk

    2008-11-21

    Finding fluence maps for intensity-modulated radiation therapy (IMRT) can be formulated as a multi-criteria optimization problem for which Pareto optimal treatment plans exist. To account for the dose-per-fraction effect of fractionated IMRT, it is desirable to exploit radiobiological treatment plan evaluation criteria based on the linear-quadratic (LQ) cell survival model as a means to balance the radiation benefits and risks in terms of biologic response. Unfortunately, the LQ-model-based radiobiological criteria are nonconvex functions, which make the optimization problem hard to solve. We apply the framework proposed by Romeijn et al (2004 Phys. Med. Biol. 49 1991-2013) to find transformations of LQ-model-based radiobiological functions and establish conditions under which transformed functions result in equivalent convex criteria that do not change the set of Pareto optimal treatment plans. The functions analysed are: the LQ-Poisson-based model for tumour control probability (TCP) with and without inter-patient heterogeneity in radiation sensitivity, the LQ-Poisson-based relative seriality s-model for normal tissue complication probability (NTCP), the equivalent uniform dose (EUD) under the LQ-Poisson model and the fractionation-corrected Probit-based model for NTCP according to Lyman, Kutcher and Burman. These functions differ from those analysed before in that they cannot be decomposed into elementary EUD or generalized-EUD functions. In addition, we show that applying increasing and concave transformations to the convexified functions is beneficial for the piecewise approximation of the Pareto efficient frontier.

  8. Field-Specific Intensity-modulated Proton Therapy Optimization Technique for Breast Cancer Patients with Tissue Expanders Containing Metal Ports.

    Science.gov (United States)

    Kirk, Maura; Freedman, Gary; Ostrander, Thorsten; Dong, Lei

    2017-09-18

    This report aims to propose and present an evaluation of a robust pencil beam scanning proton multi-field optimized treatment planning technique for postmastectomy radiation of breast cancer patients with implanted tissue expanders containing an internal metal port. Field-specific split targets were created for optimization to prevent spots from traveling through the metal port, while providing uniform coverage of the target with the use of a multi-field intensity modulated optimization approach. Two beam angles were strategically selected to provide complementary target coverage and plan robustness. The plan was compared with an independently developed photon plan and evaluated for robustness with respect to isocenter shifts, range shifts, and variation of the water-equivalent thickness of the port. The proton plan resulted in clinically acceptable target coverage and dosage to neighboring normal tissues. The D95% coverage was 95.3% in the nominal proton plan, with a worst-case coverage of 90.1% (when considering 0.3 cm isocenter shifts combined with 3.5% range uncertainty), and the coverage varied less than 1% under a hypothetically extreme variation of the port density. The proton plan had improved dose homogeneity compared with the photon plan, and reduced ipsilateral lung and mean heart doses. We demonstrated that a practical, field-specific intensity-modulated proton therapy (IMPT) optimization technique can be used to deal with the challenge of metal port in breast cancer patients with tissue expanders. The resulting proton plan has superior dosimetric characteristics over the best-case scenario photon plan, and is also robust to setup and proton range uncertainties.

  9. The Clinical and Bacteriological Factors for Optimal Levofloxacin-Containing Triple Therapy in Second-Line Helicobacter pylori Eradication

    Science.gov (United States)

    Tai, Wei-Chen; Lee, Chen-Hsiang; Chiou, Shue-Shian; Kuo, Chung-Mou; Kuo, Chung-Huang; Liang, Chih-Ming; Lu, Lung-Sheng; Chiu, Chien-Hua; Wu, Keng-Liang; Chiu, Yi-Chun; Hu, Tsung-Hui; Chuah, Seng-Kee

    2014-01-01

    Quinolone has the disadvantage of easily acquired drug resistance. It is important to prescribe it wisely for a high eradication rate. The current study aimed to determine the clinical and bacteriological factors for optimal levofloxacin-containing triple therapies in second-line H. pylori eradication. We enrolled a total of 158 H. pylori-infected patients who failed H. pylori eradication using the 7-day standard triple therapy (proton-pump inhibitor [PPI] twice daily, 500 mg clarithromycin twice daily, and 1 g amoxicillin twice daily). They were prescribed with either a 10-day (group A) or 14-day (group B) levofloxacin-containing triple therapy group (levofloxacin 500 mg once daily, amoxicillin 1 g twice daily, and esomeprazole 40 mg twice daily for 10 days) by their clinicians. Follow-up studies to assess treatment responses were carried out 8 weeks later. The eradication rates attained by groups A and B were 73.6% (95% confidence interval [CI] = 63.9–85.3%) and 90.5% (95% CI = 84.5–98.1%), respectively in the per protocol analysis (P = 0.008 in the per protocol analysis) and 67.1% (95% CI = 56.6–78.5%) and 84.8% (95% CI = 76.8–93.4%), respectively, in the intention-to-treat analysis (P = 0.009). The subgroup analysis revealed that H. pylori eradication rates for group A patients with levofloxacin-susceptible strains were 92.9% (13/14) but it dropped to 12.5% (1/8) when levofloxacin-resistant strains existed. H. pylori was eradicated among all the group B patients with levofloxacin-susceptible strains, but only half of patients with levofloxacin-resistant strains were successfully eradicated. In conclusion, this study confirms the effectiveness of 14-day treatment. Importantly, the results imply that 10-day treatment duration should be optimal if a culture can be performed to confirm the existence of susceptible strains. The duration of H. pylori eradication and levofloxacin resistance were the influencing factors for successful

  10. The clinical and bacteriological factors for optimal levofloxacin-containing triple therapy in second-line Helicobacter pylori eradication.

    Directory of Open Access Journals (Sweden)

    Wei-Chen Tai

    Full Text Available Quinolone has the disadvantage of easily acquired drug resistance. It is important to prescribe it wisely for a high eradication rate. The current study aimed to determine the clinical and bacteriological factors for optimal levofloxacin-containing triple therapies in second-line H. pylori eradication. We enrolled a total of 158 H. pylori-infected patients who failed H. pylori eradication using the 7-day standard triple therapy (proton-pump inhibitor [PPI] twice daily, 500 mg clarithromycin twice daily, and 1 g amoxicillin twice daily. They were prescribed with either a 10-day (group A or 14-day (group B levofloxacin-containing triple therapy group (levofloxacin 500 mg once daily, amoxicillin 1 g twice daily, and esomeprazole 40 mg twice daily for 10 days by their clinicians. Follow-up studies to assess treatment responses were carried out 8 weeks later. The eradication rates attained by groups A and B were 73.6% (95% confidence interval [CI]  = 63.9-85.3% and 90.5% (95% CI = 84.5-98.1%, respectively in the per protocol analysis (P = 0.008 in the per protocol analysis and 67.1% (95% CI = 56.6-78.5% and 84.8% (95% CI = 76.8-93.4%, respectively, in the intention-to-treat analysis (P = 0.009. The subgroup analysis revealed that H. pylori eradication rates for group A patients with levofloxacin-susceptible strains were 92.9% (13/14 but it dropped to 12.5% (1/8 when levofloxacin-resistant strains existed. H. pylori was eradicated among all the group B patients with levofloxacin-susceptible strains, but only half of patients with levofloxacin-resistant strains were successfully eradicated. In conclusion, this study confirms the effectiveness of 14-day treatment. Importantly, the results imply that 10-day treatment duration should be optimal if a culture can be performed to confirm the existence of susceptible strains. The duration of H. pylori eradication and levofloxacin resistance were the influencing factors for successful treatment. This study

  11. The main factors influencing canine demodicosis treatment outcome and determination of optimal therapy.

    Science.gov (United States)

    Arsenović, Milica; Pezo, Lato; Vasić, Nebojša; Ćirić, Rodoljub; Stefanović, Milan

    2015-07-01

    The main idea of this research was to evaluate the efficacy of canine demodicosis conventional treatments using mathematical analyses. All available papers published between 1980 and 2014 were used in this study. One hundred six clinical trials enrolling 3414 cases of generalized demodicosis in dogs are studied. Dogs entered in the analysis were only the ones in which the disease occurred naturally, excluding the studies in which transplantation of Demodex canis mites was done from other animals. In conventional acaricide treatments, sorted according to active substances (moxidectin, amitraz, doramectin, ivermectin, and milbemycin oxime), the way of application (spot-on, dips, orally, or subcutaneous), concentration, and interval of application were used as input parameters in mathematical modeling. Data of interest were the treatment outcome, the number of dogs that went into remission, the number of animals not responding to treatment microscopically, the average duration of therapy, the follow-up period, the number of patients with disease recurrence, the number of adverse effects, and the number of animals with side effects. Dogs lost to follow-up or when the treatment was discontinued, due to various reasons not in connection with the therapy protocol, were not considered. Statistical and mathematical analyses were applied for prediction of the drugs' effectiveness. Developed mathematical models showed satisfactorily r (2), higher than 0.87. Good evidence for recommending the use of milbemycin oxime PO (0.5 mg/kg, daily) and moxidectin spot-on (Advocate®, Bayer) weekly is found. A bit less effective therapies were based on ivermectin PO (0.5 mg/kg, daily), moxidectin PO (0.35 mg/kg, daily), and amitraz dips (0.05 % solution, weekly), respectively. It is important to keep in mind that Advocate® is recommended by the manufacturer for use in milder cases.

  12. Bisphosphonate Treatment in Osteoporosis: Optimal Duration of Therapy and the Incorporation of a Drug Holiday.

    Science.gov (United States)

    Villa, Jordan C; Gianakos, Arianna; Lane, Joseph M

    2016-02-01

    Bisphosphonates are the most widely used treatment for osteoporosis. They accumulate in the bone for years, and therefore, their inhibitory effects on osteoclasts may persist after drug discontinuation. The ideal duration of therapy remains controversial. The purpose of this study is to review the literature to determine the (1) indications for drug holiday, (2) the duration of drug holiday, (3) the evaluation during drug holiday, and (4) the proper treatment and maintenance after drug holiday. A review of two electronic databases (PubMed/MEDLINE and EMBASE) was conducted using the term "(Drug holiday)," in January 29, 2015. Inclusion criteria were as follows: (1) clinical trials and case control, (2) human studies, (3) published in a peer-review journal, and (4) written in English. Exclusion criteria were as follows: (1) case reports, (2) case series, and (3) in vitro studies. The literature supports a therapeutic pause after 3-5 years of bisphosphonate treatment in patients with minor bone deficiencies and no recent fragility fracture (low risk) and in patients with moderate bone deficiencies and/or recent fragility fracture (moderate risk). In these patients, a bone health reevaluation is recommended every 1-3 years. Patients with high fracture risk should be maintained on bisphosphonate therapy without drug holiday. The duration and length of drug holiday should be individualized for each patient. Evaluation should be based on serial bone mass measurements, bone turnover rates, and fracture history evaluation. If after drug therapy, assessments show an increased risk of fracture, the patient may benefit from initiating another treatment. Raloxifene, teriparatide, or denosumab are available options.

  13. Optimizing Radiation Therapy Quality Assurance in Clinical Trials: A TROG 08.03 RAVES Substudy

    Energy Technology Data Exchange (ETDEWEB)

    Trada, Yuvnik, E-mail: yuvnik@gmail.com [Calvary Mater Newcastle, Waratah, New South Wales (Australia); Kneebone, Andrew [Royal North Shore Hospital, St Lenoards, New South Wales (Australia); Paneghel, Andrea [Peter MacCallum Cancer Centre, Melbourne, Victoria (Australia); Pearse, Maria [Auckland Hospital, Auckland (New Zealand); Sidhom, Mark [Liverpool Hospital, Liverpool, New South Wales (Australia); Tang, Colin [Sir Charles Gairdner Hospital, Nedlands, Western Australia (Australia); Wiltshire, Kirsty; Haworth, Annette [Peter MacCallum Cancer Centre, Melbourne, Victoria (Australia); Fraser-Browne, Carol [Auckland Hospital, Auckland (New Zealand); Martin, Jarad [Calvary Mater Newcastle, Waratah, New South Wales (Australia)

    2015-12-01

    Purpose: To explore site- and clinician-level factors associated with protocol violations requiring real-time-review (RTR) resubmission in a multicenter clinical trial to help tailor future quality assurance (QA) protocols. Methods and Materials: RAVES (Radiation Therapy–Adjuvant vs Early Salvage) (Trans-Tasman Radiation Oncology Group 08.03) is a randomized trial comparing adjuvant with early salvage radiation therapy in men with positive surgical margins or pT3 disease after prostatectomy. Quality assurance in RAVES required each clinician and site to submit a credentialing dummy run (DR) and for each patient's radiation therapy plan to undergo external RTR before treatment. Prospectively defined major violations from trial protocol required remedy and resubmission. Site and clinician factors associated with RTR resubmission were examined using hierarchical modeling. Results: Data were collected from 171 consecutive patients, treated by 46 clinicians at 32 hospitals. There were 47 RTR resubmissions (27%) due to 65 major violations. The relative rate of resubmission decreased by 29% per year as the study progressed (odds ratio OR. 0.71, P=.02). The majority of resubmissions were due to contouring violations (39 of 65) and dosimetric violations (22 of 65). For each additional patient accrued, significant decreases in RTR resubmission were seen at both clinician level (OR 0.75, P=.02) and site level (OR 0.72, P=.01). The rate of resubmission due to dosimetric violations was only 1.6% after the first 5 patients. Use of IMRT was associated with lower rates of resubmission compared with 3-dimensional conformal radiation therapy (OR 0.38, P=.05). Conclusion: Several low- and high-risk factors that may assist with tailoring future clinical trial QA were identified. Because the real-time resubmission rate was largely independent of the credentialing exercise, some form of RTR QA is recommended. The greatest benefit from QA was derived early in trial activation

  14. Early detection, aggressive therapy: optimizing the management of feline mammary masses.

    Science.gov (United States)

    Giménez, Fernanda; Hecht, Silke; Craig, Linden E; Legendre, Alfred M

    2010-03-01

    This article reviews the incidence, etiology, diagnosis, treatment and prognosis of mammary tumors in cats. Approximately 80% of feline mammary masses are malignant, with adenocarcinoma being the most common tumor type. Early diagnosis is, therefore, essential to improve the prognosis and quality of life of affected cats. Surgery is the most widely used treatment for malignant tumors. However, as mammary tumors are often advanced and metastasis has already occurred by the time of diagnosis, surgery routinely does not provide a cure. Ovariohysterectomy or hormonal therapy are the treatments of choice for fibroadenomatous hyperplasia (the most common benign mass) and usually lead to a successful outcome. Copyright 2010. Published by Elsevier Ltd.

  15. Optimizing topical antifungal therapy for superficial cutaneous fungal infections: focus on topical naftifine for cutaneous dermatophytosis.

    Science.gov (United States)

    Del Rosso, James Q; Kircik, Leon H

    2013-11-01

    Superficial cutaneous fungal infections (SCFIs) are commonly encountered in clinical practice in the United States, and comprise infections of the skin by dermatophytes and yeasts. The most common organisms causing SCFI are dermatophytes, especially Trichophyton spp. With the exception of onchomycosis and tinea capitis, most cases of SCFIs are amenable to properly selected topical antifungal therapy used over an adequate period of time. A variety of topical antifungal agents are available for the treatment of SCFIs, and they encompass a few major chemical classes: the polyenes (ie, nystatin), imidazoles (ie, ketoconazole, econazole, oxiconazole, etc), allylamines (ie, naftifine, terbinafine), benzylamines (ie, butenafine), and hydroxypyridones (ie, ciclopirox). The 2 major classes that represent the majority of available topical antifungal agents are the azoles and the allylamines. Overall, the allylamines are superior to the azoles in activity against dermatophytes, although both are clinically effective. The reverse is true against yeasts such as Candida spp and Malassezia spp, although topical allylamines have proven to be efficacious in some cases of tinea versicolor and cutaneous candidiasis. Naftifine, a topical allylamine, is fungicidal in vitro against a wide spectrum of dermatophyte fungi and has been shown to be highly effective against a variety of cutaneous dermatophyte infections. Rapid onset of clinical activity and favorable data on sustained clearance of infection have been documented with naftifine. The more recent addition of naftifine 2% cream has expanded the armamentarium, with data supporting a clinically relevant therapeutic reservoir effect after completion of therapy.

  16. I-SWOT as instrument to individually optimize therapy of thoracoabdominal aortic aneurysms: Effective, norm-compliant and meeting the needs.

    Science.gov (United States)

    Sachweh, A; von Kodolitsch, Y; Kölbel, T; Larena-Avellaneda, A; Wipper, S; Bernhardt, A M; Girdauskas, E; Detter, C; Reichenspurner, H; Blankart, C R; Debus, E S

    2017-01-01

    Guidelines summarize medical evidence, they identify the most efficient therapy under study conditions and recommend this therapy for use. The physician now has the challenge to translate a therapy that is efficient under laboratory conditions to a patient who is an individual person. To accomplish this task the physician has to make sure that (I) the ideal typical therapy is applicable and effective in this individual patient taking the special features into consideration, that (II) therapy is compliant with the norm including guidelines, laws and ethical requirements (conformity) and that (III) the therapy meets the patient's needs. How can physicians together with the patients translate the medical evidence into an individually optimized therapy? At the German Aortic Center in Hamburg we use I‑SWOT as an instrument to identify such individually optimized therapy. With I‑SWOT, we present an instrument with which we have developed an (I) efficient, (II) conform and (III) needs-oriented therapeutic strategy for individual patients. I-SWOT cross-tabulates strengths (S) and weaknesses (W) related to therapy with opportunities (O) and threats (T) related to individual patients. This I‑SWOT matrix identifies four fundamental types of strategy, which comprise "SO" maximizing strengths and opportunities, "WT" minimizing weaknesses and threats, "WO" minimizing weaknesses and maximizing opportunities and "ST" maximizing strengths and minimizing threats. We discuss the case of a patient with asymptomatic thoracoabdominal aneurysm to show how I‑SWOT is used to identify an individually optimized therapy strategy.

  17. The integration of DVH-based planning aspects into a convex intensity modulated radiation therapy optimization framework.

    Science.gov (United States)

    Kratt, Karin; Scherrer, Alexander

    2009-06-21

    The formulation of intensity modulated radiation therapy (IMRT) planning aspects frequently uses the dose-volume histogram (DVH), whereas plan computations often happen in the more desirable convex IMRT optimization framework. Inspired by a recent publication of Zinchenko et al (2008 Phys. Med. Biol. 53 3231-50), this work addresses the integration of DVH-based planning aspects into this framework from a general point of view. It first provides the basic mathematical requirements on the evaluation functions in order to support such an incorporation. Then it introduces the condition number as a description for how precisely DVH-based planning aspects can be reformulated in terms of evaluation functions. Exemplary numerical studies for the generalized equivalent uniform dose and a physical constraint function show the influence of function parameter values and DVH approximation on the condition number. The work concludes by formulating the aspects that should be taken into account for an appropriate integration of DVH-based planning aspects.

  18. Simultaneous delivery time and aperture shape optimization for the volumetric-modulated arc therapy (VMAT) treatment planning problem.

    Science.gov (United States)

    Mahnam, Mehdi; Gendreau, Michel; Lahrichi, Nadia; Rousseau, Louis-Martin

    2017-06-14

    In this paper, we propose a novel heuristic algorithm for the volumetric-modulated arc therapy treatment planning problem, optimizing the trade-off between delivery time and treatment quality. We present a new mixed integer programming model in which the multi-leaf collimator leaf positions, gantry speed, and dose rate are determined simultaneously. Our heuristic is based on column generation; the aperture configuration is modeled in the columns and the dose distribution and time restriction in the rows. To reduce the number of voxels and increase the efficiency of the master model, we aggregate similar voxels using a clustering technique. The efficiency of the algorithm and the treatment quality are evaluated on a benchmark clinical prostate cancer case. The computational results show that a high-quality treatment is achievable using a four-thread CPU. Finally, we analyze the effects of the various parameters and two leaf-motion strategies.

  19. Simultaneous delivery time and aperture shape optimization for the volumetric-modulated arc therapy (VMAT) treatment planning problem

    Science.gov (United States)

    Mahnam, Mehdi; Gendreau, Michel; Lahrichi, Nadia; Rousseau, Louis-Martin

    2017-07-01

    In this paper, we propose a novel heuristic algorithm for the volumetric-modulated arc therapy treatment planning problem, optimizing the trade-off between delivery time and treatment quality. We present a new mixed integer programming model in which the multi-leaf collimator leaf positions, gantry speed, and dose rate are determined simultaneously. Our heuristic is based on column generation; the aperture configuration is modeled in the columns and the dose distribution and time restriction in the rows. To reduce the number of voxels and increase the efficiency of the master model, we aggregate similar voxels using a clustering technique. The efficiency of the algorithm and the treatment quality are evaluated on a benchmark clinical prostate cancer case. The computational results show that a high-quality treatment is achievable using a four-thread CPU. Finally, we analyze the effects of the various parameters and two leaf-motion strategies.

  20. Guaranteed epsilon-optimal treatment plans with minimum number of beams for stereotactic body radiation therapy

    CERN Document Server

    Yarmand, Hamed

    2013-01-01

    Stereotactic body radiotherapy (SBRT) is characterized by delivering a high amount of dose in a short period of time. In SBRT the dose is delivered using open fields (e.g., beam's-eye-view) known as "apertures". Mathematical methods can be used for optimizing treatment planning for delivery of sufficient dose to the cancerous cells while keeping the dose to surrounding organs at risk (OARs) minimal. Two important elements of a treatment plan are quality and delivery time. Quality of a plan is measured based on the target coverage and dose to OARs. Delivery time heavily depends on the number of beams used in the plan since the setup times for different beam directions constitute a large portion of the delivery time. Therefore the ideal plan, in which all potential beams can be used simultaneously, will be associated with a long impractical delivery time. We use the dose to OARs in the ideal plan to find the plan with the minimum number of beams which is guaranteed to be epsilon-optimal (i.e., a predetermined m...

  1. (AJST) BIOACTIVITIES OF CANDLEWOOD, ZANTHOXYLUM ...

    African Journals Online (AJOL)

    ABSTRACT:- Bioactivities of candlewood, Zanthoxylum xanthoxyloides (Lam.) solvent extracts on control of Sitophilus zeamais Mots. (Coleoptera: Curculionidae) and Callosobruchus maculatus F. (Coleoptera: Bruchidae) were assessed on maize and cowpea respectively. Of the four solvent extracts investigated, methanol ...

  2. New echocardiographic techniques in optimal patient selection for cardiac resynchronization therapy in the treatment of chronic heart failure

    Directory of Open Access Journals (Sweden)

    Petrović Milan

    2009-01-01

    Full Text Available Cardiac resynchronization therapy (CRT has important role in the contemporary treatment of heart failure, systolic dysfunction and mechanical disynchrony. Classical indications for CRT are severe heart failure (NYHA class III or IV, a broad QRS (more than 120 ms and left ejection fraction less than 35% despite optimal medical therapy. Several have studies demonstrated the important role of echocardiography in patient selection for CRT, follow up and estimation of CRT effects, as well as the optimization of biventricular pacemaker. Basically, there are three types of cardiac asynchrony: interventricular asynchrony, between the right and left ventricle, intraventricular asynchrony, between the myocardial segments within the left ventricle and atrioventricular asynchrony, between the atria and ventricles. Although many echocardiographic techniques are used in patient selection for CRT, no ideal approach has yet been found. There are several techniques and parameters used in the assessment of myocardial asynchrony: two dimensional (2D echocardiography, one dimensional echocardiography (M-mode, Doppler echocardiography, different modalities of tissue Doppler including Colour Coded Tissue Doppler Imaging - TDI, measurements of local tissue deformation indices (strain and strain rate, speckle tracking, 3D echocardiography, semiquantitative assessment of myocardial border, vector velocity imaging. Each of these techniques has advantages and limitations. A special accent in this revue is on the consensus report from the American Society of Echocardiography Dyssynchrony Writing group. According to this consensus report color coded tissue Doppler is the most appropriate technique for myocardial asynchrony estimation and patients selection for CRT. The same group recommended that definitive decision for CFT implantation should not be based only on echocardiographic analysis, but rather on the whole clinical aspect of the patient.

  3. Novel devices for individualized controlled inhalation can optimize aerosol therapy in efficacy, patient care and power of clinical trials

    Directory of Open Access Journals (Sweden)

    Fischer A

    2009-12-01

    Full Text Available Abstract In the treatment of pulmonary diseases the inhalation of aerosols plays a key role - it is the preferred route of drug delivery in asthma, chronic obstructive pulmonary disease (COPD and cystic fibrosis. But, in contrast to oral and intravenous administration drug delivery to the lungs is controlled by additional parameters. Beside its pharmacology the active agent is furthermore determined by its aerosol characteristics as particle diameter, particle density, hygroscopicity and electrical charge. The patient related factors like age and stage of pulmonary disease will be additionally affected by the individual breathing pattern and morphometry of the lower airways. A number of these parameters with essential impact on the pulmonary drug deposition can be influenced by the performance of the inhalation system. Therefore, the optimization of nebulisation technology was a major part of aerosol science in the last decade. At this time the control of inspiration volume and air flow as well as the administration of a defined aerosol bolus was in the main focus. Up to date a more efficient and a more targeted pulmonary drug deposition - e.g., in the alveoli - will be provided by novel devices which also allow shorter treatment times and a better reproducibility of the administered lung doses. By such means of precise dosing and drug targeting the efficacy of inhalation therapy can be upgraded, e.g., the continuous inhalation of budesonide in asthma. From a patients' perspective an optimized inhalation manoeuvre means less side effects, e.g., in cystic fibrosis therapy the reduced oropharyngeal tobramycin exposure causes fewer bronchial irritations. Respecting to shorter treatment times also, this result in an improved quality of life and compliance. For clinical trials the scaling down of dose variability in combination with enhanced pulmonary deposition reduces the number of patients to be included and the requirement of pharmaceutical

  4. Nutrigenomics of Neuradaptogen Amino-Acid-Therapy and Neurometabolic Optimizers: Overcoming carbohydrate bingeing and overeating through neurometabolic mechanisms

    Directory of Open Access Journals (Sweden)

    Eric R. Braverman

    2011-09-01

    Full Text Available Despite progress that has been made in the treatment of obesity, the epidemic continues to rise worldwide. While pharmacological treatment of obesity may be effective, medications may have significant side effects and can be potentially fatal. This review will provide significant evidence to substantiate the existence of Reward Deficiency Syndrome in Obesity and the role of catecholaminergic pathways in aberrant substance seeking behavior, in particular cravings for carbohydrates. The genetic basis for generalized craving behavior will be established. Evidence to support the augmentation of precursor amino acid therapy and enkephalinase, MOA and COMT inhibition leading to enhanced levels of neurotransmitters: serotonin, enkephalins, GABA and dopamine/norepinephrine as well increasing insulin sensitivity (affecting dopamineFunctional Foods in Health and Disease: 9:310-378neuronal synthesis regulation through the use of certain neurometabolic optimizers will also be provided. This review article cites many published studies to support a conceptual paradigm shift towards the use of this proposed nutrigenomic formula. The analysis and research preceding this formulation is outlined. This formulation has a generalized anti-craving effect and can inhibit carbohydrate bingeing, inducing significant healthy fat loss and prevention of relapse. This is the first time that components of this formula have been combined, at the dosage levels indicated with the goal of promoting successful and sustainable body recomposition. We are encouraging other laboratories to further evaluate Neuroadtagen Amino-Acid Therapy (NAAT/Nurometabolic optimizers as a putative anti-obesity complex in larger controlled blinded studies and await interpretation of must these needed studies.

  5. Optimal duration of therapy in the recovery period of vestibular diseases

    Directory of Open Access Journals (Sweden)

    M. V. Zamergrad

    2014-01-01

    Full Text Available Dizziness is a common symptom in neurological and general medical practice. In most cases it is caused by diseases of the central or peripheral vestibular system. The most common vestibular system diseases include benign paroxysmal postural vertigo, dizziness, Meniere's disease, vestibular neuronitis, and cerebrovascular diseases. One of the main treatments for the diseases accompanied by dizziness is vestibular rehabilitation that is a complex of exercises, the goal of which is to stimulate vestibular compensation. Adequate vestibular compensation allows a patient to get rid of dizziness and unsteadiness even though vestibular system injury is irreversible. Some medications are able to enhance the efficiency of vestibular rehabilitation. At the same time, the optimal duration of treatment for the most common vestibular disorders has not beenadequately explored. The paper gives the results of an observational program, whose purpose was to determine the optimal duration of vestibular rehabilitation in combination with the use of tanakan in patients with non-progressive unilateral peripheral vestibular disorder.Patients and methods. Data on 46 patients aged 19 to 70 years who underwent vestibular rehabilitation and took tanakan for vertigo caused by vestibular neuronitis (n = 44, labyrinthitis (n =1, or Ramsay Hunt syndrome (n = 1 were analyzed. All the patients were examined four times. The symptoms were recorded and the histories of disease were considered. The degree of vestibular disorders, including vertigo, was assessed when collecting complaints. The symptoms of vertigo were objectivized using its vertigo rating scale and five-point subjective rating scale for vertigo. All the patients underwent standard somatic and neurological examinations and videonystagmography. During the first visit after diagnosis, vestibular exercises were chosen for the patients and tanakan was used in a dose of 40 mg thrice daily to accelerate

  6. Development and optimization of targeted radionuclide tumor therapy using folate based radiopharmaceuticals

    CERN Document Server

    Reber, Josefine Astrid

    The folate receptor (FR) has been used for a quarter of a century as a tumor-associated target for selective delivery of drugs and imaging agents to cancer cells. While several folic acid radioconjugates have been successfully employed for imaging purposes in (pre)clinical studies, a therapeutic application of folic acid radioconjugates has not yet reached the critical stage which would allow a clinical translation. Due to a substantial expression of the FR in the proximal tubule cells, radiofolates accumulate in the kidneys which are at risk of damage by particle-radiation. To improve this situation, we aimed to develop and evaluate strategies for the performance of FR-targeted radionuclide therapy by decreasing the renal uptake of radiofolates and thereby reducing potential nephrotoxic effects. Two different strategies were investigated. First, the combination of radiofolates with chemotherapeutic agents such as pemetrexed (PMX) and 5-fluorouracil (5-FU) and secondly, an approach based on radioiodinated fol...

  7. Precision Medicine in Pediatric Oncology: Translating Genomic Discoveries into Optimized Therapies.

    Science.gov (United States)

    Tran, Thai Hoa; Shah, Avanthi Tayi; Loh, Mignon L

    2017-09-15

    Survival of children with cancers has dramatically improved over the past several decades. This success has been achieved through improvement of combined modalities in treatment approaches, intensification of cytotoxic chemotherapy for those with high-risk disease, and refinement of risk stratification incorporating novel biologic markers in addition to traditional clinical and histologic features. Advances in cancer genomics have shed important mechanistic insights on disease biology and have identified "driver" genomic alterations, aberrant activation of signaling pathways, and epigenetic modifiers that can be targeted by novel agents. Thus, the recently described genomic and epigenetic landscapes of many childhood cancers have expanded the paradigm of precision medicine in the hopes of improving outcomes while minimizing toxicities. In this review, we will discuss the biologic rationale for molecularly targeted therapies in genomically defined subsets of pediatric leukemias, solid tumors, and brain tumors. Clin Cancer Res; 23(18); 5329-38. ©2017 AACR . ©2017 American Association for Cancer Research.

  8. Does supplemental photodynamic therapy optimize the disinfection of bacteria and endotoxins in one-visit and two-visit root canal therapy? A randomized clinical trial.

    Science.gov (United States)

    Rabello, Diego G D; Corazza, Bruna J M; Ferreira, Luciana L; Santamaria, Mauro P; Gomes, Ana P M; Martinho, Frederico C

    2017-09-01

    To evaluate the effectiveness of supplemental photodynamic therapy (PDT) in optimizing the removal of bacteria and endotoxins from primarily infected root canals after one-visit and two-visit treatments. Twenty-four primarily infected root canals with apical periodontitis were selected and randomly divided into one-visit (n=12) and two-visit treatment groups (n=12). Chemo-mechanical preparation (CMP) was performed by using the single-file reciprocating technique+2.5% NaOCL and a final rinse with 17% EDTA. The photosensitizer agent (methylene blue 0.1mg/mL) was applied to root canals for 60s before application of laser with a potency of 60mW and energy density of 129J/cm2 for 120s after CMP in the one-visit treatment and after 14-day inter-appointment medication with Ca(OH)2+Saline solution (SSL) in the two-visit treatment. Samples were collected before and after root canal procedures. Endotoxins were quantified by chromogenic limulus amebocyte lysate assay. Culture techniques were used to determine bacterial colony-forming unit counts. Bacteria and endotoxins were detected in 100% of the initial samples, with median values of 1.97×105 CFU/mL and 24.983EU/mL, respectively. The CMP using single-file reciprocating technique was effective in the reduction of bacteria and endotoxins (All, p0.05). In the two-visit group, after 14days of inter-appointment medication with Ca(OH)2, a significant reduction in the median levels of endotoxins was found in comparison to CMP alone (from 1.041 to 0.094EU/mL) (pendotoxins (p>0.05). The photodynamic therapy optimized the disinfection of bacteria from root canals in one-visit but not for two visit treatment modality with the accomplishment of calcium hydroxide medication. Despite the type of treatment, the supplemental PDT was not effective against endotoxins. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Optimizing MIBG therapy of neuroendocrine tumors: preclinical evidence of dose maximization and synergy

    Energy Technology Data Exchange (ETDEWEB)

    Mairs, Rob J. [Department of Radiation Oncology, University of Glasgow, Glasgow (United Kingdom)], E-mail: r.mairs@beatson.gla.ac.uk; Boyd, Marie [Department of Radiation Oncology, University of Glasgow, Glasgow (United Kingdom)

    2008-08-15

    [{sup 131}I]meta-Iodobenzylguanidine ([{sup 131}I]MIBG) has been used for the therapy of tumors of neuroectodermal origin since the 1980s. Its role in the management of these malignancies remains controversial because of the large variation in response rates. Appreciation of the mode of conveyance of [{sup 131}I]MIBG via the noradrenaline transporter into malignant cells and of factors that influence the activity of the uptake mechanism has indicated various ways in which the effectiveness of this type of targeted radiotherapy may be improved. Experimental observations indicate that radiolabeling of MIBG to high specific activity reduced the amount of cold competitor, thereby increasing tumor dose and minimizing pressor effects. We observed supra-additive tumor cell kill and inhibition of tumor growth following combined topotecan and [{sup 131}I]MIBG treatment. The improved efficacy is related to topotecan's increased disruption of DNA repair. Radiation damage to targeted tumors may also be enhanced by the use of the {alpha}-particle emitter [{sup 211}At]astatine rather than {sup 131}I as radiolabel. Furthermore, recent experimental findings indicate that [{sup 123}I]MIBG may have therapeutic potential over and above its utility as an imaging agent. It has recently been demonstrated that potent cytotoxic bystander effects were induced by the intracellular concentration of [{sup 131}I]MIBG, [{sup 123}I]MIBG or meta-[{sup 211}At]astatobenzylguanidine. Identification of the nature of bystander factors could be exploited to maximize the specificity and potency of MIBG-targeted radiotherapy. By employing a range of strategies, there are good prospects for the improvement of the [{sup 131}I]MIBG therapy of neuroectodermal tumors.

  10. Optimal management of antiplatelet therapy and proton pump inhibition following percutaneous coronary intervention.

    Science.gov (United States)

    Thomas, Mark R; Storey, Robert F

    2012-02-01

    Dual antiplatelet therapy (aspirin and a P2Y(12) antagonist) is required after the insertion of a coronary artery stent. If the stent has been inserted in the context of an acute coronary syndrome (ACS), then clopidogrel or a high-potency P2Y(12) antagonist such as prasugrel or ticagrelor should be considered. Current indications for the use of prasugrel in this situation include ST elevation, diabetes, or previous stent thrombosis on clopidogrel therapy. If the stent has been inserted electively for stable ischemic heart disease, then the patient should normally receive clopidogrel. Next, it is important to consider the patient's bleeding risk. The CRUSADE score can be used to determine the likelihood of a subsequent gastrointestinal (GI) bleed. For patients treated with aspirin and clopidogrel who are at high risk of a GI bleed, the current evidence suggests that a proton pump inhibitor (PPI) is the most effective way to reduce this risk. There is evidence that omeprazole may attenuate the pharmacodynamic effect of clopidogrel and, therefore, it would be reasonable to use an alternative PPI that has less risk of negative pharmacokinetic and pharmacodynamic interaction, such as pantoprazole. If a patient is at moderate or low risk of bleeding, then a PPI should be avoided in combination with clopidogrel as the risk of negative interaction is greater than the risk of GI bleeding. There is no substantive evidence that PPIs attenuate the therapeutic effect of prasugrel or ticagrelor; therefore, patients at moderate or high risk of GI bleeding should be offered a PPI.

  11. [The optimal blood glucose target in critically ill patient: comparison of two intensive insulin therapy protocols].

    Science.gov (United States)

    Raurell Torredà, Marta; del Llano Serrano, César; Almirall Solsona, Dolors; Catalan Ibars, Rosa María; Nicolás Arfelis, José María

    2014-03-04

    Recent studies in critically ill patients receiving insulin intravenous therapy (IIT) have shown an increased incidence of severe hypoglycemia, while intermittent subcutaneous insulin «sliding scales» (conventional insulin therapy [CIT]) is associated with hyperglycemia. The objective of this study is to assess whether glycemic control range IIT can affect glucose levels and their variability and to compare it with CIT. Prospective comparative cohort study in intensive care unit, with 2 study periods: Period 1, IIT with glycemic target range 110-140 mg/dL, and Period 2, IIT of 140-180 mg/dL. In both periods CIT glycemic target was 110-180 mg/dL. We assessed severe hypoglycemia ( 216 mg/L) and the variability of blood glucose. We studied 221 patients with 12.825 blood glucose determinations. Twenty-six and 17% of patients required IIT for glycemic control in Period 1 and 2, respectively. Hypoglycemia was associated with a discontinuous nutritional intake, glycemic target 110-140 mg/dL and low body mass index (BMI) (P = .002). Hyperglycemia was exclusively associated with a history of diabetes mellitus (OR 2.6 [95% CI 1.6 to 4.5]). Glycemic variability was associated with a discontinuous nutritional intake, low BMI, CIT insulinization, diabetes mellitus, elderly and high APACHE II (P < .001). The use of IIT is useful to reduce the variability of blood glucose. Although the 140-180 mg/dL range would be more secure as to presenting greater variability and hyperglycemia, the 110-140 mg/dL range is most suitable. Copyright © 2012 Elsevier España, S.L. All rights reserved.

  12. Rationale and Design of the Left Atrial Pressure Monitoring to Optimize Heart Failure Therapy Study (LAPTOP-HF).

    Science.gov (United States)

    Maurer, Mathew S; Adamson, Philip B; Costanzo, Maria Rosa; Eigler, Neal; Gilbert, Joanne; Gold, Michael R; Klapholz, Marc; Saxon, Leslie A; Singh, Jagmeet P; Troughton, Richard; Abraham, William T

    2015-06-01

    Daily measurements of left atrial pressure (LAP) may be useful for guiding adjustments in medical therapy that prevent clinical decompensation in patients with severe heart failure (HF). LAPTOP-HF is a prospective, multicenter, randomized, controlled clinical trial in ambulatory patients with advanced heart failure in which the safety and clinical effectiveness of a physician-directed patient self-management therapeutic strategy based on LAP measured twice daily by means of an implantable sensor will be compared with a control group receiving optimal medical therapy. The trial will enroll up to 730 patients with New York Heart Association functional class III symptoms and either a hospitalization for HF during the previous 12 months or an elevated B-type natriuretic peptide level, regardless of ejection fraction, at up to 75 investigational centers. Randomization to the treatment group or control group will be at a 1:1 ratio in 3 strata based on the ejection fraction (EF > or ≤35%) and the presence of a de novo CRT device indication. LAPTOP-HF will provide essential information about the role of implantable LAP monitoring in conjunction with a new HF treatment paradigm across the spectrum of HF patients. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Antibody-Directed Effector Cell Therapy of Tumors: Analysis and Optimization Using a Physiologically Based Pharmacokinetic Model

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    Stuart W. Friedrich

    2002-01-01

    Full Text Available The failure of the cellular immune response to stop solid tumor growth has been the subject of much research. Although the mechanisms for tumor evasion of immune response are poorly understood, one viable explanation is that tumor-killing lymphocytes cannot reach the tumor cells in sufficient quantity to keep the tumor in check. Recently, the use of bifunctional antibodies. (BFAs has been proposed as a way to direct immune cells to the tumor: one arm of the antibody is specific for a known tumor-associated antigen and the other for a lymphocyte marker such as CD3. Injecting this BFA should presumably result in cross-linking of lymphocytes. (either endogenous or adoptively transferred with tumor cells, thereby enhancing therapy. Results from such an approach, however, are often disappointing- frequently there is no benefit gained by using the BFA. We have analyzed the retargeting of endogenous effector cells by BFA using a physiologically based whole-body pharmacokinetic model that accounts for interactions between all relevant species in the various organs and tumor. Our results suggest that the design of the BFA is critical and the binding constants of the antigen and lymphocyte binding epitopes need to be optimized for successful therapy.

  14. Concise Review: Optimized Strategies for Stem Cell-Based Therapy in Myocardial Repair: Clinical Translatability and Potential Limitation.

    Science.gov (United States)

    Wu, Rongrong; Hu, Xinyang; Wang, Jian'an

    2018-01-13

    Ischemic heart diseases (IHDs) remain major public health problems with high rates of morbidity and mortality worldwide. Despite significant advances, current therapeutic approaches are unable to rescue the extensive and irreversible loss of cardiomyocytes caused by severe ischemia. Over the past 16 years, stem cell-based therapy has been recognized as an innovative strategy for cardiac repair/regeneration and functional recovery after IHDs. Although substantial preclinical animal studies using a variety of stem/progenitor cells have shown promising results, there is a tremendous degree of skepticism in the clinical community as many stem cell trials do not confer any beneficial effects. How to accelerate stem cell-based therapy toward successful clinical application attracts considerate attention. However, many important issues need to be fully addressed. In this Review, we have described and compared the effects of different types of stem cells with their dose, delivery routes, and timing that have been routinely tested in recent preclinical and clinical findings. We have also discussed the potential mechanisms of action of stem cells, and explored the role and underlying regulatory components of stem cell-derived secretomes/exosomes in myocardial repair. Furthermore, we have critically reviewed the different strategies for optimizing both donor stem cells and the target cardiac microenvironments to enhance the engraftment and efficacy of stem cells, highlighting their clinical translatability and potential limitation. Stem Cells 2018. © AlphaMed Press 2018.

  15. Bioactive glasses: Frontiers and challenges

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    Larry L. Hench

    2015-11-01

    Full Text Available Bioactive glasses were discovered in 1969 and provided for the first time an alternative to nearly inert implant materials. Bioglass formed a rapid, strong and stable bond with host tissues. This article examines the frontiers of research crossed to achieve clinical use of bioactive glasses and glass-ceramics. In the 1980’s it was discovered that bioactive glasses could be used in particulate form to stimulate osteogenesis, which thereby led to the concept of regeneration of tissues. Later, it was discovered that the dissolution ions from the glasses behaved like growth factors, providing signals to the cells. This article summarizes the frontiers of knowledge crossed during four eras of development of bioactive glasses that have led from concept of bioactivity to widespread clinical and commercial use, with emphasis on the first composition, 45S5 Bioglass®. The four eras are: a discovery; b clinical application; c tissue regeneration; and d innovation. Questions still to be answered for the fourth era are included to stimulate innovation in the field and exploration of new frontiers that can be the basis for a general theory of bioactive stimulation of regeneration of tissues and application to numerous clinical needs.

  16. Bioactive proteins from pipefishes

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    E. Rethna Priya

    2013-08-01

    Full Text Available Objective: To screen antimicrobial potence of some pipefish species collected from Tuticorin coastal environment. Methods: Antimicrobial activity of pipefishes in methanol extract was investigated against 10 bacterial and 10 fungal human pathogenic strains. Results: Among the tested strains, in Centriscus scutatus, pipefish showed maximum zone of inhibition against Vibrio cholerae (8 mm and minimum in the sample of Hippichthys cyanospilos against Klebseilla pneumoniae (2 mm. In positive control, maximum zone of inhibition was recorded in Vibrio cholerae (9 mm and minimum in Klebseilla pneumoniae, and Salmonella paratyphi (5 mm. Chemical investigation indicated the presence of peptides as evidenced by ninhydrin positive spots on thin layer chromatography and presence of peptide. In SDS PAGE, in Centriscus scutatus, four bands were detected in the gel that represented the presence of proteins in the range nearly 25.8-75 kDa. In Hippichthys cyanospilos, five bands were detected in the gel that represented the presence of proteins in the range nearly 20.5-78 kDa. The result of FT-IR spectrum revealed that the pipe fishes extracts compriseed to have peptide derivatives as their predominant chemical groups. Conclusions: It can be conclude that this present investigation suggests the tested pipe fishes will be a potential source of natural bioactive compounds.

  17. Bioactive proteins from pipefishes

    Directory of Open Access Journals (Sweden)

    E. Rethna Priya

    2013-01-01

    Full Text Available Objective: To screen antimicrobial potence of some pipefish species collected from Tuticorin coastal environment. Methods: Antimicrobial activity of pipefishes in methanol extract was investigated against 10 bacterial and 10 fungal human pathogenic strains. Results: Among the tested strains, in Centriscus scutatus, pipefish showed maximum zone of inhibition against Vibrio cholerae (8 mm and minimum in the sample of Hippichthys cyanospilos against Klebseilla pneumoniae (2 mm. In positive control, maximum zone of inhibition was recorded in Vibrio cholerae (9 mm and minimum in Klebseilla pneumoniae, and Salmonella paratyphi (5 mm. Chemical investigation indicated the presence of peptides as evidenced by ninhydrin positive spots on thin layer chromatography and presence of peptide. In SDS PAGE, in Centriscus scutatus, four bands were detected in the gel that represented the presence of proteins in the range nearly 25.8-75 kDa. In Hippichthys cyanospilos, five bands were detected in the gel that represented the presence of proteins in the range nearly 20.5-78 kDa. The result of FT-IR spectrum revealed that the pipe fishes extracts compriseed to have peptide derivatives as their predominant chemical groups. Conclusions: It can be conclude that this present investigation suggests the tested pipe fishes will be a potential source of natural bioactive compounds.

  18. Continuous 4-1BB co-stimulatory signals for the optimal expansion of tumor-infiltrating lymphocytes for adoptive T-cell therapy.

    Science.gov (United States)

    Chacon, Jessica Ann; Pilon-Thomas, Shari; Sarnaik, Amod A; Radvanyi, Laszlo G

    2013-09-01

    Co-stimulation through members of the tumor necrosis factor receptor (TNFR) family appears to be critical for the generation of T cells with optimal effector-memory properties for adoptive cell therapy. Our work suggests that continuous 4-1BB/CD137 co-stimulation is required for the expansion of T cells with an optimal therapeutic profile and that the administration of 4-1BB agonists upon adoptive cell transfer further improves antitumor T-cell functions.

  19. Immunomodulation to Optimize Vascularized Composite Allograft Integration in Limb Loss Therapy

    Science.gov (United States)

    2015-10-01

    to   lower  the  risk  and  improve  the  benefits  of   patients  after   limb  reconstruction  through  transplantation.  The  study  provides  a  new...reconstruction  of  skin,   muscle ,  tendon,  bone,  nerve,  and   vessels  as  a  functional  unit  ( limb )  in  individuals  who  suffered   limb  loss.  The...2 AWARD  NUMBER:        W81XWH-­12-­2-­0058   TITLE:      Immunomodulation to Optimize Vascularized Composite Allograft Integration in Limb Loss

  20. Progression of Left Ventricular Dysfunction and Remodelling under Optimal Medical Therapy in CHF Patients: Role of Individual Genetic Background.

    Science.gov (United States)

    Rigolli, Marzia; Cicoira, Mariantonietta; Bergamini, Corinna; Chiampan, Andrea; Rossi, Andrea; Vassanelli, Corrado

    2011-01-05

    Background. Neurohormonal systems play an important role in chronic heart failure (CHF). Due to interindividual heterogeneity in the benefits of therapy, it may be hypothesized that polymorphisms of neurohormonal systems may affect left ventricular (LV) remodelling and systolic function. We aimed to assess whether genetic background of maximally treated CHF patients predicts variations in LV systolic function and volumes. Methods and Results. We prospectively studied 131 CHF outpatients on optimal treatment for at least six months. Echocardiographic evaluations were performed at baseline and after 12 months. Genotype analysis for ACE I/D, β1adrenergic receptor (AR) Arg389Gly, β2AR Arg16Gly, and β2AR Gln27Glu polymorphisms was performed. No differences in baseline characteristics were detected among subgroups. ACE II was a significant predictor of improvement of LV end-diastolic and end-systolic volume (P = .003 and P = .002, respectively) but not of LV ejection fraction (LVEF); β1AR389 GlyGly was related to improvement of LVEF (P = .02) and LV end-systolic volume (P = .01). The predictive value of polymorphisms remained after adjustment for other clinically significant predictors (P < .05 for all). Conclusions. ACE I/D and β1AR Arg389Gly polymorphisms are independent predictors of reverse remodeling and systolic function recovery in CHF patients under optimal treatment.

  1. Progression of Left Ventricular Dysfunction and Remodelling under Optimal Medical Therapy in CHF Patients: Role of Individual Genetic Background

    Directory of Open Access Journals (Sweden)

    Marzia Rigolli

    2011-01-01

    Full Text Available Background. Neurohormonal systems play an important role in chronic heart failure (CHF. Due to interindividual heterogeneity in the benefits of therapy, it may be hypothesized that polymorphisms of neurohormonal systems may affect left ventricular (LV remodelling and systolic function. We aimed to assess whether genetic background of maximally treated CHF patients predicts variations in LV systolic function and volumes. Methods and Results. We prospectively studied 131 CHF outpatients on optimal treatment for at least six months. Echocardiographic evaluations were performed at baseline and after 12 months. Genotype analysis for ACE I/D, β1adrenergic receptor (AR Arg389Gly, β2AR Arg16Gly, and β2AR Gln27Glu polymorphisms was performed. No differences in baseline characteristics were detected among subgroups. ACE II was a significant predictor of improvement of LV end-diastolic and end-systolic volume (=.003 and =.002, respectively but not of LV ejection fraction (LVEF; β1AR389 GlyGly was related to improvement of LVEF (=.02 and LV end-systolic volume (=.01. The predictive value of polymorphisms remained after adjustment for other clinically significant predictors (<.05 for all. Conclusions. ACE I/D and β1AR Arg389Gly polymorphisms are independent predictors of reverse remodeling and systolic function recovery in CHF patients under optimal treatment.

  2. Seneca Valley Virus 3Cpro Substrate Optimization Yields Efficient Substrates for Use in Peptide-Prodrug Therapy.

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    Linde A Miles

    Full Text Available The oncolytic picornavirus Seneca Valley Virus (SVV-001 demonstrates anti-tumor activity in models of small cell lung cancer (SCLC, but may ultimately need to be combined with cytotoxic therapies to improve responses observed in patients. Combining SVV-001 virotherapy with a peptide prodrug activated by the viral protease 3Cpro is a novel strategy that may increase the therapeutic potential of SVV-001. Using recombinant SVV-001 3Cpro, we measured cleavage kinetics of predicted SVV-001 3Cpro substrates. An efficient substrate, L/VP4 (kcat/KM = 1932 ± 183 M(-1s(-1, was further optimized by a P2' N→P substitution yielding L/VP4.1 (kcat/KM = 17446 ± 2203 M(-1s(-1. We also determined essential substrate amino acids by sequential N-terminal deletion and substitution of amino acids found in other picornavirus genera. A peptide corresponding to the L/VP4.1 substrate was selectively cleaved by SVV-001 3Cpro in vitro and was stable in human plasma. These data define an optimized peptide substrate for SVV-001 3Cpro, with direct implications for anti-cancer therapeutic development.

  3. Computer-Aided Optimization of Combined Anti-Retroviral Therapy for HIV: New Drugs, New Drug Targets and Drug Resistance.

    Science.gov (United States)

    Zazzi, Maurizio; Cozzi-Lepri, Alessandro; Prosperi, Mattia C F

    2016-01-01

    Resistance to antiretroviral drugs is a complex and evolving area with relevant implications in the treatment of human immunodeficiency virus (HIV) infection. Several rules, algorithms and full-fledged computer programs have been developed to assist the HIV specialist in the choice of the best patient-tailored therapy. Experts' rules and statistical/machine learning algorithms for interpreting HIV drug resistance, along with their program implementations, were retrieved from PubMed and other on-line resources to be critically reviewed in terms of technical approach, performance, usability, update, and evolution (i.e. inclusion of novel drugs or expansion to other viral agents). Several drug resistance prediction algorithms for the nucleotide/nucleoside/non-nucleoside reverse transcriptase, protease and integrase inhibitors as well as coreceptor antagonists are currently available, routinely used, and have been validated thoroughly in independent studies. Computer tools that combine single-drug genotypic/phenotypic resistance interpretation and optimize combination antiretroviral therapy have been also developed and implemented as web applications. Most of the systems have been updated timely to incorporate new drugs and few have recently been expanded to meet a similar need in the Hepatitis C area. Prototype systems aiming at predicting virological response from both virus and patient indicators have been recently developed but they are not yet being routinely used. Computing HIV genotype to predict drug susceptibility in vitro or response to combination antiretroviral therapy in vivo is a continuous and productive research field, translating into successful treatment decision support tools, an essential component of the management of HIV patients.

  4. Optimization of a nonviral transfection system to evaluate Cox-2 controlled interleukin-4 expression for osteoarthritis gene therapy in vitro.

    Science.gov (United States)

    Lang, Annemarie; Neuhaus, Johannes; Pfeiffenberger, Moritz; Schröder, Erik; Ponomarev, Igor; Weber, Yvonne; Gaber, Timo; Schmidt, Michael F G

    2014-01-01

    Gene therapy appears to have the potential for achieving a long-term remedy for osteoarthritis (OA). However, there is a risk of adverse reactions, especially when using cytomegalovirus-controlled expression. To provide a safe application, we focused on the expression of therapeutic cytokines [e.g. interleukin (IL)-4] in a disease-responsive manner by use of the previously cloned Cox-2 promoter as 'genetic switch'. In the present study, we report the functionality of a controlled gene therapeutic system in an equine osteoarthritic cell model. Different nonviral transfection reagents were tested for their efficiency on equine chondrocytes stimulated with equine IL-1β or lipopolysaccharide to create an inflammatory environment. To optimize the transfection, we successfully redesigned the vector by excluding the internal ribosomal entry site (IRES). The functionality of our Cox-2 promoter construct with respect to expressing IL-4 was proven at the mRNA and protein levels and the anti-inflammatory potential of IL-4 was confirmed by analyzing the expression of IL-1β, IL-6, IL-8, matrix metalloproteinase (MMP)-1, MMP-3 and tumor necrosis factor (TNF)-α using a quantitative polymerase chain reaction. Nonviral transfection reagents yielded transfection rates from 21% to 44% with control vectors with and without IRES, respectively. Stimulation of equine chondrocytes resulted in a 20-fold increase of mRNA expression of IL-1β. Such exogenous stimulation of chondrocytes transfected with pNCox2-IL4 led to an increase of IL-4 mRNA expression, whereas expression of inflammatory mediators decreased. The timely link between these events confirms the anti-inflammatory potential of synthesized IL-4. We consider that this approach has significant potential for translation into a useful anti-inflammation therapy. Molecular tools such as the described therapeutic plasmid pave the way for a local-controlled, self-limiting gene therapy. Copyright © 2014 John Wiley & Sons, Ltd.

  5. Robust plan optimization using edge-enhanced intensity for intrafraction organ deformation in prostate intensity-modulated radiation therapy.

    Science.gov (United States)

    Sumida, Iori; Yamaguchi, Hajime; Das, Indra J; Anetai, Yusuke; Kizaki, Hisao; Aboshi, Keiko; Tsujii, Mari; Yamada, Yuji; Tamari, Keisuke; Seo, Yuji; Isohashi, Fumiaki; Yoshioka, Yasuo; Ogawa, Kazuhiko

    2017-01-01

    This study evaluated a method for prostate intensity-modulated radiation therapy (IMRT) based on edge-enhanced (EE) intensity in the presence of intrafraction organ deformation using the data of 37 patients treated with step-and-shoot IMRT. On the assumption that the patient setup error was already accounted for by image guidance, only organ deformation over the treatment course was considered. Once the clinical target volume (CTV), rectum, and bladder were delineated and assigned dose constraints for dose optimization, each voxel in the CTV derived from the DICOM RT-dose grid could have a stochastic dose from the different voxel location according to the probability density function as an organ deformation. The stochastic dose for the CTV was calculated as the mean dose at the location through changing the voxel location randomly 1000 times. In the EE approach, the underdose region in the CTV was delineated and optimized with higher dose constraints that resulted in an edge-enhanced intensity beam to the CTV. This was compared to a planning target volume (PTV) margin (PM) approach in which a CTV to PTV margin equivalent to the magnitude of organ deformation was added to obtain an optimized dose distribution. The total monitor units, number of segments, and conformity index were compared between the two approaches, and the dose based on the organ deformation of the CTV, rectum, and bladder was evaluated. The total monitor units, number of segments, and conformity index were significantly lower with the EE approach than with the PM approach, while maintaining the dose coverage to the CTV with organ deformation. The dose to the rectum and bladder were significantly reduced in the EE approach compared with the PM approach. We conclude that the EE approach is superior to the PM with regard to intrafraction organ deformation.

  6. Cardiac resynchronization therapy and AV optimization increase myocardial oxygen consumption, but increase cardiac function more than proportionally.

    Science.gov (United States)

    Kyriacou, Andreas; Pabari, Punam A; Mayet, Jamil; Peters, Nicholas S; Davies, D Wyn; Lim, P Boon; Lefroy, David; Hughes, Alun D; Kanagaratnam, Prapa; Francis, Darrel P; Whinnett, Zachary I

    2014-02-01

    The mechanoenergetic effects of atrioventricular delay optimization during biventricular pacing ("cardiac resynchronization therapy", CRT) are unknown. Eleven patients with heart failure and left bundle branch block (LBBB) underwent invasive measurements of left ventricular (LV) developed pressure, aortic flow velocity-time-integral (VTI) and myocardial oxygen consumption (MVO2) at 4 pacing states: biventricular pacing (with VV 0 ms) at AVD 40 ms (AV-40), AVD 120 ms (AV-120, a common nominal AV delay), at their pre-identified individualised haemodynamic optimum (AV-Opt); and intrinsic conduction (LBBB). AV-120, relative to LBBB, increased LV developed pressure by a mean of 11(SEM 2)%, p=0.001, and aortic VTI by 11(SEM 3)%, p=0.002, but also increased MVO2 by 11(SEM 5)%, p=0.04. AV-Opt further increased LV developed pressure by a mean of 2(SEM 1)%, p=0.035 and aortic VTI by 4(SEM 1)%, p=0.017. MVO2 trended further up by 7(SEM 5)%, p=0.22. Mechanoenergetics at AV-40 were no different from LBBB. The 4 states lay on a straight line for Δexternal work (ΔLV developed pressure × Δaortic VTI) against ΔMVO2, with slope 1.80, significantly >1 (p=0.02). Biventricular pacing and atrioventricular delay optimization increased external cardiac work done but also myocardial oxygen consumption. Nevertheless, the increase in cardiac work was ~80% greater than the increase in oxygen consumption, signifying an improvement in cardiac mechanoenergetics. Finally, the incremental effect of optimization on external work was approximately one-third beyond that of nominal AV pacing, along the same favourable efficiency trajectory, suggesting that AV delay dominates the biventricular pacing effect - which may therefore not be mainly "resynchronization". © 2013. Published by Elsevier Ireland Ltd. All rights reserved.

  7. Bioactive dietary supplements reactivate ER expression in ER-negative breast cancer cells by active chromatin modifications.

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    Syed M Meeran

    Full Text Available Breast cancer is the most common cancer and the leading cause of cancer death in women. Although tamoxifen therapy is successful for some patients, it does not provide adequate benefit for those who have estrogen receptor (ER-negative cancers. Therefore, we approached novel treatment strategies by combining two potential bioactive dietary supplements for the reactivation of ERα expression for effective treatment of ERα-negative breast cancer with tamoxifen. Bioactive dietary supplements such as green tea polyphenols (GTPs and sulforaphane (SFN inhibit DNA methyltransferases (DNMTs and histone deacetylases (HDACs, respectively, which are of central importance to cancer prevention. In the present study, we have observed that treatment of ERα-negative breast cancer cells with GTPs and SFN alone or in combination leads to the reactivation of ERα expression. The combination of 20 µg/mL GTPs and 5 µM SFN was found to be the optimal dose of ERα-reactivation at 3 days in MDA-MB-231 cells. The reactivation of ERα expression was consistently correlated with ERα promoter hypomethylation and hyperacetylation. Chromatin immunoprecipitation (ChIP analysis of the ERα promoter revealed that GTPs and SFN altered the binding of ERα-transcriptional co-repressor complex thereby contributing to ERα-reactivation. In addition, treatment with tamoxifen in combination with GTPs and SFN significantly increased both cell death and inhibition of cellular proliferation in MDA-MB-231 cells in comparison to treatment with tamoxifen alone. Collectively, our findings suggest that a novel combination of bioactive-HDAC inhibitors with bioactive-demethylating agents is a promising strategy for the effective treatment of hormonal refractory breast cancer with available anti-estrogens.

  8. Optimization of an on-board imaging system for extremely rapid radiation therapy

    Science.gov (United States)

    Cherry Kemmerling, Erica M.; Wu, Meng; Yang, He; Maxim, Peter G.; Loo, Billy W.; Fahrig, Rebecca

    2015-01-01

    Purpose: Next-generation extremely rapid radiation therapy systems could mitigate the need for motion management, improve patient comfort during the treatment, and increase patient throughput for cost effectiveness. Such systems require an on-board imaging system that is competitively priced, fast, and of sufficiently high quality to allow good registration between the image taken on the day of treatment and the image taken the day of treatment planning. In this study, three different detectors for a custom on-board CT system were investigated to select the best design for integration with an extremely rapid radiation therapy system. Methods: Three different CT detectors are proposed: low-resolution (all 4 × 4 mm pixels), medium-resolution (a combination of 4 × 4 mm pixels and 2 × 2 mm pixels), and high-resolution (all 1 × 1 mm pixels). An in-house program was used to generate projection images of a numerical anthropomorphic phantom and to reconstruct the projections into CT datasets, henceforth called “realistic” images. Scatter was calculated using a separate Monte Carlo simulation, and the model included an antiscatter grid and bowtie filter. Diagnostic-quality images of the phantom were generated to represent the patient scan at the time of treatment planning. Commercial deformable registration software was used to register the diagnostic-quality scan to images produced by the various on-board detector configurations. The deformation fields were compared against a “gold standard” deformation field generated by registering initial and deformed images of the numerical phantoms that were used to make the diagnostic and treatment-day images. Registrations of on-board imaging system data were judged by the amount their deformation fields differed from the corresponding gold standard deformation fields—the smaller the difference, the better the system. To evaluate the registrations, the pointwise distance between gold standard and realistic registration

  9. Optimal duration of androgen deprivation therapy following radiation therapy in intermediate- or high-risk non-metastatic prostate cancer: a systematic review and meta-analysis

    Energy Technology Data Exchange (ETDEWEB)

    Leal, Frederico; Figueiredo, Maximiliano Augusto Novis de; Sasse, Andre Deeke, E-mail: sasse@cevon.com.br [Universidade Estadual de Campinas (UNICAMP), SP (Brazil)

    2015-05-15

    Objectives: to investigate current evidence on the optimal duration of adjuvant hormone deprivation for prostate cancer treated with radiation therapy with curative intent. Materials and Methods: A systematic search was performed in electronic databases. Data from randomized trials comparing different durations of hormone blockade was collected for pooled analysis. Overall survival, disease-free survival, disease-specific survival and toxicity were the outcomes of interest. Meta-analyses were performed using random-effects model. Results: Six studies met the eligibility criteria. For overall survival, the pooled data from the studies demonstrated a statistically significant benefit for longer hormone deprivation (Hazard Ratio 0.84; 95% CI 0.74 - 0.96). A statistically significant benefit was also found for disease-free survival (Hazard Ratio 0.74; 95% CI 0.62 - 0.89), and disease-specific survival (Hazard Ratio 0.73; 95% CI 0.62 - 0.85). Studies with longer blockade duration arm demonstrated greater benefit. Toxicity was low, with no increase in cardiovascular events. Conclusions: Longer duration of androgen deprivation combined to radiotherapy prolongs OS, DFS and DSS in patients with intermediate and high-risk non-metastatic prostate cancer. However, this evidence is based on trials using older radiation techniques, and further research of combination of androgen deprivation and new RT technologies may be warranted. (author)

  10. Optimization of a Neural Stem-Cell-Mediated Carboxylesterase/Irinotecan Gene Therapy for Metastatic Neuroblastoma

    Directory of Open Access Journals (Sweden)

    Margarita Gutova

    2017-03-01

    Full Text Available Despite improved survival for children with newly diagnosed neuroblastoma (NB, recurrent disease is a significant problem, with treatment options limited by anti-tumor efficacy, patient drug tolerance, and cumulative toxicity. We previously demonstrated that neural stem cells (NSCs expressing a modified rabbit carboxylesterase (rCE can distribute to metastatic NB tumor foci in multiple organs in mice and convert the prodrug irinotecan (CPT-11 to the 1,000-fold more toxic topoisomerase-1 inhibitor SN-38, resulting in significant therapeutic efficacy. We sought to extend these studies by using a clinically relevant NSC line expressing a modified human CE (hCE1m6-NSCs to establish proof of concept and identify an intravenous dose and treatment schedule that gave maximal efficacy. Human-derived NB cell lines were significantly more sensitive to treatment with hCE1m6-NSCs and irinotecan as compared with drug alone. This was supported by pharmacokinetic studies in subcutaneous NB mouse models demonstrating tumor-specific conversion of irinotecan to SN-38. Furthermore, NB-bearing mice that received repeat treatment with intravenous hCE1m6-NSCs and irinotecan showed significantly lower tumor burden (1.4-fold, p = 0.0093 and increased long-term survival compared with mice treated with drug alone. These studies support the continued development of NSC-mediated gene therapy for improved clinical outcome in NB patients.

  11. Pearls of optimizing nutrition and physical performance of older adults undergoing cancer therapy.

    Science.gov (United States)

    Vigano, Antonio; Kasvis, Popi; Di Tomasso, Jonathan; Gillis, Chelsia; Kilgour, Robert; Carli, Franco

    2017-11-01

    As the global population continues to age, the prevalence of cancer is increasing, with more than half of new cancer diagnoses occurring in those aged 65years and older. As a result of improved oncological care, a greater number of older patients undergo treatment, either chemoradiotherapy or surgery or both. The older oncology patient is not part of a homogenous group; chronological age poorly describes the health status of an individual. Comprehensive geriatric assessment (CGA) identifies domains, assessed by a multidisciplinary team, that should be considered to guide appropriate oncological treatment decisions. This paper will focus on two aspects of the CGA: the assessment of nutrition and functional status of the older patient with cancer. Optimization of both diet and physical activity may help patients improve their tolerance to oncological treatments and health-related quality of life (HRQOL). Beginning with definitions of frailty, sarcopenia, cachexia, and malnutrition, this paper will suggest standardized screening, diagnostic and interventional procedures to identify and treat these conditions in the older oncology patient. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Bioactive and inert dental glass-ceramics.

    Science.gov (United States)

    Montazerian, Maziar; Zanotto, Edgar Dutra

    2017-02-01

    The global market for dental materials is predicted to exceed 10 billion dollars by 2020. The main drivers for this growth are easing the workflow of dentists and increasing the comfort of patients. Therefore, remarkable research projects have been conducted and are currently underway to develop improved or new dental materials with enhanced properties or that can be processed using advanced technologies, such as CAD/CAM or 3D printing. Among these materials, zirconia, glass or polymer-infiltrated ceramics, and glass-ceramics (GCs) are of great importance. Dental glass-ceramics are highly attractive because they are easy to process and have outstanding esthetics, translucency, low thermal conductivity, high strength, chemical durability, biocompatibility, wear resistance, and hardness similar to that of natural teeth, and, in certain cases, these materials are bioactive. In this review article, we divide dental GCs into the following two groups: restorative and bioactive. Most restorative dental glass-ceramics (RDGCs) are inert and biocompatible and are used in the restoration and reconstruction of teeth. Bioactive dental glass-ceramics (BDGCs) display bone-bonding ability and stimulate positive biological reactions at the material/tissue interface. BDGCs are suggested for dentin hypersensitivity treatment, implant coating, bone regeneration and periodontal therapy. Throughout this paper, we elaborate on the history, processing, properties and applications of RDGCs and BDGCs. We also report on selected papers that address promising types of dental glass-ceramics. Finally, we include trends and guidance on relevant open issues and research possibilities. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 619-639, 2017. © 2016 Wiley Periodicals, Inc.

  13. How to optimize HCV therapy in genotype 1 patients with cirrhosis.

    Science.gov (United States)

    Bourlière, Marc; Wendt, Astrid; Fontaine, Hélène; Hézode, Christophe; Pol, Stanislas; Bronowicki, Jean Pierre

    2013-02-01

    Of all hepatitis C virus patients, those with cirrhosis are most in need of treatment owing to increased morbidity and mortality. Treatment with pegylated interferon and ribavirin (PEG-IFN/RBV) has clearly shown the benefits of successful treatment by improving fibrosis, causing the regression of cirrhosis and reducing and preventing cirrhosis-related complications. However, the sustained virological response (SVR) is lower in patients with cirrhosis. First generation protease inhibitors (boceprevir and telaprevir) in combination with PEG-IFN/RBV are a major advancement in the treatment of both naïve and treatment-experienced genotype 1 patients. In naïve patients, the SVR rate with the triple regimen with boceprevir increased by 14% in patients with severe fibrosis or cirrhosis compared to PEG-IFN/RBV compared by 30% in patients with mild or moderate fibrosis. The SVR rate of the triple regimen with telaprevir increased by 10-30% compared to PEG-IFN/RBV in patients with severe fibrosis or cirrhosis and by nearly 30% in patients with mild or moderate fibrosis. The greatest benefits seem to be found in patients with cirrhosis who have relapsed, and is limited in prior non-responder patients. Thus, the choice of triple therapy in the latter should be considered in relation to the increase in side effects. There are no data on the efficacy of the triple regimen in patients with decompensated cirrhosis. Results in real-life settings show that patients with cirrhosis need to be carefully followed-up during treatment due to the increase in side effects that are greater than in clinical studies. Next generation DAAs and PEG-IFN/RBV appear to be more effective and have fewer side effects in patients with cirrhosis. Ultimately, an interferon-free regimen of DAAs combinations will probably provide a SVR in patients with cirrhosis and will probably be proposed in patients with more advanced or decompensated cirrhosis. © 2012 John Wiley & Sons A/S.

  14. [The application of N-acetylcysteine in optimization of specific pharmacological therapies].

    Science.gov (United States)

    Hołyńska-Iwan, Iga; Wróblewski, Marcin; Olszewska-Słonina, Dorota; Tyrakowski, Tomasz

    2017-09-29

    Based on the analysis of data from clinical trials it could be postulated that N-acetylcysteine has a positive impact on the treatment of various diseases. However, less is known about specific molecular and physiological mechanisms underlying the reported therapeutic effects. N-acetylcysteine (NAC, N-acetyl-L-cysteine) is an amino acid derivative containing a thiol group. It is a precursor of L-cysteine and glutathione. NAC is well absorbed and safe for the body at doses up to 300 mg per kg of body weight. Side effects are relatively rare. NAC is used as an mucolytic agent in adjunctive therapy of respiratory diseases causing the retention of secretions, as well as an antidote in the treatment of paracetamol poisoning. Moreover, NAC protects against the toxic effects of reactive oxygen species and their active metabolites. NAC is involved in free radical scavenging processes via several independent mechanisms, including a direct reduction of free radicals, providing substrates for oxidation-reduction reactions and activation of antioxidant enzymes. In the blood, NAC decreases the level of low density lipoprotein peroxidation. In various tissues, NAC may increase the levels of glutathione and cysteine and stimulate the superoxide dismutase action. NAC is used as a supplement in the treatment of various diseases associated with impaired exterior and intracellular oxidative balance. NAC increases the concentrations of amino acids and their derivatives, including cysteine, cystine, and glutathione. It also stabilizes the antioxidant status of the cells and the intercellular spaces. NAC changes the levels of transcription factors, modifying the transcription of selected genes and acting on the protein translation. It works on the activation of several enzymes in the cells and outside the cells. Based on the analysis of data from clinical trials it can be concluded, that an administration of NAC may be beneficial for these groups of patients, in whom the reversible

  15. Optimizing glucocorticoid replacement therapy in severely adrenocorticotropin-deficient hypopituitary male patients.

    LENUS (Irish Health Repository)

    Behan, Lucy-Ann

    2012-02-01

    BACKGROUND: The optimal replacement regimen of hydrocortisone in adults with severe ACTH deficiency remains unknown. Management strategies vary from treatment with 15-30 mg or higher in daily divided doses, reflecting the paucity of prospective data on the adequacy of different glucocorticoid regimens. OBJECTIVE: Primarily to define the hydrocortisone regimen which results in a 24 h cortisol profile that most closely resembles that of healthy controls and secondarily to assess the impact on quality of life (QoL). DESIGN: Ten male hypopituitary patients with severe ACTH deficiency (basal cortisol <100 nm and peak response to stimulation <400 nm) were enrolled in a prospective, randomized, crossover study of 3 hydrocortisone dose regimens. Following 6 weeks of each regimen patients underwent 24 h serum cortisol sampling and QoL assessment with the Short Form 36 (SF36) and the Nottingham Health Profile (NHP) questionnaires. Free cortisol was calculated using Coolen\\'s equation. All results were compared to those of healthy, matched controls. RESULTS: Corticosteroid binding globulin (CBG) was significantly lower across all dose regimens compared to controls (P < 0.05). The lower dose regimen C (10 mg mane\\/5 mg tarde) produced a 24 h free cortisol profile (FCP) which most closely resembled that of controls. Both regimen A(20 mg mane\\/10 mg tarde) and B(10 mg mane\\/10 mg tarde) produced supraphysiological post-absorption peaks. There was no significant difference in QoL in patients between the three regimens, however energy level was significantly lower across all dose regimens compared to controls (P < 0.001). CONCLUSIONS: The lower dose of hydrocortisone (10 mg\\/5 mg) produces a more physiological cortisol profile, without compromising QoL, compared to higher doses still used in clinical practice. This may have important implications in these patients, known to have excess cardiovascular mortality.

  16. A large-scale (19)F MRI-based cell migration assay to optimize cell therapy.

    Science.gov (United States)

    Bonetto, F; Srinivas, M; Weigelin, B; Cruz, L J; Heerschap, A; Friedl, P; Figdor, C G; de Vries, I J M

    2012-09-01

    Adoptive transfer of cells for therapeutic purposes requires efficient and precise delivery to the target organ whilst preserving cell function. Therefore, therapeutically applied cells need to migrate and integrate within their target tissues after delivery, e.g. dendritic cells (DCs) need to migrate to lymph nodes to elicit an antigen-specific immune response. Previous studies have shown that inappropriate cell delivery can hinder DC migration and result in insufficient immune induction. As migration can be extremely difficult to study quantitatively in vivo, we propose an in vitro assay that reproduces key in vivo conditions to optimize cell delivery and migration in vivo. Using DC migration along a chemokine gradient, we describe here a novel (19)F MR-based, large-scale, quantitative assay to measure cell migration in a three-dimensional collagen scaffold. Unlike conventional migration assays, this set-up is amenable to both large and small cell numbers, as well as opaque tissue samples and the inclusion of chemokines or other factors. We labeled primary human DCs with a (19)F label suitable for clinical use; (0.5-15) × 10(6) cells in the scaffolds were imaged sequentially, and migration was assessed using two independent methods. We found no migration with larger numbers of cells, but up to 3% with less than one million cells. Hence, we show that the cell density in cell bolus injections has a decisive impact on migration, and this may explain the limited migration observed using large cell numbers in the clinic. Copyright © 2012 John Wiley & Sons, Ltd.

  17. Limited Impact of Setup and Range Uncertainties, Breathing Motion, and Interplay Effects in Robustly Optimized Intensity Modulated Proton Therapy for Stage III Non-small Cell Lung Cancer

    NARCIS (Netherlands)

    Inoue, Tatsuya; Widder, Joachim; van Dijk, Lisanne V; Takegawa, Hideki; Koizumi, Masahiko; Takashina, Masaaki; Usui, Keisuke; Kurokawa, Chie; Sugimoto, Satoru; Saito, Anneyuko I; Sasai, Keisuke; Van't Veld, Aart A; Langendijk, Johannes A; Korevaar, Erik W

    2016-01-01

    Purpose: To investigate the impact of setup and range uncertainties, breathing motion, and interplay effects using scanning pencil beams in robustly optimized intensity modulated proton therapy (IMPT) for stage III non-small cell lung cancer (NSCLC). Methods and Materials: Three-field IMPT plans

  18. Response to Nadler's Commentary on Arch and Craske's (2011) "Addressing Relapse in Cognitive Behavioral Therapy for Panic Disorder: Methods for Optimizing Long-Term Treatment Outcomes"

    Science.gov (United States)

    Arch, Joanna J.; Craske, Michelle G.

    2012-01-01

    Nadler (this issue), in his commentary of our article, "Addressing Relapse in Cognitive Behavioral Therapy for Panic Disorder: Methods for Optimizing Long-Term Treatment Outcomes" (Arch & Craske, 2011), argues that we misrepresent the role of panic attacks within learning theory and overlook cognitive treatment targets. He presents several case…

  19. EuroFIR-BASIS - a combined composition and biological activity database for bioactive compounds in plant-based foods

    DEFF Research Database (Denmark)

    Gry, Jørn; Black, Lucinda; Eriksen, Folmer Damsted

    2007-01-01

    Mounting evidence suggests that certain non-nutrient bioactive compounds promote optimal human health and reduce the risk of chronic disease. An Internet-deployed database, EuroFIR-BASIS, which uniquely combines food composition and biological effects data for plant-based bioactive compounds, is ...

  20. Bioactive proteins in breast milk.

    Science.gov (United States)

    Lönnerdal, Bo

    2013-03-01

    Human milk contains many proteins that have been shown to be bioactive, but it is still not known whether these activities are exerted in breast-fed infants. These bioactivities include enzyme activities, enhancement of nutrient absorption, growth stimulation, modulation of the immune system and defence against pathogens. The antimicrobial activities are very diverse, ranging from stimulation of beneficial microorganisms (i.e. prebiotic effects), killing or inhibition of growth of pathogens, to mechanisms preventing attachment or invasion of harmful microorganisms. Among the bioactive proteins are lactoferrin, lysozyme, secretory immunoglobulin A, haptocorrin, lactoperoxidase, α-lactalbumin, bile salt stimulated lipase, β- and κ-casein, and tumour growth factor β. Human milk proteins may be largely resistant against digestion in the gastrointestinal tract, be partially digested into bioactive peptides, or be more or less completely digested and utilised as a source of amino acids. These events can be studied using an in vitro digestion model, which is useful for predicting results in human infants. Some bovine milk proteins, for example, lactoferrin and tumour growth factor β, may also resist proteolysis and be capable of exerting bioactivities similar to those of human milk proteins. © 2013 The Author. Paediatrics and Child Health Division (Royal Australasian College of Physicians).

  1. The optimization of acoustic fields for ablative therapies of tumours in the upper abdomen

    Science.gov (United States)

    Gélat, P.; ter Haar, G.; Saffari, N.

    2012-12-01

    based on ray tracing and against the decomposition of the time-reversal operator (DORT). In both cases, the constrained optimization provided a superior ratio of focal peak pressure to maximum pressure magnitude on the surface of the ribs.

  2. Synthesis and in vitro bioactivity of mesoporous bioactive glass scaffolds

    Energy Technology Data Exchange (ETDEWEB)

    Shih, C.J., E-mail: cjshih@kmu.edu.tw [Department of Fragrance and Cosmetic Science, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan (China); Chen, H.T. [Department of Fragrance and Cosmetic Science, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan (China); Huang, L.F. [School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan (China); Lu, P.S.; Chang, H.F. [Department of Fragrance and Cosmetic Science, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan (China); Chang, I.L., E-mail: 84004@cch.org.tw [Department of Orthopaedic Surgery, Chang-Hua Christian Hospital, Changhua 500, Taiwan (China)

    2010-06-15

    The main objective of the present study was to determine the effect of thermal treatment procedures (calcination temperature, heating rate and duration time) on the synthesis of SiO{sub 2}-CaO-P{sub 2}O{sub 5} mesoporous bioactive glass scaffolds. This is accomplished by thermogravimetric analyses, Fourier transform infrared (FTIR) absorption spectra, X-ray diffraction (XRD) and by analysis of nitrogen adsorption/desorption isotherms. In vitro bioactivity can also be assessed by the cytotoxic effect of the glasses on the NIH-3T3 cell line, and by characterization of MC-3T3-E1 cell attachment.

  3. Optimizing Antiretroviral Therapy (ART) for Maternal and Child Health (MCH): Rationale and Design of the MCH-ART Study.

    Science.gov (United States)

    Myer, Landon; Phillips, Tamsin K; Zerbe, Allison; Ronan, Agnes; Hsiao, Nei-Yuan; Mellins, Claude A; Remien, Robert H; Le Roux, Stanzi M; Brittain, Kirsty; Ciaranello, Andrea; Petro, Greg; McIntyre, James A; Abrams, Elaine J

    2016-08-01

    Prevention of mother-to-child transmission of HIV implementation faces significant challenges globally, particularly in the context of universal lifelong antiretroviral therapy (ART) for all HIV-infected pregnant women. We describe the rationale and methods of the Maternal and Child Health-Antiretroviral Therapy (MCH-ART) study, an implementation science project examining strategies for providing HIV care and treatment to HIV-infected women who initiate ART during pregnancy and their HIV-exposed infants. MCH-ART is composed of 3 interrelated study designs across the antenatal and postnatal periods. Phase 1 is a cross-sectional evaluation of consecutive HIV-infected pregnant women seeking antenatal care; phase 2 is an observational cohort of all women from phase 1 who are eligible for initiation of ART following local guidelines; and phase 3 is a randomized trial of strategies for delivering ART to breastfeeding women from phase 2 during the postpartum period. During each phase, a set of study measurement visits is carried out separately from antenatal care and ART services; a maximum of 9 visits takes place from the beginning of antenatal care through 12 months postpartum. In parallel, in-depth interviews are used to examine issues of ART adherence and retention qualitatively, and costs and cost-effectiveness of models of care are examined. Separate substudies examine health outcomes in HIV-uninfected women and their HIV-unexposed infants, and the role of the adherence club model for long-term adherence and retention. Combining observational and experimental components, the MCH-ART study presents a novel approach to understand and optimize ART delivery for MCH.

  4. Targeted radiosensitization with PARP1 inhibition: optimization of therapy and identification of biomarkers of response in breast cancer.

    Science.gov (United States)

    Feng, Felix Y; Speers, Corey; Liu, Meilan; Jackson, William C; Moon, Dominic; Rinkinen, Jacob; Wilder-Romans, Kari; Jagsi, Reshma; Pierce, Lori J

    2014-08-01

    Sustained locoregional control of breast cancer is a significant issue for certain patients. Inhibition of PARP1 is a promising strategy for radiosensitization (RS). We sought to optimize therapy with PARP1 inhibition and radiation (RT) by establishing the most effective treatment schedule, degree of PARP1-mediated RS, and identify early biomarkers predictive of efficacy in breast cancer models. Using clonogenic survival assays, we assessed intrinsic radiosensitivity and RS induced by PARP1 inhibition in breast cancer cell lines. Potential biomarkers of response were evaluated using western blotting, flow cytometry, and immunofluorescence with validation in vivo using tumor xenograft experiments. Across a panel of BC and normal breast epithelial cell lines, the PARP1 inhibitor ABT-888 preferentially radiosensitizes breast cancer (vs. normal) cells with enhancement ratios (EnhR) up to 2.3 independent of intrinsic BC subtype or BRCA mutational status. Concurrent and adjuvant therapy resulted in the highest EnhR of all schedules tested. The degree of RS did not correlate with pretreatment markers of PARP1 activity, DNA damage/repair, or cell cycle distribution. Increases in PARP1 activity 24 h after RT were associated with sensitivity after combination treatment. Findings were confirmed in breast cancer xenograft models. Our study demonstrates that PARP1 inhibition improves the therapeutic index of RT independent of BC subtype or BRCA1 mutational status and that PARP1 activity may serve as a clinically relevant biomarker of response. These studies have led to a clinical trial (TBCRC024) incorporating intratreatment biomarker analyses of PARP1 inhibitors and RT in breast cancer patients.

  5. Design of an Yb-169 source optimized for gold nanoparticle-aided radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Reynoso, Francisco J.; Manohar, Nivedh [Nuclear/Radiological Engineering and Medical Physics Programs, Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, Georgia 30332-0405 (United States); Krishnan, Sunil [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030 (United States); Cho, Sang Hyun, E-mail: scho@mdanderson.org [Department of Radiation Physics and Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030 (United States)

    2014-10-15

    Purpose: To find an optimum design of a new high-dose rate ytterbium (Yb)-169 brachytherapy source that would maximize the dose enhancement during gold nanoparticle-aided radiation therapy (GNRT), while meeting practical constraints for manufacturing a clinically relevant brachytherapy source. Methods: Four different Yb-169 source designs were considered in this investigation. The first three source models had a single encapsulation made of one of the following materials: aluminum, titanium, and stainless steel. The last source model adopted a dual encapsulation design with an inner aluminum capsule surrounding the Yb-core and an outer titanium capsule. Monte Carlo (MC) simulations using the Monte Carlo N-Particle code version 5 (MCNP5) were conducted initially to investigate the spectral changes caused by these four source designs and the associated variations in macroscopic dose enhancement across the tumor loaded with gold nanoparticles (GNPs) at 0.7% by weight. Subsequent MC simulations were performed using the EGSnrc and NOREC codes to determine the secondary electron spectra and microscopic dose enhancement as a result of irradiating the GNP-loaded tumor with the MCNP-calculated source spectra. Results: Effects of the source filter design were apparent in the current MC results. The intensity-weighted average energy of the Yb-169 source varied from 108.9 to 122.9 keV, as the source encapsulation material changed from aluminum to stainless steel. Accordingly, the macroscopic dose enhancement calculated at 1 cm away from the source changed from 51.0% to 45.3%. The sources encapsulated by titanium and aluminum/titanium combination showed similar levels of dose enhancement, 49.3% at 1 cm, and average energies of 113.0 and 112.3 keV, respectively. While the secondary electron spectra due to the investigated source designs appeared to look similar in general, some differences were noted especially in the low energy region (<50 keV) of the spectra suggesting the

  6. The Shortest QRS Duration of an Electrocardiogram Might Be an Optimal Electrocardiographic Predictor for Response to Cardiac Resynchronization Therapy.

    Science.gov (United States)

    Chen, Jan-Yow; Lin, Kuo-Hung; Chang, Kuan-Cheng; Chou, Che-Yi

    2017-08-03

    QRS duration has been associated with the response to cardiac resynchronization therapy (CRT). However, the methods for defining QRS duration to predict the outcome of CRT have discrepancies in previous reports. The aim of this study was to determine an optimal measurement of QRS duration to predict the response to CRT.Sixty-one patients who received CRT were analyzed. All patients had class III-IV heart failure, left ventricular ejection fraction not more than 35%, and complete left bundle branch block. The shortest, longest, and average QRS durations from the 12 leads of each electrocardiogram (ECG) were measured. The responses to CRT were determined using the changes in echocardiography after 6 months. Thirty-five (57.4%) patients were responders and 26 (42.6%) patients were non-responders. The pre-procedure shortest, average, and longest QRS durations and the QRS shortening (ΔQRS) of the shortest QRS duration were significantly associated with the response to CRT in a univariate logistic regression analysis (P = 0.002, P = 0.03, P = 0.04 and P = 0.04, respectively). Based on the measurement of the area under curve of the receiver operating characteristic curve, only the pre-procedure shortest QRS duration and the ΔQRS of the shortest QRS duration showed significant discrimination for the response to CRT (P = 0.002 and P = 0.038, respectively). Multivariable logistic regression showed the pre-procedure shortest QRS duration is an independent predictor for the response to CRT.The shortest QRS duration from the 12 leads of the electrocardiogram might be an optimal measurement to predict the response to CRT.

  7. Bioactive Materials in Endodontics: An Evolving Component of Clinical Dentistry.

    Science.gov (United States)

    Mohapatra, Satyajit; Patro, Swadheena; Mishra, Sumita

    2016-06-01

    Achieving biocompatibility in a material requires an interdisciplinary approach that involves a sound knowledge of materials science, bioengineering, and biotechnology. The host microbial-material response is also critical. Endodontic treatment is a delicate procedure that must be planned and executed properly. Despite major advances in endodontic therapy in recent decades, clinicians are confronted with a complex root canal anatomy and a wide selection of endodontic filling materials that, in turn, may not be well tolerated by the periapical tissues and may evoke an immune reaction. This article discusses published reports of various bioactive materials that are used in endodontic therapy, including calcium hydroxide, mineral trioxide aggregate, a bioactive dentin substrate, calcium phosphate ceramics, and calcium phosphate cements.

  8. [OPTIMIZATION OF BRONCHODILATOR THERAPY FOR CHILDREN DURING ASTHMA EXACERBATION WITH ALLOWANCE FOR THE RISK OF DEVELOPMENT OF CARDIOHEMODYNAMIC DISORDERS].

    Science.gov (United States)

    Lebedenko, A; Semernik, O

    2015-01-01

    We have studied the effect of bronchodilator drugs representing three groups--b2-adrenomimetic (fenoterol), anticholinergic (ipratropium bromide), and combined preparation (fenoterol/ipratropium bromide)--on cardiohemodynamics in children with acute asthma exacerbation. It is established that incorrect choice of bronchodilator most significantly influences the parameters of blood pressure and blood flow rate in the pulmonary artery, mitral and tricuspid valves, and also contributes to the appearance of signs of diastolic dysfunction of the right and left ventricles. A model predicting the risk of cardiohemodynamic violations was created using the multiple regression method, which allows the probability of negative changes in the cardiovascular system on the background of bronchodilator therapy to be calculated within several minutes using data on the medical prehistory and the results of objective and instrumental examination of a patient. Using this model it is possible to optimize the bronchodilator treatment of acute asthma in children and also to prevent the formation of future complications of the cardiovascular system.

  9. The application of HP-GFC chromatographic method for the analysis of oligosaccharides in bioactive complexes

    Directory of Open Access Journals (Sweden)

    Savić Ivan

    2009-01-01

    Full Text Available The aim of this work was to optimize a GFC method for the analysis of bioactive metal (Cu, Co and Fe complexes with olygosaccharides (dextran and pullulan. Bioactive metal complexes with olygosaccharides were synthesized by original procedure. GFC was used to study the molecular weight distribution, polymerization degree of oligosaccharides and bioactive metal complexes. The metal bounding in complexes depends on the ligand polymerization degree and the presence of OH groups in coordinative sphere of the central metal ion. The interaction between oligosaccharide and metal ions are very important in veterinary medicine, agriculture, pharmacy and medicine.

  10. Simultaneous Analysis of Bioactive Markers from Orthosiphon ...

    African Journals Online (AJOL)

    Erah

    Pharmaceutical Chemistry, School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800 Minden, Penang,. Malaysia. Abstract ... the identification and quantitation of bioactive markers present in O. stamineus extracts. Four different bioactive ... Orthosiphon stamineus plant was cultivated and propagated under ...

  11. Bioactive glass coatings for orthopedic metallic implants

    Energy Technology Data Exchange (ETDEWEB)

    Lopez-Esteban, Sonia; Saiz, Eduardo; Fujino, Sigheru; Oku, Takeo; Suganuma, Katsuaki; Tomsia, Antoni P.

    2003-06-30

    The objective of this work is to develop bioactive glass coatings for metallic orthopedic implants. A new family of glasses in the SiO2-Na2O-K2O-CaO-MgO-P2O5 system has been synthesized and characterized. The glass properties (thermal expansion, softening and transformation temperatures, density and hardness) are in line with the predictions of established empirical models. The optimized firing conditions to fabricate coatings on Ti-based and Co-Cr alloys have been determined and related to the glass properties and the interfacial reactions. Excellent adhesion to alloys has been achieved through the formation of 100-200 nm thick interfacial layers (Ti5Si3 on Ti-based alloys and CrOx on Co-Cr). Finally, glass coatings, approximately 100 mu m thick, have been fabricated onto commercial Ti alloy-based dental implants.

  12. Through the looking glass; bioactive glass S53P4 (BonAlive®) in the treatment of chronic osteomyelitis.

    LENUS (Irish Health Repository)

    McAndrew, J

    2013-09-01

    In terms of eradication, osteomyelitis represents one of the most challenging infective conditions in medicine and surgery. In recent years, the use of bioactive glass in conjunction with antimicrobial therapy has emerged as a viable new treatment.

  13. Simultaneous His Bundle and Left Ventricular Pacing for Optimal Cardiac Resynchronization Therapy Delivery: Acute Hemodynamic Assessment by Pressure-Volume Loops.

    Science.gov (United States)

    Padeletti, Luigi; Pieragnoli, Paolo; Ricciardi, Giuseppe; Innocenti, Lisa; Checchi, Luca; Padeletti, Margherita; Michelucci, Antonio; Picariello, Francesco; Valsecchi, Sergio

    2016-05-01

    Previous studies have investigated the role of intrinsic conduction in optimizing cardiac resynchronization therapy. We investigated the role of fusing pacing-induced activation and intrinsic conduction in cardiac resynchronization therapy by evaluating the acute hemodynamic effects of simultaneous His-bundle (HIS) and left ventricular (LV) pacing. We studied 11 patients with systolic heart failure and left bundle-branch block scheduled for cardiac resynchronization therapy implantation. On implantation, LV pressure-volume data were determined via conductance catheter. Standard leads were placed in the right atrium, at the right ventricular apex, and in a coronary vein. An additional electrode was temporarily positioned in the HIS. The following pacing configurations were systematically assessed: standard biventricular (right ventricular apex+LV), LV-only, HIS, simultaneous HIS and LV (HIS+LV). Each configuration was compared with the AAI mode at multiple atrioventricular delays (AVD). In comparison with the AAI, right ventricular apex+LV and LV-only pacing resulted in improved stroke volume (85±32 mL and 86±33 mL versus 58±23 mL; PHIS-LV pacing improved hemodynamic indexes at all AVD (stroke volume >76 mL at all fixed intervals and 88±31 mL at optimal interval; all PHIS+LV pacing yielded improvements, regardless of AVD setting. These findings support the hypothesis of the crucial role of intrinsic right ventricular conduction in optimal cardiac resynchronization therapy delivery. © 2016 American Heart Association, Inc.

  14. Otimizando o componente farmacológico da terapia integrada da vertigem Optimizing the pharmacological component of integrated balance therapy

    Directory of Open Access Journals (Sweden)

    Maurício Malavasi Ganança

    2007-02-01

    Full Text Available A farmacoterapia é opção importante no tratamento das vestibulopatias periféricas. OBJETIVO: Identificar a medicação que otimiza a terapia integrada da vertigem (TIV na doença de Ménière e em outras vestibulopatias periféricas. MATERIAL E MÉTODO: Estudo de casos em que pacientes com doença de Ménière ou outras vestibulopatias periféricas receberam TIV com betaistina, cinarizina, clonazepam, flunarizina, Ginkgo biloba ou sem medicação durante 120 dias. RESULTADOS: Na doença de Ménière, TIV com qualquer um dos medicamentos foi mais eficaz do que TIV sem medicação, após 60 dias; a betaistina foi mais efetiva que todas as outras drogas, após 60 e 120 dias. Nas outras vestibulopatias periféricas, diferenças significantes foram observadas entre TIV com betaistina, cinarizina, clonazepam ou flunarizina e TIV sem medicação após 60 dias e todas as drogas foram mais efetivas que TIV sem medicação após 120 dias; betaistina, cinarizina ou clonazepam foram igualmente efetivos e betaistina foi mais efetiva que flunarizina e Ginkgo biloba. Os tratamentos foram bem tolerados. CONCLUSÕES: TIV incluindo medicação é mais efetiva que sem medicação na doença de Ménière ou em outras vestibulopatias periféricas. Betaistina foi o medicamento mais efetivo na doença de Ménière e tão eficaz quanto cinarizina ou clonazepam em outras vestibulopatias periféricas.Drug treatment is an important option for the treatment of peripheral vestibular diseases. AIM: To identify the drug component associated with optimal integrated balance therapy (IBT for Ménière’s disease or other peripheral vestibular disorders. MATERIALS AND METHODS: Analysis of a series of patients with Ménière’s disease patients or patients with other peripheral vestibular disorders that received IBT involving either no medication or betahistine, cinnarizine, clonazepam, flunarizine or Ginkgo biloba during 120 days. RESULTS: In Ménière’s disease

  15. Bioactivity of Minor Milk Components

    DEFF Research Database (Denmark)

    Nguyen, Duc Ninh

    of infant formula. Thereafter, bioactive milk components which were preserved in gently-processed infant formula were selected for further investigation of their immunomodulatory activity in cell and preterm pig models. We hope this project will contribute to the research on the development of new...

  16. [Nutrigenomics--bioactive dietary components].

    Science.gov (United States)

    Gętek, Monika; Czech, Natalia; Fizia, Katarzyna; Białek-Dratwa, Agnieszka; Muc-Wierzgoń, Małgorzata; Kokot, Teresa; Nowakowska-Zajdel, Ewa

    2013-04-05

    Nutrigenomics analyzes relations between diet and genes, and identifies mechanisms in which food and nutrition affect health and lifestyles and noncommunicable diseases (R. Chadwick, 2004). Bioactive dietary components are signal molecules that carry information from the external environment and affect in terms of quantity and quality in the process of gene expression. The biological effect of bioactive dietary components depends on various of physiological processes that can occur within a few genes. Polymorphism of genes can change their function and physiological response of the body for nutrients. Bioactive dietary components work on at least two levels of the expression of genes as factors regulating chromatin structure and as factors directly regulate the activity of nuclear receptors. The processes of synthesis and DNA repair are regulated by some of vitamins, macro-and micro-elements. They provide, among others, cofactors of enzymes that catalyze the replication of DNA methylation and its repair. DNA methylation profile may change under the influence of diet, single nucleotide polymorphisms and environmental factors. Bioactive dietary components may directly affect the process of gene expression by acting as ligands for nuclear receptors. Sensitive to dietary group of nuclear receptors are sensory receptors. This group includes, among others receptor PPAR (peroxisome proliferator activated), responsible for energy metabolism and receptors LXR (liver X receptor), FXR (farnesoid X receptor) and RXR, which is responsible for the metabolism of cholesterol.

  17. Planning Target Volume D95 and Mean Dose Should Be Considered for Optimal Local Control for Stereotactic Ablative Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Lina [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Zhou, Shouhao [Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Balter, Peter [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Shen, Chan [Department of Health Service Research, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Gomez, Daniel R.; Welsh, James D.; Lin, Steve H. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Chang, Joe Y., E-mail: jychang@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2016-07-15

    Purpose: To identify the optimal dose parameters predictive for local/lobar control after stereotactic ablative radiation therapy (SABR) in early-stage non-small cell lung cancer (NSCLC). Methods and Materials: This study encompassed a total of 1092 patients (1200 lesions) with NSCLC of clinical stage T1-T2 N0M0 who were treated with SABR of 50 Gy in 4 fractions or 70 Gy in 10 fractions, depending on tumor location/size, using computed tomography-based heterogeneity corrections and a convolution superposition calculation algorithm. Patients were monitored by chest CT or positron emission tomography/CT and/or biopsy after SABR. Factors predicting local/lobar recurrence (LR) were determined by competing risk multivariate analysis. Continuous variables were divided into 2 subgroups at cutoff values identified by receiver operating characteristic curves. Results: At a median follow-up time of 31.7 months (interquartile range, 14.8-51.3 months), the 5-year time to local recurrence within the same lobe and overall survival rates were 93.8% and 44.8%, respectively. Total cumulative number of patients experiencing LR was 40 (3.7%), occurring at a median time of 14.4 months (range, 4.8-46 months). Using multivariate competing risk analysis, independent predictive factors for LR after SABR were minimum biologically effective dose (BED{sub 10}) to 95% of planning target volume (PTVD95 BED{sub 10}) ≤86 Gy (corresponding to PTV D95 physics dose of 42 Gy in 4 fractions or 55 Gy in 10 fractions) and gross tumor volume ≥8.3 cm{sup 3}. The PTVmean BED{sub 10} was highly correlated with PTVD95 BED{sub 10.} In univariate analysis, a cutoff of 130 Gy for PTVmean BED{sub 10} (corresponding to PTVmean physics dose of 55 Gy in 4 fractions or 75 Gy in 10 fractions) was also significantly associated with LR. Conclusions: In addition to gross tumor volume, higher radiation dose delivered to the PTV predicts for better local/lobar control. We recommend that both PTVD95 BED

  18. Optimization of the geometry and composition of a neutron system for treatment by Boron Neutron Capture Therapy

    Directory of Open Access Journals (Sweden)

    Rohollah Gheisari

    2015-01-01

    Full Text Available Background: In the field of the treatment by Boron Neutron Capture Therapy (BNCT, an optimized neutron system was proposed. This study (simulation was conducted to optimize the geometry and composition of neutron system and increase the epithermal neutron flux for the treatment of deep tumors is performed. Materials and Methods: A neutron system for BNCT was proposed. The system included 252Cf neutron source, neutron moderator/reflector arrangement, filter and concrete. To capture fast neutrons, different neutron filters Fe, Pb, Ni and PbF2 with various thicknesses were simulated and studied. Li (with 1 mm thick was used for filtering of thermal neutrons. Bi with thickness of 1 cm was used to minimize the intensity of gamma rays. Monte Carlo simulation code MCNPX 2.4.0 was used for design of the neutron system and calculation of the neutron components at the output port of the system. Results: For different thicknesses of the filters, the fast neutron flux, the epithermal and thermal flux were calculated at the output port of the system. The spatial distribution of the fast neutron flux, the epithermal flux and gamma flux in human head phantom with the presence of 40 ppm of 10B were obtained. The present calculations showed that Pb filter (about 1 cm at the output port is suitable for fast neutron capture. The thickness of Li filter was determined due to its high absorption cross-section in thermal region. Bi was used as a gamma filter by the reason of it is good for shielding gamma rays, while having high transmission epithermal neutrons. Conclusion: The epithermal neutron flux has enhanced about 38 percent at the output port of the present system, compared with recent system proposed by Ghassoun et al. At 2 cm depth inside the head phantom, the neutron flux reaches a maximum value about . At this depth, the ratio of the thermal neutron flux to the epithermal flux is about three times, that suggests such a neutron system to treat tumors in the

  19. Advancement into the Arctic Region for Bioactive Sponge Secondary Metabolites

    Directory of Open Access Journals (Sweden)

    Mark Hamann

    2011-11-01

    Full Text Available Porifera have long been a reservoir for the discovery of bioactive compounds and drug discovery. Most research in the area has focused on sponges from tropical and temperate waters, but more recently the focus has shifted to the less accessible colder waters of the Antarctic and, to a lesser extent, the Arctic. The Antarctic region in particular has been a more popular location for natural products discovery and has provided promising candidates for drug development. This article reviews groups of bioactive compounds that have been isolated and reported from the southern reaches of the Arctic Circle, surveys the known sponge diversity present in the Arctic waters, and details a recent sponge collection by our group in the Aleutian Islands, Alaska. The collection has yielded previously undescribed sponge species along with primary activity against opportunistic infectious diseases, malaria, and HCV. The discovery of new sponge species and bioactive crude extracts gives optimism for the isolation of new bioactive compounds from a relatively unexplored source.

  20. Advancement into the Arctic Region for Bioactive Sponge Secondary Metabolites

    Science.gov (United States)

    Abbas, Samuel; Kelly, Michelle; Bowling, John; Sims, James; Waters, Amanda; Hamann, Mark

    2011-01-01

    Porifera have long been a reservoir for the discovery of bioactive compounds and drug discovery. Most research in the area has focused on sponges from tropical and temperate waters, but more recently the focus has shifted to the less accessible colder waters of the Antarctic and, to a lesser extent, the Arctic. The Antarctic region in particular has been a more popular location for natural products discovery and has provided promising candidates for drug development. This article reviews groups of bioactive compounds that have been isolated and reported from the southern reaches of the Arctic Circle, surveys the known sponge diversity present in the Arctic waters, and details a recent sponge collection by our group in the Aleutian Islands, Alaska. The collection has yielded previously undescribed sponge species along with primary activity against opportunistic infectious diseases, malaria, and HCV. The discovery of new sponge species and bioactive crude extracts gives optimism for the isolation of new bioactive compounds from a relatively unexplored source. PMID:22163194

  1. Variations in Use of Optimal Medical Therapy in Patients With Nonobstructive Coronary Artery Disease: A Population-Based Study.

    Science.gov (United States)

    Oxner, Adam; Elbaz-Greener, Gabby; Qui, Feng; Masih, Shannon; Zivkovic, Nevena; Alnasser, Sami; Cheema, Asim N; Wijeysundera, Harindra C

    2017-11-18

    There is a paucity of data on the need for optimal medical therapy (OMT) in nonobstructive coronary artery disease . We sought to understand if there was variation in the use of OMT between hospitals for patients with nonobstructive coronary artery disease, the factors associated with such variation, and its clinical consequences. Using a population-level clinical registry in Ontario, Canada, we identified all patients >66 years undergoing coronary angiography for the indication of stable angina, who had nonobstructive coronary artery disease between November 1, 2010, and October 31, 2013. Hierarchical multivariable logistic models were developed to identify the factors associated with OMT use, with median odds ratio used to quantify the degree of variation between hospitals not explained by the modeled risk factors. Clinical outcomes of interest were all-cause mortality and rehospitalization, with follow-up until March 31, 2015. Our cohort consisted of 5413 patients, of whom 2554 (47.2%) were receiving OMT within 1 year. There was a 2-fold variation in OMT across hospitals (30.4%-61.8%). The variation between hospitals was fully explained by preangiography medication use (median odds ratio of 1.21 in the null model and 1.03 in the full model). There was no difference in risk-adjusted mortality (hazard ratio, 0.94; 95% confidence interval, 0.76-1.16); however, patients receiving OMT had a lower risk of all-cause hospital readmission (hazard ratio, 0.89; 95% confidence interval, 0.84-0.95). There is wide variation in the use of OMT in patients with nonobstructive coronary artery disease, the major driver of which is differences in baseline medication use. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  2. TK.007: A novel, codon-optimized HSVtk(A168H) mutant for suicide gene therapy.

    Science.gov (United States)

    Preuss, Ellen; Treschow, Alexandra; Newrzela, Sebastian; Brücher, Daniela; Weber, Kristoffer; Felldin, Ulrika; Alici, Evren; Gahrton, Gösta; von Laer, Dorothee; Dilber, M Sirac; Fehse, Boris

    2010-08-01

    Conditional elimination of infused gene-modified alloreactive T cells, using suicide gene activation, has been shown to be an efficient strategy to abrogate severe graft-versus-host disease (GvHD) in the context of adoptive immunotherapy. To overcome shortcomings of the most widely used suicide gene, wild-type (splice-corrected) herpes simplex virus thymidine kinase (scHSVtk), we generated two new variants: the codon-optimized coHSVtk and, by introducing an additional mutation (A168H), the novel TK.007. We transduced human hematopoietic cell lines and primary T cells with retroviral "sort-suicide vectors" encoding combinations of selection markers (tCD34 and OuaSelect) with one of three HSVtk variants. In vitro we observed higher expression levels and sustained long-term expression of TK.007, indicating lower nonspecific toxicity. Also, we noted significantly improved kinetics of ganciclovir (GCV)-mediated killing for TK.007-transduced cells. In an experimental (murine) allogeneic transplantation model, TK.007-transduced T cells mediated severe GvHD, which was readily abrogated by application of GCV (10 mg/kg). Last, we established a modified allotransplantation model that allowed quantitative comparison of the in vivo activities of TK.007 versus scHSVtk. We found that TK.007 mediates both significantly faster and higher absolute killing at low GCV concentrations (10 and 25 mg/kg). In summary, we demonstrate that the novel TK.007 suicide gene combines better killing performance with reduced nonspecific toxicity (as compared with the frequently used splice-corrected wild-type scHSVtk gene), thus representing a promising alternative for suicide gene therapy.

  3. Effects of Hormone Therapy on Brain Volumes Changes of Postmenopausal Women Revealed by Optimally-Discriminative Voxel-Based Morphometry.

    Directory of Open Access Journals (Sweden)

    Tianhao Zhang

    Full Text Available The Women's Health Initiative Memory Study Magnetic Resonance Imaging (WHIMS-MRI provides an opportunity to evaluate how menopausal hormone therapy (HT affects the structure of older women's brains. Our earlier work based on region of interest (ROI analysis demonstrated potential structural changes underlying adverse effects of HT on cognition. However, the ROI-based analysis is limited in statistical power and precision, and cannot provide fine-grained mapping of whole-brain changes.We aimed to identify local structural differences between HT and placebo groups from WHIMS-MRI in a whole-brain refined level, by using a novel method, named Optimally-Discriminative Voxel-Based Analysis (ODVBA. ODVBA is a recently proposed imaging pattern analysis approach for group comparisons utilizing a spatially adaptive analysis scheme to accurately locate areas of group differences, thereby providing superior sensitivity and specificity to detect the structural brain changes over conventional methods.Women assigned to HT treatments had significant Gray Matter (GM losses compared to the placebo groups in the anterior cingulate and the adjacent medial frontal gyrus, and the orbitofrontal cortex, which persisted after multiple comparison corrections. There were no regions where HT was significantly associated with larger volumes compared to placebo, although a trend of marginal significance was found in the posterior cingulate cortical area. The CEE-Alone and CEE+MPA groups, although compared with different placebo controls, demonstrated similar effects according to the spatial patterns of structural changes.HT had adverse effects on GM volumes and risk for cognitive impairment and dementia in older women. These findings advanced our understanding of the neurobiological underpinnings of HT effects.

  4. Fourteen-day optimized levofloxacin-based therapy versus classical quadruple therapy for Helicobacter pylori treatment failures: a randomized clinical trial.

    Science.gov (United States)

    Cao, Zhijun; Chen, Qi; Zhang, Wei; Liang, Xiao; Liao, Jingxian; Liu, Wenzhong; Xiao, Shudong; Lu, Hong

    2015-01-01

    To test the efficacy of lansoprazole, bismuth, levofloxacin, and amoxicillin therapy compared to bismuth metronidazole tetracycline (BMT) quadruple therapy for second-line treatment of Helicobacter pylori infection. A total of 284 patients who failed prior H. pylori eradication were randomized to receive 14-day regimens containing lansoprazole 30 mg twice a day (b.i.d.), bismuth subcitrate 240 mg b.i.d., and either amoxcillin, 1 g b.i.d. and levofloxacin 500 mg once daily (qd) (levofloxacin/bismuth therapy) or metronidazole 400 mg four times daily (q.i.d.) and tetracycline, 500 mg q.i.d. (BMT quadruple therapy). Endoscopy and culture were performed before treatment. Antimicrobial susceptibility was by agar dilution. H. pylori status was determined 6 weeks after the end of therapy using a (13)C-urea breath test. The metronidazole, levofloxacin, tetracycline, and amoxicillin resistance rates were 85.3%, 40.2%, 1.1%, and 0.5%, respectively. The intention-to-treat and per-protocol (PP) eradication rates were 83% (95% confidence interval [CI]: 75.9-88.3%) and 88.1% (95% CI: 81.2-92.4%) (p = 0.22) for levofloxacin-bismuth (levo-bismuth) versus BMT quadruple, respectively, and PP rates were 85.4% (95% CI: 78.5-90.3%) and 90.6% (95% CI: 84.6-94.5%) (p = 0.18). Moderate and severe side effects were significantly higher with BMT quadruple than levo-bismuth (22.4% vs. 5%, p < 0.001) and higher in women (28.4%) than men (10.4%) in BMT quadruple therapy group (p = 0.015). Increasing fluoroquinolone resistance has undermined levo-bismuth quadruple therapy making BMT quadruple therapy a better choice empiric second-line therapy for H. pylori infection. However, compliance was significantly higher with levo-bismuth quadruple therapy, especially among women.

  5. Comparison of linear and nonlinear programming approaches for "worst case dose" and "minmax" robust optimization of intensity-modulated proton therapy dose distributions.

    Science.gov (United States)

    Zaghian, Maryam; Cao, Wenhua; Liu, Wei; Kardar, Laleh; Randeniya, Sharmalee; Mohan, Radhe; Lim, Gino

    2017-03-01

    Robust optimization of intensity-modulated proton therapy (IMPT) takes uncertainties into account during spot weight optimization and leads to dose distributions that are resilient to uncertainties. Previous studies demonstrated benefits of linear programming (LP) for IMPT in terms of delivery efficiency by considerably reducing the number of spots required for the same quality of plans. However, a reduction in the number of spots may lead to loss of robustness. The purpose of this study was to evaluate and compare the performance in terms of plan quality and robustness of two robust optimization approaches using LP and nonlinear programming (NLP) models. The so-called "worst case dose" and "minmax" robust optimization approaches and conventional planning target volume (PTV)-based optimization approach were applied to designing IMPT plans for five patients: two with prostate cancer, one with skull-based cancer, and two with head and neck cancer. For each approach, both LP and NLP models were used. Thus, for each case, six sets of IMPT plans were generated and assessed: LP-PTV-based, NLP-PTV-based, LP-worst case dose, NLP-worst case dose, LP-minmax, and NLP-minmax. The four robust optimization methods behaved differently from patient to patient, and no method emerged as superior to the others in terms of nominal plan quality and robustness against uncertainties. The plans generated using LP-based robust optimization were more robust regarding patient setup and range uncertainties than were those generated using NLP-based robust optimization for the prostate cancer patients. However, the robustness of plans generated using NLP-based methods was superior for the skull-based and head and neck cancer patients. Overall, LP-based methods were suitable for the less challenging cancer cases in which all uncertainty scenarios were able to satisfy tight dose constraints, while NLP performed better in more difficult cases in which most uncertainty scenarios were hard to meet

  6. Bioactive Sutures: A Review of Advances in Surgical Suture Functionalisation.

    Science.gov (United States)

    Alshomer, Feras; Madhavan, Arul; Pathan, Omar; Song, Wenhui

    2017-01-01

    Sutures have been at the forefront of surgical medicine throughout time. With recent advances in suture technology, it is possible to incorporate biologically active substances to enhance suture function and capability. Bioactive sutures represent a modality interest in controlled drug and cell delivery to traumatic sites. In this article, a comprehensive literature search of key bibliographic databases focusing on suture material fabrication and advanced modification was performed. The history, manufacturing process and cost-effectiveness of bioactive sutures are presented. Several novel modifications to enhance function in drug and growth factor delivery and cell therapy are also reviewed. Different antimicrobial drugs and anaesthetics have been shown to be effective in reducing inflammation and bacterial infection. Cellular therapy represents a unique modality augmenting the surgical repair of various soft tissue injuries. We propose a definition of bio-active sutures as biomaterials that are engineered to have controlled tissue interaction to optimise wound/defect healing, in addition to their essential function in tissue approximation. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  7. Stem cell homing-based tissue engineering using bioactive materials

    Science.gov (United States)

    Yu, Yinxian; Sun, Binbin; Yi, Chengqing; Mo, Xiumei

    2017-06-01

    Tissue engineering focuses on repairing tissue and restoring tissue functions by employing three elements: scaffolds, cells and biochemical signals. In tissue engineering, bioactive material scaffolds have been used to cure tissue and organ defects with stem cell-based therapies being one of the best documented approaches. In the review, different biomaterials which are used in several methods to fabricate tissue engineering scaffolds were explained and show good properties (biocompatibility, biodegradability, and mechanical properties etc.) for cell migration and infiltration. Stem cell homing is a recruitment process for inducing the migration of the systemically transplanted cells, or host cells, to defect sites. The mechanisms and modes of stem cell homing-based tissue engineering can be divided into two types depending on the source of the stem cells: endogenous and exogenous. Exogenous stem cell-based bioactive scaffolds have the challenge of long-term culturing in vitro and for endogenous stem cells the biochemical signal homing recruitment mechanism is not clear yet. Although the stem cell homing-based bioactive scaffolds are attractive candidates for tissue defect therapies, based on in vitro studies and animal tests, there is still a long way before clinical application.

  8. Clinically Applicable Monte Carlo–based Biological Dose Optimization for the Treatment of Head and Neck Cancers With Spot-Scanning Proton Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Wan Chan Tseung, Hok Seum, E-mail: wanchantseung.hok@mayo.edu; Ma, Jiasen; Kreofsky, Cole R.; Ma, Daniel J.; Beltran, Chris

    2016-08-01

    Purpose: Our aim is to demonstrate the feasibility of fast Monte Carlo (MC)–based inverse biological planning for the treatment of head and neck tumors in spot-scanning proton therapy. Methods and Materials: Recently, a fast and accurate graphics processor unit (GPU)–based MC simulation of proton transport was developed and used as the dose-calculation engine in a GPU-accelerated intensity modulated proton therapy (IMPT) optimizer. Besides dose, the MC can simultaneously score the dose-averaged linear energy transfer (LET{sub d}), which makes biological dose (BD) optimization possible. To convert from LET{sub d} to BD, a simple linear relation was assumed. By use of this novel optimizer, inverse biological planning was applied to 4 patients, including 2 small and 1 large thyroid tumor targets, as well as 1 glioma case. To create these plans, constraints were placed to maintain the physical dose (PD) within 1.25 times the prescription while maximizing target BD. For comparison, conventional intensity modulated radiation therapy (IMRT) and IMPT plans were also created using Eclipse (Varian Medical Systems) in each case. The same critical-structure PD constraints were used for the IMRT, IMPT, and biologically optimized plans. The BD distributions for the IMPT plans were obtained through MC recalculations. Results: Compared with standard IMPT, the biologically optimal plans for patients with small tumor targets displayed a BD escalation that was around twice the PD increase. Dose sparing to critical structures was improved compared with both IMRT and IMPT. No significant BD increase could be achieved for the large thyroid tumor case and when the presence of critical structures mitigated the contribution of additional fields. The calculation of the biologically optimized plans can be completed in a clinically viable time (<30 minutes) on a small 24-GPU system. Conclusions: By exploiting GPU acceleration, MC-based, biologically optimized plans were created for

  9. Bioactivity and fluoride release of strontium and fluoride modified Biodentine.

    Science.gov (United States)

    Simila, Hazel O; Karpukhina, Natalia; Hill, Robert G

    2018-01-01

    Biodentine™ is a novel tricalcium silicate based material used both as a coronal dentine replacement and in pulp therapy. Its multiple use in sealing perforations, pulp capping and as a temporary restoration arises from its ability to promote dentine formation and to confer an excellent marginal seal. However, there is still room for improvement of this cement as it lacks the anticariogenic effect typically conferred by fluoride ion release as seen in glass ionomer cement based dental materials. Therefore, this study was conducted to investigate the impact of bioactive glass addition to Biodentine™. was to compare the apatite formation capacity, specificity of the apatite type formed and fluoride ion release by Biodentine™ cements that have been modified by three different compositions of bioactive glasses. High fluoride, high strontium and high fluoride plus strontium containing bioactive glasses were synthesized, incorporated into Biodentine™ powder and four types of cements prepared. These cements were immersed in phosphate buffered saline solution and incubated for a period of 3 and 24h, 3, 7 and 14 days. Fourier transform infra-red spectroscopy, X-ray diffraction, magic angle spinning nuclear magnetic resonance and fluoride ion release studies were performed. Bioactive glass addition to Biodentine™ led to pronounced formation of apatite. Where the bioactive glass contained fluoride, fluorapatite and fluoride ion release were demonstrated. Eliciting fluorapatite formation and fluoride ion release from Biodentine™ is an important development as fluoride is known to have antibacterial and anticariogenic effects. Copyright © 2017 The Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

  10. Bioactivity of Minor Milk Components

    DEFF Research Database (Denmark)

    Nguyen, Duc Ninh

    . In particular, 3-15% of very low birth weight preterm infants suffer from the most servere form of intestinal inflammation, known as necrotizing enterocolitis (NEC). This disease is incurable with a high mortality rate of 15-30%. Mother’s breast milk consists of different bioactive constituents......Abstract Every year, thousands of infants are born prematurely (before the completion of 37 weeks of gestation). These preterm infants have immature gastrointestinal tract and immune system, which lead to high risks of infection, sepsis, and intestinal inflammation with high mortality rate...... several steps of thermal processing, which are known to decrease/abolish bioactivity of milk constituents. This may explain for high NEC incidence in formula-fed preterm infants. We therefore in this PhD project investigated whether gentle thermal processing conditions increase the bioavailability...

  11. Maize Bioactive Peptides against Cancer

    Science.gov (United States)

    Díaz-Gómez, Jorge L.; Castorena-Torres, Fabiola; Preciado-Ortiz, Ricardo E.; García-Lara, Silverio

    2017-06-01

    Cancer is one of the main chronic degenerative diseases worldwide. In recent years, consumption of whole-grain cereals and their derived food products has been associated with reduction risks of various types of cancer. Cereals main biomolecules includes proteins, peptides, and amino acids present in different quantities within the grain. The nutraceutical properties associated with peptides exerts biological functions that promote health and prevent this disease. In this review, we report the current status and advances on maize peptides regarding bioactive properties that have been reported such as antioxidant, antihypertensive, hepatoprotective, and anti-tumour activities. We also highlighted its biological potential through which maize bioactive peptides exert anti-cancer activity. Finally, we analyse and emphasize the possible areas of application for maize peptides.

  12. Clinical applications of bioactive milk components

    Science.gov (United States)

    Newburg, David S.

    2015-01-01

    Milk represents a unique resource for translational medicine: It contains a rich pool of biologically active molecules with demonstrated clinical benefits. The ongoing characterization of the mechanistic process through which milk components promote development and immunity has revealed numerous milk-derived compounds with potential applications as clinical therapies in infectious and inflammatory disease, cancer, and other conditions. Lactoferrin is an effective antimicrobial and antiviral agent in high-risk patient populations and a potentially potent adjuvant to chemotherapy in lung cancer. Enteric nutrition formulas supplemented with transforming growth factor β, a milk cytokine, have been shown to promote remission in pediatric Crohn's disease. A number of milk glycans, including human milk oligosaccharides, show promise in preclinical studies as antimicrobial and anti-inflammatory agents. While active preclinical investigations of human milk may soon result in large-scale production of human milk molecules, bovine milk components in many instances represent a practical source of bioactive milk compounds for use in clinical trials. This review summarizes current efforts to translate the compounds derived from human and bovine milk into effective clinical therapies. These efforts suggest a common pathway for the translation of milk-derived compounds into clinical applications. PMID:26011900

  13. Anticancer potential of bioactive peptides from animal sources (Review).

    Science.gov (United States)

    Wang, Linghong; Dong, Chao; Li, Xian; Han, Wenyan; Su, Xiulan

    2017-08-01

    Cancer is the most common cause of human death worldwide. Conventional anticancer therapies, including chemotherapy and radiation, are associated with severe side effects and toxicities as well as low specificity. Peptides are rapidly being developed as potential anticancer agents that specifically target cancer cells and are less toxic to normal tissues, thus making them a better alternative for the prevention and management of cancer. Recent research has focused on anticancer peptides from natural animal sources, such as terrestrial mammals, marine animals, amphibians, and animal venoms. However, the mode of action by which bioactive peptides inhibit the proliferation of cancer cells remains unclear. In this review, we present the animal sources from which bioactive peptides with anticancer activity are derived and discuss multiple proposed mechanisms by which these peptides exert cytotoxic effects against cancer cells.

  14. A practical cone-beam CT scatter correction method with optimized Monte Carlo simulations for image-guided radiation therapy

    Science.gov (United States)

    Xu, Yuan; Bai, Ti; Yan, Hao; Ouyang, Luo; Pompos, Arnold; Wang, Jing; Zhou, Linghong; Jiang, Steve B.; Jia, Xun

    2015-05-01

    Cone-beam CT (CBCT) has become the standard image guidance tool for patient setup in image-guided radiation therapy. However, due to its large illumination field, scattered photons severely degrade its image quality. While kernel-based scatter correction methods have been used routinely in the clinic, it is still desirable to develop Monte Carlo (MC) simulation-based methods due to their accuracy. However, the high computational burden of the MC method has prevented routine clinical application. This paper reports our recent development of a practical method of MC-based scatter estimation and removal for CBCT. In contrast with conventional MC approaches that estimate scatter signals using a scatter-contaminated CBCT image, our method used a planning CT image for MC simulation, which has the advantages of accurate image intensity and absence of image truncation. In our method, the planning CT was first rigidly registered with the CBCT. Scatter signals were then estimated via MC simulation. After scatter signals were removed from the raw CBCT projections, a corrected CBCT image was reconstructed. The entire workflow was implemented on a GPU platform for high computational efficiency. Strategies such as projection denoising, CT image downsampling, and interpolation along the angular direction were employed to further enhance the calculation speed. We studied the impact of key parameters in the workflow on the resulting accuracy and efficiency, based on which the optimal parameter values were determined. Our method was evaluated in numerical simulation, phantom, and real patient cases. In the simulation cases, our method reduced mean HU errors from 44 to 3 HU and from 78 to 9 HU in the full-fan and the half-fan cases, respectively. In both the phantom and the patient cases, image artifacts caused by scatter, such as ring artifacts around the bowtie area, were reduced. With all the techniques employed, we achieved computation time of less than 30 s including the

  15. TH-C-12A-06: Feasibility of a MLC-Based Inversely Optimized Multi-Field Grid Therapy Technique

    Energy Technology Data Exchange (ETDEWEB)

    Jin, J [Georgia Regents University, Augusta, GA (Georgia); Zhao, B; Huang, Y; Kim, J; Qin, Y; Wen, N; Ryu, S; Chetty, I [Henry Ford Health System, Detroit, MI (United States)

    2014-06-15

    Purpose: Grid therapy (GT), which generates highly spatially modulated dose distributions, can deliver single- or hypo-fractionated radiotherapy for large tumors without causing significant toxicities. GT may be applied in combination with immunotherapy, in light of recent preclinical data of synergetic interaction between radiotherapy and immunotherapy. However, conventional GT uses only one field, which does not have the advantage of multi-fields in 3D conformal-RT or IMRT. We have proposed a novel MLC-based, inverse-planned multi-field 3D GT technique. This study aims to test its deliverability and dosimetric accuracy. Methods: A lattice of small spheres was created as the boost volume within a large target. A simultaneous boost IMRT plan with 8-Gy to the target and 20-Gy to the boost volume was generated in the Eclipse treatment planning system (AAA v10) with a HD120 MLC. Nine beams were used, and the gantry and couch angles were selected so that the spheres were perfectly aligned in every beams eye view. The plan was mapped to a phantom with dose scaled. EBT3 films were calibrated and used to measure the delivered dose. Results: The IMRT plan generated a highly spatially modulated dose distribution in the target. D95%, D50%, D5% for the spheres and the targets in Gy were 18.5, 20.0, 21.4 and 7.9, 9.8, 16.1, respectively. D50% for a 1cm ring 1cm outside the target was 2.9-Gy. Film dosimetry showed good agreement between calculated and delivered dose, with an overall gamma passing rate of 99.6% (3%/1mm). The point dose differences for different spheres varied from 1–6%. Conclusion: We have demonstrated the deliverability and dose calculation accuracy of the MLC-based inversely optimized multi-field GT technique, which achieved a brachytherapy-like dose distribution. Single-fraction high dose can be delivered to the spheres in a large target with minimal dose to the surrounding normal tissue.

  16. Response surface method optimization of a novel Hypericin formulation in P123 micelles for colorectal cancer and antimicrobial photodynamic therapy.

    Science.gov (United States)

    Montanha, Maiara Camotti; Silva, Larissa Lachi; Pangoni, Fernanda Belincanta Borghi; Cesar, Gabriel Batista; Gonçalves, Renato Sonchini; Caetano, Wilker; Hioka, Noboru; Tominaga, Tania Toyomi; Consolaro, Márcia Edilaine Lopes; Diniz, Andréa; Kimura, Elza

    2017-05-01

    The photodynamic properties of Hypericin (Hyp) may be used as an alternative treatment for malignancies of the lower gastrointestinal tract and for the prevention of surgical-site infection; however, its use in photodynamic therapy has been limited because of its poor hydrosolubility. Therefore, in order to improve its water solubility and its photodynamic effect, Hyp was encapsulated in Pluronic P123 (P123) and the photodynamic effects against intestinal and epidermal bacteria and against two lineages of intestinal colon carcinoma cells were investigated. Two response surface methods (RSM) were used to achieve the best in vitro photodynamic activity against Enterococcus faecalis, Escherichia coli and Staphylococcus aureus: in the first (full 2 3 RSM), Hyp concentration (HC*), incubation time (IT*) and LED-light time (LT*) were considered as the independent variables and E. faecalis inhibition as the dependent variable. In the second (full 3 2 RSM), Hyp concentration (HC*) and P123 concentration (CC*) were considered as independent variables and E. faecalis, E. coli and S. aureus inhibition as dependent variables. The optimized experimental conditions achieved were: Hyp concentration=37.5μmol/L; P123 concentration=21.5 μmol/L and 6.3J/cm 2 , which resulted in 2.86±0.12 and 2.30±0.31CFU log-reductions of E. faecalis and S. aureus. No effect was seen against E. coli. The cytotoxic effects of Hyp/P123 were also investigated for Caco-2 and HT-29 intestinal colon carcinoma cells at Hyp/P123 concentrations of 1, 0.5, 0.25 and 0.1μmol/L for Caco-2 cells and 4, 3, 2 and 1μmol/L for HT-29 cells. The cytotoxic concentrations for 50% (CC 50 ) and 90% (CC 90 ) of Hyp/P123 were 0.443 and 0.870μmol/L for Caco-2 cells and 1.4 and 2.84μmol/L for HT-29 cells. The P123 nanocarrier played a significant role in the permeation of Hyp through the cell membrane leading to significant cell death, and showed itself to be a promising photosensitizer for PDT that could be suitable

  17. Anatomical robust optimization to account for nasal cavity filling variation during intensity-modulated proton therapy: a comparison with conventional and adaptive planning strategies.

    Science.gov (United States)

    van de Water, Steven; Albertini, Francesca; Weber, Damien Charles; Heijmen, Ben J M; Hoogeman, Mischa S; Lomax, Antony John

    2017-11-21

    The aim of this study is to develop an anatomical robust optimization method for intensity-modulated proton therapy (IMPT) that accounts for interfraction variations in nasal cavity filling, and to compare it with conventional single-field uniform dose (SFUD) optimization and online plan adaptation. We included CT data of five patients with tumors in the sinonasal region. Using the planning CT, we generated for each patient 25 'synthetic' CTs with varying nasal cavity filling. The robust optimization method available in our treatment planning system 'Erasmus-iCycle' was extended to also account for anatomical uncertainties by including (synthetic) CTs with varying patient anatomy as error scenarios in the inverse optimization. For each patient, we generated treatment plans using anatomical robust optimization and, for benchmarking, using SFUD optimization and online plan adaptation. Clinical target volume (CTV) and organ-at-risk (OAR) doses were assessed by recalculating the treatment plans on the synthetic CTs, evaluating dose distributions individually and accumulated over an entire fractionated 50-GyRBE treatment, assuming each synthetic CT to correspond to a 2-GyRBE fraction. Treatment plans were also evaluated using actual repeat CTs. Anatomical robust optimization resulted in adequate CTV doses (V95%≥98% and V107%≤2%) if at least three synthetic CTs were included in addition to the planning CT. These CTV requirements were also fulfilled for online plan adaptation, but not for the SFUD approach, even when applying a margin of 5 mm. Compared with anatomical robust optimization, OAR dose parameters for the accumulated dose distributions were on average 5.9 GyRBE (20%) higher when using SFUD optimization and on average 3.6 GyRBE (18%) lower for online plan adaptation. In conclusion, anatomical robust optimization effectively accounted for changes in nasal cavity filling during IMPT, providing substantially improved CTV and OAR doses compared with conventional

  18. Hierarchical Structures and Shaped Particles of Bioactive Glass and Its In Vitro Bioactivity

    Directory of Open Access Journals (Sweden)

    U. Boonyang

    2013-01-01

    Full Text Available In this study, bioactive glass particles with controllable structure and porosity were prepared using dual-templating methods. Block copolymers used as one template component produced mesopores in the calcined samples. Polymer colloidal crystals as the other template component yielded either three-dimensionally ordered macroporous (3DOM products or shaped bioactive glass nanoparticles. The in vitro bioactivity of these bioactive glasses was studied by soaking the samples in simulated body fluid (SBF at body temperature (37°C for varying lengths of time and monitoring the formation of bone-like apatite on the surface of the bioactive glass. A considerable bioactivity was found that all of bioactive glass samples have the ability to induce the formation of an apatite layer on its surface when in contact with SBF. The development of bone-like apatite is faster for 3DOM bioactive glasses than for nanoparticles.

  19. Bioactive proteins against pathogenic and spoilage bacteria

    OpenAIRE

    Mahmoud Z. Sitohy; Ali O. Osman; Mahgoub, Samir A.

    2014-01-01

    Background: It is likely that both human nutrition and the nutrition of livestock are benefited by the presence of bioactive proteins within their respective diet regimes. Bioactive proteins have been defined as specific protein fragments that positively impact bodily functions or conditions and may, ultimately, influence overall human health. The ingestion of bioactive proteins may have an effect on the major body systems—namely, the cardiovascular, digestive, immune and ...

  20. WE-AB-BRA-09: Sensitivity of Plan Re-Optimization to Errors in Deformable Image Registration in Online Adaptive Image-Guided Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    McClain, B; Olsen, J; Green, O; Yang, D; Santanam, L; Olsen, L; Zhao, T; Rodriguez, V; Wooten, H; Mutic, S; Kashani, R [Washington University School of Medicine, St. Louis, Missouri (United States); Victoria, J; Dempsey, J [ViewRay Incorporated, Oakwood Village, OH (United States)

    2015-06-15

    Purpose: Online adaptive therapy (ART) relies on auto-contouring using deformable image registration (DIR). DIR’s inherent uncertainties require user intervention and manual edits while the patient is on the table. We investigated the dosimetric impact of DIR errors on the quality of re-optimized plans, and used the findings to establish regions for focusing manual edits to where DIR errors can Result in clinically relevant dose differences. Methods: Our clinical implementation of online adaptive MR-IGRT involves using DIR to transfer contours from CT to daily MR, followed by a physicians’ edits. The plan is then re-optimized to meet the organs at risk (OARs) constraints. Re-optimized abdomen and pelvis plans generated based on physician edited OARs were selected as the baseline for evaluation. Plans were then re-optimized on auto-deformed contours with manual edits limited to pre-defined uniform rings (0 to 5cm) around the PTV. A 0cm ring indicates that the auto-deformed OARs were used without editing. The magnitude of the variations caused by the non-deterministic optimizer was quantified by repeat re-optimizations on the same geometry to determine the mean and standard deviation (STD). For each re-optimized plan, various volumetric parameters for the PTV, the OARs were extracted along with DVH and isodose evaluation. A plan was deemed acceptable if the variation from the baseline plan was within one STD. Results: Initial results show that for abdomen and pancreas cases, a minimum of 5cm margin around the PTV is required for contour corrections, while for pelvic and liver cases a 2–3 cm margin is sufficient. Conclusion: Focusing manual contour edits to regions of dosimetric relevance can reduce contouring time in the online ART process while maintaining a clinically comparable plan. Future work will further refine the contouring region by evaluating the path along the beams, dose gradients near the target and OAR dose metrics.

  1. Bioactive content, hepatoprotective and antioxidant activities of ...

    African Journals Online (AJOL)

    Bioactive content, hepatoprotective and antioxidant activities of whole plant extract of Micromeria fruticosa (L) Druce ssp Serpyllifolia F Lamiaceae against Carbon tetrachloride-induced hepatotoxicity in mice.

  2. Bioactive glasses materials, properties and applications

    CERN Document Server

    Ylänen, Heimo

    2011-01-01

    Due to their biocompatibility and bioactivity, bioactive glasses are used as highly effective implant materials throughout the human body to replace or repair damaged tissue. As a result, they have been in continuous use since shortly after their invention in the late 1960s and are the subject of extensive research worldwide.Bioactive glasses provides readers with a detailed review of the current status of this unique material, its properties, technologies and applications. Chapters in part one deal with the materials and mechanical properties of bioactive glass, examining topics such

  3. Optimization of the Ultrasonic-Assisted Extraction of Bioactive Flavonoids from Ampelopsis grossedentata and Subsequent Separation and Purification of Two Flavonoid Aglycones by High-Speed Counter-Current Chromatography.

    Science.gov (United States)

    Zhang, Hongbing; Xie, Guoyong; Tian, Mei; Pu, Qian; Qin, Minjian

    2016-08-20

    The fermented leaf of Ampelopsis grossedentata has been used as a beverage and folk medicine called "vine tea" in the southern region of China. In this paper, the optimum extraction conditions for the maximum recovery amounts of total flavonoids (TF), dihydromyricetin (DMY), myricitrin (MYG) and myricetin (MY) from natural Ampelopsis grossedentata leaves subjected to ultrasonic-assisted extraction (UAE) were determined and optimized by using response surface methodology. The method was employed by the Box-Behnken design (BBD) and Derringer's desirability function using methanol concentration, extraction time, liquid/solid ratio as factors and the contents of TF, DMY, MYG and MY as responses. The obtained optimum UAE conditions were as follows: a solvent of 80.87% methanol, an extraction time of 31.98 min and a liquid/solid ratio of 41.64:1 mL/g. Through analysis of the response surface, it implied that methanol concentration and the liquid/solid ratio had significant effects on TF, DMY, MYG and MY yields, whereas extraction time had relatively little effects. The established extraction and analytical methods were successfully applied to determine the contents of the total flavonoids and three individual flavonoids in 10 batches of the leaf samples of A. grossedentata from three counties in Fujian Province, China. The results suggested the variability in the quality of A. grossedentata leaves from different origins. In addition, high purities of dihydromyricetin and myricetin were simultaneously separated and purified from the extract subjected to optimized UAE, by high-speed counter-current chromatography using a solvent system of N-hexane-ethyl acetate-methanol-water (1:3:2:4; v/v/v/v). In a single operation, 200 mg of the extract were separated to yield 86.46 mg of dihydromyricetin and 3.61 mg of myricetin with the purity of 95.03% and 99.21%, respectively. The results would be beneficial for further exploiting the herbal products and controlling the quality of

  4. Long-term pain relief with optimized medical treatment including antioxidants and step-up interventional therapy in patients with chronic pancreatitis.

    Science.gov (United States)

    Shalimar; Midha, Shallu; Hasan, Ajmal; Dhingra, Rajan; Garg, Pramod Kumar

    2017-01-01

    Abdominal pain is difficult to treat in patients with chronic pancreatitis (CP). Medical therapy including antioxidants has been shown to relieve pain of CP in the short-term. Our aim was to study the long-term results of optimized medical and interventional therapy for pain relief in patients with CP with a step-up approach. All consecutive patients with CP were included prospectively in the study. They were treated medically with a well-balanced diet, pancreatic enzymes, and antioxidants (9000 IU beta-carotene, 0.54 g vitamin C, 270 IU vitamin E, 600 µg organic selenium, and 2 g methionine). Endoscopic therapy and/or surgery were offered if medical therapy failed. Pain relief was the primary outcome measure. A total of 313 patients (mean age 26.16 ± 12.17; 244 males) with CP were included; 288 (92%) patients had abdominal pain. The etiology of CP was idiopathic in 224 (71.6%) and alcohol in 82 (26.2%). At 1-year follow-up, significant pain relief was achieved in 84.7% of patients: 52.1% with medical therapy, 16.7% with endoscopic therapy, 7.6% with surgery, and 8.3% spontaneously. The mean pain score decreased from 6.36 ± 1.92 to 1.62 ± 2.10 (P treatment. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  5. Limited Impact of Setup and Range Uncertainties, Breathing Motion, and Interplay Effects in Robustly Optimized Intensity Modulated Proton Therapy for Stage III Non-small Cell Lung Cancer.

    Science.gov (United States)

    Inoue, Tatsuya; Widder, Joachim; van Dijk, Lisanne V; Takegawa, Hideki; Koizumi, Masahiko; Takashina, Masaaki; Usui, Keisuke; Kurokawa, Chie; Sugimoto, Satoru; Saito, Anneyuko I; Sasai, Keisuke; Van't Veld, Aart A; Langendijk, Johannes A; Korevaar, Erik W

    2016-11-01

    To investigate the impact of setup and range uncertainties, breathing motion, and interplay effects using scanning pencil beams in robustly optimized intensity modulated proton therapy (IMPT) for stage III non-small cell lung cancer (NSCLC). Three-field IMPT plans were created using a minimax robust optimization technique for 10 NSCLC patients. The plans accounted for 5- or 7-mm setup errors with ±3% range uncertainties. The robustness of the IMPT nominal plans was evaluated considering (1) isotropic 5-mm setup errors with ±3% range uncertainties; (2) breathing motion; (3) interplay effects; and (4) a combination of items 1 and 2. The plans were calculated using 4-dimensional and average intensity projection computed tomography images. The target coverage (TC, volume receiving 95% of prescribed dose) and homogeneity index (D2 - D98, where D2 and D98 are the least doses received by 2% and 98% of the volume) for the internal clinical target volume, and dose indexes for lung, esophagus, heart and spinal cord were compared with that of clinical volumetric modulated arc therapy plans. The TC and homogeneity index for all plans were within clinical limits when considering the breathing motion and interplay effects independently. The setup and range uncertainties had a larger effect when considering their combined effect. The TC decreased to 98% for robust 7-mm evaluations for all patients. The organ at risk dose parameters did not significantly vary between the respective robust 5-mm and robust 7-mm evaluations for the 4 error types. Compared with the volumetric modulated arc therapy plans, the IMPT plans showed better target homogeneity and mean lung and heart dose parameters reduced by about 40% and 60%, respectively. In robustly optimized IMPT for stage III NSCLC, the setup and range uncertainties, breathing motion, and interplay effects have limited impact on target coverage, dose homogeneity, and organ-at-risk dose parameters. Copyright © 2016 Elsevier Inc. All

  6. Optimized volumetric modulated arc therapy versus 3D-CRT for early stage mediastinal Hodgkin lymphoma without axillary involvement: a comparison of second cancers and heart disease risk.

    Science.gov (United States)

    Filippi, Andrea Riccardo; Ragona, Riccardo; Piva, Cristina; Scafa, Davide; Fiandra, Christian; Fusella, Marco; Giglioli, Francesca Romana; Lohr, Frank; Ricardi, Umberto

    2015-05-01

    The purpose of this study was to evaluate the risks of second cancers and cardiovascular diseases associated with an optimized volumetric modulated arc therapy (VMAT) planning solution in a selected cohort of stage I/II Hodgkin lymphoma (HL) patients treated with either involved-node or involved-site radiation therapy in comparison with 3-dimensional conformal radiation therapy (3D-CRT). Thirty-eight patients (13 males and 25 females) were included. Disease extent was mediastinum alone (n=8, 21.1%); mediastinum plus unilateral neck (n=19, 50%); mediastinum plus bilateral neck (n=11, 29.9%). Prescription dose was 30 Gy in 2-Gy fractions. Only 5 patients had mediastinal bulky disease at diagnosis (13.1%). Anteroposterior 3D-CRT was compared with a multiarc optimized VMAT solution. Lung, breast, and thyroid cancer risks were estimated by calculating a lifetime attributable risk (LAR), with a LAR ratio (LAR(VMAT)-to-LAR(3D-CRT)) as a comparative measure. Cardiac toxicity risks were estimated by calculating absolute excess risk (AER). The LAR ratio favored 3D-CRT for lung cancer induction risk in mediastinal alone (P=.004) and mediastinal plus unilateral neck (P=.02) presentations. LAR ratio for breast cancer was lower for VMAT in mediastinal plus bilateral neck presentations (P=.02), without differences for other sites. For thyroid cancer, no significant differences were observed, regardless of anatomical presentation. A significantly lower AER of cardiac (P=.038) and valvular diseases (P<.0001) was observed for VMAT regardless of disease extent. In a cohort of patients with favorable characteristics in terms of disease extent at diagnosis (large prevalence of nonbulky presentations without axillary involvement), optimized VMAT reduced heart disease risk with comparable risks of thyroid and breast cancer, with an increase in lung cancer induction probability. The results are however strongly influenced by the different anatomical presentations, supporting an

  7. Optimized Volumetric Modulated Arc Therapy Versus 3D-CRT for Early Stage Mediastinal Hodgkin Lymphoma Without Axillary Involvement: A Comparison of Second Cancers and Heart Disease Risk

    Energy Technology Data Exchange (ETDEWEB)

    Filippi, Andrea Riccardo, E-mail: andreariccardo.filippi@unito.it [Department of Oncology, Radiation Oncology, University of Torino, Torino (Italy); Ragona, Riccardo; Piva, Cristina; Scafa, Davide; Fiandra, Christian [Department of Oncology, Radiation Oncology, University of Torino, Torino (Italy); Fusella, Marco; Giglioli, Francesca Romana [Medical Physics, AOU Città della Salute e della Scienza Hospital, Torino (Italy); Lohr, Frank [Department of Radiation Oncology, University Medical Center Mannheim, University of Heidelberg, Mannheim (Germany); Ricardi, Umberto [Department of Oncology, Radiation Oncology, University of Torino, Torino (Italy)

    2015-05-01

    Purpose: The purpose of this study was to evaluate the risks of second cancers and cardiovascular diseases associated with an optimized volumetric modulated arc therapy (VMAT) planning solution in a selected cohort of stage I/II Hodgkin lymphoma (HL) patients treated with either involved-node or involved-site radiation therapy in comparison with 3-dimensional conformal radiation therapy (3D-CRT). Methods and Materials: Thirty-eight patients (13 males and 25 females) were included. Disease extent was mediastinum alone (n=8, 21.1%); mediastinum plus unilateral neck (n=19, 50%); mediastinum plus bilateral neck (n=11, 29.9%). Prescription dose was 30 Gy in 2-Gy fractions. Only 5 patients had mediastinal bulky disease at diagnosis (13.1%). Anteroposterior 3D-CRT was compared with a multiarc optimized VMAT solution. Lung, breast, and thyroid cancer risks were estimated by calculating a lifetime attributable risk (LAR), with a LAR ratio (LAR{sub VMAT}-to-LAR{sub 3D-CRT}) as a comparative measure. Cardiac toxicity risks were estimated by calculating absolute excess risk (AER). Results: The LAR ratio favored 3D-CRT for lung cancer induction risk in mediastinal alone (P=.004) and mediastinal plus unilateral neck (P=.02) presentations. LAR ratio for breast cancer was lower for VMAT in mediastinal plus bilateral neck presentations (P=.02), without differences for other sites. For thyroid cancer, no significant differences were observed, regardless of anatomical presentation. A significantly lower AER of cardiac (P=.038) and valvular diseases (P<.0001) was observed for VMAT regardless of disease extent. Conclusions: In a cohort of patients with favorable characteristics in terms of disease extent at diagnosis (large prevalence of nonbulky presentations without axillary involvement), optimized VMAT reduced heart disease risk with comparable risks of thyroid and breast cancer, with an increase in lung cancer induction probability. The results are however strongly influenced by

  8. Design of Linear Accelerator (LINAC) tanks for proton therapy via Particle Swarm Optimization (PSO) and Genetic Algorithm (GA) approaches

    Energy Technology Data Exchange (ETDEWEB)

    Castellano, T.; De Palma, L.; Laneve, D.; Strippoli, V.; Cuccovilllo, A.; Prudenzano, F. [Electrical and Information Engineering Department (DEI), Polytechnic Institute of Bari, 4 Orabona Street, CAP 70125, Bari, (Italy); Dimiccoli, V.; Losito, O.; Prisco, R. [ITEL Telecomunicazioni, 39 Labriola Street, CAP 70037, Ruvo di Puglia, Bari, (Italy)

    2015-07-01

    A homemade computer code for designing a Side- Coupled Linear Accelerator (SCL) is written. It integrates a simplified model of SCL tanks with the Particle Swarm Optimization (PSO) algorithm. The computer code main aim is to obtain useful guidelines for the design of Linear Accelerator (LINAC) resonant cavities. The design procedure, assisted via the aforesaid approach seems very promising, allowing future improvements towards the optimization of actual accelerating geometries. (authors)

  9. Bioactive Components in Fish Venoms

    Science.gov (United States)

    Ziegman, Rebekah; Alewood, Paul

    2015-01-01

    Animal venoms are widely recognized excellent resources for the discovery of novel drug leads and physiological tools. Most are comprised of a large number of components, of which the enzymes, small peptides, and proteins are studied for their important bioactivities. However, in spite of there being over 2000 venomous fish species, piscine venoms have been relatively underrepresented in the literature thus far. Most studies have explored whole or partially fractioned venom, revealing broad pharmacology, which includes cardiovascular, neuromuscular, cytotoxic, inflammatory, and nociceptive activities. Several large proteinaceous toxins, such as stonustoxin, verrucotoxin, and Sp-CTx, have been isolated from scorpaenoid fish. These form pores in cell membranes, resulting in cell death and creating a cascade of reactions that result in many, but not all, of the physiological symptoms observed from envenomation. Additionally, Natterins, a novel family of toxins possessing kininogenase activity have been found in toadfish venom. A variety of smaller protein toxins, as well as a small number of peptides, enzymes, and non-proteinaceous molecules have also been isolated from a range of fish venoms, but most remain poorly characterized. Many other bioactive fish venom components remain to be discovered and investigated. These represent an untapped treasure of potentially useful molecules. PMID:25941767

  10. Bioactive Egg Components and Inflammation

    Directory of Open Access Journals (Sweden)

    Catherine J. Andersen

    2015-09-01

    Full Text Available Inflammation is a normal acute response of the immune system to pathogens and tissue injury. However, chronic inflammation is known to play a significant role in the pathophysiology of numerous chronic diseases, such as cardiovascular disease, type 2 diabetes mellitus, and cancer. Thus, the impact of dietary factors on inflammation may provide key insight into mitigating chronic disease risk. Eggs are recognized as a functional food that contain a variety of bioactive compounds that can influence pro- and anti-inflammatory pathways. Interestingly, the effects of egg consumption on inflammation varies across different populations, including those that are classified as healthy, overweight, metabolic syndrome, and type 2 diabetic. The following review will discuss the pro- and anti-inflammatory properties of egg components, with a focus on egg phospholipids, cholesterol, the carotenoids lutein and zeaxanthin, and bioactive proteins. The effects of egg consumption of inflammation across human populations will additionally be presented. Together, these findings have implications for population-specific dietary recommendations and chronic disease risk.

  11. Bioactivity of plasma implanted biomaterials

    Science.gov (United States)

    Chu, Paul K.

    2006-01-01

    Plasma immersion ion implantation and deposition (PIII&D) is an effective technique to enhance the surface bioactivity of materials. In this paper, recent progress made in our laboratory on plasma surface modification of biomedical materials is described. NiTi alloys have unique super-elastic and shape memory properties and are suitable for orthopedic implants but the leaching of toxic Ni may pose health hazards in humans. We have recently investigated the use of acetylene, oxygen and nitrogen PIII&D to prevent out-diffusion of nickel and good results have been obtained. Silicon is the most important material in the microelectronics industry but its surface biocompatibility has not been investigated in details. We have recently performed hydrogen PIII into silicon to improve the surface bioactivity and observed biomimetic growth of apatite on the surface in simulated body fluids. Diamond-like carbon (DLC) is widely used in the industry due to its excellent mechanical properties and chemical inertness and by incorporation of elements such as nitrogen and phosphorus, the surface blood compatibility can be improved. The properties as well as in vitro biological test results are discussed in this article.

  12. The Stability of Bioactive Compounds in Spaceflight Foods

    Science.gov (United States)

    Cooper, M. R.; Douglas, G. L.

    2017-01-01

    . Because of the limited number of foods with high concentrations of the bioactive compounds, additional menu variety, formulation optimization, and reduced temperature storage will be required to ensure delivery of several bioactive compounds in the space food system. Validation of stability to five years will enable provisioning of these functional foods within the space food system for a mission to Mars.

  13. Bioactive Glasses in Dentistry: A Review

    Directory of Open Access Journals (Sweden)

    Abbasi Z

    2015-03-01

    Full Text Available Bioactive glasses are silicate-based and can form a strong chemical bond with the tissues. These biomaterials are highly biocompatible and can form a hydroxyapatite layer when implanted in the body or soaked in the simulated body fluid. Due to several disadvantages, conventional glass processing method including melting of glass components, is replaced by sol-gel method with a large number of benefits such as low processing temperature, higher purity and homogeneity and therefore better control of bioactivity. Bioactive glasses have a wide range of applications, particularly in dentistry. These glasses can be used as particulates or monolithic shapes and porous or dense constructs in different applications such as remineralization or hypersensitivity treatment. Some properties of bioactive glasses such as antibacterial properties can be promoted by adding different elements into the glass. Bioactive glasses can also be used to modify different biocompatible materials that need to be bioactive. This study reviews the significant developments of bioactive glasses in clinical application, especially dentistry. Furthermore, we will discuss the field of bioactive glasses from beginning to the current developments, which includes processing methods, applications, and properties of these glasses.

  14. Bioactive Compounds And Encapsulation Of Yanang ( Tiliacora ...

    African Journals Online (AJOL)

    The stability of bioactive compounds was evaluated using phenolic compounds, total antioxidant, carotenoids and chlorophyll. Results: The study of the bioactivity of Yanang extracts found that extraction with water was the appropriate application. The study of Yanang encapsulation demonstrated that gum Arabic, ...

  15. Mineralization and bone regeneration using a bioactive elastin-like recombinamer membrane

    NARCIS (Netherlands)

    Tejeda-Montes, E.; Klymov, A.; Nejadnik, M.R.; Alonso, M.; Rodriguez-Cabello, J.C.; Walboomers, X.F.; Mata, A.

    2014-01-01

    The search for alternative therapies to improve bone regeneration continues to be a major challenge for the medical community. Here we report on the enhanced mineralization, osteogenesis, and in vivo bone regeneration properties of a bioactive elastin-like recombinamer (ELR) membrane. Three

  16. Investigation of ethosomes as surrogate carriers for bioactives

    Directory of Open Access Journals (Sweden)

    Devina Verma

    2016-01-01

    Full Text Available Background: Ethosomal vesicular system delivering a bioactive phytochemical, chrysin, was developed for transdermal delivery to increase its permeability and penetrability. Materials and Methods: Ethosomal system was optimized by keeping lecithin and ethanol concentration as independent variable while size and size distribution were taken as dependent variables. The optimized formulation was then subjected to various in vitro characterization parameters. Results: Ethosomal vesicle with an optimum size and polydispersity index of 134 ± 35 nm and 0.153, respectively, and entrapment efficiency of 80.05 ± 2.6% was considered as optimized and subjected to characterization. The scanning electron microscopy and transmission electron microscopy showed spherical entities with uniform surface whereas in vitro permeation and retention study showed the sustained mode of drug release and better skin retention as compared to hydroethanolic solution of the drug. The confocal laser scanning microscopy study reiterated high penetrability of vesicles into the skin. Histopathological and Fourier transform infrared spectroscopy analysis revealed its mechanism of penetration. Conclusion : The study thus demonstrated the ability of the ethosomal vesicles as surrogate carriers for delivery of bioactive agents through the skin for better amelioration of skin inflammation and other diseases.

  17. The effect of sonication on bioactive compounds in carrot juice

    Directory of Open Access Journals (Sweden)

    A Ayaseh

    2016-01-01

    Full Text Available The objective of this research was to determine the effect of ultrasound treatment on bioactive compounds (including total phenolic, total flavonoids, total carotenoids, ascorbic acid of carrot juice in comparison with conventional thermal process. Carrot juice samples were sonicated according to D-optimal response surface design with processing variables of temperature (25, 37.5 and 50°C, time (10, 20 and 30 min and power (350 and 400 w at a constant frequency of 24 kHz. Results showed that ultrasound temperature (P

  18. Optimal schedules of fractionated radiation therapy by way of the greedy principle: biologically-based adaptive boosting

    Science.gov (United States)

    Hanin, Leonid; Zaider, Marco

    2014-08-01

    We revisit a long-standing problem of optimization of fractionated radiotherapy and solve it in considerable generality under the following three assumptions only: (1) repopulation of clonogenic cancer cells between radiation exposures follows linear birth-and-death Markov process; (2) clonogenic cancer cells do not interact with each other; and (3) the dose response function s(D) is decreasing and logarithmically concave. Optimal schedules of fractionated radiation identified in this work can be described by the following ‘greedy’ principle: give the maximum possible dose as soon as possible. This means that upper bounds on the total dose and the dose per fraction reflecting limitations on the damage to normal tissue, along with a lower bound on the time between successive fractions of radiation, determine the optimal radiation schedules completely. Results of this work lead to a new paradigm of dose delivery which we term optimal biologically-based adaptive boosting (OBBAB). It amounts to (a) subdividing the target into regions that are homogeneous with respect to the maximum total dose and maximum dose per fraction allowed by the anatomy and biological properties of the normal tissue within (or adjacent to) the region in question and (b) treating each region with an individual optimal schedule determined by these constraints. The fact that different regions may be treated to different total dose and dose per fraction mean that the number of fractions may also vary between regions. Numerical evidence suggests that OBBAB produces significantly larger tumor control probability than the corresponding conventional treatments.

  19. An Investigation into Spent Coffee Waste as a Renewable Source of Bioactive Compounds and Industrially Important Sugars

    OpenAIRE

    Damhan S. Scully; Jaiswal, Amit K.; Nissreen Abu-Ghannam

    2016-01-01

    Conventional coffee brewing techniques generate vast quantities of spent espresso grounds (SEGs) rich in lignocellulose and valuable bioactives. These bioactive compounds can be exploited as a nutraceutical or used in a range of food products, while breakdown of lignocellulose generates metabolizable sugars that can be used for the production of various high-value products such as biofuels, amino acids and enzymes. Response surface methodology (RSM) was used to optimize the enzymatic sacchari...

  20. Treatment Adherence as a New Choice Factor for Optimization of Oral Anticoagulation Therapy in Patients with Atrial Fibrillation and Hemostatic Gene Polymorphisms

    Directory of Open Access Journals (Sweden)

    Yu. P. Skirdenko

    2016-01-01

    Full Text Available Aim. To evaluate treatment adherence and prevalence of CYP2C9 and VKORC1 gene mutations in patients with atrial fibrillation (AF and provide rationale of choice for oral anticoagulation therapy.Material and methods. Treatment adherence was evaluated in 137 AF patients (aged 35-85 years with quantitative estimation of drug therapy adherence along with compliance to medical support and lifestyle modifications. Among them 82 patients underwent polymerase chain reaction (PCR analysis of CYP2C9 and VKORC1 gene polymorphisms.Results. Patients receiving anticoagulation therapy are characterized by lower level of adherence compared to patients without anticoagulants (65.2±19.3% vs 68.5±19.1%; Wald-Wolfowitz; p<0.05. Considering all studied parameters men are less adherent than women (54.7±18.6% vs 60.6±16.7%; Kolmogorov-Smirnov; p<0.05. Patients receiving new oral anticoagulants (NOAC have better compliance compared with patients of warfarin group. Mutations in CYP2C9 gene were detected in 32.9%, VKORC1 – in 68.3%, and their combination – in 21.9% of study participants. Warfarin therapy may be potentially dangerous in such patients due to low adherence.Conclusion. Considering high prevalence of CYP2C9 and VKORC1 gene mutations treatment adherence should be estimated to optimize choice of anticoagulation therapy. NOAC treatment should be considered in patients with low adherence for prevention of thromboembolic complications.

  1. SU-F-BRD-01: A Novel 4D Robust Optimization Mitigates Interplay Effect in Intensity-Modulated Proton Therapy for Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Liu, W; Shen, J; Stoker, J; Bues, M [Mayo Clinic Arizona, Phoenix, AZ (United States); Schild, S; Wong, W [Mayo Clinic, Phoenix, Arizona (United States); Chang, J; Liao, Z; Wen, Z; Sahoo, N [MD Anderson Cancer Center, Houston, TX (United States); Herman, M [Mayo Clinic, Rochester, MN (United States); Mohan, R [UT MD Anderson Cancer Center, Houston, TX (United States)

    2015-06-15

    Purpose: To compare the impact of interplay effect on 3D and 4D robustly optimized intensity-modulated proton therapy (IMPT) plans to treat lung cancer. Methods: Two IMPT plans were created for 11 non-small-cell-lung-cancer cases with 6–14 mm spots. 3D robust optimization generated plans on average CTs with the internal gross tumor volume density overridden to deliver 66 CGyE in 33 fractions to the internal target volume (ITV). 4D robust optimization generated plans on 4D CTs with the delivery of prescribed dose to the clinical target volume (CTV). In 4D optimization, the CTV of individual 4D CT phases received non-uniform doses to achieve a uniform cumulative dose. Dose evaluation software was developed to model time-dependent spot delivery to incorporate interplay effect with randomized starting phases of each field per fraction. Patient anatomy voxels were mapped from phase to phase via deformable image registration to score doses. Indices from dose-volume histograms were used to compare target coverage, dose homogeneity, and normal-tissue sparing. DVH indices were compared using Wilcoxon test. Results: Given the presence of interplay effect, 4D robust optimization produced IMPT plans with better target coverage and homogeneity, but slightly worse normal tissue sparing compared to 3D robust optimization (unit: Gy) [D95% ITV: 63.5 vs 62.0 (p=0.014), D5% - D95% ITV: 6.2 vs 7.3 (p=0.37), D1% spinal cord: 29.0 vs 29.5 (p=0.52), Dmean total lung: 14.8 vs 14.5 (p=0.12), D33% esophagus: 33.6 vs 33.1 (p=0.28)]. The improvement of target coverage (D95%,4D – D95%,3D) was related to the ratio RMA3/(TVx10−4), with RMA and TV being respiratory motion amplitude (RMA) and tumor volume (TV), respectively. Peak benefit was observed at ratios between 2 and 10. This corresponds to 125 – 625 cm3 TV with 0.5-cm RMA. Conclusion: 4D optimization produced more interplay-effect-resistant plans compared to 3D optimization. It is most effective when respiratory motion is modest

  2. Addressing Relapse in Cognitive Behavioral Therapy for Panic Disorder: Methods for Optimizing Long-Term Treatment Outcomes

    Science.gov (United States)

    Arch, Joanna J.; Craske, Michelle G.

    2011-01-01

    In this paper, we present a client with panic disorder and agoraphobia who relapses following a full course of cognitive behavioral therapy (CBT). To frame the client's treatment, the major components of CBT for panic disorder with or without agoraphobia (PD/A) are reviewed. Likely reasons for the treatment's failure and strategies for improving…

  3. Construction Of An Optimized Lentiviral Vector Containing Pdx-1 Gene For Transduction Of Stem Cells Towards Gene Therapy Diabetes Type 1

    Directory of Open Access Journals (Sweden)

    S Rahmati

    2013-02-01

    Full Text Available Abstract Background & aim: Nowadays, most of gene therapy protocols are performed by lentiviral vectors. One of the most important factors which is involved in pancreas development and transcription of insulin gene is pancreatic & duodenal homeobox 1 (PDX-1 transcription factor. The goal of this study was to optimize a lentiviral construct, containing pdx-1 gene, to transfect stem cells towards gene therapy of type-1 diabetes. Methods: In this experimental study, first, the pdx-1 gene was multiplied by PCR from pcDNA3.1-pdx-1 and cloned into pTG19-T vector. Then, pdx-1 was subcloned on upstream of IRES-EGFP gene into IRES2-EGFP vector. At the next step, the cloned parts of IRES-EGFP and pdx-1 were isolated and cloned into the lentiviral expression vector pSINTREM in upstream of TRE-CMV gene. After sequencing, final construct was transfected into HEK 293 cells and gene expression of pdx-1 was evaluated using flow cytometry analysis and reverse fluorescent microscopy. Results: Flow cytometry results and inverted fluorescent microscopy observing showed that pdx-1 and GFP genes are expressed in cells transfected with final recombinant construct. Conclusion: Regarding the design of this construct, to ensure long time expression with higher in vivo and in vitro expression efficiency for stem cells and also use of Tet on induced optimized system, it seems that the current construct can be among the best ones to transfect stem cells. Key words: Gene therapy, Diabetes, Stem cells

  4. Avoiding Untimely Implantable Cardioverter/Defibrillator Implantation by Intensified Heart Failure Therapy Optimization Supported by the Wearable Cardioverter/Defibrillator-The PROLONG Study.

    Science.gov (United States)

    Duncker, David; König, Thorben; Hohmann, Stephan; Bauersachs, Johann; Veltmann, Christian

    2017-01-17

    Optimal timing of implantation of an implantable cardioverter/defibrillator (ICD) after newly diagnosed heart failure is unclear given that late reverse remodelling may occur. We aimed to analyze left ventricular ejection fraction (LVEF) after diagnosis of an LVEF ≤35% during optimization of heart failure drug therapy. One hundred fifty-six patients with newly diagnosed LVEF ≤35% receiving a wearable cardioverter/defibrillator (WCD) were analyzed. WCD was prescribed for 3 months until first re-evaluation. Indications for prolongation of WCD wearing period instead of ICD implantation were: (1) LVEF at 3-month visit 30% to 35%; (2) increase in LVEF of ≥5% compared to the last visit; and (3) nonoptimized heart failure medication. Mean LVEF was 24±7% at diagnosis and 39±11% at last follow-up (mean, 12±10 months). Whereas 88 patients presented a primary preventive ICD indication (LVEF ≤35%) at 3-month follow-up, only 58 showed a persistent primary preventive ICD indication at last follow-up. This delayed improvement in LVEF was related to nonischemic origin of cardiomyopathy, New York Heart Association functional class at baseline, heart rate, better LVEF after 3 months, and higher dosages of mineralocorticoid receptor antagonist. Twelve appropriate WCD shocks for ventricular tachycardia/ventricular fibrillation occurred in 11 patients. Two patients suffered from ventricular tachycardia/ventricular fibrillation beyond 3 months after diagnosis. A relevant proportion of patients with newly diagnosed heart failure shows recovery of LVEF >35% beyond 3 months after initiation of heart failure therapy. To avoid untimely ICD implantation, prolongation of WCD period should be considered in these patients to prevent sudden cardiac death while allowing left ventricular reverse remodeling during intensified drug therapy. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  5. SU-E-J-16: Automatic Image Contrast Enhancement Based On Automatic Parameter Optimization for Radiation Therapy Setup Verification

    Energy Technology Data Exchange (ETDEWEB)

    Qiu, J [Taishan Medical University, Taian, Shandong (China); Washington University in St Louis, St Louis, MO (United States); Li, H. Harlod; Zhang, T; Yang, D [Washington University in St Louis, St Louis, MO (United States); Ma, F [Taishan Medical University, Taian, Shandong (China)

    2015-06-15

    Purpose: In RT patient setup 2D images, tissues often cannot be seen well due to the lack of image contrast. Contrast enhancement features provided by image reviewing software, e.g. Mosaiq and ARIA, require manual selection of the image processing filters and parameters thus inefficient and cannot be automated. In this work, we developed a novel method to automatically enhance the 2D RT image contrast to allow automatic verification of patient daily setups as a prerequisite step of automatic patient safety assurance. Methods: The new method is based on contrast limited adaptive histogram equalization (CLAHE) and high-pass filtering algorithms. The most important innovation is to automatically select the optimal parameters by optimizing the image contrast. The image processing procedure includes the following steps: 1) background and noise removal, 2) hi-pass filtering by subtracting the Gaussian smoothed Result, and 3) histogram equalization using CLAHE algorithm. Three parameters were determined through an iterative optimization which was based on the interior-point constrained optimization algorithm: the Gaussian smoothing weighting factor, the CLAHE algorithm block size and clip limiting parameters. The goal of the optimization is to maximize the entropy of the processed Result. Results: A total 42 RT images were processed. The results were visually evaluated by RT physicians and physicists. About 48% of the images processed by the new method were ranked as excellent. In comparison, only 29% and 18% of the images processed by the basic CLAHE algorithm and by the basic window level adjustment process, were ranked as excellent. Conclusion: This new image contrast enhancement method is robust and automatic, and is able to significantly outperform the basic CLAHE algorithm and the manual window-level adjustment process that are currently used in clinical 2D image review software tools.

  6. OPTIMAL, an occupational therapy led self-management support programme for people with multimorbidity in primary care: a randomized controlled trial.

    Science.gov (United States)

    Garvey, Jess; Connolly, Deirdre; Boland, Fiona; Smith, Susan M

    2015-05-12

    We investigated the effectiveness of an occupational therapy led self-management support programme, OPTIMAL, designed to address the challenges of living with multiple chronic conditions or multimorbidity in a primary care setting. Pragmatic feasibility randomised controlled trial including fifty participants with multimorbidity recruited from family practice and primary care settings. OPTIMAL is a six-week community-based programme, led by occupational therapy facilitators and focuses on problems associated with managing multimorbidity. The primary outcome was frequency of activity participation. Secondary outcomes included self-perception of, satisfaction with and ability to perform daily activities, independence in activities of daily living, anxiety and depression, self-efficacy, health-related quality of life, self-management support, healthcare utilisation and individualised goal attainment. Outcomes were collected within two weeks of intervention completion. There was a significant improvement in frequency of activity participation, measured using the Frenchay Activities Index, for the intervention group compared to the control group (Adjusted Mean Difference at follow up 4.22. 95% Confidence Interval 1.59-6.85). There were also significant improvements in perceptions of activity performance and satisfaction, self-efficacy, independence in daily activities and quality of life. Additionally, the intervention group demonstrated significantly higher levels of goal achievement, following the intervention. No significant differences were found between the two groups in anxiety, depression, self-management scores or healthcare utilisation. OPTIMAL significantly improved frequency of activity participation, self-efficacy and quality of life for patients with multimorbidity. Further work is required to test the sustainability of these effects over time but this study indicates that it is a promising intervention that can be delivered in primary care and community

  7. Bioactive glasses and glass-ceramics.

    Science.gov (United States)

    Rawlings, R D

    1993-01-01

    Bioactive materials are designed to induce a specific biological activity; in most cases the desired biological activity is one that will give strong bonding to bone. A range of materials has been assessed as being capable of bonding to bone, but this paper is solely concerned with bioactive glasses and glass-ceramics. Firstly, the structure and processing of glasses and glass-ceramics are described, as a basic knowledge is essential for the understanding of the development and properties of the bioactive materials. The effect of composition and structure on the bioactivity is then discussed, and it will be shown that bioactivity is associated with the formation of an apatite layer on the surface of the implant. A survey of mechanical performance demonstrates that the structure and mechanical properties of glass-ceramics depend upon whether the processing involves casting or sintering and that the strength and toughness of glass-ceramics are superior to those of glasses. Attempts to further improve the mechanical performance by the use of non-monolithic components, i.e. bioactive coatings on metal substrates and glass and glass-ceramic matrix composites, are also reviewed and are shown to have varying degrees of success. Finally, some miscellaneous applications, namely bioactive bone cements and bone fillers, are briefly covered.

  8. Clinically applicable Monte Carlo-based biological dose optimization for the treatment of head and neck cancers with spot-scanning proton therapy

    CERN Document Server

    Tseung, H Wan Chan; Kreofsky, C R; Ma, D; Beltran, C

    2016-01-01

    Purpose: To demonstrate the feasibility of fast Monte Carlo (MC) based inverse biological planning for the treatment of head and neck tumors in spot-scanning proton therapy. Methods: Recently, a fast and accurate Graphics Processor Unit (GPU)-based MC simulation of proton transport was developed and used as the dose calculation engine in a GPU-accelerated IMPT optimizer. Besides dose, the dose-averaged linear energy transfer (LETd) can be simultaneously scored, which makes biological dose (BD) optimization possible. To convert from LETd to BD, a linear relation was assumed. Using this novel optimizer, inverse biological planning was applied to 4 patients: 2 small and 1 large thyroid tumor targets, and 1 glioma case. To create these plans, constraints were placed to maintain the physical dose (PD) within 1.25 times the prescription while maximizing target BD. For comparison, conventional IMRT and IMPT plans were created for each case in Eclipse (Varian, Inc). The same critical structure PD constraints were use...

  9. Bioactive vegetable proteins and peptides in lipid-lowering; nutraceutical potential.

    Science.gov (United States)

    Ruiz Ruiz, Jorge Carlos; Betancur Ancona, David Abram; Segura Campos, Maira Rubi

    2014-04-01

    As the last century saw a decline in the burden of nutritional deficiency and infectious disease, the global burden of chronic disease, cardiovascular disease (CVD) in particular, is increasing. CVD is the leading cause of death in the developed countries. Significant research efforts on the prevention and treatment of this disease have identified elevated plasma cholesterol as a primary risk factor for CVD. Although CVD progresses with hypercholesterolemia, it seems possibility to delay and prevent its development through improvement of diet. Recent findings demonstrate that protein concentrates, protein hydrolysates, and peptides derived from vegetables may promote a significant decrease in blood cholesterol concentration. This reduction in cholesterol and lipid levels by protein, protein hydrolysates, and peptides can be the result of dietary changes, reduced cholesterol biosynthesis, changes in bile acid synthesis, and reduced absorption of lipid cholesterol and bile acid. Combination drug/diet therapies may reduce the number of drug prescriptions, the progressive rise in "optimal" drug dosage and costs associated with pharmaceutical management of disease. These bioactive vegetable proteins, hydrolysates and peptides may be used in formulation of functional foods, nutraceuticals, and natural drugs because of their health benefit effects suggesting their use as an alternative in treatment of various dyslipidemias, and a potential agent for reducing cardiovascular diseases risk factors. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  10. Peptides: Production, bioactivity, functionality, and applications

    DEFF Research Database (Denmark)

    Hajfathalian, Mona; Ghelichi, Sakhi; García Moreno, Pedro Jesús

    2017-01-01

    Production of peptides with various effects from proteins of different sources continues to receive academic attention. Researchers of different disciplines are putting increasing efforts to produce bioactive and functional peptides from different sources such as plants, animals, and food industry...... by-products. The aim of this review is to introduce production methods of hydrolysates and peptides and provide a comprehensive overview of their bioactivity in terms of their effects on immune, cardiovascular, nervous, and gastrointestinal systems. Moreover, functional and antioxidant properties...... of hydrolysates and isolated peptides are reviewed. Finally, industrial and commercial applications of bioactive peptides including their use in nutrition and production of pharmaceuticals and nutraceuticals are discussed....

  11. Bioactivities and Health Benefits of Wild Fruits

    Directory of Open Access Journals (Sweden)

    Ya Li

    2016-08-01

    Full Text Available Wild fruits are exotic or underutilized. Wild fruits contain many bioactive compounds, such as anthocyanins and flavonoids. Many studies have shown that wild fruits possess various bioactivities and health benefits, such as free radical scavenging, antioxidant, anti-inflammatory, antimicrobial, and anticancer activity. Therefore, wild fruits have the potential to be developed into functional foods or pharmaceuticals to prevent and treat several chronic diseases. In the present article, we review current knowledge about the bioactivities and health benefits of wild fruits, which is valuable for the exploitation and utilization of wild fruits.

  12. TH-A-9A-02: BEST IN PHYSICS (THERAPY) - 4D IMRT Planning Using Highly- Parallelizable Particle Swarm Optimization

    Energy Technology Data Exchange (ETDEWEB)

    Modiri, A; Gu, X; Sawant, A [UT Southwestern Medical Center, Dallas, TX (United States)

    2014-06-15

    Purpose: We present a particle swarm optimization (PSO)-based 4D IMRT planning technique designed for dynamic MLC tracking delivery to lung tumors. The key idea is to utilize the temporal dimension as an additional degree of freedom rather than a constraint in order to achieve improved sparing of organs at risk (OARs). Methods: The target and normal structures were manually contoured on each of the ten phases of a 4DCT scan acquired from a lung SBRT patient who exhibited 1.5cm tumor motion despite the use of abdominal compression. Corresponding ten IMRT plans were generated using the Eclipse treatment planning system. These plans served as initial guess solutions for the PSO algorithm. Fluence weights were optimized over the entire solution space i.e., 10 phases × 12 beams × 166 control points. The size of the solution space motivated our choice of PSO, which is a highly parallelizable stochastic global optimization technique that is well-suited for such large problems. A summed fluence map was created using an in-house B-spline deformable image registration. Each plan was compared with a corresponding, internal target volume (ITV)-based IMRT plan. Results: The PSO 4D IMRT plan yielded comparable PTV coverage and significantly higher dose—sparing for parallel and serial OARs compared to the ITV-based plan. The dose-sparing achieved via PSO-4DIMRT was: lung Dmean = 28%; lung V20 = 90%; spinal cord Dmax = 23%; esophagus Dmax = 31%; heart Dmax = 51%; heart Dmean = 64%. Conclusion: Truly 4D IMRT that uses the temporal dimension as an additional degree of freedom can achieve significant dose sparing of serial and parallel OARs. Given the large solution space, PSO represents an attractive, parallelizable tool to achieve globally optimal solutions for such problems. This work was supported through funding from the National Institutes of Health and Varian Medical Systems. Amit Sawant has research funding from Varian Medical Systems, VisionRT Ltd. and Elekta.

  13. Optimization of antiaggregant therapy in rheumatoid arthritis and coronary heart disease patients receiving nonsteroidal anti-inflammatory drugs

    Directory of Open Access Journals (Sweden)

    Tatyana Vladimirovna Kropotina

    2012-01-01

    Full Text Available Objective: to study coagulative and vascular-thrombocytic hemostases in patients with rheumatoid arthritis (RA and coronary heart disease (CHD depending on therapy with different nonsteroidal anti-inflammatory drugs (NSAIDs alone and in combination with low-dose aspirin. Subjects and methods. The trial enrolled 58 patients (43 women and 15 men with a valid diagnosis of RA. The patients' mean age was 61.2 years; the disease duration averaged 10 years. All the patients received therapy with disease-modifying antirheumatic drugs (DMARDs and NSAIDs. All had CHD; 52 of the 58 patients presented with arterial hypertension; 30 had noncoronary atherosclerosis. Cardiovascular diseases were first identified in 18 patients. All took heart medications. Coagulative and vascular-thrombocytic hemostases were studied in all the patients and the results were compared depending on to the taken NSAID (diclofenac, tenoxicam, nimesulide, meloxicam. Thirty-seven patients who had not previously received antiaggregant therapy were given aspirin in a dose of 100 mg when they were found to have platelet hyperaggregation and aggregation was restudied on aspirin therapy days 7-8. A control group consisted of 26 healthy men (mean age 55 years who received no medications. Results. In patients with RA and CHD, activated coagulative hemostasis was identified in 65.5% of cases. The signs of hypercoagulation were observed in 35 of the 58 patients. When different NSAIDs were used, the coagulative hemostatic changes were unidirectional and no statistically significant differences were found between the groups. The patients taking diclofenac, nimesulide, or meloxicam were found to have activated vascular-thrombocytic hemostasis. Those receiving tenoxicam showed a tendency towards decreased adrenaline-induced platelet aggregation (the drug's aspirin-like effect; however, no statistical processing was made because of few cases. The use of aspirin in the patients taking diclofenac

  14. Changes in Thirst Intensity During Optimization of Heart Failure Medical Therapy by Nurses at the Outpatient Clinic.

    Science.gov (United States)

    Waldréus, Nana; Hahn, Robert G; Lyngå, Patrik; van der Wal, Martje H L; Hägglund, Ewa; Jaarsma, Tiny

    2016-01-01

    Thirst can be aggravated in patients with heart failure (HF), and optimization of HF medication can have positive impact on thirst. The aims of this study were to describe changes in thirst intensity and to determine factors associated with high thirst intensity during optimization of HF medication. Patients with HF (N = 66) who were referred to an HF clinic for up-titration of HF medication were included. Data were collected during the first visit to the clinic and at the end of the treatment program. Data were dichotomized by the median visual analog scale score for thirst, dividing patients into 2 groups: low thirst intensity (0-20 mm) and high thirst intensity (>20 mm on a visual analog scale of 0-100 mm). In total, 67% of the patients reported a higher thirst intensity after the HF up-titration program. There was no difference in thirst intensity between the patients who reached target doses and those who did not. Plasma urea level (odds ratio, 1.33; 95% confidence interval, 1.07-1.65) and fluid restriction (odds ratio, 6.25; 95% confidence interval, 1.90-20.5) were independently associated with high thirst intensity in patients with HF. Thirst intensity increased in two-thirds of the patients during a time period of optimization of HF medication. Fluid restriction and plasma urea levels were associated with high thirst intensity.

  15. An optimized posterior axillary boost technique in radiation therapy to supraclavicular and axillary lymph nodes: A comparative study

    Energy Technology Data Exchange (ETDEWEB)

    Hernandez, Victor, E-mail: vhernandezmasgrau@gmail.com [Department of Medical Physics, Hospital Sant Joan de Reus, IISPV, Tarragona (Spain); Arenas, Meritxell [Department of Radiation therapy, Hospital Sant Joan de Reus, IISPV, Tarragona (Spain); Müller, Katrin [Department of Medical Physics, Hospital Sant Joan de Reus, IISPV, Tarragona (Spain); Gomez, David; Bonet, Marta [Department of Radiation therapy, Hospital Sant Joan de Reus, IISPV, Tarragona (Spain)

    2013-01-01

    To assess the advantages of an optimized posterior axillary (AX) boost technique for the irradiation of supraclavicular (SC) and AX lymph nodes. Five techniques for the treatment of SC and levels I, II, and III AX lymph nodes were evaluated for 10 patients selected at random: a direct anterior field (AP); an anterior to posterior parallel pair (AP-PA); an anterior field with a posterior axillary boost (PAB); an anterior field with an anterior axillary boost (AAB); and an optimized PAB technique (OptPAB). The target coverage, hot spots, irradiated volume, and dose to organs at risk were evaluated and a statistical analysis comparison was performed. The AP technique delivered insufficient dose to the deeper AX nodes. The AP-PA technique produced larger irradiated volumes and higher mean lung doses than the other techniques. The PAB and AAB techniques originated excessive hot spots in most of the cases. The OptPAB technique produced moderate hot spots while maintaining a similar planning target volume (PTV) coverage, irradiated volume, and dose to organs at risk. This optimized technique combines the advantages of the PAB and AP-PA techniques, with moderate hot spots, sufficient target coverage, and adequate sparing of normal tissues. The presented technique is simple, fast, and easy to implement in routine clinical practice and is superior to the techniques historically used for the treatment of SC and AX lymph nodes.

  16. Optimization of left ventricular pacing site plus multipoint pacing improves remodeling and clinical response to cardiac resynchronization therapy at 1 year.

    Science.gov (United States)

    Zanon, Francesco; Marcantoni, Lina; Baracca, Enrico; Pastore, Gianni; Lanza, Daniela; Fraccaro, Chiara; Picariello, Claudio; Conte, Luca; Aggio, Silvio; Roncon, Loris; Pacetta, Domenico; Badie, Nima; Noventa, Franco; Prinzen, Frits W

    2016-08-01

    Approximately one-third of the patients with heart failure (HF) treated with cardiac resynchronization therapy (CRT) fail to respond. Positioning the left ventricular (LV) pacing lead in the area of the latest electrical delay may improve the response to CRT. Multipoint pacing (MPP) of the LV has been shown to improve the acute hemodynamic response. The purpose of this study was to test the hypothesis that patients treated with MPP in whom LV pacing location is optimized have better long-term clinical outcomes than do patients treated with conventional CRT. We evaluated the echocardiographic and clinical response of 110 patients with HF treated for nearly 1 year with either conventional CRT (standard [STD] group, n = 54, 49%), CRT with hemodynamic and electrical optimization of the LV pacing site (optimized [OPT] group, n = 36, 33%), or OPT combined with MPP (OPT + MPP group, n = 20, 18%). Responders were classified in terms of reduction in end-systolic volume index ≥15%, reduction in New York Heart Association (NYHA) class ≥1, and Packer score variation (NYHA response with no HF-related hospitalization events or death). In STD, OPT, and OPT + MPP groups, 56%, 72%, and 90% of patients, respectively, were end-systolic volume index responders (P = .004) and 67%, 78%, and 95% were NYHA class responders (P = .012); 59%, 67%, and 90% of patients exhibited a 1-year Packer score of 0 (P = .018). These trends remained significant after adjustment for confounding factors by multivariate logistic analysis. Combining MPP with optimal positioning of the LV lead on the basis of electrical delay and hemodynamics enhances reverse remodeling and improves clinical outcomes beyond the effect due to conventional CRT. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  17. Repetitive optimizing left ventricular pacing configurations with quadripolar leads improves response to cardiac resynchronization therapy: A single-center randomized clinical trial.

    Science.gov (United States)

    Gu, Min; Jin, Han; Hua, Wei; Fan, Xiao-Han; Ding, Li-Gang; Wang, Jing; Niu, Hong-Xia; Cai, Chi; Zhang, Shu

    2017-09-01

    This study aimed to investigate whether repetitive optimizing left ventricular pacing configurations (LVPCs) with quadripolar leads (QUAD) can improve response to cardiac resynchronization therapy (CRT). Fifty-two eligible patients were enrolled and 1:1 randomized to either the quadripolar LV leads (QUAD) group or the conventional bipolar leads (CONV) group. In the QUAD group, optimization of LVPC was performed for all patients before discharge and for nonresponders at 3 months follow-up. Clinical evaluations and transthoracic echocardiograms were performed before, 3, and 6 months after CRT implantation. At 3 months follow-up, 16 of 25 (64%) patients in the CONV group (1 patient was lost to follow-up) and 18 of 26 (69%) patients in the QUAD group were classified as responders. After optimizing the LVPCs in 3-month nonresponders in the QUAD group, 21 of 26 (80.8%) patients in the QUAD group were classified as responders at 6 months as compared with 17 of 25 (68%) patients in the CONV group. Left ventricular end-systolic volume (LVESV) reduction, left ventricular ejection fraction (LVEF) increase, and New York Heart Association (NYHA) functional class reduction at 6 months were significantly greater in the QUAD group than in the CONV group (LVESV: -26.9 ± 13.8 vs -17.2 ± 13.3%; P = .013; LVEF: +12.7 ± 8.0 vs +7.8 ± 6.3 percentage points; P = .017; NYHA: -1.27 ± 0.67 vs -0.72 ± 0.54 functional classes; P = .002). Compared with conventional bipolar leads, CRT using quadripolar leads with repetitive optimized LVPCs resulted in an additional increase in LVEF and reduction in LVESV and NYHA functional class at 6-month follow-up.

  18. Limited Impact of Setup and Range Uncertainties, Breathing Motion, and Interplay Effects in Robustly Optimized Intensity Modulated Proton Therapy for Stage III Non-small Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Inoue, Tatsuya [Department of Radiology, Juntendo University Urayasu Hospital, Chiba (Japan); Widder, Joachim; Dijk, Lisanne V. van [Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Takegawa, Hideki [Department of Radiation Oncology, Kansai Medical University Hirakata Hospital, Osaka (Japan); Koizumi, Masahiko; Takashina, Masaaki [Department of Medical Physics and Engineering, Osaka University Graduate School of Medicine, Osaka (Japan); Usui, Keisuke; Kurokawa, Chie; Sugimoto, Satoru [Department of Radiation Oncology, Juntendo University Graduate School of Medicine, Tokyo (Japan); Saito, Anneyuko I. [Department of Radiology, Juntendo University Urayasu Hospital, Chiba (Japan); Department of Radiation Oncology, Juntendo University Graduate School of Medicine, Tokyo (Japan); Sasai, Keisuke [Department of Radiation Oncology, Juntendo University Graduate School of Medicine, Tokyo (Japan); Veld, Aart A. van' t; Langendijk, Johannes A. [Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Korevaar, Erik W., E-mail: e.w.korevaar@umcg.nl [Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands)

    2016-11-01

    Purpose: To investigate the impact of setup and range uncertainties, breathing motion, and interplay effects using scanning pencil beams in robustly optimized intensity modulated proton therapy (IMPT) for stage III non-small cell lung cancer (NSCLC). Methods and Materials: Three-field IMPT plans were created using a minimax robust optimization technique for 10 NSCLC patients. The plans accounted for 5- or 7-mm setup errors with ±3% range uncertainties. The robustness of the IMPT nominal plans was evaluated considering (1) isotropic 5-mm setup errors with ±3% range uncertainties; (2) breathing motion; (3) interplay effects; and (4) a combination of items 1 and 2. The plans were calculated using 4-dimensional and average intensity projection computed tomography images. The target coverage (TC, volume receiving 95% of prescribed dose) and homogeneity index (D{sub 2} − D{sub 98}, where D{sub 2} and D{sub 98} are the least doses received by 2% and 98% of the volume) for the internal clinical target volume, and dose indexes for lung, esophagus, heart and spinal cord were compared with that of clinical volumetric modulated arc therapy plans. Results: The TC and homogeneity index for all plans were within clinical limits when considering the breathing motion and interplay effects independently. The setup and range uncertainties had a larger effect when considering their combined effect. The TC decreased to <98% (clinical threshold) in 3 of 10 patients for robust 5-mm evaluations. However, the TC remained >98% for robust 7-mm evaluations for all patients. The organ at risk dose parameters did not significantly vary between the respective robust 5-mm and robust 7-mm evaluations for the 4 error types. Compared with the volumetric modulated arc therapy plans, the IMPT plans showed better target homogeneity and mean lung and heart dose parameters reduced by about 40% and 60%, respectively. Conclusions: In robustly optimized IMPT for stage III NSCLC, the setup and range

  19. Bioactive Carbohydrates and Peptides in Foods: An Overview of Sources, Downstream Processing Steps and Associated Bioactivities.

    Science.gov (United States)

    Hayes, Maria; Tiwari, Brijesh K

    2015-09-17

    Bioactive peptides and carbohydrates are sourced from a myriad of plant, animal and insects and have huge potential for use as food ingredients and pharmaceuticals. However, downstream processing bottlenecks hinder the potential use of these natural bioactive compounds and add cost to production processes. This review discusses the health benefits and bioactivities associated with peptides and carbohydrates of natural origin and downstream processing methodologies and novel processes which may be used to overcome these.

  20. Targeted therapy using nanotechnology: focus on cancer.

    Science.gov (United States)

    Sanna, Vanna; Pala, Nicolino; Sechi, Mario

    2014-01-01

    Recent advances in nanotechnology and biotechnology have contributed to the development of engineered nanoscale materials as innovative prototypes to be used for biomedical applications and optimized therapy. Due to their unique features, including a large surface area, structural properties, and a long circulation time in blood compared with small molecules, a plethora of nanomaterials has been developed, with the potential to revolutionize the diagnosis and treatment of several diseases, in particular by improving the sensitivity and recognition ability of imaging contrast agents and by selectively directing bioactive agents to biological targets. Focusing on cancer, promising nanoprototypes have been designed to overcome the lack of specificity of conventional chemotherapeutic agents, as well as for early detection of precancerous and malignant lesions. However, several obstacles, including difficulty in achieving the optimal combination of physicochemical parameters for tumor targeting, evading particle clearance mechanisms, and controlling drug release, prevent the translation of nanomedicines into therapy. In spite of this, recent efforts have been focused on developing functionalized nanoparticles for delivery of therapeutic agents to specific molecular targets overexpressed on different cancer cells. In particular, the combination of targeted and controlled-release polymer nanotechnologies has resulted in a new programmable nanotherapeutic formulation of docetaxel, namely BIND-014, which recently entered Phase II clinical testing for patients with solid tumors. BIND-014 has been developed to overcome the limitations facing delivery of nanoparticles to many neoplasms, and represents a validated example of targeted nanosystems with the optimal biophysicochemical properties needed for successful tumor eradication.

  1. Detection Optimization for Prompt Gamma Ray Imaging during Boron Neutron Capture Therapy (BNCT): A Monte Carlo simulation study

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Moo Sub; Yoon, Do Kun; Suh, Tae Suk [Catholic University of Korea, Seoul (Korea, Republic of)

    2016-05-15

    The purpose of this study was the statistical analysis of the prompt gamma ray peak induced by the boron neutron capture therapy (BNCT) from spectra using Monte Carlo simulation. For the simulation, the information of the sixteen detector materials was used to simulate spectra by the neutron capture reaction. The results in this study are the first reported data regarding the peak discrimination of 478 keV energy prompt gamma ray using the many cases. (sixteen detector materials). The reliable data based on the Monte Carlo method and statistical method with the identical conditions was deducted. Our results are important data in the BNCT study for the peak detection within actual experiments.

  2. Thiocarbamates from Moringa oleifera Seeds Bioactive against Virulent and Multidrug-Resistant Vibrio Species

    Science.gov (United States)

    de Sousa, Oscarina Viana; Hofer, Ernesto; Mafezoli, Jair; Barbosa, Francisco Geraldo

    2017-01-01

    Prospect of antibacterial agents may provide an alternative therapy for diseases caused by multidrug-resistant bacteria. This study aimed to evaluate the in vitro bioactivity of Moringa oleifera seed extracts against 100 vibrios isolated from the marine shrimp Litopenaeus vannamei. Ethanol extracts at low (MOS-E) and hot (MOS-ES) temperature are shown to be bioactive against 92% and 90% of the strains, respectively. The most efficient Minimum Inhibitory Concentration (MIC) levels of MOS-E and MOS-ES against a high percentage of strains were 32 µg mL−1. Bioguided screening of bioactive compounds showed that the ethyl acetate fraction from both extracts was the only one that showed antibacterial activity. Vibriocidal substances, niazirine and niazimicine, were isolated from the aforementioned fraction through chromatographic fractionation. PMID:28770224

  3. Assessment of nickel oxide substituted bioactive glass-ceramic on in vitro bioactivity and mechanical properties

    Energy Technology Data Exchange (ETDEWEB)

    Kumar Vyas, V.; Sampath Kumar, A.; Ali, A.; Prasad, S.; Srivastava, P.; Prasanna Mallick, S.; Ershad, Md.; Prasad Singh, S.; Pyare, R.

    2016-07-01

    Many type of oxide substituted glass-ceramics like strontium, cobalt, barium and titanium have shown bioactivity with improved mechanical properties. The present work reports the in vitro bioactivity and mechanical properties of nickel oxide substituted in bioactive glass-ceramic and results were compared with 45S5 bioactive glass-ceramic. Bioactive glass ceramics were processed through controlled crystallization of their respective bioactive glasses. The formed crystalline phases in bioactive glass-ceramics were identified using X-ray diffraction (XRD) analysis. The formation of HA layer was assessed by immersing them in the simulated body fluid (SBF) for different soaking periods. The formation of hydroxyapatite was confirmed by FTIR spectrometry, SEM and pH measurement. Densities and mechanical properties of the samples were found to increase considerably with an increasing the concentration of nickel oxide. A decrease in glass transition temperature (Tg) with NiO addition showed that the nickel oxide had acted as an intermediate in smaller quantities in the bioactive glass. The cell culture studies demonstrated that the samples containing low concentration of NiO from 0 to 1.65mol% were non-cytotoxic against osteoblast cells. Finally, this investigation clearly concluded that NiO doped bioactive glass would be potential biomaterials for biomedical applications. (Author)

  4. A simple geometric algorithm to predict optimal starting gantry angles using equiangular-spaced beams for intensity modulated radiation therapy of prostate cancer.

    Science.gov (United States)

    Potrebko, Peter S; McCurdy, Boyd M C; Butler, James B; El-Gubtan, Adel S; Nugent, Zoann

    2007-10-01

    A fast, geometric beam angle optimization (BAO) algorithm for clinical intensity-modulated radiation therapy (IMRT) was implemented on ten localized prostate cancer patients on the Radiation Therapy Oncology Group (RTOG) 0126 protocol. The BAO algorithm computed the beam intersection volume (BIV) within the rectum and bladder using five and seven equiangular-spaced beams as a function of starting gantry angle for comparison to the V 75 Gy and V 70 Gy. A mathematical theory was presented to explain the correlation of BIV with dose and dose-volume metrics. The class solution 'W' pattern in the rectal V 75 Gy and V 70 Gy as a function of starting gantry angle using five equiangular-spaced beams (with two separate minima centered near 20 degrees and 50 degrees) was reproduced by the 5 BIV within the rectum. A strong correlation was found between the rectal 5 BIV and the rectal V 75 Gy and V 70 Gy as a function of starting gantry angle. The BAO algorithm predicted the location of the two dosimetric minima in rectal V 75 Gy and V 70 Gy (optimal starting gantry angles) to within 5 degrees. It was demonstrated that the BIV geometric variations for seven equiangular-spaced beams were too small to translate into a strong dosimetric effect in the rectal V 75 Gy and V 70 Gy. The relatively flat distribution with starting gantry angle of the bladder V 75 Gy and V 70 Gy was reproduced by the bladder five and seven BIV for each patient. A geometric BAO method based on BIV has the advantage over dosimetric BAO methods of simplicity and rapid computation time. This algorithm can be used as a standalone optimization method or act as a rapid calculation filter to reduce the search space for a dosimetric BAO method. Given the clinically infeasible computation times of many dosimetric beam orientation optimization algorithms, this robust geometric BIV algorithm has the potential to facilitate beam angle selection for prostate IMRT in clinical practice.

  5. Bioactive Compounds from Marine Bacteria and Fungi

    National Research Council Canada - National Science Library

    Debbab, Abdessamad; Aly, Amal H; Lin, Wen H; Proksch, Peter

    2010-01-01

    .... Up till now, only a small number of microorganisms have been investigated for bioactive metabolites, yet a huge number of active substances with some of them featuring unique structural skeletons have been isolated...

  6. Simultaneous Analysis of Bioactive Markers from Orthosiphon ...

    African Journals Online (AJOL)

    RP-HPLC) method for the analysis of the crude extracts of Orthosiphon stamineus. Methods: A simple and facile analytical method was developed using RP- HPLC with UV detection for the identification and quantitation of bioactive markers ...

  7. Chemical constituents and bioactivities of starfish.

    Science.gov (United States)

    Dong, Guang; Xu, Tunhai; Yang, Bin; Lin, Xiuping; Zhou, Xuefeng; Yang, Xianwen; Liu, Yonghong

    2011-05-01

    Starfish have been the research topic in many chemical and pharmacological laboratories due to their complex secondary metabolites and diverse bioactivities. The aim of this review is to provide an up-to-date review on the chemistry and bioactivity of compounds isolated from all kinds of starfish to illustrate the chemodiversity and biological significance of these constituents, along with their geographical distribution where it is discernible. Copyright © 2011 Verlag Helvetica Chimica Acta AG, Zürich.

  8. Method for estimating optimal spectral and energy parameters of laser irradiation in photodynamic therapy of biological tissue

    Energy Technology Data Exchange (ETDEWEB)

    Lisenko, S A; Kugeiko, M M [Belarusian State University, Minsk (Belarus)

    2015-04-30

    We have solved the problem of layer-by-layer laser-light dosimetry in biological tissues and of selecting an individual therapeutic dose in laser therapy. A method is proposed for real-time monitoring of the radiation density in tissue layers in vivo, concentrations of its endogenous (natural) and exogenous (specially administered) chromophores, as well as in-depth distributions of the spectrum of light action on these chromophores. As the background information use is made of the spectrum of diffuse light reflected from a patient's tissue, measured by a fibre-optic spectrophotometer. The measured spectrum is quantitatively analysed by the method of approximating functions for fluxes of light multiply scattered in tissue and by a semi-analytical method for calculating the in-depth distribution of the light flux in a multi-layered medium. We have shown the possibility of employing the developed method for monitoring photosensitizer and oxyhaemoglobin concentrations in tissue, light power absorbed by chromophores in tissue layers at different depths and laser-induced changes in the tissue morphology (vascular volume content and ratios of various forms of haemoglobin) during photodynamic therapy. (biophotonics)

  9. Single Particle and PET-based Platform for Identifying Optimal Plasmonic Nano-Heaters for Photothermal Cancer Therapy

    DEFF Research Database (Denmark)

    Jørgensen, Jesper Tranekjær; Nørregaard, Kamilla; Tian, Pengfei

    2016-01-01

    Plasmonic nanoparticle-based photothermal cancer therapy is a promising new tool to inflict localized and irreversible damage to tumor tissue by hyperthermia, without harming surrounding healthy tissue. We developed a single particle and positron emission tomography (PET)-based platform to quanti......Plasmonic nanoparticle-based photothermal cancer therapy is a promising new tool to inflict localized and irreversible damage to tumor tissue by hyperthermia, without harming surrounding healthy tissue. We developed a single particle and positron emission tomography (PET)-based platform...... to quantitatively correlate the heat generation of plasmonic nanoparticles with their potential as cancer killing agents. In vitro, the heat generation and absorption cross-section of single irradiated nanoparticles were quantified using a temperature sensitive lipid-based assay and compared to their theoretically...... predicted photo-absorption. In vivo, the heat generation of irradiated nanoparticles was evaluated in human tumor xenografts in mice using 2-deoxy-2-[F-18]fluoro-D-glucose ((18)F-FDG) PET imaging. To validate the use of this platform, we quantified the photothermal efficiency of near infrared resonant...

  10. High-pressure processing as emergent technology for the extraction of bioactive ingredients from plant materials.

    Science.gov (United States)

    Jun, Xi

    2013-01-01

    High-pressure processing is a food processing technique that has shown great potentials in the food industry. Recently, it was developed to extract bioactive ingredients from plant materials, known as ultrahigh pressure extraction (UPE), taking advantages of time saving, higher extraction yields, fewer impurities in the extraction solution, minimal heat and can avoid thermal degradation on the activity and structure of bioactive components, and so on. This review provides an overview of the developments in the UPE of bioactive ingredients from plant material. Apart from a brief presentation of the theories of UPE and extraction equipment systems, the principal parameters that influence the extraction efficiency to be optimized in the UPE (e.g., solvent, pressure, temperature, extraction time, and the number of cycle) were discussed in detail, and finally the more recent applications of UPE for the extraction of active compounds from plant materials were summarized.

  11. Development of a novel technique for maxillofacial reconstruction using custom-made bioactive ceramic implants

    Science.gov (United States)

    Kulbakin, D. E.; Choinzonov, E. L.; Kulkov, S. N.; Buyakova, S. P.; Chernov, V. I.; Mukhamedov, M. R.; Buyakov, A. S.

    2017-09-01

    Recently, there has been a trend towards the search for new, safe and effective methods of reconstruction of maxillofacial defects after tumor excision. Among various materials used for bone defect reconstruction, ceramics has attached a great deal of attention. The purpose of our study was to develop a technique for personified approach to the reconstruction of maxillofacial bone defects with bioactive ceramic implants. In our study we used the technique of virtual implant planning for maxillofacial reconstruction using preoperative CT data of the patient's facial skeleton. Bioactive ceramic implant materials meet all the requirements for medical materials used in reconstructive surgery. The technique described in this paper to customize prefabricated bioactive ceramic implants enables surgeons to perform reconstruction of large postoperative defects in the maxillofacial region, thereby making custom implants suitable for any patient. The use of this technique decreases surgical time, reduces time needed for postoperative recovery, lowers overall patient morbidity and optimizes aesthetic and functional results.

  12. Advances on Bioactive Polysaccharides from Medicinal Plants.

    Science.gov (United States)

    Xie, Jian-Hua; Jin, Ming-Liang; Morris, Gordon A; Zha, Xue-Qiang; Chen, Han-Qing; Yi, Yang; Li, Jing-En; Wang, Zhi-Jun; Gao, Jie; Nie, Shao-Ping; Shang, Peng; Xie, Ming-Yong

    2016-07-29

    In recent decades, the polysaccharides from the medicinal plants have attracted a lot of attention due to their significant bioactivities, such as anti-tumor activity, antioxidant activity, anticoagulant activity, antidiabetic activity, radioprotection effect, anti-viral activity, hypolipidemic and immunomodulatory activities, which make them suitable for medicinal applications. Previous studies have also shown that medicinal plant polysaccharides are non-toxic and show no side effects. Based on these encouraging observations, most researches have been focusing on the isolation and identification of polysaccharides, as well as their bioactivities. A large number of bioactive polysaccharides with different structural features and biological effects from medicinal plants have been purified and characterized. This review provides a comprehensive summary of the most recent developments in physiochemical, structural features and biological activities of bioactive polysaccharides from a number of important medicinal plants, such as polysaccharides from Astragalus membranaceus, Dendrobium plants, Bupleurum, Cactus fruits, Acanthopanax senticosus, Angelica sinensis (Oliv.) Diels, Aloe barbadensis Miller, and Dimocarpus longan Lour. Moreover, the paper has also been focused on the applications of bioactive polysaccharides for medicinal applications. Recent studies have provided evidence that polysaccharides from medicinal plants can play a vital role in bioactivities. The contents and data will serve as a useful reference material for further investigation, production, and application of these polysaccharides in functional foods and therapeutic agents.

  13. Understanding the functional anatomy of the frontalis and glabellar complex for optimal aesthetic botulinum toxin type A therapy.

    Science.gov (United States)

    Lorenc, Z Paul; Smith, Stacy; Nestor, Mark; Nelson, Diane; Moradi, Amir

    2013-10-01

    Botulinum neurotoxin type A (BoNTA) is approved for the treatment of glabellar lines and also is commonly injected in an off-label fashion in the frontalis (i.e., frontalis epicranius) muscle to improve the appearance of horizontal forehead lines. This study aimed to review and discuss both the anatomy and physiology of the frontalis muscle and its relationship with antagonist muscles in the upper face and to provide a guide for the use of BoNTA to treat forehead rhytides while minimizing the occurrence of complications such as brow ptosis. A PubMed search was conducted to identify practitioner opinion and clinical publications on the efficacy and safety of BoNTA for aesthetic treatment of the upper face. The use of BoNTA produces durable improvement in the appearance of moderate to severe horizontal forehead lines. Dose and injection technique must be adjusted and individualized based on the variable anatomy and function/mass of muscles in the forehead and upper face as well as on patient goals. Optimal aesthetic outcomes can be achieved by skillfully balancing the opposing effects of the frontalis muscle and its intricate interactions with the procerus, corrugator supercilii, depressor supercilii, and orbicularis oculi muscles. The use of BoNTA to improve the aesthetic appearance of horizontal forehead lines is optimized when clinicians take into account variations in frontalis muscle function and position, anatomy of the brow, and proper injection technique when they devise individualized treatment regimens.

  14. Microwave extraction of bioactive compounds

    Directory of Open Access Journals (Sweden)

    Monika Blekić

    2011-01-01

    Full Text Available Microwave extraction presents novel extraction and treatment method for food processing. In paper, several examples of microwave extraction of bioactive compounds are presented. Also, novel innovative equipment for microwave extraction and hydrodiffusion with gravitation is presented. Advantage of using novel equipment for microwave extraction is shown, and it include, shorter treatment time, less usage or without any solvent use. Novel method is compared to standard extraction methods. Some positive and negative aspects of microwave heating can be observed, and also its influence on development of oxidation in sunflower oil subjected to microwave heating. Also, use of microwaves for the extraction of essential oils is shown. One can also see the advantages of solvent-free microwave extraction of essential oil from aromatic herbs in comparison with the standard extraction, and determination of antioxidant components in rice bran oil extracted by microwave-assisted method. Comparison of microwave and ultrasound extraction, as well as positive and negative aspects of the combination of microwaves and ultrasound is described.

  15. Sustained release of complexed DNA from films: Study of bioactivity and intracellular tracking.

    Science.gov (United States)

    Mondal, Debasish; Ramgopal, Yamini; Tiwari, Sandeep Kumar; Venkatraman, Subbu S

    2010-09-01

    Sustained DNA delivery from polymeric films provides a means for localized and prolonged gene therapy. However, in the case of bioactive molecules such as plasmid DNA (pDNA), there are limitations on the achievable release profiles as well as on the maintenance of bioactivity over time. In this report, the authors have investigated the bioactivity of the released DNA (naked and complexed with lipofectamine) from polymeric films using in vitro cell transfection of COS-7 cell lines. The polymeric system consists of a biodegradable semicrystalline polymer such as poly(ε-caprolactone) (PCL) with or without blended gelatin. Sustained release of lipoplexes and of pDNA is shown over several days. However, lipoplexes released from pure PCL films show no transfection on day 18, whereas lipoplexes released from PCL-gelatin films continue to transfect cells on day 18 of release. Confocal studies were used to determine the reasons for this difference in transfection efficiency, and it is proposed that association of the lipoplex with gelatin confers protection from degradation in the cytoplasm. The results also showed that the bioactivity of released lipoplexes was superior to that of the naked pDNA. For both naked pDNA and the lipoplexes, the presence of gelatin helped to maintain the bioactivity over several days.

  16. Preparation and characterization of bioactive glass nanoparticles prepared by sol-gel for biomedical applications

    Science.gov (United States)

    Luz, Gisela M.; Mano, João F.

    2011-12-01

    Bioactive glass nanoparticles (BG-NPs), based on both ternary (SiO2-CaO-P2O5) and binary (SiO2-CaO) systems, were prepared via an optimized sol-gel method. The pH of preparation and the effect of heat treatment temperature were evaluated, as well as the effect of suppressing P in the bioactivity ability of the materials. The morphology and composition of the BG-NPs were studied using FTIR, XRD and SEM. The bioactive character of these materials was accessed in vitro by analyzing the ability for apatite formation onto the surface after being immersed in simulated body fluid (SBF). XRD, EDX and SEM were used to confirm the bioactivity of the materials. The BG-NP effect on cell metabolic activity was assessed by seeding L929 cells with their leachables, proving the non-cytotoxicity of the materials. Finally the most bioactive BG-NPs developed (ternary system prepared at pH 11.5 and treated at 700 °C) were successfully combined with chitosan in the production of biomimetic nanocomposite osteoconductive membranes that could have the potential to be used in guided tissue regeneration.

  17. Preparation and characterization of bioactive glass nanoparticles prepared by sol-gel for biomedical applications.

    Science.gov (United States)

    Luz, Gisela M; Mano, João F

    2011-12-09

    Bioactive glass nanoparticles (BG-NPs), based on both ternary (SiO(2)-CaO-P(2)O(5)) and binary (SiO(2)-CaO) systems, were prepared via an optimized sol-gel method. The pH of preparation and the effect of heat treatment temperature were evaluated, as well as the effect of suppressing P in the bioactivity ability of the materials. The morphology and composition of the BG-NPs were studied using FTIR, XRD and SEM. The bioactive character of these materials was accessed in vitro by analyzing the ability for apatite formation onto the surface after being immersed in simulated body fluid (SBF). XRD, EDX and SEM were used to confirm the bioactivity of the materials. The BG-NP effect on cell metabolic activity was assessed by seeding L929 cells with their leachables, proving the non-cytotoxicity of the materials. Finally the most bioactive BG-NPs developed (ternary system prepared at pH 11.5 and treated at 700 °C) were successfully combined with chitosan in the production of biomimetic nanocomposite osteoconductive membranes that could have the potential to be used in guided tissue regeneration.

  18. Strontium-substituted bioactive glasses in vitro osteogenic and antibacterial effects.

    Science.gov (United States)

    Liu, Jie; Rawlinson, Simon C F; Hill, Robert G; Fortune, Farida

    2016-03-01

    Bioactive glass forms a bone mineral apatite interface and can be engineered to promote optimal bone regeneration. Strontium (Sr(2+)) stimulates osteoblast and inhibits osteoclast activities in vitro, and is used clinically as a treatment for osteoporosis. Dental bone defect repair requires rapid bone formation for early osseointegration but, can be subject to infection. The aim of this study was to investigate the osteogenic and antibacterial effects of strontium-substituted bioactive glasses in vitro. Strontium-substituted bioactive glasses were designed and produced. Then the osteogenic potential and antibacterial effects of bioactive glass particulates were explored. Alkaline phosphatase activity, cell number, Type I collagen and mineral nodule formation of MC3T3-E1 cells were significantly promoted by the 5% strontium-substituted glass (5Sr). Furthermore, after incubation with 0.001g and 0.01g glass particulates, the growth of sub-gingival bacteria, Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis was significantly inhibited; the antibacterial activity being dependent on the percentage of strontium in the glasses. These results show that strontium-substituted bioactive glasses significantly promote osteogenic responses of MC3T3-E1 osteoblast-like cells and inhibit the growth of A. actinomycetemcomitans and P. gingivalis. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

  19. Choices in IgG replacement therapy for primary immune deficiency diseases: subcutaneous IgG vs. intravenous IgG and selecting an optimal dose.

    Science.gov (United States)

    Berger, Melvin

    2011-12-01

    Subcutaneous IgG (SCIG) is becoming more popular, but there is still uncertainty about efficacy and optimal dosing. This review discusses recent pharmacokinetic studies and applications of SCIG therapy, and its efficacy in the context of emerging understanding of the relationship between dosing and efficacy of both intravenous IgG (IVIG) and SCIG replacement therapy for primary immunodeficiency diseases. Three preparations of IgG have been licensed in the US in the past year. Their bioavailabilities are 65-70% of that of IVIG. Pooled analyses show that the efficacy of SCIG in preventing infections is proportional to the steady-state levels achieved, and similar to that of IVIG. Pharmacokinetic studies allow estimation of doses that will yield desired serum levels with both IVIG and SCIG, and when switching from one route to another. Pooled analyses show that at equivalent total doses, weekly SCIG results in steady-state levels 10-20% higher than troughs on monthly IVIG. For most patients, the choice between routes should be based on individual preference, and the regimen should be individualized to achieve the desired outcomes.

  20. Optimal antiretroviral therapy adherence as evaluated by CASE index score tool is associated with virological suppression in HIV-infected adults in Dakar, Senegal.

    Science.gov (United States)

    Byabene, A K; Fortes-Déguénonvo, L; Niang, K; Manga, M N; Bulabula, A N H; Nachega, J B; Seydi, M

    2017-06-01

    To determine the prevalence and factors associated with optimal antiretroviral therapy (ART) adherence and virological failure (VLF) among HIV-infected adults enrolled in the national ART programme at the teaching hospital of Fann, Dakar, Senegal. Cross-sectional study from 1 September 2013 to 30 January 2014. (1) optimal ART adherence by the Center for Adherence Support Evaluation (CASE) Index Score (>10) and (2) VLF (HIV RNA > 1000 copies/ml). Diagnostic accuracy of CASE Index Score assessed using sensitivity (Se), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV) and corresponding 95% confidence intervals (CIs). Multivariate logistic regression analysis was performed to identify independent factors associated with optimal adherence and VLF. Of 98 HIV-infected patients on ART, 68% were female. The median (IQR) age was 42 (20-50) years. A total of 57 of 98 (60%) were on ART more than 3 years, and majority (88%) were on NNRTI-based first-line ART regimen. A total of 79 of 98 (80%) patients reported optimal ART adherence, and only five of 84 (5.9%) had documented VLF. Patients with VLF were significantly more likely to have suboptimal ART adherence (17.7% vs. 2.9%; P = 0.02). CASE Index Score showed the best trade-off in Se (78.9%, 95% CI: 54.4-93.9%), Sp (20.0%, 95% CI: 11.1-31.7), PPV (22.4, 95% CI: 13.1-34.2%) and NPV (76.5%, 95% CI: 50.1-93.2), when used VLF threshold of HIV RNA >50 copies/ml. Factors independently associated with VLF were CASE Index Score <10 ([aOR] = 13.0, 95% CI: 1.1-147.9; P = 0.04) and being a boosted PI-based ART regimen ([aOR] = 27.0, 95% CI: 2.4-309.4; P = 0.008). Optimal ART adherence is achievable in a high proportion of HIV-infected adults in this study population. CASE Index Score was independently associated with virological outcomes, supporting usefulness of this low-cost ART adherence monitoring tool in this setting. © 2017 John Wiley & Sons Ltd.

  1. An Automated Treatment Plan Quality Control Tool for Intensity-Modulated Radiation Therapy Using a Voxel-Weighting Factor-Based Re-Optimization Algorithm.

    Directory of Open Access Journals (Sweden)

    Ting Song

    Full Text Available Intensity-modulated radiation therapy (IMRT currently plays an important role in radiotherapy, but its treatment plan quality can vary significantly among institutions and planners. Treatment plan quality control (QC is a necessary component for individual clinics to ensure that patients receive treatments with high therapeutic gain ratios. The voxel-weighting factor-based plan re-optimization mechanism has been proved able to explore a larger Pareto surface (solution domain and therefore increase the possibility of finding an optimal treatment plan. In this study, we incorporated additional modules into an in-house developed voxel weighting factor-based re-optimization algorithm, which was enhanced as a highly automated and accurate IMRT plan QC tool (TPS-QC tool. After importing an under-assessment plan, the TPS-QC tool was able to generate a QC report within 2 minutes. This QC report contains the plan quality determination as well as information supporting the determination. Finally, the IMRT plan quality can be controlled by approving quality-passed plans and replacing quality-failed plans using the TPS-QC tool. The feasibility and accuracy of the proposed TPS-QC tool were evaluated using 25 clinically approved cervical cancer patient IMRT plans and 5 manually created poor-quality IMRT plans. The results showed high consistency between the QC report quality determinations and the actual plan quality. In the 25 clinically approved cases that the TPS-QC tool identified as passed, a greater difference could be observed for dosimetric endpoints for organs at risk (OAR than for planning target volume (PTV, implying that better dose sparing could be achieved in OAR than in PTV. In addition, the dose-volume histogram (DVH curves of the TPS-QC tool re-optimized plans satisfied the dosimetric criteria more frequently than did the under-assessment plans. In addition, the criteria for unsatisfied dosimetric endpoints in the 5 poor-quality plans could

  2. An Optimized GD2-Targeting Retroviral Cassette for More Potent and Safer Cellular Therapy of Neuroblastoma and Other Cancers.

    Directory of Open Access Journals (Sweden)

    Simon Thomas

    Full Text Available Neuroblastoma is the commonest extra cranial solid cancer of childhood. Despite escalation of treatment regimens, a significant minority of patients die of their disease. Disialoganglioside (GD2 is consistently expressed at high-levels in neuroblastoma tumors, which have been targeted with some success using therapeutic monoclonal antibodies. GD2 is also expressed in a range of other cancer but with the exception of some peripheral nerves is largely absent from non-transformed tissues. Chimeric Antigen Receptors (CARs are artificial type I proteins which graft the specificity of a monoclonal antibody onto a T-cell. Clinical data with early CAR designs directed against GD2 have shown some promise in Neuroblastoma. Here, we describe a GD2-targeting CAR retroviral cassette, which has been optimized for CAR T-cell persistence, efficacy and safety.

  3. Rigorous optimization and validation of potent RNA CAR T cell therapy for the treatment of common epithelial cancers expressing folate receptor

    Science.gov (United States)

    Schutsky, Keith; Song, De-Gang; Lynn, Rachel; Smith, Jenessa B.; Poussin, Mathilde; Figini, Mariangela; Zhao, Yangbing; Powell, Daniel J.

    2015-01-01

    Using lentiviral technology, we recently demonstrated that incorporation of CD27 costimulation into CARs greatly improves antitumor activity and T cell persistence. Still, virus-mediated gene transfer is expensive, laborious and enables long-term persistence, creating therapies which cannot be easily discontinued if toxic. To address these concerns, we utilized a non-integrating RNA platform to engineer human T cells to express FRα-specific, CD27 CARs and tested their capacity to eliminate human FRα+ cancer. Novel CARs comprised of human components were constructed, C4-27z and C4opt-27z, a codon-optimized variant created for efficient expression. Following RNA electroporation, C4-27z and C4opt-27z CAR expression is initially ubiquitous but progressively declines across T cell populations. In addition, C4-27z and C4opt-27z RNA CAR T cells secrete high levels of Th-1 cytokines and display strong cytolytic function against human FRα+ cancers in a time- and antigen-dependent manner. Further, C4-27z and C4opt-27z CAR T cells exhibit significant proliferation in vivo, facilitate the complete regression of fully disseminated human ovarian cancer xenografts in mice and reduce the progression of solid ovarian cancer. These results advocate for rapid progression of C4opt-27z RNA CAR to the clinic and establish a new paradigm for preclinical optimization and validation of RNA CAR candidates destined for clinical translation. PMID:26359629

  4. Numerical optimization of sequential cryogen spray cooling and laser irradiation for improved therapy of port wine stain.

    Science.gov (United States)

    Milanič, Matija; Jia, Wangcun; Nelson, J Stuart; Majaron, Boris

    2011-02-01

    Despite application of cryogen spray (CS) precooling, customary treatment of port wine stain (PWS) birthmarks with a single laser pulse does not result in complete lesion blanching for a majority of patients. One obvious reason is nonselective absorption by epidermal melanin, which limits the maximal safe radiant exposure. Another possible reason for treatment failure is screening of laser light within large PWS vessels, which prevents uniform heating of the entire vessel lumen. Our aim is to identify the parameters of sequential CS cooling and laser irradiation that will allow optimal photocoagulation of various PWS blood vessels with minimal risk of epidermal thermal damage. Light and heat transport in laser treatment of PWS are simulated using a custom 3D Monte Carlo model and 2D finite element method, respectively. Protein denaturation in blood and skin are calculated using the Arrhenius kinetic model with tissue-specific coefficients. Simulated PWS vessels with diameters of 30-150 µm are located at depths of 200-600 µm, and shading by nearby vessels is accounted for according to PWS histology data from the literature. For moderately pigmented and dark skin phototypes, PWS blood vessel coagulation and epidermal thermal damage are assessed for various parameters of sequential CS cooling and 532-nm laser irradiation, i.e. the number of pulses in a sequence (1-5), repetition rate (7-30 Hz), and radiant exposure. Simulations of PWS treatment in darker skin phototypes indicate specific cooling/irradiation sequences that provide significantly higher efficacy and safety as compared to the customary single-pulse approach across a wide range of PWS blood vessel diameters and depths. The optimal sequences involve three to five laser pulses at repetition rates of 10-15 Hz. Application of the identified cooling/irradiation sequences may offer improved therapeutic outcome for patients with resistant PWS, especially in darker skin phototypes. Copyright © 2011

  5. Generation of an optimized lentiviral vector encoding a high-expression factor VIII transgene for gene therapy of hemophilia A.

    Science.gov (United States)

    Johnston, J M; Denning, G; Doering, C B; Spencer, H T

    2013-06-01

    We previously compared the expression of several human factor VIII (fVIII) transgene variants and demonstrated the superior expression properties of B domain-deleted porcine fVIII. Subsequently, a hybrid human/porcine fVIII molecule (HP-fVIII) comprising 91% human amino-acid sequence was engineered to maintain the high-expression characteristics of porcine fVIII. The bioengineered construct then was used effectively to treat knockout mice with hemophilia A. In the current study, we focused on optimizing self-inactivating (SIN) lentiviral vector systems by analyzing the efficacy of various lentiviral components in terms of virus production, transduction efficiency and transgene expression. Specifically, three parameters were evaluated: (1) the woodchuck hepatitis post-transcriptional regulatory element (WPRE), (2) HIV versus SIV viral vector systems and (3) various internal promoters. The inclusion of a WPRE sequence had negligible effects on viral production and HP-fVIII expression. HIV and SIV vectors were compared and found to be similar with respect to transduction efficiency in both K562s and HEK-293T cells. However, there was an enhanced expression of HP-fVIII by the SIV system, which was evident in both K562 and BHK-M cell lines. To further compare expression of HP-fVIII from an SIV-based lentiviral system, we constructed expression vectors containing the high expression transgene and a human elongation factor-1 alpha, cytomegalovirus (CMV) or phosphoglycerate kinase promoter. Expression was significantly greater from the CMV promoter, which also yielded therapeutic levels of HP-fVIII in hemophilia A mice. Based on these studies, an optimized vector contains the HP-fVIII transgene driven by a CMV internal promoter within a SIV-based lentiviral backbone lacking a WPRE.

  6. The effect of bioactive glass content on synthesis and bioactivity of composite poly (lactic-co-glycolic acid)/bioactive glass substrate for tissue engineering.

    Science.gov (United States)

    Yao, Jun; Radin, Shula; S Leboy, Phoebe; Ducheyne, Paul

    2005-05-01

    Tissue engineering offers a promising new approach to bone tissue grafting. One material that has received attention in this regard is the polymer poly (lactic-co-glycolic acid) (PLGA). It has the advantage of controllable bioresorption and ease of processing. Another material of interest is bioactive glass (BG), which shows the ability to stimulate osteoblastic differentiation of osteoprogenitor cells. In this study, we reported on the optimal synthesis parameters and the kinetics of formation of calcium phosphate (Ca-P) phase at the surface of PLGA/BG composites. The formation of calcium phosphate layer was confirmed using scanning electron microscopy/energy dispersive X-ray analysis (SEM/EDXA). PLGA-30%BG microspheres based porous scaffolds for bone tissue engineering were examined for their ability to promote osteogenesis of marrow stromal cells (MSC). This porous scaffold supported both MSC proliferation and promoted MSC differentiation into cells expressing the osteoblast phenotype. It therefore demonstrates significant potential as a bone replacement material.

  7. A rapid and simple determination of A77 1726 in human serum by high-performance liquid chromatography and its application for optimization of leflunomide therapy

    NARCIS (Netherlands)

    van Roon, EN; Yska, JP; Raemaekers, J; Jansen, TLTA; van Wanrooy, M; Brouwers, JRBJ

    2004-01-01

    Leflunomide is a disease-modifying antirheumatic drug, which is bioactivated by fort-nation of A77 1726. In this study a rapid and simple quantitative assay using a reversed phase HPLC-UV method is validated for detection of A77 1726 in human serum. The HPLC-UV method uses a mobile phase consisting

  8. k-space sampling optimization for ultrashort TE imaging of cortical bone: Applications in radiation therapy planning and MR-based PET attenuation correction

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Lingzhi, E-mail: hlingzhi@gmail.com, E-mail: raymond.muzic@case.edu; Traughber, Melanie [Philips Healthcare, Cleveland, Ohio 44143 (United States); Su, Kuan-Hao; Pereira, Gisele C.; Grover, Anu; Traughber, Bryan; Muzic, Raymond F. Jr., E-mail: hlingzhi@gmail.com, E-mail: raymond.muzic@case.edu [University Hospitals Case Medical Center, Cleveland, Ohio 44106 (United States)

    2014-10-15

    Purpose: The ultrashort echo-time (UTE) sequence is a promising MR pulse sequence for imaging cortical bone which is otherwise difficult to image using conventional MR sequences and also poses strong attenuation for photons in radiation therapy and PET imaging. The authors report here a systematic characterization of cortical bone signal decay and a scanning time optimization strategy for the UTE sequence through k-space undersampling, which can result in up to a 75% reduction in acquisition time. Using the undersampled UTE imaging sequence, the authors also attempted to quantitatively investigate the MR properties of cortical bone in healthy volunteers, thus demonstrating the feasibility of using such a technique for generating bone-enhanced images which can be used for radiation therapy planning and attenuation correction with PET/MR. Methods: An angularly undersampled, radially encoded UTE sequence was used for scanning the brains of healthy volunteers. Quantitative MR characterization of tissue properties, including water fraction and R2{sup ∗} = 1/T2{sup ∗}, was performed by analyzing the UTE images acquired at multiple echo times. The impact of different sampling rates was evaluated through systematic comparison of the MR image quality, bone-enhanced image quality, image noise, water fraction, and R2{sup ∗} of cortical bone. Results: A reduced angular sampling rate of the UTE trajectory achieves acquisition durations in proportion to the sampling rate and in as short as 25% of the time required for full sampling using a standard Cartesian acquisition, while preserving unique MR contrast within the skull at the cost of a minimal increase in noise level. The R2{sup ∗} of human skull was measured as 0.2–0.3 ms{sup −1} depending on the specific region, which is more than ten times greater than the R2{sup ∗} of soft tissue. The water fraction in human skull was measured to be 60%–80%, which is significantly less than the >90% water fraction in

  9. Novel retinoblastoma treatment avoids chemotherapy: the effect of optimally timed combination therapy with angiogenic and glycolytic inhibitors on LHBETATAG retinoblastoma tumors

    Directory of Open Access Journals (Sweden)

    Samuel K Houston

    2011-01-01

    Full Text Available Samuel K Houston1, Yolanda Piña1, Timothy G Murray1, Hinda Boutrid1, Colleen Cebulla2, Amy C Schefler1, Wei Shi1, Magda Celdran1, William Feuer1, Jaime Merchan3, Ted J Lampidis41Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA; 2Department of Ophthalmology, The Ohio State University, Columbus, OH, USA; 3Division of Hematology/Oncology, Department of Medicine, 4Department of Cell Biology and Anatomy, University of Miami Miller School of Medicine and Sylvester Comprehensive Cancer Center, Miami, FL, USAPurpose: The purpose of this study was to evaluate the effect of optimally timed combination treatment with angiogenic and glycolytic inhibitors on tumor burden, hypoxia, and angiogenesis in advanced retinoblastoma tumors.Methods: LHBETATAG mice (n = 30 were evaluated. Mice were divided into 5 groups (n = 6 and received injections at 16 weeks of age (advanced tumors with a saline, b anecortave acetate (AA, c 2-deoxyglucose (2-DG, d AA + 2-DG (1 day post-AA treatment, or e AA + 2-DG (1 week post-AA treatment. Eyes were enucleated at 21 weeks and tumor sections were analyzed for hypoxia, angiogenesis, and tumor burden.Results: Eyes treated with 2-DG 1 day post-AA injection showed a 23% (P = 0.03 reduction in tumor burden compared with 2-DG alone and a 61% (P < 0.001 reduction compared with saline-treated eyes. Eyes treated with 2-DG 1 week post-AA injection showed no significant decrease in tumor burden compared with 2-DG alone (P = 0.21 and a 56% (P < 0.001 decrease in comparison with saline-treated eyes. 2-DG significantly reduced the total density of new blood vessels in tumors by 44% compared to saline controls (P < 0.001, but did not affect the density of mature vasculature.Conclusions: Combination therapy with angiogenic and glycolytic inhibitors significantly enhanced tumor control. Synergistic effects were shown to be dependent on the temporal course of treatment

  10. In vitro bioactivity of polymer matrices reinforced with a bioactive glass phase

    Directory of Open Access Journals (Sweden)

    Oréfice Rodrigo L.

    2000-01-01

    Full Text Available Composites that can mimic the in vitro bioactive behavior of bioactive glasses were designed to fulfill two main features of bioactive glasses that are responsible for their high bond-to-bone rates: (1 capability of providing ions such as calcium and phosphate to the nearby environment and (2 ideal surface structure that allows fast heterogeneous precipitation of hydroxy-carbonate-apatite (HCA. The novel composites were prepared by incorporating bioactive glass particles into polymer matrices. The in vitro bioactivity test was performed by introducing samples into a buffered solution as well as into a simulated body fluid solution. FTIR was used to evaluate the kinetics of HCA (hydroxy-carbonate-apatite precipitation. The results showed that the obtained composites can supply ions, such as silicates and phosphates in rates and concentrations comparable or superior than bulk bioactive glasses. Moreover, the surface chemistry of the composites was altered to mimic the surface of bioactive glasses. It was demonstrated that the in vitro bioactivity of the composites was enhanced by chemically modifying polymer surfaces through the introduction of special alkoxysilane groups.

  11. HeartSmart® for routine optimization of blood flow and facilitation of early goal-directed therapy

    Directory of Open Access Journals (Sweden)

    Kenneth Warring-Davies

    2010-08-01

    PAC thermodilution. HeartSmart® removes many of the technical barriers that prevent the routine adoption and practice of early goal-directed therapy, and represents a simple, reliable method of estimating CI and other hemodynamic variables at the bedside or in departments other than the Intensive Care Unit.Keywords: cardiac index, early goal-directed therapy, HeartSmart®, cardiodynamics, blood flow

  12. Rictor is required for optimal bone accrual in response to anti-sclerostin therapy in the mouse.

    Science.gov (United States)

    Sun, Weiwei; Shi, Yu; Lee, Wen-Chih; Lee, Seung-Yon; Long, Fanxin

    2016-04-01

    Wnt signaling has emerged as a major target pathway for the development of novel bone anabolic therapies. Neutralizing antibodies against the secreted Wnt antagonist sclerostin (Scl-Ab) increase bone mass in both animal models and humans. Because we have previously shown that Rictor-dependent mTORC2 activity contributes to Wnt signaling, we test here whether Rictor is required for Scl-Ab to promote bone anabolism. Mice with Rictor deleted in the early embryonic limb mesenchyme (Prx1-Cre;Rictor(f/f), hereafter RiCKO) were subjected to Scl-Ab treatment for 5weeks starting at 4months of age. In vivo micro-computed tomography (μCT) analyses before the treatment showed that the RiCKO mice displayed normal trabecular, but less cortical bone mass than the littermate controls. After 5weeks of treatment, Scl-Ab dose-dependently increased trabecular and cortical bone mass in both control and RiCKO mice, but the increase was significantly blunted in the latter. Dynamic histomorphometry revealed that the RiCKO mice formed less bone than the control in response to Scl-Ab. In addition, the RiCKO mice possessed fewer osteoclasts than normal under the basal condition and exhibited lesser suppression in osteoclast number by Scl-Ab. Consistent with the fewer osteoclasts in vivo, bone marrow stromal cells (BMSC) from the RiCKO mice expressed less Rankl but normal levels of Opg or M-CSF, and were less effective than the control cells in supporting osteoclastogenesis in vitro. The reliance of Rankl on Rictor appeared to be independent of Wnt-β-catenin or Wnt-mTORC2 signaling as Wnt3a had no effect on Rankl expression by BMSC from either control or RICKO mice. Overall, Rictor in the limb mesenchymal lineage is required for the normal response to the anti-sclerostin therapy in both bone formation and resorption. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Colloidal stability of nano-sized particles in the peritoneal fluid: towards optimizing drug delivery systems for intraperitoneal therapy.

    Science.gov (United States)

    Dakwar, George R; Zagato, Elisa; Delanghe, Joris; Hobel, Sabrina; Aigner, Achim; Denys, Hannelore; Braeckmans, Kevin; Ceelen, Wim; De Smedt, Stefaan C; Remaut, Katrien

    2014-07-01

    Intraperitoneal (IP) administration of nano-sized delivery vehicles containing small interfering RNA (siRNA) has recently gained attention as an alternative route for the efficient treatment of peritoneal carcinomatosis. The colloidal stability of nanomatter following IP administration has, however, not been thoroughly investigated yet. Here, enabled by advanced microscopy methods such as single particle tracking and fluorescence correlation spectroscopy, we follow the aggregation and cargo release of nano-scaled systems directly in peritoneal fluids from healthy mice and ascites fluid from a patient diagnosed with peritoneal carcinomatosis. The colloidal stability in the peritoneal fluids was systematically studied as a function of the charge (positive or negative) and poly(ethylene glycol) (PEG) degree of liposomes and polystyrene nanoparticles, and compared to human serum. Our data demonstrate strong aggregation of cationic and anionic nanoparticles in the peritoneal fluids, while only slight aggregation was observed for the PEGylated ones. PEGylated liposomes, however, lead to a fast and premature release of siRNA cargo in the peritoneal fluids. Based on our observations, we reflect on how to tailor improved delivery systems for IP therapy. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  14. Modifying the planning target volume to optimize the dose distribution in dynamic conformal arc therapy for large metastatic brain tumors.

    Science.gov (United States)

    Ogura, Kengo; Kosaka, Yasuhiro; Imagumbai, Toshiyuki; Ueki, Kazuhito; Narukami, Ryo; Hattori, Takayuki; Kokubo, Masaki

    2017-06-01

    When treating large metastatic brain tumors with stereotactic radiotherapy (SRT), high dose conformity to target is difficult to achieve. Employing a modified planning target volume (mPTV) instead of the original PTV may be one way to improve the dose distribution in linear accelerator-based SRT using a dynamic conformal technique. In this study, we quantitatively analyzed the impact of a mPTV on dose distribution. Twenty-four tumors with a maximum diameter of >2 cm were collected. For each tumor, two plans were created: one used a mPTV and the other did not. The mPTV was produced by shrinking or enlarging the original PTV according to the dose distribution in the original plan. The dose conformity was evaluated and compared between the plans using a two-sided paired t test. The conformity index defined by the Radiation Therapy Oncology Group was 1.34 ± 0.10 and 1.41 ± 0.13, and Paddick's conformity index was 0.75 ± 0.05 and 0.71 ± 0.06, for the plans with and without a mPTV, respectively. All of these improvements were statistically significant (P < 0.05). The use of a mPTV can improve target conformity when planning SRT for large metastatic brain tumors.

  15. Approaches to optimize focused extracorporeal shockwave therapy (ESWT) based on an observational study of 363 feet with recalcitrant plantar fasciitis.

    Science.gov (United States)

    Scheuer, R; Friedrich, M; Hahne, J; Holzapfel, J; Machacek, P; Ogon, M; Pallamar, M

    2016-03-01

    Extracorporeal shockwave therapy (ESWT) is an established second-line treatment option for plantar fasciitis. Longer term results of focused ESWT are rare in literature. This study assessed the treatment success-rates of single session ESWT compared to repetitive ESWT treatment sessions, the mid-term results as well as treatment- or patient-related factors influencing the outcome of focused ESWT for plantar fasciitis. 284 patients (363 feet) received ESWT for plantar fasciitis and answered a questionnaire on socio-demographic and anamnestic data immediately before as well as 19-77 weeks after the first application of ESWT. 76 percent of patients treated only once and 74 percent of all patients reported satisfying pain relief (with up to three treatment sessions). This was consistent in the mid-term and over different physicians as well as independent of assessed patient- or treatment-related factors. Applying repeated ESWT in weekly intervals by default may be helpful in reducing healing time for those patients requiring more than one treatment session. Prospective research is needed to find out whether further treatment sessions are justifiable in patients who indicate no improvement after two or three treatment sessions. In many cases, focused ESWT needs to be applied only once. Further research should focus on the number of treatment sessions as well as the minimum energy flux density needed. Copyright © 2016 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved.

  16. 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.

  17. Optimal duration of risperidone or olanzapine adjunctive therapy to mood stabilizer following remission of a manic episode: A CANMAT randomized double-blind trial.

    Science.gov (United States)

    Yatham, L N; Beaulieu, S; Schaffer, A; Kauer-Sant'Anna, M; Kapczinski, F; Lafer, B; Sharma, V; Parikh, S V; Daigneault, A; Qian, H; Bond, D J; Silverstone, P H; Walji, N; Milev, R; Baruch, P; da Cunha, A; Quevedo, J; Dias, R; Kunz, M; Young, L T; Lam, R W; Wong, H

    2016-08-01

    Atypical antipsychotic adjunctive therapy to lithium or valproate is effective in treating acute mania. Although continuation of atypical antipsychotic adjunctive therapy after mania remission reduces relapse of mood episodes, the optimal duration is unknown. As many atypical antipsychotics cause weight gain and metabolic syndrome, they should not be continued unless the benefits outweigh the risks. This 52-week double-blind placebo-controlled trial recruited patients with bipolar I disorder (n=159) who recently remitted from a manic episode during treatment with risperidone or olanzapine adjunctive therapy to lithium or valproate. Patients were randomized to one of three conditions: discontinuation of risperidone or olanzapine and substitution with placebo at (i) entry ('0-weeks' group) or (ii) at 24 weeks after entry ('24-weeks' group) or (iii) continuation of risperidone or olanzapine for the full duration of the study ('52-weeks' group). The primary outcome measure was time to relapse of any mood episode. Compared with the 0-weeks group, the time to any mood episode was significantly longer in the 24-weeks group (hazard ratio (HR) 0.53; 95% confidence interval (CI): 0.33, 0.86) and nearly so in the 52-weeks group (HR: 0.63; 95% CI: 0.39, 1.02). The relapse rate was similar in the 52-weeks group compared with the 24-weeks group (HR: 1.18; 95% CI: 0.71, 1.99); however, sub-group analysis showed discordant results between the two antipsychotics (HR: 0.48, 95% CI: 0.17; 1.32 olanzapine patients; HR: 1.85, 95% CI: 1.00, 3.41 risperidone patients). Average weight gain was 3.2 kg in the 52-weeks group compared with a weight loss of 0.2 kg in the 0-weeks and 0.1 kg in the 24-weeks groups. These findings suggest that risperidone or olanzapine adjunctive therapy for 24 weeks is beneficial but continuation of risperidone beyond this period does not reduce the risk of relapse. Whether continuation of olanzapine beyond this period reduces relapse risk remains unclear

  18. Optimized ventricular restraint therapy: adjustable restraint is superior to standard restraint in an ovine model of ischemic cardiomyopathy.

    Science.gov (United States)

    Lee, Lawrence S; Ghanta, Ravi K; Mokashi, Suyog A; Coelho-Filho, Otavio; Kwong, Raymond Y; Kwon, Michael; Guan, Jian; Liao, Ronglih; Chen, Frederick Y

    2013-03-01

    The effects of ventricular restraint level on left ventricular reverse remodeling are not known. We hypothesized that restraint level affects the degree of reverse remodeling and that restraint applied in an adjustable manner is superior to standard, nonadjustable restraint. This study was performed in 2 parts using a model of chronic heart failure in the sheep. In part I, restraint was applied at control (0 mm Hg, n = 3), low (1.5 mm Hg, n = 3), and high (3.0 mm Hg, n = 3) levels with an adjustable and measurable ventricular restraint (AMVR) device. Restraint level was not altered throughout the 2-month treatment period. Serial restraint level measurements and transthoracic echocardiography were performed. In part II, restraint was applied with the AMVR device set at 3.0 mm Hg (n = 6) and adjusted periodically to maintain that level. This was compared with restraint applied in a standard, nonadjustable manner using a mesh wrap (n = 6). All subjects were followed up for 2 months with serial magnetic resonance imaging. In part I, there was greater and earlier reverse remodeling in the high restraint group. In both groups, the rate of reverse remodeling peaked and then declined as the measured restraint level decreased with progression of reverse remodeling. In part II, adjustable restraint resulted in greater reverse remodeling than standard restraint. Left ventricular end diastolic volume decreased by 12.7% (P = .005) with adjustable restraint and by 5.7% (P = .032) with standard restraint. Left ventricular ejection fraction increased by 18.9% (P = .014) and 14.4% (P standard restraint, respectively. Restraint level affects the rate and degree of reverse remodeling and is an important determinant of therapy efficacy. Adjustable restraint is more effective than nonadjustable restraint in promoting reverse remodeling. Copyright © 2013 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

  19. External Validation and Optimization of International Consensus Clinical Target Volumes for Adjuvant Radiation Therapy in Bladder Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Reddy, Abhinav V. [Department of Radiation and Cellular Oncology, University of Chicago Pritzker School of Medicine, Chicago, Illinois (United States); Christodouleas, John P. [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Wu, Tianming [Department of Radiation and Cellular Oncology, University of Chicago Pritzker School of Medicine, Chicago, Illinois (United States); Smith, Norman D.; Steinberg, Gary D. [Section of Urology, Department of Surgery, University of Chicago Pritzker School of Medicine, Chicago, Illinois (United States); Liauw, Stanley L., E-mail: sliauw@radonc.uchicago.edu [Department of Radiation and Cellular Oncology, University of Chicago Pritzker School of Medicine, Chicago, Illinois (United States)

    2017-03-15

    Purpose: International consensus (IC) clinical target volumes (CTVs) have been proposed to standardize radiation field design in the treatment of patients at high risk of locoregional failure (LRF) after radical cystectomy. The purpose of this study was to externally validate the IC CTVs in a cohort of postsurgical patients followed up for LRF and identify revisions that might improve the IC CTVs' performance. Methods and Materials: Among 334 patients with pT3 to pT4 bladder cancer treated with radical cystectomy, LRF developed in 58 (17%), of whom 52 had computed tomography scans available for review. Images with LRF were exported into a treatment planning system, and IC CTVs were contoured and evaluated for adequacy of coverage of each LRF with respect to both the patient and each of 6 pelvic subsites: common iliac (CI) region, obturator region (OR), external and internal iliac region, presacral region, cystectomy bed, or other pelvic site. Revisions to the IC contours were proposed based on the findings. Results: Of the 52 patients with documented LRF, 13 (25%) had LRFs that were outside of the IC CTV involving 17 pelvic subsites: 5 near the CI CTV, 5 near the OR CTV, 1 near the external and internal iliac region, and 6 near the cystectomy bed. The 5 CI failures were located superior to the CTV, and the 5 OR failures were located medial to the CTV. Increasing the superior boundary of the CI to a vessel-based definition of the aortic bifurcation, as well as increasing the medial extension of the OR by an additional 9 mm, decreased the number of patients with LRF outside of the IC CTV to 7 (13%). Conclusions: Modified IC CTVs inclusive of a slight adjustment superiorly for the CI region and medially for the OR may reduce the risk of pelvic failure in patients treated with adjuvant radiation therapy.

  20. Optimization study for an epithermal neutron beam for boron neutron capture therapy at the University of Virginia Research Reactor

    Energy Technology Data Exchange (ETDEWEB)

    Burns, Jr., Thomas Dean [Univ. of Virginia, Charlottesville, VA (United States)

    1995-05-01

    The non-surgical brain cancer treatment modality, Boron Neutron Capture Therapy (BNCT), requires the use of an epithermal neutron beam. This purpose of this thesis was to design an epithermal neutron beam at the University of Virginia Research Reactor (UVAR) suitable for BNCT applications. A suitable epithermal neutron beam for BNCT must have minimal fast neutron and gamma radiation contamination, and yet retain an appreciable intensity. The low power of the UVAR core makes reaching a balance between beam quality and intensity a very challenging design endeavor. The MCNP monte carlo neutron transport code was used to develop an equivalent core radiation source, and to perform the subsequent neutron transport calculations necessary for beam model analysis and development. The code accuracy was validated by benchmarking output against experimental criticality measurements. An epithermal beam was designed for the UVAR, with performance characteristics comparable to beams at facilities with cores of higher power. The epithermal neutron intensity of this beam is 2.2 x 108 n/cm2 • s. The fast neutron and gamma radiation KERMA factors are 10 x 10-11cGy•cm2/nepi and 20 x 10-11 cGy•cm2/nepi , respectively, and the current-to-flux ratio is 0.85. This thesis has shown that the UVAR has the capability to provide BNCT treatments, however the performance characteristics of the final beam of this study were limited by the low core power.

  1. Optimized ventricular restraint therapy: Adjustable restraint is superior to standard restraint in an ovine model of ischemic cardiomyopathy

    Science.gov (United States)

    Lee, Lawrence S.; Ghanta, Ravi K.; Mokashi, Suyog A.; Coelho-Filho, Otavio; Kwong, Raymond Y.; Kwon, Michael; Guan, Jian; Liao, Ronglih; Chen, Frederick Y.

    2014-01-01

    Objective The effects of ventricular restraint level on left ventricular reverse remodeling are not known. We hypothesized that restraint level affects the degree of reverse remodeling and that restraint applied in an adjustable manner is superior to standard, nonadjustable restraint. Methods This study was performed in 2 parts using a model of chronic heart failure in the sheep. In part I, restraint was applied at control (0 mm Hg, n = 3), low (1.5 mm Hg, n = 3), and high (3.0 mm Hg, n = 3) levels with an adjustable and measurable ventricular restraint (AMVR) device. Restraint level was not altered throughout the 2-month treatment period. Serial restraint level measurements and transthoracic echocardiography were performed. In part II, restraint was applied with the AMVR device set at 3.0 mm Hg (n = 6) and adjusted periodically to maintain that level. This was compared with restraint applied in a standard, nonadjustable manner using a mesh wrap (n = 6). All subjects were followed up for 2 months with serial magnetic resonance imaging. Results In part I, there was greater and earlier reverse remodeling in the high restraint group. In both groups, the rate of reverse remodeling peaked and then declined as the measured restraint level decreased with progression of reverse remodeling. In part II, adjustable restraint resulted in greater reverse remodeling than standard restraint. Left ventricular end diastolic volume decreased by 12.7% (P = .005) with adjustable restraint and by 5.7% (P = .032) with standard restraint. Left ventricular ejection fraction increased by 18.9% (P = .014) and 14.4% (Prestraint, respectively. Conclusions Restraint level affects the rate and degree of reverse remodeling and is an important determinant of therapy efficacy. Adjustable restraint is more effective than nonadjustable restraint in promoting reverse remodeling. PMID:22698557

  2. Bioactive peptides in plant-derived foodstuffs.

    Science.gov (United States)

    Maestri, Elena; Marmiroli, Marta; Marmiroli, Nelson

    2016-09-16

    A literature survey covering the presence of bioactive peptides in plant-derived foodstuffs is presented. Examples are given of plant peptides associated with a beneficial effect on human health. The main bioactive effects of these peptides are defined and their mechanism of action described, when known. Current understanding of the way in which these molecules are adsorbed, distributed, metabolized and finally excreted is discussed. A particular focus is given to potentially immunomodulatory peptides. The leading analytical assay methods used to evaluate their activity are outlined. Inspection of crop proteomic data revealed that at least 6000 proteins may harbour bioactive peptides. The analysis of these proteins using a Gene Ontology approach has provided a number of insights regarding their occurrence and relevance. The review reports an updated survey on bioactive peptides present in food crop plants, with a particular focus on immunomodulatory peptides which might be relevant for therapeutic applications. It employs a bioinformatic approach to search for proteins of crop plants potentially harboring bioactive peptides, summarising through Gene Ontology the main classes of peptide-containing proteins in food. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Microencapsulation of bioactives for food applications.

    Science.gov (United States)

    Dias, Maria Inês; Ferreira, Isabel C F R; Barreiro, Maria Filomena

    2015-04-01

    Health issues are an emerging concern to the world population, and therefore the food industry is searching for novel food products containing health-promoting bioactive compounds, with little or no synthetic ingredients. However, there are some challenges in the development of functional foods, particularly in which the direct use of some bioactives is involved. They can show problems of instability, react with other food matrix ingredients or present strong odour and/or flavours. In this context, microencapsulation emerges as a potential approach to overcome these problems and, additionally, to provide controlled or targeted delivery or release. This work intends to contribute to the field of functional food development by performing a comprehensive review on the microencapsulation methods and materials, the bioactives used (extracts and isolated compounds) and the final application development. Although several studies dealing with microencapsulation of bioactives exist, they are mainly focused on the process development and the majority lack proof of concept for final applications. These factors, together with the lack of regulation, in Europe and in the United States, delay the development of new functional foods and, consequently, their market entry. In conclusion, the potential of microencapsulation to protect bioactive compounds ensuring their bioavailability is shown, but further studies are required, considering both its applicability and incentives by regulatory agencies.

  4. Bioactive glass-ceramics coatings on alumina

    Energy Technology Data Exchange (ETDEWEB)

    Vitale Brovarone, C.; Verne, E.; Lupo, F. [Politecnico di Torino (Italy). Materials Science and Chemical Eng. Dept.; Moisescu, C. [Jena Univ. (Germany). Otto-Schott-Inst. fuer Glaschemie; Zanardi, L.; Bosetti, M.; Cannas, M. [Eastern Piemont Univ., Novara (Italy). Medical Science Dept.

    2001-07-01

    In this work, aiming to combine the mechanical performances of alumina with the surface properties of a bioactive material, we coated full density alumina substrates by a bioactive glass-ceramic GC. This latter was specially tailored, in term of costituents and specific quantity to have a thermal expansion coefficient close to that of alumina (8.5-9{sup *}10{sup -6}/ C) which is lower than most of the bioactive glasses and glass-ceramics already in use. In this way, we sought to avoid, as much as possible, the crack formation and propagation due to residual stresses generated by the thermal expansion coefficients mismatch. Furthermore, the high reactivity of alumina toward the glass-ceramic was carefully controlled to avoid deep compositional modification of the GC that will negatively affect its bioactivity. At this purpose, an intermediate layer of an appropriate glass G was coated prior to coat the bioactive glass-ceramic. On the materials obtained, preliminary biological tests have been done to evaluate glass-ceramic biocompatibility respect to alumina. (orig.)

  5. Tantalum—A bioactive metal for implants

    Science.gov (United States)

    Balla, Vamsi Krishna; Bose, Susmita; Davies, Neal M.; Bandyopadhyay, Amit

    2010-07-01

    Metallic biomaterials currently in use for load-bearing orthopedic applications are mostly bioinert and therefore lack sufficient osseointegration. Although bioactive ceramics such as hydroxyapatite (HA) can spontaneously bond to living bone tissue, low fracture toughness of HA limits their use as a bone substitute for load-bearing applications. Surface modification techniques such as HA coating on metals are current options to improve osseointegration in load-bearing metal implants. Over the last few decades researchers have attempted to find a bioactive metal with high mechanical strength and excellent fatigue resistance that can bond chemically with surrounding bone for orthopedic applications. Recent in vitro, in vivo, and clinical studies demonstrated that tantalum is a promising metal that is bioactive. However, tantalum applications in biomedical devices have been limited by processing challenges rather than biological performances. In this article, we provide an overview of processing aspects and biological properties of tantalum for load-bearing orthopedic applications.

  6. Bioactive Proteins and Peptides from Soybeans.

    Science.gov (United States)

    Agyei, Dominic

    2015-01-01

    Dietary proteins from soybeans have been shown to offer health benefits in vivo and/or in vitro either as intact proteins or in partially digested forms also called bioactive peptides. Upon oral administration and absorption, soy-derived bioactive peptides may induce several physiological responses such as antioxidative, antimicrobial, antihypertensive, anticancer and immunomodulatory effects. There has therefore been a mounting research interest in the therapeutic potential of soy protein hydrolysates and their subsequent incorporation in functional foods and 'Food for Specified Health Uses' (FOSHU) related products where their biological activities may assist in the promotion of good health or in the control and prevention of diseases. This mini review discusses relevant patents and gives an overview on bioactive proteins and peptides obtainable from soybeans. Processes for the production and formulation of these peptides are given, together with specific examples of their therapeutic potential and possible areas of application.

  7. Bioactive proteins and peptides in foods.

    Science.gov (United States)

    Walther, Barbara; Sieber, Robert

    2011-03-01

    Increasing amounts of data demonstrate a bioactive role of proteins and peptides above and beyond their nutritional impact. The focus of the investigations has mainly been on vitamin- and mineral-binding proteins, on antimicrobial, immunosuppressing/-modulatory proteins, and on proteins with enzyme inhibitory activity as well as on hormones and growth factors from different food proteins; most research has been performed on milk proteins. Because of their molecular size, intact absorption of proteins in the human gastrointestinal tract is limited. Therefore, most of the proteins with biological functions show physiological activity in the gastrointestinal tract by enhancing nutrient absorption, inhibiting enzymes, and modulating the immune system to defend against pathogens. Peptides are released during fermentation or digestion from food proteins by proteolytic enzymes; such peptides have been found mainly in milk. Some of these released peptides exert biological activities such as opiate-like, antihypertensive, mineral-binding, antioxidative, antimicrobial, immuno-, and cytomodulating activity. Intact absorption of these smaller peptides is more likely than that of the larger proteins. Consequently, other organs than the gastrointestinal tract are possible targets for their biological functions. Bioactive proteins as well as bioactive peptides are part of a balanced diet. It is possible to accumulate bioactive peptides in food, for example by using specific microorganisms in fermented dairy products. Although bioactive peptides have been the subject of several studies in vitro and in vivo, their health potential is still under investigation. Up to now, the Commission of European Communities has not (yet) authorized any health claims for bioactive proteins and peptides from food.

  8. Optimal duration of dual anti-platelet therapy after percutaneous coronary intervention: 2016 consensus position of the Italian Society of Cardiology.

    Science.gov (United States)

    Barillà, Francesco; Pelliccia, Francesco; Borzi, Mauro; Camici, Paolo; Cas, Livio Dei; Di Biase, Matteo; Indolfi, Ciro; Mercuro, Giuseppe; Montemurro, Vincenzo; Padeletti, Luigi; Filardi, Pasquale Perrone; Vizza, Carmine D; Romeo, Francesco

    2017-01-01

    Definition of the optimal duration of dual anti-platelet therapy (DAPT) is an important clinical issue, given the large number of patients having percutaneous coronary intervention (PCI), the costs and risks of pharmacologic therapy, the consequences of stent thrombosis, and the potential benefits of DAPT in preventing ischaemic outcomes beyond stent thrombosis. Nowadays, the rationale for a prolonged duration of DAPT should be not only the prevention of stent thrombosis, but also the prevention of ischaemic events unrelated to the coronary stenosis treated with index PCI. A higher predisposition to athero-thrombosis may persist for years after an acute myocardial infarction, and even stable patients with a history of prior myocardial infarction are at high risk for major adverse cardiovascular events. Recently, results of pre-specified post-hoc analyses of randomized clinical trials, including the PEGASUS-TIMI 54 trial, have shed light on strategies of DAPT in various clinical situations, and should impact the next rounds of international guidelines, and also routine practice. Accordingly, the 2015 to 2016 the Board of the Italian Society of Cardiology addressed newer recommendations on duration of DAPT based on most recent scientific information. The document states that physicians should decide duration of DAPT on an individual basis, taking into account ischaemic and bleeding risks of any given patient. Indeed, current controversy surrounding optimal duration of DAPT clearly reflects the fact that, nowadays, a one size fits all strategy cannot be reliably applied to patients treated with PCI. Indeed, patients usually have factors for both increased ischaemic and bleeding risks that must be carefully evaluated to assess the benefit/risk ratio of prolonged DAPT. Personalized management of DAPT must be seen as a dynamic prescription with regular re-evaluations of the risk/benefit to the patient according to changes in his/her clinical profile. Also, in order to

  9. Effect of primer selection on estimates of GB virus C (GBV-C) prevalence and response to antiretroviral therapy for optimal testing for GBV-C viremia.

    Science.gov (United States)

    Souza, I E; Allen, J B; Xiang, J; Klinzman, D; Diaz, R; Zhang, S; Chaloner, K; Zdunek, D; Hess, G; Williams, C F; Benning, L; Stapleton, J T

    2006-09-01

    GB virus C (GBV-C; also called hepatitis G virus) is a common cause of infection associated with prolonged survival among HIV-infected individuals. The prevalences of GBV-C viremia vary widely in different studies, and there has been poor agreement among different laboratories performing GBV-C RNA detection in quality control studies. To determine the optimal method of measuring GBV-C RNA in clinical samples, samples obtained from 939 HIV-infected subjects were studied using reverse transcription (RT)-PCR methods amplifying four separate regions of the GBV-C genome. Primers amplifying the E2 coding region were 100% specific; however, their sensitivity was only 76.6%. In contrast, primers amplifying three additional conserved regions of the GBV-C genome (the 5' nontranslated region and the nonstructural protein-coding regions 3 and 5A) were more sensitive but produced higher rates of false-positive results. Using low-specificity primer sets influenced the significance of association between GBV-C viremia and response to antiretroviral therapy. Using a quantitative GBV-C RNA method, the GBV-C RNA concentration did not correlate with baseline or set point HIV RNA levels; however, a correlation between negative, low, and high GBV-C RNA levels and increasing reduction in HIV RNA following antiretroviral therapy was observed. Subjects with both GBV-C E2 antibody and viremia had significantly lower GBV-C RNA levels than did viremic subjects without E2 antibody. These studies demonstrate that accurate detection of GBV-C RNA by nested RT-PCR requires the use of primers representing multiple genome regions. Analyses based on testing with single primers do not lead to reliable conclusions about the association between GBV-C infection and clinical outcomes.

  10. Optimization of growth hormone dosing in children born small for gestational age: an open-label, randomized study of children during the fourth year of therapy.

    Science.gov (United States)

    Chatelain, P; Colle, M; Nako, J-P; Le Luyer, B; Wagner, K; Berlier, P; Tauber, M

    2012-01-01

    Optimal dosage for growth hormone (GH) therapy in short, prepubertal children born small for gestational age (SGA) is controversial. SGA OPTIMIS (NCT00249821) is a multicenter, open-label, parallel-group, pilot study of short children born SGA who had received recombinant human GH (r-hGH) (57 μg/kg/day) for 3 years. Children were randomized 1:1 to receive either 57 or 35 μg/kg/day r-hGH during year 4. The primary endpoint was height gain during year 4. 22 children were randomized (57 μg/kg/day, n = 10; 35 μg/kg/day, n = 12) and 21 completed the fourth year of therapy; 22 were included in efficacy analyses. During year 4, mean [standard deviation (SD)] height velocity was 6.4 (1.4) and 4.4 (1.2) cm/year (p = 0.001) and height velocity SD score (SDS) was 0.3 (0.3) and -0.1 (0.2) (p = 0.002) in the 57 and 35 μg/kg/day groups, respectively. The 57 μg/kg/day group continued with catch-up growth, had a significantly higher mean weight gain (p = 0.015) and significantly higher insulin-like growth factor-I levels at 12 months (p = 0.038). Five treatment-emergent adverse events were reported; none was serious or caused study withdrawal. Children who continued receiving 57 μg/kg/day r-hGH in year 4 had significantly greater height gain than those receiving 35 μg/kg/day r-hGH. Copyright © 2012 S. Karger AG, Basel.

  11. Comparison of 2 transvaginal surgical approaches and perioperative behavioral therapy for apical vaginal prolapse: the OPTIMAL randomized trial.

    Science.gov (United States)

    Barber, Matthew D; Brubaker, Linda; Burgio, Kathryn L; Richter, Holly E; Nygaard, Ingrid; Weidner, Alison C; Menefee, Shawn A; Lukacz, Emily S; Norton, Peggy; Schaffer, Joseph; Nguyen, John N; Borello-France, Diane; Goode, Patricia S; Jakus-Waldman, Sharon; Spino, Cathie; Warren, Lauren Klein; Gantz, Marie G; Meikle, Susan F

    2014-03-12

    More than 300,000 surgeries are performed annually in the United States for pelvic organ prolapse. Sacrospinous ligament fixation (SSLF) and uterosacral ligament suspension (ULS) are commonly performed transvaginal surgeries to correct apical prolapse. Little is known about their comparative efficacy and safety, and it is unknown whether perioperative behavioral therapy with pelvic floor muscle training (BPMT) improves outcomes of prolapse surgery. To compare outcomes between (1) SSLF and ULS and (2) perioperative BPMT and usual care in women undergoing surgery for vaginal prolapse and stress urinary incontinence. Multicenter, 2 × 2 factorial, randomized trial of 374 women undergoing surgery to treat both apical vaginal prolapse and stress urinary incontinence was conducted between 2008 and 2013 at 9 US medical centers. Two-year follow-up rate was 84.5%. The surgical intervention was transvaginal surgery including midurethral sling with randomization to SSLF (n = 186) or ULS (n = 188); the behavioral intervention was randomization to receive perioperative BPMT (n = 186) or usual care (n = 188). The primary outcome for the surgical intervention (surgical success) was defined as (1) no apical descent greater than one-third into vaginal canal or anterior or posterior vaginal wall beyond the hymen (anatomic success), (2) no bothersome vaginal bulge symptoms, and (3) no re-treatment for prolapse at 2 years. For the behavioral intervention, primary outcome at 6 months was urinary symptom scores (Urinary Distress Inventory; range 0-300, higher scores worse), and primary outcomes at 2 years were prolapse symptom scores (Pelvic Organ Prolapse Distress Inventory; range 0-300, higher scores worse) and anatomic success. At 2 years, surgical group was not significantly associated with surgical success rates (ULS, 59.2% [93/157] vs SSLF, 60.5% [92/152]; unadjusted difference, -1.3%; 95% CI, -12.2% to 9.6%; adjusted odds ratio [OR], 0.9; 95% CI, 0.6 to 1

  12. Prediction and compensation of magnetic beam deflection in MR-integrated proton therapy: a method optimized regarding accuracy, versatility and speed.

    Science.gov (United States)

    Schellhammer, Sonja M; Hoffmann, Aswin L

    2017-02-21

    The integration of magnetic resonance imaging (MRI) and proton therapy for on-line image-guidance is expected to reduce dose delivery uncertainties during treatment. Yet, the proton beam experiences a Lorentz force induced deflection inside the magnetic field of the MRI scanner, and several methods have been proposed to quantify this effect. We analyze their structural differences and compare results of both analytical and Monte Carlo models. We find that existing analytical models are limited in accuracy and applicability due to critical approximations, especially including the assumption of a uniform magnetic field. As Monte Carlo simulations are too time-consuming for routine treatment planning and on-line plan adaption, we introduce a new method to quantify and correct for the beam deflection, which is optimized regarding accuracy, versatility and speed. We use it to predict the trajectory of a mono-energetic proton beam of energy E 0 traversing a water phantom behind an air gap within an omnipresent uniform transverse magnetic flux density B 0. The magnetic field induced dislocation of the Bragg peak is calculated as function of E 0 and B 0 and compared to results obtained with existing analytical and Monte Carlo methods. The deviation from the Bragg peak position predicted by Monte Carlo simulations is smaller for the new model than for the analytical models by up to 2 cm. The model is faster than Monte Carlo methods, less assumptive than the analytical models and applicable to realistic magnetic fields. To compensate for the predicted Bragg peak dislocation, a numerical optimization strategy is introduced and evaluated. It includes an adjustment of both the proton beam entrance angle and energy of up to 25° and 5 MeV, depending on E 0 and B 0. This strategy is shown to effectively reposition the Bragg peak to its intended location in the presence of a magnetic field.

  13. Structure, bioactivity, and synthesis of methylated flavonoids.

    Science.gov (United States)

    Wen, Lingrong; Jiang, Yueming; Yang, Jiali; Zhao, Yupeng; Tian, Miaomiao; Yang, Bao

    2017-06-01

    Methylated flavonoids are an important type of natural flavonoid derivative with potentially multiple health benefits; among other things, they have improved bioavailability compared with flavonoid precursors. Flavonoids have been documented to have broad bioactivities, such as anticancer, immunomodulation, and antioxidant activities, that can be elevated, to a certain extent, by methylation. Understanding the structure, bioactivity, and bioavailability of methylated flavonoids, therefore, is an interesting topic with broad potential applications. Though methylated flavonoids are widely present in plants, their levels are usually low. Because developing efficient techniques to produce these chemicals would likely be beneficial, we provide an overview of their chemical and biological synthesis. © 2017 New York Academy of Sciences.

  14. Polyether ionophores-promising bioactive molecules for cancer therapy.

    Science.gov (United States)

    Huczyński, Adam

    2012-12-01

    The natural polyether ionophore antibiotics might be important chemotherapeutic agents for the treatment of cancer. In this article, the pharmacology and anticancer activity of the polyether ionophores undergoing pre-clinical evaluation are reviewed. Most of polyether ionophores have shown potent activity against the proliferation of various cancer cells, including those that display multidrug resistance (MDR) and cancer stem cells (CSC). The mechanism underlying the anticancer activity of ionophore agents can be related to their ability to form complexes with metal cations and transport them across cellular and subcellular membranes. Increasing evidence shows that the anticancer activity of polyether ionophores may be a consequence of the induction of apoptosis leading to apoptotic cell death, arresting cell cycle progression, induction of the cell oxidative stress, loss of mitochondrial membrane potential, reversion of MDR, synergistic anticancer effect with other anticancer drugs, etc. Continued investigation of the mechanisms of action and development of new polyether ionophores and their derivatives may provide more effective therapeutic drugs for cancer treatments. Copyright © 2012 Elsevier Ltd. All rights reserved.

  15. Hierarchically Nanoporous Bioactive Glasses for High Efficiency Immobilization of Enzymes

    DEFF Research Database (Denmark)

    He, W.; Min, D.D.; Zhang, X.D.

    2014-01-01

    Bioactive glasses with hierarchical nanoporosity and structures have been heavily involved in immobilization of enzymes. Because of meticulous design and ingenious hierarchical nanostructuration of porosities from yeast cell biotemplates, hierarchically nanostructured porous bioactive glasses can...

  16. 3D-Printable Bioactivated Nanocellulose-Alginate Hydrogels.

    Science.gov (United States)

    Leppiniemi, Jenni; Lahtinen, Panu; Paajanen, Antti; Mahlberg, Riitta; Metsä-Kortelainen, Sini; Pinomaa, Tatu; Pajari, Heikki; Vikholm-Lundin, Inger; Pursula, Pekka; Hytönen, Vesa P

    2017-07-05

    We describe herein a nanocellulose-alginate hydrogel suitable for 3D printing. The composition of the hydrogel was optimized based on material characterization methods and 3D printing experiments, and its behavior during the printing process was studied using computational fluid dynamics simulations. The hydrogel was biofunctionalized by the covalent coupling of an enhanced avidin protein to the cellulose nanofibrils. Ionic cross-linking of the hydrogel using calcium ions improved the performance of the material. The resulting hydrogel is suitable for 3D printing, its mechanical properties indicate good tissue compatibility, and the hydrogel absorbs water in moist conditions, suggesting potential in applications such as wound dressings. The biofunctionalization potential was shown by attaching a biotinylated fluorescent protein and a biotinylated fluorescent small molecule via avidin and monitoring the material using confocal microscopy. The 3D-printable bioactivated nanocellulose-alginate hydrogel offers a platform for the development of biomedical devices, wearable sensors, and drug-releasing materials.

  17. Characterization, Preparation, and Purification of Marine Bioactive Peptides

    OpenAIRE

    Xueqin Wang; Huahua Yu; Ronge Xing; Pengcheng Li

    2017-01-01

    Marine bioactive peptides, as a source of unique bioactive compounds, are the focus of current research. They exert various biological roles, some of the most crucial of which are antioxidant activity, antimicrobial activity, anticancer activity, antihypertensive activity, anti-inflammatory activity, and so forth, and specific characteristics of the bioactivities are described. This review also describes various manufacturing techniques for marine bioactive peptides using organic synthesis, m...

  18. Methods of Manufacturing Bioactive Gels from Extracellular Matrix Material

    Science.gov (United States)

    Kentner, Kimberly (Inventor); Stuart, Katherine A. (Inventor); Janis, Abram D. (Inventor)

    2017-01-01

    The present invention is directed to methods of manufacturing bioactive gels from ECM material, i.e., gels which retain bioactivity, and can serve as scaffolds for preclinical and clinical tissue engineering and regenerative medicine approaches to tissue reconstruction. The manufacturing methods take advantage of a new recognition that bioactive gels from ECM material can be created by digesting particularized ECM material in an alkaline environment and neutralizing to provide bioactive gels.

  19. A low elastic modulus Ti-Nb-Hf alloy bioactivated with an elastin-like

    OpenAIRE

    González, Marta; Salvagni, Emiliano; Rodríguez Cabello, J.C.; Rupérez de Gracia, Elisa; Gil Mur, Francisco Javier; Manero Planella, José María; Peña, Javier

    2012-01-01

    b-type titanium alloys with low Young’s modulus are desirable to reduce stress shielding effect and enhance bone remodeling for implants used to substitute failed hard tissue. For biomaterials application, the surface bioactivity is necessary to achieve optimal osseointegration. In the previous work, the low elastic modulus (43 GPa) Ti-25Nb-16Hf (wt %) alloy was mechanically and microstructurally characterized. In the present work, the biological behavior of Ti-25Nb- 1...

  20. Comparison of intracerebral delivery of carboplatin and photon irradiation with an optimized regimen for boron neutron capture therapy of the F98 rat glioma

    Energy Technology Data Exchange (ETDEWEB)

    Barth, Rolf F., E-mail: rolf.barth@osumc.edu [Department of Pathology, Ohio State University, 165 Hamilton Hall, 1645 Neil Avenue, Columbus, OH 43210 (United States); Yang Weilian; Huo Tianyao [Department of Pathology, Ohio State University, 165 Hamilton Hall, 1645 Neil Avenue, Columbus, OH 43210 (United States); Riley, Kent J.; Binns, Peter J. [Nuclear Reactor Laboratory, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States); Grecula, John C., E-mail: john.grecula@osumc.edu [James Cancer Hospital and Solove Research Institute, Department of Radiation Oncology, Ohio State University, Columbus, OH, 43210 (United States); Gupta, Nilendu, E-mail: nilendu.gupta@osumc.edu [James Cancer Hospital and Solove Research Institute, Department of Radiation Oncology, Ohio State University, Columbus, OH, 43210 (United States); Rousseau, Julia, E-mail: julia.rousseau@yahoo.fr [INSERM, U836, Institute of Neurosciences, Grenoble (France); Elleaume, Helene, E-mail: h.elleaume@esrf.fr [INSERM, U836, Institute of Neurosciences, Grenoble (France)

    2011-12-15

    In this report we have summarized our studies to optimize the delivery of boronophenylalanine (BPA) and sodium borocaptate (BSH) for boron neutron capture therapy (BNCT) of F98 glioma bearing rats. These results have been compared to a chemoradiotherapeutic approach using the same tumor model. The best survival data from our BNCT studies were obtained using a combination of BPA and sodium borocaptate BSH administered via the internal carotid artery, in combination with blood-brain barrier disruption (BBB-D). This treatment resulted in a mean survival time (MST) of 140 d with a 25% cure rate. The other approach combined intracerebral administration of carboplatin by either convection enhanced delivery (CED) or Alzet pump infusion, followed by external beam photon irradiation. This resulted in MSTs of 83 d and 112 d, respectively, with a cure rate of 40% for the latter. However, a significant problem that must be solved for both BNCT and this new chemoradiotherapeutic approach is how to improve drug uptake and microdistribution within the tumor.

  1. Optimized human CYP4B1 in combination with the alkylator prodrug 4-ipomeanol serves as a novel suicide gene system for adoptive T-cell therapies.

    Science.gov (United States)

    Roellecke, K; Virts, E L; Einholz, R; Edson, K Z; Altvater, B; Rossig, C; von Laer, D; Scheckenbach, K; Wagenmann, M; Reinhardt, D; Kramm, C M; Rettie, A E; Wiek, C; Hanenberg, H

    2016-07-01

    Engineering autologous or allogeneic T cells to express a suicide gene can control potential toxicity in adoptive T-cell therapies. We recently reported the development of a novel human suicide gene system that is based on an orphan human cytochrome P450 enzyme, CYP4B1, and the naturally occurring alkylator prodrug 4-ipomeanol. The goal of this study was to systematically develop a clinically applicable self-inactivating lentiviral vector for efficient co-expression of CYP4B1 as an ER-located protein with two distinct types of cell surface proteins, either MACS selection genes for donor lymphocyte infusions after allogeneic stem cell transplantation or chimeric antigen receptors for retargeting primary T cells. The U3 region of the myeloproliferative sarcoma virus in combination with the T2A site was found to drive high-level expression of our CYP4B1 mutant with truncated CD34 or CD271 as MACS suitable selection markers. This lentiviral vector backbone was also well suited for co-expression of CYP4B1 with a codon-optimized CD19 chimeric antigen receptor (CAR) construct. Finally, 4-ipomeanol efficiently induced apoptosis in primary T cells that co-express mutant CYP4B1 and the divergently located MACS selection and CAR genes. In conclusion, we here developed a clinically suited lentiviral vector that supports high-level co-expression of cell surface proteins with a potent novel human suicide gene.

  2. Managing side effects of tyrosine kinase inhibitor therapy to optimize adherence in patients with chronic myeloid leukemia: the role of the midlevel practitioner.

    Science.gov (United States)

    Cornelison, Megan; Jabbour, Elias J; Welch, Mary Alma

    2012-01-01

    In the last decade, the development of imatinib, a tyrosine kinase inhibitor, has brought about unprecedented change in the way newly diagnosed, chronic-phase chronic myeloid leukemia patients are treated. Two next-generation tyrosine kinase inhibitors, nilotinib and dasatinib, were initially indicated for imatinib-resistant or imatinib-intolerant chronic myeloid leukemia patients and recently received approval from the Food and Drug Administration for treatment of newly diagnosed, chronic-phase chronic myeloid leukemia patients. In comparison with the previous standards of care, benefits with these three tyrosine kinase inhibitors have included more rapid response rates, increased survival, and fewer side effects. The improved long-term outcomes have altered the approach to management of chronic myeloid leukemia from a progressive fatal disease with a poor prognosis to a chronic condition similar to diabetes or hypertension. Prolonged survival increases the need for patient education, support, monitoring, and assistance with adverse event management. Even low-grade side effects can adversely affect patients' quality of life and, therefore, require prompt attention to prevent long-term complications or suboptimal outcomes. New evidence has indicated that patient adherence to tyrosine kinase inhibitor therapy is essential to successful treatment. Midlevel practitioners can help to optimize outcomes by educating patients regarding the importance of adherence, performing regular monitoring, helping patients to understand their test results, and aggressively managing treatment-related side effects. Copyright © 2012 Elsevier Inc. All rights reserved.

  3. In vitro bioactivity and cytocompatibility of tricalcium silicate

    Indian Academy of Sciences (India)

    In vitro cytocompatible evaluation reveals that osteoblasts adhere and spread well on the Ca3SiO5 ceramics, indicating good bioactivity and cytocompatibility. Keywords. Tricalcium silicate; bioactivity; cytocompatibility; hydroxyapatite; osteoblasts. 1. Introduction. Up to now, many bioactive biomaterials, such as A/W glass.

  4. Investigation of bioactivity and cell effects of nano-porous sol–gel derived bioactive glass film

    Energy Technology Data Exchange (ETDEWEB)

    Ma, Zhijun, E-mail: mokuu@zju.edu.cn [State Key Laboratory of Luminescent Materials and Devices, South China University of Technology, Guangzhou, 510640 (China); Ji, Huijiao [College of Life Science, Zhejiang University, Hangzhou, 310028 (China); Hu, Xiaomeng [School of Materials Science and Engineering, South China University of Technology, Guangzhou, 510640 (China); Teng, Yu [State Key Laboratory of Luminescent Materials and Devices, South China University of Technology, Guangzhou, 510640 (China); Zhao, Guiyun; Mo, Lijuan; Zhao, Xiaoli [College of Life Science, Zhejiang University, Hangzhou, 310028 (China); Chen, Weibo [School of Materials Science and Engineering, South China University of Technology, Guangzhou, 510640 (China); Qiu, Jianrong, E-mail: qjr@scut.edu.cn [State Key Laboratory of Luminescent Materials and Devices, South China University of Technology, Guangzhou, 510640 (China); Zhang, Ming, E-mail: zhangming201201@126.com [College of Life Science, Zhejiang University, Hangzhou, 310028 (China)

    2013-11-01

    In orthopedic surgery, bioactive glass film coating is extensively studied to improve the synthetic performance of orthopedic implants. A lot of investigations have confirmed that nano-porous structure in bioactive glasses can remarkably improve their bioactivity. Nevertheless, researches on preparation of nano-porous bioactive glasses in the form of film coating and their cell response activities are scarce. Herein, we report the preparation of nano-porous bioactive glass film on commercial glass slide based on a sol–gel technique, together with the evaluation of its in vitro bioactivity through immersion in simulated body fluid and monitoring the precipitation of apatite-like layer. Cell responses of the samples, including attachment, proliferation and osteogenic differentiation, were also investigated using BMSCS (bone marrow derived mesenchymal stem cells) as a model. The results presented here provide some basic information on structural influence of bioactive glass film on the improvement of bioactivity and cellular effects.

  5. Encapsulation for preservation of functionality and targeted delivery of bioactive food components

    NARCIS (Netherlands)

    de Vos, Paul; Faas, Marijke M.; Spasojevic, Milica; Sikkema, Jan

    There has been a tremendous increase in the number of food products containing bioactive components with a health promoting or disease preventing effect. Bioactive food components can be divided into bioactive molecules and bioactive living cells (probiotics). Both bioactive molecules and bioactive

  6. Feeding tomato and broccoli powders enriched with bioactives improves bioactivity markers in rats.

    Science.gov (United States)

    Liu, Ann G; Volker, Sonja E; Jeffery, Elizabeth H; Erdman, John W

    2009-08-26

    Many studies have evaluated the cancer -preventive potential of individual bioactives from tomatoes and broccoli, but few have examined them within the context of a whole food. Male Copenhagen rats were fed diets containing 10% standard tomato powder, tomato enriched with lycopene or total carotenoids, standard broccoli floret, broccoli sprouts, or broccoli enriched with indole glucosinolates or selenium for 7 days. All broccoli diets increased the activity of colon quinone reductase (NQO1). Indole glucosinolate-enriched broccoli and selenium-enriched broccoli increased hepatic NQO1 and cytochrome P450 1A activity (P tomato diets down-regulated prostatic glutathione S-transferase P1 mRNA expression. Different tomato diets resulted in altered hepatic accumulation of lycopene, phytofluene, and phytoene. These results demonstrate that the bioactive content of vegetables affects both tissue content of bioactives and activity of detoxification enzymes. Enhancing bioactive content of tomatoes and broccoli may enhance efficacy in the prevention of prostate cancer.

  7. Glutathione conjugation as a bioactivation reaction

    NARCIS (Netherlands)

    Bladeren, P.J. van

    2000-01-01

    In general, glutathione conjugation is regarded as a detoxication reaction. However, depending on the properties of the substrate, bioactivation is also possible. Four types of activation reaction have been recognized: direct-acting compounds, conjugates that are activated through cysteine conjugate

  8. Natural bioactive compounds: antibiotics | Dezfully | Journal of ...

    African Journals Online (AJOL)

    Antibiotics are powerful therapeutic agents that are produced by diverse living organisms. Over the last several decades, natural bioactive products particularly antibiotics have continued to play a significant role in drug discovery and has expanded the process for developing drugs with high degree of therapeutic index and ...

  9. Antimicrobial Activity and Bioactive Constituents of Alectra ...

    African Journals Online (AJOL)

    Chromatographic fractionation of the methanol extract through non-polar D101 macroporous resin beads yielded three bioactive compounds: two phenolic compounds, p-coumaric acid and 3,4-dihydroxybenzoic acid, and a flavonoid, luteolin. The compounds exhibited appreciable activities against tested bacteria and fungi ...

  10. Bioactive alkaloids in vertically transmitted fungal endophytes

    Science.gov (United States)

    Plants form mutualistic symbioses with a variety of microorganisms, including endophytic fungi that live inside the plant and cause no symptoms of infection. Some endophytic fungi form defensive mutualisms based on the production of bioactive metabolites that protect the plant from herbivores in exc...

  11. Marine Bioactives and Potential Application in Sports

    Science.gov (United States)

    Gammone, Maria Alessandra; Gemello, Eugenio; Riccioni, Graziano; D’Orazio, Nicolantonio

    2014-01-01

    An enriched diet with antioxidants, such as vitamin E, vitamin C, β-carotene and phenolic compounds, has always been suggested to improve oxidative stress, preventing related diseases. In this respect, marine natural product (MNP), such as COX inhibitors, marine steroids, molecules interfering with factors involved in the modulation of gene expression (such as NF-κB), macrolides, many antioxidant agents, thermogenic substances and even substances that could help the immune system and that result in the protection of cartilage, have been recently gaining attention. The marine world represents a reserve of bioactive ingredients, with considerable potential as functional food. Substances, such as chitin, chitosan, n-3 oils, carotenoids, vitamins, minerals and bioactive peptides, can provide several health benefits, such as the reduction of cardiovascular diseases, anti-inflammatory and anticarcinogenic activities. In addition, new marine bioactive substances with potential anti-inflammatory, antioxidant and thermogenic capacity may provide health benefits and performance improvement, especially in those who practice physical activity, because of their increased free radical and Reacting Oxygen Species (ROS) production during exercise, and, particularly, in athletes. The aim of this review is to examine the potential pharmacological properties and application of many marine bioactive substances in sports. PMID:24796298

  12. Marine Bioactives and Potential Application in Sports

    Directory of Open Access Journals (Sweden)

    Maria Alessandra Gammone

    2014-04-01

    Full Text Available An enriched diet with antioxidants, such as vitamin E, vitamin C, β-carotene and phenolic compounds, has always been suggested to improve oxidative stress, preventing related diseases. In this respect, marine natural product (MNP, such as COX inhibitors, marine steroids, molecules interfering with factors involved in the modulation of gene expression (such as NF-κB, macrolides, many antioxidant agents, thermogenic substances and even substances that could help the immune system and that result in the protection of cartilage, have been recently gaining attention. The marine world represents a reserve of bioactive ingredients, with considerable potential as functional food. Substances, such as chitin, chitosan, n-3 oils, carotenoids, vitamins, minerals and bioactive peptides, can provide several health benefits, such as the reduction of cardiovascular diseases, anti-inflammatory and anticarcinogenic activities. In addition, new marine bioactive substances with potential anti-inflammatory, antioxidant and thermogenic capacity may provide health benefits and performance improvement, especially in those who practice physical activity, because of their increased free radical and Reacting Oxygen Species (ROS production during exercise, and, particularly, in athletes. The aim of this review is to examine the potential pharmacological properties and application of many marine bioactive substances in sports.

  13. Ultraviolet spectroscopic evaluation of bioactive saponin fraction ...

    African Journals Online (AJOL)

    Ultraviolet spectroscopic evaluation of bioactive saponin fraction from the aqueous extract of Vernonia amygdalina [Esteraeceae] leaf. Paul Chukwuemeka ADIUKWU 1*, Martina BONSU 1, Inemesit OKON-BEN 1,. Paul PEPRAH 1, Paapa MENSAH-KANE 1, Jonathan JATO 1 and Grace NAMBATYA 2. 1School of Pharmacy ...

  14. Interaction between bioactive glasses and human dentin.

    Science.gov (United States)

    Efflandt, S E; Magne, P; Douglas, W H; Francis, L F

    2002-06-01

    This study explores the interaction between bioactive glasses and dentin from extracted human teeth in simulated oral conditions. Bioactive glasses in the Na(2)O-CaO-P(2)O(5)-SiO(2) and MgO-CaO-P(2)O(5)-SiO(2) systems were prepared as polished disks. Teeth were prepared by grinding to expose dentin and etching with phosphoric acid. A layer of saliva was placed between the two, and the pair was secured with an elastic band and immersed in saliva at 37 degrees C for 5, 21 or 42 days. The bioactive glasses adhered to dentin, while controls showed no such interaction. A continuous interface between the bioactive glass and dentin was imaged using cryogenic-scanning electron microscopy (SEM). However, after alcohol dehydration and critical point drying, fracture occurred due to stresses from dentin shrinkage. SEM investigations showed a microstructurally different material at the fractured interface. Chemical analyses revealed that ions from the glass penetrated into the dentin and that the surface of the glass in contact with the dentin was modified. Microdiffractometry showed the presence of apatite at the interface. Bonding appears to be due to an affinity of collagen for the glass surface and chemical interaction between the dentin and glass, leading to apatite formation at the interface.

  15. Bioactive Terpenes from Marine-Derived Fungi

    Directory of Open Access Journals (Sweden)

    Ahmed M. Elissawy

    2015-04-01

    Full Text Available Marine-derived fungi continue to be a prolific source of secondary metabolites showing diverse bioactivities. Terpenoids from marine-derived fungi exhibit wide structural diversity including numerous compounds with pronounced biological activities. In this review, we survey the last five years’ reports on terpenoidal metabolites from marine-derived fungi with particular attention on those showing marked biological activities.

  16. Nutrigenomics – bioactive dietary components 

    Directory of Open Access Journals (Sweden)

    Monika Gętek

    2013-04-01

    Full Text Available Nutrigenomics analyzes relations between diet and genes, and identifies mechanisms in which food and nutrition affect health and lifestyles and noncommunicable diseases (R. Chadwick, 2004. Bioactive dietary components are signal molecules that carry information from the external environment and affect in terms of quantity and quality in the process of gene expression. The biological effect of bioactive dietary components depends on various of physiological processes that can occur within a few genes. Polymorphism of genes can change their function and physiological response of the body for nutrients.Bioactive dietary components work on at least two levels of the expression of genes as factors regulating chromatin structure and as factors directly regulate the activity of nuclear receptors. The processes of synthesis and DNA repair are regulated by some of vitamins, macro-and micro-elements. They provide, among others, cofactors of enzymes that catalyze the replication of DNA methylation and its repair. DNA methylation profile may change under the influence of diet, single nucleotide polymorphisms and environmental factors. Bioactive dietary components may directly affect the process of gene expression by acting as ligands for nuclear receptors. Sensitive to dietary group of nuclear receptors are sensory receptors. This group includes, among others receptor PPAR (peroxisome proliferator activated, responsible for energy metabolism and receptors LXR (liver X receptor, FXR (farnesoid X receptor and RXR, which is responsible for the metabolism of cholesterol.

  17. Legume bioactive compounds: influence of rhizobial inoculation

    Directory of Open Access Journals (Sweden)

    Luis R. Silva

    2017-04-01

    Full Text Available Legumes consumption has been recognized as beneficial for human health, due to their content in proteins, fiber, minerals and vitamins, and their cultivation as beneficial for sustainable agriculture due to their ability to fix atmospheric nitrogen in symbiosis with soil bacteria known as rhizobia. The inoculation with these baceria induces metabolic changes in the plant, from which the more studied to date are the increases in the nitrogen and protein contents, and has been exploited in agriculture to improve the crop yield of several legumes. Nevertheless, legumes also contain several bioactive compounds such as polysaccharides, bioactive peptides, isoflavones and other phenolic compounds, carotenoids, tocopherols and fatty acids, which makes them functional foods included into the nutraceutical products. Therefore, the study of the effect of the rhizobial inoculation in the legume bioactive compounds content is gaining interest in the last decade. Several works reported that the inoculation of different genera and species of rhizobia in several grain legumes, such as soybean, cowpea, chickpea, faba bean or peanut, produced increases in the antioxidant potential and in the content of some bioactive compounds, such as phenolics, flavonoids, organic acids, proteins and fatty acids. Therefore, the rhizobial inoculation is a good tool to enhance the yield and quality of legumes and further studies on this field will allow us to have plant probiotic bacteria that promote the plant growth of legumes improving their functionality.

  18. Bioactive compounds in whole grain wheat

    NARCIS (Netherlands)

    Mateo Anson, N.

    2010-01-01

    Bread can be healthier! Consuming whole-grain foods can prevent cardiovascular diseases, type-2 diabetes and metabolic syndrome. This is due to bioactive compounds in whole grain, such as antioxidants and anti-inflammatory compounds. We found that the different fractions of a wheat grain vary much