Science.gov

Sample records for additional therapeutic benefits

  1. Therapeutic benefits of cannabis: a patient survey.

    PubMed

    Webb, Charles W; Webb, Sandra M

    2014-04-01

    Clinical research regarding the therapeutic benefits of cannabis ("marijuana") has been almost non-existent in the United States since cannabis was given Schedule I status in the Controlled Substances Act of 1970. In order to discover the benefits and adverse effects perceived by medical cannabis patients, especially with regards to chronic pain, we hand-delivered surveys to one hundred consecutive patients who were returning for yearly re-certification for medical cannabis use in Hawai'i. The response rate was 94%. Mean and median ages were 49.3 and 51 years respectively. Ninety-seven per cent of respondents used cannabis primarily for chronic pain. Average pain improvement on a 0-10 pain scale was 5.0 (from 7.8 to 2.8), which translates to a 64% relative decrease in average pain. Half of all respondents also noted relief from stress/anxiety, and nearly half (45%) reported relief from insomnia. Most patients (71%) reported no adverse effects, while 6% reported a cough or throat irritation and 5% feared arrest even though medical cannabis is legal in Hawai'i. No serious adverse effects were reported. These results suggest that Cannabis is an extremely safe and effective medication for many chronic pain patients. Cannabis appears to alleviate pain, insomnia, and may be helpful in relieving anxiety. Cannabis has shown extreme promise in the treatment of numerous medical problems and deserves to be released from the current Schedule I federal prohibition against research and prescription.

  2. Extolling the benefits of molecular therapeutic lipidation.

    PubMed

    Avadisian, Miriam; Gunning, Patrick T

    2013-09-01

    The conjugation of drug or molecular recognition motif to a hydrophobic fatty entity, for purpose of drug-membrane localization, has been a molecular strategy utilized for targeted inhibition of pathways involved in diseased cells. In general, membrane-anchored inhibitor structures have been composed of either a lipid or sterol group coupled via a broad range of inert linkers to either a peptide or small molecule protein recognition agent. Whilst not adhering to the molecular paradigms of modern medicinal chemistry, this approach has afforded peptidic-based therapeutics with improved cellular and in vivo efficacy, leading to more selective targeting of membrane associated protein targets and the effective immobilization of cytosolic signaling proteins through membrane anchorage. The evidence suggests that membrane-anchored peptidic inhibitors are more selective, potent, structurally rigid, and possess enhanced cell permeability profiles as compared to their non-lipidated precursors. This perspectives article will review the application of lipid or sterol conjugation to peptide inhibitors (lipo-molecules) to circumvent the poor cell permeability and metabolic labilities associated with peptidic therapeutics. In addition, the concept of protein-membrane anchorage as a novel drug modality for inhibiting cytosolic signaling protein motility in cells will be reviewed and its merits as an approach to inhibiting protein complexation, protein nuclear translocation and their potential for more effective targeting of membrane associated targets.

  3. Therapeutic benefits of nanoparticles in stroke

    PubMed Central

    Panagiotou, Stavros; Saha, Sikha

    2015-01-01

    Stroke represents one of the major causes of death and disability worldwide, for which no effective treatments are available. The thrombolytic drug alteplase (tissue plasminogen activator or tPA) is the only treatment for acute ischemic stroke but its use is limited by several factors including short therapeutic window, selective efficacy, and subsequent haemorrhagic complications. Numerous preclinical studies have reported very promising results using neuroprotective agents but they have failed at clinical trials because of either safety issues or lack of efficacy. The delivery of many potentially therapeutic neuroprotectants and diagnostic compounds to the brain is restricted by the blood-brain barrier (BBB). Nanoparticles (NPs), which can readily cross the BBB without compromising its integrity, have immense applications in the treatment of ischemic stroke. In this review, potential uses of NPs will be summarized for the treatment of ischemic stroke. Additionally, an overview of targeted NPs will be provided, which could be used in the diagnosis of stroke. Finally, the potential limitations of using NPs in medical applications will be mentioned. Since the use of NPs in stroke therapy is now emerging and is still in development, this review is far from comprehensive or conclusive. Instead, examples of NPs and their current use will be provided, as well as the potentials of NPs in an effort to meet the high demand of new therapies in stroke. PMID:26041986

  4. Therapeutic benefits of regulating inflammation in autoimmunity.

    PubMed

    Nikoopour, Enayat; Schwartz, Jordan Ari; Singh, Bhagirath

    2008-09-01

    Autoimmunity results from the dysregulation of the immune system leading to tissue damage. Th1 and Th17 cells are known to be cellular mediators of inflammation in autoimmune diseases. The specific cytokine milieu within the site of inflammation or within secondary lymphatic tissues is important during the priming and effector phases of T cell response. In this review, we will address the nature of the inflammatory response in the context of autoimmune disease, specifically we will discuss the role of dendritic cells following stimulation of their innate pathogen recognition receptors in directing the development of T cell responses. We will focus on how dendritic cell subsets change the balance between major players in autoimmunity, namely Th1, Th17 and regulatory T cells. Th17 cells, once thought to only act as pathogenic effectors through production of IL-17, have been shown to have regulatory properties as well with co-production of the anti-inflammatory cytokine IL-10 by a subset now referred to as regulatory Th17 cells. IL-17 is important in the induction of autoimmune diseases such as experimental autoimmune encephalomyelitis (EAE) and inflammatory bowel disease (IBD). Study of the inflammatory process following encounter with agents that stimulate the innate immune responses such as adjuvants opens a new horizon for the discovery of therapeutic agents including those derived from microorganisms. Microbial products such as adjuvants that function as TLR ligands may stimulate the immune system by interacting with Toll-like receptors (TLR) on antigen-presenting cells. Microbial agents such as Bacille Calmette-Guérin (BCG) or Freund's adjuvant (CFA) that induce a Th17 response are protective in models of autoimmune diseases particularly EAE and type 1 diabetes (T1D). The induction of innate immunity by these microbial products alters the balance in the cytokine microenvironment and may be responsible for modulation of the inflammation and protection from

  5. Stem cell transplantation therapy for multifaceted therapeutic benefits after stroke.

    PubMed

    Wei, Ling; Wei, Zheng Z; Jiang, Michael Qize; Mohamad, Osama; Yu, Shan Ping

    2017-03-18

    One of the exciting advances in modern medicine and life science is cell-based neurovascular regeneration of damaged brain tissues and repair of neuronal structures. The progress in stem cell biology and creation of adult induced pluripotent stem (iPS) cells has significantly improved basic and pre-clinical research in disease mechanisms and generated enthusiasm for potential applications in the treatment of central nervous system (CNS) diseases including stroke. Endogenous neural stem cells and cultured stem cells are capable of self-renewal and give rise to virtually all types of cells essential for the makeup of neuronal structures. Meanwhile, stem cells and neural progenitor cells are well-known for their potential for trophic support after transplantation into the ischemic brain. Thus, stem cell-based therapies provide an attractive future for protecting and repairing damaged brain tissues after injury and in various disease states. Moreover, basic research on naïve and differentiated stem cells including iPS cells has markedly improved our understanding of cellular and molecular mechanisms of neurological disorders, and provides a platform for the discovery of novel drug targets. The latest advances indicate that combinatorial approaches using cell based therapy with additional treatments such as protective reagents, preconditioning strategies and rehabilitation therapy can significantly improve therapeutic benefits. In this review, we will discuss the characteristics of cell therapy in different ischemic models and the application of stem cells and progenitor cells as regenerative medicine for the treatment of stroke.

  6. Potential therapeutic benefits of strategies directed to mitochondria.

    PubMed

    Camara, Amadou K S; Lesnefsky, Edward J; Stowe, David F

    2010-08-01

    The mitochondrion is the most important organelle in determining continued cell survival and cell death. Mitochondrial dysfunction leads to many human maladies, including cardiovascular diseases, neurodegenerative disease, and cancer. These mitochondria-related pathologies range from early infancy to senescence. The central premise of this review is that if mitochondrial abnormalities contribute to the pathological state, alleviating the mitochondrial dysfunction would contribute to attenuating the severity or progression of the disease. Therefore, this review will examine the role of mitochondria in the etiology and progression of several diseases and explore potential therapeutic benefits of targeting mitochondria in mitigating the disease processes. Indeed, recent advances in mitochondrial biology have led to selective targeting of drugs designed to modulate and manipulate mitochondrial function and genomics for therapeutic benefit. These approaches to treat mitochondrial dysfunction rationally could lead to selective protection of cells in different tissues and various disease states. However, most of these approaches are in their infancy.

  7. The endocrine system and sarcopenia: potential therapeutic benefits.

    PubMed

    McIntire, Kevin L; Hoffman, Andrew R

    2011-12-01

    Age related muscle loss, known as sarcopenia, is a major factor in disability, loss of mobility and quality of life in the elderly. There are many proposed mechanisms of age-related muscle loss that include the endocrine system. A variety of hormones regulate growth, development and metabolism throughout the lifespan. Hormone activity may change with age as a result of reduced hormone secretion or decreased tissue responsiveness. This review will focus on the complex interplay between the endocrine system, aging and skeletal muscle and will present possible benefits of therapeutic interventions for sarcopenia.

  8. Potential Therapeutic Benefits of Strategies Directed to Mitochondria

    PubMed Central

    Lesnefsky, Edward J.; Stowe, David F.

    2010-01-01

    Abstract The mitochondrion is the most important organelle in determining continued cell survival and cell death. Mitochondrial dysfunction leads to many human maladies, including cardiovascular diseases, neurodegenerative disease, and cancer. These mitochondria-related pathologies range from early infancy to senescence. The central premise of this review is that if mitochondrial abnormalities contribute to the pathological state, alleviating the mitochondrial dysfunction would contribute to attenuating the severity or progression of the disease. Therefore, this review will examine the role of mitochondria in the etiology and progression of several diseases and explore potential therapeutic benefits of targeting mitochondria in mitigating the disease processes. Indeed, recent advances in mitochondrial biology have led to selective targeting of drugs designed to modulate and manipulate mitochondrial function and genomics for therapeutic benefit. These approaches to treat mitochondrial dysfunction rationally could lead to selective protection of cells in different tissues and various disease states. However, most of these approaches are in their infancy. Antioxid. Redox Signal. 13, 279–347. PMID:20001744

  9. Therapeutic potential and health benefits of Sargassum species

    PubMed Central

    Yende, Subhash R.; Harle, Uday N.; Chaugule, Bhupal B.

    2014-01-01

    Sargassum species are tropical and sub-tropical brown macroalgae (seaweed) of shallow marine meadow. These are nutritious and rich source of bioactive compounds such as vitamins, carotenoids, dietary fibers, proteins, and minerals. Also, many biologically active compounds like terpenoids, flavonoids, sterols, sulfated polysaccharides, polyphenols, sargaquinoic acids, sargachromenol, pheophytine were isolated from different Sargassum species. These isolated compounds exhibit diverse biological activities like analgesic, anti-inflammatory, antioxidant, neuroprotective, anti-microbial, anti-tumor, fibrinolytic, immune-modulatory, anti-coagulant, hepatoprotective, anti-viral activity etc., Hence, Sargassum species have great potential to be used in pharmaceutical and neutralceutical areas. This review paper explores the current knowledge of phytochemical, therapeutic potential, and health benefits of different species of genus Sargassum. PMID:24600190

  10. Benefits of additives application during combustion of phytomass

    NASA Astrophysics Data System (ADS)

    Palacka, Matej; Vician, Peter; Holubčík, Michal; Jandačka, Jozef

    2016-06-01

    Phytomass, particularly wheat straw as a source of energy has countless benefits, but it has many problems in its direct burn too. The worst problem is the ash flow temperature. The aim of study was to analyze and reduce the problems of the wheat straw combustion. The experiment was conducted under realistic conditions. In this paper was implemented analysis of ash features with and without adding additives into the wheat straw. Selected samples were laboratory processed and examined. The result of the work was the impact of additional additives for ash features.

  11. Potential Therapeutic Benefits of Maintaining Mitochondrial Health in Peripheral Neuropathies

    PubMed Central

    Areti, Aparna; Yerra, Veera Ganesh; Komirishetty, Prashanth; Kumar, Ashutosh

    2016-01-01

    Background: Peripheral neuropathies are a group of diseases characterized by malfunctioning of peripheral nervous system. Neuropathic pain, one of the core manifestations of peripheral neuropathy remains as the most severe disabling condition affecting the social and daily routine life of patients suffering from peripheral neuropathy. Method: The current review is aimed at unfolding the possible role of mitochondrial dysfunction in peripheral nerve damage and to discuss on the probable therapeutic strategies against neuronal mitotoxicity. The article also highlights the therapeutic significance of maintaining a healthy mitochondrial environment in neuronal cells via pharmacological management in context of peripheral neuropathies. Results: Aberrant cellular signaling coupled with changes in neurotransmission, peripheral and central sensitization are found to be responsible for the pathogenesis of variant toxic neuropathies. Current research reports have indicated the possible involvement of mitochondria mediated redox imbalance as one of the principal causes of neuropathy aetiologies. In addition to imbalance in redox homeostasis, mitochondrial dysfunction is also responsible for alterations in physiological bioenergetic metabolism, apoptosis and autophagy pathways. Conclusions: In spite of various etiological factors, mitochondrial dysfunction has been found to be a major pathomechanism underlying the neuronal dysfunction associated with peripheral neuropathies. Pharmacological modulation of mitochondria either directly or indirectly is expected to yield therapeutic relief from various primary and secondary mitochondrial diseases. PMID:26818748

  12. The therapeutic benefits of gravity in space and on earth.

    PubMed

    Kourtidou-Papadeli, C; Papadelis, C L; Vernikos, J; Bamidis, P D; Hitoglou-Antoniadou, M; Perantoni, E; Vlachogiannis, E

    2008-08-01

    The traditional scientific approach of investigating the role of a variable on a living organism is to remove it or the ability of the organism to sense it. Gravity is no exception. Access to space has made it possible for us to begin the exploration of how gravity has influenced our evolution, our genetic make-up and our physiology. Identifying the thresholds at which each body system perceives, how much, how often, how long the gravity stimulus is needed and in which direction should it be presented for maximum effectiveness, is fundamental knowledge required for using artificial gravity as a therapeutic or maintenance countermeasure treatment in exploration missions. Here on earth, although surrounded by gravity we are negligent in using gravity as it was intended, to maintain the level of health that is appropriate to living in 1G. These, changes in lifestyle or pathologies caused by various types of injury can benefit as well from artificial gravity in much the same way as we are now considering for astronauts in space.

  13. Lymphadenectomy for Adrenocortical Carcinoma: Is There a Therapeutic Benefit?

    PubMed Central

    Gerry, Jon M.; Tran, Thuy B.; Postlewait, Lauren M.; Maithel, Shishir K.; Prescott, Jason D.; Wang, Tracy S.; Glenn, Jason A.; Phay, John E.; Keplinger, Kara; Fields, Ryan C.; Jin, Linda X.; Weber, Sharon M.; Salem, Ahmed; Sicklick, Jason K.; Gad, Shady; Yopp, Adam C.; Mansour, John C.; Duh, Quan-Yang; Seiser, Natalie; Solorzano, Carmen C.; Kiernan, Colleen M.; Votanopoulos, Konstantinos I.; Levine, Edward A.; Hatzaras, Ioannis; Shenoy, Rivfka; Pawlik, Timothy M.; Norton, Jeffrey A.; Poultsides, George A.

    2017-01-01

    Background Lymph node metastasis is an established predictor of poor outcome for adrenocortical carcinoma (ACC); however, routine lymphadenectomy during surgical resection of ACC is not widely performed and its therapeutic role remains unclear. Methods Patients undergoing margin-negative resection for localized ACC were identified from a multi-institutional database. Patients were stratified into 2 groups based on the surgeon’s effort or not to perform a lymphadenectomy as documented in the operative note. Clinical, pathologic, and outcome data were compared between the 2 groups. Results Of 120 patients who met inclusion criteria from 1993 to 2014, 32 (27 %) underwent lymphadenectomy. Factors associated with lymphadenectomy were tumor size (12 vs. 9.5 cm; p = .007), palpable mass at presentation (26 vs. 12 %; p = .07), suspicious lymph nodes on preoperative imaging (44 vs. 7 %; p < .001), and need for multivisceral resection (78 vs. 36 %; p <.001). Median number of lymph nodes harvested was higher in the lymphadenectomy group (5.5 vs. 0; p < .001). In-hospital mortality (0 vs. 1.3 %; p =.72) and grade 3/4 complication rates (0 vs. 12 %; p = .061) were not significantly different. Patients who underwent lymphadenectomy had improved overall survival (5-year 76 vs. 59 %; p = .041). The benefit of lymphadenectomy on overall survival persisted on multivariate analysis (HR = 0.17; p = .006) controlling for adverse preoperative and intraoperative factors associated with lymphadenectomy, such as tumor size, palpable mass, irregular tumor edges, suspicious nodes on imaging, and multivisceral resection. Conclusions In this multicenter study of adrenocortical carcinoma patients undergoing R0 resection, the surgeon’s effort to dissect peritumoral lymph nodes was independently associated with improved overall survival. PMID:27590329

  14. Additionality of global benefits and financial additionality in the context of the AIJ negotiations

    SciTech Connect

    Puhl, I.

    1996-12-31

    The Conference of the Party at their first meeting (COP1) took a decision regarding criteria for joint implementation as indicated in Art. 4.2 (a) of the FCCC which established a pilot phase for activities implemented jointly (AIJ) under the pilot phase. Besides some more technical issues this decision specified that such measures should bring about real, measurable and long-term environmental benefits related to the mitigation of climate change that would not have occurred in the absence of such activities. It also established that the financing of AIJ shall be additional to the financial obligations of developed country parties. These two requirements are called the additionality criteria for AIJ. The first refers to the realness of GHG emission abatement (which means reduction compared to a baseline) whereas the second describes that funds earmarked for AIJ have no other objective (i.e. profit making, export promotion) but to reduce GHG emissions to avoid the free-riding of investors and subsequently developed country parties. The reporting framework as well as the reporting requirements under national programs do not specify further the two types of additionality and even though research focuses on issues like baseline determination there has been no attempt so far to identify approaches which contribute towards defining strict and practicable methods and guidelines to frame additionality criteria. The first FCCC assessment of pilot project reporting revealed that in the reporting of activities, emissions additionality often remained unclear, especially in cases where AIJ was only a portion of an existing or already planned project, and that there is a point about how to account for financial additionality. It subsequently proposed to develop a uniform approach to baseline determination and the assessment of emission (reduction) additionality and financial additionality.

  15. Benefits of additional courses of systemic azithromycin in periodontal disease case report.

    PubMed

    Schmidt, Edgard F; Bretz, Walter A

    2007-01-01

    The strong association of subgingival anaerobic bacteria, such as Porphyromonas gingivalis, Treponema denticola and Tannerella forsythia, with destructive periodontal disease has been well documented in the literature. Several double-blind studies have also shown the beneficial use of systemic antimicrobials that are active against these microorganisms in conjunction with conventional periodontal treatment, especially when periodontal abscesses and/or suppuration upon probing are present. Four cases with periodontal abscesses were treated with scaling/root planing in conjunction with systemic azithromycin. Partial improvement led to retreatment with two additional courses of azithromycin. Bone formation was noted on periapical radiographs after the patients took additional courses of azithromycin. In view of the benefits of using additional courses of azithromycin in the treatment of destructive periodontal disease, we conclude that the single course of systemic antimicrobials currently used in periodontal therapy may be insufficient to reach necessary therapeutic levels in infected sites.

  16. [Therapeutic and toxic theophylline levels in asthma attacks--is there a need for additional theophylline?].

    PubMed

    Zeidman, A; Gardyn, J; Fradin, Z; Fink, G; Mittelman, M

    1997-07-01

    Although first-line therapy for bronchial asthma has changed over the past decade to anti-inflammatory medication such as inhaled corticosteroids and cromolyn with possible addition of beta-agonists, theophylline is still useful and therefore widely used. However, several studies have raised serious questions regarding its efficacy in acute asthmatic exacerbations. These studies, the narrow therapeutic range of the drug, the frequency of side effects and interactions with common drugs, and individual variation in clearance and metabolism, have prompted its reevaluation in the management of asthma. Therapeutic serum levels of theophylline are between 10 to 20 mcg/ml. Most adults achieve these concentrations with daily slow-release oral theophylline preparations, 200-400 mg (approximately 10 mg/Kg) twice a day. However, when such a patient presents to the emergency room (ER) in an asthmatic attack, immediate intravenous theophylline is often given, regardless of maintenance treatment. Since the rationale for this common therapeutic approach has been challenged, the current study was undertaken. Serum theophylline levels were measured in 23 consecutive asthmatics presenting to the ER in an acute attack. 15 (68%) had therapeutic levels (above 10 mcg/ml) and 2 had toxic levels (above 20 mcg/ml), prior to receiving the standard intravenous theophylline dose given for an attack. These data indicate that most patients with bronchial asthma on oral maintenance theophylline do not require additional intravenous theophylline when in an attack. It probably will not benefit them and may even induce serious theophylline toxicity.

  17. 20 CFR 410.535 - Reductions; effect of an additional claim for benefits.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 2 2011-04-01 2011-04-01 false Reductions; effect of an additional claim for benefits. 410.535 Section 410.535 Employees' Benefits SOCIAL SECURITY ADMINISTRATION FEDERAL COAL MINE HEALTH AND SAFETY ACT OF 1969, TITLE IV-BLACK LUNG BENEFITS (1969- ) Payment of Benefits §...

  18. 20 CFR 410.535 - Reductions; effect of an additional claim for benefits.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Reductions; effect of an additional claim for benefits. 410.535 Section 410.535 Employees' Benefits SOCIAL SECURITY ADMINISTRATION FEDERAL COAL MINE HEALTH AND SAFETY ACT OF 1969, TITLE IV-BLACK LUNG BENEFITS (1969- ) Payment of Benefits §...

  19. Targeting the “Cytokine Storm” for Therapeutic Benefit

    PubMed Central

    Harrison, Kate; Oyston, Petra C.; Lukaszewski, Roman A.; Clark, Graeme C.

    2013-01-01

    Inflammation is the body's first line of defense against infection or injury, responding to challenges by activating innate and adaptive responses. Microbes have evolved a diverse range of strategies to avoid triggering inflammatory responses. However, some pathogens, such as the influenza virus and the Gram-negative bacterium Francisella tularensis, do trigger life-threatening “cytokine storms” in the host which can result in significant pathology and ultimately death. For these diseases, it has been proposed that downregulating inflammatory immune responses may improve outcome. We review some of the current candidates for treatment of cytokine storms which may prove useful in the clinic in the future and compare them to more traditional therapeutic candidates that target the pathogen rather than the host response. PMID:23283640

  20. Sesamol: an efficient antioxidant with potential therapeutic benefits.

    PubMed

    Geetha, Thiraviam; Rohit, Bhandari; Pal, Kaur Indu

    2009-07-01

    Sesamol has been shown earlier to exhibit antimutagenic (reactive oxygen mediated) and antiageing activity in our lab and it has also been found to exert chemopreventive effect. Here we report the in vitro antioxidant activity of sesamol. As most of the antioxidants act due to their property to auto-oxidise and the pro- or antioxidant activity would depend on the concentration of the agent used and the free radical source, at least 6 dilutions in concentration range of 5-1000 nmoles of sesamol were selected for each test system. Further the antioxidant activity was compared with a water soluble antioxidant (ascorbic acid). Eventhough some preliminary studies on the antioxidant activity of sesamol have been reported in DPPH assay & inhibition of lipid peroxidation, it is not complete. We, here in report comprehensively (both in terms of the no. of doses and also a variety of test systems being employed) on the antioxidant activity of sesamol. Furthermore, since all the data has been generated by the same workers and under same laboratory conditions, hence is scientifically significant. Also the process of dose selection as discussed earlier is more scientific; and the data treatment, i.e. calculation of IC(50) values and comparisons with ascorbic acid has been statistically validated. In conclusion, sesamol was found to be an efficient scavenger of the entire range of ROS in several test systems pointing towards the potential of sesamol to be developed as a possible therapeutic.

  1. 20 CFR 725.309 - Additional claims; effect of a prior denial of benefits.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Additional claims; effect of a prior denial of benefits. 725.309 Section 725.309 Employees' Benefits EMPLOYMENT STANDARDS ADMINISTRATION, DEPARTMENT OF LABOR FEDERAL COAL MINE HEALTH AND SAFETY ACT OF 1969, AS AMENDED CLAIMS FOR BENEFITS...

  2. Therapeutic Benefits of Laughter in Mental Health: A Theoretical Review.

    PubMed

    Yim, JongEun

    2016-01-01

    In modern society, fierce competition and socioeconomic interaction stress the quality of life, causing a negative influence on a person's mental health. Laughter is a positive sensation, and seems to be a useful and healthy way to overcome stress. Laughter therapy is a kind of cognitive-behavioral therapies that could make physical, psychological, and social relationships healthy, ultimately improving the quality of life. Laughter therapy, as a non-pharmacological, alternative treatment, has a positive effect on the mental health and the immune system. In addition, laughter therapy does not require specialized preparations, such as suitable facilities and equipment, and it is easily accessible and acceptable. For these reasons, the medical community has taken notice and attempted to include laughter therapy to more traditional therapies. Decreasing stress-making hormones found in the blood, laughter can mitigate the effects of stress. Laughter decreases serum levels of cortisol, epinephrine, growth hormone, and 3,4-dihydrophenylacetic acid (a major dopamine catabolite), indicating a reversal of the stress response. Depression is a disease, where neurotransmitters in the brain, such as norepinephrine, dopamine, and serotonin, are reduced, and there is something wrong in the mood control circuit of the brain. Laughter can alter dopamine and serotonin activity. Furthermore, endorphins secreted by laughter can help when people are uncomfortable or in a depressed mood. Laughter therapy is a noninvasive and non-pharmacological alternative treatment for stress and depression, representative cases that have a negative influence on mental health. In conclusion, laughter therapy is effective and scientifically supported as a single or adjuvant therapy.

  3. Increased osmolality of breast milk with therapeutic additives

    PubMed Central

    Srinivasan, L; Bokiniec, R; King, C; Weaver, G; Edwards, A

    2004-01-01

    Aim: To evaluate the changes in the osmolality of expressed breast milk (EBM) after the addition of seven additives and four proprietary fortifiers commonly used during neonatal intensive care. Methods: The osmolality of 5 ml EBM was measured with increasing doses of 6% NaCl, caffeine, sodium ironedetate, folic acid, and multivitamin drops. Sodium acid phosphate and chloral hydrate were added to 8 ml EBM, and the fortifiers were added to standard volumes of EBM. Dose-effect curves were plotted, and the volume of milk that must be added to the above additives to maintain osmolality below 400 mOsm/kg was calculated. Results: The osmolality of the pure additives ranged from 242 to 951 mOsm/kg. There was a significant increase in the osmolality of EBM with increasing doses of all additives except caffeine. The osmolality of EBM with many additives in clinically used dosages potentially exceeded 400 mOsm/kg. The greatest increase occurred with sodium ironedetate syrup, where the osmolality of EBM increased to 951.57 (25.36) mOsm/kg. Proprietary fortifiers increased the osmolality of EBM to a maximum of 395 mOsm/kg. Conclusion: Routine additives can significantly increase the osmolality of EBM to levels that exceed current guidelines for premature infant feeding. A simple guide for clinical use is presented, which indicates the amount of milk required as diluent if hyperosmolality is to be avoided. PMID:15499144

  4. Does betahistine treatment have additional benefits to vestibular rehabilitation?

    PubMed

    Karapolat, Hale; Celebisoy, Nese; Kirazli, Yesim; Bilgen, Cem; Eyigor, Sibel; Gode, Sercan; Akyuz, Aycan; Kirazli, Tayfun

    2010-08-01

    The aim of this study was to investigate the effect of high-dose betahistine treatment added to vestibular rehabilitation (VR) on the disability, balance and postural stability in patients with unilateral vestibular disorder. The VR group (group 1, n = 24) and the VR + betahistine group (group 2, n = 23) were analyzed retrospectively. All patients were evaluated before and after an 8-week customized VR in terms of disability (Dizziness Handicap Inventory, DHI), dynamic balance [Dynamic Gait Index (DGI)] and postural stability (static posturography). In group 1 and group 2, differences between DHI, DGI and falling index score on static posturography before and after the exercise program were significant (p < 0.05). In addition, a significant difference was detected only in group 2 in the variables evaluated in static posturography-Fourier 4 analysis (p < 0.05). Both VR and betahistine + VR have a positive effect on disability and balance in patients with unilateral vestibular disorder. Betahistine treatment added to VR was effective in increasing postural stability.

  5. Strength in numbers: Combining neck vibration and prism adaptation produces additive therapeutic effects in unilateral neglect

    PubMed Central

    Saevarsson, Styrmir; Kristjánsson, Árni; Halsband, Ulrike

    2010-01-01

    Unilateral neglect is a multifaceted disorder. Many authors have, for this reason, speculated that the best treatment for neglect will involve combinations of different therapeutic techniques. Two well known interventions, neck vibration (NV) and prism adaptation (PA), have often been considered to be among the most effective treatments for neglect. Here, two experiments were performed to explore possible additive benefits when these interventions are used in combination to treat chronic neglect. Both experimental groups received NV for 20 minutes, while the second group received simultaneous PA. The effects of treatment were measured with a time-restricted and feedback-based visual search task, which has previously been found to abolish the beneficial effects of PA, and with standard neglect tests. Baseline and intervention measures were performed on separate days. Findings for both groups indicated improved visual search following intervention, but the patients that underwent the combined intervention (NVPA) showed clear improvements on visual search based paper and pencil neglect tests unlike the NV-only group. Overall, our results suggest that PA strengthens the effects of NV and that feedback-based tasks do not abolish beneficial effects of PA, when NV is applied simultaneously. The results support the view that the most effective treatment for neglect will involve the combination of different treatments. PMID:20503132

  6. Defining immunological impact and therapeutic benefit of mild heating in a murine model of arthritis.

    PubMed

    Lee, Chen-Ting; Kokolus, Kathleen M; Leigh, Nicholas D; Capitano, Maegan; Hylander, Bonnie L; Repasky, Elizabeth A

    2015-01-01

    Traditional treatments, including a variety of thermal therapies have been known since ancient times to provide relief from rheumatoid arthritis (RA) symptoms. However, a general absence of information on how heating affects molecular or immunological targets relevant to RA has limited heat treatment (HT) to the category of treatments known as "alternative therapies". In this study, we evaluated the effectiveness of mild HT in a collagen-induced arthritis (CIA) model which has been used in many previous studies to evaluate newer pharmacological approaches for the treatment of RA, and tested whether inflammatory immune activity was altered. We also compared the effect of HT to methotrexate, a well characterized pharmacological treatment for RA. CIA mice were treated with either a single HT for several hours or daily 30 minute HT. Disease progression and macrophage infiltration were evaluated. We found that both HT regimens significantly reduced arthritis disease severity and macrophage infiltration into inflamed joints. Surprisingly, HT was as efficient as methotrexate in controlling disease progression. At the molecular level, HT suppressed TNF-α while increasing production of IL-10. We also observed an induction of HSP70 and a reduction in both NF-κB and HIF-1α in inflamed tissues. Additionally, using activated macrophages in vitro, we found that HT reduced production of pro-inflammatory cytokines, an effect which is correlated to induction of HSF-1 and HSP70 and inhibition of NF-κB and STAT activation. Our findings demonstrate a significant therapeutic benefit of HT in controlling arthritis progression in a clinically relevant mouse model, with an efficacy similar to methotrexate. Mechanistically, HT targets highly relevant anti-inflammatory pathways which strongly support its increased study for use in clinical trials for RA.

  7. Are There Additional Benefits from Being in Small Classes for More than One Year?

    ERIC Educational Resources Information Center

    Konstantopoulos, Spyros; Li, Wei

    2012-01-01

    Evidence from Project STAR has suggested a considerable advantage of being in small classes in early grades. However, the extra benefits of additional years in small classes have not been discussed in detail. The present study examined the additional effects of being in small classes for more than 1 year. We find that once previous grade…

  8. Cochlear Implantation among Deaf Children with Additional Disabilities: Parental Perceptions of Benefits, Challenges, and Service Provision

    ERIC Educational Resources Information Center

    Zaidman-Zait, Anat; Curle, Deirdre; Jamieson, Janet R.; Chia, Ruth; Kozak, Frederick K.

    2015-01-01

    Although increasing numbers of children with additional disabilities are receiving cochlear implants (CIs), little is known about family perspectives of the benefits and the challenges of cochlear implantation in this pediatric population. This study examines perceptions among parents of deaf children with additional disabilities regarding…

  9. The Role of Endorphins in the Pathophysiology of Shock and the Therapeutic Benefit of Opiate Antagonists,

    DTIC Science & Technology

    1980-06-01

    in rats, cats , and dogs demonstrate these therapeutic effects of naloxone across a variety of species. Additionally, naloxone treatment significantly...in rats (14,15,16) and dogs (17), and following spinal shock in rats (9,10) and cats (11,12). Since naloxone has been described as a pure opiate...rats, cats , and dogs . In addition, naloxone was shown to signifi- cantly decrease the paralysis resulting from spinal-cord injury in the cat

  10. Potential benefits of therapeutic splenectomy for patients with Hodgkin's disease and non-Hodgkin's lymphomas

    SciTech Connect

    Schreiber, D.P.; Jacobs, C.; Rosenberg, S.A.; Cox, R.S.; Hoppe, R.T.

    1985-01-01

    Thirty-four patients with Hodgkin's disease and non-Hodgkin's lymphoma underwent therapeutic splenectomies to improve hematologic tolerance for chemotherapy. The mean age was 40 years; there were 16 males and 18 females. Fourteen had Hodgkin's disease, 19 had non-Hodgkin's lymphoma, and 1 had malignant histocytosis. Nineteen had palpable splenomegaly, 19 had marrow involvement and 20 had splenic involvement by lymphoma. The following data were analyzed before and after splenectomy: mean white blood cell count (WBC) and platelet count on planned first day of cycle, delay ratio of chemotherapy delivery and percent maximal dose rate. Thirteen patients had non-Hodgkin's lymphoma, splenomegaly and positive bone marrow and showed significant benefit in all of the aforementioned parameters. Of the patients with prior irradiation, only those who completed their radiation greater than six months prior to splenectomy showed benefit. Ten patients had Hodgkin's disease, negative bone marrow and no splenomegaly. This group showed significant improvement in mean platelet count but more limited benefit in delay ratio and percent maximal dose rate. Thus, selected patients with lymphoma who are experiencing delays in chemotherapy because of poor count tolerance may benefit from splenectomy.

  11. A Qualitative Study of the Perceived Health Benefits of a Therapeutic Riding Program for Children with Autism Spectrum Disorders

    ERIC Educational Resources Information Center

    Stickney, Margaret Ann

    2010-01-01

    Therapeutic horseback riding can be recommended as a useful health promotion intervention for individuals with disabilities who face challenges to optimal health and wellness. This qualitative study examined the perceived benefits of a therapeutic riding program for children with autism spectrum disorders (ASD), with particular focus on aspects…

  12. An Investigation of the Additive Benefits of Parent Dialogic Reading Techniques in Older Preschool Children

    ERIC Educational Resources Information Center

    Switalski, Sarah O'Neill

    2012-01-01

    This study examined the additive benefit of parent dialogic reading techniques in older, high-risk preschool children using multiple baseline design across participants, a single subject research design, as was as well as pre-test and post-test measures. Five preschoolers age-eligible to begin kindergarten the following school year participated.…

  13. 20 CFR 408.808 - What happens to your SVB payments if you begin receiving additional benefit income?

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 20 Employees' Benefits 2 2013-04-01 2013-04-01 false What happens to your SVB payments if you begin receiving additional benefit income? 408.808 Section 408.808 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SPECIAL BENEFITS FOR CERTAIN WORLD WAR II VETERANS Suspensions and Terminations Suspension §...

  14. 20 CFR 408.808 - What happens to your SVB payments if you begin receiving additional benefit income?

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 20 Employees' Benefits 2 2012-04-01 2012-04-01 false What happens to your SVB payments if you begin receiving additional benefit income? 408.808 Section 408.808 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SPECIAL BENEFITS FOR CERTAIN WORLD WAR II VETERANS Suspensions and Terminations Suspension §...

  15. 20 CFR 408.808 - What happens to your SVB payments if you begin receiving additional benefit income?

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 20 Employees' Benefits 2 2014-04-01 2014-04-01 false What happens to your SVB payments if you begin receiving additional benefit income? 408.808 Section 408.808 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SPECIAL BENEFITS FOR CERTAIN WORLD WAR II VETERANS Suspensions and Terminations Suspension §...

  16. 20 CFR 408.808 - What happens to your SVB payments if you begin receiving additional benefit income?

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 2 2011-04-01 2011-04-01 false What happens to your SVB payments if you begin receiving additional benefit income? 408.808 Section 408.808 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SPECIAL BENEFITS FOR CERTAIN WORLD WAR II VETERANS Suspensions and Terminations Suspension §...

  17. 20 CFR 408.808 - What happens to your SVB payments if you begin receiving additional benefit income?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false What happens to your SVB payments if you begin receiving additional benefit income? 408.808 Section 408.808 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SPECIAL BENEFITS FOR CERTAIN WORLD WAR II VETERANS Suspensions and Terminations Suspension §...

  18. [Complementary therapies in cystic fibrosis: evidence of therapeutic benefits and treatment recommendations].

    PubMed

    Salcedo Posadas, A; Girón Moreno, R; Beltrán Bengoechea, B

    2003-01-01

    Cystic fibrosis (CF) is an autosomal-recessive disorder that predominantly affects the respiratory system. When this disease was described in 1938 the mortality rate was approximately 70 % in the first year of life. Survival has dramatically increased from a median of approximately 4 years in the 1960s to 19 years in the 1970s and 33 years in 2001 according to figures from the American Cystic Fibrosis Foundation. This impressive increase in the life expectancy of individuals with CF is undoubtedly related to recent advances in the organization of specialized CF units and to the use of new therapies against respiratory involvement.The traditional basis of treatment for CF lung disease includes nutritional support, antibiotic therapy, chest physical therapy and aerobic exercise. Preventive measures such as influenza vaccination and avoidance of tobacco smoke are also useful. Several new approaches such as ion transport therapy, protein therapy and gene therapy are currently being developed. Many studies have provided clear evidence of the therapeutic benefits of antibiotics, respiratory physiotherapy, exercise, and nutrition. In this article we review the scientific evidence on the advantages of the use of several therapeutic interventions against inflammation, increased sputum viscoelasticity and adhesiveness, and bronchial obstruction in CF patients.

  19. Passive solar addition to therapeutic pre-school. Final technical report

    SciTech Connect

    Not Available

    1983-10-01

    This project consisted of designing and constructing a passive solar system on a new classroom addition to the Peanut Butter and Jelly Therapeutic Pre-School in Albuquerque, NM. The purpose of this project was to demonstrate the applicability of solar space heating systems to large institutional buildings, and to demonstrate the energy and cost savings available through the use of such systems. Preliminary estimates indicated that the passive solar systems will provide about 90 percent of the heating and cooling needs for the new classroom addition to the school.

  20. Treatment-resistant depression in adolescents: is the addition of cognitive behavioral therapy of benefit?

    PubMed Central

    Hetrick, Sarah E; Cox, Georgina R; Merry, Sally N

    2011-01-01

    Background Many young people with major depression fail first-line treatments. Treatment-resistant depression has various definitions in the literature but typically assumes nonresponse to medication. In young people, cognitive behavioral therapy (CBT) is the recommended first-line intervention, thus the definition of treatment resistance should be expanded. Therefore, our aim was to synthesize the existing evidence of any interventions for treatment-resistant depression, broadly defined, in children and adolescents and to investigate the effectiveness of CBT in this context. Methods We used Cochrane Collaboration methodology, with electronic searches of Medline, PsycINFO, Embase, and the Cochrane Depression Anxiety and Neurosis Group trials registers. Only randomized controlled trials were included, and were assessed for risk of bias. Meta- analysis was undertaken where possible and appropriate. Results Of 953 articles retrieved, four trials were eligible for inclusion. For one study, only the trial registration document was available, because the study was never completed. All other studies were well conducted with a low risk of bias, although one study had a high dropout rate. Two studies assessed the effect of adding CBT to medication. While an assertive trial of antidepressants does appear to lead to benefit, when compared with placebo, there was no significant advantage, in either study, or in a meta-analysis of data from these trials, that clearly demonstrated an additional benefit of CBT. The third trial showed little advantage of a tricyclic antidepressant over placebo in the context of an inpatient admission. Conclusion Few randomized controlled trials have investigated interventions for treatment-resistant depression in young people, and results from these show modest benefit from antidepressants with no additional benefit over medication from CBT. Overall, there is a lack of evidence about effective interventions to treat young people who have failed to

  1. Improving depiction of benefits and harms: analyses of studies of well-known therapeutics and review of high-impact medical journals.

    PubMed

    Sedrakyan, Artyom; Shih, Chuck

    2007-10-01

    The issues of weighing benefits and harms and of shared decision-making have become increasingly important in recent years. There is limited knowledge and lack of adequate data on the most transparent method of communicating the information. In this article we discuss examples of communicating benefits and harms for well-known therapeutics, illustrating that relative risk estimates are not helpful for communicating the chance of experiencing adverse events. In addition, we show that asymmetric presentation of the data for benefits and harms is likely to bias toward showing greater benefits and diminishing the importance of the harms (or vice versa). We also present preliminary results of a brief review of high-impact medical journals that show limitations of current systematic reviews. In the review we found that every second published study does not discuss frequency data and 1 in 3 studies that report information on both benefits and harms does not report information in the same metric. We conclude that consistently depicting benefit and harm information in frequencies can substantially improve the communication of benefits and harms. Investigators should be requested to provide frequency data along with relative risk information in the publication of their scientific findings. Currently, even in the highest impact medical journals, evidence of benefits and harms is not consistently presented in ways that facilitate accurate interpretation.

  2. [Requirements for drug approval and additional benefits assessment: Regulatory aspects and experiences].

    PubMed

    Broich, K; Löbker, W; Schulte, A; Beinlich, P; Müller, T

    2016-04-01

    The early assessment of benefits of newly approved drugs with novel active substances or new applications, which came into force on 1 January 2011 still represents a challenge to all parties involved. This article highlights the definitions, regulatory requirements and interaction between drug marketing approval and early assessment of benefits in Germany. The constellation of an extensively harmonized European and even international drug authorization process with a predominantly national regulation of drug reimbursement situation inevitably causes friction, which could be markedly reduced through early joint advisory discussions during the planning phase for pivotal clinical trials. During the year 2015 the Federal Institute for Drugs and Medical Devices (BfArM) carried out 300 scientific advice procedures of which 34 were concerned with applications in the field of indications for the central nervous system (CNS). In comparison 98 advisory meetings were held by the Federal Joint Committee (G-BA) of which the BfArM provided advice in 12 instances and in 2 cases on CNS indications. Study design, endpoints and appropriate comparative therapies are the key issues in exchanges and discussions between the BfArM, the G‑BA and applicants. Under these aspects the BfArM and G‑BA promote an early and consistent involvement in early advice procedures regarding the prerequisites for drug approval and assessment of additional benefits.

  3. Addressing the stimulant treatment gap: A call to investigate the therapeutic benefits potential of cannabinoids for crack-cocaine use.

    PubMed

    Fischer, Benedikt; Kuganesan, Sharan; Gallassi, Andrea; Malcher-Lopes, Renato; van den Brink, Wim; Wood, Evan

    2015-12-01

    Crack-cocaine use is prevalent in numerous countries, yet concentrated primarily - largely within urban contexts - in the Northern and Southern regions of the Americas. It is associated with a variety of behavioral, physical and mental health and social problems which gravely affect users and their environments. Few evidence-based treatments for crack-cocaine use exist and are available to users in the reality of street drug use. Numerous pharmacological treatments have been investigated but with largely disappointing results. An important therapeutic potential for crack-cocaine use may rest in cannabinoids, which have recently seen a general resurgence for varied possible therapeutic usages for different neurological diseases. Distinct potential therapeutic benefits for crack-cocaine use and common related adverse symptoms may come specifically from cannabidiol (CBD) - one of the numerous cannabinoid components found in cannabis - with its demonstrated anxiolytic, anti-psychotic, anti-convulsant effects and potential benefits for sleep and appetite problems. The possible therapeutic prospects of cannabinoids are corroborated by observational studies from different contexts documenting crack-cocaine users' 'self-medication' efforts towards coping with crack-cocaine-related problems, including withdrawal and craving, impulsivity and paranoia. Cannabinoid therapeutics offer further benefits of being available in multiple formulations, are low in adverse risk potential, and may easily be offered in community-based settings which may add to their feasibility as interventions for - predominantly marginalized - crack-cocaine user populations. Supported by the dearth of current therapeutic options for crack-cocaine use, we are advocating for the implementation of a rigorous research program investigating the potential therapeutic benefits of cannabinoids for crack-cocaine use. Given the high prevalence of this grave substance use problem in the Americas, opportunities for

  4. A laboratory study of the perceived benefit of additional noise attenuation by houses

    NASA Technical Reports Server (NTRS)

    Flindell, I. H.

    1983-01-01

    Two Experiments were conducted to investigate the perceived benefit of additional house attenuation against aircraft flyover noise. First, subjects made annoyance judgments in a simulated living room while an operative window with real and dummy storm windows was manipulated in full view of those subjects. Second, subjects made annoyance judgments in an anechoic audiometric test chamber of frequency shaped noise signals having spectra closely matched to those of the aircraft flyover noises reproduced in the first experiment. These stimuli represented the aircraft flyover noises in levels and spectra but without the situational and visual cues present in the simulated living room. Perceptual constancy theory implies that annoyance tends to remain constant despite reductions in noise level caused by additional attenuation of which the subjects are fully aware. This theory was supported when account was taken for a reported annoyance overestimation for certain spectra and for a simulated condition cue overreaction.

  5. Charcoal addition to soils in NE England: a carbon sink with environmental co-benefits?

    PubMed

    Bell, M J; Worrall, F

    2011-04-01

    Interest in the application of biochar (charcoal produced during the pyrolysis of biomass) to agricultural land is increasing across the world, recognised as a potential way to capture and store atmospheric carbon. Its interest is heightened by its potential co-benefits for soil quality and fertility. The majority of research has however been undertaken in tropical rather than temperate regions. This study assessed the potential for lump-wood charcoal addition (as a substitute for biochar) to soil types which are typically under arable and forest land-use in North East England. The study was undertaken over a 28 week period and found: i) No significant difference in net ecosystem respiration (NER) between soils containing charcoal and those without, other than in week 1 of the trial. ii) A significantly higher dissolved organic carbon (DOC) flux from soils containing large amounts of charcoal than from those untreated, when planted with ryegrass. iii) That when increased respiration or DOC loss did occur, neither was sufficiently large to alter the carbon sink benefits of charcoal application. iv) That charcoal incorporation resulted in a significantly lower nitrate flux in soil leachate from mineral soils. v) That charcoal incorporation caused significant increases in soil pH, from 6.98 to 7.22 on bare arable soils when 87,500 kg charcoal/ha was applied. Consideration of both the carbon sink and environmental benefits observed here suggests that charcoal application to temperate soils typical of North East England should be considered as a method of carbon sequestration. Before large scale land application is encouraged, further large scale trials should be undertaken to confirm the positive results of this research.

  6. Integrating the biological characteristics of oncolytic viruses and immune cells can optimize therapeutic benefits of cell-based delivery.

    PubMed

    Thorne, S H; Contag, C H

    2008-05-01

    Despite significant advances in the development of tumor-selective agents, strategies for effective delivery of these agents across biological barriers to cells within the tumor microenvironment has been limiting. One tactical approach to overcoming biological barriers is to use cells as delivery vehicles, and a variety of different cell types have been investigated with a range of agents. In addition to transporting agents with targeted delivery, cells can also produce their own tumoricidal effect, conceal a payload from an immune response, amplify a selective agent at the target site and facilitate an antitumor immune response. We have reported a therapeutic combination consisting of cytokine induced killer cells and an oncolytic vaccinia virus with many of these features that led to therapeutic synergy in animal models of human cancer. The synergy was due to the interaction of the two agents to enhance the antitumor benefits of each individual component. As both of these agents display broad tumor-targeting potential and possess unique tumor killing mechanisms, together they were able to recognize and destroy a far greater number of malignant cells within the heterogeneous tumor than either agent alone. Effective cancer therapy will require recognition and elimination of the root of the disease, the cancer stem cell, and the combination of CIK cells and oncolytic vaccinia viruses has this potential. To create effective tumor-selective agents the viruses are modified to take advantage of the unique biology of the cancer cell. Similarly, if we are to develop targeted therapies that are sufficiently multifaceted to eliminate cancer cells at all stages of disease, we should integrate the virus into the unique biology of the cell delivery vehicle.

  7. Therapeutic Recreation in the Naturally Occurring Retirement Community (NORC): Benefitting "Aging in Place."

    ERIC Educational Resources Information Center

    Kunstler, Robin

    2002-01-01

    Describes how therapeutic recreation in naturally occurring retirement communities (neighborhoods where most residents are older) can promote healthy lifestyles, presenting a case report of an in-home therapeutic recreation program offered in conjunction with nursing and social services in a such a community and discussing implications for…

  8. [Weighing use and safety of therapeutic agents and feed additives (author's transl)].

    PubMed

    van der Wal, P

    1982-02-01

    (1) The pros and cons of using feed additives and therapeutic agents may be successfully weighed in the light of carefully considered consumer requirements. (2) The socio-economic interests of the producer and the welfare of the animal will also determine the response of the production apparatus to consumer requirements. (3) Consumption of the current amounts of products of animal origin and maintenance of price and quality will only be feasible in the event of rational large-scale production in which constituents used in nutrition, prophylaxis and therapeutics are highly important factors. (4) Using these ingredients should be preceded by accurate evaluation of their use and safety. Testing facilities, conduct of studies and reporting should be such as to make the results nationally and internationally acceptable to all those concerned. (5) In deciding whether feed constituents are acceptable in view of the established use and safety, compliance will have to be sought with those standards which are accepted in other fields of society. Measures which result in raising the price of food without actually helping to reduce the risks to the safety of man, animals and environment, are likely to be rejected by any well-informed consumer who is aware of the facts. (6) For accurate weighing of use and safety at a national level, possibilities are hardly adequate in Europe. Decisions reached within the framework of the European Community, also tuned to U.S.A.- conditions are rightly encouraged. A centrally managed professionally staffed and equipped test system in the European Community would appear to be indispensable.

  9. Delivery of therapeutic radioisotopes using nanoparticle platforms: potential benefit in systemic radiation therapy

    PubMed Central

    Zhang, Longjiang; Chen, Hongwei; Wang, Liya; Liu, Tian; Yeh, Julie; Lu, Guangming; Yang, Lily; Mao, Hui

    2010-01-01

    Radiation therapy is an effective cancer treatment option in conjunction with chemotherapy and surgery. Emerging individualized internal and systemic radiation treatment promises significant improvement in efficacy and reduction of normal tissue damage; however, it requires cancer cell targeting platforms for efficient delivery of radiation sources. With recent advances in nanoscience and nanotechnology, there is great interest in developing nanomaterials as multifunctional carriers to deliver therapeutic radioisotopes for tumor targeted radiation therapy, to monitor their delivery and tumor response to the treatment. This paper provides an overview on developing nanoparticles for carrying and delivering therapeutic radioisotopes for systemic radiation treatment. Topics discussed in the review include: selecting nanoparticles and radiotherapy isotopes, strategies for targeting nanoparticles to cancers, together with challenges and potential solutions for the in vivo delivery of nanoparticles. Some examples of using nanoparticle platforms for the delivery of therapeutic radioisotopes in preclinical studies of cancer treatment are also presented. PMID:24198480

  10. Cardiorenal axis and arrhythmias: Will renal sympathetic denervation provide additive value to the therapeutic arsenal?

    PubMed

    van Brussel, Peter M; Lieve, Krystien V V; de Winter, Robbert J; Wilde, Arthur A M

    2015-05-01

    Disruption of sympathetic tone may result in the occurrence or maintenance of cardiac arrhythmias. Multiple arrhythmic therapies that intervene by influencing cardiac sympathetic tone are common in clinical practice. These vary from pharmaceutical (β-blockers, angiotensin-converting enzyme inhibitors, and calcium antagonists) to percutaneous/surgical (cardiac sympathetic denervation) interventions. In some patients, however, these therapies have insufficient prophylactic and therapeutic capabilities. A safe and effective additional therapy wherein sympathetic drive is further attenuated would be expedient. Recently, renal sympathetic denervation (RSD) has been subject of research for various sympathetic nervous system-related diseases. By its presumed afferent and efferent sympatholytic effects, RSD might indirectly attenuate sympathetic outflow via the brain to the heart but might also reduce systemic catecholamine excretion and might therefore reduce catecholamine-sensitive arrhythmias. RSD is subject of research for various sympathetically driven arrhythmias, both supraventricular and ventricular. In this review, we give an overview of the rationale behind RSD as potential therapy in mediating arrhythmias that are triggered by a disrupted sympathetic nervous system and discuss the presently available results from animal and human studies.

  11. College and Community Partnerships: Extending the Benefits of Therapeutic Recreation to Veterans

    ERIC Educational Resources Information Center

    Fuchs, Steven J.; Cannella, Lee grace; Pisano, Susan

    2014-01-01

    In fall 2010, St. Joseph's College initiated a partnership between the college, Northport VA Medical Center, and Long Island State Veterans Home that provides a therapeutic platform for the integration of the three communities through sustainable and mutually beneficial curricular and co-curricular service and experiential learning programs. In…

  12. [Therapeutic mediation tools for the benefit of the child and teenager].

    PubMed

    Rocaboy, Claudette

    2016-01-01

    Therapeutic mediation is a tool adapted to teenagers with a chronic disease such as diabetes. Psychodrama, dramatherapy and photolanguage in particular, enable them to express themselves more freely through both speech and body, thanks to the enjoyment they get from the game, the reassurance provided by the group, the structured setting and the spontaneity they allow.

  13. The Therapeutic Benefits of Free or Informal Writing among Selected Eighth Graders.

    ERIC Educational Resources Information Center

    Brand, Alice Glarden

    Sixteen eighth grade students participated in a five-month experiment to determine whether informal writing has therapeutic effects on students' perceptions of how they view themselves and their personal problems. The students were selected on the basis of teacher opinion, learning ability, and student cooperation. Eight students were used as a…

  14. Cardiovascular pleiotropic actions of DPP-4 inhibitors: a step at the cutting edge in understanding their additional therapeutic potentials.

    PubMed

    Balakumar, Pitchai; Dhanaraj, Sokkalingam A

    2013-09-01

    Dipeptidyl peptidase 4 (DPP-4) is a serine protease enzyme expressed widely in many tissues, including the cardiovascular system. The incretin hormones such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are released from the small intestine into the vasculature during a meal, and these incretins have a potential to release insulin from pancreatic beta cells of islets of Langerhans, affording a glucose-lowering action. However, both incretins are hurriedly degraded by the DPP-4. Inhibitors of DPP-4, therefore, enhance the bioavailability of GLP-1 and GIP, and thus have been approved for better glycemic management in patients afflicted with type 2 diabetes mellitus (T2DM). Five different DPP-4 inhibitors, often called as 'gliptins', namely sitagliptin, vildagliptin, saxagliptin, linagliptin and alogliptin have been approved hitherto for clinical use. These drugs are used along with diet and exercise to lower blood sugar in diabetic subjects. T2DM is intricately related with an increased risk of cardiovascular disease. Growing body of evidence suggests that gliptins, in addition to their persuasive anti-diabetic action, have a beneficial pleiotropic action on the heart and vessels. In view of the fact of cardiovascular disease susceptibility of patients afflicted with T2DM, gliptins might offer additional therapeutic benefits in treating diabetic cardiovascular complications. Exploring further the cardiovascular pleiotropic potentials of gliptins might open a panorama in impeccably employing these agents for the dual management of T2DM and T2DM-associated perilous cardiovascular complications. This review will shed lights on the newly identified beneficial pleiotropic actions of gliptins on the cardiovascular system.

  15. Therapeutic benefits in thalassemic mice transplanted with long term cultured bone marrow cells

    PubMed Central

    Hatada, Seigo; Walton, William; Hatada, Tomoko; Wofford, Anne; Fox, Raymond; Liu, Naiyou; Lill, Michael C.; Fair, Jeffery H.; Kirby, Suzanne L.; Smithies, Oliver

    2011-01-01

    Objective Autologous bone marrow (BM) cells with a faulty gene corrected by gene targeting could provide a powerful therapeutic option for patients with genetic blood diseases. Achieving this goal is hindered by the low abundance of therapeutically useful BM cells and the difficulty of maintaining them in tissue culture long enough for completing gene targeting without them differentiating. Our objective was to devise a simple long-term culture system, using unfractioned BM cells, that maintains and expands therapeutically useful cells for ≥4 weeks. Materials and Methods From 2 to 60 million BM cells from wild-type (WT) mice, or from mice carrying a truncated erythropoietin receptor transgene (tEpoR-tg), were plated with or without irradiated fetal-liver derived AFT024 stromal cells in 25 cm2 culture flasks. Four-week cultured cells were analyzed and transplanted into sublethally irradiated thalassemic mice (1 million cells / mouse). Results After 4 weeks, the cultures with AFT024 cells had extensive “cobblestone” areas. Optimum expansion of Sca-1 positive cells was 5.5-fold with 20 × 106 WT cells/flask and 27-fold with 2 × 106 tEpoR-tg cells. More than 85% of thalassemic mice transplanted with either type of cells had almost complete reversal of their thalassemic phenotype for at least 6 months, including blood smear dysmorphology, reticulocytosis, high ferritin plasma levels and hepatic/renal hemosiderosis. Conclusion When plated at high cell densities on irradiated fetal-liver derived stromal cells, BM cells from WT mice maintain their therapeutic potential for 4 weeks in culture, which is sufficient time for correction of a faulty gene by targeting. PMID:21184801

  16. [Ketogenic diets: additional benefits to the weight loss and unfounded secondary effects].

    PubMed

    Pérez-Guisado, Joaquin

    2008-12-01

    It is also necessary to emphasize that as well as the weight loss, ketogenic diets are healthier because they promote a non-atherogenic lipid profile, lower blood pressure and diminish resistance to insulin with an improvement in blood levels of glucose and insulin. Such diets also have antineoplastic benefits, do not alter renal or liver functions, do not produce metabolic acidosis by Ketosis, have many neurological benefits in central nervous system, do not produce osteoporosis and could increase the perfomance in aerobic sports.

  17. Redox chemistry of green tea polyphenols: therapeutic benefits in neurodegenerative diseases.

    PubMed

    Hügel, H M; Jackson, N

    2012-05-01

    Evidence for the medicinal and health benefits of polyphenols in green tea for the prevention of chronic diseases such as heart disease, various types of cancer and neurodegenerative diseases is advancing. Their in vivo effectiveness and molecular mechanisms are difficult to elucidate and remain a challenging task. We review the redox responsiveness and amyloid protein perturbation biophysical properties of the major green tea polyphenol constituent (-)- epigallocatechin-3-gallate [EGCG].

  18. Benefits from additives and xylanase during enzymatic hydrolysis of bamboo shoot and mature bamboo.

    PubMed

    Li, Kena; Wang, Xiao; Wang, Jingfeng; Zhang, Junhua

    2015-09-01

    Effects of additives (BSA, PEG 6000, and Tween 80) on enzymatic hydrolysis of bamboo shoot and mature bamboo fractions (bamboo green, bamboo timber, bamboo yellow, bamboo node, and bamboo branches) by cellulases and/or xylanase were evaluated. The addition of additives was comparable to the increase of cellulase loadings in the conversion of cellulose and xylan in bamboo fractions. Supplementation of xylanase (1 mg/g DM) with cellulases (10 FPU/g DM) in the hydrolysis of bamboo fractions was more efficient than addition of additives in the production of glucose and xylose. Moreover, addition of additives could further increase the glucose release from different bamboo fractions by cellulases and xylanase. Bamboo green exhibited the lowest hydrolyzability. Almost all of the polysaccharides in pretreated bamboo shoot fractions were hydrolyzed by cellulases with the addition of additives or xylanase. Additives and xylanase showed great potential for reducing cellulase requirement in the hydrolysis of bamboo.

  19. [Sensory integration: benefits and effectiveness of therapeutic management in sensory processing disorders].

    PubMed

    Tudela-Torras, M; Abad-Mas, L; Tudela-Torras, E

    2017-02-24

    Today, the fact that sensory integration difficulties with a neurological basis exist and that they seriously condition the development of those individuals who suffer from them is widely accepted and acknowledged as being obvious by the vast majority of professionals working in the field of community healthcare. However, less is known and there is more controversy about effective treatments that can be applied to them. This is because many professionals criticise the fact that there is not enough scientific evidence to prove, both quantitatively and empirically, the outcomes of the interventions implemented as alternatives to pharmacological therapy. Consequently, when the symptoms and repercussions on the quality of life deriving from a distorted sensory integration are really disabling for the person, pharmacological treatment is used as the only possible approach, with the side effects that this entails. The reason for this is largely the fact that little is known about other effective therapeutic approaches, such as occupational therapy based on sensory integration.

  20. The possible therapeutic benefits of utilizing motion gaming systems on pediatric patients presenting autism.

    PubMed

    Crowder, Stephen A; Merritte, Kristin

    2013-09-01

    Autism is a pervasive developmental disorder that affects a growing number of children in the United States each year. It is characterized by substantive differences in brain structure and function that lead to long-term cognitive and social deficits. These differences, combined with the increasing prevalence of autism in children, warrant the need for development of innovative, cost-effective and widely available alternative and complementary therapies. Motion gaming has the potential to be highly efficacious as a therapeutic technique to aid in developing memory, facial recognition, motor skills and social integration in the pediatric autistic population. This paper outlines the major deficits in the brains of individuals with autism and describes how the use of motion gaming could capitalize on the individual strengths of each patient, leading to improvements in a variety of deficits.

  1. Benefits and challenges of starting a new therapeutic apheresis service in a resource-constrained setting.

    PubMed

    Arogundade, Fatiu A; Sanusi, Abubakr A; Oguntola, Stephen O; Omotoso, Bolanle A; Abdel-Rahman, Emaad M; Akinsola, Adewale; Balogun, Rasheed A

    2014-08-01

    Therapeutic apheresis (TA) refers to a group of extracorporeal blood treatment modalities with clinical indications for which the clinicians' knowledge, availability and applicability vary widely worldwide. Therapeutic plasma exchange (TPE), the most common TA technique, is neither readily available nor affordable in many parts of Africa. This article focuses on the challenges of starting a TPE program in a resource-constrained economy and the result of a survey of Nigerian nephrology professionals on TPE. A critical appraisal of published manuscripts from Nigeria on TA was undertaken to assess uses, methods, and challenges encountered followed by a survey of the perceptions of Nigerian nephrology professionals on TPE. Survey results: 56.7% of respondents had very little or no knowledge of TPE; 40.5% moderate and only 2.7% admitting to having a good knowledge. Only 18.9% of respondents have ever participated or observed a TPE procedure with the remaining 81.1% not having any exposure to the procedure. A vast majority of the respondents 97.3% felt they needed better exposure and training in TPE and its applications. Among consultants, 56% had little knowledge, 88% had never participated or observed the TPE procedure, and 94% felt they needed better exposure and training. There is significant limitation in accessibility, availability, and use of TPE in Nigeria; knowledge of TPE and its applications is minimal among nephrology professionals. Efforts should be concentrated on improving the knowledge and availability of TPE in resource-constrained economy like Nigeria. Centers that would be able to manage cases requiring TA should be developed.

  2. 42 CFR 408.21 - Reduction in Medicare Part B premium as an additional benefit under Medicare+Choice plans.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 2 2010-10-01 2010-10-01 false Reduction in Medicare Part B premium as an additional benefit under Medicare+Choice plans. 408.21 Section 408.21 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES MEDICARE PROGRAM PREMIUMS FOR SUPPLEMENTARY MEDICAL INSURANCE Amount of Monthly Premiums...

  3. Revisiting the Dialogue on the Transition from Coteaching to Inservice Teaching: New Frameworks, Additional Benefits and Emergent Issues

    ERIC Educational Resources Information Center

    Wassell, Beth; LaVan, Sarah Kate

    2009-01-01

    In this rejoinder, we respond to the major points made by Gallo-Fox (this forum), Beers (this forum), Carambo and Stickney (this forum), and Murphy, Carlisle and Beggs (this forum). We focus primarily on the benefits and considerations that stem from employing additional theoretical frameworks for analyzing research in coteaching. We also address…

  4. Therapeutic benefits of a component of coffee in a rat model of Alzheimer's disease.

    PubMed

    Basurto-Islas, Gustavo; Blanchard, Julie; Tung, Yunn Chyn; Fernandez, Jose R; Voronkov, Michael; Stock, Maxwell; Zhang, Sherry; Stock, Jeffry B; Iqbal, Khalid

    2014-12-01

    A minor component of coffee unrelated to caffeine, eicosanoyl-5-hydroxytryptamide (EHT), provides protection in a rat model for Alzheimer's disease (AD). In this model, viral expression of the phosphoprotein phosphatase 2A (PP2A) endogenous inhibitor, the I2(PP2A), or SET protein in the brains of rats leads to several characteristic features of AD including cognitive impairment, tau hyperphosphorylation, and elevated levels of cytoplasmic amyloid-β protein. Dietary supplementation with EHT for 6-12 months resulted in substantial amelioration of all these defects. The beneficial effects of EHT could be associated with its ability to increase PP2A activity by inhibiting the demethylation of its catalytic subunit PP2Ac. These findings raise the possibility that EHT may make a substantial contribution to the apparent neuroprotective benefits associated with coffee consumption as evidenced by numerous epidemiologic studies indicating that coffee drinkers have substantially lowered risk of developing AD.

  5. Omega-3 fatty acids: Mechanisms of benefit and therapeutic effects in pediatric and adult NAFLD.

    PubMed

    Nobili, Valerio; Alisi, Anna; Musso, Giovanni; Scorletti, Eleonora; Calder, Philip C; Byrne, Christopher D

    2016-01-01

    Non-alcoholic fatty liver disease (NAFLD) is currently considered the most common liver disease in industrialized countries, and it is estimated that it will become the most frequent indication for liver transplantation in the next decade. NAFLD may be associated with moderate (i.e. steatosis) to severe (i.e. steatohepatitis and fibrosis) liver damage and affects all age groups. Furthermore, subjects with NAFLD may be at a greater risk of other obesity-related complications later in life, and people with obesity and obesity-related complications (e.g. metabolic syndrome, type 2 diabetes and cardiovascular disease) are at increased risk of developing NAFLD. To date, there is no licensed treatment for NAFLD and therapy has been mainly centered on weight loss and increased physical activity. Unfortunately, it is often difficult for patients to adhere to the advised lifestyle changes. Therefore, based on the known pathogenesis of NAFLD, several clinical trials with different nutritional supplementation and prescribed drugs have been undertaken or are currently underway. Experimental evidence has emerged about the health benefits of omega-3 fatty acids, a group of polyunsaturated fatty acids that are important for a number of health-related functions. Omega-3 fatty acids are present in some foods (oils, nuts and seeds) that also contain omega-6 fatty acids, and the best sources of exclusively omega-3 fatty acids are oily fish, krill oil and algae. In this review, we provide a brief overview of the pathogenesis of NAFLD, and we also discuss the molecular and clinical evidence for the benefits of different omega-3 fatty acid preparations in NAFLD.

  6. No benefit of therapeutic vaccination in clinically healthy cats persistently infected with feline leukemia virus.

    PubMed

    Helfer-Hungerbuehler, A Katrin; Spiri, Andrea M; Riond, Barbara; Grest, Paula; Boretti, Felicitas S; Hofmann-Lehmann, Regina

    2015-03-24

    Therapeutic vaccinations have a potential application in infections where no curative treatment is available. In contrast to HIV, efficacious vaccines for a cat retrovirus, feline leukemia virus (FeLV), are commercially available. However, the infection is still prevalent, and no effective treatment of the infection is known. By vaccinating persistently FeLV-infected cats and presenting FeLV antigens to the immune system of the host, e.g., in the form of recombinant and/or adjuvanted antigens, we intended to shift the balance toward an advantage of the host so that persistent infection could be overcome by the infected cat. Two commercially available FeLV vaccines efficacious in protecting naïve cats from FeLV infection were tested in six experimentally and persistently FeLV-infected cats: first, a canarypox-vectored vaccine, and second, an adjuvanted, recombinant envelope vaccine was repeatedly administered with the aim to stimulate the immune system. No beneficial effects on p27 antigen and plasma viral RNA loads, anti-FeLV antibodies, or life expectancy of the cats were detected. The cats were unable to overcome or decrease viremia. Some cats developed antibodies to FeLV antigens although not protective. Thus, we cannot recommend vaccinating persistently FeLV-infected cats as a means of improving their FeLV status, quality of life or life expectancy. We suggest testing of all cats for FeLV infection prior to FeLV vaccination.

  7. Intermittent Hypoxia in Childhood: The Harmful Consequences Versus Potential Benefits of Therapeutic Uses

    PubMed Central

    Serebrovskaya, Tatiana V.; Xi, Lei

    2015-01-01

    Intermittent hypoxia (IH) often occurs in early infancy in both preterm and term infants and especially at 36–44 weeks postmenstrual age. These episodes of IH could result from sleep-disordered breathing or may be temporally unrelated to apnea or bradycardia events. There are numerous reports indicating adverse effects of IH on development, behavior, academic achievement, and cognition in children with sleep apnea syndrome. It remains uncertain about the exact causative relationship between the neurocognitive and behavioral morbidities and IH and/or its associated sleep fragmentation. On the other hand, well-controlled and moderate IH conditioning/training has been used in sick children for treating their various forms of bronchial asthma, allergic dermatoses, autoimmune thyroiditis, cerebral palsy, and obesity. This review article provides an updated and impartial analysis on the currently available evidence in supporting either side of the seemingly contradictory scenarios. We wish to stimulate a comprehensive understanding of such a complex physiological phenomenon as intermittent hypoxia, which may be accompanied by other confounding factors (e.g., hypercapnia, polycythemia), in order to prevent or reduce its harmful consequences, while maximizing its potential utility as an effective therapeutic tool in pediatric patients. PMID:26042211

  8. Therapeutic benefit of preventive telehealth counseling in the Community Outreach Heart Health and Risk Reduction Trial.

    PubMed

    Nolan, Robert P; Upshur, Ross E G; Lynn, Hazel; Crichton, Thomas; Rukholm, Ellen; Stewart, Donna E; Alter, David A; Chessex, Caroline; Harvey, Paula J; Grace, Sherry L; Picard, Louise; Michel, Isabelle; Angus, Jan; Corace, Kim; Barry-Bianchi, Susan M; Chen, Maggie H

    2011-03-01

    We evaluated whether telehealth counseling augments lifestyle change and risk factor decrease in subjects at high risk for primary or secondary cardiovascular events compared to a recommended guideline for brief preventive counseling. Subjects at high risk or with coronary heart disease (35 to 74 years of age, n = 680) were randomized to active control (risk factor feedback, brief advice, handouts) or telehealth lifestyle counseling (active control plus 6 weekly 1-hour teleconferenced sessions to groups of 4 to 8 subjects). Primary outcome was questionnaire assessment of adherence to daily exercise/physical activity and diet (daily vegetable and fruit intake and restriction of fat and salt) after treatment and at 6-month follow-up. Secondary outcomes were systolic and diastolic blood pressures, ratio of total to high-density lipoprotein cholesterol, and 10-year absolute risk for coronary disease. After treatment and at 6-month follow-up, adherence increased for telehealth versus control in exercise (29.3% and 18.4% vs 2.5% and 9.3%, respectively, odds ratio 1.60, 95% confidence interval 1.2 to 2.1) and diet (37.1% and 38.1% vs 16.7% and 33.3%, respectively, odds ratio 1.41, 95% confidence interval 1.1 to 1.9). Telehealth versus control had greater 6-month decreases in blood pressure (mean ± SE, systolic -4.8 ± 0.8 vs -2.8 ± 0.9 mm Hg, p = 0.04; diastolic -2.7 ± 0.5 vs -1.5 ± 0.6 mm Hg, p = 0.04). Decreases in cholesterol ratio and 10-year absolute risk were significant for the 2 groups. In conclusion, telehealth counseling augments therapeutic lifestyle change in subjects at high risk for cardiovascular events compared to a recommended guideline for brief preventive counseling.

  9. The potential health benefit of polyisoprenylated benzophenones from Garcinia and related genera: ethnobotanical and therapeutic importance.

    PubMed

    Kumar, Satyanshu; Sharma, Shelly; Chattopadhyay, Sunil Kumar

    2013-09-01

    fruits, which may be useful for predicting other medicinal uses, potential drug or food interactions and may benefit people where the fruits are prevalent and healthcare resources are scarce.

  10. Do Glioma Patients Derive Any Therapeutic Benefit From Taking a Higher Cumulative Dose of Temozolomide Regimens?

    PubMed Central

    Sun, Hao; Du, Shasha; Liao, Guixiang; Xie, Xiao; Ren, Chen; Yuan, Ya Wei

    2015-01-01

    Abstract Temozolomide (TMZ) is an oral alkylating agent with established effects on the central nervous system of glioblastoma (GBM) patients. Clinical trials have demonstrated a significant impact on overall survival (OS) with TMZ. Ever since, several TMZ regimens have been designed to improve treatment efficacy by increasing the cumulative dose per cycle. We report a meta-analysis to systematically evaluate different treatment schedules of TMZ in GBM patients. All searches that were conducted in the Cochrane library, Science Direct, and PubMed Databases, and 3 randomized controlled trials (1141 patients) were included. OS and progression-free survival (PFS) were the primary outcomes to be pooled. Unexpectedly, this analysis did not reveal any OS or PFS advantage for the high cumulative dose (HCD) regimen compared with the normal cumulative dose regimen (1141 total patients; hazard ratio [HR] 1.07, 95% CI 0.94–1.22, P = 0.31). Then after analyzing the characteristics of the results from each trial, we found that the regimen with a higher peak concentration during a short-term period (daily doses ≥150 mg/m2/d within ≤7 days/cycle) always had a more superior clinical benefit. So we generated a new pooled HR of 1.10 with a 95% CI of 0.96–1.25 (P = 0.17), which prefers the high peak concentration schedule even without a significant difference. The adverse outcome also indicates a significant increased risk of leukopenia (risk ratio 1.59, 95% CI 1.03–2.46, P = 0.04) among the HCD group. Our study suggests that increasing the cumulative dose per cycle is not an ideal way to improve the efficacy of TMZ, and it will lead to increased risk for leukopenia. Future trials should be designed to examine schedules of higher peak concentration rather than the cumulative dose per cycle. PMID:25997057

  11. Benefits of Therapeutic Drug Monitoring of Vancomycin: A Systematic Review and Meta-Analysis

    PubMed Central

    Ye, Zhi-Kang; Tang, Hui-Lin; Zhai, Suo-Di

    2013-01-01

    Background and Objective The necessity of therapeutic drug monitoring (TDM) for vancomycin is controversial. The objective of the current review was to evaluate the available evidence for the necessity of TDM in patients given vancomycin to treat Gram-positive infections. Methods Medline, Embase, Web of Sciences, the Cochrane Library and two Chinese literature databases (CNKI, CBM) were searched. Randomized controlled studies and observational studies that compared the clinical outcomes of TDM groups vs. non-TDM groups were included. Two reviewers independently extracted the data. The primary outcome was clinical efficacy of therapy. Secondary outcomes included vancomycin associated nephrotoxicity, duration of vancomycin therapy, length of hospital stay, and mortality. Meta-analysis was performed using the Mantel-Haenszel fixed effect method (FEM). Odds ratios (ORs) or weighted mean differences (WMD) with 95% confidence intervals (95%CIs) were calculated for categorical and continuous outcomes, respectively. Results One randomized controlled trial (RCT) and five cohort studies were included in the meta-analysis. Compared with non-TDM groups, TDM groups had significantly higher rates of clinical efficacy (OR = 2.62, 95%CI 1.34–5.11 P = 0.005) and decreased rates of nephrotoxicity (OR = 0.25, 95%CI 0.13–0.48 P<0.0001). Subgroup analyses showed that TDM group had significantly higher rates of clinical efficacy in both cohort studies subgroup (OR = 3.04, 95%CI 1.34–6.90) and in Asian population subgroup (OR = 3.04, 95%CI 1.34–6.90). TDM group had significantly decreased rates of nephrotoxicity in all subgroup. There was no significant difference in duration of vancomycin therapy (WMD = −0.40, 95%CI −2.83–2.02 P = 0.74) or length of stay (WMD = −1.01, 95%CI −7.51-5.49 P = 0.76) between TDM and non-TDM groups. Subgroup analyses showed there were no differences in duration of vancomycin therapy. Only one study reported

  12. Evaluation of the benefit of addition of clidinium C to a Helicobacter pylori eradication regimen

    PubMed Central

    Chorami, Maryam; Naderi, Nosratollah; Moghimi-Dehkordi, Bijan; Mirsattari, Dariush; Shalmani, Hamid Mohaghegh

    2013-01-01

    Aim This study aimed to evaluate the success of H.pylori eradication therapy in patients with dyspepsia by therapeutics regimes with and without clidinium C. Background Helicobacter pylori infections are reported in all parts of the world. Appropriate antibiotic therapy can treat infection. The ideal treatment regimen has not been specified. Patients and methods In a randomized, double blind clinical trials study, 250 patients with dyspepsia were enrolled. All patients were treated by Omeprazole, Metronidazole, Amoxicillin and Bismuth (OMAB) for two weeks. One tablet clidinium C before each meal was added to this regimen in the intervention group (A). Urea Breath Test (UBT) was carried out after 8-12 weeks after treatment for evaluation of H.pylori eradication. Results 132 patients in the intervention group (A) and 118 patients in the control group (B) were enrolled to the study. The rate of eradication in group A was significantly higher than group B (62.1% vs. 50%, p=0.04). Conclusion The results supported the effect of clidinium C for increasing of helicobacter pylori eradication, but further studies need to be performed. PMID:24834261

  13. Therapeutic benefits of the group B3 vitamin nicotinamide in mice with lethal endotoxemia and polymicrobial sepsis.

    PubMed

    Yuan, Hongmei; Wan, Jingyuan; Li, Longjiang; Ge, Pu; Li, Hongzhong; Zhang, Li

    2012-03-01

    Nicotinamide (NAM) is a group B3 vitamin involved in a wide range of biological processes. Recently, the anti-inflammatory properties of NAM have been revealed. In this study, we investigated the therapeutic effects of NAM in murine models of endotoxemia and sepsis. Endotoxemic liver injury was induced by intraperitoneal injection of lipopolysaccharide (LPS) into D-galactosamine (D-Gal)-sensitized mice. Lethal endotoxemia was induced by intraperitoneal administration of LPS at a dose of 20 mg/kg. Polymicrobial sepsis was induced by cecal ligation and puncture (CLP). In mice challenged with LPS/D-Gal, treatment with NAM significantly deceased serum aminotransferases level and alleviated hepatic lesions. NAM also reduced serum tumor necrosis factor-α level and attenuated apoptosis in liver, as assessed by terminal deoxynucleotidyl transferase-mediated nucleotide nick end labeling (TUNEL) staining and measurements of caspases activities. Survival analysis indicated that NAM reduced the mortality rate of LPS/D-Gal-challenged mice. In mice with lethal endotoxemia, NAM reduced serum level of pro-inflammatory cytokines and multiple organ damage as evidence by improved morphological lesion, reduced lung wet to dry ratio as well as decreased serum level of aminotransferase and blood urea nitrogen. In survival analysis, treatment with NAM increased the survival rate of mice with lethal endotoxemia or CLP-induced polymicrobial sepsis. Taken together, treatment with NAM might provide therapeutic benefits in sepsis, which attenuated inflammatory injury and improved the survival rate.

  14. A Pilot Test of the Additive Benefits of Physical Exercise to CBT for OCD.

    PubMed

    Rector, Neil A; Richter, Margaret A; Lerman, Bethany; Regev, Rotem

    2015-01-01

    The majority of "responders" to first-line cognitive-behavioural therapy (CBT) and pharmacological treatments for obsessive-compulsive disorder (OCD) are left with residual symptoms that are clinically relevant and disabling. Therefore, there is pressing need for widely accessible efficacious alternative and/or adjunctive treatments for OCD. Accumulating evidence suggests that physical exercise may be one such intervention in the mood and anxiety disorders broadly, although we are aware of only two positive small-scale pilot studies that have tested its clinical benefits in OCD. This pilot study aimed to test the feasibility and preliminary efficacy of adding a structured physical exercise programme to CBT for OCD. A standard CBT group was delivered concurrently with a 12-week customized exercise programme to 11 participants. The exercise regimen was individualized for each participant based on peak heart rate measured using an incremental maximal exercise test. Reports of exercise adherence across the 12-week regimen exceeded 80%. A paired-samples t-test indicated very large treatment effects in Yale-Brown Obsessive-Compulsive Scale scores from pre- to post-treatment in CBT group cohorts led by expert CBT OCD specialists (d = 2.55) and junior CBT clinician non-OCD specialists (d = 2.12). These treatment effects are very large and exceed effects typically observed with individual and group-based CBT for OCD based on leading meta-analytic reviews, as well as previously obtained treatment effects for CBT using the same recruitment protocol without exercise. As such, this pilot work demonstrates the feasibility and significant potential clinical utility of a 12-week aerobic exercise programme delivered in conjunction with CBT for OCD.

  15. Additives

    NASA Technical Reports Server (NTRS)

    Smalheer, C. V.

    1973-01-01

    The chemistry of lubricant additives is discussed to show what the additives are chemically and what functions they perform in the lubrication of various kinds of equipment. Current theories regarding the mode of action of lubricant additives are presented. The additive groups discussed include the following: (1) detergents and dispersants, (2) corrosion inhibitors, (3) antioxidants, (4) viscosity index improvers, (5) pour point depressants, and (6) antifouling agents.

  16. The potential therapeutic benefits of vitamin D in the treatment of estrogen receptor positive breast cancer.

    PubMed

    Krishnan, Aruna V; Swami, Srilatha; Feldman, David

    2012-09-01

    Calcitriol (1,25-dihydroxyvitamin D(3)), the hormonally active form of vitamin D, inhibits the growth of many malignant cells including breast cancer (BCa) cells. The mechanisms of calcitriol anticancer actions include cell cycle arrest, stimulation of apoptosis and inhibition of invasion, metastasis and angiogenesis. In addition we have discovered new pathways of calcitriol action that are especially relevant in inhibiting the growth of estrogen receptor positive (ER+) BCa cells. Calcitriol suppresses COX-2 expression and increases that of 15-PGDH thereby reducing the levels of inflammatory prostaglandins (PGs). Our in vitro and in vivo studies show that calcitriol decreases the expression of aromatase, the enzyme that catalyzes estrogen synthesis selectively in BCa cells and in the mammary adipose tissue surrounding BCa, by a direct repression of aromatase transcription via promoter II as well as an indirect effect due to the reduction in the levels of PGs, which are major stimulator of aromatase transcription through promoter II. Calcitriol down-regulates the expression of ERα and thereby attenuates estrogen signaling in BCa cells including the proliferative stimulus provided by estrogens. Thus the inhibition of estrogen synthesis and signaling by calcitriol and its anti-inflammatory actions will play an important role in inhibiting ER+BCa. We hypothesize that dietary vitamin D would exhibit similar anticancer activity due to the presence of the enzyme 25-hydroxyvitamin D-1α-hydroxylase (CYP27B1) in breast cells ensuring conversion of circulating 25-hydroxyvitamin D to calcitriol locally within the breast micro-environment where it can act in a paracrine manner to inhibit BCa growth. Cell culture and in vivo data in mice strongly suggest that calcitriol and dietary vitamin D would play a beneficial role in the prevention and/or treatment of ER+BCa in women.

  17. Benefits of neutral electrolyzed oxidizing water as a drinking water additive for broiler chickens.

    PubMed

    Bügener, E; Kump, A Wilms-Schulze; Casteel, M; Klein, G

    2014-09-01

    In the wake of discussion about the use of drugs in food-producing farms, it seems to be more and more important to search for alternatives and supportive measures to improve health. In this field trial, the influence of electrolyzed oxidizing (EO) water on water quality, drug consumption, mortality, and performance parameters such as BW and feed conversion rate was investigated on 2 broiler farms. At each farm, 3 rearing periods were included in the study. With EO water as the water additive, the total viable cell count and the number of Escherichia coli in drinking water samples were reduced compared with the respective control group. The frequency of treatment days was represented by the number of used daily doses per population and showed lower values in EO-water-treated groups at both farms. Furthermore, the addition of EO water resulted in a lower mortality rate. In terms of analyzed performance parameters, no significant differences were determined. In this study, the use of EO water improved drinking water quality and seemed to reduce the drug use without showing negative effects on performance parameters and mortality rates.

  18. Statins Have No Additional Benefit for Pulmonary Hypertension: A Meta-Analysis of Randomized Controlled Trials

    PubMed Central

    Wang, Lin; Qu, Moying; Chen, Yao; Zhou, Yaxiong; Wan, Zhi

    2016-01-01

    Objectives We performed a meta-analysis to explore the effects of adding statins to standard treatment on adult patients of pulmonary hypertension (PH). Methods A systematic search up to December, 2015 of Medline, EMBASE, Cochrane Database of Systematic reviews and Cochrane Central Register of Controlled Trials was performed to identify randomized controlled trials with PH patients treated with statins. Results Five studies involving 425 patients were included into this meta-analysis. The results of our analysis showed that the statins can’t significantly increase 6-minute walking distance (6MWD, mean difference [MD] = -0.33 [CI: -18.25 to 17.59]), decrease the BORG dyspnea score (MD = -0.72 [CI: -2.28 to 0.85]), the clinical worsening risk (11% in statins vs. 10.1% in controls, Risk ratio = 1.06 [CI: 0.61, 1.83]), or the systolic pulmonary arterial pressure (SPAP) (MD = -0.72 [CI: -2.28 to 0.85]). Subgroup analysis for PH due to COPD or non-COPD also showed no significance. Conclusions Statins have no additional beneficial effect on standard therapy for PH, but the results from subgroup of PH due to COPD seem intriguing and further study with larger sample size and longer follow-up is suggested. PMID:27992469

  19. Additive benefits of autonomy support and enhanced expectancies for motor learning.

    PubMed

    Wulf, Gabriele; Chiviacowsky, Suzete; Cardozo, Priscila Lopes

    2014-10-01

    Two factors that have been shown to facilitate motor learning are autonomy support (AS) and enhanced expectancies (EE) for performance. We examined the individual and combined influences of these factors. In a 2 × 2 design, participants learning a novel motor skill (throwing with the non-dominant arm) were or were not provided a choice (AS) about the ball color on each of 6 10-trial blocks during practice, and were or were not given bogus positive social-comparative feedback (EE). This resulted in four groups: AS/EE, AS, EE, and C (control). One day after the practice phase, participants completed 10 retention and 10 transfer trials. The distance to the target--a bull's eye with a 1m radius and 10 concentric circles--was 7.5m during practice and retention, and 8.5m during transfer. Autonomy support and enhanced expectancies had additive advantages for learning, with both main effects being significant for retention and transfer. On both tests, the AS/EE group showed the greatest throwing accuracy. Also, the accuracy scores of the AS and EE groups were higher than those of the C group. Furthermore, self-efficacy measured after practice and before retention and transfer was increased by both AS and EE. Thus, supporting learners' need for autonomy by given them a small choice--even though it was not directly related to task performance--and enhancing their performance expectancies appeared to independently influence learning.

  20. Meditation as a therapeutic intervention for adults at risk for Alzheimer's disease - potential benefits and underlying mechanisms.

    PubMed

    Innes, Kim E; Selfe, Terry Kit

    2014-01-01

    Alzheimer's disease (AD) is a chronic, progressive, brain disorder that affects at least 5.3 million Americans at an estimated cost of $148 billion, figures that are expected to rise steeply in coming years. Despite decades of research, there is still no cure for AD, and effective therapies for preventing or slowing progression of cognitive decline in at-risk populations remain elusive. Although the etiology of AD remains uncertain, chronic stress, sleep deficits, and mood disturbance, conditions common in those with cognitive impairment, have been prospectively linked to the development and progression of both chronic illness and memory loss and are significant predictors of AD. Therapies such as meditation that specifically target these risk factors may thus hold promise for slowing and possibly preventing cognitive decline in those at risk. In this study, we briefly review the existing evidence regarding the potential utility of meditation as a therapeutic intervention for those with and at risk for AD, discuss possible mechanisms underlying the observed benefits of meditation, and outline directions for future research.

  1. Meditation as a Therapeutic Intervention for Adults at Risk for Alzheimer’s Disease – Potential Benefits and Underlying Mechanisms

    PubMed Central

    Innes, Kim E.; Selfe, Terry Kit

    2014-01-01

    Alzheimer’s disease (AD) is a chronic, progressive, brain disorder that affects at least 5.3 million Americans at an estimated cost of $148 billion, figures that are expected to rise steeply in coming years. Despite decades of research, there is still no cure for AD, and effective therapies for preventing or slowing progression of cognitive decline in at-risk populations remain elusive. Although the etiology of AD remains uncertain, chronic stress, sleep deficits, and mood disturbance, conditions common in those with cognitive impairment, have been prospectively linked to the development and progression of both chronic illness and memory loss and are significant predictors of AD. Therapies such as meditation that specifically target these risk factors may thus hold promise for slowing and possibly preventing cognitive decline in those at risk. In this study, we briefly review the existing evidence regarding the potential utility of meditation as a therapeutic intervention for those with and at risk for AD, discuss possible mechanisms underlying the observed benefits of meditation, and outline directions for future research. PMID:24795656

  2. Pharmacogenomics in the assessment of therapeutic risks versus benefits: inside the United States Food and Drug Administration.

    PubMed

    Zineh, Issam; Pacanowski, Michael A

    2011-08-01

    Pharmacogenomics is the study of how genetic variations influence responses to drugs, diagnostics, or biologic agents. The field of pharmacogenomics has significant potential to enhance drug development and aid in making regulatory decisions. The United States Food and Drug Administration (FDA) has supported pharmacogenomics for nearly a decade by providing regulatory advice and reviewing applications, with the intent of discovering and applying genetic determinants of treatment effects. The FDA will continue to develop policies and processes centered on genomics and individualized therapeutics to guide rational drug development. It will also continue to inform the public of clinically relevant pharmacogenomic issues through various mechanisms of communication, such as drug labeling. In this review, we provide a perspective on several pharmacogenomic activities at the FDA. In addition, we attempt to clarify what we believe are several misperceptions regarding the FDA's pharmacogenomic initiatives. We hope this perspective provides a window into some ways in which the FDA is enabling individualized therapeutics through its mission-critical activities.

  3. Simultaneous interpenetrating silicone hydrogel based on radical/addition polymerization for extended release of ocular therapeutics.

    PubMed

    Xu, Jinku; Zhang, Leilei; Zhang, Yongchun; Li, Tianduo; Huo, Guanghua

    2014-01-01

    Hydrogels with interpenetrating network (IPN) can overcome thermodynamic incompatibility and obtain transparent materials with limited phase separation. In this report, hydroxyl-grafting polysiloxane (HPSO) was synthesized and transparent silicone hydrogels with interpenetrating network were simultaneously prepared based on radical polymerization of methacrylic monomer of 3-methacryloxypropyl tris(trimethylsiloxy)silane/N,N-dimethylacrylamide and addition polymerization of HPSO/isophorone diisocyanate. The silicone hydrogels were characterized by dehydration kinetics, tensile tester, light transmittance, ion permeability, oxygen permeability, and lysozyme deposition. The results show that increasing the proportion of hydrophobic network of HPSO in the IPN silicone hydrogel decreases equilibrium swelling ratio, ion permeability, Young's modulus, and lysozyme deposition; on the contrary, increased tensile strength, elongation at break and oxygen permeability. Puerarin and ketoconazole were used as models to evaluate the drug loading and in vitro release behavior of the silicone hydrogels. It is revealed that the amount of loaded drugs in the hydrogel decreases with the increase of HPSO network in the hydrogels. All the silicone hydrogels exhibit extended release behavior, especially for ketoconazole, the in vitro release is divided into two phases corresponding to the rapid release at initial 24 h and relatively slow release from 125 to 360 h.

  4. [Pregnant opioid addicted patients and additional drug intake. Part I. Toxic effects and therapeutic consequences].

    PubMed

    Hoell, Imke; Havemann-Reinecke, Ursula

    2011-10-01

    Opioid dependent patients often are dependent from the illegal consumption of heroin and, in addition, perform a polytoxicomanic way of consuming drugs. They suffer of various somatic and psychiatric diseases. Moreover, pregnancies of drug addicted women are classified as high-risk pregnancies. With respect to the particular consumed drug substances other than opioids during pregnancy variable forms of teratogenic and toxic effects can be assigned to the baby. Critical values of maternal substance abuse referring to fetal impairment do not exist. With regard to the possible teratogenic and toxic fetal effects of maternal consume of alcohol, tobacco, sedativa, cannabis, cocaine and amphetamines, withdrawal treatment of polytoxicomanic pregnant patients under inpatient medical supervision including medication if necessary represent the first-line-treatment. With respect to smoking, it is possible to detoxicate the patients also by an outpatient treatment. However, referring to heroin addiction, a maintenance therapy with L-methadone, D/L-methadone or buprenorphine should be preferred since fetal withdrawal symptoms of opioids otherwise can cause severe complications which even can lead to the loss of the fetus and also increase the risks for the mother. Increasing the dose of the opioid substitute may be necessary, for example, to avoid premature uterus contractions. It is to be pointed out that substitution treatment with methadone or buprenorphine also improve the medicinal compliance and psychosocial circumstances of the pregnant patients. Subsequent to delivery, the maintenance treatment should initially be pursued over a further period of time. In the follow up, the question of continuing with maintenance treatment or starting a withdrawal treatment of opioids should be discussed on an individual basis. To sum up, proceeded interdisciplinary care during pregnancy and afterwards by all the professions involved like general practioners as well as social workers

  5. Additional benefit of yoga to standard lifestyle modification on blood pressure in prehypertensive subjects: a randomized controlled study.

    PubMed

    Thiyagarajan, Ramkumar; Pal, Pravati; Pal, Gopal Krushna; Subramanian, Senthil Kumar; Trakroo, Madanmohan; Bobby, Zachariah; Das, Ashok Kumar

    2015-01-01

    High blood pressure (BP) is a known risk factor for cardiovascular disease morbidity. Considering the growing evidence of nonpharmacological interventions in the management of high BP, we designed a randomized, parallel active-controlled study on the effect of yoga and standard lifestyle modification (LSM) on BP and heart rate in individuals with prehypertension (systolic BP 120-139 mm Hg and/or diastolic BP 80-89 mm Hg). Volunteers (20-60 years) of both genders without any known cardiovascular disease were randomized into either LSM group (n = 92) or LSM+yoga group (n = 92). Before the intervention, age, waist circumference, physical activity, BP and fasting plasma glucose and lipids were comparable between the groups. After 12 weeks of intervention, we observed a significant reduction in the BP and heart rate in both the groups. Further, the reduction in systolic BP was significantly more in LSM+yoga group (6 mm Hg) as compared with LSM group (4 mm Hg). In addition, 13 prehypertensives became normotensives in LSM+yoga group and four in LSM group. The results indicate efficacy of nonpharmacological intervention and the additional benefit of yoga to standard LSM. Further research in this field may add to the level of evidence on the benefit of yoga, in the reduction of BP in high BP subjects, in the scientific literature.

  6. Additive neuroprotection of a 20-HETE inhibitor with delayed therapeutic hypothermia after hypoxia-ischemia in neonatal piglets

    PubMed Central

    Zhu, Junchao; Wang, Bing; Lee, Jeong-Hoo; Armstrong, Jillian S.; Kulikowicz, Ewa; Bhalala, Utpal S.; Martin, Lee J.; Koehler, Raymond C.; Yang, Zeng-Jin

    2015-01-01

    The severity of perinatal hypoxia-ischemia and the delay in initiating therapeutic hypothermia limit the efficacy of hypothermia. After hypoxia-ischemia in neonatal piglets, the arachidonic acid metabolite, 20-hydroxyeicosatetraenoic acid (20-HETE), has been found to contribute to oxidative stress at 3 hours of reoxygenation and to eventual neurodegeneration. We tested whether early administration of a 20-HETE-synthesis inhibitor after reoxygenation augments neuroprotection with 3-hour delayed hypothermia. In two hypothermic groups, whole body cooling from 38.5 to 34°C was initiated 3 hours after hypoxia-ischemia. Rewarming occurred from 20 to 24 hours; then anesthesia was discontinued. One hypothermic group received a 20-HETE inhibitor at 5 minutes after reoxygenation. A sham-operated group and another hypoxia-ischemia group remained normothermic. At 10 days of recovery, resuscitated piglets with delayed hypothermia alone had significantly greater viable neuronal density in putamen, caudate nucleus, sensorimotor cortex, CA3 hippocampus, and thalamus than did piglets with normothermic recovery, but the values remained less than those in the sham-operated group. In piglets administered the 20-HETE inhibitor before hypothermia, the density of viable neurons in putamen, cortex, and thalamus was significantly greater than in the group with hypothermia alone. Cytochrome P450 4A, which can synthesize 20-HETE, was expressed in piglet neurons in these regions. We conclude that early treatment with a 20-HETE inhibitor enhances the therapeutic benefit of delayed hypothermia in protecting neurons in brain regions known to be particularly vulnerable to hypoxia-ischemia in term newborns. PMID:25721266

  7. Can homeopathy bring additional benefits to thalassemic patients on hydroxyurea therapy? Encouraging results of a preliminary study.

    PubMed

    Banerjee, Antara; Chakrabarty, Sudipa Basu; Karmakar, Susanta Roy; Chakrabarty, Amit; Biswas, Surjyo Jyoti; Haque, Saiful; Das, Debarsi; Paul, Saili; Mandal, Biswapati; Naoual, Boujedaini; Belon, Philippe; Khuda-Bukhsh, Anisur Rahman

    2010-03-01

    Several homeopathic remedies, namely, Pulsatilla Nigricans (30th potency), Ceanothus Americanus (both mother tincture and 6th potency) and Ferrum Metallicum (30th potency) selected as per similia principles were administered to 38 thalassemic patients receiving Hydroxyurea (HU) therapy for a varying period of time. Levels of serum ferritin (SF), fetal hemoglobin (HbF), hemoglobin (Hb), platelet count (PC), mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), mean corpuscular hemoglobin (MCH), white blood cell (WBC) count, bilirubin content, alanine amino transferase (ALT), aspartate amino transferase (AST) and serum total protein content of patients were determined before and 3 months after administration of the homeopathic remedies in combination with HU to evaluate additional benefits, if any, derived by the homeopathic remedies, by comparing the data with those of 38 subjects receiving only HU therapy. Preliminary results indicated that there was a significant decrease in the SF and increase in HbF levels in the combined, treated subjects. Although the changes in other parameters were not so significant, there was a significant decrease in size of spleen in most patients with spleenomegaly and improvement in general health conditions along with an increased gap between transfusions in most patients receiving the combined homeopathic treatment. The homeopathic remedies being inexpensive and without any known side-effects seem to have great potentials in bringing additional benefits to thalassemic patients; particularly in the developing world where blood transfusions suffer from inadequate screening and fall short of the stringent safety standards followed in the developed countries. Further independent studies are encouraged.

  8. Therapeutic benefit observed with the CFTR potentiator, ivacaftor, in a CF patient homozygous for the W1282X CFTR nonsense mutation.

    PubMed

    Mutyam, Venkateshwar; Libby, Emily Falk; Peng, Ning; Hadjiliadis, Denis; Bonk, Michael; Solomon, George M; Rowe, Steven M

    2017-01-01

    Premature termination codons (PTCs) in cystic fibrosis transmembrane conductance regulator (CFTR) gene result in nonfunctional CFTR protein and are the proximate cause of ~11% of CF causing alleles. Aminoglycosides and other novel agents are known to induce translational readthrough of PTCs, a potential therapeutic approach. Among PTCs, W1282X CFTR is unique, as it is a C-terminal CFTR mutation that can exhibit partial activity, even in the truncated state. The potentiator ivacaftor (VX-770) is approved for treating CF patients with G551D and other gating mutations. Based on previous studies demonstrating the beneficial effect of ivacaftor for PTC mutations following readthrough in vitro, we hypothesized that ivacaftor may enhance CFTR activity in CF patients expressing W1282X CFTR, and could be further enhanced by readthrough. Ivacaftor significantly increased CFTR activity in W1282X-expressing cells compared to R1162X CFTR cells, and was further enhanced by readthrough with the aminoglycoside G418. Primary nasal epithelial cells from a W1282X homozygous patient showed improved CFTR function in the presence of ivacaftor. Upon ivacaftor administration to the same patient, there was significant improvement in pulmonary exacerbation frequency, BMI, and insulin requirement, whereas FEV1 remained stable over 3years. These studies suggest that ivacaftor may have moderate clinical benefit in patients with preserved expression of the W1282X CFTR mutation by stimulating residual activity of the truncated protein, suggesting the need for further studies including the addition of efficacious readthrough agents.

  9. The neuroprotective benefit from pioglitazone (PIO) addition on the alpha lipoic acid (ALA)-based treatment in experimental diabetic rats.

    PubMed

    Jin, Heung Yong; Lee, Kyung Ae; Wu, Jin Zu; Baek, Hong Sun; Park, Tae Sun

    2014-12-01

    In this study, we investigated the combined effect of pioglitazone (PIO) with alpha lipoic acid (ALA) on the peripheral nerves of diabetic rats. Animals were divided into 8 groups (N = 6-8) and designated according to ALA (100 mg/kg/day) and PIO (10 mg/kg/day) treatment: Normal, Normal + ALA, Normal + PIO, Normal + ALA + PIO, DM, DM + ALA, DM + PIO, and DM + ALA + PIO. After 24 weeks, current perception threshold, mechanical allodynia, oxidative stresses, intraepidermal nerve fiber density (IENFD), and axonal morphology in the sciatic nerve were compared among groups. IENFD in the DM + ALA + PIO group was significantly less reduced than in other DM groups (7.61 ± 0.52 vs. 5.62 ± 0.96, 5.56 ± 0.60, and 7.10 ± 0.70 for DM, DM + ALA, and DM + PIO, respectively P < 0.05). The mean myelinated axonal area in the sciatic nerves was significantly higher in the DM + ALA + PIO group compared with non-treated DM group (70.2 ± 3.46 vs. 61.1 ± 2.91, P < 0.05) although significant differences were not present between combination therapy and monotherapy independent of ALA or PIO. Our results demonstrated that combination therapy using PIO based on ALA can give an additional benefit in peripheral nerve preservation in diabetes. Moreover, PIO can be preferentially considered when additional glucose-lowering agent is required in DPN patients treated with ALA.

  10. Successful implementation of biochar carbon sequestration in European soils requires additional benefits and close collaboration with the bioenergy sector

    NASA Astrophysics Data System (ADS)

    Hauggaard-Nielsen, Henrik; Müller-Stöver, Dorette; Bruun, Esben W.; Petersen, Carsten T.

    2014-05-01

    Biochar soil application has been proposed as a measure to mitigate climate change and on the same time improve soil fertility by increased soil carbon sequestration. However, while on tropical soils the beneficial effects of biochar application on crop growth often become immediately apparent, it has been shown to be more difficult to demonstrate these effects on the more fertile soils in temperate regions. Therefore and because of the lack of carbon credits for farmers, it is necessary to link biochar application to additional benefits, both related to agricultural as well as to bioenergy production. Thermal gasification of biomass is an efficient (95% energy efficiency) and flexible way (able to cope with many different and otherwise difficult-to-handle biomass fuels) to generate bioenergy, while producing a valuable by-product - gasification biochar, containing recalcitrant carbon and essential crop nutrients. The use of the residual char product in agricultural soils will add value to the technology as well as result in additional soil benefits such as providing plant nutrients and improving soil water-holding capacity while reducing leaching risks. From a soil column (30 x 130 cm) experiment with gasification straw biochar amendment to coarse sandy subsoil increased root density of barley at critical depths in the soil profile reducing the mechanical resistance was shown, increasing yields, and the soil's capacity to store plant available water. Incorporation of residuals from a bioenergy technology like gasification show great potentials to reduce subsoil constraints increasing yield potentials on poor soils. Another advantage currently not appropriately utilized is recovery of phosphorus (P). In a recent pot experiments char products originating from low-temperature gasification of various biofuels were evaluated for their suitability as P fertilizers. Wheat straw gasification biochar generally had a low P content but a high P plant availability. To improve

  11. Combinatorial therapeutic activation with heparin and AICAR stimulates additive effects on utrophin A expression in dystrophic muscles.

    PubMed

    Péladeau, Christine; Ahmed, Aatika; Amirouche, Adel; Crawford Parks, Tara E; Bronicki, Lucas M; Ljubicic, Vladimir; Renaud, Jean-Marc; Jasmin, Bernard J

    2016-01-01

    Upregulation of utrophin A is an attractive therapeutic strategy for treating Duchenne muscular dystrophy (DMD). Over the years, several studies revealed that utrophin A is regulated by multiple transcriptional and post-transcriptional mechanisms, and that pharmacological modulation of these pathways stimulates utrophin A expression in dystrophic muscle. In particular, we recently showed that activation of p38 signaling causes an increase in the levels of utrophin A mRNAs and protein by decreasing the functional availability of the destabilizing RNA-binding protein called K-homology splicing regulatory protein, thereby resulting in increases in the stability of existing mRNAs. Here, we treated 6-week-old mdx mice for 4 weeks with the clinically used anticoagulant drug heparin known to activate p38 mitogen-activated protein kinase, and determined the impact of this pharmacological intervention on the dystrophic phenotype. Our results show that heparin treatment of mdx mice caused a significant ∼1.5- to 3-fold increase in utrophin A expression in diaphragm, extensor digitorum longus and tibialis anterior (TA) muscles. In agreement with these findings, heparin-treated diaphragm and TA muscle fibers showed an accumulation of utrophin A and β-dystroglycan along their sarcolemma and displayed improved morphology and structural integrity. Moreover, combinatorial drug treatment using both heparin and 5-amino-4-imidazolecarboxamide riboside (AICAR), the latter targeting 5' adenosine monophosphate-activated protein kinase and the transcriptional activation of utrophin A, caused an additive effect on utrophin A expression in dystrophic muscle. These findings establish that heparin is a relevant therapeutic agent for treating DMD, and illustrate that combinatorial treatment of heparin with AICAR may serve as an effective strategy to further increase utrophin A expression in dystrophic muscle via activation of distinct signaling pathways.

  12. Early treatment with addition of low dose prednisolone to methotrexate improves therapeutic outcome in severe psoriatic arthritis.

    PubMed

    Mahajan, Vikram K; Sharma, Anju Lath; Chauhan, Pushpinder S; Mehta, Karaninder S; Sharma, Nand Lal

    2013-05-01

    Psoriatic arthritis (PsA) is increasingly being recognized to cause progressive joint damage and disability. PsA unresponsive to non-steroidal anti-inflammatory drugs (NSAIDs), the conventional first-line choice of treatment, is usually managed with disease-modifying antirheumatic drugs (DMARDs) especially methotrexate. An 18-year-old HIV-negative male had progressively severe PsA of 4-month duration that was nearly confining him to a wheel chair. He did not respond to multiple NSAIDs, alone or in combination with methotrexate (15 mg/week), given for 4 weeks. Addition of prednisolone (10 mg on alternate days) controlled his symptoms within a week. The NSAIDs could be withdrawn after 4 weeks as the treatment progressed. The doses were tapered for methotrexate (5 mg/week) and prednisolone (2.5 mg on alternate days) every 8 weekly subsequently during 15 months of follow-up without recurrence/deformities or drug toxicity. For years, the use of corticosteroids in psoriasis has been criticized for their propensity to exacerbate the skin disease on withdrawal. However, monitored use of corticosteroids, even in low doses, combined with DMARDs may be a good therapeutic option in early stage of the PsA rather than 'steroid rescue' later. This will help in early control of joint inflammation, prevent joint damage and maintain long-term good functional capacity and quality of life. This may be useful when the cost or availability of biologics precludes their use. However, we discourage the use of corticosteroids as monotherapy.

  13. Combination therapy of angiotensin II receptor blocker and calcium channel blocker exerts pleiotropic therapeutic effects in addition to blood pressure lowering: amlodipine and candesartan trial in Yokohama (ACTY).

    PubMed

    Maeda, Akinobu; Tamura, Kouichi; Kanaoka, Tomohiko; Ohsawa, Masato; Haku, Sona; Azushima, Kengo; Dejima, Toru; Wakui, Hiromichi; Yanagi, Mai; Okano, Yasuko; Fujikawa, Tetsuya; Toya, Yoshiyuki; Mizushima, Shunsaku; Tochikubo, Osamu; Umemura, Satoshi

    2012-01-01

    Recent guidelines recommend combination antihypertensive therapy to achieve the target blood pressure (BP) and to suppress target organ damage. This study aimed to examine the beneficial effects of combination therapy with candesartan and amlodipine on BP control and markers of target organ function in Japanese essential hypertensive patients (N = 20) who did not achieve the target BP level during the monotherapy period with either candesartan or amlodipine. After the monotherapy period, for patients already being treated with amlodipine, a once-daily 8 mg dose of candesartan was added on during the combination therapy period (angiotensin II receptor blocker [ARB] add-on group, N = 10), and a once-daily 5 mg dose of amlodipine was added on for those already being treated with candesartan (calcium channel blocker [CCB] add-on group, N = 10). Combination therapy with candesartan and amlodipine for 12 weeks significantly decreased clinic and home systolic blood pressure (SBP) and diastolic blood pressure (DBP). In addition, the combination therapy was able to significantly reduce urine albumin excretion without decrease in estimated glomerular filtration ratio and resulted in significant improvements in brachial-ankle pulse wave velocity, central SBP, and insulin sensitivity. Furthermore, the CCB add-on group showed a significantly greater decrease in clinic and home DBP than the ARB add-on group. The calcium channel blocker add-on group also exhibited better improvements in vascular functional parameters than the ARB add-on group. These results suggest that combination therapy with candesartan and amlodipine is an efficient therapeutic strategy for hypertension with pleiotropic benefits.

  14. Biomimetic Particles as Therapeutics

    PubMed Central

    Green, Jordan J.

    2015-01-01

    In recent years, there have been major advances in the development of novel nanoparticle and microparticle-based therapeutics. An emerging paradigm is the incorporation of biomimetic features into these synthetic therapeutic constructs to enable them to better interface with biological systems. Through the control of size, shape, and material consistency, particle cores have been generated that better mimic natural cells and viruses. In addition, there have been significant advances in biomimetic surface functionalization of particles through the integration of bio-inspired artificial cell membranes and naturally derived cell membranes. Biomimetic technologies enable therapeutic particles to have increased potency to benefit human health. PMID:26277289

  15. Biomimetic particles as therapeutics.

    PubMed

    Meyer, Randall A; Sunshine, Joel C; Green, Jordan J

    2015-09-01

    In recent years, there have been major advances in the development of novel nanoparticle- and microparticle-based therapeutics. An emerging paradigm is the incorporation of biomimetic features into these synthetic therapeutic constructs to enable them to better interface with biological systems. Through the control of size, shape, and material consistency, particle cores have been generated that better mimic natural cells and viruses. In addition, there have been significant advances in biomimetic surface functionalization of particles through the integration of bio-inspired artificial cell membranes and naturally derived cell membranes. Biomimetic technologies enable therapeutic particles to have increased potency to benefit human health.

  16. Providing additional information about the benefits of statins in a leaflet for patients with coronary heart disease: a qualitative study of the impact on attitudes and beliefs

    PubMed Central

    Dickinson, Rebecca; Raynor, David K; MacDonald, Jan

    2016-01-01

    Objective To explore the impact of providing additional information about the potential benefits of simvastatin in a patient leaflet on attitudes and beliefs. Design Interview-based study using a generic qualitative approach and framework analysis. Participants 21 participants receiving a prescription for simvastatin were recruited from a general practitioner practice (from a total of 120). 8 participants were women; the age range was 55–92. Intervention Participants were provided with leaflets showing one of 3 types of additional benefit information: (1) textual statement, (2) number needed to treat (NNT) or (3) natural frequency. Semistructured interviews explored patient's attitudes and beliefs. Results A descriptive narrative of preferences for format suggested patients prefer textual as opposed to numerical benefit information. Significant barriers to the acceptance of numerical benefit information included difficulty in understanding the numbers. Patients overestimated the benefits of statins and expressed surprise at the numerical information. Conclusions Textual information was preferred but numerical information, in particular in the form of a natural frequency, may help patients make judgements about their medicines. NNTs were found to be very difficult to understand. This raises the prospect that some patients might reject medicines because of disappointment with the perceived low benefits of their medicines. The self-reported impact on behaviour appeared minimal with reports of intentions to ‘do what the doctor tells me’. Further research is needed to explore the impact of such statements on people who are yet to be prescribed a statin. PMID:27913558

  17. Existing and potential therapeutic uses for N-acetylcysteine: the need for conversion to intracellular glutathione for antioxidant benefits.

    PubMed

    Rushworth, Gordon F; Megson, Ian L

    2014-02-01

    N-acetyl-l-cysteine (NAC) has long been used therapeutically for the treatment of acetaminophen (paracetamol) overdose, acting as a precursor for the substrate (l-cysteine) in synthesis of hepatic glutathione (GSH) depleted through drug conjugation. Other therapeutic uses of NAC have also emerged, including the alleviation of clinical symptoms of cystic fibrosis through cysteine-mediated disruption of disulfide cross-bridges in the glycoprotein matrix in mucus. More recently, however, a wide range of clinical studies have reported on the use of NAC as an antioxidant, most notably in the protection against contrast-induced nephropathy and thrombosis. The results from these studies are conflicting and a consensus is yet to be reached regarding the merits or otherwise of NAC in the antioxidant setting. This review seeks to re-evaluate the mechanism of action of NAC as a precursor for GSH synthesis in the context of its activity as an "antioxidant". Results from recent studies are examined to establish whether the pre-requisites for effective NAC-induced antioxidant activity (i.e. GSH depletion and the presence of functional metabolic pathways for conversion of NAC to GSH) have received adequate consideration in the interpretation of the data. A key conclusion is a reinforcement of the concept that NAC should not be considered to be a powerful antioxidant in its own right: its strength is the targeted replenishment of GSH in deficient cells and it is likely to be ineffective in cells replete in GSH.

  18. Natural antioxidants as food and feed additives to promote health benefits and quality of meat products: A review.

    PubMed

    Jiang, Jiang; Xiong, Youling L

    2016-10-01

    Fresh and processed meats offer numerous nutritional and health benefits and provide unique eating satisfaction in the lifestyle of the modern society. However, consumption of red meat including processed products is subjected to increasing scrutiny due to the health risks associated with cytotoxins that potentially could be generated during meat preparation. Evidence from recent studies suggests free radical pathways as a plausible mechanism for toxin formation, and antioxidants have shown promise to mitigate process-generated chemical hazards. The present review discusses the involvements of lipid and protein oxidation in meat quality, nutrition, safety, and organoleptic properties; animal production and meat processing strategies which incorporate natural antioxidants to enhance the nutritional and health benefits of meat; and the application of mixed or purified natural antioxidants to eliminate or minimize the formation of carcinogens for chemical safety of cooked and processed meats.

  19. SOCIAL SECURITY DISABILITY; Additional Outreach and Collaboration on Sharing Medical Records Would Improve Wounded Warriors’ Access to Benefits

    DTIC Science & Technology

    2009-09-01

    Record MEB medical evaluation board MTF military treatment facility NHIN Nationwide Health Information Network ODAR Office of Disability...outreach and case management policies at each agency. We selected seven DOD and five VA medical treatment facilities in order to examine local-level...for benefits in cases when an applicant is receiving military pay, but is also receiving medical treatment or is on limited duty status, SSA assesses

  20. [Impact of early benefit assessment on patients with epilepsy in Germany: Current healthcare provision and therapeutic needs].

    PubMed

    Strzelczyk, A; Hamer, H M

    2016-04-01

    Epilepsy is one of the most common chronic neurological diseases and represents a significant burden for patients, their families and society. In more than 75 % of patients anticonvulsant therapy consists of valproate, carbamazepine, lamotrigine or levetiracetam. There is a need for polytherapy in drug-refractory patients and they suffer from negative effects on quality of life and employment that is associated with high indirect costs. To allow a comprehensive treatment in this patient group, access to new anticonvulsants with novel modes of action is needed; however, all applications for new antiepileptic drugs failed to prove added benefits during the Pharmaceutical Market Restructuring Act (AMNOG) in Germany. One of the main reasons is the mandatory definition of a standard comparative therapy. It remains unclear whether there will be studies in the future which will fulfill the requirements of the current version of AMNOG. Observational studies after approval and marketing of new antiepileptic drugs could be better alternatives to prove added benefits for individual patients in the current German healthcare system.

  1. Tandem oleosin genes in a cluster acquired in Brassicaceae created tapetosomes and conferred additive benefit of pollen vigor

    PubMed Central

    Huang, Chien Yu; Chen, Pei-Ying; Huang, Ming-Der; Tsou, Chih-Hua; Jane, Wann-Neng; Huang, Anthony H. C.

    2013-01-01

    During evolution, genomes expanded via whole-genome, segmental, tandem, and individual-gene duplications, and the emerged redundant paralogs would be eliminated or retained owing to selective neutrality or adaptive benefit and further functional divergence. Here we show that tandem paralogs can contribute adaptive quantitative benefit and thus have been retained in a lineage-specific manner. In Brassicaceae, a tandem oleosin gene cluster of five to nine paralogs encodes ample tapetum-specific oleosins located in abundant organelles called tapetosomes in flower anthers. Tapetosomes coordinate the storage of lipids and flavonoids and their transport to the adjacent maturing pollen as the coat to serve various functions. Transfer-DNA and siRNA mutants of Arabidopsis thaliana with knockout and knockdown of different tandem oleosin paralogs had quantitative and correlated loss of organized structures of the tapetosomes, pollen-coat materials, and pollen tolerance to dehydration. Complementation with the knockout paralog restored the losses. Cleomaceae is the family closest to Brassicaceae. Cleome species did not contain the tandem oleosin gene cluster, tapetum oleosin transcripts, tapetosomes, or pollen tolerant to dehydration. Cleome hassleriana transformed with an Arabidopsis oleosin gene for tapetum expression possessed primitive tapetosomes and pollen tolerant to dehydration. We propose that during early evolution of Brassicaceae, a duplicate oleosin gene mutated from expression in seed to the tapetum. The tapetum oleosin generated primitive tapetosomes that organized stored lipids and flavonoids for their effective transfer to the pollen surface for greater pollen vitality. The resulting adaptive benefit led to retention of tandem-duplicated oleosin genes for production of more oleosin and modern tapetosomes. PMID:23940319

  2. Worms as therapeutic agents for allergy and asthma: understanding why benefits in animal studies have not translated into clinical success.

    PubMed

    Evans, Holly; Mitre, Edward

    2015-02-01

    Helminth infections are associated with decreased rates of autoimmunity and allergy, and several clinical studies have demonstrated that intentional infection with helminths can reduce symptoms of autoimmune diseases. In contrast, though numerous animal studies have demonstrated that helminth infections ameliorate allergic diseases, clinical trials in humans have not shown benefit. In this article, we review in detail the 2 human studies that have prospectively tested whether helminth infections protect against allergy. We next review the research designs and results obtained from animal studies, and compare these to the human trials. We then postulate possible reasons for the lack of efficacy observed in clinical trials to date and discuss potential future areas of research in this field.

  3. Biomarkers to improve the benefit/risk balance for approved therapeutics: a US FDA perspective on personalized medicine.

    PubMed

    Sapsford, Kim E; Tezak, Zivana; Kondratovich, Marina; Pacanowski, Michael A; Zineh, Issam; Mansfield, Elizabeth

    2010-11-01

    This article highlights a current US FDA perspective concerning the use of biomarker-based diagnostics for personalized medicine. Specifically, current biomarkers that have application for improving the benefit/risk profile of already approved drugs are discussed. The success of biomarkers for use in personalized medicine depends on many factors, including proper evaluation of the usefulness of the biomarker for assessing the event of interest, and the safety and effectiveness of the diagnostic device used to measure the biomarker, which includes appropriate analytical and clinical validation. These points along with the many regulatory concerns regarding co-labeling of drugs and devices and future aspects, such as co-development, will be discussed in this regulatory science focus.

  4. State of the art of Ready-to-Use Therapeutic Food: a tool for nutraceuticals addition to foodstuff.

    PubMed

    Santini, Antonello; Novellino, Ettore; Armini, Vincenzo; Ritieni, Alberto

    2013-10-15

    Therapeutic foodstuff are a challenge for the use of food and functional food ingredients in the therapy of different pathologies. Ready-to-Use Therapeutic Food (RUTF) are a mixture of nutrients designed and primarily addressed to the therapy of the severe acute malnutrition. The main ingredients of the formulation are powdered milk, peanuts butter, vegetal oil, sugar, and a mix of vitamins, salts, and minerals. The potential of this food are the low percentage of free water and the high energy and nutritional density. The high cost of the powdered milk, and the food safety problems connected to the onset of toxigenic moulds on the peanuts butter, slowed down considerably the widespread and homogenous diffusion of this product. This paper presents the state of the art of RUTF, reviews the different proposed recipes, suggests some possible new formulations as an alternative of novel recipes for this promising food.

  5. Nutritional, Health, and Technological Functionality of Lupin Flour Addition to Bread and Other Baked Products: Benefits and Challenges.

    PubMed

    Villarino, C B J; Jayasena, V; Coorey, R; Chakrabarti-Bell, S; Johnson, S K

    2016-01-01

    Lupin is an undervalued legume despite its high protein and dietary fiber content and potential health benefits. This review focuses on the nutritional value, health benefits, and technological effects of incorporating lupin flour into wheat-based bread. Results of clinical studies suggest that consuming lupin compared to wheat bread and other baked products reduce chronic disease risk markers; possibly due to increased protein and dietary fiber and bioactive compounds. However, lupin protein allergy has also been recorded. Bread quality has been improved when 10% lupin flour is substituted for refined wheat flour; possibly due to lupin-wheat protein cross-linking assisting bread volume and the high water-binding capacity (WBC) of lupin fiber delaying staling. Above 10% substitution appears to reduce bread quality due to lupin proteins low elasticity and the high WBC of its dietary fiber interrupting gluten network development. Gaps in understanding of the role of lupin flour in bread quality include the optimal formulation and processing conditions to maximize lupin incorporation, role of protein cross-linking, antistaling functionality, and bioactivity of its γ-conglutin protein.

  6. Vitamin D, Cognition and Alzheimer’s Disease: The Therapeutic Benefit is in the D-Tails

    PubMed Central

    Landel, Véréna; Annweiler, Cédric; Millet, Pascal; Morello, Maria; Féron, François

    2016-01-01

    Since its discovery during the epidemic of rickets in the early 1920s, the physiological effects of vitamin D on calcium/phosphorus homeostasis have been thoroughly studied. Along with the understanding of its actions on skeletal diseases and advances in cellular and molecular biology, this misnamed vitamin has gained attention as a potential player in a growing number of physiological processes and a variety of diseases. During the last 25 years, vitamin D has emerged as a serious candidate in nervous system development and function and a therapeutic tool in a number of neurological pathologies. More recently, experimental and pre-clinical data suggest a link between vitamin D status and cognitive function. Human studies strongly support a correlation between low levels of circulating 25-hydroxyvitamin D (25(OH)D) and cognitive impairment or dementia in aging populations. In parallel, animal studies show that supplementation with vitamin D is protective against biological processes associated with Alzheimer’s disease (AD) and enhances learning and memory performance in various animal models of aging and AD. These experimental observations support multiple mechanisms by which vitamin D can act against neurodegenerative processes. However, clinical interventional studies are disappointing and fail to associate increased 25(OH)D levels with improved cognitive outcomes. This review collects the current available data from both animal and human studies and discusses the considerations that future studies examining the effects of vitamin D status on neurocognitive function might consider. PMID:27176073

  7. Addition of Everolimus Post VEGFR Inhibition Treatment Failure in Advanced Sarcoma Patients Who Previously Benefited from VEGFR Inhibition: A Case Series

    PubMed Central

    Hays, John L.; Chen, James L.

    2016-01-01

    Background Patients with metastatic sarcoma who progress on vascular endothelial growth factor receptor inhibitors (VEGFRi) have limited treatment options. Upregulation of the mTOR pathway has been demonstrated to be a means of resistance to targeted VEGFRi in metastatic sarcoma. Patients and methods Retrospective cohort study to evaluate the clinical benefit at four months of combining mTOR inhibition (mTORi) via everolimus with VEGFRi in patients who have derived benefit from single-agent VEGFRi but have progressed. Patients with recurrent, metastatic soft tissue or bone sarcomas who progressed after deriving clinical benefit to VEGFRi beyond 12 weeks were continued on VEGFRi with the addition of everolimus (5 mg daily). Progression free survival was measured from start of VEGFRi to disease progression on single agent VEGFRi as well as from the addition of everolimus therapy to disease progression or drug discontinuation due to toxicity. Clinical benefit was defined as stable disease or partial response at 4 months. Results Nine patients were evaluated. Two patients did not tolerate therapy due to GI toxicity and one elected to discontinue therapy. Of the remaining six patients, the clinical benefit rate at four months was 50%. Progression free survival (PFS) for these patients was 3.1 months ranging from 0.5 to 7.2 months with one patient remaining on combination therapy. Conclusion In this heavily pre-treated, advanced sarcoma population, the addition of mTOR inhibition to VEGFRi based therapy resulted in a clinical benefit for a subset of patients. Prospective studies will be needed to verify these results. PMID:27295141

  8. Development and Qualification of a Specialized Gas Turbine Test Stand to Research the Potential Benefits of Nanocatalyst Fuel Additives

    DTIC Science & Technology

    2007-12-01

    71 ix LIST OF FIGURES Figure 1. Activation Energy Affect on Residence Time (from Davis...altered on a molecular level in order to achieve higher catalytic energies or increase operating ranges. The use of nanocatalysts as a means of...stored fuel. Anti- oxidants can also act to inhibit the formation of peroxide compounds. 3. Static dissipater additives reduce the effects of static

  9. Risk-Benefit Profile of Direct-Acting Oral Anticoagulants in Established Therapeutic Indications: An Overview of Systematic Reviews and Observational Studies.

    PubMed

    Raschi, Emanuel; Bianchin, Matteo; Ageno, Walter; De Ponti, Roberto; De Ponti, Fabrizio

    2016-12-01

    Since 2008, the direct-acting oral anticoagulants (DOACs) have expanded the therapeutic options of cardiovascular diseases with recognized clinical and epidemiological impact, such as non-valvular atrial fibrillation (NVAF) and venous thromboembolism (VTE), and also in the preventive setting of orthopedic surgical patients. The large body of evidence, not only from pivotal clinical trials but also from 'real-world' postmarketing observational findings (e.g. analytical epidemiological studies and registry data) gathered to date allow for a first attempt at verifying a posteriori whether or not the pharmacological advantages of the DOACs actually translate into therapeutic innovation, with relevant implications for clinicians, regulators and patients. This review aims to synthesize the risk-benefit profile of DOACs in the aforementioned consolidated indications through an 'evidence summary' approach gathering the existent evidence-based data, particularly systematic reviews with meta-analyses of randomized controlled trials, as well as observational studies, comparing DOACs with vitamin K antagonists. Clinical evidence will be discussed and compared with major international guidelines to identify whether an update is needed. Controversial clinically relevant safety issues will be also examined in order to highlight current challenges and unsettled questions (e.g. actual bleeding risk in susceptible populations). It is anticipated that the large number of publications on NVAF or VTE (44 systematic reviews with meta-analyses and 12 observational studies retained in our analysis) suggests the potential existence of overlapping studies and calls for common criteria to qualitatively and quantitatively assess discordances, thus guiding future research.

  10. A comparison of the additional protocols of the five nuclear weapon states and the ensuing safeguards benefits to international nonproliferation efforts

    SciTech Connect

    Uribe, Eva C; Sandoval, M Analisa; Sandoval, Marisa N; Boyer, Brian D; Leitch, Rosalyn M

    2009-01-01

    With the 6 January 2009 entry into force of the Additional Protocol by the United States of America, all five declared Nuclear Weapon States that are part of the Nonproliferation Treaty have signed, ratified, and put into force the Additional Protocol. This paper makes a comparison of the strengths and weaknesses of the five Additional Protocols in force by the five Nuclear Weapon States with respect to the benefits to international nonproliferation aims. This paper also documents the added safeguards burden to the five declared Nuclear Weapon States that these Additional Protocols put on the states with respect to access to their civilian nuclear programs and the hosting of complementary access activities as part of the Additional Protocol.

  11. Revisiting automated G-protein coupled receptor modeling: the benefit of additional template structures for a neurokinin-1 receptor model.

    PubMed

    Kneissl, Benny; Leonhardt, Bettina; Hildebrandt, Andreas; Tautermann, Christofer S

    2009-05-28

    The feasibility of automated procedures for the modeling of G-protein coupled receptors (GPCR) is investigated on the example of the human neurokinin-1 (NK1) receptor. We use a combined method of homology modeling and molecular docking and analyze the information content of the resulting docking complexes regarding the binding mode for further refinements. Moreover, we explore the impact of different template structures, the bovine rhodopsin structure, the human beta(2) adrenergic receptor, and in particular a combination of both templates to include backbone flexibility in the target conformational space. Our results for NK1 modeling demonstrate that model selection from a set of decoys can in general not solely rely on docking experiments but still requires additional mutagenesis data. However, an enrichment factor of 2.6 in a nearly fully automated approach indicates that reasonable models can be created automatically if both available templates are used for model construction. Thus, the recently resolved GPCR structures open new ways to improve the model building fundamentally.

  12. The central nervous system--an additional consideration in 'rotator cuff tendinopathy' and a potential basis for understanding response to loaded therapeutic exercise.

    PubMed

    Littlewood, Chris; Malliaras, Peter; Bateman, Marcus; Stace, Richmond; May, Stephen; Walters, Stephen

    2013-12-01

    Tendinopathy is a term used to describe a painful tendon disorder but despite being a well-recognised clinical presentation, a definitive understanding of the pathoaetiology of rotator cuff tendinopathy remains elusive. Current explanatory models, which relate to peripherally driven nocioceptive mechanisms secondary to structural abnormality, or failed healing, appear inadequate on their own in the context of current literature. In light of these limitations this paper presents an extension to current models that incorporates the integral role of the central nervous system in the pain experience. The role of the central nervous system (CNS) is described and justified along with a potential rationale to explain the favourable response to loaded therapeutic exercises demonstrated by previous studies. This additional consideration has the potential to offer a useful way to explain pain to patients, for clinicians to prescribe appropriate therapeutic management strategies and for researchers to advance knowledge in relation to this clinically challenging problem.

  13. Non-additive benefit or cost? Disentangling the indirect effects that occur when plants bearing extrafloral nectaries and honeydew-producing insects share exotic ant mutualists

    PubMed Central

    Savage, Amy M.; Rudgers, Jennifer A.

    2013-01-01

    Background and Aims In complex communities, organisms often form mutualisms with multiple different partners simultaneously. Non-additive effects may emerge among species linked by these positive interactions. Ants commonly participate in mutualisms with both honeydew-producing insects (HPI) and their extrafloral nectary (EFN)-bearing host plants. Consequently, HPI and EFN-bearing plants may experience non-additive benefits or costs when these groups co-occur. The outcomes of these interactions are likely to be influenced by variation in preferences among ants for honeydew vs. nectar. In this study, a test was made for non-additive effects on HPI and EFN-bearing plants resulting from sharing exotic ant guards. Preferences of the dominant exotic ant species for nectar vs. honeydew resources were also examined. Methods Ant access, HPI and nectar availability were manipulated on the EFN-bearing shrub, Morinda citrifolia, and ant and HPI abundances, herbivory and plant growth were assessed. Ant-tending behaviours toward HPI across an experimental gradient of nectar availability were also tracked in order to investigate mechanisms underlying ant responses. Key Results The dominant ant species, Anoplolepis gracilipes, differed from less invasive ants in response to multiple mutualists, with reductions in plot-wide abundances when nectar was reduced, but no response to HPI reduction. Conversely, at sites where A. gracilipes was absent or rare, abundances of less invasive ants increased when nectar was reduced, but declined when HPI were reduced. Non-additive benefits were found at sites dominated by A. gracilipes, but only for M. citrifolia plants. Responses of HPI at these sites supported predictions of the non-additive cost model. Interestingly, the opposite non-additive patterns emerged at sites dominated by other ants. Conclusions It was demonstrated that strong non-additive benefits and costs can both occur when a plant and herbivore share mutualist partners. These

  14. A cost-benefit analysis of blood donor vaccination as an alternative to additional DNA testing for reducing transfusion transmission of hepatitis B virus.

    PubMed

    Fischinger, J M; Stephan, B; Wasserscheid, K; Eichler, H; Gärtner, B C

    2010-11-16

    A survey-based, cost-benefit analysis was performed comparing blood screening strategies with vaccination strategies for the reduction of transfusion transmission of HBV. 231 whole blood donors and 126 apheresis donors were eligible and completed a questionnaire detailing their donation habits. The cost-benefit analysis included current mandatory HBV testing (HbsAg+anti-Hbc, A1), A1 with additional nucleic acid testing (NAT) for minipool (A2) or individual donation testing (A3), as well as HBV vaccination strategies using time-dependant (B1) or titre dependent booster vaccination solely (B2), or B2 in addition to current mandatory testing procedures (B3). Different cost models were applied using a 5% rate of discount. Absolute costs for current mandatory testing procedures (A1) over 20 years in Germany were €1009 million. Additional NAT would lead to incremental costs of 43% (A2) or 339% (A3), respectively. Vaccination strategies B1 and B2 showed cost-reductions relative to A1 of 30% and 14%, respectively. The number of remaining HBV infections could be reduced from 360 (for A1) to 13, using vaccination, compared with 144 or 105 remaining infections for A2 or A3, respectively. Absolute cost per prevented infection is similar (€2.0 million) for A2 and B3. HBV vaccination offers the near-elimination of transfusion infections while representing a potential cost-reduction.

  15. A Multicenter, Prospective, Randomized Controlled Trial to Evaluate the Additional Benefit of a Multistrain Synbiotic (Prodefen®) in the Clinical Management of Acute Viral Diarrhea in Children

    PubMed Central

    García-Menor, Emilia; García-Marín, Fátima; Vecino-López, Raquel; Horcajo-Martínez, Gloria; de Ibarrondo Guerrica-Echevarría, María-José; Gómez-González, Pedro; Velasco-Ortega, Syra; Suárez-Almarza, Javier; Nieto-Magro, Concepción

    2016-01-01

    This randomized, open-label study evaluated the additional benefits of the synbiotic Prodefen® in the clinical management of acute diarrhea of suspected viral origin in children between 6 months and 12 years of age. Study outcomes included the duration of diarrhea, the recovery from diarrhea, and the tolerability and acceptance of the treatment. The proportion of patients without diarrhea over the study period was greater in the synbiotic group than in the control group at all study time points, showing a statistically significant difference on the fifth day (95% vs 79%, p < 0.001). The duration of diarrhea (median and interquartile range) was reduced by 1 day in the synbiotic-treated patients (3 [2-5] vs 4 [3-5], p = 0.377). The tolerability of the treatment regimen, as evaluated by the parents, was significantly better in those receiving the synbiotic than in the control group. Overall, 96% of the parents of children receiving the synbiotic reported being satisfied to very satisfied with the treatment regimen. The results of this study indicate that the addition of the synbiotic Prodefen® is a well-tolerated and well-accepted approach that provides an additional benefit to the standard supportive therapy in the management of acute viral diarrhea in children. PMID:28229091

  16. Angolan Cymbopogon citratus used for therapeutic benefits: nutritional composition and influence of solvents in phytochemicals content and antioxidant activity of leaf extracts.

    PubMed

    Soares, Marta O; Alves, Rita C; Pires, Pedro C; Oliveira, M Beatriz P P; Vinha, Ana F

    2013-10-01

    Folk medicine is a relevant and effective part of indigenous healthcare systems which are, in practice, totally dependent on traditional healers. An outstanding coincidence between indigenous medicinal plant uses and scientifically proved pharmacological properties of several phytochemicals has been observed along the years. This work focused on the leaves of a medicinal plant traditionally used for therapeutic benefits (Angolan Cymbopogon citratus), in order to evaluate their nutritional value. The bioactive phytochemical composition and antioxidant activity of leaf extracts prepared with different solvents (water, methanol and ethanol) were also evaluated. The plant leaves contained ∼60% of carbohydrates, protein (∼20%), fat (∼5%), ash (∼4%) and moisture (∼9%). The phytochemicals screening revealed the presence of tannins, flavonoids, and terpenoids in all extracts. Methanolic extracts also contained alkaloids and steroids. Several methods were used to evaluate total antioxidant capacity of the different extracts (DPPH·, NO·, and H₂O₂ scavenging assays, reducing power, and FRAP). Ethanolic extracts presented a significantly higher antioxidant activity (p<0.05) except for FRAP, in which the best results were achieved by the aqueous extracts. Methanolic extracts showed the lowest radical scavenging activities for both DPPH· and NO· radicals.

  17. No Additional Benefit of Repeat-Sprint Training in Hypoxia than in Normoxia on Sea-Level Repeat-Sprint Ability

    PubMed Central

    Goods, Paul S.R.; Dawson, Brian; Landers, Grant J.; Gore, Christopher J.; Peeling, Peter

    2015-01-01

    To assess the impact of ‘top-up’ normoxic or hypoxic repeat-sprint training on sea-level repeat-sprint ability, thirty team sport athletes were randomly split into three groups, which were matched in running repeat-sprint ability (RSA), cycling RSA and 20 m shuttle run performance. Two groups then performed 15 maximal cycling repeat-sprint training sessions over 5 weeks, in either normoxia (NORM) or hypoxia (HYP), while a third group acted as a control (CON). In the post-training cycling RSA test, both NORM (13.6%; p = 0.0001, and 8.6%; p = 0.001) and HYP (10.3%; p = 0.007, and 4.7%; p = 0.046) significantly improved overall mean and peak power output, respectively, whereas CON did not change (1.4%; p = 0.528, and -1.1%; p = 0.571, respectively); with only NORM demonstrating a moderate effect for improved mean and peak power output compared to CON. Running RSA demonstrated no significant between group differences; however, the mean sprint times improved significantly from pre- to post-training for CON (1.1%), NORM (1.8%), and HYP (2.3%). Finally, there were no group differences in 20 m shuttle run performance. In conclusion, ‘top-up’ training improved performance in a task-specific activity (i.e. cycling); however, there was no additional benefit of conducting this ‘top-up’ training in hypoxia, since cycle RSA improved similarly in both HYP and NORM conditions. Regardless, the ‘top-up’ training had no significant impact on running RSA, therefore the use of cycle repeat-sprint training should be discouraged for team sport athletes due to limitations in specificity. Key points ‘Top-up’ repeat-sprint training performed on a cycle ergometer enhances cycle repeat-sprint ability compared to team sport training only in football players. The addition of moderate hypoxia to repeat-sprint training provides no additional performance benefits to sea-level repeat-sprint ability or endurance performance than normoxic repeat-sprint training.

  18. No Additional Benefit of Repeat-Sprint Training in Hypoxia than in Normoxia on Sea-Level Repeat-Sprint Ability.

    PubMed

    Goods, Paul S R; Dawson, Brian; Landers, Grant J; Gore, Christopher J; Peeling, Peter

    2015-09-01

    To assess the impact of 'top-up' normoxic or hypoxic repeat-sprint training on sea-level repeat-sprint ability, thirty team sport athletes were randomly split into three groups, which were matched in running repeat-sprint ability (RSA), cycling RSA and 20 m shuttle run performance. Two groups then performed 15 maximal cycling repeat-sprint training sessions over 5 weeks, in either normoxia (NORM) or hypoxia (HYP), while a third group acted as a control (CON). In the post-training cycling RSA test, both NORM (13.6%; p = 0.0001, and 8.6%; p = 0.001) and HYP (10.3%; p = 0.007, and 4.7%; p = 0.046) significantly improved overall mean and peak power output, respectively, whereas CON did not change (1.4%; p = 0.528, and -1.1%; p = 0.571, respectively); with only NORM demonstrating a moderate effect for improved mean and peak power output compared to CON. Running RSA demonstrated no significant between group differences; however, the mean sprint times improved significantly from pre- to post-training for CON (1.1%), NORM (1.8%), and HYP (2.3%). Finally, there were no group differences in 20 m shuttle run performance. In conclusion, 'top-up' training improved performance in a task-specific activity (i.e. cycling); however, there was no additional benefit of conducting this 'top-up' training in hypoxia, since cycle RSA improved similarly in both HYP and NORM conditions. Regardless, the 'top-up' training had no significant impact on running RSA, therefore the use of cycle repeat-sprint training should be discouraged for team sport athletes due to limitations in specificity. Key points'Top-up' repeat-sprint training performed on a cycle ergometer enhances cycle repeat-sprint ability compared to team sport training only in football players.The addition of moderate hypoxia to repeat-sprint training provides no additional performance benefits to sea-level repeat-sprint ability or endurance performance than normoxic repeat-sprint training.'Top-up' cycling repeat-sprint training

  19. The benefits of an additional worker are task-dependent: assessing low-back injury risks during prefabricated (panelized) wall construction.

    PubMed

    Kim, Sunwook; Nussbaum, Maury A; Jia, Bochen

    2012-09-01

    Team manual material handling is a common practice in residential construction where prefabricated building components (e.g., wall panels) are increasingly used. As part of a larger effort to enable proactive control of ergonomic exposures among workers handling panels, this study explored the effects of additional workers on injury risks during team-based panel erection tasks, specifically by quantifying how injury risks are affected by increasing the number of workers (by one, above the nominal or most common number). Twenty-four participants completed panel erection tasks with and without an additional worker under different panel mass and size conditions. Four risk assessment methods were employed that emphasized the low back. Though including an additional worker generally reduced injury risk across several panel masses and sizes, the magnitude of these benefits varied depending on the specific task and exhibited somewhat high variability within a given task. These results suggest that a simple, generalizable recommendation regarding team-based panel erection tasks is not warranted. Rather, a more systems-level approach accounting for both injury risk and productivity (a strength of panelized wall systems) should be undertaken.

  20. TU-EF-304-11: Therapeutic Benefits of Collimation in Spot Scanning Proton Therapy in the Treatment of Brain Cancer

    SciTech Connect

    Moignier, A; Gelover, E; Wang, D; Flynn, R; Hyer, D; Kirk, M; Lin, L; Solberg, T; Lin, A

    2015-06-15

    Purpose: A dynamic collimation system (DCS) based on two orthogonal pairs of mobile trimmer blades has recently been proposed to reduce the lateral penumbra in spot scanning proton therapy (SSPT). The purpose of this work is to quantify the therapeutic benefit of using the DCS for SSPT of brain cancer by comparing un-collimated and collimated treatment plans. Methods: Un-collimated and collimated brain treatment plans were created for five patients, previously treated with SSPT, using an in-house treatment planning system capable of modeling collimated and un-collimated beamlets. Un-collimated plans reproduced the clinically delivered plans in terms of target coverage and organ-at-risk (OAR) sparing, whereas collimated plans were re-optimized to improve the organ-at-risk sparing while maintaining target coverage. Physical and biological comparison metrics such as dose distribution conformity, mean and maximum doses, normal tissue complication probability (NTCP) and risk of secondary brain cancer were used to evaluate the plans. Results: The DCS systematically improved the dose distribution conformity while preserving the target coverage. The average reduction of the mean dose to the 10-mm ring surrounding the target and the healthy brain were 7.1% (95% CI: 4.2%–9.9%; p<0.01) and 14.3% (95% CI: 7.8%–20.8%; p<0.01), respectively. This yielded an average reduction of 12.0% (95% CI: 8.2%–15.7%; p<0.01) for the brain necrosis NTCP using the Flickinger model, and 14.2% (95% CI: 7.7%–20.8%; p<0.01) for the risk of secondary brain cancer. The average maximum dose reductions for the brainstem, chiasm, optic nerves, cochleae and pituitary gland when comparing un-collimated and collimated plans were 14.3%, 10.4%, 11.2%, 13.0%, 12.9% and 3.4%, respectively. Evaluating individual plans using the Lyman-Kutcher-Burman NTCP model also yielded improvements. Conclusion: The lateral penumbra reduction performed by the DCS increases the normal tissue sparing capabilities of

  1. Designer Self-Assemble Peptides Maximize the Therapeutic Benefits of Neural Stem Cell Transplantation for Alzheimer's Disease via Enhancing Neuron Differentiation and Paracrine Action.

    PubMed

    Cui, Guo-hong; Shao, Shui-jin; Yang, Jia-jun; Liu, Jian-ren; Guo, Hai-dong

    2016-03-01

    maximize the therapeutic benefits of NSC transplantation for AD through improving the survival and differentiation of transplanted stem cells and promoting the effects of neuroprotection, anti-neuroinflammatory and paracrine action. Our results may have important clinical implications for the design of future NSC-based strategies using the biomaterials for various neurodegenerative diseases including AD.

  2. Performance appraisal system for therapeutic recreation.

    PubMed

    Conway, M

    1985-01-01

    Therapeutic Recreation professionals continually strive for effective performance standards for their clients. In addition to standards for clients, Therapeutic Recreation Specialists must also develop performance standards for themselves to meet the continual challenge of accountability in the 80's. This paper identifies the need to develop a performance appraisal system as well as the benefits. The elements of the standards include: specificity, observability, measurability, attainment and mutual determination. The paper also reviews the process of assignment of relative weights, categories of review and detailed standards for the Director of Therapeutic Recreation and Therapeutic Recreation Specialist at the Rehabilitation Institute of Detroit.

  3. Boron Neutron Capture Therapty (BNCT) in an Oral Precancer Model: Therapeutic Benefits and Potential Toxicity of a Double Application of BNCT with a Six-Week Interval

    SciTech Connect

    Andrea Monti Hughes; Emiliano C.C. Pozzi; Elisa M. Heber; Silvia Thorp; Marcelo Miller; Maria E. Itoiz; Romina F. Aromando; Ana J. Molinari; Marcela A. Garabalino; David W. Nigg; Veronica A. Trivillin; Amanda E. Schwint

    2011-11-01

    Given the clinical relevance of locoregional recurrences in head and neck cancer, we developed a novel experimental model of premalignant tissue in the hamster cheek pouch for long-term studies and demonstrated the partial inhibitory effect of a single application of Boron Neutron Capture Therapy (BNCT) on tumor development from premalignant tissue. The aim of the present study was to evaluate the effect of a double application of BNCT with a 6 week interval in terms of inhibitory effect on tumor development, toxicity and DNA synthesis. We performed a double application, 6 weeks apart, of (1) BNCT mediated by boronophenylalanine (BPA-BNCT); (2) BNCT mediated by the combined application of decahydrodecaborate (GB-10) and BPA [(GB-10 + BPA)-BNCT] or (3) beam-only, at RA-3 nuclear reactor and followed the animals for 8 months. The control group was cancerized and sham-irradiated. BPA-BNCT, (GB- 10 + BPA)-BNCT and beam-only induced a reduction in tumor development from premalignant tissue that persisted until 8, 3, and 2 months respectively. An early maximum inhibition of 100% was observed for all 3 protocols. No normal tissue radiotoxicity was detected. Reversible mucositis was observed in premalignant tissue, peaking at 1 week and resolving by the third week after each irradiation. Mucositis after the second application was not exacerbated by the first application. DNA synthesis was significantly reduced in premalignant tissue 8 months post-BNCT. A double application of BPA-BNCT and (GB-10 + BPA)-BNCT, 6 weeks apart, could be used therapeutically at no additional cost in terms of radiotoxicity in normal and dose-limiting tissues.

  4. β-Lactam antibiotics and vancomycin inhibit the growth of planktonic and biofilm Candida spp.: an additional benefit of antibiotic-lock therapy?

    PubMed

    Sidrim, José J C; Teixeira, Carlos E C; Cordeiro, Rossana A; Brilhante, Raimunda S N; Castelo-Branco, Débora S C M; Bandeira, Silviane P; Alencar, Lucas P; Oliveira, Jonathas S; Monteiro, André J; Moreira, José L B; Bandeira, Tereza J P G; Rocha, Marcos F G

    2015-04-01

    The aim of this study was to evaluate the effects of cefepime, meropenem, piperacillin/tazobactam (TZP) and vancomycin on strains of Candida albicans and Candida tropicalis in planktonic and biofilm forms. Twenty azole-derivative-resistant strains of C. albicans (n=10) and C. tropicalis (n=10) were tested. The susceptibility of planktonic Candida spp. to the antibacterial agents was investigated by broth microdilution. The XTT reduction assay was performed to evaluate the viability of growing and mature biofilms following exposure to these drugs. Minimum inhibitory concentrations (MICs) ranged from 0.5 mg/mL to 2 mg/mL for cefepime, TZP and vancomycin and from 0.5 mg/mL to 1 mg/mL for meropenem and the drugs also caused statistically significant reductions in biofilm cellular activity both in growing and mature biofilm. Since all of the tested drugs are commonly used in patients with hospital-acquired infections and in those with catheter-related infections under antibiotic-lock therapy, it may be possible to obtain an additional benefit from antibiotic-lock therapy with these drugs, namely the control of Candida biofilm formation.

  5. Kinesio Taping Does Not Provide Additional Benefits in Patients With Chronic Low Back Pain Who Receive Exercise and Manual Therapy: A Randomized Controlled Trial.

    PubMed

    Added, Marco Aurélio Nemitalla; Costa, Leonardo Oliveira Pena; de Freitas, Diego Galace; Fukuda, Thiago Yukio; Monteiro, Renan Lima; Salomão, Evelyn Cassia; de Medeiros, Flávia Cordeiro; Costa, Lucíola da Cunha Menezes

    2016-07-01

    Study Design Randomized controlled trial. Background Many clinical practice guidelines endorse both manual therapy and exercise as effective treatment options for patients with low back pain. To optimize the effects of the treatments recommended by the guidelines, a new intervention known as Kinesio Taping is being widely used in these patients. Objectives To determine the effectiveness of Kinesio Taping in patients with chronic nonspecific low back pain when added to a physical therapy program consisting of exercise and manual therapy. Methods One hundred forty-eight patients with chronic nonspecific low back pain were randomly allocated to receive 10 (twice weekly) sessions of physical therapy, consisting of exercise and manual therapy, or the same treatment with the addition of Kinesio Taping applied to the lower back. The primary outcomes were pain intensity and disability (5 weeks after randomization) and the secondary outcomes were pain intensity, disability (3 months and 6 months after randomization), global perceived effect, and satisfaction with care (5 weeks after treatment). Data were collected by a blinded assessor. Results No between-group differences were observed in the primary outcomes of pain intensity (mean difference, -0.01 points; 95% confidence interval [CI]: -0.88, 0.85) or disability (mean difference, 1.14 points; 95% CI: -0.85, 3.13) at 5 weeks' follow-up. In addition, no between-group differences were observed for any of the other outcomes evaluated, except for disability 6 months after randomization (mean difference, 2.01 points; 95% CI: 0.03, 4.00) in favor of the control group. Conclusion Patients who received a physical therapy program consisting of exercise and manual therapy did not get additional benefit from the use of Kinesio Taping. Level of Evidence Therapy, level 1b. Prospectively registered May 28, 2013 at www.ClinicalTrials.gov (NCT01866332). J Orthop Sports Phys Ther 2016;46(7):506-513. Epub 6 Jun 2016. doi:10.2519/jospt.2016.6590.

  6. In dermographic urticaria H2 receptor antagonists have a small but therapeutically irrelevant additional effect compared with H1 antagonists alone.

    PubMed

    Sharpe, G R; Shuster, S

    1993-11-01

    Two studies of the additional effect of an H2 receptor antagonist when given in combination with an H1 antagonist were undertaken in dermographic urticaria. Using a randomized, double-blind, crossover design in 19 patients, a combination of cetirizine (10 mg at night) and ranitidine (150 mg twice daily) was compared with a combination of cetirizine (10 mg at night) and placebo. The addition of ranitidine did not produce any significant difference in linear analogue scores for weal, itch or sleep disturbance. There was a significant depression of the frictional force/wealing response curve with an increase in wealing threshold (P < 0.0001) following the addition of H2 blockade. The wealing threshold was 54.7 +/- 4.4 (mean +/- SEM) g/mm2 for the H1 antagonist alone, and 73.2 +/- 5.7 for the combination of H1 and H2 antagonists. In a second similar study involving nine different patients, comparing terfenadine (120 mg twice daily) with a combination of terfenadine and ranitidine (150 mg twice daily), the weal threshold was 59.8 +/- 6.6 for the H1 antagonist alone, and 73.0 +/- 6.4 for the combination of H1 and H2 antagonists. Thus, in dermographic urticaria, adding an H2 antagonist to treatment with a potent H1 antagonist gives a small, significant reduction in wealing response, but no symptomatic benefit. We conclude that involvement of the H2 receptor in this urticarial disease is minimal, and does not justify the use of H2 receptor antagonists.

  7. Radiation Therapy in the Management of Head-and-Neck Cancer of Unknown Primary Origin: How Does the Addition of Concurrent Chemotherapy Affect the Therapeutic Ratio?

    SciTech Connect

    Chen, Allen M.; Farwell, D. Gregory; Lau, Derick H.; Li Baoqing; Luu, Quang; Donald, Paul J.

    2011-10-01

    Purpose: To determine how the addition of cisplatin-based concurrent chemotherapy to radiation therapy influences outcomes among a cohort of patients treated for head-and-neck cancer of unknown primary origin. Methods and Materials: The medical records of 60 consecutive patients treated by radiation therapy for squamous cell carcinoma of the head and neck presenting as cervical lymph node metastasis of occult primary origin were reviewed. Thirty-two patients (53%) were treated by concurrent chemoradiation, and 28 patients (47%) were treated by radiation therapy alone. Forty-five patients (75%) received radiation therapy after surgical resection, and 15 patients (25%) received primary radiation therapy. Thirty-five patients (58%) were treated by intensity-modulated radiotherapy. Results: The 2-year estimates of overall survival, local-regional control, and progression-free survival were 89%, 89%, and 79%, respectively, among patients treated by chemoradiation, compared to 90%, 92%, and 83%, respectively, among patients treated by radiation therapy alone (p > 0.05, for all). Exploratory analysis failed to identify any subset of patients who benefited from the addition of concurrent chemotherapy to radiation therapy. The use of concurrent chemotherapy was associated with a significantly increased incidence of Grade 3+ acute and late toxicity (p < 0.001, for both). Conclusions: Concurrent chemoradiation is associated with significant toxicity without a clear advantage to overall survival, local-regional control, and progression-free survival in the treatment of head-and-neck cancer of unknown primary origin. Although selection bias cannot be ignored, prospective data are needed to further address this question.

  8. Expression of the fusogenic p14 FAST protein from a replication-defective adenovirus vector does not provide a therapeutic benefit in an immunocompetent mouse model of cancer

    PubMed Central

    Wong, C M; Nash, L A; Del Papa, J; Poulin, K L; Falls, T; Bell, J C; Parks, R J

    2016-01-01

    When injected directly into a tumor mass, adenovirus (Ad) vectors only transduce cells immediately along the injection tract. Expression of fusogenic proteins from the Ad vector can lead to syncytium formation, which efficiently spreads the therapeutic effect. Fusogenic proteins can also cause cancer cell death directly, and enhance the release of exosome-like particles containing tumor-associated antigens, which boosts the anti-tumor immune response. In this study, we have examined whether delivery of an early region 1 (E1)-deleted, replication-defective Ad vector encoding the reptilian reovirus p14 fusion-associated small transmembrane (FAST) protein can provide therapeutic efficacy in an immunocompetent mouse tumor model. A high multiplicity of infection of AdFAST is required to induce cell fusion in mouse mammary carcinoma 4T1 cells in vitro, and FAST protein expression caused a modest reduction in cell membrane integrity and metabolic activity compared with cells infected with a control vector. Cells expressing FAST protein released significantly higher quantities of exosomes. In immunocompetent Balb/C mice harboring subcutaneous 4T1 tumors, AdFAST did not induce detectable cancer cell fusion, promote tumor regression or prolong mouse survival compared with untreated mice. This study suggests that in the context of the 4T1 model, Ad-mediated FAST protein expression did not elicit a therapeutic effect. PMID:27740615

  9. The benefit of combinations of oximes for the reactivating and therapeutic efficacy of antidotal treatment of sarin poisoning in rats and mice.

    PubMed

    Kassa, Jiri; Karasova, Jana Zdarova; Sepsova, Vendula; Caisberger, Filip

    2011-07-01

    The influence of the combinations of oximes on the reactivating and therapeutic efficacy of antidotal treament of acute sarin poisoning was evaluated in this study. The ability of two combinations of oximes (HI-6 + trimedoxime and HI-6 + K203) to reactivate sarin-inhibited acetylcholinesterase and reduce acute toxicity of sarin was compared with the reactivating and therapeutic efficacy of antidotal treatment involving single oxime (HI-6, trimedoxime, K203) using in vivo methods. Studies determining percentage of reactivation of sarin-inhibited blood and tissue acetylcholinesterase in poisoned rats showed that the reactivating efficacy of the combination of oximes involving HI-6 and K203 is slightly higher than the reactivating efficacy of the most effective individual oxime in diaphragm and brain but the difference between them is not significant. The ability of combination of oximes involving HI-6 and trimedoxime to reactivate sarin-inhibited acetylcholinesterase roughly corresponds to the reactivating effects of the most effective individual oxime in blood as well as tissues. Moreover, both combinations of oximes were found to be as efficacious in the reduction of acute lethal toxic effects in sarin-poisoned mice as the most effective individual oxime. A comparison of reactivating and therapeutic efficacy of individual oximes showed that the oxime HI-6 is markedly more effective than the oxime K203 and trimedoxime. Based on the obtained data, we conclude that the antidotal treatment involving chosen combinations of oximes does not significantly influence the ability of the most effective individual oxime (HI-6) to reactivate sarin-inhibited rat acetylcholinesterase and to reduce acute toxicity of sarin in mice.

  10. Development of a Novel Orthotopic Non-small Cell Lung Cancer Model and Therapeutic Benefit of 2′-(2-bromohexadecanoyl)-Docetaxel Conjugate Nanoparticles

    PubMed Central

    Peng, Lei; Feng, Lan; Yuan, Hong; Benhabbour, Soumya R.; Mumper, Russell J.

    2014-01-01

    The aims of these studies were to establish an orthotopic non-small-cell lung cancer (NSCLC) mouse model, and to investigate the therapeutic efficacy of lipid-based nanoparticles (NPs) containing 2′-(2-bromohexadecanoyl)-docetaxel (Br-C16-DX) in this new model. A novel orthotopic NSCLC model was established in nude mice through dorsal side injection of luciferase-expressing A549 cells. The model was characterized by survival study, histological staining, bioluminescence imaging and PET/CT imaging. The therapeutic efficacy of the Br-C16-DX NPs versus Taxotere® was investigated in this model. The results demonstrated that mouse survival time was significantly prolonged by weekly intravenous administration of the NPs or Taxotere. Furthermore, the NPs group had 35 days longer progression-free survival and 27 days longer median survival compared to the Taxotere group. It was concluded that the developed orthotopic NSCLC model represents a feasible, reproducible, and clinically-relevant experimental mouse model to test current and potential therapies including nanomedicines. PMID:24709328

  11. Online Self-Report Data for Duchenne Muscular Dystrophy Confirms Natural History and Can Be Used to Assess for Therapeutic Benefits

    PubMed Central

    Wang, Richard T.; Silverstein Fadlon, Cheri A.; Ulm, J. Wes; Jankovic, Ivana; Eskin, Ascia; Lu, Ake; Rangel Miller, Vanessa; Cantor, Rita M.; Li, Ning; Elashoff, Robert; Martin, Anne S.; Peay, Holly L.; Halnon, Nancy; Nelson, Stanley F.

    2014-01-01

    To assess the utility of online patient self-report outcomes in a rare disease, we attempted to observe the effects of corticosteroids in delaying age at fulltime wheelchair use in Duchenne muscular dystrophy (DMD) using data from 1,057 males from DuchenneConnect, an online registry. Data collected were compared to prior natural history data in regard to age at diagnosis, mutation spectrum, and age at loss of ambulation. Because registrants reported differences in steroid and other medication usage, as well as age and ambulation status, we could explore these data for correlations with age at loss of ambulation. Using multivariate analysis, current steroid usage was the most significant and largest independent predictor of improved wheelchair-free survival. Thus, these online self-report data were sufficient to retrospectively observe that current steroid use by patients with DMD is associated with a delay in loss of ambulation. Comparing commonly used steroid drugs, deflazacort prolonged ambulation longer than prednisone (median 14 years and 13 years, respectively). Further, use of Vitamin D and Coenzyme Q10, insurance status, and age at diagnosis after 4 years were also significant, but smaller, independent predictors of longer wheelchair-free survival. Nine other common supplements were also individually tested but had lower study power. This study demonstrates the utility of DuchenneConnect data to observe therapeutic differences, and highlights needs for improvement in quality and quantity of patient-report data, which may allow exploration of drug/therapeutic practice combinations impractical to study in clinical trial settings. Further, with the low barrier to participation, we anticipate substantial growth in the dataset in the coming years. PMID:25635234

  12. HSP70 and modified HPV 16 E7 fusion gene without the addition of a signal peptide gene sequence as a candidate therapeutic tumor vaccine.

    PubMed

    Zong, Jinbao; Wang, Changyuan; Wang, Qingyong; Peng, Qinglin; Xu, Yufei; Xie, Xixiu; Xu, Xuemei

    2013-12-01

    Millions of women are currently infected with high-risk human papillomavirus (HPV), which is considered to be a major risk factor for cervical cancer. Thus, it is urgent to develop therapeutic vaccines to eliminate the established infections or HPV-related diseases. In the present study, using the mycobacterium tuberculosis heat shock protein 70 (MtHSP70) gene linked to the modified HPV 16 E7 (mE7) gene, we generated two potential therapeutic HPV DNA vaccines, mE7/MtHSP70 and SigmE7/MtHSP70, the latter was linked to the signal peptide gene sequence of human CD33 at the upstream of the fusion gene. We found that vaccination with the mE7/MtHSP70 DNA vaccine induced a stronger E7-specific CD8+ T cell response and resulted in a more significant therapeutic effect against E7-expressing tumor cells in mice. Our results demonstrated that HSP70 can play a more important role in mE7 and MtHSP70 fusion DNA vaccine without the help of a signal peptide. This may facilitate the use of HSP70 and serve as a significant reference for future study.

  13. Targeting caspase-3 as dual therapeutic benefits by RNAi facilitating brain-targeted nanoparticles in a rat model of Parkinson's disease.

    PubMed

    Liu, Yang; Guo, Yubo; An, Sai; Kuang, Yuyang; He, Xi; Ma, Haojun; Li, Jianfeng; Lu, Jing; Lv, Jing; Zhang, Ning; Jiang, Chen

    2013-01-01

    The activation of caspase-3 is an important hallmark in Parkinson's disease. It could induce neuron death by apoptosis and microglia activation by inflammation. As a result, inhibition the activation of caspase-3 would exert synergistic dual effect in brain in order to prevent the progress of Parkinson's disease. Silencing caspase-3 genes by RNA interference could inhibit the activation of caspase-3. We developed a brain-targeted gene delivery system based on non-viral gene vector, dendrigraft poly-L-lysines. A rabies virus glycoprotein peptide with 29 amino-acid linked to dendrigraft poly-L-lysines could render gene vectors the ability to get across the blood brain barrier by specific receptor mediated transcytosis. The resultant brain-targeted vector was complexed with caspase-3 short hairpin RNA coding plasmid DNA, yielding nanoparticles. In vivo imaging analysis indicated the targeted nanoparticles could accumulate in brain more efficiently than non-targeted ones. A multiple dosing regimen by weekly intravenous administration of the nanoparticles could reduce activated casapse-3 levels, significantly improve locomotor activity and rescue dopaminergic neuronal loss and in Parkinson's disease rats' brain. These results indicated the rabies virus glycoprotein peptide modified brain-targeted nanoparticles were promising gene delivery system for RNA interference to achieve anti-apoptotic and anti-inflammation synergistic therapeutic effects by down-regulation the expression and activation of caspase-3.

  14. Cinnamon may have therapeutic benefits on lipid profile, liver enzymes, insulin resistance, and high-sensitivity C-reactive protein in nonalcoholic fatty liver disease patients.

    PubMed

    Askari, Faezeh; Rashidkhani, Bahram; Hekmatdoost, Azita

    2014-02-01

    Nonalcoholic fatty liver disease (NAFLD) is the most prevalent cause of hepatic injury in the world. One of the most important therapeutic strategies for this disease is modulating insulin resistance and oxidative stress. In this study, we investigated the hypothesis that supplementation with cinnamon exerts an insulin sensitizer effect in patients with NAFLD. In a double-blind, placebo-controlled trial with two parallel groups, fifty patients with NAFLD were randomized to receive daily supplementation with either two capsules of cinnamon (each capsule contain 750 mg cinnamon) or 2 placebo capsules, daily for 12 weeks. During the intervention, all patients were given advice on how to implement a balanced diet and physical activity into their daily lives. In the treatment group (P < .05), significant decreases in HOMA (Homeostatic Model Assessment) index, FBS (fasting blood glucose), total cholesterol, triglyceride, ALT (alanine aminotransferase), AST (aspartate aminotransferase), GGT (gamma glutamine transpeptidase), and high-sensitivity C-reactive protein were seen, but there was no significant change in serum high-density lipoproteins levels (P = .122). In both groups, low-density lipoproteins decreased significantly (P < .05). In conclusion, the study suggests that taking 1500 mg cinnamon daily may be effective in improving NAFLD characteristics.

  15. Benefit of therapeutic drug monitoring of protease inhibitors in HIV-infected patients depends on PI used in HAART regimen--ANRS 111 trial

    PubMed Central

    Duval, Xavier; Mentré, France; Rey, Elisabeth; Auleley, Solange; Peytavin, Gilles; Biour, Michel; Métro, Annie; Goujard, Cecile; Taburet, Anne-Marie; Lascoux, Cecile; Panhard, Xaviere; Tréluyer, Jean-Marc; Salmon-Céron, Dominique

    2009-01-01

    Due to high inter-patient variability, and efficacy-concentration and toxicity-concentration relationships, optimization of HIV-protease inhibitor doses based on plasma concentrations could be beneficial. During a 48-week open prospective non-randomized interventional study of 115 protease inhibitor-naïve patients initiating an indinavir/ritonavir or lopinavir/ritonavir or nelfinavir containing therapy, protease inhibitor dose was modified when plasma trough concentrations (Ctrough) at week 2, 8, 16 and 24 were outside predefined optimal concentration ranges. Failure of the strategy was defined as the proportions of patients with HIV-RNA above 200 copies/ml from week 24 to 48 and/or experiencing grade 2, 3 or 4 PI-related adverse events during the study; proportion of patients with last Ctrough measurement outside the concentration range was determined at each visit. Virological failure and/or occurrence of adverse event were observed in 37/94 assessable patients (39% CI95%: 29.4–50.0). In the on-treatment analysis, failure of the strategy was noted in 16% of indinavir/r or lopinavir/r treated patients (8/51; CI95% 7.0–28.6; virological failure: 2; adverse event: 6) but in 44% of nelfinavir-treated patients (11/25; CI95%: 24.4–65.1; virological failure: 10; adverse event: 1); Ctrough concentrations outside the range were less frequent at the last measurement than at W2 (41% versus 66%; p < 0.05) with proportions of 35% for indinavir/r or lopinavir/r treated patients, but 57% for nelfinavir treated patients. The proposed strategy of therapeutic drug monitoring may be beneficial to indinavir/r and lopinavir/r-treated patients, but for nelfinavir failed to move concentrations into the predefined range and to produce the expected virological success. PMID:19709326

  16. Addition of Autologous Mesenchymal Stem Cells to Whole Blood for Bio-Enhanced ACL Repair has No Benefit in the Porcine Model

    PubMed Central

    Proffen, Benedikt L.; Vavken, Patrick; Haslauer, Carla M.; Fleming, Braden C.; Harris, Chad E.; Machan, Jason T.; Murray, Martha M.

    2015-01-01

    Background Co-culture of mesenchymal stem cells (MSCs) from the retropatellar fat pad and peripheral blood has been shown to stimulate anterior cruciate ligament (ACL) fibroblast proliferation and collagen production in vitro. Current techniques of bio-enhanced ACL repair in animal studies involve adding a biologic scaffold, in this case an extracellular matrix based scaffold saturated with autologous whole blood, to a simple suture repair of the ligament. Whether the enrichment of whole blood with MSCs would further improve the in vivo results of bio-enhanced ACL repair was investigated. Hypothesis/Purpose The hypothesis was that the addition of MSCs derived from adipose tissue or peripheral blood to the blood-extracellular matrix composite, which is used in bio-enhanced ACL repair to stimulate healing, would improve the biomechanical properties of a bio-enhanced ACL repair after 15 weeks of healing. Study Design Controlled laboratory study. Methods Twenty-four adolescent Yucatan mini-pigs underwent ACL transection followed by: 1) bio-enhanced ACL repair, 2) bio-enhanced ACL repair with the addition of autologous adipose-derived MSCs and 3) bio-enhanced ACL repair with the addition of autologous peripheral blood derived MSCs. After fifteen weeks of healing, structural properties of the ACL (yield & failure load, linear stiffness) were measured. Cell and vascular density were measured in the repaired ACL via histology, and its tissue structure was qualitatively evaluated using the Advanced Ligament Maturity Index. Results After fifteen weeks of healing, there were no significant improvements in the biomechanical or histological properties with the addition of adipose-derived MSCs. The only significant change with the addition of peripheral blood MSCs was an increase in knee anteroposterior (AP) laxity when measured at 30 degrees of flexion. Conclusions These findings suggest that the addition of adipose or peripheral blood MSCs to whole blood prior to saturation of

  17. Exendin-4 therapy still offered an additional benefit on reducing transverse aortic constriction-induced cardiac hypertrophy-caused myocardial damage in DPP-4 deficient rats

    PubMed Central

    Lu, Hung-I; Chung, Sheng-Ying; Chen, Yi-Ling; Huang, Tein-Hung; Zhen, Yen-Yi; Liu, Chu-Feng; Chang, Meng-Wei; Chen, Yung-Lung; Sheu, Jiunn-Jye; Chua, Sarah; Yip, Hon-Kan; Lee, Fan-Yen

    2016-01-01

    Inhibition of dipeptidyl peptidase-IV (DPP-4) enzyme activity has been revealed to protect myocardium from ischemia-reperfusion through enhancing the endogenous glucagon-like peptide-1 (GLP-1) level. However, whether exogenous supply of exendin-4, an analogue of GLP-1, would still offer benefit for protecting myocardial damage from trans-aortic constriction (TAC)-induced hypertrophic cardiomyopathy in preexistence of DPP-4 deficiency (DPP-4D) remained unclear. Male-adult (DPP-4D) rats (n = 32) were randomized into group 1 [sham control (SC)], group 2 (DPP-4D + TAC), group 3 [DPP-4D + TAC + exendin-4 10 µg/day], and group 4 [DPP-4D + TAC + exendin-4 10 µg + exendin-9-39 10 µg/day]. The rats were sacrificed by day 60 after last echocardiographic examination. By day 60 after TAC, left ventricular ejection fraction (LVEF) (%) was highest in group 1 and lowest in group 2, and significantly lower in group 4 than that in group 3 (all p < 0.001). The protein expressions of oxidative stress (oxidized protein, NOX-1, NOX-2), inflammatory (MMP-9, TNF-α, NF-κB), apoptotic (Bax, cleaved caspase 3 and PARP), fibrotic (TGF-β, Smad3), heart failure (BNP, β-MHC), DNA damaged (γ-H2AX) and ischemic stress (p-P38, p-Akt, p53, ATM) biomarkers showed an opposite pattern of LVEF among the four groups (all p < 0.03). Fibrotic area (by Masson’s trichrome, Sirius red), and cellular expressions of DNA-damaged markers (Ki-67+, γ-H2AX+, CD90+/53BP1+) displayed an identical pattern, whereas cellular expressions of angiogenesis (CD31+, α-SMA+) and sarcomere length exhibited an opposite pattern compared to that of oxidative stress among the four groups (all p < 0.001). Take altogether, Exendin-4 effectively suppressed TAC-induced pathological cardiac hypertrophy in DPP-4D rat. PMID:27158369

  18. Additional effects of taurine on the benefits of BCAA intake for the delayed-onset muscle soreness and muscle damage induced by high-intensity eccentric exercise.

    PubMed

    Ra, Song-Gyu; Miyazaki, Teruo; Ishikura, Keisuke; Nagayama, Hisashi; Suzuki, Takafumi; Maeda, Seiji; Ito, Masaharu; Matsuzaki, Yasushi; Ohmori, Hajime

    2013-01-01

    Taurine (TAU) has a lot of the biological, physiological, and pharmocological functions including anti-inflammatory and anti-oxidative stress. Although previous studies have appreciated the effectiveness of branched-chain amino acids (BCAA) on the delayed-onset muscle soreness (DOMS), consistent finding has not still convinced. The aim of this study was to examine the additional effect of TAU with BCAA on the DOMS and muscle damages after eccentric exercise. Thirty-six untrained male volunteers were equally divided into four groups, and ingested a combination with 2.0 g TAU (or placebo) and 3.2 g BCAA (or placebo), thrice a day, 2 weeks prior to and 4 days after elbow flexion eccentric exercise. Following the period after eccentric exercise, the physiological and blood biochemical markers for DOMS and muscle damage showed improvement in the combination of TAU and BCAA supplementation rather than in the single or placebo supplementations. In conclusion, additional supplement of TAU with BCAA would be a useful way to attenuate DOMS and muscle damages induced by high-intensity exercise.

  19. The electrochemical reactions of pure In with Li and Na: anomalous electrolyte decomposition, benefits of FEC additive, phase transitions and electrode performance

    SciTech Connect

    Hawks, Samantha A; Baggetto, Loic; Bridges, Craig A; Veith, Gabriel M

    2014-01-01

    Indium thin films are evaluated as an anode material for Li-ion and Na-ion batteries (theoretical capacities of 1012 mAh g-1 for Li and 467 mAh g-1 for Na). The native surface oxides are responsible for the anomalous electrolyte decomposition during the first cycle while oxidized In species are found to be responsible for the electrolyte decomposition during the subsequent cycles. The presence of 5wt% FEC electrolyte additive suppresses the occurrence of the anomalous electrolyte decomposition during the first cycle but is not sufficient to prevent the decomposition upon further cycling from 0 to 2 V. Prevention of the anomalous decomposition can be achieved by restricting the charge cut-off, for instance at 1.1 V, or by using larger amounts of FEC. The In films show moderately good capacity retention with storage capacities when cycled with Li (950 mAh g-1) but significantly less when cycled with Na (125 mAh g-1). XRD data reveal that several known Li-In phases (i.e LiIn, Li3In2, LiIn2 and Li13In3) form during the electrochemical reaction. In contrast, the reaction with Na is severely limited. The largest amount of inserted Na is evidenced for cells short-circuited 40 hrs at 65C, for which the XRD data show the coexistence of NaIn, In, and an unknown phase. During cycling, mechanical degradation due to repeated expansion/shrinkage, evidenced by SEM, coupled with SEI formation is the primary source of the capacity fade. Finally, we show that the In thin films exhibit very high rate capability for both Li (100 C) and Na (30 C).

  20. Combined intensive blood pressure and glycemic control does not produce an additive benefit on microvascular outcomes in type 2 diabetic patients.

    PubMed

    Ismail-Beigi, Faramarz; Craven, Timothy E; O'Connor, Patrick J; Karl, Diane; Calles-Escandon, Jorge; Hramiak, Irene; Genuth, Saul; Cushman, William C; Gerstein, Hertzel C; Probstfield, Jeffrey L; Katz, Lois; Schubart, Ulrich

    2012-03-01

    A reduction of either blood pressure or glycemia decreases some microvascular complications of type 2 diabetes, and we studied here their combined effects. In total, 4733 older adults with established type 2 diabetes and hypertension were randomly assigned to intensive (systolic blood pressure less than 120 mm Hg) or standard (systolic blood pressure less than 140 mm Hg) blood pressure control, and separately to intensive (HbA1c less than 0.060) or standard (HbA1c 0.070-0.079) glycemic control. Prespecified microvascular outcomes were a composite of renal failure and retinopathy and nine single outcomes. Proportional hazard regression models were used without correction for type I error due to multiple tests. During a mean follow-up of 4.7 years, the primary outcome occurred in 11.4% of intensive and 10.9% of standard blood pressure patients (hazard ratio 1.08), and in 11.1% of intensive and 11.2% of standard glycemia control patients. Intensive blood pressure control only reduced the incidence of microalbuminuria (hazard ratio 0.84), and intensive glycemic control reduced the incidence of macroalbuminuria and a few other microvascular outcomes. There was no interaction between blood pressure and glycemic control, and neither treatment prevented renal failure. Thus, in older patients with established type 2 diabetes and hypertension, intensive blood pressure control improved only 1 of 10 prespecified microvascular outcomes. None of the outcomes were significantly reduced by simultaneous intensive treatment of glycemia and blood pressure, signifying the lack of an additional beneficial effect from combined treatment.

  1. The electrochemical reactions of pure indium with Li and Na: Anomalous electrolyte decomposition, benefits of FEC additive, phase transitions and electrode performance

    NASA Astrophysics Data System (ADS)

    Webb, Samantha A.; Baggetto, Loïc; Bridges, Craig A.; Veith, Gabriel M.

    2014-02-01

    Indium thin films were evaluated as an anode material for Li-ion and Na-ion batteries (theoretical capacities of 1012 mAh g-1 for Li and 467 mAh g-1 for Na). XRD data reveal that several known Li-In phases (LiIn, Li3In2, LiIn2 and Li13In3) form providing 950 mAh g-1 reversible capacity. In contrast, the reaction with Na is severely limited (75-125 mAh g-1). XRD data of short-circuited cells (40 h at 65 °C) show the coexistence of NaIn, In, and an unknown NaxIn phase. In electrodes exhibit anomalous electrolyte decomposition characterized by large discharge plateaus at 1.4 V vs Li/Li+ and 0.9 V vs Na/Na+. The presence of 5 wt% fluoroethylene carbonate additive suppresses the occurrence of the electrolyte decomposition during the first cycle but does not necessarily prevent it upon further cycling. Prevention of the anomalous decomposition can be achieved by restricting the (dis)charge voltages, increasing the current or by using larger amounts of FEC. The native surface oxides (In2O3) are responsible for the pronounced electrolyte decomposition during the first cycle while other In3+ species are responsible during the subsequent cycles. We also show that indium electrodes can exhibit very high rate capability for both Li (100 C-rate) and Na (30 C-rate).

  2. Cannabinoid receptor 1 antagonist treatment induces glucagon release and shows an additive therapeutic effect with GLP-1 agonist in diet-induced obese mice.

    PubMed

    Patel, Kartikkumar Navinchandra; Joharapurkar, Amit Arvind; Patel, Vishal; Kshirsagar, Samadhan Govind; Bahekar, Rajesh; Srivastava, Brijesh Kumar; Jain, Mukul R

    2014-12-01

    Cannabinoid 1 (CB1) receptor antagonists reduce body weight and improve insulin sensitivity. Preclinical data indicates that an acute dose of CB1 antagonist rimonabant causes an increase in blood glucose. A stable analog of glucagon-like peptide 1 (GLP-1), exendin-4 improves glucose-stimulated insulin secretion in pancreas, and reduces appetite through activation of GLP-1 receptors in the central nervous system and liver. We hypothesized that the insulin secretagogue effect of GLP-1 agonist exendin-4 may synergize with the insulin-sensitizing action of rimonabant. Intraperitoneal as well as intracerebroventricular administration of rimonabant increased serum glucose upon glucose challenge in overnight fasted, diet-induced obese C57 mice, with concomitant rise in serum glucagon levels. Exendin-4 reversed the acute hyperglycemia induced by rimonabant. The combination of exendin-4 and rimonabant showed an additive effect in the food intake, and sustained body weight reduction upon repeated dosing. The acute efficacy of both the compounds was additive for inducing nausea-like symptoms in conditioned aversion test in mice, whereas exendin-4 treatment antagonized the effect of rimonabant on forced swim test upon chronic dosing. Thus, the addition of exendin-4 to rimonabant produces greater reduction in food intake owing to increased aversion, but reduces the other central nervous system side effects of rimonabant. The hyperglucagonemia induced by rimonabant is partially responsible for enhancing the antiobesity effect of exendin-4.

  3. The Additive Inflammatory In Vivo and In Vitro Effects of IL-7 and TSLP in Arthritis Underscore the Therapeutic Rationale for Dual Blockade

    PubMed Central

    Hillen, Maarten R.; Hartgring, Sarita A. Y.; Willis, Cynthia R.; Radstake, Timothy R. D. J.; Hack, Cornelis E.; Lafeber, Floris P. J. G.; van Roon, Joel A. G

    2015-01-01

    Introduction The cytokines interleukin (IL)-7 and thymic stromal lymphopoietin (TSLP) signal through the IL-7R subunit and play proinflammatory roles in experimental arthritis and rheumatoid arthritis (RA). We evaluated the effect of inhibition of IL-7R- and TSLPR-signalling as well as simultaneous inhibition of IL-7R- and TSLPR-signalling in murine experimental arthritis. In addition, the effects of IL-7 and TSLP in human RA dendritic cell (DC)/T-cell co-cultures were studied. Methods Arthritis was induced with proteoglycan in wildtype mice (WT) and in mice deficient for the TSLP receptor subunit (TSLPR-/-). Both mice genotypes were treated with anti-IL-7R or phosphate buffered saline. Arthritis severity was assessed and local and circulating cytokines were measured. Autologous CD1c-positive DCs and CD4 T-cells were isolated from peripheral blood of RA patients and were co-cultured in the presence of IL-7, TSLP or both and proliferation and cytokine production were assessed. Results Arthritis severity and immunopathology were decreased in WT mice treated with anti-IL-7R, in TSLPR-/- mice, and the most robustly in TSLPR-/- mice treated with anti-IL-7R. This was associated with strongly decreased levels of IL-17, IL-6 and CD40L. In human DC/T-cell co-cultures, TSLP and IL-7 additively increased T-cell proliferation and production of Th17-associated cytokines, chemokines and tissue destruction factors. Conclusion TSLP and IL-7 have an additive effect on the production of Th17-cytokines in a human in vitro model, and enhance arthritis in mice linked with enhanced inflammation and immunopathology. As both cytokines signal via the IL-7R, these data urge for IL-7R-targeting to prevent the activity of both cytokines in RA. PMID:26110994

  4. Biofeedback Training and Therapeutic Gains: Clinical Impressions.

    ERIC Educational Resources Information Center

    Romano, John L.

    1982-01-01

    Discusses several indirect benefits of clinical biofeedback training and their role in the therapeutic process. Suggests these secondary benefits may give biofeedback a distinctive advantage over other therapeutic interventions. Argues that these benefits are as important to the client's long-term emotional and physical health as is symptom…

  5. [Additional administration of dutasteride in patients with benign prostatic hyperplasia who did not respond sufficiently to α1-adrenoceptor antagonist : investigation of clinical factors affecting the therapeutic effect of dutasteride].

    PubMed

    Masuda, Mitsunobu; Murai, Tetsuo; Osada, Yutaka; Kawai, Masaki; Kasuga, Jun; Yokomizo, Yumiko; Kuroda, Shinnosuke; Nakamura, Mami; Noguchi, Go

    2014-02-01

    We performed additional administration of dutasteride in patients who did not respond sufficiently to α1-adrenoceptor antagonist treatment for lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) (LUTS/BPH). Among 76 registered patients, efficacy was analyzed in 58 patients. International Prostate Symptom Score (IPSS), subscores for voiding and storage symptoms and quality of life (QOL) on the IPSS, and Overactive Bladder Symptom Score (OABSS) were all significantly improved from the third month of administration compared to the time of initiating additional administration of dutasteride. Additional administration of dutasteride also significantly reduced prostate volume, and residual urine with the exception of the sixth month after administration. Age at initiation of administration and voiding symptom subscore on the IPSS were clinical factors affecting the therapeutic effects of dutasteride. The rate of improvement with treatment decreased with increasing age at initiation of dutasteride administration, and increased as voiding symptom subscore on the IPSS increased. Therefore, additional administration of dutasteride appears useful for cases of LUTS/BPH in which a sufficient response is not achieved with α1-adrenoceptor antagonist treatment. Because patients who have severe voiding symptoms or begin dutasteride at an early age may be expected to respond particularly well to dutasteride in terms of clinical efficacy, they were considered to be suitable targets for additional administration.

  6. Therapeutic Recombinant Monoclonal Antibodies

    ERIC Educational Resources Information Center

    Bakhtiar, Ray

    2012-01-01

    During the last two decades, the rapid growth of biotechnology-derived techniques has led to a myriad of therapeutic recombinant monoclonal antibodies with significant clinical benefits. Recombinant monoclonal antibodies can be obtained from a number of natural sources such as animal cell cultures using recombinant DNA engineering. In contrast to…

  7. Health Benefits of Fiber Fermentation.

    PubMed

    Dahl, Wendy J; Agro, Nicole C; Eliasson, Åsa M; Mialki, Kaley L; Olivera, Joseph D; Rusch, Carley T; Young, Carly N

    2017-02-01

    Although fiber is well recognized for its effect on laxation, increasing evidence supports the role of fiber in the prevention and treatment of chronic disease. The aim of this review is to provide an overview of the health benefits of fiber and its fermentation, and describe how the products of fermentation may influence disease risk and treatment. Higher fiber intakes are associated with decreased risk of cardiovascular disease, type 2 diabetes, and some forms of cancer. Fiber may also have a role in lowering blood pressure and in preventing obesity by limiting weight gain. Fiber is effective in managing blood glucose in type 2 diabetes, useful for weight loss, and may provide therapeutic adjunctive roles in kidney and liver disease. In addition, higher fiber diets are not contraindicated in inflammatory bowel disease or irritable bowel syndrome and may provide some benefit. Common to the associations with disease reduction is fermentation of fiber and its potential to modulate microbiota and its activities and inflammation, specifically the production of anti-inflammatory short chain fatty acids, primarily from saccharolytic fermentation, versus the deleterious products of proteolytic activity. Because fiber intake is inversely associated with all-cause mortality, mechanisms by which fiber may reduce chronic disease risk and provide therapeutic benefit to those with chronic disease need further elucidation and large, randomized controlled trials are needed to confirm causality.Teaching Points• Strong evidence supports the association between higher fiber diets and reduced risk of cardiovascular disease, type 2 diabetes, and some forms of cancer.• Higher fiber intakes are associated with lower body weight and body mass index, and some types of fiber may facilitate weight loss.• Fiber is recommended as an adjunctive medical nutritional therapy for type 2 diabetes, chronic kidney disease, and certain liver diseases.• Fermentation and the resulting shifts in

  8. Potlining Additives

    SciTech Connect

    Rudolf Keller

    2004-08-10

    In this project, a concept to improve the performance of aluminum production cells by introducing potlining additives was examined and tested. Boron oxide was added to cathode blocks, and titanium was dissolved in the metal pool; this resulted in the formation of titanium diboride and caused the molten aluminum to wet the carbonaceous cathode surface. Such wetting reportedly leads to operational improvements and extended cell life. In addition, boron oxide suppresses cyanide formation. This final report presents and discusses the results of this project. Substantial economic benefits for the practical implementation of the technology are projected, especially for modern cells with graphitized blocks. For example, with an energy savings of about 5% and an increase in pot life from 1500 to 2500 days, a cost savings of $ 0.023 per pound of aluminum produced is projected for a 200 kA pot.

  9. Yoga: a therapeutic approach.

    PubMed

    Nayak, Nirmala N; Shankar, Kamala

    2004-11-01

    Yoga, practiced widely in the East, is now popular in the West as part of a healthy lifestyle. This article brings a medical perspective to the practice of yoga. Selected yoga postures that are believed to benefit certain medical conditions are highlighted. In addition, the philosophy, general guidelines, and medical benefits of yoga practice are described.

  10. Non-valvular atrial fibrillation patients with none or one additional risk factor of the CHA2DS2-VASc score. A comprehensive net clinical benefit analysis for warfarin, aspirin, or no therapy.

    PubMed

    Lip, Gregory Y H; Skjøth, Flemming; Nielsen, Peter B; Larsen, Torben Bjerregaard

    2015-10-01

    Oral anticoagulation (OAC) to prevent stroke has to be balanced against the potential harm of serious bleeding, especially intracranial haemorrhage (ICH). We determined the net clinical benefit (NCB) balancing effectiveness and safety of no antithrombotic therapy, aspirin and warfarin in AF patients with none or one stroke risk factor. Using Danish registries, we determined NCB using various definitions intrinsic to our cohort (Danish weights at 1 and 5 year follow-up), with risk weights which were derived from the hazard ratio (HR) of death following an event, relative to HR of death after ischaemic stroke. When aspirin was compared to no treatment, NCB was neutral or negative for both risk strata. For warfarin vs no treatment, NCB using Danish weights was neutral where no risk factors were present and using five years follow-up. For one stroke risk factor, NCB was positive for warfarin vs no treatment, for one year and five year follow-up. For warfarin vs aspirin use in patients with no risk factors, NCB was positive with one year follow-up, but neutral with five year follow-up. With one risk factor, NCB was generally positive for warfarin vs aspirin. In conclusion, we show a positive overall advantage (i.e. positive NCB) of effective stroke prevention with OAC, compared to no therapy or aspirin with one additional stroke risk factor, using Danish weights. 'Low risk' AF patients with no additional stroke risk factors (i.e.CHA2DS2-VASc 0 in males, 1 in females) do not derive any advantage (neutral or negative NCB) with aspirin, nor with warfarin therapy in the long run.

  11. Current therapeutic paradigms in glioblastoma.

    PubMed

    Quick, Allison; Patel, Disha; Hadziahmetovic, Mersiha; Chakravarti, Arnab; Mehta, Minesh

    2010-01-01

    Glioblastoma (GBM), a WHO grade IV malignant glioma, is the most common and lethal adult primary brain tumor. Median survival rates range from 12-15 months. The current standard of care for GBM has evolved from resection followed by adjuvant radiotherapy to resection, concurrent adjuvant chemotherapy (temozolomide) and radiation, and additional adjuvant chemotherapy. The expression of specific molecular biomarkers, especially O-6-methylguanine methyltransferase (MGMT) status, may determine the response of the tumor to treatment, and helps in identifying the magnitude of benefit from this regimen. By identifying further biological subtypes of GBM at the molecular level, specific targeted therapies could be developed and used in the future for more individualized therapeutic regimens. This article will review the current therapies for GBM and the investigation of new molecular and targeted therapies, such as EGFR inhibitors, mTOR/PI3Kinase inhibitors, and anti-angiogenesis agents.

  12. The Process of Teaching Therapeutic Horseback Riding.

    ERIC Educational Resources Information Center

    Renker, Lorraine

    Therapeutic horseback riding for persons with disabilities provides physical, mental, social, and emotional benefits. Most research in this area has focused on the product or benefits of therapeutic riding, while the process of teaching horseback riding has received little attention. Research from the fields of regular education, special…

  13. Therapeutic cancer vaccines

    PubMed Central

    Melief, Cornelis J.M.; van Hall, Thorbald; Arens, Ramon; Ossendorp, Ferry; van der Burg, Sjoerd H.

    2015-01-01

    The clinical benefit of therapeutic cancer vaccines has been established. Whereas regression of lesions was shown for premalignant lesions caused by HPV, clinical benefit in cancer patients was mostly noted as prolonged survival. Suboptimal vaccine design and an immunosuppressive cancer microenvironment are the root causes of the lack of cancer eradication. Effective cancer vaccines deliver concentrated antigen to both HLA class I and II molecules of DCs, promoting both CD4 and CD8 T cell responses. Optimal vaccine platforms include DNA and RNA vaccines and synthetic long peptides. Antigens of choice include mutant sequences, selected cancer testis antigens, and viral antigens. Drugs or physical treatments can mitigate the immunosuppressive cancer microenvironment and include chemotherapeutics, radiation, indoleamine 2,3-dioxygenase (IDO) inhibitors, inhibitors of T cell checkpoints, agonists of selected TNF receptor family members, and inhibitors of undesirable cytokines. The specificity of therapeutic vaccination combined with such immunomodulation offers an attractive avenue for the development of future cancer therapies. PMID:26214521

  14. Microbial synthetic biology for human therapeutics.

    PubMed

    Jain, Aastha; Bhatia, Pooja; Chugh, Archana

    2012-06-01

    The emerging field of synthetic biology holds tremendous potential for developing novel drugs to treat various human conditions. The current study discusses the scope of synthetic biology for human therapeutics via microbial approach. In this context, synthetic biology aims at designing, engineering and building new microbial synthetic cells that do not pre-exist in nature as well as re-engineer existing microbes for synthesis of therapeutic products. It is expected that the construction of novel microbial genetic circuitry for human therapeutics will greatly benefit from the data generated by 'omics' approaches and multidisciplinary nature of synthetic biology. Development of novel antimicrobial drugs and vaccines by engineering microbial systems are a promising area of research in the field of synthetic biology for human theragnostics. Expression of plant based medicinal compounds in the microbial system using synthetic biology tools is another avenue dealt in the present study. Additionally, the study suggest that the traditional medicinal knowledge can do value addition for developing novel drugs in the microbial systems using synthetic biology tools. The presented work envisions the success of synthetic biology for human therapeutics via microbial approach in a holistic manner. Keeping this in view, various legal and socio-ethical concerns emerging from the use of synthetic biology via microbial approach such as patenting, biosafety and biosecurity issues have been touched upon in the later sections.

  15. Therapeutic modulation of tissue kallikrein expression.

    PubMed

    Campbell, Duncan J

    2016-12-01

    The kallikrein kinin system has cardioprotective actions and mediates in part the cardioprotection produced by angiotensin converting enzyme inhibitors and angiotensin type 1 receptor blockers. Additional approaches to exploit the cardioprotective effects of the kallikrein kinin system include the administration of tissue kallikrein and kinin receptor agonists. The renin inhibitor aliskiren was recently shown to increase cardiac tissue kallikrein expression and bradykinin levels, and to reduce myocardial ischemia-reperfusion injury by bradykinin B2 receptor- and angiotensin AT2 receptor-mediated mechanisms. Thus, aliskiren represents a prototype drug for the modulation of tissue kallikrein expression for therapeutic benefit.

  16. A panic attack in therapeutic recreation over being considered therapeutic.

    PubMed

    Lee, L L

    1987-01-01

    Ancillary professions have been called upon to account for therapeutic benefits from their services or be eliminated from the health care system. A singular focus on therapy, however, would negate the unique contribution of therapeutic recreation within, while simultaneously restricting services to health care settings. It is proposed that panic over therapeutic recreation services meeting health care goals has hindered evaluation and solidification of the leisure-based philosophy presented in the NTRS Philosophical Position Statement (NTRS, 1982). It is argued that emphasizing the leisure orientation of the philosophical position statement can secure therapeutic recreation's position within, yet, not deny services to those outside of the health care system. An overview is presented on the adequacy of the position statement philosophy for therapeutic recreation. A potential danger of attempting to explain therapeutic recreation in terms of non-leisure based philosophies is also discussed.

  17. Cloning for therapeutic purposes: ethical and policy considerations.

    PubMed

    Hanson, M J

    2001-01-01

    This essay reviews how cloning techniques may be used for therapeutic purposes, analyzes ethical implications, and makes recommendations for public policy discourse. Although cloning may bring many potential benefits, they remain uncertain. Furthermore, human embryo research is morally problematic. Therefore, alternatives to human cloning for therapeutic aims should be sought at present. In addition to central ethical issues, public discourse should maintain an emphasis on the value of the human embryo over scientific expediency, the relativity of health, and the principle of justice. Society should support the laudable mission of medical research, while also attending to the moral concerns often threatened by the promises of scientific progress.

  18. Therapeutic Recreation

    ERIC Educational Resources Information Center

    Parks and Recreation, 1971

    1971-01-01

    Graphic profiles of (1) the professional membership of the National Therapeutic Recreation Society, (2) state-level employment opportunities in the field, and (3) educational opportunities at U.S. colleges and universities. (MB)

  19. [Nuclear transfer and therapeutic cloning].

    PubMed

    Xu, Xiao-Ming; Lei, An-Min; Hua, Jin-Lian; Dou, Zhong-Ying

    2005-03-01

    Nuclear transfer and therapeutic cloning have widespread and attractive prospects in animal agriculture and biomedical applications. We reviewed that the quality of oocytes and nuclear reprogramming of somatic donor cells were the main reasons of the common abnormalities in cloned animals and the low efficiency of cloning and showed the problems and outlets in therapeutic cloning, such as some basic problems in nuclear transfer affected clinical applications of therapeutic cloning. Study on isolation and culture of nuclear transfer embryonic stem (ntES) cells and specific differentiation of ntES cells into important functional cells should be emphasized and could enhance the efficiency. Adult stem cells could help to cure some great diseases, but could not replace therapeutic cloning. Ethics also impeded the development of therapeutic cloning. It is necessary to improve many techniques and reinforce the research of some basic theories, then somatic nuclear transfer and therapeutic cloning may apply to agriculture reproduction and benefit to human life better.

  20. MACROMOLECULAR THERAPEUTICS

    PubMed Central

    Yang, Jiyuan; Kopeček, Jindřich

    2014-01-01

    This review covers water-soluble polymer-drug conjugates and macromolecules that possess biological activity without attached low molecular weight drugs. The main design principles of traditional and backbone degradable polymer-drug conjugates as well as the development of a new paradigm in nanomedicines – (low molecular weight) drug-free macromolecular therapeutics are discussed. To address the biological features of cancer, macromolecular therapeutics directed to stem/progenitor cells and the tumor microenvironment are deliberated. Finally, the future perspectives of the field are briefly debated. PMID:24747162

  1. Macromolecular therapeutics.

    PubMed

    Yang, Jiyuan; Kopeček, Jindřich

    2014-09-28

    This review covers water-soluble polymer-drug conjugates and macromolecules that possess biological activity without attached low molecular weight drugs. The main design principles of traditional and backbone degradable polymer-drug conjugates as well as the development of a new paradigm in nanomedicines - (low molecular weight) drug-free macromolecular therapeutics are discussed. To address the biological features of cancer, macromolecular therapeutics directed to stem/progenitor cells and the tumor microenvironment are deliberated. Finally, the future perspectives of the field are briefly debated.

  2. Technology Benefits

    NASA Technical Reports Server (NTRS)

    Haller, William

    2001-01-01

    An assessment was recently performed by NASA s Inter-Center Systems Analysis Team to quantify the potential emission reduction benefits from technologies being developed under UEET. The CO2 and LTO NO, reductions were estimated for 4 vehicles: a 50-passenger regional jet, a twin-engine, long-range subsonic transport, a high-speed (Mach 2.4) civil transport and a supersonic (Mach 2) business jet. The results of the assessment confirm that the current portfolio of technologies within the UEET program provides an opportunity for substantial reductions in CO2 and NO, emissions.

  3. Therapeutic Nanodevices

    NASA Astrophysics Data System (ADS)

    Lee, Stephen C.; Ruegsegger, Mark; Barnes, Philip D.; Smith, Bryan R.; Ferrari, Mauro

    Therapeutic nanotechnology offers minimally invasive therapies with high densities of function concentrated in small volumes, features that may reduce patient morbidity and mortality. Unlike other areas of nanotechnology, novel physical properties associated with nanoscale dimensionality are not the raison d'etre of therapeutic nanotechnology, whereas the aggregation of multiple biochemical (or comparably precise) functions into controlled nanoarchitectures is. Multifunctionality is a hallmark of emerging nanotherapeutic devices, and multifunctionality can allow nanotherapeutic devices to perform multi-step work processes, with each functional component contributing to one or more nanodevice subroutine such that, in aggregate, subroutines sum to a cogent work process. Cannonical nanotherapeutic subroutines include tethering (targeting) to sites of disease, dispensing measured doses of drug (or bioactive compound), detection of residual disease after therapy and communication with an external clinician/operator. Emerging nanotherapeutics thus blur the boundaries between medical devices and traditional pharmaceuticals. Assembly of therapeutic nanodevices generally exploits either (bio)material self assembly properties or chemoselective bioconjugation techniques, or both. Given the complexity, composition, and the necessity for their tight chemical and structural definition inherent in the nature of nanotherapeutics, their cost of goods (COGs) might exceed that of (already expensive) biologics. Early therapeutic nanodevices will likely be applied to disease states which exhibit significant unmet patient need (cancer and cardiovascular disease), while application to other disease states well-served by conventional therapy may await perfection of nanotherapeutic design and assembly protocols.

  4. Therapeutic Nanodevices

    NASA Astrophysics Data System (ADS)

    Lee, Stephen; Ruegsegger, Mark; Barnes, Philip; Smith, Bryan; Ferrari, Mauro

    Therapeutic nanotechnology offers minimally invasive therapies with high densities of function concentrated in small volumes, features that may reduce patient morbidity and mortality. Unlike other areas of nanotechnology, novel physical properties associated with nanoscale dimensionality are not the raison d'être of therapeutic nanotechnology, whereas the aggregation of multiple biochemical (or comparably precise) functions into controlled nanoarchitectures is. Multifunctionality is a hallmark of emerging nanotherapeutic devices, and multifunctionality can allow nanotherapeutic devices to perform multistep work processes, with each functional component contributing to one or more nanodevice subroutine such that, in aggregate, subroutines sum to a cogent work process. Cannonical nanotherapeutic subroutines include tethering (targeting) to sites of disease, dispensing measured doses of drug (or bioactive compound), detection of residual disease after therapy and communication with an external clinician/operator. Emerging nanotherapeutics thus blur the boundaries between medical devices and traditional pharmaceuticals. Assembly of therapeutic nanodevices generally exploits either (bio)material self-assembly properties or chemoselective bioconjugation techniques, or both. Given the complexity, composition, and the necessity for their tight chemical and structural definition inherent in the nature of nanotherapeutics, their cost of goods (COGs) might exceed that of (already expensive) biologics. Early therapeutic nanodevices will likely be applied to disease states which exhibit significant unmet patient need (cancer and cardiovascular disease), while application to other disease states well-served by conventional therapy may await perfection of nanotherapeutic design and assembly protocols.

  5. Therapeutic uses of contraceptive steroids.

    PubMed

    Starks, G C

    1984-09-01

    During the past 20 years, contraceptive steroids have undergone significant changes as the result of an increased understanding of their metabolic, pharmacologic, and hormonal activities. During this time, prospective and retrospective epidemiologic studies have elucidated several noncontraceptive health benefits of oral contraceptive steroids, including their therapeutic effects for endometriosis, dysmenorrhea, polycystic ovarian disease, and benign breast disease. From this review it appears that the benefits of oral contraceptive steroids in young, healthy, nonsmoking women far outweigh their more publicized, infrequent risks.

  6. Therapeutic proteins.

    PubMed

    Dimitrov, Dimiter S

    2012-01-01

    Protein-based therapeutics are highly successful in clinic and currently enjoy unprecedented recognition of their potential. More than 100 genuine and similar number of modified therapeutic proteins are approved for clinical use in the European Union and the USA with 2010 sales of US$108 bln; monoclonal antibodies (mAbs) accounted for almost half (48%) of the sales. Based on their pharmacological activity, they can be divided into five groups: (a) replacing a protein that is deficient or abnormal; (b) augmenting an existing pathway; (c) providing a novel function or activity; (d) interfering with a molecule or organism; and (e) delivering other compounds or proteins, such as a radionuclide, cytotoxic drug, or effector proteins. Therapeutic proteins can also be grouped based on their molecular types that include antibody-based drugs, Fc fusion proteins, anticoagulants, blood factors, bone morphogenetic proteins, engineered protein scaffolds, enzymes, growth factors, hormones, interferons, interleukins, and thrombolytics. They can also be classified based on their molecular mechanism of activity as (a) binding non-covalently to target, e.g., mAbs; (b) affecting covalent bonds, e.g., enzymes; and (c) exerting activity without specific interactions, e.g., serum albumin. Most protein therapeutics currently on the market are recombinant and hundreds of them are in clinical trials for therapy of cancers, immune disorders, infections, and other diseases. New engineered proteins, including bispecific mAbs and multispecific fusion proteins, mAbs conjugated with small molecule drugs, and proteins with optimized pharmacokinetics, are currently under development. However, in the last several decades, there are no conceptually new methodological developments comparable, e.g., to genetic engineering leading to the development of recombinant therapeutic proteins. It appears that a paradigm change in methodologies and understanding of mechanisms is needed to overcome major

  7. Therapeutic Recreation Majors' Work Preference.

    ERIC Educational Resources Information Center

    Barber, Elizabeth H.; Magafas, Anita

    1992-01-01

    Investigates the client age/disability work preference of 76 therapeutic recreation undergraduate students at 3 universities. Results indicate a preference to work with younger clients, disability groups, and physically impaired clients. Chronically ill clients were last in work preference. Students need exposure to the benefits of working with…

  8. Engineering human cells for in vivo secretion of antibody and non-antibody therapeutic proteins.

    PubMed

    Sánchez-Martín, David; Sanz, Laura; Álvarez-Vallina, Luis

    2011-12-01

    Purified proteins such as antibodies are widely used as therapeutic agents in clinical medicine. However, clinical-grade proteins for therapeutic use require sophisticated technologies and are extremely expensive to produce. In vivo secretion of therapeutic proteins by genetically engineered human cells may advantageously replace injection of highly purified proteins. The use of gene transfer methods circumvents problems related to large-scale production and purification and offers additional benefits by achieving sustained concentrations of therapeutic protein with a syngenic glycosylation pattern that make the protein potentially less immunogenic. The feasibility of the in vivo production of therapeutic proteins by diverse cells/tissues has now been demonstrated using different techniques, such as ex vivo genetically modified cells and in vivo gene transfer mediated by viral vectors.

  9. Two concepts of therapeutic optimism

    PubMed Central

    Jansen, Lynn A

    2011-01-01

    Researchers and ethicists have long been concerned about the expectations for direct medical benefit expressed by participants in early phase clinical trials. Early work on the issue considered the possibility that participants misunderstand the purpose of clinical research or that they are misinformed about the prospects for medical benefit from these trials. Recently, however, attention has turned to the possibility that research participants are simply expressing optimism or hope about their participation in these trials. The ethical significance of this therapeutic optimism remains unclear. This paper argues that there are two distinct phenomena that can be associated with the term ‘therapeutic optimism’—one is ethically benign and the other is potentially worrisome. Distinguishing these two phenomena is crucial for understanding the nature and ethical significance of therapeutic optimism. The failure to draw a distinction between these phenomena also helps to explain why different writers on the topic often speak past one another. PMID:21551464

  10. Use of informed consent with therapeutic paradox.

    PubMed

    Farkas, M M

    1992-01-01

    Debate persists in the literature and among clinicians about the ethical appropriateness of paradoxical interventions. It has been suggested that informed consent with therapeutic paradox would alleviate ethical concerns of deception, manipulation, harm to the client, and withholding of information from the client in therapy. The purpose of this study was to explore health care consumer reactions to the benefits and risks of therapeutic paradox as stated in a consent for treatment form. The study explored the responses of 32 medical patients to a hypothetical consent for treatment form for therapeutic paradox. Data were collected in a brief semistructured interview after subjects read the hypothetical consent form. Utilizing a case study, the investigator then offered an example of a successful paradoxical intervention and additional subject comments were solicited. Content analysis of the responses was made. Health care consumers had mixed responses to the consent form. While the consent form served as an obstacle for some consumers, many were willing to sign the consent form and accept treatment even though they had internal reservations and questions. Appropriateness of the consent form format is discussed.

  11. The Therapeutic Recreation Professional: Microcomputer Applications.

    ERIC Educational Resources Information Center

    Beland, Robert M.

    1984-01-01

    Therapeutic recreation professionals can work with computer specialists to develop uses for microcomputers with special populations. Computers can help sensory-impaired individuals, physically disabled, the aged, and special education students. Computer professionals benefit from receiving feedback from therapeutic recreation professionals on…

  12. RNAi therapeutics for CNS disorders.

    PubMed

    Boudreau, Ryan L; Davidson, Beverly L

    2010-06-18

    RNA interference (RNAi) is a process of sequence-specific gene silencing and serves as a powerful molecular tool to manipulate gene expression in vitro and in vivo. RNAi technologies have been applied to study gene function and validate drug targets. Researchers are investigating RNAi-based compounds as novel therapeutics to treat a variety of human diseases that are currently lacking sufficient treatment. To date, numerous studies support that RNAi therapeutics can improve disease phenotypes in various rodent models of human disease. Here, we focus on the development of RNAi-based therapies aimed at treating neurological disorders for which reduction of mutant or toxic gene expression may provide clinical benefit. We review RNAi-based gene-silencing strategies, proof-of-concept studies testing therapeutic RNAi for CNS disorders, and highlight the most recent research aimed at transitioning RNAi-based therapeutics toward clinical trials.

  13. Antioxidant therapeutics for schizophrenia.

    PubMed

    Reddy, Ravinder; Reddy, Rajiv

    2011-10-01

    Pharmaceutical treatment for millions worldwide who have schizophrenia is limited to a handful of antipsychotics. Despite the proven efficacy of these drugs, the overall outcome for schizophrenia remains suboptimal. Thus, alternative treatment options are urgently needed. One possible approach may be antioxidant therapy. The extant evidence for the role of oxidative stress in the pathophysiology of schizophrenia offers a hypothesis-derived therapeutic approach in the form of antioxidants. Vitamins C and E, for example, are suitable for human clinical trials because they are readily available, inexpensive, and relatively safe. Research into the therapeutic use of antioxidants in schizophrenia can be grouped into two main clusters: for psychopathology and for side effects. Of these studies, some have been carefully conducted, but majority are open label. Use of antioxidants for treatment-related side effects has been more extensively investigated. The totality of the evidence to date suggests that specific antioxidants, such as N-acetyl cysteine, may offer tangible benefits for the clinical syndrome of schizophrenia, and vitamin E may offer salutary effects on glycemic effects of antipsychotics. However, a great deal of fundamental clinical research remains to be done before antioxidants can be routinely used therapeutically for schizophrenia and treatment-related complications.

  14. Therapeutic use of cannabis: clarifying the debate.

    PubMed

    Gowing, L R; Ali, R L; Christie, P; White, J M

    1998-12-01

    The debate regarding therapeutic use of cannabis is being confused by a lack of distinction between therapeutic and social use of cannabis. Separate consideration of therapeutic and social use would enable strategies to minimise any negative social impact of therapeutic use. For therapeutic use of cannabis to be considered on its own merits, greater emphasis needs to be placed on scientific evidence of therapeutic efficacy. At present the evidence is limited, it mostly relates to the use of synthetic cannabinoids, and much of it fails to compare cannabis with the best therapies available for the conditions of interest. Claims of therapeutic efficacy tend to be based on opinion and anecdote rather than the results of controlled studies. Further research is needed to clarify the potential therapeutic benefits, to enable claims of therapeutic use to be objectively assessed and to enable informed decisions to be made about the relative risks and benefits for any individual using cannabis for therapeutic purposes. Further research is required to clarify the efficacy of pure, synthetic cannabinoids compared to cannabis, the most effective route of administration, and the importance of delivering a known dose. The most likely value of cannabis is as an adjunct, rather than a replacement for, current medical approaches. The potential therapeutic benefits of cannabis will be greatest for those conditions where long-term cannabis use, with its attendant health risks, is not an issue and where the patient has the capacity to titrate dose against symptoms. There is sufficient evidence of potential therapeutic benefit to justify the facilitation of further research.

  15. Food additives

    PubMed Central

    Spencer, Michael

    1974-01-01

    Food additives are discussed from the food technology point of view. The reasons for their use are summarized: (1) to protect food from chemical and microbiological attack; (2) to even out seasonal supplies; (3) to improve their eating quality; (4) to improve their nutritional value. The various types of food additives are considered, e.g. colours, flavours, emulsifiers, bread and flour additives, preservatives, and nutritional additives. The paper concludes with consideration of those circumstances in which the use of additives is (a) justified and (b) unjustified. PMID:4467857

  16. Biobased lubricant additives

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fully biobased lubricants are those formulated using all biobased ingredients, i.e. biobased base oils and biobased additives. Such formulations provide the maximum environmental, safety, and economic benefits expected from a biobased product. Currently, there are a number of biobased base oils that...

  17. Cystic fibrosis therapeutics: the road ahead.

    PubMed

    Hoffman, Lucas R; Ramsey, Bonnie W

    2013-01-01

    A great deal of excitement and hope has followed the successful trials and US Food and Drug Administration approval of the drug ivacaftor (Kalydeco), the first therapy available that targets the underlying defect that causes cystic fibrosis (CF). Although this drug has currently demonstrated a clinical benefit for a small minority of the CF population, the developmental pathway established by ivacaftor paves the way for other CF transmembrane conductance regulator (CFTR) modulators that may benefit many more patients. In addition to investigating CFTR modulators, researchers are actively developing numerous other innovative CF therapies. In this review, we use the catalog of treatments currently under evaluation with the support of the Cystic Fibrosis Foundation, known as the Cystic Fibrosis Foundation Therapeutics Pipeline, as a platform to discuss the variety of candidate treatments for CF lung disease that promise to improve CF care. Many of these approaches target the individual components of the relentless cycle of airway obstruction, inflammation, and infection characteristic of lung disease in CF, whereas others are aimed directly at the gene defect, or the resulting dysfunctional protein, that instigates this cycle. We discuss how new findings from the laboratory have informed not only the development of novel therapeutics, but also the rationales for their use and the outcomes used to measure their effects. By reviewing the breadth of candidate treatments currently in development, as well as the recent progress in CF therapies reflected by the evolution of the therapeutics pipeline over the past few years, we hope to build upon the optimism and anticipation generated by the recent success of Kalydeco.

  18. Therapeutic targets in systemic sclerosis

    PubMed Central

    Denton, Christopher P

    2007-01-01

    The precise aetiology of systemic sclerosis (SSc) remains elusive, but significant advances over the past few years have improved our understanding of the underlying pathogenic processes and identified key pathways and mediators that are potential therapeutic targets. The situation is complicated by the clinical heterogeneity of SSc and the differential pathogenesis that underlies the two commonest subsets, namely diffuse and limited cutaneous disease. However, there are common mediators that could be targeted to provide clinical benefit in both types of disease. To date, clinical success with therapies directed against logical profibrotic mediators, such as connective tissue growth factor and transforming growth factor-β, is yet to be reported, although studies are ongoing. More promising clinical results have been obtained with the dual endothelin receptor antagonist bosentan, which has been shown to manage two vascular complications of SSc effectively: pulmonary arterial hypertension and digital ulceration. It remains to be determined whether the identification of additional mediators merely furthers our knowledge of the natural history of SSc or presents targets that can be manipulated to manage SSc patients effectively. PMID:17767744

  19. Relational mindfulness, spirituality, and the therapeutic bond.

    PubMed

    Falb, Melissa D; Pargament, Kenneth I

    2012-12-01

    Mindfulness training, which emphasizes deliberate non-judgmental attention to present moment experiences, has become increasingly mainstream over the past several decades. With accumulating evidence for the physical and mental health benefits of mindfulness, it has been integrated into medical and psychological treatments and is increasingly accepted in the fields of psychology and psychiatry. However, several elements of mindfulness practice which potentially contribute to its benefits have been largely neglected. These include the connections between mindfulness, interpersonal relationships, spirituality, and the psychotherapeutic alliance. The emerging concept of "relational mindfulness" focuses attention on the oft-neglected interpersonal aspects of mindfulness practices. Relational mindfulness is potentially relevant to the psychotherapeutic process, due to its cultivation of the types of qualities that enhance the therapeutic relationship, including warmth, empathy, curiosity, acceptance, self-attunement, and emotional intelligence. In addition, mindfulness practices, especially relational ones, can contribute to the development of spiritual qualities, such as transcendence, boundlessness, ultimacy, and interconnectedness. Several recent studies suggest that meditation/mindfulness interventions may be explained and or enhanced by an emphasis on spiritual components. In this paper, we suggest that focusing on the oft-neglected relational and spiritual aspects of mindfulness practice has the potential to deepen its benefits, especially within the context of the psychotherapeutic relationship.

  20. Level 1 Therapeutic Model site.

    PubMed

    Hall, Philip S; DeJong, Judith A

    2006-01-01

    This site is an intertribal residential grant school annually enrolling over 250 students in grades 1-8 from tribes located in three states on the Northern Great Plains. From its inception in 1890, the boarding school's mission has been to provide services for young children in need of a safe and supportive living and learning environment. For over a decade, this site has used strategies centered on respecting children, structuring students' time, and providing the therapeutic benefits of a well-maintained campus. This site also has a long history of believing in each child's inherent value and potential. When Therapeutic Residential Model funding commenced at the midpoint of the 2002-2003 school year, L1 focused these new resources on strengthening and refining its program. The number of personnel positions increased from 98 to 135, with new positions principally going to dormitory staff and four Masters-level counselor positions. This increase in staff allowed L1 to proactively address the children's developmental needs. The site also adopted and implemented the Applied Humanism caregiving model. In accordance with Applied Humanism, an interview was utilized that allowed the site to identify and hire applicants possessing the attitudes and skills necessary to be good caregivers, existing staff were trained so that they understood the kind of caregiving that would be expected of them, supervision procedures and practices were implemented that supported and encouraged good caregivers and provided time-limited assistance to those who were not, and relevant agency policies and procedures were revised as needed to align with the Applied Humanism philosophy. In addition, the Morningside program was brought in to systematically address the students' academic lags in reading. The results of implementing the Therapeutic Residential Model were a reduction in behavioral incidents, a decrease in the amount of money spent on external mental health services, an increase in the

  1. Clinical impacts of additive use of olmesartan in hypertensive patients with chronic heart failure: the supplemental benefit of an angiotensin receptor blocker in hypertensive patients with stable heart failure using olmesartan (SUPPORT) trial.

    PubMed

    Sakata, Yasuhiko; Shiba, Nobuyuki; Takahashi, Jun; Miyata, Satoshi; Nochioka, Kotaro; Miura, Masanobu; Takada, Tsuyoshi; Saga, Chiharu; Shinozaki, Tsuyoshi; Sugi, Masafumi; Nakagawa, Makoto; Sekiguchi, Nobuyo; Komaru, Tatsuya; Kato, Atsushi; Fukuchi, Mitsumasa; Nozaki, Eiji; Hiramoto, Tetsuya; Inoue, Kanichi; Goto, Toshikazu; Ohe, Masatoshi; Tamaki, Kenji; Ibayashi, Setsuro; Ishide, Nobumasa; Maruyama, Yukio; Tsuji, Ichiro; Shimokawa, Hiroaki

    2015-04-14

    We examined whether an additive treatment with an angiotensin receptor blocker, olmesartan, reduces the mortality and morbidity in hypertensive patients with chronic heart failure (CHF) treated with angiotensin-converting enzyme (ACE) inhibitors, β-blockers, or both. In this prospective, randomized, open-label, blinded endpoint study, a total of 1147 hypertensive patients with symptomatic CHF (mean age 66 years, 75% male) were randomized to the addition of olmesartan (n = 578) to baseline therapy vs. control (n = 569). The primary endpoint was a composite of all-cause death, non-fatal acute myocardial infarction, non-fatal stroke, and hospitalization for worsening heart failure. During a median follow-up of 4.4 years, the primary endpoint occurred in 192 patients (33.2%) in the olmesartan group and in 166 patients (29.2%) in the control group [hazard ratio (HR) 1.18; 95% confidence interval (CI), 0.96-1.46, P = 0.112], while renal dysfunction developed more frequently in the olmesartan group (16.8 vs. 10.7%, HR 1.64; 95% CI 1.19-2.26, P = 0.003). Subgroup analysis revealed that addition of olmesartan to combination of ACE inhibitors and β-blockers was associated with increased incidence of the primary endpoint (38.1 vs. 28.2%, HR 1.47; 95% CI 1.11-1.95, P = 0.006), all-cause death (19.4 vs. 13.5%, HR 1.50; 95% CI 1.01-2.23, P = 0.046), and renal dysfunction (21.1 vs. 12.5%, HR 1.85; 95% CI 1.24-2.76, P = 0.003). Additive use of olmesartan did not improve clinical outcomes but worsened renal function in hypertensive CHF patients treated with evidence-based medications. Particularly, the triple combination therapy with olmesartan, ACE inhibitors and β-blockers was associated with increased adverse cardiac events. This study is registered at clinicaltrials.gov-NCT00417222.

  2. Food additives

    MedlinePlus

    ... or natural. Natural food additives include: Herbs or spices to add flavor to foods Vinegar for pickling ... Certain colors improve the appearance of foods. Many spices, as well as natural and man-made flavors, ...

  3. Transdermal delivery of therapeutic agent

    NASA Technical Reports Server (NTRS)

    Kwiatkowski, Krzysztof C. (Inventor); Hayes, Ryan T. (Inventor); Magnuson, James W. (Inventor); Giletto, Anthony (Inventor)

    2008-01-01

    A device for the transdermal delivery of a therapeutic agent to a biological subject that includes a first electrode comprising a first array of electrically conductive microprojections for providing electrical communication through a skin portion of the subject to a second electrode comprising a second array of electrically conductive microprojections. Additionally, a reservoir for holding the therapeutic agent surrounding the first electrode and a pulse generator for providing an exponential decay pulse between the first and second electrodes may be provided. A method includes the steps of piercing a stratum corneum layer of skin with two arrays of conductive microprojections, encapsulating the therapeutic agent into biocompatible charged carriers, surrounding the conductive microprojections with the therapeutic agent, generating an exponential decay pulse between the two arrays of conductive microprojections to create a non-uniform electrical field and electrokinetically driving the therapeutic agent through the stratum corneum layer of skin.

  4. [Assessment of benefit and efficiency of innovative medical devices].

    PubMed

    Perleth, M; Lühmann, D

    2010-08-01

    Medical devices cover a wide spectrum of products with very different diagnostic and therapeutic applications. However, for market licensing, uniform rules apply. Uniform rules are also valid for coverage decisions in German health care. In this article, the criteria for the assessment of benefit and efficiency of innovative biomedical technologies are described from the perspective of the statutory health insurance system. The key concepts relevant in the mandatory health insurance' "innovation"' "benefit", and "economic efficiency" are characterized. Only measurable effects of an intervention which lead to a more than marginal improvement in prognosis, symptoms, or quality of life as compared to a standard treatment are considered as beneficial. An innovative device is, therefore, subject to a benefit assessment if it is not yet reimbursed (or not yet part of the benefit package), when it is relevant to the health care system and a high public interest exists. In addition, it is important to consider a positive benefit assessment as a part of the value added chain to avoid conflicts of interest. Within the scope of early technology assessment, some conclusions can already be drawn in the early developmental stage of a device.

  5. Combination treatment with herbal medicines and Western medicines in atopic dermatitis: Benefits and considerations.

    PubMed

    Kim, Jung-Hoon; Kim, Hyungwoo

    2016-05-01

    Herbal medicines (HMs) are often used in combination with Western medicines (WMs) to improve therapeutic efficacies of orthodox medicines. This review discussed the current status of combination treatment with HMs and WMs in clinical practices. The influence of HMs on bioavailability of WMs was also discussed from the pharmacokinetic point of view. In addition, benefits and considerations of combination treatment were discussed using data obtained from clinical trials and randomized controlled trials of HMs treatment in skin diseases.

  6. Therapeutic Hypothermia for Neuroprotection

    PubMed Central

    Karnatovskaia, Lioudmila V.; Wartenberg, Katja E.

    2014-01-01

    The earliest recorded application of therapeutic hypothermia in medicine spans about 5000 years; however, its use has become widespread since 2002, following the demonstration of both safety and efficacy of regimens requiring only a mild (32°C-35°C) degree of cooling after cardiac arrest. We review the mechanisms by which hypothermia confers neuroprotection as well as its physiological effects by body system and its associated risks. With regard to clinical applications, we present evidence on the role of hypothermia in traumatic brain injury, intracranial pressure elevation, stroke, subarachnoid hemorrhage, spinal cord injury, hepatic encephalopathy, and neonatal peripartum encephalopathy. Based on the current knowledge and areas undergoing or in need of further exploration, we feel that therapeutic hypothermia holds promise in the treatment of patients with various forms of neurologic injury; however, additional quality studies are needed before its true role is fully known. PMID:24982721

  7. Inhalation delivery of protein therapeutics.

    PubMed

    Kane, Colleen; O'Neil, Karyn; Conk, Michelle; Picha, Kristen

    2013-04-01

    Inhaled therapeutics are used routinely to treat a variety of pulmonary diseases including asthma, COPD and cystic fibrosis. In addition, biological therapies represent the fastest growing segment of approved pharmaceuticals. However, despite the increased availability of biological therapies, nearly all inhaled therapeutics are small molecule drugs with only a single inhaled protein therapeutic approved. There remains a significant unmet need for therapeutics in pulmonary diseases, and biological therapies with potential to alter disease progression represent a significant opportunity to treat these challenging diseases. This review provides a background into efforts to develop inhaled biological therapies and highlights some of the associated challenges. In addition, we speculate on the ideal properties of a biologic therapy for inhaled delivery.

  8. Neurological benefits of omega-3 fatty acids.

    PubMed

    Dyall, S C; Michael-Titus, A T

    2008-01-01

    The central nervous system is highly enriched in long-chain polyunsaturated fatty acid (PUFA) of the omega-6 and omega-3 series. The presence of these fatty acids as structural components of neuronal membranes influences cellular function both directly, through effects on membrane properties, and also by acting as a precursor pool for lipid-derived messengers. An adequate intake of omega-3 PUFA is essential for optimal visual function and neural development. Furthermore, there is increasing evidence that increased intake of the long-chain omega-3 PUFA, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), may confer benefits in a variety of psychiatric and neurological disorders, and in particular neurodegenerative conditions. However, the mechanisms underlying these beneficial effects are still poorly understood. Recent evidence also indicates that in addition to the positive effects seen in chronic neurodegenerative conditions, omega-3 PUFA may also have significant neuroprotective potential in acute neurological injury. Thus, these compounds offer an intriguing prospect as potentially new therapeutic approaches in both chronic and acute conditions. The purpose of this article is to review the current evidence of the neurological benefits of omega-3 PUFA, looking specifically at neurodegenerative conditions and acute neurological injury.

  9. Therapeutic Engagement as a Predictor of Retention in Adolescent Therapeutic Community Treatment

    ERIC Educational Resources Information Center

    Abdel-Salam, Sami; Gunter, Whitney D.

    2014-01-01

    The adolescent drug problem places a huge toll on society and a heavy burden on the criminal justice system. Research regarding the benefits of therapeutic community (TC) treatment for adolescents has shown it to be effective. Despite the ability of therapeutic communities to lower drug relapse and reduce criminality, a great deal remains unknown…

  10. Phosphazene additives

    DOEpatents

    Harrup, Mason K; Rollins, Harry W

    2013-11-26

    An additive comprising a phosphazene compound that has at least two reactive functional groups and at least one capping functional group bonded to phosphorus atoms of the phosphazene compound. One of the at least two reactive functional groups is configured to react with cellulose and the other of the at least two reactive functional groups is configured to react with a resin, such as an amine resin of a polycarboxylic acid resin. The at least one capping functional group is selected from the group consisting of a short chain ether group, an alkoxy group, or an aryloxy group. Also disclosed are an additive-resin admixture, a method of treating a wood product, and a wood product.

  11. Improving therapeutic outcomes in autism spectrum disorders: Enhancing social communication and sensory processing through the use of interactive robots.

    PubMed

    Sartorato, Felippe; Przybylowski, Leon; Sarko, Diana K

    2017-02-07

    For children with autism spectrum disorders (ASDs), social robots are increasingly utilized as therapeutic tools in order to enhance social skills and communication. Robots have been shown to generate a number of social and behavioral benefits in children with ASD including heightened engagement, increased attention, and decreased social anxiety. Although social robots appear to be effective social reinforcement tools in assistive therapies, the perceptual mechanism underlying these benefits remains unknown. To date, social robot studies have primarily relied on expertise in fields such as engineering and clinical psychology, with measures of social robot efficacy principally limited to qualitative observational assessments of children's interactions with robots. In this review, we examine a range of socially interactive robots that currently have the most widespread use as well as the utility of these robots and their therapeutic effects. In addition, given that social interactions rely on audiovisual communication, we discuss how enhanced sensory processing and integration of robotic social cues may underlie the perceptual and behavioral benefits that social robots confer. Although overall multisensory processing (including audiovisual integration) is impaired in individuals with ASD, social robot interactions may provide therapeutic benefits by allowing audiovisual social cues to be experienced through a simplified version of a human interaction. By applying systems neuroscience tools to identify, analyze, and extend the multisensory perceptual substrates that may underlie the therapeutic benefits of social robots, future studies have the potential to strengthen the clinical utility of social robots for individuals with ASD.

  12. Circumventing Brain Barriers: Nanovehicles for Retroaxonal Therapeutic Delivery.

    PubMed

    Ovsepian, Saak V; O'Leary, Valerie B; Ntziachristos, Vasilis; Dolly, J Oliver

    2016-11-01

    In addition to safeguarding the central nervous system (CNS) from the vast majority of pathogens and toxins, transvascular barriers impose immense challenges to the delivery of beneficial cargo. A few toxins and neurotropic viruses capable of penetrating the brain have proved to be potentially valuable for neuron targeting and enhanced transfer of restorative medicine and therapeutic genes. Here we review molecular concepts and implications of the highly neurotropic tetanus toxin (TeTx) and botulinum neurotoxins (BoNTs) and their ability to infiltrate and migrate throughout neurons. We discuss recent applications of their detoxified variants as versatile nanovehicles for retroaxonal delivery of therapeutics to motor neurons and synapses. Continued advances in research on these remarkable agents in preclinical trials might facilitate their future use for medical benefit.

  13. Proteases as therapeutics

    PubMed Central

    Craik, Charles S.; Page, Michael J.; Madison, Edwin L.

    2015-01-01

    Proteases are an expanding class of drugs that hold great promise. The U.S. FDA (Food and Drug Administration) has approved 12 protease therapies, and a number of next generation or completely new proteases are in clinical development. Although they are a well-recognized class of targets for inhibitors, proteases themselves have not typically been considered as a drug class despite their application in the clinic over the last several decades; initially as plasma fractions and later as purified products. Although the predominant use of proteases has been in treating cardiovascular disease, they are also emerging as useful agents in the treatment of sepsis, digestive disorders, inflammation, cystic fibrosis, retinal disorders, psoriasis and other diseases. In the present review, we outline the history of proteases as therapeutics, provide an overview of their current clinical application, and describe several approaches to improve and expand their clinical application. Undoubtedly, our ability to harness proteolysis for disease treatment will increase with our understanding of protease biology and the molecular mechanisms responsible. New technologies for rationally engineering proteases, as well as improved delivery options, will expand greatly the potential applications of these enzymes. The recognition that proteases are, in fact, an established class of safe and efficacious drugs will stimulate investigation of additional therapeutic applications for these enzymes. Proteases therefore have a bright future as a distinct therapeutic class with diverse clinical applications. PMID:21406063

  14. The Therapeutic Roller Coaster

    PubMed Central

    CHU, JAMES A.

    1992-01-01

    Survivors of severe childhood abuse often encounter profound difficulties. In addition to posttraumatic and dissociative symptomatology, abuse survivors frequently have characterologic problems, particularly regarding self-care and maintaining relationships. Backgrounds of abuse, abandonment, and betrayal are often recapitulated and reenacted in therapy, making the therapeutic experience arduous and confusing for therapists and patients. Efforts must be directed at building an adequate psychotherapeutic foundation before undertaking exploration and abreaction of past traumatic experiences. This discussion sets out a model for treatment of childhood abuse survivors, describing stages of treatment and suggesting interventions. Common treatment dilemmas or "traps" are discussed, with recommendations for their resolution. PMID:22700116

  15. Therapeutic Process During Exposure: Habituation Model

    PubMed Central

    Benito, Kristen G.; Walther, Michael

    2015-01-01

    The current paper outlines the habituation model of exposure process, which is a behavioral model emphasizing use of individually tailored functional analysis during exposures. This is a model of therapeutic process rather than one meant to explain the mechanism of change underlying exposure-based treatments. Habitation, or a natural decrease in anxiety level in the absence of anxiety-reducing behavior, might be best understood as an intermediate treatment outcome that informs therapeutic process, rather than as a mechanism of change. The habituation model purports that three conditions are necessary for optimal benefit from exposures: 1) fear activation, 2) minimization of anxiety-reducing behaviors, and 3) habituation. We describe prescribed therapist and client behaviors as those that increase or maintain anxiety level during an exposure (and therefore, facilitate habituation), and proscribed therapist and client behaviors as those that decrease anxiety during an exposure (and therefore, impede habituation). We illustrate model-consistent behaviors in the case of Monica, as well as outline the existing research support and call for additional research to further test the tenets of the habituation model as described in this paper. PMID:26258012

  16. Ethyl Pyruvate Provides Therapeutic Benefits to Resuscitation Fluids

    DTIC Science & Technology

    2009-02-01

    hours after resuscitation. Characteristic pathological markers of hemorrhage were assessed by blood chemistry at three hours after hemorrhage, as...Cardiopulmonary Bypass. J Cardiothorac Vasc Anesth, 2008. 11 Figure Legends. Figure 1 Blood chemistry analyses during resuscitation. Blood from

  17. Therapeutic benefit of melatonin in refractory central serous chorioretinopathy

    PubMed Central

    Gramajo, A L; Marquez, G E; Torres, V E; Juárez, C P; Rosenstein, R E; Luna, J D

    2015-01-01

    Purpose To evaluate the efficacy and safety of melatonin for the treatment of chronic central serous chorioretinopathy (CSCR). Methods Prospective comparative case series. A total of 13 patients with chronic CSCR were treated for 1 month: 8 patients were treated orally with 3 mg melatonin t.i.d., and 5 with placebo. All patients had 20/40 or worse Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA) in the affected eye or presented an incapacitating scotoma. Most of the patients had previous failed treatments for their condition. Observational procedures included ETDRS BCVA, and complete ophthalmic examination. Optical coherence tomography (OCT) was performed at day 1 and week 4. Fluorescein angiography was performed at baseline only for diagnostic purposes. Data were subjected to two-sample t-test statistical analysis. P-values of <0.05 were considered statistically significant. Results At 1-month follow-up, BCVA significantly improved in 87.5% of patients treated with melatonin (7 of 8 patients, P<0.05). All patients showed a mean significant reduction (P<0.01) of central macular thickness (CMT) when compared with the baseline, with 3 patients (37.5%) exhibiting complete resolution of subretinal fluid at 1-month follow-up. No significant side effects were observed. No changes in BCVA or CMT were noted in the control group. Conclusions These results suggest that melatonin is safe, well tolerated, and effective in the treatment of chronic CSCR, as it significantly improved BCVA and CMT in patients with this pathology. Further evaluations with longer follow-up and a larger patient population are desirable. PMID:26160525

  18. Benefits and risks of circumcision.

    PubMed Central

    Warner, E.; Strashin, E.

    1981-01-01

    Circumcisions are performed either prophylactically in the neonatal period or therapeutically at a later age. About 10% of males not circumcised at birth will eventually require circumcision. The present neonatal circumcision rate is about 80% in the United States and 40% in Canada. The single most important determinant of whether a newborn male will be circumcised is the attitude of the attending physician. The literature was reviewed to determine the proven benefits of circumcision and to compare these with the known risks. Circumcising the newborn facilitates penile hygiene, prevents cancer of the penis and decreases the incidence of genital herpes in later life. Whether it decreases the incidence of cancer of the cervix is still uncertain. More important, neonatal circumcision is associated with much lower morbidity and mortality and with lower costs than therapeutic circumcision. Thus, prophylactic circumcision is recommended for the male population as a whole. PMID:7037142

  19. Treatment of apogeotropic benign positional vertigo: comparison of therapeutic head-shaking and modified Semont maneuver.

    PubMed

    Oh, S-Y; Kim, Ji-Soo; Jeong, S-H; Oh, Y-M; Choi, K-D; Kim, B-K; Lee, S-H; Lee, H-S; Moon, I-S; Lee, J-J

    2009-08-01

    Several methods of physiotherapy have been advanced for apogeotropic type benign positional vertigo involving the horizontal semicircular canal (HC-BPV). The aim of this study was to determine the therapeutic efficacies of the proposed maneuvers in apogeotropic HC-BPV. Using a prospective randomized trial involving seven nationwide dizziness clinics in Korea, we compared the immediate efficacies of head-shaking and modified Semont maneuvers in 103 consecutive patients with apogeotropic HC-BPV. We also determined an additional therapeutic benefit of mastoid oscillation while the patients without response to both maneuvers were performing the Brandt-Daroff exercise. Successful treatment was defined as resolution of positional vertigo and nystagmus, or as transition into geotropic HC-BPV. Results showed that head shaking was more effective than the modified Semont maneuver (37.3 vs. 17.3%, P = 0.02). However, therapeutic efficacy did not differ between the maneuvers after the initial non-responders switched over to the other maneuver (23.3 vs. 25.0%, P = 0.861). Mastoid oscillation provided no additional benefit while the patients without response to both maneuvers were performing the Brandt-Daroff exercise. Most positional vertigos resolved within a week (89.4%) irrespective of the treatment modalities applied and all showed resolution within 28 days. The head-shaking maneuver described here proved more effective than the modified Semont maneuver in treating apogeotropic HC-BPV. Mastoid vibration conferred no additional benefit during the Brandt-Daroff exercise.

  20. Addition of Rice Bran Arabinoxylan to Curcumin Therapy May Be of Benefit to Patients With Early-Stage B-Cell Lymphoid Malignancies (Monoclonal Gammopathy of Undetermined Significance, Smoldering Multiple Myeloma, or Stage 0/1 Chronic Lymphocytic Leukemia): A Preliminary Clinical Study.

    PubMed

    Golombick, Terry; Diamond, Terrence H; Manoharan, Arumugam; Ramakrishna, Rajeev

    2016-06-01

    Hypothesis Prior studies on patients with early B-cell lymphoid malignancies suggest that early intervention with curcumin may lead to delay in progressive disease and prolonged survival. These patients are characterized by increased susceptibility to infections. Rice bran arabinoxylan (Ribraxx) has been shown to have immunostimulatory, anti-inflammatory, and proapoptotic effects. We postulated that addition of Ribraxx to curcumin therapy may be of benefit. Study design Monoclonal gammopathy of undetermined significance (MGUS)/smoldering multiple myeloma (SMM) or stage 0/1 chronic lymphocytic leukemia (CLL) patients who had been on oral curcumin therapy for a period of 6 months or more were administered both curcumin (as Curcuforte) and Ribraxx. Methods Ten MGUS/SMM patients and 10 patients with stage 0/1 CLL were administered 6 g of curcumin and 2 g Ribraxx daily. Blood samples were collected at baseline and at 2-month intervals for a period of 6 months, and various markers were monitored. MGUS/SMM patients included full blood count (FBC); paraprotein; free light chains/ratio; C-reactive protein (CRP)and erythrocyte sedimentation rate (ESR); B2 microglobulin and immunological markers. Markers monitored for stage 0/1 CLL were FBC, CRP and ESR, and immunological markers. Results Of 10 MGUS/SMM patients,5 (50%) were neutropenic at baseline, and the Curcuforte/Ribraxx combination therapy showed an increased neutrophil count, varying between 10% and 90% among 8 of the 10 (80%) MGUS/SMM patients. An additional benefit of the combination therapy was the potent effect in reducing the raised ESR in 4 (44%) of the MGUS/SMM patients. Conclusion Addition of Ribraxx to curcumin therapy may be of benefit to patients with early-stage B-cell lymphoid malignancies.

  1. HPV vaccine cross-protection: Highlights on additional clinical benefit.

    PubMed

    De Vincenzo, Rosa; Ricci, Caterina; Conte, Carmine; Scambia, Giovanni

    2013-09-01

    Prophylactic human papillomavirus (HPV) vaccines are administered in vaccination programs, targeted at young adolescent girls before sexual exposure, and in catch-up programs for young women in some countries. All the data indicate that HPV-virus-like particles (VLPs) effectively prevent papillomavirus infections with a high level of antibodies and safety. Since non-vaccine HPV types are responsible for about 30% of cervical cancers, cross-protection would potentially enhance primary cervical cancer prevention efforts. High levels of specific neutralizing antibodies can be generated after immunization with HPV VLPs. Immunity to HPV is type-specific. However, if we consider the phylogenetic tree including the different HPV types, we realize that a certain degree of cross-protection is possible, due to the high homology of some viral types with vaccine ones. The assessment of cross-protective properties of HPV vaccines is an extremely important matter, which has also increased public health implications and could add further value to their preventive potential. The impact of cross-protection is mostly represented by a reduction of cervical intraepithelial neoplasia CIN2-3 more than what expected. In this article we review the mechanisms and the effectiveness of Bivalent (HPV-16/-18) and Quadrivalent (HPV-6/-11/-16/-18) HPV vaccine cross-protection, focusing on the critical aspects and the potential biases in clinical trials, in order to understand how cross-protection could impact on clinical outcomes and on the new perspectives in post-vaccine era.

  2. Curcumin Nanomedicine: A Road to Cancer Therapeutics

    PubMed Central

    Yallapu, Murali M.; Jaggi, Meena; Chauhan, Subhash C.

    2013-01-01

    Cancer is the second leading cause of death in the United States. Conventional therapies cause widespread systemic toxicity and lead to serious side effects which prohibit their long term use. Additionally, in many circumstances tumor resistance and recurrence is commonly observed. Therefore, there is an urgent need to identify suitable anticancer therapies that are highly precise with minimal side effects. Curcumin is a natural polyphenol molecule derived from the Curcuma longa plant which exhibits anticancer, chemo-preventive, chemo- and radio-sensitization properties. Curcumin’s widespread availability, safety, low cost and multiple cancer fighting functions justify its development as a drug for cancer treatment. However, various basic and clinical studies elucidate curcumin’s limited efficacy due to its low solubility, high rate of metabolism, poor bioavailability and pharmacokinetics. A growing list of nanomedicine(s) using first line therapeutic drugs have been approved or are under consideration by the Food and Drug Administration (FDA) to improve human health. These nanotechnology strategies may help to overcome challenges and ease the translation of curcumin from bench to clinical application. Prominent research is reviewed which shows that advanced drug delivery of curcumin (curcumin nanoformulations or curcumin nanomedicine) is able to leverage therapeutic benefits by improving bioavailability and pharmacokinetics which in turn improves binding, internalization and targeting of tumor(s). Outcomes using these novel drug delivery systems have been discussed in detail. This review also describes the tumor-specific drug delivery system(s) that can be highly effective in destroying tumors. Such new approaches are expected to lead to clinical trials and to improve cancer therapeutics. PMID:23116309

  3. Quantify information system benefits

    SciTech Connect

    Koppel, L.B.

    1995-06-01

    What are information systems and how do they relate to control systems? How do information systems produce benefits in hydrocarbon processing? What are some examples of benefit-generating information system applications? Information System Benefits (ISBEN) is a structured methodology for estimating information system benefits in hydrocarbon processing. The paper discusses information and control systems, information system benefits and applications, objectives, strategies and measures of ISBEN, ISBEN business drivers, ISBEN database, ISBEN methodology, and implementation.

  4. [Health security--GMOs in therapeutics].

    PubMed

    Trouvin, J-H

    2003-03-01

    The recent progress in human therapeutics has been made possible thanks to molecular biology and its use in producing proteins having the same sequence and structure as that of human proteins. The use of GMOs allows production of proteins with high added value in therapeutics, which are of satisfactory quality. GMOs may also be directly administered to patients as gene therapy vectors. However, the use of GMOs in therapeutics must take into consideration some risks, particularly those of microbiological contamination, of neo-antigenicity as well as environmental risks with regard to the way of use of the GMO. Nevertheless, those risks are taken in due consideration in the development of these new medicinal products; solutions have been found to allow their use in therapeutics with a very positive benefit/risk ratio. Medicinal products from biotechnology have enabled considerable therapeutic progress without compromising health security.

  5. [Sanitary safety of GMOs used in therapeutics].

    PubMed

    Trouvin, Jean-Hugues

    2002-01-01

    The recent progress in human therapeutics has been made possible thanks to molecular biology and its use in producing proteins having the same sequence and structure as that of human proteins. The use of GMOs allows production of proteins with high added value in therapeutics, which are of satisfactory quality. GMOs may also be directly administered to patients as gene therapy vectors. However, the use of GMOs in therapeutics must take into consideration some risks, particularly those of microbiological contamination, of neo-antigenicity as well as environmental risks with regard to the way of use of the GMO. Nevertheless, those risks are taken in due consideration in the development of those new medicinal products; solutions have been found to allow their use in therapeutics with a very positive benefit/risk ratio. Medicinal products from biotechnology have permitted considerable therapeutic progress without compromising health security.

  6. Ca(2+)-activated K(+) channels as therapeutic targets for myocardial and vascular protection.

    PubMed

    Clements, Richard T; Terentyev, Dmitry; Sellke, Frank W

    2015-01-01

    Small- and large-conductance Ca(2+)-activated K(+)channels (SKCa and BKCa, respectively) may be important targets for therapeutic interventions in a variety of cardiac conditions. In cardiomyocytes, BKCa channels are localized to mitochondria where they beneficially modulate reactive oxygen species, mitochondrial Ca(2+), and respiration. In vascular smooth muscle cells, BKCa channels regulate vascular tone and promote vasodilation. Activation of BKCa channels has demonstrated significant cardioprotection following ischemic injury, including improved function and reduced infarct size. SKCa channels are expressed in both the membrane and mitochondria of cardiomyocytes. Modulation of cardiomyocyte SKCa channels may be beneficial for arrhythmia, heart failure, and ischemia. Mitochondrial SKCa channels may provide similar benefit to BKCa channels. In addition, activation of SKCa channels on the endothelium promotes vasodilation. This mini-review focuses on the modulation of cardiomyocyte BKCa and SKCa channels for cardioprotection and briefly address associated potential therapeutic benefits in the coronary circulation.

  7. Phytonutrients as therapeutic agents.

    PubMed

    Gupta, Charu; Prakash, Dhan

    2014-09-01

    Nutrients present in various foods plays an important role in maintaining the normal functions of the human body. The major nutrients present in foods include carbohydrates, proteins, lipids, vitamins, and minerals. Besides these, there are some bioactive food components known as "phytonutrients" that play an important role in human health. They have tremendous impact on the health care system and may provide medical health benefits including the prevention and/or treatment of disease and various physiological disorders. Phytonutrients play a positive role by maintaining and modulating immune function to prevent specific diseases. Being natural products, they hold a great promise in clinical therapy as they possess no side effects that are usually associated with chemotherapy or radiotherapy. They are also comparatively cheap and thus significantly reduce health care cost. Phytonutrients are the plant nutrients with specific biological activities that support human health. Some of the important bioactive phytonutrients include polyphenols, terpenoids, resveratrol, flavonoids, isoflavonoids, carotenoids, limonoids, glucosinolates, phytoestrogens, phytosterols, anthocyanins, ω-3 fatty acids, and probiotics. They play specific pharmacological effects in human health such as anti-microbial, anti-oxidants, anti-inflammatory, antiallergic, anti-spasmodic, anti-cancer, anti-aging, hepatoprotective, hypolipidemic, neuroprotective, hypotensive, diabetes, osteoporosis, CNS stimulant, analgesic, protection from UVB-induced carcinogenesis, immuno-modulator, and carminative. This mini-review attempts to summarize the major important types of phytonutrients and their role in promoting human health and as therapeutic agents along with the current market trend and commercialization.

  8. Mechanisms of Plasma Therapeutics

    NASA Astrophysics Data System (ADS)

    Graves, David

    2015-09-01

    In this talk, I address research directed towards biomedical applications of atmospheric pressure plasma such as sterilization, surgery, wound healing and anti-cancer therapy. The field has seen remarkable growth in the last 3-5 years, but the mechanisms responsible for the biomedical effects have remained mysterious. It is known that plasmas readily create reactive oxygen species (ROS) and reactive nitrogen species (RNS). ROS and RNS (or RONS), in addition to a suite of other radical and non-radical reactive species, are essential actors in an important sub-field of aerobic biology termed ``redox'' (or oxidation-reduction) biology. It is postulated that cold atmospheric plasma (CAP) can trigger a therapeutic shielding response in tissue in part by creating a time- and space-localized, burst-like form of oxy-nitrosative stress on near-surface exposed cells through the flux of plasma-generated RONS. RONS-exposed surface layers of cells communicate to the deeper levels of tissue via a form of the ``bystander effect,'' similar to responses to other forms of cell stress. In this proposed model of CAP therapeutics, the plasma stimulates a cellular survival mechanism through which aerobic organisms shield themselves from infection and other challenges.

  9. [Cerebral oedema: new therapeutic ways].

    PubMed

    Quintard, H; Ichai, C

    2014-06-01

    Cerebral oedema (CO) after brain injury can occur from different ways. The vasogenic and cytotoxic oedema are usually described but osmotic and hydrostatic CO, respectively secondary to plasmatic hypotonia or increase in blood pressure, can also be encountered. Addition of these several mechanisms can worsen injuries. Consequences are major, leading quickly to death secondary to intracerebral hypertension and later to neuropsychic sequelae. So therapeutic care to control this phenomenon is essential and osmotherapy is actually the only way. A better understanding of physiopathological disorders, particularly energetic ways (lactate), aquaporine function, inflammation lead to new therapeutic hopes. The promising experimental results need now to be confirmed by clinical data.

  10. Refactoring and Its Benefits

    SciTech Connect

    Veerraju, R. P. S. P.; Rao, A. Srinivasa; Murali, G.

    2010-10-26

    Refactoring is a disciplined technique for restructuring an existing body of code, altering its internal structure without changing its external behavior. It improves internal code structure without altering its external functionality by transforming functions and rethinking algorithms. It is an iterative process. Refactoring include reducing scope, replacing complex instructions with simpler or built-in instructions, and combining multiple statements into one statement. By transforming the code with refactoring techniques it will be faster to change, execute, and download. It is an excellent best practice to adopt for programmers wanting to improve their productivity. Refactoring is similar to things like performance optimizations, which are also behavior- preserving transformations. It also helps us find bugs when we are trying to fix a bug in difficult-to-understand code. By cleaning things up, we make it easier to expose the bug. Refactoring improves the quality of application design and implementation. In general, three cases concerning refactoring. Iterative refactoring, Refactoring when is necessary, Not refactor.Mr. Martin Fowler identifies four key reasons to refractor. Refactoring improves the design of software, makes software easier to understand, helps us find bugs and also helps in executing the program faster. There is an additional benefit of refactoring. It changes the way a developer thinks about the implementation when not refactoring. There are the three types of refactorings. 1) Code refactoring: It often referred to simply as refactoring. This is the refactoring of programming source code. 2) Database refactoring: It is a simple change to a database schema that improves its design while retaining both its behavioral and informational semantics. 3) User interface (UI) refactoring: It is a simple change to the UI which retains its semantics. Finally, we conclude the benefits of Refactoring are: Improves the design of software, Makes software

  11. Nitroxyl (HNO) Releasing Therapeutics | NCI Technology Transfer Center | TTC

    Cancer.gov

    The National Cancer Institute''s Laboratory of Comparative Carcinogenesis is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize agents that generate HNO in physiological media for therapeutic benefit.

  12. Therapeutic intraspinal microstimulation improves forelimb function after cervical contusion injury

    NASA Astrophysics Data System (ADS)

    Kasten, M. R.; Sunshine, M. D.; Secrist, E. S.; Horner, P. J.; Moritz, C. T.

    2013-08-01

    Objective. Intraspinal microstimulation (ISMS) is a promising method for activating the spinal cord distal to an injury. The objectives of this study were to examine the ability of chronically implanted stimulating wires within the cervical spinal cord to (1) directly produce forelimb movements, and (2) assess whether ISMS stimulation could improve subsequent volitional control of paretic extremities following injury. Approach. We developed a technique for implanting intraspinal stimulating electrodes within the cervical spinal cord segments C6-T1 of Long-Evans rats. Beginning 4 weeks after a severe cervical contusion injury at C4-C5, animals in the treatment condition received therapeutic ISMS 7 hours/day, 5 days/week for the following 12 weeks. Main results. Over 12 weeks of therapeutic ISMS, stimulus-evoked forelimb movements were relatively stable. We also explored whether therapeutic ISMS promoted recovery of forelimb reaching movements. Animals receiving daily therapeutic ISMS performed significantly better than unstimulated animals during behavioural tests conducted without stimulation. Quantitative video analysis of forelimb movements showed that stimulated animals performed better in the movements reinforced by stimulation, including extending the elbow to advance the forelimb and opening the digits. While threshold current to elicit forelimb movement gradually increased over time, no differences were observed between chronically stimulated and unstimulated electrodes suggesting that no additional tissue damage was produced by the electrical stimulation. Significance. The results indicate that therapeutic intraspinal stimulation delivered via chronic microwire implants within the cervical spinal cord confers benefits extending beyond the period of stimulation, suggesting future strategies for neural devices to promote sustained recovery after injury.

  13. How Exercise Can Benefit Older Patients. A Practical Approach.

    ERIC Educational Resources Information Center

    Barry, Henry C.; And Others

    1993-01-01

    Physical activity has preventive and therapeutic benefits for the frail elderly. Physicians must educate patients about exercise benefits. Walking, flexibility, and strength training can prevent muscle weakness and impaired gait and balance. Changes in functional capacity can create greater independence in daily living. Physical activity also…

  14. Therapeutic use of nicergoline.

    PubMed

    Winblad, Bengt; Fioravanti, Mario; Dolezal, Tomas; Logina, Inara; Milanov, Ivan Gospodinov; Popescu, Dinu Cristian; Solomon, Alina

    2008-01-01

    The ergot alkaloid derivative nicergoline became clinically available about 35 years ago in the 1970s. Nicergoline has a broad spectrum of action: (i) as an alpha(1)-adrenoceptor antagonist, it induces vasodilation and increases arterial blood flow; (ii) it enhances cholinergic and catecholaminergic neurotransmitter function; (iii) it inhibits platelet aggregation; (iv) it promotes metabolic activity, resulting in increased utilization of oxygen and glucose; and (v) it has neurotrophic and antioxidant properties. Acting on several basic pathophysiological mechanisms, nicergoline has therapeutic potential in a number of disorders. This article provides an overview of the published clinical evidence relating to the efficacy and safety of nicergoline (30 mg twice daily) in the treatment of dementia (including Alzheimer's disease and vascular dementia) and vascular and balance disorders. For dementia of different aetiologies, the therapeutic benefit of nicergoline has been established, with up to 89% of patients showing improvements in cognition and behaviour. After as little as 2 months of treatment, symptom improvement is apparent compared with placebo, and most patients are still improved or stable after 12 months. Concomitant neurophysiological changes in the brain indicate (after only 4-8 weeks' treatment) improved vigilance and information processing. In patients with balance disorders, mean improvements of 44-78% in symptom severity and quality of life have been observed with nicergoline. Although clinical experience with nicergoline in vascular disorders is limited to relatively short-term, small-scale studies, it has been successfully used in rehabilitation therapy of patients with chronic ischaemic stroke. Open-label evaluations suggest that nicergoline may also be valuable in glaucoma, depression and peripheral arterio-pathy. Adverse events of nicergoline, if any, are related to the central nervous system, the metabolic system and the overall body. Most are

  15. Therapeutic recreation treats depression in the elderly.

    PubMed

    Johnson, C D

    1999-01-01

    Therapeutic recreation can be an effective method to treat depression in elderly home care patients. Home care is the fastest growing component in the Medicare budget. The co-occurrence of physically limiting conditions and depression in the elderly is well documented. Untreated depression carries an enormous risk and cost. Therapeutic recreation is an ideal psychosocial treatment for use in the home care setting because of its effectiveness and versatility. Certified therapeutic recreation specialists use various interventions such as poetry, music, and exercise as part of a treatment team. In addition to effectively managing depression, therapeutic recreation can be beneficial in reducing the effects of many concurrent physical conditions.

  16. Benefit of Blood Pressure Control in Diabetic Patients.

    PubMed

    Kintscher, Ulrich

    2015-07-01

    The coexistence of arterial hypertension and diabetes represents a devastating partnership for cardiovascular health. Thus, blood pressure and blood glucose control are essential therapeutic goals to reduce cardiovascular risk and other diabetes-related endpoints in these patients. The major benefit of blood pressure lowering in diabetes comes from a marked reduction of cardiovascular and renal endpoints. New target blood pressure values to achieve maximum cardiovascular and renal protection will be discussed. In addition to the reduction of macrovascular endpoints, blood pressure lowering therapy in diabetic patients has also been discussed to improve microvascular diseases during diabetes, in particular microalbuminuria or diabetic retinopathy. However, current clinical trial evidence is less robust than for macrovascular disease. Clinical studies showed controversial results, and will be discussed. Finally, new data from the ADVANCE-ON study about the long-term, sustained benefit of blood pressure lowering in hypertensive, diabetic patients has been recently published, and will be evaluated in the context of previous evidence. In summary, the present article will discuss selected new topics in the field of hypertension and diabetes focusing on the benefits achieved by blood pressure lowering in these patients.

  17. The Benefits of Meditation for Outdoor Education.

    ERIC Educational Resources Information Center

    Ettenger, Jim

    Outdoor education is not merely about learning outdoor skills; it should also involve self-reflective activities. Meditation is a technique used for self-reflection, has many proven psychological and physiological benefits, and would be a good addition to any wilderness program. Research has shown that the psychological benefits of meditation…

  18. Modulators of alternative splicing as novel therapeutics in cancer.

    PubMed

    Oltean, Sebastian

    2015-10-10

    Alternative splicing (AS), the process of removing introns from pre-mRNA and re-arrangement of exons to give several types of mature transcripts, has been described more than 40 years ago. However, until recently, it has not been clear how extensive it is. Genome-wide studies have now conclusively shown that more than 90% of genes are alternatively spliced in humans. This makes AS one of the main drivers of proteomic diversity and, consequently, determinant of cellular function repertoire. Unsurprisingly, given its extent, numerous splice isoforms have been described to be associated with several diseases including cancer. Many of them have antagonistic functions, e.g., pro- and anti-angiogenic or pro- and anti-apoptotic. Additionally several splice factors have been recently described to have oncogene or tumour suppressors activities, like SF3B1 which is frequently mutated in myelodysplastic syndromes. Beside the implications for cancer pathogenesis, de-regulated AS is recognized as one of the novel areas of cell biology where therapeutic manipulations may be designed. This editorial discusses the possibilities of manipulation of AS for therapeutic benefit in cancer. Approaches involving the use of oligonucleotides as well as small molecule splicing modulators are presented as well as thoughts on how specificity might be accomplished in splicing therapeutics.

  19. Spinal muscular atrophy: from tissue specificity to therapeutic strategies

    PubMed Central

    Iascone, Daniel M.; Lee, Justin C.

    2015-01-01

    Spinal muscular atrophy (SMA) is the most frequent genetic cause of death in infants and toddlers. All cases of spinal muscular atrophy result from reductions in levels of the survival motor neuron (SMN) protein, and so SMN upregulation is a focus of many preclinical and clinical studies. We examine four issues that may be important in planning for therapeutic success. First, neuromuscular phenotypes in the SMNΔ7 mouse model closely match those in human patients but peripheral disease manifestations differ, suggesting that endpoints other than mouse lifespan may be more useful in predicting clinical outcome. Second, SMN plays important roles in multiple central and peripheral cell types, not just motor neurons, and it remains unclear which of these cell types need to be targeted therapeutically. Third, should SMN-restoration therapy not be effective in all patients, blocking molecular changes downstream of SMN reduction may confer significant benefit, making it important to evaluate therapeutic targets other than SMN. Lastly, for patients whose disease progression is slowed, but who retain significant motor dysfunction, additional approaches used to enhance regeneration of the neuromuscular system may be of value. PMID:25705387

  20. Should academic therapeutic patents go to the highest bidder?

    PubMed

    Collinsworth, Bryan; Crager, Sara E

    2014-05-01

    Universities conduct biomedical research with the self-stated goal of disseminating the benefits to the global public. Licensing therapeutic patents to the highest bidder is counterproductive to this aim, as it prioritizes income maximization over dissemination. We believe that licensing strategies focused on promoting broad access to university-discovered therapeutics better serve both the mission of universities and the public good.

  1. An antidote approach to reduce risk and broaden utility of antibody based therapeutics.

    PubMed

    Portnoff, Alyse D; Gao, Cuihua; Borrok, M Jack; Gao, Xizhe; Gao, Changshou; Rainey, G Jonah

    2017-03-03

    Antibody therapeutics offer safe and effective treatment options for a broad range of diseases. One of the greatest benefits of antibody therapeutics is their extraordinarily long serum half-life, allowing infrequent dosing with long-lasting effects. One characteristic of antibodies that drives long half-life is the ability to interact with the recycling receptor, FcRn, in a pH-dependent manner. The benefit of long half-life, however, carries with it liabilities. While the positive effects of antibody therapeutics are long-lasting, any acute adverse events or chronic negative impacts, such as immunosuppression in the face of an infection, are also long-lasting. Therefore, we sought to develop antibodies with a chemical handle that alone would enjoy the long half-life of normal antibodies, but upon addition of a small-molecule antidote, would interact with the chemical handle and inhibit the antibody recycling mechanism thus leading to rapid degradation and shortened half-life in vivo. Here we present a proof of concept study where we identify sites to incorporate a nnAA that can be chemically modified to modulate FcRn interaction in vitro and antibody half-life in vivo. This is an important first step in developing safer therapeutics, and the next step will be development of technology that can perform the modifying chemistry in vivo.

  2. Therapeutic Uses of Music with Older Adults. Second Edition

    ERIC Educational Resources Information Center

    Clair, Alicia Ann; Memmott, Jenny

    2008-01-01

    In this comprehensively updated second edition, written by Alicia Ann Clair and Jenny Memmott the extraordinary benefits of music therapy for older adults are detailed. "Therapeutic Uses of Music with Older Adults" not only examines these benefits but also clarifies the reasons that music is beneficial. This important book shows both informal and…

  3. Gardening as a therapeutic intervention in mental health.

    PubMed

    Page, Mathew

    This article describes why one low-secure unit chose to initiate a horticultural therapy project and organise it as a 'workers' cooperative'. The therapeutic benefits of gardening are explored, particularly focusing on the social benefits. The article also discusses the issue of hope, which is an intrinsic requirement in gardening.

  4. National Water Quality Benefits

    EPA Science Inventory

    This project will provide the basis for advancing the goal of producing tools in support of quantifying and valuing changes in water quality for EPA regulations. It will also identify specific data and modeling gaps and Improve benefits estimation for more complete benefit-cost a...

  5. Educational Reform: Who Benefits?

    ERIC Educational Resources Information Center

    Steffy, Betty E.

    1994-01-01

    Uses Blau and Scott concept of "cui bono" to describe who has benefited from 1990 Kentucky Education Reform Act. In eyes of legislators, everyone would benefit, and the economically depressed state would prosper. As implementation of KERA progresses, it is becoming increasingly clear that mandated changes may be structural and may…

  6. Hospital benefit segmentation.

    PubMed

    Finn, D W; Lamb, C W

    1986-12-01

    Market segmentation is an important topic to both health care practitioners and researchers. The authors explore the relative importance that health care consumers attach to various benefits available in a major metropolitan area hospital. The purposes of the study are to test, and provide data to illustrate, the efficacy of one approach to hospital benefit segmentation analysis.

  7. Ultrasound: A Revenant Therapeutic Modality in Dentistry

    PubMed Central

    Rastogi, Trisha; Beeraka, Kartheeki; Penumatcha, Mohan Raju; Olepu, Sanjeeva Rao

    2016-01-01

    An ultrasound (US) gives a visible image of the organs that are present inside the body. In medicine it serves for diagnosing and also its therapeutic benefits are well established for bone healing, osteointegration and soft tissue healing. In dentistry it is widely used for diagnostic purposes. When it was discovered it was introduced for therapeutic purposes, but due to lack of clinical studies its use as therapy was remittent in dentistry. The aim of the present paper was to establish the efficiency of therapeutic US in maxillofacial region for alleviating the pain and to see the other applications. Our search included the English terms like ultrasonography, applications, dentistry in Google search engine, PubMed and Medline from 1980 to 2015. We found very few articles showing the effects of therapeutic Ultrasound (US) in treatment of pain and healing in dentistry. We concluded that clinical benefits of in vivo studies were very little and demands further rigorous research to strive for the therapeutic success of US. PMID:27630969

  8. Salivary epithelial cells: an unassuming target site for gene therapeutics

    PubMed Central

    Perez, Paola; Rowzee, Anne M.; Zheng, Changyu; Adriaansen, Janik; Baum, Bruce J.

    2010-01-01

    Salivary glands are classical exocrine glands whose external secretions result in the production of saliva. However, in addition to the secretion of exocrine proteins, salivary epithelial cells are also capable of secreting proteins internally, into the bloodstream. This brief review examines the potential for using salivary epithelial cells as a target site for in situ gene transfer, with an ultimate goal of producing therapeutic proteins for treating both systemic and upper gastrointestinal tract disorders. The review discusses the protein secretory pathways reported to be present in salivary epithelial cells, the viral gene transfer vectors shown useful for transducing these cells, model transgenic secretory proteins examined, and some clinical conditions that might benefit from such salivary gland gene transfer. PMID:20219693

  9. Trends in Therapeutic Recreation.

    ERIC Educational Resources Information Center

    Smith, Ralph W.

    1995-01-01

    Discusses the implications of the rapid, dramatic changes taking place in therapeutic recreation for individuals with physical disabilities. The article notes the impact of changes in managed care, examines programming trends in therapeutic recreation (adventure/outdoor education, competitive sports, handcycling, health enhancement activities, and…

  10. Therapeutic Recreation Practicum Manual.

    ERIC Educational Resources Information Center

    Schneegas, Kay

    This manual provides information on the practicum program offered by Moraine Valley Community College (MVCC) for students in its therapeutic recreation program. Sections I and II outline the rationale and goals for providing practical, on-the-job work experiences for therapeutic recreation students. Section III specifies MVCC's responsibilities…

  11. Chicanoizing the Therapeutic Community

    ERIC Educational Resources Information Center

    Aron, William S.; And Others

    1974-01-01

    Focusing on the drug addiction problem and its antecedent conditions in a Chicano population, the article examines several therapeutic interventions suggested by these conditions and indicates how they might be incorporated into a drug addiction Therapeutic Community treatment program designed to meet the needs of Chicano drug addicts. (Author/NQ)

  12. Impact of Therapeutic Camping

    ERIC Educational Resources Information Center

    Shniderman, Craig M.

    1974-01-01

    There has been little interest in, and only slight illumination of, the impact of therapeutic camping for emotionally disturbed children. This study seeks to validate the belief that camping is therapeutic. Subjects were 52 boys, 5 to 11 1/2 years of age. Results support the hypothesis. (Author/HMV)

  13. Therapeutic potential of cannabis-related drugs.

    PubMed

    Alexander, Stephen P H

    2016-01-04

    In this review, I will consider the dual nature of Cannabis and cannabinoids. The duality arises from the potential and actuality of cannabinoids in the laboratory and clinic and the 'abuse' of Cannabis outside the clinic. The therapeutic areas currently best associated with exploitation of Cannabis-related medicines include pain, epilepsy, feeding disorders, multiple sclerosis and glaucoma. As with every other medicinal drug of course, the 'trick' will be to maximise the benefit and minimise the cost. After millennia of proximity and exploitation of the Cannabis plant, we are still playing catch up with an understanding of its potential influence for medicinal benefit.

  14. Medicare Hospice Benefits

    MedlinePlus

    ... 4 Care for a condition other than your terminal illness ......................................... 4 How your Medicare hospice benefit works ..................................................... ... care, counseling, drugs, equipment, and supplies for the terminal illness and related conditions. ■■ Care is generally provided ...

  15. Benefits of CHP Partnership

    EPA Pesticide Factsheets

    Learn about the benefits of being a EPA CHP Partner, which include expert advice and answers to questions, CHP news, marketing resources, publicity and recognition, and being associated with EPA through a demonstrated commitment to CHP.

  16. Benefits of breastfeeding

    MedlinePlus

    Experts say that breastfeeding your baby is good for you and your baby. If you breastfeed for any length of time, no matter ... is, you and your baby will benefit from breastfeeding. Learn about breastfeeding your baby and decide if ...

  17. Military Retirement Benefits.

    DTIC Science & Technology

    1984-05-17

    55, before they qualify for retirement benefits. 5 2. Approximately 94% of companies allow early retirement with reduced pensions. The Hay-Huggins...data indicate that the most common basis for eligibility for reduced early retirement is a combination of age and service (72% of plans). The most common...combination is age 55 and ten years of service. 13 • . . . . . . . . " " - .. . . . " . . . ’ For those companies providing early retirement benefits

  18. Therapeutic clowning in paediatric practice.

    PubMed

    Finlay, Fiona; Baverstock, Anna; Lenton, Simon

    2014-10-01

    Over the past 30 years, there has been much research into the health benefits of humour and laughter. Although often viewed very positively, rigorous evaluation of the therapeutic effect of clowning is complex. Clowning is a multi-modal intervention, which may have an impact on medical conditions, procedures, family functioning and health care teams. Clowns help children to adapt to their hospital surroundings and can distract from, and demystify, painful or frightening procedures through 'doses of fun' to complement traditional clinical interventions. This paper provides a review of the paediatric literature and reveals studies looking at the effect of clown interventions on various practical procedures and individual medical conditions, and the effects of clowning within clinical teams.

  19. Therapeutic efficacy of TBC3711 in monocrotaline-induced pulmonary hypertension

    PubMed Central

    2011-01-01

    Background Endothelin-1 signalling plays an important role in pathogenesis of pulmonary hypertension. Although different endothelin-A receptor antagonists are developed, a novel therapeutic option to cure the disease is still needed. This study aims to investigate the therapeutic efficacy of the selective endothelin-A receptor antagonist TBC3711 in monocrotaline-induced pulmonary hypertension in rats. Methods Monocrotaline-injected male Sprague-Dawley rats were randomized and treated orally from day 21 to 35 either with TBC3711 (Dose: 30 mg/kg body weight/day) or placebo. Echocardiographic measurements of different hemodynamic and right-heart hypertrophy parameters were performed. After day 35, rats were sacrificed for invasive hemodynamic and right-heart hypertrophy measurements. Additionally, histologic assessment of pulmonary vascular and right-heart remodelling was performed. Results The novel endothelin-A receptor antagonist TBC3711 significantly attenuated monocrotaline-induced pulmonary hypertension, as evident from improved hemodynamics and right-heart hypertrophy in comparison with placebo group. In addition, muscularization and medial wall thickness of distal pulmonary vessels were ameliorated. The histologic evaluation of the right ventricle showed a significant reduction in fibrosis and cardiomyocyte size, suggesting an improvement in right-heart remodelling. Conclusion The results of this study suggest that the selective endothelin-A receptor antagonist TBC3711 demonstrates therapeutic benefit in rats with established pulmonary hypertension, thus representing a useful therapeutic approach for treatment of pulmonary hypertension. PMID:21699729

  20. [Therapeutic indications for managing symptoms: fatigue].

    PubMed

    Waubant, E

    2001-09-01

    Fatigue is a common complaint in patients affected by multiple sclerosis. Its mechanisms are poorly understood and are likely diverse. The term "fatigue" has been used for asthenia at rest but also for fatigability during exercise. Amantadine is the only drug that has a proven therapeutic benefit in randomized, double blind, controlled trials. Inhibitors of serotonin re-uptake are used pragmatically because of the relationship between fatigue and depression. Aminopyridins may improve fatigability, mainly at the level of lower limbs.

  1. [Therapeutic Aggressiveness and Liquid Oncology].

    PubMed

    Barón Duarte, F J; Rodríguez Calvo, M S; Amor Pan, J R

    2017-01-01

    Aggressiveness criteria proposed in the scientific literature a decade ago provide a quality judgment and are a reference in the care of patients with advanced cancer, but their use is not generalized in the evaluation of Oncology Services. In this paper we analyze the therapeutic aggressiveness, according to standard criteria, in 1.001 patients with advanced cancer who died in our Institution between 2010 and 2013. The results seem to show that aggressiveness at the end of life is present more frequently than experts recommend. About 25% of patients fulfill at least one criterion of aggressiveness. This result could be explained by a liquid Oncology which does not prioritize the patient as a moral subject in the clinical appointment. Medical care is oriented to necessities and must be articulated in a model focused on dignity and communication. Its implementation through Advanced Care Planning, consideration of patient's values and preferences, and Limitation of therapeutic effort are ways to reduce aggressiveness and improve clinical practice at the end of life. We need to encourage synergic and proactive attitudes, adding the best of cancer research with the best clinical care for the benefit of human being, moral subject and main goal of Medicine.

  2. New piezoelectric transducers for therapeutic ultrasound.

    PubMed

    Chapelon, J Y; Cathignol, D; Cain, C; Ebbini, E; Kluiwstra, J U; Sapozhnikov, O A; Fleury, G; Berriet, R; Chupin, L; Guey, J L

    2000-01-01

    Therapeutic ultrasound (US) has been of increasing interest during the past few years. However, the development of this technique depends on the availability of high-performance transducers. These transducers have to be optimised for focusing and steering high-power ultrasonic energy within the target volume. Recently developed high-power 1-3 piezocomposite materials bring to therapeutic US the exceptional electroacoustical properties of piezocomposite technology: these are high efficiency, large bandwidth, predictable beam pattern, more flexibility in terms of shaping and definition of sampling in annular arrays, linear arrays or matrix arrays. The construction and evaluation of several prototypes illustrates the benefit of this new approach that opens the way to further progress in therapeutic US.

  3. Electronic access to food and cash benefits.

    PubMed

    MaloneBeach, Eileen E; Frank, Cindy S; Heuberger, Roschelle A

    2012-01-01

    The authors' purpose was to examine access to Family Independence Program and Food benefits in relation to customer service and an automated helpline. In addition, participants identified impediments and limitations to the receipt of services. Two hundred forty-four surveys were mailed to recipients of over-the-counter electronic benefit transfer cards; 58 were returned. The findings indicate that when customers (age 21-92) received assistance navigating the electronic benefits transfer system from local office staff, they were able to obtain benefits successfully. Negative credit/debit card history and touchtone phones were related to difficulty using the system. The results suggest that the local office and the contracted service provider (automatic helpline) need to provide assistance that promotes greater autonomy for the customer to make successful transitions to benefits that are delivered electronically.

  4. Perceived risk, dread, and benefits

    SciTech Connect

    Gregory, R. ); Mendelsohn, R. )

    1993-06-01

    This paper uses regression techniques to take a second look at a classic risk-perception data set originally collected by Paul Slovic, Sarah Lichtenstein, and Baruch Fischhoff. As discussed in earlier studies, the attributes expected mortality, effects on future generations, immediacy, and catastrophic potential all significantly affect risk ratings. However, the authors find that perceived risk and dread show different regression patterns; most importantly, only perceived risk ratings correlate with expected mortality. In addition, average risk ratings are found to be significantly affected by perceived individual benefits, which suggests that perceptions of risk are net rather than gross indicators of harm. 14 refs., 3 tabs.

  5. Fundamentals and health benefits of xanthohumol, a natural product derived from hops and beer.

    PubMed

    Magalhães, Paulo J; Carvalho, Daniel O; Cruz, José M; Guido, Luís F; Barros, Aquiles A

    2009-05-01

    In recent years, there has been a growing interest in phenolic compounds and their presumed role in the prevention of various degenerative diseases, such as cancer and cardiovascular diseases. Xanthohumol, a prenylated chalcone from hops and beer, is among the phenolic compounds which have received the most attention in recent years. This compound has a range of interesting biological properties that may have therapeutic utility. Based on the health-promoting properties of xanthohumol, the production of a beer enriched in this substance would be of huge interest to the brewing industry, for the benefits this could bring to consumer's health. This paper reviews recent and important data with respect to the health benefits or biological activities of xanthohumol and beer. In addition, an overview of the chemistry and biotechnological aspects of xanthohumol is presented.

  6. Benefits of infant massage.

    PubMed

    Day, Jane

    2014-05-01

    After spending three months as a clinical midwifery tutor at a remote hospital in Zambia, where I helped to train student midwives and other students, my interest in infant massage was ignited, having witnessed the benefits of massage to both mother and baby. Once back in the UK, I trained and qualified as a massage instructor with an international infant massage training organisation, which has led me to work extensively with parents and babies, offering one-to-one and group courses. It has been a privilege to be able to teach parents the valuable skill of infant massage, and consequently pass on the benefits both physiological and psychosocial.

  7. Noncaloric Benefits of Carbohydrates.

    PubMed

    Reddy, B Ravinder

    2015-01-01

    Noncaloric benefits of carbohydrates are due to the presence of dietary fibers, which are a heterogeneous group of natural food sources and form an important component of a healthy diet. They differ in physiochemical properties such as solubility, fermentability and viscosity. They have a wide range of physiological effects resulting in gastrointestinal and systemic benefits. These include appetite, satiety, bowel transit time and function, production of short-chain fatty acids and certain vitamins, and effects on gut microbiota, immunity and inflammation, as well as mineral absorption. They also help to control the glycemic status and serum lipid levels, resulting in reduced incidence rates of atherosclerosis, hypertension, stroke and cardiovascular diseases.

  8. Modular Cre/lox system and genetic therapeutics for colorectal cancer.

    PubMed

    Bordonaro, Michael

    2009-01-01

    The Cre/lox system is a powerful tool for targeting therapeutic effectors in a wide variety of human disorders. I review a Cre/lox Wnt-targeted system that has shown promise against Wnt-positive colorectal cancer cell lines. In addition to Wnt-specific targeting of cell death inducers, the modular nature of this gene therapy model system can be exploited by designing positive and negative feedback loops to either amplify or inhibit Wnt activity for experimental or therapeutic benefit. I discuss the structural components and performance parameters of the system, the implication of these findings with respect to cancer stem cells, as well as the general applicability of this system to any disorder characterized by differential gene expression. I also consider the issue of gene delivery as well as in vivo testing requirements necessary for the further characterization and development of this system.

  9. Gene- and stem cell-based therapeutics for cartilage regeneration and repair.

    PubMed

    Tang, Ying; Wang, Bing

    2015-04-15

    Cell-based regeneration of damaged or diseased articular cartilage still faces significant clinical challenge due to inadequate environmental regulation of stem cell proliferation and chondrogenic differentiation. The role of insulin-like growth factor in critical steps of human bone marrow-derived mesenchymal stem cell chondrogenesis has potential in optimizing the therapeutic use of mesenchymal stem cells in cartilage disorders. In addition to the previously described benefits of recombinant adeno-associated viral vector for in vivo gene therapy, demonstrated by Frisch and colleagues, such vector is also a safe and efficient delivery system for the genetic modification of human bone marrow-derived mesenchymal stem cells via ex vivo insulin-like growth factor 1 gene transfer, so that implanted mesenchymal stem cells continuously release a therapeutic level of insulin-like growth factor 1 to achieve sustained mesenchymal stem cell chondrogenesis for cartilage regeneration.

  10. Regulatory T Cells in the Tumor Microenvironment and Cancer Progression: Role and Therapeutic Targeting

    PubMed Central

    Chaudhary, Belal; Elkord, Eyad

    2016-01-01

    Recent years have seen significant efforts in understanding and modulating the immune response in cancer. In this context, immunosuppressive cells, including regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs), have come under intense investigation for their proposed roles in suppressing tumor-specific immune responses and establishing an immunosuppressive tumor microenvironment, thus enabling tumor immune evasion. Additionally, recent evidence indicates that Tregs comprise diverse and heterogeneous subsets; phenotypically and functionally distinct subsets of tumor-infiltrating Tregs could contribute differently to cancer prognosis and clinical outcomes. Understanding Treg biology in the setting of cancer, and specifically the tumor microenvironment, is important for designing effective cancer therapies. In this review, we critically examine the role of Tregs in the tumor microenvironment and in cancer progression focusing on human studies. We also discuss the impact of current therapeutic modalities on Treg biology and the therapeutic opportunities for targeting Tregs to enhance anti-tumor immune responses and clinical benefits. PMID:27509527

  11. Therapeutic effect of llama derived VHH fragments against Streptococcus mutans on the development of dental caries.

    PubMed

    Krüger, Carina; Hultberg, Anna; Marcotte, Harold; Hermans, Pim; Bezemer, Sandra; Frenken, Leon G J; Hammarström, Lennart

    2006-10-01

    Streptococcus mutans is the main cause of dental caries. We evaluated the therapeutic effect of variable regions of a llama heavy chain antibody fragments directed against S. mutans named S36-VHH (S for Streptococcus) alone or fused with glucose oxidase (GOx) from Aspergillus niger. Western blot analysis and ELISA revealed binding of the S36-VHH to the streptococcal antigen I/II adhesin molecule of S. mutans serotype C. In a rat-desalivated caries model, daily administration of S36-VHH significantly reduced the development of smooth surface caries. No additional therapeutic effect of GOx was observed. Our results suggest that llama VHH antibodies may be a potential benefit as prophylaxis against dental caries.

  12. [Costs and benefits of measles vaccination].

    PubMed

    Ambrosch, F; Wiedermann, G; Harasek, G

    1978-02-23

    Former calculations of the medical benefit of measles immunization, concerning frequency of measles complications, effectiveness and risk of vaccination, showed that measles vaccination is a very useful measure. As the decision to introduce vaccination on a broad scale depends on financial deliberations, too, a cost-benefit analysis for Austria has been performed and the cost-benefit ratio as well as the cost-benefit difference calculated. The costs of measles vaccination which is performed mainly by private pediatricians at the present time, include costs of vaccine, physician and additional antipyretic and is 257.90 AS. The average costs of therapy per child consist of home treatment (287.20 AS), hospital treatment (162.50 AS) and care of residual cerebral damage (88.50 AS). Together with the costs of one week vacation which is warranted in Austria for the nursing of a sick child once a year, this makes a total sum of 1081.--AS. From these data the cost-benefit ratio was calculated by 2.95, the cost-benefit difference by 715.--AS per child. 5 years after the start of general measles vaccination of 1 year old children the accumulated costs of vaccination are equalled by the profit gained by prevention of the disease. The annual cost-benefit difference is positive after 3 years. 10 years after introduction of general vaccination the accumulated cost-benefit difference in Austria would be approximately 167 Mill. AS.

  13. 29 CFR 4.52 - Fringe benefit determinations.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 1 2010-07-01 2010-07-01 true Fringe benefit determinations. 4.52 Section 4.52 Labor... Procedures § 4.52 Fringe benefit determinations. (a) Wage determinations issued pursuant to the Service... addition, wage determinations contain a prescribed minimum rate for all other benefits, such as...

  14. 20 CFR 404.1919 - How benefits are recomputed.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false How benefits are recomputed. 404.1919 Section 404.1919 Employees' Benefits SOCIAL SECURITY ADMINISTRATION FEDERAL OLD-AGE, SURVIVORS AND DISABILITY... will recompute the pro rata PIA only if the inclusion of the additional earnings results in an...

  15. COGNITION AS A THERAPEUTIC TARGET IN LATE-LIFE DEPRESSION: POTENTIAL FOR NICOTINIC THERAPEUTICS

    PubMed Central

    Zurkovsky, Lilia; Taylor, Warren D.; Newhouse, Paul A.

    2013-01-01

    Depression is associated with impairments to cognition and brain function at any age, but such impairments in the elderly are particularly problematic because of the additional burden of normal cognitive aging and in some cases, structural brain pathology. Individuals with late-life depression exhibit impairments in cognition and brain structural integrity, alongside mood dysfunction. Antidepressant treatment improves symptoms in some but not all patients, and those who benefit may not return to the cognitive and functional level of nondepressed elderly. Thus, for comprehensive treatment of late-life depression, it may be necessary to address both the affective and cognitive deficits. In this review, we propose a model for the treatment of late-life depression in which nicotinic stimulation is used to improve cognitive performance and improve the efficacy of an antidepressant treatment of the syndrome of late-life depression. The cholinergic system is well-established as important to cognition. Although muscarinic stimulation may exacerbate depressive symptoms, nicotinic stimulation may improve cognition and neural functioning without a detriment to mood. While some studies of nicotinic subtype specific receptor agonists have shown promise in improving cognitive performance, less is known regarding how nicotinic receptor stimulation affects cognition in depressed elderly patients. Late-life depression thus represents a new therapeutic target for the development of nicotinic agonist drugs and parallel treatment of cognitive dysfunction along with medical and psychological approaches to treating mood dysfunction may be necessary to ensure full resolution of depressive illness in aging. PMID:23933385

  16. Bioengineering Lantibiotics for Therapeutic Success

    PubMed Central

    Field, Des; Cotter, Paul D.; Hill, Colin; Ross, R. P.

    2015-01-01

    Several examples of highly modified antimicrobial peptides have been described. While many such peptides are non-ribosomally synthesized, ribosomally synthesized equivalents are being discovered with increased frequency. Of the latter group, the lantibiotics continue to attract most attention. In the present review, we discuss the implementation of in vivo and in vitro engineering systems to alter, and even enhance, the antimicrobial activity, antibacterial spectrum and physico-chemical properties, including heat stability, solubility, diffusion and protease resistance, of these compounds. Additionally, we discuss the potential applications of these lantibiotics for use as therapeutics. PMID:26640466

  17. Developing Therapeutic Vaccines Against Alzheimer's Disease

    PubMed Central

    Wisniewski, Thomas; Drummond, Eleanor

    2016-01-01

    Summary Alzheimer's disease (AD) is the most common form of dementia worldwide. It is characterized by an imbalance between the production and clearance of amyloid β (Aβ) and tau proteins. In AD these normal proteins accumulate, leading to aggregation and a conformational change forming oligomeric and fibrillary species with a high β-sheet content. Active and passive immunotherapeutic approaches result in dramatic reduction of Aβ pathology in AD animal models. However, there is much more limited evidence in human studies of significant clinical benefits from these strategies and it is becoming apparent that they may only be effective very early in AD. Vaccination targeting only tau pathology has shown benefits in some mouse studies but human studies are limited. Greater therapeutic efficacy for the next generation of vaccine approaches will likely benefit from specifically targeting the most toxic species of Aβ and tau, ideally simultaneously. PMID:26577574

  18. Developing therapeutic vaccines against Alzheimer's disease.

    PubMed

    Wisniewski, Thomas; Drummond, Eleanor

    2016-01-01

    Alzheimer's disease (AD) is the most common form of dementia worldwide. It is characterized by an imbalance between the production and clearance of amyloid β (Aβ) and tau proteins. In AD these normal proteins accumulate, leading to aggregation and a conformational change forming oligomeric and fibrillary species with a high β-sheet content. Active and passive immunotherapeutic approaches result in dramatic reduction of Aβ pathology in AD animal models. However, there is much more limited evidence in human studies of significant clinical benefits from these strategies and it is becoming apparent that they may only be effective very early in AD. Vaccination targeting only tau pathology has shown benefits in some mouse studies but human studies are limited. Greater therapeutic efficacy for the next generation of vaccine approaches will likely benefit from specifically targeting the most toxic species of Aβ and tau, ideally simultaneously.

  19. Benefits of Geothermal Energy

    SciTech Connect

    2004-07-01

    One of the principal benefits of geothermal power plants is that they provide baseload power. Baseload power plants provide power all or most of the time and contrast with peaker plants which turn on or off as demand rises, or peaks, throughout the day. Geothermal plants contrast with other renewable energy resources like wind and solar energy that generate power intermittently.

  20. The Benefits of Latin?

    ERIC Educational Resources Information Center

    Holliday, Lisa R.

    2012-01-01

    Classicists have long claimed that the study of Latin has benefits that exceed knowledge of the language itself, and in the current economic times, these claims are made with urgency. Indeed, many contend that Latin improves English grammar and writing skills, cognitive abilities, and develops transferable skills necessary for success in the…

  1. GIO benefits the USGS

    USGS Publications Warehouse

    McDermott, M.P.

    2004-01-01

    The Geographic Information Office (GIO) benefits the U.S. Geological Survey (USGS) by providing access to and delivery of USGS information and services, safety and security of USGS data and information, support for USGS science, and coordination of partnerships through Federal interagency data committees.

  2. Benefits of Java

    MedlinePlus

    ... Training and Recovery Exercise Topics Fueling Your Workout Benefits of Physical Activity Exercise Nutrition Top Articles Man running - Protein and the Athlete - How Much Do You Need? Protein and the Athlete — How Much Do You Need? stop watch - Timing Your Pre- and Post-Workout ... of Java Published September 29, 2014 Print Email ...

  3. Costs and benefits

    NASA Technical Reports Server (NTRS)

    1975-01-01

    Two models of cost benefit analysis are illustrated and the application of these models to assessing the economic scope of space applications programs was discussed. Four major areas cited as improvable through space derived information - food supply and distribution, energy sources, mineral reserves, and communication and navigation were - discussed. Specific illustrations are given for agriculture and maritime traffic.

  4. Benefits of Conducting Research.

    ERIC Educational Resources Information Center

    Anderson, Frances E.

    2001-01-01

    Metaphors for researchers, such as a crusader; a traveler; an explorer; a miner; an astronaut; a biblical Daniel; a Samurai; and an archaeologist are discussed. Benefits of conducting research are enumerated, including building the knowledge base for art therapy; increasing professional opportunities; improving client care; and advancing the…

  5. The Benefits of Bilingualism.

    ERIC Educational Resources Information Center

    Zelasko, Nancy

    1998-01-01

    This paper presents the academic benefits of bilingual education gained by language-minority students, highlighting school districts that have had great success with bilingual education and discussing the negative consequences of the proposed English for Children initiative, which would end bilingual education and instead provide intensive…

  6. Space for Mankind's Benefit.

    ERIC Educational Resources Information Center

    von Puttkamer, Jesco, Ed.; McCullough, Thomas J., Ed.

    Presented are the proceedings of the first international Congress on "Space for Mankind's Benefit" organized by the Huntsville Association of Technical Societies and held November 15-19, 1971, at Huntsville, Alabama. Following introductory statements, a total of 45 articles read in 10 sessions are incorporated. The session headings are: Man in…

  7. Are Therapeutic Motivation and Having One’s Own Doctor as Researcher Sources of Therapeutic Misconception?

    PubMed Central

    Kim, Scott Y H; De Vries, Raymond; Parnami, Sonali; Wilson, Renee; Kim, H Myra; Frank, Samuel; Holloway, Robert G; Kieburtz, Karl

    2014-01-01

    Background Desire for improvement in one’s illness and having one’s own doctor functioning as a researcher are thought to promote therapeutic misconception (TM), a phenomenon in which research subjects are said to conflate research with treatment. Purpose To examine whether subjects’ therapeutic motivation and own doctor functioning as researcher are associated with TM. Methods We interviewed 90 persons with advanced Parkinson Disease (PD) enrolled or intending to enroll in sham surgery controlled neurosurgical trials, using qualitative interviews. Subjects were compared by motivation (primarily therapeutic versus primarily altruistic or dually motivated by altruistic and therapeutic motivation) and by doctor status (own doctor as site investigator versus not) on the following: understanding of purpose of study; understanding of research procedures; perception of chance of direct benefit; and recollection and perceptions concerning the risks. Results 60% had primarily therapeutic motivation and 44% had their own doctor as the site investigator, but neither were generally associated with increased TM responses. Overall level of understanding of purpose and procedures of research were high. Subjects responded with generally high estimates of probability of direct benefit but their rationales were personal and complex. The therapeutic-motivation group was more sensitive to risks. Five (5.6%) subjects provided incorrect answers to the question about purpose of research and yet showed excellent understanding of research procedures. Conclusions In persons with PD involved in sham surgery clinical trials, being primarily motivated by desire for direct benefit to one’s illness or having one’s own doctor as the site investigator were not associated with greater TM responses. PMID:24855070

  8. Genetic determinants and potential therapeutic targets for pancreatic adenocarcinoma

    PubMed Central

    Reznik, Robert; Hendifar, Andrew E.; Tuli, Richard

    2014-01-01

    Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer deaths in both men and women in the United States, carrying a 5-year survival rate of approximately 5%, which is the poorest prognosis of any solid tumor type. Given the dismal prognosis associated with PDAC, a more thorough understanding of risk factors and genetic predisposition has important implications not only for cancer prevention, but also for screening techniques and the development of personalized therapies. While screening of the general population is not recommended or practicable with current diagnostic methods, studies are ongoing to evaluate its usefulness in people with at least 5- to 10-fold increased risk of PDAC. In order to help identify high-risk populations who would be most likely to benefit from early detection screening tests for pancreatic cancer, discovery of additional pancreatic cancer susceptibility genes is crucial. Thus, specific gene-based, gene-product, and marker-based testing for the early detection of pancreatic cancer are currently being developed, with the potential for these to be useful as potential therapeutic targets as well. The goal of this review is to provide an overview of the genetic basis for PDAC with a focus on germline and familial determinants. A discussion of potential therapeutic targets and future directions in screening and treatment is also provided. PMID:24624093

  9. Triggered release of therapeutic antibodies from nanodiamond complexes.

    PubMed

    Smith, Adrienne H; Robinson, Erik M; Zhang, Xue-Qing; Chow, Edward K; Lin, Yang; Osawa, Eiji; Xi, Jianzhong; Ho, Dean

    2011-07-01

    Recent reports have revealed that detonation nanodiamonds (NDs) can serve as efficient, biocompatible, and versatile drug delivery platforms. Consequently, further investigations exploring additional therapeutic applications are warranted. Current limitations associated with the non-specific nature of intravenous drugs limit the potential of certain pharmacological agents. One such treatment that could benefit from a stable delivery platform is antibody (Ab) therapy. Determination of Ab adsorption and desorption to a ND surface was subsequently examined using the transforming growth factor β (TGF-β) antibody as a model therapeutic. ND-Ab complexes were found to be stable in water through enzyme-linked immunosorbent assays (ELISAs), UV-vis spectroscopy and TEM, with no Ab released after ten days. Released Abs were detected in extreme pH solutions (3.5), DMEM (+) serum with pH levels ranging from 4 to 10.5, and inorganic saline solutions. Preserved activity of Abs released in DMEM (+) serum was confirmed using an ELISA. These results suggest ND-Ab complexes are synthesized and stabilized in water and are triggered to release active Abs upon exposure to physiological conditions.

  10. Therapeutic applications of whey protein.

    PubMed

    Marshall, Keri

    2004-06-01

    Whey, a protein complex derived from milk, is being touted as a functional food with a number of health benefits. The biological components of whey, including lactoferrin, beta-lactoglobulin, alpha-lactalbumin, glycomacropeptide, and immunoglobulins, demonstrate a range of immune-enhancing properties. In addition, whey has the ability to act as an antioxidant, antihypertensive, antitumor, hypolipidemic, antiviral, antibacterial, and chelating agent. The primary mechanism by which whey is thought to exert its effects is by intracellular conversion of the amino acid cysteine to glutathione, a potent intracellular antioxidant. A number of clinical trials have successfully been performed using whey in the treatment of cancer, HIV, hepatitis B, cardiovascular disease, osteoporosis, and as an antimicrobial agent. Whey protein has also exhibited benefit in the arena of exercise performance and enhancement.

  11. Effects of language concordance and interpreter use on therapeutic alliance in Spanish-speaking integrated behavioral health care patients.

    PubMed

    Villalobos, Bianca T; Bridges, Ana J; Anastasia, Elizabeth A; Ojeda, Carlos A; Rodriguez, Juventino Hernandez; Gomez, Debbie

    2016-02-01

    The discrepancy between the growing number of Spanish speakers in the U.S. and the availability of bilingual providers creates a barrier to accessing quality mental health care. Use of interpreters provides one strategy for overcoming this linguistic barrier; however, concerns about whether sessions with interpreters, versus bilingual providers, impede therapeutic alliance remain. The current study explored associations between the use of interpreters and therapeutic alliance in a sample of 458 Spanish-speaking patients seen for integrated behavioral health visits at primary care clinics. Patients completed a brief (4 item) therapeutic alliance scale at their behavioral health appointment. In addition, to supplement the quantitative study data, a pilot study of 30 qualitative interviews was conducted with a new sample of 10 Spanish-speaking patients, 10 behavioral health consultants (BHCs), and 10 trained interpreters. Quantitative results showed that interpreter use did not relate to therapeutic alliance, even when controlling for relevant demographic variables. However, qualitative interviews suggested major themes regarding the relative benefits and challenges of using interpreters for patients, interpreters, and BHCs. In interviews, patients expressed a strong preference for bilingual providers. Benefits included greater privacy, sense of trust, and accuracy of communication. However, in their absence, interpreters were seen as increasing access to services and facilitating communication with providers, thereby addressing the behavioral health needs of patients with limited English proficiency. BHCs and interpreters emphasized the importance of interpreter training and a good collaborative relationship with interpreters to minimize negative effects on the quality of care.

  12. The importance of considering non-monetary costs and benefits in selecting pharmacologic interventions in mental health.

    PubMed

    Pleil, A M

    1995-01-01

    The continuing increase in health care costs has focused more attention on the value associated with a therapeutic intervention in addition to its clinical efficacy and safety. Although safety and efficacy are important, the effectiveness of an intervention in practice is the yardstick for assessing a therapy's societal benefit. In measuring effectiveness outcomes, all the relevant costs and benefits must be considered, including those that extend beyond the direct costs of care. Patient quality of life and, related to it, work productivity are two additional outcomes worthy of consideration. This article presents a discussion of several economic approaches to measuring indirect costs, the relationship between indirect costs and quality of life, and the relevance of such evaluations in the area of mental health, and offers recommendations for researchers.

  13. University Benefits Survey: Part I (All Benefits Excluding Pensions).

    ERIC Educational Resources Information Center

    University of Western Ontario, London.

    Information on all benefits, excluding pensions, provided by 16 Ontario universities is presented. The following general questions concerning benefits are covered: administration and insurance plans, communication of benefit programs to employees, proposed changes in benefits, provision of life and dismemberment insurance, and maternity leave…

  14. University Benefits Survey. Part I (All Benefits Excluding Pensions).

    ERIC Educational Resources Information Center

    University of Western Ontario, London.

    Results of a 1984 survey of benefits, excluding pensions, for 17 Ontario, Canada, universities are presented. Information is provided on the following areas: questions on general benefits, such as insurance plans, communication of benefits, proposed changes in benefits, provision of life and dismemberment insurance, and maternity leave policy;…

  15. Exubera. Inhale therapeutic systems.

    PubMed

    Bindra, Sanjit; Cefalu, William T

    2002-05-01

    Inhale, in colaboration with Pfizer and Aventis Pharma (formerly Hoechst Marion Roussel; HMR), is developing an insulin formulation utilizing its pulmonary delivery technology for macromolecules for the potential treatment of type I and II diabetes. By July 2001, the phase III program had been completed and the companies had begun to assemble data for MAA and NDA filings; however, it was already clear at this time that additional data might be required for filing. By December 2001, it had been decided that the NDA should include an increased level of controlled, long-term pulmonary safety data in diabetic patients and a major study was planned to be completed in 2002, with the NDA filed thereafter (during 2002). US-05997848 was issued to Inhale Therapeutic Systems in December 1999, and corresponds to WO-09524183, filed in February 1995. Equivalent applications have appeared to date in Australia, Brazil, Canada, China, Czech Republic, Europe, Finland, Hungary, Japan, Norway, New Zealand, Poland and South Africa. This family of applications is specific to pulmonary delivery of insulin. In February 1999, Lehman Brothers gave this inhaled insulin a 60% probability of reaching market, with a possible launch date of 2001. The analysts estimated peak sales at $3 billion in 2011. In May 2000, Aventis predicted that estimated peak sales would be in excess of $1 billion. In February 2000, Merrill Lynch expected product launch in 2002 and predicted that it would be a multibillion-dollar product. Analysts Merril Lynch predicted, in September and November 2000, that the product would be launched by 2002, with sales in that year of e75 million, rising to euro 500 million in 2004. In April 2001, Merrill Lynch predicted that filing for this drug would occur in 2001. Following the report of the potential delay in regulatory filing, issued in July 2001, Deutsche Banc Alex Brown predicted a filing would take place in the fourth quarter of 2002 and launch would take place in the first

  16. The redox biology network in cancer pathophysiology and therapeutics

    PubMed Central

    Manda, Gina; Isvoranu, Gheorghita; Comanescu, Maria Victoria; Manea, Adrian; Debelec Butuner, Bilge; Korkmaz, Kemal Sami

    2015-01-01

    The review pinpoints operational concepts related to the redox biology network applied to the pathophysiology and therapeutics of solid tumors. A sophisticated network of intrinsic and extrinsic cues, integrated in the tumor niche, drives tumorigenesis and tumor progression. Critical mutations and distorted redox signaling pathways orchestrate pathologic events inside cancer cells, resulting in resistance to stress and death signals, aberrant proliferation and efficient repair mechanisms. Additionally, the complex inter-cellular crosstalk within the tumor niche, mediated by cytokines, redox-sensitive danger signals (HMGB1) and exosomes, under the pressure of multiple stresses (oxidative, inflammatory, metabolic), greatly contributes to the malignant phenotype. The tumor-associated inflammatory stress and its suppressive action on the anti-tumor immune response are highlighted. We further emphasize that ROS may act either as supporter or enemy of cancer cells, depending on the context. Oxidative stress-based therapies, such as radiotherapy and photodynamic therapy, take advantage of the cytotoxic face of ROS for killing tumor cells by a non-physiologically sudden, localized and intense oxidative burst. The type of tumor cell death elicited by these therapies is discussed. Therapy outcome depends on the differential sensitivity to oxidative stress of particular tumor cells, such as cancer stem cells, and therefore co-therapies that transiently down-regulate their intrinsic antioxidant system hold great promise. We draw attention on the consequences of the damage signals delivered by oxidative stress-injured cells to neighboring and distant cells, and emphasize the benefits of therapeutically triggered immunologic cell death in metastatic cancer. An integrative approach should be applied when designing therapeutic strategies in cancer, taking into consideration the mutational, metabolic, inflammatory and oxidative status of tumor cells, cellular heterogeneity and the

  17. The redox biology network in cancer pathophysiology and therapeutics.

    PubMed

    Manda, Gina; Isvoranu, Gheorghita; Comanescu, Maria Victoria; Manea, Adrian; Debelec Butuner, Bilge; Korkmaz, Kemal Sami

    2015-08-01

    The review pinpoints operational concepts related to the redox biology network applied to the pathophysiology and therapeutics of solid tumors. A sophisticated network of intrinsic and extrinsic cues, integrated in the tumor niche, drives tumorigenesis and tumor progression. Critical mutations and distorted redox signaling pathways orchestrate pathologic events inside cancer cells, resulting in resistance to stress and death signals, aberrant proliferation and efficient repair mechanisms. Additionally, the complex inter-cellular crosstalk within the tumor niche, mediated by cytokines, redox-sensitive danger signals (HMGB1) and exosomes, under the pressure of multiple stresses (oxidative, inflammatory, metabolic), greatly contributes to the malignant phenotype. The tumor-associated inflammatory stress and its suppressive action on the anti-tumor immune response are highlighted. We further emphasize that ROS may act either as supporter or enemy of cancer cells, depending on the context. Oxidative stress-based therapies, such as radiotherapy and photodynamic therapy, take advantage of the cytotoxic face of ROS for killing tumor cells by a non-physiologically sudden, localized and intense oxidative burst. The type of tumor cell death elicited by these therapies is discussed. Therapy outcome depends on the differential sensitivity to oxidative stress of particular tumor cells, such as cancer stem cells, and therefore co-therapies that transiently down-regulate their intrinsic antioxidant system hold great promise. We draw attention on the consequences of the damage signals delivered by oxidative stress-injured cells to neighboring and distant cells, and emphasize the benefits of therapeutically triggered immunologic cell death in metastatic cancer. An integrative approach should be applied when designing therapeutic strategies in cancer, taking into consideration the mutational, metabolic, inflammatory and oxidative status of tumor cells, cellular heterogeneity and the

  18. Video Captions Benefit Everyone

    PubMed Central

    Gernsbacher, Morton Ann

    2016-01-01

    Video captions, also known as same-language subtitles, benefit everyone who watches videos (children, adolescents, college students, and adults). More than 100 empirical studies document that captioning a video improves comprehension of, attention to, and memory for the video. Captions are particularly beneficial for persons watching videos in their non-native language, for children and adults learning to read, and for persons who are D/deaf or hard of hearing. However, despite U.S. laws, which require captioning in most workplace and educational contexts, many video audiences and video creators are naïve about the legal mandate to caption, much less the empirical benefit of captions. PMID:28066803

  19. Pluristem Therapeutics, Inc.

    PubMed

    Prather, William

    2008-01-01

    Pluristem Therapeutics, Inc., based in Haifa, Israel, is a regenerative, biotherapeutics Company dedicated to the commercialization of nonpersonalized (allogeneic) cell therapy products. The Company is expanding noncontroversial placental-derived mesenchymal stem cells via a proprietary 3D process, named PluriX, into therapeutics for a variety of degenerative, malignant and autoimmune disorders. Pluristem will be conducting Phase I trials in the USA with its first product, PLX-I, which addresses the global shortfall of matched tissue for bone marrow transplantation by improving the engraftment of hematopoietic stem cells contained in umbilical cord blood.

  20. Therapeutics for cognitive aging.

    PubMed

    Shineman, Diana W; Salthouse, Timothy A; Launer, Lenore J; Hof, Patrick R; Bartzokis, George; Kleiman, Robin; Luine, Victoria; Buccafusco, Jerry J; Small, Gary W; Aisen, Paul S; Lowe, David A; Fillit, Howard M

    2010-04-01

    This review summarizes the scientific talks presented at the conference "Therapeutics for Cognitive Aging," hosted by the New York Academy of Sciences and the Alzheimer's Drug Discovery Foundation on May 15, 2009. Attended by scientists from industry and academia, as well as by a number of lay people-approximately 200 in all-the conference specifically tackled the many aspects of developing therapeutic interventions for cognitive impairment. Discussion also focused on how to define cognitive aging and whether it should be considered a treatable, tractable disease.

  1. DELIVERY OF THERAPEUTIC PROTEINS

    PubMed Central

    Pisal, Dipak S.; Kosloski, Matthew P.; Balu-Iyer, Sathy V.

    2009-01-01

    The safety and efficacy of protein therapeutics are limited by three interrelated pharmaceutical issues, in vitro and in vivo instability, immunogenicity and shorter half-lives. Novel drug modifications for overcoming these issues are under investigation and include covalent attachment of poly(ethylene glycol) (PEG), polysialic acid, or glycolic acid, as well as developing new formulations containing nanoparticulate or colloidal systems (e.g. liposomes, polymeric microspheres, polymeric nanoparticles). Such strategies have the potential to develop as next generation protein therapeutics. This review includes a general discussion on these delivery approaches. PMID:20049941

  2. Therapeutic Antioxidant Medical Gas

    PubMed Central

    Nakao, Atsunori; Sugimoto, Ryujiro; Billiar, Timothy R; McCurry, Kenneth R

    2009-01-01

    Medical gases are pharmaceutical gaseous molecules which offer solutions to medical needs and include traditional gases, such as oxygen and nitrous oxide, as well as gases with recently discovered roles as biological messenger molecules, such as carbon monoxide, nitric oxide and hydrogen sulphide. Medical gas therapy is a relatively unexplored field of medicine; however, a recent increasing in the number of publications on medical gas therapies clearly indicate that there are significant opportunities for use of gases as therapeutic tools for a variety of disease conditions. In this article, we review the recent advances in research on medical gases with antioxidant properties and discuss their clinical applications and therapeutic properties. PMID:19177183

  3. Benefits of NSF work

    NASA Astrophysics Data System (ADS)

    Packard, Ted

    This fall I will leave my rotatorship as Associate Director for Chemical Oceanography at the National Science Foundation. I have very much enjoyed my duty and want to outline for those who may become “rotators” some of the job's benefits, since NSF is now seeking applicants to replace me. Batiza, Rea and Rumble [Eos, 69, 801, 1988] have discussed the rotator's experience; my comments supplement their points.The most important benefit in working at NSF is the breadth of vision you acquire. This is important for researchers, because it pulls you away from your narrowly focused subfield and forces you to review again, as you did as a graduate student, your entire field. For teachers, this benefit is equally important, because you will keep up with current research even while away from teaching your up-to-date balanced courses. During my stay here I have reviewed proposals to study trace metals scavenging, gas exchange, sediment traps, biochemical cycling, stable and unstable isotopes, lipid biomarkers, sediment diagenesis, anoxic redox processes, and many other exciting topics. Some research areas, such as the vent and seep studies, had not been conceived when I was a graduate student in the sixties, so my experience here has been, in fact, a real sabbatical.

  4. Capturing patient benefits of treatment.

    PubMed

    Carr, Alan; Wolfaardt, John; Garrett, Neal

    2011-01-01

    Findings from the Academy of Osseointegration State of the Science on Implant Dentistry Conference clearly demonstrate that data are lacking regarding both quality of design and adequate outcome measures (standardization, validity, and relevance to patient) to support an evidence-based systematic evaluation of implant efficacy. Despite the dearth of controlled trials and the variability in defining implant survival/success, the preponderance of evidence is viewed as lending support for consideration of dental implant therapy as a safe and predictable alternative to conventional restorations for many applications. However, this minimal conclusion undermines the best intentions of the dental profession, which is striving to substantiate to the patient, third-party providers, and the government the relative benefits and risks of various prosthetic treatment alternatives. The conclusions of multiple consensus conferences have repeatedly stressed that additional research with good strength of evidence following a broad spectrum of outcomes is vital to extend the breadth of conclusions regarding dental implant treatment efficacy. However, without a set of consensus-based core outcome measures addressing pertinent clinical and patient-centered factors, future expensive, time-consuming, and technically complex clinical studies may suffer the same critical flaws seen in the current body of research. It may be possible and useful to establish a core set of well-defined, discriminatory, and feasible outcome measures for common utilization and a hierarchy of additional recommended outcome measures for specific benefit categories. Such a standardized group of outcome measures would be likely to significantly enhance the potential for future research. In addition, with the formation of consensus guidelines, there would be an opportunity for scientific journals to promote the quality of implant dentistry research by suggesting the inclusion of these core outcome measures in

  5. Combined oral contraceptives: health benefits beyond contraception.

    PubMed

    Caserta, D; Ralli, E; Matteucci, E; Bordi, G; Mallozzi, M; Moscarini, M

    2014-09-01

    It has been recognized for over 50 years that combined oral contraceptives (COCs) are also capable of offering health benefits beyond contraception through the treatment and prevention of several gynaecological and medical disorders. During the last years a constant attention was given to the adverse effects of COCs, whereas their non-contraceptive benefits were underestimated. To date, most women are still unaware of the therapeutic uses of hormonal contraceptives, while on the contrary there is an extensive and constantly increasing of these non-contraceptive health benefits. This review summarizes the conditions of special interest for physicians, including dysmenorrhoea, menorrhagia, hyperandrogenism (acne, hirsutism, polycystic ovary syndrome), functional ovarian cysts, endometriosis, premenstrual syndrome, myomas, pelvic inflammatory disease, bone mineral density, benign breast disease and endometrial/ovarian and colorectal cancer. The benefits of COCs in rheumatoid arthritis, multiple sclerosis, menstrual migraine and in perimenopause have also been treated for more comprehensive information. Using COCs specifically for non-contraceptive indications is still outside the product licence in the majority of cases. We strongly believe that these aspects are not of minor relevance and they deserve a special consideration by health providers and by the mass media, which have the main responsibility in the diffusion of scientific information. Thus, counseling and education are necessary to help women make well-informed health-care decisions and it is also crucial to increase awareness among general practitioners and gynaecologists.

  6. Developing Therapeutic Listening

    ERIC Educational Resources Information Center

    Lee, Billy; Prior, Seamus

    2013-01-01

    We present an experience-near account of the development of therapeutic listening in first year counselling students. A phenomenological approach was employed to articulate the trainees' lived experiences of their learning. Six students who had just completed a one-year postgraduate certificate in counselling skills were interviewed and the…

  7. Measuring Therapeutic Effectiveness.

    ERIC Educational Resources Information Center

    Callister, Sheldon L.

    In the recent past, there has been a great deal of effort directed toward developing techniques for documenting therapeutic outcome. Funding sources and the general public seem to be demanding more meaningful data which indicate, in a clear manner, whether or not the services they are paying for are of value. Mental health centers, like other…

  8. Antibody Therapeutics in Oncology

    PubMed Central

    Wold, Erik D; Smider, Vaughn V; Felding, Brunhilde H

    2016-01-01

    One of the newer classes of targeted cancer therapeutics is monoclonal antibodies. Monoclonal antibody therapeutics are a successful and rapidly expanding drug class due to their high specificity, activity, favourable pharmacokinetics, and standardized manufacturing processes. Antibodies are capable of recruiting the immune system to attack cancer cells through complement-dependent cytotoxicity or antibody dependent cellular cytotoxicity. In an ideal scenario the initial tumor cell destruction induced by administration of a therapeutic antibody can result in uptake of tumor associated antigens by antigen-presenting cells, establishing a prolonged memory effect. Mechanisms of direct tumor cell killing by antibodies include antibody recognition of cell surface bound enzymes to neutralize enzyme activity and signaling, or induction of receptor agonist or antagonist activity. Both approaches result in cellular apoptosis. In another and very direct approach, antibodies are used to deliver drugs to target cells and cause cell death. Such antibody drug conjugates (ADCs) direct cytotoxic compounds to tumor cells, after selective binding to cell surface antigens, internalization, and intracellular drug release. Efficacy and safety of ADCs for cancer therapy has recently been greatly advanced based on innovative approaches for site-specific drug conjugation to the antibody structure. This technology enabled rational optimization of function and pharmacokinetics of the resulting conjugates, and is now beginning to yield therapeutics with defined, uniform molecular characteristics, and unprecedented promise to advance cancer treatment. PMID:27081677

  9. Would banning atrazine benefit farmers?

    PubMed

    Ackerman, Frank; Whited, Melissa; Knight, Patrick

    2014-01-01

    Atrazine, an herbicide used on most of the US corn (maize) crop, is the subject of ongoing controversy, with increasing documentation of its potentially harmful health and environmental impacts. Supporters of atrazine often claim that it is of great value to farmers; most recently, Syngenta, the producer of atrazine, sponsored an "Atrazine Benefits Team" (ABT) of researchers who released a set of five papers in 2011, reporting huge economic benefits from atrazine use in US agriculture. A critical review of the ABT papers shows that they have underestimated the growing problem of atrazine-resistant weeds, offered only a partial review of the effectiveness of alternative herbicides, and ignored the promising option of nonchemical weed management techniques. In addition, the most complete economic analysis in the ABT papers implies that withdrawal of atrazine would lead to a decrease in corn yields of 4.4% and an increase in corn prices of 8.0%. The result would be an increase in corn growers' revenues, equal to US$1.7 billion annually under ABT assumptions. Price impacts on consumers would be minimal: at current levels of ethanol production and use, gasoline prices would rise by no more than US$0.03 per gallon; beef prices would rise by an estimated US$0.01 for a 4-ounce hamburger and US$0.05 for an 8-ounce steak. Thus withdrawal of atrazine would boost farm revenues, while only changing consumer prices by pennies.

  10. Would banning atrazine benefit farmers?

    PubMed Central

    Ackerman, Frank; Whited, Melissa; Knight, Patrick

    2014-01-01

    Atrazine, an herbicide used on most of the US corn (maize) crop, is the subject of ongoing controversy, with increasing documentation of its potentially harmful health and environmental impacts. Supporters of atrazine often claim that it is of great value to farmers; most recently, Syngenta, the producer of atrazine, sponsored an “Atrazine Benefits Team” (ABT) of researchers who released a set of five papers in 2011, reporting huge economic benefits from atrazine use in US agriculture. A critical review of the ABT papers shows that they have underestimated the growing problem of atrazine-resistant weeds, offered only a partial review of the effectiveness of alternative herbicides, and ignored the promising option of non-chemical weed management techniques. In addition, the most complete economic analysis in the ABT papers implies that withdrawal of atrazine would lead to a decrease in corn yields of 4.4% and an increase in corn prices of 8.0%. The result would be an increase in corn growers’ revenues, equal to US$1.7 billion annually under ABT assumptions. Price impacts on consumers would be minimal: at current levels of ethanol production and use, gasoline prices would rise by no more than US$0.03 per gallon; beef prices would rise by an estimated US$0.01 for a 4-ounce hamburger and US$0.05 for an 8-ounce steak. Thus withdrawal of atrazine would boost farm revenues, while only changing consumer prices by pennies. PMID:24804340

  11. Space exercise and Earth benefits.

    PubMed

    Macias, Brandon R; Groppo, Eli R; Eastlack, Robert K; Watenpaugh, Donald E; Lee, Stuart M C; Schneider, Suzanne M; Boda, Wanda L; Smith, Scott M; Cutuk, Adnan; Pedowitz, Robert A; Meyer, R Scott; Hargens, Alan R

    2005-08-01

    The detrimental impact of long duration space flight on physiological systems necessitates the development of exercise countermeasures to protect work capabilities in gravity fields of Earth, Moon and Mars. The respective rates of physiological deconditioning for different organ systems during space flight has been described as a result of data collected during and after missions on the Space Shuttle, International Space Station, Mir, and bed rest studies on Earth. An integrated countermeasure that simulates the body's hydrostatic pressure gradient, provides mechanical stress to the bones and muscles, and stimulates the neurovestibular system may be critical for maintaining health and well being of crew during long-duration space travel, such as a mission to Mars. Here we review the results of our studies to date of an integrated exercise countermeasure for space flight, lower body negative pressure (LBNP) treadmill exercise, and potential benefits of its application to athletic training on Earth. Additionally, we review the benefits of Lower Body Positive Pressure (LBPP) exercise for rehabilitation of postoperative patients. Presented first are preliminary data from a 30-day bed rest study evaluating the efficacy of LBNP exercise as an integrated exercise countermeasure for the deconditioning effects of microgravity. Next, we review upright LBNP exercise as a training modality for athletes by evaluating effects on the cardiovascular system and gait mechanics. Finally, LBPP exercise as a rehabilitation device is examined with reference to gait mechanics and safety in two groups of postoperative patients.

  12. Amendments to excepted benefits. Final rules.

    PubMed

    2014-10-01

    This document contains final regulations that amend the regulations regarding excepted benefits under the Employee Retirement Income Security Act of 1974, the Internal Revenue Code (the Code), and the Public Health Service Act. Excepted benefits are generally exempt from the health reform requirements that were added to those laws by the Health Insurance Portability and Accountability Act and the Patient Protection and Affordable Care Act. In addition, eligibility for excepted benefits does not preclude an individual from eligibility for a premium tax credit under section 36B of the Code if an individual chooses to enroll in coverage under a Qualified Health Plan through an Affordable Insurance Exchange. These regulations finalize some but not all of the proposed rules with minor modifications; additional guidance on limited wraparound coverage is forthcoming.

  13. Therapeutic experiences of community gardens: putting flow in its place.

    PubMed

    Pitt, Hannah

    2014-05-01

    This paper develops the concept of therapeutic place experiences by considering the role of activity. Research of community gardening finds that particular tasks are therapeutic and exhibit the characteristics of flow, but those who lack influence over their community gardening are less likely to benefit from flow as their sense of control is reduced. The notion of emplaced flow is proposed to locate individual experiences amongst socio-spatial factors which limit self-determinacy and therefore affect wellbeing. Emplacing flow prompts critical reflection on who is excluded from therapeutic place experiences, and whether sites offering momentary escape have an enduring impact on wellbeing.

  14. Nonhematological benefits of iron.

    PubMed

    Agarwal, Rajiv

    2007-01-01

    Iron deficiency anemia is common in people with chronic kidney disease (CKD) and its importance in supporting erythropoiesis is unquestioned especially in those patients treated with erythropoietin. Clinical symptomatology such as fatigability, cold intolerance, failure to concentrate and poor effort intolerance is often attributed to anemia or uremia. That iron deficiency, per se, can cause these symptoms is poorly recognized. Clinical and animal studies that support the benefits of iron supplementation, independent of increasing hemoglobin, such as those on immune function, physical performance, thermoregulation, cognition, and restless leg syndrome and aluminum absorption is the subject of this narrative review.

  15. The new regulation to investigate potentially beneficial diagnostic and therapeutic methods in Germany: up to international standard?

    PubMed

    Olberg, Britta; Perleth, Matthias; Busse, Reinhard

    2014-08-01

    Funding of diagnostic and therapeutic methods in Germany's statutory health insurance (SHI) follows a dichotomy: in outpatient care, only methods with proven benefit are reimbursed while in inpatient care, all methods may be provided unless they are excluded due to proven harm or lack of benefit. In January 2012, a new section 137e was added to the Social Code Book V (SGB V), allowing for the inclusion of innovative and potentially beneficial diagnostic or therapeutic methods in the SHI benefit basket, while additional evidence regarding their effectiveness and safety must be gathered. In 2013, the Federal Joint Committee (G-BA) has specified the details of this new approach, which can be considered a variety of "Coverage with Evidence Development" (CED). Our comparison with CED schemes in selected countries reveals a dependence of the CED implementation on the encompassing healthcare system. However, we identify a clear legislative foundation, a definitive decision-making body, the possibility to obtain public funding, and the preference for high quality study designs as constituting factors of an emerging international standard for CED. In addition, it is necessary to ensure the suitability of circumstances and technologies for the successful application of CED in a clear and transparent way.

  16. Silk-elastin-like protein biomaterials for the controlled delivery of therapeutics

    PubMed Central

    Huang, Wenwen; Rollett, Alexandra; Kaplan, David L.

    2015-01-01

    Introduction Genetically engineered biomaterials are useful for controlled delivery owing to their rational design, tunable structure-function, biocompatibility, degradability and target specificity. Silk-elastin-like proteins (SELPs), a family of genetically engineered recombinant protein polymers, possess these properties. Additionally, given the benefits of combining semicrystalline silk-blocks and elastomeric elastin-blocks, SELPs possess multi-stimuli responsive properties and tenability, thereby, becoming promising candidates for targeted cancer therapeutics delivery and controlled gene release. Areas covered An overview of SELP biomaterials for drug delivery and gene release is provided. Biosynthetic strategies used for SELP production, fundamental physicochemical properties, and self-assembly mechanisms are discussed. The review focuses on sequence-structure-function relationships, stimuli responsive features, and current and potential drug delivery applications. Expert opinion The tunable material properties allow SELPs to be pursued as promising biomaterials for nano-carriers and injectable drug release systems. Current applications of SELPs have focused on thermally-triggered biomaterial formats for the delivery of therapeutics, based on local hyperthermia in tumors or infections. Other prominent controlled release applications of SELPs as injectable hydrogels for gene release have also been pursued. Further biomedical applications that utilize other stimuli to trigger the reversible material responses of SELPs for targeted delivery, including pH, ionic strength, redox, enzymatic stimuli and electric field, are in progress. Exploiting these additional stimuli responsive features will provide a broader range of functional biomaterials for controlled therapeutics release and tissue regeneration. PMID:25476201

  17. Maintenance therapy in ovarian cancer: Molecular basis and therapeutic approach

    PubMed Central

    BINASCHI, MONICA; SIMONELLI, CECILIA; GOSO, CRISTINA; BIGIONI, MARIO; MAGGI, CARLO ALBERTO

    2011-01-01

    Ovarian cancer has the highest mortality rate among gynaecological tumours despite the fact that the majority of patients with advanced disease achieve complete remission after first-line surgery and chemotherapy. Unfortunately, disease recurrence occurs in the majority of patients and second-line treatments are not curative. Clearly, the persistence of dormant and drug-resistant cells after front-line treatments results in the inability to cure the disease. The identification of cancer-initiating cells or cancer stem cells as key players in the development of recurrence has opened up a novel field of research aimed at identifying additional innovative therapeutic approaches. Strategies of maintenance therapy to extend the survival of patients have been studied, but to date no overall survival benefit has been detected. Currently, numerous clinical trials have just been completed or are ongoing involving patients achieving a complete clinical response after first-line chemotherapy in order to evaluate the efficacy of different therapeutic approaches in terms of disease-free survival and overall survival. At the 2010 ASCO meeting, the first positive results of a phase III clinical trial in this setting were presented: bevacizumab (15 mg/kg i.v. every 21 days) added to first-line chemotherapy and continued for an additional 15 cycles was found to prolong progression-free survival of 3.8 months in comparison to 6 cycles of chemotherapy alone or only 6 cycles of chemotherapy plus bevacizumab. In addition, positive results were announced for a second phase III trial testing bevacizumab in the same setting, but at half dose. The final assessment of the overall clinical benefit and the approval of bevacizumab in maintenance therapy by regulatory agencies is expected to be positive, as are the final results of abagovomab phase III trial MIMOSA, another antibody-based therapy tested as a maintenance treatment for advanced ovarian cancer patients. Encouraging preliminary

  18. Sustainable Facility Development: Perceived Benefits and Challenges

    ERIC Educational Resources Information Center

    Stinnett, Brad; Gibson, Fred

    2016-01-01

    Purpose: The purpose of this paper is to assess the perceived benefits and challenges of implementing sustainable initiatives in collegiate recreational sports facilities. Additionally, this paper intends to contribute to the evolving field of facility sustainability in higher education. Design/methodology/approach The design included qualitative…

  19. The Benefit of Forgetting

    PubMed Central

    Williams, Melonie; Hong, Sang W.; Kang, Min-Suk; Carlisle, Nancy B.; Woodman, Geoffrey F.

    2012-01-01

    Recent research using change-detection tasks has shown that a directed-forgetting cue, indicating that a subset of the information stored in memory can be forgotten, significantly benefits the other information stored in visual working memory. How do these directed-forgetting cues aid the memory representations that are retained? We addressed this question in the present study by using a recall paradigm to measure the nature of the retained memory representations. Our results demonstrate that a directed-forgetting cue leads to higher fidelity representations of the remaining items and a lower probability of dropping these representations from memory. Next, we show that this is possible because the to-be-forgotten item is expelled from visual working memory following the cue allowing maintenance mechanisms to be focused on only the items that remain in visual working memory. Thus, the present findings show that cues to forget benefit the remaining information in visual working memory by fundamentally improving their quality relative to conditions in which just as many items are encoded but no cue is provided. PMID:23208769

  20. Imaging enabled platforms for development of therapeutics

    NASA Astrophysics Data System (ADS)

    Celli, Jonathan; Rizvi, Imran; Blanden, Adam R.; Evans, Conor L.; Abu-Yousif, Adnan O.; Spring, Bryan Q.; Muzikansky, Alona; Pogue, Brian W.; Finkelstein, Dianne M.; Hasan, Tayyaba

    2011-03-01

    Advances in imaging and spectroscopic technologies have enabled the optimization of many therapeutic modalities in cancer and noncancer pathologies either by earlier disease detection or by allowing therapy monitoring. Amongst the therapeutic options benefiting from developments in imaging technologies, photodynamic therapy (PDT) is exceptional. PDT is a photochemistry-based therapeutic approach where a light-sensitive molecule (photosensitizer) is activated with light of appropriate energy (wavelength) to produce reactive molecular species such as free radicals and singlet oxygen. These molecular entities then react with biological targets such as DNA, membranes and other cellular components to impair their function and lead to eventual cell and tissue death. Development of PDT-based imaging also provides a platform for rapid screening of new therapeutics in novel in vitro models prior to expensive and labor-intensive animal studies. In this study we demonstrate how an imaging platform can be used for strategizing a novel combination treatment strategy for multifocal ovarian cancer. Using an in vitro 3D model for micrometastatic ovarian cancer in conjunction with quantitative imaging we examine dose and scheduling strategies for PDT in combination with carboplatin, a chemotherapeutic agent presently in clinical use for management of this deadly form of cancer.

  1. Optimizing mesenchymal stem cell-based therapeutics.

    PubMed

    Wagner, Joseph; Kean, Thomas; Young, Randell; Dennis, James E; Caplan, Arnold I

    2009-10-01

    Mesenchymal stem cell (MSC)-based therapeutics are showing significant benefit in multiple clinical trials conducted by both academic and commercial organizations, but obstacles remain for their large-scale commercial implementation. Recent studies have attempted to optimize MSC-based therapeutics by either enhancing their potency or increasing their delivery to target tissues. Overexpression of trophic factors or in vitro exposure to potency-enhancing factors are two approaches that are demonstrating success in preclinical animal models. Delivery enhancement strategies involving tissue-specific cytokine pathways or binding sites are also showing promise. Each of these strategies has its own set of distinct advantages and disadvantages when viewed with a mindset of ultimate commercialization and clinical utility.

  2. Therapeutic targets in malignant glioblastoma microenvironment.

    PubMed

    Barcellos-Hoff, Mary Helen; Newcomb, Elizabeth W; Zagzag, David; Narayana, Ashwatha

    2009-07-01

    There is considerable evidence that the tissue microenvironment can suppress cancer and that microenvironment disruption is required for cancer growth and progression. Distortion of the microenvironment by tumor cells can promote growth, recruit nonmalignant cells that provide physiological resources, and facilitate invasion. Compared with the variable routes taken by cells to become cancers, the response of normal tissue to cancer is relatively consistent such that controlling cancer may be more readily achieved indirectly via the microenvironment. Here, we discuss 3 ideas about how the microenvironment, consisting of a vasculature, inflammatory cells, immune cells, growth factors, and extracellular matrix, might provide therapeutic targets in glioblastoma (GBM) in the context of radiotherapy (RT): (1) viable therapeutic targets exist in the GBM microenvironment, (2) RT alters the microenvironment of tissues and tumors; and (3) a potential benefit may be achieved by targeting the microenvironments induced by RT.

  3. Placebo analgesia: cognitive influences on therapeutic outcome.

    PubMed

    Watson, Alison; Power, Andrea; Brown, Christopher; El-Deredy, Wael; Jones, Anthony

    2012-03-30

    The therapeutic response to a drug treatment is a mixture of direct pharmacological action and placebo effect. Therefore, harnessing the positive aspects of the placebo effect and reducing the negative ones could potentially benefit the patient. This article is aimed at providing an overview for clinicians of the importance of contextual psychosocial variables in determining treatment response, and the specific focus is on determinants of the placebo response. A better understanding of the physiological, psychological, and social mechanisms of placebo may aid in predicting which contexts have the greatest potential for inducing positive treatment responses. We examine the evidence for the role of psychological traits, including optimism, pessimism, and the effect of patient expectations on therapeutic outcome. We discuss the importance of the patient-practitioner relationship and how this can be used to enhance the placebo effect, and we consider the ethical challenges of using placebos in clinical practice.

  4. Juvenile onset spondyloarthropathies: therapeutic aspects

    PubMed Central

    Burgos-Vargas, R

    2002-01-01

    Juvenile onset spondyloarthropathy (SpA) is a term that refers to a group of human leucocyte antigen (HLA)-B27 associated inflammatory disorders affecting children under the age of 16 years, producing a continuum of clinical symptoms through adulthood. This disease is characterised by enthesopathy and arthropathy affecting the joints of the lower extremities and seronegativity for IgM rheumatoid factor and antinuclear antibodies. Children usually present with undifferentiated SpA and progress to differentiated forms over time. Except for the prevalence of some clinical features at onset, the pathogenic and clinical aspects of juvenile onset SpAs resemble those of the adult disease. Thus application of the same or similar therapeutic measures for both juvenile and adult onset SpAs seems logical. Current treatments for juvenile onset SpA provide symptomatic improvement, but do not alter disease progression. The increased expression of tumour necrosis factor alpha (TNFα) in synovial tissue of patients with adult and juvenile onset SpA and its correlation with infiltration of inflammatory mediators into the synovia suggest a significant pathogenic role of this cytokine. Clinical trials of anti-TNFα antibody (infliximab) therapy in patients with adult onset SpA have demonstrated significant clinical improvement in inflammatory pain, function, disease activity, and quality of life in correlation with histological and immunohistochemical evidence of modulation of synovial inflammatory processes. These promising findings suggest that anti-TNFα therapy may confer similar benefits in patients with juvenile onset SpA. PMID:12381509

  5. Multistage vector (MSV) therapeutics.

    PubMed

    Wolfram, Joy; Shen, Haifa; Ferrari, Mauro

    2015-12-10

    One of the greatest challenges in the field of medicine is obtaining controlled distribution of systemically administered therapeutic agents within the body. Indeed, biological barriers such as physical compartmentalization, pressure gradients, and excretion pathways adversely affect localized delivery of drugs to pathological tissue. The diverse nature of these barriers requires the use of multifunctional drug delivery vehicles that can overcome a wide range of sequential obstacles. In this review, we explore the role of multifunctionality in nanomedicine by primarily focusing on multistage vectors (MSVs). The MSV is an example of a promising therapeutic platform that incorporates several components, including a microparticle, nanoparticles, and small molecules. In particular, these components are activated in a sequential manner in order to successively address transport barriers.

  6. Multistage vector (MSV) therapeutics

    PubMed Central

    Wolfram, Joy; Shen, Haifa; Ferrari, Mauro

    2015-01-01

    One of the greatest challenges in the field of medicine is obtaining controlled distribution of systemically administered therapeutic agents within the body. Indeed, biological barriers such as physical compartmentalization, pressure gradients, and excretion pathways adversely affect localized delivery of drugs to pathological tissue. The diverse nature of these barriers requires the use of multifunctional drug delivery vehicles that can overcome a wide range of sequential obstacles. In this review, we explore the role of multifunctionality in nanomedicine by primarily focusing on multistage vectors (MSVs). The MSV is an example of a promising therapeutic platform that incorporates several components, including a microparticle, nanoparticles, and small molecules. In particular, these components are activated in a sequential manner in order to successively address transport barriers. PMID:26264836

  7. Platelet-delivered therapeutics.

    PubMed

    Lyde, R; Sabatino, D; Sullivan, S K; Poncz, M

    2015-06-01

    We have proposed that modified platelets could potentially be used to correct intrinsic platelet defects as well as for targeted delivery of therapeutic molecules to sights of vascular injury. Ectopic expression of proteins within α-granules prior to platelet activation has been achieved for several proteins, including urokinase, factor (F) VIII, and partially for FIX. Potential uses of platelet-directed therapeutics will be discussed, focusing on targeted delivery of urokinase as a thromboprophylactic agent and FVIII for the treatment of hemophilia A patients with intractable inhibitors. This presentation will discuss new strategies that may be useful in the care of patients with vascular injury as well as remaining challenges and limitations of these approaches.

  8. Harnessing telomerase in cancer therapeutics.

    PubMed

    Fakhoury, Johans; Nimmo, Graeme A M; Autexier, Chantal

    2007-07-01

    Telomerase is an attractive target for anti-cancer therapeutics due to its requirement for cellular immortalization and expression in greater than 85% of human neoplasms. Though initially promising, strategies that inhibit telomerase with either small molecules or antisense oligonucleotides have a major limitation, namely the lag time required for telomere shortening before cellular effects are attained. As alternative approaches, immunotherapy and gene therapy have been tailored to exploit, rather than antagonize telomerase expression and/or activity. Immunotherapy requires the presence of the catalytic subunit of telomerase, hTERT, to elicit an immune response directed towards hTERT peptide-presenting cells. hTERT promoter-driven gene therapy and mutant telomerase RNA (hTR) gene therapy depend on the innate telomerase activity of cancer cells to drive the expression of pro-apoptotic genes and to synthesize mutated DNA sequences onto telomeres, respectively. In addition, we will discuss telomestatin, a G-quadruplex binding ligand that may exert anti-proliferative effects independently of telomere shortening. In this review, the progress, advantages, and limitations of these strategies in the ongoing effort to develop clinically relevant telomerase-based cancer therapeutics will be examined.

  9. Therapeutic Robotics: A Technology Push

    PubMed Central

    Krebs, Hermano Igo; Hogan, Neville

    2009-01-01

    In this paper, we present a retrospective and chronological review of our efforts to revolutionize the way physical medicine is practiced by developing and deploying therapeutic robots. We present a sample of our clinical results with well over 300 stroke patients, both inpatients and outpatients, proving that movement therapy has a measurable and significant impact on recovery following brain injury. Bolstered by this result, we embarked on a two-pronged approach: 1) to determine what constitutes best therapy practice and 2) to develop additional therapeutic robots. We review our robots developed over the past 15 years and their unique characteristics. All are configured both to deliver reproducible therapy but also to measure outcomes with minimal encumbrance, thus providing critical measurement tools to help unravel the key question posed under the first prong: what constitutes “best practice”? We believe that a “gym” of robots like these will become a central feature of physical medicine and the rehabilitation clinic within the next ten years. PMID:19779587

  10. Oncolytic vaccinia virus as a vector for therapeutic sodium iodide symporter gene therapy in prostate cancer

    PubMed Central

    Mansfield, D C; Kyula, J N; Rosenfelder, N; Chao-Chu, J; Kramer-Marek, G; Khan, A A; Roulstone, V; McLaughlin, M; Melcher, A A; Vile, R G; Pandha, H S; Khoo, V; Harrington, K J

    2016-01-01

    Oncolytic strains of vaccinia virus are currently in clinical development with clear evidence of safety and promising signs of efficacy. Addition of therapeutic genes to the viral genome may increase the therapeutic efficacy of vaccinia. We evaluated the therapeutic potential of vaccinia virus expressing the sodium iodide symporter (NIS) in prostate cancer models, combining oncolysis, external beam radiotherapy and NIS-mediated radioiodide therapy. The NIS-expressing vaccinia virus (VV-NIS), GLV-1h153, was tested in in vitro analyzes of viral cell killing, combination with radiotherapy, NIS expression, cellular radioiodide uptake and apoptotic cell death in PC3, DU145, LNCaP and WPMY-1 human prostate cell lines. In vivo experiments were carried out in PC3 xenografts in CD1 nude mice to assess NIS expression and tumor radioiodide uptake. In addition, the therapeutic benefit of radioiodide treatment in combination with viral oncolysis and external beam radiotherapy was measured. In vitro viral cell killing of prostate cancers was dose- and time-dependent and was through apoptotic mechanisms. Importantly, combined virus therapy and iodizing radiation did not adversely affect oncolysis. NIS gene expression in infected cells was functional and mediated uptake of radioiodide both in vitro and in vivo. Therapy experiments with both xenograft and immunocompetent Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) mouse models showed that the addition of radioiodide to VV-NIS-infected tumors was more effective than each single-agent therapy, restricting tumor growth and increasing survival. In conclusion, VV-NIS is effective in prostate cancer models. This treatment modality would be an attractive complement to existing clinical radiotherapy practice. PMID:26814609

  11. Oncolytic vaccinia virus as a vector for therapeutic sodium iodide symporter gene therapy in prostate cancer.

    PubMed

    Mansfield, D C; Kyula, J N; Rosenfelder, N; Chao-Chu, J; Kramer-Marek, G; Khan, A A; Roulstone, V; McLaughlin, M; Melcher, A A; Vile, R G; Pandha, H S; Khoo, V; Harrington, K J

    2016-04-01

    Oncolytic strains of vaccinia virus are currently in clinical development with clear evidence of safety and promising signs of efficacy. Addition of therapeutic genes to the viral genome may increase the therapeutic efficacy of vaccinia. We evaluated the therapeutic potential of vaccinia virus expressing the sodium iodide symporter (NIS) in prostate cancer models, combining oncolysis, external beam radiotherapy and NIS-mediated radioiodide therapy. The NIS-expressing vaccinia virus (VV-NIS), GLV-1h153, was tested in in vitro analyzes of viral cell killing, combination with radiotherapy, NIS expression, cellular radioiodide uptake and apoptotic cell death in PC3, DU145, LNCaP and WPMY-1 human prostate cell lines. In vivo experiments were carried out in PC3 xenografts in CD1 nude mice to assess NIS expression and tumor radioiodide uptake. In addition, the therapeutic benefit of radioiodide treatment in combination with viral oncolysis and external beam radiotherapy was measured. In vitro viral cell killing of prostate cancers was dose- and time-dependent and was through apoptotic mechanisms. Importantly, combined virus therapy and iodizing radiation did not adversely affect oncolysis. NIS gene expression in infected cells was functional and mediated uptake of radioiodide both in vitro and in vivo. Therapy experiments with both xenograft and immunocompetent Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) mouse models showed that the addition of radioiodide to VV-NIS-infected tumors was more effective than each single-agent therapy, restricting tumor growth and increasing survival. In conclusion, VV-NIS is effective in prostate cancer models. This treatment modality would be an attractive complement to existing clinical radiotherapy practice.

  12. University Benefits Survey. Part I (All Benefits Excluding Pensions).

    ERIC Educational Resources Information Center

    University of Western Ontario, London.

    Results of a 1986 survey of benefits, excluding pensions, for 17 Ontario, Canada, universities are presented. Information is provided on the following areas: whether the university self- administers insurance plans, communication of benefits, proposed changes in benefits, provision of accidental death and dismemberment insurance, maternity leave…

  13. University Benefits Survey, Part I (All Benefits Excluding Pensions).

    ERIC Educational Resources Information Center

    University of Western Ontario, London.

    The results of a survey of benefits, excluding pensions, for 17 Ontario, Canada, universities are presented. Information is provided on the following areas: whether the university self-administers insurance plans, communication of benefits, proposed changes in benefits, provision of life and dismemberment insurance, maternity leave policy, Ontario…

  14. University Benefits Survey. Part I (All Benefits Excluding Pensions).

    ERIC Educational Resources Information Center

    University of Western Ontario, London.

    Results of a 1985 survey of benefits, excluding pensions, for 17 Ontario, Canada, universities are presented. Information is provided on the following areas: whether the university self-administers insurance plans, communication of information on benefits, proposed changes in benefits, provision of accidental death and dismemberment insurance,…

  15. University Benefits Survey. Part 1 (All Benefits Excluding Pensions).

    ERIC Educational Resources Information Center

    University of Western Ontario, London.

    Results of a 1983 survey of benefits, excluding pensions, for 17 Ontario, Canada, universities are presented. Information is provided on the following areas: whether the university self-administers insurance plans, communication of benefits, proposed changes in benefits, provision of life and dismemberment insurance, maternity leave policy,…

  16. Polycyclic peptide therapeutics.

    PubMed

    Baeriswyl, Vanessa; Heinis, Christian

    2013-03-01

    Owing to their excellent binding properties, high stability, and low off-target toxicity, polycyclic peptides are an attractive molecule format for the development of therapeutics. Currently, only a handful of polycyclic peptides are used in the clinic; examples include the antibiotic vancomycin, the anticancer drugs actinomycin D and romidepsin, and the analgesic agent ziconotide. All clinically used polycyclic peptide drugs are derived from natural sources, such as soil bacteria in the case of vancomycin, actinomycin D and romidepsin, or the venom of a fish-hunting coil snail in the case of ziconotide. Unfortunately, nature provides peptide macrocyclic ligands for only a small fraction of therapeutic targets. For the generation of ligands of targets of choice, researchers have inserted artificial binding sites into natural polycyclic peptide scaffolds, such as cystine knot proteins, using rational design or directed evolution approaches. More recently, large combinatorial libraries of genetically encoded bicyclic peptides have been generated de novo and screened by phage display. In this Minireview, the properties of existing polycyclic peptide drugs are discussed and related to their interesting molecular architectures. Furthermore, technologies that allow the development of unnatural polycyclic peptide ligands are discussed. Recent application of these technologies has generated promising results, suggesting that polycyclic peptide therapeutics could potentially be developed for a broad range of diseases.

  17. Therapeutic antibody engineering

    PubMed Central

    Parren, Paul W.H.I.; Lugovskoy, Alexey A.

    2013-01-01

    It is an important event in any knowledge area when an authority in the field decides that it is time to share all accumulated knowledge and learnings by writing a text book. This does not occur often in the biopharmaceutical industry, likely due to both the highly dynamic environment with tight timelines and policies and procedures at many pharmaceutical companies that hamper knowledge sharing. To take on a task like this successfully, a strong drive combined with a desire and talent to teach, but also an accommodating and stimulating environment is required. Luckily for those interested in therapeutic monoclonal antibodies, Dr. William R. Strohl decided about two years ago that the time was right to write a book about the past, present and future of these fascinating molecules. Dr. Strohl’s great expertise and passion for biotechnology is evident from his life story and his strong academic and industry track record. Dr. Strohl pioneered natural product biotechnology, first in academia as a full professor of microbiology and biochemistry at Ohio State University in Columbus, Ohio and later in industry while at Merck. Despite his notable advances in recombinant natural products, industry interest in this area waned and in 2001 Dr. Strohl sought new opportunities by entering the field of antibody therapeutics. He initiated antibody discovery through phage display at Merck, and then moved to Centocor Research and Development Inc. (now Janssen Biotech, Inc.) in 2008 to head Biologics Research, where he now directs the discovery of innovative therapeutic antibody candidates.

  18. Sleep Physiology, Abnormal States, and Therapeutic Interventions

    PubMed Central

    Wickboldt, Alvah T.; Bowen, Alex F.; Kaye, Aaron J.; Kaye, Adam M.; Rivera Bueno, Franklin; Kaye, Alan D.

    2012-01-01

    Sleep is essential. Unfortunately, a significant portion of the population experiences altered sleep states that often result in a multitude of health-related issues. The regulation of sleep and sleep-wake cycles is an area of intense research, and many options for treatment are available. The following review summarizes the current understanding of normal and abnormal sleep-related conditions and the available treatment options. All clinicians managing patients must recommend appropriate therapeutic interventions for abnormal sleep states. Clinicians' solid understanding of sleep physiology, abnormal sleep states, and treatments will greatly benefit patients regardless of their disease process. PMID:22778676

  19. NASA Benefits Earth

    NASA Technical Reports Server (NTRS)

    Robinson, Julie A.

    2009-01-01

    This slide presentation reviews several ways in which NASA research has benefited Earth and made life on Earth better. These innovations include: solar panels, recycled pavement, thermometer pill, invisible braces for straightening teeth, LASIK, aerodynamic helmets and tires for bicycles, cataract detection, technology that was used to remove Anthrax spores from mail handling facilities, study of atomic oxygen erosion of materials has informed the restoration of artwork, macroencapsulation (a potential mechanism to deliver anti cancer drugs to specific sites), and research on a salmonella vaccine. With research on the International Space Station just beginning, there will be opportunities for entrepreneurs and other government agencies to access space for their research and development. As well as NASA continuing its own research on human health and technology development.

  20. Atomic Bomb Health Benefits

    PubMed Central

    Luckey, T. D.

    2008-01-01

    Media reports of deaths and devastation produced by atomic bombs convinced people around the world that all ionizing radiation is harmful. This concentrated attention on fear of miniscule doses of radiation. Soon the linear no threshold (LNT) paradigm was converted into laws. Scientifically valid information about the health benefits from low dose irradiation was ignored. Here are studies which show increased health in Japanese survivors of atomic bombs. Parameters include decreased mutation, leukemia and solid tissue cancer mortality rates, and increased average lifespan. Each study exhibits a threshold that repudiates the LNT dogma. The average threshold for acute exposures to atomic bombs is about 100 cSv. Conclusions from these studies of atomic bomb survivors are: One burst of low dose irradiation elicits a lifetime of improved health.Improved health from low dose irradiation negates the LNT paradigm.Effective triage should include radiation hormesis for survivor treatment. PMID:19088902

  1. Atomic bomb health benefits.

    PubMed

    Luckey, T D

    2008-01-01

    Media reports of deaths and devastation produced by atomic bombs convinced people around the world that all ionizing radiation is harmful. This concentrated attention on fear of miniscule doses of radiation. Soon the linear no threshold (LNT) paradigm was converted into laws. Scientifically valid information about the health benefits from low dose irradiation was ignored. Here are studies which show increased health in Japanese survivors of atomic bombs. Parameters include decreased mutation, leukemia and solid tissue cancer mortality rates, and increased average lifespan. Each study exhibits a threshold that repudiates the LNT dogma. The average threshold for acute exposures to atomic bombs is about 100 cSv. Conclusions from these studies of atomic bomb survivors are: One burst of low dose irradiation elicits a lifetime of improved health.Improved health from low dose irradiation negates the LNT paradigm.Effective triage should include radiation hormesis for survivor treatment.

  2. Hurricanes benefit bleached corals.

    PubMed

    Manzello, Derek P; Brandt, Marilyn; Smith, Tyler B; Lirman, Diego; Hendee, James C; Nemeth, Richard S

    2007-07-17

    Recent, global mass-mortalities of reef corals due to record warm sea temperatures have led researchers to consider global warming as one of the most significant threats to the persistence of coral reef ecosystems. The passage of a hurricane can alleviate thermal stress on coral reefs, highlighting the potential for hurricane-associated cooling to mitigate climate change impacts. We provide evidence that hurricane-induced cooling was responsible for the documented differences in the extent and recovery time of coral bleaching between the Florida Reef Tract and the U.S. Virgin Islands during the Caribbean-wide 2005 bleaching event. These results are the only known scenario where the effects of a hurricane can benefit a stressed marine community.

  3. NASA Technology Benefits Orthotics

    NASA Technical Reports Server (NTRS)

    Myers, Neill; Shadoan, Michael

    1998-01-01

    Engineers at NASA's Marshall Space Flight Center (MSFC) in Huntsville, Alabama have designed a knee brace to aid in the rehabilitation of medical patients. The device, called the Selectively Lockable Knee Brace, was designed for knee injury and stroke patients but may potentially serve in many more patient applications. Individuals with sports related injuries, spinal cord injuries and birth defects, such as spina bifida, may also benefit from the device. The Selectively Lockable Knee Brace is designed to provide secure support to the patient when weight is applied to the leg; however; when the leg is not supporting weight, the device allows free motion of the knee joint. Braces currently on the market lock the knee in a rigid, straight or bent position, or by manually pulling a pin, allow continuous free joint motion.

  4. Benefits for People with Disabilities

    MedlinePlus

    ... you worked long enough and paid Social Security taxes. Supplemental Security Income pays benefits based on financial ... Education Benefits For Children With Disabilities Professional Relations Green Book - Consultative Examinations: Guide For Health Professionals Blue ...

  5. Landfill Gas Energy Benefits Calculator

    EPA Pesticide Factsheets

    This page contains the LFG Energy Benefits Calculator to estimate direct, avoided, and total greenhouse gas reductions, as well as environmental and energy benefits, for a landfill gas energy project.

  6. Therapeutic options for lip augmentation.

    PubMed

    Segall, Lorne; Ellis, David A F

    2007-11-01

    Aesthetic ideals vary with emerging fashion trends and within different cultures. However, over the past few decades, fuller lips have been considered a desirable trait. Many younger patients are presenting for lip augmentation to achieve the sought-after look commonly seen in many fashion magazines. In addition, as individuals age, they lose lip volume, with a thinning of the red lip, some effacement of the vermillion border, and elongation and flattening of the white portion of the lip. Rejuvenation of the lips plays a key role in restoring a more youthful appearance. As a result, lip augmentation appeals to a wide spectrum of patients who present with various different aesthetic goals and expectations. Numerous therapeutic options exist for aesthetic lip augmentation, ranging from temporary and permanent injectable fillers to implants and other surgical techniques.

  7. Emerging therapeutic options for asthma.

    PubMed

    Colice, Gene L

    2011-04-01

    Asthma is characterized by eosinophilic airway inflammation and elevated serum immunoglobulin E (IgE) levels. Due to these pathologic features, the foundation of asthma treatment has historically been anti-inflammatory therapy with inhaled corticosteroids (ICSs). Numerous factors in addition to IgE and eosinophils, however, likely play important roles in mediating the airway inflammatory response characteristic of asthma. ICSs are effective therapy for some patients with persistent asthma, but clinical trials have shown that even increasing doses of ICSs under carefully controlled situations does not always result in acceptable asthma control. Consequently, other classes of medications, in addition to ICSs, are recommended in those patients with more severe asthma. The class of medication most commonly used in more severe asthma, along with ICSs, is long-acting inhaled beta2-agonists, but leukotriene modifying agents and anti-IgE monoclonal antibodies may also be used. Agents such as tiotropium, a long-acting inhaled anti-muscarinic agent, and those aimed at inhibiting cytokines, such as mepoluzimab, daclizumab, and etanercept, hold promise in the treatment of asthma. Other agents under investigation include phosphodiesterase type 4 inhibitors and oligonucleotides. Bronchial thermoplasty, a nonpharmacologic option, may also be beneficial in patients with poorly controlled asthma. As our understanding of the complex pathophysiology of asthma increases, it will enable the development of novel therapeutic approaches for patients who are not responding well to traditional treatments. Although more studies are necessary to ensure the efficacy and safety of both pharmacologic and nonpharmacologic approaches, there is future promise for therapeutic advances in severe, persistent asthma.

  8. Dual-Action Cephalosporin Utilizing a Novel Therapeutic Principle

    PubMed Central

    Greenwood, D.; O'Grady, F.

    1976-01-01

    A new cephalosporin is described that overcomes, in a novel way, the general susceptibility of this group of agents to enterobacterial β-lactamases. The new compound carries a substituent that is released on cleavage of the β-lactam ring and then exhibits antibacterial activity in its own right. The possible therapeutic benefits of such an antibiotic are discussed. PMID:791095

  9. [INVITED] Lasers in additive manufacturing

    NASA Astrophysics Data System (ADS)

    Pinkerton, Andrew J.

    2016-04-01

    Additive manufacturing is a topic of considerable ongoing interest, with forecasts predicting it to have major impact on industry in the future. This paper focusses on the current status and potential future development of the technology, with particular reference to the role of lasers within it. It begins by making clear the types and roles of lasers in the different categories of additive manufacturing. This is followed by concise reviews of the economic benefits and disadvantages of the technology, current state of the market and use of additive manufacturing in different industries. Details of these fields are referenced rather than expanded in detail. The paper continues, focusing on current indicators to the future of additive manufacturing. Barriers to its development, trends and opportunities in major industrial sectors, and wider opportunities for its development are covered. Evidence indicates that additive manufacturing may not become the dominant manufacturing technology in all industries, but represents an excellent opportunity for lasers to increase their influence in manufacturing as a whole.

  10. College and University Fringe Benefits

    ERIC Educational Resources Information Center

    Middleditch, Leigh B., Jr.

    1973-01-01

    As the number and level of fringe benefits increases, particularly in the retirement sphere, institutions must keep in mind that today's commitment will be felt in tomorrow's budget. The range of employee benefits available are analyzed with regard to cost: unfunded benefits (vacations, leave), government programs, insurance, retirement plans, and…

  11. [Therapeutic abortion, unjustified absence in health policy].

    PubMed

    Chávez-Alvarado, Susana

    2013-07-01

    Although abortion for health reasons is not considered a crime in Peru, the State does not allow its inclusion in public policy, thus violating women's right to terminate a pregnancy when it affects their health. When examining the article in the Criminal Code which decriminalizes this type of abortion, provisions are identified which protect women and set the conditions to offer this type of service. This document sets the debate about the arguments used by the Peruvian State for not approving a therapeutic abortion protocol which would regulate the provision and financing of therapeutic abortion in public services, and explains why this obligation should be complied with, based on the conceptual framework of "health exception" In addition, it presents two cases brought before the judicial court in which the Peruvian State was found guilty of violating the human rights of two adolescents to whom a therapeutic abortion was denied.

  12. 20 CFR 416.2035 - Optional supplementation: Additional State options.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 2 2011-04-01 2011-04-01 false Optional supplementation: Additional State options. 416.2035 Section 416.2035 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SUPPLEMENTAL... § 416.2035 Optional supplementation: Additional State options. (a) Residency requirement. A State...

  13. 20 CFR 416.2035 - Optional supplementation: Additional State options.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Optional supplementation: Additional State options. 416.2035 Section 416.2035 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SUPPLEMENTAL... § 416.2035 Optional supplementation: Additional State options. (a) Residency requirement. A State...

  14. 20 CFR 416.2035 - Optional supplementation: Additional State options.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 20 Employees' Benefits 2 2012-04-01 2012-04-01 false Optional supplementation: Additional State options. 416.2035 Section 416.2035 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SUPPLEMENTAL... § 416.2035 Optional supplementation: Additional State options. (a) Residency requirement. A State...

  15. 20 CFR 416.2035 - Optional supplementation: Additional State options.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 20 Employees' Benefits 2 2013-04-01 2013-04-01 false Optional supplementation: Additional State options. 416.2035 Section 416.2035 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SUPPLEMENTAL... § 416.2035 Optional supplementation: Additional State options. (a) Residency requirement. A State...

  16. 20 CFR 416.2035 - Optional supplementation: Additional State options.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 20 Employees' Benefits 2 2014-04-01 2014-04-01 false Optional supplementation: Additional State options. 416.2035 Section 416.2035 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SUPPLEMENTAL... § 416.2035 Optional supplementation: Additional State options. (a) Residency requirement. A State...

  17. Mentoring practices benefiting pediatric nurses.

    PubMed

    Weese, Meghan M; Jakubik, Louise D; Eliades, Aris B; Huth, Jennifer J

    2015-01-01

    Previous studies examining predictors of pediatric nurse protégé mentoring benefits demonstrated that protégé perception of quality was the single best predictor of mentoring benefits. The ability to identify the mentoring practices that predict specific benefits for individual nurses provides a better understanding of how mentoring relationships can be leveraged within health care organizations promoting mutual mentoring benefits. This descriptive correlational, non-experimental study of nurses at a northeast Ohio, Magnet® recognized, free-standing pediatric hospital advances nursing science by demonstrating how mentoring practices benefit pediatric nurse protégés.

  18. The AGNP-TDM expert group consensus guidelines: therapeutic drug monitoring in psychiatry.

    PubMed

    Baumann, P; Hiemke, C; Ulrich, S; Eckermann, G; Gaertner, I; Gerlach, M; Kuss, H-J; Laux, G; Müller-Oerlinghausen, B; Rao, M L; Riederer, P; Zernig, G

    2004-11-01

    Therapeutic Drug Monitoring (TDM) is a valid tool to optimise pharmacotherapy. It enables the clinician to adjust the dosage of drugs according to the characteristics of the individual patient. In psychiatry, TDM is an established procedure for lithium, some antidepressants and antipsychotics. In spite of its obvious advantages, however, the use of TDM in everyday clinical practice is far from optimal. The interdisciplinary TDM group of the Arbeitsgemeinschaft fur Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP) has therefore worked out consensus guidelines to assist psychiatrists and laboratories involved in psychotropic drug analysis to optimise the use of TDM of psychotropic drugs. Five research-based levels of recommendation were defined with regard to routine monitoring of plasma concentrations for dose titration of 65 psychoactive drugs: (1) strongly recommended, (2) recommended, (3) useful, (4) probably useful and (5) not recommended. A second approach defined indications to use TDM, e. g. control of compliance, lack of clinical response or adverse effects at recommended doses, drug interactions, pharmacovigilance programs, presence of a genetic particularity concerning the drug metabolism, children, adolescents and elderly patients. Indications for TDM are relevant for all drugs either with or without validated therapeutic ranges. When studies on therapeutic ranges are lacking, target ranges should be plasma concentrations that are normally observed at therapeutic doses of the drug. Therapeutic ranges of plasma concentrations that are considered to be optimal for treatment are proposed for those drugs, for which the evaluation of the literature demonstrated strong evidence. Moreover, situations are defined when pharmacogenetic (phenotyping or genotyping) tests are informative in addition to TDM. Finally, practical instructions are given how to use TDM. They consider preparation of TDM, analytical procedures, reporting and interpretation of results

  19. Therapeutic Targeting of the Axonal and Microvascular Change Associated with Repetitive Mild Traumatic Brain Injury

    PubMed Central

    Miyauchi, Takashi; Wei, Enoch P.

    2013-01-01

    Abstract Recent interest in mild traumatic brain injury (mTBI) has increased the recognition that repetitive mTBI occurring within the sports and military settings can exacerbate the adverse consequences of the initial injury. While multiple studies have recently reported the pathological, metabolic, and functional changes associated with repetitive mTBI, no consideration has been given to the development of therapeutic approaches to attenuate these abnormalities. In this study, we used the model of repetitive impact acceleration insult previously reported by our laboratory to cause no initial structural and functional changes, yet evoke dramatic change following second insult of the same intensity. Using this model, we employed established neuroprotective agents including FK506 and hypothermia that were administered 1 h after the second insult. Following either therapeutic intervention, changes of cerebral vascular reactivity to acetylcholine were assessed through a cranial window. Following the completion of the vascular studies, the animals were prepared to access the numbers of amyloid precursor protein (APP) positive axons, a marker of axonal damage. Following repetitive injury, cerebral vascular reactivity was dramatically preserved by either therapeutic intervention or the combination thereof compared to control group in which no intervention was employed. Similarly, APP density was significantly lower in the therapeutic intervention group compared in controls. Although the individual use of FK506 or hypothermia exerted significant protection, no additive benefit was found when both therapies were combined. In sum, the current study demonstrates that the exacerbated pathophysiological changes associated with repetitive mTBI can be therapeutically targeted. PMID:23796228

  20. EVITA: a tool for the early EValuation of pharmaceutical Innovations with regard to Therapeutic Advantage

    PubMed Central

    2010-01-01

    Background New drugs are generally claimed to represent a therapeutic innovation. However, scientific evidence of a substantial clinical advantage is often lacking. This may be the result of using inadequate control groups or surrogate outcomes only in the clinical trials. In view of this, EVITA was developed as a user-friendly transparent tool for the early evaluation of the additional therapeutic value of a new drug. Methods EVITA does not evaluate a new compound per se but in an approved indication in comparison with existing therapeutic strategies. Placebo as a comparator is accepted only in the absence of an established therapy or if employed in an add-on strategy on top. The evaluation attributes rating points to the drug in question, taking into consideration both therapeutic benefit and risk profile. The compound scores positive points for superiority in efficiency and/or adverse effects as demonstrated in randomized controlled trials (RCTs), whilst negative points are awarded for inferiority and/or an unfavorable risk profile. The evaluation follows an algorithm considering the clinical relevance of the outcomes, the strength of the therapeutic effect and the number of RCTs performed. Categories for therapeutic aim and disease severity, although essential parts of the EVITA assessment, are attributed but do not influence the EVITA score which is presented as a color-coded bar graph. In case the available data were unsuitable for an EVITA calculation, a traffic-type yield sign is assigned instead to criticize such practice. The results are presented online http://www.evita-report.de together with all RCTs considered as well as the reasons for excluding a given RCT from the evaluation. This allows for immediate revision in response to justified criticism and simplifies the inclusion of new data. Results As examples, four compounds which received approval within the last years were evaluated for one of their clinical indications: lenalidomide, pioglitazone

  1. Workers compensation: coverage, benefits, and costs, 1982

    SciTech Connect

    Price, D.N.

    1984-12-01

    Workers compensation provides medical care and income maintenance protection to workers disabled from work-related injury or illness. This program is of considerable interest to the Social Security Administration (SSA) from several perspectives. For example, since 1965 Social Security Disability Insurance (DI) benefits and workers compensation payments have been integrated. Information on the experience under workers compensation provides a framework for examining questions concerning gaps and overlaps in the Nation's social insurance system. In addition, since December 1969 SSA has administered claims filed through 1973 under part B of the Black Lung program--the program providing income maintenance protection to coal miners disabled by pneumoconiosis. The workers compensation experience reported here consists of information on benefits for work-related injury and disease, including data on the combined benefits paid under the entire Federal Black Lung program administered by the Labor Department and SSA.

  2. 45 CFR 148.220 - Excepted benefits.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... insurance. These benefits include the following: (1) Limited scope dental or vision benefits. These benefits are dental or vision benefits that are limited in scope to a narrow range or type of benefits that...

  3. Separate spheres and indirect benefits

    PubMed Central

    Brock, Dan W

    2003-01-01

    On any plausible account of the basis for health care resource prioritization, the benefits and costs of different alternative resource uses are relevant considerations in the prioritization process. Consequentialists hold that the maximization of benefits with available resources is the only relevant consideration. Non-consequentialists do not reject the relevance of consequences of benefits and costs, but insist that other considerations, and in particular the distribution of benefits and costs, are morally important as well. Whatever one's particular account of morally justified standards for the prioritization of different health interventions, we must be able to measure those interventions' benefits and costs. There are many theoretical and practical difficulties in that measurement, such as how to weigh extending life against improving health and quality of life as well as how different quality of life improvements should be valued, but they are not my concern here. This paper addresses two related issues in assessing benefits and costs for health resource prioritization. First, should benefits be restricted only to health benefits, or include as well other non health benefits such as economic benefits to employers from reducing the lost work time due to illness of their employees? I shall call this the Separate Spheres problem. Second, should only the direct benefits, such as extending life or reducing disability, and direct costs, such as costs of medical personnel and supplies, of health interventions be counted, or should other indirect benefits and costs be counted as well? I shall call this the Indirect Benefits problem. These two issues can have great importance for a ranking of different health interventions by either a cost/benefit or cost effectiveness analysis (CEA) standard. PMID:12773217

  4. Therapeutic endoscopy in gastroenterology.

    PubMed

    Celiński, K; Cichoz-Lach, H

    2007-08-01

    The role of therapeutic endoscopy in current gastroenterology is very important. Therapuetic endoscopy is useful in treatment of gastrointestinal bleeding. Endoscopic control of gastrointestinal bleeding includes the following procedures of haemostasis techniques: photocoagulation, electrocoagulation, thermocoagulation and injection method. Owing to these procedures mortality has significantly decreased. Endoscopic hemostasis eliminates the risk of surgery, is less expensive and better tolerated by patients. Colonoscopic polypectomy is a widely used technique. By removal of polyps the incidence of colon cancer can be decreased. The "hot biopsy" forceps can be used to excise polyps of up to 6 mm. Larger polyps can be removed safely by snare electrocautery and retrieved for histologic study. Endoscopic retrograde cholangiopancreatography has a therapeutic application designed to cut the sphincter of Oddi fibers of the distal common bile duct, what is indicated currently in choledocholithiasis and papillary stenosis with ascending cholangitis, acute gallstone pancreatitis. Endoscopic sphincterotomy in now an established procedure that is indicated in patients with common bile duct calculi. Endoscopic decompression of the biliary tree - dilatation benign structures of the biliary tree with baloon catheters and placement an internal endoprothesis allows the nonoperative decompression and significant palliation for patients with obstructing tumors.

  5. Person-centered Therapeutics

    PubMed Central

    Cloninger, C. Robert; Cloninger, Kevin M.

    2015-01-01

    A clinician’s effectiveness in treatment depends substantially on his or her attitude toward -- and understanding of -- the patient as a person endowed with self-awareness and the will to direct his or her own future. The assessment of personality in the therapeutic encounter is a crucial foundation for forming an effective working alliance with shared goals. Helping a person to reflect on their personality provides a mirror image of their strengths and weaknesses in adapting to life’s many challenges. The Temperament and Character Inventory (TCI) provides an effective way to describe personality thoroughly and to predict both the positive and negative aspects of health. Strengths and weaknesses in TCI personality traits allow strong predictions of individual differences of all aspects of well-being. Diverse therapeutic techniques, such as diet, exercise, mood self-regulation, meditation, or acts of kindness, influence health and personality development in ways that are largely indistinguishable from one another or from effective allopathic treatments. Hence the development of well-being appears to be the result of activating a synergistic set of mechanisms of well-being, which are expressed as fuller functioning, plasticity, and virtue in adapting to life’s challenges PMID:26052429

  6. Engineering therapeutic protein disaggregases

    PubMed Central

    Shorter, James

    2016-01-01

    Therapeutic agents are urgently required to cure several common and fatal neurodegenerative disorders caused by protein misfolding and aggregation, including amyotrophic lateral sclerosis (ALS), Parkinson’s disease (PD), and Alzheimer’s disease (AD). Protein disaggregases that reverse protein misfolding and restore proteins to native structure, function, and localization could mitigate neurodegeneration by simultaneously reversing 1) any toxic gain of function of the misfolded form and 2) any loss of function due to misfolding. Potentiated variants of Hsp104, a hexameric AAA+ ATPase and protein disaggregase from yeast, have been engineered to robustly disaggregate misfolded proteins connected with ALS (e.g., TDP-43 and FUS) and PD (e.g., α-synuclein). However, Hsp104 has no metazoan homologue. Metazoa possess protein disaggregase systems distinct from Hsp104, including Hsp110, Hsp70, and Hsp40, as well as HtrA1, which might be harnessed to reverse deleterious protein misfolding. Nevertheless, vicissitudes of aging, environment, or genetics conspire to negate these disaggregase systems in neurodegenerative disease. Thus, engineering potentiated human protein disaggregases or isolating small-molecule enhancers of their activity could yield transformative therapeutics for ALS, PD, and AD. PMID:27255695

  7. Nitrones as Therapeutics

    PubMed Central

    Floyd, Robert A.; Kopke, Richard D.; Choi, Chul-Hee; Foster, Steven B.; Doblas, Sabrina; Towner, Rheal A.

    2008-01-01

    Nitrones have the general chemical formula X-CH=NO-Y. They were first used to trap free radicals in chemical systems and then subsequently in biochemical systems. More recently several nitrones including PBN (α-phenyl-tert-butylnitrone) have been shown to have potent biological activity in many experimental animal models. Many diseases of aging including stroke, cancer development, Parkinson’s disease and Alzheimer’s disease are known to have enhanced levels of free radicals and oxidative stress. Some derivatives of PBN are significantly more potent than PBN and have undergone extensive commercial development in stroke. Recent research has shown that PBN-related nitrones also have anti-cancer activity in several experimental cancer models and have potential as therapeutics in some cancers. Also in recent observations nitrones have been shown to act synergistically in combination with antioxidants in the prevention of acute acoustic noise induced hearing loss. The mechanistic basis of the potent biological activity of PBN-related nitrones is not known. Even though PBN-related nitrones do decrease oxidative stress and oxidative damage, their potent biological anti-inflammatory activity and their ability to alter cellular signaling processes can not readily be explained by conventional notions of free radical trapping biochemistry. This review is focused on our observations and others where the use of selected nitrones as novel therapeutics have been evaluated in experimental models in the context of free radical biochemical and cellular processes considered important in pathologic conditions and age-related diseases. PMID:18793715

  8. Combination therapeutics in complex diseases.

    PubMed

    He, Bing; Lu, Cheng; Zheng, Guang; He, Xiaojuan; Wang, Maolin; Chen, Gao; Zhang, Ge; Lu, Aiping

    2016-12-01

    The biological redundancies in molecular networks of complex diseases limit the efficacy of many single drug therapies. Combination therapeutics, as a common therapeutic method, involve pharmacological intervention using several drugs that interact with multiple targets in the molecular networks of diseases and may achieve better efficacy and/or less toxicity than monotherapy in practice. The development of combination therapeutics is complicated by several critical issues, including identifying multiple targets, targeting strategies and the drug combination. This review summarizes the current achievements in combination therapeutics, with a particular emphasis on the efforts to develop combination therapeutics for complex diseases.

  9. Additive Similarity Trees

    ERIC Educational Resources Information Center

    Sattath, Shmuel; Tversky, Amos

    1977-01-01

    Tree representations of similarity data are investigated. Hierarchical clustering is critically examined, and a more general procedure, called the additive tree, is presented. The additive tree representation is then compared to multidimensional scaling. (Author/JKS)

  10. Nutritional benefits of exercise.

    PubMed

    Shephard, R J

    1989-03-01

    Specific nutritional benefits of regular exercise include the control of obesity and its complications, the improvement of blood lipid profile, the optimization of micro-nutrient intake and the assurance of a maximum quality-adjusted life-expectancy. While epidemiologists interpret various weight for height ratios in terms of obesity, such data can be misleading, particularly in older people (where an accumulation of fat is masked by lean tissue loss). Skinfold calipers provide a more unequivocal index of the amount and distribution of subcutaneous fat. Arguments against the treatment of obesity by exercise include the large energy yield of fat, the potential for compensating changes of resting metabolism, and an inherently high "set-point" of fat stores in the obese. Exercise cannot achieve rapid fat loss, but it has several advantages over other types of treatment, including the positive nature of the prescription, the associated elevation of mood and suppression of appetite, the conservation of lean tissue, and the establishment of an improved lifestyle. Moreover, blood pressure is reduced, insulin needs are decreased in the diabetic, and favourable changes of lipid profile are observed. Total cholesterol levels are not affected by exercise if body mass is held constant, but (provided a weekly threshold of exercise is exceeded) there is an increase of HDL cholesterol, particularly HDL-2 cholesterol. The intake of vitamins and most other micronutrients is increased by a high daily energy expenditure. Frank anaemia is not common in athletes, but a low iron saturation may be an indication for dietary supplements.(ABSTRACT TRUNCATED AT 250 WORDS)

  11. Assessing the carbon benefit of saltmarsh restoration

    NASA Astrophysics Data System (ADS)

    Taylor, Benjamin; Paterson, David; Hanley, Nicholas

    2016-04-01

    The quantification of carbon sequestration rates in coastal ecosystems is required to better realise their potential role in climate change mitigation. Through accurate valuation this service can be fully appreciated and perhaps help facilitate efforts to restore vulnerable ecosystems such as saltmarshes. Vegetated coastal ecosystems are suggested to account for approximately 50% of oceanic sedimentary carbon despite their 2% areal extent. Saltmarshes, conservatively estimated to store 430 ± 30 Tg C in surface sediment deposits, have experienced extensive decline in the recent past; through processes such as land use change and coastal squeeze. Saltmarsh habitats offer a range of services that benefit society and the natural world, making their conservation meaningful and beneficial. The associated costs of restoration projects could, in part, be subsidised through payment for ecosystem services, specifically Blue carbon. Additional storage is generated through the (re)vegetation of mudflat areas leading to an altered ecosystem state and function; providing similar benefits to natural saltmarsh areas. The Eden Estuary, Fife, Scotland has been a site of saltmarsh restoration since 2000; providing a temporal and spatial scale to evaluate these additional benefits. The study is being conducted to quantify the carbon benefit of restoration efforts and provide an insight into the evolution of this benefit through sites of different ages. Seasonal sediment deposition and settlement rates are measured across the estuary in: mudflat, young planted saltmarsh, old planted saltmarsh and extant high marsh areas. Carbon values being derived from loss on ignition organic content values. Samples are taken across a tidal cycle on a seasonal basis; providing data on tidal influence, vegetation condition effects and climatic factors on sedimentation and carbon sequestration rates. These data will inform on the annual characteristics of sedimentary processes in the estuary and be

  12. Corticosteroids: clinical pharmacology and therapeutic use.

    PubMed

    Swartz, S L; Dluhy, R G

    1978-09-01

    or total withdrawal of the steroid therapy may be associated with exacerbation of the underlying disease or with a steroid withdrawal syndrome. An additional important point to remember in any withdrawal programme is that the steroid dosage should be appropriately increased for an exacerbation of the underlying disease or for intercurrent major stress. Alternate day therapy is recommended as a steroid maintenance programme for patients requiring high dose glucocorticoid therapy over a prolonged period of time. Thus, it is usually employed to maintain a therapeutic benefit which had previously been extablished by daily steroid treatment. Complications resulting from corticosteroid therapy include: (1) proximal muscle weakness; (2) osteopenia; (3) unmasking of latent diabetes mellitus; (4) sodium retention and/or elevation of mean arterial blood pressure; (5) adverse psychiatric reactions; (6) development of glaucoma; and (7) reactivation of latent infections (such as tuberculosis).

  13. ANTIOXIDANT THERAPEUTIC ADVANCES IN COPD

    PubMed Central

    Rahman, Irfan

    2009-01-01

    Chronic obstructive pulmonary disease (COPD) is associated with high incidence of morbidity and mortality. Oxidative stress is intimately associated with the progression and exacerbation of COPD and therefore targeting oxidative stress with antioxidants or boosting the endogenous levels of antioxidants is likely to have beneficial outcome in the treatment of COPD. Among the various antioxidants tried so far, thiol antioxidants and mucolytic agents, such as glutathione, N-acetyl-L-cysteine, N-acystelyn, erdosteine, fudosteine, and carbocysteine; Nrf2 activators, and dietary polyphenols (curcumin, resveratrol, green tea, and catechins/quercetin) have been reported to increase intracellular thiol status alongwith induction of GSH biosynthesis. Such an elevation in the thiol status in turn leads to detoxification of free radicals and oxidants as well as inhibition of ongoing inflammatory responses. In addition, specific spin traps, such as a-phenyl-N-tert-butyl nitrone, a catalytic antioxidant (ECSOD mimetic), porphyrins (AEOL 10150 and AEOL 10113), and a SOD mimetic M40419 have also been reported to inhibit cigarette smoke-induced inflammatory responses in vivo in the lung. Since a variety of oxidants, free radicals and aldehydes are implicated in the pathogenesis of COPD; it is possible that therapeutic administration of multiple antioxidants and mucolytics will be effective in management of COPD. However, a successful outcome will critically depend upon the choice of antioxidant therapy for a particular clinical phenotype of COPD, whose pathophysiology should be first properly understood. This article will review the various approaches adopted to enhance lung antioxidant levels, antioxidant therapeutic advances and recent past clinical trials of antioxidant compounds in COPD. PMID:19124382

  14. Radiobiological speculations on therapeutic total body irradiation

    SciTech Connect

    Vriesendorp, H.M. )

    1990-01-01

    Unexpected total body irradiation (TBI) of human beings, involved in nuclear warfare or in accidents in nuclear reactors can be lethal. In the 1950s, bone marrow transplantation was discovered as a potentially life saving procedure after TBI in the dose range of 5.0 to 12.0 Gy. Since that time, deliberate or therapeutic TBI has been used to condition patients with a lethal bone marrow disorder for bone marrow replacement. The therapeutic ratio of TBI followed by bone marrow transplantation is small. Many potentially lethal complications can occur, such as acute TBI side effects, late TBI side effects or immunological complications of bone marrow transplantation such as graft versus host disease or graft rejection. The benefits of TBI and bone marrow transplantation are that they offer a chance for cure of previously lethal bone marrow disorders. The optimal parameters for TBI remain to be defined. The review discusses the current clinical and experimental animal data, as they relate to the future definition of less toxic TBI procedures with a better therapeutic ratio. Different TBI procedures are required for patients with malignant vs. non-malignant disorders or for patients with histoincompatible vs. histocompatible bone marrow donors.77 references.

  15. Polymer therapeutics in surgery: the next frontier

    PubMed Central

    Conlan, R. Steven; Whitaker, Iain S.

    2016-01-01

    Abstract Polymer therapeutics is a successful branch of nanomedicine, which is now established in several facets of everyday practice. However, to our knowledge, no literature regarding the application of the underpinning principles, general safety, and potential of this versatile class to the perioperative patient has been published. This study provides an overview of polymer therapeutics applied to clinical surgery, including the evolution of this demand‐oriented scientific field, cutting‐edge concepts, its implications, and limitations, illustrated by products already in clinical use and promising ones in development. In particular, the effect of design of polymer therapeutics on biophysical and biochemical properties, the potential for targeted delivery, smart release, and safety are addressed. Emphasis is made on principles, giving examples in salient areas of demand in current surgical practice. Exposure of the practising surgeon to this versatile class is crucial to evaluate and maximise the benefits that this established field presents and to attract a new generation of clinician–scientists with the necessary knowledge mix to drive highly successful innovation. PMID:27588210

  16. Therapeutic Potential of α-Crystallin

    PubMed Central

    Nagaraj, Ram H.; Nahomi, Rooban B.; Mueller, Niklaus H.; Raghavan, Cibin T.; Ammar, David A.; Petrash, J. Mark

    2015-01-01

    Background The findings that α-crystallins are multi-functional proteins with diverse biological functions have generated considerable interest in understanding their role in health and disease. Recent studies have shown that chaperone peptides of α-crystallin could be delivered into cultured cells and in experimental animals with beneficial effects against protein aggregation, oxidation, inflammation and apoptosis. Scope of Review In this review, we will summarize the latest developments on the therapeutic potential of α-crystallins and their functional peptides. Major conclusions α-Crystallins and their functional peptides have shown significant favorable effects against several diseases. Their targeted delivery to tissues would be of great therapeutic benefit. However, α-crystallins can also function as disease-causing proteins. These seemingly contradictory functions must be carefully considered prior to their therapeutic use. General significance αA and αB-Crystallin are members of the small heat shock protein family. These proteins exhibit molecular chaperone and anti-apoptotic activities. The core crystallin domain within these proteins is largely responsible for these prosperities. Recent studies have identified peptides within the crystallin domain of both α- and αB-crystallins with remarkable chaperone and anti-apoptotic activities. Administration of α-crystallin or their functional peptides have shown substantial inhibition of pathologies in several diseases. However, α-crystallins have been shown to promote disease-causing pathways. These two sides of the proteins are discussed in this review. PMID:25840354

  17. Therapeutic drug monitoring for antidepressant drug treatment.

    PubMed

    Ostad Haji, Elnaz; Hiemke, Christoph; Pfuhlmann, Bruno

    2012-01-01

    The aim of antidepressant drug treatment is to produce remission without causing adverse effects during the acute phase of the illness and to prevent relapses or recurrences during continuation or maintenance therapy. To achieve these goals, drug choice and dosage must be optimized for each patient individually. Therapeutic drug monitoring (TDM), which is based on the assumption that clinical effects correlate better with blood levels than doses, can be helpful. When using tricyclic antidepressant drugs TDM enhances safety and efficacy. For newer antidepressant drugs, however, it is a matter of debate to which extend TDM can have beneficial effects. For many antidepressants there exist carefully designed studies concerning the relationship between plasma concentration and clinical effects that allow the definition of recommended therapeutic ranges of the plasma concentration. In some drugs however, concentration-effect studies are lacking so far, but target ranges resulting from clinically relevant plasma concentrations or from pharmacokinetic studies could be provided. During the last years, knowledge on therapeutic references ranges in blood towards TDM guided treatment has markedly improved for new antidepressant drugs, and many specific indications have been defined for useful TDM. Recently published guidelines describe the best practice of TDM for neuropsychiatric drugs. The aim of this review is to summarize the current status of TDM for antidepressant drugs and discuss the literature with regard to response optimization, pharmacovigilance and economic benefits and with regard to needs for further research.

  18. 29 CFR 825.213 - Employer recovery of benefit costs.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 3 2011-07-01 2011-07-01 false Employer recovery of benefit costs. 825.213 Section 825.213... Leave Act § 825.213 Employer recovery of benefit costs. (a) In addition to the circumstances discussed... not unpaid, recovery of health insurance premiums does not apply to such paid leave. (e) The...

  19. Education Finance Policy: Financing the Nonmarket and Social Benefits

    ERIC Educational Resources Information Center

    McMahon, Walter W.

    2006-01-01

    This article complements the one written by George Psacharopoulos. It builds on the market returns to education that are measured by increments to earnings and to pure economic growth. It considers the additional nonmarket private returns to education, but it also considers the social benefits of education that benefit others in the community and…

  20. 29 CFR 4.52 - Fringe benefit determinations.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... addition, wage determinations contain a prescribed minimum rate for all other benefits, such as insurance... insurance, and workers' compensation payments and similar statutory benefits), based upon the sum of the... in private industry, nationwide (and excluding ECI components for supplemental pay, such as...

  1. Polyimide processing additives

    NASA Technical Reports Server (NTRS)

    Pratt, J. R.; St. Clair, T. L.; Burks, H. D.; Stoakley, D. M.

    1987-01-01

    A method has been found for enhancing the melt flow of thermoplastic polyimides during processing. A high molecular weight 422 copoly(amic acid) or copolyimide was fused with approximately 0.05 to 5 pct by weight of a low molecular weight amic acid or imide additive, and this melt was studied by capillary rheometry. Excellent flow and improved composite properties on graphite resulted from the addition of a PMDA-aniline additive to LARC-TPI. Solution viscosity studies imply that amic acid additives temporarily lower molecular weight and, hence, enlarge the processing window. Thus, compositions containing the additive have a lower melt viscosity for a longer time than those unmodified.

  2. [Food additives and healthiness].

    PubMed

    Heinonen, Marina

    2014-01-01

    Additives are used for improving food structure or preventing its spoilage, for example. Many substances used as additives are also naturally present in food. The safety of additives is evaluated according to commonly agreed principles. If high concentrations of an additive cause adverse health effects for humans, a limit of acceptable daily intake (ADI) is set for it. An additive is a risk only when ADI is exceeded. The healthiness of food is measured on the basis of nutrient density and scientifically proven effects.

  3. Antibody Engineering and Therapeutics

    PubMed Central

    Almagro, Juan Carlos; Gilliland, Gary L; Breden, Felix; Scott, Jamie K; Sok, Devin; Pauthner, Matthias; Reichert, Janice M; Helguera, Gustavo; Andrabi, Raiees; Mabry, Robert; Bléry, Mathieu; Voss, James E; Laurén, Juha; Abuqayyas, Lubna; Barghorn, Stefan; Ben-Jacob, Eshel; Crowe, James E; Huston, James S; Johnston, Stephen Albert; Krauland, Eric; Lund-Johansen, Fridtjof; Marasco, Wayne A; Parren, Paul WHI; Xu, Kai Y

    2014-01-01

    The 24th Antibody Engineering & Therapeutics meeting brought together a broad range of participants who were updated on the latest advances in antibody research and development. Organized by IBC Life Sciences, the gathering is the annual meeting of The Antibody Society, which serves as the scientific sponsor. Preconference workshops on 3D modeling and delineation of clonal lineages were featured, and the conference included sessions on a wide variety of topics relevant to researchers, including systems biology; antibody deep sequencing and repertoires; the effects of antibody gene variation and usage on antibody response; directed evolution; knowledge-based design; antibodies in a complex environment; polyreactive antibodies and polyspecificity; the interface between antibody therapy and cellular immunity in cancer; antibodies in cardiometabolic medicine; antibody pharmacokinetics, distribution and off-target toxicity; optimizing antibody formats for immunotherapy; polyclonals, oligoclonals and bispecifics; antibody discovery platforms; and antibody-drug conjugates. PMID:24589717

  4. Outpatient therapeutic nuclear oncology.

    PubMed

    Turner, J Harvey

    2012-05-01

    In the beginning, nuclear medicine was radionuclide therapy, which has evolved into molecular tumour-targeted control of metastatic cancer. Safe, efficacious, clinical practice of therapeutic nuclear oncology may now be based upon accurate personalised dosimetry by quantitative gamma SPECT/CT imaging to prescribe tumoricidal activities without critical organ toxicity. Preferred therapy radionuclides possess gamma emission of modest energy and abundance to enable quantitative SPECT/CT imaging for calculation of the beta therapy dosimetry, without radiation exposure risk to hospital personnel, carers, family or members of the public. The safety of outpatient radiopharmaceutical therapy of cancer with Iodine-131, Samarium-153, Holmium-166, Rhenium-186, Rhenium-188, Lutetium-177 and Indium-111 is reviewed. Measured activity release rates and radiation exposure to carers and the public are all within recommendations and guidelines of international regulatory agencies and, when permitted by local regulatory authorities allow cost-effective, safe, outpatient radionuclide therapy of cancer without isolation in hospital.

  5. Mitochondrial Energetics and Therapeutics

    PubMed Central

    Wallace, Douglas C.; Fan, Weiwei; Procaccio, Vincent

    2011-01-01

    Mitochondrial dysfunction has been linked to a wide range of degenerative and metabolic diseases, cancer, and aging. All these clinical manifestations arise from the central role of bioenergetics in cell biology. Although genetic therapies are maturing as the rules of bioenergetic genetics are clarified, metabolic therapies have been ineffectual. This failure results from our limited appreciation of the role of bioenergetics as the interface between the environment and the cell. A systems approach, which, ironically, was first successfully applied over 80 years ago with the introduction of the ketogenic diet, is required. Analysis of the many ways that a shift from carbohydrate glycolytic metabolism to fatty acid and ketone oxidative metabolism may modulate metabolism, signal transduction pathways, and the epigenome gives us an appreciation of the ketogenic diet and the potential for bioenergetic therapeutics. PMID:20078222

  6. Antimicrobial peptides: therapeutic potentials.

    PubMed

    Kang, Su-Jin; Park, Sung Jean; Mishig-Ochir, Tsogbadrakh; Lee, Bong-Jin

    2014-12-01

    The increasing appearance of multidrug-resistant pathogens has created an urgent need for suitable alternatives to current antibiotics. Antimicrobial peptides (AMPs), which act as defensive weapons against microbes, have received great attention because of broad-spectrum activities, unique action mechanisms and rare antibiotic-resistant variants. Despite desirable characteristics, they have shown limitations in pharmaceutical development due to toxicity, stability and manufacturing costs. Because of these drawbacks, only a few AMPs have been tested in Phase III clinical trials and no AMPs have been approved by the US FDA yet. However, these obstacles could be overcome by well-known methods such as changing physicochemical characteristics and introducing nonnatural amino acids, acetylation or amidation, as well as modern techniques like molecular targeted AMPs, liposomal formulations and drug delivery systems. Thus, the current challenge in this field is to develop therapeutic AMPs at a reasonable cost as well as to overcome the limitations.

  7. Aptamers in Therapeutics

    PubMed Central

    2016-01-01

    Aptamers are single strand DNA or RNA molecules, selected by an iterative process known as Systematic Evolution of Ligands by Exponential Enrichment (SELEX). Due to various advantages of aptamers such as high temperature stability, animal free, cost effective production and its high affinity and selectivity for its target make them attractive alternatives to monoclonal antibody for use in diagnostic and therapeutic purposes. Aptamer has been generated against vesicular endothelial growth factor 165 involved in age related macular degeneracy. Macugen was the first FDA approved aptamer based drug that was commercialized. Later other aptamers were also developed against blood clotting proteins, cancer proteins, antibody E, agents involved in diabetes nephropathy, autoantibodies involved in autoimmune disorders, etc. Aptamers have also been developed against viruses and could work with other antiviral agents in treating infections. PMID:27504277

  8. Microfabricated therapeutic actuators

    DOEpatents

    Lee, Abraham P.; Northrup, M. Allen; Ciarlo, Dino R.; Krulevitch, Peter A.; Benett, William J.

    1999-01-01

    Microfabricated therapeutic actuators are fabricated using a shape memory polymer (SMP), a polyurethane-based material that undergoes a phase transformation at a specified temperature (Tg). At a temperature above temperature Tg material is soft and can be easily reshaped into another configuration. As the temperature is lowered below temperature Tg the new shape is fixed and locked in as long as the material stays below temperature Tg. Upon reheating the material to a temperature above Tg, the material will return to its original shape. By the use of such SMP material, SMP microtubing can be used as a release actuator for the delivery of embolic coils through catheters into aneurysms, for example. The microtubing can be manufactured in various sizes and the phase change temperature Tg is determinate for an intended temperature target and intended use.

  9. Microfabricated therapeutic actuators

    DOEpatents

    Lee, A.P.; Northrup, M.A.; Ciarlo, D.R.; Krulevitch, P.A.; Benett, W.J.

    1999-06-15

    Microfabricated therapeutic actuators are fabricated using a shape memory polymer (SMP), a polyurethane-based material that undergoes a phase transformation at a specified temperature (Tg). At a temperature above temperature Tg material is soft and can be easily reshaped into another configuration. As the temperature is lowered below temperature Tg the new shape is fixed and locked in as long as the material stays below temperature Tg. Upon reheating the material to a temperature above Tg, the material will return to its original shape. By the use of such SMP material, SMP microtubing can be used as a release actuator for the delivery of embolic coils through catheters into aneurysms, for example. The microtubing can be manufactured in various sizes and the phase change temperature Tg is determinate for an intended temperature target and intended use. 8 figs.

  10. Race-based therapeutics.

    PubMed

    Yancy, Clyde W

    2008-08-01

    The issue of race in medicine is problematic. Race is not a physiologic grouping, and all persons of a given race do not necessarily share the same clinical phenotype or genetic substrate. Despite clear signals that certain risk factors and diseases vary as a function of race, translating those differences into race-based therapeutics has been awkward and has done little to change the natural history of cardiovascular disease as it affects special populations. Among the varied special populations, the African American population appears to have the most significant and adverse variances for cardiovascular disease as well as worrisome signals that drug responsiveness varies. Recent guideline statements have now acknowledged certain treatment options that are most appropriate for African Americans with cardiovascular disease, especially hypertension and heart failure. As more physiologic markers of disease and drug responsiveness become available, the need for racial designations in medicine may lessen, and therapies can be optimized for all patients without regard to race or ethnicity.

  11. Therapeutic potential of ginseng in the management of cardiovascular disorders.

    PubMed

    Karmazyn, Morris; Moey, Melissa; Gan, Xiaohong Tracey

    2011-10-22

    Although employed in Asian societies for thousands of years, the use of ginseng as an herbal medication for a variety of disorders has increased tremendously worldwide in recent years. Ginseng belongs to the genus Panax, of which there exists a variety, generally reflecting their geographic origin. North American ginseng (Panax quinquefolius) and Asian ginseng (Panax ginseng) are two such varieties possessing a plethora of pharmacological properties, which are attributed primarily to the presence of different ginsenosides that bestow these ginsengs with distinct pharmacodynamic profiles. The many cardiovascular benefits attributed to ginseng include cardioprotection, antihypertensive effects, and attenuation of myocardial hypertrophy and heart failure. Experimental studies have revealed a number of beneficial properties of ginseng, particularly in the area of cardiac protection, where ginseng and ginsenosides have been shown to protect the ischaemic and reperfused heart in a variety of experimental models. Emerging evidence also suggests that ginseng attenuates myocardial hypertrophy, thus blunting the remodelling and heart failure processes. However, clinical evidence of efficacy is not convincing, likely owing primarily to the paucity of well designed, randomized, controlled clinical trials. Adding to the complexity in understanding the cardiovascular effects of ginseng is the fact that each of the different ginseng varieties possesses distinct cardiovascular properties, as a result of their respective ginsenoside composition, rendering it difficult to assign a general, common cardiovascular effect to ginseng. Additional challenges include the identification of mechanisms (likely multifaceted) that account for the effects of ginseng and determining which ginsenoside(s) mediate these cardiovascular properties. These concerns notwithstanding, the potential cardiovascular benefit of ginseng is worthy of further studies in view of its possible development as a

  12. Who Benefits from Volunteering? Variations in Perceived Benefits

    ERIC Educational Resources Information Center

    Morrow-Howell, Nancy; Hong, Song-Iee; Tang, Fengyan

    2009-01-01

    Purpose: The purpose of this study was to document the benefits of volunteering perceived by older adults and to explain variation in these self-perceived benefits. Design and Methods: This is a quantitative study of 13 volunteer programs and 401 older adults serving in those programs. Program directors completed telephone interviews, and older…

  13. Social Work Practice in the Digital Age: Therapeutic E-Mail as a Direct Practice Methodology

    ERIC Educational Resources Information Center

    Mattison, Marian

    2012-01-01

    The author addresses the risks and benefits of incorporating therapeutic e-mail communication into clinical social work practice. Consumer demand for online clinical services is growing faster than the professional response. E-mail, when used as an adjunct to traditional meetings with clients, offers distinct advantages and risks. Benefits include…

  14. Preclinical evaluation of potential therapeutic targets in dedifferentiated liposarcoma

    PubMed Central

    Hanes, Robert; Grad, Iwona; Lorenz, Susanne; Stratford, Eva W.; Munthe, Else; Reddy, Chilamakuri Chandra Sekhar; Meza-Zepeda, Leonardo A.; Myklebost, Ola

    2016-01-01

    Sarcomas are rare cancers with limited treatment options. Patients are generally treated by chemotherapy and/or radiotherapy in combination with surgery, and would benefit from new personalized approaches. In this study we demonstrate the potential of combining personal genomic characterization of patient tumors to identify targetable mutations with in vitro testing of specific drugs in patient-derived cell lines. We have analyzed three metastases from a patient with high-grade metastatic dedifferentiated liposarcoma (DDLPS) by exome and transcriptome sequencing as well as DNA copy number analysis. Genomic aberrations of several potentially targetable genes, including amplification of KITLG and FRS2, in addition to amplification of CDK4 and MDM2, characteristic of this disease, were identified. We evaluated the efficacy of drugs targeting these aberrations or the corresponding signaling pathways in a cell line derived from the patient. Interestingly, the pan-FGFR inhibitor NVP-BGJ398, which targets FGFR upstream of FRS2, strongly inhibited cell proliferation in vitro and induced an accumulation of cells into the G0 phase of the cell cycle. This study indicates that FGFR inhibitors have therapeutic potential in the treatment of DDLPS with amplified FRS2. PMID:27409346

  15. Therapeutic Decisions In Multiple Sclerosis: Moving Beyond Efficacy

    PubMed Central

    Brück, Wolfgang; Ralf, Gold; Lund, Brett T.; Celia, Oreja-Guevara; Prat, Alexandre; Spencer, Collin M.; Steinman, Lawrence; Mar, Tintoré; Vollmer, Timothy; Weber, Martin S.; Weiner, Leslie P.; Ziemssen, Tjalf; Zamvil, Scott S.

    2014-01-01

    Importance Several innovative disease-modifying treatments (DMTs) for relapsing remitting multiple sclerosis (RRMS) have been licensed recently, or are in late-stage development. The molecular targets of several of these DMTs are well defined. All affect at least one of four properties: (1) immune cell trafficking, (2) cell depletion, (3) immune cell function, or (4) cell replication. In contrast to β-interferons and glatiramer acetate, the first generation DMTs, several newer therapies are imbued with safety issues. In addition to efficacy, understanding the relationship between the mechanism of action (MOA) of the DMTs and their safety profile is essential for decision-making in patient care. Objective In this article, we relate safety issues of newer DMTs to their pharmacological characteristics, including molecular targets, MOA, chemical structure, and metabolism. Some newer DMTs also represent repurposing or modifications of previous treatments used in other diseases. Here, we describe how identification and understanding of adverse events (AEs) observed with these established drugs within the same class, provide clues regarding safety and toxicities of newer MS therapeutics. Conclusions and relevance While understanding mechanisms underlying DMT toxicities is incomplete, it is important to further develop this knowledge to minimize risk to patients, and to ensure future therapies have the most advantageous risk-benefit profiles. Recognizing the individual classes of DMTs described here may be beneficial when considering use of such agents sequentially and possibly in combination. PMID:23921521

  16. Synthetic and natural iron chelators: therapeutic potential and clinical use

    PubMed Central

    Hatcher, Heather C; Singh, Ravi N; Torti, Frank M; Torti, Suzy V

    2013-01-01

    Iron-chelation therapy has its origins in the treatment of iron-overload syndromes. For many years, the standard for this purpose has been deferoxamine. Recently, considerable progress has been made in identifying synthetic chelators with improved pharmacologic properties relative to deferoxamine. Most notable are deferasirox (Exjade®) and deferiprone (Ferriprox®), which are now available clinically. In addition to treatment of iron overload, there is an emerging role for iron chelators in the treatment of diseases characterized by oxidative stress, including cardiovascular disease, atherosclerosis, neurodegenerative diseases and cancer. While iron is not regarded as the underlying cause of these diseases, it does play an important role in disease progression, either through promotion of cellular growth and proliferation or through participation in redox reactions that catalyze the formation of reactive oxygen species and increase oxidative stress. Thus, iron chelators may be of therapeutic benefit in many of these conditions. Phytochemicals, many of which bind iron, may also owe some of their beneficial properties to iron chelation. This review will focus on the advances in iron-chelation therapy for the treatment of iron-overload disease and cancer, as well as neurodegenerative and chronic inflammatory diseases. Established and novel iron chelators will be discussed, as well as the emerging role of dietary plant polyphenols that effectively modulate iron biochemistry. PMID:21425984

  17. Iron deficiency: an emerging therapeutic target in heart failure.

    PubMed

    Cohen-Solal, Alain; Leclercq, Christophe; Deray, Gilbert; Lasocki, Sigismond; Zambrowski, Jean-Jacques; Mebazaa, Alexandre; de Groote, Pascal; Damy, Thibaud; Galinier, Michel

    2014-09-15

    In patients with heart failure, iron deficiency is frequent but overlooked, with a prevalence of 30%-50%. Since it contributes to cardiac and peripheral muscle dysfunction, iron deficiency is associated with poorer clinical outcomes and a greater risk of death, independent of haemoglobin level. Therefore, iron deficiency emerges as a new comorbidity and a therapeutic target of chronic heart failure in addition to chronic renal insufficiency, anaemia and diabetes. In a series of placebo-controlled, randomised studies in patients with heart failure and iron deficiency, intravenous iron had a favourable effect on exercise capacity, functional class, LVEF, renal function and quality of life. These clinical studies were performed in the context of a renewed interest in iron metabolism. During the past 10 years, knowledge about the transport, storage and homeostasis of iron has improved dramatically, and new molecules involved in iron metabolism have been described (eg, hepcidin, ferroportin, divalent metal transporter 1). Recent European guidelines recommend the monitoring of iron parameters (ie, serum ferritin, transferrin saturation) for all patients with heart failure. Ongoing clinical trials will explore the benefits of iron deficiency correction on various heart failure parameters.

  18. The Vegetative State and Stem Cells: Therapeutic Considerations

    PubMed Central

    Hazell, Alan S.

    2016-01-01

    The vegetative state (VS), also known as “unresponsive wakefulness syndrome,” is considered one of the most devastating outcomes of acquired brain injury. While diagnosis of this condition is generally well-defined clinically, patients often appear to be awake despite an absence of behavioral signs of awareness, which to the family can be confusing, leading them to believe the loved one is aware of their surroundings. This inequality of agreement can be very distressing. Currently, no cure for the VS is available; as a result, patients may remain in this condition for the rest of their lives, which in some cases amount to decades. Recent advances in stem cell approaches for the treatment of other neurological conditions may now provide an opportunity to intervene in this syndrome. This mini review will address the development of VS, its diagnosis, affected cerebral structures, and the underlying basis of how stem cells can offer therapeutic promise that would take advantage of the often long-term features associated with this maladie to effect a repair of the severely damaged circuitry. In addition, current limitations of this treatment strategy, including a lack of animal models, few long-term clinical studies that might identify benefits of stem cell treatment, and the potential for development of tumors are considered. PMID:27602016

  19. Trends in Mitochondrial Therapeutics for Neurological Disease.

    PubMed

    Leitão-Rocha, Ana; Guedes-Dias, Pedro; Pinho, Brígida R; Oliveira, Jorge M A

    2015-01-01

    Neuronal homeostasis is critically dependent on healthy mitochondria. Mutations in mitochondrial DNA (mtDNA), in nuclear-encoded mitochondrial components, and age-dependent mitochondrial damage, have all been connected with neurological disorders. These include not only typical mitochondrial syndromes with neurological features such as encephalomyopathy, myoclonic epilepsy, neuropathy and ataxia; but also secondary mitochondrial involvement in neurodegenerative disorders such as Alzheimer's, Parkinson's and Huntington's disease. Unravelling the molecular aetiology of mitochondrial dysfunction opens new therapeutic prospects for diseases thus far lacking effective treatments. In this review we address recent advances on preventive strategies, such as pronuclear, spindle-chromosome complex, or polar body genome transfer to replace mtDNA and avoid disease transmission to newborns; we also address experimental mitochondrial therapeutics aiming to benefit symptomatic patients and prevent disease manifestation in those at risk. Specifically, we focus on: (1) gene therapy to reduce mutant mtDNA, such as anti-replicative therapies and mitochondriatargeted nucleases allowing favourable heteroplasmic shifts; (2) allotopic expression of recoded wild-type mitochondrial genes, including targeted tRNAs and xenotopic expression of cognate genes to compensate for pathogenic mutations; (3) mitochondria targeted-peptides and lipophilic cations for in vivo delivery of antioxidants or other putative therapeutics; and (4) modulation of mitochondrial dynamics at the level of biogenesis, fission, fusion, movement and mitophagy. Further advances in therapeutic development are hindered by scarce in vivo models for mitochondrial disease, with the bulk of available data coming from cellular models. Nevertheless, wherever available, we also address data from in vivo experiments and clinical trials, focusing on neurological disease models.

  20. Fc gamma receptors: glycobiology and therapeutic prospects

    PubMed Central

    Hayes, Jerrard M; Wormald, Mark R; Rudd, Pauline M; Davey, Gavin P

    2016-01-01

    Therapeutic antibodies hold great promise for the treatment of cancer and autoimmune diseases, and developments in antibody–drug conjugates and bispecific antibodies continue to enhance treatment options for patients. Immunoglobulin (Ig) G antibodies are proteins with complex modifications, which have a significant impact on their function. The most important of these modifications is glycosylation, the addition of conserved glycans to the antibody Fc region, which is critical for its interaction with the immune system and induction of effector activities such as antibody-dependent cell cytotoxicity, complement activation and phagocytosis. Communication of IgG antibodies with the immune system is controlled and mediated by Fc gamma receptors (FcγRs), membrane-bound proteins, which relay the information sensed and gathered by antibodies to the immune system. These receptors are also glycoproteins and provide a link between the innate and adaptive immune systems. Recent information suggests that this receptor glycan modification is also important for the interaction with antibodies and downstream immune response. In this study, the current knowledge on FcγR glycosylation is discussed, and some insight into its role and influence on the interaction properties with IgG, particularly in the context of biotherapeutics, is provided. For the purpose of this study, other Fc receptors such as FcαR, FcεR or FcRn are not discussed extensively, as IgG-based antibodies are currently the only therapeutic antibody-based products on the market. In addition, FcγRs as therapeutics and therapeutic targets are discussed, and insight into and comment on the therapeutic aspects of receptor glycosylation are provided. PMID:27895507

  1. The Therapeutic Potential of Cannabinoids for Movement Disorders

    PubMed Central

    Kluger, Benzi; Triolo, Piera; Jones, Wallace; Jankovic, Joseph

    2014-01-01

    Background There is growing interest in the therapeutic potential of marijuana (cannabis) and cannabinoid-based chemicals within the medical community and particularly for neurologic conditions. This interest is driven both by changes in the legal status of cannabis in many areas and increasing research into the roles of endocannabinoids within the central nervous system and their potential as symptomatic and/or neuroprotective therapies. We review basic science, preclinical and clinical studies on the therapeutic potential of cannabinoids specifically as it relates to movement disorders. Results The pharmacology of cannabis is complex with over 60 neuroactive chemicals identified to date. The endocannabinoid system modulates neurotransmission involved in motor function, particularly within the basal ganglia. Preclinical research in animal models of several movement disorders have shown variable evidence for symptomatic benefits but more consistently suggest potential neuroprotective effects in several animal models of Parkinson’s (PD) and Huntington’s disease (HD). Clinical observations and clinical trials of cannabinoid-based therapies suggests a possible benefit of cannabinoids for tics and probably no benefit for tremor in multiple sclerosis or dyskinesias or motor symptoms in PD. Data are insufficient to draw conclusions regarding HD, dystonia or ataxia and nonexistent for myoclonus or restless legs syndrome. Conclusions Despite the widespread publicity about the medical benefits of cannabinoids, further preclinical and clinical research is needed to better characterize the pharmacological, physiological and therapeutic effects of this class of drugs in movement disorders. PMID:25649017

  2. The therapeutic potential of cannabinoids for movement disorders.

    PubMed

    Kluger, Benzi; Triolo, Piera; Jones, Wallace; Jankovic, Joseph

    2015-03-01

    There is growing interest in the therapeutic potential of marijuana (cannabis) and cannabinoid-based chemicals within the medical community and, particularly, for neurological conditions. This interest is driven both by changes in the legal status of cannabis in many areas and increasing research into the roles of endocannabinoids within the central nervous system and their potential as symptomatic and/or neuroprotective therapies. We review basic science as well as preclinical and clinical studies on the therapeutic potential of cannabinoids specifically as it relates to movement disorders. The pharmacology of cannabis is complex, with over 60 neuroactive chemicals identified to date. The endocannabinoid system modulates neurotransmission involved in motor function, particularly within the basal ganglia. Preclinical research in animal models of several movement disorders have shown variable evidence for symptomatic benefits, but more consistently suggest potential neuroprotective effects in several animal models of Parkinson's (PD) and Huntington's disease (HD). Clinical observations and clinical trials of cannabinoid-based therapies suggests a possible benefit of cannabinoids for tics and probably no benefit for tremor in multiple sclerosis or dyskinesias or motor symptoms in PD. Data are insufficient to draw conclusions regarding HD, dystonia, or ataxia and nonexistent for myoclonus or RLS. Despite the widespread publicity about the medical benefits of cannabinoids, further preclinical and clinical research is needed to better characterize the pharmacological, physiological, and therapeutic effects of this class of drugs in movement disorders.

  3. Functional correlates of the therapeutic and adverse effects evoked by thalamic stimulation for essential tremor

    PubMed Central

    Gibson, William S.; Jo, Hang Joon; Testini, Paola; Cho, Shinho; Felmlee, Joel P.; Welker, Kirk M.; Klassen, Bryan T.; Min, Hoon-Ki

    2016-01-01

    Deep brain stimulation is an established neurosurgical therapy for movement disorders including essential tremor and Parkinson’s disease. While typically highly effective, deep brain stimulation can sometimes yield suboptimal therapeutic benefit and can cause adverse effects. In this study, we tested the hypothesis that intraoperative functional magnetic resonance imaging could be used to detect deep brain stimulation-evoked changes in functional and effective connectivity that would correlate with the therapeutic and adverse effects of stimulation. Ten patients receiving deep brain stimulation of the ventralis intermedius thalamic nucleus for essential tremor underwent functional magnetic resonance imaging during stimulation applied at a series of stimulation localizations, followed by evaluation of deep brain stimulation-evoked therapeutic and adverse effects. Correlations between the therapeutic effectiveness of deep brain stimulation (3 months postoperatively) and deep brain stimulation-evoked changes in functional and effective connectivity were assessed using region of interest-based correlation analysis and dynamic causal modelling, respectively. Further, we investigated whether brain regions might exist in which activation resulting from deep brain stimulation might correlate with the presence of paraesthesias, the most common deep brain stimulation-evoked adverse effect. Thalamic deep brain stimulation resulted in activation within established nodes of the tremor circuit: sensorimotor cortex, thalamus, contralateral cerebellar cortex and deep cerebellar nuclei (FDR q < 0.05). Stimulation-evoked activation in all these regions of interest, as well as activation within the supplementary motor area, brainstem, and inferior frontal gyrus, exhibited significant correlations with the long-term therapeutic effectiveness of deep brain stimulation (P < 0.05), with the strongest correlation (P < 0.001) observed within the contralateral cerebellum. Dynamic causal

  4. Gauging Technology Costs and Benefits

    ERIC Educational Resources Information Center

    Kaestner, Rich

    2007-01-01

    Regardless of the role technology plays in a school district, district personnel should know the costs associated with technology, understand the consequences of technology purchases, and be able to measure the benefits of technology, so they can make more informed decisions. However, determining costs and benefits of current technology or…

  5. Who Benefits from Pension Enhancements?

    ERIC Educational Resources Information Center

    Koedel, Cory; Ni, Shawn; Podgursky, Michael

    2014-01-01

    During the late 1990s public pension funds across the United States accrued large actuarial surpluses. The seemingly flush conditions of the pension funds led legislators in most states to substantially improve retirement benefits for public workers, including teachers. In this study we examine the benefit enhancements to the teacher pension…

  6. Family Literacy Programs: Who Benefits?

    ERIC Educational Resources Information Center

    Padak, Nancy; Rasinski, Tim

    Designing and delivering literacy programs that benefit both parents (or other family members) and children makes sense. But do family literacy programs really work? And if so, who benefits? The concept of family literacy is firmly rooted in a substantial research base from several disciplines, including adult literacy, emergent literacy, child…

  7. Taxability of Educational Benefits Trusts

    ERIC Educational Resources Information Center

    Temple Law Quarterly, 1976

    1976-01-01

    Corporations have found the promise of providing a college education to the children of employees--without the recognition of income to the parent-employee--to be a popular fringe benefit. The Internal Revenue Service has attacked educational benefit trusts in Revenue Ruling 75-448. Implications are discussed. (LBH)

  8. Increasing Enrollment through Benefit Segmentation.

    ERIC Educational Resources Information Center

    Goodnow, Betty

    1982-01-01

    The applicability of benefit segmentation, a market research technique which groups people according to benefits expected from a program offering, was tested at the College of DuPage. Preferences and demographic characteristics were analyzed and program improvements adopted, increasing enrollment by 20 percent. (Author/SK)

  9. Polylactides in additive biomanufacturing.

    PubMed

    Poh, Patrina S P; Chhaya, Mohit P; Wunner, Felix M; De-Juan-Pardo, Elena M; Schilling, Arndt F; Schantz, Jan-Thorsten; van Griensven, Martijn; Hutmacher, Dietmar W

    2016-12-15

    New advanced manufacturing technologies under the alias of additive biomanufacturing allow the design and fabrication of a range of products from pre-operative models, cutting guides and medical devices to scaffolds. The process of printing in 3 dimensions of cells, extracellular matrix (ECM) and biomaterials (bioinks, powders, etc.) to generate in vitro and/or in vivo tissue analogue structures has been termed bioprinting. To further advance in additive biomanufacturing, there are many aspects that we can learn from the wider additive manufacturing (AM) industry, which have progressed tremendously since its introduction into the manufacturing sector. First, this review gives an overview of additive manufacturing and both industry and academia efforts in addressing specific challenges in the AM technologies to drive toward AM-enabled industrial revolution. After which, considerations of poly(lactides) as a biomaterial in additive biomanufacturing are discussed. Challenges in wider additive biomanufacturing field are discussed in terms of (a) biomaterials; (b) computer-aided design, engineering and manufacturing; (c) AM and additive biomanufacturing printers hardware; and (d) system integration. Finally, the outlook for additive biomanufacturing was discussed.

  10. Additive Manufactured Product Integrity

    NASA Technical Reports Server (NTRS)

    Waller, Jess; Wells, Doug; James, Steve; Nichols, Charles

    2017-01-01

    NASA is providing key leadership in an international effort linking NASA and non-NASA resources to speed adoption of additive manufacturing (AM) to meet NASA's mission goals. Participants include industry, NASA's space partners, other government agencies, standards organizations and academia. Nondestructive Evaluation (NDE) is identified as a universal need for all aspects of additive manufacturing.

  11. Therapeutic cloning: The ethical limits

    SciTech Connect

    Whittaker, Peter A. . E-mail: p.whittaker@lancaster.ac.uk

    2005-09-01

    A brief outline of stem cells, stem cell therapy and therapeutic cloning is given. The position of therapeutic cloning with regard to other embryonic manipulations - IVF-based reproduction, embryonic stem formation from IVF embryos and reproductive cloning - is indicated. The main ethically challenging stages in therapeutic cloning are considered to be the nuclear transfer process including the source of eggs for this and the destruction of an embryo to provide stem cells for therapeutic use. The extremely polarised nature of the debate regarding the status of an early human embryo is noted, and some potential alternative strategies for preparing immunocompatible pluripotent stem cells are indicated.

  12. Clinical applications of therapeutic phlebotomy

    PubMed Central

    Kim, Kyung Hee; Oh, Ki Young

    2016-01-01

    Phlebotomy is the removal of blood from the body, and therapeutic phlebotomy is the preferred treatment for blood disorders in which the removal of red blood cells or serum iron is the most efficient method for managing the symptoms and complications. Therapeutic phlebotomy is currently indicated for the treatment of hemochromatosis, polycythemia vera, porphyria cutanea tarda, sickle cell disease, and nonalcoholic fatty liver disease with hyperferritinemia. This review discusses therapeutic phlebotomy and the related disorders and also offers guidelines for establishing a therapeutic phlebotomy program. PMID:27486346

  13. [Costs and benefits of smoking].

    PubMed

    Polder, J J; van Gils, P F; Kok, L; Talhout, R; Feenstra, T L

    2017-01-01

    - Two recent societal cost-benefit analyses have documented the costs of smoking and the cost-effectiveness of preventing smoking.- Smoking costs the Netherlands society EUR 33 billion per year.- The majority of this is the monetary value of health loss; these are "soft" euros that cannot be re-spent.- There is not a great deal of difference between costs and benefits when expressed in "hard" euros, which means that there is no clear business case for anti-smoking policy.- The greatest benefit of discouraging smoking is improved health for the individual and increased productivity for the business sector; however, the benefits cannot be easily realised, because even in the most favourable scenario the number of smokers will decrease slowly.- Excise duties seem to offer the most promising avenue for combating smoking. The benefits of anti-smoking policy, therefore, consist mainly of tax revenues for the government.- Stringent policy is required to transform tax revenues into health gains.

  14. Designing phage therapeutics.

    PubMed

    Goodridge, Lawrence D

    2010-01-01

    Phage therapy is the application of phages to bodies, substances, or environments to effect the biocontrol of pathogenic or nuisance bacteria. To be effective, phages, minimally, must be capable of attaching to bacteria (adsorption), killing those bacteria (usually associated with phage infection), and otherwise surviving (resisting decay) until they achieve attachment and subsequent killing. While a strength of phage therapy is that phages that possess appropriate properties can be chosen from a large diversity of naturally occurring phages, a more rational approach to phage therapy also can include post-isolation manipulation of phages genetically, phenotypically, or in terms of combining different products into a single formulation. Genetic manipulation, especially in these modern times, can involve genetic engineering, though a more traditional approach involves the selection of spontaneously occurring phage mutants during serial transfer protocols. While genetic modification typically is done to give rise to phenotypic changes in phages, phage phenotype alone can also be modified in vitro, prior to phage application for therapeutic purposes, as for the sake of improving phage lethality (such as by linking phage virions to antibacterial chemicals such as chloramphenicol) or survival capabilities (e.g., via virion PEGylation). Finally, phages, both naturally occurring isolates or otherwise modified constructs, can be combined into cocktails which provide collectively enhanced capabilities such as expanded overall host range. Generally these strategies represent different routes towards improving phage therapy formulations and thereby efficacy through informed design.

  15. Plasmids encoding therapeutic agents

    DOEpatents

    Keener, William K.

    2007-08-07

    Plasmids encoding anti-HIV and anti-anthrax therapeutic agents are disclosed. Plasmid pWKK-500 encodes a fusion protein containing DP178 as a targeting moiety, the ricin A chain, an HIV protease cleavable linker, and a truncated ricin B chain. N-terminal extensions of the fusion protein include the maltose binding protein and a Factor Xa protease site. C-terminal extensions include a hydrophobic linker, an L domain motif peptide, a KDEL ER retention signal, another Factor Xa protease site, an out-of-frame buforin II coding sequence, the lacZ.alpha. peptide, and a polyhistidine tag. More than twenty derivatives of plasmid pWKK-500 are described. Plasmids pWKK-700 and pWKK-800 are similar to pWKK-500 wherein the DP178-encoding sequence is substituted by RANTES- and SDF-1-encoding sequences, respectively. Plasmid pWKK-900 is similar to pWKK-500 wherein the HIV protease cleavable linker is substituted by a lethal factor (LF) peptide-cleavable linker.

  16. Therapeutic antibody technology 97.

    PubMed

    Larrick, J W; Gavilondo, J

    1998-01-01

    Almost 200 antibody aficionados attended the Therapeutic Antibody Technology 97 meeting, held September 21-24, 1997 at the Holiday Inn, Union Square in the heart of San Francisco, CA. The meeting was sponsored by the Palo Alto Institute of Molecular Medicine and organized by James W. Larrick (PAIMM) and Dennis R. Burton (Scripps Research Institute). The meeting featured excellent discussions on many interesting talks and a number of poster presentations. It is likely that another meeting will be organized in 2 years, however in the meantime, an effort is underway to organize a 'Virtual Antibody Society' to be set up on the web server at Scripps Research Institute in La Jolla, CA (Questions and comments on this project can be sent to: Jwlarrick@aol.com or Burton@scripps.edu). Richard Lerner (Scripps) gave the keynote address on 'Catalytic Antibodies', describing recent work with Carlos Barbas on so-called reactive immunization to generate a high activity aldolase catalytic antibody. This antibody, soon to be described in an article in Science, is the first commercially available catalytic antibody.

  17. Leech Therapeutic Applications

    PubMed Central

    Abdualkader, A. M.; Ghawi, A. M.; Alaama, M.; Awang, M.; Merzouk, A.

    2013-01-01

    Hematophagous animals including leeches have been known to possess biologically active compounds in their secretions, especially in their saliva. The blood-sucking annelids, leeches have been used for therapeutic purposes since the beginning of civilization. Ancient Egyptian, Indian, Greek and Arab physicians used leeches for a wide range of diseases starting from the conventional use for bleeding to systemic ailments, such as skin diseases, nervous system abnormalities, urinary and reproductive system problems, inflammation, and dental problems. Recently, extensive researches on leech saliva unveiled the presence of a variety of bioactive peptides and proteins involving antithrombin (hirudin, bufrudin), antiplatelet (calin, saratin), factor Xa inhibitors (lefaxin), antibacterial (theromacin, theromyzin) and others. Consequently, leech has made a comeback as a new remedy for many chronic and life-threatening abnormalities, such as cardiovascular problems, cancer, metastasis, and infectious diseases. In the 20th century, leech therapy has established itself in plastic and microsurgery as a protective tool against venous congestion and served to salvage the replanted digits and flaps. Many clinics for plastic surgery all over the world started to use leeches for cosmetic purposes. Despite the efficacious properties of leech therapy, the safety, and complications of leeching are still controversial. PMID:24019559

  18. The public library as therapeutic landscape: a qualitative case study.

    PubMed

    Brewster, Liz

    2014-03-01

    The idea of the therapeutic landscape has been widely used to describe the relationship between place and improvements in mental health. This paper uses data from a qualitative study conducted with people with mental health problems to outline the role of the public library as a therapeutic landscape. It situates the public library as a space that is simultaneously familiar and welcoming, comforting and calming, and empowering. Further, the paper reflects on the impact of proposed library closures in light of these previously hidden benefits, thinking about the library's role as an environment and not as a service provider.

  19. Design considerations for PAMAM dendrimer therapeutics.

    PubMed

    Goonewardena, Sascha N; Kratz, Jeremy D; Zong, Hong; Desai, Ankur M; Tang, Shengzhuang; Emery, Sarah; Baker, James R; Huang, Baohua

    2013-05-15

    We have previously shown that methotrexate (MTX) conjugated to a cancer-specific poly amido amine (PAMAM) dendrimer has a higher therapeutic index than MTX alone. Unfortunately, these therapeutics have been difficult to advance because of the complicated syntheses and an incomplete understanding of the dendrimer properties. We wished to address these obstacles by using copper-free click chemistry to functionalize the dendrimer scaffolds and to exploring the effects of two dendrimer properties (the targeting ligand and drug linkage) on cytotoxicity. We conjugated either ester or amide-linker modified MTX to dendrimer scaffolds with or without folic acid (FA). Because of multivalency, the FA and MTX functionalized dendrimers had similar capacities to target the folate receptor on cancer cells. Additionally, we found that the ester- and amide-linker modified MTX compounds had similar cytotoxicity but the dendrimer-ester MTX conjugates were much more cytotoxic than the dendrimer-amide MTX conjugates. These results clarify the impact of these properties on therapeutic efficacy and will allow us to design more effective polymer therapeutics.

  20. Determinants of immunogenic response to protein therapeutics.

    PubMed

    Singh, Satish K; Cousens, Leslie P; Alvarez, David; Mahajan, Pramod B

    2012-09-01

    Protein therapeutics occupy a very significant position in the biopharmaceutical market. In addition to the preclinical, clinical and post marketing challenges common to other drugs, unwanted immunogenicity is known to affect efficacy and/or safety of most biotherapeutics. A standard set of immunogenicity risk factors are routinely used to inform monitoring strategies in clinical studies. A number of in-silico, in vivo and in vitro approaches have also been employed to predict immunogenicity of biotherapeutics, but with limited success. Emerging data also indicates the role of immune tolerance mechanisms and impact of several product-related factors on modulating host immune responses. Thus, a comprehensive discussion of the impact of innate and adaptive mechanisms and molecules involved in induction of host immune responses on immunogenicity of protein therapeutics is needed. A detailed understanding of these issues is essential in order to fully exploit the therapeutic potential of this class of drugs. This Roundtable Session was designed to provide a common platform for discussing basic immunobiological and pharmacological issues related to the role of biotherapeutic-associated risk factors, as well as host immune system in immunogenicity against protein therapeutics. The session included overview presentations from three speakers, followed by a panel discussion with audience participation.

  1. Targeting cellular metabolism to improve cancer therapeutics.

    PubMed

    Zhao, Y; Butler, E B; Tan, M

    2013-03-07

    The metabolic properties of cancer cells diverge significantly from those of normal cells. Energy production in cancer cells is abnormally dependent on aerobic glycolysis. In addition to the dependency on glycolysis, cancer cells have other atypical metabolic characteristics such as increased fatty acid synthesis and increased rates of glutamine metabolism. Emerging evidence shows that many features characteristic to cancer cells, such as dysregulated Warburg-like glucose metabolism, fatty acid synthesis and glutaminolysis are linked to therapeutic resistance in cancer treatment. Therefore, targeting cellular metabolism may improve the response to cancer therapeutics and the combination of chemotherapeutic drugs with cellular metabolism inhibitors may represent a promising strategy to overcome drug resistance in cancer therapy. Recently, several review articles have summarized the anticancer targets in the metabolic pathways and metabolic inhibitor-induced cell death pathways, however, the dysregulated metabolism in therapeutic resistance, which is a highly clinical relevant area in cancer metabolism research, has not been specifically addressed. From this unique angle, this review article will discuss the relationship between dysregulated cellular metabolism and cancer drug resistance and how targeting of metabolic enzymes, such as glucose transporters, hexokinase, pyruvate kinase M2, lactate dehydrogenase A, pyruvate dehydrogenase kinase, fatty acid synthase and glutaminase can enhance the efficacy of common therapeutic agents or overcome resistance to chemotherapy or radiotherapy.

  2. Therapeutic gold, silver, and platinum nanoparticles.

    PubMed

    Yamada, Miko; Foote, Matthew; Prow, Tarl W

    2015-01-01

    There are an abundance of nanoparticle technologies being developed for use as part of therapeutic strategies. This review focuses on a narrow class of metal nanoparticles that have therapeutic potential that is a consequence of elemental composition and size. The most widely known of these are gold nanoshells that have been developed over the last two decades for photothermal ablation in superficial cancers. The therapeutic effect is the outcome of the thickness and diameter of the gold shell that enables fine tuning of the plasmon resonance. When these metal nanoparticles are exposed to the relevant wavelength of light, their temperature rapidly increases. This in turn induces a localized photothermal ablation that kills the surrounding tumor tissue. Similarly, gold nanoparticles have been developed to enhance radiotherapy. The high-Z nature of gold dramatically increases the photoelectric cross-section. Thus, the photoelectric effects are significantly increased. The outcome of these interactions is enhanced tumor killing with lower doses of radiation, all while sparing tissue without gold nanoparticles. Silver nanoparticles have been used for their wound healing properties in addition to enhancing the tumor-killing effects of anticancer drugs. Finally, platinum nanoparticles are thought to serve as a reservoir for platinum ions that can induce DNA damage in cancer cells. The future is bright with the path to clinical trials is largely cleared for some of the less complex therapeutic metal nanoparticle systems.

  3. Hydration benefits to courtship feeding in crickets

    PubMed Central

    Ivy, T. M.; Johnson, J. C.; Sakaluk, S. K.

    1999-01-01

    The spermatophore transferred by male decorated crickets (Gryllodes sigillatus) at mating includes a large gelatinous spermatophylax that the female consumes after copulation. Although previous studies have shown that G. sigillatus females gain no nutritional benefits from consuming food gifts, there may be other benefits to their consumption. We examined potential hydration benefits to females by experimentally manipulating both the availability of water and the number of food gifts that females consumed, and by measuring their effect on female fitness. Analysis of the number of nymphs produced by females revealed a significant interaction between the number of spermatophylaxes consumed and water availability. When spermatophylaxes were not provided, females given water ad libitum produced significantly more nymphs than females subjected to water stress. Female longevity was significantly affected by water availability, with an increase in the availability of water corresponding to a significant increase in female longevity. These data suggest that female G. sigillatus accrue fitness benefits by consuming spermatophylaxes when alternative sources of water are unavailable. In addition, females appear to allocate water contained in spermatophylaxes towards reproduction as opposed to survival.

  4. Therapeutic Hypothermia in Spinal Cord Injury: The Status of Its Use and Open Questions

    PubMed Central

    Wang, Jiaqiong; Pearse, Damien D.

    2015-01-01

    Spinal cord injury (SCI) is a major health problem and is associated with a diversity of neurological symptoms. Pathophysiologically, dysfunction after SCI results from the culmination of tissue damage produced both by the primary insult and a range of secondary injury mechanisms. The application of hypothermia has been demonstrated to be neuroprotective after SCI in both experimental and human studies. The myriad of protective mechanisms of hypothermia include the slowing down of metabolism, decreasing free radical generation, inhibiting excitotoxicity and apoptosis, ameliorating inflammation, preserving the blood spinal cord barrier, inhibiting astrogliosis, promoting angiogenesis, as well as decreasing axonal damage and encouraging neurogenesis. Hypothermia has also been combined with other interventions, such as antioxidants, anesthetics, alkalinization and cell transplantation for additional benefit. Although a large body of work has reported on the effectiveness of hypothermia as a neuroprotective approach after SCI and its application has been translated to the clinic, a number of questions still remain regarding its use, including the identification of hypothermia’s therapeutic window, optimal duration and the most appropriate rewarming rate. In addition, it is necessary to investigate the neuroprotective effect of combining therapeutic hypothermia with other treatment strategies for putative synergies, particularly those involving neurorepair. PMID:26213924

  5. Statins: perspectives in cancer therapeutics.

    PubMed

    Corcos, Laurent; Le Jossic-Corcos, Catherine

    2013-10-01

    Virtually any cell type in a mammalian organism uses Acetyl CoA to yield mevalonate, through the activity of the 3-hydroxy-3-methyl-glutaryl-CoA reductase enzyme and, ultimately, cholesterol. Statins have long and quite successfully been used as cholesterol lowering drugs. They reversibly inhibit the 3-hydroxy-3-methyl-glutaryl-CoA reductase activity, which is rate limiting in the early steps of the cholesterol synthesis pathway. In addition to these effects, it has also been amply shown that statins may efficiently trigger cancer cell apoptosis, making them a plausible therapeutic option for the treatment of cancer. Whether statins may prevent cancer occurrence is a matter of debate and an unanswered question; undoubtedly experimental models have clearly demonstrated the potential of statins as direct cytotoxic agents, which can reduce tumour development or metastasis spread, even more so when combined with cytotoxic drugs. Until now, however, only few data in humans support the idea that statins could rightfully belong to the group of anticancer drugs. Nevertheless, as cancer cell metabolism is being thoroughly revisited, the mevalonate pathway has recently been reported as truly oncogenic, presenting the attractive possibility that mevalonate pathway inhibitors, such as statins, may join the ranks of anticancer drugs.

  6. Targeting microenvironment in cancer therapeutics

    PubMed Central

    Martin, Matthew; Wei, Han; Lu, Tao

    2016-01-01

    During development of a novel treatment for cancer patients, the tumor microenvironment and its interaction with the tumor cells must be considered. Aspects such as the extracellular matrix (ECM), the epithelial-mesenchymal transition (EMT), secreted factors, cancer-associated fibroblasts (CAFs), the host immune response, and tumor-associated microphages (TAM) are critical for cancer progression and metastasis. Additionally, signaling pathways such as the nuclear factor κB (NF-κB), transforming growth factor β (TGFβ), and tumor necrosis factor α (TNFα) can promote further cytokine release in the tumor environment, and impact tumor progression greatly. Importantly, cytokine overexpression has been linked to drug resistance in cancers and is therefore an attractive target for combinational therapies. Specific inhibitors of cytokines involved in signaling between tumor cells and the microenvironment have not been studied in depth and have great potential for use in personalized medicines. Together, the interactions between the microenvironment and tumors are critical for tumor growth and promotion and should be taken into serious consideration for future novel therapeutic approaches. PMID:27270649

  7. Polyimide processing additives

    NASA Technical Reports Server (NTRS)

    Fletcher, James C. (Inventor); Pratt, J. Richard (Inventor); St.clair, Terry L. (Inventor); Stoakley, Diane M. (Inventor); Burks, Harold D. (Inventor)

    1992-01-01

    A process for preparing polyimides having enhanced melt flow properties is described. The process consists of heating a mixture of a high molecular weight poly-(amic acid) or polyimide with a low molecular weight amic acid or imide additive in the range of 0.05 to 15 percent by weight of additive. The polyimide powders so obtained show improved processability, as evidenced by lower melt viscosity by capillary rheometry. Likewise, films prepared from mixtures of polymers with additives show improved processability with earlier onset of stretching by TMA.

  8. Polyimide processing additives

    NASA Technical Reports Server (NTRS)

    Pratt, J. Richard (Inventor); St.clair, Terry L. (Inventor); Stoakley, Diane M. (Inventor); Burks, Harold D. (Inventor)

    1993-01-01

    A process for preparing polyimides having enhanced melt flow properties is described. The process consists of heating a mixture of a high molecular weight poly-(amic acid) or polyimide with a low molecular weight amic acid or imide additive in the range of 0.05 to 15 percent by weight of the additive. The polyimide powders so obtained show improved processability, as evidenced by lower melt viscosity by capillary rheometry. Likewise, films prepared from mixtures of polymers with additives show improved processability with earlier onset of stretching by TMA.

  9. The Pharmaceutical Benefits Scheme 2003-2004.

    PubMed

    Harvey, Ken J

    2005-01-12

    The Pharmaceutical Benefits Scheme (PBS) grew by 8% in 2003-04; a slower rate than the 12.0% pa average growth over the last decade. Nevertheless, the sustainability of the Scheme remained an ongoing concern given an aging population and the continued introduction of useful (but increasingly expensive) new medicines. There was also concern that the Australia-United States Free Trade Agreement could place further pressure on the Scheme. In 2003, as in 2002, the government proposed a 27% increase in PBS patient co-payments and safety-net thresholds in order to transfer more of the cost of the PBS from the government to consumers. While this measure was initially blocked by the Senate, the forthcoming election resulted in the Labor Party eventually supporting this policy. Recommendations of the Pharmaceutical Benefits Advisory Committee to list, not list or defer a decision to list a medicine on the PBS were made publicly available for the first time and the full cost of PBS medicines appeared on medicine labels if the price was greater than the co-payment. Pharmaceutical reform in Victorian public hospitals designed to minimise PBS cost-shifting was evaluated and extended to other States and Territories. Programs promoting the quality use of medicines were further developed coordinated by the National Prescribing Service, Australian Divisions of General Practice and the Pharmacy Guild of Australia. The extensive uptake of computerised prescribing software by GPs produced benefits but also problems. The latter included pharmaceutical promotion occurring at the time of prescribing, failure to incorporate key sources of objective therapeutic information in the software and gross variation in the ability of various programs to detect important drug-drug interactions. These issues remain to be tackled.

  10. Food Additives and Hyperkinesis

    ERIC Educational Resources Information Center

    Wender, Ester H.

    1977-01-01

    The hypothesis that food additives are causally associated with hyperkinesis and learning disabilities in children is reviewed, and available data are summarized. Available from: American Medical Association 535 North Dearborn Street Chicago, Illinois 60610. (JG)

  11. Smog control fuel additives

    SciTech Connect

    Lundby, W.

    1993-06-29

    A method is described of controlling, reducing or eliminating, ozone and related smog resulting from photochemical reactions between ozone and automotive or industrial gases comprising the addition of iodine or compounds of iodine to hydrocarbon-base fuels prior to or during combustion in an amount of about 1 part iodine per 240 to 10,000,000 parts fuel, by weight, to be accomplished by: (a) the addition of these inhibitors during or after the refining or manufacturing process of liquid fuels; (b) the production of these inhibitors for addition into fuel tanks, such as automotive or industrial tanks; or (c) the addition of these inhibitors into combustion chambers of equipment utilizing solid fuels for the purpose of reducing ozone.

  12. Novel therapeutics in metastatic colorectal cancer: molecular insights and pharmacogenomic implications.

    PubMed

    Hanna, Diana L; Lenz, Heinz-Josef

    2016-08-01

    Although the survival of metastatic colorectal cancer (mCRC) patients has improved five-fold over the last century, CRC remains a significant global health burden. Impressive strides have been made in identifying new regimens, employing maintenance strategies to limit treatment toxicities, and combining multidisciplinary approaches to achieve cure in oligometastatic disease. Attempts at personalized integration of targeted agents have been limited by the ability to identify molecularly enriched patient populations most likely to benefit. In this review, we discuss novel therapeutics and regimens recently approved and in development for mCRC. In addition, we discuss using older agents in novel combination and maintenance strategies, and highlight evidence for implementing pharmacogenomic data and non-invasive monitoring into the personalized management of mCRC patients.

  13. On the TRAIL to successful cancer therapy? Predicting and counteracting resistance against TRAIL-based therapeutics

    PubMed Central

    Dimberg, Lina Y.; Anderson, Charles K.; Camidge, Ross; Behbakht, Kian; Thorburn, Andrew; Ford, Heide L.

    2015-01-01

    TRAIL and agonistic antibodies against TRAIL death receptors kill tumor cells while causing virtually no damage to normal cells. Several novel drugs targeting TRAIL receptors are currently in clinical trials. However, TRAIL resistance is a common obstacle in TRAIL based therapy and limits the efficiency of these drugs. In this review article we discuss different mechanisms of TRAIL resistance and how they can be predicted and therapeutically circumvented. In addition, we provide a brief overview of all TRAIL based clinical trials conducted so far. It is apparent that although the effects of TRAIL therapy are disappointingly modest overall, a small subset of patients responds very well to TRAIL. We argue that the true potential of targeting TRAIL death receptors in cancer can only be reached when we find efficient ways to select for those patients that are most likely to benefit from the treatment. To achieve this, it is crucial to identify biomarkers that can help us predict TRAIL sensitivity. PMID:22580613

  14. Therapeutic Devices for Epilepsy

    PubMed Central

    Fisher, Robert S.

    2011-01-01

    Therapeutic devices provide new options for treating drug-resistant epilepsy. These devices act by a variety of mechanisms to modulate neuronal activity. Only vagus nerve stimulation, which continues to develop new technology, is approved for use in the United States. Deep brain stimulation (DBS) of anterior thalamus for partial epilepsy recently was approved in Europe and several other countries. Responsive neurostimulation, which delivers stimuli to one or two seizure foci in response to a detected seizure, recently completed a successful multicenter trial. Several other trials of brain stimulation are in planning or underway. Transcutaneous magnetic stimulation (TMS) may provide a noninvasive method to stimulate cortex. Controlled studies of TMS split on efficacy, and may depend on whether a seizure focus is near a possible region for stimulation. Seizure detection devices in the form of “shake” detectors via portable accelerometers can provide notification of an ongoing tonic-clonic seizure, or peace of mind in the absence of notification. Prediction of seizures from various aspects of EEG is in early stages. Prediction appears to be possible in a subpopulation of people with refractory seizures and a clinical trial of an implantable prediction device is underway. Cooling of neocortex or hippocampus reversibly can attenuate epileptiform EEG activity and seizures, but engineering problems remain in its implementation. Optogenetics is a new technique that can control excitability of specific populations of neurons with light. Inhibition of epileptiform activity has been demonstrated in hippocampal slices, but use in humans will require more work. In general, devices provide useful palliation for otherwise uncontrollable seizures, but with a different risk profile than with most drugs. Optimizing the place of devices in therapy for epilepsy will require further development and clinical experience. PMID:22367987

  15. Mitochondrial diseases: therapeutic approaches.

    PubMed

    DiMauro, Salvatore; Mancuso, Michelangelo

    2007-06-01

    Therapy of mitochondrial encephalomyopathies (defined restrictively as defects of the mitochondrial respiratory chain) is woefully inadequate, despite great progress in our understanding of the molecular bases of these disorders. In this review, we consider sequentially several different therapeutic approaches. Palliative therapy is dictated by good medical practice and includes anticonvulsant medication, control of endocrine dysfunction, and surgical procedures. Removal of noxious metabolites is centered on combating lactic acidosis, but extends to other metabolites. Attempts to bypass blocks in the respiratory chain by administration of electron acceptors have not been successful, but this may be amenable to genetic engineering. Administration of metabolites and cofactors is the mainstay of real-life therapy and is especially important in disorders due to primary deficiencies of specific compounds, such as carnitine or coenzyme Q10. There is increasing interest in the administration of reactive oxygen species scavengers both in primary mitochondrial diseases and in neurodegenerative diseases directly or indirectly related to mitochondrial dysfunction. Aerobic exercise and physical therapy prevent or correct deconditioning and improve exercise tolerance in patients with mitochondrial myopathies due to mitochondrial DNA (mtDNA) mutations. Gene therapy is a challenge because of polyplasmy and heteroplasmy, but interesting experimental approaches are being pursued and include, for example, decreasing the ratio of mutant to wild-type mitochondrial genomes (gene shifting), converting mutated mtDNA genes into normal nuclear DNA genes (allotopic expression), importing cognate genes from other species, or correcting mtDNA mutations with specific restriction endonucleases. Germline therapy raises ethical problems but is being considered for prevention of maternal transmission of mtDNA mutations. Preventive therapy through genetic counseling and prenatal diagnosis is

  16. Benefits of Suffering: Communicator Suffering. Benefiting, and Influence.

    DTIC Science & Technology

    1980-07-01

    political figures such as Ghandl or Mao have become almost legendary. Of particular interest is that this suffering has generally preceded the leader’s...Method Subjects One hundred and sixty introductory psychology students at Purdue Benefits of Suffering 6 University participated in the study in...observed Benefits of Suffering 13 effects. STUDY 2 Method Subjects One hundred and sixty eight introductory psychology students at Purdue University

  17. The Evolution of Therapeutic Recreation.

    ERIC Educational Resources Information Center

    Riley, Bob; Skalko, Thomas K.

    1998-01-01

    Reviews elements that impact the delivery of therapeutic recreation services, emphasizing elements that are external to the discipline and influence practice and elements that are internal to the discipline and must be addressed if therapeutic recreation is to continue its evolution as a competitive health and human service discipline.…

  18. Toward Constructing the Therapeutic System.

    ERIC Educational Resources Information Center

    Andolfi, Maurizio; Angelo, Claudio

    1988-01-01

    Describes the therapist as an active participant in the construction of the therapeutic system, explaining how the therapist constructs complex relationships within the evolving therapeutic process. Reevaluates the importance of the individual in the family as an agent of change and as a mediator of triangular relational messages. (Author/NB)

  19. Benefit adequacy among elderly Social Security retired-worker beneficiaries and the SSI federal benefit rate.

    PubMed

    Rupp, Kalman; Strand, Alexander; Davies, Paul; Sears, Jim

    2007-01-01

    administrative simplicity behind these screening errors also results in additional program cost that may be perceived as substantial. We estimate that an FBR-level minimum benefit would increase aggregate program cost for retired workers aged 65 or older by roughly 2 percent. There are two fundamental reasons for these findings. First, the concept of an FBR-level minimum benefit looks at the individual or married couple in artificial isolation; however, the family is the main consumption unit in our society. The income of an unmarried partner or family members other than a married spouse is ignored. Second, individuals and couples may also have income from sources other than Social Security or SSI, which is also ignored by a simple FBR-based minimum benefit concept. The substantial empirical magnitude of measurement error arising from these conceptual simplifications naturally leads to the assessment of the tradeoff between target effectiveness and administrative simplicity. To facilitate this analysis, we simulate the potential effect of alternative screening methods designed to increase target effectiveness; while reducing program cost, such alternatives also may increase administrative complexity. For example, considering the combined Social Security benefit of a married couple (rather than looking at the husband and wife in isolation) might substantially increase target effectiveness with a relatively small increase in administrative complexity. Adding a family income screen might increase administrative complexity to a greater degree, but also would increase target effectiveness dramatically. The results also suggest that at some point adding new screens-such as a comprehensive asset test-may drastically increase administrative complexity with diminishing returns in terms of increased target effectiveness and reduced program cost. Whether a broad-based minimum benefit concept that is not tied to previous work experience is perceived by policymakers as desirable or not may

  20. The benefits of mobile communications

    NASA Astrophysics Data System (ADS)

    1985-04-01

    The benefits offered by mobile communications facilities are compared to conventionally priced networks. Sweden, the UK and Eire were taken as examples of markets that are respectively leading, growing and restrictive. The three major benefits identified are higher profits for commercial organizations from cost savings and improved productivity, the prevention and minimization of damage to life and property, and better social contacts for people isolated from communities. Case studies provide examples of the benefits different occupational and social groups acquire from mobile communications in each country. The studies were also used to project future growth in the uptake and range of mobile communications facilities offered in each country.

  1. Potential Benefits of Commissioning California Homes

    SciTech Connect

    Matson, Nance; Wray, Craig; Walker, Iain; Sherman, Max

    2002-01-01

    Commissioning California's houses can result in better performing systems and houses. In turn, this will result in more efficient use of energy, carbon emission reductions, and improved occupant comfort. In particular, commissioning houses can save a significant amount of HVAC-related energy (15 to 30% in existing houses, 10 to 20% in new conventional houses, and up to 8% in advanced energy efficiency houses). The process that we considered includes corrective measures that could be implemented together during construction or during a single site visit (e.g., air tightening, duct sealing, and refrigerant and air handler airflow corrections in a new or existing house). Taking advantage of additional, more complex opportunities (e.g., installing new windows in an existing house, replacing the heating and air conditioning system in a new or existing house) can result in additional HVAC-related energy savings (60 to 75% in existing houses, and 50 to 60% in new conventional houses). The commissioning-related system and house performance improvements and energy savings translate to additional benefits throughout California and beyond. By applying commissioning principles to their work, the building community (builders and contractors) benefit from reduced callbacks and lower warranty costs. HERS raters and inspectors will have access to an expanded market sector. As the commissioning process rectifies construction defects and code problems, building code officials benefit from better compliance with codes. The utilities benefit from reduced peak demand, which can translate into lower energy acquisition costs. As houses perform closer to expectations, governmental bodies (e.g., the California Energy Commission and the Air Resources Board) benefit from greater assurance that actual energy consumption and carbon emissions are closer to the levels mandated in codes and standards, resulting in better achievement of state energy conservation and environmental goals. California

  2. Metrics for antibody therapeutics development.

    PubMed

    Reichert, Janice M

    2010-01-01

    A wide variety of full-size monoclonal antibodies (mAbs) and therapeutics derived from alternative antibody formats can be produced through genetic and biological engineering techniques. These molecules are now filling the preclinical and clinical pipelines of every major pharmaceutical company and many biotechnology firms. Metrics for the development of antibody therapeutics, including averages for the number of candidates entering clinical study and development phase lengths for mAbs approved in the United States, were derived from analysis of a dataset of over 600 therapeutic mAbs that entered clinical study sponsored, at least in part, by commercial firms. The results presented provide an overview of the field and context for the evaluation of on-going and prospective mAb development programs. The expansion of therapeutic antibody use through supplemental marketing approvals and the increase in the study of therapeutics derived from alternative antibody formats are discussed.

  3. Bacteriophage Procurement for Therapeutic Purposes

    PubMed Central

    Weber-Dąbrowska, Beata; Jończyk-Matysiak, Ewa; Żaczek, Maciej; Łobocka, Małgorzata; Łusiak-Szelachowska, Marzanna; Górski, Andrzej

    2016-01-01

    Bacteriophages (phages), discovered 100 years ago, are able to infect and destroy only bacterial cells. In the current crisis of antibiotic efficacy, phage therapy is considered as a supplementary or even alternative therapeutic approach. Evolution of multidrug-resistant and pandrug-resistant bacterial strains poses a real threat, so it is extremely important to have the possibility to isolate new phages for therapeutic purposes. Our phage laboratory and therapy center has extensive experience with phage isolation, characterization, and therapeutic application. In this article we present current progress in bacteriophages isolation and use for therapeutic purposes, our experience in this field and its practical implications for phage therapy. We attempt to summarize the state of the art: properties of phages, the methods for their isolation, criteria of phage selection for therapeutic purposes and limitations of their use. Perspectives for the use of genetically engineered phages to specifically target bacterial virulence-associated genes are also briefly presented. PMID:27570518

  4. Pharmacokinetic and pharmacodynamic considerations for the next generation protein therapeutics

    PubMed Central

    Shah, Dhaval K.

    2015-01-01

    Increasingly sophisticated protein engineering efforts have been undertaken lately to generate protein therapeutics with desired properties. This has resulted in the discovery of the next generation of protein therapeutics, which include: engineered antibodies, immunoconjugates, bi/multi-specific proteins, antibody mimetic novel scaffolds, and engineered ligands/receptors. These novel protein therapeutics possess unique physicochemical properties and act via a unique mechanism-of-action, which collectively makes their pharmacokinetics (PK) and pharmacodynamics (PD) different than other established biological molecules. Consequently, in order to support the discovery and development of these next generation molecules, it becomes important to understand the determinants controlling their PK/PD. This review discusses the determinants that a PK/PD scientist should consider during the design and development of next generation protein therapeutics. In addition, the role of systems PK/PD models in enabling rational development of the next generation protein therapeutics is emphasized. PMID:26373957

  5. Pharmacokinetic and pharmacodynamic considerations for the next generation protein therapeutics.

    PubMed

    Shah, Dhaval K

    2015-10-01

    Increasingly sophisticated protein engineering efforts have been undertaken lately to generate protein therapeutics with desired properties. This has resulted in the discovery of the next generation of protein therapeutics, which include: engineered antibodies, immunoconjugates, bi/multi-specific proteins, antibody mimetic novel scaffolds, and engineered ligands/receptors. These novel protein therapeutics possess unique physicochemical properties and act via a unique mechanism-of-action, which collectively makes their pharmacokinetics (PK) and pharmacodynamics (PD) different than other established biological molecules. Consequently, in order to support the discovery and development of these next generation molecules, it becomes important to understand the determinants controlling their PK/PD. This review discusses the determinants that a PK/PD scientist should consider during the design and development of next generation protein therapeutics. In addition, the role of systems PK/PD models in enabling rational development of the next generation protein therapeutics is emphasized.

  6. Novel therapeutic strategies using hypomethylating agents in the treatment of myelodysplastic syndrome.

    PubMed

    Ishikawa, Takayuki

    2014-02-01

    Myelodysplastic syndrome (MDS) is a clonal hematopoietic neoplasm with high rates of leukemic transformation. MDS had been an intractable disease for which the mainstream of therapeutic approach was best supportive care. Recently, however, treatment of hematological malignancies has benefited from advances in molecular targeted drug discovery such as the revolutionary drug imatinib for chronic myeloid leukemia, and from the reappraisal of forgotten drugs such as thalidomide for multiple myeloma. Two azanucleotide drugs, azacitidine (AZA) and decitabine, were created as anti-neoplastic drugs in the 1960s with little success. In the 1980s, they were reassessed as hypomethylating agents (HMAs), and the introduction of low-dose schedules of them has shown dramatic effects in the delay of leukemic evolution for high-risk MDS. AZA was approved in Japan in March 2011 and has become a standard drug of choice in the treatment of high-risk MDS. Its position as a treatment for low-risk MDS remains to be established. Only half of patients with high-risk MDS can gain benefit from AZA. For example, those with complex karyotypes experience only a limited extension in survival. In addition, AZA resistance develops sooner or later. To achieve a more sustained disease control of high-risk MDS, the combined use of HMAs with other therapeutic approaches will be inevitable. Clinical trials of histone deacetylase inhibitors, lenalidomide, thrombopoietin agonists, or anticancer drugs in combination with HMAs are ongoing. In addition, HMAs are being used as a bridging therapy prior to allogeneic stem cell transplantation (AHSCT) and the salvage therapy of relapsed disease after AHSCT. Thus, HMAs will continue to be key drugs for the management of MDS.

  7. Novel small molecule therapeutics in rheumatoid arthritis.

    PubMed

    Kelly, Victoria; Genovese, Mark

    2013-07-01

    A new wave of emerging therapies for the treatment of autoimmune and inflammatory diseases is under development. These therapies interrupt intracellular signalling through kinase inhibition. By interrupting one or more kinases it is possible to modulate the function of cellular structures such as surface receptors, signalling proteins and transcription of nuclear proteins and thus influence the behaviour of the cell types targeted. With these advances comes the significant potential to develop highly effective orally bioavailable therapeutics. The targets generating the greatest enthusiasm at this time for the treatment of autoimmune and inflammatory diseases include Janus-associated kinase, spleen tyrosine kinase, phosphodiesterase-4, Bruton's tyrosine kinase and phosphatidylinositol-3 kinase. Ultimately human trials will help us understand the potential risks and benefits of these novel approaches across a number of diseases.

  8. Inflammation and therapeutic vaccination in CNS diseases

    NASA Astrophysics Data System (ADS)

    Weiner, Howard L.; Selkoe, Dennis J.

    2002-12-01

    The spectrum of inflammatory diseases of the central nervous system has been steadily expanding from classical autoimmune disorders such as multiple sclerosis to far more diverse diseases. Evidence now suggests that syndromes such as Alzheimer's disease and stroke have important inflammatory and immune components and may be amenable to treatment by anti-inflammatory and immunotherapeutic approaches. The notion of 'vaccinating' individuals against a neurodegenerative disorder such as Alzheimer's disease is a marked departure from classical thinking about mechanism and treatment, and yet therapeutic vaccines for both Alzheimer's disease and multiple sclerosis have been validated in animal models and are in the clinic. Such approaches, however, have the potential to induce unwanted inflammatory responses as well as to provide benefit.

  9. Garlic: a review of potential therapeutic effects

    PubMed Central

    Bayan, Leyla; Koulivand, Peir Hossain; Gorji, Ali

    2014-01-01

    Throughout history, many different cultures have recognized the potential use of garlic for prevention and treatment of different diseases. Recent studies support the effects of garlic and its extracts in a wide range of applications. These studies raised the possibility of revival of garlic therapeutic values in different diseases. Different compounds in garlic are thought to reduce the risk for cardiovascular diseases, have anti-tumor and anti-microbial effects, and show benefit on high blood glucose concentration. However, the exact mechanism of all ingredients and their long-term effects are not fully understood. Further studies are needed to elucidate the pathophysiological mechanisms of action of garlic as well as its efficacy and safety in treatment of various diseases. PMID:25050296

  10. Group Sparse Additive Models

    PubMed Central

    Yin, Junming; Chen, Xi; Xing, Eric P.

    2016-01-01

    We consider the problem of sparse variable selection in nonparametric additive models, with the prior knowledge of the structure among the covariates to encourage those variables within a group to be selected jointly. Previous works either study the group sparsity in the parametric setting (e.g., group lasso), or address the problem in the nonparametric setting without exploiting the structural information (e.g., sparse additive models). In this paper, we present a new method, called group sparse additive models (GroupSpAM), which can handle group sparsity in additive models. We generalize the ℓ1/ℓ2 norm to Hilbert spaces as the sparsity-inducing penalty in GroupSpAM. Moreover, we derive a novel thresholding condition for identifying the functional sparsity at the group level, and propose an efficient block coordinate descent algorithm for constructing the estimate. We demonstrate by simulation that GroupSpAM substantially outperforms the competing methods in terms of support recovery and prediction accuracy in additive models, and also conduct a comparative experiment on a real breast cancer dataset.

  11. Additive Manufacturing Infrared Inspection

    NASA Technical Reports Server (NTRS)

    Gaddy, Darrell

    2014-01-01

    Additive manufacturing is a rapid prototyping technology that allows parts to be built in a series of thin layers from plastic, ceramics, and metallics. Metallic additive manufacturing is an emerging form of rapid prototyping that allows complex structures to be built using various metallic powders. Significant time and cost savings have also been observed using the metallic additive manufacturing compared with traditional techniques. Development of the metallic additive manufacturing technology has advanced significantly over the last decade, although many of the techniques to inspect parts made from these processes have not advanced significantly or have limitations. Several external geometry inspection techniques exist such as Coordinate Measurement Machines (CMM), Laser Scanners, Structured Light Scanning Systems, or even traditional calipers and gages. All of the aforementioned techniques are limited to external geometry and contours or must use a contact probe to inspect limited internal dimensions. This presentation will document the development of a process for real-time dimensional inspection technique and digital quality record of the additive manufacturing process using Infrared camera imaging and processing techniques.

  12. [Air humidifier--benefit or risk?].

    PubMed

    Fidler, A H

    1989-12-01

    Indoor air pollution has become an issue of growing importance for the scientific community. A recent publication of a report of the US Environmental Protection Agency (EPA) showed evidence that portable ultrasonic humidifiers may play a significant role as health hazards as far as indoor air pollution with heavy metal particles is concerned. Especially if the manufacturers' guidelines are not followed strictly and the device is operated with tap water, indoor particle concentrations may reach up to 50 times US outdoor standards for toxic particle concentration. This paper highlights potential risks and benefits of various types of humidifiers, both in private and hospital settings, emphasizing that risks of air humidification in certain situations might outweigh anticipated benefits. The health policy implication of these findings should lead to a more critical application of air humidification in the health care environment and in addition to that, promote better information of the customer about safe operation and useful indications of such devices.

  13. 20 CFR 416.263 - No additional application needed.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false No additional application needed. 416.263 Section 416.263 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SUPPLEMENTAL SECURITY INCOME FOR THE AGED, BLIND, AND DISABLED Eligibility Special Provisions for People Who Work Despite A...

  14. Benefits of Green Power Partnership

    EPA Pesticide Factsheets

    The U.S. EPA's Green Power Partnership is a voluntary partnership program designed to reduce the environmental impact of electricity generation by promoting renewable energy. Learn about the benefits of becoming a Green Power Partner.

  15. Employee Benefit Reporting After ERISA

    ERIC Educational Resources Information Center

    Steen, Wesley W.

    1976-01-01

    The statutory reporting requirements of ERISA and some of the regulations recently promulgated are discussed. All type of employee benefit plans are covered. For journal availability see HE 508 741. (LBH)

  16. Phenylethynyl Containing Reactive Additives

    NASA Technical Reports Server (NTRS)

    Connell, John W. (Inventor); Smith, Joseph G., Jr. (Inventor); Hergenrother, Paul M. (Inventor)

    2002-01-01

    Phenylethynyl containing reactive additives were prepared from aromatic diamine, containing phenylethvnvl groups and various ratios of phthalic anhydride and 4-phenylethynviphthalic anhydride in glacial acetic acid to form the imide in one step or in N-methyl-2-pvrrolidinone to form the amide acid intermediate. The reactive additives were mixed in various amounts (10% to 90%) with oligomers containing either terminal or pendent phenylethynyl groups (or both) to reduce the melt viscosity and thereby enhance processability. Upon thermal cure, the additives react and become chemically incorporated into the matrix and effect an increase in crosslink density relative to that of the host resin. This resultant increase in crosslink density has advantageous consequences on the cured resin properties such as higher glass transition temperature and higher modulus as compared to that of the host resin.

  17. Fused Lasso Additive Model

    PubMed Central

    Petersen, Ashley; Witten, Daniela; Simon, Noah

    2016-01-01

    We consider the problem of predicting an outcome variable using p covariates that are measured on n independent observations, in a setting in which additive, flexible, and interpretable fits are desired. We propose the fused lasso additive model (FLAM), in which each additive function is estimated to be piecewise constant with a small number of adaptively-chosen knots. FLAM is the solution to a convex optimization problem, for which a simple algorithm with guaranteed convergence to a global optimum is provided. FLAM is shown to be consistent in high dimensions, and an unbiased estimator of its degrees of freedom is proposed. We evaluate the performance of FLAM in a simulation study and on two data sets. Supplemental materials are available online, and the R package flam is available on CRAN. PMID:28239246

  18. Phenylethynyl Containing Reactive Additives

    NASA Technical Reports Server (NTRS)

    Connell, John W. (Inventor); Smith, Joseph G., Jr. (Inventor); Hergenrother, Paul M. (Inventor)

    2002-01-01

    Phenylethynyl containing reactive additives were prepared from aromatic diamines containing phenylethynyl groups and various ratios of phthalic anhydride and 4-phenylethynylphthalic anhydride in glacial acetic acid to form the imide in one step or in N-methyl-2-pyrrolidi none to form the amide acid intermediate. The reactive additives were mixed in various amounts (10% to 90%) with oligomers containing either terminal or pendent phenylethynyl groups (or both) to reduce the melt viscosity and thereby enhance processability. Upon thermal cure, the additives react and become chemically incorporated into the matrix and effect an increase in crosslink density relative to that of the host resin. This resultant increase in crosslink density has advantageous consequences on the cured resin properties such as higher glass transition temperature and higher modulus as compared to that of the host resin.

  19. Therapeutics for alcoholism: what's the future?

    PubMed

    Lawrence, Andrew J

    2007-01-01

    As with other addictions, human alcoholism is characterised as a chronically relapsing condition. Consequently, the therapeutic goal is the development of clinically effective, safe drugs that promote high adherence rates and prevent relapse. These products can then be used in conjunction with psychosocial approaches. In this review, preclinical studies are highlighted that indicate the mechanism of action of currently used anti-craving medications or demonstrate the potential of novel pharmacological agents for the treatment of alcohol use disorders. While current pharmacological strategies are far from ideal, there are a number of candidate molecules that may ultimately be developed into therapeutic agents. In addition, prescribing clinicians should also consider strategies such as combinations of various drugs to aid in the regulation of aberrant alcohol consumption.

  20. Additives in plastics.

    PubMed Central

    Deanin, R D

    1975-01-01

    The polymers used in plastics are generally harmless. However, they are rarely used in pure form. In almost all commercial plastics, they are "compounded" with monomeric ingredients to improve their processing and end-use performance. In order of total volume used, these monomeric additives may be classified as follows: reinforcing fibers, fillers, and coupling agents; plasticizers; colorants; stabilizers (halogen stabilizers, antioxidants, ultraviolet absorbers, and biological preservatives); processing aids (lubricants, others, and flow controls); flame retardants, peroxides; and antistats. Some information is already available, and much more is needed, on potential toxicity and safe handling of these additives during processing and manufacture of plastics products. PMID:1175566

  1. Additives in plastics.

    PubMed

    Deanin, R D

    1975-06-01

    The polymers used in plastics are generally harmless. However, they are rarely used in pure form. In almost all commercial plastics, they are "compounded" with monomeric ingredients to improve their processing and end-use performance. In order of total volume used, these monomeric additives may be classified as follows: reinforcing fibers, fillers, and coupling agents; plasticizers; colorants; stabilizers (halogen stabilizers, antioxidants, ultraviolet absorbers, and biological preservatives); processing aids (lubricants, others, and flow controls); flame retardants, peroxides; and antistats. Some information is already available, and much more is needed, on potential toxicity and safe handling of these additives during processing and manufacture of plastics products.

  2. [Procedures and methods of benefit assessments for medicines in Germany].

    PubMed

    Bekkering, G E; Kleijnen, J

    2008-12-01

    comparison with other medicines and treatment forms under consideration of the additional therapeutic benefit for the patients. 3. The minimum criteria for assessing patient benefit are improvements in the state of health, shortening the duration of illness, extension of the duration of life, reduction of side effects and improvements in quality of life. EBM refers to the application of the best available evidence to answer a research question, which can inform questions about the care of patients. The optimal design, even for effectiveness questions, is not always the randomised, controlled trial (RCT) but depends on the research question and the outcomes of interest. To increase transparency for each question, the levels of evidence examined should be made explicit. There is no empirical evidence to support the use of cutoff points with respect to the number of studies before making recommendations. To get the best available evidence for the research question(s), all relevant evidence should be considered for each question, and the best available evidence should be used to answer the question. Separate levels of evidence may have to be used for each outcome. There are many ways in which bias can be introduced in systematic reviews. Some types of bias can be prevented, other types can only be reported and, for some, the influence of the bias can be investigated. Reviews must show that potential sources of bias have been dealt with adequately. Methods used by other agencies that perform benefit assessments are useful to interpret the term 'international standards' to which the institute must comply. The National Institute for Health and Clinical Excellence (NICE) is a good example in this respect. NICE shows that it is possible to have transparent procedures for benefit assessments but that this requires detailed documentation. NICE has implemented an open procedure with respect to the comments of reviewers, which makes the procedure transparent. Although the Institute for

  3. Food biotechnology: benefits and concerns.

    PubMed

    Falk, Michael C; Chassy, Bruce M; Harlander, Susan K; Hoban, Thomas J; McGloughlin, Martina N; Akhlaghi, Amin R

    2002-06-01

    Recent advances in agricultural biotechnology have highlighted the need for experimental evidence and sound scientific judgment to assess the benefits and risks to society. Nutrition scientists and other animal biologists need a balanced understanding of the issues to participate in this assessment. To date most modifications to crop plants have benefited producers. Crops have been engineered to decrease pesticide and herbicide usage, protect against stressors, enhance yields and extend shelf life. Beyond the environmental benefits of decreased pesticide and herbicide application, consumers stand to benefit by development of food crops with increased nutritional value, medicinal properties, enhanced taste and esthetic appeal. There remains concern that these benefits come with a cost to the environment or increased risk to the consumer. Most U.S. consumers are not aware of the extent that genetically modified foods have entered the marketplace. Consumer awareness of biotechnology seems to have increased over the last decade, yet most consumers remain confused over the science. Concern over the impact on the safety of the food supply remains low in the United States, but is substantially elevated in Europe. Before a genetically engineered crop is introduced into commerce it must pass regulatory scrutiny by as many as four different federal regulatory bodies to ensure a safe food supply and minimize the risk to the environment. Key areas for more research are evaluation of the nutritional benefits of new crops, further investigation of the environmental impact, and development of better techniques to identify and track genetically engineered products.

  4. Macrophage differentiation and function in atherosclerosis; opportunities for therapeutic intervention?

    PubMed Central

    Williams, Howell J.; Fisher, Edward A.; Greaves, David R.

    2013-01-01

    The macrophage is exquisitely sensitive to its microenvironment, as demonstrated primarily through in vitro study. Changes in macrophage phenotype and function within the atherosclerotic plaque have profound consequences for plaque biology, including rupture and arterial thrombosis leading to clinical events such as myocardial infarction. We review the evidence for dynamic changes in macrophage numbers and macrophage differentiation within the atherosclerotic plaque microenvironment and discuss potential approaches to target macrophage differentiation for therapeutic benefit in cardiovascular disease. PMID:22572544

  5. Therapeutic Modulation of Gut Microbiota in Functional Bowel Disorders

    PubMed Central

    Lee, Hyo Jeong; Choi, Jong Kyoung; Ryu, Han Seung; Choi, Chang Hwan; Kang, Eun Hee; Park, Kyung Sik; Min, Yang Won; Hong, Kyoung Sup

    2017-01-01

    Functional bowel disorders (FBDs) are functional gastrointestinal disorders with symptoms attributable to the middle or lower gastrointestinal tract. These include irritable bowel syndrome, functional bloating, functional constipation, functional diarrhea, and unspecified FBD. Increasing evidence has emerged of late that intestinal microbiota is involved in the pathogenesis of FBDs. In this review, the therapeutic benefits and future perspectives of the currently available strategies for modifying the gut microbiota in FBDs are described, focusing primarily on irritable bowel syndrome and functional constipation. PMID:28049862

  6. Medical decision support systems and therapeutics: The role of autopilots.

    PubMed

    Woosley, R L; Whyte, J; Mohamadi, A; Romero, K

    2016-02-01

    For decades, medical practice has increasingly relied on prescription medicines to treat, cure, or prevent illness but their net benefit is reduced by prescribing errors that result in adverse drug reactions (ADRs) and tens of thousands of deaths each year. Optimal prescribing requires effective management of massive amounts of data. Clinical decision support systems (CDSS) can help manage information and support optimal therapeutic decisions before errors are made by operating as the prescribers' "autopilot."

  7. Community Health Care: Therapeutic Opportunities in the Human Microbiome

    PubMed Central

    Sonnenburg, Justin L.; Fischbach, Michael A.

    2012-01-01

    We are never alone. Humans coexist with diverse microbial species that live within and upon us—our so-called microbiota. It is now clear that this microbial community is essentially another organ that plays a fundamental role in human physiology and disease. Basic and translational research efforts have begun to focus on deciphering mechanisms of microbiome function—and learning how to manipulate it to benefit human health. In this Perspective, we discuss therapeutic opportunities in the human microbiome. PMID:21490274

  8. Therapeutic Modulation of Gut Microbiota in Functional Bowel Disorders.

    PubMed

    Lee, Hyo Jeong; Choi, Jong Kyoung; Ryu, Han Seung; Choi, Chang Hwan; Kang, Eun Hee; Park, Kyung Sik; Min, Yang Won; Hong, Kyoung Sup

    2017-01-30

    Functional bowel disorders (FBDs) are functional gastrointestinal disorders with symptoms attributable to the middle or lower gastrointestinal tract. These include irritable bowel syndrome, functional bloating, functional constipation, functional diarrhea, and unspecified FBD. Increasing evidence has emerged of late that intestinal microbiota is involved in the pathogenesis of FBDs. In this review, the therapeutic benefits and future perspectives of the currently available strategies for modifying the gut microbiota in FBDs are described, focusing primarily on irritable bowel syndrome and functional constipation.

  9. Overview of Therapeutic Ultrasound Applications and Safety Considerations

    PubMed Central

    Miller, Douglas; Smith, Nadine; Bailey, Michael; Czarnota, Gregory; Hynynen, Kullervo; Makin, Inder

    2013-01-01

    Summary Applications of ultrasound in medicine for therapeutic purposes have been an accepted and beneficial use of ultrasonic biological effects for many years. Low power ultrasound of about 1 MHz frequency has been widely applied since the 1950s for physical therapy in conditions such as tendinitis or bursitis. In the 1980s, high pressure-amplitude shockwaves came into use for mechanically resolving kidney stones, and “lithotripsy” rapidly replaced surgery as the most frequent treatment choice. The use of ultrasonic energy for therapy continues to expand, and approved applications now include uterine fibroid ablation, cataract removal (phacoemulsification), surgical tissue cutting and hemostasis, transdermal drug delivery, and bone fracture healing, among others. Undesirable bioeffects can occur including burns for thermal-based therapies and significant hemorrhage for mechanical-based therapies (e. g. lithotripsy). In all these therapeutic applications for bioeffects of ultrasound, standardization, ultrasound dosimetry, benefits assurance and side-effects risk minimization must be carefully considered in order to insure an optimal benefit to risk ratio for the patient. Therapeutic ultrasound typically has well-defined benefits and risks, and therefore presents a tractable safety problem to the clinician. However, safety information can be scattered, confusing or subject to commercial conflict of interest. Of paramount importance for managing this problem is the communication of practical safety information by authoritative groups, such as the AIUM, to the medical ultrasound community. In this overview, the Bioeffects Committee outlines the wide range of therapeutic ultrasound methods, which are in clinical use or under study, and provides general guidance for assuring therapeutic ultrasound safety. PMID:22441920

  10. Overview of therapeutic ultrasound applications and safety considerations.

    PubMed

    Miller, Douglas L; Smith, Nadine B; Bailey, Michael R; Czarnota, Gregory J; Hynynen, Kullervo; Makin, Inder Raj S

    2012-04-01

    Applications of ultrasound in medicine for therapeutic purposes have been accepted and beneficial uses of ultrasonic biological effects for many years. Low-power ultrasound of about 1 MHz has been widely applied since the 1950s for physical therapy in conditions such as tendinitis and bursitis. In the 1980s, high-pressure-amplitude shock waves came into use for mechanically resolving kidney stones, and "lithotripsy" rapidly replaced surgery as the most frequent treatment choice. The use of ultrasonic energy for therapy continues to expand, and approved applications now include uterine fibroid ablation, cataract removal (phacoemulsification), surgical tissue cutting and hemostasis, transdermal drug delivery, and bone fracture healing, among others. Undesirable bioeffects can occur, including burns from thermal-based therapies and severe hemorrhage from mechanical-based therapies (eg, lithotripsy). In all of these therapeutic applications of ultrasound bioeffects, standardization, ultrasound dosimetry, benefits assurance, and side-effect risk minimization must be carefully considered to ensure an optimal benefit to risk ratio for the patient. Therapeutic ultrasound typically has well-defined benefits and risks and therefore presents a manageable safety problem to the clinician. However, safety information can be scattered, confusing, or subject to commercial conflicts of interest. Of paramount importance for managing this problem is the communication of practical safety information by authoritative groups, such as the American Institute of Ultrasound in Medicine, to the medical ultrasound community. In this overview, the Bioeffects Committee of the American Institute of Ultrasound in Medicine outlines the wide range of therapeutic ultrasound methods, which are in clinical use or under study, and provides general guidance for ensuring therapeutic ultrasound safety.

  11. Personalized Therapeutic Cocktail of Wild Environmental Phages Rescues Mice from Acinetobacter baumannii Wound Infections

    PubMed Central

    Regeimbal, James M.; Jacobs, Anna C.; Corey, Brendan W.; Henry, Matthew S.; Thompson, Mitchell G.; Pavlicek, Rebecca L.; Quinones, Javier; Hannah, Ryan M.; Ghebremedhin, Meron; Crane, Nicole J.; Zurawski, Daniel V.; Teneza-Mora, Nimfa C.; Hall, Eric R.

    2016-01-01

    Multidrug-resistant bacterial pathogens are an increasing threat to public health, and lytic bacteriophages have reemerged as a potential therapeutic option. In this work, we isolated and assembled a five-member cocktail of wild phages against Acinetobacter baumannii and demonstrated therapeutic efficacy in a mouse full-thickness dorsal infected wound model. The cocktail lowers the bioburden in the wound, prevents the spread of infection and necrosis to surrounding tissue, and decreases infection-associated morbidity. Interestingly, this effective cocktail is composed of four phages that do not kill the parent strain of the infection and one phage that simply delays bacterial growth in vitro via a strong but incomplete selection event. The cocktail here appears to function in a combinatorial manner, as one constituent phage targets capsulated A. baumannii bacteria and selects for loss of receptor, shifting the population to an uncapsulated state that is then sensitized to the remaining four phages in the cocktail. Additionally, capsule is a known virulence factor for A. baumannii, and we demonstrated that the emergent uncapsulated bacteria are avirulent in a Galleria mellonella model. These results highlight the importance of anticipating population changes during phage therapy and designing intelligent cocktails to control emergent strains, as well as the benefits of using phages that target virulence factors. Because of the efficacy of this cocktail isolated from a limited environmental pool, we have established a pipeline for developing new phage therapeutics against additional clinically relevant multidrug-resistant pathogens by using environmental phages sourced from around the globe. PMID:27431214

  12. Historical review: Cytokines as therapeutics and targets of therapeutics.

    PubMed

    Vilcek, Jan; Feldmann, Marc

    2004-04-01

    Cytokine research has spawned the introduction of new therapies that have revolutionized the treatment of many important diseases. These therapeutic advances have resulted from two very different strategies. The first therapeutic strategy embodies the administration of purified, recombinant cytokines. The second relies on the administration of therapeutics that inhibit the harmful effects of upregulated, endogenous cytokines. Examples of successful cytokine therapeutics include hematopoietic growth factors (colony stimulating factors) and interferons. Prime examples of cytokine antagonists that have profoundly altered the treatment of some inflammatory disorders are agents that inhibit the effects of tumor necrosis factor (TNF). In this article, we highlight some of the studies that have been responsible for the introduction of cytokine and anti-cytokine therapies, with emphasis on the development of interferons and anti-TNF agents.

  13. More Than Additional Space...

    ERIC Educational Resources Information Center

    CEFP Journal, 1973

    1973-01-01

    A much needed addition to the Jamestown Elementary School turned out to be more than an expansion of walls for more space. A new educational program, a limited budget, and a short time line were tackled on a team approach basis and were successfully resolved. (Author)

  14. The social dimensions of therapeutic horticulture.

    PubMed

    Harris, Holly

    2017-02-22

    Harnessing nature to promote mental health is increasingly seen as a sustainable solution to healthcare across the industrialised world. The benefits of these approaches to well-being include reduced symptoms of anxiety, depression and improved social functioning. Many studies assume that contact with nature is the main therapeutic component of these interventions yet 'green care' programmes typically include activities not based on 'nature' that may contribute to positive outcomes. This study explored the views of service users participating in a Therapeutic Horticultural programme on what factors promoted their engagement in the project, to identify variables other than 'nature' that may be responsible for successful engagement in these programmes. A secondary aim was to assess the significance 'nature' plays including, for example whether a prior interest in horticultural-related activities, such as gardening, is significant. Two focus groups were held with mental health service users (n = 15) attending a gardening project in south-east England. Findings revealed that the social element of the project was the key facilitator to engagement; the flexible structure of the gardening project was also significant and allowed service users to feel empowered. 'Nature' evoked a sense of calm and provided participants with a non-threatening space that was engaging.

  15. Carcinogenesis and therapeutics: the microbiota perspective.

    PubMed

    Tsilimigras, Matthew C B; Fodor, Anthony; Jobin, Christian

    2017-02-22

    Cancer arises from the acquisition of multiple genetic and epigenetic changes in host cells over the span of many years, promoting oncogenic traits and carcinogenesis. Most cancers develop following random somatic alterations of key oncogenic genes, which are favoured by a number of risk factors, including lifestyle, diet and inflammation. Importantly, the environment where tumours evolve provides a unique source of signalling cues that affects cancer cell growth, survival, movement and metastasis. Recently, there has been increased interest in how the microbiota, the collection of microorganisms inhabiting the host body surface and cavities, shapes a micro-environment for host cells that can either promote or prevent cancer formation. The microbiota, particularly the intestinal biota, plays a central role in host physiology, and the composition and activity of this consortium of microorganisms is directly influenced by known cancer risk factors such as lifestyle, diet and inflammation. In this REVIEW, we discuss the pro- and anticarcinogenic role of the microbiota, as well as highlighting the therapeutic potential of microorganisms in tumourigenesis. The broad impacts, and, at times, opposing roles of the microbiota in carcinogenesis serve to illustrate the complex and sometimes conflicted relationship between microorganisms and the host-a relationship that could potentially be harnessed for therapeutic benefits.

  16. Oxidative stress: Biomarkers and novel therapeutic pathways.

    PubMed

    Maiese, Kenneth; Chong, Zhao Zhong; Hou, Jinling; Shang, Yan Chen

    2010-03-01

    Oxidative stress significantly impacts multiple cellular pathways that can lead to the initiation and progression of varied disorders throughout the body. It therefore becomes imperative to elucidate the components and function of novel therapeutic strategies against oxidative stress to further clinical diagnosis and care. In particular, both the growth factor and cytokine erythropoietin (EPO) and members of the mammalian forkhead transcription factors of the O class (FoxOs) may offer the greatest promise for new treatment regimens since these agents and the cellular pathways they oversee cover a range of critical functions that directly influence progenitor cell development, cell survival and degeneration, metabolism, immune function, and cancer cell invasion. Furthermore, both EPO and FoxOs function not only as therapeutic targets, but also as biomarkers of disease onset and progression, since their cellular pathways are closely linked and overlap with several unique signal transduction pathways. However, biological outcome with EPO and FoxOs may sometimes be both unexpected and undesirable that can raise caution for these agents and warrant further investigations. Here we present the exciting as well as complicated role EPO and FoxOs possess to uncover the benefits as well as the risks of these agents for cell biology and clinical care in processes that range from stem cell development to uncontrolled cellular proliferation.

  17. OXIDATIVE STRESS: BIOMARKERS AND NOVEL THERAPEUTIC PATHWAYS

    PubMed Central

    Maiese, Kenneth; Chong, Zhao Zhong; Hou, Jinling; Shang, Yan Chen

    2010-01-01

    Oxidative stress significantly impacts multiple cellular pathways that can lead to the initiation and progression of varied disorders throughout the body. It therefore becomes imperative to elucidate the components and function of novel therapeutic strategies against oxidative stress to further clinical diagnosis and care. In particular, both the growth factor and cytokine erythropoietin (EPO) and members of the mammalian forkhead transcription factors of the O class (FoxOs) may offer the greatest promise for new treatment regimens since these agents and the cellular pathways they oversee cover a range of critical functions that directly influence progenitor cell development, cell survival and degeneration, metabolism, immune function, and cancer cell invasion. Furthermore, both EPO and FoxOs function not only as therapeutic targets, but also as biomarkers of disease onset and progression, since their cellular pathways are closely linked and overlap with several unique signal transduction pathways. However, biological outcome with EPO and FoxOs may sometimes be both unexpected and undesirable that can raise caution for these agents and warrant further investigations. Here we present the exciting as well as complicated role EPO and FoxOs possess to uncover the benefits as well as the risks of these agents for cell biology and clinical care in processes that range from stem cell development to uncontrolled cellular proliferation. PMID:20064603

  18. Chaperones as potential therapeutics for Krabbe disease.

    PubMed

    Graziano, Adriana Carol Eleonora; Pannuzzo, Giovanna; Avola, Rosanna; Cardile, Venera

    2016-11-01

    Krabbe's disease (KD) is an autosomal recessive, neurodegenerative disorder. It is classified among the lysosomal storage diseases (LSDs). It was first described in , but the genetic defect for the galactocerebrosidase (GALC) gene was not discovered until the beginning of the 1970s, 20 years before the GALC cloning. Recently, in 2011, the crystal structures of the GALC enzyme and the GALC-product complex were obtained. For this, compared with other LSDs, the research on possible therapeutic interventions is much more recent. Thus, it is not surprising that some treatment options are still under preclinical investigation, whereas their relevance for other pathologies of the same group has already been tested in clinical studies. This is specifically the case for pharmacological chaperone therapy (PCT), a promising strategy for selectively correcting defective protein folding and trafficking and for enhancing enzyme activity by small molecules. These compounds bind directly to a partially folded biosynthetic intermediate, stabilize the protein, and allow completion of the folding process to yield a functional protein. Here, we review the chaperones that have demonstrated potential therapeutics during preclinical studies for KD, underscoring the requirement to invigorate research for KD-addressed PCT that will benefit from recent insights into the molecular understanding of GALC structure, drug design, and development in cellular models. © 2016 Wiley Periodicals, Inc.

  19. Nucleic acids as therapeutic agents.

    PubMed

    Alvarez-Salas, Luis M

    2008-01-01

    Therapeutic nucleic acids (TNAs) and its precursors are applied to treat several pathologies and infections. TNA-based therapy has different rationales and mechanisms and can be classified into three main groups: 1) Therapeutic nucleotides and nucleosides; 2) Therapeutic oligonucleotides; and 3) Therapeutic polynucleotides. This review will focus in those TNAs that have reached clinical trials with anticancer and antiviral protocols, the two most common applications of TNAs. Although therapeutic nucleotides and nucleosides that interfere with nucleic acid metabolism and DNA polymerization have been successfully used as anticancer and antiviral drugs, they often produce toxic secondary effects related to dosage and continuous use. The use of oligonucleotides such as ribozyme and antisense oligodeoxynucleotides (AS-ODNs) showed promise as therapeutic moieties but faced several issues such as nuclease sensitivity, off-target effects and efficient delivery. Nevertheless, immunostimulatory oligodeoxynucleotides and AS-ODNs represent the most successful group of therapeutic oligonucleotides in the clinic. A newer group of therapeutic oligonucleotides, the aptamers, is rapidly advancing towards early detection and treatment alternatives the have reached the commercial interest. Despite the very high in vitro efficiency of small interfering RNAs (siRNAs) they present issues with intracellular target accessibility, specificity and delivery. DNA vaccines showed great promise, but they resulted in very poor responses in the clinic and further development is uncertain. Despite their many issues, the exquisite specificity and versatility of therapeutic oligonucleotides attracts a great deal of research and resources that will certainly convert them in the TNA of choice for treating cancer and viral diseases in the near future.

  20. Do drug advertisements provide therapeutic information?

    PubMed

    Stimson, G V

    1977-03-01

    In this study of advertisements appearing in medical periodicals and by direct mail advertising to general practitioners, Dr. Stimson, a sociologist, concludes that from what is intended to provide therapeutic information hardly any therapeutic information is provided. He reminds the reader of the safeguards which surround all drug advertising by law and by the code of practice of the Association of the British Pharmaceutical Industry but these safeguards do not appear to control real or potential sins of omission. Frequently in these advertisements the literature relating to the drug is quoted but Dr. Stimson found that it was difficult to trace all the papers quoted in different types of medical library. (Some references quoted were to unpublished papers but surely the blame should be shared in this situation?) Dr. Stimson also gives a vivid and fascinating glimpse of what he calls the 'images and stereotypes' of the patients who, it is claimed, would benefit from the drug being advertised. Certainly most general practitioners must be aware that when they prescribe that image is displaced by an individual but the portrait gallery is indeed depressing. However, to balance these advertisements drug companies issue data sheets which must be more informative than advertisements and conform to regulations in their format. Unfortunately data sheets are only issued every 15 months whereas the 'average general practitioner is potentially exposed to 1,300 advertisements every month'. In other words, the data sheet and not the advertisement should be the guideline but it arrives too infrequently to offset the lack of therapeutic information contained in advertisements.

  1. 20 CFR 437.6 - Additions and exceptions.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... Employees' Benefits SOCIAL SECURITY ADMINISTRATION UNIFORM ADMINISTRATIVE REQUIREMENTS FOR GRANTS AND... classes of grants and grantees subject to this part, SSA may not impose additional administrative requirements except in codified regulations published in the Federal Register. (b) Exceptions for classes...

  2. 20 CFR 437.6 - Additions and exceptions.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... Employees' Benefits SOCIAL SECURITY ADMINISTRATION UNIFORM ADMINISTRATIVE REQUIREMENTS FOR GRANTS AND... classes of grants and grantees subject to this part, SSA may not impose additional administrative requirements except in codified regulations published in the Federal Register. (b) Exceptions for classes...

  3. 20 CFR 437.6 - Additions and exceptions.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... Employees' Benefits SOCIAL SECURITY ADMINISTRATION UNIFORM ADMINISTRATIVE REQUIREMENTS FOR GRANTS AND... classes of grants and grantees subject to this part, SSA may not impose additional administrative requirements except in codified regulations published in the Federal Register. (b) Exceptions for classes...

  4. 20 CFR 437.6 - Additions and exceptions.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Employees' Benefits SOCIAL SECURITY ADMINISTRATION UNIFORM ADMINISTRATIVE REQUIREMENTS FOR GRANTS AND... classes of grants and grantees subject to this part, SSA may not impose additional administrative requirements except in codified regulations published in the Federal Register. (b) Exceptions for classes...

  5. 20 CFR 437.6 - Additions and exceptions.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Employees' Benefits SOCIAL SECURITY ADMINISTRATION UNIFORM ADMINISTRATIVE REQUIREMENTS FOR GRANTS AND... classes of grants and grantees subject to this part, SSA may not impose additional administrative requirements except in codified regulations published in the Federal Register. (b) Exceptions for classes...

  6. [Therapeutic management of neurodermatitis atopica].

    PubMed

    Kägi, M K

    1998-08-01

    The therapy of atopic dermatitis remains a challenge. The success of any therapeutic concept is based on a broad and early diagnostic approach which allows to rule out relevant provocation factors and allergens. During remission periods the regular use of a topical basic therapy consisting of drug-free emolients is recommended. Topical corticosteroids as well as systemic or local antimicrobial therapy and antihistamines are essential during periods of acute exacerbations. Although during the last years a great number of new therapeutic approaches have been published, data of most of these therapeutic modalities are not sufficient to allow an unrestricted use in all patients with atopic dermatitis.

  7. Molecular Targets in Alzheimer's Disease: From Pathogenesis to Therapeutics.

    PubMed

    Cheng, Xuan; Zhang, Lu; Lian, Ya-Jun

    2015-01-01

    Alzheimer's disease (AD) is characterized by progressive cognitive decline usually beginning with impairment in the ability to form recent memories. Nonavailability of definitive therapeutic strategy urges developing pharmacological targets based on cell signaling pathways. A great revival of interest in nutraceuticals and adjuvant therapy has been put forward. Tea polyphenols for their multiple health benefits have also attracted the attention of researchers. Tea catechins showed enough potentiality to be used in future as therapeutic targets to provide neuroprotection against AD. This review attempts to present a concise map of different receptor signaling pathways associated with AD with an insight into drug designing based on the proposed signaling pathways, molecular mechanistic details of AD pathogenesis, and a scientific rationale for using tea polyphenols as proposed therapeutic agents in AD.

  8. Nanotechnology and regenerative therapeutics in plastic surgery: The next frontier

    PubMed Central

    Tan, Aaron; Chawla, Reema; Natasha, G; Mahdibeiraghdar, Sara; Jeyaraj, Rebecca; Rajadas, Jayakumar; Hamblin, Michael R.; Seifalian, Alexander M.

    2015-01-01

    Summary The rapid ascent of nanotechnology and regenerative therapeutics as applied to medicine and surgery has seen an exponential rise in the scale of research generated in this field. This is evidenced not only by the sheer volume of papers dedicated to nanotechnology but also in a large number of new journals dedicated to nanotechnology and regenerative therapeutics specifically to medicine and surgery. Aspects of nanotechnology that have already brought benefits to these areas include advanced drug delivery platforms, molecular imaging and materials engineering for surgical implants. Particular areas of interest include nerve regeneration, burns and wound care, artificial skin with nanoelectronic sensors and head and neck surgery. This study presents a review of nanotechnology and regenerative therapeutics, with focus on its applications and implications in plastic surgery. PMID:26422652

  9. [Objectives and therapeutic strategy in type 2 diabetes mellitus].

    PubMed

    Calvo Romero, J M; Lima Rodríguez, E M

    2001-07-01

    United Kingdom Prospective Diabetes Study (UKPDS) has demonstrated definitively that patients with type 2 diabetes mellitus (DM) benefit from intensive blood glucose control, because it diminishes the risk to develop microvascular complications. The therapeutic targets in the type 2 DM have been modified in order to reduce the risk of these complications. However, aggressive treatment may be disastrous for patients with microvascular complications and/or an increased risk of hypoglycemic unawareness, and neither it would be advised in older patients or with short life expectancy. The available drugs for treatment of type 2 DM offer many options for achieving these therapeutic targets, based on the need of the individual patient. In this job we review the targets in the metabolic control of type 2 DM and their backgrounds, and we describe briefly the therapeutic strategy recommended for reaching these targets, with special attention to the new oral antidiabetic agents (repaglinide and thiazolidinediones).

  10. Asparaginase pharmacokinetics and implications of therapeutic drug monitoring.

    PubMed

    Asselin, Barbara; Rizzari, Carmelo

    2015-01-01

    Asparaginase is widely used in chemotherapeutic regimens for the treatment of acute lymphoblastic leukemia (ALL) and has led to a substantial improvement in cure rates, especially in children. Optimal therapeutic effects depend on a complete and sustained depletion of serum asparagine. However, pronounced interpatient variability, differences in pharmacokinetic properties between asparaginases and the formation of asparaginase antibodies make it difficult to predict the degree of asparagine depletion that will result from a given dose of asparaginase. The pharmacological principles underlying asparaginase therapy in the treatment of ALL are summarized in this article. A better understanding of the many factors that influence asparaginase activity and subsequent asparagine depletion may allow physicians to tailor treatment to the individual, maximizing therapeutic effect and minimizing treatment-related toxicity. Therapeutic drug monitoring provides a means of assessing a patient's current depletion status and can be used to better evaluate the potential benefit of treatment adjustments.

  11. Nanotechnology and regenerative therapeutics in plastic surgery: The next frontier.

    PubMed

    Tan, Aaron; Chawla, Reema; G, Natasha; Mahdibeiraghdar, Sara; Jeyaraj, Rebecca; Rajadas, Jayakumar; Hamblin, Michael R; Seifalian, Alexander M

    2016-01-01

    The rapid ascent of nanotechnology and regenerative therapeutics as applied to medicine and surgery has seen an exponential rise in the scale of research generated in this field. This is evidenced not only by the sheer volume of papers dedicated to nanotechnology but also in a large number of new journals dedicated to nanotechnology and regenerative therapeutics specifically to medicine and surgery. Aspects of nanotechnology that have already brought benefits to these areas include advanced drug delivery platforms, molecular imaging and materials engineering for surgical implants. Particular areas of interest include nerve regeneration, burns and wound care, artificial skin with nanoelectronic sensors and head and neck surgery. This study presents a review of nanotechnology and regenerative therapeutics, with focus on its applications and implications in plastic surgery.

  12. Repurposing antipsychotics as glioblastoma therapeutics: Potentials and challenges

    PubMed Central

    LEE, JIN-KU; NAM, DO-HYUN; LEE, JEONGWU

    2016-01-01

    Glioblastoma multiforme (GBM) is the most common and most lethal primary brain tumor, with tragically little therapeutic progress over the last 30 years. Surgery provides a modest benefit, and GBM cells are resistant to radiation and chemotherapy. Despite significant development of the molecularly targeting strategies, the clinical outcome of GBM patients remains dismal. The challenges inherent in developing effective GBM treatments have become increasingly clear, and include resistance to standard treatments, the blood-brain barrier, resistance of GBM stem-like cells, and the genetic complexity and molecular adaptability of GBM. Recent studies have collectively suggested that certain antipsychotics harbor antitumor effects and have potential utilities as anti-GBM therapeutics. In the present review, the anti-tumorigenic effects and putative mechanisms of antipsychotics, and the challenges for the potential use of antipsychotic drugs as anti-GBM therapeutics are reviewed. PMID:26893731

  13. Words matter: distinguishing "personalized medicine" and "biologically personalized therapeutics".

    PubMed

    Cherny, Nathan I; de Vries, Elisabeth G E; Emanuel, Linda; Fallowfield, Lesley; Francis, Prudence A; Gabizon, Alberto; Piccart, Martine J; Sidransky, David; Soussan-Gutman, Lior; Tziraki, Chariklia

    2014-12-01

    "Personalized medicine" has become a generic term referring to techniques that evaluate either the host or the disease to enhance the likelihood of beneficial patient outcomes from treatment interventions. There is, however, much more to personalization of care than just identifying the biotherapeutic strategy with the highest likelihood of benefit. In its new meaning, "personalized medicine" could overshadow the individually tailored, whole-person care that is at the bedrock of what people need and want when they are ill. Since names and definitional terms set the scope of the discourse, they have the power to define what personalized medicine includes or does not include, thus influencing the scope of the professional purview regarding the delivery of personalized care. Taxonomic accuracy is important in understanding the differences between therapeutic interventions that are distinguishable in their aims, indications, scope, benefits, and risks. In order to restore the due emphasis to the patient and his or her needs, we assert that it is necessary, albeit belated, to deconflate the contemporary term "personalized medicine" by taxonomizing this therapeutic strategy more accurately as "biologically personalized therapeutics" (BPT). The scope of truly personalized medicine and its relationship to biologically personalized therapeutics is described, emphasizing that the best of care must give due recognition and emphasis to both BPT and truly personalized medicine.

  14. 26 CFR 1.436-1 - Limits on benefits and benefit accruals under single employer defined benefit plans.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 5 2013-04-01 2013-04-01 false Limits on benefits and benefit accruals under... § 1.436-1 Limits on benefits and benefit accruals under single employer defined benefit plans. (a...) Limitations on prohibited payments. (1) AFTAP less than 60 percent. (2) Bankruptcy. (3) Limited payment...

  15. Pharmacology and therapeutics of bronchodilators.

    PubMed

    Cazzola, Mario; Page, Clive P; Calzetta, Luigino; Matera, M Gabriella

    2012-07-01

    Bronchodilators are central in the treatment of of airways disorders. They are the mainstay of the current management of chronic obstructive pulmonary disease (COPD) and are critical in the symptomatic management of asthma, although controversies around the use of these drugs remain. Bronchodilators work through their direct relaxation effect on airway smooth muscle cells. at present, three major classes of bronchodilators, β(2)-adrenoceptor (AR) agonists, muscarinic receptor antagonists, and xanthines are available and can be used individually or in combination. The use of the inhaled route is currently preferred to minimize systemic effects. Fast- and short-acting agents are best used for rescue of symptoms, whereas long-acting agents are best used for maintenance therapy. It has proven difficult to discover novel classes of bronchodilator drugs, although potential new targets are emerging. Consequently, the logical approach has been to improve the existing bronchodilators, although several novel broncholytic classes are under development. An important step in simplifying asthma and COPD management and improving adherence with prescribed therapy is to reduce the dose frequency to the minimum necessary to maintain disease control. Therefore, the incorporation of once-daily dose administration is an important strategy to improve adherence. Several once-daily β(2)-AR agonists or ultra-long-acting β(2)-AR-agonists (LABAs), such as indacaterol, olodaterol, and vilanterol, are already in the market or under development for the treatment of COPD and asthma, but current recommendations suggest the use of LABAs only in combination with an inhaled corticosteroid. In addition, some new potentially long-acting antimuscarinic agents, such as glycopyrronium bromide (NVA-237), aclidinium bromide, and umeclidinium bromide (GSK573719), are under development, as well as combinations of several classes of long-acting bronchodilator drugs, in an attempt to simplify treatment

  16. Therapeutic targeting of replicative immortality.

    PubMed

    Yaswen, Paul; MacKenzie, Karen L; Keith, W Nicol; Hentosh, Patricia; Rodier, Francis; Zhu, Jiyue; Firestone, Gary L; Matheu, Ander; Carnero, Amancio; Bilsland, Alan; Sundin, Tabetha; Honoki, Kanya; Fujii, Hiromasa; Georgakilas, Alexandros G; Amedei, Amedeo; Amin, Amr; Helferich, Bill; Boosani, Chandra S; Guha, Gunjan; Ciriolo, Maria Rosa; Chen, Sophie; Mohammed, Sulma I; Azmi, Asfar S; Bhakta, Dipita; Halicka, Dorota; Niccolai, Elena; Aquilano, Katia; Ashraf, S Salman; Nowsheen, Somaira; Yang, Xujuan

    2015-12-01

    One of the hallmarks of malignant cell populations is the ability to undergo continuous proliferation. This property allows clonal lineages to acquire sequential aberrations that can fuel increasingly autonomous growth, invasiveness, and therapeutic resistance. Innate cellular mechanisms have evolved to regulate replicative potential as a hedge against malignant progression. When activated in the absence of normal terminal differentiation cues, these mechanisms can result in a state of persistent cytostasis. This state, termed "senescence," can be triggered by intrinsic cellular processes such as telomere dysfunction and oncogene expression, and by exogenous factors such as DNA damaging agents or oxidative environments. Despite differences in upstream signaling, senescence often involves convergent interdependent activation of tumor suppressors p53 and p16/pRB, but can be induced, albeit with reduced sensitivity, when these suppressors are compromised. Doses of conventional genotoxic drugs required to achieve cancer cell senescence are often much lower than doses required to achieve outright cell death. Additional therapies, such as those targeting cyclin dependent kinases or components of the PI3K signaling pathway, may induce senescence specifically in cancer cells by circumventing defects in tumor suppressor pathways or exploiting cancer cells' heightened requirements for telomerase. Such treatments sufficient to induce cancer cell senescence could provide increased patient survival with fewer and less severe side effects than conventional cytotoxic regimens. This positive aspect is countered by important caveats regarding senescence reversibility, genomic instability, and paracrine effects that may increase heterogeneity and adaptive resistance of surviving cancer cells. Nevertheless, agents that effectively disrupt replicative immortality will likely be valuable components of new combinatorial approaches to cancer therapy.

  17. Therapeutic targeting of replicative immortality

    PubMed Central

    Yaswen, Paul; MacKenzie, Karen L.; Keith, W. Nicol; Hentosh, Patricia; Rodier, Francis; Zhu, Jiyue; Firestone, Gary L.; Matheu, Ander; Carnero, Amancio; Bilsland, Alan; Sundin, Tabetha; Honoki, Kanya; Fujii, Hiromasa; Georgakilas, Alexandros G.; Amedei, Amedeo; Amin, Amr; Helferich, Bill; Boosani, Chandra S.; Guha, Gunjan; Ciriolo, Maria Rosa; Chen, Sophie; Mohammed, Sulma I.; Azmi, Asfar S.; Bhakta, Dipita; Halicka, Dorota; Niccolai, Elena; Aquilano, Katia; Ashraf, S. Salman; Nowsheen, Somaira; Yang, Xujuan

    2015-01-01

    One of the hallmarks of malignant cell populations is the ability to undergo continuous proliferation. This property allows clonal lineages to acquire sequential aberrations that can fuel increasingly autonomous growth, invasiveness, and therapeutic resistance. Innate cellular mechanisms have evolved to regulate replicative potential as a hedge against malignant progression. When activated in the absence of normal terminal differentiation cues, these mechanisms can result in a state of persistent cytostasis. This state, termed “senescence,” can be triggered by intrinsic cellular processes such as telomere dysfunction and oncogene expression, and by exogenous factors such as DNA damaging agents or oxidative environments. Despite differences in upstream signaling, senescence often involves convergent interdependent activation of tumor suppressors p53 and p16/pRB, but can be induced, albeit with reduced sensitivity, when these suppressors are compromised. Doses of conventional genotoxic drugs required to achieve cancer cell senescence are often much lower than doses required to achieve outright cell death. Additional therapies, such as those targeting cyclin dependent kinases or components of the PI3K signaling pathway, may induce senescence specifically in cancer cells by circumventing defects in tumor suppressor pathways or exploiting cancer cells’ heightened requirements for telomerase. Such treatments sufficient to induce cancer cell senescence could provide increased patient survival with fewer and less severe side effects than conventional cytotoxic regimens. This positive aspect is countered by important caveats regarding senescence reversibility, genomic instability, and paracrine effects that may increase heterogeneity and adaptive resistance of surviving cancer cells. Nevertheless, agents that effectively disrupt replicative immortality will likely be valuable components of new combinatorial approaches to cancer therapy. PMID:25869441

  18. Effect of Therapeutic Modalities on Patients With Patellofemoral Pain Syndrome

    PubMed Central

    Lake, David A.; Wofford, Nancy H.

    2011-01-01

    Context: Patellofemoral pain syndrome (PFPS) is a common orthopaedic condition for which operative and nonoperative treatments have been used. Therapeutic modalities have been recommended for the treatment of patients with PFPS—including cold, ultrasound, phonophoresis, iontophoresis, neuromuscular electrical stimulation, electrical stimulation for pain control, electromyographic biofeedback, and laser. Objective: To determine the effectiveness of therapeutic modalities for the treatment of patients with PFPS. Data Sources: In May and August 2010, Medline was searched using the following databases: PubMed, CINAHL, Web of Science Citation Index, Science Direct, ProQuest Nursing & Allied Health, and Your Journals@OVID. Study Selection: Selected studies were randomized controlled trials that used a therapeutic modality to treat patients with PFPS. The review included articles with all outcome measures relevant for the PFPS patient: knee extension and flexion strength (isokinetic and isometric), patellofemoral pain assessment during activities of daily life, functional tests (eg, squats), Kujala patellofemoral score, and electromyographic recording from knee flexors and extensors and quadriceps femoris cross-sectional areas. Data Extraction: Authors conducted independent quality appraisals of studies using the PEDro Scale and a system designed for analysis of studies on interventions for patellofemoral pain. Results: Twelve studies met criteria: 1 on the effects of cold and ultrasound together, ice alone, iontophoresis, and phonophoresis; 3, neuromuscular electrical stimulation; 4, electromyographic biofeedback; 3, electrical stimulation for control of pain; and 1, laser. Discussion: Most studies were of low to moderate quality. Some reported that therapeutic modalities, when combined with other treatments, may be of some benefit for pain management or other symptoms. There was no consistent evidence of any beneficial effect when a therapeutic modality was used alone

  19. Vinyl capped addition polyimides

    NASA Technical Reports Server (NTRS)

    Vannucci, Raymond D. (Inventor); Malarik, Diane C. (Inventor); Delvigs, Peter (Inventor)

    1991-01-01

    Polyimide resins (PMR) are generally useful where high strength and temperature capabilities are required (at temperatures up to about 700 F). Polyimide resins are particularly useful in applications such as jet engine compressor components, for example, blades, vanes, air seals, air splitters, and engine casing parts. Aromatic vinyl capped addition polyimides are obtained by reacting a diamine, an ester of tetracarboxylic acid, and an aromatic vinyl compound. Low void materials with improved oxidative stability when exposed to 700 F air may be fabricated as fiber reinforced high molecular weight capped polyimide composites. The aromatic vinyl capped polyimides are provided with a more aromatic nature and are more thermally stable than highly aliphatic, norbornenyl-type end-capped polyimides employed in PMR resins. The substitution of aromatic vinyl end-caps for norbornenyl end-caps in addition polyimides results in polymers with improved oxidative stability.

  20. Electrophilic addition of astatine

    SciTech Connect

    Norseev, Yu.V.; Vasaros, L.; Nhan, D.D.; Huan, N.K.

    1988-03-01

    It has been shown for the first time that astatine is capable of undergoing addition reactions to unsaturated hydrocarbons. A new compound of astatine, viz., ethylene astatohydrin, has been obtained, and its retention numbers of squalane, Apiezon, and tricresyl phosphate have been found. The influence of various factors on the formation of ethylene astatohydrin has been studied. It has been concluded on the basis of the results obtained that the univalent cations of astatine in an acidic medium is protonated hypoastatous acid.

  1. Functional Generalized Additive Models.

    PubMed

    McLean, Mathew W; Hooker, Giles; Staicu, Ana-Maria; Scheipl, Fabian; Ruppert, David

    2014-01-01

    We introduce the functional generalized additive model (FGAM), a novel regression model for association studies between a scalar response and a functional predictor. We model the link-transformed mean response as the integral with respect to t of F{X(t), t} where F(·,·) is an unknown regression function and X(t) is a functional covariate. Rather than having an additive model in a finite number of principal components as in Müller and Yao (2008), our model incorporates the functional predictor directly and thus our model can be viewed as the natural functional extension of generalized additive models. We estimate F(·,·) using tensor-product B-splines with roughness penalties. A pointwise quantile transformation of the functional predictor is also considered to ensure each tensor-product B-spline has observed data on its support. The methods are evaluated using simulated data and their predictive performance is compared with other competing scalar-on-function regression alternatives. We illustrate the usefulness of our approach through an application to brain tractography, where X(t) is a signal from diffusion tensor imaging at position, t, along a tract in the brain. In one example, the response is disease-status (case or control) and in a second example, it is the score on a cognitive test. R code for performing the simulations and fitting the FGAM can be found in supplemental materials available online.

  2. How to Use Equipment Therapeutically.

    ERIC Educational Resources Information Center

    Bowne, Douglas

    1986-01-01

    Shares therapeutic and economic practices surrounding equipment used in New York's Higher Horizons adventure program of therapy for troubled youth. Encourages educators, therapists, and administrators to explore relationship between equipment selection, program goals, and clients. (NEC)

  3. Mesenchymal Stem Cells as Therapeutics

    PubMed Central

    Parekkadan, Biju; Milwid, Jack M.

    2013-01-01

    Mesenchymal stem cells (MSCs) are multipotent cells that are being clinically explored as a new therapeutic for treating a variety of immune-mediated diseases. First heralded as a regenerative therapy for skeletal tissue repair, MSCs have recently been shown to modulate endogenous tissue and immune cells. Preclinical studies of the mechanism of action suggest that the therapeutic effects afforded by MSC transplantation are short-lived and related to dynamic, paracrine interactions between MSCs and host cells. Therefore, representations of MSCs as drug-loaded particles may allow for pharmacokinetic models to predict the therapeutic activity of MSC transplants as a function of drug delivery mode. By integrating principles of MSC biology, therapy, and engineering, the field is armed to usher in the next generation of stem cell therapeutics. PMID:20415588

  4. Therapeutic Recreation and Adult Education.

    ERIC Educational Resources Information Center

    Jones, David

    1993-01-01

    Therapeutic recreation is a means of empowering individuals with disabilities through arts or sports. The field has developed differently in the United States and the United Kingdom; the former emphasizes professionalization and the latter the right to adult education. (SK)

  5. Targeted Strategies for Henipavirus Therapeutics

    PubMed Central

    Bossart, Katharine N; Bingham, John; Middleton, Deborah

    2007-01-01

    Hendra and Nipah viruses are related emergent paramyxoviruses that infect and cause disease in animals and humans. Disease manifests as a generalized vasculitis affecting multiple organs, but is the most severe in the respiratory and central nervous systems. The high case fatality and person-to-person transmission associated with the most recent NiV outbreaks, and the recent re-emergence of HeV, emphasize the importance and necessity of effective therapeutics for these novel agents. In recent years henipavirus research has revealed a more complete understanding of pathogenesis and, as a consequence, viable approaches towards vaccines and therapeutics have emerged. All strategies target early steps in viral replication including receptor binding and membrane fusion. Animal models have been developed, some of which may prove more valuable than others for evaluating the efficacy of therapeutic agents and regimes. Assessments of protective host immunity and drug pharmacokinetics will be crucial to the further advancement of therapeutic compounds. PMID:19440455

  6. Therapeutic targeting of ERBB2 in breast cancer: understanding resistance in the laboratory and combating it in the clinic.

    PubMed

    Fabi, Alessandra; Mottolese, Marcella; Segatto, Oreste

    2014-07-01

    ERBB2 gene amplification occurs in about one quarter of breast carcinomas (BCs) and identifies a distinct clinical subset of BC. The introduction in the clinic of Trastuzumab, a humanized monoclonal antibody (mAb) directed to the ERBB2 extracellular domain, has had a great impact on the therapeutic management of ERBB2+ BC. Yet, not all patients respond to Trastuzumab and resistance develops also among patients that initially benefit from Trastuzumab-based regimens. Pre-clinical studies have discovered several mechanisms through which tumor cells may escape from Trastuzumab-mediated ERBB2 inhibition. These include rewiring of the ErbB signaling network, loss of ERBB2 expression, expression of ERBB2 isoforms refractory to Trastuzumab inhibition, vicarious signaling by non-ErbB tyrosine kinases and constitutive activation of downstream signaling routes, such as the PI3K pathway. While the relative contribution of each of these mechanisms to establishing Trastuzumab resistance in the clinical setting is not fully understood, much attention has been focused on abating resistance by achieving complete blockade of ERBB2-containing dimers. This approach, propelled by the development of novel anti-ERBB2 therapeutics, has led to the recent approval of Lapatinib, Pertuzumab and T-DM1 as additional anti-ERBB2 therapeutics in BC. However, full success is far from being achieved and resistance to ERBB2 targeting remains a relevant problem in the clinical management of BC. Herein, we provide an overview of biological and molecular bases underpinning resistance to ERBB2 therapeutics in BC, discuss outstanding issues in the field of ERBB2 therapeutic targeting and elaborate on future directions of translational research on ERBB2+ breast cancer.

  7. Therapeutic Vaccines for Chronic Infections

    NASA Astrophysics Data System (ADS)

    Autran, Brigitte; Carcelain, Guislaine; Combadiere, Béhazine; Debre, Patrice

    2004-07-01

    Therapeutic vaccines aim to prevent severe complications of a chronic infection by reinforcing host defenses when some immune control, albeit insufficient, can already be demonstrated and when a conventional antimicrobial therapy either is not available or has limited efficacy. We focus on the rationale and challenges behind this still controversial strategy and provide examples from three major chronic infectious diseases-human immunodeficiency virus, hepatitis B virus, and human papillomavirus-for which the efficacy of therapeutic vaccines is currently being evaluated.

  8. Pharmacology and potential therapeutic applications of nitric oxide-releasing non-steroidal anti-inflammatory and related nitric oxide-donating drugs

    PubMed Central

    Keeble, J E; Moore, P K

    2002-01-01

    This review examines the biological significance, therapeutic potential and mechanism(s) of action of a range of nitric oxide-releasing non-steroidal anti-inflammatory drugs (NO-NSAID) and related nitric oxide-releasing donating drugs (NODD). The slow release of nitric oxide (NO) from these compounds leads to subtle changes in the profile of pharmacological activity of the parent, non-steroidal anti-inflammatory drugs (NSAID). For example, compared with NSAID, NO-NSAID cause markedly diminished gastrointestinal toxicity and improved anti-inflammatory and anti-nociceptive efficacy. In addition, nitroparacetamol exhibits hepatoprotection as opposed to the hepatotoxic activity of paracetamol. The possibility that NO-NSAID or NODD may be of therapeutic benefit in a wide variety of disease states including pain and inflammation, thrombosis and restenosis, neurodegenerative diseases of the central nervous system, colitis, cancer, urinary incontinence, liver disease, impotence, bronchial asthma and osteoporosis is discussed. PMID:12237248

  9. Materials for Diabetes Therapeutics

    PubMed Central

    Bratlie, Kaitlin M.; York, Roger L.; Invernale, Michael A.; Langer, Robert

    2013-01-01

    This review is focused on the materials and methods used to fabricate closed-loop systems for type 1 diabetes therapy. Herein, we give a brief overview of current methods used for patient care and discuss two types of possible treatments and the materials used for these therapies–(i) artificial pancreases, comprised of insulin producing cells embedded in a polymeric biomaterial, and (ii) totally synthetic pancreases formulated by integrating continuous glucose monitors with controlled insulin release through degradable polymers and glucose-responsive polymer systems. Both the artificial and the completely synthetic pancreas have two major design requirements: the device must be both biocompatible and be permeable to small molecules and proteins, such as insulin. Several polymers and fabrication methods of artificial pancreases are discussed: microencapsulation, conformal coatings, and planar sheets. We also review the two components of a completely synthetic pancreas. Several types of glucose sensing systems (including materials used for electrochemical, optical, and chemical sensing platforms) are discussed, in addition to various polymer-based release systems (including ethylene-vinyl acetate, polyanhydrides, and phenylboronic acid containing hydrogels). PMID:23184741

  10. Benefits of exercise during pregnancy.

    PubMed

    Prather, Heidi; Spitznagle, Tracy; Hunt, Devyani

    2012-11-01

    There is a direct link between healthy mothers and healthy infants. Exercise and appropriate nutrition are important contributors to maternal physical and psychological health. The benefits and potential risks of exercise during pregnancy have gained even more attention, with a number of studies having been published after the 2002 American College of Obstetrics and Gynecologists guidelines. A review of the literature was conducted by using PubMed, Scopus, and Embase to assess the literature regarding the benefits of exercise during pregnancy. The search revealed 219 publications, which the authors then narrowed to 125 publications. The purpose of this review is to briefly summarize the known benefits of exercise to the mother, fetus, and newborn.

  11. Health benefits of Moringa oleifera.

    PubMed

    Abdull Razis, Ahmad Faizal; Ibrahim, Muhammad Din; Kntayya, Saie Brindha

    2014-01-01

    Phytomedicines are believed to have benefits over conventional drugs and are regaining interest in current research. Moringa oleifera is a multi-purpose herbal plant used as human food and an alternative for medicinal purposes worldwide. It has been identified by researchers as a plant with numerous health benefits including nutritional and medicinal advantages. Moringa oleifera contains essential amino acids, carotenoids in leaves, and components with nutraceutical properties, supporting the idea of using this plant as a nutritional supplement or constituent in food preparation. Some nutritional evaluation has been carried out in leaves and stem. An important factor that accounts for the medicinal uses of Moringa oleifera is its very wide range of vital antioxidants, antibiotics and nutrients including vitamins and minerals. Almost all parts from Moringa can be used as a source for nutrition with other useful values. This mini-review elaborate on details its health benefits.

  12. 31 CFR 29.343 - Disability benefits.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false Disability benefits. 29.343 Section... Federal Benefit Payments § 29.343 Disability benefits. (a) The general rule that Federal Benefit Payments... retirement and separated on June 30, 1997, does not apply to disability benefits prior to optional...

  13. 22 CFR 20.4 - Retirement benefits.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 22 Foreign Relations 1 2012-04-01 2012-04-01 false Retirement benefits. 20.4 Section 20.4 Foreign Relations DEPARTMENT OF STATE PERSONNEL BENEFITS FOR CERTAIN FORMER SPOUSES § 20.4 Retirement benefits. (a...) Reduction of benefits. If retirement benefits of a principal are reduced because of reemployment,...

  14. 22 CFR 20.4 - Retirement benefits.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 22 Foreign Relations 1 2014-04-01 2014-04-01 false Retirement benefits. 20.4 Section 20.4 Foreign Relations DEPARTMENT OF STATE PERSONNEL BENEFITS FOR CERTAIN FORMER SPOUSES § 20.4 Retirement benefits. (a...) Reduction of benefits. If retirement benefits of a principal are reduced because of reemployment,...

  15. 22 CFR 20.4 - Retirement benefits.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 22 Foreign Relations 1 2013-04-01 2013-04-01 false Retirement benefits. 20.4 Section 20.4 Foreign Relations DEPARTMENT OF STATE PERSONNEL BENEFITS FOR CERTAIN FORMER SPOUSES § 20.4 Retirement benefits. (a...) Reduction of benefits. If retirement benefits of a principal are reduced because of reemployment,...

  16. 22 CFR 20.4 - Retirement benefits.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Retirement benefits. 20.4 Section 20.4 Foreign Relations DEPARTMENT OF STATE PERSONNEL BENEFITS FOR CERTAIN FORMER SPOUSES § 20.4 Retirement benefits. (a...) Reduction of benefits. If retirement benefits of a principal are reduced because of reemployment,...

  17. 22 CFR 20.4 - Retirement benefits.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 22 Foreign Relations 1 2011-04-01 2011-04-01 false Retirement benefits. 20.4 Section 20.4 Foreign Relations DEPARTMENT OF STATE PERSONNEL BENEFITS FOR CERTAIN FORMER SPOUSES § 20.4 Retirement benefits. (a...) Reduction of benefits. If retirement benefits of a principal are reduced because of reemployment,...

  18. 31 CFR 29.343 - Disability benefits.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 31 Money and Finance: Treasury 1 2012-07-01 2012-07-01 false Disability benefits. 29.343 Section... Federal Benefit Payments § 29.343 Disability benefits. (a) The general rule that Federal Benefit Payments... retirement and separated on June 30, 1997, does not apply to disability benefits prior to optional...

  19. 31 CFR 29.343 - Disability benefits.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 31 Money and Finance: Treasury 1 2011-07-01 2011-07-01 false Disability benefits. 29.343 Section... Federal Benefit Payments § 29.343 Disability benefits. (a) The general rule that Federal Benefit Payments... retirement and separated on June 30, 1997, does not apply to disability benefits prior to optional...

  20. Siloxane containing addition polyimides

    NASA Technical Reports Server (NTRS)

    Maudgal, S.; St. Clair, T. L.

    1984-01-01

    Addition polyimide oligomers have been synthesized from bis(gamma-aminopropyl) tetramethyldisiloxane and 3, 3', 4, 4'-benzophenonetetracarboxylic dianhydride using a variety of latent crosslinking groups as endcappers. The prepolymers were isolated and characterized for solubility (in amide, chlorinated and ether solvents), melt flow and cure properties. The most promising systems, maleimide and acetylene terminated prepolymers, were selected for detailed study. Graphite cloth reinforced composites were prepared and properties compared with those of graphite/Kerimid 601, a commercially available bismaleimide. Mixtures of the maleimide terminated system with Kerimid 601, in varying proportions, were also studied.