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Sample records for additional therapeutic benefit

  1. Sinigrin and Its Therapeutic Benefits.

    PubMed

    Mazumder, Anisha; Dwivedi, Anupma; du Plessis, Jeanetta

    2016-01-01

    Sinigrin (allyl-glucosinolate or 2-propenyl-glucosinolate) is a natural aliphatic glucosinolate present in plants of the Brassicaceae family, such as broccoli and brussels sprouts, and the seeds of Brassica nigra (mustard seeds) which contain high amounts of sinigrin. Since ancient times, mustard has been used by mankind for its culinary, as well as medicinal, properties. It has been systematically described and evaluated in the classical Ayurvedic texts. Studies conducted on the pharmacological activities of sinigrin have revealed anti-cancer, antibacterial, antifungal, antioxidant, anti-inflammatory, wound healing properties and biofumigation. This current review will bring concise information about the known therapeutic activities of sinigrin. However, the information on known biological activities is very limited and, hence, further studies still need to be conducted and its molecular mechanisms also need to be explored. This review on the therapeutic benefits of sinigrin can summarize current knowledge about this unique phytocompounds. PMID:27043505

  2. Enactments in Psychoanalysis: Therapeutic Benefits.

    PubMed

    Stern, Stanley

    2016-01-01

    The therapeutic benefits of enactments are addressed. Relevant literature reveals disparate conceptions about the nature and use of enactments. Clarification of the term is discussed. This analyst's theoretical and technical evolution is addressed; it is inextricably related to using enactments. How can it not be? A taxonomy of enactments is presented. The article considers that enactments may be fundamental in the evolution from orthodox to contemporary analytic technique. Assumptions underlying enactments are explored, as are guidelines for using enactments. Finally, the article posits that enactments have widened the scope of analysis and contributed to its vitality. PMID:27200466

  3. 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. PMID:24765558

  4. 42 CFR 417.592 - Additional benefits requirement.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 3 2012-10-01 2012-10-01 false Additional benefits requirement. 417.592 Section... PLANS, AND HEALTH CARE PREPAYMENT PLANS Medicare Payment: Risk Basis § 417.592 Additional benefits...) Additional benefits. Provide its Medicare enrollees with additional benefits in accordance with paragraph...

  5. Therapeutic benefits of budesonide in gastroenterology.

    PubMed

    O'Donnell, Sarah; O'Morain, Colm A

    2010-07-01

    Budesonide is a synthetic steroid of the glucocorticoid family with a high topical anti-inflammatory activity. Enteric-coated formulations resist gastric-acid degradation, delivering active drug to the small intestine and proximal colon. Budesonide has a high first-pass metabolism with minimal systemic absorption. It is therefore felt to cause fewer side effects than traditional glucocorticosteroids and to be generally well tolerated. The aim of this paper is to examine the utility of this medication in frequently encountered gastrointestinal conditions: Crohn's disease, ulcerative colitis, microscopic colitis and eosinophilic oesophagitis. A Medline search was performed to find published original research and review articles relating to the use budesonide in common gastroenterological conditions. The results showed that budesonide is efficacious in the induction and short-term maintenance of Crohn's disease. Budesonide is the best-documented treatment for microscopic colitis. It is well proven to be effective in the induction of remission in collagenous colitis but its use in lymphocytic colitis remains less well documented. In conclusion, budesonide is an effective glucocorticosteroid therapy for many chronic gastrointestinal diseases. In combination with its efficacy, the low incidence of serious side effects associated with this drug should keep it at the forefront in the therapeutic arsenal of any gastroenterologist. PMID:23251737

  6. 42 CFR 417.592 - Additional benefits requirement.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 3 2010-10-01 2010-10-01 false Additional benefits requirement. 417.592 Section... HEALTH CARE PREPAYMENT PLANS Medicare Payment: Risk Basis § 417.592 Additional benefits requirement. (a... benefits. Provide its Medicare enrollees with additional benefits in accordance with paragraph (c) of...

  7. Galantamine: additional benefits to patients with Alzheimer's disease.

    PubMed

    Lilienfeld, S; Parys, W

    2000-09-01

    Galantamine, a novel treatment for Alzheimer's disease (AD), has a dual mechanism of action, combining allosteric modulation of nicotinic acetylcholine receptors with reversible, competitive inhibition of acetylcholinesterase. In the Phase III clinical trial programme, over 3,000 patients with mild-to-moderate AD were enrolled in one of five randomized, controlled, double-blind studies. Using the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) to assess memory and other cognitive functions, galantamine was found to be significantly superior to placebo in all five studies at doses of 16, 24 and 32 mg/day. In all studies, galantamine-treated patients maintained their cognitive function, whereas the placebo-treated patients experienced a significant deterioration in ADAS-cog scores. The 32-mg/day dose was not associated with any additional cognitive benefit. Pooled data from two 6-month studies (n = 1,269), which were of identical design, show that the therapeutic benefits of galantamine are sustained for the duration of treatment. The treatment effect (galantamine-placebo difference on ADAS-cog) for the pooled data was approximately 4 points. Clinical benefit was seen in all levels of disease severity, with a 7-point advantage over placebo on ADAS-cog for patients with moderately severe disease. Galantamine was well tolerated, with most patients completing the 6-month studies. The long-term effects of galantamine have been evaluated in a 12-month study. Patients who completed one of the pivotal 6-month studies (n = 353) were entered into a 6-month open-label extension. Cognitive and daily function were maintained throughout the 12 months in patients who received galantamine 24 mg/day. This sustained level of benefit may reflect galantamine's dual effect on the cholinergic system. Data from a 5-month, placebo-controlled study have also shown that galantamine produces significant benefits on behavioural symptoms. The persistence and range of

  8. Additional Treatments Offer Little Benefit for Pancreatic Cancer: Study

    MedlinePlus

    ... 158633.html Additional Treatments Offer Little Benefit for Pancreatic Cancer: Study Neither extra chemotherapy drug nor add-on ... 2016 (HealthDay News) -- Additional treatments for locally advanced pancreatic cancer don't appear to boost survival, a new ...

  9. 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

  10. 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

  11. Stevioside and related compounds: therapeutic benefits beyond sweetness.

    PubMed

    Chatsudthipong, Varanuj; Muanprasat, Chatchai

    2009-01-01

    Stevioside, an abundant component of Stevia rebaudiana leaf, has become well-known for its intense sweetness (250-300 times sweeter than sucrose) and is used as a non-caloric sweetener in several countries. A number of studies have suggested that, beside sweetness, stevioside along with related compounds, which include rebaudioside A (second most abundant component of S. rebaudiana leaf), steviol and isosteviol (metabolic components of stevioside) may also offer therapeutic benefits, as they have anti-hyperglycemic, anti-hypertensive, anti-inflammatory, anti-tumor, anti-diarrheal, diuretic, and immunomodulatory actions. It is of interest to note that their effects on plasma glucose level and blood pressure are only observed when these parameters are higher than normal. As steviol can interact with drug transporters, its role as a drug modulator is proposed. This review summarizes the current knowledge of the pharmacological actions, therapeutic applications, pharmacokinetics and safety of stevioside and related compounds. Although much progress has been made concerning their biological and pharmacological effects, questions regarding chemical purity and safety remain unsolved. These issues are discussed to help guide future research directions. PMID:19000919

  12. 45 CFR 155.170 - Additional required benefits.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 45 Public Welfare 1 2013-10-01 2013-10-01 false Additional required benefits. 155.170 Section 155.170 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES REQUIREMENTS RELATING TO HEALTH CARE ACCESS EXCHANGE ESTABLISHMENT STANDARDS AND OTHER RELATED STANDARDS UNDER THE AFFORDABLE CARE ACT...

  13. 45 CFR 155.170 - Additional required benefits.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 45 Public Welfare 1 2014-10-01 2014-10-01 false Additional required benefits. 155.170 Section 155.170 Public Welfare Department of Health and Human Services REQUIREMENTS RELATING TO HEALTH CARE ACCESS EXCHANGE ESTABLISHMENT STANDARDS AND OTHER RELATED STANDARDS UNDER THE AFFORDABLE CARE ACT...

  14. Prescribing for unlabeled conditions: patient benefit or therapeutic roulette?

    PubMed

    Serradell, J; Rucker, T D

    1990-01-01

    There is ample evidence that prescribed medications are employed for uses far broader than the approved label indications in the U.S. An enormous research agenda thus exists that should be addressed in the not-too-distant future. In fact, it seems essential that operation of the Medicare Catastrophic Drug Benefit program be designed with the best available knowledge in this area. Perhaps it might be appropriate for several universities, the U.S. Pharmacopeial Convention, and/or the FDA to establish a center to study this question. This model has been applied with clinical/surgical registries, with adverse reaction reporting, and with device failures. We need a rational, science-compatible, and uniform policy free of political and emotional arguments to address the issue of handling, monitoring, and regulating the use of drugs for unlabeled conditions. Comprehensive data should be provided for policy makers, regulators, payers, and clinicians in their evaluating the use of different drug products. Even a brief glance at any page from the National Disease and Therapeutic Index shows intended use that would cause most experts to react in disbelief. Further, there seem to be relatively few instances in which the use of a given pharmaceutical for an unlabeled indication would qualify as a drug of choice in the first place. The therapeutic and economic consequences of the use of legend drugs for unlabeled indications are difficult to document. We do know that a significant proportion of hospital admissions and days can be traced to the inappropriate use of pharmaceutical products but the net impact of our subject on institution cost has not been established.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:10106657

  15. 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.

  16. Three-dimensional echocardiography: the benefits of the additional dimension.

    PubMed

    Lang, Roberto M; Mor-Avi, Victor; Sugeng, Lissa; Nieman, Petra S; Sahn, David J

    2006-11-21

    Over the past 3 decades, echocardiography has become a major diagnostic tool in the arsenal of clinical cardiology for real-time imaging of cardiac dynamics. More and more, cardiologists' decisions are based on images created from ultrasound wave reflections. From the time ultrasound imaging technology provided the first insight into the human heart, our diagnostic capabilities have increased exponentially as a result of our growing knowledge and developing technology. One of the most significant developments of the last decades was the introduction of 3-dimensional (3D) imaging and its evolution from slow and labor-intense off-line reconstruction to real-time volumetric imaging. While continuing its meteoric rise instigated by constant technological refinements and continuing increase in computing power, this tool is guaranteed to be integrated in routine clinical practice. The major proven advantage of this technique is the improvement in the accuracy of the echocardiographic evaluation of cardiac chamber volumes, which is achieved by eliminating the need for geometric modeling and the errors caused by foreshortened views. Another benefit of 3D imaging is the realistic and unique comprehensive views of cardiac valves and congenital abnormalities. In addition, 3D imaging is extremely useful in the intraoperative and postoperative settings because it allows immediate feedback on the effectiveness of surgical interventions. In this article, we review the published reports that have provided the scientific basis for the clinical use of 3D ultrasound imaging of the heart and discuss its potential future applications. PMID:17112995

  17. Dopaminergic differentiation of stem cells from human deciduous teeth and their therapeutic benefits for Parkinsonian rats.

    PubMed

    Fujii, Hiromi; Matsubara, Kohki; Sakai, Kiyoshi; Ito, Mikako; Ohno, Kinji; Ueda, Minoru; Yamamoto, Akihito

    2015-07-10

    Parkinson's disease (PD) is a progressive neurodegenerative disorder caused by the loss of nigrostriatal dopaminergic (DAergic) neurons and the depletion of striatal dopamine. Here we show that DAergic-neuron-like cells could be efficiently induced from stem cells derived from human exfoliated deciduous teeth (SHEDs), and that these induced cells had therapeutic benefits in a 6-OHDA-induced Parkinsonian rat model. In our protocol, EGF and bFGF signaling activated the SHED's expression of proneural genes, Ngn2 and Mash1, and subsequent treatment with brain-derived neurotrophic factor (BDNF) promoted their maturation into DAergic neuron-like SHEDs (dSHEDs). A hypoxic DAergic differentiation protocol improved cell viability and enhanced the expression of multiple neurotrophic factors, including BDNF, GDNF, NT-3, and HGF. Engrafted dSHEDs survived in the striatum of Parkinsonian rats, improved the DA level more efficiently than engrafted undifferentiated SHEDs, and promoted the recovery from neurological deficits. Our findings further suggested that paracrine effects of dSHEDs contributed to neuroprotection against 6-OHDA-induced neurodegeneration and to nigrostriatal tract restoration. In addition, we found that the conditioned medium derived from dSHEDs protected primary neurons against 6-OHDA toxicity and accelerated neurite outgrowth in vitro. Thus, our data suggest that stem cells derived from dental pulp may have therapeutic benefits for PD. PMID:25863132

  18. 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.

  19. 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 §...

  20. 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 §...

  1. Cystic Fibrosis Transmembrane Conductance Regulator Activation by Roflumilast Contributes to Therapeutic Benefit in Chronic Bronchitis

    PubMed Central

    Lambert, James A.; Raju, S. Vamsee; Tang, Li Ping; McNicholas, Carmel M.; Li, Yao; Courville, Clifford A.; Farris, Roopan F.; Coricor, George E.; Smoot, Lisa H.; Mazur, Marina M.; Dransfield, Mark T.; Bolger, Graeme B.

    2014-01-01

    Cigarette smoking causes acquired cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction and is associated with delayed mucociliary clearance and chronic bronchitis. Roflumilast is a clinically approved phosphodiesterase 4 inhibitor that improves lung function in patients with chronic bronchitis. We hypothesized that its therapeutic benefit was related in part to activation of CFTR. Primary human bronchial epithelial (HBE) cells, Calu-3, and T84 monolayers were exposed to whole cigarette smoke (WCS) or air with or without roflumilast treatment. CFTR-dependent ion transport was measured in modified Ussing chambers. Airway surface liquid (ASL) was determined by confocal microscopy. Intestinal fluid secretion of ligated murine intestine was monitored ex vivo. Roflumilast activated CFTR-dependent anion transport in normal HBE cells with a half maximal effective concentration of 2.9 nM. Roflumilast partially restored CFTR activity in WCS-exposed HBE cells (5.3 ± 1.1 μA/cm2 vs. 1.2 ± 0.2 μA/cm2 [control]; P < 0.05) and was additive with ivacaftor, a specific CFTR potentiator approved for the treatment of CF. Roflumilast improved the depleted ASL depth of HBE monolayers exposed to WCS (9.0 ± 3.1 μm vs. 5.6 ± 2.0 μm [control]; P < 0.05), achieving 79% of that observed in air controls. CFTR activation by roflumilast also induced CFTR-dependent fluid secretion in murine intestine, increasing the wet:dry ratio and the diameter of ligated murine segments. Roflumilast activates CFTR-mediated anion transport in airway and intestinal epithelia via a cyclic adenosine monophosphate–dependent pathway and partially reverses the deleterious effects of WCS, resulting in augmented ASL depth. Roflumilast may benefit patients with chronic obstructive pulmonary disease with chronic bronchitis by activating CFTR, which may also underlie noninfectious diarrhea caused by roflumilast. PMID:24106801

  2. Defining Immunological Impact and Therapeutic Benefit of Mild Heating in a Murine Model of Arthritis

    PubMed Central

    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. PMID:25793532

  3. Measuring the patient health, societal and economic benefits of US pediatric therapeutics legislation.

    PubMed

    Vernon, John A; Shortenhaus, Scott H; Mayer, Mark H; Allen, Albert J; Golec, Joseph H

    2012-10-01

    Through at least the mid-1990s, children were often referred to as 'therapeutic orphans' for whom many treatments were administered without the benefit of appropriate studies to guide drug labeling for dosing and other critical therapeutic decisions. At that time, there were no incentives for manufacturers to pursue such work, nor regulatory requirements to compel these studies. Congress addressed this by including an important provision titled the Best Pharmaceuticals for Children Act (BPCA) in the 1997 Food and Drug Administration Modernization and Accountability Act. This was complemented by another key piece of legislation, the Pediatric Research Equity Act (PREA) in 2003. The former Act and its successors created an incentive for firms to study on-patent drugs in pediatric populations by extending the market exclusivity of a medicine by 6 months. The latter was a requirement that provided the US FDA with the authority to require studies of drugs in children if an adult indication also occurs in children. In the current paper, we consider the effects of both pieces of legislation in terms of the health, societal, and economic benefits they have likely imparted and will continue to provide in the future. We conclude that the gains have been substantial - both in terms of safer and more effective use of medicines in children and in terms of new research that has been incentivized by the BPCA exclusivity provision. We estimate the gross economic benefits from the latter alone to be approximately $US360 billion. PMID:22775493

  4. Multitarget strategies in Alzheimer's disease: benefits and challenges on the road to therapeutics.

    PubMed

    Rosini, Michela; Simoni, Elena; Caporaso, Roberta; Minarini, Anna

    2016-04-01

    Alzheimer's disease is a multifactorial syndrome, for which effective cures are urgently needed. Seeking for enhanced therapeutic efficacy, multitarget drugs have been increasingly sought after over the last decades. They offer the attractive prospect of tackling intricate network effects, but with the benefits of a single-molecule therapy. Herein, we highlight relevant progress in the field, focusing on acetylcholinesterase inhibition and amyloid pathways as two pivotal features in multitarget design strategies. We also discuss the intertwined relationship between selected molecular targets and give a brief glimpse into the power of multitarget agents as pharmacological probes of Alzheimer's disease molecular mechanisms. PMID:27079260

  5. 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.

  6. [Potential clinical benefit of therapeutic drug monitoring of imatinib in oncology].

    PubMed

    Turjap, M; Juřica, J; Demlová, R

    2015-01-01

    Imatinib mesylate is a competitive inhibitor of BCR/ ABL tyrosine kinase and inhibits also several receptor tyrosin kinases. Since its launch to the market, imatinib has proven to be very valuable in the treatment of Philadelphia chromosome (BCR/ ABL) -  positive (Ph+) chronic myeloid leukemia and Kit (CD117) positive gastrointestinal stromal tumors. The drug is metabolized by cytochrome P450, and there are many clinically important pharmacokinetic drug-drug interactions described in the literature. Frequent polypharmacy in oncological patients increases probability of such interactions, and also adherence may play its role during longterm treatment. Fixed dosing therapeutic regimens fail to respect known interindividual variability in pharmacokinetics of the drug and thus, some patients may not achieve sufficient plasma concentrations. Based on current evidence, there seems to be a relationship between plasma concentration and clinical response to imatinib. Therefore, imatinib appears to be suitable candidate for therapeutic drug monitoring. Here, we present an overview of pharmacokinetics, drug-drug interactions and current knowledge and suggestions on therapeutic drug monitor-ing of imatinib, its potential benefits and limitations. PMID:25882020

  7. 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…

  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. 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…

  10. Cochlear implantation among deaf children with additional disabilities: parental perceptions of benefits, challenges, and service provision.

    PubMed

    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 satisfaction with service provision, benefits, and challenges of the CI process. This was a mixed-methods study, which included a survey and interviews. Twenty-three families of deaf children with additional disabilities participated in this study, and 17 of these parents participated in in-depth interviews regarding their child's experience with the CI, including benefits and challenges. Interviews were analyzed through inductive thematic analysis. Parent-perceived benefits of cochlear implantation included children's improved sound awareness, communication skills, and greater well-being compared to preimplantation status. However, the majority of families felt that they and their children were not receiving enough services. Major challenges included managing funding; coping with limited availability of specialized services, particularly in rural areas; and continuing concerns about the child's communication, social skills, and academic performance. Results suggest that children with additional disabilities benefit from CIs, but they and their families also face unique challenges that professionals should consider when working with these families. PMID:25225328

  11. Therapeutic potential of resveratrol in obesity and type 2 diabetes: new avenues for health benefits?

    PubMed

    Timmers, Silvie; Hesselink, Matthijs K C; Schrauwen, Patrick

    2013-07-01

    The number of people suffering from metabolic disorders is dramatically increasing worldwide. The need for new therapeutic strategies to combat this growing epidemic of metabolic diseases is therefore also increasing. In 2003, resveratrol was discovered to be a small molecule activator of sirtuin 1 (SIRT1), an important molecular target regulating cellular energy metabolism and mitochondrial homeostasis. Rodent studies have clearly demonstrated the potential of resveratrol to improve various metabolic health parameters. To date, however, only limited clinical data are available that have systematically examined the health benefits of resveratrol in metabolically challenged humans. This short review will give an overview of the currently available clinical studies examining the effects of resveratrol on obesity and type 2 diabetes from a human perspective. PMID:23855469

  12. Cystamine and Intrabody Co-treatment Confers Additional Benefits in a Fly Model of Huntington’s Disease

    PubMed Central

    Bortvedt, S. F.; McLear, J. A.; Messer, A.; Ahern-Rindell, A. J.; Wolfgang, W. J.

    2010-01-01

    Huntington’s disease (HD) is a lethal, neurodegenerative disorder caused by expansion of the polyglutamine repeat in the Huntingtin gene (HTT), leading to mutant protein misfolding, aggregation, and neuronal death. Feeding a Drosophila HD-model cystamine, or expressing a transgene encoding the anti-htt intracellular antibody (intrabody) C4-scFv in the nervous system, demonstrated therapeutic potential, but suppression of pathology was incomplete. We hypothesized that a combinatorial approach entailing drug and intrabody administration could enhance rescue of HD pathology in flies and that timing of treatment would affect outcomes. Feeding cystamine to adult HD flies expressing the intrabody resulted in a significant, additional rescue of photoreceptor neurodegeneration, but no additional benefit in longevity. Feeding cystamine during both larval and adult stages produced the converse result: longevity was significantly improved, but increased photoreceptor survival was not. We conclude that cystamine-intrabody combination therapies can be effective, reducing neurodegeneration and prolonging survival, depending on administration protocols. PMID:20399860

  13. Study on the Therapeutic Benefit on Lactoferrin in Patients with Colorectal Cancer Receiving Chemotherapy

    PubMed Central

    Moastafa, Tarek M.; El-Sissy, Alaa El-Din Elsayed; El-Saeed, Gehan K.; Koura, Mai Salah El-Din

    2014-01-01

    A double-blinded parallel randomized controlled clinical trial was conducted on two groups of colorectal cancer patients to study the therapeutic benefit of orally administered bovine lactoferrin (bLF) on colorectal cancer patients having age ranges from 20 to 71 years and who received 5-fluorouracil and leucovorin calcium. Test group (15 patients) received oral bLF 250 mg/day beside chemotherapy for three months. Control group (15 patients) received chemotherapy only. Serum lactoferrin (LF), serum glutathione-s-transferase enzyme (GST), interferon gamma (INF-γ), tumor marker carcinoembryonic antigen (CEA), renal function tests, hepatic function tests, and complete blood count were measured for both groups before and at the end of the trial. Although, there was a significant effect of oral bLF (250 mg/day) that indicated a significant improvement in mean percent of change of all parameters 3 months after treatment, there was no significant difference between results of patients in the test group and patients in the control group after treatment. This result suggests that oral bLF has significant therapeutic effect on colorectal cancer patients. Our study suggests that daily administration of bLF showed a clinically beneficial effect to colorectal cancer patients with better disease prognosis but that needs further looking into.

  14. 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.

  15. 42 CFR 417.442 - Risk HMO's and CMP's: Conditions for provision of additional benefits.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 3 2012-10-01 2012-10-01 false Risk HMO's and CMP's: Conditions for provision of additional benefits. 417.442 Section 417.442 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICARE PROGRAM (CONTINUED) HEALTH MAINTENANCE ORGANIZATIONS, COMPETITIVE MEDICAL PLANS,...

  16. 42 CFR 417.442 - Risk HMO's and CMP's: Conditions for provision of additional benefits.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 3 2010-10-01 2010-10-01 false Risk HMO's and CMP's: Conditions for provision of... Medicare Contract § 417.442 Risk HMO's and CMP's: Conditions for provision of additional benefits. (a) General rule. Except as provided in paragraph (b) of this section, a risk HMO or CMP must, during...

  17. 42 CFR 417.442 - Risk HMO's and CMP's: Conditions for provision of additional benefits.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 3 2011-10-01 2011-10-01 false Risk HMO's and CMP's: Conditions for provision of... Medicare Contract § 417.442 Risk HMO's and CMP's: Conditions for provision of additional benefits. (a) General rule. Except as provided in paragraph (b) of this section, a risk HMO or CMP must, during...

  18. 42 CFR 417.442 - Risk HMO's and CMP's: Conditions for provision of additional benefits.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 3 2013-10-01 2013-10-01 false Risk HMO's and CMP's: Conditions for provision of additional benefits. 417.442 Section 417.442 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICARE PROGRAM (CONTINUED) HEALTH MAINTENANCE ORGANIZATIONS, COMPETITIVE MEDICAL PLANS,...

  19. 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.…

  20. 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 §...

  1. 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 §...

  2. 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 §...

  3. 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 §...

  4. 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 §...

  5. Targeting smooth muscle microRNAs for therapeutic benefit in vascular disease.

    PubMed

    Albinsson, Sebastian; Swärd, Karl

    2013-09-01

    In view of the bioinformatic projection that a third of all protein coding genes and essentially all biological pathways are under control of microRNAs (miRNAs), it is not surprising that this class of small RNAs plays roles in vascular disease progression. MiRNAs have been shown to be involved in cholesterol turnover, thrombosis, glucose homeostasis and vascular function. Some miRNAs appear to be specific for certain cells, and the role that such cell-specific miRNAs play in vascular disease is only beginning to be appreciated. A notable example is the miR-143/145 cluster which is enriched in mature and highly differentiated smooth muscle cells (SMCs). Here we outline and discuss the recent literature on SMC-expressed miRNAs in major vascular diseases, including atherosclerosis, neointima formation, aortic aneurysm formation, and pulmonary arterial hypertension. Forced expression of miR-145 emerges as a promising strategy for reduction and stabilization of atherosclerotic plaques as well as for reducing neointimal hyperplasia. It is concluded that if obstacles in the form of delivery and untoward effects of antimirs and mimics can be overcome, the outlook for targeting of SMC-specific miRNAs for therapeutic benefit in vascular disease is bright. PMID:23611811

  6. 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

  7. 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

  8. Searching for additional endocrine functions of the skeleton: genetic approaches and implications for therapeutics

    PubMed Central

    Wei, Jianwen; Flaherty, Stephen; Karsenty, Gerard

    2016-01-01

    Our knowledge of whole organism physiology has greatly advanced in the past decades through mouse genetics. In particular, genetic studies have revealed that most organs interact with one another through hormones in order to maintain normal physiological functions and the homeostasis of the entire organism. Remarkably, through these studies many unexpected novel endocrine means to regulate physiological functions have been uncovered. The skeletal system is one example. In this article, we review a series of studies that over the years have identified bone as an endocrine organ. The mechanism of action, pathological relevance, and therapeutic implications of the functions of the bone-derived hormone osteocalcin are discussed. In the last part of this review we discuss the possibility that additional endocrine functions of the skeleton may exist.

  9. Additive benefits of external focus and enhanced performance expectancy for motor learning.

    PubMed

    Pascua, Luigi A M; Wulf, Gabriele; Lewthwaite, Rebecca

    2015-01-01

    The authors examined the individual and combined influences of 2 factors that have been shown to benefit motor learning: an external focus of attention and enhanced performance expectancies. Another purpose of this study was to gain further insight into the mechanisms underlying these variables. In a factorial design, participants learning a novel motor skill (i.e., throwing with the non-dominant arm) were or were not given external focus instructions, and were or were not provided bogus positive social-comparative feedback to enhance their expectancies. This resulted in 4 groups: external focus, enhanced expectancy, external focus/enhanced expectancy and control. External focus instructions and enhanced expectancies had additive benefits for learning: the external focus/enhanced expectancy group demonstrated the greatest throwing accuracy on both retention and transfer tests, while the accuracy scores of the external focus and enhanced expectancy groups were lower, but higher than those of the control group. Furthermore, self-efficacy was increased by both external focus and enhanced expectancy, and predicted retention and transfer performance. Positive affect was heightened in the enhanced expectancy and external focus/enhanced expectancy groups after practice and predicted transfer performance. The findings suggest that the learning benefits of an external focus and enhanced expectancies mediate learning through partially different mechanisms. PMID:24875153

  10. [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. PMID:27003322

  11. 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.

  12. [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. PMID:7058519

  13. Addition of Azathioprine to Corticosteroids Does Not Benefit Patients with IgA Nephropathy

    PubMed Central

    Andrulli, Simeone; Pani, Antonello; Scaini, Patrizia; Del Vecchio, Lucia; Fogazzi, Giambattista; Vogt, Bruno; De Cristofaro, Vincenzo; Allegri, Landino; Cirami, Lino; Procaccini, Aldo Deni; Locatelli, Francesco

    2010-01-01

    The optimal treatment for IgA nephropathy (IgAN) remains unknown. Some patients respond to corticosteroids, suggesting that more aggressive treatment may provide additional benefit. We performed a randomized, multicenter, controlled trial to determine whether adding azathioprine to steroids improves renal outcome. We randomly assigned 207 IgAN patients with creatinine ≤2.0 mg/dl and proteinuria ≥1.0 g/d to either (1) a 3-day pulse of methylprednisolone in months 1, 3, and 5 in addition to both oral prednisone 0.5 mg/kg every other day and azathioprine 1.5 mg/kg per day for 6 months (n = 101, group 1) or (2) steroids alone on the same schedule (n = 106, group 2). The primary outcome was renal survival (time to 50% increase in plasma creatinine from baseline); secondary outcomes were changes in proteinuria over time and safety. After a median follow-up of 4.9 years, the primary endpoint occurred in 13 patients in group 1 (12.9%, 95% CI 7.5 to 20.9%) and 12 patients in group 2 (11.3%, CI 6.5 to 18.9%) (P = 0.83). Five-year cumulative renal survival was similar between groups (88 versus 89%; P = 0.83). Multivariate Cox regression analysis revealed that female gender, systolic BP, number of antihypertensive drugs, ACE inhibitor use, and proteinuria during follow-up predicted the risk of reaching the primary endpoint. Treatment significantly decreased proteinuria from 2.00 to 1.07 g/d during follow-up (P < 0.001) on average, with no difference between groups. Treatment-related adverse events were more frequent among those receiving azathioprine. In summary, adding low-dose azathioprine to corticosteroids for 6 months does not provide additional benefit to patients with IgAN and may increase the risk for adverse events. PMID:20634300

  14. 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

  15. 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.…

  16. [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. PMID:26776691

  17. Improved Therapeutic Benefits by Combining Physical Cooling With Pharmacological Hypothermia After Severe Stroke in Rats

    PubMed Central

    Lee, Jin Hwan; Wei, Ling; Gu, Xiaohuan; Won, Soonmi; Wei, Zheng Zachory; Dix, Thomas A.

    2016-01-01

    Background and Purpose— Therapeutic hypothermia is a promising strategy for treatment of acute stroke. Clinical translation of therapeutic hypothermia, however, has been hindered because of the lack of efficiency and adverse effects. We sought to enhance the clinical potential of therapeutic hypothermia by combining physical cooling (PC) with pharmacologically induced hypothermia after ischemic stroke. Methods— Wistar rats were subjected to 90-minute middle cerebral artery occlusion by insertion of an intraluminal filament. Mild-to-moderate hypothermia was induced 120 minutes after the onset of stroke by PC alone, a neurotensin receptor 1 (NTR1) agonist HPI-201 (formally ABS-201) alone or the combination of both. The outcomes of stroke were evaluated at 3 and 21 days after stroke. Results— PC or HPI-201 each showed hypothermic effect and neuroprotection in stroke rats. The combination of PC and HPI-201 exhibited synergistic effects in cooling process, reduced infarct formation, cell death, and blood-brain barrier damages and improved functional recovery after stroke. Importantly, coapplied HPI-201 completely inhibited PC-associated shivering and tachycardia. Conclusions— The centrally acting hypothermic drug HPI-201 greatly enhanced the efficiency and efficacy of conventional PC; this combined cooling therapy may facilitate clinical translation of hypothermic treatment for stroke. PMID:27301934

  18. 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]. PMID:22303970

  19. Molecular pathways: targeting resistance in the androgen receptor for therapeutic benefit.

    PubMed

    Mostaghel, Elahe A; Plymate, Stephen R; Montgomery, Bruce

    2014-02-15

    Androgen receptor signaling is critical in the development and progression of prostate cancer, leading to intensive efforts to elucidate all potential points of inflection for therapeutic intervention. These efforts have revealed new mechanisms of resistance and raise the possibility that known mechanisms may become even more relevant in the context of effective androgen receptor suppression. These mechanisms include tumoral appropriation of alternative androgen sources, alterations in androgen receptor expression, androgen receptor mutations, truncated androgen receptor variants, alterations and cross-talk in recruitment of cofactors to androgen receptor binding sites in the genome, and androgen receptor-driven oncogenic gene fusions. New agents such as enzalutamide, EPI-001, androgen receptor-specific peptidomimetics, novel HSP90 inhibitors, and PARP inhibitors, as well as new approaches to cotargeting the androgen receptor pathway, point to the potential for more complete and durable control of androgen receptor-mediated growth. PMID:24305618

  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. PMID:24027887

  1. Therapeutic targeting of the mTOR-signalling pathway in cancer: benefits and limitations

    PubMed Central

    Moschetta, M; Reale, A; Marasco, C; Vacca, A; Carratù, M R

    2014-01-01

    The mammalian target of rapamycin (mTOR) plays an important role in the regulation of protein translation, cell growth and metabolism. The mTOR protein forms two distinct multi-subunit complexes: mTORC1 and mTORC2. The mTORC1 complex is activated by diverse stimuli, such as growth factors, nutrients, energy and stress signals; and essential signalling pathways, such as PI3K and MAPK, in order to control cell growth, proliferation and survival. mTORC1 also activates S6K1 and 4EBP1, which are involved in mRNA translation. The mTORC2 complex is resistant to rapamycin inhibitory activity and is generally insensitive to nutrient- and energy-dependent signals. It activates PKC-α and Akt and regulates the actin cytoskeleton. Deregulation of the mTOR-signalling pathway (PI3K amplification/mutation, PTEN loss of function, Akt overexpression, and S6K1, 4EBP1 and eIF4E overexpression) is common in cancer, and alterations in components of the mTOR pathway have a major role in tumour progression. Therefore, mTOR is an appealing therapeutic target in many tumours. Here we summarize the upstream regulators and downstream effectors of the mTORC1 and mTORC2 pathways, the role of mTOR in cancer, and the potential therapeutic values and issues related to the novel agents targeting the mTOR-signalling pathway. PMID:24780124

  2. 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. PMID:26463349

  3. Therapeutic Benefits of Induced Pluripotent Stem Cells in Monocrotaline-Induced Pulmonary Arterial Hypertension.

    PubMed

    Huang, Wei-Chun; Ke, Meng-Wei; Cheng, Chin-Chang; Chiou, Shih-Hwa; Wann, Shue-Ren; Shu, Chih-Wen; Chiou, Kuan-Rau; Tseng, Ching-Jiunn; Pan, Hung-Wei; Mar, Guang-Yuan; Liu, Chun-Peng

    2016-01-01

    Pulmonary arterial hypertension (PAH) is characterized by progressive increases in vascular resistance and the remodeling of pulmonary arteries. The accumulation of inflammatory cells in the lung and elevated levels of inflammatory cytokines in the bloodstream suggest that inflammation may play a role in PAH. In this study, the benefits of induced pluripotent stem cells (iPSCs) and iPSC-conditioned medium (iPSC CM) were explored in monocrotaline (MCT)-induced PAH rats. We demonstrated that both iPSCs and iPSC CM significantly reduced the right ventricular systolic pressure and ameliorated the hypertrophy of the right ventricle in MCT-induced PAH rats in models of both disease prevention and disease reversal. In the prevention of MCT-induced PAH, iPSC-based therapy led to the decreased accumulation of inflammatory cells and down-regulated the expression of the IL-1β, IL-6, IL-12α, IL-12β, IL-23 and IFNγ genes in lung specimens, which implied that iPSC-based therapy may be involved in the regulation of inflammation. NF-κB signaling is essential to the inflammatory cascade, which is activated via the phosphorylation of the NF-κB molecule. Using the chemical inhibitor specifically blocked the phosphorylation of NF-κB, and in vitro assays of cultured human M1 macrophages implied that the anti-inflammation effect of iPSC-based therapy may contribute to the disturbance of NF-κB activation. Here, we showed that iPSC-based therapy could restore the hemodynamic function of right ventricle with benefits for preventing the ongoing inflammation in the lungs of MCT-induced PAH rats by regulating NF-κB phosphorylation. PMID:26840075

  4. 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

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

    PubMed

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

    2016-05-11

    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

  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. PMID:25698488

  7. Intermittent hypoxia in childhood: the harmful consequences versus potential benefits of therapeutic uses.

    PubMed

    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. [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. PMID:19368291

  9. 20 CFR 725.309 - Additional claims; effect of a prior denial of benefits.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ..., DEPARTMENT OF LABOR FEDERAL COAL MINE HEALTH AND SAFETY ACT OF 1969, AS AMENDED CLAIMS FOR BENEFITS UNDER... (child), and 725.222 (parent, brother, or sister)) has changed since the date upon which the order..., child, parent, brother, or sister shall be denied unless the applicable conditions of entitlement...

  10. [Therapeutic benefit of touch-massage in the overall management of demented elderly].

    PubMed

    Malaquin-Pavan, E

    1997-06-01

    This detailed research tries out a "Touch-Massage" action about the studies of reflex and estimates the repercussion this action may have as regards the abnormal behaviour (either in connection with wandering and/or restlessness and/or shouting) of the Elderly who stay in a same place and show cognitive deficiency in connection with an Alzheimer's dementia. In order to check the "intra personal" consequences this action may have, 4 elderly people were chosen and an experimental estimate with different levels was made with them. Two sessions a week of 30 minutes each during 6 months (51 sessions) were suggested that is to say a total of 204 sessions. The effects of this approach regarding the different abnormal behaviour are estimated on one hand from a special clinical grid which assess the different reactions, verbal or not, which occurred during the session. On the other hand the effects are observed directly fifteen minutes after the session. The results are explained, first, for each person and compared between each other; then they are explained according to a collective way regarding the 4 old people. What emerges from all that is that for the whole sessions which were proposed, the activity was accepted at 95%. During the session, the signs showing physical relaxation (59%), sleepiness (34%), research of different manners to communicate with us (59%), stop or decrease of the abnormal behaviour (79%) prove the actual benefit the activity brings during thirty minutes. Fifteen minutes after the session, the signs showing physical relaxation (52%), sleepiness (42%), research of different manners to communicate with us (23%), stop or decrease of the abnormal behaviour (70%) are always significant. In view of the above results, we can stay this new approach using the activity of "Touch Massage" brings a further possibility of nursing care and can help to answer the question "how to take in charge every day an elderly demented patient". PMID:9326100

  11. 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

  12. 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…

  13. 42 CFR 408.21 - Reduction in Medicare Part B premium as an additional benefit under Medicare+Choice plans.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 2 2013-10-01 2013-10-01 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...

  14. 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.

  15. 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

  16. Steroids augment relengthening of contracted airway smooth muscle: potential additional mechanism of benefit in asthma.

    PubMed

    Lakser, O J; Dowell, M L; Hoyte, F L; Chen, B; Lavoie, T L; Ferreira, C; Pinto, L H; Dulin, N O; Kogut, P; Churchill, J; Mitchell, R W; Solway, J

    2008-11-01

    Breathing (especially deep breathing) antagonises development and persistence of airflow obstruction during bronchoconstrictor stimulation. Force fluctuations imposed on contracted airway smooth muscle (ASM) in vitro result in its relengthening, a phenomenon called force fluctuation-induced relengthening (FFIR). Because breathing imposes similar force fluctuations on contracted ASM within intact lungs, FFIR represents a likely mechanism by which breathing antagonises bronchoconstriction. While this bronchoprotective effect appears to be impaired in asthma, corticosteroid treatment can restore the ability of deep breaths to reverse artificially induced bronchoconstriction in asthmatic subjects. It has previously been demonstrated that FFIR is physiologically regulated through the p38 mitogen-activated protein kinase (MAPK) signalling pathway. While the beneficial effects of corticosteroids have been attributed to suppression of airway inflammation, the current authors hypothesised that alternatively they might exert their action directly on ASM by augmenting FFIR as a result of inhibiting p38 MAPK signalling. This possibility was tested in the present study by measuring relengthening in contracted canine tracheal smooth muscle (TSM) strips. The results indicate that dexamethasone treatment significantly augmented FFIR of contracted canine TSM. Canine tracheal ASM cells treated with dexamethasone demonstrated increased MAPK phosphatase-1 expression and decreased p38 MAPK activity, as reflected in reduced phosphorylation of the p38 MAPK downstream target, heat shock protein 27. These results suggest that corticosteroids may exert part of their therapeutic effect through direct action on airway smooth muscle, by decreasing p38 mitogen-activated protein kinase activity and thus increasing force fluctuation-induced relengthening. PMID:18768574

  17. News Note: Addition of drug to standard chemo for prostate cancer shows no benefit

    Cancer.gov

    Prostate cancer patients in a phase 3 trial who were non-responsive to hormone therapy and received the investigational agent atrasentan in addition to a standard chemotherapy regimen, did not have longer survival or longer progression-free survival compared to the patients on the same chemotherapy regimen and a placebo. This determination was made by the trial’s Data and Safety Monitoring Committee (DSMC) based on a planned interim analysis of the trial.

  18. Work while receiving disability insurance benefits: additional findings from the New Beneficiary Followup Survey.

    PubMed

    Schechter, E S

    1997-01-01

    From the foregoing analyses, the following picture emerges about persons who work after award of DI benefits: Almost one-quarter of the sample population attempted to reenter the labor force in the 10-year NBS-NBF period. The higher the level of education, the greater the proportion of persons who worked. Younger beneficiaries were more likely to work than older beneficiaries. About half of the beneficiaries who worked did so on a full-time (40-hour-or-more per week) basis. Most beneficiaries worked because of financial need. The profile of reasons for working did not vary across demographic groups and aspects of the first job held. Most beneficiaries began working without attributing this decision to an improvement in their health. Individuals pursued different methods of job search. No single approach emerged as the most successful. Job search modes did not vary for different groups and different jobs. Four activities were most likely to lead to job offers: persons checking where they had worked before, asking a friend, answering an ad, and following up a vocational rehabilitation lead. These findings were not conclusive because small numbers of persons engaged in these activities. Thirty percent of DI workers returned to their preentitlement employer. The beneficiaries' first postentitlement jobs had less exertion, fewer hours, and lower pay than did their job held prior to award. The likelihood of working was the same across a broad range of disabling health conditions. In terms of work return policy, formal work return programs aimed at young beneficiaries and those with higher levels of educational attainment would produce the greatest number of job placements. It appears that no targeting of programs is necessary along gender lines. The anomalous finding of an absence of the relationship between improvement in health and labor-force reentry requires further investigation. Any followup in this area of inquiry should plan to have the data collected close to

  19. 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. PMID:25738234

  20. Therapeutic benefit of a dissociated glucocorticoid and the relevance of in vitro separation of transrepression from transactivation activity.

    PubMed

    Belvisi, M G; Wicks, S L; Battram, C H; Bottoms, S E; Redford, J E; Woodman, P; Brown, T J; Webber, S E; Foster, M L

    2001-02-01

    Glucocorticoids (GCs) are the mainstay of asthma therapy; however, major side effects limit their therapeutic use. GCs influence the expression of genes either by transactivation or transrepression. The antiinflammatory effects of steroids are thought to be due to transrepression and the side effects, transactivation. Recently, a compound, RU 24858, has been identified that demonstrated dissociation between transactivation and transrepression in vitro. RU 24858 exerts strong AP-1 inhibition (transrepression), but little or no transactivation. We investigated whether this improved in vitro profile results in the maintenance of antiinflammatory activity (evaluated in the Sephadex model of lung edema) with reduced systemic toxicity (evaluated by loss in body weight, thymus involution, and bone turnover) compared with standard GCs. RU 24858 exhibits comparable antiinflammatory activity to the standard steroid, budesonide. However, the systemic changes observed indicate that transactivation events do occur with this GC with similar potency to the standard steroids. In addition, the GCs profiled showed no differentiation on quantitative osteopenia of the femur. These results suggest that in vitro separation of transrepression from transactivation activity does not translate to an increased therapeutic ratio for GCs in vivo or that adverse effects are a consequence of transrepression. PMID:11160246

  1. Revisiting the dialogue on the transition from coteaching to inservice teaching: new frameworks, additional benefits and emergent issues

    NASA Astrophysics Data System (ADS)

    Wassell, Beth; Lavan, Sarah Kate

    2009-06-01

    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 some of the future directions that should be explored in coteaching research.

  2. 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

  3. Addition of low dose hCG to rFSh benefits older women during ovarian stimulation for IVF

    PubMed Central

    2012-01-01

    Background To compare the outcome of IVF cycles in women receiving controlled ovarian stimulation with recFSH or recFSH plus low dose hCG. Methods A retrospective case control study, performed at a private practice affiliated with an academic institute. Patients were infertile women who were treated with IVF/ICSI and controlled ovarian stimulation in a long GnRH agonist protocol using either low dose hCG in addition to recFSH [N = 88] or recFSH alone [N = 99]. Primary outcomes were mean FSH dose, number of mature eggs, number of fertilized eggs, and serum levels of estradiol. Secondary outcomes were endometrial thickness, cycle cancellations and pregnancy rates. Results A significant increase in number of mature and fertilized eggs was observed in women over 40 years of age using low dose hCG in addition to recFSH. The estradiol level was significantly higher on the day of hCG administration and the serum level of FSH on cycle day 7 and on the day of hCG administration were lower. Conclusion Addition of low dose hCG to recFSH compared with recFSH alone significantly modified cycle characteristics in patients >/= 40 years and could be of potential benefit for IVF cycles in older infertile women. PMID:22866896

  4. 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. PMID:18955271

  5. Early Treatment with Addition of Low Dose Prednisolone to Methotrexate Improves Therapeutic Outcome in Severe Psoriatic Arthritis

    PubMed Central

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

    2013-01-01

    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. PMID:23723489

  6. 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

  7. 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

  8. 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. PMID:22571446

  9. Analysis of pre-treatment markers predictive of treatment benefit for the therapeutic cancer vaccine MVA-5T4 (TroVax).

    PubMed

    Harrop, Richard; Treasure, Peter; de Belin, Jackie; Kelleher, Michelle; Bolton, Gemma; Naylor, Stuart; Shingler, William H

    2012-12-01

    Cancer vaccines such as MVA-5T4 (TroVax(®)) must induce an efficacious immune response to deliver therapeutic benefit. The identification of biomarkers that impact on the clinical and/or immunological efficacy of cancer vaccines is required in order to select patients who are most likely to benefit from this treatment modality. Here, we sought to identify a predictor of treatment benefit for renal cancer patients treated with MVA-5T4. Statistical modeling was undertaken using data from a phase III trial in which patients requiring first-line treatment for metastatic renal cell carcinoma were randomized 1:1 to receive MVA-5T4 or placebo alongside sunitinib, IL-2 or IFN-α. Numerous pre-treatment factors associated with inflammatory anemia (e.g., CRP, hemoglobin, hematocrit, IL-6, ferritin, platelets) demonstrated a significant relationship with tumor burden and patient survival. From these prognostic factors, the pre-treatment mean corpuscular hemoglobin concentration (MCHC) was found to be the best predictor of treatment benefit (P < 0.01) for MVA-5T4 treated patients and also correlated positively with tumor shrinkage (P < 0.001). Furthermore, MCHC levels showed a significant positive association with 5T4 antibody response (P = 0.01). The latter result was confirmed using an independent data set comprising phase II trials of MVA-5T4 in patients with colorectal, renal and prostate cancers. Retrospective analyses demonstrated that RCC patients who had very large tumor burdens and low MCHC levels received little or no benefit from treatment with MVA-5T4; however, patients with smaller tumor burdens and normal MCHC levels received substantial benefit from treatment with MVA-5T4. PMID:22692758

  10. 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. PMID:24080471

  11. Possible therapeutic benefits of adenosine-potentiating drugs in reducing age-related degenerative disease in dogs and cats.

    PubMed

    Scaramuzzi, R J; Baker, D J

    2003-10-01

    Adenosine is a ubiquitous, biologically important molecule that is a precursor of other biologically active molecules. It also is a component of some co-factors and has distinct physiological actions in its own right. Levels are maintained by synthesis from dietary precursors and re-cycling. The daily turnover of adenosine is very high. Adenosine can act either as a hormone by binding to adenosine receptors, four adenosine receptor subtypes have been identified, and as an intracellular modulator, after transport into the cell by membrane transporter proteins. One of the principal intracellular actions of adenosine is inhibition of the enzyme phosphodiesterase. Extracellular adenosine also has specific neuromodulatory actions on dopamine and glutamate. Selective and nonselective agonists and antagonists of adenosine are available. The tasks of developing, evaluating and exploiting the therapeutic potential of these compounds is still in its infancy. Adenosine has actions in the central nervous system (CNS), heart and vascular system, skeletal muscle and the immune system and the presence of receptors suggests potential actions in the gonads and other organs. Adenosine agonists improve tissue perfusion through actions on vascular smooth muscle and erythrocyte fluidity and they can be used to improve the quality of life in aged dogs. This article reviews the therapeutic potential of adenosine-potentiating drugs in the treatment of age-related conditions in companion animals, some of which may be exacerbated by castration or spaying at an early age. PMID:14633184

  12. Long-Term Consequences of Developmental Alcohol Exposure on Brain Structure and Function: Therapeutic Benefits of Physical Activity

    PubMed Central

    Klintsova, Anna Y.; Hamilton, Gillian F.; Boschen, Karen E.

    2012-01-01

    Developmental alcohol exposure both early in life and during adolescence can have a devastating impact on normal brain structure and functioning, leading to behavioral and cognitive impairments that persist throughout the lifespan. This review discusses human work as well as animal models used to investigate the effect of alcohol exposure at various time points during development, as well as specific behavioral and neuroanatomical deficits caused by alcohol exposure. Further, cellular and molecular mediators contributing to these alcohol-induced changes are examined, such as neurotrophic factors and apoptotic markers. Next, this review seeks to support the use of aerobic exercise as a potential therapeutic intervention for alcohol-related impairments. To date, few interventions, behavioral or pharmacological, have been proven effective in mitigating some alcohol-related deficits. Exercise is a simple therapy that can be used across species and also across socioeconomic status. It has a profoundly positive influence on many measures of learning and neuroplasticity; in particular, those measures damaged by alcohol exposure. This review discusses current evidence that exercise may mitigate damage caused by developmental alcohol exposure and is a promising therapeutic target for future research and intervention strategies. PMID:24961305

  13. 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. PMID:23692774

  14. Impact of the quebec school-based hepatitis B immunization program and potential benefit of the addition of an infant immunization program.

    PubMed

    Gîlca, Vladimir; Duval, Bernard; Boulianne, Nicole; Dion, Réjean; De Serres, Gaston

    2006-04-01

    Ten years after a school-based hepatitis B immunization program was implemented, we conducted a study to assess the impact of the program, vaccine failures, risk factors and the number of cases potentially preventable by the addition of an infant vaccination program. The preteen vaccination program is highly effective. An infant immunization program would bring additional benefits. PMID:16567995

  15. Therapeutic benefits of combined treatment with tissue plasminogen activator and 2-(4-methoxyphenyl)ethyl-2-acetamido-2-deoxy-β-d-pyranoside in an animal model of ischemic stroke.

    PubMed

    Yu, Shu; Liu, Xin; Shen, Yuntian; Xu, Hui; Yang, Yumin; Ding, Fei

    2016-07-01

    Tissue plasminogen activator (tPA) is the only approved therapy for acute ischemic stroke, but tPA therapy is limited by a short therapeutic window and some adverse side effects. 2-(4-Methoxyphenyl)ethyl-2-acetamido-2-deoxy-β-d-pyranoside, a salidroside analog (code-named SalA-4g), has shown potent neuroprotective effects. In this study, a rat model of embolic middle cerebral artery occlusion (MCAO) was used to mimic ischemic stroke. The embolic MCAO rats were intravenously (iv) injected with tPA alone, SalA-4g alone, or a combination of tPA and SalA-4g. Compared to treatment with tPA alone at 4h post MCAO, combined treatment with tPA at 4h post MCAO and SalA-4g starting at 4h post MCAO and continuing for 3days at an interval of 24h significantly reduced neurological deficits and infarct volume, and significantly inhibited the intracerebral bleeding, edema formation, neuronal loss, and cellular apoptosis in the ischemic brain. Our results suggested that additive neuroprotective actions of SalA-4g contributed to widening the therapeutic window of tPA therapy and ameliorating its side effects in treating MCAO rats. The therapeutic benefits of combined treatment with tPA and SalA-4g for ischemic stroke might be associated with its effects on cerebral glucose metabolism. PMID:27060484

  16. Lymphedema Prevalence and Treatment Benefits in Cancer: Impact of a Therapeutic Intervention on Health Outcomes and Costs

    PubMed Central

    Brayton, Kimberly M.; Hirsch, Alan T.; O′Brien, Patricia J.; Cheville, Andrea; Karaca-Mandic, Pinar; Rockson, Stanley G.

    2014-01-01

    Background Lymphedema is a common complication of cancer therapeutics; its prevalence, treatment outcomes, and costs have been poorly defined. The objective of this study was to examine lymphedema prevalence among cancer survivors and to characterize changes in clinical outcomes and costs associated with a defined therapeutic intervention (use of a pneumatic compression devices [PCD]) in a representative, privately insured population. Methods and Findings Retrospective analysis of de-identified health claims data from a large national insurer for calendar years 2007 through 2013. Patients were required to have 12 months of continuous insurance coverage prior to PCD receipt (baseline), as well as a 12-month follow-up period. Analyses were performed for individuals with cancer-related lymphedema (n = 1,065). Lymphedema prevalence was calculated: number of patients with a lymphedema claim in a calendar year divided by total number of enrollees. The impact of PCD use was evaluated by comparing rates of a pre-specified set of health outcomes and costs for the 12 months before and after, respectively, PCD receipt. Lymphedema prevalence among cancer survivors increased from 0.95% in 2007 to 1.24% in 2013. PCD use was associated with decreases in rates of hospitalizations (45% to 32%, p<0.0001), outpatient hospital visits (95% to 90%, p<0.0001), cellulitis diagnoses (28% to 22%, p = 0.003), and physical therapy use (50% to 41%, p<0.0001). The average baseline health care costs were high ($53,422) but decreased in the year after PCD acquisition (−$11,833, p<0.0001). Conclusions Lymphedema is a prevalent medical condition that is often a defining attribute of cancer survivorship. The problem is associated with high health care costs; Treatment (in this instance, use of PCD) is associated with significant decreases in adverse clinical outcomes and costs. PMID:25470383

  17. [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. PMID:26927680

  18. Mycophenolate mofetil and curcumin provide comparable therapeutic benefit in experimental chronic kidney disease: role of Nrf2-Keap1 and renal dopamine pathways.

    PubMed

    Tapia, Edilia; García-Arroyo, Fernando; Silverio, Octaviano; Rodríguez-Alcocer, Alma N; Jiménez-Flores, Ana B; Cristobal, Magdalena; Arellano, Abraham S; Soto, Virgilia; Osorio-Alonso, Horacio; Molina-Jijón, Eduardo; Pedraza-Chaverri, José; Sanchez-Lozada, Laura G

    2016-07-01

    Increased oxidative stress and inflammation have an important role in the pathophysiology of chronic kidney disease (CKD). On the other hand, more affordable therapeutic alternatives for treating this disease are urgently needed. Therefore, we compared the therapeutic efficacy of curcumin and mycophenolate mofetil (MMF) in 5/6 nephrectomy (5/6 Nx) model of CKD. Also, we evaluated whether both compounds provide benefit through the preservation of similar antioxidant mechanisms. Four groups of male Wistar were studied over a period of 4 wk. Control sham group (n= 12), 5/6 Nx (n = 12), 5/6 Nx + MMF (30 mg/k BW/day, n = 11) and 5/6 Nx + Curcumin (120 mg/k BW/day, n = 12). Renal function and markers of oxidative stress and inflammation were evaluated. Also Nrf2-Keap1 and renal dopamine, antioxidant pathways were assessed. 5/6 Nx induced an altered renal autoregulation response, proteinuria, and hypertension; these effects were in association with increased oxidative stress, endothelial dysfunction and renal inflammation. The mechanisms associated with these alterations included a reduced nuclear translocation of Nrf2 and hyperphosphorylation of dopamine D1 receptor with a concurrent overactivation of renal NADPH oxidase. Treatments with MMF and curcumin provided equivalent therapeutic efficacy as both prevented functional renal alterations as well as preserved antioxidant capacity and avoided renal inflammatory infiltration. Moreover, both treatments preserved Nrf2-Keap1 and renal dopamine antioxidant pathways. In summary, therapeutic strategies aimed to preserve renal antioxidant pathways can help to retard the progression of CKD. PMID:27050624

  19. Therapeutic Benefit of Extended Thymosin β4 Treatment Is Independent of Blood Glucose Level in Mice with Diabetic Peripheral Neuropathy

    PubMed Central

    Wang, Lei; Chopp, Michael; Jia, Longfei; Lu, Xuerong; Szalad, Alexandra; Zhang, Yi; Zhang, RuiLan; Zhang, Zheng Gang

    2015-01-01

    Peripheral neuropathy is a chronic complication of diabetes mellitus. To investigated the efficacy and safety of the extended treatment of diabetic peripheral neuropathy with thymosin β4 (Tβ4), male diabetic mice (db/db) at the age of 24 weeks were treated with Tβ4 or saline for 16 consecutive weeks. Treatment of diabetic mice with Tβ4 significantly improved motor (MCV) and sensory (SCV) conduction velocity in the sciatic nerve and the thermal and mechanical latency. However, Tβ4 treatment did not significantly alter blood glucose levels. Treatment with Tβ4 significantly increased intraepidermal nerve fiber density. Furthermore, Tβ4 counteracted the diabetes-induced axon diameter and myelin thickness reductions and the g-ratio increase in sciatic nerve. In vitro, compared with dorsal root ganglia (DRG) neurons derived from nondiabetic mice, DRG neurons derived from diabetic mice exhibited significantly decreased neurite outgrowth, whereas Tβ4 promoted neurite growth in these diabetic DRG neurons. Blockage of the Ang1/Tie2 signaling pathway with a neutralized antibody against Tie2 abolished Tβ4-increased neurite outgrowth. Our data demonstrate that extended Tβ4 treatment ameliorates diabetic-induced axonal degeneration and demyelination, which likely contribute to therapeutic effect of Tβ4 on diabetic neuropathy. The Ang1/Tie2 pathway may mediate Tβ4-induced axonal remodeling. PMID:25945352

  20. 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

  1. Therapeutic benefit of lentiviral-mediated neonatal intracerebral gene therapy in a mouse model of globoid cell leukodystrophy

    PubMed Central

    Lattanzi, Annalisa; Salvagno, Camilla; Maderna, Claudio; Benedicenti, Fabrizio; Morena, Francesco; Kulik, Willem; Naldini, Luigi; Montini, Eugenio; Martino, Sabata; Gritti, Angela

    2014-01-01

    Globoid cell leukodystrophy (GLD) is an inherited lysosomal storage disease caused by β-galactocerebrosidase (GALC) deficiency. Gene therapy (GT) should provide rapid, extensive and lifetime GALC supply in central nervous system (CNS) tissues to prevent or halt irreversible neurologic progression. Here we used a lentiviral vector (LV) to transfer a functional GALC gene in the brain of Twitcher mice, a severe GLD model. A single injection of LV.GALC in the external capsule of Twitcher neonates resulted in robust transduction of neural cells with minimal and transient activation of inflammatory and immune response. Importantly, we documented a proficient transduction of proliferating and post-mitotic oligodendroglia, a relevant target cell type in GLD. GALC activity (30–50% of physiological levels) was restored in the whole CNS of treated mice as early as 8 days post-injection. The early and stable enzymatic supply ensured partial clearance of storage and reduction of psychosine levels, translating in amelioration of histopathology and enhanced lifespan. At 6 months post-injection in non-affected mice, LV genome persisted exclusively in the injected region, where transduced cells overexpressed GALC. Integration site analysis in transduced brain tissues showed no aberrant clonal expansion and preferential targeting of neural-specific genes. This study establishes neonatal LV-mediated intracerebral GT as a rapid, effective and safe therapeutic intervention to correct CNS pathology in GLD and provides a strong rationale for its application in this and similar leukodystrophies, alone or in combination with therapies targeting the somatic pathology, with the final aim of providing an effective and timely treatment of these global disorders. PMID:24463623

  2. Benefit of hepatitis C virus core antigen assay in prediction of therapeutic response to interferon and ribavirin combination therapy.

    PubMed

    Takahashi, Masahiko; Saito, Hidetsugu; Higashimoto, Makiko; Atsukawa, Kazuhiro; Ishii, Hiromasa

    2005-01-01

    A highly sensitive second-generation hepatitis C virus (HCV) core antigen assay has recently been developed. We compared viral disappearance and first-phase kinetics between commercially available core antigen (Ag) assays, Lumipulse Ortho HCV Ag (Lumipulse-Ag), and a quantitative HCV RNA PCR assay, Cobas Amplicor HCV Monitor test, version 2 (Amplicor M), to estimate the predictive benefit of a sustained viral response (SVR) and non-SVR in 44 genotype 1b patients treated with interferon (IFN) and ribavirin. HCV core Ag negativity could predict SVR on day 1 (sensitivity = 100%, specificity = 85.0%, accuracy = 86.4%), whereas RNA negativity could predict SVR on day 7 (sensitivity = 100%, specificity = 87.2%, accuracy = 88.6%). None of the patients who had detectable serum core Ag or RNA on day 14 achieved SVR (specificity = 100%). The predictive accuracy on day 14 was higher by RNA negativity (93.2%) than that by core Ag negativity (75.0%). The combined predictive criterion of both viral load decline during the first 24 h and basal viral load was also predictive for SVR; the sensitivities of Lumipulse-Ag and Amplicor-M were 45.5 and 47.6%, respectively, and the specificity was 100%. Amplicor-M had better predictive accuracy than Lumipulse-Ag in 2-week disappearance tests because it had better sensitivity. On the other hand, estimates of kinetic parameters were similar regardless of the detection method. Although the correlations between Lumipulse-Ag and Amplicor-M were good both before and 24 h after IFN administration, HCV core Ag seemed to be relatively lower 24 h after IFN administration than before administration. Lumipulse-Ag seems to be useful for detecting the HCV concentration during IFN therapy; however, we still need to understand the characteristics of the assay. PMID:15634970

  3. 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. PMID:27091079

  4. Preintubation Application of Oral Chlorhexidine Does Not Provide Additional Benefit in Prevention of Early-Onset Ventilator-Associated Pneumonia

    PubMed Central

    Grap, Mary Jo; Sessler, Curtis N.; Elswick, Ronald K.; Mangar, Devanand; Karlnoski-Everall, Rachel; Cairns, Paula

    2015-01-01

    BACKGROUND: Daily application of oral chlorhexidine gluconate (CHX) following intubation to reduce the risk of ventilator-associated pneumonia (VAP) is now the standard of care in many ICUs. This randomized clinical trial evaluated the benefit of adding a preintubation CHX dose to the known benefit of postintubation CHX to reduce the risk of early-onset VAP. A secondary aim was to test the effect of a preintubation oral application of CHX on early endotracheal tube (ETT) colonization. METHODS: Subjects (N = 314) were recruited from two teaching hospitals and were randomly assigned to oral application of 5 mL CHX 0.12% solution before intubation (intervention group, n = 157), or to a control group (n = 157) who received no CHX before intubation. All subjects received CHX bid after intubation. Groups were compared using a repeated-measures model with Clinical Pulmonary Infection Score (CPIS) as the response variable. In a planned subset of subjects, ETTs were cultured at extubation. RESULTS: Application of a preintubation dose of CHX did not provide benefit over the intervention period beyond that afforded by daily oral CHX following intubation. ETT colonization at extubation was < 20% in both groups (no statistically significant difference). Mean CPIS remained below 6 (VAP threshold score) in both groups. CONCLUSIONS: Although it is feasible to deliver CHX prior to intubation (including emergent or urgent intubation), the results suggest that preintubation CHX may be inconsequential when the ventilator bundle, including daily oral CHX, is in place. During the preintubation period, providers should focus their attention on other critical activities. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00893763; URL: www.clinicaltrials.gov PMID:25317722

  5. Therapeutic benefit of decitabine, a hypomethylating agent, in patients with high-risk primary myelofibrosis and myeloproliferative neoplasm in accelerated or blastic/acute myeloid leukemia phase.

    PubMed

    Badar, Talha; Kantarjian, Hagop M; Ravandi, Farhad; Jabbour, Elias; Borthakur, Gautam; Cortes, Jorge E; Pemmaraju, Naveen; Pierce, Sherry R; Newberry, Kate J; Daver, Naval; Verstovsek, Srdan

    2015-09-01

    Myeloproliferative neoplasm (MPN) transformed to acute myeloid leukemia (MPN-AML), MPN in accelerated phase (MPN-AP), and high-risk primary myelofibrosis (PMF) are associated with a poor response to therapy and very short survival. Several reports have suggested clinical activity of hypomethylating agents in these patients. We conducted a retrospective study of 21 patients with MPN-AML, 13 with MPN-AP and 11 with DIPSS-plus high-risk PMF treated with decitabine at our institution over the last 7 years and evaluated their clinical outcomes. Six patients (29%) with MPN-AML responded to decitabine (3 CR, 2 CRi, and 1 PR); median response duration was 7 months. The median overall survival (OS) was significantly higher in those who responded (10.5 vs 4 months). Among patients with MPN-AP, 8 patients (62%) benefited; the median response duration was 6.5 months. The median OS was 11.8 months in responders vs 4.7 months in non-responders. Among patients with DIPSS-plus high-risk PMF, 9 (82%) benefited; the median response duration was 9 months. The median OS was 32 months in responders vs 16.3 months in non-responders. Decitabine is a viable therapeutic option for patients with MPN-AML, MP-AP and high-risk PMF. Prospective clinical studies combining decitabine with other clinically active agents are needed to improve overall outcome. PMID:26183878

  6. 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. PMID:25675266

  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. Spermine metabolism and radiation-derived reactive oxygen species for future therapeutic implications in cancer: an additive or adaptive response.

    PubMed

    Amendola, Roberto; Cervelli, Manuela; Tempera, Giampiero; Fratini, Emiliano; Varesio, Luigi; Mariottini, Paolo; Agostinelli, Enzo

    2014-03-01

    Destruction of cells by irradiation-induced radical formation is one of the most frequent interventions in cancer therapy. An alternative to irradiation-induced radical formation is in principle drug-induced formation of radicals, and the formation of toxic metabolites by enzyme catalyzed reactions. Thus, combination therapy targeting polyamine metabolism could represent a promising strategy to fight hyper-proliferative disease. The aim of this work is to discuss and evaluate whether the presence of a DNA damage provoked by enzymatic ROS overproduction may act as an additive or adaptive response upon radiation and combination of hyperthermia with lysosomotropic compounds may improve the cytocidal effect of polyamines oxidation metabolites. Low level of X-irradiations delivers challenging dose of damage and an additive or adaptive response with the chronic damage induced by spermine oxidase overexpression depending on the deficiency of the DNA repair mechanisms. Since reactive oxygen species lead to membrane destabilization and cell death, we discuss the effects of BSAO and spermine association in multidrug resistant cells that resulted more sensitive to spermine metabolites than their wild-type counterparts, due to an increased mitochondrial activity. Since mammal spermine oxidase is differentially activated in a tissue specific manner, and cancer cells can differ in term of DNA repair capability, it could be of interest to open a scientific debate to use combinatory treatments to alter spermine metabolism and deliver differential response. PMID:23999645

  9. 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.

  10. 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. PMID:23911554

  11. Therapeutic benefits by human mesenchymal stem cells (hMSCs) and Ang-1 gene-modified hMSCs after cerebral ischemia.

    PubMed

    Onda, Toshiyuki; Honmou, Osamu; Harada, Kuniaki; Houkin, Kiyohiro; Hamada, Hirofumi; Kocsis, Jeffery D

    2008-02-01

    Transplantation of human mesenchymal stem cells (hMSCs) prepared from adult bone marrow has been reported to ameliorate functional deficits after cerebral artery occlusion in rats. Although several hypotheses to account for these therapeutic effects have been suggested, current thinking is that both neuroprotection and angiogenesis are primarily responsible. In this study, we compared the effects of hMSCs and angiopoietin-1 gene-modified hMSCs (Ang-hMSCs) intravenously infused into rats 6 h after permanent middle cerebral artery occlusion. Magnetic resonance imaging and histologic analyses revealed that rats receiving hMSCs or Ang-hMSCs exhibited comparable reduction in gross lesion volume as compared with the control group. Although both cell types indeed improved angiogenesis near the border of the ischemic lesions, neovascularization and regional cerebral blood flow were greater in some border areas in Ang-hMSC group. Both hMSC- and Ang-hMSC-treated rats showed greater improved functional recovery in the treadmill stress test than did control rats, but the Ang-hMSC group was greater. These results indicate the intravenous administration of genetically modified hMSCs to express angiopoietin has a similar effect on reducing lesion volume as hMSCs, but the Ang-hMSC group showed enhanced regions of increased angiogenesis at the lesion border, and modest additional improvement in functional outcome. PMID:17637706

  12. 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

  13. 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.

  14. 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. PMID:25586060

  15. Therapeutic benefit of balneotherapy and hydrotherapy in the management of fibromyalgia syndrome: a qualitative systematic review and meta-analysis of randomized controlled trials

    PubMed Central

    2014-01-01

    Introduction In the present systematic review and meta-analysis, we assessed the effectiveness of different forms of balneotherapy (BT) and hydrotherapy (HT) in the management of fibromyalgia syndrome (FMS). Methods A systematic literature search was conducted through April 2013 (Medline via Pubmed, Cochrane Central Register of Controlled Trials, EMBASE, and CAMBASE). Standardized mean differences (SMDs) and 95% confidence intervals (CIs) were calculated using a random-effects model. Results Meta-analysis showed moderate-to-strong evidence for a small reduction in pain (SMD −0.42; 95% CI [−0.61, −0.24]; P < 0.00001; I2 = 0%) with regard to HT (8 studies, 462 participants; 3 low-risk studies, 223 participants), and moderate-to-strong evidence for a small improvement in health-related quality of life (HRQOL; 7 studies, 398 participants; 3 low-risk studies, 223 participants) at the end of treatment (SMD −0.40; 95% CI [−0.62, −0.18]; P = 0.0004; I2 = 15%). No effect was seen at the end of treatment for depressive symptoms and tender point count (TPC). BT in mineral/thermal water (5 studies, 177 participants; 3 high-risk and 2 unclear risk studies) showed moderate evidence for a medium-to-large size reduction in pain and TPC at the end of treatment: SMD −0.84; 95% CI [−1.36, −0.31]; P = 0.002; I2 = 63% and SMD −0.83; 95% CI [−1.42, −0.24]; P = 0.006; I2 = 71%. After sensitivity analysis, and excluding one study, the effect size for pain decreased: SMD −0.58; 95% CI [−0.91, −0.26], P = 0.0004; I2 = 0. Moderate evidence is given for a medium improvement of HRQOL (SMD −0.78; 95% CI [−1.13, −0.43]; P < 0.0001; I2 = 0%). A significant effect on depressive symptoms was not found. The improvements for pain could be maintained at follow-up with smaller effects. Conclusions High-quality studies with larger sample sizes are needed to confirm the therapeutic benefit of BT and HT, with focus on long

  16. Lack of Benefit for the Addition of Androgen Deprivation Therapy to Dose-Escalated Radiotherapy in the Treatment of Intermediate- and High-Risk Prostate Cancer

    SciTech Connect

    Krauss, Daniel; Kestin, Larry; Ye, Hong; Brabbins, Donald; Ghilezan, Michel; Gustafson, Gary; Vicini, Frank; Martinez, Alvaro

    2011-07-15

    Purpose: Assessment of androgen deprivation therapy (ADT) benefits for prostate cancer treated with dose-escalated radiotherapy (RT). Methods and Materials: From 1991 to 2004, 1,044 patients with intermediate- (n = 782) or high-risk (n = 262) prostate cancer were treated with dose-escalated RT at William Beaumont Hospital. Patients received external-beam RT (EBRT) alone, brachytherapy (high or low dose rate), or high dose rate brachytherapy plus pelvic EBRT. Intermediate-risk patients had Gleason score 7, prostate-specific antigen (PSA) 10.0-19.9 ng/mL, or Stage T2b-T2c. High-risk patients had Gleason score 8-10, PSA {>=}20, or Stage T3. Patients were additionally divided specifically by Gleason score, presence of palpable disease, and PSA level to further define subgroups benefitting from ADT. Results: Median follow-up was 5 years; 420 patients received ADT + dose-escalated RT, and 624 received dose-escalated RT alone. For all patients, no advantages in any clinical endpoints at 8 years were associated with ADT administration. No differences in any endpoints were associated with ADT administration based on intermediate- vs. high-risk group or RT modality when analyzed separately. Patients with palpable disease plus Gleason {>=}8 demonstrated improved clinical failure rates and a trend toward improved survival with ADT. Intermediate-risk patients treated with brachytherapy alone had improved biochemical control when ADT was given. Conclusion: Benefits of ADT in the setting of dose-escalated RT remain poorly defined. This question must continue to be addressed in prospective study.

  17. 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. PMID:22226545

  18. 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.

  19. 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.

  20. Cyclic nucleotide phosphodiesterase (PDE) isozymes as targets of the intracellular signalling network: benefits of PDE inhibitors in various diseases and perspectives for future therapeutic developments

    PubMed Central

    Keravis, Thérèse; Lugnier, Claire

    2012-01-01

    Cyclic nucleotide phosphodiesterases (PDEs) that specifically inactivate the intracellular messengers cAMP and cGMP in a compartmentalized manner represent an important enzyme class constituted by 11 gene-related families of isozymes (PDE1 to PDE11). Downstream receptors, PDEs play a major role in controlling the signalosome at various levels of phosphorylations and protein/protein interactions. Due to the multiplicity of isozymes, their various intracellular regulations and their different cellular and subcellular distributions, PDEs represent interesting targets in intracellular pathways. Therefore, the investigation of PDE isozyme alterations related to various pathologies and the design of specific PDE inhibitors might lead to the development of new specific therapeutic strategies in numerous pathologies. This manuscript (i) overviews the different PDEs including their endogenous regulations and their specific inhibitors; (ii) analyses the intracellular implications of PDEs in regulating signalling cascades in pathogenesis, exemplified by two diseases affecting cell cycle and proliferation; and (iii) discusses perspectives for future therapeutic developments. PMID:22014080

  1. 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

  2. Cystic Fibrosis Therapeutics

    PubMed Central

    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. PMID:23276843

  3. Therapeutic benefits of an oral vitamin B1 derivative for human T lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis (HAM/TSP).

    PubMed

    Kira, Jun-Ichi

    2013-01-01

    Prosultiamine, a vitamin B1 derivative, has long been used for beriberi neuropathy and Wernicke's encephalopathy. Based on the finding that prosultiamine induces apoptosis in human T lymphotropic virus type I (HTLV-I)-infected T cells, Nakamura et al. conducted a clinical trial of prosultiamine in patients with HTLV-I-associated myelopathy (HAM)/tropical spastic paraparesis (TSP). In this open-label, single arm study enrolling 24 HAM/TSP patients recently published in BMC Medicine, oral prosultiamine (300 mg/day for 12 weeks) was found to be effective by neurological, urological and virological evaluations. Notably, it increased detrusor pressure, bladder capacity and maximum flow rate, and improved detrusor overactivity and detrusor-sphincter dyssynergia. A significant decrease in HTLV-I copy numbers in peripheral blood following the treatment provided a rationale for using the drug. The trial has some limitations, such as the small numbers of participants, the open-label design, the lack of a placebo arm, and the short trial period. Nevertheless, the observation that such a safe, cheap drug may have excellent therapeutic effects on HAM/TSP, a chronic devastating illness occurring mainly in developing countries, provides support for future large-scale randomized controlled trials.Please see related research: http://www.biomedcentral.com/1741-7015/11/182. PMID:23945332

  4. 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. PMID:23675438

  5. Do Recent Advances in Diagnostic and Therapeutic Procedures Negate the Benefit of Postmastectomy Radiotherapy in N1 Patients With a Low Risk of Locoregional Recurrence?

    PubMed Central

    Chang, Jee Suk; Lee, Jeongshim; Kim, Kyung Hwan; Sohn, Joo Hyuk; Kim, Seung Il; Park, Byeong-Woo; Chung, Hyun Cheol; Keum, Ki Chang; Suh, Chang-Ok; Kim, Yong Bae

    2015-01-01

    Abstract Recent advances in breast cancer management might make the use of postmastectomy radiotherapy (PMRT) redundant in the treatment of pT1/T2N1 patients. We investigated the impact of PMRT on disease-free survival (DFS) in these patients who have a low risk of locoregional recurrence (LRR) after contemporary multidisciplinary management. Between 1998 and 2011, 1123 patients underwent upfront surgery for pathologically diagnosed pT1/T2N1 breast cancer, at a single institution. A retrospective review was performed on 692 patients who had a mastectomy with axillary lymph node (LN) clearance. Most patients received adjuvant systemic chemotherapy and/or endocrine therapy. PMRT was administered to 17.8% of the patients. The median follow-up time was 98 months. The entire cohort was divided into 2 groups, the early-era (1998–2003) and late-era (2004–2011) cohorts. Grouping was based on the use of modern therapies since 2004 including sentinel LN (SLN) biopsy, anthracycline/taxane-based chemotherapy, and aromatase inhibitors. Late-era patients had a significantly lower 5-year LRR compared with early-era patients (3.2% vs 10.3%, respectively; P < 0.001). In late-era patients, although PMRT did not significantly reduce the 5-year LRR rate (1% vs 3.8%, respectively), it did improve the 5-year DFS rate (96.1% vs 87.5%, respectively). After controlling for all clinicopathological variables, PMRT was independently associated with improved DFS. In subgroup analysis, depending on the presence of micro- or macrometastasis in the axillary nodes, the benefit of PMRT was most apparent in patients with macrometastasis (hazard ratio, 0.19). In the late-era cohort with no PMRT, the 3-year distant metastasis risk increased according to LN tumor burden (0%, 5.2%, and 9.8% in micrometastasis, SLN macrometastasis, and non-SLN macrometastasis, respectively). Advanced surgical and systemic therapies might not negate the benefit of PMRT in recently diagnosed pN1 patients who have a

  6. 38 CFR 3.361 - Benefits under 38 U.S.C. 1151(a) for additional disability or death due to hospital care, medical...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    .... 1151(a) for additional disability or death due to hospital care, medical or surgical treatment.... 1151(a) for additional disability or death due to hospital care, medical or surgical treatment..., VA compares the veteran's condition immediately before the beginning of the hospital care, medical...

  7. 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

  8. 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

  9. The Benefit of a Human Bone Marrow Stem Cells Concentrate in addition to an Inorganic Scaffold for Bone Regeneration: An In Vitro Study

    PubMed Central

    Torres, J.; Lopes, A.; Lopes, M. A.; Gutierres, M.; Cabral, A. T.; Fernandes, M. H.; Monteiro, E.; van Eck, C. F.; Santos, J. D.

    2015-01-01

    Background. This work compares the osteoblastic behaviour of a bone marrow (BM) aspirate and a prepared BM concentrate of nucleated cells associated with a glass reinforced hydroxyapatite composite (GRHC) in a microporous pellet formulation. Methods. BM aspirate (30 mL) was collected during 3 orthopedic surgical procedures, and a concentration system was used to achieve 3 rapid preparations of a concentrate of nucleated cells (3 mL) from the BM aspirates. The BM aspirates (53% cell viability; 2.7 × 106 nucleated cell/mL) and the BM concentrates (76% cell viability; 2 × 107 nucleated cell/mL) were cultured over glass reinforced hydroxyapatite pellets, at the same volume/mass ratio, for 30 days. Cultures performed in standard tissue culture plates were used as control. Results. The colonized BM concentrate/material constructs exhibited a representative osteoblastic proliferation/differentiation pathway, evidenced by a high alkaline phosphatase (ALP) activity, expression of collagen type 1, ALP, BMP-2, M-CSF, RANKL, and OPG, and formation of a calcium phosphate mineralized matrix. A clear improved behaviour was noticed compared to the BM aspirate/material constructs. Conclusions. The results suggest the benefit of using an autologous BM concentrate/material construct in the clinical setting, in bone regeneration applications. PMID:25685773

  10. The benefit of a human bone marrow stem cells concentrate in addition to an inorganic scaffold for bone regeneration: an in vitro study.

    PubMed

    Torres, J; Lopes, A; Lopes, M A; Gutierres, M; Cabral, A T; Fernandes, M H; Monteiro, E; van Eck, C F; Santos, J D

    2015-01-01

    Background. This work compares the osteoblastic behaviour of a bone marrow (BM) aspirate and a prepared BM concentrate of nucleated cells associated with a glass reinforced hydroxyapatite composite (GRHC) in a microporous pellet formulation. Methods. BM aspirate (30 mL) was collected during 3 orthopedic surgical procedures, and a concentration system was used to achieve 3 rapid preparations of a concentrate of nucleated cells (3 mL) from the BM aspirates. The BM aspirates (53% cell viability; 2.7 × 10(6) nucleated cell/mL) and the BM concentrates (76% cell viability; 2 × 10(7) nucleated cell/mL) were cultured over glass reinforced hydroxyapatite pellets, at the same volume/mass ratio, for 30 days. Cultures performed in standard tissue culture plates were used as control. Results. The colonized BM concentrate/material constructs exhibited a representative osteoblastic proliferation/differentiation pathway, evidenced by a high alkaline phosphatase (ALP) activity, expression of collagen type 1, ALP, BMP-2, M-CSF, RANKL, and OPG, and formation of a calcium phosphate mineralized matrix. A clear improved behaviour was noticed compared to the BM aspirate/material constructs. Conclusions. The results suggest the benefit of using an autologous BM concentrate/material construct in the clinical setting, in bone regeneration applications. PMID:25685773

  11. 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

    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-4(D)) remained unclear. Male-adult (DPP-4(D)) rats (n = 32) were randomized into group 1 [sham control (SC)], group 2 (DPP-4(D) + TAC), group 3 [DPP-4(D) + TAC + exendin-4 10 µg/day], and group 4 [DPP-4(D) + 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-4(D) rat. PMID:27158369

  12. The benefits of a therapeutic garden.

    PubMed

    2016-07-20

    Can an indoor garden room reduce patients' physical and verbal aggression? Elaine Cole, writing in Nursing Older People, discusses how an indoor sensory garden (and a coloured toilet door) led to a reduction in incidents of verbal aggression by 59%. PMID:27440369

  13. 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

  14. 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…

  15. Aortic arch calcification on chest X-ray combined with coronary calcium score show additional benefit for diagnosis and outcome in patients with angina

    PubMed Central

    Woo, Jong Shin; Kim, Weon; Kwon, Se Hwan; Youn, Hyo Chul; Kim, Hyun Soo; Kim, Jin Bae; Kim, Soo Joong; Kim, Woo-Shik; Kim, Kwon Sam

    2016-01-01

    Background The coronary artery calcium (CAC) and aortic arch calcification (AoAC) are individually associated with cardiovascular disease and outcome. This study investigated the predictive value of AoAC combined with CAC for cardiovascular diagnosis and outcome in patients with angina. Methods A total of 2018 stable angina patients who underwent chest X-ray and cardiac multi-detector computed tomography were followed up for four years to assess adverse events, which were categorized as cardiac death, stroke, myocardial infarction, or repeated revascularization. The extent of AoAC on chest X-ray was graded on a scale from 0 to 3. Results During the four years of follow-up, 620 patients were treated by coronary stenting and 153 (7%) adverse events occurred. A higher grade of AoAC was associated with a higher CAC score. Cox regression showed that the CAC score, but not AoAC, were associated with adverse events. In patients with CAC score < 400, AoAC showed an additive predictive value in detecting significant coronary artery disease (CAD). A gradual increases in the risk of adverse events were noted if AoAC was present in patients with similar CAC score. Conclusions As AoAC is strongly correlated with the CAC score regardless of age or gender, careful evaluation of CAD would be required in patients with AoAC on conventional chest X-rays. PMID:27103916

  16. 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…

  17. [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. PMID:24755815

  18. 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).

  19. 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.

  20. 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…

  1. 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. PMID:23730360

  2. 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

  3. Pigeon therapeutics.

    PubMed

    Harlin, R W

    2000-01-01

    This article examines therapeutics for pigeons, discussing their physiology and reproduction, housing, and nutrition. The author also looks at ways to prevent infection, while discussing treatments for various viral diseases, such as paramyxovirus and pigeon herpesvirus, bacterial infections, such as paratyphoid, and parasitic diseases. Drug dosages are listed for antibiotics, antifungals, antiparasitics, and vaccines. PMID:11228828

  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 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.

  6. Feedlot therapeutics.

    PubMed

    Apley, M D; Fajt, V R

    1998-07-01

    This article discusses therapeutic approaches to conditions commonly encountered in feedlots. Challenges discussed include bovine respiratory complex, tracheal edema, atypical interstitial pneumonia, footrot, toe abscesses, mycoplasma arthritis, cardiovascular disease, lactic acidosis, bloat, coccidiosis, central nervous system diseases, abscesses and cellulitis, pregnancy management and abortion, and ocular disease. PMID:9704416

  7. Therapeutic perspectives

    PubMed Central

    Fiore, Carmelo E.; Pennisi, Pietra; Tinè, Marianna

    2008-01-01

    Osteoporosis and atherosclerosis are linked by biological association. This encourages the search for therapeutic strategies having both cardiovascular and skeletal beneficial effects. Among drugs that may concordantly enhance bone density and reduce the progression of atherosclerosis we can include bisphosphonates (BP), statins, β -blockers, and possibly anti-RANKL antibodies. Available data come from experimental animals and human studies. All these treatments however lack controlled clinical studies designed to demonstrate dual-action effects. PMID:22460845

  8. Thymoquinone and its therapeutic potentials.

    PubMed

    Darakhshan, Sara; Bidmeshki Pour, Ali; Hosseinzadeh Colagar, Abasalt; Sisakhtnezhad, Sajjad

    2015-01-01

    Herbal medicine has attracted great attention in the recent years and is increasingly used as alternatives to chemical drugs. Several lines of evidence support the positive impact of medicinal plants in the prevention and cure of a wide range of diseases. Thymoquinone (TQ) is the most abundant constituent of the volatile oil of Nigella sativa seeds and most properties of N sativa are mainly attributed to TQ. A number of pharmacological actions of TQ have been investigated including anti-oxidant, anti-inflammatory, immunomodulatory, anti-histaminic, anti-microbial and anti-tumor effects. It has also gastroprotective, hepatoprotective, nephroprotective and neuroprotective activities. In addition, positive effects of TQ in cardiovascular disorders, diabetes, reproductive disorders and respiratory ailments, as well as in the treatment of bone complications as well as fibrosis have been shown. In addition, a large body of data shows that TQ has very low adverse effects and no serious toxicity. More recently, a great deal of attention has been given to this dietary phytochemical with an increasing interest to investigate it in pre-clinical and clinical researches for assessing its health benefits. Here we report on and analyze numerous properties of the active ingredient of N. sativa seeds, TQ, in the context of its therapeutic potentials for a wide range of illnesses. We also summarize the drug's possible mechanisms of action. The evidence reported sugests that TQ should be developed as a novel drug in clinical trials. PMID:25829334

  9. Therapeutic alliance.

    PubMed

    Fox, Valerie

    2002-01-01

    I have been very fortunate in my journey of mental illness. I respond well to medication, but I don't think that is the complete answer to living successfully with serious, persistent mental illness. I believe a person's environment is also of utmost importance, enabling the person suffering with mental illness to continually grow in life. I found early in my struggle with mental illness a psychiatrist with whom I have always had a very good rapport. Until recently I didn't know that what I have with this psychiatrist is professionally known as a therapeutic alliance. Over the years, when I need someone to talk over anything that is troubling to me, I seek my psychiatrist. A therapeutic alliance is non-judgmental; it is nourishing; and finally it is a relationship of complete trust. Perhaps persons reading this article who have never experienced this alliance will seek it. I believe it can make an insecure person secure; a frightened person less frightened; and allow a person to continue the journey of mental health with a sense of belief in oneself. PMID:12433224

  10. Medicaid Benefits

    MedlinePlus

    ... Topic Eligibility Benefits Cost Sharing Waivers Long Term Services and Supports Delivery Systems Quality of Care Data and Systems Enrollment Strategies Access to Care Program Integrity Financing and ... type, amount, duration, and scope of services within broad federal guidelines. States are required to ...

  11. Snoezelen: benefits for nursing older clients.

    PubMed

    Morrissey, M; Biela, C

    1997-10-01

    In this article, the authors examine the possible benefits of Snoezelen for older clients. The authors suggest that nurses can be instrumental in developing and creating innovative therapeutic environments for this vulnerable client group. PMID:9370672

  12. Topics in Microeconometrics: Estimation of a Dynamic Model of Occupational Transitions, Wage and Non-Wage Benefits Cross Validation Bandwidth Selection for Derivatives of Various Dimensional Densities Testing the Additive Separability of the Teacher Value Added Effect Semiparametrically

    ERIC Educational Resources Information Center

    Baird, Matthew David

    2012-01-01

    I study three separate questions in this dissertation. In Chapter 1, I develop and estimate a structural dynamic model of occupation and job choice to test hypotheses of the importance of wages and non-wages and learning in occupational transitions, and find that wages are approximately 3 times as important as non-wage benefits in decisions and…

  13. 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

  14. 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. PMID:23174445

  15. 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.

  16. 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.

  17. 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

  18. Epigenomes as therapeutic targets.

    PubMed

    Hamm, Christopher A; Costa, Fabricio F

    2015-07-01

    Epigenetics is a molecular phenomenon that pertains to heritable changes in gene expression that do not involve changes in the DNA sequence. Epigenetic modifications in a whole genome, known as the epigenome, play an essential role in the regulation of gene expression in both normal development and disease. Traditional epigenetic changes include DNA methylation and histone modifications. Recent evidence reveals that other players, such as non-coding RNAs, may have an epigenetic regulatory role. Aberrant epigenetic signaling is becoming to be known as a central component of human disease, and the reversible nature of the epigenetic modifications provides an exciting opportunity for the development of clinically relevant therapeutics. Current epigenetic therapies provide a clinical benefit through disrupting DNA methyltransferases or histone deacetylases. However, the emergence of next-generation epigenetic therapies provides an opportunity to more effectively disrupt epigenetic disease states. Novel epigenetic therapies may improve drug targeting and drug delivery, optimize dosing schedules, and improve the efficacy of preexisting treatment modalities (chemotherapy, radiation, and immunotherapy). This review discusses the epigenetic mechanisms that contribute to the disease, available epigenetic therapies, epigenetic therapies currently in development, and the potential future use of epigenetic therapeutics in a clinical setting. PMID:25797698

  19. The oral health benefits of chewing gum.

    PubMed

    Dodds, Michael W J

    2012-01-01

    The use of sugar-free gum provides a proven anti-caries benefit, but other oral health effects are less clearly elucidated. Chewing sugar-free chewing gum promotes a strong flow of stimulated saliva, which helps to provide a number of dental benefits: first, the higher flow rate promotes more rapid oral clearance of sugars; second, the high pH and buffering capacity of the stimulated saliva help to neutralise plaque pH after a sugar challenge; and, lastly, studies have shown enhanced remineralisation of early caries-like lesions and ultimately prospective clinical trials have shown reduced caries incidence in children chewing sugar-free gum. This paper reviews the scientific evidence for these functional claims and discusses other benefits, including plaque and extrinsic stain reduction, along with the possibility of adding specific active agents, including fluoride, antimicrobials, urea and calcium phosphates, to enhance these inherent effects. The evidence for a specific effect of xylitol as a caries-therapeutic agent is also discussed. In conclusion, it is asserted that chewing gum has a place as an additional mode of dental disease prevention to be used in conjunction with the more traditional preventive methods. PMID:23573702

  20. 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…

  1. Food additives

    MedlinePlus

    Food additives are substances that become part of a food product when they are added during the processing or making of that food. "Direct" food additives are often added during processing to: Add nutrients ...

  2. Therapeutic Drug Monitoring

    MedlinePlus

    ... be limited. Home Visit Global Sites Search Help? Therapeutic Drug Monitoring Share this page: Was this page ... Monitored Drugs | Common Questions | Related Pages What is therapeutic drug monitoring? Therapeutic drug monitoring is the measurement ...

  3. 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

  4. 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

  5. 20 CFR 802.215 - Additional briefs.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 3 2011-04-01 2011-04-01 false Additional briefs. 802.215 Section 802.215 Employees' Benefits BENEFITS REVIEW BOARD, DEPARTMENT OF LABOR RULES OF PRACTICE AND PROCEDURE Prereview Procedures Initial Processing § 802.215 Additional briefs. Additional briefs may be filed or ordered in...

  6. 20 CFR 802.215 - Additional briefs.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Additional briefs. 802.215 Section 802.215 Employees' Benefits BENEFITS REVIEW BOARD, DEPARTMENT OF LABOR RULES OF PRACTICE AND PROCEDURE Prereview Procedures Initial Processing § 802.215 Additional briefs. Additional briefs may be filed or ordered in...

  7. 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...

  8. Hypoxic Conditioning as a New Therapeutic Modality

    PubMed Central

    Verges, Samuel; Chacaroun, Samarmar; Godin-Ribuot, Diane; Baillieul, Sébastien

    2015-01-01

    Preconditioning refers to a procedure by which a single noxious stimulus below the threshold of damage is applied to the tissue in order to increase resistance to the same or even different noxious stimuli given above the threshold of damage. Hypoxic preconditioning relies on complex and active defenses that organisms have developed to counter the adverse consequences of oxygen deprivation. The protection it confers against ischemic attack for instance as well as the underlying biological mechanisms have been extensively investigated in animal models. Based on these data, hypoxic conditioning (consisting in recurrent exposure to hypoxia) has been suggested a potential non-pharmacological therapeutic intervention to enhance some physiological functions in individuals in whom acute or chronic pathological events are anticipated or existing. In addition to healthy subjects, some benefits have been reported in patients with cardiovascular and pulmonary diseases as well as in overweight and obese individuals. Hypoxic conditioning consisting in sessions of intermittent exposure to moderate hypoxia repeated over several weeks may induce hematological, vascular, metabolic, and neurological effects. This review addresses the existing evidence regarding the use of hypoxic conditioning as a potential therapeutic modality, and emphasizes on many remaining issues to clarify and future researches to be performed in the field. PMID:26157787

  9. Who benefits from child benefit?

    PubMed

    Blow, Laura; Walker, Ian; Zhu, Yu

    2012-01-01

    Governments, over much of the developed world, make significant financial transfers to parents with dependent children. For example, in the United States the recently introduced Child Tax Credit (CTC), which goes to almost all children, costs almost $1 billion each week, or about 0.4% of GNP. The United Kingdom has even more generous transfers and spends an average of about $30 a week on each of about 8 million children—about 1% of GNP. The typical rationale given for these transfers is that they are good for our children and here we investigate the effect of such transfers on household spending patterns. In the United Kingdom such transfers, known as Child Benefit (CB), have been simple lump sum universal payments for a continuous period of more than 20 years. We do indeed find that CB is spent differently from other income—paradoxically, it appears to be spent disproportionately on adult-assignable goods. In fact, we estimate that as much as half of a marginal dollar of CB is spent on alcohol. We resolve this puzzle by showing that the effect is confined to unanticipated variation in CB so we infer that parents are sufficiently altruistic toward their children that they completely insure them against shocks. PMID:22329051

  10. 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

  11. Curcumin nanomedicine: a road to cancer therapeutics.

    PubMed

    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, chemopreventive, 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

  12. Coenzyme Q addition to an n-6 PUFA-rich diet resembles benefits on age-related mitochondrial DNA deletion and oxidative stress of a MUFA-rich diet in rat heart.

    PubMed

    Quiles, José L; Pamplona, Reinald; Ramirez-Tortosa, M Carmen; Naudí, Alba; Portero-Otin, Manuel; Araujo-Nepomuceno, Eduardo; López-Frías, Magdalena; Battino, Maurizio; Ochoa, Julio J

    2010-01-01

    Age-related changes in cardiomyocytes reduce the capacity to recover from acute injury or to adapt during chronic disease in advanced age. N-6 polyunsaturated fatty acids (n-6PUFA) lead to higher lipid peroxidation during aging than the less oxidizable monounsaturated fatty acids (MUFA); and coenzyme Q (CoQ)-supplemented n-6PUFA lengthens the lifespan and reduces peroxidation in comparison to non-supplemented n-6PUFA. Here, lifelong feeding on MUFA, n-6PUFA, and n-6 PUFA+CoQ was compared regarding age-related alterations in rat heart. Less mitochondrial area and perimeter were reported for aged n-6 PUFA-fed animals while MUFA led to a higher density of mitochondrial cristae. Mitochondrial complexes and cytochrome c oxidase activity decreased with aging (except complex I and cytochrome c oxidase in n-6 PUFA+CoQ), while increased apoptosis-inducing factor was found with aging. MUFA led to lower mitochondrial DNA-deletion frequency. The lowest hydroperoxide levels for aged animals were found for n-6 PUFA+CoQ, which also showed lower concentrations than did n-6 PUFA. For protein oxidation, specific carbonyl compounds were lower in aged animals; meanwhile lipoxidation-derived protein-oxidation markers were higher. The results suggest that MUFA can protect mitochondria from age-related changes, and that CoQ supplementation to n-6 PUFA partially resembles MUFA benefits. Moreover, under our experimental conditions, lipid-derived oxidative damage appears to be more important than the pure protein-derived oxidative damage during aging. PMID:19948181

  13. Food additives.

    PubMed

    Berglund, F

    1978-01-01

    The use of additives to food fulfils many purposes, as shown by the index issued by the Codex Committee on Food Additives: Acids, bases and salts; Preservatives, Antioxidants and antioxidant synergists; Anticaking agents; Colours; Emulfifiers; Thickening agents; Flour-treatment agents; Extraction solvents; Carrier solvents; Flavours (synthetic); Flavour enhancers; Non-nutritive sweeteners; Processing aids; Enzyme preparations. Many additives occur naturally in foods, but this does not exclude toxicity at higher levels. Some food additives are nutrients, or even essential nutritents, e.g. NaCl. Examples are known of food additives causing toxicity in man even when used according to regulations, e.g. cobalt in beer. In other instances, poisoning has been due to carry-over, e.g. by nitrate in cheese whey - when used for artificial feed for infants. Poisonings also occur as the result of the permitted substance being added at too high levels, by accident or carelessness, e.g. nitrite in fish. Finally, there are examples of hypersensitivity to food additives, e.g. to tartrazine and other food colours. The toxicological evaluation, based on animal feeding studies, may be complicated by impurities, e.g. orthotoluene-sulfonamide in saccharin; by transformation or disappearance of the additive in food processing in storage, e.g. bisulfite in raisins; by reaction products with food constituents, e.g. formation of ethylurethane from diethyl pyrocarbonate; by metabolic transformation products, e.g. formation in the gut of cyclohexylamine from cyclamate. Metabolic end products may differ in experimental animals and in man: guanylic acid and inosinic acid are metabolized to allantoin in the rat but to uric acid in man. The magnitude of the safety margin in man of the Acceptable Daily Intake (ADI) is not identical to the "safety factor" used when calculating the ADI. The symptoms of Chinese Restaurant Syndrome, although not hazardous, furthermore illustrate that the whole ADI

  14. Frankincense--therapeutic properties.

    PubMed

    Al-Yasiry, Ali Ridha Mustafa; Kiczorowska, Bożena

    2016-01-01

    Recently, increasing interest in natural dietary and therapeutic preparations used as dietary supplements has been observed. One of them is frankincense. This traditional medicine of the East is believed to have anti-inflammatory, expectorant, antiseptic, and even anxiolytic and anti-neurotic effects. The present study aims to verify the reported therapeutic properties of Boswellia resin and describe its chemical composition based on available scientific studies. The main component of frankincense is oil (60%). It contains mono- (13%) and diterpenes (40%) as well as ethyl acetate (21.4%), octyl acetate (13.4%) and methylanisole (7.6%). The highest biological activity among terpenes is characteristic of 11-keto-ß-acetyl-beta-boswellic acid, acetyl-11-keto-ß-boswellic acid and acetyl-α-boswellic acid. Contemporary studies have shown that resin indeed has an analgesic, tranquilising and anti-bacterial effects. From the point of view of therapeutic properties, extracts from Boswellia serrata and Boswellia carterii are reported to be particularly useful. They reduce inflammatory conditions in the course of rheumatism by inhibiting leukocyte elastase and degrading glycosaminoglycans. Boswellia preparations inhibit 5-lipoxygenase and prevent the release of leukotrienes, thus having an anti-inflammatory effect in ulcerative colitis, irritable bowel syndrome, bronchitis and sinusitis. Inhalation and consumption of Boswellia olibanum reduces the risk of asthma. In addition, boswellic acids have an antiproliferative effect on tumours. They inhibit proliferation of tumour cells of the leukaemia and glioblastoma subset. They have an anti-tumour effect since they inhibit topoisomerase I and II-alpha and stimulate programmed cell death (apoptosis). PMID:27117114

  15. Scenario Writing: A Therapeutic Application.

    ERIC Educational Resources Information Center

    Haddock, Billy D.

    1989-01-01

    Introduces scenario writing as useful therapeutic technique. Presents case study of woman in midst of divorce and custody fight to illustrate context in which technique was applied. Suggests additional applications. Concludes that good response is more likely for clients who possess good writing skills although other clients may use their own…

  16. [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. PMID:12669359

  17. [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. PMID:12668948

  18. 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

  19. 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.

  20. Experimental Therapeutics for Dystonia

    PubMed Central

    Jinnah, H. A.; Hess, Ellen J.

    2008-01-01

    Dystonia is a neurological syndrome characterized by excessive involuntary muscle contractions leading to twisting movements and unnatural postures. It has many different clinical manifestations, and many different causes. More than 3 million people worldwide suffer from dystonia, yet there are few broadly effective treatments. In the past decade, progress in research has advanced our understanding of the pathogenesis of dystonia to a point where drug discovery efforts are now feasible. There are several strategies that can be used to develop novel therapeutics for dystonia. Existing therapies have only modest efficacy, but may be refined and improved to increase benefits while reducing side effects. Identifying rational targets for drug intervention based on the pathogenesis of dystonia is another strategy. The surge in both basic and clinical research discoveries has provided insights at all levels including etiological, physiological and nosological, to enable such a targeted approach. The empirical approach to drug discovery is complementary to the rational approach whereby compounds are identified using a non-mechanistic strategy. [MD1] With the recent development of multiple animal models of dystonia, it is now possible to develop assays and perform drug screens on vast number of compounds. This multifaceted approach to drug discovery in dystonia will likely provide lead compounds that can then be translated for clinical use. PMID:18394563

  1. Phosphazene additives

    SciTech Connect

    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.

  2. Therapeutic drug levels

    MedlinePlus

    ... medlineplus.gov/ency/article/003430.htm Therapeutic drug levels To use the sharing features on this page, please enable JavaScript. Therapeutic drug levels are lab tests to look for the presence ...

  3. 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

  4. 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.

  5. Cardiovascular benefits of exercise.

    PubMed

    Agarwal, Shashi K

    2012-01-01

    Regular physical activity during leisure time has been shown to be associated with better health outcomes. The American Heart Association, the Centers for Disease Control and Prevention and the American College of Sports Medicine all recommend regular physical activity of moderate intensity for the prevention and complementary treatment of several diseases. The therapeutic role of exercise in maintaining good health and treating diseases is not new. The benefits of physical activity date back to Susruta, a 600 BC physician in India, who prescribed exercise to patients. Hippocrates (460-377 BC) wrote "in order to remain healthy, the entire day should be devoted exclusively to ways and means of increasing one's strength and staying healthy, and the best way to do so is through physical exercise." Plato (427-347 BC) referred to medicine as a sister art to physical exercise while the noted ancient Greek physician Galen (129-217 AD) penned several essays on aerobic fitness and strengthening muscles. This article briefly reviews the beneficial effects of physical activity on cardiovascular diseases. PMID:22807642

  6. 77 FR 27785 - Request for Information Regarding the NIH-Industry Program To Discover New Therapeutic Uses for...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-11

    ... program will focus on discovering new therapeutic uses of existing molecules (Therapeutics Discovery). The... be submitted electronically to Therapeutics.Discovery@nih.gov . For additional information, please... (Therapeutics Discovery). Many discontinued compounds and biologics that have already been tested in...

  7. 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.

  8. Benefits of quitting tobacco

    MedlinePlus

    ... your risk of many serious health problems . THE BENEFITS OF QUITTING You may enjoy the following when ... about $2,000 a year on cigarettes. HEALTH BENEFITS Some health benefits begin almost immediately. Every week, ...

  9. Benefits of quitting tobacco

    MedlinePlus

    ... your risk of many serious health problems . THE BENEFITS OF QUITTING Your breath, clothes, and hair will ... about $1,800 a year on cigarettes. HEALTH BENEFITS Some health benefits begin almost immediately. Every week, ...

  10. 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. PMID:27154182

  11. Therapeutic Applications of Carbon Monoxide

    PubMed Central

    Knauert, Melissa; Vangala, Sandeep; Haslip, Maria; Lee, Patty J.

    2013-01-01

    Heme oxygenase-1 (HO-1) is a regulated enzyme induced in multiple stress states. Carbon monoxide (CO) is a product of HO catalysis of heme. In many circumstances, CO appears to functionally replace HO-1, and CO is known to have endogenous anti-inflammatory, anti-apoptotic, and antiproliferative effects. CO is well studied in anoxia-reoxygenation and ischemia-reperfusion models and has advanced to phase II trials for treatment of several clinical entities. In alternative injury models, laboratories have used sepsis, acute lung injury, and systemic inflammatory challenges to assess the ability of CO to rescue cells, organs, and organisms. Hopefully, the research supporting the protective effects of CO in animal models will translate into therapeutic benefits for patients. Preclinical studies of CO are now moving towards more complex damage models that reflect polymicrobial sepsis or two-step injuries, such as sepsis complicated by acute respiratory distress syndrome. Furthermore, co-treatment and post-treatment with CO are being explored in which the insult occurs before there is an opportunity to intervene therapeutically. The aim of this review is to discuss the potential therapeutic implications of CO with a focus on lung injury and sepsis-related models. PMID:24648866

  12. 20 CFR 226.12 - Employee vested dual benefit.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 20 Employees' Benefits 1 2013-04-01 2012-04-01 true Employee vested dual benefit. 226.12 Section 226.12 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE RAILROAD RETIREMENT ACT... vested dual benefit. (a) General. An employee vested dual benefit is payable, in addition to tiers I...

  13. 20 CFR 226.12 - Employee vested dual benefit.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 1 2011-04-01 2011-04-01 false Employee vested dual benefit. 226.12 Section 226.12 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE RAILROAD RETIREMENT ACT... vested dual benefit. (a) General. An employee vested dual benefit is payable, in addition to tiers I...

  14. [Porphyria cutanea tarda: the benefit of additional diagnostics].

    PubMed

    Vossen, Allard R J V; Boesten, Lianne S M; Siersema, Peter D; Nellen, Ruud G L

    2016-01-01

    The porphyrias are a clinically and genetically heterogeneous group of relatively rare metabolic diseases that result from disorders in the biosynthesis of haeme. Porphyria cutanea tarda (PCT) is the most common type, accounting for 80-90% of all porphyrias, and is essentially an acquired disease, although PCT can also occur on a familial basis. We describe a 71-year-old female and a 62-year-old male patient, both of whom had several risk factors for developing PCT, ranging from iron overload due to a mutation in the hereditary haemochromatosis protein (HFE) gene, alcohol use, smoking, and exogenous oestrogen, to persistent hepatitis C infection. The clinical relevance of the several diagnostic modalities is important in PCT. Diagnostic evaluation is important in order to confirm the diagnosis, but also to evaluate the treatment response in the context of long-term follow-up in the prevention of late complications of PCT, i.e. hepatocellular carcinoma. PMID:26840933

  15. Additional Treatments Offer Little Benefit for Pancreatic Cancer: Study

    MedlinePlus

    ... of gastroenterology-pancreatology at Beaujon Hospital, in Clichy, France. The study was funded by the pharmaceutical company ... D., department of gastroenterology-pancreatology, Beaujon Hospital, Clichy, France; Deborah Schrag, M.D., M.P.H., chief ...

  16. Enhancing Therapeutic Impact and Therapeutic Alliance Through Electronic Mail Homework Assignments

    PubMed Central

    Murdoch, Janice W.; Connor-Greene, Patricia A.

    2000-01-01

    Homework assignments can enhance therapeutic impact and increase therapy effectiveness by encouraging patients to focus on therapy-related issues between sessions. Computer technology provides a new avenue for reporting, monitoring, and feedback of patient homework assignments through electronic mail (e- mail). In two case examples, e-mail was used as an extension of therapy to enhance patient involvement in treatment. In both cases, patient reports suggest that therapeutic alliance and therapeutic impact improved with the use of e-mail homework reporting. The costs and benefits of the use of e-mail as an adjunct to therapy are discussed. PMID:11069136

  17. Bioengineering Beige Adipose Tissue Therapeutics.

    PubMed

    Tharp, Kevin M; Stahl, Andreas

    2015-01-01

    Unlocking the therapeutic potential of brown/beige adipose tissue requires technological advancements that enable the controlled expansion of this uniquely thermogenic tissue. Transplantation of brown fat in small animal model systems has confirmed the expectation that brown fat expansion could possibly provide a novel therapeutic to combat obesity and related disorders. Expansion and/or stimulation of uncoupling protein-1 (UCP1)-positive adipose tissues have repeatedly demonstrated physiologically beneficial reductions in circulating glucose and lipids. The recent discovery that brown adipose tissue (BAT)-derived secreted factors positively alter whole body metabolism further expands potential benefits of brown or beige/brite adipose expansion. Unfortunately, there are no sources of transplantable BATs for human therapeutic purposes at this time. Recent developments in bioengineering, including novel hyaluronic acid-based hydrogels, have enabled non-immunogenic, functional tissue allografts that can be used to generate large quantities of UCP1-positive adipose tissue. These sophisticated tissue-engineering systems have provided the methodology to develop metabolically active brown or beige/brite adipose tissue implants with the potential to be used as a metabolic therapy. Unlike the pharmacological browning of white adipose depots, implantation of bioengineered UCP1-positive adipose tissues offers a spatially controlled therapeutic. Moving forward, new insights into the mechanisms by which extracellular cues govern stem-cell differentiation and progenitor cell recruitment may enable cell-free matrix implant approaches, which generate a niche sufficient to recruit white adipose tissue-derived stem cells and support their differentiation into functional beige/brite adipose tissues. This review summarizes clinically relevant discoveries in tissue-engineering and biology leading toward the recent development of biomaterial supported beige adipose tissue implants and

  18. Bioengineering Beige Adipose Tissue Therapeutics

    PubMed Central

    Tharp, Kevin M.; Stahl, Andreas

    2015-01-01

    Unlocking the therapeutic potential of brown/beige adipose tissue requires technological advancements that enable the controlled expansion of this uniquely thermogenic tissue. Transplantation of brown fat in small animal model systems has confirmed the expectation that brown fat expansion could possibly provide a novel therapeutic to combat obesity and related disorders. Expansion and/or stimulation of uncoupling protein-1 (UCP1)-positive adipose tissues have repeatedly demonstrated physiologically beneficial reductions in circulating glucose and lipids. The recent discovery that brown adipose tissue (BAT)-derived secreted factors positively alter whole body metabolism further expands potential benefits of brown or beige/brite adipose expansion. Unfortunately, there are no sources of transplantable BATs for human therapeutic purposes at this time. Recent developments in bioengineering, including novel hyaluronic acid-based hydrogels, have enabled non-immunogenic, functional tissue allografts that can be used to generate large quantities of UCP1-positive adipose tissue. These sophisticated tissue-engineering systems have provided the methodology to develop metabolically active brown or beige/brite adipose tissue implants with the potential to be used as a metabolic therapy. Unlike the pharmacological browning of white adipose depots, implantation of bioengineered UCP1-positive adipose tissues offers a spatially controlled therapeutic. Moving forward, new insights into the mechanisms by which extracellular cues govern stem-cell differentiation and progenitor cell recruitment may enable cell-free matrix implant approaches, which generate a niche sufficient to recruit white adipose tissue-derived stem cells and support their differentiation into functional beige/brite adipose tissues. This review summarizes clinically relevant discoveries in tissue-engineering and biology leading toward the recent development of biomaterial supported beige adipose tissue implants and

  19. Ethical Perspectives on RNA Interference Therapeutics

    PubMed Central

    Ebbesen, Mette; Jensen, Thomas G.; Andersen, Svend; Pedersen, Finn Skou

    2008-01-01

    RNA interference is a mechanism for controlling normal gene expression which has recently begun to be employed as a potential therapeutic agent for a wide range of disorders, including cancer, infectious diseases and metabolic disorders. Clinical trials with RNA interference have begun. However, challenges such as off-target effects, toxicity and safe delivery methods have to be overcome before RNA interference can be considered as a conventional drug. So, if RNA interference is to be used therapeutically, we should perform a risk-benefit analysis. It is ethically relevant to perform a risk-benefit analysis since ethical obligations about not inflicting harm and promoting good are generally accepted. But the ethical issues in RNA interference therapeutics not only include a risk-benefit analysis, but also considerations about respecting the autonomy of the patient and considerations about justice with regard to the inclusion criteria for participation in clinical trials and health care allocation. RNA interference is considered a new and promising therapeutic approach, but the ethical issues of this method have not been greatly discussed, so this article analyses these issues using the bioethical theory of principles of the American bioethicists, Tom L. Beauchamp and James F. Childress. PMID:18612370

  20. 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.

  1. Current therapeutic procedures in Dravet syndrome.

    PubMed

    Chiron, Catherine

    2011-04-01

    Dravet syndrome is a highly pharmaco-resistant form of epilepsy. Valproate and benzodiazepines are the first-line treatment but are usually insufficient therapeutic options. Lamotrigine, carbamazepine and high doses of intravenous phenobarbital can aggravate seizures and should be avoided. Topiramate, levetiracetam, bromide and ketogenic diet also provide substantial efficacy as adjunctive therapy and procedures. Stiripentol is the only new drug to demonstrate efficacy when combined with valproate and clobazam, as shown in two independent double-blind controlled trials dedicated to Dravet children. In order to avoid side effects (mainly loss of appetite and loss of weight) resulting from the inhibition of cytochromes P450 by stiripentol, the prescribed doses of valproate and clobazam should be reduced. Stiripentol has a proper antiepileptic effect and enhances GABAergic neurotransmission by acting on the alpha-3 subunit of GABA(A) receptors. Stiripentol was approved as an orphan drug in Europe in 2007 for adjunctive therapy in Dravet syndrome. More than 500 Dravet patients have currently been satisfactorily treated and recent experiments in Japan have confirmed stiripentol's benefit. In practice, valproate should be initiated at the first onset of complicated febrile seizure in Dravet patients. Relapses justify the addition of clobazam and stiripentol when available. Topiramate and a ketogenic diet are alternatives in pharmaco-resistant cases. PMID:21504427

  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. 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…

  4. 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)

  5. Cytokines and therapeutic oligonucleotides.

    PubMed

    Hartmann, G; Bidlingmaier, M; Eigler, A; Hacker, U; Endres, S

    1997-12-01

    Therapeutic oligonucleotides - short strands of synthetic nucleic acids - encompass antisense and aptamer oligonucleotides. Antisense oligonucleotides are designed to bind to target RNA by complementary base pairing and to inhibit translation of the target protein. Antisense oligonucleotides enable specific inhibition of cytokine synthesis. In contrast, aptamer oligonucleotides are able to bind directly to specific proteins. This binding depends on the sequence of the oligonucleotide. Aptamer oligonucleotides with CpG motifs can exert strong immunostimulatory effects. Both kinds of therapeutic oligonucleotides - antisense and aptamer oligonucleotides - provide promising tools to modulate immunological functions. Recently, therapeutic oligonucleotides have moved towards clinical application. An antisense oligonucleotide directed against the proinflammatory intercellular adhesion molecule 1 (ICAM-1) is currently being tested in clinical trials for therapy of inflammatory disease. Immunostimulatory aptamer oligonucleotides are in preclinical development for immunotherapy. In the present review we summarize the application of therapeutic oligonucleotides to modulate immunological functions. We include technological aspects as well as current therapeutic concepts and clinical studies. PMID:9740353

  6. Reporting therapeutic discourse in a therapeutic community.

    PubMed

    Chapman, G E

    1988-03-01

    Research in nurses' communications has concentrated on nurse to patient interactions. Those few studies which focus on nurse to nurse communications seem to be generated by a pragmatic and normative concern with effective information sharing. In this paper, which describes one aspect of a larger case study of a hospital-based therapeutic community, the description and analysis of nurses' reports flows not from a normative model of professional practice, but rather an exploration of how professional practice is articulated as discourse in nurses' written accounts. Foucault's ideas about therapeutic discourse inform the theoretical framework of the research. Ethnomethodological concerns with the importance of documentary analysis provide the methodological rationale for examining nurses' 24-hour report documents, as official discourse, reflecting therapeutic practice in this setting. A content analysis of nurses' reports, collected over a period of 4 months, demonstrated the importance of domesticity and ordinary everyday activities in nurses' accounts of hospital life. Disruption to the 'life as usual' domesticity in the community seemed to be associated with admission to and discharge from the hospital when interpersonal and interactional changes between patients occur. It is suggested that nurses in general hospital wards and more orthodox psychiatric settings might usefully consider the impact of admissions and discharges on the group of patients they manage, and make this a discursive focus of their work. PMID:3372900

  7. Myc proteins as therapeutic targets

    PubMed Central

    Gustafson, WC; Weiss, WA

    2010-01-01

    Myc proteins (c-myc, Mycn and Mycl) target proliferative and apoptotic pathways vital for progression in cancer. Amplification of the MYCN gene has emerged as one of the clearest indicators of aggressive and chemotherapy-refractory disease in children with neuroblastoma, the most common extracranial solid tumor of childhood. Phosphorylation and ubiquitin-mediated modulation of Myc protein influence stability and represent potential targets for therapeutic intervention. Phosphorylation of Myc proteins is controlled in-part by the receptor tyrosine kinase/phosphatidylinositol 3-kinase/Akt/mTOR signaling, with additional contributions from Aurora A kinase. Myc proteins regulate apoptosis in part through interactions with the p53/Mdm2/Arf signaling pathway. Mutation in p53 is commonly observed in patients with relapsed neuroblastoma, contributing to both biology and therapeutic resistance. This review examines Myc function and regulation in neuroblastoma, and discusses emerging therapies that target Mycn. PMID:20101214

  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. Therapeutic interventions in cerebral palsy.

    PubMed

    Patel, Dilip R

    2005-11-01

    Various therapeutic interventions have been used in the management of children with cerebral palsy. Traditional physiotherapy and occupational therapy are widely used interventions and have been shown to be of benefit in the treatment of cerebral palsy. Evidence in support of the effectiveness of the neurodevelopmental treatment is equivocal at best. There is evidence to support the use and effectiveness of neuromuscular electrical stimulation in children with cerebral palsy. The effectiveness of many other interventions used in the treatment of cerebral palsy has not been clearly established based on well-controlled trials. These include: sensory integration, body-weight support treadmill training, conductive education, constraint-induced therapy, hyperbaric oxygen therapy, and the Vojta method. This article provides an overview of salient aspects of popular interventions used in the management of children with cerebral palsy. PMID:16391455

  10. Therapeutic potential of cannabis-related drugs.

    PubMed

    Alexander, Stephen P H

    2016-01-01

    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. PMID:26216862

  11. Benefits Outgrow Salaries

    ERIC Educational Resources Information Center

    Chemical and Engineering News, 1973

    1973-01-01

    Discusses employee benefits offered to various manufacturing industry workers, especially for chemical professionals. Indicates that in the chemicals and allied products industry, such benefits averaged more than 30 percent of payroll in 1971. (CC)

  12. 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…

  13. Rituximab's new therapeutic target: the podocyte actin cytoskeleton.

    PubMed

    Chan, Andrew C

    2011-06-01

    Therapeutic off-target activities are well recognized for small-molecule drugs. In contrast, monoclonal antibodies (mAbs) traditionally are believed to act specifically and lack off-target therapeutic effects. In this issue of Science Translational Medicine, Fornoni et al. show therapeutic benefit, through an off-target-mediated mechanism, of the mAb drug rituximab in recurrent focal segmental glomerulosclerosis (FSGS) after kidney transplantation. These data shed new light on FSGS pathogenesis and suggest new therapeutic interventions for proteinuric diseases. PMID:21632983

  14. New therapeutic agents for hypertension

    PubMed Central

    REID, JOHN L.

    1996-01-01

    1Over the last 40 years a range of therapeutic strategies has been introduced for the long term treatment of hypertension. 2Although safe effective agents are available a significant number of patients are unable or unwilling to take these drugs as long term treatment. 3Both insufficient efficacy and adverse effects justify the search for new antihypertensive strategies. 4Recent developments include orally active angiotensin (AT1) receptor antagonists (ARA) which appear to offer the benefits of prevention of angiotensin II effects without the adverse effects of bradykinin potentiation, such as cough, which limit the usefulness of angiotensin converting enzyme (ACE) inhibitors. 5Imidazoline receptor agonists offer the potential of centrally active antihypertensives without the adverse effects of sedation and dry mouth. Further clinical experience is necessary to confirm whether the clinical efficacy and good tolerability are confirmed with long term use. 6Both ARA and imidazoline preferring substances offer the bonus of a desirable haemodynamic profile in patients with heart failure and may open new therapeutic avenues in the management of cardiac failure. PMID:8807142

  15. The Therapeutic Value of Pets

    PubMed Central

    Fitzgerald, Faith T.

    1986-01-01

    While domestic pets are capable of transmitting disease and inflicting injury, they may also be of benefit to human health. Studies suggest that companion animals, in addition to their well-known role as helpers to the handicapped, may alleviate depression, solace the lonely, facilitate psycho-therapy, socialize criminals, lower blood pressure, increase survivorship from myocardial infarction and ease the social pain of aging in our society. PMID:3953064

  16. Therapeutics in Huntington's Disease.

    PubMed

    Killoran, Annie; Biglan, Kevin M

    2012-02-01

    OPINION STATEMENT: There is no specific treatment for Huntington's disease (HD). Its many symptoms of motor, psychiatric, and cognitive deterioration are managed with symptomatic relief, rehabilitation, and support. The only drug approved by the US Food and Drug Administration (FDA) for the treatment of HD is an antichoreic agent, tetrabenazine, but this drug is used sparingly because of uneasiness regarding its propensity to cause depression and suicidality in this population, which is already at risk for these complications. Neuroleptics are still first-line treatments for chorea accompanied by comorbid depression and/or behavioral or psychotic symptoms, as is often the case. Psychiatric features, which have a significant impact on a patient's professional and personal life, often become the major focus of management. In addition to neuroleptics, commonly used medications include antidepressants, mood stabilizers, anxiolytics, and psychostimulants. In contrast, few treatment options are available for cognitive impairment in HD; this remains an important and largely unmet therapeutic need. HD patients typically lack insight into their disease manifestations, failing to recognize their need for treatment, and possibly even arguing against it. Multipurpose medications are employed advantageously to simplify the medication regimen, so as to facilitate compliance and not overwhelm the patient. For example, haloperidol can be prescribed for a patient with chorea, agitation, and anorexia, rather than targeting each symptom with a different drug. This approach also limits the potential for adverse effects, which can be difficult to distinguish from the features of the disease itself. With HD's complexity, it is best managed with a multidisciplinary approach that includes a movement disorders specialist, a genetic counselor, a mental health professional, a physical therapist, and a social worker for support and coordination of services. As the disease progresses, there

  17. Engineering antibody therapeutics.

    PubMed

    Chiu, Mark L; Gilliland, Gary L

    2016-06-01

    The successful introduction of antibody-based protein therapeutics into the arsenal of treatments for patients has within a few decades fostered intense innovation in the production and engineering of antibodies. Reviewed here are the methods currently used to produce antibodies along with how our knowledge of the structural and functional characterization of immunoglobulins has resulted in the engineering of antibodies to produce protein therapeutics with unique properties, both biological and biophysical, that are leading to novel therapeutic approaches. Antibody engineering includes the introduction of the antibody combining site (variable regions) into a host of architectures including bi and multi-specific formats that further impact the therapeutic properties leading to further advantages and successes in patient treatment. PMID:27525816

  18. 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

  19. Are therapeutic communities therapeutic for women?

    PubMed Central

    Eliason, Michele J

    2006-01-01

    This paper addresses the growing phenomena of therapeutic community (TC) treatment approaches for women in correctional settings. Although rapidly increasing in number across the country, there is very little empirical research to support the effectiveness of TC treatment for women. Therefore, the literature on the efficacy and effectiveness of TC treatment for women is reviewed in relation to the literature on women's treatment issues. The literature review highlights the gaps where TC treatment ignores or exacerbates issues that are common to addicted women, or uses methods that may be contradictory to women's recovery. PMID:16722560

  20. Differences between invasive lobular and invasive ductal carcinoma of the breast: results and therapeutic implications

    PubMed Central

    Barroso-Sousa, Romualdo; Metzger-Filho, Otto

    2016-01-01

    Invasive lobular carcinoma (ILC) is the second most common histologic subtype of breast cancer (BC): ILC differs from invasive ductal carcinoma (IDC) in its clinicopathological characteristics and responsiveness to systemic therapy. From the clinical standpoint, data suggest that ILC derives a distinct benefit from systemic therapy compared to IDC. In addition, comprehensive molecular analyses have been reported for ILCs, confirming that these tumors have specific genomic profiles compared to IDC. Despite these differences, clinical trials and practical clinical guidelines tend to treat BC as a single entity. Here we discuss these clinical and molecular data and their therapeutic implications. PMID:27482285

  1. Fibromyalgia syndrome: novel therapeutic targets.

    PubMed

    Ablin, Jacob N; Häuser, Winfried

    2016-05-01

    Fibromyalgia syndrome (FMS) is a chronic disorder characterized by widespread pain and tenderness, accompanied by disturbed sleep, chronic fatigue and multiple additional functional symptoms. FMS continues to pose an unmet need regarding pharmacological treatment and many patients fail to achieve sufficient relief from existing treatments. As FMS is considered to be a condition in which pain amplification occurs within the CNS, therapeutic interventions, both pharmacological and otherwise, have revolved around attempts to influence pain processing in the CNS. In the current review, we present an update on novel targets in the search for effective treatment of FMS. PMID:27296699

  2. 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

  3. 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…

  4. Performance Boosting Additive

    NASA Technical Reports Server (NTRS)

    1999-01-01

    Mainstream Engineering Corporation was awarded Phase I and Phase II contracts from Goddard Space Flight Center's Small Business Innovation Research (SBIR) program in early 1990. With support from the SBIR program, Mainstream Engineering Corporation has developed a unique low cost additive, QwikBoost (TM), that increases the performance of air conditioners, heat pumps, refrigerators, and freezers. Because of the energy and environmental benefits of QwikBoost, Mainstream received the Tibbetts Award at a White House Ceremony on October 16, 1997. QwikBoost was introduced at the 1998 International Air Conditioning, Heating, and Refrigeration Exposition. QwikBoost is packaged in a handy 3-ounce can (pressurized with R-134a) and will be available for automotive air conditioning systems in summer 1998.

  5. Structural changes in the German pharmaceutical market: price setting mechanisms based on the early benefit evaluation.

    PubMed

    Henschke, Cornelia; Sundmacher, Leonie; Busse, Reinhard

    2013-03-01

    In the past, free price setting mechanisms in Germany led to high prices of patented pharmaceuticals and to increasing expenditures in the pharmaceutical sector. In order to control patented pharmaceutical prices and to curb increasing pharmaceutical spending, the Act for Restructuring the Pharmaceutical Market in Statutory Health Insurance (AMNOG) came into effect on 1st January 2011. In a structured dossier, pharmaceutical manufacturers have to demonstrate the additional therapeutic benefit of the newly approved pharmaceutical compared to its appropriate comparator. According to the level of additional benefit, pharmaceuticals will be subject to price negotiations between the Federal Association of Statutory Health Insurance Funds and the pharmaceutical company concerned (or assigned to a reference price group in case of no additional benefit). Therefore, the health care reform is a first step to decision making based on "value for money". The process of price setting based on early benefit evaluation has an impact on the German as well as the European pharmaceutical markets. Therefore, these structural changes in Germany are of importance for pricing decisions in many European countries both from a political point of view and for strategic planning for pharmaceutical manufacturers, which may have an effect on insured patients' access to pharmaceuticals. PMID:23339876

  6. 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

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

    PubMed

    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

  8. 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

  9. 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

  10. Benefits of Java

    MedlinePlus

    ... and Facts Fitness Fitness Find out more Categories Sports and Performance Training and Recovery Exercise Topics Fueling Your Workout Benefits of Physical Activity Exercise Nutrition Top Articles Man ...

  11. 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

  12. Therapeutics for cognitive aging

    PubMed Central

    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.

    2011-01-01

    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. PMID:20392284

  13. Advances in Therapeutic Cholangioscopy

    PubMed Central

    Moura, Renata Nobre; de Moura, Eduardo Guimarães Hourneaux

    2016-01-01

    Nowadays, cholangioscopy is an established modality in diagnostic and treatment of pancreaticobiliary diseases. The more widespread use and the recent development of new technologies and accessories had renewed the interest of endoscopic visualization of the biliary tract, increasing the range of indications and therapeutic procedures, such as diagnostic of indeterminate biliary strictures, lithotripsy of difficult bile duct stones, ablative techniques for intraductal malignancies, removal of foreign bodies and gallbladder drainage. These endoscopic interventions will probably be the last frontier in the near future. This paper presents the new advances in therapeutic cholangioscopy, focusing on the current clinical applications and on research areas. PMID:27403156

  14. 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

  15. Proliferative retinopathies: animal models and therapeutic opportunities.

    PubMed

    Villacampa, Pilar; Haurigot, Virginia; Bosch, Fatima

    2015-01-01

    Proliferative retinopathies are the leading causes of blindness in Western societies. The development of new, more efficacious treatments that take advantage of recent advances in the fields of gene and cell therapy requires further investigations on the mechanisms underlying disease onset and progression, and adequate animal models that recapitulate the pathogenesis of human proliferative retinopathy and allow evaluation of the long-term therapeutic benefits that these therapies can offer. Unfortunately, most models of retinal neovascularization have short-term evolution and diabetic rodents show a very mild retinal phenotype, limited to non-proliferative changes, and do not develop proliferative retinopathy at all. Transgenic mice overexpressing Insulin-like Growth Factor-I (IGF-I) in the retina (TgIGF-I) constitute the only rodent model currently available that develops most of the retinal alterations observed in diabetic eyes, with a temporal evolution that resembles that of the human disease. TgIGF-I have retinal vascular alterations that progress as animals age from non-proliferative to proliferative disease, making these mice an excellent model of proliferative retinopathy that, due to its slow progression, allows long-term evaluation of novel antiangiogenic therapies. At the molecular level, transgenic retinas recapitulate a variety of changes that are also observed in diabetic retinas, which reinforces the validity of this model. In addition to vascular and glial alterations, Tg-IGF-I mice show progressive neurodegeneration that leads to blindness in old animals. Thus, TgIGF-I are a useful model for testing the long-term efficacy and safety of innovative antiangiogenic, glial-modulating and neuroprotective therapies for the treatment of diabetic retinopathy and other retinal proliferative disorders. PMID:25760215

  16. 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

  17. 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

  18. Gold nanoparticles: A critical review of therapeutic applications and toxicological aspects.

    PubMed

    Hornos Carneiro, Maria Fernanda; Barbosa, Fernando

    2016-01-01

    Gold (Au) compounds have been utilized as effective therapeutic agents for the treatment of some inflammatory diseases such as rheumatoid arthritis. However, Au compound use has become limited due to associated high incidence of side effects. Recent development of nanomaterials for therapeutic use with Au-containing drugs is improving the beneficial actions and reducing toxic properties of these agents. Lower toxicity in conjunction with anti-inflammatory and antiangiogenic effects was reported to occur with gold nanoparticles (AuNP) treatment. However, despite this therapeutic potential, safety of AuNP remains to be determined, since the balance between therapeutic properties and development of adverse effects is not well established. Several variables that drive this benefit-risk balance, including physicochemical characteristics of nanoparticles such as size, shape, surface area, and chemistry, are poorly described in the scientific literature. Moreover, therapeutic and toxicological data were obtained employing nonstandardized or poorly described protocols with different experimental settings (animal species/cell type, route and time of exposure). In contrast, effective and safe application of AuNP may be established only after elucidation of various physicochemical properties of each specific AuNP, and determination of respective kinetics and interaction of compound with target tissue. This critical review conveys the state of the art, the therapeutic use, and adverse effects mediated by AuNP, with primary emphasis on anti-inflammatory and antiangiogenic potential, highlighting the limitations/gaps in the scientific literature concerning important points: (i) selection of experimental designs (in vitro and in vivo models) and (ii) consideration of different physicochemical properties of AuNP that are often disregarded in many scientific publications. In addition, prospects and future needs for research in this area are provided. PMID:27282429

  19. Therapeutic efficacy of a therapeutic cooking group from the patients' perspective.

    PubMed

    Hill, Kimberly H; O'Brien, Kimberly A; Yurt, Roger W

    2007-01-01

    The purpose of this study was to evaluate the therapeutic efficacy of the cooking group from the burn survivors' perspective. By incorporating concepts of kitchen skills, energy conservation, and desensitization techniques, the cooking group can assist patients with the functional use of their hands, standing tolerance, return to former vocational activities, and socialization with other patients. A questionnaire was developed based on commonly expressed benefits of cooking group. Areas of interest included decreasing anxiety in the kitchen, distraction from their burns, socializing with other burn survivors, and the physical benefits of participating in the group. The results of this study indicate that participants regard the therapeutic cooking group as a valuable treatment modality that effectively combines functional activities with socialization to decrease burn related anxiety and increase motion in a supportive environment for patients with burns. PMID:17351453

  20. 20 CFR 901.72 - Additional rules.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 3 2011-04-01 2011-04-01 false Additional rules. 901.72 Section 901.72... Additional rules. The Joint Board may, in notice or other guidance of general applicability, provide additional rules regarding the enrollment of actuaries. Effective Date Note: At 76 FR 17776, Mar. 31,...

  1. 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. PMID:24583563

  2. 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. PMID:26149015

  3. Therapeutic antibodies against cancer

    PubMed Central

    Adler, Mark J.; Dimitrov, Dimiter S.

    2012-01-01

    Antibody-based therapeutics against cancer are highly successful in clinic and currently enjoy unprecedented recognition of their potential; 13 monoclonal antibodies (mAbs) have been approved for clinical use in the European Union and in the United States (one, mylotarg, was withdrawn from market in 2010). Three of the mAbs (bevacizumab, rituximab, trastuzumab) are in the top six selling protein therapeutics with sales in 2010 of more than $5 bln each. Hundreds of mAbs including bispecific mAbs and multispecific fusion proteins, mAbs conjugated with small molecule drugs and mAbs with optimized pharmacokinetics are in clinical trials. However, challenges remain and it appears that deeper understanding of mechanisms is needed to overcome major problems including resistance to therapy, access to targets, complexity of biological systems and individual variations. PMID:22520975

  4. 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. PMID:26264836

  5. Strategies for therapeutic hypometabothermia

    PubMed Central

    Liu, Shimin; Chen, Jiang-Fan

    2013-01-01

    Although therapeutic hypothermia and metabolic suppression have shown robust neuroprotection in experimental brain ischemia, systemic complications have limited their use in treating acute stroke patients. The core temperature and basic metabolic rate are tightly regulated and maintained in a very stable level in mammals. Simply lowering body temperature or metabolic rate is actually a brutal therapy that may cause more systemic as well as regional problems other than providing protection. These problems are commonly seen in hypothermia and barbiturate coma. The main innovative concept of this review is to propose thermogenically optimal and synergistic reduction of core temperature and metabolic rate in therapeutic hypometabothermia using novel and clinically practical approaches. When metabolism and body temperature are reduced in a systematically synergistic manner, the outcome will be maximal protection and safe recovery, which happen in natural process, such as in hibernation, daily torpor and estivation. PMID:24179563

  6. Therapeutic targets for premature ejaculation.

    PubMed

    Andersson, Karl-Erik; Abdel-Hamid, Ibrahim A

    2011-09-01

    Premature ejaculation (PE) is the most common male sexual complaint, and may exert a profound negative impact on the man's life and partnership. Using currently available treatment alternatives (e.g., selective serotonin uptake inhibitor, agents acting locally on the penis), PE can be treated in most, but not all patients. However, since long term success rates have been disappointing, and the only approved treatment so far is the short-acting selective serotonin re-uptake inhibitor dapoxetine, there is currently an intensive search for new treatment modalities. Selection of the most promising therapeutic targets from a host of current and potential candidates depends heavily on their roles in the pathophysiology of PE. Possible central nervous targets that will be discussed are serotonin transporters, and CNS receptors for 5-HT(IA) and 5-HT(1B), dopamine, oxytocin, opioids, neurokinin-1, and glutamate. Putative peripheral targets include α(1)-adrenoceptors, phosphodiestrase enzymes, Rho kinases, purinergic (P2X) receptors, and penile sensory nerves. It is clear that exploiting the full therapeutic potential of these targets will require additional basic and clinical research. PMID:21816550

  7. 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

  8. Exercise: Benefits of Exercise

    MedlinePlus Videos and Cool Tools

    ... show that people with arthritis, heart disease, or diabetes benefit from regular exercise. Exercise also helps people ... or difficulty walking. To learn about exercise and diabetes, see "Exercise and Type 2 Diabetes" from Go4Life®, ...

  9. 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 ...

  10. 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.

  11. 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. PMID:23355488

  12. New therapeutic agents for acromegaly.

    PubMed

    Melmed, Shlomo

    2016-02-01

    The currently available somatostatin receptor ligands (SRLs) and growth hormone (GH) antagonists are used to control levels of GH and insulin-like growth factor 1 (IGF-1) in patients with acromegaly. However, these therapies are limited by wide variations in efficacy, associated adverse effects and the need for frequent injections. A phase III trial of oral octreotide capsules demonstrated that this treatment can safely sustain suppressed levels of GH and IGF-1 and reduce the severity of symptoms in patients with acromegaly previously controlled by injectable SRL therapy, with the added benefit of no injection-site reactions. Phase I and phase II trials of the pan-selective SRL DG3173, the liquid crystal octreotide depot CAM2029 and an antisense oligonucleotide directed against the GH receptor have shown that these agents can be used to achieve biochemical suppression in acromegaly and have favourable safety profiles. This Review outlines the need for new therapeutic agents for patients with acromegaly, reviews clinical trial data of investigational agents and considers how these therapies might best be integrated into clinical practice. PMID:26610414

  13. Cold as a therapeutic agent.

    PubMed

    Wang, H; Olivero, W; Wang, D; Lanzino, G

    2006-05-01

    The use of cold as a therapeutic agent has a long and colorful history. The Edwin Smith Papyrus, the most ancient medical text known, dated 3500 B.C., made numerous references to the use of cold as therapy. Baron de Larrey, a French army surgeon during Napoleon's Russian campaign, packed the limbs in ice prior to amputations to render the procedures painless. In the early twentieth century, a neurosurgeon, Temple Fay, pioneered "human refrigeration" as a treatment for malignancies and head injuries. In 1961, Irving Cooper developed the first closed cryoprobe system and ushered in the modern era of cryogenic surgery with his imperturbable convictions. Fay's early work fell victim to the disruptive sequel of the World War II. The Nazis confiscated his data (presented before the Third International Cancer Congress in 1939) forwarded to Belgium for publication and brutally applied his refrigeration techniques experimentally without any benefit of anesthesia in the concentration camps, especially Dachau. Hypothermia became associated in the public mind with the atrocities exposed at the war trials in Nürnberg. After lying dormant for decades, the interest was rekindled in the late 80s when mild hypothermia was shown to confer dramatic neuroprotection in a number of experimental models of brain injury. With several large multi-center clinical studies currently under way, hypothermia is receiving unprecedented attention from the medical and scientific communities. PMID:16489500

  14. 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

  15. Placebo analgesia: cognitive influences on therapeutic outcome.

    PubMed

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

    2012-01-01

    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. PMID:22494482

  16. Therapeutic drug monitoring in neonates.

    PubMed

    Pauwels, Steven; Allegaert, Karel

    2016-04-01

    Therapeutic drug monitoring (TDM) aims to integrate drug measurement results into clinical decision making. The basic rules apply when using TDM in neonates (aminoglycosides, vancomycin, phenobarbital, digoxin), but additional factors should also be taken into account. First, due to both pharmacokinetic variability and non-pharmacokinetic factors, the correlation between dosage and concentration is poor in neonates, but can be overcome with the use of more complex, validated dosing regimens. Second, the time to reach steady state is prolonged, especially when no loading dose is used. Consequently, the timing of TDM sampling is important in this population. Third, the target concentration may be uncertain (vancomycin) or depend on specific factors (phenobarbital during whole body cooling). Finally, because of differences in matrix composition (eg, protein, bilirubin), assay-related inaccuracies may be different in neonates. We anticipate that complex validated dosing regimens, with subsequent TDM sampling and Bayesian forecasting, are the next step in tailoring pharmacotherapy to individual neonates. PMID:26803050

  17. 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. PMID:24880719

  18. 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. PMID:21761958

  19. 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. PMID:22873934

  20. Sleep physiology, abnormal States, and therapeutic interventions.

    PubMed

    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

  1. 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

  2. Cardiovascular Pharmacogenomics: The Future of Cardiovascular Therapeutics?

    PubMed Central

    Roden, Dan M.

    2012-01-01

    Responses to drug therapy vary from benefit to no effect to adverse effects which can be serious or occasionally fatal. Increasing evidence supports the idea that genetic variants can play a major role in this spectrum of responses. Well-studied examples in cardiovascular therapeutics include predictors of steady-state warfarin dosage, predictors of reduced efficacy among patients receiving clopidogrel for drug eluting stents, and predictors of some serious adverse drug effects. This review summarizes contemporary approaches to identifying and validating genetic predictors of variability in response to drug treatment. Approaches to incorporating this new knowledge into clinical care, and the barriers to this concept, are addressed. PMID:23200096

  3. 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

  4. 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. PMID:26814609

  5. 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.

  6. Psychodynamic Perspective on Therapeutic Boundaries

    PubMed Central

    Bridges, Nancy A.

    1999-01-01

    Discussion of boundaries in therapeutic work most often focuses on boundary maintenance, risk management factors, and boundary violations. The psychodynamic meaning and clinical management of boundaries in therapeutic relationships remains a neglected area of discourse. Clinical vignettes will illustrate a psychodynamic, developmental-relational perspective using boundary dilemmas to deepen and advance the therapeutic process. This article contributes to the dialogue about the process of making meaning and constructing therapeutically useful and creative boundaries that further the psychotherapeutic process. PMID:10523432

  7. Therapeutic Hypothermia as a Neuroprotective Strategy in Neonatal Hypoxic-Ischemic Brain Injury and Traumatic Brain Injury

    PubMed Central

    Ma, H.; Sinha, B.; Pandya, R.S.; Lin, N.; Popp, A.J.; Li, J.; Yao, J.; Wang, X.

    2014-01-01

    Evidence shows that artificially lowering body and brain temperature can significantly reduce the deleterious effects of brain injury in both newborns and adults. Although the benefits of therapeutic hypothermia have long been known and applied clinically, the underlying molecular mechanisms have yet to be elucidated. Hypoxic-ischemic brain injury and traumatic brain injury both trigger a series of biochemical and molecular events that cause additional brain insult. Induction of therapeutic hypothermia seems to ameliorate the molecular cascade that culminates in neuronal damage. Hypothermia attenuates the toxicity produced by the initial injury that would normally produce reactive oxygen species, neurotransmitters, inflammatory mediators, and apoptosis. Experiments have been performed on various depths and levels of hypothermia to explore neuroprotection. This review summarizes what is currently known about the beneficial effects of therapeutic hypothermia in experimental models of neonatal hypoxic-ischemic brain injury and traumatic brain injury, and explores the molecular mechanisms that could become the targets of novel therapies. In addition, this review summarizes the clinical implications of therapeutic hypothermia in newborn hypoxic-ischemic encephalopathy and adult traumatic brain injury. PMID:22834830

  8. Telomerase and cancer therapeutics.

    PubMed

    Harley, Calvin B

    2008-03-01

    Telomerase is an attractive cancer target as it appears to be required in essentially all tumours for immortalization of a subset of cells, including cancer stem cells. Moreover, differences in telomerase expression, telomere length and cell kinetics between normal and tumour tissues suggest that targeting telomerase would be relatively safe. Clinical trials are ongoing with a potent and specific telomerase inhibitor, GRN163L, and with several versions of telomerase therapeutic vaccines. The prospect of adding telomerase-based therapies to the growing list of new anticancer products is promising, but what are the advantages and limitations of different approaches, and which patients are the most likely to respond? PMID:18256617

  9. [Achievement of therapeutic objectives].

    PubMed

    Mantilla, Teresa

    2014-07-01

    Therapeutic objectives for patients with atherogenic dyslipidemia are achieved by improving patient compliance and adherence. Clinical practice guidelines address the importance of treatment compliance for achieving objectives. The combination of a fixed dose of pravastatin and fenofibrate increases the adherence by simplifying the drug regimen and reducing the number of daily doses. The good tolerance, the cost of the combination and the possibility of adjusting the administration to the patient's lifestyle helps achieve the objectives for these patients with high cardiovascular risk. PMID:25043543

  10. Revitalizing Psychiatric Therapeutics

    PubMed Central

    Hyman, Steven E

    2014-01-01

    Despite high prevalence and enormous unmet medical need, the pharmaceutical industry has recently de-emphasized neuropsychiatric disorders as ‘too difficult' a challenge to warrant major investment. Here I describe major obstacles to drug discovery and development including a lack of new molecular targets, shortcomings of current animal models, and the lack of biomarkers for clinical trials. My major focus, however, is on new technologies and scientific approaches to neuropsychiatric disorders that give promise for revitalizing therapeutics and may thus answer industry's concerns. PMID:24317307

  11. [Is therapeutic deadlock inevitable?].

    PubMed

    Vignat, Jean-Pierre

    2016-01-01

    Many long-term treatments appear to be an expression of therapeutic deadlock. The situation leads to a questioning of the concept of chronicity and the identification of the determining factors of situations which are apparently blocked, marked by the search for solutions taking a back seat to the taking of action. The interaction between patients' mental apparatus and the care apparatus lies at the heart of the question, interpreted from an institutional, collective and individual perspective, supported by the clinical and psychopathological approach, and the return to the prioritisation of the thought. PMID:27389427

  12. Therapeutic Endoscopic Ultrasound

    PubMed Central

    Cheriyan, Danny

    2015-01-01

    Endoscopic ultrasound (EUS) technology has evolved dramatically over the past 20 years, from being a supplementary diagnostic aid available only in large medical centers to being a core diagnostic and therapeutic tool that is widely available. Although formal recommendations and practice guidelines have not been developed, there are considerable data supporting the use of EUS for its technical accuracy in diagnosing pancreaticobiliary and gastrointestinal pathology. Endosonography is now routine practice not only for pathologic diagnosis and tumor staging but also for drainage of cystic lesions and celiac plexus neurolysis. In this article, we cover the use of EUS in biliary and pancreatic intervention, ablative therapy, enterostomy, and vascular intervention. PMID:27118942

  13. [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. PMID:24100828

  14. Is Payment a Benefit?

    PubMed Central

    Wertheimer, Alan

    2011-01-01

    What I call “the standard view” claims that IRBs should not regard financial payment as a benefit to subjects for the purpose of risk/benefit assessment. Although the standard view is universally accepted, there is little defense of that view in the canonical documents of research ethics or the scholarly literature. This article claims that insofar as IRBs should be concerned with the interests and autonomy of research subjects, they should reject the standard view and adopt “the incorporation view.” The incorporation view is more consistent with the underlying soft-paternalist justification for risk-benefit assessment and demonstrates respect for the autonomy of prospective subjects. Adoption of the standard view precludes protocols that advance the interests of subjects, investigators, and society. After considering several objections to the argument, I consider several arguments for the standard view that do not appeal to the interests and autonomy of research subjects. PMID:21726261

  15. 29 CFR 825.213 - Employer recovery of benefit costs.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 3 2010-07-01 2010-07-01 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... (share of) health benefit premium payments made on the employee's behalf during a period of unpaid...

  16. AMUM LECTURE: Therapeutic ultrasound

    NASA Astrophysics Data System (ADS)

    Crum, Lawrence A.

    2004-01-01

    The use of ultrasound in medicine is now quite commonplace, especially with the recent introduction of small, portable and relatively inexpensive, hand-held diagnostic imaging devices. Moreover, ultrasound has expanded beyond the imaging realm, with methods and applications extending to novel therapeutic and surgical uses. These applications broadly include: tissue ablation, acoustocautery, lipoplasty, site-specific and ultrasound mediated drug activity, extracorporeal lithotripsy, and the enhancement of natural physiological functions such as wound healing and tissue regeneration. A particularly attractive aspect of this technology is that diagnostic and therapeutic systems can be combined to produce totally non-invasive, imageguided therapy. This general lecture will review a number of these exciting new applications of ultrasound and address some of the basic scientific questions and future challenges in developing these methods and technologies for general use in our society. We shall particularly emphasize the use of High Intensity Focused Ultrasound (HIFU) in the treatment of benign and malignant tumors as well as the introduction of acoustic hemostasis, especially in organs which are difficult to treat using conventional medical and surgical techniques.

  17. Winnicott's therapeutic consultations revisited.

    PubMed

    Brafman, A H

    1997-08-01

    Winnicott described in his book 'Therapeutic Consultations' (1971) how a diagnostic assessment of a referred child developed into a fruitful therapeutic intervention when he was able to discover the unconscious fantasy that underlay the child's symptoms. Because these were children who were, essentially, developing normally, he used the word 'knot' to depict the obstacle the child had met. Any conflicts the parents might have were not explored in that context. This work present cases in which child and parents are seen together for the diagnostic assessment. The child's feelings about his world and his difficulties are explored through a variety of techniques including drawings. In the same interview, an analytic enquiry into the parents' history and also their views of the child reveals how the child's fantasies and the parents' past experiences interact and create a mutually reinforcing vicious circle. In other words, the 'knot' involves all of them. If the child's unconscious fantasy can be verbalised and if the parents are able to approach the child in a manner that acknowledges the child's real needs, the 'knot' disappears and normal development can be resumed. PMID:9306188

  18. Engineering therapeutic protein disaggregases.

    PubMed

    Shorter, James

    2016-05-15

    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

  19. 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

  20. Pharmacogenetics approach to therapeutics.

    PubMed

    Koo, Seok Hwee; Lee, Edmund Jon Deoon

    2006-01-01

    1. Pharmacogenetics refers to the study of genetically controlled variations in drug response. Functional variants caused by single nucleotide polymorphisms (SNPs) in genes encoding drug-metabolising enzymes, transporters, ion channels and drug receptors have been known to be associated with interindividual and interethnic variation in drug response. Genetic variations in these genes play a role in influencing the efficacy and toxicity of medications. 2. Rapid, precise and cost-effective high-throughput technological platforms are essential for performing large-scale mutational analysis of genetic markers involved in the aetiology of variable responses to drug therapy. 3. The application of a pharmacogenetics approach to therapeutics in general clinical practice is still far from being achieved today owing to various constraints, such as limited accessibility of technology, inadequate knowledge, ambiguity of the role of variants and ethical concerns. 4. Drug actions are determined by the interplay of several genes encoding different proteins involved in various biochemical pathways. With rapidly emerging SNP discovery technological platforms and widespread knowledge on the role of SNPs in disease susceptibility and variability in drug response, the pharmacogenetics approach to therapeutics is anticipated to take off in the not-too-distant future. This will present profound clinical, economic and social implications for health care. PMID:16700889

  1. 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

  2. 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. PMID:24873112

  3. Clinical evaluation of therapeutic cancer vaccines

    PubMed Central

    Ogi, Chizuru; Aruga, Atsushi

    2013-01-01

    Therapeutic cancer vaccines are an immunotherapy that targets tumor antigens to induce an active immune response. To date, Provenge® is the only therapeutic cancer vaccine approved by the United States Food and Drug Administration. Although therapeutic cancer vaccines have not been approved by the European Medicines Agency (EMA), they have been approved in several countries other than the United States (US) and the European Union (EU). Provenge® is the only approved cancer vaccine that showed significant primary endpoint efficacy in a phase III study at the time of approval. Retrospective analysis of 23 completed or terminated phase III studies showed that 74% (17/23) failed to demonstrate significant efficacy in the primary endpoint. The reasons for failure were surveyed in 13 of the 17 studies. Despite efforts to minimize tumor burden, including surgery and induction chemotherapy before therapeutic cancer vaccine therapy, 69% (9/13) of the phase III studies failed. These findings indicate that tumor burden may not be the only prognostic factor. Immunological response has often been used as a predictive factor, and a small number of sub-group analyses have succeeded in showing that immunological response is associated with the efficacy of therapeutic cancer vaccines. Being a prognostic factor, inclusion of immunological response in addition to tumor stage in the eligibility criteria or sub-group analysis may minimize study population heterogeneity, a key factor in the success of phase III studies. PMID:23454867

  4. Innovative therapeutic strategies for recessive dystrophic epidermolysis bullosa.

    PubMed

    Larcher, F; Del Río, M

    2015-06-01

    Recessive dystrophic epidermolysis bullosa (RDEB) is among the most serious rare skin diseases. It is also the rare skin disease for which most effort has been expended in developing advanced therapeutic interventions. RDEB is caused by collagen VII deficiency resulting from COL7A1 mutations. Therapeutic approaches seek to replenish collagen VII and thus restore dermal-epidermal adhesion. Therapeutic options under development include protein therapy and different cell-based and gene-based therapies. In addition to treating skin defects, some of these therapies may also target internal mucosa. In the coming years, these novel therapeutic approaches should substantially improve the quality of life of patients with RDEB. PMID:25796272

  5. 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

  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. 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.

  8. 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…

  9. Teacher Retirement Benefits

    ERIC Educational Resources Information Center

    Costrell, Robert; Podgursky, Michael

    2009-01-01

    The ongoing global financial crisis is forcing many employers, from General Motors to local general stores, to take a hard look at the costs of the compensation packages they offer employees. For public school systems, this will entail a consideration of fringe benefit costs, which in recent years have become an increasingly important component of…

  10. 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.

  11. 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…

  12. 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

  13. Aescin: pharmacology, pharmacokinetics and therapeutic profile.

    PubMed

    Sirtori, C R

    2001-09-01

    Aescin, the major active principle from Aesculus hippocastanum (Hippocastanaceae) the horse chestnut tree, has shown satisfactory evidence for a clinically significant activity in chronic venous insufficiency (CVI), haemorrhoids and post-operative oedema. In one controlled trial aescin was shown to be as effective as compression therapy as an alternative to medical treatment for CVI. The therapeutic benefit is well supported by a number of experimental investigations in different animal models, indicative of clearcut anti-oedematous, anti-inflammatory and venotonic properties, mainly related to the molecular mechanism of the agent, allowing improved entry of ions into channels, thus raising venous tension in both in vitro and in vivo conditions. Other mechanisms, i.e. release of PGF(2) from veins, antagonism to 5-HT and histamine, reduced catabolism of tissue mucopolysaccharides, further underline the wide ranging mechanisms of the therapeutic activity of aescin. The excellent tolerability of aescin in the clinic indicates this treatment is of definite clinical benefit in patients with clinical conditions resulting in CVI, haemorrhoids or peripheral oedema formation. PMID:11529685

  14. The therapeutic potential of regulated hypothermia.

    PubMed

    Gordon, C J

    2001-03-01

    Reducing body temperature of rodents has been found to improve their survival to ischaemia, hypoxia, chemical toxicants, and many other types of insults. Larger species, including humans, may also benefit from a lower body temperature when recovering from CNS ischaemia and other traumatic insults. Rodents subjected to these insults undergo a regulated hypothermic response (that is, decrease in set point temperature) characterised by preference for cooler ambient temperatures, peripheral vasodilatation, and reduced metabolic rate. However, forced hypothermia (that is, body temperature forced below set point) is the only method used in the study and treatment of human pathological insults. The therapeutic efficacy of the hypothermic treatment is likely to be influenced by the nature of the reduction in body temperature (that is, forced versus regulated). Homeostatic mechanisms counter forced reductions in body temperature resulting in physiological stress and decreased efficacy of the hypothermic treatment. On the other hand, regulated hypothermia would seem to be the best means of achieving a therapeutic benefit because thermal homeostatic systems mediate a controlled reduction in core temperature. PMID:11300205

  15. Microfabricated therapeutic actuators

    SciTech Connect

    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.

  16. 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.

  17. 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

  18. 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

  19. Homocystinuria: Therapeutic approach.

    PubMed

    Kumar, Tarun; Sharma, Gurumayum Suraj; Singh, Laishram Rajendrakumar

    2016-07-01

    Homocystinuria is a disorder of sulfur metabolism pathway caused by deficiency of cystathionine β-synthase (CBS). It is characterized by increased accumulation of homocysteine (Hcy) in the cells and plasma. Increased homocysteine results in various vascular and neurological complications. Present strategies to lower cellular and plasma homocysteine levels include vitamin B6 intake, dietary methionine restriction, betaine supplementation, folate and vitamin B12 administration. However, these strategies are inefficient for treatment of homocystinuria. In recent years, advances have been made towards developing new strategies to treat homocystinuria. These mainly include functional restoration to mutant CBS, enhanced clearance of Hcy from the body, prevention of N-homocysteinylation-induced toxicity and inhibition of homocysteine-induced oxidative stress. In this review, we have exclusively discussed the recent advances that have been achieved towards the treatment of homocystinuria. The review is an attempt to help clinicians in developing effective therapeutic strategies and designing novel drugs against homocystinuria. PMID:27059523

  20. 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

  1. Principles of therapeutics.

    PubMed

    Miller, T R

    1992-12-01

    Topical administration of drugs is the treatment of choice for diseases of the anterior segment. Drug levels attained by this means are usually of short duration, however, necessitating frequent therapy or continuous perfusion if prolonged drug levels are required. A drug-delivery device (collagen shield or contact lens) or subconjunctival injections can be used to augment topical therapy if frequent treatment is not possible. Subconjunctival injections are recommended for drugs that have low solubility and, hence, low corneal penetration. Retrobulbar injections are seldom indicated, except for regional anesthesia. Systemic administration is useful for anti-inflammatory therapy but it may be difficult to establish therapeutic levels of antibiotic agents in the eye because of the blood-ocular barrier. In severe cases, intraocular injection may be required. PMID:1458325

  2. Physiological and therapeutic effects of carnosine on cardiometabolic risk and disease.

    PubMed

    Baye, Estifanos; Ukropcova, Barbara; Ukropec, Jozef; Hipkiss, Alan; Aldini, Giancarlo; de Courten, Barbora

    2016-05-01

    Obesity, type 2 diabetes (T2DM) and cardiovascular disease (CVD) are the most common preventable causes of morbidity and mortality worldwide. They represent major public health threat to our society. Increasing prevalence of obesity and T2DM contributes to escalating morbidity and mortality from CVD and stroke. Carnosine (β-alanyl-L-histidine) is a dipeptide with anti-inflammatory, antioxidant, anti-glycation, anti-ischaemic and chelating roles and is available as an over-the-counter food supplement. Animal evidence suggests that carnosine may offer many promising therapeutic benefits for multiple chronic diseases due to these properties. Carnosine, traditionally used in exercise physiology to increase exercise performance, has potential preventative and therapeutic benefits in obesity, insulin resistance, T2DM and diabetic microvascular and macrovascular complications (CVD and stroke) as well as number of neurological and mental health conditions. However, relatively little evidence is available in humans. Thus, future studies should focus on well-designed clinical trials to confirm or refute a potential role of carnosine in the prevention and treatment of chronic diseases in humans, in addition to advancing knowledge from the basic science and animal studies. PMID:26984320

  3. Antioxidant therapeutics: Pandora's box.

    PubMed

    Day, Brian J

    2014-01-01

    Evolution has favored the utilization of dioxygen (O2) in the development of complex multicellular organisms. O2 is actually a toxic mutagenic gas that is highly oxidizing and combustible. It is thought that plants are largely to blame for polluting the earth's atmosphere with O2 owing to the development of photosynthesis by blue-green algae over 2 billion years ago. The rise of the plants and atmospheric O2 levels placed evolutionary stress on organisms to adapt or become extinct. This implies that all the surviving creatures on our planet are mutants that have adapted to the "abnormal biology" of O2. Much of the adaptation to the presence of O2 in biological systems comes from well-coordinated antioxidant and repair systems that focus on converting O2 to its most reduced form, water (H2O), and the repair and replacement of damaged cellular macromolecules. Biological systems have also harnessed O2's reactive properties for energy production, xenobiotic metabolism, and host defense and as a signaling messenger and redox modulator of a number of cell signaling pathways. Many of these systems involve electron transport systems and offer many different mechanisms by which antioxidant therapeutics can alternatively produce an antioxidant effect without directly scavenging oxygen-derived reactive species. It is likely that each agent will have a different set of mechanisms that may change depending on the model of oxidative stress, organ system, or disease state. An important point is that all biological processes of aerobes have coevolved with O2 and this creates a Pandora's box for trying to understand the mechanism(s) of action of antioxidants being developed as therapeutic agents. PMID:23856377

  4. GTI-2040. Lorus Therapeutics.

    PubMed

    Orr, R M

    2001-10-01

    Loris Therapeutics (formerly GeneSense Therapeutics) is developing the antisense oligonucleotide GTI-2040, directed against the R2 component of ribonucleotide reductase, for the potential treatment of cancer [348194]. It is in phase I/II trials [353796] and Lorus had anticipated phase II trials would be initiated in July 2001. By August 2001, GTI-2040 was undergoing a phase II trial as a monotherapy for the potential treatment of renal cell carcinoma, and was about to enter a phase II combination study for this indication with capecitabine (Hoffmann-La Roche). At this time, the company was also planning a phase II trial to study the drug's potential in the treatment of colorectal cancer [418739]. GTI-2040 has been tested in nine different tumor models, including tumors derived from colon, liver, lung, breast, kidney and ovary. Depending on the tumor model, significant inhibition of tumor growth, disease stabilization and dramatic tumor regressions was observed [347683]. Lorus filed an IND to commence phase I/II trials with GTI-2040 in the US in November 1999 [347683], and received approval for the trials in December 1999 [349623]. As of January 2000, these trials had commenced at the University of Chicago Cancer Research Center; it was reported in February 2000 that dosing to date had been well tolerated with no apparent safety concerns [357449]. Lorus has entered into a strategic supply alliance with Proligo to provide the higher volumes of drug product required for the planned multiple phase II trials [385976]. In February 1998, Genesense (now Lorus) received patent WO-09805769. Loris also received a patent (subsequently identified as WO-00047733) from the USPTO in January 2000, entitled 'Antitumor antisense sequences directed against components of ribonucleotide reductase' covering the design and use of unique antisense anticancer drugs, including GTI-2040 and GTI-2501 [353538]. PMID:11890366

  5. Home Monitoring for Cardiovascular Implantable Electronic Devices: Benefits to Patients and to Their Follow-up Clinic.

    PubMed

    Leahy, Robin A; Davenport, Elizabeth E

    2015-01-01

    Recent technological advances in the management of patients with cardiovascular implantable electronic devices (CIEDs) have expanded clinicians' ability to remotely monitor patients with CIEDs. Remote monitoring, in addition to periodic in-person device evaluation, provides many advantages to patients and clinicians. Aside from the therapeutic and diagnostic benefits of pacemakers, implantable cardioverter-defibrillators, cardiac resynchronization therapy devices, and implantable loop recorders, improvement in clinical outcomes, clinical efficiencies, and patient experience can be realized with the adoption of remote CIED monitoring. These advantages create significant value to both patients and CIED follow-up centers. PMID:26484995

  6. 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;…

  7. Therapeutic recreation treatment time during inpatient rehabilitation

    PubMed Central

    Gassaway, Julie; Dijkers, Marcel; Rider, Cecelia; Edens, Kelly; Cahow, Claire; Joyce, Joan

    2011-01-01

    Objective Following spinal cord injury (SCI), certified therapeutic recreation specialists (CTRSs) work with patients during rehabilitation to re-create leisure lifestyles. Although there is much literature available to describe the benefits of recreation, little has been written about the process of inpatient or outpatient rehabilitation therapeutic recreation (TR) programs or the effectiveness of such programs. To delineate how TR time is used during inpatient rehabilitation for SCI. Methods Six rehabilitation centers enrolled 600 patients with traumatic SCI for an observational study. CTRSs documented time spent on each of a set of specific TR activities during each patient encounter. Patterns of time use are described, for all patients and by neurologic category. Ordinary least-squares stepwise regression models are used to identify patient and injury characteristics predictive of total treatment time (overall and average per week) and time spent in TR activities. Results Ninety-four percent of patients enrolled in the SCIRehab study participated in TR. Patients received a mean total of 17.5 hours of TR; significant differences were seen in the amount of time spent in each activity among and within neurologic groups. The majority (76%) of patients participated in at least one structured therapeutic outing. Patient and injury characteristics explained little of the variation in time spent within activities. Conclusion The large amount of variability seen in TR treatment time within and among injury group categories, which is not explained well by patient and injury characteristics, sets the stage for future analyses to associate treatments with outcomes. PMID:21675356

  8. 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

  9. Oral Therapeutics for Rhinosinusitis with Nasal Polyposis.

    PubMed

    Thomas, Andrew J; Alt, Jeremiah A

    2016-01-01

    Oral therapeutics for chronic rhinosinusitis with nasal polyps (CRSwNP) include oral corticosteroids (OCS), antibiotics, antifungals and anti-leukotrienes. Of these treatments, the strongest evidence exists to support the use of a short course of OCS for treatment of CRSwNP, and OCS are the most consistently recommended oral therapy in practice guidelines. Antibiotics have demonstrated some utility, which appears more likely related to an anti-inflammatory rather than antimicrobial effect. The non-macrolide antibiotics lack sufficient evidence to support their use, though among this class doxycycline has some limited evidence of benefit in CRSwNP. Greater evidence exists for the use of macrolide antibiotics which have shown reduction of subjective and objective measures of CRSwNP severity. A short course of a macrolide should be considered as an option. Oral antifungals are not recommended in the treatment of CRSwNP given disappointing results and known potential adverse effects, except in allergic fungal rhinosinusitis where they may play a role. Leukotriene antagonists have demonstrated some promise in the treatment of CRSwNP, though studies are limited, but should be considered a potentially useful oral therapeutic. The current level of evidence for these oral therapeutic options for CRSwNP is reviewed in this chapter. PMID:27466856

  10. 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.

  11. Therapeutic advances for the tumors associated with neurofibromatosis type 1, type 2, and schwannomatosis.

    PubMed

    Blakeley, Jaishri O; Plotkin, Scott R

    2016-05-01

    Neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2), and schwannomatosis (SWN) are tumor-suppressor syndromes. Each syndrome is an orphan disease; however, the tumors that arise within them represent the most common tumors of the nervous system worldwide. Systematic investigation of the pathways impacted by the loss of function of neurofibromin (encoded byNF1) and merlin (encoded byNF2) have led to therapeutic advances for patients with NF1 and NF2. In the syndrome of SWN, the genetic landscape is more complex, with 2 known causative genes (SMARCB1andLZTR1) accounting for up to 50% of familial SWN patients. The understanding of the molecular underpinnings of these syndromes is developing rapidly and offers more therapeutic options for the patients. In addition, common sporadic cancers harbor somatic alterations inNF1(ie, glioblastoma, breast cancer, melanoma),NF2(ie, meningioma, mesothelioma) andSMARCB1(ie, atypical teratoid/rhabdoid tumors) such that advances in management of syndromic tumors may benefit patients both with and without germline mutations. In this review, we discuss the clinical and genetic features of NF1, NF2 and SWN, the therapeutic advances for the tumors that arise within these syndromes and the interaction between these rare tumor syndromes and the common tumors that share these mutations. PMID:26851632

  12. Hypoxia inducible factor-1 alpha as a therapeutic target in multiple myeloma

    PubMed Central

    Terragna, Carolina; Martello, Marina; Dico, Angela F.; Solaini, Giancarlo; Baracca, Alessandra; Sgarbi, Gianluca; Pasquinelli, Gianandrea; Valente, Sabrina; Zamagni, Elena; Tacchetti, Paola; Martinelli, Giovanni; Cavo, Michele

    2014-01-01

    The increasing importance of hypoxia-inducible factor-1α (HIF-1α) in tumorigenesis raises the possibility that agents which specifically inhibit this transcription factor, would provide significant therapeutic benefit. The constitutive expression of HIF-1α in about 35% of Multiple Myeloma (MM) patients suggests HIF-1α suppression might be part of a therapeutic strategy. Accordingly, we explored the effect of EZN-2968, a small 3rd generation antisense oligonucleotide against HIF-1α, in a panel of MM cell lines and primary patients samples. Here, we demonstrated that EZN-2968 is highly specific for HIF-1α mRNA and that exposure of MM cells to EZN-2968 resulted in an efficient and homogeneous loading of the cells showing a long lasting low HIF-1α protein level. In MM cells, HIF-1α suppression induced a permanent cell cycle arrest by prolonging S-phase through cyclin A modulation and in addition it induced a mild apoptotic cell death. Moreover, HIF-1α suppression caused a metabolic shift that leaded to increased production of ATP by oxidative phosphorylation (i.e. Warburg effect reversion), that was confirmed by the observed mitochondrial membrane potential decrease. These results show that HIF-1α is an important player in MM homeostasis and that its inhibition by small antisense oligonucleotides provides a rationale for novel therapeutic strategy to improving MM treatment. PMID:24732040

  13. Lactic acid bacteria as mucosal delivery vehicles: a realistic therapeutic option.

    PubMed

    Wang, Miao; Gao, Zeqian; Zhang, Yongguang; Pan, Li

    2016-07-01

    Recombinant lactic acid bacteria (LAB), in particular lactococci and lactobacilli, have gained increasing interest as mucosal delivery vehicles in recent years. With the development of mucosal vaccines, studies on LAB expression systems have been mainly focused on the generation of genetic tools for antigen expression in different locations. Recombinant LAB show advantages in a wide range of aspects over other mucosal delivery systems and represent an attractive candidate for the delivery of therapeutic and prophylactic molecules in different applications. Here, we review the recent data on the use of recombinant LAB as mucosal delivery vectors and the associated health benefits, including the prevention and treatment of inflammatory bowel diseases (IBDs), autoimmune disorders, and infections by pathogenic microorganisms from mucosal surfaces. In addition, we discuss the use of LAB as vehicles to deliver DNA directly to eukaryotic cells. Researches from the last 5 years demonstrate that LAB as vectors for mucosal delivery of therapeutic molecules seem to be a realistic therapeutic option both in human and animal diseases. PMID:27154346

  14. CXCL11-Armed oncolytic poxvirus elicits potent antitumor immunity and shows enhanced therapeutic efficacy

    PubMed Central

    Liu, Zuqiang; Ravindranathan, Roshni; Li, Jun; Kalinski, Pawel; Guo, Z. Sheng; Bartlett, David L.

    2016-01-01

    ABSTRACT We have armed a tumor-selective oncolytic vaccinia virus (vvDD) with the chemokine (CK) CXCL11, in order to enhance its ability to attract CXCR3+ antitumor CTLs and possibly NK cells to the tumor microenvironment (TME) and improve its therapeutic efficacy. As expected, vvDD-CXCL11 attracted high numbers of tumor-specific T cells to the TME in a murine AB12 mesothelioma model. Intratumoral virus-directed CXCL11 expression enhanced local numbers of CD8+ CTLs and levels of granzyme B, while reducing expression of several suppressive molecules, TGF-β, COX2, and CCL22 in the TME. Unexpectedly, we observed that vvDD-CXCL11, but not parental vvDD, induced a systemic increase in tumor-specific IFNγ-producing CD8+ T cells in the spleen and other lymph organs, indicating the induction of systemic antitumor immunity. This effect was associated with enhanced therapeutic efficacy and a survival benefit in tumor-bearing mice treated with vvDD-CXCL11, mediated by CD8+ T cells and IFNγ, but not CD4+ T cells. These results demonstrate that intratumoral expression of CXCL11, in addition to promoting local trafficking of T cells and to a lesser extent NK cells, has a novel function as a factor eliciting systemic immunity to cancer-associated antigens. Our data provide a rationale for expressing CXCL11 to enhance the therapeutic efficacy of oncolytic viruses (OVs) and cancer vaccines. PMID:27141352

  15. 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

  16. Low temperature benefits discussed.

    PubMed

    2016-03-01

    At a recent educational workshop event hosted by Advanced Sterilization Products, expert speakers including Authorising Engineers, and delegates, discussed some of their experiences of low temperature sterilisation of 'hi-tech' medical devices, and highlighted the benefits of a process which allows decontamination of instruments and, for example, parts of robotic surgery systems, that cannot be decontaminated using standard methods. Also examined,and reported on here in an article that first appeared in HEJ's sister publication, The Clinical Services Journal, were some of the disadvantages of low temperature sterilisation, the key considerations and options when choosing such a system, and a focus on how the technology's use had benefited a major London-based NHS Trust. PMID:27132304

  17. Harnessing natural ventilation benefits.

    PubMed

    O'Leary, John

    2013-04-01

    Making sure that a healthcare establishment has a good supply of clean fresh air is an important factor in keeping patients, staff, and visitors, free from the negative effects of CO2 and other contaminants. John O'Leary of Trend Controls, a major international supplier of building energy management solutions (BEMS), examines the growing use of natural ventilation, and the health, energy-saving, and financial benefits, that it offers. PMID:23678661

  18. [The nurses involved in therapeutic innovation].

    PubMed

    Cheron, Coralie

    2016-03-01

    Clinical research nurses (CRNs) play an important role within the teams involved in the fight against cancer and in therapeutic innovation. In the dermatology department of the Gustave-Roussy Institute, patients treated for melanoma and taking part in clinical trials are supported along their care pathway by a CRN who, in addition to her clinical expertise, acts as a link between the different players concerned. PMID:26944642

  19. Health benefits of probiotics.

    PubMed

    Goldin, B R

    1998-10-01

    This paper reviews the evidence for the claims of health benefits derived from the use of probiotics. A brief history of probiotics and the types of probiotics currently used and the criteria for the selection of probiotics is discussed. The ability of probiotics to enhance the nutritional content and bioavailability of nutrients and the scientific evidence for the usefulness of probiotics in alleviating the symptoms of lactose intolerance and in enhancing growth development is examined. The remainder of the review focuses on studies of a specific probiotic, Lactobacillus GG which has been extensively investigated for its health benefits in humans and animals. These studies severe as a model for the potential benefits of probiotics. The ability of Lactobacillus GG to treat or prevent diarrhoeal disease, to serve as an adjuvant for vaccines, to prevent rotavirus-induced diarrhoea, to prevent milk-based allergic reactions, alcohol-induced liver disease and colon cancer are presented. The review concludes with a discussion of the data supporting the safety of probiotics. PMID:9924285

  20. 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.

  1. Translating neoadjuvant therapy into survival benefits: one size does not fit all.

    PubMed

    De Mattos-Arruda, Leticia; Shen, Ronglai; Reis-Filho, Jorge S; Cortés, Javier

    2016-09-01

    Neoadjuvant therapy has been established as an effective therapeutic approach for patients with locally advanced breast cancer. Similar outcomes between neoadjuvant and adjuvant chemotherapy have been demonstrated in several trials. Nevertheless, neoadjuvant therapy has some advantages over adjuvant therapy, including tumour downstaging, in vivo assessment of therapeutic efficacy, reduced treatment durations, and the need to enrol fewer patients for clinical trials to reach their preplanned objectives. The number of neoadjuvant trials in patients with breast cancer has increased substantially in the past 5 years, particularly in the context of HER2-positive disease. Substantial improvements in the pathological complete response rate to anti-HER2 therapy, a proposed surrogate end point for long-term clinical benefit, have been observed with neoadjuvant dual-agent HER2 blockade. Thus, it was hypothesized that this approach would provide additional survival benefits over standard-of-care therapy with the anti-HER2 antibody trastuzumab in the adjuvant setting. Emerging data, however, are calling this notion into question. We discuss potential reasons why results of neoadjuvant trials of targeted therapies have not been mirrored in the adjuvant setting, and other than inherent differences in clinical-trial designs and statistical power, we consider how the biology of the disease, patient characteristics, and drug administration and schedule might influence the results. PMID:27000962

  2. 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

  3. Therapeutic proteins: A to Z.

    PubMed

    Ozgur, Aykut; Tutar, Yusuf

    2013-12-01

    In recent years, therapeutic proteins have become an important growing class of drugs in the pharmaceutics industry. The development of recombinant DNA technology has caused to appreciation of therapeutic value of many proteins and peptides in medicine. Currently, approximately 100 therapeutic proteins obtained approval from Food and Drug Administration (FDA) and they are widely used in the treatment of various diseases such as cancer, diabetes, anemia and infections. This paper will summarize the production processes, pharmaceuticals and physicochemical properties and important classes of therapeutic proteins with their potential use in clinical applications. PMID:24261980

  4. 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.

  5. [Hypercholesterolemia: a therapeutic approach].

    PubMed

    Moráis López, A; Lama More, R A; Dalmau Serra, J

    2009-05-01

    High blood cholesterol levels represent an important cardiovascular risk factor. Hypercholesterolemia is defined as levels of total cholesterol and low-density lipoprotein cholesterol above 95th percentile for age and gender. For the paediatric population, selective screening is recommended in children older than 2 years who are overweight, with a family history of early cardiovascular disease or whose parents have high cholesterol levels. Initial therapeutic approach includes diet therapy, appropriate physical activity and healthy lifestyle changes. Drug treatment should be considered in children from the age of 10 who, after having followed appropriate diet recommendations, still have very high LDL-cholesterol levels or moderately high levels with concomitant risk factors. In case of extremely high LDL-cholesterol levels, drug treatment should be taken into consideration at earlier ages (8 years old). Modest response is usually observed with bile acid-binding resins. Statins can be considered first-choice drugs, once evidence on their efficacy and safety has been shown. PMID:19427823

  6. [Liver metastasis: therapeutic strategy].

    PubMed

    Gennari, L; Doci, R; Bignami, P

    1996-01-01

    The liver is one of the most frequent sites of metastatic growth, in particular from digestive malignancies (DM). The first goal is to reduce the incidence of metastases. Adjuvant systemic chemotherapies have been demonstrated to reduce the recurrence rate and to improve survival in Dukes C colon cancer. Fluorouracil is the pivot of adjuvant treatment modulated by Leucovorin or Levamisol. A short postoperative administration of fluorouracil by intraportal route has been tested, but the results are controversial. Adjuvant treatments for different DM are under investigation. When hepatic metastases are clinically evident, therapeutic decisions depend on several factors: site and nature of primary, extent of hepatic and extrahepatic disease, patient characteristics, efficacy of treatments. A staging system should be adopted to allow a rational approach. In selected cases a locoregional treatment can achieve consistent results. Hepatic Intrarterial Chemotherapy (HIAC) for colorectal metastases achieves objective responses in more than 50% of patients. Survival seems positively affected. When feasible, Ro hepatic resection is the most effective treatment, five-year survival rate being about 30% when metastases are from colorectal cancer. Since the liver is the most frequent site of recurrence after resection, repeat resection have been successfully performed. PMID:9214269

  7. 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.

  8. 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

  9. Therapeutic Cancer Vaccines.

    PubMed

    Ye, Zhenlong; Li, Zhong; Jin, Huajun; Qian, Qijun

    2016-01-01

    Cancer is one of the major leading death causes of diseases. Prevention and treatment of cancer is an important way to decrease the incidence of tumorigenesis and prolong patients' lives. Subversive achievements on cancer immunotherapy have recently been paid much attention after many failures in basic and clinical researches. Based on deep analysis of genomics and proteomics of tumor antigens, a variety of cancer vaccines targeting tumor antigens have been tested in preclinical and human clinical trials. Many therapeutic cancer vaccines alone or combination with other conventional treatments for cancer obtained spectacular efficacy, indicating the tremendously potential application in clinic. With the illustration of underlying mechanisms of cancer immune regulation, valid, controllable, and persistent cancer vaccines will play important roles in cancer treatment, survival extension and relapse and cancer prevention. This chapter mainly summarizes the recent progresses and developments on cancer vaccine research and clinical application, thus exploring the existing obstacles in cancer vaccine research and promoting the efficacy of cancer vaccine. PMID:27240458

  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. 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. PMID:24804340

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

    PubMed

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

    2016-08-01

    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

  13. Combined analgesics in (headache) pain therapy: shotgun approach or precise multi-target therapeutics?

    PubMed Central

    2011-01-01

    Background Pain in general and headache in particular are characterized by a change in activity in brain areas involved in pain processing. The therapeutic challenge is to identify drugs with molecular targets that restore the healthy state, resulting in meaningful pain relief or even freedom from pain. Different aspects of pain perception, i.e. sensory and affective components, also explain why there is not just one single target structure for therapeutic approaches to pain. A network of brain areas ("pain matrix") are involved in pain perception and pain control. This diversification of the pain system explains why a wide range of molecularly different substances can be used in the treatment of different pain states and why in recent years more and more studies have described a superior efficacy of a precise multi-target combination therapy compared to therapy with monotherapeutics. Discussion In this article, we discuss the available literature on the effects of several fixed-dose combinations in the treatment of headaches and discuss the evidence in support of the role of combination therapy in the pharmacotherapy of pain, particularly of headaches. The scientific rationale behind multi-target combinations is the therapeutic benefit that could not be achieved by the individual constituents and that the single substances of the combinations act together additively or even multiplicatively and cooperate to achieve a completeness of the desired therapeutic effect. As an example the fixesd-dose combination of acetylsalicylic acid (ASA), paracetamol (acetaminophen) and caffeine is reviewed in detail. The major advantage of using such a fixed combination is that the active ingredients act on different but distinct molecular targets and thus are able to act on more signalling cascades involved in pain than most single analgesics without adding more side effects to the therapy. Summary Multitarget therapeutics like combined analgesics broaden the array of therapeutic

  14. 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

  15. 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. PMID:22770604

  16. 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. PMID:25521618

  17. Emerging Mitochondrial Therapeutic Targets in Optic Neuropathies.

    PubMed

    Lopez Sanchez, M I G; Crowston, J G; Mackey, D A; Trounce, I A

    2016-09-01

    Optic neuropathies are an important cause of blindness worldwide. The study of the most common inherited mitochondrial optic neuropathies, Leber hereditary optic neuropathy (LHON) and autosomal dominant optic atrophy (ADOA) has highlighted a fundamental role for mitochondrial function in the survival of the affected neuron-the retinal ganglion cell. A picture is now emerging that links mitochondrial dysfunction to optic nerve disease and other neurodegenerative processes. Insights gained from the peculiar susceptibility of retinal ganglion cells to mitochondrial dysfunction are likely to inform therapeutic development for glaucoma and other common neurodegenerative diseases of aging. Despite it being a fast-evolving field of research, a lack of access to human ocular tissues and limited animal models of mitochondrial disease have prevented direct retinal ganglion cell experimentation and delayed the development of efficient therapeutic strategies to prevent vision loss. Currently, there are no approved treatments for mitochondrial disease, including optic neuropathies caused by primary or secondary mitochondrial dysfunction. Recent advances in eye research have provided important insights into the molecular mechanisms that mediate pathogenesis, and new therapeutic strategies including gene correction approaches are currently being investigated. Here, we review the general principles of mitochondrial biology relevant to retinal ganglion cell function and provide an overview of the major optic neuropathies with mitochondrial involvement, LHON and ADOA, whilst highlighting the emerging link between mitochondrial dysfunction and glaucoma. The pharmacological strategies currently being trialed to improve mitochondrial dysfunction in these optic neuropathies are discussed in addition to emerging therapeutic approaches to preserve retinal ganglion cell function. PMID:27288727

  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. 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

  20. 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

  1. SCI: Present and Future Therapeutic Devices and Prostheses

    PubMed Central

    Giszter, Simon F.

    2008-01-01

    Summary A range of passive and active devices are under development, or are already in clinical use, to partially restore function after SCI (SCI). Prosthetic devices to promote host tissue regeneration and plasticity and reconnection are under development, comprising bioengineered bridging materials free of cells. Alternatively, artificial electrical stimulation and robotic bridges may be used, upon which we focus here. A range of neuroprostheses interfacing either with CNS or PNS both above and below the lesion are under investigation and are at different stages of development or translation to the clinic. In addition, there are orthotic and robotic devices which are being developed and tested in laboratory and clinic that can provide mechanical assistance, training or substitution after SCI. The range of different approaches employed draw on many different aspects of our current but limited understanding of neural regeneration and plasticity, and spinal cord function and interactions with cortex. The best therapeutic practice will ultimately likely depend on combinations of these approaches and technologies and on balancing the combined effects of these on the biological mechanisms and their interactions after injury. An increased understanding of plasticity of brain and spinal cord, and of the behavior of innate modular mechanisms in intact and injured systems, will likely assist future developments. We review the range of device designs under development and in use, the basic understanding of spinal cord organization and plasticity, the problems and design issues in device interactions with the nervous system, and the possible benefits of active motor devices. PMID:18164494

  2. Risk Factors and Therapeutic Targets in Pancreatic Cancer

    PubMed Central

    Wörmann, Sonja Maria; Algül, Hana

    2013-01-01

    Pancreatic cancer (PC) is one of the most challenging tumor entities worldwide, characterized as a highly aggressive disease with dismal overall prognosis and an incidence rate equalling mortality rate. Over the last decade, substantial progress has been made to define the morphological changes and key genetic events in pancreatic carcinogenesis. And yet, it is still unclear what factors trigger PC. Some risk factors appear to be associated with sex, age, race/ethnicity, or other rare genetic conditions. Additionally, modifying factors such as smoking, obesity, diabetes, occupational risk factors, etc., increase the potential for acquiring genetic mutations that may result in PC. Another hallmark of PC is its poor response to radio- and chemo-therapy. Current chemotherapeutic regimens could not provide substantial survival benefit with a clear increase in overall survival. Recently, several new approaches to significantly improve the clinical outcome of PC have been described involving downstream signaling cascades desmoplasia and stromal response as well as tumor microenvironment, immune response, vasculature, and angiogenesis. This review summarizes major risk factors for PC and tries to illuminate relevant targets considerable for new therapeutic approaches. PMID:24303367

  3. The Vegetative State and Stem Cells: Therapeutic Considerations.

    PubMed

    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

  4. 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. PMID:25649017

  5. 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

  6. 7 CFR 783.8 - Multiple benefits.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... loans or payments resulting from purchase of the additional coverage insurance, as defined in 7 CFR 400... SPECIAL PROGRAMS TREE ASSISTANCE PROGRAM § 783.8 Multiple benefits. Persons may not receive or retain payments for production losses from trees, vines and bushes under this part if they have been...

  7. Alzheimer's disease & metals: therapeutic opportunities

    PubMed Central

    Kenche, Vijaya B; Barnham, Kevin J

    2011-01-01

    Alzheimer's disease (AD) is the most common age related neurodegenerative disease. Currently, there are no disease modifying drugs, existing therapies only offer short-term symptomatic relief. Two of the pathognomonic indicators of AD are the presence of extracellular protein aggregates consisting primarily of the Aβ peptide and oxidative stress. Both of these phenomena can potentially be explained by the interactions of Aβ with metal ions. In addition, metal ions play a pivotal role in synaptic function and their homeostasis is tightly regulated. A breakdown in this metal homeostasis and the generation of toxic Aβ oligomers are likely to be responsible for the synaptic dysfunction associated with AD. Therefore, approaches that are designed to prevent Aβ metal interactions, inhibiting the formation of toxic Aβ species as well as restoring metal homeostasis may have potential as disease modifying strategies for treating AD. This review summarizes the physiological and pathological interactions that metal ions play in synaptic function with particular emphasis placed on interactions with Aβ. A variety of therapeutic strategies designed to address these pathological processes are also described. The most advanced of these strategies is the so-called ‘metal protein attenuating compound’ approach, with the lead molecule PBT2 having successfully completed early phase clinical trials. The success of these various strategies suggests that manipulating metal ion interactions offers multiple opportunities to develop disease modifying therapies for AD. PMID:21232050

  8. Pharmacy benefit management companies.

    PubMed

    Taniguchi, R

    1995-09-01

    The principal services offered by pharmacy benefit management companies (PBMs) are described. A PBM contracts with employers, insurers, and others to provide accessible and cost-effective benefits to those groups' members. PBMs vary in their organization and services because they originate from different types of businesses. Many PBMs have been formed by publicly traded companies that have combined traditional ways of controlling cost and use, such as formularies, with new elements to form organizations whose primary function is managing the pharmacy benefit. Often, the PBM is paid a fixed amount for which it must provide all contracted services. PBMs may provide pharmacy services themselves (e.g., mail order prescription service is offered by Medco, one of the largest PBMs); more often, they subcontract with others to provide certain services. Full-service PBMs have the following functions: establishing networks of pharmacies for use by plan members; processing claims electronically at the time a prescription is filled and thus maintaining a database on drug use and cost; using these data to generate various reports; encouraging the use of generic products; managing existing formularies, helping to establish customized formularies, or providing a national formulary; providing information to support formulary guidelines (counter-detailing); offering programs in which prescriptions for maintenance medications are filled less frequently with larger amounts, often by mail order; negotiating volume-based rebates from manufacturers; performing drug-use review; developing disease management programs based on clinical practice guidelines and measurements of patient outcome; and evaluating outcomes by combining data on drug therapy with information about other parts of the patient's care.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8528857

  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. 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

  11. 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…

  12. Bacteriophage Procurement for Therapeutic Purposes.

    PubMed

    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

  13. 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

  14. Therapeutic cloning: promises and issues

    PubMed Central

    Kfoury, Charlotte

    2007-01-01

    Advances in biotechnology necessitate both an understanding of scientific principles and ethical implications to be clinically applicable in medicine. In this regard, therapeutic cloning offers significant potential in regenerative medicine by circumventing immunorejection, and in the cure of genetic disorders when used in conjunction with gene therapy. Therapeutic cloning in the context of cell replacement therapy holds a huge potential for de novo organogenesis and the permanent treatment of Parkinson’s disease, Duchenne muscular dystrophy, and diabetes mellitus as shown by in vivo studies. Scientific roadblocks impeding advancement in therapeutic cloning are tumorigenicity, epigenetic reprogramming, mitochondrial heteroplasmy, interspecies pathogen transfer, low oocyte availability. Therapeutic cloning is also often tied to ethical considerations concerning the source, destruction and moral status of IVF embryos based on the argument of potential. Legislative and funding issues are also addressed. Future considerations would include a distinction between therapeutic and reproductive cloning in legislative formulations. PMID:18523539

  15. 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. PMID:20930555

  16. Validation of the patient benefit index for the assessment of patient-relevant benefit in the treatment of psoriasis.

    PubMed

    Feuerhahn, Julia; Blome, Christine; Radtke, Marc; Augustin, Matthias

    2012-08-01

    Empirical evidence of the efficacy of drugs and therapeutic procedures becomes more important in industrial countries. The assessment of patient benefit from the patient's perspective is of particular relevance. The Patient Benefit Index (PBI) for skin diseases is a validated instrument to assess patient-relevant benefit in patients with skin diseases. So far, no instrument for the assessment of patient-relevant needs and benefits in patients with psoriasis has been published. Objective of the study was the validation of an instrument to assess patient benefit in psoriasis treatment. Patient-relevant treatment needs and benefits in psoriasis patients were recorded with the PBI questionnaire in two studies conducted in 2007. Treatment goals and benefits were used to calculate an importance-weighted PBI. Data of n = 2,009 patients in the cross-sectional study and n = 93 patients in the longitudinal study were used to test validity, feasibility and reliability of the PBI. The PBI was feasible with a rate of missing values ≤1.5 % in PNQ and ≤2.0 % in PBQ. The subscales of the PBI were internally consistent (Cronbach's alpha = 0.68-0.87). The PBI showed convergent validity regarding the quality of life, psoriasis area and severity index, and two single questions on treatment benefit used in the longitudinal study. The PBI is a suitable instrument for the assessment of patient-reported benefit in the treatment of psoriasis. PMID:22722916

  17. Patients with borderline personality disorder who are chronically suicidal: therapeutic alliance and therapeutic limits.

    PubMed

    Jimenez, Xavier F

    2013-01-01

    Therapeutic work with patients who are chronically suicidal and have borderline personality disorder (BPD) is challenging, and clinicians often resort to setting firm limits or excessively cautious interventions in efforts to prevent manipulation, regression, or over-dependence. Litigation and malpractice fears reinforce these stances, and reduced compensation for additional time and energy devoted to patients adds further disincentives to sole providers. However, elements of the working alliance and therapeutic limits are within the therapist's control. A case vignette illustrates an individual therapist's modification of usual therapeutic limits while working with a chronically suicidal patient with BPD within a dialectical behavior therapy (DBT) framework over a 16-week period. Discussions regarding the case, interventions used, DBT, and legality concerns follow. PMID:23909059

  18. Developing a competitive benefits program.

    PubMed

    Hills, Laura Sachs

    2005-01-01

    Offering your employees the right fringe benefits can help staff morale soar, foster loyalty, and increase the chances that a top-notch job applicant will say yes to your job offer. This article suggests practical ways to offer a competitive benefits program without breaking the bank. It includes guidance about specific benefits and suggests a dozen more extra benefits employees value and a sample cafeteria-style fringe benefits plan. Finally, the article includes guidelines about creating and using your own benefits statement with your staff; along with a model statement form you can use or adapt to your needs. PMID:15779518

  19. Direct therapeutic intervention for advanced pancreatic cancer

    PubMed Central

    Takakura, Kazuki; Koido, Shigeo

    2015-01-01

    Currently, chemotherapy is an accredited, standard treatment for unresectable, advanced pancreatic cancer (PC). However, it has been still showed treatment-resistance and followed dismal prognosis in many cases. Therefore, some sort of new, additional treatments are needed for the better therapeutic results for advanced PC. According to the previous reports, it is obvious that interventional endoscopic ultrasonography (EUS) is a well-established, helpful and low-risky procedure in general. As the additional treatments of the conventional therapy for advanced PC, many therapeutic strategies, such as immunotherapies, molecular biological therapies, physiochemical therapies, radioactive therapies, using siRNA, using autophagy have been developing in recent years. Moreover, the efficacy of the other potential therapeutic targets for PC using EUS-fine needle injection, for example, intra-tumoral chemotherapeutic agents (paclitaxel, irinotecan), several ablative energies (radiofrequency ablation and cryothermal treatment, neodymium-doped yttrium aluminum garnet laser, high-intensity focused ultrasound), etc., has already been showed in animal models. Delivering these promising treatments reliably inside tumor, interventional EUS may probably be indispensable existence for the treatment of locally advanced PC in near future. PMID:26677434

  20. Direct therapeutic intervention for advanced pancreatic cancer.

    PubMed

    Takakura, Kazuki; Koido, Shigeo

    2015-12-10

    Currently, chemotherapy is an accredited, standard treatment for unresectable, advanced pancreatic cancer (PC). However, it has been still showed treatment-resistance and followed dismal prognosis in many cases. Therefore, some sort of new, additional treatments are needed for the better therapeutic results for advanced PC. According to the previous reports, it is obvious that interventional endoscopic ultrasonography (EUS) is a well-established, helpful and low-risky procedure in general. As the additional treatments of the conventional therapy for advanced PC, many therapeutic strategies, such as immunotherapies, molecular biological therapies, physiochemical therapies, radioactive therapies, using siRNA, using autophagy have been developing in recent years. Moreover, the efficacy of the other potential therapeutic targets for PC using EUS-fine needle injection, for example, intra-tumoral chemotherapeutic agents (paclitaxel, irinotecan), several ablative energies (radiofrequency ablation and cryothermal treatment, neodymium-doped yttrium aluminum garnet laser, high-intensity focused ultrasound), etc., has already been showed in animal models. Delivering these promising treatments reliably inside tumor, interventional EUS may probably be indispensable existence for the treatment of locally advanced PC in near future. PMID:26677434

  1. Cost Benefit Model Development. Cost Benefit Study. Final Report.

    ERIC Educational Resources Information Center

    Marson, Arthur A.; And Others

    Through an analysis of the economic costs and benefits of five vocational-technical programs, it was shown that the benefits of a vocational-technical education outweigh the costs. Four programs showing greater benefits than costs were auto body (courses at two technical institutes), materials management, and electronic servicing. Clothing…

  2. 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…

  3. 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,…

  4. 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,…

  5. Therapeutic postprostatectomy irradiation.

    PubMed

    Youssef, Emad; Forman, Jeffrey D; Tekyi-Mensah, Samuel; Bolton, Susan; Hart, Kim

    2002-06-01

    involvement, pathological stage, surgical margin, and perineural invasion. Upon multivariate analysis, only preradiation therapy PSA (P < 0.001) and the PSA trend during radiation therapy (P < 0.001) were significant factors. The results of therapeutic radiation for patients with elevated postprostatectomy PSA levels are sufficiently poor; other strategies should be explored as alternatives, including early adjuvant postprostatectomy irradiation or the use of combined hormonal and radiation therapy in the salvage situation. PMID:15046710

  6. Therapeutic antibodies in ophthalmology

    PubMed Central

    Magdelaine-Beuzelin, Charlotte; Pinault, Coralie; Paintaud, Gilles

    2010-01-01

    More than a century after the first successful use of serotherapy, antibody-based therapy has been renewed by the availability of recombinant monoclonal antibodies. As in the past, current clinical experience has prompted new pharmacological questions and induced much debate among practitioners, notably in the field of ophthalmology. An examination of the history of antibodies as treatments for ocular disorders reveals interesting parallels to the modern era. The fact that a treatment administered by a systemic route could be efficacious in a local disease was not widely accepted and the “chemical” nature of antibodies was not clearly understood in the late 19th century. Clinical studies by Henry Coppez, a Belgian ophthalmologist, established in 1894 that antidiphtheric antitoxins could be used to treat conjunctival diphtheria. Nearly 20 years later, Coppez and Danis described age-related macular degeneration, a disorder which today benefits from ranibizumab therapy. The product, a locally-administered recombinant monoclonal Fab fragment, is directed against vascular endothelial growth factor A. Interestingly, its full-size counterpart, bevacizumab, which is approved for the treatment of solid tumors, has also demonstrated efficacy in age-related macular degeneration when administered either intravenously or locally, which raises new questions about antibody pharmacology and biodistribution. In order to shed some light on this debate, we recount the early history of serotherapy applied to ophthalmology, review the exact molecular differences between ranibizumab and bevacizumab, and discuss what is known about IgG and the blood-retina barrier and the possible role of FcRn, an IgG transporter. PMID:21358858

  7. 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

  8. Questions and answers on employee benefit issues.

    PubMed

    1994-06-01

    This Issue Brief addresses 19 topics in the areas of pensions, health insurance, and other benefits. In addition to the topics listed below, the report includes data on the prevalence of benefits, tax incentives associated with benefits, lump-sum distributions, number of private pension plans, pension coverage rates, 401(k) plans, employer spending on group health insurance, self-insured health plans, employer initiatives to reduce health care costs, and employers' response to the retiree health benefits accounting rule, and flexible benefits plans. In 1992, U.S. employers (public and private) spent $629 billion for noncash benefits, representing nearly 18 percent of total compensation, excluding paid time off. In 1992, 71 percent of the 50.1 million individuals aged 55 and over received retirement benefits, including distributions from private and public pensions, annuities, individual retirement accounts, Keoghs, 401(k)s, and Social Security. Among the 76 percent of all private pension plan participants who participated in a single plan, 30 percent named a defined benefit plan as their pension plan type, 58 percent named a defined contribution plan as their pension plan type, and 12 percent did not know their plan type. Private and public pension funds held more than $4.6 trillion in assets at the end of 1993. The 1993 year-end assets are more than triple the asset level of 1983 (nominal terms). According to the Congressional Budget Office, U.S. expenditures on health care were expected to have reached $898 billion in 1993, up from $751.8 billion in 1991, an increase of 19.4 percent in nominal terms. PMID:10134782

  9. Benefits of Metformin Use for Cholangiocarcinoma.

    PubMed

    Kaewpitoon, Soraya J; Loyd, Ryan A; Rujirakul, Ratana; Panpimanmas, Sukij; Matrakool, Likit; Tongtawee, Taweesak; Kootanavanichpong, Nusorn; Kompor, Ponthip; Chavengkun, Wasugree; Kujapun, Jirawoot; Norkaew, Jun; Ponphimai, Sukanya; Padchasuwan, Natnapa; Pholsripradit, Poowadol; Eksanti, Thawatchai; Phatisena, Tanida; Kaewpitoon, Natthawut

    2015-01-01

    Metformin is an oral anti-hyperglycemic agent, which is the most commonly prescribed medication in the treatment of type-2 diabetes mellitus. It is purportedly associated with a reduced risk for various cancers, mainly exerting anti-proliferation effects on various human cancer cell types, such as pancreas, prostate, breast, stomach and liver. This mini-review highlights the risk and benefit of metformin used for cholangiocarcinoma (CCA) prevention and therapy. The results indicated metformin might be a quite promising strategy CCA prevention and treatment, one mechanism being inhibition of CCA tumor growth by cell cycle arrest in both in vitro and in vivo. The AMPK/mTORC1 pathway in intrahepatic CCA cells is targeted by metformin. Furthermore, metformin inhibited CCA tumor growth via the regulation of Drosha-mediated expression of multiple carcinogenic miRNAs. The use of metformin seems to be safe in patients with cirrhosis, and provides a survival benefit. Once hepatic malignancies are already established, metformin does not offer any therapeutic potential. Clinical trials and epidemiological studies of the benefit of metformin use for CCA should be conducted. To date, whether metformin as a prospective chemotherapeutic for CCA is still questionable and waits further atttention. PMID:26745042

  10. Therapeutic failure in familial type II hyperlipoproteinemia.

    PubMed

    Witters, L A; Herbert, P N; Shulman, R S; Krauss, R M; Levy, R I

    1976-09-01

    The extended use of diet and cholestyramine therapy in familial type II hyperlipoproteinemia was examined in patients who previously participated in a short-term, double-blind trial. A striking secondary failure in therapeutic response during 4 yr of use of this therapy was noted with plasma cholesterol rising an average of 15%. A 3 mo, out-patient, follow-up study designed to reinforce patient motivation and dietary and drug adherence resulted in a prompt but partial reversal of this therapeutic deterioration in 16 patients. Additional inpatient studies confirmed that patient noncompliance with the dietary regimen was the major factor responsible for the secondary failure. Cholestyramine together with a low cholesterol diet can be an effective agent in familial type II hyperlipoproteinemia, given a comprehensive program of out-patient follow-up with continued emphasis on dietary principles and drug adherence. PMID:183084

  11. 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.

  12. 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. PMID:17606914

  13. 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

  14. Hurricanes benefit bleached corals

    PubMed Central

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

    2007-01-01

    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. PMID:17606914

  15. 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.

  16. Therapeutic Approach of Nanotechnology for Oxidative Stress Induced Ocular Neurodegenerative Diseases.

    PubMed

    Mitra, Rajendra N; Conley, Shannon M; Naash, Muna I

    2016-01-01

    Oxidative stress plays a role in many different forms of neurodegenerative ocular disease. The imbalance between the generation of endogenous reactive oxygen species (ROS) and their corresponding neutralization by endogenous antioxidant defense systems leads to cellular oxidative stress, oxidation of different bio-macromolecules, and eventually retinal disease. As a result, the administration of supplemental endogenous antioxidant materials or exogenous ROS scavengers is an interesting therapeutic approach for the treatment of forms of ocular disease associated with oxidative stress. Thus far, different dietary antioxidant supplements have been proven to be clinically reliable and effective, and different antioxidant gene therapy approaches are under investigation. In addition, various metal oxide nanoparticles were shown to be effective in defending against oxidative stress-associated injury. These benefits are due to free radical scavenging properties of the materials arising from non-stoichiometric crystal defects and oxygen deficiencies. Here we discuss the application of this approach to the protection of the retina. PMID:26427447

  17. 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. PMID:27031164

  18. Prognostic and Therapeutic Implications of Frailty in Older Adults with Heart Failure.

    PubMed

    Goldfarb, Michael; Sheppard, Richard; Afilalo, Jonathan

    2015-11-01

    Frailty is increasingly recognized in older adults with cardiovascular disease, particularly in those with heart failure (HF). A growing body of evidence has shown that frailty has a negative effect on survival, hospitalizations, disability, and quality of life. Beyond frailty, additional domains captured by a comprehensive geriatric assessment contribute incremental value in predicting outcomes and identifying treatment targets. Exercise training is ideally suited to this setting as it can concomitantly improve physical frailty and HF symptoms. Multidisciplinary disease management programs offer a number of benefits for frail HF patients; invasive procedures carry a higher risk of morbidity than in non-frail counterparts, and evidence-based drugs and devices have an uncertain value and warrant further research. While more data accrues, difficult therapeutic decisions should be individualized using a shared patient-centered decision making approach. PMID:26346250

  19. 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

  20. 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.

  1. [Benign thyroid nodules: diagnostic and therapeutic approach].

    PubMed

    Durante, Cosimo; Cava, Francesco; Paciaroni, Alessandra; Filetti, Sebastiano

    2008-05-01

    In the last years an increase in thyroid nodules detection has been reported from several epidemiological studies. This trend is largely due to the routine use of diagnostic sonography procedures in clinical practice. Thyroid nodules, both palpable or not palpable, rarely turn out to be malignant. Fine-needle aspiration cytology (FNAc) plays a central role in establishing the nature of the nodule. Excluded the presence of malignant lesions, which are generally treated with surgery, physicians are faced with a variety of therapeutic options, and choosing the optimal approach can be a difficult task. These include a periodic follow-up alone without treatment, the iodine supplementation, the thyroid-hormone suppressive therapy, the radioiodine administration, the percutaneous ethanol injections, and the new technique of laser photocoagulation. In all cases, decisions on the management of benign thyroid nodules should always be based on clinical target and a careful analysis of benefits and risks to the patient. PMID:18581970

  2. 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. PMID:18991725

  3. 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; Hernandez Rodriguez, Juventino; 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. (PsycINFO Database Record PMID:26349073

  4. 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…

  5. Societal benefits of space technology

    NASA Astrophysics Data System (ADS)

    Karnik, Kiran

    The introduction of any new technology inevitably leads to a number of benefits. Space technology has provided such benefits in fair abundance, and in a number of fields. In assessing benefits, however, it is necessary to differentiate between individual or corporate/commercial benefits and social benefits, since the two may not always by synonymous. This paper aims to examine the benefits derived through applications of space technology from this point of view. It takes India as a case-study and describes the benefits that have accrued from the use of space technology, beginning with the Indo-U.S. Satellite Instructional Television Experiment (SITE, 1975-1976). It discusses the various gains from the on-going, operational multi-purpose INSAT system, and examines in-depth the issues like: what are the benefits, who benefits (i.e. which section of society) and how much. While the paper focuses mainly on the areas of broadcasting and telecommunications, it also touches on benefits from remote sensing and meteorology. It covers, in particular, the benefits expected to be derived from the Indian Remote Sensing satellites (IRS), the first of which was launched in March 1988. In the final section, the paper seeks to analyse the Indian experience from the view point of a more generalized perspective: the use of space technology in a developing country environment. Based on this, it draws certain conclusions about the benefits from space technology that may be generally applicable to most developing countries.

  6. Therapeutic Targeting of Mitochondrial Superoxide in Hypertension

    PubMed Central

    Dikalova, Anna E.; Bikineyeva, Alfiya T.; Budzyn, Klaudia; Nazarewicz, Rafal R.; McCann, Louise; Lewis, William; Harrison, David G.; Dikalov, Sergey I.

    2010-01-01

    Rationale: Superoxide (O2∸) has been implicated in the pathogenesis of many human diseases including hypertension, however commonly employed antioxidants have proven ineffective in clinical trials. It is possible that these agents are not adequately delivered to the subcellular sites of superoxide production. Objective: Because the mitochondria are important sources of reactive oxygen species, we postulated that mitochondrial targeting of superoxide scavenging would have therapeutic benefit. Methods and Results: In this study, we found that the hormone angiotensin II increased endothelial mitochondrial superoxide production. Treatment with the mitochondrial targeted antioxidant mitoTEMPO decreased mitochondrial O2∸, inhibited the total cellular O2∸, reduced cellular NADPH oxidase activity and restored the level of bioavailable NO. These effects were mimicked by overexpressing the mitochondrial MnSOD (SOD2), while SOD2 depletion with siRNA increased both basal and angiotensin II-stimulated cellular O2∸. Treatment of mice in vivo with mitoTEMPO attenuated hypertension when given at the onset of angiotensin II infusion and decreased blood pressure by 30 mm Hg following establishment of both angiotensin II-induced and DOCA-salt hypertension, while a similar dose of non-targeted TEMPOL was not effective. In vivo, mitoTEMPO decreased vascular O2∸, increased vascular NO• production and improved endothelial-dependent relaxation. Interestingly, transgenic mice overexpressing mitochondrial SOD2 demonstrated attenuated angiotensin II-induced hypertension and vascular oxidative stress similar to mice treated with mitoTEMPO. Conclusions: These studies show that mitochondrial O2∸ is important for the development of hypertension and that antioxidant strategies specifically targeting this organelle could have therapeutic benefit in this and possibly other diseases. PMID:20448215

  7. Recent Progress in Nanomedicine: Therapeutic, Diagnostic and Theranostic Applications

    PubMed Central

    Rizzo, Larissa Y.; Theek, Benjamin; Storm, Gert; Kiessling, Fabian; Lammers, Twan

    2013-01-01

    In recent years, the use of nanomedicine formulations for therapeutic and diagnostic applications has increased exponentially. Many different systems and strategies have been developed for drug targeting to pathological sites, as well as for visualizing and quantifying important (patho-) physiological processes. In addition, ever more efforts have been undertaken to combine diagnostic and therapeutic properties within a single nanomedicine formulation. These so-called nanotheranostics are able to provide valuable information on drug delivery, drug release and drug efficacy, and they are considered to be highly useful for personalizing nanomedicine-based (chemo-) therapeutic interventions. PMID:23578464

  8. [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. PMID:24772784

  9. 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.

  10. The news advances on Alzheimer's disease's therapeutics.

    PubMed

    Sun, H-Q; Zhang, X; Huang, W-J; Chen, W-W

    2016-05-01

    Alzheimer's disease (AD) is a multifaceted disorder, characterized by the failure of memory and dementia. AD affects mostly elder above 65 years of age and is confirmed by post-mortem detection in the brain, of extracellular senile plaques of amyloid-beta (Aβ) and intracellular neurofibrillary tangles. These pathological hallmarks appear in the brain when the disease is already installed. The difficulty of earlier diagnosis and possibly, the poor understanding of the disease etiology, limit the benefits afforded by available treatments. Indeed, several putative drugs resulting from thorough investigations in preclinical studies have failed to produce clinical results, suggesting the development of further therapeutic alternatives. Recently, the regular practice of physical activity has been shown as one of the effective preventive or curative mean against AD. This finding rekindles the debate on the place of the intrinsic vascular component in the AD pathogenesis which is an aspect of the disease often considered as a distinct pathology. A new integrative conception of the disease may offer an advantage to current therapies which may gain in potency if combined in a multi-target manner to yield true improvements. This review will revisit the pathophysiology of AD and discuss the advanced therapeutics currently in use. PMID:27212186

  11. Therapeutic Bronchoscopy for Malignant Central Airway Obstruction

    PubMed Central

    Ernst, Armin; Grosu, Horiana B.; Lei, Xiudong; Diaz-Mendoza, Javier; Slade, Mark; Gildea, Thomas R.; Machuzak, Michael S.; Jimenez, Carlos A.; Toth, Jennifer; Kovitz, Kevin L.; Ray, Cynthia; Greenhill, Sara; Casal, Roberto F.; Almeida, Francisco A.; Wahidi, Momen M.; Eapen, George A.; Feller-Kopman, David; Morice, Rodolfo C.; Benzaquen, Sadia; Tremblay, Alain; Simoff, Michael; Kovitz, Kevin; Greenhill, Sara; Gildea, Thomas R.; Machuzak, Michael; Almeida, Francisco A.; Cicenia, Joseph; Wahidi, Momen; Mahmood, Kamran; MacEachern, Paul; Tremblay, Alain; Simoff, Michael; Diaz-Mendoza, Javier; Ray, Cynthia; Feller-Kopman, David; Yarmus, Lonny; Estrada-Y-Martin, Rosa; Casal, Roberto F.; Toth, Jennifer; Karunakara, Raj; Slade, Mark; Ernst, Armin; Rafeq, Samaan; Ost, David; Eapen, George A.; Jimenez, Carlos A.; Morice, Rodolfo C.; Benzaquen, Sadia; Puchalski, Jonathan

    2015-01-01

    BACKGROUND: There is significant variation between physicians in terms of how they perform therapeutic bronchoscopy, but there are few data on whether these differences impact effectiveness. METHODS: This was a multicenter registry study of patients undergoing therapeutic bronchoscopy for malignant central airway obstruction. The primary outcome was technical success, defined as reopening the airway lumen to > 50% of normal. Secondary outcomes were dyspnea as measured by the Borg score and health-related quality of life (HRQOL) as measured by the SF-6D. RESULTS: Fifteen centers performed 1,115 procedures on 947 patients. Technical success was achieved in 93% of procedures. Center success rates ranged from 90% to 98% (P = .02). Endobronchial obstruction and stent placement were associated with success, whereas American Society of Anesthesiology (ASA) score > 3, renal failure, primary lung cancer, left mainstem disease, and tracheoesophageal fistula were associated with failure. Clinically significant improvements in dyspnea occurred in 90 of 187 patients measured (48%). Greater baseline dyspnea was associated with greater improvements in dyspnea, whereas smoking, having multiple cancers, and lobar obstruction were associated with smaller improvements. Clinically significant improvements in HRQOL occurred in 76 of 183 patients measured (42%). Greater baseline dyspnea was associated with greater improvements in HRQOL, and lobar obstruction was associated with smaller improvements. CONCLUSIONS: Technical success rates were high overall, with the highest success rates associated with stent placement and endobronchial obstruction. Therapeutic bronchoscopy should not be withheld from patients based solely on an assessment of risk, since patients with the most dyspnea and lowest functional status benefitted the most. PMID:25358019

  12. 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. PMID:870694

  13. Molecular testing to optimize therapeutic decision making in advanced colorectal cancer

    PubMed Central

    Kim, Edward J.

    2016-01-01

    Colorectal cancer (CRC) is a leading cause of cancer death in the United States. In recent years, therapeutic advances have prolonged the survival of patients with advanced disease. Along with the addition of new treatments, an increasing body of literature explores the potential benefit of using molecular testing to define tumor, circulating, or host biomarkers of benefit to specific treatment strategies. At present, testing for specific mutations in exons 2, 3, and 4 of KRAS and NRAS has become accepted practice to select patients for treatment with epidermal growth factor receptor (EGFR)-targeted agents. Additionally, testing for the BRAF V600E mutation is used to refine decisions based on patient prognosis. The presence of the uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) *28 polymorphism is associated with toxicity from irinotecan, although it has not been universally applied. Nonetheless, molecular markers to predict response and toxicity of cytotoxic therapy are evolving. While the development of selection biomarkers for anti-angiogenic treatments has not proved fruitful to date, improved development strategies and novel targeted agents are anticipated to revolutionize the approach to treatment of advanced CRC in the near future. This review summarizes currently available data to select treatment strategies in patients with advanced CRC. PMID:27034809

  14. Molecular testing to optimize therapeutic decision making in advanced colorectal cancer.

    PubMed

    Semrad, Thomas J; Kim, Edward J

    2016-04-01

    Colorectal cancer (CRC) is a leading cause of cancer death in the United States. In recent years, therapeutic advances have prolonged the survival of patients with advanced disease. Along with the addition of new treatments, an increasing body of literature explores the potential benefit of using molecular testing to define tumor, circulating, or host biomarkers of benefit to specific treatment strategies. At present, testing for specific mutations in exons 2, 3, and 4 of KRAS and NRAS has become accepted practice to select patients for treatment with epidermal growth factor receptor (EGFR)-targeted agents. Additionally, testing for the BRAF V600E mutation is used to refine decisions based on patient prognosis. The presence of the uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) *28 polymorphism is associated with toxicity from irinotecan, although it has not been universally applied. Nonetheless, molecular markers to predict response and toxicity of cytotoxic therapy are evolving. While the development of selection biomarkers for anti-angiogenic treatments has not proved fruitful to date, improved development strategies and novel targeted agents are anticipated to revolutionize the approach to treatment of advanced CRC in the near future. This review summarizes currently available data to select treatment strategies in patients with advanced CRC. PMID:27034809

  15. [Idiopathic calcium nephrolithiasis: therapeutic aspects].

    PubMed

    Jaeger, P; Portmann, L; Burckhardt, P

    1983-11-26

    The 75% of the renal stone formers have a so-called idiopathic calcium urolithiasis. The majority of these patients, however, do have a detectable biochemical disorder such as hypercalciuria, hyperuricosuria or hyperoxaluria. A high fluid intake unequivocally represents the first step in the therapeutic approach to these patients. Nevertheless, the detection of any type of biochemical disturbance is of great importance since the addition of a specific therapy will then become possible. Patients with absorptive idiopathic hypercalciuria will be advised to decrease their intake of dairy products as a function of the degree of calcium hyperabsorption, and simultaneously the major dietary sources of oxalate such as chocolate, spinach, rhubarb and asparagus will be eliminated; neutral orthophosphates (3-4 times 500 mg/d) or a thiazide, resp. an analogue as chlorthalidone (50 mg/d) are reasonable alternatives. Renal idiopathic hypercalciuria should be treated, according to the authors, with chlorthalidone (50 mg/d), with or without allopurinol (300 mg/d) depending on the presence of concomitant hyperuricosuria. Patients with dietary idiopathic hypercalciuria should be advised to better equilibrate the various components of their dietary intake. Finally, patients with isolated idiopathic hyperuricosuria whose disease would remain active despite a high fluid intake should receive allopurinol (300 mg/d). The treatment of isolated idiopathic hyperoxaluria is not yet well established. Two main arguments favor this so to say "tailored" approach to the idiopathic stone former: first, some metabolic disturbances are causally related to a particularly active and severe urolithiasis, whereas others are less so; second, the lack of efficacy of some types of treatment appears more and more to be due to insufficient screening of the patients before starting a given treatment. PMID:6658421

  16. 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

  17. 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. PMID:25869441

  18. 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

  19. 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.

  20. 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

  1. 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

  2. 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. PMID:26422652

  3. Asparaginase pharmacokinetics and implications of therapeutic drug monitoring

    PubMed Central

    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. PMID:25586605

  4. 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

  5. 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.

  6. [Therapeutic touch and anorexia nervosa].

    PubMed

    Satori, Nadine

    2016-01-01

    An innovative practice, therapeutic touch has been used for around ten years in the treatment of eating disorders. Delivered by nurse clinicians having received specific training, this approach is based on nursing diagnoses which identify the major symptoms of this pathology. The support is built around the body and its perceptions. Through the helping relationship, it mobilises the patient's resources to favour a relationship of trust, a letting-go, physical, psychological and emotional relaxation, and improves the therapeutic alliance. PMID:27615696

  7. 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...

  8. 45 CFR 148.220 - Excepted benefits.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 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...

  9. Health benefits of tennis

    PubMed Central

    Pluim, Babette M; Staal, J Bart; Marks, Bonita L; Miller, Stuart; Miley, Dave

    2007-01-01

    The aim of the study was to explore the role of tennis in the promotion of health and prevention of disease. The focus was on risk factors and diseases related to a sedentary lifestyle, including low fitness levels, obesity, hyperlipidaemia, hypertension, diabetes mellitus, cardiovascular disease, and osteoporosis. A literature search was undertaken to retrieve relevant articles. Structured computer searches of PubMed, Embase, and CINAHL were undertaken, along with hand searching of key journals and reference lists to locate relevant studies published up to March 2007. These had to be cohort studies (of either cross sectional or longitudinal design), case–control studies, or experimental studies. Twenty four studies were identified that dealt with physical fitness of tennis players, including 17 on intensity of play and 16 on maximum oxygen uptake; 17 investigated the relation between tennis and (risk factors for) cardiovascular disease; and 22 examined the effect of tennis on bone health. People who choose to play tennis appear to have significant health benefits, including improved aerobic fitness, a lower body fat percentage, a more favourable lipid profile, reduced risk for developing cardiovascular disease, and improved bone health. PMID:17504788

  10. 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

  11. 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

  12. 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

  13. Social Security's special minimum benefit.

    PubMed

    Olsen, K A; Hoffmeyer, D

    Social Security's special minimum primary insurance amount (PIA) provision was enacted in 1972 to increase the adequacy of benefits for regular long-term, low-earning covered workers and their dependents or survivors. At the time, Social Security also had a regular minimum benefit provision for persons with low lifetime average earnings and their families. Concerns were rising that the low lifetime average earnings of many regular minimum beneficiaries resulted from sporadic attachment to the covered workforce rather than from low wages. The special minimum benefit was seen as a way to reward regular, low-earning workers without providing the windfalls that would have resulted from raising the regular minimum benefit to a much higher level. The regular minimum benefit was subsequently eliminated for workers reaching age 62, becoming disabled, or dying after 1981. Under current law, the special minimum benefit will phase out over time, although it is not clear from the legislative history that this was Congress's explicit intent. The phaseout results from two factors: (1) special minimum benefits are paid only if they are higher than benefits payable under the regular PIA formula, and (2) the value of the regular PIA formula, which is indexed to wages before benefit eligibility, has increased faster than that of the special minimum PIA, which is indexed to inflation. Under the Social Security Trustees' 2000 intermediate assumptions, the special minimum benefit will cease to be payable to retired workers attaining eligibility in 2013 and later. Their benefits will always be larger under the regular benefit formula. As policymakers consider Social Security solvency initiatives--particularly proposals that would reduce benefits or introduce investment risk--interest may increase in restoring some type of special minimum benefit as a targeted protection for long-term low earners. Two of the three reform proposals offered by the President's Commission to Strengthen

  14. Additive usage levels.

    PubMed

    Langlais, R

    1996-01-01

    With the adoption of the European Parliament and Council Directives on sweeteners, colours and miscellaneous additives the Commission is now embarking on the project of coordinating the activities of the European Union Member States in the collection of the data that are to make up the report on food additive intake requested by the European Parliament. This presentation looks at the inventory of available sources on additive use levels and concludes that for the time being national legislation is still the best source of information considering that the directives have yet to be transposed into national legislation. Furthermore, this presentation covers the correlation of the food categories as found in the additives directives with those used by national consumption surveys and finds that in a number of instances this correlation still leaves a lot to be desired. The intake of additives via food ingestion and the intake of substances which are chemically identical to additives but which occur naturally in fruits and vegetables is found in a number of cases to be higher than the intake of additives added during the manufacture of foodstuffs. While the difficulties are recognized in contributing to the compilation of food additive intake data, industry as a whole, i.e. the food manufacturing and food additive manufacturing industries, are confident that in a concerted effort, use data on food additives by industry can be made available. Lastly, the paper points out that with the transportation of the additives directives into national legislation and the time by which the food industry will be able to make use of the new food legislative environment several years will still go by; food additives use data by the food industry will thus have to be reviewed at the beginning of the next century. PMID:8792135

  15. 20 CFR 408.305 - Why do you need to file an application to receive benefits?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Why do you need to file an application to receive benefits? 408.305 Section 408.305 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SPECIAL... need to file an application to receive benefits? In addition to meeting other requirements, you...

  16. An additional middle cuneiform?

    PubMed Central

    Brookes-Fazakerley, S.D.; Jackson, G.E.; Platt, S.R.

    2015-01-01

    Additional cuneiform bones of the foot have been described in reference to the medial bipartite cuneiform or as small accessory ossicles. An additional middle cuneiform has not been previously documented. We present the case of a patient with an additional ossicle that has the appearance and location of an additional middle cuneiform. Recognizing such an anatomical anomaly is essential for ruling out second metatarsal base or middle cuneiform fractures and for the preoperative planning of arthrodesis or open reduction and internal fixation procedures in this anatomical location. PMID:26224890

  17. 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

  18. Therapeutic drug monitoring and tyrosine kinase inhibitors

    PubMed Central

    Herviou, Pauline; Thivat, Emilie; Richard, Damien; Roche, Lucie; Dohou, Joyce; Pouget, Mélanie; Eschalier, Alain; Durando, Xavier; Authier, Nicolas

    2016-01-01

    The therapeutic activity of drugs can be optimized by establishing an individualized dosage, based on the measurement of the drug concentration in the serum, particularly if the drugs are characterized by an inter-individual variation in pharmacokinetics that results in an under- or overexposure to treatment. In recent years, several tyrosine kinase inhibitors (TKIs) have been developed to block intracellular signaling pathways in tumor cells. These oral drugs are candidates for therapeutic drug monitoring (TDM) due to their high inter-individual variability for therapeutic and toxic effects. Following a literature search on PubMed, studies on TKIs and their pharmacokinetic characteristics, plasma quantification and inter-individual variability was studied. TDM is commonly used in various medical fields, including cardiology and psychiatry, but is not often applied in oncology. Plasma concentration monitoring has been thoroughly studied for imatinib, in order to evaluate the usefulness of TDM. The measurement of plasma concentration can be performed by various analytical techniques, with liquid chromatography-mass spectrometry being the reference method. This method is currently used to monitor the efficacy and tolerability of imatinib treatments. Although TDM is already being used for imatinib, additional studies are required in order to improve this practice with the inclusion of other TKIs. PMID:27446421

  19. Interleukin-6 as a therapeutic target.

    PubMed

    Rossi, Jean-François; Lu, Zhao-Yang; Jourdan, Michel; Klein, Bernard

    2015-03-15

    Human IL6 is a cytokine produced by many cell types that has pleiotropic effects. In agreement, anti-IL6 therapy reduces inflammation, hepatic acute phase proteins, and anemia and has antiangiogenic effects. Blocking IL6 has demonstrated therapeutic efficacy with drug registration in Castleman disease and inflammatory diseases (rheumatoid arthritis) without major toxicity. Interestingly, the inhibition of C-reactive protein (CRP) production is a trustworthy surrogate marker of anti-IL6 therapy efficacy. Clinically registered IL6 inhibitors include siltuximab, an anti-IL6 mAb, and tocilizumab, an anti-IL6R mAb. In various cancers, in particular plasma cell cancers, large randomized trials showed no efficacy of IL6 inhibitors, despite a full inhibition of CRP production in treated patients in vivo, the numerous data showing an involvement of IL6 in these diseases, and initial short-term treatments demonstrating a dramatic inhibition of cancer cell proliferation in vivo. A likely explanation is the plasticity of cancer cells, with the presence of various subclones, making the outgrowth of cancer subclones possible using growth factors other than IL6. In addition, current therapeutic strategies used in these cancers already target IL6 activity. Thus, anti-IL6 therapeutics are able to neutralize IL6 production in vivo and are safe and useful in inflammatory diseases and Castleman disease. PMID:25589616

  20. Development of Therapeutic Splice-Switching Oligonucleotides

    PubMed Central

    Kryczka, Adrianna; Liu, Yuqi; Badi, Yusef E.; Wong, Jessie J.; Owen, James S.; Khoo, Bernard

    2014-01-01

    Abstract Synthetic splice-switching oligonucleotides (SSOs) target nuclear pre-mRNA molecules to change exon splicing and generate an alternative protein isoform. Clinical trials with two competitive SSO drugs are underway to treat Duchenne muscular dystrophy (DMD). Beyond DMD, many additional therapeutic applications are possible, with some in phase 1 clinical trials or advanced preclinical evaluation. Here, we present an overview of the central factors involved in developing therapeutic SSOs for the treatment of diseases. The selection of susceptible pre-mRNA target sequences, as well as the design and chemical modification of SSOs to increase SSO stability and effectiveness, are key initial considerations. Identification of effective SSO target sequences is still largely empirical and published guidelines are not a universal guarantee for success. Specifically, exon-targeted SSOs, which are successful in modifying dystrophin splicing, can be ineffective for splice-switching in other contexts. Chemical modifications, importantly, are associated with certain characteristic toxicities, which need to be addressed as target diseases require chronic treatment with SSOs. Moreover, SSO delivery in adequate quantities to the nucleus of target cells without toxicity can prove difficult. Last, the means by which these SSOs are administered needs to be acceptable to the patient. Engineering an efficient therapeutic SSO, therefore, necessarily entails a compromise between desirable qualities and effectiveness. Here, we describe how the application of optimal solutions may differ from case to case. PMID:24826963

  1. 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…

  2. Carbamate deposit control additives

    SciTech Connect

    Honnen, L.R.; Lewis, R.A.

    1980-11-25

    Deposit control additives for internal combustion engines are provided which maintain cleanliness of intake systems without contributing to combustion chamber deposits. The additives are poly(oxyalkylene) carbamates comprising a hydrocarbyloxyterminated poly(Oxyalkylene) chain of 2-5 carbon oxyalkylene units bonded through an oxycarbonyl group to a nitrogen atom of ethylenediamine.

  3. Therapeutic Strategies for Targeting Ras Proteins

    PubMed Central

    Gysin, Stephan; Salt, Megan; Young, Amy; McCormick, Frank

    2011-01-01

    Ras genes are frequently activated in cancer. Attempts to develop drugs that target mutant Ras proteins have, so far, been unsuccessful. Tumors bearing these mutations, therefore, remain among the most difficult to treat. Most efforts to block activated Ras have focused on pathways downstream. Drugs that inhibit Raf kinase have shown clinical benefit in the treatment of malignant melanoma. However, these drugs have failed to show clinical benefit in Ras mutant tumors. It remains unclear to what extent Ras depends on Raf kinase for transforming activity, even though Raf proteins bind directly to Ras and are certainly major effectors of Ras action in normal cells and in development. Furthermore, Raf kinase inhibitors can lead to paradoxical activation of the MAPK pathway. MEK inhibitors block the Ras-MAPK pathway, but often activate the PI3’-kinase, and have shown little clinical benefit as single agents. This activation is mediated by EGF-R and other receptor tyrosine kinases through relief of a negative feedback loop from ERK. Drug combinations that target multiple points within the Ras signaling network are likely to be necessary to achieve substantial clinical benefit. Other effectors may also contribute to Ras signaling and provide a source of targets. In addition, unbiased screens for genes necessary for Ras transformation have revealed new potential targets and have added to our understanding of Ras cancer biology. PMID:21779505

  4. 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

  5. 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.

  6. 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.

  7. Successful Use of Therapeutic Hypothermia in a Pregnant Patient.

    PubMed

    Oguayo, Kevin N; Oyetayo, Ola O; Stewart, David; Costa, Steven M; Jones, Richard O

    2015-08-01

    Out-of-hospital cardiac arrest is a leading cause of death in the United States. Pregnant women are not immune to cardiac arrest, and the treatment of such patients can be difficult. Pregnancy is a relative contraindication to the use of therapeutic hypothermia after cardiac arrest. A 20-year-old woman who was 18 weeks pregnant had an out-of-hospital cardiac arrest. Upon her arrival at the emergency department, she was resuscitated and her circulation returned spontaneously, but her score on the Glasgow Coma Scale was 3. After adequate family discussion of the risks and benefits of therapeutic hypothermia, a decision was made to initiate therapeutic hypothermia per established protocol for 24 hours. The patient was successfully cooled and rewarmed. By the time she was discharged, she had experienced complete neurologic recovery, apart from some short-term memory loss. Subsequently, at 40 weeks, she delivered vaginally a 7-lb 3-oz girl whose Apgar scores were 8 and 9, at 1 and 5 minutes respectively. To our knowledge, this is only the 3rd reported case of a successful outcome following the initiation of therapeutic hypothermia for out-of-hospital cardiac arrest in a pregnant woman. On the basis of this and previous reports of successful outcomes, we recommend that therapeutic hypothermia be considered an option in the management of out-of-hospital cardiac arrest in the pregnant population. To facilitate a successful outcome, a multidisciplinary approach involving cardiology, emergency medicine, obstetrics, and neurology should be used. PMID:26413021

  8. Approaches to improve development methods for therapeutic cancer vaccines.

    PubMed

    Ogi, Chizuru; Aruga, Atsushi

    2015-04-01

    Therapeutic cancer vaccines are an immunotherapy that amplify or induce an active immune response against tumors. Notably, limitations in the methodology for existing anti-cancer drugs may subsist while applying them to cancer vaccine therapy. A retrospective analysis was performed using information obtained from ClinicalTrials.gov, PubMed, and published articles. Our research evaluated the optimal methodologies for therapeutic cancer vaccines based on (1) patient populations, (2) immune monitoring, (3) tumor response evaluation, and (4) supplementary therapies. Failure to optimize these methodologies at an early phase may impact development at later stages; thus, we have proposed some points to be considered during the early phase. Moreover, we compared our proposal with the guidance for industry issued by the US Food and Drug Administration in October 2011 entitled "Clinical Considerations for Therapeutic Cancer Vaccines". Consequently, while our research was aligned with the guidance, we hope it provides further insights in order to predict the risks and benefits and facilitate decisions for a new technology. We identified the following points for consideration: (1) include in the selection criteria the immunological stage with a prognostic value, which is as important as the tumor stage; (2) select immunological assays such as phenotype analysis of lymphocytes, based on their features and standardize assay methods; (3) utilize optimal response criteria for immunotherapy in therapeutic cancer vaccine trials; and (4) consider supplementary therapies, including immune checkpoint inhibitors, for future therapeutic cancer vaccines. PMID:25746315

  9. Yoga school of thought and psychiatry: Therapeutic potential.

    PubMed

    Rao, Naren P; Varambally, Shivarama; Gangadhar, Bangalore N

    2013-01-01

    Yoga is a traditional life-style practice used for spiritual reasons. However, the physical components like the asanas and pranayaamas have demonstrated physiological and therapeutic effects. There is evidence for Yoga as being a potent antidepressant that matches with drugs. In depressive disorder, yoga 'corrects' an underlying cognitive physiology. In schizophrenia patients, yoga has benefits as an add-on intervention in pharmacologically stabilized subjects. The effects are particularly notable on negative symptoms. Yoga also helps to correct social cognition. Yoga can be introduced early in the treatment of psychosis with some benefits. Elevation of oxytocin may be a mechanism of yoga effects in schizophrenia. Certain components of yoga have demonstrated neurobiological effects similar to those of vagal stimulation, indicating this (indirect or autogenous vagal stimulation) as a possible mechanism of its action. It is time, psychiatrists exploited the benefits if yoga for a comprehensive care in their patients. PMID:23858245

  10. 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.

  11. 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)

  12. Additional Types of Neuropathy

    MedlinePlus

    ... A A Listen En Español Additional Types of Neuropathy Charcot's Joint Charcot's Joint, also called neuropathic arthropathy, ... can stop bone destruction and aid healing. Cranial Neuropathy Cranial neuropathy affects the 12 pairs of nerves ...

  13. Open Mind, Open Heart: An Anthropological Study of the Therapeutics of Meditation Practice in the US

    PubMed Central

    Myers, Neely; Lewis, Sara; Dutton, MaryAnn

    2015-01-01

    Based on ethnographic fieldwork and interviews collected with meditation teachers and students in the United States, this article will argue that active training in meditation-based practices occasions the opportunity for people with traumatic stress to develop a stronger mind-body connection through heightened somatic awareness and a focus on the present moment that they find to be therapeutic. Three important themes related to healing through meditation for trauma emerged from the data and centered around the ways our interlocutors attempted to realign their sense of self, mind and body, after a traumatic experience. The themes helped explain why US women perceive meditation as therapeutic for trauma, namely that the practice of meditation enables one to focus on the lived present rather than traumatic memories, to accept pain and “open” one's heart, and to make use of silence instead of speech as a healing modality. As meditation practices increasingly enter global popular culture, promoted for postulated health benefits, the driving question of this research—how meditation may perpetuate human resilience for women who have experienced trauma based on their own perspectives of meditation practices—is a critical addition to the literature. PMID:25613595

  14. Recent Trends in Therapeutic Approaches for Diabetes Management: A Comprehensive Update

    PubMed Central

    Tiwari, Pragya

    2015-01-01

    Diabetes highlights a growing epidemic imposing serious social economic crisis to the countries around the globe. Despite scientific breakthroughs, better healthcare facilities, and improved literacy rate, the disease continues to burden several sections, especially middle and low income countries. The present trends indicate the rise in premature death, posing a major threat to global development. Scientific and technological advances have witnessed the development of newer generation of drugs like sulphonylureas, biguanides, alpha glucosidase inhibitors, and thiazolidinediones with significant efficacy in reducing hyperglycemia. Recent approaches in drug discovery have contributed to the development of new class of therapeutics like Incretin mimetics, Amylin analogues, GIP analogs, Peroxisome proliferator activated receptors, and dipeptidyl peptidase-4 inhibitor as targets for potential drugs in diabetes treatment. Subsequently, the identification and clinical investigation of bioactive substances from plants have revolutionized the research on drug discovery and lead identification for diabetes management. With a focus on the emerging trends, the review article explores the current statistical prevalence of the disease, discussing the benefits and limitations of the commercially available drugs. Additionally, the critical areas in clinical diabetology are discussed, with respect to prospects of statins, nanotechnology, and stem cell technology as next generation therapeutics and why the herbal formulations are consistently popular choice for diabetes medication and management. PMID:26273667

  15. Therapeutic strategies for anchored kinases and phosphatases: exploiting short linear motifs and intrinsic disorder

    PubMed Central

    Nygren, Patrick J.; Scott, John D.

    2015-01-01

    Phosphorylation events that occur in response to the second messenger cAMP are controlled spatially and temporally by protein kinase A (PKA) interacting with A-kinase anchoring proteins (AKAPs). Recent advances in understanding the structural basis for this interaction have reinforced the hypothesis that AKAPs create spatially constrained signaling microdomains. This has led to the realization that the PKA/AKAP interface is a potential drug target for modulating a plethora of cell-signaling events. Pharmacological disruption of kinase–AKAP interactions has previously been explored for disease treatment and remains an interesting area of research. However, disrupting or enhancing the association of phosphatases with AKAPs is a therapeutic concept of equal promise, particularly since they oppose the actions of many anchored kinases. Accordingly, numerous AKAPs bind phosphatases such as protein phosphatase 1 (PP1), calcineurin (PP2B), and PP2A. These multimodal signaling hubs are equally able to control the addition of phosphate groups onto target substrates, as well as the removal of these phosphate groups. In this review, we describe recent advances in structural analysis of kinase and phosphatase interactions with AKAPs, and suggest future possibilities for targeting these interactions for therapeutic benefit. PMID:26283967

  16. Open Mind, Open Heart: An Anthropological Study of the Therapeutics of Meditation Practice in the US.

    PubMed

    Myers, Neely; Lewis, Sara; Dutton, Mary Ann

    2015-09-01

    Based on ethnographic fieldwork and interviews collected with meditation teachers and students in the United States, this article will argue that active training in meditation-based practices occasions the opportunity for people with traumatic stress to develop a stronger mind-body connection through heightened somatic awareness and a focus on the present moment that they find to be therapeutic. Three important themes related to healing through meditation for trauma emerged from the data and centered around the ways our interlocutors attempted to realign their sense of self, mind and body, after a traumatic experience. The themes helped explain why US women perceive meditation as therapeutic for trauma, namely that the practice of meditation enables one to focus on the lived present rather than traumatic memories, to accept pain and "open" one's heart, and to make use of silence instead of speech as a healing modality. As meditation practices increasingly enter global popular culture, promoted for postulated health benefits, the driving question of this research--how meditation may perpetuate human resilience for women who have experienced trauma based on their own perspectives of meditation practices--is a critical addition to the literature. PMID:25613595

  17. What Lives On Our Skin: Ecology, Genomics and Therapeutic Opportunities Of the Skin Microbiome

    PubMed Central

    Scharschmidt, Tiffany C.; Fischbach, Michael A.

    2013-01-01

    Our skin is home to a rich community of microorganisms. Recent advances in sequencing technology have allowed more accurate enumeration of these human-associated microbiota and investigation of their genomic content. Staphylococcus, Corynebacterium and Propionibacterium represent the dominant bacterial genera on skin and illustrate how bacteria adapt to life in this harsh environment and also provide us with unique benefits. In healthy states, our skin peacefully co-exists with commensal bacteria while fending off potentially dangerous invaders. Disruption of this equilibrium, termed “dysbiosis”, can result from changes in the composition of our skin bacteria, an altered immune response to them, or both and may be a driving factor in certain types of inflammatory skin disease. Engineering topical therapeutics to favourably influence the composition of our skin flora and optimize interactions with them represents a real therapeutic opportunity for the field of dermatology and warrants additional investigation into skin microbial ecology and disease mechanisms related to host-microbe dysbiosis. PMID:24273587

  18. Recent Trends in Therapeutic Approaches for Diabetes Management: A Comprehensive Update.

    PubMed

    Tiwari, Pragya

    2015-01-01

    Diabetes highlights a growing epidemic imposing serious social economic crisis to the countries around the globe. Despite scientific breakthroughs, better healthcare facilities, and improved literacy rate, the disease continues to burden several sections, especially middle and low income countries. The present trends indicate the rise in premature death, posing a major threat to global development. Scientific and technological advances have witnessed the development of newer generation of drugs like sulphonylureas, biguanides, alpha glucosidase inhibitors, and thiazolidinediones with significant efficacy in reducing hyperglycemia. Recent approaches in drug discovery have contributed to the development of new class of therapeutics like Incretin mimetics, Amylin analogues, GIP analogs, Peroxisome proliferator activated receptors, and dipeptidyl peptidase-4 inhibitor as targets for potential drugs in diabetes treatment. Subsequently, the identification and clinical investigation of bioactive substances from plants have revolutionized the research on drug discovery and lead identification for diabetes management. With a focus on the emerging trends, the review article explores the current statistical prevalence of the disease, discussing the benefits and limitations of the commercially available drugs. Additionally, the critical areas in clinical diabetology are discussed, with respect to prospects of statins, nanotechnology, and stem cell technology as next generation therapeutics and why the herbal formulations are consistently popular choice for diabetes medication and management. PMID:26273667

  19. [Therapeutic potential of optogenetic neuromodulation].

    PubMed

    Vandecasteele, Marie; Senova, Yann-Suhan; Palfi, Stéphane; Dugué, Guillaume P

    2015-04-01

    Optogenetic neuromodulation techniques, which have emerged during the last 15 years, have considerably enhanced our ability to probe the functioning of neural circuits by allowing the excitation and inhibition of genetically-defined neuronal populations using light. Having gained tremendous popularity in the field of fundamental neuroscience, these techniques are now opening new therapeutic avenues. Optogenetic neuromodulation is a method of choice for studying the physiopathology of neurological and neuropsychiatric disorders in a range of animal models, and could accelerate the discovery of new therapeutic strategies. New therapeutic protocols employing optogenetic neuromodulation may also emerge in the near future, offering promising alternative approaches for disorders which lack appropriate treatments, such as pharmacoresistant epilepsy and inherited retinal degeneration. PMID:25958759

  20. Therapeutic cloning and reproductive liberty.

    PubMed

    Sparrow, Robert

    2009-04-01

    Concern for "reproductive liberty" suggests that decisions about embryos should normally be made by the persons who would be the genetic parents of the child that would be brought into existence if the embryo were brought to term. Therapeutic cloning would involve creating and destroying an embryo, which, if brought to term, would be the offspring of the genetic parents of the person undergoing therapy. I argue that central arguments in debates about parenthood and genetics therefore suggest that therapeutic cloning would be prima facie unethical unless it occurred with the consent of the parents of the person being cloned. Alternatively, if therapeutic cloning is thought to be legitimate, this undermines the case for some uses of reproductive cloning by implying that the genetic relation it establishes between clones and DNA donors does not carry the same moral weight as it does in cases of normal reproduction. PMID:19240247

  1. Oligonucleotide conjugates for therapeutic applications

    PubMed Central

    Winkler, Johannes

    2013-01-01

    Insufficient pharmacokinetic properties and poor cellular uptake are the main hurdles for successful therapeutic development of oligonucleotide agents. The covalent attachment of various ligands designed to influence the biodistribution and cellular uptake or for targeting specific tissues is an attractive possibility to advance therapeutic applications and to expand development options. In contrast to advanced formulations, which often consist of multiple reagents and are sensitive to a variety of preparation conditions, oligonucleotide conjugates are defined molecules, enabling structure-based analytics and quality control techniques. This review gives an overview of current developments of oligonucleotide conjugates for therapeutic applications. Attached ligands comprise peptides, proteins, carbohydrates, aptamers and small molecules, including cholesterol, tocopherol and folic acid. Important linkage types and conjugation methods are summarized. The distinct ligands directly influence biochemical parameters, uptake machanisms and pharmacokinetic properties. PMID:23883124

  2. gp130 receptor ligands as potential therapeutic targets for obesity

    PubMed Central

    Febbraio, Mark A.

    2007-01-01

    Obesity and its related cluster of pathophysiologic conditions including insulin resistance, glucose intolerance, dyslipidemia, and hypertension are recognized as growing threats to world health. It is now estimated that 10% of the world’s population is overweight or obese. As a result, new therapeutic options for the treatment of obesity are clearly warranted. Recent research has focused on the role that gp130 receptor ligands may play as potential therapeutic targets in obesity. One cytokine in particular, ciliary neurotrophic factor (CNTF), acts both centrally and peripherally and mimics the biologic actions of the appetite control hormone leptin, but unlike leptin, CNTF appears to be effective in obesity and as such may have therapeutic potential. In addition, CNTF suppresses inflammatory signaling cascades associated with lipid accumulation in liver and skeletal muscle. This review examines the potential role of gp130 receptor ligands as part of a therapeutic strategy to treat obesity. PMID:17404609

  3. [Multiple sclerosis: potential therapeutic options and update of ongoing studies].

    PubMed

    Wiendl, H; Lehmann, H C; Hohlfeld, R; Hartung, H-P; Kieseier, B C

    2004-06-01

    The therapeutic options for the treatment of multiple sclerosis (MS) have experienced enormous progress over recent years. Despite these encouraging developments, available therapies are only partially effective, and the ultimate goal of curing MS is still far from being attained. The improved understanding of the cellular and molecular mechanisms of MS (immune) pathogenesis together with recent shifts in paradigms led to a variety of new therapeutic targets and approaches. In addition to modulation of the inflammatory process, therapeutic approaches focussing on active neuroprotection, remyelinization, and regeneration have become increasingly important. Based on current concepts of the MS pathogenesis, this article summarizes new therapeutic approaches. Substances and strategies currently tested in clinical trials are reviewed. PMID:15257377

  4. Therapeutic touch and post-Hurricane Hugo stress.

    PubMed

    Olson, M; Sneed, N; Bonadonna, R; Ratliff, J; Dias, J

    1992-06-01

    This repeated-session design sought to answer questions about the effectiveness of therapeutic touch in reduction of stress for 23 individuals following a natural disaster. In addition, methodological issues related to the average length of time for a therapeutic-touch treatment and a method of documenting the nonverbal interaction between subject and toucher were investigated. Findings indicate that stressed people report themselves to be less stressed following therapeutic touch (p = .05). Time of therapeutic-touch intervention varied significantly between the touchers, with a range of 6.8 to 20 minutes. Qualitative data examining the interaction of toucher and subject raised a number of questions that require further study. PMID:1301421

  5. Therapeutic target database update 2014: a resource for targeted therapeutics

    PubMed Central

    Qin, Chu; Zhang, Cheng; Zhu, Feng; Xu, Feng; Chen, Shang Ying; Zhang, Peng; Li, Ying Hong; Yang, Sheng Yong; Wei, Yu Quan; Tao, Lin; Chen, Yu Zong

    2014-01-01

    Here we describe an update of the Therapeutic Target Database (http://bidd.nus.edu.sg/group/ttd/ttd.asp) for better serving the bench-to-clinic communities and for enabling more convenient data access, processing and exchange. Extensive efforts from the research, industry, clinical, regulatory and management communities have been collectively directed at the discovery, investigation, application, monitoring and management of targeted therapeutics. Increasing efforts have been directed at the development of stratified and personalized medicines. These efforts may be facilitated by the knowledge of the efficacy targets and biomarkers of targeted therapeutics. Therefore, we added search tools for using the International Classification of Disease ICD-10-CM and ICD-9-CM codes to retrieve the target, biomarker and drug information (currently enabling the search of almost 900 targets, 1800 biomarkers and 6000 drugs related to 900 disease conditions). We added information of almost 1800 biomarkers for 300 disease conditions and 200 drug scaffolds for 700 drugs. We significantly expanded Therapeutic Target Database data contents to cover >2300 targets (388 successful and 461 clinical trial targets), 20 600 drugs (2003 approved and 3147 clinical trial drugs), 20 000 multitarget agents against almost 400 target-pairs and the activity data of 1400 agents against 300 cell lines. PMID:24265219

  6. A Therapeutic Approach to Teaching Poetry: Individual Development, Psychology, and Social Reparation. Psychoanalysis, Education and Social Transformation

    ERIC Educational Resources Information Center

    Williams, Todd O.

    2012-01-01

    A Therapeutic Approach to Teaching Poetry develops a poetry pedagogy that offers significant benefits to students by helping them to achieve a sense of renewal (a deeper awareness of self and potentials) and reparation (a realistic, but positive and proactive worldview). Todd O. Williams offers a thorough examination of the therapeutic potential…

  7. Data Safety Monitoring Boards and Other Study Methodologies that Address Subject Safety in "High-Risk" Therapeutic Trials in Youths

    ERIC Educational Resources Information Center

    Carandang, Carlo; Santor, Darcy; Gardner, David M.; Carrey, Normand; Kutcher, Stan

    2007-01-01

    The underlying proposition for any experimental/therapeutic trial is the uncertainty that the risks of treatment will be outweighed by its benefits. For some therapeutic interventions (e.g., exercise programs, vitamin supplementation), the potential for treatment-emergent adverse events may prima facie be low or negligible, whereas for others…

  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. 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)

  10. 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…

  11. Fringe Benefits. SPEC Kit 50.

    ERIC Educational Resources Information Center

    Association of Research Libraries, Washington, DC. Office of Management Studies.

    Based on analyses of 91 documents on fringe benefits received from member libraries of the Association of Research Libraries (ARL) in 1978, a concise summary presents observations and statistics on sabbatical leaves, insurance, retirement, education and campus-related benefits, trends, and needs. It is concluded that pressures for improving fringe…

  12. 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…

  13. 78 FR 76574 - Burial Benefits

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-18

    ... rewrite in plain language its regulations that govern entitlement to monetary burial benefits, which... published in the Federal Register on April 8, 2008 (73 FR 19,021), VA proposed to reorganize and rewrite in plain language provisions applicable to burial benefits. This proposed rule would build upon...

  14. 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.

  15. 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. PMID:15679896

  16. Myostatin/activin pathway antagonism: molecular basis and therapeutic potential.

    PubMed

    Han, H Q; Zhou, Xiaolan; Mitch, William E; Goldberg, Alfred L

    2013-10-01

    Muscle wasting is associated with a wide range of catabolic diseases. This debilitating loss of muscle mass and functional capacity reduces the quality of life and increases the risks of morbidity and mortality. Major progress has been made in understanding the biochemical mechanisms and signaling pathways regulating muscle protein balance under normal conditions and the enhanced protein loss in atrophying muscles. It is now clear that activation of myostatin/activin signaling is critical in triggering the accelerated muscle catabolism that causes muscle loss in multiple disease states. Binding of myostatin and activin to the ActRIIB receptor complex on muscle cell membrane leads to activation of Smad2/3-mediated transcription, which in turn stimulates FoxO-dependent transcription and enhanced muscle protein breakdown via ubiquitin-proteasome system and autophagy. In addition, Smad activation inhibits muscle protein synthesis by suppressing Akt signaling. Pharmacological blockade of the myostatin/activin-ActRIIB pathway has been shown to prevent or reverse the loss of muscle mass and strength in various disease models including cancer cachexia and renal failure. Moreover, it can markedly prolong the lifespan of animals with cancer-associated muscle loss. Furthermore, inhibiting myostatin/activin actions also improves insulin sensitivity, reduces excessive adiposity, attenuates systemic inflammation, and accelerates bone fracture healing in disease models. Based on these exciting advances, the potential therapeutic benefits of myostatin/activin antagonism are now being tested in multiple clinical settings. This article is part of a Directed Issue entitled: Molecular basis of muscle wasting. PMID:23721881

  17. Highway noise barrier perceived benefit

    NASA Astrophysics Data System (ADS)

    May, D. N.; Osman, M. M.

    1980-05-01

    A laboratory experiment was performed in which 82 subjects judged the benefit of a noise barrier by listening to tape recordings of before-barrier and after-barrier traffic noise. These perceived benefit judgments were related by regression analysis to the barrier attenuation, the before-barrier traffic sound level, and a music background level, all of which were varied over the course of the experiment. Prediction equations were developed for barrier benefit in terms of these sound levels, their purpose being to provide a model for barrier benefit that can be used in barrier site selection and design. An unexpected finding was that barrier benefit was highest when before-barrier sound levels were lowest: i.e., subjects preferred a noise barrier that solved a moderate noise problem over an equally-attenuating barrier that only partially solved a more severe noise problem.

  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 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.

  19. 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 SECURITY INCOME FOR THE AGED, BLIND, AND DISABLED State Supplementation Provisions; Agreement;...

  20. 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 SECURITY INCOME FOR THE AGED, BLIND, AND DISABLED State Supplementation Provisions; Agreement;...

  1. 20 CFR 725.607 - Payments in addition to compensation.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... MINE HEALTH AND SAFETY ACT OF 1969, AS AMENDED CLAIMS FOR BENEFITS UNDER PART C OF TITLE IV OF THE FEDERAL MINE SAFETY AND HEALTH ACT, AS AMENDED Enforcement of Liability; Reports § 725.607 Payments in... time as, but in addition to, such benefits, unless review of the order making such award is sought...

  2. 20 CFR 416.263 - No additional application needed.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 20 Employees' Benefits 2 2012-04-01 2012-04-01 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...

  3. 20 CFR 416.263 - No additional application needed.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 20 Employees' Benefits 2 2014-04-01 2014-04-01 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...

  4. 20 CFR 416.263 - No additional application needed.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 2 2011-04-01 2011-04-01 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...

  5. 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...

  6. 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

  7. 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.

  8. Sports Health Benefits of Vitamin D

    PubMed Central

    Shuler, Franklin D.; Wingate, Matthew K.; Moore, G. Hunter; Giangarra, Charles

    2012-01-01

    Context: Vitamin D is a potent secosteroid hormone that provides many skeletal and extraskeletal health benefits. Musculoskeletal injury prevention and recovery are potentially affected by sufficient circulating levels of the storage form of vitamin D: 25-hydroxyvitamin D3, or 25(OH)D. Vitamin D deficiency can exist among young, active, and healthy people, which may put them at increased risk for injury and prolonged recovery. Evidence Aquisition: PubMed was searched using vitamin D and skeletal muscle, vitamin D and athletic performance, and vitamin D review articles. Studies from the 1930s to 2012 were used for the review. Results: There is strong correlation between vitamin D sufficiency and optimal muscle function. Increasing levels of vitamin D reduce inflammation, pain, and myopathy while increasing muscle protein synthesis, ATP concentration, strength, jump height, jump velocity, jump power, exercise capacity, and physical performance. 25(OH)D levels above 40 ng/mL are required for fracture prevention, including stress fractures. Optimal musculoskeletal benefits occur at 25(OH)D levels above the current definition of sufficiency (> 30 ng/mL) with no reported sports health benefits above 50 ng/mL. Conclusions: Vitamin D deficiency is common in athletes. For athletes presenting with stress fractures, musculoskeletal pain, and frequent illness, one should have a heightened awareness of the additional likely diagnosis of vitamin D deficiency. Correction of this deficiency is completed by standardized and supervised oral supplementation protocols producing significant musculoskeletal sports health benefits. PMID:24179588

  9. Therapy Talk: Analyzing Therapeutic Discourse

    ERIC Educational Resources Information Center

    Leahy, Margaret M.

    2004-01-01

    Therapeutic discourse is the talk-in-interaction that represents the social practice between clinician and client. This article invites speech-language pathologists to apply their knowledge of language to analyzing therapy talk and to learn how talking practices shape clinical roles and identities. A range of qualitative research approaches,…

  10. DYNAMIC EQUILIBRIUM IN THERAPEUTIC SITUATIONS.

    ERIC Educational Resources Information Center

    CARROLL, EDWARD J.

    THE CONCEPT OF DYNAMIC EQUILIBRIUM IS USED TO EXAMINE THE OCCURRENCE OF CHANGE IN A THERAPEUTIC INTERVIEW AND TO PROPOSE A THEORY OF THERAPY. BY ANALYZING THE WORKINGS OF THE PSYCHOSOCIAL SYSTEM THROUGH THE GENERAL SYSTEMS THEORY, IT IS POSSIBLE TO SEE HOW CHANGE OCCURS IN AN INDIVIDUAL FAMILY OR COMMUNITY. APPLIED TO A FAMILY INTERVIEW, THE MODEL…

  11. Therapeutic role of dietary fibre.

    PubMed Central

    Hunt, R.; Fedorak, R.; Frohlich, J.; McLennan, C.; Pavilanis, A.

    1993-01-01

    The current status of dietary fibre and fibre supplements in health and disease is reported, and the components of dietary fibre and its respective mechanical and metabolic effects with emphasis on its therapeutic potential are reviewed. Practical management guidelines are provided to help physicians encourage patients identified as having fibre deficiency to increase dietary fibre intake to the recommended level. PMID:8388284

  12. Therapeutic Potential of Human Adipose-Derived Stem Cells (ADSCs) from Cancer Patients: A Pilot Study

    PubMed Central

    García-Contreras, Marta; Vera-Donoso, César David; Hernández-Andreu, José Miguel; García-Verdugo, José Manuel; Oltra, Elisa

    2014-01-01

    Mesenchymal stem cells from adipose tissue (ADSCs) are an important source of cells for regenerative medicine. The therapeutic effect of culture-expanded adipose derived stem cells has been shown; however, optimal xeno-free culture conditions remain to be determined. Cancer patients, specifically those undergoing invasive surgery, constitute a subgroup of patients who could benefit from autologous stem cell transplantation. Although regenerative potential of their ADSCs could be affected by the disease and/or treatment, we are not aware of any study that has evaluated the therapeutic potential of ADSCs isolated from cancer patients in reference to that of ADSCs derived from healthy subjects. Here we report that ADSCs isolated from subabdominal adipose tissue of patients with urological neoplasms yielded similar growth kinetics, presented equivalent mesenchymal surface markers and showed similar differentiation potential into distinct mesodermal cell lineages: adipocytes, chondroblasts and osteoblasts than ADSCs isolated from adipose tissue of age-matched non-oncogenic participants, all under xeno-free growth culture conditions. Molecular karyotyping of patient expanded ADSCs genomes showed no disease-related alterations indicating their safety. In addition, vesicles <100 nm identified as exosomes (EXOs) which may be at least partly responsible for the attributed therapeutic paracrine effects of the ADSCs were effectively isolated from ADSCs and showed equivalent miRNA content regardless they were derived from cancer patients or non-oncogenic participants indicating that the repair capabilities of xeno-free expanded ADSCs are not compromised by patient condition and therefore their xeno-free culture expanded ADSCs should be suitable for autologous stem cell transplantation in a clinical setting. PMID:25412325

  13. Therapeutic hypothermia and targeted temperature management in traumatic brain injury: Clinical challenges for successful translation.

    PubMed

    Dietrich, W Dalton; Bramlett, Helen M

    2016-06-01

    The use of therapeutic hypothermia (TH) and targeted temperature management (TTM) for severe traumatic brain injury (TBI) has been tested in a variety of preclinical and clinical situations. Early preclinical studies showed that mild reductions in brain temperature after moderate to severe TBI improved histopathological outcomes and reduced neurological deficits. Investigative studies have also reported that reductions in post-traumatic temperature attenuated multiple secondary injury mechanisms including excitotoxicity, free radical generation, apoptotic cell death, and inflammation. In addition, while elevations in post-traumatic temperature heightened secondary injury mechanisms, the successful implementation of TTM strategies in injured patients to reduce fever burden appear to be beneficial. While TH has been successfully tested in a number of single institutional clinical TBI studies, larger randomized multicenter trials have failed to demonstrate the benefits of therapeutic hypothermia. The use of TH and TTM for treating TBI continues to evolve and a number of factors including patient selection and the timing of the TH appear to be critical in successful trial design. Based on available data, it is apparent that TH and TTM strategies for treating severely injured patients is an important therapeutic consideration that requires more basic and clinical research. Current research involves the evaluation of alternative cooling strategies including pharmacologically-induced hypothermia and the combination of TH or TTM approaches with more selective neuroprotective or reparative treatments. This manuscript summarizes the preclinical and clinical literature emphasizing the importance of brain temperature in modifying secondary injury mechanisms and in improving traumatic outcomes in severely injured patients. This article is part of a Special Issue entitled SI:Brain injury and recovery. PMID:26746342

  14. Should Therapeutic Drug Monitoring for Monoclonal Antibodies Remain the Exception or Become the Norm?

    PubMed

    Stroh, M; Lum, B L

    2016-09-01

    Therapeutic drug monitoring (TDM) aims to maintain circulating drug concentrations at a desired level to optimize clinical outcome. The vast majority of marketed drugs do not require TDM, suggesting the clinical benefit of TDM has not been sufficiently demonstrated in most cases. With the continued emergence and prominence of monoclonal antibodies (mAbs) as drugs, especially in inflammation and cancer therapeutic areas, we are at a juncture to consider applicability of TDM for mAbs. PMID:26971373

  15. Multifunctional fuel additives

    SciTech Connect

    Baillargeon, D.J.; Cardis, A.B.; Heck, D.B.

    1991-03-26

    This paper discusses a composition comprising a major amount of a liquid hydrocarbyl fuel and a minor low-temperature flow properties improving amount of an additive product of the reaction of a suitable diol and product of a benzophenone tetracarboxylic dianhydride and a long-chain hydrocarbyl aminoalcohol.

  16. Nicotinic Acid-Mediated Activation of Both Membrane and Nuclear Receptors towards Therapeutic Glucocorticoid Mimetics for Treating Multiple Sclerosis

    PubMed Central

    Penberthy, W. Todd

    2009-01-01

    Acute attacks of multiple sclerosis (MS) are most commonly treated with glucocorticoids, which can provide life-saving albeit only temporary symptomatic relief. The mechanism of action (MOA) is now known to involve induction of indoleamine 2,3-dioxygenase (IDO) and interleukin-10 (IL-10), where IL-10 requires subsequent heme oxygenase-1 (HMOX-1) induction. Ectopic expression studies reveal that even small changes in expression of IDO, HMOX-1, or mitochondrial superoxide dismutase (SOD2) can prevent demyelination in experimental autoimmune encephalomyelitis (EAE) animal models of MS. An alternative to glucocorticoids is needed for a long-term treatment of MS. A distinctly short list of endogenous activators of both membrane G-protein-coupled receptors and nuclear peroxisome proliferating antigen receptors (PPARs) demonstrably ameliorate EAE pathogenesis by MOAs resembling that of glucocorticoids. These dual activators and potential MS therapeutics include endocannabinoids and the prostaglandin 15-deoxy-Δ12,14-PGJ2. Nicotinamide profoundly ameliorates and prevents autoimmune-mediated demyelination in EAE via maintaining levels of nicotinamide adenine dinucleotide (NAD), without activating PPAR nor any G-protein-coupled receptor. By comparison, nicotinic acid provides even greater levels of NAD than nicotinamide in many tissues, while additionally activating the PPARγ-dependent pathway already shown to provide relief in animal models of MS after activation of GPR109a/HM74a. Thus nicotinic acid is uniquely suited for providing therapeutic relief in MS. However nicotinic acid is unexamined in MS research. Nicotinic acid penetrates the blood brain barrier, cures pellagric dementia, has been used for over 50 years clinically without toxicity, and raises HDL concentrations to a greater degree than any pharmaceutical, thus providing unparalleled benefits against lipodystrophy. Summary analysis reveals that the expected therapeutic benefits of high-dose nicotinic acid

  17. 38 CFR 3.650 - Rate for additional dependent.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... be effective from the date of potential entitlement of the additional dependent. (2) Where benefits... for periods prior to the date the full rate is awarded shall be the difference between the...

  18. 38 CFR 3.650 - Rate for additional dependent.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... be effective from the date of potential entitlement of the additional dependent. (2) Where benefits... for periods prior to the date the full rate is awarded shall be the difference between the...

  19. 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

  20. 29 CFR 4022.24 - Benefit increases.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 9 2010-07-01 2010-07-01 false Benefit increases. 4022.24 Section 4022.24 Labor Regulations Relating to Labor (Continued) PENSION BENEFIT GUARANTY CORPORATION COVERAGE AND BENEFITS BENEFITS PAYABLE IN TERMINATED SINGLE-EMPLOYER PLANS Limitations on Guaranteed Benefits § 4022.24 Benefit...

  1. 29 CFR 4022.24 - Benefit increases.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 9 2012-07-01 2012-07-01 false Benefit increases. 4022.24 Section 4022.24 Labor Regulations Relating to Labor (Continued) PENSION BENEFIT GUARANTY CORPORATION COVERAGE AND BENEFITS BENEFITS PAYABLE IN TERMINATED SINGLE-EMPLOYER PLANS Limitations on Guaranteed Benefits § 4022.24 Benefit...

  2. 29 CFR 4022.24 - Benefit increases.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 29 Labor 9 2013-07-01 2013-07-01 false Benefit increases. 4022.24 Section 4022.24 Labor Regulations Relating to Labor (Continued) PENSION BENEFIT GUARANTY CORPORATION COVERAGE AND BENEFITS BENEFITS PAYABLE IN TERMINATED SINGLE-EMPLOYER PLANS Limitations on Guaranteed Benefits § 4022.24 Benefit...

  3. 29 CFR 4022.24 - Benefit increases.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 9 2014-07-01 2014-07-01 false Benefit increases. 4022.24 Section 4022.24 Labor Regulations Relating to Labor (Continued) PENSION BENEFIT GUARANTY CORPORATION COVERAGE AND BENEFITS BENEFITS PAYABLE IN TERMINATED SINGLE-EMPLOYER PLANS Limitations on Guaranteed Benefits § 4022.24 Benefit...

  4. 29 CFR 4022.24 - Benefit increases.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 9 2011-07-01 2011-07-01 false Benefit increases. 4022.24 Section 4022.24 Labor Regulations Relating to Labor (Continued) PENSION BENEFIT GUARANTY CORPORATION COVERAGE AND BENEFITS BENEFITS PAYABLE IN TERMINATED SINGLE-EMPLOYER PLANS Limitations on Guaranteed Benefits § 4022.24 Benefit...

  5. The therapeutic misconception, beneficence, and respect.

    PubMed

    Fried, E

    2001-01-01

    In order to provide benefits to society, human medical trials must place subjects at risk of harm. This activity is thought to be justified in part by the consent of the subjects involved. But, studies have shown that most such consents are based on a therapeutic misconception (TM); the false belief of subjects that their researchers will act as their personal physicians (seeking their benefit and protecting them from harm), rather than placing them at risk of harm for the good of others. Toleration by researchers of the TM in their subjects is a form of "informational manipulation" that renders consent procedures disrespectful to subject autonomy. Consent obtained from subjects who labor under a TM is neither voluntary nor informed; as long as they have not been disabused of the TM, the action they take in enrolling in a trial is not the one they intend nor is it autonomously chosen. Changes in consent procedures should be adopted to ensure that all subjects are aware inter alia that (a) the health interests of future patients (as well as the researchers' and their sponsors' financial interests) may be more important to researchers than the interest of a subject in his or her health, and (b) normal subjects neither understand nor believe this when told. Close attention to the response of prospective subjects to this information should allow for the exclusion of all but the truly altruistic. However, the result of conscientious implementation of such policies would likely be that human medical research could no longer be conducted on more than a minimal level. PMID:12481794

  6. [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

  7. Procedures and methods of benefit assessments for medicines in Germany.

    PubMed

    Bekkering, Geertruida E; Kleijnen, Jos

    2008-11-01

    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 Quality and Efficiency

  8. Boron addition to alloys

    SciTech Connect

    Coad, B. C.

    1985-08-20

    A process for addition of boron to an alloy which involves forming a melt of the alloy and a reactive metal, selected from the group consisting of aluminum, titanium, zirconium and mixtures thereof to the melt, maintaining the resulting reactive mixture in the molten state and reacting the boric oxide with the reactive metal to convert at least a portion of the boric oxide to boron which dissolves in the resulting melt, and to convert at least portion of the reactive metal to the reactive metal oxide, which oxide remains with the resulting melt, and pouring the resulting melt into a gas stream to form a first atomized powder which is subsequently remelted with further addition of boric oxide, re-atomized, and thus reprocessed to convert essentially all the reactive metal to metal oxide to produce a powdered alloy containing specified amounts of boron.

  9. Tackifier for addition polyimides

    NASA Technical Reports Server (NTRS)

    Butler, J. M.; St.clair, T. L.

    1980-01-01

    A modification to the addition polyimide, LaRC-160, was prepared to improve tack and drape and increase prepeg out-time. The essentially solventless, high viscosity laminating resin is synthesized from low cost liquid monomers. The modified version takes advantage of a reactive, liquid plasticizer which is used in place of solvent and helps solve a major problem of maintaining good prepeg tack and drape, or the ability of the prepeg to adhere to adjacent plies and conform to a desired shape during the lay up process. This alternate solventless approach allows both longer life of the polymer prepeg and the processing of low void laminates. This approach appears to be applicable to all addition polyimide systems.

  10. 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.

  11. [Biologically active food additives].

    PubMed

    Velichko, M A; Shevchenko, V P

    1998-07-01

    More than half out of 40 projects for the medical science development by the year of 2000 have been connected with the bio-active edible additives that are called "the food of XXI century", non-pharmacological means for many diseases. Most of these additives--nutricevtics and parapharmacevtics--are intended for the enrichment of food rations for the sick or healthy people. The ecologicaly safest and most effective are combined domestic adaptogens with immuno-modulating and antioxidating action that give anabolic and stimulating effect,--"leveton", "phytoton" and "adapton". The MKTs-229 tablets are residue discharge means. For atherosclerosis and general adiposis they recommend "tsar tablets" and "aiconol (ikhtien)"--on the base of cod-liver oil or "splat" made out of seaweed (algae). All these preparations have been clinically tested and received hygiene certificates from the Institute of Dietology of the Russian Academy of Medical Science. PMID:9752776

  12. Evolving Role of Ultrasound in Therapeutic Injections of the Upper Extremity.

    PubMed

    Wilson, David J; Scully, William F; Rawlings, John M

    2015-11-01

    Ultrasound machines are creating more refined pictures and becoming more user-friendly and readily accessible. As a result, ultrasound is being increasingly used for therapeutic purposes. One example involves the use of ultrasound guidance in musculoskeletal interventional procedures, such as joint injections, tendon sheath injections, and peripheral nerve blocks. Technical considerations and therapeutic results have been described for multiple locations about the upper extremities, with varying levels of success. The implementation of ultrasound-guided injections in the orthopedist's clinic has therapeutic, financial, and provider role implications. Given these potential benefits, orthopedic providers, both in practice and residency, would benefit from increased exposure and education in ultrasound use. Ultrasound provides the benefit of real-time, dynamic imaging without the radiation exposure of fluoroscopy, and ultrasound-guided injections can be performed in the office, as opposed to the operating room, which is frequently required when using fluoroscopy. A basic knowledge of the principles and terms used in ultrasound is required. With these simple principles, a practitioner can review techniques for specific areas of the musculoskeletal system and begin using ultrasound to guide injections. Many locations for diagnostic and/or therapeutic injections in the upper extremities have improved accuracy and benefit with the use of ultrasound vs blind techniques, although a few have not been shown to have a significant difference in the literature. The educational and professional implications can be significant, but these potential benefits need to be carefully weighed against costs by each orthopedic practice. PMID:26558666

  13. 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.

  14. Hydrocarbon fuel additive

    SciTech Connect

    Ambrogio, S.

    1989-02-28

    This patent describes the method of fuel storage or combustion, wherein the fuel supply contains small amounts of water, the step of adding to the fuel supply an additive comprising a blend of a hydrophilic agent chosen from the group of ethylene glycol, n-butyl alcohol, and cellosolve in the range of 22-37% by weight; ethoxylated nonylphenol in the range of 26-35% by weight; nonylphenol polyethylene glycol ether in the range of 32-43% by weight.

  15. 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. PMID:24729671

  16. Therapeutic efficacy of vincamine in dementia.

    PubMed

    Fischhof, P K; Möslinger-Gehmayr, R; Herrmann, W M; Friedmann, A; Russmann, D L

    1996-01-01

    This trial was performed to investigate the therapeutic efficacy of vincamine in the treatment of primary degenerative and vascular dementia. 152 male and female patients aged between 50 and 85 years from two psychogeriatric centers and two nursing homes were initially included in the trial and screened for eligibility. 142 patients completed the trial. Clinical diagnosis was established according to DSM-III-R criteria. Allocation of the patients to the primary degenerative dementia of the Alzheimer type (DAT) group or the multi-infarct dementia (MID) group was based on computed tomography scans, electroencephalographic findings and the Hachinski Ischemic Score. In a 12-week double-blind treatment either 30 mg vincamine or placebo was given twice daily. Confirmatory statistics included item 2 of the Clinical Global Impression (CGI), the total score of the Sandoz Clinical Assessment Geriatric (SCAG) scale, the subscale 'need for help' of the nurse's rating of geriatric patients (Beurteilungsskala für geriatrische Patienten; BGP) and the total score of the Short Cognitive Performance Test (Syndrom-Kurztest; SKT). In addition, data on tolerance and on therapy response were evaluated based on descriptive statistics. The therapeutic efficacy of vincamine was clearly demonstrated by confirmatory analysis as the drug was statistically significantly superior to placebo in all four target variables. The clinical relevance of the outcome was further underlined by the results of the responder analysis of the variables SCAG, BGP and SKT. Based on the results of this trial, it can be accepted that the therapeutic effect of vincamine is superior to placebo in patients with mild to moderate dementia of degenerative and vascular etiologies. PMID:8884757

  17. SATPdb: a database of structurally annotated therapeutic peptides.

    PubMed

    Singh, Sandeep; Chaudhary, Kumardeep; Dhanda, Sandeep Kumar; Bhalla, Sherry; Usmani, Salman Sadullah; Gautam, Ankur; Tuknait, Abhishek; Agrawal, Piyush; Mathur, Deepika; Raghava, Gajendra P S

    2016-01-01

    SATPdb (http://crdd.osdd.net/raghava/satpdb/) is a database of structurally annotated therapeutic peptides, curated from 22 public domain peptide databases/datasets including 9 of our own. The current version holds 19192 unique experimentally validated therapeutic peptide sequences having length between 2 and 50 amino acids. It covers peptides having natural, non-natural and modified residues. These peptides were systematically grouped into 10 categories based on their major function or therapeutic property like 1099 anticancer, 10585 antimicrobial, 1642 drug delivery and 1698 antihypertensive peptides. We assigned or annotated structure of these therapeutic peptides using structural databases (Protein Data Bank) and state-of-the-art structure prediction methods like I-TASSER, HHsearch and PEPstrMOD. In addition, SATPdb facilitates users in performing various tasks that include: (i) structure and sequence similarity search, (ii) peptide browsing based on their function and properties, (iii) identification of moonlighting peptides and (iv) searching of peptides having desired structure and therapeutic activities. We hope this database will be useful for researchers working in the field of peptide-based therapeutics. PMID:26527728

  18. SATPdb: a database of structurally annotated therapeutic peptides

    PubMed Central

    Singh, Sandeep; Chaudhary, Kumardeep; Dhanda, Sandeep Kumar; Bhalla, Sherry; Usmani, Salman Sadullah; Gautam, Ankur; Tuknait, Abhishek; Agrawal, Piyush; Mathur, Deepika; Raghava, Gajendra P.S.

    2016-01-01

    SATPdb (http://crdd.osdd.net/raghava/satpdb/) is a database of structurally annotated therapeutic peptides, curated from 22 public domain peptide databases/datasets including 9 of our own. The current version holds 19192 unique experimentally validated therapeutic peptide sequences having length between 2 and 50 amino acids. It covers peptides having natural, non-natural and modified residues. These peptides were systematically grouped into 10 categories based on their major function or therapeutic property like 1099 anticancer, 10585 antimicrobial, 1642 drug delivery and 1698 antihypertensive peptides. We assigned or annotated structure of these therapeutic peptides using structural databases (Protein Data Bank) and state-of-the-art structure prediction methods like I-TASSER, HHsearch and PEPstrMOD. In addition, SATPdb facilitates users in performing various tasks that include: (i) structure and sequence similarity search, (ii) peptide browsing based on their function and properties, (iii) identification of moonlighting peptides and (iv) searching of peptides having desired structure and therapeutic activities. We hope this database will be useful for researchers working in the field of peptide-based therapeutics. PMID:26527728

  19. Therapeutic engagement: Perspectives from adolescents with eating disorders.

    PubMed

    Zaitsoff, Shannon; Yiu, Angelina; Pullmer, Rachelle; Geller, Josie; Menna, Rosanne

    2015-12-15

    This study aimed to identify factors that adolescents with eating disorders (ED) consider important for therapeutic engagement, and to examine similarities and differences in the number of identified factors considered important for therapeutic engagement based on diagnostic status and readiness and motivation to change dietary restriction behaviors. Treatment seeking adolescent females (n=34, Mage=16.33, SD=1.34) with an ED were prompted to generate responses to 4 constructs related to therapeutic engagement: (1) Trust, (2) Agreement on therapeutic goals, (3) Confidence in Ability to Change and (4) Feelings of Inclusion in therapeutic decisions. A coding scheme for each construct was developed using a random sample of responses, and each category within a construct was rated as present or absent for each participant. Frequencies and percentages of participants who reported each category within each construct are reported. Additionally, findings indicate that the top two out of three categories reported within each construct were the same between participants with AN versus EDNOS, and between participants high and low in readiness and motivation to change dietary restriction behaviors. This study is a first step in identifying aspects of therapeutic engagement that are important to adolescents with ED, which may differ from adults. PMID:26493323

  20. New Therapeutic Approaches for Advanced Gastrointestinal Stromal Tumors (GISTs)

    PubMed Central

    Somaiah, Neeta

    2010-01-01

    Synopsis The management of advanced GIST is increasingly complex due to imatinib refractory disease. Primary resistance to imatinib is uncommon, and most patients progress after development of additional genetic changes. This article reviews management strategies including surgical approaches, local modalities for progressive liver metastases, as well as novel therapeutic agents. PMID:19248977