WorldWideScience

Sample records for promising clinical potential

  1. Hsp90 as a Gatekeeper of Tumor Angiogenesis: Clinical Promise and Potential Pitfalls

    Directory of Open Access Journals (Sweden)

    J. E. Bohonowych

    2010-01-01

    Full Text Available Tumor vascularization is an essential modulator of early tumor growth, progression, and therapeutic outcome. Although antiangiogenic treatments appear promising, intrinsic and acquired tumor resistance contributes to treatment failure. Clinical inhibition of the molecular chaperone heat shock protein 90 (Hsp90 provides an opportunity to target multiple aspects of this signaling resiliency, which may elicit more robust and enduring tumor repression relative to effects elicited by specifically targeted agents. This review highlights several primary effectors of angiogenesis modulated by Hsp90 and describes the clinical challenges posed by the redundant circuitry of these pathways. The four main topics addressed include (1 Hsp90-mediated regulation of HIF/VEGF signaling, (2 chaperone-dependent regulation of HIF-independent VEGF-mediated angiogenesis, (3 Hsp90-dependent targeting of key proangiogenic receptor tyrosine kinases and modulation of drug resistance, and (4 consideration of factors such as tumor microenvironment that pose several challenges for the clinical efficacy of anti-angiogenic therapy and Hsp90-targeted strategies.

  2. TH-C-BRF-01: The Promise and Potential Pitfalls of Deformable Image Registration in Clinical Practice

    International Nuclear Information System (INIS)

    Brock, K; Oldham, M; Cai, J; Pouliot, J

    2014-01-01

    Accurate and robust deformable image registration (DIR) is a key enabling technique in the clinical realization of two approaches for advancing radiation therapy treatment efficacy: adaptive radiation therapy and treatment response assessment. Currently there are a wide variety of DIR methods including the categories of splines, optical/diffusion, free-form, and biomechanical algorithms. All methods aim to translate information between image sets (including multi-modal data) in the presence of spatial deformation of tissues. However, recent research has shown that different DIR algorithms can yield substantially different results for the same reference deformation, and that DIR performance can be site and application dependent. As a result, errors can occur, and subsequent patient treatment can be compromised. There is a clear need for greater understanding of appropriate use of DIR techniques, as well as effective methods of validation, evaluation, and improvement. In this session, we will review the state-of-the-art concerning DIR development, clinical application, and performance evaluation. Novel DIR methods and evaluating technologies will be reviewed. Learning Objectives: To understand the underlying principles and physics of current DIR techniques To explore potential clinical applications and areas of high impact for DIR To investigate sources of uncertainty, appropriate usage, and methods for validating and evaluating DIR performance

  3. Hyperthermia: Clinical promise and current challenges

    International Nuclear Information System (INIS)

    Kapp, D.S.

    1987-01-01

    Local-regional hyperthermia (HT) when used in conjunction with radiation therapy (XRT), has been shown in numerous clinical trials to result in considerable improvement in response rates and local tumor control rates when compared with treatment by XRT alone. Although considerable progress has been made in understanding the biological basis for hyperthermia induced cytotoxicity and radiosensitization, additional research remains in establishing the optimal treatment schedules for the clinical utilization of HT-XRT. The number of HT treatments; the sequencing of HT and XRT; the frequency of administration of HT; and the ideal temperature-time parameters all remain to be better defined for the clinical setting. The role of tumor blood flow on the thermal distributions also warrants further investigation. In addition, considerable effort is needed to improve hyperthermia equipment in order to provide more uniform therapeutic temperature distributions (temperatures ≥42.5%C). Better heating equipment is particularly needed for the treatment of deep seeted tumors. Pertinent clinical literature will be presented summarizing the clinical promise of hyperthermia and the above mentioned clinical challenges

  4. Technology's Potential, Promise for Enhancing Student Learning

    Science.gov (United States)

    Golden, Michael

    2004-01-01

    Technology is a tool that has the potential to empower educational leaders at all levels--whether they are superintendents, principals, teachers, board members or state officials--as well as to redefine what education means in the 21st century. Technology provides more accurate information and advanced communication capabilities. Technology can be…

  5. Modelling of potentially promising SARS protease inhibitors

    International Nuclear Information System (INIS)

    Plewczynski, Dariusz; Hoffmann, Marcin; Grotthuss, Marcin von; Knizewski, Lukasz; Rychewski, Leszek; Eitner, Krystian; Ginalski, Krzysztof

    2007-01-01

    In many cases, at the beginning of a high throughput screening experiment some information about active molecules is already available. Active compounds (such as substrate analogues, natural products and inhibitors of related proteins) are often identified in low throughput validation studies on a biochemical target. Sometimes the additional structural information is also available from crystallographic studies on protein and ligand complexes. In addition, the structural or sequence similarity of various protein targets yields a novel possibility for drug discovery. Co-crystallized compounds from homologous proteins can be used to design leads for a new target without co-crystallized ligands. In this paper we evaluate how far such an approach can be used in a real drug campaign, with severe acute respiratory syndrome (SARS) coronavirus providing an example. Our method is able to construct small molecules as plausible inhibitors solely on the basis of the set of ligands from crystallized complexes of a protein target, and other proteins from its structurally homologous family. The accuracy and sensitivity of the method are estimated here by the subsequent use of an electronic high throughput screening flexible docking algorithm. The best performing ligands are then used for a very restrictive similarity search for potential inhibitors of the SARS protease within the million compounds from the Ligand.Info small molecule meta-database. The selected molecules can be passed on for further experimental validation

  6. Modelling of potentially promising SARS protease inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Plewczynski, Dariusz [Interdisciplinary Centre for Mathematical and Computational Modelling, ICM, Warsaw University, Pawinskiego 5a Street, 02-106 Warsaw (Poland); Hoffmann, Marcin [BioInfoBank Institute, Limanowskiego 24A/16, 60-744 Poznan (Poland); Grotthuss, Marcin von [BioInfoBank Institute, Limanowskiego 24A/16, 60-744 Poznan (Poland); Knizewski, Lukasz [Interdisciplinary Centre for Mathematical and Computational Modelling, ICM, Warsaw University, Pawinskiego 5a Street, 02-106 Warsaw (Poland); Rychewski, Leszek [BioInfoBank Institute, Limanowskiego 24A/16, 60-744 Poznan (Poland); Eitner, Krystian [BioInfoBank Institute, Limanowskiego 24A/16, 60-744 Poznan (Poland); Ginalski, Krzysztof [Interdisciplinary Centre for Mathematical and Computational Modelling, ICM, Warsaw University, Pawinskiego 5a Street, 02-106 Warsaw (Poland)

    2007-07-18

    In many cases, at the beginning of a high throughput screening experiment some information about active molecules is already available. Active compounds (such as substrate analogues, natural products and inhibitors of related proteins) are often identified in low throughput validation studies on a biochemical target. Sometimes the additional structural information is also available from crystallographic studies on protein and ligand complexes. In addition, the structural or sequence similarity of various protein targets yields a novel possibility for drug discovery. Co-crystallized compounds from homologous proteins can be used to design leads for a new target without co-crystallized ligands. In this paper we evaluate how far such an approach can be used in a real drug campaign, with severe acute respiratory syndrome (SARS) coronavirus providing an example. Our method is able to construct small molecules as plausible inhibitors solely on the basis of the set of ligands from crystallized complexes of a protein target, and other proteins from its structurally homologous family. The accuracy and sensitivity of the method are estimated here by the subsequent use of an electronic high throughput screening flexible docking algorithm. The best performing ligands are then used for a very restrictive similarity search for potential inhibitors of the SARS protease within the million compounds from the Ligand.Info small molecule meta-database. The selected molecules can be passed on for further experimental validation.

  7. Multivariate meta-analysis: Potential and promise

    Science.gov (United States)

    Jackson, Dan; Riley, Richard; White, Ian R

    2011-01-01

    The multivariate random effects model is a generalization of the standard univariate model. Multivariate meta-analysis is becoming more commonly used and the techniques and related computer software, although continually under development, are now in place. In order to raise awareness of the multivariate methods, and discuss their advantages and disadvantages, we organized a one day ‘Multivariate meta-analysis’ event at the Royal Statistical Society. In addition to disseminating the most recent developments, we also received an abundance of comments, concerns, insights, critiques and encouragement. This article provides a balanced account of the day's discourse. By giving others the opportunity to respond to our assessment, we hope to ensure that the various view points and opinions are aired before multivariate meta-analysis simply becomes another widely used de facto method without any proper consideration of it by the medical statistics community. We describe the areas of application that multivariate meta-analysis has found, the methods available, the difficulties typically encountered and the arguments for and against the multivariate methods, using four representative but contrasting examples. We conclude that the multivariate methods can be useful, and in particular can provide estimates with better statistical properties, but also that these benefits come at the price of making more assumptions which do not result in better inference in every case. Although there is evidence that multivariate meta-analysis has considerable potential, it must be even more carefully applied than its univariate counterpart in practice. Copyright © 2011 John Wiley & Sons, Ltd. PMID:21268052

  8. Big data analytics in healthcare: promise and potential.

    Science.gov (United States)

    Raghupathi, Wullianallur; Raghupathi, Viju

    2014-01-01

    To describe the promise and potential of big data analytics in healthcare. The paper describes the nascent field of big data analytics in healthcare, discusses the benefits, outlines an architectural framework and methodology, describes examples reported in the literature, briefly discusses the challenges, and offers conclusions. The paper provides a broad overview of big data analytics for healthcare researchers and practitioners. Big data analytics in healthcare is evolving into a promising field for providing insight from very large data sets and improving outcomes while reducing costs. Its potential is great; however there remain challenges to overcome.

  9. Monoclonal Antibody Shows Promise as Potential Therapeutic for MERS | Poster

    Science.gov (United States)

    A monoclonal antibody has proven effective in preventing Middle Eastern Respiratory Syndrome (MERS) in lab animals, suggesting further development as a potential intervention for the deadly disease in humans, according to new research. MERS is a newly emerged coronavirus first detected in humans in 2012. Most cases have occurred in the Middle East, but the disease has appeared elsewhere. In all, MERS has infected more than 1,700 individuals and killed more than 600, according to the World Health Organization. No vaccines or antiviral therapies currently exist. Several candidate vaccines are being developed, and some have been tested in animal models, a prerequisite to human clinical trials.

  10. Gold nanoparticles in breast cancer treatment: Promise and potential pitfalls

    Science.gov (United States)

    Lee, Jihyoun; Chatterjee, Dev Kumar; Lee, Min Hyuk; Krishnan, Sunil

    2014-01-01

    Despite remarkable achievements in the treatment of breast cancer, some obstacles still remain. Gold nanoparticles may prove valuable in addressing these problems owing to their unique characteristics, including their enhanced permeability and retention in tumor tissue, their light absorbance and surface plasmon resonance in near-infrared light, their interaction with radiation to generate secondary electrons, and their ability to be conjugated with drugs or other agents. Herein, we discuss some basic concepts of gold nanoparticles, and early results from studies regarding their use in breast cancer, including toxicity and side effects. We also discuss these particles’ potential clinical applications. PMID:24556077

  11. Pharmacogenetics in drug regulation: promise, potential and pitfalls

    Science.gov (United States)

    Shah, Rashmi R

    2005-01-01

    Pharmacogenetic factors operate at pharmacokinetic as well as pharmacodynamic levels—the two components of the dose–response curve of a drug. Polymorphisms in drug metabolizing enzymes, transporters and/or pharmacological targets of drugs may profoundly influence the dose–response relationship between individuals. For some drugs, although retrospective data from case studies suggests that these polymorphisms are frequently associated with adverse drug reactions or failure of efficacy, the clinical utility of such data remains unproven. There is, therefore, an urgent need for prospective data to determine whether pre-treatment genotyping can improve therapy. Various regulatory guidelines already recommend exploration of the role of genetic factors when investigating a drug for its pharmacokinetics, pharmacodynamics, dose–response relationship and drug interaction potential. Arising from the global heterogeneity in the frequency of variant alleles, regulatory guidelines also require the sponsors to provide additional information, usually pharmacogenetic bridging data, to determine whether data from one ethnic population can be extrapolated to another. At present, sponsors explore pharmacogenetic influences in early clinical pharmacokinetic studies but rarely do they carry the findings forward when designing dose–response studies or pivotal studies. When appropriate, regulatory authorities include genotype-specific recommendations in the prescribing information. Sometimes, this may include the need to adjust a dose in some genotypes under specific circumstances. Detailed references to pharmacogenetics in prescribing information and pharmacogenetically based prescribing in routine therapeutics will require robust prospective data from well-designed studies. With greater integration of pharmacogenetics in drug development, regulatory authorities expect to receive more detailed genetic data. This is likely to complicate the drug evaluation process as well as

  12. Clinical laboratory analytics: Challenges and promise for an emerging discipline

    Directory of Open Access Journals (Sweden)

    Brian H Shirts

    2015-01-01

    Full Text Available The clinical laboratory is a major source of health care data. Increasingly these data are being integrated with other data to inform health system-wide actions meant to improve diagnostic test utilization, service efficiency, and "meaningful use." The Academy of Clinical Laboratory Physicians and Scientists hosted a satellite meeting on clinical laboratory analytics in conjunction with their annual meeting on May 29, 2014 in San Francisco. There were 80 registrants for the clinical laboratory analytics meeting. The meeting featured short presentations on current trends in clinical laboratory analytics and several panel discussions on data science in laboratory medicine, laboratory data and its role in the larger healthcare system, integrating laboratory analytics, and data sharing for collaborative analytics. One main goal of meeting was to have an open forum of leaders that work with the "big data" clinical laboratories produce. This article summarizes the proceedings of the meeting and content discussed.

  13. OSTEOARTHRITIS: CURRENT CLINICAL CONCEPT AND SOME PROMISING THERAPEUTIC APPROACHES

    Directory of Open Access Journals (Sweden)

    A. E. Karateev

    2018-01-01

    Full Text Available In recent years, there has been a trend toward changing the clinical concept of osteoarthritis (OA. This disease has been considered as an age-related disease and the long-term result of a current pathological process for a very long time. However, many experts are now inclined to consider it necessary to identify the early, pre-X-ray stage of OA, when adequate treatment may not only halt the progression, but also achieve the regression of joint structural changes. This review deals with a number of pathogenetic and clinical aspects of the early stages of OA, which are important for timely diagnosis and pathogenetic therapy choice. It also considers some therapeutic approaches, both a "classic" and recently actively discussed methods for using platelet-rich plasma and autologous chondrocyte transplantation.

  14. Clinical PET/CT imaging. Promises and misconceptions

    International Nuclear Information System (INIS)

    Czernin, J.; Auerbach, M.A.

    2005-01-01

    PET/CT is now established as the most important imaging tool in oncology. PET/CT stages and restages cancer with a higher accuracy than PET or CT alone. The sometimes irrational approach to combine state of the art PET with the highest end CT devices should give way to a more reasonable equipment design tailored towards the specific clinical indications in well-defined patient populations. The continuing success of molecular PET/CT now depends more upon advances in molecular imaging with the introduction of targeted imaging probes for individualized therapy approaches in cancer patients and less upon technological advances of imaging equipment. (orig.)

  15. Promising Potential of Dietary (Poly)Phenolic Compounds in the Prevention and Treatment of Diabetes Mellitus.

    Science.gov (United States)

    Dias, Tania R; Alves, Marco G; Casal, Susana; Oliveira, Pedro F; Silva, Branca M

    2017-01-01

    The incidence of diabetes mellitus (DM) is reaching alarming proportions worldwide, particularly because it is increasingly affecting younger people. This reflects the sedentary lifestyle and inappropriate dietary habits, especially due to the advent of processed foods in modern societies. Thus, unsurprisingly, the first medical recommendation to patients with clinically evident DM is the alteration in their eating behaviour, particularly regarding carbohydrates and total energy intake. Despite individual and cultural preferences, human diet makes available a large amount of phytochemicals with therapeutic potential. Phenolic compounds are the most abundant class of phytochemicals in edible plants, fruits and beverages. These compounds have strong antioxidant and anti-inflammatory activities that have been associated with specific features of their chemical structure. Among others, such properties make them promising antidiabetic agents and several mechanisms of action have already been proposed. Herein, we discuss the recent findings on the potential of dietary phenolic compounds for the prevention and/or treatment of (pre)diabetes, and associated complications. A broad range of studies supports the innate potential of phenolic compounds to protect against DM-associated deleterious effects. Their antidiabetic activity has been demonstrated by: i) regulation of carbohydrate metabolism; ii) improvement of glucose uptake; iii) protection of pancreatic β-cells; iv) enhancement of insulin action and v) regulation of crucial signalling pathways to cell homeostasis. Dietary phenolic compounds constitute an easy, safe and cost-effective way to combat the worrying scenario of DM. The interesting particularities of phenolic compounds reinforce the implementation of a (poly)phenolic-rich nutritional regime, not only for (pre)diabetic patients, but also for non-diabetic people. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  16. MicroRNA: a new and promising potential biomarker for diagnosis and prognosis of ovarian cancer

    International Nuclear Information System (INIS)

    Pal, Manish K.; Jaiswar, Shyam P.; Dwivedi, Vinaya N.; Tripathi, Amit K.; Dwivedi, Ashish; Sankhwar, Pushplata

    2015-01-01

    Epithelial ovarian cancer (EOC) is the leading cause of death among all gynecological malignancies. Despite the technological and medical advances over the past four decades, such as the development of several biological markers (mRNA and proteins biomarkers), the mortality rate of ovarian cancer remains a challenge because of its late diagnosis, which is specifically attributed to low specificities and sensitivities. Under this compulsive scenario, recent advances in expression biology have shifted in identifying and developing specific and sensitive biomarkers, such as microRNAs (miRNAs) for cancer diagnosis and prognosis. MiRNAs are a novel class of small non-coding RNAs that deregulate gene expression at the posttranscriptional level, either by translational repression or by mRNA degradation. These mechanisms may be involved in a complex cascade of cellular events associated with the pathophysiology of many types of cancer. MiRNAs are easily detectable in tissue and blood samples of cancer patients. Therefore, miRNAs hold good promise as potential biomarkers in ovarian cancer. In this review, we attempted to provide a comprehensive profile of key miRNAs involved in ovarian carcinoma to establish miRNAs as more reliable non-invasive clinical biomarkers for early detection of ovarian cancer compared with protein and DNA biomarkers

  17. Toward cardiovascular MRI at 7 T: clinical needs, technical solutions and research promises

    International Nuclear Information System (INIS)

    Niendorf, Thoralf; Sodickson, Daniel K.; Krombach, Gabriele A.; Schulz-Menger, Jeanette

    2010-01-01

    To consider potential clinical needs, technical solutions and research promises of ultrahigh-field strength cardiovascular MR (CMR). A literature review is given, surveying advantages and disadvantages of CMR at ultrahigh fields (UHF). Key concepts, emerging technologies, practical considerations and applications of UHF CMR are provided. Examples of UHF CMR imaging strategies and their added value are demonstrated, including the numerous unsolved problems. A concluding section explores future directions in UHF CMR. UHF CMR can be regarded as one of the most challenging MRI applications. Image quality achievable at UHF is not always exclusively defined by signal-to-noise considerations. Some of the inherent advantages of UHF MRI are offset by practical challenges. But UHF CMR can boast advantages over its kindred lower field counterparts by trading the traits of high magnetic fields for increased temporal and/or spatial resolution. CMR at ultrahigh-field strengths is a powerful motivator, since speed and signal may be invested to overcome the fundamental constraints that continue to hamper traditional CMR. If practical challenges can be overcome, UHF CMR will help to open the door to new approaches for basic science and clinical research. (orig.)

  18. Promising Metabolite Profiles in the Plasma and CSF of Early Clinical Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    Daniel Stoessel

    2018-03-01

    Full Text Available Parkinson's disease (PD shows high heterogeneity with regard to the underlying molecular pathogenesis involving multiple pathways and mechanisms. Diagnosis is still challenging and rests entirely on clinical features. Thus, there is an urgent need for robust diagnostic biofluid markers. Untargeted metabolomics allows establishing low-molecular compound biomarkers in a wide range of complex diseases by the measurement of various molecular classes in biofluids such as blood plasma, serum, and cerebrospinal fluid (CSF. Here, we applied untargeted high-resolution mass spectrometry to determine plasma and CSF metabolite profiles. We semiquantitatively determined small-molecule levels (≤1.5 kDa in the plasma and CSF from early PD patients (disease duration 0–4 years; n = 80 and 40, respectively, and sex- and age-matched controls (n = 76 and 38, respectively. We performed statistical analyses utilizing partial least square and random forest analysis with a 70/30 training and testing split approach, leading to the identification of 20 promising plasma and 14 CSF metabolites. These metabolites differentiated the test set with an AUC of 0.8 (plasma and 0.9 (CSF. Characteristics of the metabolites indicate perturbations in the glycerophospholipid, sphingolipid, and amino acid metabolism in PD, which underscores the high power of metabolomic approaches. Further studies will enable to develop a potential metabolite-based biomarker panel specific for PD.

  19. Clinical manufacturing of CAR T cells: foundation of a promising therapy

    Science.gov (United States)

    Wang, Xiuyan; Rivière, Isabelle

    2016-01-01

    The treatment of cancer patients with autologous T cells expressing a chimeric antigen receptor (CAR) is one of the most promising adoptive cellular therapy approaches. Reproducible manufacturing of high-quality, clinical-grade CAR-T cell products is a prerequisite for the wide application of this technology. Product quality needs to be built-in within every step of the manufacturing process. We summarize herein the requirements and logistics to be considered, as well as the state of the art manufacturing platforms available. CAR-T cell therapy may be on the verge of becoming standard of care for a few clinical indications. Yet, many challenges pertaining to manufacturing standardization and product characterization remain to be overcome in order to achieve broad usage and eventual commercialization of this therapeutic modality. PMID:27347557

  20. Clinical manufacturing of CAR T cells: foundation of a promising therapy

    Directory of Open Access Journals (Sweden)

    Xiuyan Wang

    2016-01-01

    Full Text Available The treatment of cancer patients with autologous T cells expressing a chimeric antigen receptor (CAR is one of the most promising adoptive cellular therapy approaches. Reproducible manufacturing of high-quality, clinical-grade CAR-T cell products is a prerequisite for the wide application of this technology. Product quality needs to be built-in within every step of the manufacturing process. We summarize herein the requirements and logistics to be considered, as well as the state of the art manufacturing platforms available. CAR-T cell therapy may be on the verge of becoming standard of care for a few clinical indications. Yet, many challenges pertaining to manufacturing standardization and product characterization remain to be overcome in order to achieve broad usage and eventual commercialization of this therapeutic modality.

  1. Molecular epigenetics in the management of ovarian cancer: Are we investigating a rational clinical promise?

    Directory of Open Access Journals (Sweden)

    Ha eNguyen

    2014-04-01

    Full Text Available Epigenetics is essentially a phenotypical change in gene expression without any alteration of the DNA sequence; the emergence of epigenetics in cancer research and mainstream oncology is fueling new hope. However, it is not yet known whether this knowledge will translate to improved clinical management of ovarian cancer. In this malignancy, women are still undergoing chemotherapy similar to what was approved in 1978, which to this day represents one of the biggest breakthroughs for treating ovarian cancer. While liquid tumors are benefitting from epigenetically-related therapies, solid tumors like ovarian cancer are not (yet?. Herein we will review the science of molecular epigenetics, especially DNA methylation, histone modifications and microRNA, but also include transcription factors since they, too, are important in ovarian cancer. Preclinical and clinical research on the role of epigenetic modifications is summarized as well. Sadly, ovarian cancer remains an idiopathic disease, for the most part, and there are many areas of patient management which could benefit from improved technology. This review will also highlight the evidence suggesting that epigenetics may have preclinical utility in pharmacology and clinical applications for prognosis and diagnosis. Lastly, drugs currently in clinical trials (i.e. histone deacetylase inhibitors are discussed along with the promise for epigenetics in the exploitation of chemoresistance. Whether epigenetics will ultimately be the answer to better management in ovarian cancer is currently unknown; what we have now is hope.

  2. Biomedical and Clinical Promises of Human Pluripotent Stem Cells for Neurological Disorders

    Directory of Open Access Journals (Sweden)

    Nopporn Jongkamonwiwat

    2013-01-01

    Full Text Available Neurological disorders are characterized by the chronic and progressive loss of neuronal structures and functions. There is a variability of the onsets and causes of clinical manifestations. Cell therapy has brought a new concept to overcome brain diseases, but the advancement of this therapy is limited by the demands of specialized neurons. Human pluripotent stem cells (hPSCs have been promised as a renewable resource for generating human neurons for both laboratory and clinical purposes. By the modulations of appropriate signalling pathways, desired neuron subtypes can be obtained, and induced pluripotent stem cells (iPSCs provide genetically matched neurons for treating patients. These hPSC-derived neurons can also be used for disease modeling and drug screening. Since the most urgent problem today in transplantation is the lack of suitable donor organs and tissues, the derivation of neural progenitor cells from hPSCs has opened a new avenue for regenerative medicine. In this review, we summarize the recent reports that show how to generate neural derivatives from hPSCs, and discuss the current evidence of using these cells in animal studies. We also highlight the possibilities and concerns of translating these hPSC-derived neurons for biomedical and clinical uses in order to fight against neurological disorders.

  3. Allogeneic tumor cell vaccines: the promise and limitations in clinical trials.

    Science.gov (United States)

    Srivatsan, Sanjay; Patel, Jaina M; Bozeman, Erica N; Imasuen, Imade E; He, Sara; Daniels, Danielle; Selvaraj, Periasamy

    2014-01-01

    The high mortality rate associated with cancer and its resistance to conventional treatments such as radiation and chemotherapy has led to the investigation of a variety of anti-cancer immunotherapies. The development of novel immunotherapies has been bolstered by the discovery of tumor-associated antigens (TAAs), through gene sequencing and proteomics. One such immunotherapy employs established allogeneic human cancer cell lines to induce antitumor immunity in patients through TAA presentation. Allogeneic cancer immunotherapies are desirable in a clinical setting due to their ease of production and availability. This review aims to summarize clinical trials of allogeneic tumor immunotherapies in various cancer types. To date, clinical trials have shown limited success due potentially to extensive degrees of inter- and intra-tumoral heterogeneity found among cancer patients. However, these clinical results provide guidance for the rational design and creation of more effective allogeneic tumor immunotherapies for use as monotherapies or in combination with other therapies.

  4. Organotin(IV) Carboxylates as Promising Potential Drug Candidates in the Field of Cancer Chemotherapy.

    Science.gov (United States)

    Sirajuddin, Muhammad; Ali, Saqib

    2016-01-01

    Medicinal inorganic chemistry plays an important role in exploring the properties of metal ions for the designing of new drugs. The field has been stimulated by the success of cis-platin, the world best selling anticancer drug and platinum complexes with reduced toxicity, oral activity and activity against resistant tumors are currently on clinical trial. The use of cis-platin is, however, severely limited by its toxic side-effects. This has stimulated chemists to employ different strategies in the development of new metal-based anticancer agents with different mechanisms of action. The discovery of new non-covalent interactions with the classical target, DNA, was the first developing step in the treatment of cancer. The use of organometallic compounds as a medicine is very common now a days because it offers potential advantages over the more common organic-based drugs. In this article we have highlighted the anticancer activity of the organotin(IV) carboxylates published in the last few years (from 2008 to 2016). In most cases they present lower IC50 values than those of cisplatin, which indicates their high activity against the cancer cell lines. The summarized data reveal that every year new organotin(IV) carboxylate complexes are synthesized with the aim of new anticancer agent with much better results than the than the corresponding activity of cis-platin or other clinically approved drugs. In addition to the advantages of high activity, compared to the platinum compound, tin complexes are much cheaper. Thus by using organotin carboxylate for clinical medicine, cost reduction, dosage reduction and effect enhancement will be reached. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  5. The self-regulating brain and neurofeedback: Experimental science and clinical promise.

    Science.gov (United States)

    Thibault, Robert T; Lifshitz, Michael; Raz, Amir

    2016-01-01

    Neurofeedback, one of the primary examples of self-regulation, designates a collection of techniques that train the brain and help to improve its function. Since coming on the scene in the 1960s, electroencephalography-neurofeedback has become a treatment vehicle for a host of mental disorders; however, its clinical effectiveness remains controversial. Modern imaging technologies of the living human brain (e.g., real-time functional magnetic resonance imaging) and increasingly rigorous research protocols that utilize such methodologies begin to shed light on the underlying mechanisms that may facilitate more effective clinical applications. In this paper we focus on recent technological advances in the field of human brain imaging and discuss how these modern methods may influence the field of neurofeedback. Toward this end, we outline the state of the evidence and sketch out future directions to further explore the potential merits of this contentious therapeutic prospect. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. New phytochemicals as potential human anti-aging compounds: Reality, promise, and challenges.

    Science.gov (United States)

    Corrêa, Rúbia C G; Peralta, Rosane M; Haminiuk, Charles W I; Maciel, Giselle Maria; Bracht, Adelar; Ferreira, Isabel C F R

    2018-04-13

    Aging is an inevitable process influenced by genetic, lifestyle, and environmental factors. Indirect evidence shows that several phytochemicals can have anti-aging capabilities, although direct evidence in this field is still limited. This report aims to provide a critical review on aspects related to the use of novel phytochemicals as anti-aging agents, to discuss the obstacles found when performing most anti-aging study protocols in humans, and to analyze future perspectives. In addition to the extensively studied resveratrol, epicatechin, quercetin, and curcumin, new phytochemicals have been reported to act as anti-aging agents, such as the amino acid L-theanine isolated from green tea, and the lignans arctigenin and matairesinol isolated from Arctium lappa seeds. Furthermore, this review discusses the application of several new extracts rich in phytochemicals with potential use in anti-aging therapies. Finally, this review also discusses the most important biomarkers to test anti-aging interventions, the necessity of conducting epidemiological studies and the need of clinical trials with adequate study protocols for humans.

  7. Three New Escherichia coli Phages from the Human Gut Show Promising Potential for Phage Therapy.

    Directory of Open Access Journals (Sweden)

    Marion Dalmasso

    Full Text Available With the emergence of multi-drug resistant bacteria the use of bacteriophages (phages is gaining renewed interest as promising anti-microbial agents. The aim of this study was to isolate and characterize phages from human fecal samples. Three new coliphages, ɸAPCEc01, ɸAPCEc02 and ɸAPCEc03, were isolated. Their phenotypic and genomic characteristics, and lytic activity against biofilm, and in combination with ciprofloxacin, were investigated. All three phages reduced the growth of E. coli strain DPC6051 at multiplicity of infection (MOI between 10-3 and 105. A cocktail of all three phages completely inhibited the growth of E. coli. The phage cocktail also reduced biofilm formation and prevented the emergence of phage-resistant mutants which occurred with single phage. When combined with ciprofloxacin, phage alone or in cocktail inhibited the growth of E. coli and prevented the emergence of resistant mutants. These three new phages are promising biocontrol agents for E. coli infections.

  8. Phosphatidylcholines as regulators of glucose and lipid homeostasis: Promises and potential risks

    NARCIS (Netherlands)

    Hohenester, Simon; Beuers, Ulrich

    2011-01-01

    Nuclear hormone receptors regulate diverse metabolic pathways and the orphan nuclear receptor LRH-1 (also known as NR5A2) regulates bile acid biosynthesis. Structural studies have identified phospholipids as potential LRH-1 ligands, but their functional relevance is unclear. Here we show that an

  9. Mentoring for Young People Leaving Foster Care: Promise and Potential Pitfalls

    Science.gov (United States)

    Spencer, Renee; Collins, Mary Elizabeth; Ward, Rolanda; Smashnaya, Svetlana

    2010-01-01

    Mentoring for youths transitioning out of the foster care system has been growing in popularity as mentoring programs have enjoyed unprecedented growth in recent years. However, the existing empirical literature on the conditions associated with more effective youth mentoring relationships and the potential for harm in their absence should give us…

  10. Moringa oleifera with promising neuronal survival and neurite outgrowth promoting potentials.

    Science.gov (United States)

    Hannan, Md Abdul; Kang, Ji-Young; Mohibbullah, Md; Hong, Yong-Ki; Lee, Hyunsook; Choi, Jae-Suk; Choi, In Soon; Moon, Il Soo

    2014-02-27

    Moringa oleifera Lam. (Moringaceae) by virtue of its high nutritional as well as ethnomedical values has been gaining profound interest both in nutrition and medicinal research. The leaf of this plant is used in ayurvedic medicine to treat paralysis, nervous debility and other nerve disorders. In addition, research evidence also suggests the nootropic as well as neuroprotective roles of Moringa oleifera leaf in animal models. The aim of the present study was to evaluate the effect of Moringa oleifera leaf in the primary hippocampal neurons regarding its neurotrophic and neuroprotective properties. The primary culture of embryonic hippocampal neurons was incubated with the ethanol extract of Moringa oleifera leaf (MOE). After an indicated time, cultures were either stained directly with a lipophilic dye, DiO, or fixed and immunolabeled to visualize the neuronal morphology. Morphometric analyses for neurite maturation and synaptogenesis were performed using Image J software. Neuronal viability was evaluated using trypan blue exclusion and lactate dehydrogenase assays. MOE promoted neurite outgrowth in a concentration-dependent manner with an optimal concentration of 30 μg/mL. As a very initial effect, MOE significantly promoted the earlier stages of neuronal differentiation. Subsequently, MOE significantly increased the number and length of dendrites, the length of axon, and the number and length of both dendrite and axonal branches, and eventually facilitated synaptogenesis. The β-carotene, one major compound of MOE, promoted neuritogensis, but the increase was not comparable with the effect of MOE. In addition, MOE supported neuronal survival by protecting neurons from naturally occurring cell death in vitro. Our findings indicate that MOE promotes axodendritic maturation as well as provides neuroprotection suggesting a promising pharmacological importance of this nutritionally and ethnomedically important plant for the well-being of nervous system. Copyright

  11. Are research papers reporting results from nutrigenetics clinical research a potential source of biohype?

    Science.gov (United States)

    Stenne, R; Hurlimann, T; Godard, Béatrice

    2012-01-01

    Nutrigenetics is a promising field, but the achievability of expected benefits is challenged by the methodological limitations that are associated with clinical research in that field. The mere existence of these limitations suggests that promises about potential outcomes may be premature. Thus, benefits claimed in scientific journal articles in which these limitations are not acknowledged might stimulate biohype. This article aims to examine whether nutrigenetics clinical research articles are a potential source of biohype. Of the 173 articles identified, 16 contained claims in which clinical applications were extrapolated from study results. The methodological limitations being incompletely acknowledged, these articles could potentially be a source of biohype.

  12. The Promise and Potential Perils of Big Data for Advancing Symptom Management Research in Populations at Risk for Health Disparities.

    Science.gov (United States)

    Bakken, Suzanne; Reame, Nancy

    2016-01-01

    Symptom management research is a core area of nursing science and one of the priorities for the National Institute of Nursing Research, which specifically focuses on understanding the biological and behavioral aspects of symptoms such as pain and fatigue, with the goal of developing new knowledge and new strategies for improving patient health and quality of life. The types and volume of data related to the symptom experience, symptom management strategies, and outcomes are increasingly accessible for research. Traditional data streams are now complemented by consumer-generated (i.e., quantified self) and "omic" data streams. Thus, the data available for symptom science can be considered big data. The purposes of this chapter are to (a) briefly summarize the current drivers for the use of big data in research; (b) describe the promise of big data and associated data science methods for advancing symptom management research; (c) explicate the potential perils of big data and data science from the perspective of the ethical principles of autonomy, beneficence, and justice; and (d) illustrate strategies for balancing the promise and the perils of big data through a case study of a community at high risk for health disparities. Big data and associated data science methods offer the promise of multidimensional data sources and new methods to address significant research gaps in symptom management. If nurse scientists wish to apply big data and data science methods to advance symptom management research and promote health equity, they must carefully consider both the promise and perils.

  13. Arbuscular mycorrhizal association enhances drought tolerance potential of promising bioenergy grass (Saccharum arundinaceum retz.).

    Science.gov (United States)

    Mirshad, P P; Puthur, Jos T

    2016-07-01

    The influence of arbuscular mycorrhizal fungi (AMF) (Glomus spp.) on some physiological and biochemical characteristics of bioenergy grass Saccharum arundinaceum subjected to drought stress was studied. The symbiotic association of Glomus spp. was established with S. arundinaceum, a potential bioenergy grass as evident from the increase in percentage of root infection and distribution frequency of vesicles when compared with non-arbuscular mycorrhizal plants. AMF-treated plants exhibited an enhanced accumulation of osmolytes such as sugars and proline and also increased protein content under drought. AMF association significantly increased the accumulation of non-enzymatic antioxidants like phenols, ascorbate and glutathione as well as enhanced the activities of antioxidant enzymes such as SOD (superoxide dismutase), APX (ascorbate peroxidase) and GPX (guaiacol peroxidase) resulting in reduced lipid peroxidation in S. arundinaceum. AMF symbiosis also ameliorated the drought-induced reduction of total chlorophyll content and activities of photosystem I and II. The maximum quantum efficiency of PS II (F v/F m) and potential photochemical efficiency (F v/F o) were higher in AMF plants as compared to non-AMF plants under drought stress. These results indicate that AMF association alleviate drought stress in S. arundinaceum by the accumulation of osmolytes and non-enzymatic antioxidants and enhanced activities of antioxidant enzymes, and hence, the photosynthetic efficiency is improved resulting in increased biomass production. AMF association with energy grasses also improves the acclimatization of S. arundinaceum for growing in marginal lands of drought-affected soils.

  14. A road for a promising future for China's primates: The potential for restoration.

    Science.gov (United States)

    Chapman, Colin A

    2018-07-18

    China is one of the most dynamic countries of the world and it shelters some amazing levels of biodiversity, including some very special primate species. However, primarily as a result of forest loss, most of which occurred in historical times, approximately 70% of China's primate species have less than 3 000 individuals. Here I evaluate one road for future conservation/development that could produce very positive gains for China's primates; namely forest restoration. I argue that for a large scale restoration project to be possible two conditions must be met; the right societal conditions must exist and the right knowledge must be in hand. This evaluation suggests that the restoration of native forest to support many of China's primates holds great potential to advance conservation goals and to promote primate population recovery.

  15. Evaluating Potential Production of Mid-Late Maturing Minituber of Potato Cultivars and Promising Clones under Aeroponic System

    Directory of Open Access Journals (Sweden)

    D. HassanPanah

    2014-10-01

    Full Text Available This study was performed to investigate potential production of mid-late maturing promising mini-tuber clones and cultivars under aeroponic system during 2011-2013 in both laboratory and greenhouse of Ardabil Sabalan Behparvar Company. Five clones and cultivars (three promising clones 397009-3, 397082-10 and 397081-1, and two cultivars, Khavaran and Agria were evaluated in completely randomized designs with three replications. During growing period and after harvesting the crop some important traits like plant height, main stem number per plant, mini-tuber number and weight per square meter, mean mini-tuber weight per square meter and storability of mini-tubers were measured. Analysis of variance showed that mini-tuber number and weight per square meter, mean mini-tuber weight per square meter, plant height and main stem number per plant among clones and cultivars were significantly different. The mid-late maturity promising clones of 397081-1 and 397009-3 produced higher mini-tuber number per square meter (2766 and 2141 mini-tubers, respectively, mini-tuber weight per square meter (11400 and 16500 g, respectively than the remaining types. Mid-late maturity promising clone of 397081-1 also produced higher mean mini-tuber weight per square meter (5.59 g and plant height (174 cm as compared with the others. The differences per square meter in the number of mini-tuber of mid-late maturing promising clones of 397081-1 and 397009-3 with Agria cultivar were about 1166 and 541, respectively. Mean mini-tuber weight per square meter in aeroponic system was 6.16 grams.

  16. The missing link between submarine volcano and promising geothermal potential in Jinshan, Northern Taiwan

    Science.gov (United States)

    Wang, S. C.; Hutchings, L.; Chang, C. C.; Lee, C. S.

    2017-12-01

    The Tatun volcanic group (TVG) and the Keelung submarine volcano (KSV) are active volcanoes and surrounding three nuclear plant sites in north Taiwan. The famous Jinshan-Wanli hot springs locates between TVG and KSV, moreover, the geochemical anomalies of acidic boiling springs on the seacoast infer that the origin is from magmatic fluids, sea water and meteoric water mixture, strongly implying that mantle fluids ascends into the shallow crust. The evidence for a magma chamber, submarine volcano, and boiling springs have a close spatial relationship. Based on UNECE specifications to Geothermal Energy Resources (2016), the Jinshan-Wanli geothermal area could be classified as Known Geothermal Energy Source for geothermal direct use and Potential Geothermal Energy Source for conventional geothermal system. High resolution reservoir exploration and modeling in Jinshan-Wanli geothermal area is developing for drilling risk mitigation. The geothermal team of National Taiwan Ocean University and local experts are cooperating for further exploration drilling and geothermal source evaluation. Keywords: geothermal resource evaluation, Jinshan-Wanli geothermal area, submarine volcano

  17. Engaging First-year University Students in Research: Promise, Potentials, and Pitfalls

    Directory of Open Access Journals (Sweden)

    Sarah L. Sangster

    2016-06-01

    Full Text Available In 2014, the Undergraduate Research Initiative at the University of Saskatchewan implemented a pilot project to organize, support, and promote curriculum-based research experience as an integral aspect of participating first-year courses. The framework for the course-based initiative was the research arc; usually in groups, students in these classes would develop a research question, investigate it using discipline-appropriate methodologies, and disseminate the results. Nine classes (Agriculture, Animal Bioscience, Environmental Science, Women’s and Gender Studies, Psychology, Kinesiology, and Interdisciplinary Studies participated in this program pilot. There were four key agents in the program: faculty instructors, research coaches, students in participating first-year classes, and university administrative staff. This preliminary evaluation of the pilot suggests that first-year undergraduate research experiences have potential to benefit the undergraduate student participants as well as the faculty and research coaches involved. The primary benefits that faculty reported experiencing included an increased interest in ways to engage learners, reexamination of and reflection on their teaching strategies, the pragmatic support of a research coach helping with their work load, and an invigoration of their research. The primary benefits to research coaches included enhancement of their professional skills, experience in lesson planning and facilitation, CV building, and an ideology shift in how to best facilitate learning for undergraduate students. The most prominent benefits for undergraduate students appeared to be that they gained a better idea about how researchers think and work, that they increased their understanding of how research works, and that their own research and professional skills had improved. Early, bottom-up evaluation identified characteristics of implementation that appear to best facilitate achievement of the initiative

  18. Clinical Case Vignettes: A Promising Tool to Assess Competence in the Management of Agitation.

    Science.gov (United States)

    Sowden, Gillian L; Vestal, Heather S; Stoklosa, Joseph B; Valcourt, Stephanie C; Peabody, John W; Keary, Christopher J; Nejad, Shamim H; Caminis, Argyro; Huffman, Jeff C

    2017-06-01

    While standardized patients (SPs) remain the gold standard for assessing clinical competence in a standardized setting, clinical case vignettes that allow free-text, open-ended written responses are more resource- and time-efficient assessment tools. It remains unknown, however, whether this is a valid method for assessing competence in the management of agitation. Twenty-six psychiatry residents partook in a randomized controlled study evaluating a simulation-based teaching intervention on the management of agitated patients. Competence in the management of agitation was assessed using three separate modalities: simulation with SPs, open-ended clinical vignettes, and self-report questionnaires. Performance on clinical vignettes correlated significantly with SP-based assessments (r = 0.59, p = 0.002); self-report questionnaires that assessed one's own ability to manage agitation did not correlate with SP-based assessments (r = -0.06, p = 0.77). Standardized clinical vignettes may be a simple, time-efficient, and valid tool for assessing residents' competence in the management of agitation.

  19. Health information exchanges--Unfulfilled promise as a data source for clinical research.

    Science.gov (United States)

    Parker, Carol; Weiner, Michael; Reeves, Mathew

    2016-03-01

    To determine the use of health information exchange organizations (HIEs) to support and conduct clinical research. This scoping review included US-based studies published between January 2003 and March 2014 that used data from an HIE to address at least one of three categories of research: clinical or epidemiological research, financial evaluation, or utilization of health services. Eligibility was not restricted to research on HIEs. Studies with research questions outside of the evaluation of HIEs themselves were sought. Eighteen articles met final study inclusion criteria from an initial list of 847 hits. Fifteen studies addressed a clinical or epidemiological research question, 6 addressed a financial consideration, and 8 addressed a utilization issue. Considerable overlap was found among the research categories: 13 articles addressed more than one category. Of the eighteen included studies, only two used HIE data to answer a research objective that was NOT specific to HIE use. Research designs were varied and ranged from observational studies, such as cohort and cross-sectional studies, to randomized trials. The 18 articles represent the involvement of a small number of HIEs; 7 of the studies were from a single HIE. This review demonstrates that HIE-provided information is available and used to answer clinical or epidemiological, financial, or utilization-based research questions; however, the majority of the studies using HIE data are done with the primary goal of evaluating the use and impact of HIEs on health care delivery and outcomes. As HIEs mature and become integrated parts of the health care industry, the authors anticipate that fewer studies will be published that describe or validate the role of HIEs, and more will use HIEs as multi-institutional data sources for conducting clinical research and improving health services and clinical outcomes. Articles identified in this review indicate the limited extent that HIE data are being used for clinical

  20. Premise and promise of mesenchymal stem cell-based therapies in clinical vascularized composite allotransplantation.

    Science.gov (United States)

    Schweizer, Riccardo; Gorantla, Vijay S; Plock, Jan A

    2015-12-01

    Over the past decade, clinical vascularized composite allotransplantation (VCA) has enabled functional and quality of life restoration in a wide range of indications secondary to devastating tissue loss. However, the spectre of toxicity and long-term complications of chronic immunosuppression has curtailed the momentum of VCA. This study summarizes the literature evidence behind successful mesenchymal stem cell (MSC)-based cell therapies highlighting their multipronged immunomodulatory, restorative and regenerative characteristics with special emphasis towards VCA applications. Experimental and clinical studies in solid organs and VCA have confirmed that MSCs facilitate immunosuppression-free allograft survival or tolerance, stimulate peripheral nerve regeneration, attenuate ischaemia-reperfusion injury, and improve tissue healing after surgery. It has been hypothesized that MSC-induced long-term operational tolerance in experimental VCA is mediated by induction of mixed donor-specific chimerism and regulatory T-cell mechanisms. All these characteristics of MSCs could thus help expand the scope and clinical feasibility of VCA. Cellular therapies, especially those focusing on MSCs, are emerging in solid organ transplantation including VCA. Although some clinical trials have begun to assess the effects of MSCs in solid organ transplantation, much scientific domain remains uncharted, especially for VCA.

  1. Interprofessional Clinical Ethics Education: The Promise of Cross-Disciplinary Problem-Based Learning.

    Science.gov (United States)

    Kurtz, Melissa J; Starbird, Laura E

    2016-09-01

    A review of Lin et al.'s pilot study exploring the effects of an interprofessional, problem-based learning clinical ethics curriculum on Taiwanese medical and nursing students' attitudes towards interprofessional collaboration highlights the benefits of interprofessional collaboration and offers insight into how problem-based learning might be universally applied in ethics education. Interprofessional collaboration is an ideal approach for exploring ethical dilemmas because it involves all relevant professionals in discussions about ethical values that arise in patient care. Interprofessional ethics collaboration is challenging to implement, however, given time constraints and organizational and practice demands. Nevertheless, we suggest that when professionals collaborate, they can collectively express greater commitment to the patient. We also suggest future research avenues that can explore additional benefits of interprofessional collaboration in clinical ethics. © 2016 American Medical Association. All Rights Reserved.

  2. Curcumin as a clinically-promising anti-cancer agent: pharmacokinetics and drug interactions.

    Science.gov (United States)

    Adiwidjaja, Jeffry; McLachlan, Andrew J; Boddy, Alan V

    2017-09-01

    Curcumin has been extensively studied for its anti-cancer properties. While a diverse array of in vitro and preclinical research support the prospect of curcumin use as an anti-cancer therapeutic, most human studies have failed to meet the intended clinical expectation. Poor systemic availability of orally-administered curcumin may account for this disparity. Areas covered: This descriptive review aims to concisely summarise available clinical studies investigating curcumin pharmacokinetics when administered in different formulations. A critical analysis of pharmacokinetic- and pharmacodynamic-based interactions of curcumin with concomitantly administered drugs is also provided. Expert opinion: The encouraging clinical results of curcumin administration are currently limited to people with colorectal cancer, given that sufficient curcumin concentrations persist in colonic mucosa. Higher parent curcumin systemic exposure, which can be achieved by several newer formulations, has important implications for optimal treatment of cancers other than those in gastrointestinal tract. Curcumin-drug pharmacokinetic interactions are also almost exclusively in the enterocytes, owing to extensive first pass metabolism and poor curcumin bioavailability. Greater scope of these interactions, i.e. modulation of the systemic elimination of co-administered drugs, may be expected from more-bioavailable curcumin formulations. Further studies are still warranted, especially with newer formulations to support the inclusion of curcumin in cancer therapy regimens.

  3. Systematic Evaluation of Promising Clinical Trials-Gene Silencing for the Treatment of Glioblastoma.

    Science.gov (United States)

    Karaarslan, Numan; Yilmaz, Ibrahim; Ozbek, Hanefi; Caliskan, Tezcan; Topuk, Savas; Sirin, Duygu Yasar; Ates, Ozkan

    2018-04-06

    The aim of this study was to systematically investigate the role of artificial small interfering RNA (siRNA) molecules in glioblastoma treatment and to give a detailed overview of the literature concerning studies performed in this field worldwide in the last 31 years. Articles about clinical trials conducted between December 1, 1949 and November 8, 2017, were identified from the Cochrane Collaboration, the Cochrane Library, Ovid MEDLINE, ProQuest, the National Library of Medicine, and PubMed electronic databases, using the terms "post transcriptional gene silencing," "small interfering RNA," "siRNA," and "glioblastoma," either individually or combined (\\"OR\\" and \\"AND"), without language and country restrictions. Articles that met the examination criteria were included in the study. After descriptive statistical evaluation, the results were reported in frequency (%). After scanning 2.752 articles, five articles were found that met the research criteria. Examination of full texts of the five identified articles provided no sufficient evidence for research conducted with regard to the use of gene silencing via siRNAs in glioblastoma treatment. To be able to evaluate the clinical use of siRNAs, there is an urgent need for in-vivo studies and for trials with randomized, controlled, and clinical designs that provide long-term functional outcomes.

  4. An access to a library of novel triterpene derivatives with a promising pharmacological potential by Ugi and Passerini multicomponent reactions.

    Science.gov (United States)

    Wiemann, Jana; Heller, Lucie; Csuk, René

    2018-04-25

    The promising combination of natural product leads and their derivatization by isocyanide-based multicomponent reactions (IMCRs) has gained interest in accessing diversity-oriented libraries with auspicious pharmacological potential. Therefore, a set of 34 Ugi and 3 Passerini products was successfully synthesized starting from naturally occurring triterpenoids, i.e. oleanolic acid (OA) and maslinic acid (MA), followed by a biological evaluation of the novel α-acylamino carboxamides and the α-acyloxy carboxamides in colorimetric SRB assays to determine their cytotoxic potential. Especially, the MA-Ugi products 6a, 6b and 7b showed a remarkable cytotoxicity for A2780 ovarian carcinoma cells in a low μM range. Compounds 6a and 7b induced programmed cell death in part through the apoptosis pathway. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  5. Nano-technology contributions towards the development of high performance radioisotope generators: The future promise to meet the continuing clinical demand.

    Science.gov (United States)

    Sakr, Tamer M; Nawar, Mohamed F; Fasih, T W; El-Bayoumy, S; Abd El-Rehim, H A

    2017-11-01

    Nanostructured materials attracted considerable attention because of its high surface area to volume ratio resulting from their nano-scale dimensions. This class of sorbents is expected to have a potential impact on enhancement the efficacy of radioisotope generators for diagnostic and therapeutic applications in nuclear medicine. This review provides a summary on the importance of nanostructured materials as effective sorbents for the development of clinical-scale radioisotope generators and outlining the assessment of recent developments, key challenges and promising access to the near future. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Satellite provided customer promises services, a forecast of potential domestic demand through the year 2000. Volume 4: Sensitivity analysis

    Science.gov (United States)

    Kratochvil, D.; Bowyer, J.; Bhushan, C.; Steinnagel, K.; Kaushal, D.; Al-Kinani, G.

    1984-03-01

    The overall purpose was to forecast the potential United States domestic telecommunications demand for satellite provided customer promises voice, data and video services through the year 2000, so that this information on service demand would be available to aid in NASA program planning. To accomplish this overall purpose the following objectives were achieved: (1) development of a forecast of the total domestic telecommunications demand; (2) identification of that portion of the telecommunications demand suitable for transmission by satellite systems; (3) identification of that portion of the satellite market addressable by consumer promises service (CPS) systems; (4) identification of that portion of the satellite market addressable by Ka-band CPS system; and (5) postulation of a Ka-band CPS network on a nationwide and local level. The approach employed included the use of a variety of forecasting models, a parametric cost model, a market distribution model and a network optimization model. Forecasts were developed for: 1980, 1990, and 2000; voice, data and video services; terrestrial and satellite delivery modes; and C, Ku and Ka-bands.

  7. The potential of infant fMRI research and the study of early life stress as a promising exemplar

    Directory of Open Access Journals (Sweden)

    Alice M. Graham

    2015-04-01

    Full Text Available Functional magnetic resonance imaging (fMRI research with infants and toddlers has increased rapidly over the past decade, and provided a unique window into early brain development. In the current report, we review the state of the literature, which has established the feasibility and utility of task-based fMRI and resting state functional connectivity MRI (rs-fcMRI during early periods of brain maturation. These methodologies have been successfully applied beginning in the neonatal period to increase understanding of how the brain both responds to environmental stimuli, and becomes organized into large-scale functional systems that support complex behaviors. We discuss the methodological challenges posed by this promising area of research. We also highlight that despite these challenges, early work indicates a strong potential for these methods to influence multiple research domains. As an example, we focus on the study of early life stress and its influence on brain development and mental health outcomes. We illustrate the promise of these methodologies for building on, and making important contributions to, the existing literature in this field.

  8. Radiotherapy-induced xerostomia, pre-clinical promise of LMS-611.

    Science.gov (United States)

    Paterson, Claire; Caldwell, B; Porteous, S; McLean, A; Messow, C M; Thomson, M

    2016-02-01

    Radiotherapy-induced xerostomia (RIX) is the most common permanent side effect of radiotherapy (RT) to the head and neck (H&N). There is no effective topical treatment. LMS-611 is a mimetic of a natural lamellar body which prevents thick secretions like saliva from congesting organs. The primary objective of this study was to assess saliva properties before and during RT to the H&N. The secondary objectives were to re-assess saliva properties with the addition of LMS-611, measure inter-patient variability, correlate patient-reported symptoms with laboratory measurements and design subsequent first-in-human clinical trial of LMS-611. Patients with H&N cancer receiving RT as primary treatment were recruited. Patients completed the Groningen RIX (GRIX) questionnaire and provided saliva samples at baseline and weeks 2, 4 and 6 of RT. Saliva adhesiveness and viscosity were tested by measuring time taken to travel 5 cm down an inclined plane. Thirty patients were enrolled. The inclined plane test (IPT) results (s) were as follows: baseline 31.3, week 2 49.7, week 4 51.1 and week 6 55.7. Wide inter-patient variability was seen at baseline. GRIX scores increased as RT progressed. Spearman rank correlation coefficient of inclined plane tests with GRIX scores was -0.06 at baseline, 0.25 at week 2, 0.12 at week 4 and 0.08 at week 6. LMS-611 concentrations of 10 and 20 mg/ml significantly reduced IPT times on saliva samples. Saliva becomes more visco-adhesive and RIX worsens as RT progresses. There is little correlation between objective and subjective measures of RIX. The addition of LMS-611 to thick, sticky saliva restores its fluidity ex vivo. This warrants in vivo analysis of the effect of LMS-611 upon RIX.

  9. From Retreat Center to Clinic to Boardroom? Perils and Promises of the Modern Mindfulness Movement

    Directory of Open Access Journals (Sweden)

    Norman A. S. Farb

    2014-11-01

    Full Text Available From its venerable Buddhist roots, mindfulness training (MT has spread rapidly across the globe in the past few decades due to its strong salutary claim, i.e., the notion that meditation practice is an efficacious means for self-improvement. However, concerns have arisen that the appropriation of MT techniques from classical Buddhist tradition into modern secular practice has diluted the benefits of these practices. The “great danger” to the movement is that inadequately adapted MT techniques, combined with unreasonable inflation of expectations regarding MT’s benefits, may undermine MT’s true potential to effect positive change in the world. And yet, these concerns can be mitigated by consideration of the salutary claim as a persistent “quality check” on MT efficacy. It is argued that scientific investigation can take an important role in delineating the necessary characteristics for fulfilling mindfulness’ salutary claim, as well as identifying contraindicated techniques and risk factors for training. By accepting that we cannot control the spread of MT into commercial domains, researchers may still work to distinguish “right” from “wrong” mindfulness through empirical study. In this way, modern science may help to realize the salutary claim and even contribute to classical Buddhist conceptions of mindfulness, advancing our understanding of how best to promote well-being.

  10. Potential benefits and risks of clinical xenotransplantation

    Directory of Open Access Journals (Sweden)

    Cooper DKC

    2012-07-01

    Full Text Available David KC Cooper,1 David Ayares21Thomas E Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA, USA; 2Revivicor, Blacksburg, VA, USAAbstract: The transplantation of organs and cells from pigs into humans could overcome the critical and continuing problem of the lack of availability of deceased human organs and cells for clinical transplantation. Developments in the genetic engineering of pigs have enabled considerable progress to be made in the experimental laboratory in overcoming the immune barriers to successful xenotransplantation. With regard to pig organ xenotransplantation, antibody- and cell-mediated rejection have largely been overcome, and the current major barrier is the development of coagulation dysregulation. This is believed to be due to a combination of immune activation of the vascular endothelial cells of the graft and molecular incompatibilities between the pig and primate coagulation–anticoagulation systems. Pigs with new genetic modifications specifically directed to this problem are now becoming available. With regard to less complex tissues, such as islets (for the treatment of diabetes, neuronal cells (for the treatment of Parkinson's disease, and corneas, the remaining barriers are less problematic, and graft survival in nonhuman primate models extends for >1 year in all three cases. In planning the initial clinical trials, consideration will be concentrated on the risk–benefit ratio, based to a large extent on the results of preclinical studies in nonhuman primates. If the benefit to the patient is anticipated to be high, eg, insulin-independent control of glycemia, and the potential risks low, eg, minimal risk of transfer of a porcine infectious agent, then a clinical trial would be justified.Keywords: infection, pigs, genetically-engineered, xenotransplantation, islets, xenotransplantation, organs

  11. USING MOBILE PHONES TO PROMOTE LIFE SKILLS EDUCATION AMONG OPEN SCHOOLING STUDENTS: Promises, Possibilities, and Potential Strategies

    Directory of Open Access Journals (Sweden)

    Pradeep Kumar MISRA

    2013-07-01

    Full Text Available Across the globe, life skills education has been usually developed as part of a school initiative designed to support the healthy psychosocial development of children and adolescents. In other side, formal education system not always provides young people with good opportunities to become confident and realize their potentials. In this back drop, the biggest challenge is to identify the best strategies for providing effective life skills education to those many children who never attend secondary school or reach an age of high vulnerability and risk taking behaviour in the years immediately before reaching secondary school. Considering the situation that in different parts of the world, majority of the youths is having a mobile or will have a mobile soon, the researcher is of the view that mobile phones can be a viable option to offer life skills education to open schooling students coming from different cultural and social settings and backgrounds. Following this approach, present paper mainly discusses about: promises offered by mobile phones for life skills education; possibilities for using mobile phones as an effective, efficient and economical option for offering life skills education; and potential strategies to offer mobile phones supported life skills education to open schooling students.

  12. Toxicology and clinical potential of nanoparticles

    Science.gov (United States)

    Yildirimer, Lara; Thanh, Nguyen T.K.; Loizidou, Marilena; Seifalian, Alexander M.

    2011-01-01

    Summary In recent years, nanoparticles (NPs) have increasingly found practical applications in technology, research and medicine. The small particle size coupled to their unique chemical and physical properties is thought to underlie their exploitable biomedical activities. Here, we review current toxicity studies of NPs with clinical potential. Mechanisms of cytotoxicity are discussed and the problem of extrapolating knowledge gained from cell-based studies into a human scenario is highlighted. The so-called ‘proof-of-principle’ approach, whereby ultra-high NP concentrations are used to ensure cytotoxicity, is evaluated on the basis of two considerations; firstly, from a scientific perspective, the concentrations used are in no way related to the actual doses required which, in many instances, discourages further vital investigations. Secondly, these inaccurate results cast doubt on the science of nanomedicine and thus, quite dangerously, encourage unnecessary alarm in the public. In this context, the discrepancies between in vitro and in vivo results are described along with the need for a unifying protocol for reliable and realistic toxicity reports. PMID:23293661

  13. Promising approaches to circumvent the blood-brain barrier: progress, pitfalls and clinical prospects in brain cancer.

    Science.gov (United States)

    Papademetriou, Iason T; Porter, Tyrone

    2015-01-01

    Brain drug delivery is a major challenge for therapy of central nervous system (CNS) diseases. Biochemical modifications of drugs or drug nanocarriers, methods of local delivery, and blood-brain barrier (BBB) disruption with focused ultrasound and microbubbles are promising approaches which enhance transport or bypass the BBB. These approaches are discussed in the context of brain cancer as an example in CNS drug development. Targeting to receptors enabling transport across the BBB offers noninvasive delivery of small molecule and biological cancer therapeutics. Local delivery methods enable high dose delivery while avoiding systemic exposure. BBB disruption with focused ultrasound and microbubbles offers local and noninvasive treatment. Clinical trials show the prospects of these technologies and point to challenges for the future.

  14. Identification of potentially safe promising fungal cell factories for the production of polyketide natural food colorants using chemotaxonomic rationale

    Directory of Open Access Journals (Sweden)

    Frisvad Jens C

    2009-04-01

    of chemotaxonomic tools and a priori knowledge of fungal extrolites is a rational approach towards selection of fungal polyketide pigment producers considering the enormous chemical diversity and biodiversity of ascomycetous fungi. This rationale could be very handy for the selection of potentially safe fungal cell factories not only for polyketide pigments but also for the other industrially important polyketides; the molecular and genetic basis for the biosynthesis of which has not yet been examined in detail. In addition, 4 out of the 10 chemotaxonomically selected promising Penicillium strains were shown to produce extracellular pigments in the liquid media using a solid support indicating future cell factory possibilities for polyketide natural food colorants.

  15. Natural killer cells as a promising tool to tackle cancer-A review of sources, methodologies, and potentials.

    Science.gov (United States)

    Preethy, Senthilkumar; Dedeepiya, Vidyasagar Devaprasad; Senthilkumar, Rajappa; Rajmohan, Mathaiyan; Karthick, Ramalingam; Terunuma, Hiroshi; Abraham, Samuel J K

    2017-07-04

    Immune cell-based therapies are emerging as a promising tool to tackle malignancies, both solid tumors and selected hematological tumors. Vast experiences in literature have documented their safety and added survival benefits when such cell-based therapies are combined with the existing treatment options. Numerous methodologies of processing and in vitro expansion protocols of immune cells, such as the dendritic cells, natural killer (NK) cells, NKT cells, αβ T cells, so-called activated T lymphocytes, γδ T cells, cytotoxic T lymphocytes, and lymphokine-activated killer cells, have been reported for use in cell-based therapies. Among this handful of immune cells of significance, the NK cells stand apart from the rest for not only their direct cytotoxic ability against cancer cells but also their added advantage, which includes their capability of (i) action through both innate and adaptive immune mechanism, (ii) tackling viruses too, giving benefits in conditions where viral infections culminate in cancer, and (iii) destroying cancer stem cells, thereby preventing resistance to chemotherapy and radiotherapy. This review thoroughly analyses the sources of such NK cells, methods for expansion, and the future potentials of taking the in vitro expanded allogeneic NK cells with good cytotoxic ability as a drug for treating cancer and/or viral infection and even as a prophylactic tool for prevention of cancer after initial remission.

  16. Ten years of progress and promise of induced pluripotent stem cells: historical origins, characteristics, mechanisms, limitations, and potential applications

    Directory of Open Access Journals (Sweden)

    Adekunle Ebenezer Omole

    2018-05-01

    Full Text Available The discovery of induced pluripotent stem cells (iPSCs by Shinya Yamanaka in 2006 was heralded as a major breakthrough of the decade in stem cell research. The ability to reprogram human somatic cells to a pluripotent embryonic stem cell-like state through the ectopic expression of a combination of embryonic transcription factors was greeted with great excitement by scientists and bioethicists. The reprogramming technology offers the opportunity to generate patient-specific stem cells for modeling human diseases, drug development and screening, and individualized regenerative cell therapy. However, fundamental questions have been raised regarding the molecular mechanism of iPSCs generation, a process still poorly understood by scientists. The efficiency of reprogramming of iPSCs remains low due to the effect of various barriers to reprogramming. There is also the risk of chromosomal instability and oncogenic transformation associated with the use of viral vectors, such as retrovirus and lentivirus, which deliver the reprogramming transcription factors by integration in the host cell genome. These challenges can hinder the therapeutic prospects and promise of iPSCs and their clinical applications. Consequently, extensive studies have been done to elucidate the molecular mechanism of reprogramming and novel strategies have been identified which help to improve the efficiency of reprogramming methods and overcome the safety concerns linked with iPSC generation. Distinct barriers and enhancers of reprogramming have been elucidated, and non-integrating reprogramming methods have been reported. Here, we summarize the progress and the recent advances that have been made over the last 10 years in the iPSC field, with emphasis on the molecular mechanism of reprogramming, strategies to improve the efficiency of reprogramming, characteristics and limitations of iPSCs, and the progress made in the applications of iPSCs in the field of disease modelling

  17. Ten years of progress and promise of induced pluripotent stem cells: historical origins, characteristics, mechanisms, limitations, and potential applications.

    Science.gov (United States)

    Omole, Adekunle Ebenezer; Fakoya, Adegbenro Omotuyi John

    2018-01-01

    The discovery of induced pluripotent stem cells (iPSCs) by Shinya Yamanaka in 2006 was heralded as a major breakthrough of the decade in stem cell research. The ability to reprogram human somatic cells to a pluripotent embryonic stem cell-like state through the ectopic expression of a combination of embryonic transcription factors was greeted with great excitement by scientists and bioethicists. The reprogramming technology offers the opportunity to generate patient-specific stem cells for modeling human diseases, drug development and screening, and individualized regenerative cell therapy. However, fundamental questions have been raised regarding the molecular mechanism of iPSCs generation, a process still poorly understood by scientists. The efficiency of reprogramming of iPSCs remains low due to the effect of various barriers to reprogramming. There is also the risk of chromosomal instability and oncogenic transformation associated with the use of viral vectors, such as retrovirus and lentivirus, which deliver the reprogramming transcription factors by integration in the host cell genome. These challenges can hinder the therapeutic prospects and promise of iPSCs and their clinical applications. Consequently, extensive studies have been done to elucidate the molecular mechanism of reprogramming and novel strategies have been identified which help to improve the efficiency of reprogramming methods and overcome the safety concerns linked with iPSC generation. Distinct barriers and enhancers of reprogramming have been elucidated, and non-integrating reprogramming methods have been reported. Here, we summarize the progress and the recent advances that have been made over the last 10 years in the iPSC field, with emphasis on the molecular mechanism of reprogramming, strategies to improve the efficiency of reprogramming, characteristics and limitations of iPSCs, and the progress made in the applications of iPSCs in the field of disease modelling, drug discovery and

  18. Will dapivirine redeem the promises of anti-HIV microbicides? Overview of product design and clinical testing.

    Science.gov (United States)

    das Neves, José; Martins, João Pedro; Sarmento, Bruno

    2016-08-01

    Microbicides are being developed in order to prevent sexual transmission of HIV. Dapivirine, a non-nucleoside reverse transcriptase inhibitor, is one of the leading drug candidates in the field, currently being tested in various dosage forms, namely vaginal rings, gels, and films. In particular, a ring allowing sustained drug release for 1month is in an advanced stage of clinical testing. Two parallel phase III clinical trials are underway in sub-Saharan Africa and results are expected to be released in early 2016. This article overviews the development of dapivirine and its multiple products as potential microbicides, with particular emphasis being placed on clinical evaluation. Also, critical aspects regarding regulatory approval, manufacturing, distribution, and access are discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Fuzzy promises

    DEFF Research Database (Denmark)

    Anker, Thomas Boysen; Kappel, Klemens; Eadie, Douglas

    2012-01-01

    as narrative material to communicate self-identity. Finally, (c) we propose that brands deliver fuzzy experiential promises through effectively motivating consumers to adopt and play a social role implicitly suggested and facilitated by the brand. A promise is an inherently ethical concept and the article...... concludes with an in-depth discussion of fuzzy brand promises as two-way ethical commitments that put requirements on both brands and consumers....

  20. Bacillus subtilis spore with surface display of paramyosin from Clonorchis sinensis potentializes a promising oral vaccine candidate.

    Science.gov (United States)

    Sun, Hengchang; Lin, Zhipeng; Zhao, Lu; Chen, Tingjin; Shang, Mei; Jiang, Hongye; Tang, Zeli; Zhou, Xinyi; Shi, Mengchen; Zhou, Lina; Ren, Pengli; Qu, Honglin; Lin, Jinsi; Li, Xuerong; Xu, Jin; Huang, Yan; Yu, Xinbing

    2018-03-07

    Clonorchiasis caused by Clonorchis sinensis has become increasingly prevalent in recent years. Effective prevention strategies are urgently needed to control this food-borne infectious disease. Previous studies indicated that paramyosin of C. sinensis (CsPmy) is a potential vaccine candidate. We constructed a recombinant plasmid of PEB03-CotC-CsPmy, transformed it into Bacillus subtilis WB600 strain (B.s-CotC-CsPmy), and confirmed CsPmy expression on the spore surface by SDS-PAGE, Western blotting and immunofluorescence assay. The immune response and protective efficacy of the recombinant spore were investigated in BALB/c mice after intragastrical or intraperitoneal immunization. Additionally, biochemical enzyme activities in sera, the intestinal histopathology and gut microflora of spore-treated mice were investigated. CsPmy was successfully expressed on the spore surface and the fusion protein on the spore surface with thermostability. Specific IgG in sera and intestinal mucus were increased after intraperitoneal and intragastrical immunization. The sIgA level in intestinal mucus, feces and bile of B.s-CotC-CsPmy orally treated mice were also significantly raised. Furthermore, numerous IgA-secreting cells were detected in intestinal mucosa of intragastrically immunized mice. No inflammatory injury was observed in the intestinal tissues and there was no significant difference in levels of enzyme-indicated liver function among the groups. Additionally, the diversity and abundance of gut microbiota were not changed after oral immunization. Intragastric and intraperitoneal immunization of B.s-CotC-CsPmy spores in mice resulted in egg reduction rates of 48.3 and 51.2% after challenge infection, respectively. Liver fibrosis degree in B.s-CotC-CsPmy spores treated groups was also significantly reduced. CsPmy expressed on the spore surface maintained its immunogenicity. Both intragastrical and intraperitoneal immunization with B.s-CotC-CsPmy spores induced systemic and

  1. Optical coherence tomography: potentialities in clinical practice

    Science.gov (United States)

    Zagaynova, Elena; Gladkova, Natalia D.; Shakhov, Andrey; Terentjeva, Anna; Snopova, Ludmila B.; Kuznetzova, Irina A.; Streltzova, Olga; Shakhova, Natalia M.; Kamensky, Vladislav A.; Gelikonov, Grigory V.; Gelikonov, Valentin M.; Kuranov, Roman V.; Myakov, Alex

    2004-08-01

    Clinical studies using OCT involved 2000 patients in various fields of medicine such as gastroenterology, urology, laryngology, gynecology, dermatology, stomatology, etc. Layered high-contrast images were typical for benign epithelial conditions. OCT distinguish in mucosae: epithelium, connective tissue layer, and smooth-muscle layer. Various benign processes occurring in mucosa manifest in OCT images as changes in the epithelial height, scattering properties and the course of the basement membrane. Lack of the layered structural pattern is the main criterion for dysplastic / malignant images. In clinic: OCT data may be critical for choosing a tissue site for excisional biopsy, OCT can detect tumor borders and their linear dimensions, OCT can be used to plan a resection line in operations and to control adequacy of resection, to monitor whether reparative processes are timely and adequate. OCT sensitivity of the uterine cervix, urinary bladder and larynx is 82, 98, 77%, respectively, specificity - 78, 71, 96%, diagnostic accuracy - 81, 85, 87% with significantly good agreement index of clinicians kappa - 0.65, 0.79, 0.83 (confidence intervals: 0.57-0.73; 0.71-0.88; 0.74-0.91). Error in detection of high grade dysplasia and microinvasive cancer is 21.4% in average. Additional modification of OCT (cross-polarisation OCT, OCM), development of the procedure (biotissue compression, application of chemical agents) can improve the specificity and sensitivity of traditional modality.

  2. Pharmacogenetics: progress, pitfalls and clinical potential for coronary heart disease.

    Science.gov (United States)

    Humphries, Steve E; Hingorani, Aroon

    2006-02-01

    Much has been written about the potential of pharmacogenetic testing to inform therapy based on an individual's genetic makeup, and to decide the most effective choice of available drugs, or to avoid dangerous side effects. Currently, there is little hard data for either in the field of cardiovascular disease. The usual approach has been opportunistic use of drug trials in unrelated patients, and to look for differences in response or outcome by "candidate gene" genotype, for example genes coding for drug metabolising enzymes (activators and metabolisers), and enzymes and receptors involved in lipid metabolism, adrenergic response, etc. As with all association studies, initially promising results have often failed the test of replication in larger studies, and the relationship between the CETP Taq-I variant and response to statins has now been disproved. The strongest data to date is the report [Chasman, D.I., Posada, D., Subrahmanyan, L., Cook, N.R., Stanton Jr., V.P., Ridker, P.M., 2004. Pharmacogenetic study of statin therapy and cholesterol reduction. J. Am. Med. Assoc. 291, 2821-2827] of a poorer cholesterol-lowering response to Pravastatin in the 7% of patients carrying a certain haplotype of the HMG CoA reductase gene (14% fall versus 19%), but if this is overcome simply by a higher dose, it is of little clinical relevance. Currently, the best example of avoiding side effects is determining genotype at the CYP2C9 locus with respect of warfarin treatment, since carriers for functional variants (>20% of the population) require lower doses for optimal anticoagulation, and homozygotes, although rare, may well experience serious bleeding if given a usual dose. The full potential of this field will only be realised with much further work.

  3. Humanized CD7 nanobody-based immunotoxins exhibit promising anti-T-cell acute lymphoblastic leukemia potential.

    Science.gov (United States)

    Yu, Yuan; Li, Jialu; Zhu, Xuejun; Tang, Xiaowen; Bao, Yangyi; Sun, Xiang; Huang, Yuhui; Tian, Fang; Liu, Xiaomei; Yang, Lin

    2017-01-01

    Nanobodies, named as VHHs (variable domain of heavy chain of HCAb [heavy-chain antibodies]), are derived from heavy-chain-only antibodies that circulate in sera of camelids. Their exceptional physicochemical properties, possibility of humanization, and unique antigen recognition properties make them excellent candidates for targeted delivery of biologically active components, including immunotoxins. In our previous efforts, we have successfully generated the monovalent and bivalent CD7 nanobody-based immunotoxins, which can effectively trigger the apoptosis of CD7-positive malignant cells. To pursue the possibility of translating those immunotoxins into clinics, we humanized the nanobody sequences (designated as dhuVHH6) as well as further truncated the Pseudomonas exotoxin A (PE)-derived PE38 toxin to produce a more protease-resistant form, which is named as PE-LR, by deleting majority of PE domain II. Three new types of immunotoxins, dhuVHH6-PE38, dVHH6-PE-LR, and dhuVHH6-PE-LR, were successfully constructed. These recombinant immunotoxins were expressed in Escherichia coli and showed that nanobody immunotoxins have the benefits of easy soluble expression in a prokaryotic expression system. Flow cytometry results revealed that all immunotoxins still maintained the ability to bind specifically to CD7-positive T lymphocyte strains without binding to CD7-negative control cells. Laser scanning confocal microscopy revealed that these proteins can be endocytosed into the cytoplasm after binding with CD7-positive cells and that this phenomenon was not observed in CD7-negative cells. WST-8 experiments showed that all immunotoxins retained the highly effective and specific growth inhibition activity in CD7-positive cell lines and primary T-cell acute lymphoblastic leukemia (T-ALL) cells. Further in vivo animal model experiments showed that humanized dhuVHH6-PE38 immunotoxin can tolerate higher doses and extend the survival of NOD-Prkdc em26 Il2rg em26 Nju (NCG) mice

  4. Identification of potentially safe promising fungal cell factories for the production of polyketide natural food colorants using chemotaxonomic rationale

    DEFF Research Database (Denmark)

    Mapari, Sameer Shamsuddin; Meyer, Anne S.; Thrane, Ulf

    2009-01-01

    Background: Colorants derived from natural sources look set to overtake synthetic colorants in market value as manufacturers continue to meet the rising demand for clean label ingredients-particularly in food applications. Many ascomycetous fungi naturally synthesize and secrete pigments and thus...... has not yet been examined in detail. In addition, 4 out of the 10 chemotaxonomically selected promising Penicillium strains were shown to produce extracellular pigments in the liquid media using a solid support indicating future cell factory possibilities for polyketide natural food colorants....... provide readily available additional and/or alternative sources of natural colorants that are independent of agro-climatic conditions. With an appropriately selected fungus; using in particular chemotaxonomy as a guide, the fungal natural colorants could be produced in high yields by using the optimized...

  5. Humanized CD7 nanobody-based immunotoxins exhibit promising anti-T-cell acute lymphoblastic leukemia potential

    Directory of Open Access Journals (Sweden)

    Yu Y

    2017-03-01

    Full Text Available Yuan Yu,1–3 Jialu Li,1–3 Xuejun Zhu,4 Xiaowen Tang,2,5 Yangyi Bao,6 Xiang Sun,6 Yuhui Huang,1,2 Fang Tian,4 Xiaomei Liu,1,2 Lin Yang1–3 1The Cyrus Tang Hematology Center, 2Collaborative Innovation Center of Hematology, Soochow University, 3Suzhou Cancer Immunotherapy and Diagnosis Engineering Center, Suzhou, 4Central Laboratory, Department of Hematology, The Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing, 5Department of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, 6Department of Hematology-Oncology, The First People’s Hospital of Hefei, Hefei, People’s Republic of China Background: Nanobodies, named as VHHs (variable domain of heavy chain of HCAb [heavy-chain antibodies], are derived from heavy-chain-only antibodies that circulate in sera of camelids. Their exceptional physicochemical properties, possibility of humanization, and unique antigen recognition properties make them excellent candidates for targeted delivery of biologically active components, including immunotoxins. In our previous efforts, we have successfully generated the monovalent and bivalent CD7 nanobody-based immunotoxins, which can effectively trigger the apoptosis of CD7-positive malignant cells. To pursue the possibility of translating those immunotoxins into clinics, we humanized the nanobody sequences (designated as dhuVHH6 as well as further truncated the Pseudomonas exotoxin A (PE-derived PE38 toxin to produce a more protease-resistant form, which is named as PE-LR, by deleting majority of PE domain II. Methods and results: Three new types of immunotoxins, dhuVHH6-PE38, dVHH6-PE-LR, and dhuVHH6-PE-LR, were successfully constructed. These recombinant immunotoxins were expressed in Escherichia coli and showed that nanobody immunotoxins have the benefits of easy soluble expression in a prokaryotic expression system. Flow cytometry results revealed that

  6. Promising approaches to circumvent the blood-brain barrier: progress, pitfalls and clinical prospects in brain cancer

    OpenAIRE

    Papademetriou, Iason T; Porter, Tyrone

    2015-01-01

    Brain drug delivery is a major challenge for therapy of central nervous system (CNS) diseases. Biochemical modifications of drugs or drug nanocarriers, methods of local delivery, and blood–brain barrier (BBB) disruption with focused ultrasound and microbubbles are promising approaches which enhance transport or bypass the BBB. These approaches are discussed in the context of brain cancer as an example in CNS drug development. Targeting to receptors enabling transport across the BBB offers non...

  7. Three-Dimensional Patient-Derived In Vitro Sarcoma Models: Promising Tools for Improving Clinical Tumor Management

    Directory of Open Access Journals (Sweden)

    Manuela Gaebler

    2017-09-01

    Full Text Available Over the past decade, the development of new targeted therapeutics directed against specific molecular pathways involved in tumor cell proliferation and survival has allowed an essential improvement in carcinoma treatment. Unfortunately, the scenario is different for sarcomas, a group of malignant neoplasms originating from mesenchymal cells, for which the main therapeutic approach still consists in the combination of surgery, chemotherapy, and radiation therapy. The lack of innovative approaches in sarcoma treatment stems from the high degree of heterogeneity of this tumor type, with more that 70 different histopathological subtypes, and the limited knowledge of the molecular drivers of tumor development and progression. Currently, molecular therapies are available mainly for the treatment of gastrointestinal stromal tumor, a soft-tissue malignancy characterized by an activating mutation of the tyrosine kinase KIT. Since the first application of this approach, a strong effort has been made to understand sarcoma molecular alterations that can be potential targets for therapy. The low incidence combined with the high level of histopathological heterogeneity makes the development of clinical trials for sarcomas very challenging. For this reason, preclinical studies are needed to better understand tumor biology with the aim to develop new targeted therapeutics. Currently, these studies are mainly based on in vitro testing, since cell lines, and in particular patient-derived models, represent a reliable and easy to handle tool for investigation. In the present review, we summarize the most important models currently available in the field, focusing in particular on the three-dimensional spheroid/organoid model. This innovative approach for studying tumor biology better represents tissue architecture and cell–cell as well as cell–microenvironment crosstalk, which are fundamental steps for tumor cell proliferation and survival.

  8. Evaluating the promise and pitfalls of a potential climate change-tolerant sea urchin fishery in southern California.

    Science.gov (United States)

    Sato, Kirk N; Powell, Jackson; Rudie, Dave; Levin, Lisa A

    2018-05-01

    Marine fishery stakeholders are beginning to consider and implement adaptation strategies in the face of growing consumer demand and potential deleterious climate change impacts such as ocean warming, ocean acidification, and deoxygenation. This study investigates the potential for development of a novel climate change - tolerant sea urchin fishery in southern California based on Strongylocentrotus fragilis (pink sea urchin), a deep-sea species whose peak density was found to coincide with a current trap-based spot prawn fishery ( Pandalus platyceros ) in the 200-300-m depth range. Here we outline potential criteria for a climate change - tolerant fishery by examining the distribution, life-history attributes, and marketable qualities of S. fragilis in southern California. We provide evidence of seasonality of gonad production and demonstrate that peak gonad production occurs in the winter season. S. fragilis likely spawns in the spring season as evidenced by consistent minimum gonad indices in the spring/summer seasons across 4 years of sampling (2012-2016). The resiliency of S. fragilis to predicted future increases in acidity and decreases in oxygen was supported by high species abundance, albeit reduced relative growth rate estimates at water depths (485-510 m) subject to low oxygen (11.7-16.9 µmol kg -1 ) and pH Total (climate-tolerant fishery development in an attempt to inform future urchin fishery stakeholders.

  9. Posttransplant oxygen inhalation improves the outcome of subcutaneous islet transplantation: A promising clinical alternative to the conventional intrahepatic site.

    Science.gov (United States)

    Komatsu, H; Rawson, J; Barriga, A; Gonzalez, N; Mendez, D; Li, J; Omori, K; Kandeel, F; Mullen, Y

    2018-04-01

    Subcutaneous tissue is a promising site for islet transplantation, due to its large area and accessibility, which allows minimally invasive procedures for transplantation, graft monitoring, and removal of malignancies as needed. However, relative to the conventional intrahepatic transplantation site, the subcutaneous site requires a large number of islets to achieve engraftment success and diabetes reversal, due to hypoxia and low vascularity. We report that the efficiency of subcutaneous islet transplantation in a Lewis rat model is significantly improved by treating recipients with inhaled 50% oxygen, in conjunction with prevascularization of the graft bed by agarose-basic fibroblast growth factor. Administration of 50% oxygen increased oxygen tension in the subcutaneous site to 140 mm Hg, compared to 45 mm Hg under ambient air. In vitro, islets cultured under 140 mm Hg oxygen showed reduced central necrosis and increased insulin release, compared to those maintained in 45 mm Hg oxygen. Six hundred syngeneic islets subcutaneously transplanted into the prevascularized graft bed reversed diabetes when combined with postoperative 50% oxygen inhalation for 3 days, a number comparable to that required for intrahepatic transplantation; in the absence of oxygen treatment, diabetes was not reversed. Thus, we show oxygen inhalation to be a simple and promising approach to successfully establishing subcutaneous islet transplantation. © 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.

  10. Immunomodulatory nutraceuticals with potential clinical use for dogs and cats

    Directory of Open Access Journals (Sweden)

    Leandro Zaine

    2014-09-01

    Full Text Available The use of nutraceuticals in veterinary medicine is growing and is assumed that they could aid in clinical treatment. This review aims to describe some nutraceuticals that act on the immunity of dogs and cats and show the possible benefits as an adjuvant treatment for some diseases. The action of some yeast derivates as immunomodulators, especially the beta-glucan fraction, was already proved to occur in dogs and cats, being beneficial as an adjuvant therapy in many clinical conditions. Omega-3 polyunsatured fatty acids, possibly the mostly used nutraceuticals, can improve the condition in some diseases, such as hypertension, renal, cardiac, gastrointestinal and autoimmune diseases, arthritis and cancer. Vitamin E has antioxidant and immunomodulatory action and can aid in the treatment of dermatologic and hepatobiliar conditions. The use of carotenoids, which have similar action to vitamin E, can be of interest for being potent antioxidants and might be helpful for enhancing immune response against microorganisms and also act preventing tumors. Despite it are still needed clinical trials to better understand the real benefits of nutraceuticals supplementation in each specific disease, the comprehension of the mechanisms by which they act indicates they are promising for clinical use.

  11. Promising Biomolecules.

    Science.gov (United States)

    Oliveira, Isabel; Carvalho, Ana L; Radhouani, Hajer; Gonçalves, Cristiana; Oliveira, J Miguel; Reis, Rui L

    2018-01-01

    The osteochondral defect (OD) comprises the articular cartilage and its subchondral bone. The treatment of these lesions remains as one of the most problematic clinical issues, since these defects include different tissues, requiring distinct healing approaches. Among the growing applications of regenerative medicine, clinical articular cartilage repair has been used for two decades, and it is an effective example of translational medicine; one of the most used cell-based repair strategies includes implantation of autologous cells in degradable scaffolds such as alginate, agarose, collagen, chitosan, chondroitin sulfate, cellulose, silk fibroin, hyaluronic acid, and gelatin, among others. Concerning the repair of osteochondral defects, tissue engineering and regenerative medicine started to design single- or bi-phased scaffold constructs, often containing hydroxyapatite-collagen composites, usually used as a bone substitute. Biomolecules such as natural and synthetic have been explored to recreate the cartilage-bone interface through multilayered biomimetic scaffolds. In this chapter, a succinct description about the most relevant natural and synthetic biomolecules used on cartilage and bone repair, describing the procedures to obtain these biomolecules, their chemical structure, common modifications to improve its characteristics, and also their application in the biomedical fields, is given.

  12. ENRICH: A promising oncology nurse training program to implement ASCO clinical practice guidelines on fertility for AYA cancer patients.

    Science.gov (United States)

    Vadaparampil, Susan T; Gwede, Clement K; Meade, Cathy; Kelvin, Joanne; Reich, Richard R; Reinecke, Joyce; Bowman, Meghan; Sehovic, Ivana; Quinn, Gwendolyn P

    2016-11-01

    We describe the impact of ENRICH (Educating Nurses about Reproductive Issues in Cancer Healthcare), a web-based communication-skill-building curriculum for oncology nurses regarding AYA fertility and other reproductive health issues. Participants completed an 8-week course that incorporated didactic content, case studies, and interactive learning. Each learner completed a pre- and post-test assessing knowledge and a 6-month follow-up survey assessing learner behaviors and institutional changes. Out of 77 participants, the majority (72%) scored higher on the post-test. Fifty-four participants completed the follow-up survey: 41% reviewed current institutional practices, 20% formed a committee, and 37% gathered patient materials or financial resources (22%). Participants also reported new policies (30%), in-service education (37%), new patient education materials (26%), a patient navigator role (28%), and workplace collaborations with reproductive specialists (46%). ENRICH improved nurses' knowledge and involvement in activities addressing fertility needs of oncology patients. Our study provides a readily accessible model to prepare oncology nurses to integrate American Society of Clinical Oncology guidelines and improve Quality Oncology Practice Initiative measures related to fertility. Nurses will be better prepared to discuss important survivorship issues related to fertility and reproductive health, leading to improved quality of life outcomes for AYAs. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  13. Breath acetone as a potential marker in clinical practice.

    Science.gov (United States)

    Ruzsányi, Veronika; Péter Kalapos, Miklós

    2017-06-01

    In recent decades, two facts have changed the opinion of researchers about the function of acetone in humans. Firstly, it has turned out that acetone cannot be regarded as simply a waste product of metabolism, because there are several pathways in which acetone is produced or broken down. Secondly, methods have emerged making possible its detection in exhaled breath, thereby offering an attractive alternative to investigation of blood and urine samples. From a clinical point of view the measurement of breath acetone levels is important, but there are limitations to its wide application. These limitations can be divided into two classes, technical and biological limits. The technical limits include the storage of samples, detection threshold, standardization of clinical settings, and the price of instruments. When considering the biological ranges of acetone, personal factors such as race, age, gender, weight, food consumption, medication, illicit drugs, and even profession/class have to be taken into account to use concentration information for disorders. In some diseases such as diabetes mellitus and lung cancer, as well as in nutrition-related behavior such as starvation and ketogenic diet, breath acetone has been extensively examined. At the same time, there is a lack of investigations in other cases in which ketosis is also evident, such as in alcoholism or an inborn error of metabolism. In summary, the detection of acetone in exhaled breath is a useful and promising tool for diagnosis and it can be used as a marker to follow the effectiveness of treatments in some disorders. However, further endeavors are needed for clarification of the exact distribution of acetone in different body compartments and evaluation of its complex role in humans, especially in those cases in which a ketotic state also occurs.

  14. Molecular biology of breast cancer stem cells: potential clinical applications.

    Science.gov (United States)

    Nguyen, Nam P; Almeida, Fabio S; Chi, Alex; Nguyen, Ly M; Cohen, Deirdre; Karlsson, Ulf; Vinh-Hung, Vincent

    2010-10-01

    Breast cancer stem cells (CSC) have been postulated recently as responsible for failure of breast cancer treatment. The purpose of this study is to review breast CSCs molecular biology with respect to their mechanism of resistance to conventional therapy, and to develop treatment strategies that may improve survival of breast cancer patients. A literature search has identified in vitro and in vivo studies of breast CSCs. Breast CSCs overexpress breast cancer resistance protein (BCRP) which allows cancer cells to transport actively chemotherapy agents out of the cells. Radioresistance is modulated through activation of Wnt signaling pathway and overexpression of genes coding for glutathione. Lapatinib can selectively target HER-2 positive breast CSCs and improves disease-free survival in these patients. Metformin may target basal type breast CSCs. Parthenolide and oncolytic viruses are promising targeting agents for breast CSCs. Future clinical trials for breast cancer should include anti-cancer stem cells targeting agents in addition to conventional chemotherapy. Hypofractionation radiotherapy may be indicated for residual disease post chemotherapy. 2010 Elsevier Ltd. All rights reserved.

  15. Updates on ultrasound research in implant dentistry: a systematic review of potential clinical indications.

    Science.gov (United States)

    Bhaskar, Vaishnavi; Chan, Hsun-Liang; MacEachern, Mark; Kripfgans, Oliver D

    2018-05-23

    Ultrasonography has shown promising diagnostic value in dental implant imaging research; however, exactly how ultrasound was used and at what stage of implant therapy it can be applied has not been systematically evaluated. Therefore, the aim of this review is to investigate potential indications of ultrasound use in the three implant treatment phases, namely planning, intraoperative and postoperative phase. Eligible manuscripts were searched in major databases with a combination of key words related to the use of ultrasound imaging in implant therapy. An initial search yielded 414 articles, after further review, 28 articles were finally included for this systematic review. Ultrasound was found valuable, though at various development stages, for evaluating (1) soft tissues, (2) hard tissues (3) vital structures and (4) implant stability. B-mode, the main function to image anatomical structures of interest, has been evaluated in pre-clinical and clinical studies. Quantitative ultrasound parameters, e.g. sound speed and amplitude, are being developed to evaluate implant-bone stability, mainly in simulation and pre-clinical studies. Ultrasound could be potentially useful in all 3 treatment phases. In the planning phase, ultrasound could evaluate vital structures, tissue biotype, ridge width/density, and cortical bone thickness. During surgery, it can provide feedback by identifying vital structures and bone boundary. At follow-up visits, it could evaluate marginal bone level and implant stability. Understanding the current status of ultrasound imaging research for implant therapy would be extremely beneficial for accelerating translational research and its use in dental clinics.

  16. 7T: Physics, safety, and potential clinical applications.

    Science.gov (United States)

    Kraff, Oliver; Quick, Harald H

    2017-12-01

    With more than 60 installed magnetic resonance imaging (MRI) systems worldwide operating at a magnetic field strength of 7T or higher, ultrahigh-field (UHF) MRI has been established as a platform for clinically oriented research in recent years. Profound technical and methodological developments have helped overcome the inherent physical challenges of UHF radiofrequency (RF) signal homogenization in the human body. The ongoing development of dedicated RF coil arrays was pivotal in realizing UHF body MRI, beyond mere brain imaging applications. Another precondition to clinical application of 7T MRI is the safety testing of implants and the establishment of safety concepts. Against this backdrop, 7T MRI and MR spectroscopy (MRS) recently have demonstrated capabilities and potentials for clinical diagnostics in a variety of studies. This article provides an overview of the immanent physical challenges of 7T UHF MRI and discusses recent technical solutions and safety concepts. Furthermore, recent clinically oriented studies are highlighted that span a broad application spectrum from 7T UHF brain to body MRI. 4 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2017;46:1573-1589. © 2017 International Society for Magnetic Resonance in Medicine.

  17. Conducting qualitative research within Clinical Trials Units: avoiding potential pitfalls.

    Science.gov (United States)

    Cooper, Cindy; O'Cathain, Alicia; Hind, Danny; Adamson, Joy; Lawton, Julia; Baird, Wendy

    2014-07-01

    The value of using qualitative research within or alongside randomised controlled trials (RCTs) is becoming more widely accepted. Qualitative research may be conducted concurrently with pilot or full RCTs to understand the feasibility and acceptability of the interventions being tested, or to improve trial conduct. Clinical Trials Units (CTUs) in the United Kingdom (UK) manage large numbers of RCTs and, increasingly, manage the qualitative research or collaborate with qualitative researchers external to the CTU. CTUs are beginning to explicitly manage the process, for example, through the use of standard operating procedures for designing and implementing qualitative research with trials. We reviewed the experiences of two UK Clinical Research Collaboration (UKCRC) registered CTUs of conducting qualitative research concurrently with RCTs. Drawing on experiences gained from 15 studies, we identify the potential for the qualitative research to undermine the successful completion or scientific integrity of RCTs. We show that potential problems can arise from feedback of interim or final qualitative findings to members of the trial team or beyond, in particular reporting qualitative findings whilst the trial is on-going. The problems include: We make recommendations for improving the management of qualitative research within CTUs. Copyright © 2014. Published by Elsevier Inc.

  18. Identification and Pathogenic Potential of Clinical Bacillus and Paenibacillus Isolates.

    Directory of Open Access Journals (Sweden)

    Francesco Celandroni

    Full Text Available The soil-related Bacillus and Paenibacillus species have increasingly been implicated in various human diseases. Nevertheless, their identification still poses problems in the clinical microbiology laboratory and, with the exception of Bacillus anthracis and Bacillus cereus, little is known on their pathogenicity for humans. In this study, we evaluated the use of matrix-assisted laser desorption-ionization time of flight mass spectrometry (MALDI-TOF MS in the identification of clinical isolates of these genera and conducted genotypic and phenotypic analyses to highlight specific virulence properties. Seventy-five clinical isolates were subjected to biochemical and MALDI-TOF MS identification. 16S rDNA sequencing and supplemental tests were used to solve any discrepancies or failures in the identification results. MALDI-TOF MS significantly outperformed classical biochemical testing for correct species identification and no misidentification was obtained. One third of the collected strains belonged to the B. cereus species, but also Bacillus pumilus and Bacillus subtilis were isolated at high rate. Antimicrobial susceptibility testing showed that all the B. cereus, B. licheniformis, B. simplex, B. mycoides, Paenibacillus glucanolyticus and Paenibacillus lautus isolates are resistant to penicillin. The evaluation of toxin/enzyme secretion, toxin-encoding genes, motility, and biofilm formation revealed that B. cereus displays the highest virulence potential. However, although generally considered nonpathogenic, most of the other species were shown to swim, swarm, produce biofilms, and secrete proteases that can have a role in bacterial virulence. In conclusion, MALDI-TOF MS appears useful for fast and accurate identification of Bacillus and Paenibacillus strains whose virulence properties make them of increasing clinical relevance.

  19. Potential clinical impact of normal-tissue intrinsic radiosensitivity testing

    International Nuclear Information System (INIS)

    Bentzen, Soeren M.

    1997-01-01

    A critical appraisal is given of the possible benefit from a reliable pre-treatment knowledge of individual normal-tissue sensitivity to radiotherapy. The considerations are in part, but not exclusively, based on the recent experience with in vitro colony-forming assays of the surviving fraction at 2 Gy, the SF 2 . Three strategies are reviewed: (1) to screen for rare cases with extreme radiosensitivity, so-called over-reactors, and treat these with reduced total dose, (2) to identify the sensitive tail of the distribution of 'normal' radiosensitivities, refer these patients to other treatment, and to escalate the dose to the remaining patients, or (3) to individualize dose prescriptions based on individual radiosensitivity, i.e. treating to isoeffect rather than to a specific dose-fractionation schedule. It is shown that these strategies will have a small, if any, impact on routine radiotherapy. Screening for over-reactors is hampered by the low prevalence of these among otherwise un-selected patients that leads to a low positive predictive value of in vitro radiosensitivity assays. It is argued, that this problem may persist even if the noise on current assays could be reduced to (the unrealistic value of) zero, simply because of the large biological variation in SF 2 . Removing the sensitive tail of the patient population, will only have a minor effect on the dose that could be delivered to the remaining patients, because of the sigmoid shape of empirical dose-response relationships. Finally, individualizing dose prescriptions based exclusively on information from a normal-tissue radiosensitivity assay, leads to a nearly symmetrical distribution of dose-changes that would produce a very small gain, or even a loss, of tumor control probability if implemented in the clinic. From a theoretical point of view, other strategies could be devised and some of these are considered in this review. Right now the most promising clinical use of in vitro radiosensitivity

  20. Diethylglyoxal bis(guanylhydrazone): a novel highly potent inhibitor of S-adenosylmethionine decarboxylase with promising properties for potential chemotherapeutic use.

    Science.gov (United States)

    Elo, H; Mutikainen, I; Alhonen-Hongisto, L; Laine, R; Jänne, J

    1988-07-01

    Diethylglyoxal bis(guanylhydrazone) (DEGBG), a novel analog of the antileukemic agent methylglyoxal bis(guanylhydrazone) (MGBG) was synthesized. It was found to be the most powerful inhibitor of yeast S-adenosylmethionine decarboxylase (AdoMetDC) so far studied (Ki approx. 9 nM). This property, together with the finding that the compound is a weaker inhibitor of intestinal diamine oxidase than are MGBG and its glyoxal, ethylglyoxal and ethylmethylglyoxal analogs, makes the compound a promising candidate as a polyamine antimetabolite for chemotherapy studies. DEGBG was also found to potentiate the antiproliferative effect of the ornithine decarboxylase inhibitor alpha-difluoromethyl ornithine against mouse L1210 leukemia cells in vitro. DEGBG increased several-fold the intracellular putrescine concentration of cultured L1210 cells, just as MGBG and its ethylglyoxal analog are known to do. The results strongly suggest that DEGBG is worth further studies. Combined with previous studies, they also made possible the construction of some empirical rules concerning the structure-activity relationships of bis(guanylhydrazone) type inhibitors of AdoMetDC. The identity of DEGBG was confirmed by a single-crystal X-ray analysis and by 1H- and 13C-NMR spectroscopy. It consisted of the same isomer as MGBG and several of its analogs are known to consist of.

  1. Mesenchymal stem cells: biological characteristics and potential clinical applications

    DEFF Research Database (Denmark)

    Kassem, Moustapha

    2004-01-01

    are among the first stem cell types to be introduced in the clinic. Several studies have demonstrated the possible use of MSC in systemic transplantation for systemic diseases, local implantation for local tissue defects, as a vehicle for genes in gene therapy protocols or to generate transplantable tissues...... and organs in tissue engineering protocols. Before their widespread use in therapy, methods allowing the generation of large number of cells without affecting their differentiation potential as well as technologies that overcome immunological rejection (in case allogenic transplantation) must be developed.......Mesenchymal stem cells (MSC) are clonogenic, non-hematpoietic stem cells present in the bone marrow and are able to differentiate into multiple mesoderm-type cell lineages, for example, osteoblasts, chondrocytes, endothelial-cells and also non-mesoderm-type lineages, for example, neuronal...

  2. Spinal Cord Stimulation: Clinical Efficacy and Potential Mechanisms.

    Science.gov (United States)

    Sdrulla, Andrei D; Guan, Yun; Raja, Srinivasa N

    2018-03-11

    Spinal cord stimulation (SCS) is a minimally invasive therapy used for the treatment of chronic neuropathic pain. SCS is a safe and effective alternative to medications such as opioids, and multiple randomized controlled studies have demonstrated efficacy for difficult-to-treat neuropathic conditions such as failed back surgery syndrome. Conventional SCS is believed mediate pain relief via activation of dorsal column Aβ fibers, resulting in variable effects on sensory and pain thresholds, and measurable alterations in higher order cortical processing. Although potentiation of inhibition, as suggested by Wall and Melzack's gate control theory, continues to be the leading explanatory model, other segmental and supraspinal mechanisms have been described. Novel, non-standard, stimulation waveforms such as high-frequency and burst have been shown in some studies to be clinically superior to conventional SCS, however their mechanisms of action remain to be determined. Additional studies are needed, both mechanistic and clinical, to better understand optimal stimulation strategies for different neuropathic conditions, improve patient selection and optimize efficacy. © 2018 World Institute of Pain.

  3. Clinical diagnostic potentials of thyroid ultrasonography and scintigraphy; An evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Torizuka, Tatsuo; Kasagi, Kanji; Hatabu, Hiroto; Misaki, Takashi; Iida, Yasuhiro; Konishi, Junji (Kyoto Univ. (Japan). Hospital); Endo, Keigo

    1993-06-01

    This prospective study was designed to evaluate the potential contributions of high resolution ultrasonography (US) and Tc-99m scintigraphy in the routine diagnosis of thyroid disease. The diagnostic impacts of US and Tc-99m scintigraphy results in 177 patients visiting our thyroid clinic were assessed and scored according to the following criteria: when the information provided by either test supported, confirmed or changed the initial clinical diagnosis, they received scores of 2, 3 and 4 respectively, while score 1 was given when the test itself was useless for the differential diagnosis. US identified focal lesions that both palpation and scintigraphy had failed to detect in 14 (12.1%) of 116 patients with diffuse thyroid diseases, suggesting the necessity of Hashimoto's thyroiditis, adenoma, adenocarcinoma and adenomatous goiter, and vice versa in the diagnosis of hyperthyroid and euthyroid Graves's diseases. Thus, the advantages of US over scintigraphy for morphological evaluation were confirmed. US was particularly useful for the differential diagnosis of adenomatous goiter from Hashimoto's thyroiditis or a single nodular disease. In contrast, scintigraphy gave functional images, being especially helpful for the differential diagnosis of thyrotoxicosis. (author).

  4. Profile of bosutinib and its clinical potential in the treatment of chronic myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Keller-von Amsberg G

    2013-03-01

    Full Text Available Gunhild Keller-von Amsberg,1 Steffen Koschmieder21Department of Hematology and Oncology, University Cancer Center Hamburg, University Hospital Hamburg Eppendorf, 2Department of Medicine (Hematology, Oncology, and Stem Cell Transplantation, University Medical Center of Aachen and RWTH Aachen University, Aachen, GermanyAbstract: Bosutinib (SKI-606 is an orally available, once-daily, dual Src and Abl kinase inhibitor with promising clinical potential in first-, second-, and third-line treatment of chronic myeloid leukemia (CML. Bosutinib effectively inhibits wild-type BCR-ABL and most imatinib-resistant BCR-ABL mutations except for V299L and T315I. Low hematologic toxicity is a remarkable characteristic of this novel second-generation tyrosine kinase inhibitor, and this has been ascribed to its minimal activity against the platelet-derived growth factor receptor and KIT. Low-grade, typically self-limiting diarrhea, which usually appears within the first few weeks after treatment initiation, represents the predominant toxicity of bosutinib. Other treatment-associated adverse events are mostly mild to moderate. Bosutinib has been approved by the US Food and Drug Administration for the treatment of chronic, accelerated, or blast phase Philadelphia chromosome-positive CML in adult patients with resistance or intolerance to prior therapy. This review summarizes the main properties of bosutinib and the currently available data on its clinical potential in the treatment of CML.Keywords: bosutinib, chronic myeloid leukemia, BCR-ABL, Src/Abl kinase inhibitor, point mutation, imatinib resistance

  5. The promising anticancer drug 3-bromopyruvate is metabolized through glutathione conjugation which affects chemoresistance and clinical practice: An evidence-based view.

    Science.gov (United States)

    El Sayed, Salah Mohamed; Baghdadi, Hussam; Zolaly, Mohammed; Almaramhy, Hamdi H; Ayat, Mongi; Donki, Jagadish G

    2017-03-01

    3-Bromopyruvate (3BP) is a promising effective anticancer drug against many different tumors in children and adults. 3BP exhibited strong anticancer effects in both preclinical and human studies e.g. energy depletion, oxidative stress, anti-angiogenesis, anti-metastatic effects, targeting cancer stem cells and antagonizing the Warburg effect. There is no report about 3BP metabolism to guide researchers and oncologists to improve clinical practice and prevent drug resistance. In this article, we provide evidences that 3BP is metabolized through glutathione (GSH) conjugation as a novel report where 3BP was confirmed to be attached to GSH followed by permanent loss of pharmacological effects in a picture similar to cisplatin. Both cisplatin and 3BP are alkylating agents. Reported decrease in endogenous cellular GSH content upon 3BP treatment was confirmed to be due to the formation of 3BP-GSH complex i.e. GSH consumption for conjugation with 3BP. Cancer cells having high endogenous GSH exhibit resistance to 3BP while 3BP sensitive cells acquire resistance upon adding exogenous GSH. Being a thiol blocker, 3BP may attack thiol groups in tissues and serum proteins e.g. albumin and GSH. That may decrease 3BP-induced anticancer effects and the functions of those proteins. We proved here that 3BP metabolism is different from metabolism of hydroxypyruvate that results from metabolism of D-serine using D-amino acid oxidase. Clinically, 3BP administration should be monitored during albumin infusion and protein therapy where GSH should be added to emergency medications. GSH exerts many physiological effects and is safe for human administration both orally and intravenously. Based on that, reported GSH-induced inhibition of 3BP effects makes 3BP effects reversible, easily monitored and easily controlled. This confers a superiority of 3BP over many anticancer agents. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Clinical Potential of Hyperbaric Pressure-Treated Whey Protein

    Science.gov (United States)

    Piccolomini, André F.; Kubow, Stan; Lands, Larry C.

    2015-01-01

    Whey protein (WP) from cow’s milk is a rich source of essential and branched chain amino acids. Whey protein isolates (WPI) has been demonstrated to support muscle accretion, antioxidant activity, and immune modulation. However, whey is not readily digestible due to its tight conformational structure. Treatment of WPI with hyperbaric pressure results in protein unfolding. This enhances protein digestion, and results in an altered spectrum of released peptides, and greater release of essential and branched chain amino acids. Pressurized whey protein isolates (pWPI), through a series of cell culture, animal models and clinical studies, have been demonstrated to enhance muscle accretion, reduce inflammation, improve immunity, and decrease fatigue. It is also conceivable that pWPI would be more accessible to digestive enzymes, which would allow for a more rapid proteolysis of the proteins and an increased or altered release of small bioactive peptides. The altered profile of peptides released from WP digestion could thus play a role in the modulation of the immune response and tissue glutathione (GSH) concentrations. The research to date presents potentially interesting applications for the development of new functional foods based on hyperbaric treatment of WPI to produce products with more potent nutritional and nutraceutical properties. PMID:27417773

  7. Mammography - recent technical developments and their clinical potential

    Energy Technology Data Exchange (ETDEWEB)

    Hemdal, Bengt; Mattsson, Soeren [Malmoe Univ. Hospital (Sweden). Dept. of Radiation Physics; Andersson, Ingvar [Malmoe Univ. Hospital (Sweden). Dept. of Diagnostic Radiology; Thilander Klang, Anne [Sahlgrenska Univ. Hospital, Goeteborg (Sweden). Dept. of Medical Physics and Biomedical Engineering; Bengtsson, Gert; Jarlman, O. [Lund Univ. Hospital (Sweden). Dept. of Diagnostic Radiology; Leitz, Wolfram [Swedish Radiation Protection Authority, Stockholm (Sweden); Bjurstam, Nils [Univ. of North Norway, Troms (Norway). Dept. of Radiology

    2002-05-01

    The recent technical developments in digital as well as screen-film X-ray mammography have been reviewed in order to evaluate their clinical potential and to analyse possible lines for future development. Material and methods: The scientific literature has been reviewed, conferences covered and contacts with colleagues developed. Companies in the field have been inquired and invited for presentations. Own experience has been gathered from different screen-film and digital mammography systems. Results and conclusions: Although there are important complementary techniques such as ultrasound and magnetic resonance imaging (MRI), X-ray mammography is still the golden standard for breast imaging. It is relatively simple and cost-effective, and it is presently the only realistic technique for screening in a large scale. It is still largely the only technique that can detect breast cancer in a pre invasive stage. Equipment for digital mammography is commercially available both with small area and full field technique (FFDM). The development of FFDM systems is now intense, as well as the development of dedicated workstations and computer-aided detection (CAD). In spite of this, the introduction of digital mammography has been very slow compared to most other X-ray examinations due to high costs and technical challenges to meet the high demands on image quality and dose in mammography as well as the demands on specialised workflow support for screening mammography and suitable display techniques. Film reading of digital mammograms has been the most common display mode so far, but to take full advantage of the digital concept, diagnostic as well as logistic, monitor reading must be applied. There is a potential of FFDM systems for significantly higher image quality or significantly lower dose than screen-film mammography (SFM), or both. Further research is necessary to fully use this potential. The investment costs are much higher for digital than screen-film mammography

  8. Mammography - recent technical developments and their clinical potential

    International Nuclear Information System (INIS)

    Hemdal, Bengt; Mattsson, Soeren; Bjurstam, Nils

    2002-05-01

    The recent technical developments in digital as well as screen-film X-ray mammography have been reviewed in order to evaluate their clinical potential and to analyse possible lines for future development. Material and methods: The scientific literature has been reviewed, conferences covered and contacts with colleagues developed. Companies in the field have been inquired and invited for presentations. Own experience has been gathered from different screen-film and digital mammography systems. Results and conclusions: Although there are important complementary techniques such as ultrasound and magnetic resonance imaging (MRI), X-ray mammography is still the golden standard for breast imaging. It is relatively simple and cost-effective, and it is presently the only realistic technique for screening in a large scale. It is still largely the only technique that can detect breast cancer in a pre invasive stage. Equipment for digital mammography is commercially available both with small area and full field technique (FFDM). The development of FFDM systems is now intense, as well as the development of dedicated workstations and computer-aided detection (CAD). In spite of this, the introduction of digital mammography has been very slow compared to most other X-ray examinations due to high costs and technical challenges to meet the high demands on image quality and dose in mammography as well as the demands on specialised workflow support for screening mammography and suitable display techniques. Film reading of digital mammograms has been the most common display mode so far, but to take full advantage of the digital concept, diagnostic as well as logistic, monitor reading must be applied. There is a potential of FFDM systems for significantly higher image quality or significantly lower dose than screen-film mammography (SFM), or both. Further research is necessary to fully use this potential. The investment costs are much higher for digital than screen-film mammography

  9. Long-term potentiation and long-term depression: a clinical perspective

    Directory of Open Access Journals (Sweden)

    Timothy V.P. Bliss

    2011-01-01

    Full Text Available Long-term potentiation and long-term depression are enduring changes in synaptic strength, induced by specific patterns of synaptic activity, that have received much attention as cellular models of information storage in the central nervous system. Work in a number of brain regions, from the spinal cord to the cerebral cortex, and in many animal species, ranging from invertebrates to humans, has demonstrated a reliable capacity for chemical synapses to undergo lasting changes in efficacy in response to a variety of induction protocols. In addition to their physiological relevance, long-term potentiation and depression may have important clinical applications. A growing insight into the molecular mechanisms underlying these processes, and technological advances in non-invasive manipulation of brain activity, now puts us at the threshold of harnessing long-term potentiation and depression and other forms of synaptic, cellular and circuit plasticity to manipulate synaptic strength in the human nervous system. Drugs may be used to erase or treat pathological synaptic states and non-invasive stimulation devices may be used to artificially induce synaptic plasticity to ameliorate conditions arising from disrupted synaptic drive. These approaches hold promise for the treatment of a variety of neurological conditions, including neuropathic pain, epilepsy, depression, amblyopia, tinnitus and stroke.

  10. Transient receptor potential ankyrin 1 receptor activation in vitro and in vivo by pro-tussive agents: GRC 17536 as a promising anti-tussive therapeutic.

    Directory of Open Access Journals (Sweden)

    Indranil Mukhopadhyay

    Full Text Available Cough is a protective reflex action that helps clear the respiratory tract which is continuously exposed to airborne environmental irritants. However, chronic cough presents itself as a disease in its own right and despite its global occurrence; the molecular mechanisms responsible for cough are not completely understood. Transient receptor potential ankyrin1 (TRPA1 is robustly expressed in the neuronal as well as non-neuronal cells of the respiratory tract and is a sensor of a wide range of environmental irritants. It is fast getting acceptance as a key biological sensor of a variety of pro-tussive agents often implicated in miscellaneous chronic cough conditions. In the present study, we demonstrate in vitro direct functional activation of TRPA1 receptor by citric acid which is routinely used to evoke cough in preclinical and clinical studies. We also show for the first time that a potent and selective TRPA1 antagonist GRC 17536 inhibits citric acid induced cellular Ca(+2 influx in TRPA1 expressing cells and the citric acid induced cough response in guinea pigs. Hence our data provides a mechanistic link between TRPA1 receptor activation in vitro and cough response induced in vivo by citric acid. Furthermore, we also show evidence for TRPA1 activation in vitro by the TLR4, TLR7 and TLR8 ligands which are implicated in bacterial/respiratory virus pathogenesis often resulting in chronic cough. In conclusion, this study highlights the potential utility of TRPA1 antagonist such as GRC 17536 in the treatment of miscellaneous chronic cough conditions arising due to diverse causes but commonly driven via TRPA1.

  11. Targeting poly(ADP-ribose)polymerase1 in neurological diseases: A promising trove for new pharmacological interventions to enter clinical translation.

    Science.gov (United States)

    Sriram, Chandra Shekhar; Jangra, Ashok; Kasala, Eshvendar Reddy; Bodduluru, Lakshmi Narendra; Bezbaruah, Babul Kumar

    2014-10-01

    The highly conserved abundant nuclear protein poly(ADP-ribose)polymerase1 (PARP1) functions at the center of cellular stress response and is mainly implied in DNA damage repair mechanism. Apart from its involvement in DNA damage repair, it does sway multiple vital cellular processes such as cell death pathways, cell aging, insulator function, chromatin modification, transcription and mitotic apparatus function. Since brain is the principal organ vulnerable to oxidative stress and inflammatory responses, upon stress encounters robust DNA damage can occur and intense PARP1 activation may result that will lead to various CNS diseases. In the context of soaring interest towards PARP1 as a therapeutic target for newer pharmacological interventions, here in the present review, we are attempting to give a silhouette of the role of PARP1 in the neurological diseases and the potential of its inhibitors to enter clinical translation, along with its structural and functional aspects. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Clinical potential of implantable wireless sensors for orthopedic treatments.

    Science.gov (United States)

    Karipott, Salil Sidharthan; Nelson, Bradley D; Guldberg, Robert E; Ong, Keat Ghee

    2018-04-01

    Implantable wireless sensors have been used for real-time monitoring of chemicals and physical conditions of bones, tendons and muscles to diagnose and study orthopedic diseases and injuries. Due to the importance of these sensors in orthopedic care, a critical review, which not only analyzes the underlying technologies but also their clinical implementations and challenges, will provide a landscape view on their current state and their future clinical role. Areas covered: By conducting an extensive literature search and following the leaders of orthopedic implantable wireless sensors, this review covers the battery-powered and battery-free wireless implantable sensor technologies, and describes their implementation for hips, knees, spine, and shoulder stress/strain monitoring. Their advantages, limitations, and clinical challenges are also described. Expert commentary: Currently, implantable wireless sensors are mostly limited for scientific investigations and demonstrative experiments. Although rapid advancement in sensors and wireless technologies will push the reliability and practicality of these sensors for clinical realization, regulatory constraints and financial viability in medical device industry may curtail their continuous adoption for clinical orthopedic applications. In the next five years, these sensors are expected to gain increased interest from researchers, but wide clinical adoption is still unlikely.

  13. Maximising the potential of part-time clinical teachers.

    Science.gov (United States)

    Patston, Philip; Holmes, David; Maalhagh-Fard, Ahmad; Ting, Kang; Ziccardi, Vincent B

    2010-12-01

    A problem faced by health professions education throughout the world is a lack of full-time clinical teachers. This is particularly serious in dentistry and nursing, but is increasingly also true in medicine. To make up for this shortfall there is a growing reliance on part-time clinical teachers. Part-time clinical teachers are essential for the education of students. However, compared with their full-time counterparts, the part-time teachers are often not adequately prepared for their roles as educators within the context of the clinical curriculum. They might not be trained in the latest educational practices, and may be unprepared for the time needed to excel as teachers and mentors. As part-time teachers take on more responsibility, it is important that they take part in orientation and training sessions to assist them in developing the skills they need to succeed. This will require a significant commitment from the institution as well as the part-time teacher, but is critical for maintaining the academic quality of the clinical training programmes. This also represents an untapped area for research into how to ensure the success of part-time clinical teachers. © Blackwell Publishing Ltd 2010.

  14. Potential Targets' Analysis Reveals Dual PI3K/mTOR Pathway Inhibition as a Promising Therapeutic Strategy for Uterine Leiomyosarcomas-an ENITEC Group Initiative

    NARCIS (Netherlands)

    Cuppens, T.; Annibali, D.; Coosemans, A.; Trovik, J.; Haar, N. Ter; Colas, E.; Garcia-Jimenez, A.; Vijver, K. van der; Kruitwagen, R.P.; Brinkhuis, M.; Zikan, M.; Dundr, P.; Huvila, J.; Carpen, O.; Haybaeck, J.; Moinfar, F.; Salvesen, H.B.; Stukan, M.; Mestdagh, C.; Zweemer, R.P.; Massuger, L.F.A.G.; Mallmann, M.R.; Wardelmann, E.; Mints, M.; Verbist, G.; Thomas, D; Gomme, E.; Hermans, E; Moerman, P.; Bosse, T.; Amant, F.

    2017-01-01

    Purpose: Uterine sarcomas are rare and heterogeneous tumors characterized by an aggressive clinical behavior. Their high rates of recurrence and mortality point to the urgent need for novel targeted therapies and alternative treatment strategies. However, no molecular prognostic or predictive

  15. Potential use of recombinant human interleukin-6 in clinical oncology

    NARCIS (Netherlands)

    Veldhuis, GJ; Willemse, PHB; Mulder, NH; Limburg, PC; deVries, EGE

    Recombinant human IL-6 (rhIL-6) is a pleiotropic cytokine with stimulatory actions on the hematopoietic system, the immune system and hepatocytes. Clinical interest in the use of this cytokine was raised because of its thrombopoietic properties and also because of its anti-tumor activity, which was

  16. Potential biomarkers for the clinical prognosis of severe dengue

    Directory of Open Access Journals (Sweden)

    Mayara Marques Carneiro da Silva

    2013-09-01

    Full Text Available Currently, several assays can confirm acute dengue infection at the point-of-care. However, none of these assays can predict the severity of the disease symptoms. A prognosis test that predicts the likelihood of a dengue patient to develop a severe form of the disease could permit more efficient patient triage and treatment. We hypothesise that mRNA expression of apoptosis and innate immune response-related genes will be differentially regulated during the early stages of dengue and might predict the clinical outcome. Aiming to identify biomarkers for dengue prognosis, we extracted mRNA from the peripheral blood mononuclear cells of mild and severe dengue patients during the febrile stage of the disease to measure the expression levels of selected genes by quantitative polymerase chain reaction. The selected candidate biomarkers were previously identified by our group as differentially expressed in microarray studies. We verified that the mRNA coding for CFD, MAGED1, PSMB9, PRDX4 and FCGR3B were differentially expressed between patients who developed clinical symptoms associated with the mild type of dengue and patients who showed clinical symptoms associated with severe dengue. We suggest that this gene expression panel could putatively serve as biomarkers for the clinical prognosis of dengue haemorrhagic fever.

  17. Promising change, delivering continuity

    DEFF Research Database (Denmark)

    Lund, Jens Friis; Sungusia, Eliezeri; Mabele, Mathew Bukhi

    2017-01-01

    REDD+ is an ambition to reduce carbon emissions from deforestation and forest degradation in the Global South. This ambition has generated unprecedented commitment of political support and financial funds for the forest-development sector. Many academics and people-centered advocacy organizations...... have conceptualized REDD+ as an example of ‘‘green grabbing” and have voiced fears of a potential global rush for land and trees. In this paper we argue that, in practice and up until now, REDD+ resembles longstanding dynamics of the development and conservation industry, where the promise of change...... becomes a discursive commodity that is constantly reproduced and used to generate value and appropriate financial resources. We thus argue for a re-conceptualization of REDD+ as a conservation fad within the broader political economy of development and conservation. We derive this argument from a study...

  18. Human reporter genes: potential use in clinical studies

    Energy Technology Data Exchange (ETDEWEB)

    Serganova, Inna [Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021 (United States); Ponomarev, Vladimir [Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021 (United States); Blasberg, Ronald [Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021 (United States); Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021 (United States)], E-mail: blasberg@neuro1.mskcc.org

    2007-10-15

    The clinical application of positron-emission-tomography-based reporter gene imaging will expand over the next several years. The translation of reporter gene imaging technology into clinical applications is the focus of this review, with emphasis on the development and use of human reporter genes. Human reporter genes will play an increasingly more important role in this development, and it is likely that one or more reporter systems (human gene and complimentary radiopharmaceutical) will take leading roles. Three classes of human reporter genes are discussed and compared: receptors, transporters and enzymes. Examples of highly expressed cell membrane receptors include specific membrane somatostatin receptors (hSSTrs). The transporter group includes the sodium iodide symporter (hNIS) and the norepinephrine transporter (hNET). The endogenous enzyme classification includes human mitochondrial thymidine kinase 2 (hTK2). In addition, we also discuss the nonhuman dopamine 2 receptor and two viral reporter genes, the wild-type herpes simplex virus 1 thymidine kinase (HSV1-tk) gene and the HSV1-tk mutant (HSV1-sr39tk). Initial applications of reporter gene imaging in patients will be developed within two different clinical disciplines: (a) gene therapy and (b) adoptive cell-based therapies. These studies will benefit from the availability of efficient human reporter systems that can provide critical monitoring information for adenoviral-based, retroviral-based and lenteviral-based gene therapies, oncolytic bacterial and viral therapies, and adoptive cell-based therapies. Translational applications of noninvasive in vivo reporter gene imaging are likely to include: (a) quantitative monitoring of gene therapy vectors for targeting and transduction efficacy in clinical protocols by imaging the location, extent and duration of transgene expression; (b) monitoring of cell trafficking, targeting, replication and activation in adoptive T-cell and stem/progenitor cell therapies

  19. Human reporter genes: potential use in clinical studies

    International Nuclear Information System (INIS)

    Serganova, Inna; Ponomarev, Vladimir; Blasberg, Ronald

    2007-01-01

    The clinical application of positron-emission-tomography-based reporter gene imaging will expand over the next several years. The translation of reporter gene imaging technology into clinical applications is the focus of this review, with emphasis on the development and use of human reporter genes. Human reporter genes will play an increasingly more important role in this development, and it is likely that one or more reporter systems (human gene and complimentary radiopharmaceutical) will take leading roles. Three classes of human reporter genes are discussed and compared: receptors, transporters and enzymes. Examples of highly expressed cell membrane receptors include specific membrane somatostatin receptors (hSSTrs). The transporter group includes the sodium iodide symporter (hNIS) and the norepinephrine transporter (hNET). The endogenous enzyme classification includes human mitochondrial thymidine kinase 2 (hTK2). In addition, we also discuss the nonhuman dopamine 2 receptor and two viral reporter genes, the wild-type herpes simplex virus 1 thymidine kinase (HSV1-tk) gene and the HSV1-tk mutant (HSV1-sr39tk). Initial applications of reporter gene imaging in patients will be developed within two different clinical disciplines: (a) gene therapy and (b) adoptive cell-based therapies. These studies will benefit from the availability of efficient human reporter systems that can provide critical monitoring information for adenoviral-based, retroviral-based and lenteviral-based gene therapies, oncolytic bacterial and viral therapies, and adoptive cell-based therapies. Translational applications of noninvasive in vivo reporter gene imaging are likely to include: (a) quantitative monitoring of gene therapy vectors for targeting and transduction efficacy in clinical protocols by imaging the location, extent and duration of transgene expression; (b) monitoring of cell trafficking, targeting, replication and activation in adoptive T-cell and stem/progenitor cell therapies

  20. Amyotrophic lateral sclerosis and the clinical potential of dexpramipexole

    Directory of Open Access Journals (Sweden)

    Corcia P

    2012-08-01

    Full Text Available Philippe Corcia,1 Paul H Gordon21Centre SLA, CHRU de Tours, Tours, France; UMR INSERM U930, Université François Rabelais de Tours (PC, Tours, France; 2AP-HP, Hôpital de la Pitié-Salpêtrière, Département des Maladies du Système Nerveux (PHG, Paris, FranceAbstract: Amyotrophic lateral sclerosis (ALS is a neurodegenerative disorder that leads to progressive weakness from loss of motor neurons and death on average in less than 3 years after symptom onset. No clear causes have been found and just one medication, riluzole, extends survival. Researchers have identified some of the cellular processes that occur after disease onset, including mitochondrial dysfunction, protein aggregation, oxidative stress, excitotoxicity, inflammation, and apoptosis. Mitochondrial disease may be a primary event in neurodegeneration or occur secondary to other cellular processes, and may itself contribute to oxidative stress, excitotoxicity, and apoptosis. Clinical trials currently aim to slow disease progression by testing drugs that impact one or more of these pathways. While every agent tested in the 18 years after the approval of riluzole has been ineffective, basic and clinical research methods in ALS have become dramatically more sophisticated. Dexpramipexole (RPPX, the R(+ enantiomer of pramiprexole, which is approved for symptomatic treatment of Parkinson disease, carries perhaps the currently largest body of pre- and early clinical data that support testing in ALS. The neuroprotective properties of RPPX in various models of neurodegeneration, including the ALS murine model, may be produced through protective actions on mitochondria. Early phase trials in human ALS suggest that the drug can be taken safely by patients in doses that provide neuroprotection in preclinical models. A Phase III trial to test the efficacy of RPPX in ALS is underway.Keywords: dexpramipexole, amyotrophic lateral sclerosis, survival, clinical trials, neurodegeneration

  1. Elicited vs. voluntary promises

    NARCIS (Netherlands)

    Ismayilov, H.; Potters, Jan

    2017-01-01

    We set up an experiment with pre-play communication to study the impact of promise elicitation by trustors from trustees on trust and trustworthiness. When given the opportunity a majority of trustors solicits a promise from the trustee. This drives up the promise making rate by trustees to almost

  2. Antimicrobial potentials of silver colloidal (nanorods) on clinical ...

    African Journals Online (AJOL)

    Antimicrobial resistance in developing countries has long been an issue of major concern. Nanotechnology has become an eye opener for the intervention on multiple drug resistance organisms. In this study we investigated the antimicrobial potentials of Silver Nitrate (nanorods) solution used in managing infectious ...

  3. The potential of SGLT2 inhibitors in phase II clinical development for treating type 2 diabetes.

    Science.gov (United States)

    Pafili, K; Maltezos, E; Papanas, N

    2016-10-01

    There is now an abundance of anti-diabetic agents. However, only few patients achieve glycemic targets. Moreover, current glucose-lowering agents mainly depend upon insulin secretion or function. Sodium glucose co-transporter type 2 (SGLT2) inhibitors present a novel glucose-lowering therapy, inducing glycosuria in an insulin-independent fashion. In this review, the authors discuss the key efficacy and safety data from phase II clinical trials in type 2 diabetes mellitus (T2DM) of the main SGLT2 inhibitors approved or currently in development, and provide a rationale for their use in T2DM. Despite the very promising characteristics of this new therapeutic class, a number of issues await consideration. One important question is what to expect from head-to-head comparison data. We also need to know if dual inhibition of SGLT1/SGLT2 is more efficacious in reducing HbA1c and how this therapy affects metabolic and cardiovascular parameters. Additionally, several SGLT2 agents that have not yet come to market have hitherto been evaluated in Asian populations, whereas approved SGLT2 inhibitors have been frequently studied in other populations, including Caucasian subjects. Thus, we need more information on the potential role of ethnicity on their efficacy and safety.

  4. What are the potential benefits of clinical beta-cell imaging in diabetes mellitus?

    Science.gov (United States)

    Göke, Burkhard

    2010-05-01

    Previously, studies of the endocrine pancreatic beta-cell were mainly performed ex vivo by morphological means. This data supported the analysis of pathophysiological changes in the pancreatic islet during insults such as diabetes mellitus. Metabolic testing of the pancreatic islet by assaying hormone parameters such als plasma insulin or C-peptide combined with more or less sophisticated calculations allowed conclusions about states of insulin resistance or secretory failure. It also allowed certain correlations of endocrine function with beta-cell mass. Today, with firmer pathophysiological concepts about beta-cell failure, modern protocols of islet transplantation, and drugs on the market coming with promises of preservation or even expansion of beta-cell mass in diabetes mellitus it has become very attractive to search for tools measuring beta-cell mass, if possible even repeatingly in the same organism in vivo. From a clinical point of view, the potential of pancreatic beta-cell mass imaging technologies is looked upon with high expectations. Methodologically, the decisive question is whether it is likely that future beta-cell imaging will provide significant advantages over the metabolic methods already in hand. With new in vivo tools, studies of beta-cell mass and function may offer even new approaches stratifying patients to anti-diabetic therapies.

  5. High-throughput molecular analysis in lung cancer: insights into biology and potential clinical applications.

    Science.gov (United States)

    Ocak, S; Sos, M L; Thomas, R K; Massion, P P

    2009-08-01

    During the last decade, high-throughput technologies including genomic, epigenomic, transcriptomic and proteomic have been applied to further our understanding of the molecular pathogenesis of this heterogeneous disease, and to develop strategies that aim to improve the management of patients with lung cancer. Ultimately, these approaches should lead to sensitive, specific and noninvasive methods for early diagnosis, and facilitate the prediction of response to therapy and outcome, as well as the identification of potential novel therapeutic targets. Genomic studies were the first to move this field forward by providing novel insights into the molecular biology of lung cancer and by generating candidate biomarkers of disease progression. Lung carcinogenesis is driven by genetic and epigenetic alterations that cause aberrant gene function; however, the challenge remains to pinpoint the key regulatory control mechanisms and to distinguish driver from passenger alterations that may have a small but additive effect on cancer development. Epigenetic regulation by DNA methylation and histone modifications modulate chromatin structure and, in turn, either activate or silence gene expression. Proteomic approaches critically complement these molecular studies, as the phenotype of a cancer cell is determined by proteins and cannot be predicted by genomics or transcriptomics alone. The present article focuses on the technological platforms available and some proposed clinical applications. We illustrate herein how the "-omics" have revolutionised our approach to lung cancer biology and hold promise for personalised management of lung cancer.

  6. Development of a portable blood irradiator for potential clinical uses

    Energy Technology Data Exchange (ETDEWEB)

    Hungate, F.P.

    1988-12-01

    This document provides an account of the development of a fully portable blood irradiator and the evaluation of its safety and efficacy when implanted in goats, sheep, a baboon and dogs. The program was initiated because the control of lymphocyte populations by irradiation is a potential method for improving success in organ or tissue transplantation and for treating a variety of blood diseases. 15 refs., 27 figs., 2 tabs.

  7. Transvaginal organ extraction: potential for broad clinical application.

    Science.gov (United States)

    Jacobsen, Garth R; Barajas-Gamboa, Juan S; Coker, Alisa M; Cheverie, Joslin; Macias, C Aitor; Sandler, Bryan J; Talamini, Mark A; Horgan, Santiago

    2014-02-01

    Natural orifice transluminal endoscopic surgery procedures have evolved over the past few years. A transvaginal approach is a promising alternative for intraperitoneal procedures. Our objective was to evaluate the safety and feasibility of transvaginal organ extraction. This institutional review board-approved protocol involved retrospective review of an ongoing prospective study. Female subjects who presented to our hospital for elective cholecystectomy, appendectomy, or sleeve gastrectomy were offered participation in the study. Eligible patients met the following criteria: age between 18 and 75, diagnosis of gallbladder disease, acute appendicitis, or morbid obesity who desired surgical treatment. A hybrid transvaginal natural orifice approach was used in this series. Thirty-four women underwent transvaginal organ extraction between September 2007 and January 2012. The mean age was 40 ± 12.1 years (range 23-63 years). The mean body mass index was 27 ± 6.4 kg/m(2) (range 16-43 kg/m(2)). All patients had an American Society of Anesthesiologists classification of two or below. The mean operative time for cholecystectomy, appendectomy, and sleeve gastrectomy was 90, 71, and 135 min, respectively. There were no conversions to open operation and no intraoperative complications. The mean hospital stay was 2 days for all cases. Patients were followed for a mean of 24 months (range 1-61 months). There were two pregnancies and two successful vaginal deliveries. Six patients (18 %) had minor complaints of spotting or heavy menses in the immediate postoperative period that resolved with conservative measures. There were no abdominal wall complications. There were no long-term complications and no mortalities. This initial experience suggests that this surgical approach is safe, does not increase length of stay, and has no long-term vaginal complications. Given this attractive profile, a transvaginal approach may prove to be a superior mode of organ extraction

  8. Clinical potential of sodium-glucose cotransporter 2 inhibitors in the management of type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Kim Y

    2012-08-01

    insulin, and as a monotherapy for metformin-intolerant patients. Clinical research also remains to be carried out on the long-term effects of glucosuria and other potential effects of SGLT2 inhibitors, especially in view of the observed increase in the incidence of bladder and breast cancer. SGLT2 inhibitors represent a promising approach for the treatment of diabetes, and could potentially be an addition to existing therapies.Keywords: sodium-glucose cotransporter type 2, SGLT2, inhibitors, kidney, glucosuria, oral diabetes agent, weight loss

  9. Intermittent Feeding Schedules—Behavioural Consequences and Potential Clinical Significance

    Directory of Open Access Journals (Sweden)

    Michelle Murphy

    2014-03-01

    Full Text Available Food availability and associated sensory cues such as olfaction are known to trigger a range of hormonal and behavioural responses. When food availability is predictable these physiological and behavioural responses can become entrained to set times and occur in anticipation of food rather than being dependent on the food-related cues. Here we summarise the range of physiological and behavioural responses to food when the time of its availability is unpredictable, and consider the potential to manipulate feeding patterns for benefit in metabolic and mental health.

  10. In vitro evaluation of the cyto-genotoxic potential of Ruthenium(II) SCAR complexes: a promising class of antituberculosis agents.

    Science.gov (United States)

    De Grandis, Rone Aparecido; Resende, Flávia Aparecida; da Silva, Monize Martins; Pavan, Fernando Rogério; Batista, Alzir Azevedo; Varanda, Eliana Aparecida

    2016-03-01

    Tuberculosis is a top infectious disease killer worldwide, caused by the bacteria Mycobacterium tuberculosis. Increasing incidences of multiple drug-resistance (MDR) strains are emerging as one of the major public health threats. However, the drugs in use are still incapable of controlling the appalling upsurge of MDR. In recent years a marked number of research groups have devoted their attention toward the development of specific and cost-effective antimicrobial agents against targeted MDR-Tuberculosis. In previous studies, ruthenium(II) complexes (SCAR) have shown a promising activity against MDR-Tuberculosis although few studies have indeed considered ruthenium toxicity. Therefore, within the preclinical requirements, we have sought to determine the cyto-genotoxicity of three SCAR complexes in this present study. The treatment with the SCARs induced a concentration-dependent decrease in cell viability in CHO-K1 and HepG2 cells. Based on the clonogenic survival, SCAR 5 was found to be more cytotoxic while SCAR 6 exhibited selectivity action on tumor cells. Although SCAR 4 and 5 did not indicate any mutagenic activity as evidenced by the Ames and Cytokinesis block micronucleus cytome assays, the complex SCAR 6 was found to engender a frameshift mutation detected by Salmonella typhimurium in the presence of S9. Similarly, we observed a chromosomal damage in HepG2 cells with significant increases of micronuclei and nucleoplasmic bridges. These data indicate that SCAR 4 and 5 complexes did not show genotoxicity in our models while SCAR 6 was considered mutagenic. This study presented a comprehensive genotoxic evaluation of SCAR complexes were shown to be genotoxic in vitro. All in all, further studies are required to fully elucidate how the properties can affect human health. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Major adverse cardiovascular event reduction with GLP-1 and SGLT2 agents: evidence and clinical potential

    Science.gov (United States)

    Røder, Michael E.

    2017-01-01

    Treatment of patients with type 2 diabetes is directed against treating symptoms of hyperglycemia, minimizing the risk of hypoglycemia, and the risk of microvascular and macrovascular complications. The majority of patients with type 2 diabetes die from cardiovascular or cerebrovascular disease. Future therapies should therefore focus on reducing cardiovascular morbidity in this high-risk population. Glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose co-transporter 2 inhibitors (SGLT2-i) are two drug classes with proven antihyperglycemic effect in type 2 diabetes. However, these drugs seem to have other effects such as weight reduction, low risk of hypoglycemia, and blood pressure reduction. Emerging evidence suggests pleiotropic effects, which potentially could be important in reducing cardiovascular risk. Prompted by regulatory authorities demanding cardiovascular outcome trials (CVOTs) assessing the cardiovascular safety of new antihyperglycemic drug candidates, many CVOTs are ongoing and a few of these are finalized. Somewhat surprising recent CVOTs in both drug classes have shown promising data on cardiovascular morbidity and mortality in patients with a very high risk of cardiovascular events. It is uncertain whether this is a class effect of the two drug classes, and it is yet unproven whether long-term cardiovascular benefits of these drugs can be extrapolated to populations at lower risk of cardiovascular disease. The aim of the present review is to give an overview of our current knowledge of the GLP-1RA and SGLT2-i classes, with specific focus on mechanisms of action, effects on cardiovascular risk factors and cardiovascular morbidity and mortality from the CVOTs presently available. The clinical potential of these data is discussed. PMID:29344329

  12. Proven and potential clinical benefits of washing red blood cells before transfusion: current perspectives

    Directory of Open Access Journals (Sweden)

    Schmidt AE

    2016-08-01

    Full Text Available Amy E Schmidt, Majed A Refaai, Scott A Kirkley, Neil Blumberg Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY, USA Abstract: Red blood cells (RBCs are washed for a variety of reasons such as to remove excess potassium, cytokines, and other allergen proteins from the supernatant and/or to mitigate the effects of the storage lesion. The storage lesion is a product of RBC aging and include leakage of potassium and chloride from the RBCs, depletion of 2,3-diphosphoglycerate and adenosine triphosphate, loss of phospholipids and cholesterol, exposure of phosphatidylserine, elaboration of lipid mediators, loss of glutathione, autoxidation of hemoglobin to methemoglobin contributing to decreased blood flow viscosity and adherence to endothelial cells, increased microparticle formation, and disruption of NO-mediated vasodilation. A storage lesion is thought to be caused in part by oxidative stress, which is characterized by functional and structural changes to the RBCs. The effects of the RBC storage lesion on patient morbidity and mortality have been studied intensively with mixed results. Here, we will summarize the potential benefits of RBC washing. Notably, all patient-based studies on washed RBCs are single-center, small randomized studies or observational data, which await replication and tests of generalizability. Some of the most promising preliminary data suggest that washed transfusions of red cells and platelets reduce mortality in low risk, younger patients with acute myeloid leukemia, mitigate lung injury, and substantially reduce mortality in cardiac surgery. Larger randomized trials to replicate or refute these findings are urgently needed and, most importantly, have the potential to strikingly improve clinical outcomes following transfusion. Keywords: washed blood, transfusion, immunomodulation, red blood cell

  13. Fructose use in clinical nutrition: metabolic effects and potential consequences.

    Science.gov (United States)

    Moulin, Sandra; Seematter, Gérald; Seyssel, Kevin

    2017-07-01

    The current article presents recent findings on the metabolic effects of fructose. Fructose has always been considered as a simple 'caloric' hexose only metabolized by splanchnic tissues. Nevertheless, there is growing evidence that fructose acts as a second messenger and induces effects throughout the human body. Recent discoveries made possible with the evolution of technology have highlighted that fructose induces pleiotropic effects on different tissues. The fact that all these tissues express the specific fructose carrier GLUT5 let us reconsider that fructose is not only a caloric hexose, but could also be a potential actor of some behaviors and metabolic pathways. The physiological relevance of fructose as a metabolic driver is pertinent regarding recent scientific literature.

  14. Targeted treatment for chronic lymphocytic leukemia: clinical potential of obinutuzumab

    Directory of Open Access Journals (Sweden)

    Smolej L

    2014-12-01

    Full Text Available Lukáš Smolej 4th Department of Internal Medicine – Hematology, University Hospital Hradec Králové and Charles University in Prague, Faculty of Medicine in Hradec Králové, Hradec Králové, Czech Republic Abstract: Introduction of targeted agents revolutionized the treatment of chronic lymphocytic leukemia (CLL in the past decade. Addition of chimeric monoclonal anti-CD20 antibody rituximab to chemotherapy significantly improved efficacy including overall survival (OS in untreated fit patients; humanized anti-CD52 antibody alemtuzumab and fully human anti-CD20 antibody ofatumumab lead to improvement in refractory disease. Novel small molecule inhibitors such as ibrutinib and idelalisib demonstrated excellent activity and were very recently licensed in relapsed/refractory CLL. Obinutuzumab (GA101 is the newest monoclonal antibody approved for the treatment of CLL. This novel, glycoengineered, type II humanized anti-CD20 antibody is characterized by enhanced antibody-dependent cellular cytotoxicity and direct induction of cell death compared to type I antibodies. Combination of obinutuzumab and chlorambucil yielded significantly better OS in comparison to chlorambucil monotherapy in untreated comorbid patients. These results led to approval of obinuzutumab for the treatment of CLL. Numerous clinical trials combining obinutuzumab with other cytotoxic drugs and novel small molecules are currently under way. This review focuses on the role of obinutuzumab in the treatment of CLL. Keywords: chronic lymphocytic leukemia, anti-CD20 antibodies, chlorambucil, rituximab, ofatumumab, obinutuzumab, overall survival

  15. Potential and clinical utility of stem cells in cardiovascular disease

    Directory of Open Access Journals (Sweden)

    Korff Krause

    2010-03-01

    Full Text Available Korff Krause, Carsten Schneider, Kai Jaquet, Karl-Heinz KuckHanseatic Heart Center Hamburg, Department of Cardiology, Asklepios Hospital St. Georg, Hamburg, GermanyAbstract: The recent identification of bone marrow-derived adult stem cells and other types of stem cells that could improve heart function after transplantation have raised high expectations. The basic mechanisms have been studied mostly in murine models. However, these experiments revealed controversial results on transdifferentiation vs transfusion of adult stem cells vs paracrine effects of these cells, which is still being debated. Moreover, the reproducibility of these results in precisely translated large animal models is still less well investigated. Despite these weaknesses results of several clinical trials including several hundreds of patients with ischemic heart disease have been published. However, there are no solid data showing that any of these approaches can regenerate human myocardium. Even the effectiveness of cell therapy in these approaches is doubtful. In future we need in this important field of regenerative medicine: i more experimental data in large animals that are closer to the anatomy and physiology of humans, including data on dose effects, comparison of different cell types and different delivery routes; ii a better understanding of the molecular mechanisms involved in the fate of transplanted cells; iii more intensive research on genuine regenerative medicine, applying genetic regulation and cell engineering.Keywords: stem cells, cardiovascular disease

  16. Biochar from Biomass and its Potential Agronomic and Environmental Use in Washington: A Promising Alternative to Drawdown Carbon from the Atmosphere and Develop a New Industry

    Energy Technology Data Exchange (ETDEWEB)

    Amonette, James E. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Garcia-Perez, Manuel [Washington State Univ., Pullman, WA (United States); Sjoding, David [Washington State Energy Program Office, Olympia, WA (United States); Fuchs, Mark R. [Washington Dept. of Ecology, Spokane, WA (United States)

    2016-03-04

    Climate change is one of the most serious issues facing the world today. Increasing concentrations of carbon dioxide (CO2) and other long-lived greenhouse gases (GHGs) in the atmosphere continue to warm the planet and destabilize the climate. It has been estimated that the impact from this warming could cost the state 10 billion per year by 2020, and 16 billion per year by 2040. Long-term solutions to the climate problem likely will require that large quantities of CO2 be removed from the atmosphere. In fact, massive CO2 drawdowns from the atmosphere have occurred in earth’s recent past from events occurring in our hemisphere. Studies of those analogs provide insight into the potential magnitude for specific actions to drawdown significant CO2 from the atmosphere. One of these potential actions is the large-scale production of biochar from abundant woody biomass waste and its storage in soils, where it remains stable for hundreds to thousands of years. Moreover, for the carbon emission intensity of Washington’s fuel mix, biochar production from biomass is twice as effective in offsetting GHG emissions as complete biomass combustion of the same biomass. Washington State has large quantities of wood waste biomass that could be purposed for production of combined heat/power/biochar (CHPB) through existing biomass boilers. We propose to 1) evaluate the quantities of Washington wood waste biomass, 2) inventory existing boiler capacity and assess the technical merits and challenges to repurpose the boilers to CHPB, and 3) apply literature values and analog biochar examples to better quantify the extent of CO2 drawdown that could be achieved in Washington State over the next century using engineered biochar. This white paper explores the potential to replicate the historical drawdowns of atmospheric CO2, a topic the authors think should be part of current climate-change mitigation discussions. This

  17. MicroRNAs in Taenia solium Neurocysticercosis: Insights as Promising Agents in Host-Parasite Interaction and Their Potential as Biomarkers

    Directory of Open Access Journals (Sweden)

    Renzo Gutierrez-Loli

    2017-09-01

    Full Text Available MicroRNAs (miRNAs are short, endogenous, non-coding, single-stranded RNAs involved in post-transcriptional gene regulation. Although, several miRNAs have been identified in parasitic helminths, there is little information about their identification and function in Taenia. Furthermore, the impact of miRNAs in neurocysticercosis, the brain infection caused by larvae of Taenia solium is still unknown. During chronic infection, T. solium may activate numerous mechanisms aimed to modulate host immune responses. Helminthic miRNAs might also have effects on host mRNA expression and thus play an important role regulating host-parasite interactions. Also, the diagnosis of this disease is difficult and it usually requires neuroimaging and confirmatory serology. Since miRNAs are stable when released, they can be detected in body fluids and therefore have potential to diagnose infection, determine parasite burden, and ascertain effectiveness of treatment or disease progression, for instance. This review discusses the potential roles of miRNAs in T. solium infection, including regulation of host-parasite relationships and their eventual use as diagnostic or disease biomarkers. Additionally, we summarize the bioinformatics resources available for identification of T. solium miRNAs and prediction of their targets.

  18. MicroRNAs in Taenia solium Neurocysticercosis: Insights as Promising Agents in Host-Parasite Interaction and Their Potential as Biomarkers.

    Science.gov (United States)

    Gutierrez-Loli, Renzo; Orrego, Miguel A; Sevillano-Quispe, Oscar G; Herrera-Arrasco, Luis; Guerra-Giraldez, Cristina

    2017-01-01

    MicroRNAs (miRNAs) are short, endogenous, non-coding, single-stranded RNAs involved in post-transcriptional gene regulation. Although, several miRNAs have been identified in parasitic helminths, there is little information about their identification and function in Taenia . Furthermore, the impact of miRNAs in neurocysticercosis, the brain infection caused by larvae of Taenia solium is still unknown. During chronic infection, T. solium may activate numerous mechanisms aimed to modulate host immune responses. Helminthic miRNAs might also have effects on host mRNA expression and thus play an important role regulating host-parasite interactions. Also, the diagnosis of this disease is difficult and it usually requires neuroimaging and confirmatory serology. Since miRNAs are stable when released, they can be detected in body fluids and therefore have potential to diagnose infection, determine parasite burden, and ascertain effectiveness of treatment or disease progression, for instance. This review discusses the potential roles of miRNAs in T. solium infection, including regulation of host-parasite relationships and their eventual use as diagnostic or disease biomarkers. Additionally, we summarize the bioinformatics resources available for identification of T. solium miRNAs and prediction of their targets.

  19. Potential clinical efficacy of intensity-modulated conformal therapy

    International Nuclear Information System (INIS)

    Meeks, Sanford L.; Buatti, John M.; Bova, Francis J.; Friedman, William A.; Mendenhall, William M.; Zlotecki, Robert A.

    1998-01-01

    Purpose: The purpose of this study was to examine the potential benefit of using intensity-modulated conformal therapy for a variety of lesions currently treated with stereotactic radiosurgery or conventional radiotherapy. Methods and Materials: Intensity-modulated conformal treatment plans were generated for small intracranial lesions, as well as head and neck, lung, breast, and prostate cases, using the Peacock Plan[reg] treatment-planning system (Nomos Corporation). For small intracranial lesions, intensity-modulated conformal treatment plans were compared with stereotactic radiosurgery treatment plans generated for patient treatment at the University of Florida Shands Cancer Center. For other sites (head and neck, lung, breast, and prostate), plans generated using the Peacock Plan[reg] were compared with conventional treatment plans, as well as beam's-eye-view conformal treatment plans. Plan comparisons were accomplished through conventional qualitative review of two-dimensional (2D) dose distributions in conjunction with quantitative techniques, such as dose-volume histograms, dosimetric statistics, normal tissue complication probabilities, tumor control probabilities, and objective numerical scoring. Results: For small intracranial lesions, there is little difference between intensity-modulated conformal treatment planning and radiosurgery treatment planning in the conformation of high isodose lines with the target volume. However, stereotactic treatment planning provides a steeper dose gradient outside the target volume and, hence, a lower normal tissue toxicity index. For extracranial sites, objective numerical scores for beam's-eye-view and intensity-modulated conformal planning techniques are superior to scores for conventional treatment plans. The beam's-eye-view planning technique prevents geographic target misses and better excludes healthy tissues from the treatment portal. Compared with scores for the beam's-eye-view planning technique, scores for

  20. Keeping the Promise

    Science.gov (United States)

    Whissemore, Tabitha

    2016-01-01

    Since its launch in September 2015, Heads Up America has collected information on nearly 125 promise programs across the country, many of which were instituted long before President Barack Obama announced the America's College Promise (ACP) plan in 2015. At least 27 new free community college programs have launched in states, communities, and at…

  1. Capparis spinosa L. in A Systematic Review: A Xerophilous Species of Multi Values and Promising Potentialities for Agrosystems under the Threat of Global Warming

    Directory of Open Access Journals (Sweden)

    Stephanie Chedraoui

    2017-10-01

    Full Text Available Caper (Capparis spinosa L. is a xerophytic shrub with a remarkable adaptability to harsh environments. This plant species is of great interest for its medicinal/pharmacological properties and its culinary uses. Its phytochemical importance relies on many bioactive components present in different organs and its cultivation can be of considerable economic value. Moreover, taxonomic identification of C. spinosa L. has been difficult due to its wide heterogeneity, and many authors fell into confusion due to the scarcity of genetic studies. The present review summarizes information concerning C. spinosa L. including agronomic performance, botanical description, taxonomical approaches, traditional pharmacological uses, phytochemical evaluation and genetic studies. This knowledge represents an important tool for further research studies and agronomic development on this indigenous species with respect to the emerging climatic change in the Eastern Mediterranean countries. Indeed, this world region is particularly under the threat of global warming and it appears necessary to rethink agricultural systems to adapt them to current and futures challenging environmental conditions. Capparis spinosa L. could be a part of this approach. So, this review presents a state of the art considering caper as a potential interesting crop under arid or semi-arid regions (such as Eastern Mediterranean countries within the climate change context. The aim is to raise awareness in the scientific community (geneticists, physiologists, ecophysiologists, agronomists, … about the caper strengths and interest to the development of this shrub as a crop.

  2. Capparis spinosa L. in A Systematic Review: A Xerophilous Species of Multi Values and Promising Potentialities for Agrosystems under the Threat of Global Warming.

    Science.gov (United States)

    Chedraoui, Stephanie; Abi-Rizk, Alain; El-Beyrouthy, Marc; Chalak, Lamis; Ouaini, Naim; Rajjou, Loïc

    2017-01-01

    Caper ( Capparis spinosa L.) is a xerophytic shrub with a remarkable adaptability to harsh environments. This plant species is of great interest for its medicinal/pharmacological properties and its culinary uses. Its phytochemical importance relies on many bioactive components present in different organs and its cultivation can be of considerable economic value. Moreover, taxonomic identification of C. spinosa L. has been difficult due to its wide heterogeneity, and many authors fell into confusion due to the scarcity of genetic studies. The present review summarizes information concerning C. spinosa L. including agronomic performance, botanical description, taxonomical approaches, traditional pharmacological uses, phytochemical evaluation and genetic studies. This knowledge represents an important tool for further research studies and agronomic development on this indigenous species with respect to the emerging climatic change in the Eastern Mediterranean countries. Indeed, this world region is particularly under the threat of global warming and it appears necessary to rethink agricultural systems to adapt them to current and futures challenging environmental conditions. Capparis spinosa L. could be a part of this approach. So, this review presents a state of the art considering caper as a potential interesting crop under arid or semi-arid regions (such as Eastern Mediterranean countries) within the climate change context. The aim is to raise awareness in the scientific community (geneticists, physiologists, ecophysiologists, agronomists, …) about the caper strengths and interest to the development of this shrub as a crop.

  3. The medicinal chemistry and neuropharmacology of kratom: A preliminary discussion of a promising medicinal plant and analysis of its potential for abuse.

    Science.gov (United States)

    Kruegel, Andrew C; Grundmann, Oliver

    2017-08-19

    The leaves of Mitragyna speciosa (commonly known as kratom), a tree endogenous to parts of Southeast Asia, have been used traditionally for their stimulant, mood-elevating, and analgesic effects and have recently attracted significant attention due to increased use in Western cultures as an alternative medicine. The plant's active alkaloid constituents, mitragynine and 7-hydroxymitragynine, have been shown to modulate opioid receptors, acting as partial agonists at mu-opioid receptors and competitive antagonists at kappa- and delta-opioid receptors. Furthermore, both alkaloids are G protein-biased agonists of the mu-opioid receptor and therefore, may induce less respiratory depression than classical opioid agonists. The Mitragyna alkaloids also appear to exert diverse activities at other brain receptors (including adrenergic, serotonergic, and dopaminergic receptors), which may explain the complex pharmacological profile of raw kratom extracts, although characterization of effects at these other targets remains extremely limited. Through allometric scaling, doses of pure mitragynine and 7-hydroxymitragynine used in animal studies can be related to single doses of raw kratom plant commonly consumed by humans, permitting preliminary interpretation of expected behavioral and physiological effects in man based on this preclinical data and comparison to both anecdotal human experience and multiple epidemiological surveys. Kratom exposure alone has not been causally associated with human fatalities to date. However, further research is needed to clarify the complex mechanism of action of the Mitragyna alkaloids and unlock their full therapeutic potential. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Olive-pomace harbors bacteria with the potential for hydrocarbon-biodegradation, nitrogen-fixation and mercury-resistance: promising material for waste-oil-bioremediation.

    Science.gov (United States)

    Dashti, Narjes; Ali, Nedaa; Khanafer, Majida; Al-Awadhi, Husain; Sorkhoh, Naser; Radwan, Samir

    2015-05-15

    Olive-pomace, a waste by-product of olive oil industry, took up >40% of its weight crude oil. Meanwhile, this material harbored a rich and diverse hydrocarbonoclastic bacterial population in the magnitude of 10(6) to 10(7) cells g(-1). Using this material for bioaugmentation of batch cultures in crude oil-containing mineral medium, resulted in the consumption of 12.9, 21.5, 28.3, and 43% oil after 2, 4, 6 and 8 months, respectively. Similar oil-consumption values, namely 11.0, 29.3, 34.7 and 43.9%, respectively, were recorded when a NaNO3-free medium was used instead of the complete medium. Hydrocarbonoclastic bacteria involved in those bioremediation processes, as characterized by their 16S rRNA-gene sequences, belonged to the genera Agrococcus, Pseudomonas, Cellulosimicrobium, Streptococcus, Sinorhizobium, Olivibacter, Ochrobactrum, Rhizobium, Pleomorphomonas, Azoarcus, Starkeya and others. Many of the bacterial species belonging to those genera were diazotrophic; they proved to contain the nifH-genes in their genomes. Still other bacterial species could tolerate the heavy metal mercury. The dynamic changes of the proportions of various species during 8 months of incubation were recorded. The culture-independent, phylogenetic analysis of the bacterioflora gave lists different from those recorded by the culture-dependent method. Nevertheless, those lists comprised among others, several genera known for their hydrocarbonoclastic potential, e.g. Pseudomonas, Mycobacterium, Sphingobium, and Citrobacter. It was concluded that olive-pomace could be applied in oil-remediation, not only as a physical sorbent, but also for bioaugmentation purposes as a biological source of hydrocarbonoclastic bacteria. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Anodal sensory nerve action potentials: From physiological understanding to potential clinical applicability.

    Science.gov (United States)

    Leote, Joao; Pereira, Pedro; Cabib, Christopher; Cipullo, Federica; Valls-Sole, Josep

    2016-06-01

    Low-intensity electrical stimuli of digital nerves may generate a double peak potential (DPp), composed of a cathodal (caAP) and an anodal (anAP) potential in orthodromic recordings. We studied the effects on caAP and anAP of stimuli of variable intensity, duration, and frequency. We also applied a conditioning stimulus to study potential differences in recovery time. The anAP was obtained in 33 of 40 healthy subjects (82.5%) and 4 of 20 patients with various types of sensory neuropathies (20%). Changes in stimulus duration and intensity had reciprocal effects on the amplitude of the anAP and the caAP. There were significant differences in recovery time between caAP and anAP after a conditioning stimulus. The caAP and anAP are 2 interdependent waveforms generated by different effects of the same stimulus over axons at the verge of depolarization. Muscle Nerve 53: 897-905, 2016. © 2015 Wiley Periodicals, Inc.

  6. Promise Zones for Applicants

    Data.gov (United States)

    Department of Housing and Urban Development — This tool assists applicants to HUD's Promise Zone initiative prepare data to submit with their application by allowing applicants to draw the exact location of the...

  7. Care and feeding of the endocannabinoid system: a systematic review of potential clinical interventions that upregulate the endocannabinoid system.

    Science.gov (United States)

    McPartland, John M; Guy, Geoffrey W; Di Marzo, Vincenzo

    2014-01-01

    The "classic" endocannabinoid (eCB) system includes the cannabinoid receptors CB1 and CB2, the eCB ligands anandamide (AEA) and 2-arachidonoylglycerol (2-AG), and their metabolic enzymes. An emerging literature documents the "eCB deficiency syndrome" as an etiology in migraine, fibromyalgia, irritable bowel syndrome, psychological disorders, and other conditions. We performed a systematic review of clinical interventions that enhance the eCB system--ways to upregulate cannabinoid receptors, increase ligand synthesis, or inhibit ligand degradation. We searched PubMed for clinical trials, observational studies, and preclinical research. Data synthesis was qualitative. Exclusion criteria limited the results to 184 in vitro studies, 102 in vivo animal studies, and 36 human studies. Evidence indicates that several classes of pharmaceuticals upregulate the eCB system, including analgesics (acetaminophen, non-steroidal anti-inflammatory drugs, opioids, glucocorticoids), antidepressants, antipsychotics, anxiolytics, and anticonvulsants. Clinical interventions characterized as "complementary and alternative medicine" also upregulate the eCB system: massage and manipulation, acupuncture, dietary supplements, and herbal medicines. Lifestyle modification (diet, weight control, exercise, and the use of psychoactive substances--alcohol, tobacco, coffee, cannabis) also modulate the eCB system. Few clinical trials have assessed interventions that upregulate the eCB system. Many preclinical studies point to other potential approaches; human trials are needed to explore these promising interventions.

  8. Care and feeding of the endocannabinoid system: a systematic review of potential clinical interventions that upregulate the endocannabinoid system.

    Directory of Open Access Journals (Sweden)

    John M McPartland

    Full Text Available The "classic" endocannabinoid (eCB system includes the cannabinoid receptors CB1 and CB2, the eCB ligands anandamide (AEA and 2-arachidonoylglycerol (2-AG, and their metabolic enzymes. An emerging literature documents the "eCB deficiency syndrome" as an etiology in migraine, fibromyalgia, irritable bowel syndrome, psychological disorders, and other conditions. We performed a systematic review of clinical interventions that enhance the eCB system--ways to upregulate cannabinoid receptors, increase ligand synthesis, or inhibit ligand degradation.We searched PubMed for clinical trials, observational studies, and preclinical research. Data synthesis was qualitative. Exclusion criteria limited the results to 184 in vitro studies, 102 in vivo animal studies, and 36 human studies. Evidence indicates that several classes of pharmaceuticals upregulate the eCB system, including analgesics (acetaminophen, non-steroidal anti-inflammatory drugs, opioids, glucocorticoids, antidepressants, antipsychotics, anxiolytics, and anticonvulsants. Clinical interventions characterized as "complementary and alternative medicine" also upregulate the eCB system: massage and manipulation, acupuncture, dietary supplements, and herbal medicines. Lifestyle modification (diet, weight control, exercise, and the use of psychoactive substances--alcohol, tobacco, coffee, cannabis also modulate the eCB system.Few clinical trials have assessed interventions that upregulate the eCB system. Many preclinical studies point to other potential approaches; human trials are needed to explore these promising interventions.

  9. Tolerogenic Dendritic Cells as a Promising Antigen-Specific Therapy in the Treatment of Multiple Sclerosis and Neuromyelitis Optica From Preclinical to Clinical Trials

    Directory of Open Access Journals (Sweden)

    Georgina Flórez-Grau

    2018-05-01

    Full Text Available The identification of activated T-lymphocytes restricted to myelin-derived immunogenic peptides in multiple sclerosis (MS and aquaporin-4 water channel in neuromyelitis optica (NMO in the blood of patients opened the possibility for developing highly selective and disease-specific therapeutic approaches. Antigen presenting cells and in particular dendritic cells (DCs represent a strategy to inhibit pro-inflammatory T helper cells. DCs are located in peripheral and lymphoid tissues and are essential for homeostasis of T cell-dependent immune responses. The expression of a particular set of receptors involved in pathogen recognition confers to DCs the property to initiate immune responses. However, in the absence of danger signals different DC subsets have been revealed to induce active tolerance by inducing regulatory T cells, inhibiting pro-inflammatory T helper cells responses or both. Interestingly, several protocols to generate clinical-grade tolerogenic DC (Tol-DC in vitro have been described, offering the possibility to restore the homeostasis to central nervous system-related antigens. In this review, we discuss about different DC subsets and their role in tolerance induction, the different protocols to generate Tol-DCs and preclinical studies in animal models as well as describe recent characterization of Tol-DCs for clinical application in autoimmune diseases and in particular in MS and NMO patients. In addition, we discuss the clinical trials ongoing based on Tol-DCs to treat different autoimmune diseases.

  10. Artificial Intelligence in Surgery: Promises and Perils.

    Science.gov (United States)

    Hashimoto, Daniel A; Rosman, Guy; Rus, Daniela; Meireles, Ozanan R

    2018-07-01

    The aim of this review was to summarize major topics in artificial intelligence (AI), including their applications and limitations in surgery. This paper reviews the key capabilities of AI to help surgeons understand and critically evaluate new AI applications and to contribute to new developments. AI is composed of various subfields that each provide potential solutions to clinical problems. Each of the core subfields of AI reviewed in this piece has also been used in other industries such as the autonomous car, social networks, and deep learning computers. A review of AI papers across computer science, statistics, and medical sources was conducted to identify key concepts and techniques within AI that are driving innovation across industries, including surgery. Limitations and challenges of working with AI were also reviewed. Four main subfields of AI were defined: (1) machine learning, (2) artificial neural networks, (3) natural language processing, and (4) computer vision. Their current and future applications to surgical practice were introduced, including big data analytics and clinical decision support systems. The implications of AI for surgeons and the role of surgeons in advancing the technology to optimize clinical effectiveness were discussed. Surgeons are well positioned to help integrate AI into modern practice. Surgeons should partner with data scientists to capture data across phases of care and to provide clinical context, for AI has the potential to revolutionize the way surgery is taught and practiced with the promise of a future optimized for the highest quality patient care.

  11. Clinical decision support systems for primary care: the identification of promising application areas and an initial design of a CDSS for lower back pain

    NARCIS (Netherlands)

    Oude Nijeweme-d'Hollosy, W.; Velsen, L. van; Swinkels, I.C.S.; Hermens, H.

    2015-01-01

    Decision support technology has the potential to change the way professionals treat patients for the better. We questioned thirty-three healthcare professionals on their view about the usage of eHealth technology within their daily practice, and areas in which decision support can play a role, to

  12. Clinically relevant potential drug-drug interactions among outpatients: A nationwide database study.

    Science.gov (United States)

    Jazbar, Janja; Locatelli, Igor; Horvat, Nejc; Kos, Mitja

    2018-06-01

    Adverse drug events due to drug-drug interactions (DDIs) represent a considerable public health burden, also in Slovenia. A better understanding of the most frequently occurring potential DDIs may enable safer pharmacotherapy and minimize drug-related problems. The aim of this study was to evaluate the prevalence and predictors of potential DDIs among outpatients in Slovenia. An analysis of potential DDIs was performed using health claims data on prescription drugs from a nationwide database. The Lexi-Interact Module was used as the reference source of interactions. The influence of patient-specific predictors on the risk of potential clinically relevant DDIs was evaluated using logistic regression model. The study population included 1,179,803 outpatients who received 15,811,979 prescriptions. The total number of potential DDI cases identified was 3,974,994, of which 15.6% were potentially clinically relevant. Altogether, 9.3% (N = 191,213) of the total population in Slovenia is exposed to clinically relevant potential DDIs, and the proportion is higher among women and the elderly. After adjustment for cofactors, higher number of medications and older age are associated with higher odds of clinically relevant potential DDIs. The burden of DDIs is highest with drug combinations that increase risk of bleeding, enhance CNS depression or anticholinergic effects or cause cardiovascular complications. The current study revealed that 1 in 10 individuals in the total Slovenian population is exposed to clinically relevant potential DDIs yearly. Taking into account the literature based conservative estimate that approximately 1% of potential DDIs result in negative health outcomes, roughly 1800 individuals in Slovenia experience an adverse health outcome each year as a result of clinically relevant potential interactions alone. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Promising adoption of an electronic clinical decision support system for antenatal and intrapartum care in rural primary healthcare facilities in sub-Saharan Africa: The QUALMAT experience.

    Science.gov (United States)

    Sukums, Felix; Mensah, Nathan; Mpembeni, Rose; Massawe, Siriel; Duysburgh, Els; Williams, Afua; Kaltschmidt, Jens; Loukanova, Svetla; Haefeli, Walter E; Blank, Antje

    2015-09-01

    The QUALMAT project has successfully implemented an electronic clinical decision support system (eCDSS) for antenatal and intrapartum care in two sub-Saharan African countries. The system was introduced to facilitate adherence to clinical practice guidelines and to support decision making during client encounter to bridge the know-do gap of health workers. This study aimed to describe health workers' acceptance and use of the eCDSS for maternal care in rural primary health care (PHC) facilities of Ghana and Tanzania and to identify factors affecting successful adoption of such a system. This longitudinal study was conducted in Lindi rural district in Tanzania and Kassena-Nankana district in Ghana between October 2011 and December 2013 employing mixed methods. The study population included healthcare workers who were involved in the provision of maternal care in six rural PHC facilities from one district in each country where the eCDSS was implemented. All eCDSS users participated in the study with 61 and 56 participants at the midterm and final assessment, respectively. After several rounds of user training and support the eCDSS has been successfully adopted and constantly used during patient care in antenatal clinics and maternity wards. The eCDSS was used in 71% (2703/3798) and 59% (14,189/24,204) of all ANC clients in Tanzania and Ghana respectively, while it was also used in 83% (1185/1427) and 67% (1435/2144) of all deliveries in Tanzania and in Ghana, respectively. Several barriers reported to hinder eCDSS use were related to individual users, tasks, technology, and organization attributes. Implementation of an eCDSS in resource-constrained PHC facilities in sub-Saharan Africa was successful and the health workers accepted and continuously used the system for maternal care. Facilitators for eCDSS use included sufficient training and regular support whereas the challenges to sustained use were unreliable power supply and perceived high workload. However our

  14. Promising More Information

    Science.gov (United States)

    2003-01-01

    When NASA needed a real-time, online database system capable of tracking documentation changes in its propulsion test facilities, engineers at Stennis Space Center joined with ECT International, of Brookfield, Wisconsin, to create a solution. Through NASA's Dual-Use Program, ECT developed Exdata, a software program that works within the company's existing Promise software. Exdata not only satisfied NASA s requirements, but also expanded ECT s commercial product line. Promise, ECT s primary product, is an intelligent software program with specialized functions for designing and documenting electrical control systems. An addon to AutoCAD software, Promis e generates control system schematics, panel layouts, bills of material, wire lists, and terminal plans. The drawing functions include symbol libraries, macros, and automatic line breaking. Primary Promise customers include manufacturing companies, utilities, and other organizations with complex processes to control.

  15. Harnessing Cerebrospinal Fluid Biomarkers in Clinical Trials for Treating Alzheimer's and Parkinson's Diseases: Potential and Challenges.

    Science.gov (United States)

    Kim, Dana; Kim, Young Sam; Shin, Dong Wun; Park, Chang Shin; Kang, Ju Hee

    2016-10-01

    No disease-modifying therapies (DMT) for neurodegenerative diseases (NDs) have been established, particularly for Alzheimer's disease (AD) and Parkinson's disease (PD). It is unclear why candidate drugs that successfully demonstrate therapeutic effects in animal models fail to show disease-modifying effects in clinical trials. To overcome this hurdle, patients with homogeneous pathologies should be detected as early as possible. The early detection of AD patients using sufficiently tested biomarkers could demonstrate the potential usefulness of combining biomarkers with clinical measures as a diagnostic tool. Cerebrospinal fluid (CSF) biomarkers for NDs are being incorporated in clinical trials designed with the aim of detecting patients earlier, evaluating target engagement, collecting homogeneous patients, facilitating prevention trials, and testing the potential of surrogate markers relative to clinical measures. In this review we summarize the latest information on CSF biomarkers in NDs, particularly AD and PD, and their use in clinical trials. The large number of issues related to CSF biomarker measurements and applications has resulted in relatively few clinical trials on CSF biomarkers being conducted. However, the available CSF biomarker data obtained in clinical trials support the advantages of incorporating CSF biomarkers in clinical trials, even though the data have mostly been obtained in AD trials. We describe the current issues with and ongoing efforts for the use of CSF biomarkers in clinical trials and the plans to harness CSF biomarkers for the development of DMT and clinical routines. This effort requires nationwide, global, and multidisciplinary efforts in academia, industry, and regulatory agencies to facilitate a new era.

  16. The clinical role of microRNA-21 as a promising biomarker in the diagnosis and prognosis of colorectal cancer: a systematic review and meta-analysis.

    Science.gov (United States)

    Peng, Qiliang; Zhang, Xueli; Min, Ming; Zou, Li; Shen, Peipei; Zhu, Yaqun

    2017-07-04

    This systematic analysis aimed to investigate the value of microRNA-21 (miR-21) in colorectal cancer for multiple purposes, including diagnosis and prognosis, as well as its predictive power in combination biomarkers. Fifty-seven eligible studies were included in our meta-analysis, including 25 studies for diagnostic meta-analysis and 32 for prognostic meta-analysis. For the diagnostic meta-analysis of miR-21 alone, the overall pooled results for sensitivity, specificity, and area under the curve (AUC) were 0.64 (95% CI: 0.53-0.74), 0.85 (0.79-0.90), and 0.85 (0.81-0.87), respectively. Circulating samples presented corresponding values of 0.72 (0.63-0.79), 0.84 (0.78-0.89), and 0.86 (0.83-0.89), respectively. For the diagnostic meta-analysis of miR-21-related combination biomarkers, the above three parameters were 0.79 (0.69-0.86), 0.79 (0.68-0.87), and 0.86 (0.83-0.89), respectively. Notably, subgroup analysis suggested that miRNA combination markers in circulation exhibited high predictive power, with sensitivity of 0.85 (0.70-0.93), specificity of 0.86 (0.77-0.92), and AUC of 0.92 (0.89-0.94). For the prognostic meta-analysis, patients with higher expression of miR-21 had significant shorter disease-free survival [DFS; pooled hazard ratio (HR): 1.60; 95% CI: 1.20-2.15] and overall survival (OS; 1.54; 1.27-1.86). The combined HR in tissues for DFS and OS were 1.76 (1.31-2.36) and 1.58 (1.30-1.93), respectively. Our comprehensive systematic review revealed that circulating miR-21 may be suitable as a diagnostic biomarker, while tissue miR-21 could be a prognostic marker for colorectal cancer. In addition, miRNA combination biomarkers may provide a new approach for clinical application.

  17. Clinical potential of naloxegol in the management of opioid-induced bowel dysfunction

    Directory of Open Access Journals (Sweden)

    Poulsen JL

    2014-09-01

    Full Text Available Jakob Lykke Poulsen,1 Christina Brock,1,2 Anne Estrup Olesen,1,2 Matias Nilsson,1 Asbjørn Mohr Drewes1,3 1Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark; 2Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark; 3Department of Clinical Medicine, Aalborg University, Aalborg, DenmarkAbstract: Opioid-induced bowel dysfunction (OIBD is a burdensome condition which limits the therapeutic benefit of analgesia. It affects the entire gastrointestinal tract, predominantly by activating opioid receptors in the enteric nervous system, resulting in a wide range of symptoms, such as reflux, bloating, abdominal cramping, hard, dry stools, and incomplete evacuation. The majority of studies evaluating OIBD focus on constipation experienced in approximately 60% of patients. Nevertheless, other presentations of OIBD seem to be equally frequent. Furthermore, laxative treatment is often insufficient, which in many patients results in decreased quality of life and discontinuation of opioid treatment. Novel mechanism-based pharmacological approaches targeting the gastrointestinal opioid receptors have been marketed recently and even more are in the pipeline. One strategy is prolonged release formulation of the opioid antagonist naloxone (which has limited systemic absorption and oxycodone in a combined tablet. Another approach is peripherally acting, µ-opioid receptor antagonists (PAMORAs that selectively target µ-opioid receptors in the gastrointestinal tract. However, in Europe the only PAMORA approved for OIBD is the subcutaneously administered methylnaltrexone. Alvimopan is an oral PAMORA, but only approved in the US for postoperative ileus in hospitalized patients. Finally, naloxegol is a novel, oral PAMORA expected to be approved soon. In this review, the prevalence and pathophysiology of OIBD is presented. As PAMORAs seem to be a promising approach, their potential

  18. Evaluating sub-clinical cognitive dysfunction and event-related potentials (P300) in clinically isolated syndrome.

    Science.gov (United States)

    Kocer, Belgin; Unal, Tugba; Nazliel, Bijen; Biyikli, Zeynep; Yesilbudak, Zulal; Karakas, Sirel; Irkec, Ceyla

    2008-12-01

    This study investigated the presence of sub-clinical cognitive dysfunction in patients with clinically isolated syndrome (CIS) and the abnormalities of cognitive event-related potentials (ERPs). Subclinical cognitive dysfunction was assessed in 20 patients with CIS and in 20 healthy controls. Patients had impairments in verbal learning and long-term memory, evaluating attention, executive function and visuospatial skills, in decreasing order of frequency. SDLT and SIT were the most, and COWAT and BNT were the least affected tests. The N200 and P200 latencies were prolonged, and N100, N200 and P200 amplitudes were reduced in the patients relative to the controls, from the Fz, Cz and Pz electrode positions (p<0.05). Detailed cognitive testing is valuable in determining subclinical cognitive dysfunction in CIS patients. ERP abnormalities as well as abnormalities in detailed cognitivetesting in patients with CIS are helpful in the diagnosis of sub-clinical cognitive dysfunction.

  19. Realizing the promises of marine biotechnology

    NARCIS (Netherlands)

    Luiten, EEM; Akkerman, [No Value; Koulman, A; Kamermans, P; Reith, H; Barbosa, MJ; Sipkema, D; Wijffels, RH

    High-quality research in the field of marine biotechnology is one of the key-factors for successful innovation in exploiting the vast diversity of marine life. However, fascinating scientific research with promising results and claims on promising potential applications (e.g. for pharmaceuticals,

  20. Realizing the promises of marine biotechnology

    NARCIS (Netherlands)

    Luiten, E.E.M.; Akkerman, I.; Koulman, A.; Kamermans, P.; Reith, H.; Barbosa, M.J.; Sipkema, D.; Wijffels, R.H.

    2003-01-01

    High-quality research in the field of marine biotechnology is one of the key-factors for successful innovation in exploiting the vast diversity of marine life. However, fascinating scientific research with promising results and claims on promising potential applications (e.g. for pharmaceuticals,

  1. Potential Impact on Clinical Decision Making via a Genome-Wide Expression Profiling: A Case Report

    Directory of Open Access Journals (Sweden)

    Hyun Kim

    2016-11-01

    Full Text Available Management of men with prostate cancer is fraught with uncertainty as physicians and patients balance efficacy with potential toxicity and diminished quality of life. Utilization of genomics as a prognostic biomarker has improved the informed decision-making process by enabling more rationale treatment choices. Recently investigations have begun to determine whether genomic information from tumor transcriptome data can be used to impact clinical decision-making beyond prognosis. Here we discuss the potential of genomics to alter management of a patient who presented with high-risk prostate adenocarcinoma. We suggest that this information help selecting patients for advanced imaging, chemotherapies, or clinical trial.

  2. Human Amniotic Membrane-Derived Products in Sports Medicine: Basic Science, Early Results, and Potential Clinical Applications.

    Science.gov (United States)

    Riboh, Jonathan C; Saltzman, Bryan M; Yanke, Adam B; Cole, Brian J

    2016-09-01

    Amniotic membrane (AM)-derived products have been successfully used in ophthalmology, plastic surgery, and wound care, but little is known about their potential applications in orthopaedic sports medicine. To provide an updated review of the basic science and preclinical and clinical data supporting the use of AM-derived products and to review their current applications in sports medicine. Systematic review. A systematic search of the literature was conducted using the Medline, EMBASE, and Cochrane databases. The search term amniotic membrane was used alone and in conjunction with stem cell, orthopaedic, tissue engineering, scaffold, and sports medicine. The search identified 6870 articles, 80 of which, after screening of the titles and abstracts, were considered relevant to this study. Fifty-five articles described the anatomy, basic science, and nonorthopaedic applications of AM-derived products. Twenty-five articles described preclinical and clinical trials of AM-derived products for orthopaedic sports medicine. Because the level of evidence obtained from this search was not adequate for systematic review or meta-analysis, a current concepts review on the anatomy, physiology, and clinical uses of AM-derived products is presented. Amniotic membranes have many promising applications in sports medicine. They are a source of pluripotent cells, highly organized collagen, antifibrotic and anti-inflammatory cytokines, immunomodulators, and matrix proteins. These properties may make it beneficial when applied as tissue engineering scaffolds, improving tissue organization in healing, and treatment of the arthritic joint. The current body of evidence in sports medicine is heavily biased toward in vitro and animal studies, with little to no human clinical data. Nonetheless, 14 companies or distributors offer commercial AM products. The preparation and formulation of these products alter their biological and mechanical properties, and a thorough understanding of these

  3. Systematic review of induced pluripotent stem cell technology as a potential clinical therapy for spinal cord injury.

    Science.gov (United States)

    Kramer, Anne S; Harvey, Alan R; Plant, Giles W; Hodgetts, Stuart I

    2013-01-01

    Transplantation therapies aimed at repairing neurodegenerative and neuropathological conditions of the central nervous system (CNS) have utilized and tested a variety of cell candidates, each with its own unique set of advantages and disadvantages. The use and popularity of each cell type is guided by a number of factors including the nature of the experimental model, neuroprotection capacity, the ability to promote plasticity and guided axonal growth, and the cells' myelination capability. The promise of stem cells, with their reported ability to give rise to neuronal lineages to replace lost endogenous cells and myelin, integrate into host tissue, restore functional connectivity, and provide trophic support to enhance and direct intrinsic regenerative ability, has been seen as a most encouraging step forward. The advent of the induced pluripotent stem cell (iPSC), which represents the ability to "reprogram" somatic cells into a pluripotent state, hails the arrival of a new cell transplantation candidate for potential clinical application in therapies designed to promote repair and/or regeneration of the CNS. Since the initial development of iPSC technology, these cells have been extensively characterized in vitro and in a number of pathological conditions and were originally reported to be equivalent to embryonic stem cells (ESCs). This review highlights emerging evidence that suggests iPSCs are not necessarily indistinguishable from ESCs and may occupy a different "state" of pluripotency with differences in gene expression, methylation patterns, and genomic aberrations, which may reflect incomplete reprogramming and may therefore impact on the regenerative potential of these donor cells in therapies. It also highlights the limitations of current technologies used to generate these cells. Moreover, we provide a systematic review of the state of play with regard to the use of iPSCs in the treatment of neurodegenerative and neuropathological conditions. The

  4. Potential Immune Biomarkers in Diagnosis and Clinical Management for Systemic Lupus Erythematosus

    Directory of Open Access Journals (Sweden)

    Zecevic Lamija

    2018-04-01

    Full Text Available Background: There is still no reliable, specific biomarker for precision diagnosis and clinical monitoring of systemic lupus erythematosus. The aim of this study was to investigate the importance of the determination of immunofenotypic profiles (T, B lymphocytes and NK cells and serum cytokine concentrations (IL-17 and IFN-alpha as potential biomarkers for this disease.

  5. Proton therapy for head and neck cancer: Rationale, potential indications, practical considerations, and current clinical evidence

    International Nuclear Information System (INIS)

    Mendenhall, Nancy P.; Malyapa, Robert S.; Su, Zhong; Yeung, Daniel; Mendenhall, William M.; Li, Zuofeng

    2011-01-01

    There is a strong rationale for potential benefits from proton therapy (PT) for selected cancers of the head and neck because of the opportunity to improve the therapeutic ratio by improving radiation dose distributions and because of the significant differences in radiation dose distribution achievable with x-ray-based radiation therapy (RT) and PT. Comparisons of dose distributions between x-ray-based and PT plans in selected cases show specific benefits in dose distribution likely to translate into improved clinical outcomes. However, the use of PT in head and neck cancers requires special considerations in the simulation and treatment planning process, and currently available PT technology may not permit realization of the maximum potential benefits of PT. To date, few clinical data are available, but early clinical experiences in sinonasal tumors in particular suggest significant improvements in both disease control and radiation-related toxicity

  6. Proton therapy for head and neck cancer: Rationale, potential indications, practical considerations, and current clinical evidence

    Energy Technology Data Exchange (ETDEWEB)

    Mendenhall, Nancy P.; Malyapa, Robert S.; Su, Zhong; Yeung, Daniel; Mendenhall, William M.; Li, Zuofeng (Univ. of Florida Proton Therapy Inst., Jacksonville, Florida (United States)), e-mail: menden@shands.ufl.edu

    2011-08-15

    There is a strong rationale for potential benefits from proton therapy (PT) for selected cancers of the head and neck because of the opportunity to improve the therapeutic ratio by improving radiation dose distributions and because of the significant differences in radiation dose distribution achievable with x-ray-based radiation therapy (RT) and PT. Comparisons of dose distributions between x-ray-based and PT plans in selected cases show specific benefits in dose distribution likely to translate into improved clinical outcomes. However, the use of PT in head and neck cancers requires special considerations in the simulation and treatment planning process, and currently available PT technology may not permit realization of the maximum potential benefits of PT. To date, few clinical data are available, but early clinical experiences in sinonasal tumors in particular suggest significant improvements in both disease control and radiation-related toxicity

  7. Harnessing the potential clinical use of medicinal plants as anti-diabetic agents

    Directory of Open Access Journals (Sweden)

    Campbell-Tofte JI

    2012-08-01

    Full Text Available Joan IA Campbell-Tofte,1 Per Mølgaard,2 Kaj Winther11Department of Clinical Biochemistry, Frederiksberg University Hospital, Frederiksberg, Denmark; 2Department of Medicinal Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, Copenhagen, DenmarkAbstract: Diabetes is a metabolic disorder arising from complex interactions between multiple genetic and/or environmental factors. The characteristic high blood sugar levels result from either lack of the hormone insulin (type 1 diabetes, T1D, or because body tissues do not respond to the hormone (type 2 diabetes, T2D. T1D patients currently need exogenous insulin for life, while for T2D patients who do not respond to diet and exercise regimes, oral anti-diabetic drugs (OADs and sometimes insulin are administered to help keep their blood glucose as normal as possible. As neither the administration of insulin nor OADs is curative, many patients develop tissue degenerative processes that result in life-threatening diabetes comorbidities. Several surveys of medicinal plants used as anti-diabetic agents amongst different peoples have been published. Some of this interest is driven by the ongoing diabetes pandemic coupled with the inadequacies associated with the current state of-the-art care and management of the syndrome. However, there is a huge cleft between traditional medicine and modern (Western medicine, with the latter understandably demanding meaningful and scientific validation of anecdotal evidence for acceptance of the former. The main problems for clinical evaluation of medicinal plants with promising anti-diabetic properties reside both with the complexity of components of the plant materials and with the lack of full understanding of the diabetes disease etiology. This review is therefore focused on why research activities involving an integration of Systems Biology-based technologies of pharmacogenomics, metabolomics, and bioinformatics with standard clinical data

  8. Prevalence of Potential and Clinically Relevant Statin-Drug Interactions in Frail and Robust Older Inpatients.

    Science.gov (United States)

    Thai, Michele; Hilmer, Sarah; Pearson, Sallie-Anne; Reeve, Emily; Gnjidic, Danijela

    2015-10-01

    A significant proportion of older people are prescribed statins and are also exposed to polypharmacy, placing them at increased risk of statin-drug interactions. To describe the prevalence rates of potential and clinically relevant statin-drug interactions in older inpatients according to frailty status. A cross-sectional study of patients aged ≥65 years who were prescribed a statin and were admitted to a teaching hospital between 30 July and 10 October 2014 in Sydney, Australia, was conducted. Data on socio-demographics, comorbidities and medications were collected using a standardized questionnaire. Potential statin-drug interactions were defined if listed in the Australian Medicines Handbook and three international drug information sources: the British National Formulary, Drug Interaction Facts and Drug-Reax(®). Clinically relevant statin-drug interactions were defined as interactions with the highest severity rating in at least two of the three international drug information sources. Frailty was assessed using the Reported Edmonton Frail Scale. A total of 180 participants were recruited (median age 78 years, interquartile range 14), 35.0% frail and 65.0% robust. Potential statin-drug interactions were identified in 10% of participants, 12.7% of frail participants and 8.5% of robust participants. Clinically relevant statin-drug interactions were identified in 7.8% of participants, 9.5% of frail participants and 6.8% of robust participants. Depending on the drug information source used, the prevalence rates of potential and clinically relevant statin-drug interactions ranged between 14.4 and 35.6% and between 14.4 and 20.6%, respectively. In our study of frail and robust older inpatients taking statins, the overall prevalence of potential statin-drug interactions was low and varied significantly according to the drug information source used.

  9. Immunosuppression by hypoxic cell radiosensitizers: a phenomenon of potential clinical importance

    International Nuclear Information System (INIS)

    Rockwell, S.; Kapp, D.S.

    1982-01-01

    The nitroimidazoles metronidazole, misonidazol, and desmethyl misonidazole are currently undergoing clinical trials as possible adjuncts to radiotherapy. Ongoing clinical trials are evaluating the effectiveness of these agents and also documenting the pharmacokinetics and toxicities of radiosensitizing doses of these drugs in man. A variety of toxic effects have been noted in man, including anorexia, nausea and vomiting, peripheral neuropathy, central nervous system symptoms, ototoxicity, allergy, and fear. Laboratory studies have also suggested that these agents have potential to be mutagenic, carcinogenic, and teratogenic. In the editorial presented, the author attempts to draw attention to an additional toxic effect of nitroimidazoles - the inhibition of cell-mediated immune responses

  10. The potential of telehealth for 'business as usual' in outpatient clinics.

    Science.gov (United States)

    Day, Karen; Kerr, Patricia

    2012-04-01

    A six-month pilot study was conducted to ascertain the value of using high-definition videoconferencing equipment in an outpatients' setting. The videoconferencing equipment, which included digital biometric equipment, was installed in the outpatient clinics of a remote health service in New Zealand. Use of the equipment was evaluated using action research techniques. Clinicians were interviewed about their assessment of the equipment's usefulness. Patients and their carers completed questionnaires about their clinic experience. During the pilot trial, 109 patients were seen in 25 clinics of six different specialities. Questionnaire results showed that patients and their companions had a good user experience, similar to a face-to-face appointment. Clinicians found that the large screen, sense of proximity, video clarity and definition, and lack of sound/picture lag worked well for certain types of outpatients' clinics, e.g. methadone maintenance clinics. The need for process changes made it difficult to turn telehealth into business as usual in an environment built for face-to-face appointments. We conclude that videoconference equipment has potential to become integral to outpatients' clinics.

  11. Clinical evidence of the efficacy of everolimus and its potential in the treatment of breast cancer

    Directory of Open Access Journals (Sweden)

    Saksena R

    2013-05-01

    Full Text Available Rujuta Saksena, Serena T WongThe Cancer Institute of New Jersey, New Brunswick, NJ, USAAbstract: The PI3K/Akt/mTOR (phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin pathway regulates several key cellular functions and its dysregulation creates an environment that promotes tumorigenesis as well as resistance to therapy. The mTOR inhibitor everolimus has emerged as a promising agent in the treatment of breast cancer and was recently approved in combination with exemestane for advanced hormone receptor–positive disease after progression on a nonsteroidal aromatase inhibitor. Everolimus may also be effective in combination with cytotoxic and human epidermal growth factor receptor-2-directed therapies for the treatment of other subtypes of breast cancer. This paper highlights preclinical and clinical data that have emerged on the role of mTOR inhibition in breast cancer. Although generally well tolerated, everolimus carries a unique side effect profile of which both patients and providers should be made aware. Recommendations related to the administration of everolimus in the clinical setting are also discussed.Keywords: everolimus, breast cancer, mTOR inhibition

  12. Clinical proteomics

    DEFF Research Database (Denmark)

    Albrethsen, Jakob; Frederiksen, Hanne; Johannsen, Trine Holm

    2018-01-01

    Clinical proteomics aims to deliver cost-effective multiplexing of potentially hundreds of diagnostic proteins, including distinct protein isoforms. The analytical strategy known as targeted proteomics is particularly promising because it is compatible with robust mass spectrometry (MS)-platforms...... standards and calibrants. The present challenge is to examine if targeted proteomics of IGF-I can truly measure up to the routine performance that must be expected from a clinical testing platform.......Clinical proteomics aims to deliver cost-effective multiplexing of potentially hundreds of diagnostic proteins, including distinct protein isoforms. The analytical strategy known as targeted proteomics is particularly promising because it is compatible with robust mass spectrometry (MS......)-platforms already implemented in many clinical laboratories for routine quantitation of small molecules (i.e. uHPLC coupled to triple-quadrupole MS). Progress in targeted proteomics of circulating insulin-like growth factor 1 (IGF-I) have provided valuable insights about tryptic peptides, transitions, internal...

  13. The potential role for a pharmacist in a multidisciplinary general practitioner super clinic.

    Science.gov (United States)

    Bajorek, Beata; LeMay, Kate; Gunn, Kate; Armour, Carol

    2015-01-01

    The Australian government's General Practitioner (GP) super clinics programme aims to provide well-integrated, multidisciplinary, patient-centred care for people with chronic disease. However, there is no research into the current role of pharmacists in this setting. To explore the perspectives of GP super clinic staff on current and potential (future) pharmacist-led services provided in this setting. Individual interviews (facilitated using a semi-structured interview guide and thematically analysed) were conducted with purposively sampled staff of a GP super clinic in a semirural location in the state of New South Wales, until theme saturation. Participating staff included (n=9): three GPs, one pharmacist, one nurse, one business manager, and three reception staff. Three themes emerged conveying perspectives on: working relationships between staff; a pharmacist's current role; and potential future roles for a pharmacist. All clinic staff actively engaged the pharmacist in their "team approach". Currently established roles for home medicines reviews (HMRs) and drug information were well supported, but needed to be expanded, for example, with formalised case conferences between GPs, pharmacists, and other staff. New roles needed be explored in auditing medication use, optimising medication records, specialised drug information, dispensing, and prescribing. Although GPs had differing views about opportunities for pharmacists' prescribing in this setting, they saw several benefits to this service, such as reducing the time pressure on GPs to enable more effective consultations. Results suggest a pharmacist's services can potentially be better used within the multidisciplinary super clinic model of care to address current gaps within the semi-rural practice setting. Any future role for the pharmacist could be addressed as part of a formalised, strategic approach to creating an integrated healthcare team, with attention to funding and government legislation.

  14. [Clinical treatment adherence of health care workers and students exposed to potentially infectious biological material].

    Science.gov (United States)

    Almeida, Maria Cristina Mendes de; Canini, Silvia Rita Marin da Silva; Reis, Renata Karina; Toffano, Silmara Elaine Malaguti; Pereira, Fernanda Maria Vieira; Gir, Elucir

    2015-04-01

    To assess adherence to clinical appointments by health care workers (HCW) and students who suffered accidents with potentially infectious biological material. A retrospective cross-sectional study that assessed clinical records of accidents involving biological material between 2005 and 2010 in a specialized unit. A total of 461 individuals exposed to biological material were treated, of which 389 (84.4%) were HCWs and 72 (15.6%) students. Of the 461 exposed individuals, 307 (66.6%) attended a follow-up appointment. Individuals who had suffered an accident with a known source patient were 29 times more likely to show up to their scheduled follow-up appointments (OR: 29.98; CI95%: 16.09-55.83). The predictor in both univariate and multivariate analyses for adherence to clinical follow-up appointment was having a known source patient with nonreactive serology for the human immunodeficiency virus and/or hepatitis B and C.

  15. Opportunities for Cancer-relevant Innovative Technologies with Transformative Potential | Office of Cancer Clinical Proteomics Research

    Science.gov (United States)

    The National Cancer Institute (NCI) is seeking input from the community on identifying priorities with regards to supporting innovative technology development for cancer-relevant research. While the NCI provides support for technology development through a variety of mechanisms, it is important to understand whether or not these are sufficient for catalyzing and supporting the development of tools with significant potential for advancing important fields of cancer research or clinical care.

  16. "Smart Pills" Promising, Problematic

    Science.gov (United States)

    Sparks, Sarah D.

    2012-01-01

    An explosion in the variety and availability of cognitive-enhancing drugs, from prescriptions like Ritalin to commercial drinks like NeuroFuel, raises concerns for scientists and educators alike--not just over the potential for abuse, but also over what educators and researchers consider, and how they approach, normal achievement. Evidence is…

  17. [Recommendations for the clinical use of motor evoked potentials in multiple sclerosis].

    Science.gov (United States)

    Fernández, V; Valls-Sole, J; Relova, J L; Raguer, N; Miralles, F; Dinca, L; Taramundi, S; Costa-Frossard, L; Ferrandiz, M; Ramió-Torrentà, Ll; Villoslada, P; Saiz, A; Calles, C; Antigüedad, A; Alvarez-Cermeño, J C; Prieto, J M; Izquierdo, G; Montalbán, X; Fernández, O

    2013-09-01

    To establish clinical guidelines for the clinical use and interpretation of motor evoked potentials (MEP) in diagnosing and monitoring patients with multiple sclerosis (MS). Recommendations for MEP use and interpretation will help us rationalise and optimise resources used in MS patient diagnosis and follow up. We completed an extensive literature review and pooled our own data to produce a consensus statement with recommendations for the clinical use of MEPs in the study of MS. MEPs, in addition to spinal and cranial magnetic resonance imaging (MRI), help us diagnose and assess MS patients whose disease initially presents as spinal cord syndrome and those with non-specific brain MRI findings, or a normal brain MRI and clinical signs of MS. Whenever possible, a multimodal evoked potential study should be performed on patients with suspected MS in order to demonstrate involvement of the motor pathway which supports a diagnosis of dissemination in space. Copyright © 2012 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

  18. Cannabidiol: promise and pitfalls.

    Science.gov (United States)

    Welty, Timothy E; Luebke, Adrienne; Gidal, Barry E

    2014-09-01

    Over the past few years, increasing public and political pressure has supported legalization of medical marijuana. One of the main thrusts in this effort has related to the treatment of refractory epilepsy-especially in children with Dravet syndrome-using cannabidiol (CBD). Despite initiatives in numerous states to at least legalize possession of CBD oil for treating epilepsy, little published evidence is available to prove or disprove the efficacy and safety of CBD in patients with epilepsy. This review highlights some of the basic science theory behind the use of CBD, summarizes published data on clinical use of CBD for epilepsy, and highlights issues related to the use of currently available CBD products. Cannabidiol is the major nonpsychoactive component of Cannabis sativa. Over the centuries, a number of medicinal preparations derived from C. sativa have been employed for a variety of disorders, including gout, rheumatism, malaria, pain, and fever. These preparations were widely employed as analgesics by Western medical practitioners in the 19(th) century (1). More recently, there is clinical evidence suggesting efficacy in HIV-associated neuropathic pain, as well as spasms associated with multiple sclerosis (1).

  19. Clinical and Laboratory Potential Predictors of Blood Culture Positivity in Under Five Children with Clinically Severe Pneumonia - Khartoum -Sudan.

    Science.gov (United States)

    Salih, Karimeldin Mohamed Ali; El-Samani, El-Fatih; Bilal, Jalal Ali; Eldouch, Widad; Ibrahim, Salah Ahmed

    2015-08-01

    Blood culture is necessary for appropriate management of clinically severe pneumonia in children under five years of age. However, in limited resource countries it might be unduly costly and waste of valuable time because of the high negative culture rate. This study aims to identify clinical and laboratory parameters that potentially predict a positive blood culture in cases of severe pneumonia. A hospital based study, enrolled 189 cases satisfying the WHO definition of severe pneumonia. Age, gender, clinical history, physical examination, temperature, complete blood count, C-reactive protein, blood culture and Chest X Ray for all the patients were recorded. Forty one patients had positive blood culture giving a prevalence of 21.7%. All variables were used in a dichotomous manner. White Blood Count (WBC) more than 20 000, very high C-reactive protein (C-RP ≥8mg/L) and Temperature more than 40(o)C, had a positive predictive value of 46.1%, 44.3% and 40.0% respectively for a positive culture as well as a Negative Predictive Value of 91.1%, 91.6% and 91.7% respectively. The WBC more than 20 000 and temperature above 40(o)C had a significant association with a positive blood culture. Their adjusted Odds Ratios were 3.9 (95% CI: 1.4-10.90) and 3.1 (95% CI: 1.2-8.4) respectively. This was not the case for C-RP (Odds Ratio=2.2, 95% CI: 0.7-2.2) or positive Chest X Ray (Odds Ratio=1.5, 95% CI: 0.6-3.6). Temperature of more than 40(o)C, Very high C-RP and WBC of more than 20 000 are good indicators of a potential positive blood culture. It is therefore recommended that further research be undertaken to refine these predictors as screening tools before resorting to blood culture. It is also recommended that antibiotic treatment may be initiated on the basis of the high temperature and WBC, while waiting for the culture results.

  20. Potential of Mass Spectrometry in Developing Clinical Laboratory Biomarkers of Nonvolatiles in Exhaled Breath.

    Science.gov (United States)

    Beck, Olof; Olin, Anna-Carin; Mirgorodskaya, Ekaterina

    2016-01-01

    Exhaled breath contains nonvolatile substances that are part of aerosol particles of submicrometer size. These particles are formed and exhaled as a result of normal breathing and contain material from distal airways of the respiratory system. Exhaled breath can be used to monitor biomarkers of both endogenous and exogenous origin and constitutes an attractive specimen for medical investigations. This review summarizes the present status regarding potential biomarkers of nonvolatile compounds in exhaled breath. The field of exhaled breath condensate is briefly reviewed, together with more recent work on more selective collection procedures for exhaled particles. The relation of these particles to the surfactant in the terminal parts of the respiratory system is described. The literature on potential endogenous low molecular weight compounds as well as protein biomarkers is reviewed. The possibility to measure exposure to therapeutic and abused drugs is demonstrated. Finally, the potential future role and importance of mass spectrometry is discussed. Nonvolatile compounds exit the lung as aerosol particles that can be sampled easily and selectively. The clinical applications of potential biomarkers in exhaled breath comprise diagnosis of disease, monitoring of disease progress, monitoring of drug therapy, and toxicological investigations. © 2015 American Association for Clinical Chemistry.

  1. Potential consequences of clinical application of artificial gametes: a systematic review of stakeholder views.

    Science.gov (United States)

    Hendriks, Saskia; Dondorp, Wybo; de Wert, Guido; Hamer, Geert; Repping, Sjoerd; Dancet, Eline A F

    2015-01-01

    Recent progress in the formation of artificial gametes, i.e. gametes generated from progenitors or somatic cells, has led to scientific and societal discussion about their use in medically assisted reproduction. In animals, live births have already been achieved using artificial gametes of varying (cell type) sources and biological research seems to be progressing steadily toward clinical application in humans. Artificial gametes could potentially help not only infertile heterosexual couples of reproductive age of which one or both partners lacks functional gametes, but also post-menopausal women and same-sex couples, to conceive a child who will be genetically related to them. But as clinical application of these new technologies may have wider societal consequences, a proactive consideration of the possible impact seems timely and important. This review aims to contribute to this by providing a systematic overview of the potential consequences of clinical application of artificial gametes anticipated by different stakeholders. The electronic database 'Medline/Pubmed' was systematically searched with medical subject heading terms (MesH) for articles published in English between January 1970 and December 2013. Articles were selected based on eligibility and reference lists of eligible studies were hand searched. The reported potential consequences of clinical application of artificial gametes were extracted from the articles and were grouped into categories by content analysis. Per category, we noted which stakeholders referred to which potential consequences, based on author affiliations and, if applicable, study participants. The systematic search yielded 2424 articles, and 84 studies were included after screening. Nine positive consequences, 21 specific consequences requiring consideration and 22 recommendations referring to clinical application of artificial gametes were documented. All positive consequences, consequences requiring consideration and

  2. A diterpenoid taxodone from Metasequoia glyptostroboides with antimycotic potential against clinical isolates of Candida species.

    Science.gov (United States)

    Bajpai, V K; Park, Y-H; Kang, S C

    2015-03-01

    The increasing importance of clinical isolates of Candida species and emerging resistance of Candida species to current synthetic antifungal agents have stimulated the search for safer and more effective alternative drugs from natural sources. This study was directed towards exploring the antimycotic potential of a diterpenoid compound taxodone isolated from Metasequoia glyptostroboides against pathogenic isolates of Candida species. Antimycotic efficacy of taxodone was evaluated by disc diffusion assay, determination of minimum inhibitory (MIC) and minimum fungicidal (MFC) concentrations, and cell viability assay. To confirm a partial antimycotic mode of action of taxodone, the efficacy of taxodone was determined by measuring the release of 260 nm absorbing materials from the selected Candida species as compared to control. The taxodone at the concentration of 400 μg/disc displayed potential antimycotic effect against the tested clinical and pathogenic isolates of Candida species as diameters of zones of inhibitions, which were found in the range of 11 ± 0.0 to 12.6 ± 0.5mm. The MIC and MFC values of taxodone against the tested clinical isolates were found in the range of 250 to 1000 and 500 to 2000μ g/mL, respectively. On the other hand, the MIC and MFC values of positive control (amphotericin B) against the tested Candida isolates were found in the range of 62.5 to 250 and 500 to 2000 μg/mL. On the viable counts of the tested fungal isolates, the taxodone exerted significant antimycotic effect. Elaborative study of partial mode of action conducted onto the release of 260nm materials (DNA and RNA) revealed potential detrimental effect of taxodone on the membrane integrity of the tested pathogens at MIC concentration. With respect to the antimycotic effect of taxodone against pathogenic and clinical isolates of Candida species, it might be confirmed that bioactive compound taxodone present in M. glyptostroboides holds therapeutic value of medicinal

  3. Profiles in fibromyalgia: algometry, auditory evoked potentials and clinical characterization of different subtypes.

    Science.gov (United States)

    Triñanes, Yolanda; González-Villar, Alberto; Gómez-Perretta, Claudio; Carrillo-de-la-Peña, María T

    2014-11-01

    The heterogeneity found in fibromyalgia (FM) patients has led to the investigation of disease subgroups, mainly based on clinical features. The aim of this study was to test the hypothesis that clinical FM subgroups are associated with different underlying pathophysiological mechanisms. Sixty-three FM patients were classified in type I or type II, according to the Fibromyalgia Impact Questionnaire (FIQ), and in mild/moderate versus severe FM, according to the severity of three cardinal symptoms considered in the American College of Rheumatology (ACR) 2010 criteria (unrefreshed sleep, cognitive problems and fatigue). To validate the subgroups obtained by these two classifications, we calculated the area under the receiver operating characteristic curves for various clinical variables and for two potential biomarkers of FM: Response to experimental pressure pain (algometry) and the amplitude/intensity slopes of the auditory evoked potentials (AEPs) obtained to stimuli of increasing intensity. The variables that best discriminated type I versus type II were those related to depression, while the indices of clinical or experimental pain (threshold or tolerance) did not significantly differ between them. The variables that best discriminated the mild/moderate versus severe subgroups were those related to the algometry. The AEPs did not allow discrimination among the generated subsets. The FIQ-based classification allows the identification of subgroups that differ in psychological distress, while the index based on the ACR 2010 criteria seems to be useful to characterize the severity of FM mainly based on hyperalgesia. The incorporation of potential biomarkers to generate or validate classification criteria is crucial to advance in the knowledge of FM and in the understanding of pathophysiological pathways.

  4. Vaccines: an ongoing promise?

    Science.gov (United States)

    Alsahli, M; Farrell, R J; Michetti, P

    2001-01-01

    Over the past decade, intensive research has focused on developing a vaccine therapy for Helicobacter pylori. Substantial unresolved questions cloud the current approach, and the development of a vaccine against this unique organism has proved very challenging. Many candidate vaccines have been tested in animal models. The immunogenicity and the safety of some vaccine formulations have been recently evaluated through clinical trials, and the efficacy of these vaccine therapies in humans will be determined in the near future. This article will provide an overview of the current knowledge of natural and vaccine-induced immune responses to H. pylori infection. It will also review past vaccine successes and failures in animal models and the limited experience to date in using vaccine therapy in humans. Several obstacles to H. pylori vaccine development efforts along with the future direction of these efforts will be discussed. Copyright 2001 S. Karger AG, Basel

  5. Linear Energy Transfer-Guided Optimization in Intensity Modulated Proton Therapy: Feasibility Study and Clinical Potential

    Energy Technology Data Exchange (ETDEWEB)

    Giantsoudi, Drosoula, E-mail: dgiantsoudi@partners.org [Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (United States); Grassberger, Clemens; Craft, David; Niemierko, Andrzej; Trofimov, Alexei; Paganetti, Harald [Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (United States)

    2013-09-01

    Purpose: To investigate the feasibility and potential clinical benefit of linear energy transfer (LET) guided plan optimization in intensity modulated proton therapy (IMPT). Methods and Materials: A multicriteria optimization (MCO) module was used to generate a series of Pareto-optimal IMPT base plans (BPs), corresponding to defined objectives, for 5 patients with head-and-neck cancer and 2 with pancreatic cancer. A Monte Carlo platform was used to calculate dose and LET distributions for each BP. A custom-designed MCO navigation module allowed the user to interpolate between BPs to produce deliverable Pareto-optimal solutions. Differences among the BPs were evaluated for each patient, based on dose–volume and LET–volume histograms and 3-dimensional distributions. An LET-based relative biological effectiveness (RBE) model was used to evaluate the potential clinical benefit when navigating the space of Pareto-optimal BPs. Results: The mean LET values for the target varied up to 30% among the BPs for the head-and-neck patients and up to 14% for the pancreatic cancer patients. Variations were more prominent in organs at risk (OARs), where mean LET values differed by a factor of up to 2 among the BPs for the same patient. An inverse relation between dose and LET distributions for the OARs was typically observed. Accounting for LET-dependent variable RBE values, a potential improvement on RBE-weighted dose of up to 40%, averaged over several structures under study, was noticed during MCO navigation. Conclusions: We present a novel strategy for optimizing proton therapy to maximize dose-averaged LET in tumor targets while simultaneously minimizing dose-averaged LET in normal tissue structures. MCO BPs show substantial LET variations, leading to potentially significant differences in RBE-weighted doses. Pareto-surface navigation, using both dose and LET distributions for guidance, provides the means for evaluating a large variety of deliverable plans and aids in

  6. Linear Energy Transfer-Guided Optimization in Intensity Modulated Proton Therapy: Feasibility Study and Clinical Potential

    International Nuclear Information System (INIS)

    Giantsoudi, Drosoula; Grassberger, Clemens; Craft, David; Niemierko, Andrzej; Trofimov, Alexei; Paganetti, Harald

    2013-01-01

    Purpose: To investigate the feasibility and potential clinical benefit of linear energy transfer (LET) guided plan optimization in intensity modulated proton therapy (IMPT). Methods and Materials: A multicriteria optimization (MCO) module was used to generate a series of Pareto-optimal IMPT base plans (BPs), corresponding to defined objectives, for 5 patients with head-and-neck cancer and 2 with pancreatic cancer. A Monte Carlo platform was used to calculate dose and LET distributions for each BP. A custom-designed MCO navigation module allowed the user to interpolate between BPs to produce deliverable Pareto-optimal solutions. Differences among the BPs were evaluated for each patient, based on dose–volume and LET–volume histograms and 3-dimensional distributions. An LET-based relative biological effectiveness (RBE) model was used to evaluate the potential clinical benefit when navigating the space of Pareto-optimal BPs. Results: The mean LET values for the target varied up to 30% among the BPs for the head-and-neck patients and up to 14% for the pancreatic cancer patients. Variations were more prominent in organs at risk (OARs), where mean LET values differed by a factor of up to 2 among the BPs for the same patient. An inverse relation between dose and LET distributions for the OARs was typically observed. Accounting for LET-dependent variable RBE values, a potential improvement on RBE-weighted dose of up to 40%, averaged over several structures under study, was noticed during MCO navigation. Conclusions: We present a novel strategy for optimizing proton therapy to maximize dose-averaged LET in tumor targets while simultaneously minimizing dose-averaged LET in normal tissue structures. MCO BPs show substantial LET variations, leading to potentially significant differences in RBE-weighted doses. Pareto-surface navigation, using both dose and LET distributions for guidance, provides the means for evaluating a large variety of deliverable plans and aids in

  7. Multimodal assessment of SERS nanoparticle biodistribution post ingestion reveals new potential for clinical translation of Raman imaging.

    Science.gov (United States)

    Campbell, Jos L; SoRelle, Elliott D; Ilovich, Ohad; Liba, Orly; James, Michelle L; Qiu, Zhen; Perez, Valerie; Chan, Carmel T; de la Zerda, Adam; Zavaleta, Cristina

    2017-08-01

    Despite extensive research and development, new nano-based diagnostic contrast agents have faced major barriers in gaining regulatory approval due to their potential systemic toxicity and prolonged retention in vital organs. Here we use five independent biodistribution techniques to demonstrate that oral ingestion of one such agent, gold-silica Raman nanoparticles, results in complete clearance with no systemic toxicity in living mice. The oral delivery mimics topical administration to the oral cavity and gastrointestinal (GI) tract as an alternative to intravenous injection. Biodistribution and clearance profiles of orally (OR) vs. intravenously (IV) administered Raman nanoparticles were assayed over the course of 48 h. Mice given either an IV or oral dose of Raman nanoparticles radiolabeled with approximately 100 μCi (3.7MBq) of 64 Cu were imaged with dynamic microPET immediately post nanoparticle administration. Static microPET images were also acquired at 2 h, 5 h, 24 h and 48 h. Mice were sacrificed post imaging and various analyses were performed on the excised organs to determine nanoparticle localization. The results from microPET imaging, gamma counting, Raman imaging, ICP-MS, and hyperspectral imaging of tissue sections all correlated to reveal no evidence of systemic distribution of Raman nanoparticles after oral administration and complete clearance from the GI tract within 24 h. Paired with the unique signals and multiplexing potential of Raman nanoparticles, this approach holds great promise for realizing targeted imaging of tumors and dysplastic tissues within the oral cavity and GI-tract. Moreover, these results suggest a viable path for the first translation of high-sensitivity Raman contrast imaging into clinical practice. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Cast iron promises

    Directory of Open Access Journals (Sweden)

    Andrew Hawker

    2007-09-01

    Events in the ten years prior to this disaster still have some resonance today. Ambitions to exploit new technology are not always matched by foresight in the planning, financing or management of projects. Contracts may be based on wrong assumptions, and prove difficult to enforce. Once a project has gathered momentum, those working on it may fear that any attempt to draw attention to risks or defects will be seen as disloyal. When work is completed, it cannot be assumed that formal inspections will reveal potential flaws, or that those using the technology will appreciate the need to follow the procedures laid down for them. Some possible parallels with recent experiences in NHS computing are noted.

  9. Passing through the renal clearance barrier: toward ultrasmall sizes with stable ligands for potential clinical applications

    Directory of Open Access Journals (Sweden)

    Zhang XD

    2014-04-01

    Full Text Available Xiao-Dong Zhang,1 Jiang Yang,2 Sha-Sha Song,1 Wei Long,1 Jie Chen,1 Xiu Shen,1 Hao Wang,1 Yuan-Ming Sun,1 Pei-Xun Liu,1 Saijun Fan11Tianjin Key Laboratory of Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, People's Republic of China; 2Department of Biological Systems Engineering, University of Wisconsin-Madison, Madison, WI, USAAbstract: The use of nanoparticles holds promise for medical applications, such as X-ray imaging, photothermal therapy and radiotherapy. However, the in vivo toxicity of inorganic nanoparticles raises some concern regarding undesirable side effects which prevent their further medical application. Ultrasmall sub-5.5 nm particles can pass through the barrier for renal clearance, minimizing their toxicity. In this letter we address some recent interesting work regarding in vivo toxicity and renal clearance, and discuss the possible strategy of utilizing ultrasmall nanomaterials. We propose that small hydrodynamic sized nanoclusters can achieve both nontoxic and therapeutic clinical features.Keywords: in vivo clearance, gold nanoparticles, small size

  10. Clinically Relevant Pharmacological Strategies That Reverse MDMA-Induced Brain Hyperthermia Potentiated by Social Interaction.

    Science.gov (United States)

    Kiyatkin, Eugene A; Ren, Suelynn; Wakabayashi, Ken T; Baumann, Michael H; Shaham, Yavin

    2016-01-01

    MDMA-induced hyperthermia is highly variable, unpredictable, and greatly potentiated by the social and environmental conditions of recreational drug use. Current strategies to treat pathological MDMA-induced hyperthermia in humans are palliative and marginally effective, and there are no specific pharmacological treatments to counteract this potentially life-threatening condition. Here, we tested the efficacy of mixed adrenoceptor blockers carvedilol and labetalol, and the atypical antipsychotic clozapine, in reversing MDMA-induced brain and body hyperthermia. We injected rats with a moderate non-toxic dose of MDMA (9 mg/kg) during social interaction, and we administered potential treatment drugs after the development of robust hyperthermia (>2.5 °C), thus mimicking the clinical situation of acute MDMA intoxication. Brain temperature was our primary focus, but we also simultaneously recorded temperatures from the deep temporal muscle and skin, allowing us to determine the basic physiological mechanisms of the treatment drug action. Carvedilol was modestly effective in attenuating MDMA-induced hyperthermia by moderately inhibiting skin vasoconstriction, and labetalol was ineffective. In contrast, clozapine induced a marked and immediate reversal of MDMA-induced hyperthermia via inhibition of brain metabolic activation and blockade of skin vasoconstriction. Our findings suggest that clozapine, and related centrally acting drugs, might be highly effective for reversing MDMA-induced brain and body hyperthermia in emergency clinical situations, with possible life-saving results.

  11. Potentiating antibiotics in drug-resistant clinical isolates via stimuli-activated superoxide generation.

    Science.gov (United States)

    Courtney, Colleen M; Goodman, Samuel M; Nagy, Toni A; Levy, Max; Bhusal, Pallavi; Madinger, Nancy E; Detweiler, Corrella S; Nagpal, Prashant; Chatterjee, Anushree

    2017-10-01

    The rise of multidrug-resistant (MDR) bacteria is a growing concern to global health and is exacerbated by the lack of new antibiotics. To treat already pervasive MDR infections, new classes of antibiotics or antibiotic adjuvants are needed. Reactive oxygen species (ROS) have been shown to play a role during antibacterial action; however, it is not yet understood whether ROS contribute directly to or are an outcome of bacterial lethality caused by antibiotics. We show that a light-activated nanoparticle, designed to produce tunable flux of specific ROS, superoxide, potentiates the activity of antibiotics in clinical MDR isolates of Escherichia coli , Salmonella enterica , and Klebsiella pneumoniae . Despite the high degree of antibiotic resistance in these isolates, we observed a synergistic interaction between both bactericidal and bacteriostatic antibiotics with varied mechanisms of action and our superoxide-producing nanoparticles in more than 75% of combinations. As a result of this potentiation, the effective antibiotic concentration of the clinical isolates was reduced up to 1000-fold below their respective sensitive/resistant breakpoint. Further, superoxide-generating nanoparticles in combination with ciprofloxacin reduced bacterial load in epithelial cells infected with S. enterica serovar Typhimurium and increased Caenorhabditis elegans survival upon infection with S. enterica serovar Enteriditis, compared to antibiotic alone. This demonstration highlights the ability to engineer superoxide generation to potentiate antibiotic activity and combat highly drug-resistant bacterial pathogens.

  12. Clinical usefulness and feasibility of time-frequency analysis of chemosensory event-related potentials.

    Science.gov (United States)

    Huart, C; Rombaux, Ph; Hummel, T; Mouraux, A

    2013-09-01

    The clinical usefulness of olfactory event-related brain potentials (OERPs) to assess olfactory function is limited by the relatively low signal-to-noise ratio of the responses identified using conventional time-domain averaging. Recently, it was shown that time-frequency analysis of the obtained EEG signals can markedly improve the signal-to-noise ratio of OERPs in healthy controls, because it enhances both phase-locked and non phase-locked EEG responses. The aim of the present study was to investigate the clinical usefulness of this approach and evaluate its feasibility in a clinical setting. We retrospectively analysed EEG recordings obtained from 45 patients (15 anosmic, 15 hyposmic and 15 normos- mic). The responses to olfactory stimulation were analysed using conventional time-domain analysis and joint time-frequency analysis. The ability of the two methods to discriminate between anosmic, hyposmic and normosmic patients was assessed using a Receiver Operating Characteristic analysis. The discrimination performance of OERPs identified using conventional time-domain averaging was poor. In contrast, the discrimination performance of the EEG response identified in the time-frequency domain was relatively high. Furthermore, we found a significant correlation between the magnitude of this response and the psychophysical olfactory score. Time-frequency analysis of the EEG responses to olfactory stimulation could be used as an effective and reliable diagnostic tool for the objective clinical evaluation of olfactory function in patients.

  13. Post-use assay of vaginal rings (VRs) as a potential measure of clinical trial adherence.

    Science.gov (United States)

    Spence, Patrick; Nel, Annalene; van Niekerk, Neliëtte; Derrick, Tiffany; Wilder, Susan; Devlin, Bríd

    2016-06-05

    Adherence measurement for microbicide use within the clinical trial setting remains a challenge for the HIV prevention field. This paper describes an assay method used for determining residual dapivirine levels in post-use vaginal rings from clinical trials conducted with the Dapivirine Vaginal Matrix Ring-004 developed by the International Partnership for Microbicides to prevent male to female HIV transmission. Post-use assay results from three Ring-004 clinical trials showed that of the 25mg drug load, approximately 4mg of dapivirine is released from the matrix ring over a 28-day use period. Data obtained by both in vitro and in vivo studies indicate that dapivirine is released according to a diffusion mechanism, as determined by conformance of both data sets to the Higuchi equation. This, coupled with the low variability associated with batch production over two manufacturing sites and 20 batches of material, provides evidence that post-use ring analysis can contribute to the assessment of adherence to ring use. Limitations of this method include the potential of intra-participant and inter-participant variability and uncertainty associated with measuring the low amount of dapivirine actually released relative to the drug load. Therefore, residual drug levels should not serve as the only direct measurement for microbicide adherence in vaginal ring clinical trials but should preferably be used as part of a multi-pronged approach towards understanding and assessing adherence to vaginal ring use. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  14. Mechanism of Action and Clinical Potential of Fingolimod for the Treatment of Stroke

    Directory of Open Access Journals (Sweden)

    Wentao Li

    2016-08-01

    Full Text Available Fingolimod (FTY720 is an orally bio-available immunomodulatory drug currently approved by the FDA for the treatment of multiple sclerosis. Currently, there is a significant interest in the potential benefits of FTY720 on stroke outcomes. FTY720 and the sphingolipid signaling pathway it modulates has a ubiquitous presence in the central nervous system and both rodent models and pilot clinical trials seem to indicate that the drug may improve overall functional recovery in different stroke subtypes. Although the precise mechanisms behind these beneficial effects are yet unclear, there is evidence that FTY720 has a role in regulating cerebrovascular responses, blood brain barrier permeability, and cell survival in the event of cerebrovascular insult. In this article, we critically review the data obtained from the latest laboratory findings and clinical trials involving both ischemic and hemorrhagic stroke, and attempt to form a cohesive picture of FTY720’s mechanisms of action in stroke

  15. PATIENTS WITH SUSPECTED METAL IMPLANT ALLERGY: POTENTIAL CLINICAL PICTURES AND ALLERGOLOGICAL DIAGNOSTIC APPROACH (REVIEW

    Directory of Open Access Journals (Sweden)

    P. Thomas

    2014-01-01

    Full Text Available The focus of this review are allergic complications following insertion of metallic orthopedic implants. Such potential allergic reactions encompass eczema, impaired wound and fracture healing, infection-mimicking reactions, effusions, pain and loosening. Nickel, cobalt and chromium seem to be the predominant eliciting allergens. Allergy might be considered prior to planned orthopaedic surgery or in patients with complications following arthroplasty We recommend, that differential diagnoses - in particular infection -should always be excluded in cooperation with surgery collegues. The clinical work up of a patient suspected of suffering from metal implant allergy should include a combined evaluation of medical history, clinical findings, patch testing and histology In vitro testing, namely the lymphocyte transformation test (LTT, can indicate metal sensitization, but needs careful interpretation.

  16. Cast iron promises.

    Science.gov (United States)

    Hawker, Andrew

    2007-01-01

    During the Victorian era, a fiercely competitive industry emerged to build and operate Britain's railways. Many of the design and construction skills required were still fairly rudimentary, and were typically developed through practical experience. The resulting mix of entrepreneurship and new technology reshaped the landscape, but often in ways which proved hazardous for passengers. Minor accidents were commonplace, and a number of major failures occurred, one such being the collapse of the Tay Bridge, in 1879. Events in the ten years prior to this disaster still have some resonance today. Ambitions to exploit new technology are not always matched by foresight in the planning, financing or management of projects. Contracts may be based on wrong assumptions, and prove difficult to enforce. Once a project has gathered momentum, those working on it may fear that any attempt to draw attention to risks or defects will be seen as disloyal. When work is completed, it cannot be assumed that formal inspections will reveal potential flaws, or that those using the technology will appreciate the need to follow the procedures laid down for them. Some possible parallels with recent experiences in NHS computing are noted.

  17. TH-B-BRC-01: How to Identify and Resolve Potential Clinical Errors

    Energy Technology Data Exchange (ETDEWEB)

    Das, I. [NYU Langone Medical Center, New York, NY (United States)

    2016-06-15

    Radiation treatment consists of a chain of events influenced by the quality of machine operation, beam data commissioning, machine calibration, patient specific data, simulation, treatment planning, imaging and treatment delivery. There is always a chance that the clinical medical physicist may make or fail to detect an error in one of the events that may impact on the patient’s treatment. In the clinical scenario, errors may be systematic and, without peer review, may have a low detectability because they are not part of routine QA procedures. During treatment, there might be errors on machine that needs attention. External reviews of some of the treatment delivery components by independent reviewers, like IROC, can detect errors, but may not be timely. The goal of this session is to help junior clinical physicists identify potential errors as well as the approach of quality assurance to perform a root cause analysis to find and eliminate an error and to continually monitor for errors. A compilation of potential errors will be presented by examples of the thought process required to spot the error and determine the root cause. Examples may include unusual machine operation, erratic electrometer reading, consistent lower electron output, variation in photon output, body parts inadvertently left in beam, unusual treatment plan, poor normalization, hot spots etc. Awareness of the possibility and detection of error in any link of the treatment process chain will help improve the safe and accurate delivery of radiation to patients. Four experts will discuss how to identify errors in four areas of clinical treatment. D. Followill, NIH grant CA 180803.

  18. TH-B-BRC-01: How to Identify and Resolve Potential Clinical Errors

    International Nuclear Information System (INIS)

    Das, I.

    2016-01-01

    Radiation treatment consists of a chain of events influenced by the quality of machine operation, beam data commissioning, machine calibration, patient specific data, simulation, treatment planning, imaging and treatment delivery. There is always a chance that the clinical medical physicist may make or fail to detect an error in one of the events that may impact on the patient’s treatment. In the clinical scenario, errors may be systematic and, without peer review, may have a low detectability because they are not part of routine QA procedures. During treatment, there might be errors on machine that needs attention. External reviews of some of the treatment delivery components by independent reviewers, like IROC, can detect errors, but may not be timely. The goal of this session is to help junior clinical physicists identify potential errors as well as the approach of quality assurance to perform a root cause analysis to find and eliminate an error and to continually monitor for errors. A compilation of potential errors will be presented by examples of the thought process required to spot the error and determine the root cause. Examples may include unusual machine operation, erratic electrometer reading, consistent lower electron output, variation in photon output, body parts inadvertently left in beam, unusual treatment plan, poor normalization, hot spots etc. Awareness of the possibility and detection of error in any link of the treatment process chain will help improve the safe and accurate delivery of radiation to patients. Four experts will discuss how to identify errors in four areas of clinical treatment. D. Followill, NIH grant CA 180803

  19. Diagnostic accuracy of clinical and blood examination for sepsis in potentially infected neonates

    Directory of Open Access Journals (Sweden)

    Ari Mulyani

    2006-10-01

    Full Text Available Background Neonatal sepsis remains a diagnostic challenge due to its nonspesific symptoms and signs. Blood culture as the gold standard is still a problem because it takes time, is expensive, and not every health facility is able to perionn. Objective To evaluate the diagnostic accuracy of clinical symptoms, hematologic findings, and C-reactive protein (CRP in neonatal sepsis. Methods Samples were taken from potentially infected neonates admitted to the Matemal-Perinatal Unit of Sardjito Hospital, between December 1st, 2000 and March 31st, 2001 using at least one of the criteria: prematurity, very low birth weight infants, matemal pyrexia during delivery, premature membrane rupture, or thick, cloudy amniotic fluid. Clinical symptoms, total leukocyte, neutrophil, platelet count, CRP, and blood culture as the gold standard were examined. Results Among 99 neonates enrolled, the sensitivity, specificity, positive and negative predictive value of clinical symptoms were 79.3%, 75.7%, 57.5%, and 89.9%, respectively; leukopenia/leukocytosis were 27.6%, 85.7%, 44.4%, and 74.1%; neutropenia! neutrophilia were 41.4%, 71.4%, 37.5%, and 74.6%; thrombocytopenia were 79.3%, 51.8%, 40.4%, and 85.7%; positive CRP were 58.6%,78.6%,53.1%, and 82.1%. Parallel tests increased the sensitivity up to 89.7%. Specificity, positive and negative predictive value, and likelihood ratio were 44.3%, 40%, 91.2%, and 1.6, respectively. Serial tests increased the specificity up to 88.6%. Sensitivity, positive and negative predictive value, and likelihood ratio were 58.6%, 68%, 83.8%, and 5.1, respectively. Conclusion Clinical sepsis, thrombocytopenia, and CRP are sufficiently accurate as diagnostic tests for sepsis in potentially infected neonates. Parallel tests will increase the sensitivity, while serial tests increase the specificity.

  20. The Promises of Biology and the Biology of Promises

    DEFF Research Database (Denmark)

    Lee, Jieun

    2015-01-01

    commitments with differently imagined futures. I argue that promises are constitutive of the stem cell biology, rather than being derivative of it. Since the biological concept of stem cells is predicated on the future that they promise, the biological life of stem cells is inextricably intertwined...... patients’ bodies in anticipation of materializing the promises of stem cell biology, they are produced as a new form of biovaluable. The promises of biology move beyond the closed circuit of scientific knowledge production, and proliferate in the speculative marketplaces of promises. Part II looks at how...... of technologized biology and biological time can appear promising with the backdrop of the imagined intransigence of social, political, and economic order in the Korean society....

  1. Clinical potential of lixisenatide once daily treatment for type 2 diabetes mellitus

    DEFF Research Database (Denmark)

    Petersen, Andreas Brønden; Christensen, Mikkel

    2013-01-01

    The glucagon-like peptide (GLP)-1 receptor agonist lixisenatide (Lyxumia(®)) was approved for marketing by the European Medicines Agency in February 2013 and has been evaluated in a clinical study program called GetGoal. Lixisenatide activates the GLP-1 receptor and thereby exercises the range of...... of lixisenatide seems to be in combination with basal insulin. A large multicenter study will determine the future potential of lixisenatide in preventing cardiovascular events and mortality, in patients with type 2 diabetes and recent acute coronary syndrome....

  2. Radotinib and its clinical potential in chronic-phase chronic myeloid leukemia patients: an update.

    Science.gov (United States)

    Eskazan, Ahmet Emre; Keskin, Dilek

    2017-09-01

    Although imatinib has dramatically improved major outcomes in patients with chronic myeloid leukemia (CML), there are newer tyrosine kinase inhibitors (TKIs) approved worldwide for the treatment of resistant cases, and two second-generation TKIs (dasatinib, nilotinib) are approved in some nations for treating patients in the upfront setting. Radotinib (IY5511HCL, Supect® ) is a novel and selective second-generation BCR-ABL1 TKI, which is currently approved in Korea for the treatment of patients with CML both in the upfront and salvage settings. This review mainly focuses on the clinical potential of radotinib in patients with CML in chronic phase in terms of efficacy and safety.

  3. A scoping review of the potential for chart stimulated recall as a clinical research method.

    Science.gov (United States)

    Sinnott, Carol; Kelly, Martina A; Bradley, Colin P

    2017-08-22

    Chart-stimulated recall (CSR) is a case-based interviewing technique, which is used in the assessment of clinical decision-making in medical education and professional certification. Increasingly, clinical decision-making is a concern for clinical research in primary care. In this study, we review the prior application and utility of CSR as a technique for research interviews in primary care. Following Arksey & O'Malley's method for scoping reviews, we searched seven databases, grey literature, reference lists, and contacted experts in the field. We excluded studies on medical education or competence assessment. Retrieved citations were screened by one reviewer and full texts were ordered for all potentially relevant abstracts. Two researchers independently reviewed full texts and performed data extraction and quality appraisal if inclusion criteria were met. Data were collated and summarised using a published framework on the reporting of qualitative interview techniques, which was chosen a priori. The preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines informed the review report. From an initial list of 789 citations, eight studies using CSR in research interviews were included in the review: six from North America, one from the Netherlands, and one from Ireland. The most common purpose of included studies was to examine the influence of guidelines on physicians' decisions. The number of interviewees ranged from seven to twenty nine, while the number of charts discussed per interview ranged from one to twelve. CSR gave insights into physicians' reasoning for actions taken or not taken; the unrecorded social and clinical influences on decisions; and discrepancies between physicians' real and perceived practice. Ethical concerns and the training and influence of the researcher were poorly discussed in most of the studies. Potential pitfalls included the risk of recall, selection and observation biases. Despite the proven validity

  4. Prevention of hepatocellular carcinoma: potential targets, experimental models, and clinical challenges

    Science.gov (United States)

    Hoshida, Yujin; Fuchs, Bryan C.; Tanabe, Kenneth K.

    2013-01-01

    Chronic fibrotic liver diseases such as viral hepatitis eventually develop liver cirrhosis, which causes occurrence of hepatocellular carcinoma (HCC). Given the limited therapeutic efficacy in advanced HCC, prevention of HCC development could be an effective strategy for improving patient prognosis. However, there is still no established therapy to meet the goal. Studies have elucidated a wide variety of molecular mechanisms and signaling pathways involved in HCC development. Genetically-engineered or chemically-treated experimental models of cirrhosis and HCC have been developed and shown their potential value in investigating molecular therapeutic targets and diagnostic biomarkers for HCC prevention. In this review, we overview potential targets of prevention and currently available experimental models, and discuss strategies to translate the findings into clinical practice. PMID:22873223

  5. Angiotensin receptor-neprilysin inhibitors: clinical potential in heart failure and beyond

    Directory of Open Access Journals (Sweden)

    Singh JSS

    2015-06-01

    Full Text Available Jagdeep SS Singh, Chim C Lang Division of Cardiovascular and Diabetes Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK Abstract: Heart failure remains a major concern across the globe as life expectancies and delivery of health care continue to improve. There has been a dearth of new developments in heart failure therapies in the last decade until last year, with the release of the results from the PARADIGM-HF Trial heralding the arrival of a promising new class of drug, ie, the angiotensin receptor-neprilysin inhibitor. In this review, we discuss the evolution of our incremental understanding of the neurohormonal mechanisms involved in the pathophysiology of heart failure, which has led to our success in modulating its various pathways. We start by examining the renin-angiotensin-aldosterone system, followed by the challenges of modulating the natriuretic peptide system. We then delve deeper into the pharmacology and mechanisms by which angiotensin receptor-neprilysin inhibitors achieve their significant cardiovascular benefits. Finally, we also consider the potential application of this new class of drug in other areas, such as heart failure with preserved ejection fraction, hypertension, patients with renal impairment, and following myocardial infarction. Keywords: heart failure, angiotensin receptor-neprilysin inhibitor, heart failure with preserved ejection fraction, nesiritide, candoxatril, omapatrilat, hypertension, renal impairment, myocardial infarction

  6. Promising pesticide results

    International Nuclear Information System (INIS)

    Wallace, Paula

    2012-01-01

    wastewater. For example, DDT has been linked to diabetes and liver, pancreatic and breast cancer, and is a 'probable' carcinogen, according to the US Environmental Protection Agency.” DDT has a half-life of up to 30 years in soil, which means only half its toxicity is naturally depleted through chemical breakdown over a 30-year period. Arsenic, however, which was used in DDT pesticides, does not breakdown at all over time. Moreover, epidemiological studies suggest that DDT and DDE cause serious illness. “Perhaps more worrying is the finding that DDT and its breakdown products are transported from warmer to colder climates around the world by a process called global distillation, thereby concentrating in colder climates and accumulating in the food web, leading to long-term ecological damage,” said Barros. By reducing DDT in the environment, these findings have the potential to aid in the sustainable global management of legacy pesticide contamination. For example, Virotec notes there are some 347 former cattle dip sites inthe region of Kyogle Shire Council in northern NSW, 259 in Lismore Shire Council and a further 211 in Richmond Valley Shire Council. The number of sheep dip sites throughout NSW and Queensland, which are also contaminated with arsenic and DDT, are of a comparable scale. Barros went on to point out that while the treatment of arsenic in soil is relatively straightforward, irrespective of whether treated in situ or ex situ, the treatment of DDT in soil is highly problematic. “Most soil treatments designed to destroy organic compounds in soil involve the introduction of key bacterial agents, because lower sources of energy simply do not have the requisite power to breakdown the long-chain organic molecules. However, as DDT is a pesticide it tends to kill both indigenous and introduced bacteria before they can break down the DDT molecule, thereby eliminating the source of potential remediation,” said Barros. Another challenge relates to the stability

  7. [Potential antimicrobial drug interactions in clinical practice: consequences of polypharmacy and multidrug resistance].

    Science.gov (United States)

    Martínez-Múgica, Cristina

    2015-12-01

    Polypharmacy is a growing problem nowadays, which can increase the risk of potential drug interactions, and result in a loss of effectiveness. This is particularly relevant to the anti-infective therapy, especially when infection is produced by resistant bacteria, because therapeutic options are limited and interactions can cause treatment failure. All antimicrobial prescriptions were retrospectively reviewed during a week in the Pharmacy Department, in order to detect potential drug-interactions and analysing their clinical significance. A total of 314 antimicrobial prescriptions from 151 patients were checked. There was at least one potential interaction detected in 40% of patients, being more frequent and severe in those infected with multidrug-resistant microorganisms. Drugs most commonly involved were quinolones, azoles, linezolid and vancomycin. Potential drug interactions with antimicrobial agents are a frequent problem that can result in a loss of effectiveness. This is why they should be detected and avoided when possible, in order to optimize antimicrobial therapy, especially in case of multidrug resistant infections.

  8. Uterine transplantation: a promising surrogate to surrogacy?

    Science.gov (United States)

    Grynberg, Michael; Ayoubi, Jean-Marc; Bulletti, Carlo; Frydman, Rene; Fanchin, Renato

    2011-03-01

    Infertility due to the inability of the uterus to carry a pregnancy ranks among the most unresolved issues in reproductive medicine. It affects millions of women worldwide who have congenital or acquired uterine affections, often requiring hysterectomy, and potentially represents a considerable fraction of the general infertile population. Patients suffering from severe uterine infertility are currently compelled to go through gestational surrogacy or adoption; both approaches, unfortunately, deprive them of the maternal experience of pregnancy and birth. Uterine transplantation represents an outstanding, yet complex, perspective to alleviating definitive uterine infertility. In the past decades, a number of scientific experiments conducted both in animals and women, focusing on uterine transplantation, have led to promising results. Collectively, these findings undoubtedly constitute a sound basis to clinically apply uterine transplantation in the near future. This paper is, however, an overview not only of the extent and limitations of accumulated scientific knowledge on uterine transplantation, but also its ethical implications, in an effort to define the actual place of such an approach among the therapeutic arsenal for alleviating infertility. © 2011 New York Academy of Sciences.

  9. Constructing a Local Potential Participant Registry to Improve Alzheimer's Disease Clinical Research Recruitment.

    Science.gov (United States)

    Grill, Joshua D; Hoang, Dan; Gillen, Daniel L; Cox, Chelsea G; Gombosev, Adrijana; Klein, Kirsten; O'Leary, Steve; Witbracht, Megan; Pierce, Aimee

    2018-01-01

    Potential participant registries are tools to address the challenge of slow recruitment to clinical research. In particular, registries may aid recruitment to secondary prevention clinical trials for Alzheimer's disease (AD), which enroll cognitively normal older individuals meeting specific genetic or biomarker criteria. Evidence of registry effectiveness is sparse, as is guidance on optimal designs or methods of conduct. We report our experiences of developing a novel local potential participant registry that implemented online enrollment and data collection. In the first year of operation, 957 individuals submitted email addresses to the registry, of whom 592 self-reported demographic, family history, and medical data. In addition, registrants provided information related to their interest and willingness to be contacted about studies. Local earned media and community education were the most effective methods of recruitment into the registry. Seventy-six (26%) of 298 registrants contacted about studies in the first year enrolled in those studies. One hundred twenty-nine registrants were invited to enroll in a preclinical AD trial, of whom 25 (18%) screened and 6 were randomized. These results indicate that registries can aid recruitment and provide needed guidance for investigators initiating new local registries.

  10. Human iPS Cell-Derived Germ Cells: Current Status and Clinical Potential

    Directory of Open Access Journals (Sweden)

    Tetsuya Ishii

    2014-10-01

    Full Text Available Recently, fertile spermatozoa and oocytes were generated from mouse induced pluripotent (iPS cells using a combined in vitro and in vivo induction system. With regard to germ cell induction from human iPS cells, progress has been made particularly in the male germline, demonstrating in vitro generation of haploid, round spermatids. Although iPS-derived germ cells are expected to be developed to yield a form of assisted reproductive technology (ART that can address unmet reproductive needs, genetic and/or epigenetic instabilities abound in iPS cell generation and germ cell induction. In addition, there is still room to improve the induction protocol in the female germline. However, rapid advances in stem cell research are likely to make such obstacles surmountable, potentially translating induced germ cells into the clinical setting in the immediate future. This review examines the current status of the induction of germ cells from human iPS cells and discusses the clinical potential, as well as future directions.

  11. Clinical potential of meningioma genomic insights: a practical review for neurosurgeons.

    Science.gov (United States)

    Karsy, Michael; Azab, Mohammed A; Abou-Al-Shaar, Hussam; Guan, Jian; Eli, Ilyas; Jensen, Randy L; Ormond, D Ryan

    2018-06-01

    Meningiomas are among the most common intracranial pathological conditions, accounting for 36% of intracranial lesions treated by neurosurgeons. Although the majority of these lesions are benign, the classical categorization of tumors by histological type or World Health Organization (WHO) grade has not fully captured the potential for meningioma progression and recurrence. Many targeted treatments have failed to generate a long-lasting effect on these tumors. Recently, several seminal studies evaluating the genomics of intracranial meningiomas have rapidly changed the understanding of the disease. The importance of NF2 (neurofibromin 2), TRAF7 (tumor necrosis factor [TNF] receptor-associated factor 7), KLF4 (Kruppel-like factor 4), AKT1, SMO (smoothened), PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha), and POLR2 (RNA polymerase II subunit A) demonstrates that there are at least 6 distinct mutational classes of meningiomas. In addition, 6 methylation classes of meningioma have been appreciated, enabling improved prediction of prognosis compared with traditional WHO grades. Genomic studies have shed light on the nature of recurrent meningioma, distinct intracranial locations and mutational patterns, and a potential embryonic cancer stem cell-like origin. However, despite these exciting findings, the clinical relevance of these findings remains elusive. The authors review the key findings from recent genomic studies in meningiomas, specifically focusing on how these findings relate to clinical insights for the practicing neurosurgeon.

  12. Human Induced Pluripotent Stem Cells from Basic Research to Potential Clinical Applications in Cancer

    Directory of Open Access Journals (Sweden)

    Teresa de Souza Fernandez

    2013-01-01

    Full Text Available The human induced pluripotent stem cells (hiPSCs are derived from a direct reprogramming of human somatic cells to a pluripotent stage through ectopic expression of specific transcription factors. These cells have two important properties, which are the self-renewal capacity and the ability to differentiate into any cell type of the human body. So, the discovery of hiPSCs opens new opportunities in biomedical sciences, since these cells may be useful for understanding the mechanisms of diseases in the production of new diseases models, in drug development/drug toxicity tests, gene therapies, and cell replacement therapies. However, the hiPSCs technology has limitations including the potential for the development of genetic and epigenetic abnormalities leading to tumorigenicity. Nowadays, basic research in the hiPSCs field has made progress in the application of new strategies with the aim to enable an efficient production of high-quality of hiPSCs for safety and efficacy, necessary to the future application for clinical practice. In this review, we show the recent advances in hiPSCs’ basic research and some potential clinical applications focusing on cancer. We also present the importance of the use of statistical methods to evaluate the possible validation for the hiPSCs for future therapeutic use toward personalized cell therapies.

  13. Recent Progress in Lab-on-a-Chip Technology and Its Potential Application to Clinical Diagnoses

    Directory of Open Access Journals (Sweden)

    Nae Yoon Lee

    2013-03-01

    Full Text Available We present the construction of the lab-on-a-chip (LOC system, a state-of-the-art technology that uses polymer materials (i.e., poly[dimethylsiloxane] for the miniaturization of conventional laboratory apparatuses, and show the potential use of these microfluidic devices in clinical applications. In particular, we introduce the independent unit components of the LOC system and demonstrate how each component can be functionally integrated into one monolithic system for the realization of a LOC system. In specific, we demonstrate microscale polymerase chain reaction with the use of a single heater, a microscale sample injection device with a disposable plastic syringe and a strategy for device assembly under environmentally mild conditions assisted by surface modification techniques. In this way, we endeavor to construct a totally integrated, disposable microfluidic system operated by a single mode, the pressure, which can be applied on-site with enhanced device portability and disposability and with simple and rapid operation for medical and clinical diagnoses, potentially extending its application to urodynamic studies in molecular level.

  14. Improving the Clinical Pharmacologic Assessment of Abuse Potential: Part 1: Regulatory Context and Risk Management.

    Science.gov (United States)

    Sellers, Edward M

    2018-02-01

    This article brings to the attention of drug developers the Food and Drug Administration's (FDA's) recent final Guidance to Industry on Assessment of Abuse Potential and provides practical suggestions about compliance with the Guidance. The Guidance areas are reviewed, analyzed, and placed in the context of current scientific knowledge and best practices to mitigate regulatory risk. The Guidance provides substantial new detail on what needs to be done at all stages of drug development for central nervous system-active drugs. However, because many psychopharmacologic agents have unique preclinical and clinical features, the plan for each agent needs to be not only carefully prepared but also reviewed and approved by the FDA. Examples are provided where assumptions about interpretation of the Guidance can delay development. If the expertise and experience needed for assessing abuse potential during drug development do not exist within a company, external preclinical and clinical expert should be involved. Consultation with the FDA is encouraged and important because the specific requirements for each drug will vary.

  15. Oral administration of drugs with hypersensitivity potential induces germinal center hyperplasia in secondary lymphoid organ/tissue in Brown Norway rats, and this histological lesion is a promising candidate as a predictive biomarker for drug hypersensitivity occurrence in humans

    International Nuclear Information System (INIS)

    Tamura, Akitoshi; Miyawaki, Izuru; Yamada, Toru; Kimura, Juki; Funabashi, Hitoshi

    2013-01-01

    It is important to evaluate the potential of drug hypersensitivity as well as other adverse effects during the preclinical stage of the drug development process, but validated methods are not available yet. In the present study we examined whether it would be possible to develop a new predictive model of drug hypersensitivity using Brown Norway (BN) rats. As representative drugs with hypersensitivity potential in humans, phenytoin (PHT), carbamazepine (CBZ), amoxicillin (AMX), and sulfamethoxazole (SMX) were orally administered to BN rats for 28 days to investigate their effects on these animals by examinations including observation of clinical signs, hematology, determination of serum IgE levels, histology, and flow cytometric analysis. Skin rashes were not observed in any animals treated with these drugs. Increases in the number of circulating inflammatory cells and serum IgE level did not necessarily occur in the animals treated with these drugs. However, histological examination revealed that germinal center hyperplasia was commonly induced in secondary lymphoid organs/tissues in the animals treated with these drugs. In cytometric analysis, changes in proportions of lymphocyte subsets were noted in the spleen of the animals treated with PHT or CBZ during the early period of administration. The results indicated that the potential of drug hypersensitivity was identified in BN rat by performing histological examination of secondary lymphoid organs/tissues. Data obtained herein suggested that drugs with hypersensitivity potential in humans gained immune reactivity in BN rat, and the germinal center hyperplasia induced by administration of these drugs may serve as a predictive biomarker for drug hypersensitivity occurrence. - Highlights: • We tested Brown Norway rats as a candidate model for predicting drug hypersensitivity. • The allergic drugs did not induce skin rash, whereas D-penicillamine did so in the rats. • Some of allergic drugs increased

  16. Oral administration of drugs with hypersensitivity potential induces germinal center hyperplasia in secondary lymphoid organ/tissue in Brown Norway rats, and this histological lesion is a promising candidate as a predictive biomarker for drug hypersensitivity occurrence in humans

    Energy Technology Data Exchange (ETDEWEB)

    Tamura, Akitoshi, E-mail: akitoshi-tamura@ds-pharma.co.jp; Miyawaki, Izuru; Yamada, Toru; Kimura, Juki; Funabashi, Hitoshi

    2013-08-15

    It is important to evaluate the potential of drug hypersensitivity as well as other adverse effects during the preclinical stage of the drug development process, but validated methods are not available yet. In the present study we examined whether it would be possible to develop a new predictive model of drug hypersensitivity using Brown Norway (BN) rats. As representative drugs with hypersensitivity potential in humans, phenytoin (PHT), carbamazepine (CBZ), amoxicillin (AMX), and sulfamethoxazole (SMX) were orally administered to BN rats for 28 days to investigate their effects on these animals by examinations including observation of clinical signs, hematology, determination of serum IgE levels, histology, and flow cytometric analysis. Skin rashes were not observed in any animals treated with these drugs. Increases in the number of circulating inflammatory cells and serum IgE level did not necessarily occur in the animals treated with these drugs. However, histological examination revealed that germinal center hyperplasia was commonly induced in secondary lymphoid organs/tissues in the animals treated with these drugs. In cytometric analysis, changes in proportions of lymphocyte subsets were noted in the spleen of the animals treated with PHT or CBZ during the early period of administration. The results indicated that the potential of drug hypersensitivity was identified in BN rat by performing histological examination of secondary lymphoid organs/tissues. Data obtained herein suggested that drugs with hypersensitivity potential in humans gained immune reactivity in BN rat, and the germinal center hyperplasia induced by administration of these drugs may serve as a predictive biomarker for drug hypersensitivity occurrence. - Highlights: • We tested Brown Norway rats as a candidate model for predicting drug hypersensitivity. • The allergic drugs did not induce skin rash, whereas D-penicillamine did so in the rats. • Some of allergic drugs increased

  17. A clinically feasible method for the detection of potential collision in proton therapy

    Energy Technology Data Exchange (ETDEWEB)

    Zou Wei; Lin Haibo; Plastaras, John P.; Wang Huanshu; Bui, Viet; Vapiwala, Neha; McDonough, James; Tochner, Zelig; Both, Stefan [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania 19104 (United States); Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania 19104 (United States) and Department of Mechanical Engineering, Drexel University, Philadelphia, Pennsylvania 19104 (United States); Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania 19104 (United States)

    2012-11-15

    Purpose: Potential collision between the patient/couch and the gantry could delay the start of the treatment and reduce clinical efficiency. The ability to accurately detect possible collisions during the treatment planning phase is desired. Such collision detection should account for the specific proton gantry design, the treatment beam configuration, couch orientation, and the patient specific geometry. In this paper the authors developed an approach to detect possible patient-machine collisions using patient treatment plan data. Methods: The geometry of the machine and the patient was reconstructed relative to the isocenter of the proton treatment room. The surface contour of the gantry was first captured from the proton computer aided design and reconstructed to account for specific gantry rotation, snout position, collimator rotation, and range compensator dimensions based on the patient treatment plan data. The patient body and couch contours were captured from the patient's CT DICOM structure file. They were reconstructed relative to the isocenter taking into account treatment couch rotation. For potential collision that occurs at body portions where no CT images exist, scout images are used to construct the body contour. A software program was developed using a ray casting algorithm that was applied to detect collisions by determining if any of the patient and couch contour points fall into the spatial polygons formed by the proton gantry surfaces. Results: Twenty-four patient plans with or without potential collisions were retrospectively identified and analyzed using the collision detection software. In addition, five collision cases were artificially generated using an anthropomorphic phantom. The program successfully detected the collisions in all cases. The calculation time for each case was within 20 s. The software program was implemented in the authors' clinic to detect patient-gantry or gantry-couch collisions in the treatment planning

  18. Clinical treatment adherence of health care workers and students exposed to potentially infectious biological material

    Directory of Open Access Journals (Sweden)

    Maria Cristina Mendes de Almeida

    2015-04-01

    Full Text Available OBJECTIVE To assess adherence to clinical appointments by health care workers (HCW and students who suffered accidents with potentially infectious biological material. METHOD A retrospective cross-sectional study that assessed clinical records of accidents involving biological material between 2005 and 2010 in a specialized unit. RESULTS A total of 461 individuals exposed to biological material were treated, of which 389 (84.4% were HCWs and 72 (15.6% students. Of the 461 exposed individuals, 307 (66.6% attended a follow-up appointment. Individuals who had suffered an accident with a known source patient were 29 times more likely to show up to their scheduled follow-up appointments (OR: 29.98; CI95%: 16.09-55.83. CONCLUSION The predictor in both univariate and multivariate analyses for adherence to clinical follow-up appointment was having a known source patient with nonreactive serology for the human immunodeficiency virus and/or hepatitis B and C.

  19. Epicardial fat and atrial fibrillation: current evidence, potential mechanisms, clinical implications, and future directions.

    Science.gov (United States)

    Wong, Christopher X; Ganesan, Anand N; Selvanayagam, Joseph B

    2017-05-01

    Obesity is increasingly recognized as a major modifiable determinant of atrial fibrillation (AF). Although body mass index and other clinical measures are useful indications of general adiposity, much recent interest has focused on epicardial fat, a distinct adipose tissue depot that can be readily assessed using non-invasive imaging techniques. A growing body of data from epidemiological and clinical studies has demonstrated that epicardial fat is consistently associated with the presence, severity, and recurrence of AF across a range of clinical settings. Evidence from basic science and translational studies has also suggested that arrhythmogenic mechanisms may involve adipocyte infiltration, pro-fibrotic, and pro-inflammatory paracrine effects, oxidative stress, and other pathways. Despite these advances, however, significant uncertainty exists and many questions remain unanswered. In this article, we review our present understanding of epicardial fat, including its classification and quantification, existing evidence implicating its role in AF, potential mechanisms, implications for clinicians, and future directions for research. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

  20. Construction and Potential Applications of Biosensors for Proteins in Clinical Laboratory Diagnosis.

    Science.gov (United States)

    Liu, Xuan; Jiang, Hui

    2017-12-04

    Biosensors for proteins have shown attractive advantages compared to traditional techniques in clinical laboratory diagnosis. In virtue of modern fabrication modes and detection techniques, various immunosensing platforms have been reported on basis of the specific recognition between antigen-antibody pairs. In addition to profit from the development of nanotechnology and molecular biology, diverse fabrication and signal amplification strategies have been designed for detection of protein antigens, which has led to great achievements in fast quantitative and simultaneous testing with extremely high sensitivity and specificity. Besides antigens, determination of antibodies also possesses great significance for clinical laboratory diagnosis. In this review, we will categorize recent immunosensors for proteins by different detection techniques. The basic conception of detection techniques, sensing mechanisms, and the relevant signal amplification strategies are introduced. Since antibodies and antigens have an equal position to each other in immunosensing, all biosensing strategies for antigens can be extended to antibodies under appropriate optimizations. Biosensors for antibodies are summarized, focusing on potential applications in clinical laboratory diagnosis, such as a series of biomarkers for infectious diseases and autoimmune diseases, and an evaluation of vaccine immunity. The excellent performances of these biosensors provide a prospective space for future antibody-detection-based disease serodiagnosis.

  1. Application of the MALDI Biotyper to clinical microbiology: progress and potential.

    Science.gov (United States)

    Kostrzewa, Markus

    2018-03-01

    The introduction of the MALDI Biotyper in laboratories substantially changed microbiology practice, this has been called a revolution. The system accelerated diagnostic while costs were reduced and accuracy was increased. In just a few years MALDI-TOF MS became the first-line identification tool for microorganisms. Ten years after its introduction, more than 2000 MALDI Biotyper systems are installed in laboratories which are performing routine diagnostic, and the number is still increasing. Areas covered: This article summarises changes in clinical microbiology introduced by the MALDI Biotyper and its effects, as it has been published in peer reviewed articles found in PubMed. Further, the potential of novel developments to increase the value of the system is described. Expert commentary: The MALDI Biotyper has significantly improved clinical microbiology in the area of microorganism identification. Now new developments and applications, e.g. for typing and resistance testing, might further increase its value in clinical microbiology. The systems might get the central diagnostic analyser which is getting integrated into the widely automated microbiology laboratories of the future.

  2. Stem cell transplantation for amyotrophic lateral sclerosis: therapeutic potential and perspectives on clinical translation.

    Science.gov (United States)

    Faravelli, Irene; Riboldi, Giulietta; Nizzardo, Monica; Simone, Chiara; Zanetta, Chiara; Bresolin, Nereo; Comi, Giacomo P; Corti, Stefania

    2014-09-01

    Amyotrophic lateral sclerosis (ALS) is a fatal neurological disease characterized by degeneration of upper and lower motor neurons. There are currently no clinically impactful treatments for this disorder. Death occurs 3-5 years after diagnosis, usually due to respiratory failure. ALS pathogenesis seems to involve several pathological mechanisms (i.e., oxidative stress, inflammation, and loss of the glial neurotrophic support, glutamate toxicity) with different contributions from environmental and genetic factors. This multifaceted combination highlights the concept that an effective therapeutic approach should counteract simultaneously different aspects: stem cell therapies are able to maintain or rescue motor neuron function and modulate toxicity in the central nervous system (CNS) at the same time, eventually representing the most comprehensive therapeutic approach for ALS. To achieve an effective cell-mediated therapy suitable for clinical applications, several issues must be addressed, including the identification of the most performing cell source, a feasible administration protocol, and the definition of therapeutic mechanisms. The method of cell delivery represents a major issue in developing cell-mediated approaches since the cells, to be effective, need to be spread across the CNS, targeting both lower and upper motor neurons. On the other hand, there is the need to define a strategy that could provide a whole distribution without being too invasive or burdened by side effects. Here, we review the recent advances regarding the therapeutic potential of stem cells for ALS with a focus on the minimally invasive strategies that could facilitate an extensive translation to their clinical application.

  3. Potential Clinical and Economic Impact of Switching Branded Medications to Generics

    Science.gov (United States)

    Straka, Robert J.; Keohane, Denis J.; Liu, Larry Z.

    2017-01-01

    Switching branded to generic medications has become a common cost-containment measure. Although this is an important objective for health care systems worldwide, the impact of this practice on patient outcomes needs to be carefully considered. We reviewed the literature summarizing the potential clinical and economic consequences of switching from branded to generic medications on patient outcomes. A literature search of peer-reviewed articles published 2003–2013 using key words of “generic switching” or “substitution” was conducted using PubMed, OvidSP, and ScienceDirect. Of 30 articles identified and reviewed, most were related to the diseases of the central nervous system, especially epilepsy. Based on our review, potential impacts of switching fell into 3 broad categories: patient attitudes and adherence, clinical and safety outcomes, and cost and resource utilization. Although in many cases generics may represent an appropriate alternative to branded products, this may not always be the case. Specifically, several studies suggested that switching may negatively impact medication adherence, whereas other studies found that generic switching was associated with poorer clinical outcomes and more adverse events. In some instances, switching accomplished cost savings but did so at increased total cost of care because of increased physician visits or hospitalizations. Although in many cases generics may represent an appropriate alternative, mandatory generic switching may lead to unintended consequences, especially in certain therapeutic areas. Although further study is warranted, based on our review, it may be medically justifiable for physicians and patients to retain the right to request the branded product in certain cases. PMID:26099048

  4. Examining the potential clinical value of curcumin in the prevention and diagnosis of Alzheimer's disease.

    Science.gov (United States)

    Goozee, K G; Shah, T M; Sohrabi, H R; Rainey-Smith, S R; Brown, B; Verdile, G; Martins, R N

    2016-02-14

    Curcumin derived from turmeric is well documented for its anti-carcinogenic, antioxidant and anti-inflammatory properties. Recent studies show that curcumin also possesses neuroprotective and cognitive-enhancing properties that may help delay or prevent neurodegenerative diseases, including Alzheimer's disease (AD). Currently, clinical diagnosis of AD is onerous, and it is primarily based on the exclusion of other causes of dementia. In addition, phase III clinical trials of potential treatments have mostly failed, leaving disease-modifying interventions elusive. AD can be characterised neuropathologically by the deposition of extracellular β amyloid (Aβ) plaques and intracellular accumulation of tau-containing neurofibrillary tangles. Disruptions in Aβ metabolism/clearance contribute to AD pathogenesis. In vitro studies have shown that Aβ metabolism is altered by curcumin, and animal studies report that curcumin may influence brain function and the development of dementia, because of its antioxidant and anti-inflammatory properties, as well as its ability to influence Aβ metabolism. However, clinical studies of curcumin have revealed limited effects to date, most likely because of curcumin's relatively low solubility and bioavailability, and because of selection of cohorts with diagnosed AD, in whom there is already major neuropathology. However, the fresh approach of targeting early AD pathology (by treating healthy, pre-clinical and mild cognitive impairment-stage cohorts) combined with new curcumin formulations that increase bioavailability is renewing optimism concerning curcumin-based therapy. The aim of this paper is to review the current evidence supporting an association between curcumin and modulation of AD pathology, including in vitro and in vivo studies. We also review the use of curcumin in emerging retinal imaging technology, as a fluorochrome for AD diagnostics.

  5. UFT and leucovorin: a review of its clinical development and therapeutic potential in the oral treatment of cancer.

    Science.gov (United States)

    Hoff, P M; Pazdur, R; Benner, S E; Canetta, R

    1998-07-01

    UFT is an oral antineoplastic drug combining uracil and tegafur in a 4:1 molar ratio. Tegafur acts as a prodrug of 5-fluorouracil (5-FU), being slowly metabolized by cytochrome P450 to 5-FU. Uracil competitively inhibits the metabolism of 5-FU, resulting in increased plasma and tumor 5-FU concentrations. At equimolar doses, higher peak plasma 5-FU concentrations are achieved with UFT plus oral leucovorin with similar systemic 5-FU exposure compared with low-dose continuous 5-FU infusions. The elimination half-life of 5-FU following UFT administration is approximately 7 h compared with 0.2 h with i.v. 5-FU. In phase II studies of UFT plus oral leucovorin for the treatment of advanced colorectal cancer, response rates ranged from 25 to 42%. UFT plus oral leucovorin is well tolerated, with manageable diarrhea being the only dose-limiting toxicity; the regimen is not associated with significant myelosuppression, mucositis, hand-foot syndrome or alopecia. UFT, with or without leucovorin, has also been evaluated alone or in combination with other cytotoxic agents for the treatment of advanced lung, breast and gastric cancers. UFT has also been evaluated as adjuvant therapy for colorectal, breast, gastric, head and neck, and superficial bladder cancers. UFT plus leucovorin offers patients an entirely oral cancer treatment, and appears to provide potential advantages over bolus 5-FU regimens with regard to toxicity and convenience of administration. These benefits should be advantageous in the adjuvant setting, as well as in advanced disease settings in which palliation is an important consideration. Ongoing clinical trials will further define the role of this promising oral treatment regimen.

  6. The epigenetic promise for prostate cancer diagnosis.

    Science.gov (United States)

    Van Neste, Leander; Herman, James G; Otto, Gaëtan; Bigley, Joseph W; Epstein, Jonathan I; Van Criekinge, Wim

    2012-08-01

    Prostate cancer is the most common cancer diagnosis in men and a leading cause of death. Improvements in disease management would have a significant impact and could be facilitated by the development of biomarkers, whether for diagnostic, prognostic, or predictive purposes. The blood-based prostate biomarker PSA has been part of clinical practice for over two decades, although it is surrounded by controversy. While debates of usefulness are ongoing, alternatives should be explored. Particularly with recent recommendations against routine PSA-testing, the time is ripe to explore promising biomarkers to yield a more efficient and accurate screening for detection and management of prostate cancer. Epigenetic changes, more specifically DNA methylation, are amongst the most common alterations in human cancer. These changes are associated with transcriptional silencing of genes, leading to an altered cellular biology. One gene in particular, GSTP1, has been widely studied in prostate cancer. Therefore a meta-analysis has been conducted to examine the role of this and other genes and the potential contribution to prostate cancer management and screening refinement. More than 30 independent, peer reviewed studies have reported a consistently high sensitivity and specificity of GSTP1 hypermethylation in prostatectomy or biopsy tissue. The meta-analysis combined and compared these results. GSTP1 methylation detection can serve an important role in prostate cancer managment. The meta-analysis clearly confirmed a link between tissue DNA hypermethylation of this and other genes and prostate cancer. Detection of DNA methylation in genes, including GSTP1, could serve an important role in clinical practice. Copyright © 2011 Wiley Periodicals, Inc.

  7. Beat-to-beat variability of cardiac action potential duration: underlying mechanism and clinical implications.

    Science.gov (United States)

    Nánási, Péter P; Magyar, János; Varró, András; Ördög, Balázs

    2017-10-01

    Beat-to-beat variability of cardiac action potential duration (short-term variability, SV) is a common feature of various cardiac preparations, including the human heart. Although it is believed to be one of the best arrhythmia predictors, the underlying mechanisms are not fully understood at present. The magnitude of SV is basically determined by the intensity of cell-to-cell coupling in multicellular preparations and by the duration of the action potential (APD). To compensate for the APD-dependent nature of SV, the concept of relative SV (RSV) has been introduced by normalizing the changes of SV to the concomitant changes in APD. RSV is reduced by I Ca , I Kr , and I Ks while increased by I Na , suggesting that ion currents involved in the negative feedback regulation of APD tend to keep RSV at a low level. RSV is also influenced by intracellular calcium concentration and tissue redox potential. The clinical implications of APD variability is discussed in detail.

  8. Potential role of a pharmacist to enhance medication-related aspects of clinical trials conducted in a dedicated clinical research unit

    Directory of Open Access Journals (Sweden)

    Kimberly A. Redic, PharmD

    2017-06-01

    Conclusions: This pilot study showed potential roles for pharmacy personnel involvement in medication reconciliation in the clinical research setting. Pharmacists have the opportunity to ensure that IDs are accurately included in patient medication lists and to identify the use of potential protocol prohibited concomitant medications.

  9. Miscellaneous conditions of the shoulder: Anatomical, clinical, and pictorial review emphasizing potential pitfalls in imaging diagnosis

    International Nuclear Information System (INIS)

    Farid, Nikdokht; Bruce, Dean; Chung, Christine B.

    2008-01-01

    The purpose of this article is to review the key imaging findings in major categories of pathology affecting the shoulder joint including hydroxyapatite deposition disease, rotator cuff interval pathology, acromioclavicular joint pathology, glenohumeral osteoarthrosis, and synovial inflammatory processes, with specific emphasis on findings that have associated pitfalls in imaging diagnosis. The pathophysiology and clinical manifestations of the above mentioned categories of pathology will be reviewed, followed in each section by a detailed pictorial review of the key imaging findings in each category including plain film, computed tomography, and magnetic resonance imaging findings as applicable. Imaging challenges that relate to both diagnosis and characterization will be addressed with each type of pathology. The goal is that after reading this article, the reader will be able to recognize the key imaging findings in major categories of pathology affecting the shoulder joint and will become familiar with the potential pitfalls in their imaging diagnosis

  10. Miscellaneous conditions of the shoulder: Anatomical, clinical, and pictorial review emphasizing potential pitfalls in imaging diagnosis

    Energy Technology Data Exchange (ETDEWEB)

    Farid, Nikdokht [University of California San Diego, Department of Radiology, 200 West Arbor Drive, San Diego, CA 92103 (United States); VA Healthcare System San Diego, Department of Radiology, 3350 La Jolla Village Drive, La Jolla, CA 92161 (United States); Bruce, Dean [University of California San Diego, Department of Radiology, 200 West Arbor Drive, San Diego, CA 92103 (United States); VA Healthcare System San Diego, Department of Radiology, 3350 La Jolla Village Drive, La Jolla, CA 92161 (United States); University of Alberta, Edmonton, Alberta (Canada); Chung, Christine B. [University of California San Diego, Department of Radiology, 200 West Arbor Drive, San Diego, CA 92103 (United States); VA Healthcare System San Diego, Department of Radiology, 3350 La Jolla Village Drive, La Jolla, CA 92161 (United States)], E-mail: cbchung@ucsd.edu

    2008-10-15

    The purpose of this article is to review the key imaging findings in major categories of pathology affecting the shoulder joint including hydroxyapatite deposition disease, rotator cuff interval pathology, acromioclavicular joint pathology, glenohumeral osteoarthrosis, and synovial inflammatory processes, with specific emphasis on findings that have associated pitfalls in imaging diagnosis. The pathophysiology and clinical manifestations of the above mentioned categories of pathology will be reviewed, followed in each section by a detailed pictorial review of the key imaging findings in each category including plain film, computed tomography, and magnetic resonance imaging findings as applicable. Imaging challenges that relate to both diagnosis and characterization will be addressed with each type of pathology. The goal is that after reading this article, the reader will be able to recognize the key imaging findings in major categories of pathology affecting the shoulder joint and will become familiar with the potential pitfalls in their imaging diagnosis.

  11. Diffusion and Perfusion MR Imaging in Acute Stroke: Clinical Utility and Potential Limitations for Treatment Selection

    DEFF Research Database (Denmark)

    Bateman, Mathew; Slater, Lee-Anne; Leslie-Mazwi, Thabele M

    2017-01-01

    Magnetic resonance (MR) diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) offer unique insight into acute ischemic stroke pathophysiology. These techniques may offer the ability to apply pathophysiology to accurately individualize acute stroke reperfusion treatment, including ...... to be investigated in ongoing randomized controlled trials, and continued research into these techniques will help achieve the goal of tissue-based decision making and individualized acute stroke treatment....... extending the opportunity of reperfusion treatment to well beyond the current time-based treatment windows. This review examines the use of DWI and PWI in the major stroke trials, their current clinical utility, and potential limitations for reperfusion treatment selection. DWI and PWI continue...

  12. Controversies surrounding the clinical potential of cinnamon for the management of diabetes.

    Science.gov (United States)

    Rafehi, H; Ververis, K; Karagiannis, T C

    2012-06-01

    Obesity levels have increased significantly in the past five decades and are predicted to continue rising, resulting in important health implications. In particular, this has translated to an increase in the occurrence of type II diabetes mellitus (T2D). To alleviate associated problems, certain nutraceuticals have been considered as potential adjuncts or alternatives to conventional prescription drugs. Cinnamon, a commonly consumed spice originating from South East Asia, is currently being investigated as a potential preventative supplement and treatment for insulin resistance, metabolic syndrome and T2D. Extensive in vitro evidence has shown that cinnamon may improve insulin resistance by preventing and reversing impairments in insulin signalling in skeletal muscle. In adipose tissue, it has been shown that cinnamon increases the expression of peroxisome proliferator-activated receptors including, PPARγ. This is comparable to the action of commonly used thiazolinediones, which are PPAR agonists. Studies have also shown that cinnamon has potent anti-inflammatory properties. However, numerous human clinical trials with cinnamon have been conducted with varying findings. While some studies have showed no beneficial effect, others have indicated improvements in cholesterol levels, systolic blood pressure, insulin sensitivity and postprandial glucose levels with cinnamon. However, the only measurement consistently improved by cinnamon consumption is fasting glucose levels. While it is still premature to suggest the use of cinnamon supplementation based on the evidence, further investigation into mechanisms of action is warranted. Apart from further characterization of genetic and epigenetic changes in model systems, systematic large-scale clinical trials are required. In this study, we discuss the mechanisms of action of cinnamon in the context of T2D and we highlight some of the associated controversies. © 2011 Blackwell Publishing Ltd.

  13. Transforming Experience: The Potential of Augmented Reality and Virtual Reality for Enhancing Personal and Clinical Change.

    Science.gov (United States)

    Riva, Giuseppe; Baños, Rosa M; Botella, Cristina; Mantovani, Fabrizia; Gaggioli, Andrea

    2016-01-01

    During life, many personal changes occur. These include changing house, school, work, and even friends and partners. However, the daily experience shows clearly that, in some situations, subjects are unable to change even if they want to. The recent advances in psychology and neuroscience are now providing a better view of personal change, the change affecting our assumptive world: (a) the focus of personal change is reducing the distance between self and reality (conflict); (b) this reduction is achieved through (1) an intense focus on the particular experience creating the conflict or (2) an internal or external reorganization of this experience; (c) personal change requires a progression through a series of different stages that however happen in discontinuous and non-linear ways; and (d) clinical psychology is often used to facilitate personal change when subjects are unable to move forward. Starting from these premises, the aim of this paper is to review the potential of virtuality for enhancing the processes of personal and clinical change. First, the paper focuses on the two leading virtual technologies - augmented reality (AR) and virtual reality (VR) - exploring their current uses in behavioral health and the outcomes of the 28 available systematic reviews and meta-analyses. Then the paper discusses the added value provided by VR and AR in transforming our external experience by focusing on the high level of personal efficacy and self-reflectiveness generated by their sense of presence and emotional engagement. Finally, it outlines the potential future use of virtuality for transforming our inner experience by structuring, altering, and/or replacing our bodily self-consciousness. The final outcome may be a new generation of transformative experiences that provide knowledge that is epistemically inaccessible to the individual until he or she has that experience, while at the same time transforming the individual's worldview.

  14. Transforming Experience: The Potential of Augmented Reality and Virtual Reality for Enhancing Personal and Clinical Change

    Directory of Open Access Journals (Sweden)

    Giuseppe Riva

    2016-09-01

    Full Text Available During our life we undergo many personal changes: we change our house, our school, our work and even our friends and partners. However, our daily experience shows clearly that in some situations subjects are unable to change even if they want to. The recent advances in psychology and neuroscience are now providing a better view of personal change, the change affecting our assumptive world: a the focus of personal change is reducing the distance between self and reality (conflict; b this reduction is achieved through (1 an intense focus on the particular experience creating the conflict or (2 an internal or external reorganization of this experience; c personal change requires a progression through a series of different stages; d clinical psychology is often used to facilitate personal change when subjects are unable to move forward. Starting from these premises, the aim of this paper is to review the potential of virtuality for enhancing the processes of personal and clinical change. First, the paper will focus on the two leading virtual technologies – Augmented Reality (AR and Virtual Reality (VR – exploring their current uses in behavioral health and the outcomes of the 28 available systematic reviews and meta-analyses. Then the paper discusses the added value provided by VR and AR in transforming our external experience, by focusing on the high level of self-reflectiveness and personal efficacy induced by their emotional engagement and sense of presence. Finally, it outlines the potential future use of virtuality for transforming our inner experience by structuring, altering and/or replacing our bodily self-consciousness. The final outcome may be a new generation of transformative experiences that provide knowledge that is epistemically inaccessible to the individual until he or she has that experience, while at the same time transforming the individual’s worldview.

  15. Clinical potential of regulatory T cell therapy in liver diseases: An overview and current perspectives

    Directory of Open Access Journals (Sweden)

    Hannah Claire Jeffery

    2016-09-01

    Full Text Available The increasing demand for liver transplantation and the decline in donor organs has highlighted the need for alternative novel therapies to prevent chronic active hepatitis, which eventually leads to liver cirrhosis and liver cancer. Liver histology of chronic hepatitis is composed of both effector and regulatory lymphocytes. The human liver contains different subsets of effector lymphocytes, that are kept in check by a subpopulation of T cells known as Regulatory T cells (Treg. The balance of effector and regulatory lymphocytes generally determines the outcome of hepatic inflammation: resolution, fulminant hepatitis or chronic active hepatitis. Thus, maintaining and adjusting this balance is crucial in immunological manipulation of liver diseases. One of the options to restore this balance is to enrich Treg in the liver disease patients.Advances in the knowledge of Treg biology and development of clinical grade isolation reagents, cell sorting equipment and Good Manufacturing Practice (GMP facilities have paved the way to apply Treg cells as a potential therapy to restore peripheral self-tolerance in autoimmune liver diseases, chronic rejection and post-transplantation. Past and on-going studies have applied Treg in type-1 diabetes mellitus, systemic lupus erythematosus, graft versus host diseases (GVHD and solid organ transplantations. There have not been any new therapies for the autoimmune liver diseases for more than three decades; thus the clinical potential for the application of autologous Treg cell therapy to treat autoimmune liver disease is an attractive and novel option. However, it is fundamental to understand the deep immunology, genetic profiles, biology, homing behavior and microenvironment of Treg before applying the cells to the patients.

  16. Clinical efficacy of implementing Bio Immune(G)ene MEDicine in the treatment of chronic asthma with the objective of reducing or removing effectively corticosteroid therapy: A novel approach and promising results.

    Science.gov (United States)

    Glady, Gilbert

    2018-06-01

    Asthma is one of the diseases that demonstrates a wide range of variation in its clinical expression, in addition to an important heterogeneity in the pathophysiological mechanisms present in each case. The ever-increasing knowledge of the molecular signalling routes and the development of the Bio Immune(G)ene Medicine [BI(G)MED] therapy in line with this knowledge has revealed a whole novel potential set of self-regulation biological molecules, that may be used to promote the physiological immunogenic self-regulation mechanisms and re-establish the homeostatic balance at a genomic, proteomic and cellular level. The aim of the present study is to demonstrate that the sublingual use of a therapeutic protocol based on BI(G)MED regulatory BIMUREGs in the treatment of chronic asthma may reduce or suppress corticosteroid therapy and avoid its harmful side effects which some patients suffer when using this treatment on a long-term basis. The clinical efficacy of BI(G)MED for chronic asthma was evaluated through a multi-centre study carried out in 2016 implementing a 6-month BI(G)MED treatment protocol for Bronchial Asthma. A total of 61 patients from private medical centres and of European countries including Germany, Austria, France, Belgium and Spain participated. The manuscript describes in detail the clinical efficacy of Bio Immune(G)ene regulatory BI(G)MED treatment protocol that allows the reduction or total removal of the corticosteroid dose in patients with chronic asthma. No adverse reactions were observed. The BI(G)MED regulatory therapy brings novel therapeutic possibilities as an effective and safe treatment of chronic asthma. BI(G)MED was demonstrated to significantly reduce asthma severity when parameter compositions were all analysed by categorical outcomes. Therefore, it is considered a good therapeutic alternative for patients who respond poorly to steroids.

  17. Hepatocellular carcinoma displays distinct DNA methylation signatures with potential as clinical predictors.

    Directory of Open Access Journals (Sweden)

    Hector Hernandez-Vargas

    Full Text Available BACKGROUND: Hepatocellular carcinoma (HCC is characterized by late detection and fast progression, and it is believed that epigenetic disruption may be the cause of its molecular and clinicopathological heterogeneity. A better understanding of the global deregulation of methylation states and how they correlate with disease progression will aid in the design of strategies for earlier detection and better therapeutic decisions. METHODS AND FINDINGS: We characterized the changes in promoter methylation in a series of 30 HCC tumors and their respective surrounding tissue and identified methylation signatures associated with major risk factors and clinical correlates. A wide panel of cancer-related gene promoters was analyzed using Illumina bead array technology, and CpG sites were then selected according to their ability to classify clinicopathological parameters. An independent series of HCC tumors and matched surrounding tissue was used for validation of the signatures. We were able to develop and validate a signature of methylation in HCC. This signature distinguished HCC from surrounding tissue and from other tumor types, and was independent of risk factors. However, aberrant methylation of an independent subset of promoters was associated with tumor progression and etiological risk factors (HBV or HCV infection and alcohol consumption. Interestingly, distinct methylation of an independent panel of gene promoters was strongly correlated with survival after cancer therapy. CONCLUSION: Our study shows that HCC tumors exhibit specific DNA methylation signatures associated with major risk factors and tumor progression stage, with potential clinical applications in diagnosis and prognosis.

  18. Potentially three distinct roles for hypoxic cell sensitizers in the clinic

    International Nuclear Information System (INIS)

    Chapman, J.D.; Raleigh, J.A.; Pedersen, J.E.; Ngan, J.; Shum, F.Y.

    1979-01-01

    Nitroaromatic drugs have been applied to radiation therapy on the basis of their effectiveness to enhance radiation damages selectively in hypoxic mammalian cells at nontoxic concentration. Such sensitizers could improve the rate of local tumor control by conventional radiotherapy in such cases that the resistance due to hypoxia in a limiting factor. The selective cytotoxicity of the drug to hypoxic cells is the second distinct action. A third potential role for nitroaromatic drugs could involve their use for the diagnosis of the number and location of hypoxic cells within tumors. The gain in therapeutic ratio by a factor from 5 to 10 is necessary before the full clinical impact of hypoxic cell radiosensitizers can be evaluated. The drugs selected for the use as clinical radiosensitizers were originally developed as the antibacterial agents with selective activity against anaerobes. The hypoxic cells in tumors are usually resistant to chemotherapy as well as resistant to radiation, and this specific drug action of sensitizers combined with that of an agent effective against oxygenated and cycling cells could possibly produce improved tumor cures. Electron-affinitive chemicals become selectively bound to the macromolecules of hypoxic mammalian cells by radiation-induced chemical reaction. This technique was used to identify by autoradiographic procedures the location of the radioactive nitrofurazone bound to hypoxic cells within multicellular spheroids. (Yamashita, S.)

  19. Automation of the consensus guidelines in diabetes care: potential impact on clinical inertia.

    Science.gov (United States)

    Albisser, A Michael; Inhaber, Francine

    2010-01-01

    To propose that automation of the consensus guidelines and mandated targets (CG&MT) in glycemia, hemoglobin A1c, and body weight will facilitate optimal clinical management of patients with diabetes. (1) A simplified method for capturing diabetes outcomes at home was devised, (2) relevant portions of the CG&MT were translated into computer code and automated, and (3) algorithms were applied to transform data from self-monitoring of blood glucose into circadian profiles and hemoglobin A1c levels. (4) The resulting procedures were integrated into a USB memory drive for use by health-care providers at the point of care. For input from patients, a simple form is used to capture data on diabetes outcomes, including blood glucose measurements before and after meals and at bedtime, medication, and lifestyle events in a structured fashion. At each encounter with a health-care provider, the patient's data are transferred into the device and become available to assist in identifying deviations from mandated targets, potential risks of hypoglycemia, and necessary prescription changes. Preliminary observations during a 2 1/2-year period from a community support group dedicated to glycemic control on 20 unselected patients (10 with and 10 without use of the device) are summarized. With use of the automated information, the health professional is supported at the point of care to achieve better, safer outcomes and practice evidence-based medicine entirely in lockstep with the CG&MT. This automation helps to overcome clinical inertia.

  20. Clinical investigations of the therapeutic potential of ayahuasca: rationale and regulatory challenges.

    Science.gov (United States)

    McKenna, Dennis J

    2004-05-01

    Ayahuasca is a hallucinogenic beverage that is prominent in the ethnomedicine and shamanism of indigenous Amazonian tribes. Its unique pharmacology depends on the oral activity of the hallucinogen, N,N-dimethyltryptamine (DMT), which results from inhibition of monoamine oxidase (MAO) by beta-carboline alkaloids. MAO is the enzyme that normally degrades DMT in the liver and gut. Ayahuasca has long been integrated into mestizo folk medicine in the northwest Amazon. In Brazil, it is used as a sacrament by several syncretic churches. Some of these organizations have incorporated in the United States. The recreational and religious use of ayahuasca in the United States, as well as "ayahuasca tourism" in the Amazon, is increasing. The current legal status of ayahuasca or its source plants in the United States is unclear, although DMT is a Schedule I controlled substance. One ayahuasca church has received favorable rulings in 2 federal courts in response to its petition to the Department of Justice for the right to use ayahuasca under the Religious Freedom Restoration Act. A biomedical study of one of the churches, the Uñiao do Vegetal (UDV), indicated that ayahuasca may have therapeutic applications for the treatment of alcoholism, substance abuse, and possibly other disorders. Clinical studies conducted in Spain have demonstrated that ayahuasca can be used safely in normal healthy adults, but have done little to clarify its potential therapeutic uses. Because of ayahuasca's ill-defined legal status and variable botanical and chemical composition, clinical investigations in the United States, ideally under an approved Investigational New Drug (IND) protocol, are complicated by both regulatory and methodological issues. This article provides an overview of ayahuasca and discusses some of the challenges that must be overcome before it can be clinically investigated in the United States.

  1. Potential facilitators and barriers to adopting standard treatment guidelines in clinical practice.

    Science.gov (United States)

    Sharma, Sangeeta; Pandit, Ajay; Tabassum, Fauzia

    2017-04-18

    Purpose The purpose of this paper is to assess medicines information sources accessed by clinicians, if sources differed in theory and practice and to find out the barriers and facilitators to effective guideline adoption. Design/methodology/approach In all, 183 doctors were surveyed. Barriers and facilitators were classified as: communication; potential adopters; innovation; organization characteristics and environmental/social/economic context. Findings Most of the clinicians accessed multiple information sources including standard treatment guidelines, but also consulted seniors/colleagues in practice. The top three factors influencing clinical practice guideline adoption were innovation characteristics, environmental context and individual characteristics. The respondents differed in the following areas: concerns about flexibility offered by the guideline; denying patients' individuality; professional autonomy; insights into gaps in current practice and evidence-based practice; changing practices with little or no benefit. Barriers included negative staff attitudes/beliefs, guideline integration into organizational structures/processes, time/resource constraints. Fearing third parties (government and insurance companies) restricting medicines reimbursement and poor liability protection offered by the guidelines emerged as the barriers. Facilitators include aligning organizational structures/processes with the innovation; providing leadership support to guide diffusion; increasing awareness and enabling early innovation during pre/in-service training, with regular feedback on outcomes and use. Practical implications Guideline adoption in clinical practice is partly within doctors' control. There are other key prevailing factors in the local context such as environmental, social context, professional and organizational culture affecting its adoption. Organizational policy and accreditation standards necessitating adherence can serve as a driver. Originality

  2. Potential clinical and economic effects of homocyst(e)ine lowering.

    Science.gov (United States)

    Nallamothu, B K; Fendrick, A M; Rubenfire, M; Saint, S; Bandekar, R R; Omenn, G S

    Elevated total homocyst(e)ine levels (>/=11 micromol/L) have been identified as a potential risk factor for coronary heart disease. However, the benefits expected from lowering homocyst(e)ine levels with folic acid and vitamin B(12) supplementation have yet to be demonstrated in clinical trials. We constructed a decision analytic model to estimate the clinical benefits and economic costs of 2 homocyst(e)ine-lowering strategies: (1) "treat all"-no screening, daily supplementation with folic acid (400 microg) and vitamin B(12) (cyanocobalamin; 500 microg) for all; (2) "screen and treat"-screening, followed by daily supplementation with folic acid and vitamin B(12) for individuals with elevated homocyst(e)ine levels. Simulated cohorts of 40-year-old men and 50-year-old women in the general population were evaluated. In the base-case analysis, we assumed that lowering elevated levels would reduce excess coronary heart disease risk by 40%; however, this assumption and others were evaluated across a broad range of potential values using sensitivity analysis. Primary outcomes were discounted costs per life-year saved. Although the treat-all strategy was slightly more effective overall, the screen and treat strategy resulted in a much lower cost per life-year saved ($13,600 in men and $27,500 in women) when compared with no intervention. Incremental cost-effectiveness ratios for the treat-all strategy compared with the screen and treat strategy were more than $500,000 per life-year saved in both cohorts. Sensitivity analysis showed that cost-effectiveness ratios for the screen and treat strategy remained less than $50,000 per life-year saved under several unfavorable scenarios, such as when effective homocyst(e)ine lowering was assumed to reduce the relative risk of coronary heart disease-related death by only 11% in men or 23% in women. Homocyst(e)ine lowering with folic acid and vitamin B(12) supplementation could result in substantial clinical benefits at reasonable

  3. A novel design for randomized immuno-oncology clinical trials with potentially delayed treatment effects

    Directory of Open Access Journals (Sweden)

    Pei He

    2015-10-01

    Full Text Available The semi-parametric proportional hazards model is widely adopted in randomized clinical trials with time-to-event outcomes, and the log-rank test is frequently used to detect a potential treatment effect. Immuno-oncology therapies pose unique challenges to the design of a trial as the treatment effect may be delayed, which violates the proportional hazards assumption, and the log-rank test has been shown to markedly lose power under the non-proportional hazards setting. A novel design and analysis approach for immuno-oncology trials is proposed through a piecewise treatment effect function, which is capable of detecting a potentially delayed treatment effect. The number of events required for the trial will be determined to ensure sufficient power for both the overall log-rank test without a delayed effect and the test beyond the delayed period when such a delay exists. The existence of a treatment delay is determined by a likelihood ratio test with resampling. Numerical results show that the proposed design adequately controls the Type I error rate, has a minimal loss in power under the proportional hazards setting and is markedly more powerful than the log-rank test with a delayed treatment effect.

  4. Clinically targeted screening for congenital CMV - potential for integration into the National Hearing Screening Programme.

    Science.gov (United States)

    Kadambari, S; Luck, S; Davis, A; Williams, Ej; Berrington, J; Griffiths, Pd; Sharland, M

    2013-10-01

    Screening for a condition should only be undertaken if certain strict criteria are met. Congenital CMV (cCMV) is a leading cause of sensorineuronal hearing loss (SNHL) and meets many of these criteria, but is not currently screened for in the UK. Ganciclovir reduces CMV-induced progressive SNHL if treatment is begun in the first month of life. The Newborn Hearing Screening Programme (NHSP) has been shown to identify SNHL at the earliest possible age. The potential of integrating screening for cCMV into the NHSP is discussed to consolidate the link between screening, early diagnosis and management. The early diagnosis and treatment of cCMV may prevent a small proportion of late SNHL. In the absence of any screening programme, we provide evidence that clinically targeted screening through the NHSP is a potential option in the UK, enhancing the diagnostic pathway and enabling appropriate early treatment to reduce long-term morbidity. ©2013 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  5. Emerging treatments for advanced pancreatic cancer: clinical potential of albumin-bound paclitaxel

    Directory of Open Access Journals (Sweden)

    Fontana E

    2014-06-01

    Full Text Available Elisa Fontana, Francesco Sclafani, David Cunningham Department of Medicine, The Royal Marsden NHS Foundation Trust, London and Surrey, UK Abstract: The management of pancreatic cancer has historically represented a major challenge for oncologists. The inherent aggressiveness of this tumor and the fibrotic features of the surrounding stromal tissue have significantly limited the impact of standard chemotherapy. Moreover, the paucity of available tumor tissue has hampered a better understanding of the biology of this disease as well as the development of new treatment strategies. Recently, the therapeutic landscape of metastatic pancreatic cancer has been enriched by two new combination regimens (FOLFIRINOX and gemcitabine-nab-paclitaxel which have been demonstrated to improve the outcome in patients with good performance status. Moreover, the peritumoral stroma has been increasingly recognized as a potential therapeutic target for this disease, and several new agents targeting stromal components are currently under investigation. In this paper, we review the current treatment options for advanced pancreatic cancer, highlight the role of the peritumoral stroma, and discuss the clinical potential of nab-paclitaxel and antistromal treatment strategies. Keywords: pancreatic cancer, nab-paclitaxel, stroma, SPARC

  6. Antimicrobial Potential of Momordica charantia L. against Multiresistant Standard Species and Clinical Isolates.

    Science.gov (United States)

    Lucena Filho, José Hardman Sátiro de; Lima, Rennaly de Freitas; Medeiros, Ana Claudia Dantas de; Pereira, Jozinete Vieira; Granville-Garcia, Ana Flávia; Costa, Edja Maria Melo de Brito

    2015-11-01

    The aim of the present study was to evaluate the antibacterial and antifungal potential in vitro of Momordica charantia L. against the microorganisms of clinical interest (standard strains and multiresistant isolates) in order to aggregate scientific information in relation to its use as a therapeutic product. M. charantia L. plant material was acquired in municipality of Malta, Paraiba, Brazil. The extract was obtained through maceration, filtration and then concentrated under reduced pressure in a rotary evaporator, resulting in a dough, and was then dried in an oven for 72 hours at 40°C. Antimicrobial action of ethanolic extract of seed M. charantia L. was evaluated based on the minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and minimum fungicidal concentration (MFC) against standard strains of bacteria, isolates multiresistant bacteria and Candida species, by microdilution in broth method. All organisms were sensitive to the extract, being considered strong antimicrobial activity (MIC and MBC/MFC charantia L. showed strong antimicrobial potential, with bactericidal and fungicidal profile, there is the prospect to constitute a new therapeutic strategy for the control of infections, particularly in multiresistant strains. The use of medicinal plants in treatment of infectious processes have an important function nowadays, due to the limitations of the use of synthetic antibiotics available, related specifically to the microbial resistance emergence.

  7. Improving the Clinical Pharmacologic Assessment of Abuse Potential: Part 2: Optimizing the Design of Human Abuse Potential Studies.

    Science.gov (United States)

    Sellers, Edward M

    2018-04-01

    This article discusses the conduct of a human abuse potential study as outlined in the Food and Drug Administration Final Guidance to Industry on Assessment of Abuse Potential. In addition, areas where alternative approaches should be considered are proposed. The design, end points, conduct, and interpretation of the human abuse potential study were reviewed, analyzed, and placed in the context of current scientific knowledge and best practices to mitigate regulatory risk and expedite drug development. The guidance is based on regulatory needs and current scientific practices. However, the reliability and utility of such studies can be improved with better subject selection, data collection, standardization of data collection and staff training, and a better understanding of the measurement properties of the dependent measures. The guidance provides a useful framework for conduct of human abuse potential studies. However, design assumptions, poor choice of end points, failure to consider alternate approaches, and limited experience with interpretation can result in an inadequate study or one that does not fairly represent the abuse potential of a new chemical entity. Methodologic development is needed to strengthen the regulatory framework. The Food and Drug Administration or the National Institutes on Drug Abuse could take a targeted initiative to encourage this work.

  8. Political Reputations and Campaign Promises

    OpenAIRE

    Aragones, Enriqueta; Palfrey, Thomas R.; Postlewaite, Andrew

    2006-01-01

    We analyze conditions under which candidates' reputations may affect voters' beliefs over what policy will be implemented by the winning candidate of an election. We develop a model of repeated elections with complete information in which candidates are purely ideological. We analyze an equilibrium in which voters' strategies involve a credible threat to punish candidates who renege on their campaign promises and in which all campaign promises are believed by voters and honored by candidates....

  9. Clinical assessment of the effect of digital filtering on the detection of ventricular late potentials

    Directory of Open Access Journals (Sweden)

    P.R. Benchimol-Barbosa

    2002-11-01

    Full Text Available Ventricular late potentials are low-amplitude signals originating from damaged myocardium and detected on the body surface by ECG filtering and averaging. Digital filters present in commercial equipment may interfere with the ability of arrhythmia stratification. We compared 40-Hz BiSpec (BI and classical 40- to 250-Hz band-pass Butterworth bidirectional (BD filters in terms of impact on time domain variables and diagnostic properties. In a transverse retrospective age-adjusted case-control study, 221 subjects with sinus rhythm without bundle branch block were divided into three groups after signal-averaged ECG acquisition: GI (N = 40, clinically normal controls, GII (N = 158, subjects with coronary heart disease without sustained monomorphic ventricular tachycardia (SMVT, and GIII (N = 23, subjects with heart disease and documented SMVT. Conventional variables analyzed from vector magnitude data after averaging to 0.3 µV final noise were obtained by application of each filter to the averaged signal, and evaluated in pairs by numerical comparison and by diagnostic agreement assessment, using conventional and optimized thresholds of normality. Significant differences were found between BI and BD variables in all groups, with diagnostic results showing significant disagreement between both filters [kappa value of 0.61 (P<0.05 for GII and 0.31 for GIII (P = NS]. Sensitivity for SMVT was lower with BI than with BD (65.2 vs 91.3%, respectively, P<0.05. Filters provided significantly different numerical and diagnostic results and the BI filter showed only limited clinical application to risk stratification of ventricular arrhythmia.

  10. Alterations in neuropeptides in aging and disease. Pathophysiology and potential for clinical intervention.

    Science.gov (United States)

    Leake, A; Ferrier, I N

    1993-01-01

    Marked specific and selective changes in the levels of some neuropeptides in age-related diseases, such as senile dementia of the Alzheimer (SDAT) or Lewy body (SDLT) types, Parkinson's disease, Huntington's disease and major depressive disorder, versus normal aging have been noted. However, the levels of most neuropeptides are normal. The only 2 peptides consistently altered in SDAT are somatostatin and corticotrophin-releasing hormone both of which are reduced. In Huntington's disease, the level of substance P in the basal ganglia is reduced suggesting a preferential vulnerability of spiny neurones in this disease. In Parkinson's disease, substance P is attenuated in the basal ganglia while somatostatin is reduced in the neocortex. These and other results suggest that substance P deficits are related to movement disorders while somatostatin deficits are related to cognitive impairment. SDLT is a type of dementia with features common to both SDAT and Parkinson's disease, although the changes in neuropeptides suggest that neurochemically the disease is more closely related to SDAT. In major depressive disorder, the level of corticotrophin-releasing hormone is reduced while there is a reciprocal increase in corticotrophin-releasing hormone receptors suggesting that the neurones remain functional. Potential clinical intervention has been limited by problems such as poor penetration of agents into the brain and the short half-lives of neuropeptide agonists and antagonists. However, some currently available agents may act, at least in part, through modulation of neuropeptide pathways, e.g. carbamazepine and alprazolam both modulate the corticotrophin-releasing hormone system in animals, and both have clinically proven antidepressant activity.

  11. Clinical definition of respiratory viral infections in young children and potential bronchiolitis misclassification.

    Science.gov (United States)

    Megalaa, Rosemary; Perez, Geovanny F; Kilaikode-Cheruveettara, Sasikumar; Kotwal, Nidhi; Rodriguez-Martinez, Carlos E; Nino, Gustavo

    2018-01-01

    Viral respiratory infections are often grouped as a single respiratory syndrome named 'viral bronchiolitis', independently of the viral etiology or individual risk factors. Clinical trials and guidelines have used a more stringent definition of viral bronchiolitis, including only the first episode of wheezing in children less than 12 months of age without concomitant respiratory comorbidities. There is increasing evidence suggesting that this definition is not being followed by pediatric care providers, but it is unclear to what extent viral respiratory infections are currently misclassified as viral bronchiolitis using standard definitions. We conducted a retrospective analysis of hospitalized young children (≤3 years) due to viral respiratory infections. Bronchiolitis was defined as the first wheezing episode less than 12 months of age. Demographic variables and comorbidities were obtained by electronic medical record review. The study comprised a total of 513 hospitalizations (n=453). Viral bronchiolitis was diagnosed in 144 admissions (28.1%). Notably, we identified that the majority of children diagnosed with bronchiolitis (63%) were misclassified as they had prior episodes of wheezing. Many children with bronchiolitis misclassification had significant comorbidities, including prematurity (51%), neuromuscular conditions (9.8%), and congenital heart disease (9.8%). Misclassification of bronchiolitis is a common problem that may lead to inappropriate management of viral respiratory infections in young children. A comprehensive approach that takes into consideration viral etiology and individual risk factors may lead to a more accurate clinical assessment of this condition and would potentially prevent bronchiolitis misclassification. © American Federation for Medical Research (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  12. Clinical realism: a new literary genre and a potential tool for encouraging empathy in medical students.

    Science.gov (United States)

    McDonald, Paula; Ashton, Katy; Barratt, Rachel; Doyle, Simon; Imeson, Dorrie; Meir, Amos; Risser, Gregoire

    2015-07-03

    Empathy has been re-discovered as a desirable quality in doctors. A number of approaches using the medical humanities have been advocated to teach empathy to medical students. This paper describes a new approach using the medium of creative writing and a new narrative genre: clinical realism. Third year students were offered a four week long Student Selected Component (SSC) in Narrative Medicine and Creative Writing. The creative writing element included researching and creating a character with a life-changing physical disorder without making the disorder the focus of the writing. The age, gender, social circumstances and physical disorder of a character were randomly allocated to each student. The students wrote repeated assignments in the first person, writing as their character and including details of living with the disorder in all of their narratives. This article is based on the work produced by the 2013 cohort of students taking the course, and on their reflections on the process of creating their characters. Their output was analysed thematically using a constructivist approach to meaning making. This preliminary analysis suggests that the students created convincing and detailed narratives which included rich information about living with a chronic disorder. Although the writing assignments were generic, they introduced a number of themes relating to illness, including stigma, personal identity and narrative wreckage. Some students reported that they found it difficult to relate to "their" character initially, but their empathy for the character increased as the SSC progressed. Clinical realism combined with repeated writing exercises about the same character is a potential tool for helping to develop empathy in medical students and merits further investigation.

  13. A rat retinal damage model predicts for potential clinical visual disturbances induced by Hsp90 inhibitors

    International Nuclear Information System (INIS)

    Zhou, Dan; Liu, Yuan; Ye, Josephine; Ying, Weiwen; Ogawa, Luisa Shin; Inoue, Takayo; Tatsuta, Noriaki; Wada, Yumiko; Koya, Keizo; Huang, Qin; Bates, Richard C.; Sonderfan, Andrew J.

    2013-01-01

    In human trials certain heat shock protein 90 (Hsp90) inhibitors, including 17-DMAG and NVP-AUY922, have caused visual disorders indicative of retinal dysfunction; others such as 17-AAG and ganetespib have not. To understand these safety profile differences we evaluated histopathological changes and exposure profiles of four Hsp90 inhibitors, with or without clinical reports of adverse ocular effects, using a rat retinal model. Retinal morphology, Hsp70 expression (a surrogate marker of Hsp90 inhibition), apoptotic induction and pharmacokinetic drug exposure analysis were examined in rats treated with the ansamycins 17-DMAG and 17-AAG, or with the second-generation compounds NVP-AUY922 and ganetespib. Both 17-DMAG and NVP-AUY922 induced strong yet restricted retinal Hsp70 up-regulation and promoted marked photoreceptor cell death 24 h after the final dose. In contrast, neither 17-AAG nor ganetespib elicited photoreceptor injury. When the relationship between drug distribution and photoreceptor degeneration was examined, 17-DMAG and NVP-AUY922 showed substantial retinal accumulation, with high retina/plasma (R/P) ratios and slow elimination rates, such that 51% of 17-DMAG and 65% of NVP-AUY922 present at 30 min post-injection were retained in the retina 6 h post-dose. For 17-AAG and ganetespib, retinal elimination was rapid (90% and 70% of drugs eliminated from the retina at 6 h, respectively) which correlated with lower R/P ratios. These findings indicate that prolonged inhibition of Hsp90 activity in the eye results in photoreceptor cell death. Moreover, the results suggest that the retina/plasma exposure ratio and retinal elimination rate profiles of Hsp90 inhibitors, irrespective of their chemical class, may predict for ocular toxicity potential. - Highlights: • In human trials some Hsp90 inhibitors cause visual disorders, others do not. • Prolonged inhibition of Hsp90 in the rat eye results in photoreceptor cell death. • Retina/plasma ratio and retinal

  14. Clinical investigation of TROP-2 as an independent biomarker and potential therapeutic target in colon cancer.

    Science.gov (United States)

    Zhao, Peng; Yu, Hai-Zheng; Cai, Jian-Hui

    2015-09-01

    Colon cancer is associated with a severe demographic and economic burden worldwide. The pathogenesis of colon cancer is highly complex and involves sequential genetic and epigenetic mechanisms. Despite extensive investigation, the pathogenesis of colon cancer remains to be elucidated. As the third most common type of cancer worldwide, the treatment options for colon cancer are currently limited. Human trophoblast cell‑surface marker (TROP‑2), is a cell‑surface transmembrane glycoprotein overexpressed by several types of epithelial carcinoma. In addition, TROP‑2 has been demonstrated to be associated with tumorigenesis and invasiveness in solid types of tumor. The aim of the present study was to investigate the protein expression of TROP‑2 in colon cancer tissues, and further explore the association between the expression of TROP‑2 and clinicopathological features of patients with colon cancer. The expression and localization of the TROP‑2 protein was examined using western blot analysis and immunofluorescence staining. Finally, the expression of TROP‑2 expression was correlated to conventional clinicopathological features of colon cancer using a χ2 test. The results revealed that TROP‑2 protein was expressed at high levels in the colon cancer tissues, which was associated with the development and pathological process of colon cancer. Therefore, TROP‑2 may be used as a biomarker to determine the clinical prognosis, and as a potential therapeutic target in colon cancer.

  15. ATF1 and RAS in exosomes are potential clinical diagnostic markers for cervical cancer.

    Science.gov (United States)

    Shi, Yanhua; Wang, Wei; Yang, Baozhi; Tian, Hongge

    2017-10-01

    Cervical cancer is one of the most common cancers among women worldwide. It is highly lethal yet can be treated when found in early stage. Thus, early detection is of significant important for early diagnosis of cervical cancer. Exosomes have been used as biomarkers in clinical diagnosis. It is unknown that whether blood exosomes associated with cervical cancer can be detected and if these exosomes can accurately represent the developmental stage of cervical cancer. Mouse models were made out of a relapsed cervical cancer patient's tumour sample for original and recurrent cervical cancer, and gene analysis in both tumours and exosomes in these mouse models were performed. We found that activating transcription factor 1 (ATF1) and RAS genes were significantly up-regulated in tumours of both primary and recurrent cervical cancer mouse model, and they can also be detected in the blood exosomes of the mouse model. Our results indicated that ATF1 and RAS could be potential candidate biomarkers for cervical cancer in early diagnosis. ATF1 and RAS genes were found significantly elevated in tumours of primary and recurrent cervical cancer mouse model, and they were also detected in the blood exosomes. Therefore, ATF1 and RAS could be used as a diagnostic marker for cervical cancer in the future. Copyright © 2017 John Wiley & Sons, Ltd.

  16. Proton therapy of cancer: Potential clinical advantages and cost-effectiveness

    International Nuclear Information System (INIS)

    Lundkvist, Jonas; Ekman, Mattias; Rehn Ericsson, Suzanne; Glimelius, Bengt; Akademiska sjukhuset, Uppsala

    2005-01-01

    Proton therapy may offer potential clinical advantages compared with conventional radiation therapy for many cancer patients. Due to the large investment costs for building a proton therapy facility, however, the treatment cost with proton radiation is higher than with conventional radiation. It is therefore important to evaluate whether the medical benefits of proton therapy are large enough to motivate the higher costs. We assessed the cost-effectiveness of proton therapy in the treatment of four different cancers: left-sided breast cancer, prostate cancer, head and neck cancer, and childhood medulloblastoma. A Markov cohort simulation model was created for each cancer type and used to simulate the life of patients treated with radiation. Cost and quality adjusted life years (QALYs) were used as primary outcome measures. The results indicated that proton therapy was cost-effective if appropriate risk groups were chosen. The average cost per QALY gained for the four types of cancer assessed was about Euro 10,130. If the value of a QALY was set to Euro 55,000, the total yearly net benefit of treating 925 cancer patients with the four types of cancer was about Euro 20.8 million. Investment in a proton facility may thus be cost-effective. The results must be interpreted with caution, since there is a lack of data, and consequently large uncertainties in the assumptions used

  17. Methodology optimization and diversification for the investigation of virulence potential in Haemophilus influenzae clinical strains.

    Science.gov (United States)

    Giucă, Mihaela Cristina; Străuţ, Monica; Surdeanu, Maria; Nica, Maria; Ungureanu, Vasilica; Mihăescu, Grigore

    2011-01-01

    Ten Haemophilus influenzae strains were isolated from patients aged between 1.6 - 24 years, with various diagnoses (acute meningitis, acute upper respiratory infection, otitis media and acute sinusitis). Identification was based on phenotypic and molecular characteristics; antibiotic susceptibility testing was performed by diffusion method according to CLSI standards 2011 for seven antibiotics. The results of molecular testing showed that all the studied strains produced an amplicon of 1000 bp with ompP2 primers indicating that all strains were H. influenzae. For six strains, the PCR amplicon obtained with bexA specific primers, proving that the strains were capsulated. The results of phenotypic testing showed that four strains were ampicillin nonsusceptible and (beta-lactamase-positive. The virulence potential of H. influenzae clinical strains was investigated by phenotypic methods, including the assessment of the soluble virulence factors on specific media containing the biochemical substratum for the investigated enzymatic factor, as well as the adherence and invasion capacity to HeLa cells monolayer using Cravioto modified method. The studied strains exhibited mainly a diffuse adherence pattern and different adherence indexes. Interestingly, two strains isolated from the same pacient (blood and CSF) showed a different degree of invasiveness, the strain isolated from blood being 20 times more invasive than the one isolated from CSF.

  18. Promising Products for Printing and Publishing Market

    Directory of Open Access Journals (Sweden)

    Renata Činčikaitė

    2011-04-01

    Full Text Available The article surveys printing and publishing market and its strong and weak aspects. The concept of a new product is described as well as its lifetime and the necessity of its introduction to the market. The enterprise X operating on the market is analyzed, its strong and weak characteristics are presented. The segmentation of the company consumers is performed. On the basis of the performed analysis the potential promising company products are defined.Article in Lithuanian

  19. Stem Cell Therapy: A Promising Therapeutic Method for Intracerebral Hemorrhage.

    Science.gov (United States)

    Gao, Liansheng; Xu, Weilin; Li, Tao; Chen, Jingyin; Shao, Anwen; Yan, Feng; Chen, Gao

    2018-01-01

    Spontaneous intracerebral hemorrhage (ICH) is one type of the most devastating cerebrovascular diseases worldwide, which causes high morbidity and mortality. However, efficient treatment is still lacking. Stem cell therapy has shown good neuroprotective and neurorestorative effect in ICH and is a promising treatment. In this study, our aim was to review the therapeutic effects, strategies, related mechanisms and safety issues of various types of stem cell for ICH treatment. Numerous studies had demonstrated the therapeutic effects of diverse stem cell types in ICH. The potential mechanisms include tissue repair and replacement, neurotrophy, promotion of neurogenesis and angiogenesis, anti-apoptosis, immunoregulation and anti-inflammation and so forth. The microenvironment of the central nervous system (CNS) can also influence the effects of stem cell therapy. The detailed therapeutic strategies for ICH treatment such as cell type, the number of cells, time window, and the routes of medication delivery, varied greatly among different studies and had not been determined. Moreover, the safety issues of stem cell therapy for ICH should not be ignored. Stem cell therapy showed good therapeutic effect in ICH, making it a promising treatment. However, safety should be carefully evaluated, and more clinical trials are required before stem cell therapy can be extensively applied to clinical use.

  20. Mastering JavaScript promises

    CERN Document Server

    Hussain, Muzzamil

    2015-01-01

    This book is for all the software and web engineers wanting to apply the promises paradigm to their next project and get the best outcome from it. This book also acts as a reference for the engineers who are already using promises in their projects and want to improve their current knowledge to reach the next level. To get the most benefit from this book, you should know basic programming concepts, have a familiarity with JavaScript, and a good understanding of HTML.

  1. [Radiation-induced bystander effect: the important part of ionizing radiation response. Potential clinical implications].

    Science.gov (United States)

    Wideł, Maria; Przybyszewski, Waldemar; Rzeszowska-Wolny, Joanna

    2009-08-18

    It has long been a central radiobiological dogma that the damaging effects of ionizing radiation, such as cell death, cytogenetic changes, apoptosis, mutagenesis, and carcinogenesis, are the results of the direct ionization of cell structures, particularly DNA, or indirect damage via water radiolysis products. However, several years ago attention turned to a third mechanism of radiation, termed the "bystander effect" or "radiation-induced bystander effect" (RIBE). This is induced by agents and signals emitted by directly irradiated cells and manifests as a lowering of survival, cytogenetic damage, apoptosis enhancement, and biochemical changes in neighboring non-irradiated cells. The bystander effect is mainly observed in in vitro experiments using very low doses of alpha particles (range; mGy, cGy), but also after conventional irradiation (X-rays, gamma rays) at low as well as conventional doses. The mechanisms responsible for the bystander effect are complex and still poorly understood. It is believed that molecular signals released from irradiated cells induce different signaling ways in non-irradiated neighboring cells, leading to the observed events. The molecular signals may be transmitted through gap junction intercellular communication and through a medium transfer mechanism. The nature of these transmitted factors are diverse, and still not definitely established. It seems that RIBE may have important clinical implications for health risk associated with radiation exposure. Potentially, this effect may have important implications in the creation of whole-body or localized side effects in tissues beyond the irradiation field and also in low-dose radiological and radioisotope diagnostics. Factors emitted by irradiated cells may result in the risk of genetic instability, mutations, and second primary cancer induction. They might also have their own part in inducing and extending post-radiation side effects in normal tissue. The bystander effect may be a

  2. Radiation-induced bystander effect: The important part of ionizing radiation response. Potential clinical implications

    Directory of Open Access Journals (Sweden)

    Maria Wideł

    2009-08-01

    Full Text Available It has long been a central radiobiological dogma that the damaging effects of ionizing radiation, such as cell death, cytogenetic changes, apoptosis, mutagenesis, and carcinogenesis, are the results of the direct ionization of cell structures, particularly DNA, or indirect damage via water radiolysis products. However, several years ago attention turned to a third mechanism of radiation, termed the “bystander effect” or “radiation-induced bystander effect” (RIBE. This is induced by agents and signals emitted by directly irradiated cells and manifests as a lowering of survival, cytogenetic damage, apoptosis enhancement, and biochemical changes in neighboring non-irradiated cells. The bystander effect is mainly observed in in vitro experiments using very low doses of alpha particles (range; mGy, cGy, but also after conventional irradiation (X-rays, gamma rays at low as well as conventional doses. The mechanisms responsible for the bystander effect are complex and still poorly understood. It is believed that molecular signals released from irradiated cells induce different signaling ways in non-irradiated neighboring cells, leading to the observed events. The molecular signals may be transmitted through gap junction intercellular communication and through a medium transfer mechanism. The nature of these transmitted factors are diverse, and still not defi nitely established. It seems that RIBE may have important clinical implications for health risk associated with radiation exposure. Potentially, this effectmay have important implications in the creation of whole-body or localized side effects in tissues beyond the irradiation fi eld and also in low-dose radiological and radioisotope diagnostics. Factors emitted by irradiated cells may result in the risk of genetic instability, mutations, and second primary cancer induction. They might also have their own part in inducing and extending post-radiation side effects in normal tissue. The

  3. Antimicrobial potential of Dialium guineense (Wild.) stem bark on some clinical isolates in Nigeria.

    Science.gov (United States)

    Olajubu, Fa; Akpan, I; Ojo, DA; Oluwalana, Sa

    2012-01-01

    The persistent increase in the number of antibiotic-resistant strains of microorganisms has led to the development of more potent but also more expensive antibiotics. In most developing countries of the world these antibiotics are not readily affordable, thus making compliance difficult. This calls for research into alternative sources of antimicrobials. Dialium guineense is a shrub of the family Leguminosae. Its stem bark is used for the treatment of cough, toothache, and bronchitis. Despite the acclaimed efficacy of D guineense, there is no scientific evidence in its support. This work was carried out to assess the antimicrobial activity of D guineense in vitro against some clinical isolates. D guineense stem bark was collected and 50 gm of air-dried and powdered stem bark of the plant was soaked for 72 hours in 1 l of each of the six solvents used in this study. Each mixture was refluxed, agitated at 200 rpm for 1 hour, filtered using Whatman No. 1 filter paper and, finally, freeze dried. The extracts were then tested for antimicrobial activity using the agar diffusion method. The highest percentage yield of 23.2% was obtained with ethanol. Phytochemical screening showed that D guineense contains anthraquinone, alkaloids, flavonoids, tannins, and saponins. The antimicrobial activity of the extracts revealed a broad spectrum of activity, with Salmonella typhi and Staphylococcus aureusa showing the greatest zones of inhibition (18.0 mm). Only Candida albicans among the fungi tested was inhibited by the extract. The greatest zone of inhibition among the fractions was 16.0 mm. D guineense exhibited bactericidal activity at the 7th and 9th hours against Streptococcus pneumoniae and S. aureus 25923 while the 10th hour against S. typhi and C. albicans. The greatest activity was noted against S pneumoniae, where there was reduced viable cell count after 6 hours of exposure. Stem bark extract of D guineense (Wild.) has the potential to be developed into an antimicrobial

  4. Can the Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) be used to accurately report clinic total reproductive potential (TRP)?

    Science.gov (United States)

    Stern, Judy E; Hickman, Timothy N; Kinzer, Donna; Penzias, Alan S; Ball, G David; Gibbons, William E

    2012-04-01

    To assess whether total reproductive potential (TRP), the chance of a live birth from each fresh cycle (fresh cycle plus frozen transfers), could be calculated from the national Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) database and whether information not available in SART CORS resulted in significant changes to the TRP calculation. Retrospective study using SART CORS and clinic data. Three assisted reproductive technology clinics. Women undergoing ART. None. Two- and three-year TRPs for 2005 and 2006 were calculated according to patient age at cycle start by linking fresh to frozen cycles up to first live birth. Clinic records were used to adjust for (remove) frozen cycles that used more than one fresh cycle as a source of embryos and for any embryos donated to other patients or research or shipped to another facility before a live birth. TRP was higher than fresh per-cycle rates for most ages at all clinics, although accuracy was compromised when there were fewer than 20 cycles per category. Two- and 3-year TRPs differed in only 2 of 24 calculations. Adjusted TRPs differed less than three percentage points from unadjusted TRPs when volume was sufficient. Clinic TRP can be calculated from SART CORS. Data suggest that calculations of clinic TRP from the national dataset would be meaningful. Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  5. CpG Methylation Analysis—Current Status of Clinical Assays and Potential Applications in Molecular Diagnostics

    Science.gov (United States)

    Sepulveda, Antonia R.; Jones, Dan; Ogino, Shuji; Samowitz, Wade; Gulley, Margaret L.; Edwards, Robin; Levenson, Victor; Pratt, Victoria M.; Yang, Bin; Nafa, Khedoudja; Yan, Liying; Vitazka, Patrick

    2009-01-01

    Methylation of CpG islands in gene promoter regions is a major molecular mechanism of gene silencing and underlies both cancer development and progression. In molecular oncology, testing for the CpG methylation of tissue DNA has emerged as a clinically useful tool for tumor detection, outcome prediction, and treatment selection, as well as for assessing the efficacy of treatment with the use of demethylating agents and monitoring for tumor recurrence. In addition, because CpG methylation occurs early in pre-neoplastic tissues, methylation tests may be useful as markers of cancer risk in patients with either infectious or inflammatory conditions. The Methylation Working Group of the Clinical Practice Committee of the Association of Molecular Pathology has reviewed the current state of clinical testing in this area. We report here our summary of both the advantages and disadvantages of various methods, as well as the needs for standardization and reporting. We then conclude by summarizing the most promising areas for future clinical testing in cancer molecular diagnostics. PMID:19541921

  6. Preclinical Evaluation of Raman Nanoparticle Biodistribution for their Potential Use in Clinical Endoscopy Imaging

    DEFF Research Database (Denmark)

    Zavaleta, Cristina L; Hartman, Keith B; Miao, Zheng

    2011-01-01

    Raman imaging offers unsurpassed sensitivity and multiplexing capabilities. However, its limited depth of light penetration makes direct clinical translation challenging. Therefore, a more suitable way to harness its attributes in a clinical setting would be to couple Raman spectroscopy with endo...

  7. Clinical potential of eliglustat tartrate in the treatment of type 1 Gaucher disease

    Directory of Open Access Journals (Sweden)

    Kaplan P

    2014-05-01

    counts, and bone density, as well as decreases in biomarkers of Gaucher disease activity. Few adverse events, none of which was serious, have been reported. Eliglustat tartrate has the clinical potential to enable a larger number of patients with type 1 Gaucher disease to be treated successfully.Keywords: type 1 Gaucher disease, substrate reduction therapy, eliglustat tartrate

  8. Nuclear energy: obstacles and promises

    International Nuclear Information System (INIS)

    Bacher, P.

    2003-01-01

    Nuclear energy has distinctive merits (sustainable resources, low costs, no greenhouse gases) but its development must overcome serious hurdles (fear of accidents, radio-phobia, waste management). The large unit size of present-day reactors is compatible only with large electrical grids, and involves a high capital cost. Taking into account these different factors, the paper outlines how nuclear energy may contribute to the reduction of greenhouse gases, and which are the most promising developments. (author)

  9. The promise of cyborg intelligence.

    Science.gov (United States)

    Brown, Michael F; Brown, Alexander A

    2017-03-01

    Yu et al. (2016) demonstrated that algorithms designed to find efficient routes in standard mazes can be integrated with the natural processes controlling rat navigation and spatial choices, and they pointed out the promise of such "cyborg intelligence" for biorobotic applications. Here, we briefly describe Yu et al.'s work, explore its relevance to the study of comparative cognition, and indicate how work involving cyborg intelligence would benefit from interdisciplinary collaboration between behavioral scientists and engineers.

  10. Freedom: A Promise of Possibility.

    Science.gov (United States)

    Bunkers, Sandra Schmidt

    2015-10-01

    The idea of freedom as a promise of possibility is explored in this column. The core concepts from a research study on considering tomorrow (Bunkers, 1998) coupled with humanbecoming community change processes (Parse, 2003) are used to illuminate this notion. The importance of intentionality in human freedom is discussed from both a human science and a natural science perspective. © The Author(s) 2015.

  11. Targeting aerobic glycolysis: 3-bromopyruvate as a promising anticancer drug.

    Science.gov (United States)

    Cardaci, Simone; Desideri, Enrico; Ciriolo, Maria Rosa

    2012-02-01

    The Warburg effect refers to the phenomenon whereby cancer cells avidly take up glucose and produce lactic acid under aerobic conditions. Although the molecular mechanisms underlying tumor reliance on glycolysis remains not completely clear, its inhibition opens feasible therapeutic windows for cancer treatment. Indeed, several small molecules have emerged by combinatorial studies exhibiting promising anticancer activity both in vitro and in vivo, as a single agent or in combination with other therapeutic modalities. Therefore, besides reviewing the alterations of glycolysis that occur with malignant transformation, this manuscript aims at recapitulating the most effective pharmacological therapeutics of its targeting. In particular, we describe the principal mechanisms of action and the main targets of 3-bromopyruvate, an alkylating agent with impressive antitumor effects in several models of animal tumors. Moreover, we discuss the chemo-potentiating strategies that would make unparalleled the putative therapeutic efficacy of its use in clinical settings.

  12. Newly Emerging Immune Checkpoints: Promises for Future Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Robert J. Torphy

    2017-12-01

    Full Text Available Cancer immunotherapy has been a great breakthrough, with immune checkpoint inhibitors leading the way. Despite the clinical effectiveness of certain immune checkpoint inhibitors, the overall response rate remains low, and the effectiveness of immunotherapies for many tumors has been disappointing. There is substantial interest in looking for additional immune checkpoint molecules that may act as therapeutic targets for cancer. Recent advances during the last decade have identified several novel immune checkpoint targets, including lymphocyte activation gene-3 (LAG-3, B and T lymphocyte attenuator (BTLA, programmed death-1 homolog (PD-1H, T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIM-3/carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1, and the poliovirus receptor (PVR-like receptors. The investigations into these molecules have generated promising results in preclinical studies. Herein, we will summarize our current progress and understanding of these newly-characterized immune checkpoints and their potential application in cancer immunotherapy.

  13. ROCK inhibition in models of neurodegeneration and its potential for clinical translation.

    Science.gov (United States)

    Koch, Jan Christoph; Tatenhorst, Lars; Roser, Anna-Elisa; Saal, Kim-Ann; Tönges, Lars; Lingor, Paul

    2018-04-03

    Neurodegenerative disorders like Parkinson's disease, Alzheimer's disease, or amyotrophic lateral sclerosis are affecting a rapidly increasing population worldwide. While common pathomechanisms such as protein aggregation, axonal degeneration, dysfunction of protein clearing and an altered immune response have been characterized, no disease-modifying therapies have been developed so far. Interestingly, a significant involvement of the Rho kinase (ROCK) signaling pathway has been described in all of these mechanisms making it a promising target for new therapeutic approaches. In this article, we first review current knowledge of the involvement of ROCK in neurodegenerative disorders and the utility of its inhibition as a disease-modifying therapy in different neurodegenerative disorders. After a detailed description of the biochemical characteristics of ROCK and its molecular interactors, differences of ROCK-expression under physiological and pathological conditions are compared. Next, different pharmacological and molecular-genetic strategies to inhibit ROCK-function are discussed, focusing on pharmacological ROCK-inhibitors. The role of the ROCK-pathway in cellular processes that are central in neurodegenerative disorders pathology like axonal degeneration, autophagy, synaptic and glial function is explained in detail. Finally, all available data on ROCK-inhibition in different animal models of neurodegenerative disorders is reviewed and first approaches for translation into human patients are discussed. Taken together, there is now extensive evidence from preclinical studies in several neurodegenerative disorders that characterize ROCK as a promising drug target for further translational research in neurodegenerative disorders. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  14. Mathematical Profiles and Problem Solving Abilities of Mathematically Promising Students

    Science.gov (United States)

    Budak, Ibrahim

    2012-01-01

    Mathematically promising students are defined as those who have the potential to become the leaders and problem solvers of the future. The purpose of this research is to reveal what problem solving abilities mathematically promising students show in solving non-routine problems and type of profiles they present in the classroom and during problem…

  15. Innovating information-delivery for potential clinical trials participants. What do patients want from multi-media resources?

    Science.gov (United States)

    Shneerson, Catherine; Windle, Richard; Cox, Karen

    2013-01-01

    To discover whether the provision of clinical trials information via a multi-media platform could better meet the needs, preferences and practices of potential cancer trial participants. A mixed qualitative and quantitative questionnaire was delivered to 72 participants from cancer support groups to elicit views on the provision and design features of multimedia resources in delivering clinical trials information. Perceived lack of information is an expressed barrier to clinical trials participation. Multimedia resources were viewed positively as a way to address this barrier by most potential clinical trials participants; in particular by helping to align information to individual needs, promote active engagement with information, and by allowing more control of the learning experience. Whilst text remained the most valued attribute of any resource, other highly rated attributes included the resource being simple to use, easily accessible, having a clear focus, incorporating examples and visual aids, and being interactive. Provision of support for the learning resource was also rated highly. As in other areas, such as education, multimedia resources may enhance the delivery and acceptance of information regarding clinical trials. Better alignment of information may have a positive impact on recruitment and retention into clinical trials. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  16. Quality of clinical supervision and counselor emotional exhaustion: the potential mediating roles of organizational and occupational commitment.

    Science.gov (United States)

    Knudsen, Hannah K; Roman, Paul M; Abraham, Amanda J

    2013-01-01

    Counselor emotional exhaustion has negative implications for treatment organizations as well as the health of counselors. Quality clinical supervision is protective against emotional exhaustion, but research on the mediating mechanisms between supervision and exhaustion is limited. Drawing upon data from 934 counselors affiliated with treatment programs in the National Institute on Drug Abuse's Clinical Trials Network (CTN), this study examined commitment to the treatment organization and commitment to the counseling occupation as potential mediators of the relationship between quality clinical supervision and emotional exhaustion. The final ordinary least squares (OLS) regression model, which accounted for the nesting of counselors within treatment organizations, indicated that these two types of commitment were plausible mediators of the association between clinical supervision and exhaustion. Higher quality clinical supervision was strongly correlated with commitment to the treatment organization as well as commitment to the occupation of SUD counseling. These findings suggest that quality clinical supervision has the potential to yield important benefits for counselor well-being by strengthening ties to both their employing organization as well the larger treatment field, but longitudinal research is needed to establish these causal relationships. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. Protocolised Management In Sepsis (ProMISe): a multicentre randomised controlled trial of the clinical effectiveness and cost-effectiveness of early, goal-directed, protocolised resuscitation for emerging septic shock.

    Science.gov (United States)

    Mouncey, Paul R; Osborn, Tiffany M; Power, G Sarah; Harrison, David A; Sadique, M Zia; Grieve, Richard D; Jahan, Rahi; Tan, Jermaine C K; Harvey, Sheila E; Bell, Derek; Bion, Julian F; Coats, Timothy J; Singer, Mervyn; Young, J Duncan; Rowan, Kathryn M

    2015-11-01

    Early goal-directed therapy (EGDT) is recommended in international guidance for the resuscitation of patients presenting with early septic shock. However, adoption has been limited and uncertainty remains over its clinical effectiveness and cost-effectiveness. The primary objective was to estimate the effect of EGDT compared with usual resuscitation on mortality at 90 days following randomisation and on incremental cost-effectiveness at 1 year. The secondary objectives were to compare EGDT with usual resuscitation for requirement for, and duration of, critical care unit organ support; length of stay in the emergency department (ED), critical care unit and acute hospital; health-related quality of life, resource use and costs at 90 days and at 1 year; all-cause mortality at 28 days, at acute hospital discharge and at 1 year; and estimated lifetime incremental cost-effectiveness. A pragmatic, open, multicentre, parallel-group randomised controlled trial with an integrated economic evaluation. Fifty-six NHS hospitals in England. A total of 1260 patients who presented at EDs with septic shock. EGDT (n = 630) or usual resuscitation (n = 630). Patients were randomly allocated 1 : 1. All-cause mortality at 90 days after randomisation and incremental net benefit (at £20,000 per quality-adjusted life-year) at 1 year. Following withdrawals, data on 1243 (EGDT, n = 623; usual resuscitation, n = 620) patients were included in the analysis. By 90 days, 184 (29.5%) in the EGDT and 181 (29.2%) patients in the usual-resuscitation group had died [p = 0.90; absolute risk reduction -0.3%, 95% confidence interval (CI) -5.4 to 4.7; relative risk 1.01, 95% CI 0.85 to 1.20]. Treatment intensity was greater for the EGDT group, indicated by the increased use of intravenous fluids, vasoactive drugs and red blood cell transfusions. Increased treatment intensity was reflected by significantly higher Sequential Organ Failure Assessment scores and more advanced

  18. Clinical performance of antibodies to prothrombin and thrombin in Chinese patients with antiphospholipid syndrome: potential interest in discriminating patients with thrombotic events and non-thrombotic events.

    Science.gov (United States)

    Zhang, Shulan; Wu, Ziyan; Li, Jing; Li, Ping; Chen, Si; Wen, Xiaoting; Li, Liubing; Zhang, Wen; Zhao, Jiuliang; Zhang, Fengchun; Li, Yongzhe

    2017-04-01

    A hallmark feature of antiphospholipid syndrome (APS) is the presence of a wide spectrum of antiphospholipid antibodies. In this study, we evaluated the clinical relevance of antibodies to prothrombin (PT) (aPT) and thrombin (aThr) in Chinese patients with APS. A total of 229 subjects were tested, including 86 patients with APS [35 patients with primary APS (PAPS), 51 patients with APS associated with other diseases (APSAOD)], 104 patients with non-APS diseases (disease controls), and 39 healthy controls. Serum IgG/IgM/IgA aPT and aThr were determined by ELISA. The levels of both IgG/IgM/IgA aPT and IgG/IgM/IgA aThr were significantly increased in patients with PAPS and APSAOD compared with patients with non-APS thrombosis and non-APS PRM, and HC. Both IgG aPT and IgG aThr exhibited promising diagnostic potentials for APS with sensitivities and specificities of 16.3 and 95.8% (IgG aPT), and 19.8 and 99.3% (IgG aThr), respectively. Importantly, both IgG aPT (OR 4.06; 95% CI 1.49-11.05) and IgG aThr (OR 4.49; 95% CI 1.62-12.45) were significantly correlated with arterial, but not venous, thrombotic events. Our findings highlighted that IgG aPT and IgG aThr could serve as promising biomarkers to identify patients at risk of arterial thrombosis in China.

  19. Chitin fulfilling a biomaterials promise

    CERN Document Server

    Khor, Eugene

    2001-01-01

    The second edition of Chitin underscores the important factors for standardizing chitin processing and characterization. It captures the essential interplay between chitin's assets and limitations as a biomaterial, placing the past promises of chitin in perspective, addressing its present realities and offering insight into what is required to realize chitin's destiny (including its derivative, chitosan) as a biomaterial of the twenty-first century. This book is an ideal guide for both industrialists and researchers with a vested interest in commercializing chitin.An upd

  20. Analysis of Potential Drug-Drug Interactions and Its Clinical Manifestation of Pediatric Prescription on 2 Pharmacies in Bandung

    Directory of Open Access Journals (Sweden)

    Melisa I. Barliana

    2013-09-01

    Full Text Available The potential of Drug-Drug Interactions (DDI in prescription have high incidence around the world, including Indonesia. However, scientific evidence regarding DDI in Indonesia is not available. Therefore, in this study we have conducted survey in 2 pharmacies in Bandung against pediatric prescription given by pediatrician. These prescriptions then analyzed the potential for DDI contained in the prescription and clinical manifestation. The analysis showed that in pharmacy A, there are 33 prescriptions (from a total of 155 prescriptions that have potential DDI, or approximately 21.19% (2 prescriptions have the potential DDI major categories, 23 prescriptions categorized as moderate, and 8 prescriptions as minor. In Pharmacy B, there are 6 prescriptions (from a total of 40 prescriptions or 15% of potential DDI (4 prescriptions categorized as moderate and 2 prescriptions as minor. This result showed that potential DDI happened less than 50% in pediatric prescription from both pharmacies. However, this should get attention because DDI should not happen in a prescription considering its clinical manifestations caused by DDI. Moreover, current pharmaceutical care refers to patient oriented than product oriented. In addition, further study for the pediatric prescription on DDI incidence in large scale need to be investigated.

  1. Clinical potential for imaging in patients with asthma and other lung disorders.

    Science.gov (United States)

    DeBoer, Emily M; Spielberg, David R; Brody, Alan S

    2017-01-01

    The ability of lung imaging to phenotype patients, determine prognosis, and predict response to treatment is expanding in clinical and translational research. The purpose of this perspective is to describe current imaging modalities that might be useful clinical tools in patients with asthma and other lung disorders and to explore some of the new developments in imaging modalities of the lung. These imaging modalities include chest radiography, computed tomography, lung magnetic resonance imaging, electrical impedance tomography, bronchoscopy, and others. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  2. Potential clinical usefulness of new glandular and circulating parathyroid peptides illuminated by sequence specific radioimmunoassay

    International Nuclear Information System (INIS)

    Lindall, A.W.; Cecchettin, M.

    1981-01-01

    It is now well known that human PTH peptides constitute a heterogeneous population of fragments of the eighty-four amino acid molecules. Over the years, considerable confusion has resulted from measurements made in both clinical and experimental settings with radioimmunoassays of either undefined or partially-defined specificity for a particular region of the intact molecule. The approach of the authors has been to make use of modern technology to synthesize peptide fragments that mimic portions of native molecules, and to use these fragments in RIA. A more detailed description of a portion of this work will appear in the Journal of Clinical Endocrinology and Metabolism. (Auth.)

  3. Assessment by human research ethics committees of potential conflicts of interest arising from pharmaceutical sponsorship of clinical research.

    Science.gov (United States)

    Newcombe, J P; Kerridge, I H

    2007-01-01

    Conflicts of interest arising from pharmaceutical industry sponsorship of clinical research have the potential to bias research outcomes and ultimately prejudice patient care. It is unknown how Australian Human Research Ethics Committees (HREC) assess and manage such conflicts of interest. We aimed to gain an understanding of how HREC approach the problem of potential conflicts of interest arising from pharmaceutical sponsorship of clinical research. We conducted a survey of HREC chairpersons in New South Wales. HREC vary widely in their approaches to conflicts of interest, including in their use of National Health and Medical Research Council guidelines, which were often misinterpreted or overlooked. Many committees rely primarily on researchers disclosing potential conflicts of interest, whereas a majority of HREC use disclosure to research participants as the primary tool for preventing and managing conflicts of interest. Almost no HREC place limitations on researcher relationships with pharmaceutical companies. These findings suggest reluctance on the part of HREC to regulate many potential conflicts of interest between researchers and pharmaceutical sponsors, which may arise from uncertainty regarding the meaning or significance of conflicts of interest in research, from ambiguity surrounding the role of HREC in assessing and managing conflicts of interest in research or from misinterpretation or ignorance of current National Health and Medical Research Council guidelines. Further review of policies and practices in this important area may prove beneficial in safeguarding clinical research and patient care while promoting continuing constructive engagement with the pharmaceutical industry.

  4. Comparison of Clinical Characteristics among Subtypes of Visual Symptoms in Patients with Transient Ischemic Attack: Analysis of the PROspective Multicenter registry to Identify Subsequent cardiovascular Events after TIA (PROMISE-TIA) Registry.

    Science.gov (United States)

    Tanaka, Koji; Uehara, Toshiyuki; Kimura, Kazumi; Okada, Yasushi; Hasegawa, Yasuhiro; Tanahashi, Norio; Suzuki, Akifumi; Nakagawara, Jyoji; Arii, Kazumasa; Nagahiro, Shinji; Ogasawara, Kuniaki; Uchiyama, Shinichiro; Matsumoto, Masayasu; Iihara, Koji; Toyoda, Kazunori; Minematsu, Kazuo

    2018-06-01

    A transient visual symptom (TVS) is a clinical manifestation of transient ischemic attack (TIA). The aim of this study was to investigate differences in clinical characteristics among subtypes of TVS using multicenter TIA registry data. Patients with TIA visiting within 7 days of onset were prospectively enrolled from 57 hospitals between June 2011 and December 2013. Clinical characteristics were compared between patients with 3 major subtypes of TVS (transient monocular blindness [TMB], homonymous lateral hemianopia [HLH], and diplopia). Of 1365 patients, 106 (7.8%) had TVS, including 40 TMB (38%), 34 HLH (32%), 17 diplopia (16%), and 15 others/unknown (14%). Ninety-one patients with 1 of the 3 major subtypes of TVS were included. Symptoms persisted on arrival in 12 (13%) patients. Isolated TVS was significantly more common in TMB than in HLH and diplopia (88%, 62%, and 0%, respectively; P TIA multicenter cohort. Some differences in clinical characteristics were found among subtypes of TVS. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  5. Potential of adaptive clinical trial designs in pharmacogenetic research, A simulation based on the IPASS trial

    NARCIS (Netherlands)

    Van Der Baan, Frederieke H.; Knol, Mirjam J.|info:eu-repo/dai/nl/304820350; Klungel, Olaf H.|info:eu-repo/dai/nl/181447649; Egberts, Toine C.G.|info:eu-repo/dai/nl/162850050; Grobbee, Diederick E.; Roes, Kit C.B.

    2011-01-01

    Background: An adaptive clinical trial design that allows population enrichment after interim analysis can be advantageous in pharmacogenetic research if previous evidence is not strong enough to exclude part of the patient population beforehand.With this design, underpowered studies or unnecessary

  6. Cannabidiol as a Promising Strategy to Treat and Prevent Movement Disorders?

    Directory of Open Access Journals (Sweden)

    Fernanda F. Peres

    2018-05-01

    Full Text Available Movement disorders such as Parkinson's disease and dyskinesia are highly debilitating conditions linked to oxidative stress and neurodegeneration. When available, the pharmacological therapies for these disorders are still mainly symptomatic, do not benefit all patients and induce severe side effects. Cannabidiol is a non-psychotomimetic compound from Cannabis sativa that presents antipsychotic, anxiolytic, anti-inflammatory, and neuroprotective effects. Although the studies that investigate the effects of this compound on movement disorders are surprisingly few, cannabidiol emerges as a promising compound to treat and/or prevent them. Here, we review these clinical and pre-clinical studies and draw attention to the potential of cannabidiol in this field.

  7. Potential Strategies to Address the Major Clinical Barriers Facing Stem Cell Regenerative Therapy for Cardiovascular Disease: A Review.

    Science.gov (United States)

    Nguyen, Patricia K; Neofytou, Evgenios; Rhee, June-Wha; Wu, Joseph C

    2016-11-01

    Although progress continues to be made in the field of stem cell regenerative medicine for the treatment of cardiovascular disease, significant barriers to clinical implementation still exist. To summarize the current barriers to the clinical implementation of stem cell therapy in patients with cardiovascular disease and to discuss potential strategies to overcome them. Information for this review was obtained through a search of PubMed and the Cochrane database for English-language studies published between January 1, 2000, and July 25, 2016. Ten randomized clinical trials and 8 systematic reviews were included. One of the major clinical barriers facing the routine implementation of stem cell therapy in patients with cardiovascular disease is the limited and inconsistent benefit observed thus far. Reasons for this finding are unclear but may be owing to poor cell retention and survival, as suggested by numerous preclinical studies and a small number of human studies incorporating imaging to determine cell fate. Additional studies in humans using imaging to determine cell fate are needed to understand how these factors contribute to the limited efficacy of stem cell therapy. Treatment strategies to address poor cell retention and survival are under investigation and include the following: coadministration of immunosuppressive and prosurvival agents, delivery of cardioprotective factors packaged in exosomes rather than the cells themselves, and use of tissue-engineering strategies to provide structural support for cells. If larger grafts are achieved using these strategies, it will be imperative to carefully monitor for the potential risks of tumorigenicity, immunogenicity, and arrhythmogenicity. Despite important achievements to date, stem cell therapy is not yet ready for routine clinical implementation. Significant research is still needed to address the clinical barriers outlined herein before the next wave of large clinical trials is under way.

  8. Cell-mediated immune response: a clinical review of the therapeutic potential of human papillomavirus vaccination.

    Science.gov (United States)

    Meyer, Sonja Izquierdo; Fuglsang, Katrine; Blaakaer, Jan

    2014-12-01

    This clinical review aims to assess the efficacy of human papillomavirus 16/18 (HPV16/18) vaccination on the cell-mediated immune response in women with existing cervical intraepithelial neoplasia or cervical cancer induced by HPV16 or HPV18. A focused and thorough literature search conducted in five different databases found 996 publications. Six relevant articles were chosen for further review. In total, 154 patients (>18 years of age) were enrolled in prospective study trials with 3-15 months of follow up. The vaccine applications were administered two to four times. The vaccines contained different combinations of HPV16 and HPV18 and early proteins, E6 and E7. The primary outcome was the cell-mediated immune response. Correlation to clinical outcome (histopathology) and human leukocyte antigen genes were secondary endpoints. All vaccines triggered a detectable cell-mediated immune response, some of which were statistically significant. Correlations between immunological response and clinical outcome (histopathology) were not significant, so neoplasms may not be susceptible to vaccine-generated cytotoxic T cells (CD8(+)). Prophylactic HPV vaccines have been introduced to reduce the incidence of cervical cancer in young women. Women already infected with HPV could benefit from a therapeutic HPV vaccination. Hence, it is important to continue the development of therapeutic HPV vaccines to lower the rate of HPV-associated malignancies and crucial to evaluate vaccine efficacy clinically. This clinical review represents an attempt to elucidate the theories supporting the development of an HPV vaccine with a therapeutic effect on human papillomavirus-induced malignancies of the cervix. © 2014 Nordic Federation of Societies of Obstetrics and Gynecology.

  9. Reaching their potential: Perceived impact of a collaborative academic-clinical partnership programme for early career nurses in New Zealand.

    Science.gov (United States)

    McKillop, Ann; Doughty, Lesley; Atherfold, Cheryl; Shaw, Kathy

    2016-01-01

    The dynamic nature of healthcare ensures that early career nurses enter an uncertain and complex world of practice and consequently require support to develop their practice, build confidence and reach their potential. The New Zealand Nurse Entry to Practice programme for registered nurses in their first year of practice has been operating since 2005 to enable safe and confident practice, improve the quality of care, and positively impact on recruitment and retention. This academic and clinical programme was offered as a partnership between a university and a clinical provider with postgraduate academic credits gained. The aim of this study was to explore the perceived impact of postgraduate university education for early career nurses in one regional health area of New Zealand. Participants were registered nurses who had completed the early career nurse programme and their clinical preceptors. The research was conducted via an online survey of 248 nurses and three focus groups to explore how the programme was experienced and its impact on knowledge and practice. Early career nurses and their preceptors found that the programme enables improved knowledge and skills of patient assessment, application of critical thinking to clinical practice, perceived improvement in patient care delivery and outcomes, enhanced interprofessional communication and knowledge sharing, and had a positive impact on professional awareness and career planning. This clinical-academic partnership positively impacted on the clinical practice and transition experience of early career nurses and was closely aligned to an organization's strategic plan for nursing workforce development. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Adipose-derived adult stem cells: available technologies for potential clinical regenerative applications in dentistry.

    Science.gov (United States)

    Catalano, Enrico; Cochis, Andrea; Varoni, Elena; Rimondini, Lia; Carrassi, Antonio; Azzimonti, Barbara

    2013-01-01

    Tissue homeostasis depends closely on the activity and welfare of adult stem cells. These cells represent a promising tool for biomedical research since they can aid in treatment and promote the regeneration of damaged organs in many human disorders. Adult stem cells indefinitely preserve their ability to self-renew and differentiate into various phenotypes; this capacity could be promoted in vitro by particular culture conditions (differentiation media) or spontaneously induced in vivo by exploiting the biochemical and mechanical properties of the tissue in which the stem cells are implanted. Among the different sources of adult stem cells, adipose tissue is an attractive possibility thanks to its ready availability and the standard extraction techniques at our disposal today. This review discusses the isolation, characterization, and differentiation of human adipose-derived adult stem cells, as well as regeneration strategies, therapeutic uses, and adverse effects of their delivery. In particular, since oral disorders (e.g., trauma, erosion, and chronic periodontitis) often cause the loss of dental tissue along with functional, phonetic, and aesthetic impairment, this review focuses on the application of human adipose-derived adult stem cells, alone or in combination with biomaterials, in treating oral diseases.

  11. Potential of garlic (Allium sativum in lowering high blood pressure: mechanisms of action and clinical relevance

    Directory of Open Access Journals (Sweden)

    Ried K

    2014-12-01

    Full Text Available Karin Ried, Peter Fakler National Institute of Integrative Medicine, Melbourne, VIC, Australia Abstract: Garlic supplements have shown promise in the treatment of uncontrolled hypertension, lowering blood pressure (BP by about 10 mmHg systolic and 8 mmHg diastolic, similar to standard BP medication. Aged garlic extract, which contains S-allylcysteine as the bioactive sulfur compound, in particular is standardizable and highly tolerable, with little or no known harmful interaction when taken with other BP-reducing or blood-thinning medication. Here we describe biologically plausible mechanisms of garlic's BP-lowering effect. Garlic-derived polysulfides stimulate the production of the vascular gasotransmitter hydrogen sulfide (H2S and enhance the regulation of endothelial nitric oxide (NO, which induce smooth muscle cell relaxation, vasodilation, and BP reduction. Several dietary and genetic factors influence the efficiency of the H2S and NO signaling pathways and may contribute to the development of hypertension. Sulfur deficiency might play a part in the etiology of hypertension, and could be alleviated with supplementation of organosulfur compounds derived from garlic. Keywords: garlic, S-allylcysteine, hydrogen sulfide (H2S, nitric oxide (NO, redox signaling, hypertension

  12. Exploring the potential duty of care in clinical genomics under UK law.

    Science.gov (United States)

    Mitchell, Colin; Ploem, Corrette; Chico, Victoria; Ormondroyd, Elizabeth; Hall, Alison; Wallace, Susan; Fay, Michael; Goodwin, Deirdre; Bell, Jessica; Phillips, Simon; Taylor, Jenny C; Hennekam, Raoul; Kaye, Jane

    2017-09-01

    Genome-wide sequencing technologies are beginning to be used in projects that have both clinical diagnostic and research components. The clinical application of this technology, which generates a huge amount of information of varying diagnostic certainty, involves addressing a number of challenges to establish appropriate standards. In this article, we explore the way that UK law may respond to three of these key challenges and could establish new legal duties in relation to feedback of findings that are unrelated to the presenting condition (secondary, additional or incidental findings); duties towards genetic relatives as well as the patient and duties on the part of researchers and professionals who do not have direct contact with patients. When considering these issues, the courts will take account of European and international comparisons, developing guidance and relevant ethical, social and policy factors. The UK courts will also be strongly influenced by precedent set in case law.

  13. Harnessing Cerebrospinal Fluid Biomarkers in Clinical Trials for Treating Alzheimer's and Parkinson's Diseases: Potential and Challenges

    OpenAIRE

    Kim, Dana; Kim, Young-Sam; Shin, Dong Wun; Park, Chang-Shin; Kang, Ju-Hee

    2016-01-01

    No disease-modifying therapies (DMT) for neurodegenerative diseases (NDs) have been established, particularly for Alzheimer's disease (AD) and Parkinson's disease (PD). It is unclear why candidate drugs that successfully demonstrate therapeutic effects in animal models fail to show disease-modifying effects in clinical trials. To overcome this hurdle, patients with homogeneous pathologies should be detected as early as possible. The early detection of AD patients using sufficiently tested bio...

  14. Prehospital Ultrasound in Trauma: A Review of Current and Potential Future Clinical Applications

    Directory of Open Access Journals (Sweden)

    Tharwat El Zahran

    2018-01-01

    Full Text Available Ultrasound (US is an essential tool for evaluating trauma patients in the hospital setting. Many previous in-hospital studies have been extrapolated to out of hospital setting to improve diagnostic accuracy in prehospital and austere environments. This review article presents the role of prehospital US in blunt and penetrating trauma management with emphasis on its current clinical applications, challenges, and future implications of such use.

  15. Genetics in endocrinology: genetic variation in deiodinases: a systematic review of potential clinical effects in humans.

    Science.gov (United States)

    Verloop, Herman; Dekkers, Olaf M; Peeters, Robin P; Schoones, Jan W; Smit, Johannes W A

    2014-09-01

    Iodothyronine deiodinases represent a family of selenoproteins involved in peripheral and local homeostasis of thyroid hormone action. Deiodinases are expressed in multiple organs and thyroid hormone affects numerous biological systems, thus genetic variation in deiodinases may affect multiple clinical endpoints. Interest in clinical effects of genetic variation in deiodinases has clearly increased. We aimed to provide an overview for the role of deiodinase polymorphisms in human physiology and morbidity. In this systematic review, studies evaluating the relationship between deiodinase polymorphisms and clinical parameters in humans were eligible. No restrictions on publication date were imposed. The following databases were searched up to August 2013: Pubmed, EMBASE (OVID-version), Web of Science, COCHRANE Library, CINAHL (EbscoHOST-version), Academic Search Premier (EbscoHOST-version), and ScienceDirect. Deiodinase physiology at molecular and tissue level is described, and finally the role of these polymorphisms in pathophysiological conditions is reviewed. Deiodinase type 1 (D1) polymorphisms particularly show moderate-to-strong relationships with thyroid hormone parameters, IGF1 production, and risk for depression. D2 variants correlate with thyroid hormone levels, insulin resistance, bipolar mood disorder, psychological well-being, mental retardation, hypertension, and risk for osteoarthritis. D3 polymorphisms showed no relationship with inter-individual variation in serum thyroid hormone parameters. One D3 polymorphism was associated with risk for osteoarthritis. Genetic deiodinase profiles only explain a small proportion of inter-individual variations in serum thyroid hormone levels. Evidence suggests a role of genetic deiodinase variants in certain pathophysiological conditions. The value for determination of deiodinase polymorphism in clinical practice needs further investigation. © 2014 European Society of Endocrinology.

  16. Theileriosis in six dogs in South Africa and its potential clinical significance

    Directory of Open Access Journals (Sweden)

    Chantal T. Rosa

    2014-08-01

    Full Text Available Theileriosis is a tick-borne disease caused by a piroplasma of the genus Theileria that can causeanaemia and thrombocytopenia. Its clinical importance for dogs’ remains poorly understood,as only some develop clinical signs. In this study, physical and laboratory findings, treatment and outcomes of six client-owned diseased dogs presented at the Onderstepoort Veterinary Academic Hospital are described retrospectively. In the dogs, Theileria species (n = 4and Theileria equi (n = 2 were detected by a polymerase chain reaction (PCR-reverse blothybridisation assay in blood samples, whilst PCR for Babesia, Anaplasma and Ehrlichia were negative. The most common physical findings were pale mucous membranes (five out of six dogs, bleeding tendencies (five out of six dogs and lethargy (three out of six dogs. All dogs were thrombocytopenic [median 59.5 x 109/L (range 13–199] and five out of six dogs were anaemic [median haematocrit 18% (range 5–32]. Bone marrow core biopsies performed in two dogs showed myelofibrosis. Theileriosis was treated with imidocarb dipropionate and the suspected secondary immune-mediated haematological disorders with prednisolone and azathioprine. Five dogs achieved clinical cure and post-treatment PCR performed in three out of five dogs confirmed absence of circulating parasitaemia. An immune-mediated response to Theileria species is thought to result in anaemia and/or thrombocytopenia in diseased dogs with theileriosis. A bleeding tendency, most likely secondary to thrombocytopenia and/or thrombocytopathy, was the most significant clinical finding in these cases. The link between thrombocytopenia, anaemia and myelofibrosis in theileriosis requires further investigation and theileriosis should be considered a differential diagnosis for dogs presenting with anaemia and/or thrombocytopenia in endemic tick-borne disease areas.

  17. MFTF-progress and promise

    International Nuclear Information System (INIS)

    Thomassen, K.I.

    1980-01-01

    The Mirror Fusion Test Facility (MFTF) has been in construction at Lawrence Livermore National Laboratory (LLNL) for 3 years, and most of the major subsystems are nearing completion. Recently, the scope of this project was expanded to meet new objectives, principally to reach plasma conditions corresponding to energy break-even. To fulfill this promise, the single-cell minimum-B mirror configuration will be replaced with a tandem mirror configuration (MFTF-B). The facility must accordingly be expanded to accomodate the new geometry. This paper briefly discusses the status of the major MFTF subsystems and describes how most of the technological objectives of MFTF will be demonstrated before we install the additional systems necessary to make the tandem. It also summarizes the major features of the expanded facility

  18. The promising opportunity of dismantlement

    International Nuclear Information System (INIS)

    Anon.

    2009-01-01

    Civil engineering, mechanics and waste conditioning companies are thriving around the market of nuclear facilities dismantlement which is promised to a huge development in the coming decade. This paper presents a map of the opportunities of the dismantlement market throughout Europe (research and power reactors, fuel fabrication plants, spent fuel reprocessing plants) and a cost estimation of a given dismantling work with respect to the different steps of the work. In France a small core of about twenty companies is involved in nuclear dismantlement but the French market is also looking towards foreign specialists of this activity. The British market is also targeted by the French companies but for all the actors the technological or commercial advance gained today will be determining for the future markets. (J.S.)

  19. The potential of predictive analytics to provide clinical decision support in depression treatment planning.

    Science.gov (United States)

    Kessler, Ronald C

    2018-01-01

    To review progress developing clinical decision support tools for personalized treatment of major depressive disorder (MDD). Over the years, a variety of individual indicators ranging from biomarkers to clinical observations and self-report scales have been used to predict various aspects of differential MDD treatment response. Most of this work focused on predicting remission either with antidepressant medications versus psychotherapy, some antidepressant medications versus others, some psychotherapies versus others, and combination therapies versus monotherapies. However, to date, none of the individual predictors in these studies has been strong enough to guide optimal treatment selection for most patients. Interest consequently turned to decision support tools made up of multiple predictors, but the development of such tools has been hampered by small study sample sizes. Design recommendations are made here for future studies to address this problem. Recommendations include using large prospective observational studies followed by pragmatic trials rather than smaller, expensive controlled treatment trials for preliminary development of decision support tools; basing these tools on comprehensive batteries of inexpensive self-report and clinical predictors (e.g., self-administered performance-based neurocognitive tests) versus expensive biomarkers; and reserving biomarker assessments for targeted studies of patients not well classified by inexpensive predictor batteries.

  20. Reflective THz and MR imaging of burn wounds: a potential clinical validation of THz contrast mechanisms

    Science.gov (United States)

    Bajwa, Neha; Nowroozi, Bryan; Sung, Shijun; Garritano, James; Maccabi, Ashkan; Tewari, Priyamvada; Culjat, Martin; Singh, Rahul; Alger, Jeffry; Grundfest, Warren; Taylor, Zachary

    2012-10-01

    Terahertz (THz) imaging is an expanding area of research in the field of medical imaging due to its high sensitivity to changes in tissue water content. Previously reported in vivo rat studies demonstrate that spatially resolved hydration mapping with THz illumination can be used to rapidly and accurately detect fluid shifts following induction of burns and provide highly resolved spatial and temporal characterization of edematous tissue. THz imagery of partial and full thickness burn wounds acquired by our group correlate well with burn severity and suggest that hydration gradients are responsible for the observed contrast. This research aims to confirm the dominant contrast mechanism of THz burn imaging using a clinically accepted diagnostic method that relies on tissue water content for contrast generation to support the translation of this technology to clinical application. The hydration contrast sensing capabilities of magnetic resonance imaging (MRI), specifically T2 relaxation times and proton density values N(H), are well established and provide measures of mobile water content, lending MRI as a suitable method to validate hydration states of skin burns. This paper presents correlational studies performed with MR imaging of ex vivo porcine skin that confirm tissue hydration as the principal sensing mechanism in THz burn imaging. Insights from this preliminary research will be used to lay the groundwork for future, parallel MRI and THz imaging of in vivo rat models to further substantiate the clinical efficacy of reflective THz imaging in burn wound care.

  1. In vitro, in vivo, and clinical studies of tedizolid to assess the potential for peripheral or central monoamine oxidase interactions.

    Science.gov (United States)

    Flanagan, S; Bartizal, K; Minassian, S L; Fang, E; Prokocimer, P

    2013-07-01

    Tedizolid phosphate is a novel oxazolidinone prodrug whose active moiety, tedizolid, has improved potency against Gram-positive pathogens and pharmacokinetics, allowing once-daily administration. Given linezolid warnings for drug-drug and drug-food interactions mediated by monoamine oxidase (MAO) inhibition, including sporadic serotonergic toxicity, these studies evaluated tedizolid for potential MAO interactions. In vitro, tedizolid and linezolid were reversible inhibitors of human MAO-A and MAO-B; the 50% inhibitory concentration (IC50) for tedizolid was 8.7 μM for MAO-A and 5.7 μM for MAO-B and 46.0 and 2.1 μM, respectively, with linezolid. Tedizolid phosphate was negative in the mouse head twitch model of serotonergic activity. Two randomized placebo-controlled crossover clinical studies assessed the potential of 200 mg/day tedizolid phosphate (at steady state) to enhance pressor responses to coadministered oral tyramine or pseudoephedrine. Sensitivity to tyramine was determined by comparing the concentration of tyramine required to elicit a ≥ 30-mmHg increase in systolic blood pressure (TYR30) when administered with placebo versus tedizolid phosphate. The geometric mean tyramine sensitivity ratio (placebo TYR30/tedizolid phosphate TYR30) was 1.33; a ratio of ≥ 2 is considered clinically relevant. In the pseudoephedrine study, mean maximum systolic blood pressure was not significantly different when pseudoephedrine was coadministered with tedizolid phosphate versus placebo. In summary, tedizolid is a weak, reversible inhibitor of MAO-A and MAO-B in vitro. Provocative testing in humans and animal models failed to uncover significant signals that would suggest potential for hypertensive or serotonergic adverse consequences at the therapeutic dose of tedizolid phosphate. Clinical studies are registered at www.clinicaltrials.gov as NCT01539473 (tyramine interaction study conducted at Covance Clinical Research Center, Evansville, IN) and NCT01577459

  2. Comparison of clinical, magnetic resonance and evoked potentials data in a case of valproic-acid-related hyperammonemic coma

    International Nuclear Information System (INIS)

    Hantson, Philippe; Grandin, Cecile; Duprez, Thierry; Nassogne, Marie-Cecile; Guerit, Jean-Michel

    2005-01-01

    Magnetic resonance (MR) multimodality evoked potentials (MEPs) and clinical findings were correlated in a 47-year-old epileptic man in whom parenteral valproic acid (VPA) therapy induced severe comatose hyperammonemic encephalopathy without biological signs of hepatotoxicity (or hepatocytic dysfunction). Although the plasma VPA level remained within a normal therapeutic range, the ammoniemia increased to a toxic peak level at 411 μmol/l 24 h after symptom onset, requiring VPA therapy discontinuation. Brain MR monitoring demonstrated early cytotoxic edema evolving into delayed vasogenic edema and final brain atrophy. Concomitantly to abnormalities within the brainstem on MR images, an increase in brainstem conduction at MEPs and clinical disturbance of brainstem reflexes were observed at the initial phase of the disease course. Later, the resolution of the MR and MEPs abnormalities paralleled the clinical recovery of the reflexes. (orig.)

  3. Comparison of clinical, magnetic resonance and evoked potentials data in a case of valproic-acid-related hyperammonemic coma

    Energy Technology Data Exchange (ETDEWEB)

    Hantson, Philippe [Universite Catholique de Louvain, Department of Intensive Care, Cliniques Saint-Luc, Brussels (Belgium); Grandin, Cecile; Duprez, Thierry [Universite Catholique de Louvain, Department of Neuroradiology, Cliniques Saint-Luc, Brussels (Belgium); Nassogne, Marie-Cecile [Universite Catholique de Louvain, Department of Pediatric Neurology, Cliniques Saint-Luc, Brussels (Belgium); Guerit, Jean-Michel [Universite Catholique de Louvain, Laboratory of Neurophysiology, Cliniques Saint-Luc, Brussels (Belgium)

    2005-01-01

    Magnetic resonance (MR) multimodality evoked potentials (MEPs) and clinical findings were correlated in a 47-year-old epileptic man in whom parenteral valproic acid (VPA) therapy induced severe comatose hyperammonemic encephalopathy without biological signs of hepatotoxicity (or hepatocytic dysfunction). Although the plasma VPA level remained within a normal therapeutic range, the ammoniemia increased to a toxic peak level at 411 {mu}mol/l 24 h after symptom onset, requiring VPA therapy discontinuation. Brain MR monitoring demonstrated early cytotoxic edema evolving into delayed vasogenic edema and final brain atrophy. Concomitantly to abnormalities within the brainstem on MR images, an increase in brainstem conduction at MEPs and clinical disturbance of brainstem reflexes were observed at the initial phase of the disease course. Later, the resolution of the MR and MEPs abnormalities paralleled the clinical recovery of the reflexes. (orig.)

  4. Prevalence and clinical outcomes of patients with multiple potential causes of syncope

    NARCIS (Netherlands)

    Chen, Lin Y.; Gersh, Bernard J.; Hodge, David O.; Wieling, Wouter; Hammill, Stephen C.; Shen, Win-Kuang

    2003-01-01

    Objective: To determine the prevalence, predictors, and prognosis of patients with multiple potential causes of syncope. Patients and Methods: This is a retrospective cohort study with prospective follow-up of consecutive patients with syncope of uncertain cause who were referred to the

  5. High throughput static and dynamic small animal imaging using clinical PET/CT: potential preclinical applications

    International Nuclear Information System (INIS)

    Aide, Nicolas; Desmonts, Cedric; Agostini, Denis; Bardet, Stephane; Bouvard, Gerard; Beauregard, Jean-Mathieu; Roselt, Peter; Neels, Oliver; Beyer, Thomas; Kinross, Kathryn; Hicks, Rodney J.

    2010-01-01

    The objective of the study was to evaluate state-of-the-art clinical PET/CT technology in performing static and dynamic imaging of several mice simultaneously. A mouse-sized phantom was imaged mimicking simultaneous imaging of three mice with computation of recovery coefficients (RCs) and spillover ratios (SORs). Fifteen mice harbouring abdominal or subcutaneous tumours were imaged on clinical PET/CT with point spread function (PSF) reconstruction after injection of [18F]fluorodeoxyglucose or [18F]fluorothymidine. Three of these mice were imaged alone and simultaneously at radial positions -5, 0 and 5 cm. The remaining 12 tumour-bearing mice were imaged in groups of 3 to establish the quantitative accuracy of PET data using ex vivo gamma counting as the reference. Finally, a dynamic scan was performed in three mice simultaneously after the injection of 68 Ga-ethylenediaminetetraacetic acid (EDTA). For typical lesion sizes of 7-8 mm phantom experiments indicated RCs of 0.42 and 0.76 for ordered subsets expectation maximization (OSEM) and PSF reconstruction, respectively. For PSF reconstruction, SOR air and SOR water were 5.3 and 7.5%, respectively. A strong correlation (r 2 = 0.97, p 2 = 0.98; slope = 0.89, p 2 = 0.96; slope = 0.62, p 68 Ga-EDTA dynamic acquisition. New generation clinical PET/CT can be used for simultaneous imaging of multiple small animals in experiments requiring high throughput and where a dedicated small animal PET system is not available. (orig.)

  6. Proteomic profiling in multiple sclerosis clinical courses reveals potential biomarkers of neurodegeneration.

    Directory of Open Access Journals (Sweden)

    Maria Liguori

    Full Text Available The aim of our project was to perform an exploratory analysis of the cerebrospinal fluid (CSF proteomic profiles of Multiple Sclerosis (MS patients, collected in different phases of their clinical course, in order to investigate the existence of peculiar profiles characterizing the different MS phenotypes. The study was carried out on 24 Clinically Isolated Syndrome (CIS, 16 Relapsing Remitting (RR MS, 11 Progressive (Pr MS patients. The CSF samples were analysed using the Matrix Assisted Laser Desorption Ionisation Time Of Flight (MALDI-TOF mass spectrometer in linear mode geometry and in delayed extraction mode (m/z range: 1000-25000 Da. Peak lists were imported for normalization and statistical analysis. CSF data were correlated with demographic, clinical and MRI parameters. The evaluation of MALDI-TOF spectra revealed 348 peak signals with relative intensity ≥ 1% in the study range. The peak intensity of the signals corresponding to Secretogranin II and Protein 7B2 were significantly upregulated in RRMS patients compared to PrMS (p<0.05, whereas the signals of Fibrinogen and Fibrinopeptide A were significantly downregulated in CIS compared to PrMS patients (p<0.04. Additionally, the intensity of the Tymosin β4 peak was the only signal to be significantly discriminated between the CIS and RRMS patients (p = 0.013. Although with caution due to the relatively small size of the study populations, and considering that not all the findings remained significant after adjustment for multiple comparisons, in our opinion this mass spectrometry evaluation confirms that this technique may provide useful and important information to improve our understanding of the complex pathogenesis of MS.

  7. Diffusion weighted imaging demystified. The technique and potential clinical applications for soft tissue imaging

    Energy Technology Data Exchange (ETDEWEB)

    Ahlawat, Shivani [The Johns Hopkins Medical Institutions, The Russell H. Morgan Department of Radiology and Radiological Science, Baltimore, MD (United States); Fayad, Laura M. [The Johns Hopkins Medical Institutions, The Russell H. Morgan Department of Radiology and Radiological Science, Baltimore, MD (United States); The Johns Hopkins Medical Institutions, Department of Oncology, Baltimore, MD (United States); The Johns Hopkins Medical Institutions, Department of Orthopaedic Surgery, Baltimore, MD (United States)

    2018-03-15

    Diffusion-weighted imaging (DWI) is a fast, non-contrast technique that is readily available and easy to integrate into an existing imaging protocol. DWI with apparent diffusion coefficient (ADC) mapping offers a quantitative metric for soft tissue evaluation and provides information regarding the cellularity of a region of interest. There are several available methods of performing DWI, and artifacts and pitfalls must be considered when interpreting DWI studies. This review article will review the various techniques of DWI acquisition and utility of qualitative as well as quantitative methods of image interpretation, with emphasis on optimal methods for ADC measurement. The current clinical applications for DWI are primarily related to oncologic evaluation: For the assessment of de novo soft tissue masses, ADC mapping can serve as a useful adjunct technique to routine anatomic sequences for lesion characterization as cyst or solid and, if solid, benign or malignant. For treated soft tissue masses, the role of DWI/ADC mapping in the assessment of treatment response as well as recurrent or residual neoplasm in the setting of operative management is discussed, especially when intravenous contrast medium cannot be given. Emerging DWI applications for non-neoplastic clinical indications are also reviewed. (orig.)

  8. Diffusion weighted imaging demystified. The technique and potential clinical applications for soft tissue imaging

    International Nuclear Information System (INIS)

    Ahlawat, Shivani; Fayad, Laura M.

    2018-01-01

    Diffusion-weighted imaging (DWI) is a fast, non-contrast technique that is readily available and easy to integrate into an existing imaging protocol. DWI with apparent diffusion coefficient (ADC) mapping offers a quantitative metric for soft tissue evaluation and provides information regarding the cellularity of a region of interest. There are several available methods of performing DWI, and artifacts and pitfalls must be considered when interpreting DWI studies. This review article will review the various techniques of DWI acquisition and utility of qualitative as well as quantitative methods of image interpretation, with emphasis on optimal methods for ADC measurement. The current clinical applications for DWI are primarily related to oncologic evaluation: For the assessment of de novo soft tissue masses, ADC mapping can serve as a useful adjunct technique to routine anatomic sequences for lesion characterization as cyst or solid and, if solid, benign or malignant. For treated soft tissue masses, the role of DWI/ADC mapping in the assessment of treatment response as well as recurrent or residual neoplasm in the setting of operative management is discussed, especially when intravenous contrast medium cannot be given. Emerging DWI applications for non-neoplastic clinical indications are also reviewed. (orig.)

  9. Bicuspid aortic valve syndrome and fibrillinopathies: potential impact on clinical approach

    Directory of Open Access Journals (Sweden)

    Rosina De Cario

    2014-01-01

    Full Text Available Bicuspid aortic valve (BAV is a common heterogeneous disorder whose natural history is determined by hemodynamic valvular impairment and/or increased prevalence of aortic abnormalities ranging from dilatation to aneurysm and dissection. BAV-related aortopathy is frequently associated with relevant aortic pathologic changes leading to structural alterations, characteristic degenerative lesions and histological changes of the aorta very similar to those identified and described in patients with Marfan syndrome (MFS, an inherited connective tissue disorder associated with mutations in fibrillin 1 (FBN1 gene in more than 90% of patients. Recently, a 4-fold increase in the prevalence of BAV in MFS patients has been reported. Subsequently, pathogenetic FBN1 mutations in patients with BAV and aortic dilatation/aneurysm in whom MFS and other more severe type 1 fibrillinopathies were clinically excluded have been identified. In this review we discuss how this evidence, together with that of the wide heterogeneity in pathogenetic mechanisms of BAV-related aortopathy, may impact the clinical management of BAV.

  10. Microscope use in clinical veterinary practice and potential implications for veterinary school curricula.

    Science.gov (United States)

    Stewart, Sherry M; Dowers, Kristy L; Cerda, Jacey R; Schoenfeld-Tacher, Regina M; Kogan, Lori R

    2014-01-01

    Microscopy (skill of using a microscope) and the concepts of cytology (study of cells) and histology (study of tissues) are most often taught in professional veterinary medicine programs through the traditional method of glass slides and light microscopes. Several limiting factors in veterinary training programs are encouraging educators to explore innovative options for teaching microscopy skills and the concepts of cytology and histology. An anonymous online survey was administered through the Colorado Veterinary Medical Association to Colorado veterinarians working in private practice. It was designed to assess their current usage of microscopes for cytological and histological evaluation of specimens and their perceptions of microscope use in their veterinary education. The first part of the survey was answered by 183 veterinarians, with 104 indicating they had an onsite diagnostic lab. Analysis pertaining to the use of the microscope in practice and in veterinary programs was conducted on this subset. Most respondents felt the amount of time spent in the curriculum using a microscope was just right for basic microscope use and using the microscope for viewing and learning about normal and abnormal histological sections and clinical cytology. Participants felt more emphasis could be placed on clinical and diagnostic cytology. Study results suggest that practicing veterinarians frequently use microscopes for a wide variety of cytological diagnostics. However, only two respondents indicated they prepared samples for histological evaluation. Veterinary schools should consider these results against the backdrop of pressure to implement innovative teaching techniques to meet the changing needs of the profession.

  11. Therapeutic Potential of Tolerogenic Dendritic Cells in IBD: From Animal Models to Clinical Application

    Directory of Open Access Journals (Sweden)

    Raquel Cabezón

    2013-01-01

    Full Text Available The gut mucosa undergoes continuous antigenic exposure from food antigens, commensal flora derived ligands, and pathogens. This constant stimulation results in controlled inflammatory responses that are effectively suppressed by multiple factors. This tight regulation, necessary to maintain intestinal homeostasis, is affected during inflammatory bowel diseases (IBD resulting in altered immune responses to harmless microorganisms. Dendritic cells (DCs are sentinels of immunity, located in peripheral and lymphoid tissues, which are essential for homeostasis of T cell-dependent immune responses. The expression of a particular set of pathogen recognition receptors allows DCs to initiate immune responses. However, in the absence of danger signals, different DC subsets can induce active tolerance by inducing regulatory T cells (Treg, inhibiting inflammatory T helper cell responses, or both. Interestingly, several protocols to generate clinical grade tolerogenic DC (tol-DCs in vitro have been described, opening the possibility to restore the intestinal homeostasis to bacterial flora by cellular therapy. In this review, we discuss different DC subsets and their role in IBD. Additionally, we will review preclinical studies performed in animal models while describing recent characterization of tol-DCs from Crohn’s disease patients for clinical application.

  12. Amniotic membrane-derived stem cells: immunomodulatory properties and potential clinical application

    Directory of Open Access Journals (Sweden)

    Insausti CL

    2014-03-01

    Full Text Available Carmen L Insausti,1 Miguel Blanquer,1 Ana M García-Hernández,1 Gregorio Castellanos,2 José M Moraleda11Unidad de Trasplante Hematopoyético y Terapia Celular, 2Servicio de Cirugía, Hospital Clínico Universitario Virgen de la Arrixaca, IMIB, Campus Mare Nostrum, Universidad de Murcia, El Palmar, Murcia, SpainAbstract: Epithelial and mesenchymal cells isolated from the amniotic membrane (AM possess stem cell characteristics, differentiation potential toward lineages of different germ layers, and immunomodulatory properties. While their expansion and differentiation potential have been well studied and characterized, knowledge about their immunomodulatory properties and the mechanisms involved is still incomplete. These mechanisms have been evaluated on various target cells of the innate and the adaptive system and in animal models of different inflammatory diseases. Some results have evidenced that the immunomodulatory effect of AM-derived cells is dependent on cell-cell contact, but many of them have demonstrated that these properties are mediated through the secretion of suppressive molecules. In this review, we present an update on the described immunomodulatory properties of the derived amniotic cells and some of the proposed involved mechanisms. Furthermore, we describe some assays in animal models of different inflammatory diseases which reveal the potential use of these cells to treat such diseases.Keywords: epithelial cells, mesenchymal cells, cell therapy, immunomodulation

  13. The life cycles of six multi-center adaptive clinical trials focused on neurological emergencies developed for the Advancing Regulatory Science initiative of the National Institutes of Health and US Food and Drug Administration: Case studies from the Adaptive Designs Accelerating Promising Treatments Into Trials Project.

    Science.gov (United States)

    Guetterman, Timothy C; Fetters, Michael D; Mawocha, Samkeliso; Legocki, Laurie J; Barsan, William G; Lewis, Roger J; Berry, Donald A; Meurer, William J

    2017-01-01

    Clinical trials are complicated, expensive, time-consuming, and frequently do not lead to discoveries that improve the health of patients with disease. Adaptive clinical trials have emerged as a methodology to provide more flexibility in design elements to better answer scientific questions regarding whether new treatments are efficacious. Limited observational data exist that describe the complex process of designing adaptive clinical trials. To address these issues, the Adaptive Designs Accelerating Promising Treatments Into Trials project developed six, tailored, flexible, adaptive, phase-III clinical trials for neurological emergencies, and investigators prospectively monitored and observed the processes. The objective of this work is to describe the adaptive design development process, the final design, and the current status of the adaptive trial designs that were developed. To observe and reflect upon the trial development process, we employed a rich, mixed methods evaluation that combined quantitative data from visual analog scale to assess attitudes about adaptive trials, along with in-depth qualitative data about the development process gathered from observations. The Adaptive Designs Accelerating Promising Treatments Into Trials team developed six adaptive clinical trial designs. Across the six designs, 53 attitude surveys were completed at baseline and after the trial planning process completed. Compared to baseline, the participants believed significantly more strongly that the adaptive designs would be accepted by National Institutes of Health review panels and non-researcher clinicians. In addition, after the trial planning process, the participants more strongly believed that the adaptive design would meet the scientific and medical goals of the studies. Introducing the adaptive design at early conceptualization proved critical to successful adoption and implementation of that trial. Involving key stakeholders from several scientific domains early

  14. Modulation of the activity of N-methyl-D-aspartate receptors as a novel treatment option for depression: current clinical evidence and therapeutic potential of rapastinel (GLYX-13

    Directory of Open Access Journals (Sweden)

    Vasilescu AN

    2017-03-01

    Full Text Available Andrei-Nicolae Vasilescu,1,* Nina Schweinfurth,2,* Stefan Borgwardt,2,* Peter Gass,1 Undine E Lang,2,* Dragos Inta,1,2,* Sarah Eckart2,* 1Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany; 2Department of Psychiatry (Universitäre Psychiatrische Kliniken, University of Basel, Basel, Switzerland *These authors contributed equally to this work Abstract: Classical monoaminergic antidepressants show several disadvantages, such as protracted onset of therapeutic action. Conversely, the fast and sustained antidepressant effect of the N-methyl-d-aspartate receptor (NMDAR antagonist ketamine raises vast interest in understanding the role of the glutamate system in mood disorders. Indeed, numerous data support the existence of glutamatergic dysfunction in major depressive disorder (MDD. Drawback to this short-latency therapy is its side effect profile, especially the psychotomimetic action, which seriously hampers the common and widespread clinical use of ketamine. Therefore, there is a substantial need for alternative glutamatergic antidepressants with milder side effects. In this article, we review evidence that implicates NMDARs in the prospective treatment of MDD with focus on rapastinel (formerly known as GLYX-13, a novel synthetic NMDAR modulator with fast antidepressant effect, which acts by enhancing NMDAR function as opposed to blocking it. We summarize and discuss current clinical and animal studies regarding the therapeutic potential of rapastinel not only in MDD but also in other psychiatric disorders, such as obsessive–compulsive disorder and posttraumatic stress disorder. Additionally, we discuss current data concerning the molecular mechanisms underlying the antidepressant effect of rapastinel, highlighting common aspects as well as differences to ketamine. In 2016, rapastinel received the Breakthrough Therapy designation for the treatment

  15. Medical big data: promise and challenges

    Directory of Open Access Journals (Sweden)

    Choong Ho Lee

    2017-03-01

    Full Text Available The concept of big data, commonly characterized by volume, variety, velocity, and veracity, goes far beyond the data type and includes the aspects of data analysis, such as hypothesis-generating, rather than hypothesis-testing. Big data focuses on temporal stability of the association, rather than on causal relationship and underlying probability distribution assumptions are frequently not required. Medical big data as material to be analyzed has various features that are not only distinct from big data of other disciplines, but also distinct from traditional clinical epidemiology. Big data technology has many areas of application in healthcare, such as predictive modeling and clinical decision support, disease or safety surveillance, public health, and research. Big data analytics frequently exploits analytic methods developed in data mining, including classification, clustering, and regression. Medical big data analyses are complicated by many technical issues, such as missing values, curse of dimensionality, and bias control, and share the inherent limitations of observation study, namely the inability to test causality resulting from residual confounding and reverse causation. Recently, propensity score analysis and instrumental variable analysis have been introduced to overcome these limitations, and they have accomplished a great deal. Many challenges, such as the absence of evidence of practical benefits of big data, methodological issues including legal and ethical issues, and clinical integration and utility issues, must be overcome to realize the promise of medical big data as the fuel of a continuous learning healthcare system that will improve patient outcome and reduce waste in areas including nephrology.

  16. Medical big data: promise and challenges.

    Science.gov (United States)

    Lee, Choong Ho; Yoon, Hyung-Jin

    2017-03-01

    The concept of big data, commonly characterized by volume, variety, velocity, and veracity, goes far beyond the data type and includes the aspects of data analysis, such as hypothesis-generating, rather than hypothesis-testing. Big data focuses on temporal stability of the association, rather than on causal relationship and underlying probability distribution assumptions are frequently not required. Medical big data as material to be analyzed has various features that are not only distinct from big data of other disciplines, but also distinct from traditional clinical epidemiology. Big data technology has many areas of application in healthcare, such as predictive modeling and clinical decision support, disease or safety surveillance, public health, and research. Big data analytics frequently exploits analytic methods developed in data mining, including classification, clustering, and regression. Medical big data analyses are complicated by many technical issues, such as missing values, curse of dimensionality, and bias control, and share the inherent limitations of observation study, namely the inability to test causality resulting from residual confounding and reverse causation. Recently, propensity score analysis and instrumental variable analysis have been introduced to overcome these limitations, and they have accomplished a great deal. Many challenges, such as the absence of evidence of practical benefits of big data, methodological issues including legal and ethical issues, and clinical integration and utility issues, must be overcome to realize the promise of medical big data as the fuel of a continuous learning healthcare system that will improve patient outcome and reduce waste in areas including nephrology.

  17. Electrocorticographic Temporal Alteration Mapping: A Clinical Technique for Mapping the Motor Cortex with Movement-Related Cortical Potentials

    Directory of Open Access Journals (Sweden)

    Zehan Wu

    2017-06-01

    Full Text Available We propose electrocorticographic temporal alteration mapping (ETAM for motor cortex mapping by utilizing movement-related cortical potentials (MRCPs within the low-frequency band [0.05-3] Hz. This MRCP waveform-based temporal domain approach was compared with the state-of-the-art electrocorticographic frequency alteration mapping (EFAM, which is based on frequency spectrum dynamics. Five patients (two epilepsy cases and three tumor cases were enrolled in the study. Each patient underwent intraoperative direct electrocortical stimulation (DECS procedure for motor cortex localization. Moreover, the patients were required to perform simple brisk wrist extension task during awake craniotomy surgery. Cross-validation results showed that the proposed ETAM method had high sensitivity (81.8% and specificity (94.3% in identifying sites which exhibited positive DECS motor responses. Moreover, although the sensitivity of the ETAM and EFAM approaches was not significantly different, ETAM had greater specificity compared with EFAM (94.3 vs. 86.1%. These results indicate that for the intraoperative functional brain mapping, ETAM is a promising novel approach for motor cortex localization with the potential to reduce the need for cortical electrical stimulation.

  18. NEW METABOLIC INDEX USE POTENTIALITIES IN EVALUATION OF INSULIN RESISTANCE IN CLINICAL PRACTICE

    Directory of Open Access Journals (Sweden)

    G. E. Roytberg

    2015-09-01

    Full Text Available Early diagnostics of insulin resistance (IR is one of the methods of primary prevention of cardio-vascular diseases and type 2 diabetes mellitus. The HOMA-IR index and ratio of plasma triglyceride to high-density lipoprotein cholesterol concentration are the most frequently used indices in clinical and epidemiological scientific research. Prognostic value and efficacy of these tests as a screening method are not high. What method of IR detection should be used in clinical practice and how to interpret received values of the indices is still a matter of dispute.Aim. To evaluate informative value, sensitivity and specificity of a new metabolic index (MI for IR estimation in comparison with the calculated HOMA-IR index.Material and methods. A total of 845 patients (298 men, 547 women were enrolled into the further study after an outpatient regular medical check-up of 2,615 persons. Mean age of the patients was 45.77±12.18 years, body mass index – 28.95±1.44 kg/m2. To evaluate lipid and carbohydrate metabolism blood chemistry parameters were assessed. IR was determined by the Homeostasis Model Assessment (HOMA-IR and an oblique calculated index based on lipid metabolism parameters. In accordance with the developed screening method of IR detection (invention patent № 2493566 MI considering carbohydrate and lipid changes was proposed.Results. Calculation of MI and its threshold level was performed by analysis of a characteristic curve. Graphical dependence between sensitivity and specificity of the proposed index was demonstrated: sensitivity of the test was 75.7%, specificity – 89.1%. Probability of IR at MI value >7.0 was 63.5% (positive predictive value, probability of IR absence at the index value ≤7.0 was 93.6% (negative predictive value. The general accuracy of the test, which is characterized by the area under the characteristic curve, was 0.881 with 95%-confidence interval within 0.854-0.905.Conclusion. The importance of negative

  19. NEW METABOLIC INDEX USE POTENTIALITIES IN EVALUATION OF INSULIN RESISTANCE IN CLINICAL PRACTICE

    Directory of Open Access Journals (Sweden)

    G. E. Roytberg

    2014-01-01

    Full Text Available Early diagnostics of insulin resistance (IR is one of the methods of primary prevention of cardio-vascular diseases and type 2 diabetes mellitus. The HOMA-IR index and ratio of plasma triglyceride to high-density lipoprotein cholesterol concentration are the most frequently used indices in clinical and epidemiological scientific research. Prognostic value and efficacy of these tests as a screening method are not high. What method of IR detection should be used in clinical practice and how to interpret received values of the indices is still a matter of dispute.Aim. To evaluate informative value, sensitivity and specificity of a new metabolic index (MI for IR estimation in comparison with the calculated HOMA-IR index.Material and methods. A total of 845 patients (298 men, 547 women were enrolled into the further study after an outpatient regular medical check-up of 2,615 persons. Mean age of the patients was 45.77±12.18 years, body mass index – 28.95±1.44 kg/m2. To evaluate lipid and carbohydrate metabolism blood chemistry parameters were assessed. IR was determined by the Homeostasis Model Assessment (HOMA-IR and an oblique calculated index based on lipid metabolism parameters. In accordance with the developed screening method of IR detection (invention patent № 2493566 MI considering carbohydrate and lipid changes was proposed.Results. Calculation of MI and its threshold level was performed by analysis of a characteristic curve. Graphical dependence between sensitivity and specificity of the proposed index was demonstrated: sensitivity of the test was 75.7%, specificity – 89.1%. Probability of IR at MI value >7.0 was 63.5% (positive predictive value, probability of IR absence at the index value ≤7.0 was 93.6% (negative predictive value. The general accuracy of the test, which is characterized by the area under the characteristic curve, was 0.881 with 95%-confidence interval within 0.854-0.905.Conclusion. The importance of negative

  20. Predicting PTSD using the New York Risk Score with genotype data: potential clinical and research opportunities

    Directory of Open Access Journals (Sweden)

    Boscarino JA

    2013-04-01

    Full Text Available Joseph A Boscarino,1,2 H Lester Kirchner,3,4 Stuart N Hoffman,5 Porat M Erlich1,4 1Center for Health Research, Geisinger Clinic, Danville, 2Department of Psychiatry, Temple University School of Medicine, Philadelphia, 3Division of Medicine, Geisinger Clinic, Danville, 4Department of Medicine, Temple University School of Medicine, Philadelphia, 5Department of Neurology, Geisinger Clinic, Danville, PA, USA Background: We previously developed a post-traumatic stress disorder (PTSD screening instrument, ie, the New York PTSD Risk Score (NYPRS, that was effective in predicting PTSD. In the present study, we assessed a version of this risk score that also included genetic information. Methods: Utilizing diagnostic testing methods, we hierarchically examined different prediction variables identified in previous NYPRS research, including genetic risk-allele information, to assess lifetime and current PTSD status among a population of trauma-exposed adults. Results: We found that, in predicting lifetime PTSD, the area under the receiver operating characteristic curve (AUC for the Primary Care PTSD Screen alone was 0.865. When we added psychosocial predictors from the original NYPRS to the model, including depression, sleep disturbance, and a measure of health care access, the AUC increased to 0.902, which was a significant improvement (P = 0.0021. When genetic information was added in the form of a count of PTSD risk alleles located within FKBP, COMT, CHRNA5, and CRHR1 genetic loci (coded 0–6, the AUC increased to 0.920, which was also a significant improvement (P = 0.0178. The results for current PTSD were similar. In the final model for current PTSD with the psychosocial risk factors included, genotype resulted in a prediction weight of 17 for each risk allele present, indicating that a person with six risk alleles or more would receive a PTSD risk score of 17 × 6 = 102, the highest risk score for any of the predictors studied. Conclusion: Genetic

  1. Complexities and potential pitfalls of clinical study design and data analysis in assisted reproduction.

    Science.gov (United States)

    Patounakis, George; Hill, Micah J

    2018-06-01

    The purpose of the current review is to describe the common pitfalls in design and statistical analysis of reproductive medicine studies. It serves to guide both authors and reviewers toward reducing the incidence of spurious statistical results and erroneous conclusions. The large amount of data gathered in IVF cycles leads to problems with multiplicity, multicollinearity, and over fitting of regression models. Furthermore, the use of the word 'trend' to describe nonsignificant results has increased in recent years. Finally, methods to accurately account for female age in infertility research models are becoming more common and necessary. The pitfalls of study design and analysis reviewed provide a framework for authors and reviewers to approach clinical research in the field of reproductive medicine. By providing a more rigorous approach to study design and analysis, the literature in reproductive medicine will have more reliable conclusions that can stand the test of time.

  2. Biology and potential clinical implications of tissue inhibitor of metalloproteinases-1 in colorectal cancer treatment

    DEFF Research Database (Denmark)

    Sørensen, Nanna Møller; Sørensen, irene Vejgaard; Würtz, Sidse Ørnbjerg

    2008-01-01

    Colorectal cancer (CRC) is the second leading cause of cancer-related death in the industrialized world. About half of "curatively" resected patients develop recurrent disease within the next 3-5 years despite the lack of clinical, histological and biochemical evidence of remaining overt disease...... after resection of the primary tumour. Availability of validated biological markers for early detection, selection for adjuvant therapy, prediction of treatment efficacy and monitoring of treatment efficacy would most probably increase survival. Tissue inhibitor of metalloproteinases-1 (TIMP-1) may...... patients, suggesting that TIMP-1 could have a tumour-promoting function. Furthermore, measurement of plasma TIMP-1 has been shown to be useful for disease detection, with a high sensitivity and high specificity for early-stage colon cancer. This review describes some basic information on the current...

  3. Towards Achieving the Full Clinical Potential of Proton Therapy by Inclusion of LET and RBE Models

    Energy Technology Data Exchange (ETDEWEB)

    Jones, Bleddyn [Gray Laboratory, CRUK/MRC Oxford Oncology Institute, The University of Oxford, ORCRB-Roosevelt Drive, Oxford OX3 7DQ (United Kingdom)

    2015-03-17

    Despite increasing use of proton therapy (PBT), several systematic literature reviews show limited gains in clinical outcomes, with publications mostly devoted to recent technical developments. The lack of randomised control studies has also hampered progress in the acceptance of PBT by many oncologists and policy makers. There remain two important uncertainties associated with PBT, namely: (1) accuracy and reproducibility of Bragg peak position (BPP); and (2) imprecise knowledge of the relative biological effect (RBE) for different tissues and tumours, and at different doses. Incorrect BPP will change dose, linear energy transfer (LET) and RBE, with risks of reduced tumour control and enhanced toxicity. These interrelationships are discussed qualitatively with respect to the ICRU target volume definitions. The internationally accepted proton RBE of 1.1 was based on assays and dose ranges unlikely to reveal the complete range of RBE in the human body. RBE values are not known for human (or animal) brain, spine, kidney, liver, intestine, etc. A simple efficiency model for estimating proton RBE values is described, based on data of Belli et al. and other authors, which allows linear increases in α and β with LET, with a gradient estimated using a saturation model from the low LET α and β radiosensitivity parameter input values, and decreasing RBE with increasing dose. To improve outcomes, 3-D dose-LET-RBE and bio-effectiveness maps are required. Validation experiments are indicated in relevant tissues. Randomised clinical studies that test the invariant 1.1 RBE allocation against higher values in late reacting tissues, and lower tumour RBE values in the case of radiosensitive tumours, are also indicated.

  4. Clinical potentials of methylator phenotype in stage 4 high-risk neuroblastoma: an open challenge.

    Directory of Open Access Journals (Sweden)

    Barbara Banelli

    Full Text Available Approximately 20% of stage 4 high-risk neuroblastoma patients are alive and disease-free 5 years after disease onset while the remaining experience rapid and fatal progression. Numerous findings underline the prognostic role of methylation of defined target genes in neuroblastoma without taking into account the clinical and biological heterogeneity of this disease. In this report we have investigated the methylation of the PCDHB cluster, the most informative member of the "Methylator Phenotype" in neuroblastoma, hypothesizing that if this epigenetic mark can predict overall and progression free survival in high-risk stage 4 neuroblastoma, it could be utilized to improve the risk stratification of the patients, alone or in conjunction with the previously identified methylation of the SFN gene (14.3.3sigma that can accurately predict outcome in these patients. We have utilized univariate and multivariate models to compare the prognostic power of PCDHB methylation in terms of overall and progression free survival, quantitatively determined by pyrosequencing, with that of other markers utilized for the patients' stratification utilizing methylation thresholds calculated on neuroblastoma at stage 1-4 and only on stage 4, high-risk patients. Our results indicate that PCDHB accurately distinguishes between high- and intermediate/low risk stage 4 neuroblastoma in agreement with the established risk stratification criteria. However PCDHB cannot predict outcome in the subgroup of stage 4 patients at high-risk whereas methylation levels of SFN are suggestive of a "methylation gradient" associated with tumor aggressiveness as suggested by the finding of a higher threshold that defines a subset of patients with an extremely severe disease (OS <24 months. Because of the heterogeneity of neuroblastoma we believe that clinically relevant methylation markers should be selected and tested on homogeneous groups of patients rather than on patients at all stages.

  5. The human immune response to streptococcal extracellular antigens: clinical, diagnostic, and potential pathogenetic implications.

    Science.gov (United States)

    Johnson, Dwight R; Kurlan, Roger; Leckman, James; Kaplan, Edward L

    2010-02-15

    Determination of an immune response to group A Streptococcus (GAS) antigens, frequently anti-streptolysin O and anti-DNase B, is crucial for documentation of bona fide GAS infection. Although the importance of immunologic confirmation of infection is widely accepted, the immediate and long-term immunokinetics of the human antibody response are incompletely documented and poorly understood. Pediatric study participants (n = 160) were followed during a 2-year study with monthly throat cultures (n = 3491) and blood samples (n = 1679) obtained every 13 weeks. Recovered GAS were characterized; serum anti-streptolysin O and anti-DNase B antibody titers were determined. Antibody titers and GAS culture results were temporally correlated and analyzed. The analyses clearly document, in some instances for the first time, that an increase in antibody titer more accurately defines infection than does an absolute titer (eg, "upper limit of normal"), that antibody titers can remain elevated for many months even without GAS, and that some individuals may harbor GAS continuously for months or years without symptoms of infection and without an associated immune response. Measuring 2 different antibodies is more accurate in defining infection. Single time-point cultures and single antibody titers are often misleading. Sequential samples more accurately define infection, allowing correlation of titer increases with temporal confirmation of GAS acquisition. Understanding kinetics of the immune response(s) to GAS infection is necessary in formulating accurate clinical diagnostic conclusions, to appropriate design of clinical and epidemiological studies examining the association of GAS with subsequent sequelae, and to providing insight into pathogenetic mechanisms associated with this important human pathogen.

  6. Towards Achieving the Full Clinical Potential of Proton Therapy by Inclusion of LET and RBE Models

    International Nuclear Information System (INIS)

    Jones, Bleddyn

    2015-01-01

    Despite increasing use of proton therapy (PBT), several systematic literature reviews show limited gains in clinical outcomes, with publications mostly devoted to recent technical developments. The lack of randomised control studies has also hampered progress in the acceptance of PBT by many oncologists and policy makers. There remain two important uncertainties associated with PBT, namely: (1) accuracy and reproducibility of Bragg peak position (BPP); and (2) imprecise knowledge of the relative biological effect (RBE) for different tissues and tumours, and at different doses. Incorrect BPP will change dose, linear energy transfer (LET) and RBE, with risks of reduced tumour control and enhanced toxicity. These interrelationships are discussed qualitatively with respect to the ICRU target volume definitions. The internationally accepted proton RBE of 1.1 was based on assays and dose ranges unlikely to reveal the complete range of RBE in the human body. RBE values are not known for human (or animal) brain, spine, kidney, liver, intestine, etc. A simple efficiency model for estimating proton RBE values is described, based on data of Belli et al. and other authors, which allows linear increases in α and β with LET, with a gradient estimated using a saturation model from the low LET α and β radiosensitivity parameter input values, and decreasing RBE with increasing dose. To improve outcomes, 3-D dose-LET-RBE and bio-effectiveness maps are required. Validation experiments are indicated in relevant tissues. Randomised clinical studies that test the invariant 1.1 RBE allocation against higher values in late reacting tissues, and lower tumour RBE values in the case of radiosensitive tumours, are also indicated

  7. Clinical Drug-Drug Pharmacokinetic Interaction Potential of Sucralfate with Other Drugs: Review and Perspectives.

    Science.gov (United States)

    Sulochana, Suresh P; Syed, Muzeeb; Chandrasekar, Devaraj V; Mullangi, Ramesh; Srinivas, Nuggehally R

    2016-10-01

    Sucralfate, a complex of aluminium hydroxide with sulfated sucrose, forms a strong gastrointestinal tract (GIT) mucosal barrier with excellent anti-ulcer property. Because sucralfate does not undergo any significant oral absorption, sucralfate resides in the GIT for a considerable length of time. The unabsorbed sucralfate may alter the pharmacokinetics of the oral drugs by impeding its absorption and reducing the oral bioavailability. Because of the increased use of sucralfate, it was important to provide a reappraisal of the published clinical drug-drug interaction studies of sucralfate with scores of drugs. This review covers several category of drugs such as non-steroidal anti-inflammatory drugs, fluoroquinolones, histamine H2-receptor blockers, macrolides, anti-fungals, anti-diabetics, salicylic acid derivatives, steroidal anti-inflammatory drugs and provides pharmacokinetic data summary along with study design, objectives and key remarks. While the loss of oral bioavailability was significant for the fluoroquinolone class, it generally varied for other classes of drugs, suggesting that impact of the co-administration of sucralfate is manageable in clinical situations. Given the technology advancement in formulation development, it may be in order feasible to develop appropriate formulation strategies to either avoid or minimize the absorption-related issues when co-administered with sucralfate. It is recommended that consideration of both in vitro and preclinical studies may be in order to gauge the level of interaction of a drug with sucralfate. Such data may aid in the development of appropriate strategies to navigate the co-administration of sucralfate with other drugs in this age of polypharmacy.

  8. Antifungal potential of eugenyl acetate against clinical isolates of Candida species.

    Science.gov (United States)

    Musthafa, Khadar Syed; Hmoteh, Jutharat; Thamjarungwong, Benjamas; Voravuthikunchai, Supayang Piyawan

    2016-10-01

    The study evaluated the efficiency of eugenyl acetate (EA), a phytochemical in clove essential oil, against clinical isolates of Candida albicans, Candida parapsilosis, Candida tropicalis, and Candida glabrata. Minimum inhibitory concentrations (MIC) of EA against Candida isolates were in the range between 0.1% and 0.4% (v/v). Spot assay further confirmed the susceptibility of Candida isolates to the compound upon treatment with respective 1 × MIC. Growth profile measured in time kill study evidence that the compound at 1 × MIC and 1/2 × MIC retarded the growth of Candida cells, divulging the fungicidal activity. Light microscopic observation demonstrated that upon treated with EA, rough cell morphology, cell damage, and fragmented patterns were observed in C. albicans, C. parapsilosis, C. tropicalis, and C. glabrata. Furthermore, unusual morphological changes of the organism were observed in scanning electron microscopic study. Therefore, it is validated that the compound could cause cell damage resulting in the cell death of Candida clinical isolates. Eventually, the compound at sub-MIC (0.0125% v/v) significantly inhibited serum-induced germ tube formation by C. albicans. Eugenyl acetate inhibited biofilm forming ability of the organisms as well as reduced the adherence of Candida cells to HaCaT keratinocytes cells. In addition, upon treatment with EA, the phagocytic activity of macrophages was increased significantly against C. albicans (P Candida infections. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Transportation and energy efficiency: Promised potentials, serious roadblocks

    Energy Technology Data Exchange (ETDEWEB)

    Kraft-Oliver, T.V.

    1995-12-31

    Transportation is both a critical element of achieving national economic development goals and a major consumer of scarce and expensive energy resources. Improvements in access and mobility from reduced congestion, higher speeds, additional non motorized and pedestrian options, and better mass transit will result in reductions in energy use in most cases. Additional improvements in vehicle efficiency are possible but will not meet the needs of the region for transportation and energy efficiency improvements in the absence of these other improvements. The barriers to success in the transport sector are obvious on a superficial level. They include lack of road space, inadequate or incomplete road networks, insufficient mass transit capacity, predation of pedestrian and nonmotorized vehicle space by motor vehicles, and financing. The lack of progress in solving many of these problems over the past ten to twenty years indicates that there are underlying issues not yet addressed. Perceptions of these problems have changed since the middle 1970s and early 1980s as international lending and technical assistance began to focus on transportation. In those early years the problems were described as financial, and `meeting demand` challenges. The World Bank is now conducting a review of their Transport Sector Policy. While the review has not progressed to a final document and certainly not to articulation or transformation of Bank policy, early drafts reflect a view that past failures to improve transportation circumstances are human resource and institutional problems.

  10. Online Training of Teachers Using OER: Promises and Potential Strategies

    Science.gov (United States)

    Misra, Pradeep Kumar

    2014-01-01

    Teacher education nowadays needs a change in vision and action to cater to the demands of changing societies. Reforms, improvements, and new approaches in teacher education are an immediate need. Online training of teachers using OER has emerged as a new approach in this direction. This approach is based on the assumption that online training will…

  11. Irradiation's promise: fewer foodborne illnesses?

    International Nuclear Information System (INIS)

    Roberts, T.

    1986-01-01

    Food irradiation offers a variety of potential benefits to the food supply. It can delay ripening and sprouting of fruits and vegetables, and substitute for chemical fumigants to kill insects. However, one of the most important benefits of food irradiation is its potential use for destroying microbial pathogens that enter the food supply, including the two most common disease causing bacteria: salmonella and campylobacter. Animal products are one of the primary carriers of pathogens. Food borne illnesses are on the rise, and irradiation of red meats and poultry could significantly reduce their occurrence. Food irradiation should be examined more closely to determine its possible benefits in curtailing microbial diseases

  12. Otolithic disease: clinical features and the role of vestibular evoked myogenic potentials.

    Science.gov (United States)

    Curthoys, Ian S; Manzari, Leonardo

    2013-07-01

    Through selective tests of the function of the canal and otolith sense organs, it is possible to assert that patient conditions are purely otolithic and that the canals are not involved. The video head impulse test selectively tests each semicircular canal; the ocular vestibular-evoked myogenic potential to 500 Hz Fz (Fz is the location on the forehead in the midline at the hairline) bone-conducted vibration (BCV) selectively tests the utricular macula and the cervical vestibular-evoked myogenic potential to 500 Hz Fz BCV selectively tests the saccular macula. The development of new specific tests of otolith function has shown that some patients may have specific deficits of just otolithic function. In the authors' experience, patients who complain strongly of postural unsteadiness should be suspected to have otolithic deficits. They may also have vertigo and in some cases have spontaneous nystagmus of peripheral origin, even though their semicircular canal function is normal. The prognosis for such patients is good. They usually appear to regain their postural stability spontaneously over weeks (or longer), even though they still have an otolithic deficit as shown by objective tests when they are free of symptoms. It is not known what procedures may accelerate the recovery of otolith function. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  13. Frozen blood products: clinically effective and potentially ideal for remote Australia.

    Science.gov (United States)

    Holley, A; Marks, D C; Johnson, L; Reade, M C; Badloe, J F; Noorman, F

    2013-01-01

    The development of effective cryopreservation techniques for both red blood cells and platelets, which maintain ex vivo biological activity, in combination with frozen plasma, provides for a unique blood banking strategy. This technology greatly enhances the storage life of these products. The rationale and potential advantages of using cryopreservation techniques for the provision of blood products to remote and military environments have been effectively demonstrated in several conflicts over the last decade. Current haemostatic resuscitation doctrine for the exsanguinating patient supports the use of red blood cells, platelets and frozen plasma early in the resuscitation. We believe an integrated fresh-frozen blood bank inventory could facilitate provision of blood products, not only in the military setting but also in regional Australia, by overcoming many logistic and geographical challenges. The processes involved in production and point of care thawing are sufficiently well developed and achievable to make this technology a viable option. The potential limitations of cryopreservation and subsequent product thawing need to be considered if such a strategy is to be developed. A substantial body of international experience using cryopreserved products in remote settings has already been accrued. This experience provides a template for the possible creation of an Australian integrated fresh-frozen blood bank inventory that could conceivably enhance the care of patients in both regional Australia and in the military setting.

  14. Magnetic resonance imaging of the lumbar spine: determining clinical impact and potential harm from overuse.

    Science.gov (United States)

    Wnuk, Nathan M; Alkasab, Tarik K; Rosenthal, Daniel I

    2018-04-18

    Lumbar spine MRI is frequently said to be "overused" in the evaluation of low-back pain, yet data concerning the extent of overuse and on potential harmful effects are lacking. To determine the proportion of examinations with a detectable impact on patient care (actionable outcomes). Retrospective cohort study PATIENT SAMPLE: 5,365 outpatient lumbar spine MR examinations OUTCOME MEASURES: Actionable outcomes included: 1) findings leading to an intervention making use of anatomical information such as surgery; 2) new diagnoses of cancer, infection, or fracture; or 3) following known lumbar spine pathology. Potential harm was assessed by identifying examinations where suspicion of cancer or infection was raised but no positive diagnosis made. A medical record aggregation/search system was used to identify lumbar spine MR examinations with positive outcome measures. Patient notes were examined to verify outcomes. A random sample was manually inspected to identify missed positive outcomes. The proportion of actionable lumbar spine MRIs was 13%, although 93% were appropriate according to American College of Radiology guidelines. Of 36 suspected cases of cancer/infection 81% were false positives. Further investigations were ordered on 59% of suspicious exams, 86% of which were false positives. The proportion of lumbar spine MR examinations that inform management is small. The false positive rate and proportion of false positives involving further investigation is high. Further study to improve the efficiency of imaging is warranted. Copyright © 2018 Elsevier Inc. All rights reserved.

  15. TRIENNIAL GROWTH AND DEVELOPMENT SYMPOSIUM: Dedifferentiated fat cells: Potential and perspectives for their use in clinical and animal science purpose.

    Science.gov (United States)

    Duarte, M S; Bueno, R; Silva, W; Campos, C F; Gionbelli, M P; Guimarães, S E F; Silva, F F; Lopes, P S; Hausman, G J; Dodson, M V

    2017-05-01

    An increasing body of evidences has demonstrated the ability of the mature adipocyte to dedifferentiate into a population of proliferative-competent cells known as dedifferentiated fat (DFAT) cells. As early as the 1970s, in vitro studies showed that DFAT cells may be obtained by ceiling culture, which takes advantage of the buoyancy property of lipid-filled cells. It was documented that DFAT cells may acquire a phenotype similar to mesenchymal stem cells and yet may differentiate into multiple cell lineages, such as skeletal and smooth muscle cells, cardiomyocytes, osteoblasts, and adipocytes. Additionally, recent studies showed the ability of isolated mature adipocytes to dedifferentiate in vivo and the capacity of the progeny cells to redifferentiate into mature adipocytes, contributing to the increase of body fatness. These findings shed light on the potential for use of DFAT cells, not only for clinical purposes but also within the animal science field, because increasing intramuscular fat without excessive increase in other fat depots is a challenge in livestock production. Knowledge of the mechanisms underlying the dedifferentiation and redifferentiation of DFAT cells will allow the development of strategies for their use for clinical and animal science purposes. In this review, we highlight several aspects of DFAT cells, their potential for clinical purposes, and their contribution to adipose tissue mass in livestock.

  16. Comparison of the Developmental Potential and Clinical Results of In Vivo Matured Oocytes Cryopreserved with Different Vitrification Media

    Directory of Open Access Journals (Sweden)

    Mei Li

    2015-01-01

    Full Text Available Background: Oocyte vitrification is widely used throughout the world, but its clinical efficacy is inconsistent and depends on the vitrification media. This study compared the developmental potential and clinical results of in vivo matured oocytes cryopreserved with different vitrification media. Methods: This retrospective study involved vitrified-warmed oocytes at one in vitro fertilization laboratory. Vitrification media kits comprised the MC kit (ethylene glycol [EG] plus 1,2-propanediol [PROH], the KT kit (EG plus dimethyl sulphoxide [DMSO], and the Modified kit (EG plus DMSO and PROH kit. Rates of oocyte survival and subsequent developmental potential were recorded and analyzed. The t-test and the Chi-square test were used to evaluate each method′s efficacy. Results: Oocyte survival rate was significantly higher for the Modified kit (92.0% than for the MC kit (88.2% (P 0.05. The high-quality embryo rate per warmed oocyte was significantly higher (23.4% in the Modified kit group than in the other groups (P 0.05. Conclusions: Modified vitrification media are efficient for oocyte vitrification and, with further verification, may be able to replace commercially available media in future clinical applications.

  17. Optimization and scale up of microfluidic nanolipomer production method for preclinical and potential clinical trials.

    Science.gov (United States)

    Gdowski, Andrew; Johnson, Kaitlyn; Shah, Sunil; Gryczynski, Ignacy; Vishwanatha, Jamboor; Ranjan, Amalendu

    2018-02-12

    The process of optimization and fabrication of nanoparticle synthesis for preclinical studies can be challenging and time consuming. Traditional small scale laboratory synthesis techniques suffer from batch to batch variability. Additionally, the parameters used in the original formulation must be re-optimized due to differences in fabrication techniques for clinical production. Several low flow microfluidic synthesis processes have been reported in recent years for developing nanoparticles that are a hybrid between polymeric nanoparticles and liposomes. However, use of high flow microfluidic synthetic techniques has not been described for this type of nanoparticle system, which we will term as nanolipomer. In this manuscript, we describe the successful optimization and functional assessment of nanolipomers fabricated using a microfluidic synthesis method under high flow parameters. The optimal total flow rate for synthesis of these nanolipomers was found to be 12 ml/min and flow rate ratio 1:1 (organic phase: aqueous phase). The PLGA polymer concentration of 10 mg/ml and a DSPE-PEG lipid concentration of 10% w/v provided optimal size, PDI and stability. Drug loading and encapsulation of a representative hydrophobic small molecule drug, curcumin, was optimized and found that high encapsulation efficiency of 58.8% and drug loading of 4.4% was achieved at 7.5% w/w initial concentration of curcumin/PLGA polymer. The final size and polydispersity index of the optimized nanolipomer was 102.11 nm and 0.126, respectively. Functional assessment of uptake of the nanolipomers in C4-2B prostate cancer cells showed uptake at 1 h and increased uptake at 24 h. The nanolipomer was more effective in the cell viability assay compared to free drug. Finally, assessment of in vivo retention in mice of these nanolipomers revealed retention for up to 2 h and were completely cleared at 24 h. In this study, we have demonstrated that a nanolipomer formulation can be successfully

  18. The treatment of Alzheimer's disease using Chinese medicinal plants: from disease models to potential clinical applications.

    Science.gov (United States)

    Su, Yang; Wang, Qiuhong; Wang, Changfu; Chan, Kelvin; Sun, Yanping; Kuang, Haixue

    2014-03-28

    Alzheimer's disease (AD) is characterized by the sustained higher nervous disorders of the activities and functions of the brain. Due to its heavy burden on society and the patients' families, it is urgent to review the treatments for AD to provide basic data for further research and new drug development. Among these treatments, Chinese Material Medica (CMM) has been traditionally clinical used in China to treat AD for a long time with obvious efficacy. With the further research reports of CMM, new therapeutic materials may be recovered from troves of CMM. However, So far, little or no review work has been reported to conclude anti-AD drugs from CMM in literature. Therefore, a systematic introduction of CMM anti-AD research progress is of great importance and necessity. This paper strives to systematically describe the progress of CMM in the treatment of AD, and lays a basis data for anti-AD drug development from CMM, and provides the essential theoretical support for the further development and utilization of CMM resources through a more comprehensive research of the variety of databases regarding CMM anti-AD effects reports. Literature survey was performed via electronic search (SciFinder®, Pubmed®, Google Scholar and Web of Science) on papers and patents and by systematic research in ethnopharmacological literature at various university libraries. This review mainly introduces the current research on the Chinese Material Medica (CMM) theoretical research on Alzheimer's disease (AD), anti-AD active constituent of CMM, anti-AD effects on AD models, anti-AD mechanism of CMM, and anti-AD effect of CMM formula. Scholars around the world have made studies on the anti-AD molecular mechanism of CMM from different pathways, and have made substantial progress. The progress not only enriched the anti-AD theory of CMM, but also provided clinical practical significance and development prospects in using CMM to treat AD. Western pure drugs cannot replace the advantages of

  19. Potential Relationship between Season of Birth and Clinical Characteristics in Major Depressive Disorder in Koreans: Results from the CRESCEND Study.

    Science.gov (United States)

    Park, Seon-Cheol; Sakong, Jeong-Kyu; Koo, Bon Hoon; Kim, Jae-Min; Jun, Tae-Youn; Lee, Min-Soo; Kim, Jung-Bum; Yim, Hyeon-Woo; Park, Yong Chon

    2016-05-01

    We aimed to examine the potential relationship between season of birth (SOB) and clinical characteristics in Korean patients with unipolar non-psychotic major depressive disorder (MDD). Using data from the Clinical Research Center for Depression (CRESCEND) study in South Korea, 891 MDD patients were divided into two groups, those born in spring/summer (n=457) and those born in autumn/winter (n=434). Measurement tools comprising the Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, Brief Psychiatric Rating Scale, Scale for Suicidal Ideation, Clinical Global Impression of severity, Social and Occupation Functional Assessment Scale, WHO Quality of Life assessment instrument-abbreviated version, Alcohol Use Disorder Identification Test, and Temperament and Character Inventory were used to evaluate depression, anxiety, overall symptoms, suicidal ideation, global severity, social function, quality of life, drinking, and temperament and character, respectively. Using independent t-tests for continuous variables and χ² tests for discrete variables, the clinical characteristics of the two groups were compared. MDD patients born in spring/summer were on average younger at onset of first depressive episode (t=2.084, p=0.038), had greater loss of concentration (χ²=4.589, p=0.032), and were more self-directed (t=2.256, p=0.025) than those born in autumn/winter. Clinically, there was a trend for the MDD patients born in spring/summer to display the contradictory characteristics of more severe clinical course and less illness burden; this may have been partly due to a paradoxical effect of the 5-HT system.

  20. Corticotropin-releasing factor peptide antagonists: design, characterization and potential clinical relevance.

    Science.gov (United States)

    Rivier, Jean E; Rivier, Catherine L

    2014-04-01

    Elusive for more than half a century, corticotropin-releasing factor (CRF) was finally isolated and characterized in 1981 from ovine hypothalami and shortly thereafter, from rat brains. Thirty years later, much has been learned about the function and localization of CRF and related family members (Urocortins 1, 2 and 3) and their 2 receptors, CRF receptor type 1 (CRFR1) and CRF receptor type 2 (CRFR2). Here, we report the stepwise development of peptide CRF agonists and antagonists, which led to the CRFR1 agonist Stressin1; the long-acting antagonists Astressin2-B which is specific for CRFR2; and Astressin B, which binds to both CRFR1 and CRFR2.This analog has potential for the treatment of CRF-dependent diseases in the periphery, such as irritable bowel syndrome. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. Maximum recovery potential of human tumor cells may predict clinical outcome in radiotherapy

    International Nuclear Information System (INIS)

    Weichselbaum, R.R.; Beckett, M.

    1987-01-01

    We studied inherent radiosensitivity/resistance (D0), ability to accumulate sublethal damage (n) and repair of potentially lethal damage (PLDR) in established human tumor cell lines as well as early passage human tumor cell lines derived from patients with known outcome following radiotherapy. Survival 24 hrs after treatment of human tumor cells with X rays in plateau phase cultures is a function of initial damage (D0, n), as well as recovery over 24 hrs (PLDR). A surviving fraction greater than .1 24 hrs following treatment with 7 Gy in plateau phase cultures is associated with tumor cell types (melanoma, osteosarcoma) with a high probability of radiotherapy failure or tumor cells derived from patients who actually failed radiotherapy. Therefore, total cellular recovery following radiation may be an important determinant of radiocurability. Accurate assays of radiotherapy outcome may need to account for all these radiobiological parameters

  2. Sensory action potentials of the maxillary nerve: a methodologic study with clinical implications

    DEFF Research Database (Denmark)

    Thygesen, Torben; Baad-Hansen, Lene; Svensson, Peter

    2009-01-01

    PURPOSE: Recently, recording of sensory nerve action potentials (SNAPs) of the inferior alveolar nerve (IAN) was described and is used as a diagnostic test of traumatic neuropathic trigeminal disorders. The technique is limited to IAN damage; therefore, we adapted the technique to the maxillary...... nerve, which is also frequently injured by either trauma or orthognathic surgery. PATIENTS AND METHODS: Fourteen healthy volunteers participated in this methodologic study in which the infraorbital nerve (ION) was stimulated with 2 needle electrodes. The SNAPs were recorded from the maxillary nerve...... difference. Repeated tests within a session test demonstrated no significant differences in the latency data (ANOVA: P= .225) or amplitude data (ANOVA: P= .44). Stimulus-response curves indicated that the SNAPs saturated at 5.1+/-4.4 mA stimulus intensity. In 1 subject, stimulation of the mental nerve...

  3. Status and promise of fuel cell technology

    Energy Technology Data Exchange (ETDEWEB)

    Williams, M.C. [National Energy Technology Lab., Pittsburgh, PA (United States). Dept. of Energy

    2001-09-01

    The niche or early entry market penetration by ONSI and its phosphoric acid fuel cell technology has proven that fuel cells are reliable and suitable for premium power and other opportunity fuel niche market applications. Now, new fuel cell technologies - solid oxide fuel cells, molten carbonate fuel cells, and polymer electrolyte fuel cells - are being developed for near-term distributed generation shortly after 2003. Some of the evolving fuel cell systems are incorporating gas turbines in hybrid configurations. The combination of the gas turbine with the fuel cell promises to lower system costs and increase efficiency to enhance market penetration. Market estimates indicate that significant early entry markets exist to sustain the initially high cost of some distributed generation technologies. However, distributed generation technologies must have low introductory first cost, low installation cost, and high system reliability to be viable options in competitive commercial and industrial markets. In the long-term, solid state fuel cell technology with stack costs under $100/kilowatt (kW) promises deeper and wider market penetration in a range of applications including a residential, auxillary power, and the mature distributed generation markets. The solid state energy conversion alliance (SECA) with its vision for fuel cells in 2010 was recently formed to commercialize solid state fuel cells and realize the full potential of the fuel cell technology. Ultimately, the SECA concept could lead to megawatt-size fuel-cell systems for commercial and industrial applications and Vision 21 fuel cell turbine hybrid energy plants in 2015. (orig.)

  4. Promises in intelligent plant control systems

    International Nuclear Information System (INIS)

    Otaduy, P.J.

    1987-01-01

    The control system is the brain of a power plant. The traditional goal of control systems has been productivity. However, in nuclear power plants the potential for disaster requires safety to be the dominant concern, and the worldwide political climate demands trustworthiness for nuclear power plants. To keep nuclear generation as a viable option for power in the future, trust is the essential critical goal which encompasses all others. In most of today's nuclear plants the control system is a hybrid of analog, digital, and human components that focuses on productivity and operates under the protective umbrella of an independent engineered safety system. Operation of the plant is complex, and frequent challenges to the safety system occur which impact on their trustworthiness. Advances in nuclear reactor design, computer sciences, and control theory, and in related technological areas such as electronics and communications as well as in data storage, retrieval, display, and analysis have opened a promise for control systems with more acceptable human brain-like capabilities to pursue the required goals. This paper elaborates on the promise of futuristic nuclear power plants with intelligent control systems and addresses design requirements and implementation approaches

  5. Deciphering spreading mechanisms in amyotrophic lateral sclerosis: clinical evidence and potential molecular processes.

    Science.gov (United States)

    Pradat, Pierre-François; Kabashi, Edor; Desnuelle, Claude

    2015-10-01

    The aim of this review is to refer to recent arguments supporting the existence of specific propagation mechanisms associated with spreading of neuron injury in amyotrophic lateral sclerosis (ALS). Misfolded ALS-linked protein accumulation can induce aggregation of their native equivalent isoforms through a mechanism analogous to the infectious prion proteins initiation and its propagation. Although ALS is clinically heterogeneous, a shared characteristic is the focal onset and the progressive extension to all body regions. Being viewed until now as just summation of the increased number of affected neurons, dispersion is now rather considered as the result of a seeded self-propagating process. A sequential regional spreading pattern is supported by the distribution of TDP-43 aggregates in ALS autopsy cases. Electrophysiology and advanced neuroimaging methods also recently provided some evidence for propagation of lesions both in the brain and spinal cord, more longitudinal studies being still needed. Lesions are supposed to spread cell-to-cell regionally or through connected neuronal pathway. At the molecular level, the prion-like spreading is an emerging mechanism hypothesis, but other machineries such as those that are in charge of dealing with misfolded proteins and secretion of deleterious peptides may be involved in the propagation of neuron loss. Deciphering the mechanisms underlying spreading of ALS symptoms is of crucial importance to better understand this neurodegenerative disease, build new and appropriate animal models and to define novel therapeutic targets.

  6. Hypnosis in the Perioperative Management of Breast Cancer Surgery: Clinical Benefits and Potential Implications

    Science.gov (United States)

    Roelants, Fabienne; Pospiech, Audrey; Momeni, Mona; Watremez, Christine

    2016-01-01

    The aim of this review is to summarize data published on the use of perioperative hypnosis in patients undergoing breast cancer surgery (BCS). Indeed, the majority of BCS patients experience stress, anxiety, nausea, vomiting, and pain. Correct management of the perioperative period and surgical removal of the primary tumor are clearly essential but can affect patients on different levels and hence have a negative impact on oncological outcomes. This review examines the effect of clinical hypnosis performed during the perioperative period. Thanks to its specific properties and techniques allowing it to be used as complementary treatment preoperatively, hypnosis has an impact most notably on distress and postoperative pain. During surgery, hypnosis may be applied to limit immunosuppression, while, in the postoperative period, it can reduce pain, anxiety, and fatigue and improve wound healing. Moreover, hypnosis is inexpensive, an important consideration given current financial concerns in healthcare. Of course, large randomized prospective studies are now needed to confirm the observed advantages of hypnosis in the field of oncology. PMID:27635132

  7. Psychological variables potentially implicated in opioid-related mortality as observed in clinical practice.

    Science.gov (United States)

    Passik, Steven D; Lowery, Amy

    2011-06-01

    Opioid-related deaths in the United States have become a public health problem, with accidental and unintended overdoses being especially troubling. Screening for psychological risk factors is an important first step in safeguarding against nonadherence practices and identifying patients who may be vulnerable to the risks associated with opioid therapy. Validated screening instruments can aid in this attempt as a complementary tool to clinicians' assessments. A structured screening is imperative as part of an assessment, as clinician judgment is not the most reliable method of identifying nonadherence. As a complement to formal screening, we present for discussion and possible future study certain psychological variables observed during years of clinical practice that may be linked to medication nonadherence and accidental overdose. These variables include catastrophizing, fear, impulsivity, attention deficit disorders, existential distress, and certain personality disorders. In our experience, chronic pain patients with dual diagnoses may become "chemical copers" as a way of coping with their negative emotion. For these patients, times of stress could lead to accidental overdose. Behavioral, cognitive-behavioral (acceptance and commitment, dialectical behavior), existential (meaning-centered, dignity), and psychotropic therapies have been effective in treating these high-risk comorbidities, while managing expectations of pain relief appears key to preventing accidental overdose. Wiley Periodicals, Inc.

  8. The capsular group B meningococcal vaccine, 4CMenB : clinical experience and potential efficacy.

    Science.gov (United States)

    Rollier, Christine S; Dold, Christina; Marsay, Leanne; Sadarangani, Manish; Pollard, Andrew J

    2015-01-01

    Capsular group B meningococcal disease is a leading cause of childhood meningitis and septicaemia. Up to 10% of sufferers die, and sequelae remain in > 30% of survivors. A vaccine, four component meningococcal group B ( 4CMenB ), designed with the aim to induce broad coverage against this highly variable bacterium, has been licensed in countries including in the European Union, Canada and Australia. Immunogenicity and safety data, published in peer-reviewed literature between 2004 and 2014, are presented in the context of the recent recommendation for the use of the vaccine in infants in the UK. 4CMenB induces significant reactogenicity when administered with routine infant vaccines, in particular with respect to fever rates. Fevers can be somewhat reduced using paracetamol. The efficacy of the vaccine is unknown but has been extrapolated from effectiveness data obtained from use of one of its components in New Zealand, immunogenicity data from clinical trials and estimation of coverage from in vitro studies. These data suggest that the vaccine will prevent a proportion of invasive meningococcal disease cases in infants and young children. Implementation and well-planned post-marketing surveillance will address uncertainties over field effectiveness.

  9. Nonword repetition in children with cochlear implants: a potential clinical marker of poor language acquisition.

    Science.gov (United States)

    Nittrouer, Susan; Caldwell-Tarr, Amanda; Sansom, Emily; Twersky, Jill; Lowenstein, Joanna H

    2014-11-01

    Cochlear implants (CIs) can facilitate the acquisition of spoken language for deaf children, but challenges remain. Language skills dependent on phonological sensitivity are most at risk for these children, so having an effective way to diagnose problems at this level would be of value for school speech-language pathologists. The goal of this study was to assess whether a nonword repetition (NWR) task could serve that purpose. Participants were 104 second graders: 49 with normal hearing (NH) and 55 with CIs. In addition to NWR, children were tested on 10 measures involving phonological awareness and processing, serial recall of words, vocabulary, reading, and grammar. Children with CIs performed more poorly than children with NH on NWR, and sensitivity to phonological structure alone explained that performance for children in both groups. For children with CIs, 2 audiological factors positively influenced outcomes on NWR: being identified with hearing loss at a younger age and having experience with wearing a hearing aid on the unimplanted ear at the time of receiving a 1st CI. NWR scores were better able to rule out than to rule in such language deficits. Well-designed NWR tasks could have clinical utility in assessments of language acquisition for school-age children with CIs.

  10. An evaluation of the infection control potential of a UV clinical podiatry unit.

    Science.gov (United States)

    Humphreys, Paul N; Davies, Chris S; Rout, Simon

    2014-02-28

    Infection control is a key issue in podiatry as it is in all forms of clinical practice. Airborne contamination may be particularly important in podiatry due to the generation of particulates during treatment. Consequently, technologies that prevent contamination in podiatry settings may have a useful role. The aims of this investigation were twofold, firstly to determine the ability of a UV cabinet to protect instruments from airborne contamination and secondly to determine its ability to remove microbes from contaminated surfaces and instruments. A UV instrument cabinet was installed in a University podiatry suite. Impact samplers and standard microbiological techniques were used to determine the nature and extent of microbial airborne contamination. Sterile filters were used to determine the ability of the UV cabinet to protect exposed surfaces. Artificially contaminated instruments were used to determine the ability of the cabinet to remove microbial contamination. Airborne bacterial contamination was dominated by Gram positive cocci including Staphylococcus aureus. Airborne fungal levels were much lower than those observed for bacteria. The UV cabinet significantly reduced (p podiatry settings due to the presence of S. aureus. The use of a UV instrument cabinet can reduce the risk of contamination by airborne microbes. The UV cabinet tested was unable to decontaminate instruments and as such could pose an infection risk if misused.

  11. The role of cannabinoids in prostate cancer: Basic science perspective and potential clinical applications

    Directory of Open Access Journals (Sweden)

    Juan A Ramos

    2012-01-01

    Full Text Available Prostate cancer is a global public health problem, and it is the most common cancer in American men and the second cause for cancer-related death. Experimental evidence shows that prostate tissue possesses cannabinoid receptors and their stimulation results in anti-androgenic effects. To review currently relevant findings related to effects of cannabinoid receptors in prostate cancer. PubMed search utilizing the terms "cannabis," "cannabinoids," "prostate cancer," and "cancer pain management," giving preference to most recent publications was done. Articles identified were screened for their relevance to the field of prostate cancer and interest to both urologist and pain specialists. Prostate cancer cells possess increased expression of both cannabinoid 1 and 2 receptors, and stimulation of these results in decrease in cell viability, increased apoptosis, and decreased androgen receptor expression and prostate-specific antigen excretion. It would be of interest to conduct clinical studies utilizing cannabinoids for patients with metastatic prostate cancer, taking advantage not only of its beneficial effects on prostate cancer but also of their analgesic properties for bone metastatic cancer pain.

  12. The pharmacokinetics and clinical efficacy of AVP-825: a potential advancement for acute treatment of migraine.

    Science.gov (United States)

    Cady, Roger

    2015-01-01

    Oral triptans have dominated the prescription market for acute treatment of migraine for nearly 25 years. Today, patients often express dissatisfaction with prescribed acute treatment in part because they do not have confidence that the therapy will provide consistent efficacy over time. Major limitations to sustained successful use of oral triptans are their relatively slow onset of meaningful clinical benefit and variable absorption/efficacy due to impaired gastrointestinal function during migraine. AVP-825, a new intranasal delivery system for sumatriptan , may be an effective alternative to oral triptans. This article reviews AVP-825, which deposits low-dose sumatriptan powder deep into the vascular mucosa of the posterior nose, allowing rapid absorption of drug into the systemic circulation. Studies suggest that AVP-825 is a highly effective, well-tolerated acute treatment for episodic migraine. Oral triptans are limited in providing effective patient-centered outcomes to migraine patients. Failed or suboptimal abortive treatment of migraine is a major driver of migraine chronification and increases in healthcare costs. AVP-825 is an easy to use, novel, breath-powered intranasal delivery system that provides early onset of efficacy with low systemic drug exposure and few triptan-associated adverse events. AVP-825 will be a welcomed therapeutic tool for the acute treatment of migraine.

  13. Submitted for your consideration: potential advantages of a novel clinical trial design and initial patient reaction

    Directory of Open Access Journals (Sweden)

    Matthew Shane Loop

    2012-08-01

    Full Text Available In many circumstances, individuals do not respond identically to the same treatment. This phenomenon, which is called treatment response heterogeneity (TRH, appears to be present in treatments for many conditions, including obesity. Estimating the total amount of TRH, predicting an individual’s response, and identifying the mediators of TRH are of interest to biomedical researchers. Clinical investigators and physicians commonly postulate that some of these mediators could be genetic. Current designs can estimate TRH as a function of specific, measurable observed factors; however, they cannot estimate the total amount of TRH, nor provide reliable estimates of individual persons’ responses. We propose a new repeated randomizations design (RRD, which can be conceived as a generalization of the Balaam design, that would allow estimates of that variability and facilitate estimation of the total amount of TRH, prediction of an individual’s response, and identification of the mediators of TRH. In a pilot study, we asked 118 subjects entering a weight loss trial for their opinion of the RRD, and they stated a preference for the RRD over the conventional 2-arm parallel groups design. Research is needed as to how the RRD will work in practice and its relative statistical properties, and we invite dialogue about it.

  14. Potential clinical impact of radionuclide imaging technologies: highlights of the ITBS 2003 meeting

    Energy Technology Data Exchange (ETDEWEB)

    Itti, Roland E-mail: roland.itti@univ-lyon1.fr

    2004-07-11

    Radiopharmaceuticals are major determinants of progress in Nuclear Medicine. Besides {sup 18}FDG, the most common PET tracer, several other molecules are under evaluation, such as {sup 18}F-fluoride for bone studies, numerous ligands for neurotransmission, {sup 18}F-DOPA for neuro-endocrine tumors or generator produced {sup 68}Ga-peptides for various cancers. Nuclear medicine gradually changes for 'molecular imaging' and medical imaging, which was at the beginning mainly anatomic, has progressed in the direction of functional and metabolic imaging. The present challenge is to achieve some degree of 'in vivo' biochemistry or even histology or genetics. The importance of anatomic/functional image fusion justifies the development of combined PET-CT instrumentation, whose objectives have to be discussed in terms of anatomical landmarks and/or additional clinical information. The question of 'hard' or 'soft' image co-registration remains open, involving not only CT, but also SPECT or MRI. Development of dedicated imaging devices, whether single photon or positron, is of major interest for breast imaging, allowing optimal imaging conditions, with results definitely superior to classical gamma-cameras or PET. The patient population concerned with scintimammography is still controversial, as well as the imaging modalities: FDG or sestaMIBI, planar or tomographic, scintillators or semi-conductors, and the research field remains open. This is also valid for external or per-operative probe systems for tumor or lymph nodes localization.

  15. Clinical Characterization of Gastric Antral Vascular Ectasia: A Potential Manifestation of the Metabolic Syndrome.

    Science.gov (United States)

    Smith, Elliot; Tekola, Bezawit; Patrie, James; Cornella, Scott; Caldwell, Stephen

    2016-12-01

    Gastric antral vascular ectasia is a relatively common endoscopic finding. Past studies have shown an association of gastric antral vascular ectasia with cirrhosis and autoimmune disorders. We aimed to re-examine these associations and to investigate a possible association of gastric antral vascular ectasia with features of the metabolic syndrome. There were 135 patients with a diagnosis of gastric antral vascular ectasia from years 1995-2013 seen at the University of Virginia who were identified from a clinical data repository and age and sex matched to a cohort of patients without gastric antral vascular ectasia undergoing endoscopy within the same time frame as the index cases. The groups were compared for comorbidities including autoimmune disease, cirrhosis, vascular disease, body mass index (BMI), diabetes mellitus, and cirrhosis due to nonalcoholic steatohepatitis. Sixty-four percent of gastric antral vascular ectasia patients were cirrhotic, compared with 14% of controls (P correlation of gastric antral vascular ectasia with features of metabolic syndrome such as diabetes, BMI, vascular disease, and nonalcoholic steatohepatitis cirrhosis. The pathophysiology of gastric antral vascular ectasia remains uncertain, but we speculate that it may be a manifestation of the metabolic syndrome. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Potential of robots as next-generation technology for clinical assessment of neurological disorders and upper-limb therapy.

    Science.gov (United States)

    Scott, Stephen H; Dukelow, Sean P

    2011-01-01

    Robotic technologies have profoundly affected the identification of fundamental properties of brain function. This success is attributable to robots being able to control the position of or forces applied to limbs, and their inherent ability to easily, objectively, and reliably quantify sensorimotor behavior. Our general hypothesis is that these same attributes make robotic technologies ideal for clinically assessing sensory, motor, and cognitive impairments in stroke and other neurological disorders. Further, they provide opportunities for novel therapeutic strategies. The present opinionated review describes how robotic technologies combined with virtual/augmented reality systems can support a broad range of behavioral tasks to objectively quantify brain function. This information could potentially be used to provide more accurate diagnostic and prognostic information than is available from current clinical assessment techniques. The review also highlights the potential benefits of robots to provide upper-limb therapy. Although the capital cost of these technologies is substantial, it pales in comparison with the potential cost reductions to the overall healthcare system that improved assessment and therapeutic interventions offer.

  17. Potential clinical applications of halichondrins in breast cancer and other neoplasms

    Directory of Open Access Journals (Sweden)

    Ortega V

    2012-02-01

    Full Text Available Vanesa Ortega1, Javier Cortés1,21Department of Oncology, Vall d’Hebrón University Hospital, Barcelona, Spain; 2Vall d’Hebron Institute of Oncology (VHIO, Barcelona, SpainAbstract: Halichondrin B is a large polyether macrolide found in a rare Japanese sponge, Halichondria okadai and has been shown to have anticancer activity. Eribulin mesylate is a completely synthetic analog of halichondrin B with a unique mechanism of action relative to other antimicrotubule agents. This new agent has demonstrated activity in preclinical studies, and it is being developed for the treatment of different tumor types. Eribulin has been approved by the United States Food and Drug Administration and the European Medicines Agency as late-line therapy for metastatic breast cancer patients previously treated with an anthracycline and a taxane. It has demonstrated superiority over other treatments in overall survival (OS (hazard ratio: 0.81, P = 0.041, leading to its regulatory approbation for clinical practice use. Median OS for the eribulin-treated group was 13.1 months versus 10.6 months in the physician’s treatment-of-choice group. Eribulin demonstrated a manageable toxicity profile. Most common adverse events associated with treatment were mild neutropenia and fatigue, mainly of grade 1 or 2. In contrast to other antimicrotubule agents, eribulin has a relatively low incidence of peripheral neuropathy and alopecia. Eribulin has been extensively studied in breast cancer and is currently being developed for treatment of other cancer types. Eribulin has demonstrated activity in Phase II trials in non-small cell lung cancer, pancreatic cancer, urothelial tract cancer, and sarcomas. Further studies in these cancers are ongoing. This article reviews pharmacology, mechanism of action, pharmacokinetics and efficacy of eribulin in breast cancer and other neoplasms.Keywords: halichondrin B, eribulin, antimicrotubule, metastatic breast cancer

  18. Developmental neurotoxicity of the organophosphorus insecticide chlorpyrifos: from clinical findings to preclinical models and potential mechanisms.

    Science.gov (United States)

    Burke, Richard D; Todd, Spencer W; Lumsden, Eric; Mullins, Roger J; Mamczarz, Jacek; Fawcett, William P; Gullapalli, Rao P; Randall, William R; Pereira, Edna F R; Albuquerque, Edson X

    2017-08-01

    Organophosphorus (OP) insecticides are pest-control agents heavily used worldwide. Unfortunately, they are also well known for the toxic effects that they can trigger in humans. Clinical manifestations of an acute exposure of humans to OP insecticides include a well-defined cholinergic crisis that develops as a result of the irreversible inhibition of acetylcholinesterase (AChE), the enzyme that hydrolyzes the neurotransmitter acetylcholine (ACh). Prolonged exposures to levels of OP insecticides that are insufficient to trigger signs of acute intoxication, which are hereafter referred to as subacute exposures, have also been associated with neurological deficits. In particular, epidemiological studies have reported statistically significant correlations between prenatal subacute exposures to OP insecticides, including chlorpyrifos, and neurological deficits that range from cognitive impairments to tremors in childhood. The primary objectives of this article are: (i) to address the short- and long-term neurological issues that have been associated with acute and subacute exposures of humans to OP insecticides, especially early in life (ii) to discuss the translational relevance of animal models of developmental exposure to OP insecticides, and (iii) to review mechanisms that are likely to contribute to the developmental neurotoxicity of OP insecticides. Most of the discussion will be focused on chlorpyrifos, the top-selling OP insecticide in the United States and throughout the world. These points are critical for the identification and development of safe and effective interventions to counter and/or prevent the neurotoxic effects of these chemicals in the developing brain. This is an article for the special issue XVth International Symposium on Cholinergic Mechanisms. © 2017 International Society for Neurochemistry.

  19. Solar power's rise and promise

    OpenAIRE

    Pernia, Ernesto M.; Generoso, Maria Janela M.

    2015-01-01

    Time was when solar energy was facilely dismissed as impractical, inefficient, and pricey. In recent years, however, innovations in technology, regulation, and financing have resulted in remarkable efficiency improvements and price reductions, thereby reversing the skepticism about this renewable energy (RE) source. In this paper, we explore how this has happened, to what extent photovoltaic solar technology has been accepted around the world, and what might be its potential for inclusive gre...

  20. An exordium to a promise

    OpenAIRE

    Moslemi, Amir Abbas

    2015-01-01

    James Joyce’s fine shades of philosophy have been neglected in recent times, especially when it comes to fill either epistemological or ontological lacuna in taxonomy as to whereabouts of his canon. Epistemology and ontology are a couple of the core areas of philosophy. Since mirroring cognitive and post-cognitive questions in postmodern literature may invite a rereading of potential authors, a historiography of "theory of knowledge" and ontological nuances is reviewed in this paper not to re...

  1. TH-B-BRC-00: How to Identify and Resolve Potential Clinical Errors Before They Impact Patients Treatment: Lessons Learned

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2016-06-15

    Radiation treatment consists of a chain of events influenced by the quality of machine operation, beam data commissioning, machine calibration, patient specific data, simulation, treatment planning, imaging and treatment delivery. There is always a chance that the clinical medical physicist may make or fail to detect an error in one of the events that may impact on the patient’s treatment. In the clinical scenario, errors may be systematic and, without peer review, may have a low detectability because they are not part of routine QA procedures. During treatment, there might be errors on machine that needs attention. External reviews of some of the treatment delivery components by independent reviewers, like IROC, can detect errors, but may not be timely. The goal of this session is to help junior clinical physicists identify potential errors as well as the approach of quality assurance to perform a root cause analysis to find and eliminate an error and to continually monitor for errors. A compilation of potential errors will be presented by examples of the thought process required to spot the error and determine the root cause. Examples may include unusual machine operation, erratic electrometer reading, consistent lower electron output, variation in photon output, body parts inadvertently left in beam, unusual treatment plan, poor normalization, hot spots etc. Awareness of the possibility and detection of error in any link of the treatment process chain will help improve the safe and accurate delivery of radiation to patients. Four experts will discuss how to identify errors in four areas of clinical treatment. D. Followill, NIH grant CA 180803.

  2. TH-B-BRC-00: How to Identify and Resolve Potential Clinical Errors Before They Impact Patients Treatment: Lessons Learned

    International Nuclear Information System (INIS)

    2016-01-01

    Radiation treatment consists of a chain of events influenced by the quality of machine operation, beam data commissioning, machine calibration, patient specific data, simulation, treatment planning, imaging and treatment delivery. There is always a chance that the clinical medical physicist may make or fail to detect an error in one of the events that may impact on the patient’s treatment. In the clinical scenario, errors may be systematic and, without peer review, may have a low detectability because they are not part of routine QA procedures. During treatment, there might be errors on machine that needs attention. External reviews of some of the treatment delivery components by independent reviewers, like IROC, can detect errors, but may not be timely. The goal of this session is to help junior clinical physicists identify potential errors as well as the approach of quality assurance to perform a root cause analysis to find and eliminate an error and to continually monitor for errors. A compilation of potential errors will be presented by examples of the thought process required to spot the error and determine the root cause. Examples may include unusual machine operation, erratic electrometer reading, consistent lower electron output, variation in photon output, body parts inadvertently left in beam, unusual treatment plan, poor normalization, hot spots etc. Awareness of the possibility and detection of error in any link of the treatment process chain will help improve the safe and accurate delivery of radiation to patients. Four experts will discuss how to identify errors in four areas of clinical treatment. D. Followill, NIH grant CA 180803

  3. Cyanobacteria: Promising biocatalysts for sustainable chemical production.

    Science.gov (United States)

    Knoot, Cory J; Ungerer, Justin; Wangikar, Pramod P; Pakrasi, Himadri B

    2018-04-06

    Cyanobacteria are photosynthetic prokaryotes showing great promise as biocatalysts for the direct conversion of CO 2 into fuels, chemicals, and other value-added products. Introduction of just a few heterologous genes can endow cyanobacteria with the ability to transform specific central metabolites into many end products. Recent engineering efforts have centered around harnessing the potential of these microbial biofactories for sustainable production of chemicals conventionally produced from fossil fuels. Here, we present an overview of the unique chemistry that cyanobacteria have been co-opted to perform. We highlight key lessons learned from these engineering efforts and discuss advantages and disadvantages of various approaches. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

  4. Halopentacenes: Promising Candidates for Organic Semiconductors

    International Nuclear Information System (INIS)

    Gong-He, Du; Zhao-Yu, Ren; Ji-Ming, Zheng; Ping, Guo

    2009-01-01

    We introduce polar substituents such as F, Cl, Br into pentacene to enhance the dissolubility in common organic solvents while retaining the high charge-carrier mobilities of pentacene. Geometric structures, dipole moments, frontier molecule orbits, ionization potentials and electron affinities, as well as reorganization energies of those molecules, and of pentacene for comparison, are successively calculated by density functional theory. The results indicate that halopentacenes have rather small reorganization energies (< 0.2 eV), and when the substituents are in position 2 or positions 2 and 9, they are polarity molecules. Thus we conjecture that they can easily be dissolved in common organic solvents, and are promising candidates for organic semiconductors. (condensed matter: electronicstructure, electrical, magnetic, and opticalproperties)

  5. Nanomedicine delivers promising treatments for rheumatoid arthritis.

    Science.gov (United States)

    Prasad, Leena Kumari; O'Mary, Hannah; Cui, Zhengrong

    2015-01-01

    An increased understanding in the pathophysiology of chronic inflammatory diseases, such as rheumatoid arthritis, reveals that the diseased tissue and the increased presence of macrophages and other overexpressed molecules within the tissue can be exploited to enhance the delivery of nanomedicine. Nanomedicine can passively accumulate into chronic inflammatory tissues via the enhanced permeability and retention phenomenon, or be surface conjugated with a ligand to actively bind to receptors overexpressed by cells within chronic inflammatory tissues, leading to increased efficacy and reduced systemic side-effects. This review highlights the research conducted over the past decade on using nanomedicine for potential treatment of rheumatoid arthritis and summarizes some of the major findings and promising opportunities on using nanomedicine to treat this prevalent and chronic disease.

  6. The potential carcinogenic risk of tanning beds: clinical guidelines and patient safety advice

    Directory of Open Access Journals (Sweden)

    Mette Mogensen

    2010-10-01

    Full Text Available Mette Mogensen1, Gregor BE Jemec21Department of Dermatology, Gentofte Hospital, Hellerup, Denmark; 2Department of Dermatology, Roskilde Hospital, Health Sciences Faculty, University of Copenhagen, Roskilde, DenmarkIntroduction: In 2009, the WHO listed ultraviolet (UV radiation as a group 1 carcinogen. In spite of this, each year, millions of people tan indoor in Western countries. The aim of this review is to summarize evidence of tanning bed carcinogenesis and to present guidelines for use of tanning beds and patient safety advice.Methods: A narrative review of the literature was conducted based on both PubMed and Medline searches and on literature review of the retrieved papers.Results: Use of indoor tanning beds represents a significant and avoidable risk factor for the development of both melanoma and nonmelanoma skin cancers. Frequent tanners are more often adolescent females. Tanning beds have additional potential adverse effects such as burns, solar skin damage, infection, and possibly also addictive behavior.Discussion: The effort in preventing UV light-induced carcinogenesis should currently be aimed at developing new strategies for public health information. Tanning beds are one preventable source of UV radiation. In the majority of people solar UV radiation continues to be the major factor and therefore anti-tanning campaigns must always include sunbathers.Keywords: tanning beds, skin cancers, melanoma, nonmelanoma

  7. The potential carcinogenic risk of tanning beds: clinical guidelines and patient safety advice

    International Nuclear Information System (INIS)

    Mogensen, Mette; Jemec, Gregor BE

    2010-01-01

    In 2009, the WHO listed ultraviolet (UV) radiation as a group 1 carcinogen. In spite of this, each year, millions of people tan indoor in Western countries. The aim of this review is to summarize evidence of tanning bed carcinogenesis and to present guidelines for use of tanning beds and patient safety advice. A narrative review of the literature was conducted based on both PubMed and Medline searches and on literature review of the retrieved papers. Use of indoor tanning beds represents a significant and avoidable risk factor for the development of both melanoma and nonmelanoma skin cancers. Frequent tanners are more often adolescent females. Tanning beds have additional potential adverse effects such as burns, solar skin damage, infection, and possibly also addictive behavior. The effort in preventing UV light-induced carcinogenesis should currently be aimed at developing new strategies for public health information. Tanning beds are one preventable source of UV radiation. In the majority of people solar UV radiation continues to be the major factor and therefore anti-tanning campaigns must always include sunbathers

  8. Clinical application of multifocal visual evoked potentials in children with epilepsy caused by intracranial disease

    International Nuclear Information System (INIS)

    Yukawa, Eiichi; Kim, Yeong-Jin; Kawasaki, Kensuke; Yoshii, Toshiaki; Hara, Yoshiaki

    2006-01-01

    We investigated whether visual field defects could be objectively evaluated using multifocal visual evoked potential (m-VEP) in two children with epilepsy caused by intracranial disease in whom it was difficult to measure the visual field. To determine normal waves in m-VEP, recording was performed using a visual evoked response imaging system (VERIS) Junior Science program (Mayo, Aichi, Japan) in 20 healthy children (20 eyes) peak latency and amplitude were used for assessment. In the two children with epilepsy, m-VEPs were recorded, and compared with the results of static perimetry or the lesions observed by Magnetic Resonance Imaging (MRI). In the 20 healthy children, there was no significant difference in the peak latency or amplitude among 4 quadrants by one-way analysis of variance. m-VEP in the children with epilepsy showed abnormal waves, corresponding to the visual field defects in the static perimetry or the lesions observed by MRI. Objective evaluation of visual field defects using m-VEP may be useful in children with epilepsy caused by intracranial disease in whom kinetic/static perimetry as a subjective examination is difficult. (author)

  9. Potential of cancer cell-derived exosomes in clinical application: a review of recent research advances.

    Science.gov (United States)

    Sun, Yu; Liu, Jing

    2014-06-01

    Exosomes are 30- to 100-nm, membrane-bound vesicles that are released by most types of cells, including tumor cells. Exosomes contain a great variety of bioactive molecules, including signal peptides, microRNA, lipids, and DNA. In cancer, tumor cells aberrantly secrete large quantities of exosomes to transport paracrine signals or to contribute to tumor-environment interaction at a distance. The goal of this review was to discuss the recent advances on the mechanism of cancer-derived exosomes in tumor regulation. Pertinent articles and abstracts were identified through searches of PubMed for literature published from 1983 to December 2013. Search terms included exosome, tumor, cancer, diagnosis, and therapy. All of the exposed evidence points to communication between cancer cells and their surroundings, either mediated by cancer cell-derived exosomes or by stromal cell-derived exosomes. This communication probably supports tumor proliferation, motility, invasion, angiogenesis, and premetastatic niche preparation. In addition, recent research implies that cancer cell-derived exosomes play a suppressive role in cancer-directed immune response. The biomarkers detected in bodily fluid-derived exosomes imply a potential for exosomes in cancer diagnosis. Also, exosomes could be used as a vehicle to selectively deliver therapeutic nucleic-acid drugs or conventional drugs for tumor therapy. The tolerability and feasibility of cancer exosomes in diagnosis and therapy need to be further evaluated. Copyright © 2014 Elsevier HS Journals, Inc. All rights reserved.

  10. Nanoparticles as potential clinical therapeutic agents in Alzheimer's disease: focus on selenium nanoparticles.

    Science.gov (United States)

    Nazıroğlu, Mustafa; Muhamad, Salina; Pecze, Laszlo

    2017-07-01

    In etiology of Alzheimer's disease (AD), involvement of amyloid β (Aβ) plaque accumulation and oxidative stress in the brain have important roles. Several nanoparticles such as titanium dioxide, silica dioxide, silver and zinc oxide have been experimentally using for treatment of neurological disease. In the last decade, there has been a great interest on combination of antioxidant bioactive compounds such as selenium (Se) and flavonoids with the oxidant nanoparticles in AD. We evaluated the most current data available on the physiological effects of oxidant and antioxidant nanoparticles. Areas covered: Oxidative nanoparticles decreased the activities of reactive oxygen species (ROS) scavenging enzymes such as glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase in the brain of rats and mice. However, Se-rich nanoparticles in small size (5-15 nm) depleted Aβ formation through decreasing ROS production. Reports on low levels of Se in blood and tissue samples and the low activities of GSH-Px, catalase and SOD enzymes in AD patients and animal models support the proposed crucial role of oxidative stress in the pathogenesis of AD. Expert commentary: In conclusion, present literature suggests that Se-rich nanoparticles appeared to be a potential therapeutic compound for the treatment of AD.

  11. Clinical impact of Positron Emission Tomography (PET) on oncological patients and their potentially application context

    International Nuclear Information System (INIS)

    Alonso, O.

    2006-01-01

    (PET) Positron Emission Tomography is a technique of nuclear medicine that has ability of detecting cancer through mechanisms based on molecular alterations of neoplastic processes. This review describes the PET Oncology applications and discusses the potential application of this technology in the sanitary and national academic framework . The most widely used in Oncology plotter is an analogue of laglucosa labelled with fluo: 18F-2-fluoro-2-Deoxy-D-glucose (FDG). In this way, the PET detects tumour retention of FDG, due to the highest glycolytic of cancer cells. In addition, the PET allow the study of the entire body at the same exploratory and some teams are coupled to systems of axial tomography (PET-CT). By ET-FDG, it is possible to diagnose, staging and restaged the majority of cancers, with diagnostic accuracy close to 90 per cent higher than the values provided by the conventional imaging techniques such. It is also possible to know early response to cancer treatments and obtain relevant medical prognosis information. (author) [es

  12. Volatile substance misuse : clinical considerations, neuropsychopharmacology and potential role of pharmacotherapy in management.

    Science.gov (United States)

    Garland, Eric L; Howard, Matthew O

    2012-11-01

    Volatile substance misuse is among the most prevalent and toxic forms of psychoactive drug use, and often results in highly deleterious social, psychological and medical consequences. The prevalence of this pernicious form of substance misuse owes in part to the fact that volatile substances of misuse are ubiquitous in the natural environment. Commonly misused commercial products include glue, shoe polish, nail polish remover, butane lighter fluid, gasoline and computer duster spray. National samples of volatile substance misusers tend to exhibit high rates of psychiatric problems and antisocial behaviour. In addition, cognitive impairments and affective dysregulation are often observed among these individuals. Volatile substances exert their complex neuropharmacological effects on dopaminergic, glutamatergic, GABAergic and serotoninergic receptor systems, as well as on cell membranes and ion channels. Concomitantly, pharmacotherapies for volatile substance abuse might profitably target a number of mechanisms, including reward circuitry in the brain, symptoms of craving and withdrawal, neuropsychiatric and emotional impairments that promote volatile substance abuse, and cognitive enhancement to rectify deficits in executive function. This review details the modes of use, subjective effects, epidemiology, adverse consequences, neuropsychopharmacology and drug treatment of volatile substance misuse, and discusses the potential role of novel forms of pharmacological intervention for this oft-overlooked public health threat of epidemic proportions.

  13. Drug-drug interactions involving lysosomes: mechanisms and potential clinical implications.

    Science.gov (United States)

    Logan, Randall; Funk, Ryan S; Axcell, Erick; Krise, Jeffrey P

    2012-08-01

    Many commercially available, weakly basic drugs have been shown to be lysosomotropic, meaning they are subject to extensive sequestration in lysosomes through an ion trapping-type mechanism. The extent of lysosomal trapping of a drug is an important therapeutic consideration because it can influence both activity and pharmacokinetic disposition. The administration of certain drugs can alter lysosomes such that their accumulation capacity for co-administered and/or secondarily administered drugs is altered. In this review the authors explore what is known regarding the mechanistic basis for drug-drug interactions involving lysosomes. Specifically, the authors address the influence of drugs on lysosomal pH, volume and lipid processing. Many drugs are known to extensively accumulate in lysosomes and significantly alter their structure and function; however, the therapeutic and toxicological implications of this remain controversial. The authors propose that drug-drug interactions involving lysosomes represent an important potential source of variability in drug activity and pharmacokinetics. Most evaluations of drug-drug interactions involving lysosomes have been performed in cultured cells and isolated tissues. More comprehensive in vivo evaluations are needed to fully explore the impact of this drug-drug interaction pathway on therapeutic outcomes.

  14. Estrogen Receptor β in Melanoma: From Molecular Insights to Potential Clinical Utility

    Directory of Open Access Journals (Sweden)

    Monica Marzagalli

    2016-10-01

    Full Text Available Cutaneous melanoma is an aggressive tumor with its incidence increasing faster than any other cancer in the past decades. Melanoma is a heterogeneous tumor, with most patients harboring mutations in the BRAF or NRAS oncogenes, leading to the overactivation of the MAPK/ERK and PI3K/Akt pathways. The current therapeutic approaches are based on therapies targeting mutated BRAF and the downstream pathway, and on monoclonal antibodies against the immune checkpoint blockade. However, treatment resistance and side effects are common events of these therapeutic strategies.Increasing evidence supports that melanoma is a hormone-related cancer. Melanoma incidence is higher in males than in females and females have a significant survival advantage over men. Estrogens exert their effects through estrogen receptors (ER and ERβ that exert opposite effects on cancer growth: ER is associated with a proliferative action and ERβ with an anticancer effect. ERβ is the predominant estrogen receptor in melanoma and its expression decreases in melanoma progression, supporting its role as a tumor suppressor. Thus, ERβ is now considered as an effective molecular target for melanoma treatment. 17β-estradiol was reported to inhibit melanoma cells proliferation. However, clinical trials did not provide the expected survival benefits. In vitro studies demonstrate that ERβ ligands inhibit the proliferation of melanoma cells harboring the NRAS (but not the BRAF mutation, suggesting that ERβ activation might impair melanoma development through the inhibition of the PI3K/Akt pathway. These data suggest that ERβ agonists might be considered as an effective treatment strategy, in combination with MAPK inhibitors, for NRAS mutant melanomas. In an era of personalized medicine, pretreatment evaluation of the expression of ER isoforms together with the concurrent oncogenic mutations should be considered before selecting the most appropriate therapeutic intervention

  15. Estrogen Receptor β in Melanoma: From Molecular Insights to Potential Clinical Utility

    Science.gov (United States)

    Marzagalli, Monica; Montagnani Marelli, Marina; Casati, Lavinia; Fontana, Fabrizio; Moretti, Roberta Manuela; Limonta, Patrizia

    2016-01-01

    Cutaneous melanoma is an aggressive tumor; its incidence has been reported to increase fast in the past decades. Melanoma is a heterogeneous tumor, with most patients harboring mutations in the BRAF or NRAS oncogenes, leading to the overactivation of the MAPK/ERK and PI3K/Akt pathways. The current therapeutic approaches are based on therapies targeting mutated BRAF and the downstream pathway, and on monoclonal antibodies against the immune checkpoint blockade. However, treatment resistance and side effects are common events of these therapeutic strategies. Increasing evidence supports that melanoma is a hormone-related cancer. Melanoma incidence is higher in males than in females, and females have a significant survival advantage over men. Estrogens exert their effects through estrogen receptors (ERα and ERβ) that affect cancer growth in an opposite way: ERα is associated with a proliferative action and ERβ with an anticancer effect. ERβ is the predominant ER in melanoma, and its expression decreases in melanoma progression, supporting its role as a tumor suppressor. Thus, ERβ is now considered as an effective molecular target for melanoma treatment. 17β-estradiol was reported to inhibit melanoma cells proliferation; however, clinical trials did not provide the expected survival benefits. In vitro studies demonstrate that ERβ ligands inhibit the proliferation of melanoma cells harboring the NRAS (but not the BRAF) mutation, suggesting that ERβ activation might impair melanoma development through the inhibition of the PI3K/Akt pathway. These data suggest that ERβ agonists might be considered as an effective treatment strategy, in combination with MAPK inhibitors, for NRAS mutant melanomas. In an era of personalized medicine, pretreatment evaluation of the expression of ER isoforms together with the concurrent oncogenic mutations should be considered before selecting the most appropriate therapeutic intervention. Natural compounds that specifically bind to

  16. Calcium sensing receptor as a novel mediator of adipose tissue dysfunction: mechanisms and potential clinical implications

    Directory of Open Access Journals (Sweden)

    Roberto Bravo

    2016-09-01

    Full Text Available Obesity is currently a serious worldwide public health problem, reaching pandemic levels. For decades, dietary and behavioral approaches have failed to prevent this disease from expanding, and health authorities are challenged by the elevated prevalence of co-morbid conditions. Understanding how obesity-associated diseases develop from a basic science approach is recognized as an urgent task to face this growing problem. White adipose tissue is an active endocrine organ, with a crucial influence on whole-body homeostasis. White adipose tissue dysfunction plays a key role linking obesity with its associated diseases such as type 2 diabetes mellitus, cardiovascular disease and some cancers. Among the regulators of white adipose tissue physiology, the calcium-sensing receptor has arisen as a potential mediator of white adipose tissue dysfunction. Expression of the receptor has been described in human preadipocytes, adipocytes, and the human adipose cell lines LS14 and SW872. The evidence suggests that calcium-sensing receptor activation in the visceral (i.e. unhealthy white adipose tissue is associated with an increased proliferation of adipose progenitor cells and elevated adipocyte differentiation. In addition, exposure of adipose cells to calcium-sensing receptor activators in vitro elevates proinflammatory cytokine expression and secretion. An increased proinflammatory environment in white adipose tissue plays a key role in the development of white adipose tissue dysfunction that leads to peripheral organ fat deposition and insulin resistance, among other consequences. We propose that calcium-sensing receptor may be one relevant therapeutic target in the struggle to confront the health consequences of the current worldwide obesity pandemic.

  17. Clinical potential of necitumumab in non-small cell lung carcinoma

    Directory of Open Access Journals (Sweden)

    Genova C

    2016-08-01

    Full Text Available Carlo Genova,1–3 Fred R Hirsch1 1Division of Medical Oncology, Department of Medicine, University of Colorado Cancer Center, Aurora, CO, USA; 2Lung Cancer Unit, IRCCS AOU San Martino IST, 3Department of Internal Medicine, School of Medicine, University of Genoa, Genoa, Italy Abstract: Despite significant progress, new therapeutic approaches for advanced non-small cell lung cancer (NSCLC are highly needed, particularly for the treatment of patients with squamous cell carcinoma. The epidermal growth factor receptor (EGFR is often overexpressed in NSCLC and represents a relevant target for specific treatments. Although EGFR mutations are more frequent in non-squamous histology, the receptor itself is more often overexpressed in squamous NSCLC. Necitumumab is a human monoclonal antibody that is able to inhibit the EGFR pathway and cause antibody-dependent cell cytotoxicity. This drug has been studied in combination with first-line chemotherapy for advanced NSCLC in two Phase III trials, and a significant survival benefit was reported in squamous NSCLC (SQUIRE trial; by contrast, necitumumab did not prove itself beneficial in non-squamous histotype (INSPIRE trial. On the basis of the SQUIRE results, necitumumab was approved in combination with cisplatin and gemcitabine as a first-line treatment for advanced squamous NSCLC, both in the US and Europe, where its availability is limited to patients with EGFR-expressing tumors. The aim of this review is to describe the tolerability and the efficacy of necitumumab by searching the available published data and define its potential role in the current landscape of NSCLC treatment. Keywords: necitumumab, EGFR, non-small cell lung cancer, monoclonal antibody, H-score

  18. Strong ion and weak acid analysis in severe preeclampsia: potential clinical significance.

    Science.gov (United States)

    Ortner, C M; Combrinck, B; Allie, S; Story, D; Landau, R; Cain, K; Dyer, R A

    2015-08-01

    The influence of common disturbances seen in preeclampsia, such as changes in strong ions and weak acids (particularly albumin) on acid-base status, has not been fully elucidated. The aims of this study were to provide a comprehensive acid-base analysis in severe preeclampsia and to identify potential new biological predictors of disease severity. Fifty women with severe preeclampsia, 25 healthy non-pregnant- and 46 healthy pregnant controls (26-40 weeks' gestation), were enrolled in this prospective case-control study. Acid-base analysis was performed by applying the physicochemical approach of Stewart and Gilfix. Mean [sd] base excess was similar in preeclamptic- and healthy pregnant women (-3.3 [2.3], and -2.8 [1.5] mEq/L respectively). In preeclampsia, there were greater offsetting contributions to the base excess, in the form of hyperchloraemia (BE(Cl) -2 [2.3] vs -0.4 [2.3] mEq/L, Palkalosis was associated with a non-reassuring/abnormal fetal heart tracing (Prespiratory and hypoalbuminaemic alkalosis that was metabolically offset by acidosis, secondary to unmeasured anions and dilution. While the overall base excess in severe preeclampsia is similar to that in healthy pregnancy, preeclampsia is associated with a greater imbalance offsetting hypoalbuminaemic alkalosis and hyperchloraemic acidosis. Rather than the absolute value of base excess, the magnitude of these opposing contributors may be a better indicator of the severity of this disease. Hypoalbuminaemic alkalosis may also be a predictor of fetal compromise. clinicaltrials.gov: NCT 02164370. © The Author 2015. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  19. Characterization of Novel PI3Kδ Inhibitors as Potential Therapeutics for SLE and Lupus Nephritis in Pre-Clinical Studies.

    Science.gov (United States)

    Haselmayer, Philipp; Camps, Montserrat; Muzerelle, Mathilde; El Bawab, Samer; Waltzinger, Caroline; Bruns, Lisa; Abla, Nada; Polokoff, Mark A; Jond-Necand, Carole; Gaudet, Marilène; Benoit, Audrey; Bertschy Meier, Dominique; Martin, Catherine; Gretener, Denise; Lombardi, Maria Stella; Grenningloh, Roland; Ladel, Christoph; Petersen, Jørgen Søberg; Gaillard, Pascale; Ji, Hong

    2014-01-01

    SLE is a complex autoimmune inflammatory disease characterized by pathogenic autoantibody production as a consequence of uncontrolled T-B cell activity and immune-complex deposition in various organs, including kidney, leading to tissue damage and function loss. There is a high unmet need for better treatment options other than corticosteroids and immunosuppressants. Phosphoinositol-3 kinase δ (PI3Kδ) is a promising target in this respect as it is essential in mediating B- and T-cell function in mouse and human. We report the identification of selective PI3Kδ inhibitors that blocked B-, T-, and plasmacytoid dendritic cell activities in human peripheral blood and in primary cell co-cultures (BioMAP(®)) without detecting signs of undesired toxicity. In an IFNα-accelerated mouse SLE model, our PI3Kδ inhibitors blocked nephritis development, whether administered at the onset of autoantibody appearance or the onset of proteinuria. Disease amelioration correlated with normalized immune cell numbers in the spleen, reduced immune-complex deposition as well as reduced inflammation, fibrosis, and tissue damage in the kidney. Improvements were similar to those achieved with a frequently prescribed drug for lupus nephritis, the potent immunosuppressant mycophenolate mofetil. Finally, we established a pharmacodynamics/pharmacokinetic/efficacy model that revealed that a sustained PI3Kδ inhibition of 50% is sufficient to achieve full efficacy in our disease model. These data demonstrate the therapeutic potential of PI3Kδ inhibitors in SLE and lupus nephritis.

  20. Triple Reuptake Inhibitors: A Premise and Promise

    Science.gov (United States)

    Marks, David M.; Patkar, Ashwin A.

    2008-01-01

    On the horizon there is a new class of psychoactive medications which work by inhibiting the neuronal reuptake of serotonin, norepinephrine, and dopamine. There are multiple potential indications for these drugs. Research suggests that they may have a role in treating depressive disorders, and it is plausible they may have potential efficacy in obesity, addiction, and pain syndromes. The current review describes some of the molecules in development presently and explores the research relevant to possible clinical uses for this class of medications. PMID:20046357

  1. Food irradiation - Problems and promises

    International Nuclear Information System (INIS)

    Hickman, J.R.

    1974-01-01

    It has been stated that food irradiation represents the most significant discovery in food processing since Nicholas Appert invented canning in 1810. Certainly it is a process with great future potential; it is attractive because it works without heating the product, it is effective within sealed containers as well as for bulk usage, and it does not leave chemical residues on the treated food. Of course, no one process can be expected to solve all problems relating to preservation of food. Ionizing radiation can be used effectively to solve many of these problems, but the process is no panacea to cure the world's food problems. Unfortunately, early ill-founded claims about irradiation led to expectations which have proved beyond the reasonable capabilities of the process. Nevertheless, the number of foods that have been successfully treated, and the broad range of effects that can be achieved by radiation processing is impressive. (author)

  2. DNM3, p65 and p53 from exosomes represent potential clinical diagnosis markers for glioblastoma multiforme

    Science.gov (United States)

    Yang, Jian-kai; Song, Jian; Huo, Hao-ran; Zhao, Yin-long; Zhang, Guang-yu; Zhao, Zong-mao; Sun, Guo-zhu; Jiao, Bao-hua

    2017-01-01

    Background: Glioblastoma multiforme (GBM) is the most aggressive and deadly primary brain cancer that arises from astrocytes and classified as grade IV. Recently, exosomes have been reported as an essential mediator in diverse cancer carcinogenesis and metastasis. However, their role in GBM is still unclear. In this study, we aimed to investigate whether blood exosomes can be potential clinical diagnostic markers for GBM. Methods: We used a xenograft orthotopic mouse model to detect the differentially expressed genes in the brain and blood exosomes of original/recurrent GBM. Results: We found that recurrent GBM had stronger growth capacity and lethality than original GBM in the mouse model. A gene microarray of original tumors and blood exosomes from GBM orthotopic xenografts results showed that DNM3, p65 and CD117 expressions increased, whereas PTEN and p53 expressions decreased in both original tumors and blood exosomes. In the recurrent GBM tumor model, DNM3 and p65 showed increased expressions, whereas ST14 and p53 showed decreased expressions in tumor and blood exosomes of the recurrent GBM mouse model. Conclusion: In summary, we found that DNM3, p65 and p53 had a similar trend in brain and blood exosomes both for original and recurrent GBM, and could serve as potential clinical diagnostic markers for GBM. PMID:29449895

  3. Telepsychiatry in the developing world: Whither promised joy?

    Directory of Open Access Journals (Sweden)

    Subho Chakrabarti

    2016-01-01

    Full Text Available Telepsychiatry, the use of information and communication technologies to provide psychiatric services from a distance, has matured as a mode of service delivery and has expanded its reach since its inception. Telepsychiatry promotes equality of access to high-quality specialized care for underserved users. It enables, empowers and brings about high levels of satisfaction among users. Telepsychiatry can deliver a broad array of clinical services and support several other nonclinical activities. Accumulated evidence demonstrates that clinical outcomes of telepsychiatric interventions are comparable to conventional treatment among patients of all ages, ethnicities, cultures, and diagnostic groups across diverse clinical settings. However, negative attitudes, concerns about the quality of the evidence, doubts about cost-effectiveness, technological vagaries, uncertainty regarding the doctor–patient alliance, and a number of legal, ethical and regulatory hurdles continue to hinder the widespread implementation of telepsychiatric services. A particularly disappointing aspect has been the lack of development of telepsychiatric services in developing countries, where they are required the most because of the large mental-health gap in care with the more traditional forms of services. Problems of costs, lack of infrastructure and connectivity, shortage of trained personnel, sociocultural differences, limited data on effectiveness, and lack of institutional support are the principal challenges to the wider adoption of telepsychiatry in these resource-constrained countries. It is evident that much more effort by all stakeholders, innovative solutions, and hybrid models of care are required before telepsychiatry is able to fulfil its true potential and bring about the promised change in mental health outcomes in the developing world.

  4. Dosimetric Comparison and Potential for Improved Clinical Outcomes of Paediatric CNS Patients Treated with Protons or IMRT

    Energy Technology Data Exchange (ETDEWEB)

    Armoogum, Kris S., E-mail: kris.armoogum@nhs.net [Department of Radiotherapy Physics, Royal Derby Hospital, Derby Hospitals NHS Foundation Trust, Uttoxeter Road, Derby DE22 3NE (United Kingdom); Thorp, Nicola [The Clatterbridge Cancer Centre NHS Foundation Trust, Clatterbridge Road, Bebington, Wirral CH63 4JY (United Kingdom)

    2015-04-28

    Background: We compare clinical outcomes of paediatric patients with CNS tumours treated with protons or IMRT. CNS tumours form the second most common group of cancers in children. Radiotherapy plays a major role in the treatment of many of these patients but also contributes to late side effects in long term survivors. Radiation dose inevitably deposited in healthy tissues outside the clinical target has been linked to detrimental late effects such as neurocognitive, behavioural and vascular effects in addition to endocrine abnormalities and second tumours. Methods: A literature search was performed using keywords: protons, IMRT, CNS and paediatric. Of 189 papers retrieved, 10 were deemed relevant based on title and abstract screening. All papers directly compared outcomes from protons with photons, five papers included medulloblastoma, four papers each included craniopharyngioma and low grade gliomas and three papers included ependymoma. Results: This review found that while proton beam therapy offered similar clinical target coverage, there was a demonstrable reduction in integral dose to normal structures. Conclusions: This in turn suggests the potential for superior long term outcomes for paediatric patients with CNS tumours both in terms of radiogenic second cancers and out-of-field adverse effects.

  5. Dosimetric Comparison and Potential for Improved Clinical Outcomes of Paediatric CNS Patients Treated with Protons or IMRT

    Directory of Open Access Journals (Sweden)

    Kris S. Armoogum

    2015-04-01

    Full Text Available Background: We compare clinical outcomes of paediatric patients with CNS tumours treated with protons or IMRT. CNS tumours form the second most common group of cancers in children. Radiotherapy plays a major role in the treatment of many of these patients but also contributes to late side effects in long term survivors. Radiation dose inevitably deposited in healthy tissues outside the clinical target has been linked to detrimental late effects such as neurocognitive, behavioural and vascular effects in addition to endocrine abnormalities and second tumours. Methods: A literature search was performed using keywords: protons, IMRT, CNS and paediatric. Of 189 papers retrieved, 10 were deemed relevant based on title and abstract screening. All papers directly compared outcomes from protons with photons, five papers included medulloblastoma, four papers each included craniopharyngioma and low grade gliomas and three papers included ependymoma. Results: This review found that while proton beam therapy offered similar clinical target coverage, there was a demonstrable reduction in integral dose to normal structures. Conclusions: This in turn suggests the potential for superior long term outcomes for paediatric patients with CNS tumours both in terms of radiogenic second cancers and out-of-field adverse effects.

  6. A protocol for a randomized clinical trial of interactive video dance: potential for effects on cognitive function.

    Science.gov (United States)

    Jovancevic, Jelena; Rosano, Caterina; Perera, Subashan; Erickson, Kirk I; Studenski, Stephanie

    2012-06-06

    Physical exercise has the potential to affect cognitive function, but most evidence to date focuses on cognitive effects of fitness training. Cognitive exercise also may influence cognitive function, but many cognitive training paradigms have failed to provide carry-over to daily cognitive function. Video games provide a broader, more contextual approach to cognitive training that may induce cognitive gains and have carry over to daily function. Most video games do not involve physical exercise, but some novel forms of interactive video games combine physical activity and cognitive challenge. This paper describes a randomized clinical trial in 168 postmenopausal sedentary overweight women that compares an interactive video dance game with brisk walking and delayed entry controls. The primary endpoint is adherence to activity at six months. Additional endpoints include aspects of physical and mental health. We focus this report primarily on the rationale and plans for assessment of multiple cognitive functions. This randomized clinical trial may provide new information about the cognitive effects of interactive videodance. It is also the first trial to examine physical and cognitive effects in older women. Interactive video games may offer novel strategies to promote physical activity and health across the life span.The study is IRB approved and the number is: PRO08080012ClinicalTrials.gov Identifier: NCT01443455.

  7. A protocol for a randomized clinical trial of interactive video dance: potential for effects on cognitive function

    Directory of Open Access Journals (Sweden)

    Jovancevic Jelena

    2012-06-01

    Full Text Available Abstract Background Physical exercise has the potential to affect cognitive function, but most evidence to date focuses on cognitive effects of fitness training. Cognitive exercise also may influence cognitive function, but many cognitive training paradigms have failed to provide carry-over to daily cognitive function. Video games provide a broader, more contextual approach to cognitive training that may induce cognitive gains and have carry over to daily function. Most video games do not involve physical exercise, but some novel forms of interactive video games combine physical activity and cognitive challenge. Methods/Design This paper describes a randomized clinical trial in 168 postmenopausal sedentary overweight women that compares an interactive video dance game with brisk walking and delayed entry controls. The primary endpoint is adherence to activity at six months. Additional endpoints include aspects of physical and mental health. We focus this report primarily on the rationale and plans for assessment of multiple cognitive functions. Discussion This randomized clinical trial may provide new information about the cognitive effects of interactive videodance. It is also the first trial to examine physical and cognitive effects in older women. Interactive video games may offer novel strategies to promote physical activity and health across the life span. The study is IRB approved and the number is: PRO08080012 ClinicalTrials.gov Identifier: NCT01443455

  8. The Potential Role of Lycopene for the Prevention and Therapy of Prostate Cancer: From Molecular Mechanisms to Clinical Evidence

    Science.gov (United States)

    Holzapfel, Nina Pauline; Holzapfel, Boris Michael; Champ, Simon; Feldthusen, Jesper; Clements, Judith; Hutmacher, Dietmar Werner

    2013-01-01

    Lycopene is a phytochemical that belongs to a group of pigments known as carotenoids. It is red, lipophilic and naturally occurring in many fruits and vegetables, with tomatoes and tomato-based products containing the highest concentrations of bioavailable lycopene. Several epidemiological studies have linked increased lycopene consumption with decreased prostate cancer risk. These findings are supported by in vitro and in vivo experiments showing that lycopene not only enhances the antioxidant response of prostate cells, but that it is even able to inhibit proliferation, induce apoptosis and decrease the metastatic capacity of prostate cancer cells. However, there is still no clearly proven clinical evidence supporting the use of lycopene in the prevention or treatment of prostate cancer, due to the only limited number of published randomized clinical trials and the varying quality of existing studies. The scope of this article is to discuss the potential impact of lycopene on prostate cancer by giving an overview about its molecular mechanisms and clinical effects. PMID:23857058

  9. Stem cell therapy in spinal cord injury: Hollow promise or promising science?

    Directory of Open Access Journals (Sweden)

    Aimee Goel

    2016-01-01

    Full Text Available Spinal cord injury (SCI remains one of the most physically, psychologically and socially debilitating conditions worldwide. While rehabilitation measures may help limit disability to some extent, there is no effective primary treatment yet available. The efficacy of stem cells as a primary therapeutic option in spinal cord injury is currently an area under much scrutiny and debate. Several laboratory and some primary clinical studies into the use of bone marrow mesenchymal stem cells or embryonic stem cell-derived oligodentrocyte precursor cells have shown some promising results in terms of remyelination and regeneration of damaged spinal nerve tracts. More recently,laboratory and early clinical experiments into the use of Olfactory Ensheathing Cells, a type of glial cell derived from olfactory bulb and mucosa have provided some phenomenal preliminary evidence as to their neuroregenerative and neural bridging capacity. This report compares and evaluates some current research into selected forms of embryonic and mesenchymal stem cell therapy as well as olfactory ensheathing cell therapy in SCI, and also highlights some legal and ethical issues surrounding their use. While early results shows promise, more rigorous large scaleclinical trials are needed to shed light on the safety, efficacy and long term viability of stem cell and cellular transplant techniques in SCI.

  10. The Promise and Perils of Stem Cell Therapeutics

    OpenAIRE

    Daley, George Q.

    2012-01-01

    Stem cells are the seeds of tissue repair and regeneration and a promising source for novel therapies. However, apart from hematopoietic stem cell (HSC) transplantation for hematologic disease, essentially all other stem cell treatments remain experimental. High hopes have inspired numerous clinical trials, but it has been difficult to obtain unequivocal evidence for robust clinical benefit, likely owing to our primitive state of knowledge about therapeutic mechanisms. Outside the standard cl...

  11. Establishing an ISO 10001-based promise in inpatients care.

    Science.gov (United States)

    Khan, Mohammad Ashiqur Rahman; Karapetrovic, Stanislav

    2015-01-01

    The purpose of this paper is to explore ISO 10001:2007 in planning, designing and developing a customer satisfaction promise (CSP) intended for inpatients care. Through meetings and interviews with research participants, who included a program manager, unit managers and registered nurses, information about potential promises and their implementation was obtained and analyzed. A number of promises were drafted and one was finally selected to be developed as a CSP. Applying the standard required adaptation and novel interpretation. Additionally, ISO 10002:2004 (Clause 7) was used to design the feedback handling activities. A promise initially chosen for development turned out to be difficult to implement, experience that helped in selecting and developing the final promise. Research participants found the ISO 10001-based method useful and comprehensible. This paper presents a specific health care example of how to adapt a standard's guideline in establishing customer promises. The authors show how a promise can be used in alleviating an existing issue (i.e. communication between carers and patients). The learning can be beneficial in various health care settings. To the knowledge, this paper shows the first example of applying ISO 10001:2007 in a health care case. A few activities suggested by the standard are further detailed, and a new activity is introduced. The integrated use of ISO 10001:2007 and 10002:2004 is presented and how one can be "augmented" by the other is demonstrated.

  12. The promise and the peril.

    Science.gov (United States)

    Whelan, D

    1998-04-01

    The medicare population represents the most important group of covered lives to most providers. Medicare is now pushing seniors to join risk-based plans, and is encouraging providers to form PSOs to contract directly with Medicare for risk-based contracts. By eliminating the commercial HMOs as the middlemen, PSOs can not only control their own destiny as providers, they can retain the risk 'profit' in the community for enhanced services or higher payments to providers. To be successful, however, PSOs must have in place the key elements to manage the organization in a managed care environment. While the task of creating a PSO can appear daunting and the risk can be real and substantial, every provider organization should examine the potential of starting or joining a PSO. The greatest risk could be the risk of doing nothing, which could lead to loss of control of the Medicare population, decreased utilization, declining payment for services, the loss of patients being directed to other providers, and the loss of the risk premium from Medicare capitation.

  13. Towards single embryo transfer? Modelling clinical outcomes of potential treatment choices using multiple data sources: predictive models and patient perspectives.

    Science.gov (United States)

    Roberts, Sa; McGowan, L; Hirst, Wm; Brison, Dr; Vail, A; Lieberman, Ba

    2010-07-01

    In vitro fertilisation (IVF) treatments involve an egg retrieval process, fertilisation and culture of the resultant embryos in the laboratory, and the transfer of embryos back to the mother over one or more transfer cycles. The first transfer is usually of fresh embryos and the remainder may be cryopreserved for future frozen cycles. Most commonly in UK practice two embryos are transferred (double embryo transfer, DET). IVF techniques have led to an increase in the number of multiple births, carrying an increased risk of maternal and infant morbidity. The UK Human Fertilisation and Embryology Authority (HFEA) has adopted a multiple birth minimisation strategy. One way of achieving this would be by increased use of single embryo transfer (SET). To collate cohort data from treatment centres and the HFEA; to develop predictive models for live birth and twinning probabilities from fresh and frozen embryo transfers and predict outcomes from treatment scenarios; to understand patients' perspectives and use the modelling results to investigate the acceptability of twin reduction policies. A multidisciplinary approach was adopted, combining statistical modelling with qualitative exploration of patients' perspectives: interviews were conducted with 27 couples at various stages of IVF treatment at both UK NHS and private clinics; datasets were collated of over 90,000 patients from the HFEA registry and nearly 9000 patients from five clinics, both over the period 2000-5; models were developed to determine live birth and twin outcomes and predict the outcomes of policies for selecting patients for SET or DET in the fresh cycle following egg retrieval and fertilisation, and the predictions were used in simulations of treatments; two focus groups were convened, one NHS and one web based on a patient organisation's website, to present the results of the statistical analyses and explore potential treatment policies. The statistical analysis revealed no characteristics that

  14. Nuclear energy: Promise and problems

    International Nuclear Information System (INIS)

    Richter, B.

    2005-01-01

    Nuclear energy is having a renaissance driven by both old fashioned supply and demand, and environmental concerns. Oil and gas prices have exploded and show no signs of returning to the levels of only a few years ago. Coal is not in short supply, but the pollution it generates has severe economic and health consequences. Concern about greenhouse gases and global warming has caused the environmental movement to begin a reassessment of the role of nuclear in the world's energy portfolio. The full potential of nuclear energy will be achieved only if governments and the public are satisfied that it is safe, that the radioactive waste can be safely disposed of, and that the risk of the proliferation of nuclear weapons is low. The first criterion has been met with designs that are inherently safer than current LWRs, primarily through design simplification, reducing the number of critical components, and advanced control and monitoring technologies. Operating safety has to be assured through good practices and a rigorous, independent inspection process. The second criterion, waste disposal, is a problem where the science and technology (S and T) communities have the primary role in a solution. Many believe that it is solved in principle, but there has as yet been no solution in practice. I will report on where I think we have gotten and what needs to be done. The third criterion, proliferation resistance, is one that the S and T communities cannot solve on their own. The best that S and T can do is to make proliferation difficult, and to make sure that any attempts are discovered early. The rest can be handled only by enforceable international agreements. Safeguards technology needs more attention. (author)

  15. Acute myeloid leukemia: advancing clinical trials and promising therapeutics

    Science.gov (United States)

    Daver, Naval; Cortes, Jorge; Kantarjian, Hagop; Ravandi, Farhad

    2016-01-01

    Recent progress in understanding the biology of acute myeloid leukemia (AML) and the identification of targetable driver mutations, leukemia specific antigens and signal transduction pathways has ushered in a new era of therapy. In many circumstances the response rates with such targeted or antibody-based therapies are superior to those achieved with standard therapy and with decreased toxicity. In this review we discuss novel therapies in AML with a focus on two major areas of unmet need: (1) single agent and combination strategies to improve frontline therapy in elderly patients with AML and (2) molecularly targeted therapies in the frontline and salvage setting in all patients with AML. PMID:26910051

  16. Bacteriophages show promise as antimicrobial agents.

    Science.gov (United States)

    Alisky, J; Iczkowski, K; Rapoport, A; Troitsky, N

    1998-01-01

    The emergence of antibiotic-resistant bacteria has prompted interest in alternatives to conventional drugs. One possible option is to use bacteriophages (phage) as antimicrobial agents. We have conducted a literature review of all Medline citations from 1966-1996 that dealt with the therapeutic use of phage. There were 27 papers from Poland, the Soviet Union, Britain and the U.S.A. The Polish and Soviets administered phage orally, topically or systemically to treat a wide variety of antibiotic-resistant pathogens in both adults and children. Infections included suppurative wound infections, gastroenteritis, sepsis, osteomyelitis, dermatitis, empyemas and pneumonia; pathogens included Staphylococcus, Streptococcus, Klebsiella, Escherichia, Proteus, Pseudomonas, Shigella and Salmonella spp. Overall, the Polish and Soviets reported success rates of 80-95% for phage therapy, with rare, reversible gastrointestinal or allergic side effects. However, efficacy of phage was determined almost exclusively by qualitative clinical assessment of patients, and details of dosages and clinical criteria were very sketchy. There were also six British reports describing controlled trials of phage in animal models (mice, guinea pigs and livestock), measuring survival rates and other objective criteria. All of the British studies raised phage against specific pathogens then used to create experimental infections. Demonstrable efficacy against Escherichia, Acinetobacter, Pseudomonas and Staphylococcus spp. was noted in these model systems. Two U.S. papers dealt with improving the bioavailability of phage. Phage is sequestered in the spleen and removed from circulation. This can be overcome by serial passage of phage through mice to isolate mutants that resist sequestration. In conclusion, bacteriophages may show promise for treating antibiotic resistant pathogens. To facilitate further progress, directions for future research are discussed and a directory of authors from the reviewed

  17. Nitrogen-Based Diazeniumdiolates: Versatile Nitric Oxide-Releasing Compounds for Biomedical Research and Potential Clinical Applications

    Science.gov (United States)

    Saavedra, Joseph E.; Keefer, Larry K.

    2002-12-01

    Nitric oxide-generating ions of the nitrogen-diazeniumdiolate class with the general structure R1R2N-[N(O)NO]1 have been prepared by exposing primary, secondary, and polyamines to nitric oxide (NO). The resulting complexes regenerate bioactive NO at physiological pH with half-lives ranging from 2 seconds to 20 hours. An important goal in our research is to deliver NO to a specific organ or cell type where it is needed without affecting other NO-sensitive parts of the anatomy. By taking advantage of the remarkable chemical versatility of diazeniumdiolates, we have developed general strategies to prepare either tissue-selective NO donor drugs or materials containing NO delivery agents that can be physically placed near the target sites. Inhibition of blood coagulation, induction of penile erection, relief of pulmonary hypertension, and reversal of cerebral vasospasm are a few examples of their potential clinical applications. See Featured Molecules.

  18. Potential clinical applications of {sup 18}F-fluorodeoxyglucose position emission tomography/magnetic resonance mammography in breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Ihn Ho; Kong, Eun Jung [Dept. of Nuclear Medicine, Yeugnam University Hospital, Daegu (Korea, Republic of)

    2017-09-15

    The whole-body positron emission tomography (PET)/magnetic resonance (MR) scan is a cutting edge technology providing comprehensive structural information from MR imaging and functional features from PET in a single session. Recent research findings and clinical experience have shown that 18F-fluorodeoxyglucose (FDG) whole-body PET/MR imaging has a diagnostic performance comparable with or superior to that of PET/CT in the field of oncology, including for breast cancer. In particular, FDG PET/MR mammography in the prone position with the breast hanging in a pendant manner can provide more comprehensive information about the metabolism, anatomy, and functional features of a breast lesion than a whole-body PET/MR scan. This article reports on current state-of-the-art PET/MR mammography in patients with breast cancer and the prospects for potential application in the future.

  19. Bioavailability of curcumin: problems and promises.

    Science.gov (United States)

    Anand, Preetha; Kunnumakkara, Ajaikumar B; Newman, Robert A; Aggarwal, Bharat B

    2007-01-01

    Curcumin, a polyphenolic compound derived from dietary spice turmeric, possesses diverse pharmacologic effects including anti-inflammatory, antioxidant, antiproliferative and antiangiogenic activities. Phase I clinical trials have shown that curcumin is safe even at high doses (12 g/day) in humans but exhibit poor bioavailability. Major reasons contributing to the low plasma and tissue levels of curcumin appear to be due to poor absorption, rapid metabolism, and rapid systemic elimination. To improve the bioavailability of curcumin, numerous approaches have been undertaken. These approaches involve, first, the use of adjuvant like piperine that interferes with glucuronidation; second, the use of liposomal curcumin; third, curcumin nanoparticles; fourth, the use of curcumin phospholipid complex; and fifth, the use of structural analogues of curcumin (e.g., EF-24). The latter has been reported to have a rapid absorption with a peak plasma half-life. Despite the lower bioavailability, therapeutic efficacy of curcumin against various human diseases, including cancer, cardiovascular diseases, diabetes, arthritis, neurological diseases and Crohn's disease, has been documented. Enhanced bioavailability of curcumin in the near future is likely to bring this promising natural product to the forefront of therapeutic agents for treatment of human disease.

  20. Chemoradiation Therapy for Potentially Resectable Gastric Cancer: Clinical Outcomes Among Patients Who Do Not Undergo Planned Surgery

    International Nuclear Information System (INIS)

    Kim, Michelle M.; Mansfield, Paul F.; Das, Prajnan; Janjan, Nora A.; Badgwell, Brian D.; Phan, Alexandria T.; Delclos, Marc E.; Maru, Dipen; Ajani, Jaffer A.; Crane, Christopher H.; Krishnan, Sunil

    2008-01-01

    Purpose: We retrospectively analyzed treatment outcomes among resectable gastric cancer patients treated preoperatively with chemoradiation therapy (CRT) but rendered ineligible for planned surgery because of clinical deterioration or development of overt metastatic disease. Methods and Materials: Between 1996 and 2004, 39 patients with potentially resectable gastric cancer received preoperative CRT but failed to undergo surgery. At baseline clinical staging, 33 (85%) patients had T3-T4 disease, and 27 (69%) patients had nodal involvement. Most patients received 45 Gy of radiotherapy with concurrent 5-fluorouracil-based chemotherapy. Twenty-one patients underwent induction chemotherapy before CRT. Actuarial times to local control (LC), distant control (DC), and overall survival (OS) were calculated by the Kaplan-Meier method. Results: The cause for surgical ineligibility was development of metastatic disease (28 patients, 72%; predominantly peritoneal, 18 patients), poor performance status (5 patients, 13%), patient/physician preference (4 patients, 10%), and treatment-related death (2 patients, 5%). With a median follow-up of 8 months (range, 1-95 months), actuarial 1-year LC, DC, and OS were 46%, 12%, and 36%, respectively. Median LC and OS were 11.0 and 10.1 months, respectively. Conclusions: Patients with potentially resectable gastric cancer treated with preoperative CRT are found to be ineligible for surgery principally because of peritoneal progression. Patients who are unable to undergo planned surgery have outcomes comparable to that of patients with advanced gastric cancer treated with chemotherapy alone. CRT provides durable LC for the majority of the remaining life of these patients

  1. Assessing emotional status following acquired brain injury: the clinical potential of the depression, anxiety and stress scales.

    Science.gov (United States)

    Ownsworth, Tamara; Little, Trudi; Turner, Ben; Hawkes, Anna; Shum, David

    2008-10-01

    To investigate the clinical potential of the Depression, Anxiety and Stress Scales (DASS 42) and its shorter version (DASS 21) for assessing emotional status following acquired brain injury. Participants included 23 individuals with traumatic brain injury (TBI), 25 individuals with brain tumour and 29 non-clinical controls. Investigations of internal consistency, test-re-test reliability, theory-consistent differences, sensitivity to change and concurrent validity were conducted. Internal consistency of the DASS was generally acceptable (r > 0.70), with the exception of the anxiety scale for the TBI sample. Test-re-test reliability (1-3 weeks) was sound for the depression scale (r > 0.75) and significant but comparatively lower for other scales (r = 0.60-0.73, p scale (p DASS in the context of hospital discharge was demonstrated for depression and stress (p 0.05). Concurrent validity with the Hospital Anxiety and Depression Scale was significant for all scales of the DASS (p DASS following ABI, further research examining the factor structure of existing and modified versions of the DASS is recommended.

  2. Intra-oral orthosis vs amitriptyline in chronic tension-type headache: a clinical and laser evoked potentials study

    Directory of Open Access Journals (Sweden)

    Sardaro Michele

    2006-05-01

    Full Text Available Abstract Background In the present study, we examined clinical and laser-evoked potentials (LEP features in two groups of chronic tension-type headache (CTTH patients treated with two different approaches: intra-oral appliance of prosthesis, aiming to reduce muscular tenderness, and 10 mg daily amitriptyline. Methods Eighteen patients with diagnosed CTTH participated in this open label, controlled study. A baseline evaluation was performed for clinical features, Total Tenderness Score (TTS and a topographic analysis of LEPs obtained manually and the pericranial points stimulation in all patients vs. healthy subjects. Thereafter, patients were randomly assigned to a two-month treatment by either amitriptyline or intra-oral appliance. Results and discussion Both the intra-oral appliance and amitriptyline significantly reduced headache frequency. The TTS was significantly reduced in the group treated with the appliance. The amplitude of P2 response elicited by stimulation of pericranial zones showed a reduction after amitriptyline treatment. Both therapies were effective in reducing headache severity, the appliance with a prevalent action on the pericranial muscular tenderness, amitriptyline reducing the activity of the central cortical structures subtending pain elaboration Conclusion The results of this study may suggest that in CTTH both the interventions at the peripheral and central levels improve the outcome of headache.

  3. In vitro and clinical evaluation of OATP-mediated drug interaction potential of sacubitril/valsartan (LCZ696).

    Science.gov (United States)

    Ayalasomayajula, S; Han, Y; Langenickel, T; Malcolm, K; Zhou, W; Hanna, I; Alexander, N; Natrillo, A; Goswami, B; Hinder, M; Sunkara, G

    2016-08-01

    Sacubitril/valsartan (LCZ696) has been recently approved for the treatment of heart failure (HF) patients with reduced ejection fraction. Several HF patients receive statins as co-medication. Because clearance of statins is meditated via OATP1B1/1B3, the inhibition potential of these transporters by LCZ696 analytes was evaluated in vitro. Furthermore, an open-label, fixed-sequence clinical study was conducted to determine the effect of LCZ696 on the exposure of simvastatin and its active metabolite simvastatin acid. In this clinical study, 26 healthy subjects received simvastatin 40 mg alone or in combination with LCZ696 or after 1 or 2 h of LCZ696 dosing. Although no significant inhibition by LBQ657 (an active metabolite of sacubitril) and valsartan was observed, sacubitril inhibited OATP1B1 and OATP1B3 in vitro, with IC50 of 1·91 and 3·81 μm, respectively. Upon co-administration of simvastatin with LCZ696, the Cmax of simvastatin and simvastatin acid decreased by 7% and 13%, respectively. When administered 1 h after LCZ696 dosing, the corresponding Cmax of simvastatin and simvastatin acid decreased by 16% and 4%, respectively. When administered 2 h after LCZ696 dosing, the Cmax of simvastatin decreased by 33% and that of simvastatin acid increased by 16%. However, no notable changes were observed in the AUCs of simvastatin or simvastatin acid upon co-administration or time-separated administration with LCZ696. No notable impact of simvastatin co-administration was observed on the pharmacokinetics of LCZ696 analytes. LCZ696 and simvastatin were generally well tolerated when administered alone or in combination. Overall, the results of this study suggest that although sacubitril inhibited OATP1B1 and OATP1B3 in vitro, it does not translate into any clinically relevant in vivo effect. © 2016 John Wiley & Sons Ltd.

  4. Autonomic regulation of brown adipose tissue thermogenesis in health and disease: potential clinical applications for altering BAT thermogenesis

    Science.gov (United States)

    Tupone, Domenico; Madden, Christopher J.; Morrison, Shaun F.

    2014-01-01

    From mouse to man, brown adipose tissue (BAT) is a significant source of thermogenesis contributing to the maintenance of the body temperature homeostasis during the challenge of low environmental temperature. In rodents, BAT thermogenesis also contributes to the febrile increase in core temperature during the immune response. BAT sympathetic nerve activity controlling BAT thermogenesis is regulated by CNS neural networks which respond reflexively to thermal afferent signals from cutaneous and body core thermoreceptors, as well as to alterations in the discharge of central neurons with intrinsic thermosensitivity. Superimposed on the core thermoregulatory circuit for the activation of BAT thermogenesis, is the permissive, modulatory influence of central neural networks controlling metabolic aspects of energy homeostasis. The recent confirmation of the presence of BAT in human and its function as an energy consuming organ have stimulated interest in the potential for the pharmacological activation of BAT to reduce adiposity in the obese. In contrast, the inhibition of BAT thermogenesis could facilitate the induction of therapeutic hypothermia for fever reduction or to improve outcomes in stroke or cardiac ischemia by reducing infarct size through a lowering of metabolic oxygen demand. This review summarizes the central circuits for the autonomic control of BAT thermogenesis and highlights the potential clinical relevance of the pharmacological inhibition or activation of BAT thermogenesis. PMID:24570653

  5. Autonomic regulation of brown adipose tissue thermogenesis in health and disease: potential clinical applications for altering BAT thermogenesis.

    Science.gov (United States)

    Tupone, Domenico; Madden, Christopher J; Morrison, Shaun F

    2014-01-01

    From mouse to man, brown adipose tissue (BAT) is a significant source of thermogenesis contributing to the maintenance of the body temperature homeostasis during the challenge of low environmental temperature. In rodents, BAT thermogenesis also contributes to the febrile increase in core temperature during the immune response. BAT sympathetic nerve activity controlling BAT thermogenesis is regulated by CNS neural networks which respond reflexively to thermal afferent signals from cutaneous and body core thermoreceptors, as well as to alterations in the discharge of central neurons with intrinsic thermosensitivity. Superimposed on the core thermoregulatory circuit for the activation of BAT thermogenesis, is the permissive, modulatory influence of central neural networks controlling metabolic aspects of energy homeostasis. The recent confirmation of the presence of BAT in human and its function as an energy consuming organ have stimulated interest in the potential for the pharmacological activation of BAT to reduce adiposity in the obese. In contrast, the inhibition of BAT thermogenesis could facilitate the induction of therapeutic hypothermia for fever reduction or to improve outcomes in stroke or cardiac ischemia by reducing infarct size through a lowering of metabolic oxygen demand. This review summarizes the central circuits for the autonomic control of BAT thermogenesis and highlights the potential clinical relevance of the pharmacological inhibition or activation of BAT thermogenesis.

  6. Horizons in clinical nanomedicine

    CERN Document Server

    Karagkiozaki, Varvara

    2014-01-01

    Nanomedicine-the application of nanotechnology to health sciences-has the potential to address many important medical problems by exploiting the advanced physicochemical characteristics of nanostructured materials and devices. It can revolutionize conventional medicine by offering cutting-edge developments in the processes of diagnosing, treating, and preventing diseases, injuries, or genetic disorders. Thus, clinical nanomedicine holds promise to preserve and improve human health.This book provides a comprehensive overview on the forefront developments of nanotechnology in various domains of

  7. Clinical relevancy and determinants of potential drug–drug interactions in chronic kidney disease patients: results from a retrospective analysis

    Directory of Open Access Journals (Sweden)

    Saleem A

    2017-02-01

    Full Text Available Ahsan Saleem,1,2 Imran Masood,1 Tahir Mehmood Khan3 1Department of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur, Pakistan; 2Pharmacy Services Department, Integrated Medical Center, The Aga Khan University Hospital, Lahore, Pakistan; 3School of Pharmacy, Monash University, Sunway Campus, Selangor, Malaysia Background: Chronic kidney disease (CKD alters the pharmacokinetic and pharmacodynamic responses of various renally excreted drugs and increases the risk of drug-related problems, such as drug–drug interactions.Objectives: To assess the pattern, determinants, and clinical relevancy of potential drug–drug interactions (pDDIs in CKD patients.Materials and methods: This study retrospectively reviewed medical charts of all CKD patients admitted in the nephrology unit of a tertiary care hospital in Pakistan from January 2013 to December 2014. The Micromedex Drug-Reax® system was used to screen patient profiles for pDDIs, and IBM SPSS version 20 was used to carry out statistical analysis.Results: We evaluated 209 medical charts and found pDDIs in nearly 78.5% CKD patients. Overall, 541 pDDIs were observed, of which, nearly 60.8% patients had moderate, 41.1% had minor, 27.8% had major, and 13.4% had contraindicated interactions. Among those interactions, 49.4% had good evidence, 44.0% had fair, 6.3% had excellent evidence, and 35.5% interactions had delayed onset of action. The potential adverse outcomes of pDDIs included postural hypotension, QT prolongation, ceftriaxone–calcium precipitation, cardiac arrhythmias, and reduction in therapeutic effectiveness. The occurrence of pDDIs was found strongly associated with the age of <60 years, number of prescribed medicines ≥5, hypertension, and the lengthy hospitalization of patients.Conclusion: The occurrence of pDDIs was high in CKD patients. It was observed that CKD patients with an older age, higher number of prescribed medicines, lengthy hospitalization, and hypertension were at

  8. Information needs for making clinical recommendations about potential drug-drug interactions: a synthesis of literature review and interviews.

    Science.gov (United States)

    Romagnoli, Katrina M; Nelson, Scott D; Hines, Lisa; Empey, Philip; Boyce, Richard D; Hochheiser, Harry

    2017-02-22

    Drug information compendia and drug-drug interaction information databases are critical resources for clinicians and pharmacists working to avoid adverse events due to exposure to potential drug-drug interactions (PDDIs). Our goal is to develop information models, annotated data, and search tools that will facilitate the interpretation of PDDI information. To better understand the information needs and work practices of specialists who search and synthesize PDDI evidence for drug information resources, we conducted an inquiry that combined a thematic analysis of published literature with unstructured interviews. Starting from an initial set of relevant articles, we developed search terms and conducted a literature search. Two reviewers conducted a thematic analysis of included articles. Unstructured interviews with drug information experts were conducted and similarly coded. Information needs, work processes, and indicators of potential strengths and weaknesses of information systems were identified. Review of 92 papers and 10 interviews identified 56 categories of information needs related to the interpretation of PDDI information including drug and interaction information; study design; evidence including clinical details, quality and content of reports, and consequences; and potential recommendations. We also identified strengths/weaknesses of PDDI information systems. We identified the kinds of information that might be most effective for summarizing PDDIs. The drug information experts we interviewed had differing goals, suggesting a need for detailed information models and flexible presentations. Several information needs not discussed in previous work were identified, including temporal overlaps in drug administration, biological plausibility of interactions, and assessment of the quality and content of reports. Richly structured depictions of PDDI information may help drug information experts more effectively interpret data and develop recommendations

  9. Candida Biofilms: Threats, Challenges, and Promising Strategies

    Science.gov (United States)

    Cavalheiro, Mafalda; Teixeira, Miguel Cacho

    2018-01-01

    Candida species are fungal pathogens known for their ability to cause superficial and systemic infections in the human host. These pathogens are able to persist inside the host due to the development of pathogenicity and multidrug resistance traits, often leading to the failure of therapeutic strategies. One specific feature of Candida species pathogenicity is their ability to form biofilms, which protects them from external factors such as host immune system defenses and antifungal drugs. This review focuses on the current threats and challenges when dealing with biofilms formed by Candida albicans, Candida glabrata, Candida tropicalis, and Candida parapsilosis, highlighting the differences between the four species. Biofilm characteristics depend on the ability of each species to produce extracellular polymeric substances (EPS) and display dimorphic growth, but also on the biofilm substratum, carbon source availability and other factors. Additionally, the transcriptional control over processes like adhesion, biofilm formation, filamentation, and EPS production displays great complexity and diversity within pathogenic yeasts of the Candida genus. These differences not only have implications in the persistence of colonization and infections but also on antifungal resistance typically found in Candida biofilm cells, potentiated by EPS, that functions as a barrier to drug diffusion, and by the overexpression of drug resistance transporters. The ability to interact with different species in in vivo Candida biofilms is also a key factor to consider when dealing with this problem. Despite many challenges, the most promising strategies that are currently available or under development to limit biofilm formation or to eradicate mature biofilms are discussed. PMID:29487851

  10. Candida Biofilms: Threats, Challenges, and Promising Strategies.

    Science.gov (United States)

    Cavalheiro, Mafalda; Teixeira, Miguel Cacho

    2018-01-01

    Candida species are fungal pathogens known for their ability to cause superficial and systemic infections in the human host. These pathogens are able to persist inside the host due to the development of pathogenicity and multidrug resistance traits, often leading to the failure of therapeutic strategies. One specific feature of Candida species pathogenicity is their ability to form biofilms, which protects them from external factors such as host immune system defenses and antifungal drugs. This review focuses on the current threats and challenges when dealing with biofilms formed by Candida albicans, Candida glabrata, Candida tropicalis , and Candida parapsilosis , highlighting the differences between the four species. Biofilm characteristics depend on the ability of each species to produce extracellular polymeric substances (EPS) and display dimorphic growth, but also on the biofilm substratum, carbon source availability and other factors. Additionally, the transcriptional control over processes like adhesion, biofilm formation, filamentation, and EPS production displays great complexity and diversity within pathogenic yeasts of the Candida genus. These differences not only have implications in the persistence of colonization and infections but also on antifungal resistance typically found in Candida biofilm cells, potentiated by EPS, that functions as a barrier to drug diffusion, and by the overexpression of drug resistance transporters. The ability to interact with different species in in vivo Candida biofilms is also a key factor to consider when dealing with this problem. Despite many challenges, the most promising strategies that are currently available or under development to limit biofilm formation or to eradicate mature biofilms are discussed.

  11. Tennessee Promise: A Response to Organizational Change

    Science.gov (United States)

    Littlepage, Ben; Clark, Teresa; Wilson, Randal; Stout, Logan

    2018-01-01

    Community colleges in Tennessee, either directly or indirectly, experienced unprecedented change as a result of Tennessee Promise. The present study explored how student support service administrators at three community colleges responded to organizational change as a result of the Tennessee Promise legislation. Investigators selected community…

  12. IL-6 is a potential marker for radiation pneumonitis: a prospective clinical study of circulating cytokines in predicting radiation pulmonary injury

    International Nuclear Information System (INIS)

    Chen Yuhchyau; Rubin, Philip; McDonald, Sandra; Finkelstein, Jacob; Smudzin, Therese; Hernady, Eric; Williams, Jacqueline

    1997-01-01

    Purpose/Objective: The use of radiotherapy in eradicating thoracic malignancy is limited by the normal lung tissue tolerance to ionizing radiation. Subacute and late radiation pulmonary toxicity manifests as radiation pneumonitis and ultimately lung fibrosis. Recently, the addition of chemotherapy or a biologic response modifier to radiation has become the standard therapy for inoperable lung cancer. The radiosensitizing effect of these agents is associated with an increased risk of radiation pulmonary injury and treatment related mortality. The search for a serum marker for predicting radiation pulmonary injury will help us understand the mechanism leading to such events and find possible interventions to prevent the adverse outcome. Unpublished data from our laboratory suggested that following a single dose of radiation, there was a dose-related elevation in IL-6 protein levels in the lung of radiation fibrosis prone mice. Based on this information, a prospective clinical study of circulating cytokine levels and its application to predict radiation induced pulmonary injury was conducted at University of Rochester. Preliminary results revealed promising information in identifying a circulating cytokine as a predictor for radiation pneumonitis. Materials and Methods: Eighteen patients receiving thoracic irradiation for primary thoracic malignancy were registered in the study. Radiation pneumonitis was determined by subjective respiratory symptoms assessed according to RTOG morbidity scoring criteria. Pretreatment and serial post-therapy chest X-ray, chest CT scan and pulmonary function tests were obtained. Radiation fibrosis was determined by radiographic changes in irradiated normal lung using a scoring system which quantified the extent of loss of air content, degree of opacification, anatomic extent of involvement, air bronchogram, pleural thickening, or effusion. Plasma levels of interleukin-6 (IL-6), tumor necrosis factor (TNF), transforming growth factor

  13. Identification of potential new protein vaccine candidates through pan-surfomic analysis of pneumococcal clinical isolates from adults.

    Directory of Open Access Journals (Sweden)

    Alfonso Olaya-Abril

    Full Text Available Purified polysaccharide and conjugate vaccines are widely used for preventing infections in adults and in children against the Gram-positive bacterium Streptococcus pneumoniae, a pathogen responsible for high morbidity and mortality rates, especially in developing countries. However, these polysaccharide-based vaccines have some important limitations, such as being serotype-dependent, being subjected to losing efficacy because of serotype replacement and high manufacturing complexity and cost. It is expected that protein-based vaccines will overcome these issues by conferring a broad coverage independent of serotype and lowering production costs. In this study, we have applied the "shaving" proteomic approach, consisting of the LC/MS/MS analysis of peptides generated by protease treatment of live cells, to a collection of 16 pneumococcal clinical isolates from adults, representing the most prevalent strains circulating in Spain during the last years. The set of unique proteins identified in all the isolates, called "pan-surfome", consisted of 254 proteins, which included most of the protective protein antigens reported so far. In search of new candidates with vaccine potential, we identified 32 that were present in at least 50% of the clinical isolates analyzed. We selected four of them (Spr0012, Spr0328, Spr0561 and SP670_2141, whose protection capacity has not yet been tested, for assaying immunogenicity in human sera. All of them induced the production of IgM antibodies in infected patients, thus indicating that they could enter the pipeline for vaccine studies. The pan-surfomic approach shows its utility in the discovery of new proteins that can elicit protection against infectious microorganisms.

  14. Longitudinal split of the posterior cruciate ligament: description of a new MR finding and evaluation of its potential clinical significance

    Energy Technology Data Exchange (ETDEWEB)

    Cha, J.H. [Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul (Korea, Republic of); Chung, H.W., E-mail: chung@amc.seoul.k [Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul (Korea, Republic of); Kwon, J.W. [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710 (Korea, Republic of); Choi, B.K.; Lee, S.H.; Shin, M.J. [Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul (Korea, Republic of)

    2011-03-15

    Aim: To evaluate the clinical significance of the intra-substance longitudinal split of the posterior cruciate ligament (LS-PCL) and to evaluate its potential clinical significance on MRI. Materials and methods: The databases of two centres were searched for LS-PCL, 6917 knee magnetic resonance imaging (MRI) examinations undertaken were retrospectively reviewed. LS-PCL was defined as increased signal intensity in a PCL in the longitudinal direction, but with an intact ligament outer surface on MRI. Twelve patients were enrolled in this study. Available arthroscopic results, degree of posterior knee instability, and changes in MRI findings, or the degree of instability during follow-up (FU), were reviewed from the patients medical records and via their MRI images. MRI images were reviewed by two musculoskeletal radiologists in consensus for presence and location of LS-PCL and any combined injuries: menisci lesions, ligament injuries, and bone marrow changes. Results: Seven of 12 patients (58.3%) had morphological or functional evidence of PCL injury or insufficiency according to the change of posterior instability on FU stress testing (n = 3), insufficiency during arthroscopy (n = 2), or decreased extent and altered shape of the PCL split on the FU MRI (n = 3). One patient revealed both change of posterior instability on FU stress testing and insufficiency during arthroscopy. Combined injuries were revealed in seven patients. Five patients had isolated LS-PCL: two patients underwent arthroscopic PCL reconstructions; and another three patients revealed knee instability on stress testing. Conclusion: Although LS-PCL has not been described before, it can be a type of partial tear of the PCL, which causes PCL insufficiency.

  15. Growth Potential of Subdural Hematomas Under Clinical Observation: Which Subdural Hematomas Tend to Grow and Why They Do.

    Science.gov (United States)

    Asan, Ziya

    2018-05-01

    To study the prognoses of patients with subdural hematoma (SDH) who were not operated on at the time of the first diagnosis and the causes of enlarged hematomas in some patients during the follow-up period. The records, service files, and radiologic examination results of the patients with diagnoses of SDH were reviewed. The SDH patients were recorded under 5 different categories: acute SDH (ASDH), subacute SDH (SSDH), chronic SDH (CSDH), acute component with chronic SDH (A-CSDH), and subacute component with chronic SDH (S-CSDH). The symptoms, clinical findings, and progression in the patients were correlated with radiologic examinations. A total of 291 patients received diagnoses of SDHs: 80 patients with acute, 29 patients with subacute, and 163 patients with chronic hematoma. Thirty-five patients had diagnoses of SDH with a combination of different components. It was determined that in the follow-up period, patients with A-CSDH showed the greatest increase in hematoma size over time and required surgical intervention the most often. SDHs reveal different prognoses in different age groups. Multicomponent SDHs are within the group that shows the greatest increase in size in the follow-up period. SDHs and CSDHs cause recurrent hemorrhages by sustaining the tension on the bridging veins. The greater the hematoma volume, the greater the growth potential of the hematoma tends to be. CSDHs that do not manifest changes in volume for a long time can be monitored without surgical intervention as long as the clinical picture remains stable. Copyright © 2018 Elsevier Inc. All rights reserved.

  16. BADERI: an online database to coordinate handsearching activities of controlled clinical trials for their potential inclusion in systematic reviews.

    Science.gov (United States)

    Pardo-Hernandez, Hector; Urrútia, Gerard; Barajas-Nava, Leticia A; Buitrago-Garcia, Diana; Garzón, Julieth Vanessa; Martínez-Zapata, María José; Bonfill, Xavier

    2017-06-13

    Systematic reviews provide the best evidence on the effect of health care interventions. They rely on comprehensive access to the available scientific literature. Electronic search strategies alone may not suffice, requiring the implementation of a handsearching approach. We have developed a database to provide an Internet-based platform from which handsearching activities can be coordinated, including a procedure to streamline the submission of these references into CENTRAL, the Cochrane Collaboration Central Register of Controlled Trials. We developed a database and a descriptive analysis. Through brainstorming and discussion among stakeholders involved in handsearching projects, we designed a database that met identified needs that had to be addressed in order to ensure the viability of handsearching activities. Three handsearching teams pilot tested the proposed database. Once the final version of the database was approved, we proceeded to train the staff involved in handsearching. The proposed database is called BADERI (Database of Iberoamerican Clinical Trials and Journals, by its initials in Spanish). BADERI was officially launched in October 2015, and it can be accessed at www.baderi.com/login.php free of cost. BADERI has an administration subsection, from which the roles of users are managed; a references subsection, where information associated to identified controlled clinical trials (CCTs) can be entered; a reports subsection, from which reports can be generated to track and analyse the results of handsearching activities; and a built-in free text search engine. BADERI allows all references to be exported in ProCite files that can be directly uploaded into CENTRAL. To date, 6284 references to CCTs have been uploaded to BADERI and sent to CENTRAL. The identified CCTs were published in a total of 420 journals related to 46 medical specialties. The year of publication ranged between 1957 and 2016. BADERI allows the efficient management of handsearching

  17. Andrographolide, a diterpene lactone from Andrographis paniculata and its therapeutic promises in cancer.

    Science.gov (United States)

    Islam, Muhammad Torequl; Ali, Eunüs S; Uddin, Shaikh Jamal; Islam, Md Amirul; Shaw, Subrata; Khan, Ishaq N; Saravi, Seyed Soheil Saeedi; Ahmad, Saheem; Rehman, Shahnawaz; Gupta, Vijai Kumar; Găman, Mihnea-Alexandru; Găman, Amelia Maria; Yele, Santosh; Das, Asish Kumar; de Castro E Sousa, João Marcelo; de Moura Dantas, Sandra Maria Mendes; Rolim, Hercília Maria Lins; de Carvalho Melo-Cavalcante, Ana Amélia; Mubarak, Mohammad S; Yarla, Nagendra Sastry; Shilpi, Jamil A; Mishra, Siddhartha Kumar; Atanasov, Atanas G; Kamal, Mohammad Amjad

    2018-04-28

    The diterpene lactone andrographolide, isolated from Andrographis paniculata, has been proven to possess several important protective biological activities, including antioxidant, anti-inflammatory, immunomodulatory, antiseptic, antimicrobial, cytotoxic, hypolipidemic, cardioprotective, hepatoprotective, and neuroprotective effects. In addition, it has been reported to play a therapeutic role in the treatment of major human diseases, such as Parkinson's disease, rheumatoid arthritis, and colitis. This systematic review aims to highlight andrographolide as a promising agent in cancer treatment. To this purpose, a number of databases were used to search for the cytotoxic/anticancer effects of andrographolide in pre-clinical and clinical studies. Among 1703 identified literature articles, 139 were included in this review; 109 were investigated as non-clinical, whereas 24, 3, and 3 were pre-clinical, clinical, and non-pre-clinical trials, respectively. Among the model systems, cultured cell lines appeared as the most frequently (79.14%) used, followed by in vivo models using rodents, among others. Furthermore, andrographolide was found to exert cytotoxic/anticancer effects on almost all types of cell lines with the underlying mechanisms involving oxidative stress, cell cycle arrest, anti-inflammatory and immune system mediated effects, apoptosis, necrosis, autophagy, inhibition of cell adhesion, proliferation, migration, invasion, anti-angiogenic activity, and other miscellaneous actions. After careful consideration of the relevant evidence, we suggest that andrographolide can be one of the potential agents in the treatment of cancer in the near future. Copyright © 2018 Elsevier B.V. All rights reserved.

  18. The Effect of Gluten-free Diet on Clinical Symptoms and the Intestinal Mucosa of Patients With Potential Celiac Disease.

    Science.gov (United States)

    Mandile, Roberta; Discepolo, Valentina; Scapaticci, Serena; Del Vecchio, Maria Rosaria; Maglio, Maria Antonia; Greco, Luigi; Troncone, Riccardo; Auricchio, Renata

    2018-04-01

    In this prospective study, we evaluated the effect of gluten-free diet (GFD) in a cohort of 65 children with potential celiac disease. Patients received GFD for signs/symptoms (N = 47) or parents' choice (N = 18). Most frequent signs/symptoms were low body mass index (36%), recurrent abdominal pain (34%), and diarrhea (19%). Of the 35/47 patients followed-up on GFD, only 54% (19/35) showed a complete clinical response. In 9 of 65 patients an intestinal biopsy was also performed after at least 1 year of GFD. No significant differences were observed in terms of Marsh grade (P = 0.33), lamina propria CD25+ cells (P = 0.80), CD3+ (P = 0.9), and γδ+ (P = 0.59) intraepithelial lymphocytes density and intestinal anti-TG2 deposits (P = 0.60). In conclusion, caution is necessary before attributing all symptoms to gluten in this condition.

  19. Microfluidic paper-based analytical devices for potential use in quantitative and direct detection of disease biomarkers in clinical analysis.

    Science.gov (United States)

    Lim, Wei Yin; Goh, Boon Tong; Khor, Sook Mei

    2017-08-15

    Clinicians, working in the health-care diagnostic systems of developing countries, currently face the challenges of rising costs, increased number of patient visits, and limited resources. A significant trend is using low-cost substrates to develop microfluidic devices for diagnostic purposes. Various fabrication techniques, materials, and detection methods have been explored to develop these devices. Microfluidic paper-based analytical devices (μPADs) have gained attention for sensing multiplex analytes, confirming diagnostic test results, rapid sample analysis, and reducing the volume of samples and analytical reagents. μPADs, which can provide accurate and reliable direct measurement without sample pretreatment, can reduce patient medical burden and yield rapid test results, aiding physicians in choosing appropriate treatment. The objectives of this review are to provide an overview of the strategies used for developing paper-based sensors with enhanced analytical performances and to discuss the current challenges, limitations, advantages, disadvantages, and future prospects of paper-based microfluidic platforms in clinical diagnostics. μPADs, with validated and justified analytical performances, can potentially improve the quality of life by providing inexpensive, rapid, portable, biodegradable, and reliable diagnostics. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Antibiotic Resistance Genetic Markers and Integrons in White Soft Cheese: Aspects of Clinical Resistome and Potentiality of Horizontal Gene Transfer.

    Science.gov (United States)

    de Paula, Ana Caroline L; Medeiros, Julliane D; de Azevedo, Analice C; de Assis Chagas, Jéssica M; da Silva, Vânia L; Diniz, Cláudio G

    2018-02-19

    Antibiotic resistance poses an important threat to global public health and has become a challenge to modern medicine. The occurrence of antibiotic-resistant bacteria in a broad range of foods has led to a growing concern about the impact that food may have as a reservoir of antibiotic resistance genes. Considering Minas Frescal Cheese (MFC)-a typical Brazilian white soft cheese-and its economic and cultural values, in this study, medically relevant antimicrobial-resistance genetic markers (AR genes) were screened, and the occurrence of integrons were evaluated in manufactured MFC using culture-independent approaches. Through a fingerprinting analysis, the tested MFCs were brand-clustered, indicating reproducibility along the production chain. A common core of resistance markers in all brands evaluated and related antimicrobials such as β-lactams, tetracyclines, quinolones, and sulfonamide was detected. Several other markers, including efflux pumps and aminoglycosides-resistance were distributed among brands. Class 1 and 2 integrons were observed, respectively, in 77% and 97% of the samples. The presence of AR genes is of special interest due to their clinical relevance. Taken together, the data may suggest that the production chain of MFC might contribute to the spread of putative drug-resistant bacteria, which could greatly impact human health. Furthermore, detection of class 1 and class 2 integrons in MFC has led to discussions about resistance gene spread in this traditional cheese, providing evidence of potential horizontal transfer of AR genes to human gut microbiota.

  1. Antibiotic Resistance Genetic Markers and Integrons in White Soft Cheese: Aspects of Clinical Resistome and Potentiality of Horizontal Gene Transfer

    Directory of Open Access Journals (Sweden)

    Ana Caroline L. de Paula

    2018-02-01

    Full Text Available Antibiotic resistance poses an important threat to global public health and has become a challenge to modern medicine. The occurrence of antibiotic-resistant bacteria in a broad range of foods has led to a growing concern about the impact that food may have as a reservoir of antibiotic resistance genes. Considering Minas Frescal Cheese (MFC—a typical Brazilian white soft cheese—and its economic and cultural values, in this study, medically relevant antimicrobial-resistance genetic markers (AR genes were screened, and the occurrence of integrons were evaluated in manufactured MFC using culture-independent approaches. Through a fingerprinting analysis, the tested MFCs were brand-clustered, indicating reproducibility along the production chain. A common core of resistance markers in all brands evaluated and related antimicrobials such as β-lactams, tetracyclines, quinolones, and sulfonamide was detected. Several other markers, including efflux pumps and aminoglycosides-resistance were distributed among brands. Class 1 and 2 integrons were observed, respectively, in 77% and 97% of the samples. The presence of AR genes is of special interest due to their clinical relevance. Taken together, the data may suggest that the production chain of MFC might contribute to the spread of putative drug-resistant bacteria, which could greatly impact human health. Furthermore, detection of class 1 and class 2 integrons in MFC has led to discussions about resistance gene spread in this traditional cheese, providing evidence of potential horizontal transfer of AR genes to human gut microbiota.

  2. Ocular vestibular evoked myogenic potential elicited from binaural air-conducted stimulations: clinical feasibility in patients with peripheral vestibular dysfunction.

    Science.gov (United States)

    Iwasaki, Shinichi; Egami, Naoya; Inoue, Aki; Kinoshita, Makoto; Fujimoto, Chisato; Murofushi, Toshihisa; Yamasoba, Tatsuya

    2013-07-01

    Ocular vestibular evoked myogenic potentials (oVEMPs) to binaural air-conducted stimulation (ACS) may provide a convenient way of assessing the crossed vestibulo-ocular reflex in patients with vestibular dysfunction as well as in healthy subjects. To investigate the clinical feasibility of using oVEMPs in response to binaural ACS to assess normal subjects and patients with vestibular dysfunction. The study investigated 24 normal subjects (14 men and 10 women, aged from 23 to 60 years) and 14 patients with unilateral peripheral vestibular dysfunction. Each subject underwent oVEMP testing in response to monaural ACS and binaural ACS (500 Hz tone burst, 135 dBSPL). In normal subjects, bilateral oVEMPs were elicited in 75% of subjects in response to monaural ACS and in 91% in response to binaural ACS. Asymmetry ratios (ARs) of the responses to binaural ACS were significantly smaller than those of the responses to monaural ACS (p binaural ACS. Approximately 30% of patients showed reduced ARs to binaural ACS relative to monaural ACS, primarily due to contamination by uncrossed responses elicited in healthy ears.

  3. A clinical case study of a Wolfram syndrome-affected family: pattern-reversal visual evoked potentials and electroretinography analysis.

    Science.gov (United States)

    Langwińska-Wośko, Ewa; Broniek-Kowalik, Karina; Szulborski, Kamil

    2012-04-01

    Wolfram syndrome (WFS), or DIDMOAD, is a rare (1/100 000 to 1/770 000), progressive neurodegenerative disorder. In its early stages, it is characterized by insulin-dependent diabetes mellitus, optic atrophy and loss of sensorineural hearing-this is followed by diabetes insipidus, progressive neurological abnormalities and other endocrine abnormalities, which occur in later years. The aim of this study was to report on the clinical and electrophysiological findings from a family with the WFS1 mutation. The five family members were subjected to a complete ophthalmic examination, which included a flash full-field electroretinogram and pattern-reversal visual evoked potentials (PVEPs) performed according to ISCEV standards. Optic atrophy was confirmed in two homozygotic patients, where P100 latencies were significantly delayed-up to 146 ms in PVEP. P100 latencies were normal in the three heterozygotic patients we examined. Curve morphology abnormalities were observed in all five patients we examined. No literature describing the morphology of PVEP in Wolfram syndrome patients was found. In flash electroretinography, scotopic and photopic responses appeared in normal morphology and value. Diabetic retinopathy was not observed in the diabetes mellitus patients.

  4. Candida Biofilms: Threats, Challenges, and Promising Strategies

    Directory of Open Access Journals (Sweden)

    Mafalda Cavalheiro

    2018-02-01

    Full Text Available Candida species are fungal pathogens known for their ability to cause superficial and systemic infections in the human host. These pathogens are able to persist inside the host due to the development of pathogenicity and multidrug resistance traits, often leading to the failure of therapeutic strategies. One specific feature of Candida species pathogenicity is their ability to form biofilms, which protects them from external factors such as host immune system defenses and antifungal drugs. This review focuses on the current threats and challenges when dealing with biofilms formed by Candida albicans, Candida glabrata, Candida tropicalis, and Candida parapsilosis, highlighting the differences between the four species. Biofilm characteristics depend on the ability of each species to produce extracellular polymeric substances (EPS and display dimorphic growth, but also on the biofilm substratum, carbon source availability and other factors. Additionally, the transcriptional control over processes like adhesion, biofilm formation, filamentation, and EPS production displays great complexity and diversity within pathogenic yeasts of the Candida genus. These differences not only have implications in the persistence of colonization and infections but also on antifungal resistance typically found in Candida biofilm cells, potentiated by EPS, that functions as a barrier to drug diffusion, and by the overexpression of drug resistance transporters. The ability to interact with different species in in vivo Candida biofilms is also a key factor to consider when dealing with this problem. Despite many challenges, the most promising strategies that are currently available or under development to limit biofilm formation or to eradicate mature biofilms are discussed.

  5. Enantioselectivity of mass spectrometry: challenges and promises.

    Science.gov (United States)

    Awad, Hanan; El-Aneed, Anas

    2013-01-01

    With the fast growing market of pure enantiomer drugs and bioactive molecules, new chiral-selective analytical tools have been instigated including the use of mass spectrometry (MS). Even though MS is one of the best analytical tools that has efficiently been used in several pharmaceutical and biological applications, traditionally MS is considered as a "chiral-blind" technique. This limitation is due to the MS inability to differentiate between two enantiomers of a chiral molecule based merely on their masses. Several approaches have been explored to assess the potential role of MS in chiral analysis. The first approach depends on the use of MS-hyphenated techniques utilizing fast and sensitive chiral separation tools such as liquid chromatography (LC), gas chromatography (GC), and capillary electrophoresis (CE) coupled to MS detector. More recently, several alternative separation techniques have been evaluated such as supercritical fluid chromatography (SFC) and capillary electrochromatography (CEC); the latter being a hybrid technique that combines the efficiency of CE with the selectivity of LC. The second approach is based on using the MS instrument solely for the chiral recognition. This method depends on the behavioral differences between enantiomers towards a foreign molecule and the ability of MS to monitor such differences. These behavioral differences can be divided into three types: (i) differences in the enantiomeric affinity for association with the chiral selector, (ii) differences of the enantiomeric exchange rate with a foreign reagent, and (iii) differences in the complex MS dissociation behaviors of the enantiomers. Most recently, ion mobility spectrometry was introduced to qualitatively and quantitatively evaluate chiral compounds. This article provides an overview of MS role in chiral analysis by discussing MS based methodologies and presenting the challenges and promises associated with each approach. © 2013 Wiley Periodicals, Inc.

  6. Financial Technology: The Promise of Blockchain

    OpenAIRE

    Demary, Markus; Demary, Vera

    2017-01-01

    Digitization affects all sectors of the economy. A new and possibly disruptive digital technology is the blockchain, a decentralized ledger, which seems to offer great promise for many financial and business applications.

  7. SGLT2 inhibitors: a promising new therapeutic option for treatment of type 2 diabetes mellitus.

    Science.gov (United States)

    Misra, Monika

    2013-03-01

    Hyperglycemia is an important pathogenic component in the development of microvascular and macrovascular complications in type 2 diabetes mellitus. Inhibition of renal tubular glucose reabsorption that leads to glycosuria has been proposed as a new mechanism to attain normoglycemia and thus prevent and diminish these complications. Sodium glucose cotransporter 2 (SGLT2) has a key role in reabsorption of glucose in kidney. Competitive inhibitors of SGLT2 have been discovered and a few of them have also been advanced in clinical trials for the treatment of diabetes. To discuss the therapeutic potential of SGLT2 inhibitors currently in clinical development. A number of preclinical and clinical studies of SGLT2 inhibitors have demonstrated a good safety profile and beneficial effects in lowering plasma glucose levels, diminishing glucotoxicity, improving glycemic control and reducing weight in diabetes. Of all the SGLT2 inhibitors, dapagliflozin is a relatively advanced compound with regards to clinical development. SGLT2 inhibitors are emerging as a promising therapeutic option for the treatment of diabetes. Their unique mechanism of action offers them the potential to be used in combination with other oral anti-diabetic drugs as well as with insulin. © 2012 The Author. JPP © 2012 Royal Pharmaceutical Society.

  8. Framing the research agenda for sickle cell trait: building on the current understanding of clinical events and their potential implications.

    Science.gov (United States)

    Goldsmith, Jonathan C; Bonham, Vence L; Joiner, Clinton H; Kato, Gregory J; Noonan, Allan S; Steinberg, Martin H

    2012-03-01

    Sickle Cell Trait (HbAS), the heterozygous state for the sickle hemoglobin beta globin gene is carried by as many as 100 million individuals including up to 25% of the population in some regions of the world (World Health Organization, Provisional agenda item 4.8, EB117/34 (22 December 2005) or World Health Organization, Provisional agenda item 11.4 (24 April 2006)). Persons with HbAS have some resistance to falciparum malaria infection in early childhood (Piel FB, Patil AP, Howes RE, et al., Nat Commun 2010;1104:1-7 and Aidoo M, Terlouw DJ, Kolczak M, et al., Lancet 2002;359:1311-1312) and as a result individuals with HbAS living in malarial endemic regions of Africa have a survival advantage over individuals with HbAA. Reports from the US emphasize possible health risks for individuals with HbAS including increased incidence of renal failure and malignancy, thromboembolic disorders, splenic infarction as a high altitude complication, and exercise-related sudden death. The National Heart, Lung, and Blood Institute, National Institutes of Health convened a workshop in Bethesda, Maryland on June 3-4, 2010, Framing the Research Agenda for Sickle Cell Trait, to review the clinical manifestations of HbAS, discuss the exercise-related sudden death reports in HbAS, and examine the public health, societal, and ethical implications of policies regarding HbAS. The goal of the workshop was to identify potential research questions to address knowledge gaps.

  9. Site selection in global clinical trials in patients hospitalized for heart failure: perceived problems and potential solutions.

    Science.gov (United States)

    Gheorghiade, Mihai; Vaduganathan, Muthiah; Greene, Stephen J; Mentz, Robert J; Adams, Kirkwood F; Anker, Stefan D; Arnold, Malcolm; Baschiera, Fabio; Cleland, John G F; Cotter, Gadi; Fonarow, Gregg C; Giordano, Christopher; Metra, Marco; Misselwitz, Frank; Mühlhofer, Eva; Nodari, Savina; Frank Peacock, W; Pieske, Burkert M; Sabbah, Hani N; Sato, Naoki; Shah, Monica R; Stockbridge, Norman L; Teerlink, John R; van Veldhuisen, Dirk J; Zalewski, Andrew; Zannad, Faiez; Butler, Javed

    2014-03-01

    There are over 1 million hospitalizations for heart failure (HF) annually in the United States alone, and a similar number has been reported in Europe. Recent clinical trials investigating novel therapies in patients with hospitalized HF (HHF) have been negative, and the post-discharge event rate remains unacceptably high. The lack of success with HHF trials stem from problems with understanding the study drug, matching the drug to the appropriate HF subgroup, and study execution. Related to the concept of study execution is the importance of including appropriate study sites in HHF trials. Often overlooked issues include consideration of the geographic region and the number of patients enrolled at each study center. Marked differences in baseline patient co-morbidities, serum biomarkers, treatment utilization and outcomes have been demonstrated across geographic regions. Furthermore, patients from sites with low recruitment may have worse outcomes compared to sites with higher enrollment patterns. Consequently, sites with poor trial enrollment may influence key patient end points and likely do not justify the costs of site training and maintenance. Accordingly, there is an unmet need to develop strategies to identify the right study sites that have acceptable patient quantity and quality. Potential approaches include, but are not limited to, establishing a pre-trial registry, developing site performance metrics, identifying a local regionally involved leader and bolstering recruitment incentives. This manuscript summarizes the roundtable discussion hosted by the Food and Drug Administration between members of academia, the National Institutes of Health, industry partners, contract research organizations and academic research organizations on the importance of selecting optimal sites for successful trials in HHF.

  10. Evaluation of the Potential Risk of Drugs to Induce Hepatotoxicity in Human?Relationships between Hepatic Steatosis Observed in Non-Clinical Toxicity Study and Hepatotoxicity in Humans-

    OpenAIRE

    Goda, Keisuke; Kobayashi, Akio; Takahashi, Akemi; Takahashi, Tadakazu; Saito, Kosuke; Maekawa, Keiko; Saito, Yoshiro; Sugai, Shoichiro

    2017-01-01

    In the development of drugs, we sometimes encounter fatty change of the hepatocytes (steatosis) which is not accompanied by degenerative change in the liver in non-clinical toxicity studies. In this study, we investigated the relationships between fatty change of the hepatocytes noted in non-clinical toxicity studies of compound X, a candidate compound in drug development, and mitochondrial dysfunction in order to estimate the potential risk of the compound to induce drug-induced liver injury...

  11. Realising the promise of Tanzania’s wildlife management areas

    DEFF Research Database (Denmark)

    Homewood, Katherine; Lund, Jens Friis; Keane, Aidan

    2017-01-01

    Tanzania’s Community Wildlife Management Areas (CWMAs) – originally called Wildlife Management Areas (WMAs) – were intended to benefit both people and wildlife. However, for their first two decades, CWMAs have been characterised by land conflict, wildlife damage to people and crops, lack of tourism...... potential and high administration costs among other negative impacts. Can rethinking how CWMAs are run bring about the benefits once promised?...

  12. Do promises matter? An exploration of the role of promises in psychological contract breach.

    Science.gov (United States)

    Montes, Samantha D; Zweig, David

    2009-09-01

    Promises are positioned centrally in the study of psychological contract breach and are argued to distinguish psychological contracts from related constructs, such as employee expectations. However, because the effects of promises and delivered inducements are confounded in most research, the role of promises in perceptions of, and reactions to, breach remains unclear. If promises are not an important determinant of employee perceptions, emotions, and behavioral intentions, this would suggest that the psychological contract breach construct might lack utility. To assess the unique role of promises, the authors manipulated promises and delivered inducements separately in hypothetical scenarios in Studies 1 (558 undergraduates) and 2 (441 employees), and they measured them separately (longitudinally) in Study 3 (383 employees). The authors' results indicate that breach perceptions do not represent a discrepancy between what employees believe they were promised and were given. In fact, breach perceptions can exist in the absence of promises. Further, promises play a negligible role in predicting feelings of violation and behavioral intentions. Contrary to the extant literature, the authors' findings suggest that promises may matter little; employees are concerned primarily with what the organization delivers.

  13. The path to fulfilling the promise

    Energy Technology Data Exchange (ETDEWEB)

    Barrett, J. [Canadian Nuclear Association, Ottawa, ON (Canada)

    2014-07-01

    'Full text:'Countries work together to develop effective governance and regulation. Canada has made big investments in these areas and it carries a premium for us. The rapid build-out of nuclear technology around the Pacific Rim holds vast promise for our populations in better climate, better air, affordable and reliable electricity, and longer lives. The biggest risk is not another accident: rather, it is the risk of failing to fulfill that promise to our people. Every country that wants the benefits of nuclear must also want to be sure that those benefits are realized and sustained by good governance and regulation. Canada has the people, laws, organizations, public institutions, and relationships that can help our partners fulfill the whole and lasting promise of nuclear technology. (author)

  14. Green and social bonds - A promising tool

    International Nuclear Information System (INIS)

    Blanc, Dominique; Barochez, Aurelie de; Cozic, Aela

    2013-11-01

    Issues of green bonds, socially responsible bonds and climate bonds are on the rise. Novethic estimates that some Euro 5 billion in such bonds has been issued since the start of 2013 by development banks, the main issuers of this type of debt. The figure is equal to over half of their total issues since 2007. Including local authorities, corporations and banks, a total Euro 8 billion of these bonds has been issued thus far in 2013. Given the size of the bond market, which the OECD estimated at Euro 95,000 billion in 2011, green and social bonds are still something of a niche but have strong growth potential. A number of large issues, from Euro 500 million to Euro 1 billion, were announced at the end of the year. Unlike conventional bonds, green and social bonds are not intended to finance all the activities of the issuer or refinance its debt. They serve instead to finance specific projects, such as producing renewable energy or adapting to climate change, the risk of which is shouldered by the issuer. This makes them an innovative instrument, used to earmark investments in projects with a direct environmental or social benefit rather than simply on the basis of the issuer's sustainable development policy. With financing being sought for the ecological transition, green and social bonds are promising instruments, sketching out at global level the shape of tools adapted to the financing of a green economy. On the strength of these advantages, the interest of responsible investors - the main target of green and social bond issuers - is growing fast. Judging by issuer press releases and the most commonly used currencies, the main subscribers today are US investors, among them CalSTRS and fund managers like Calvert Investment Management and Trillium Asset Management. European asset owners are also starting to focus on green and social bonds. A Novethic survey shows that 13% of them have already subscribed to such an issue or plan to do so. The present study

  15. Blocking TRPA1 in Respiratory Disorders: Does It Hold a Promise?

    Directory of Open Access Journals (Sweden)

    Indranil Mukhopadhyay

    2016-11-01

    Full Text Available Transient Receptor Potential Ankyrin 1 (TRPA1 ion channel is expressed abundantly on the C fibers that innervate almost entire respiratory tract starting from oral cavity and oropharynx, conducting airways in the trachea, bronchi, terminal bronchioles, respiratory bronchioles and upto alveolar ducts and alveoli. Functional presence of TRPA1 on non-neuronal cells got recognized recently. TRPA1 plays a well-recognized role of “chemosensor”, detecting presence of exogenous irritants and endogenous pro-inflammatory mediators that are implicated in airway inflammation and sensory symptoms like chronic cough, asthma, chronic obstructive pulmonary disease (COPD, allergic rhinitis and cystic fibrosis. TRPA1 can remain activated chronically due to elevated levels and continued presence of such endogenous ligands and pro-inflammatory mediators. Several selective TRPA1 antagonists have been tested in animal models of respiratory disease and their performance is very promising. Although there is no TRPA1 antagonist in advanced clinical trials or approved on market yet to treat respiratory diseases, however, limited but promising evidences available so far indicate likelihood that targeting TRPA1 may present a new therapy in treatment of respiratory diseases in near future. This review will focus on in vitro, animal and human evidences that strengthen the proposed role of TRPA1 in modulation of specific airway sensory responses and also on preclinical and clinical progress of selected TRPA1 antagonists.

  16. The potential value on medication safety of a clinical decision support system in intensive care patients with renal insufficiency.

    NARCIS (Netherlands)

    Helmons, P.J.; Grouls, R.J.E.; Roos, A.N.; Bindels, A.J.G.H.; Clercq, de P.A.; Wessels-Basten, S.J.W.; Ackerman, E.W.; Korsten, H.H.M.

    2007-01-01

    Clinical decision support systems (CDSS) are defined as electronic or non-electronic systems designed to aid in clinical decision making, using characteristics of individual patients to generate patient-specific assessments or recommendations that are then presented to clinicians for consideration

  17. [Post-marketing reevaluation for potential quality risk and quality control in clinical application of traditional Chinese medicines].

    Science.gov (United States)

    Li, Hong-jiao; He, Li-yun; Liu, Bao-yan

    2015-06-01

    The effective quality control in clinical practices is an effective guarantee for the authenticity and scientificity of the findings. The post-marketing reevaluation for traditional Chinese medicines (TCM) focuses on the efficacy, adverse reaction, combined medication and effective dose of drugs in the market by expanded clinical trials, and requires a larger sample size and a wider range of patients. Therefore, this increases the difficulty of quality control in clinical practices. With the experience in quality control in clinical practices for the post-marketing reevaluation for Kangbingdu oral for cold, researchers in this study reviewed the study purpose, project, scheme design and clinical practice process from an overall point of view, analyzed the study characteristics of the post-marketing reevaluation for TCMs and the quality control risks, designed the quality control contents with quality impacting factors, defined key review contents and summarized the precautions in clinical practices, with the aim to improve the efficiency of quality control of clinical practices. This study can provide reference to clinical units and quality control-related personnel in the post-marketing reevaluation for TCMs.

  18. Promising Compilation to ARMv8 POP

    OpenAIRE

    Podkopaev, Anton; Lahav, Ori; Vafeiadis, Viktor

    2017-01-01

    We prove the correctness of compilation of relaxed memory accesses and release-acquire fences from the "promising" semantics of [Kang et al. POPL'17] to the ARMv8 POP machine of [Flur et al. POPL'16]. The proof is highly non-trivial because both the ARMv8 POP and the promising semantics provide some extremely weak consistency guarantees for normal memory accesses; however, they do so in rather different ways. Our proof of compilation correctness to ARMv8 POP strengthens the results of the Kan...

  19. Resveratrol exhibits a strong cytotoxic activity in cultured cells and has an antiviral action against polyomavirus: potential clinical use

    Directory of Open Access Journals (Sweden)

    Galati Gaspare

    2009-07-01

    cytotoxic and inhibits, in a dose dependent fashion, the synthesis of polyomavirus DNA in the infected cell. Furthermore, this inhibition is observed at non cytotoxic concentrations of the drug. Our data imply that cyto-toxicity may be attributed to the membrane damage caused by the drug and that the transfer of polyomavirus from the endoplasmic reticulum to the cytoplasm may be hindered. In conclusion, the cytotoxic and antiviral properties of resveratrol make it a potential candidate for the clinical control of proliferative as well as viral pathologies.

  20. Clinical Language Intervention Programme (KLISA PROGRAMME to Improve Reading Skill of Students with Learning Disability with Potential in Education

    Directory of Open Access Journals (Sweden)

    Bungawali Abduh

    2017-03-01

    Full Text Available Reading is one of the fundamental skills across all subjects. A student with low competency in reading will experience difficulties in teaching and learning. The purpose of this research is to improve reading skills among student with learning disability in one secondary school in Bangi, Selangor. This action research had employed Reading Assessment Approach and descriptive analysis in data collection. Seven students with reading problem participated in this research. However, these students were having potential to be included in either Inclusive Program or Job Transition Program. Therefore, one reading program known as KLISA Program (Language Clinic Program was created and it has been implemented in classroom for 30 minutes during the first period every day. This 9-month program had employed phonics method and used a set of ‘Bacalah Anakku’ books and ABM Velcro in three phases. The reading assessment was conducted at the end of each phase to evaluate the students’ achievement in reading. The findings of this research proved that KLISA Program was effective for students’ improvement in reading. Hence, it is recommended that this program can be consistently implemented to overcome illiterate and reading disorder among primary and secondary school students. Kemahiran membaca adalah merentas semua matapelajaran. Kelemahan dalam kemahiran membaca akan menyebabkan kesulitan mengikuti pengajaran dan pembelajaran. Tujuan penelitian ini adalah untuk meningkatkan kemahiran membaca di kalangan murid-murid bermasalah pembelajaran di sebuah sekolah menengah di Bangi, Selangor. Penelitian tindakan ini menggunakan pendekatan penilaian penaksiran bacaan dan analisis deskriptif untuk mengumpul data, Seramai 7 orang murid dalam sebuah kelas terlibat dalam kajian ini. Mereka terdiri dari murid bermasalah pembelajaran yang berpotensi untuk diserapkan di dalam Program Inklusif atau Transisi pekerjaan tetapi masih tidak boleh membaca. Satu program pemulihan

  1. Prevalence of potentially inappropriate prescribing in a subpopulation of older European clinical trial participants: a cross-sectional study.

    Science.gov (United States)

    O Riordan, David; Aubert, Carole Elodie; Walsh, Kieran A; Van Dorland, Anette; Rodondi, Nicolas; Du Puy, Robert S; Poortvliet, Rosalinde K E; Gussekloo, Jacobijn; Sinnott, Carol; Byrne, Stephen; Galvin, Rose; Jukema, J Wouter; Mooijaart, Simon P; Baumgartner, Christine; McCarthy, Vera; Walsh, Elaine K; Collet, Tinh-Hai; Dekkers, Olaf M; Blum, Manuel R; Kearney, Patricia M

    2018-03-22

    To estimate and compare the prevalence and type of potentially inappropriate prescribing (PIP) and potential prescribing omissions (PPOs) among community-dwelling older adults (≥65 years) enrolled to a clinical trial in three European countries. A secondary analysis of the Thyroid Hormone Replacement for Subclinical Hypothyroidism Trial dataset. A subset of 48/80 PIP and 22/34 PPOs indicators from the Screening Tool of Older Persons Prescriptions/Screening Tool to Alert doctors to Right Treatment (STOPP/START) V2 criteria were applied to prescribed medication data for 532/737 trial participants in Ireland, Switzerland and the Netherlands. The overall prevalence of PIP was lower in the Irish participants (8.7%) compared with the Swiss (16.7%) and Dutch (12.5%) participants (P=0.15) and was not statistically significant. The overall prevalence of PPOs was approximately one-quarter in the Swiss (25.3%) and Dutch (24%) participants and lower in the Irish (14%) participants (P=0.04) and the difference was statistically significant. The hypnotic Z-drugs were the most frequent PIP in Irish participants, (3.5%, n=4), while it was non-steroidal anti-inflammatory drug and oral anticoagulant combination, sulfonylureas with a long duration of action, and benzodiazepines (all 4.3%, n=7) in Swiss, and benzodiazepines (7.1%, n=18) in Dutch participants. The most frequent PPOs in Irish participants were vitamin D and calcium in osteoporosis (3.5%, n=4). In the Swiss and Dutch participants, they were bone antiresorptive/anabolic therapy in osteoporosis (9.9%, n=16, 8.6%, n=22) respectively. The odds of any PIP after adjusting for age, sex, multimorbidity and polypharmacy were (adjusted OR (aOR)) 3.04 (95% CI 1.33 to 6.95, P<0.01) for Swiss participants and aOR 1.74 (95% CI 0.79 to 3.85, P=0.17) for Dutch participants compared with Irish participants. The odds of any PPOs were aOR 2.48 (95% CI 1.27 to 4.85, P<0.01) for Swiss participants and aOR 2.10 (95% CI 1.11 to 3.96, P=0

  2. Promising Therapeutics with Natural Bioactive Compounds for Improving Learning and Memory — A Review of Randomized Trials

    Directory of Open Access Journals (Sweden)

    Jin-Yong Choi

    2012-09-01

    Full Text Available Cognitive disorders can be associated with brain trauma, neurodegenerative disease or as a part of physiological aging. Aging in humans is generally associated with deterioration of cognitive performance and, in particular, learning and memory. Different therapeutic approaches are available to treat cognitive impairment during physiological aging and neurodegenerative or psychiatric disorders. Traditional herbal medicine and numerous plants, either directly as supplements or indirectly in the form of food, improve brain functions including memory and attention. More than a hundred herbal medicinal plants have been traditionally used for learning and memory improvement, but only a few have been tested in randomized clinical trials. Here, we will enumerate those medicinal plants that show positive effects on various cognitive functions in learning and memory clinical trials. Moreover, besides natural products that show promising effects in clinical trials, we briefly discuss medicinal plants that have promising experimental data or initial clinical data and might have potential to reach a clinical trial in the near future.

  3. Profiling inflammatory biomarkers in cervico-vaginal mucus (CVM) postpartum: Potential early indicators of bovine clinical endometritis?

    Science.gov (United States)

    Adnane, Mounir; Chapwanya, Aspinas; Kaidi, Rachid; Meade, Kieran G; O'Farrelly, Cliona

    2017-11-01

    Endometritis significantly impacts fertility and milk yield, thus reducing profitability of the dairy production. In cows that develop endometritis, normal postpartum endometrial inflammation is dysregulated. Here, we propose that endometrial inflammation is reflected in cervico-vaginal mucus (CVM) which could therefore be used as a prognostic tool. CVM was collected from 20 dairy cows (10 with clinical endometritis and 10 healthy) 7 and 21 days postpartum (DPP). Polymorphonuclear (PMN), mononuclear leukocyte and epithelial cells were counted, total protein levels were estimated and levels of IL-1β, IL-6, IL-8, serum amyloid A (SAA), haptoglobin (Hp) and C5b were analyzed by ELISA in CVM. PMN were consistently high in CVM from 7 to 21 DPP, but were higher in CVM from cows with clinical endometritis 21 DPP compared with healthy cows. In contrast, there were more epithelial cells in healthy cows 21 DPP than in clinical endometritis animals. Total protein levels decreased significantly in CVM from healthy cows between days 7 and 21 postpartum. All inflammatory biomarkers except C5b, remained high in cows with clinical endometritis from 7 to 21 DPP, indicating sustained and chronic endometrial inflammation. IL1, IL-6, IL-8 and Hp levels were higher in CVM from cows with clinical endometritis compared to healthy cows 21 DPP. Interestingly IL-1β levels were raised in CVM from clinical endometritis but not in healthy cows 7 DPP suggesting that early measurement of IL-1β levels might provide a useful predictive marker of clinical endometritis. In contrast, SAA and C5b levels were increased in healthy cows 21 DPP, compared to cows with clinical endometritis suggesting that these acute phase proteins might have an anti-inflammatory role. Our results show that CVM is convenient for profiling disease-associated changes in key inflammatory molecules postpartum and reaffirms that sustained inflammation is a key feature of clinical endometritis in the dairy cow. Copyright

  4. The potential use of ultra-low radiation dose images in digital mammography-a clinical proof-of-concept study in craniocaudal views

    NARCIS (Netherlands)

    Bluekens, A. M. J.; Veldkamp, W. J. H.; Schuur, K. H.; Karssemeijer, N.; Broeders, M. J. M.; den Heeten, G. J.

    2015-01-01

    Objective: To estimate the potential of low-dose images in digital mammography by analysing the effect of substantial dose reduction in craniocaudal (CC) views on clinical performance. Methods: At routine mammography, additional CC views were obtained with about 10% of the standard dose. Five

  5. The potential use of ultra-low radiation dose images in digital mammography--a clinical proof-of-concept study in craniocaudal views

    NARCIS (Netherlands)

    Bluekens, A.M.; Veldkamp, W.J.H.; Schuur, K.H.; Karssemeijer, N.; Broeders, M.J.; Heeten, GJ. den

    2015-01-01

    OBJECTIVE: To estimate the potential of low-dose images in digital mammography by analysing the effect of substantial dose reduction in craniocaudal (CC) views on clinical performance. METHODS: At routine mammography, additional CC views were obtained with about 10% of the standard dose. Five

  6. Therapeutic treatments potentially mediated by melatonin receptors: potential clinical uses in the prevention of osteoporosis, cancer and as an adjuvant therapy.

    Science.gov (United States)

    Witt-Enderby, Paula A; Radio, Nicholas M; Doctor, John S; Davis, Vicki L

    2006-11-01

    Melatonin's therapeutic potential is grossly underestimated because its functional roles are diverse and its mechanism(s) of action are complex and varied. Melatonin produces cellular effects via a variety of mechanisms in a receptor independent and dependent manner. In addition, melatonin is a chronobiotic agent secreted from the pineal gland during the hours of darkness. This diurnal release of melatonin impacts the sensitivity of melatonin receptors throughout a 24-hr period. This changing sensitivity probably contributes to the narrow therapeutic window for use of melatonin in treating sleep disorders, that is, at the light-to-dark (dusk) or dark-to-light (dawn) transition states. In addition to the cyclic changes in melatonin receptors, many genes cycle over the 24-hr period, independent or dependent upon the light/dark cycle. Interestingly, many of these genes support a role for melatonin in modulating metabolic and cardiovascular physiology as well as bone metabolism and immune function and detoxification of chemical agents and cancer reduction. Melatonin also enhances the actions of a variety of drugs or hormones; however, the role of melatonin receptors in modulating these processes is not known. The goal of this review is to summarize the evidence related to the utility of melatonin as a therapeutic agent by focusing on its other potential uses besides sleep disorders. In particular, its use in cancer prevention, osteoporosis and, as an adjuvant to other therapies are discussed. Also, the role that melatonin and, particularly, its receptors play in these processes are highlighted.

  7. The Promise of Zoomable User Interfaces

    Science.gov (United States)

    Bederson, Benjamin B.

    2011-01-01

    Zoomable user interfaces (ZUIs) have received a significant amount of attention in the 18 years since they were introduced. They have enjoyed some success, and elements of ZUIs are widely used in computers today, although the grand vision of a zoomable desktop has not materialised. This paper describes the premise and promise of ZUIs along with…

  8. Promising carbons for supercapacitors derived from fungi

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Hui; Wang, Xiaolei; Yang, Fan; Yang, Xiurong [State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022 (China)

    2011-06-24

    Activated carbons with promising performance in capacitors are produced from fungi via a hydrothermal assistant pyrolysis approach. This study introduces a facile strategy to discover carbonaceous materials and triggers interest in exploring fungi for material science applications. (Copyright copyright 2011 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  9. Seaweed: Promising plant of the millennium

    Digital Repository Service at National Institute of Oceanography (India)

    Dhargalkar, V.K.; Pereira, N.

    Seaweeds, one of the important marine living resources could be termed as the futuristically promising plants. These plants have been a source of food, feed and medicine in the orient as well as in the west, since ancient times. Although, seaweeds...

  10. Complexity of Propositional Proofs Under a Promise

    Czech Academy of Sciences Publication Activity Database

    Dershowitz, N.; Tzameret, Iddo

    2010-01-01

    Roč. 11, č. 3 (2010), s. 1-29 ISSN 1529-3785 Institutional research plan: CEZ:AV0Z10190503 Keywords : theory * promise problems * propositional proof complexity * random 3CNF * resolution Subject RIV: BA - General Mathematics Impact factor: 1.391, year: 2010 http://dl.acm.org/ citation .cfm?doid=1740582.1740586

  11. Complexity of Propositional Proofs Under a Promise

    Czech Academy of Sciences Publication Activity Database

    Dershowitz, N.; Tzameret, Iddo

    2010-01-01

    Roč. 11, č. 3 (2010), s. 1-29 ISSN 1529-3785 Institutional research plan: CEZ:AV0Z10190503 Keywords : theory * promise problems * propositional proof complexity * random 3CNF * resolution Subject RIV: BA - General Mathematics Impact factor: 1.391, year: 2010 http://dl.acm.org/citation.cfm?doid=1740582.1740586

  12. 76 FR 13152 - Promise Neighborhoods Program

    Science.gov (United States)

    2011-03-10

    ... comprehensive education reforms that are linked to improved educational outcomes for children and youth in... parents or family members who report talking with their child about the importance of college and career... DEPARTMENT OF EDUCATION RIN 1855-ZA07 Promise Neighborhoods Program Catalog of Federal Domestic...

  13. 4D co-registration of X-ray and MR-mammograms: initial clinical results and potential incremental diagnostic value.

    Science.gov (United States)

    Dietzel, Matthias; Hopp, Torsten; Ruiter, Nicole V; Kaiser, Clemens G; Kaiser, Werner A; Baltzer, Pascal A

    2015-01-01

    4D co-registration of X-ray- and MR-mammograms (XM and MM) is a new method of image fusion. The present study aims to evaluate its clinical feasibility, radiological accuracy, and potential clinical value. XM and MM of 25 patients were co-registered. Results were evaluated by a blinded reader. Precision of the 4D co-registration was "very good" (mean-score [ms]=7), and lesions were "easier to delineate" (ms=5). In 88.8%, "relevant additional diagnostic information" was present, accounting for a more "confident diagnosis" in 76% (ms=5). 4D co-registration is feasible, accurate, and of potential clinical value. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Perceptual Measurement in Schizophrenia: Promising Electrophysiology and Neuroimaging Paradigms From CNTRICS

    Science.gov (United States)

    Butler, Pamela D.; Chen, Yue; Ford, Judith M.; Geyer, Mark A.; Silverstein, Steven M.; Green, Michael F.

    2012-01-01

    The sixth meeting of the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS) focused on selecting promising imaging paradigms for each of the cognitive constructs selected in the first CNTRICS meeting. In the domain of perception, the 2 constructs of interest were “gain control” and “visual integration.” CNTRICS received 6 task nominations for imaging paradigms for gain control and 3 task nominations for integration. The breakout group for perception evaluated the degree to which each of these tasks met prespecified criteria. For gain control, the breakout group believed that one task (mismatch negativity) was already mature and was being incorporated into multisite clinical trials. The breakout group recommended that 1 visual task (steady-state visual evoked potentials to magnocellular- vs parvocellular-biased stimuli) and 2 auditory measures (an event-related potential (ERP) measure of corollary discharge and a functional magnetic resonance imaging (fMRI) version of prepulse inhibition of startle) be adapted for use in clinical trials in schizophrenia research. For visual integration, the breakout group recommended that fMRI and ERP versions of a contour integration test and an fMRI version of a coherent motion test be adapted for use in clinical trials. This manuscript describes the ways in which each of these tasks met the criteria used in the breakout group to evaluate and recommend tasks for further development. PMID:21890745

  15. [Absorbable coronary stents. New promising technology].

    Science.gov (United States)

    Erbel, Raimund; Böse, Dirk; Haude, Michael; Kordish, Igor; Churzidze, Sofia; Malyar, Nasser; Konorza, Thomas; Sack, Stefan

    2007-06-01

    Coronary stent implantation started in Germany 20 years ago. In the beginning, the progress was very slow and accelerated 10 years later. Meanwhile, coronary stent implantation is a standard procedure in interventional cardiology. From the beginning of permanent stent implantation, research started to provide temporary stenting of coronary arteries, first with catheter-based systems, later with stent-alone technology. Stents were produced from polymers or metal. The first polymer stent implantation failed except the Igaki-Tamai stent in Japan. Newly developed absorbable polymer stents seem to be very promising, as intravascular ultrasound (IVUS) and optical coherence tomography have demonstrated. Temporary metal stents were developed based on iron and magnesium. Currently, the iron stent is tested in peripheral arteries. The absorbable magnesium stent (Biotronik, Berlin, Germany) was tested in peripheral arteries below the knee and meanwhile in the multicenter international PROGRESS-AMS (Clinical Performance and Angiographic Results of Coronary Stenting with Absorbable Metal Stents) study. The first magnesium stent implantation was performed on July 30, 2004 after extended experimental testing in Essen. The magnesium stent behaved like a bare-metal stent with low recoil of 5-7%. The stent struts were absorbed when tested with IVUS. Stent struts were not visible by fluoroscopy or computed tomography (CT) as well as magnetic resonance imaging (MRI). That means, that the magnesium stent is invisible and therefore CT and MRI can be used for imaging of interventions. Only using micro-CT the stent struts were visible. The absorption process could be demonstrated in a patient 18 days after implantation due to suspected acute coronary syndrome, which was excluded. IVUS showed a nice open lumen. Stent struts were no longer visible, but replaced by tissue indicating the previous stent location. Coronary angiography after 4 months showed an ischemia-driven target lesion

  16. Promising Themes for Antismoking Campaigns Targeting Youth and Young Adults.

    Science.gov (United States)

    Brennan, Emily; Gibson, Laura A; Kybert-Momjian, Ani; Liu, Jiaying; Hornik, Robert C

    2017-01-01

    Behavior change campaigns typically try to change beliefs that influence behaviors, with targeted beliefs comprising the campaign theme. We present an empirical approach for choosing among a large number of potential themes, and results from the implementation of this approach for campaigns aimed at 4 behavioral targets: (1) preventing smoking initiation among youth, and (2) preventing initiation, (3) stopping progression to daily smoking and (4) encouraging cessation among young adults. An online survey of 13- to 17-year-olds and 18- to 25-year-olds in the United States (US), in which 20 potential campaign themes were represented by 154 beliefs. For each behavioral target, themes were ranked based on the strength of belief-intention and belief-behavior associations and size of the population not already endorsing the beliefs. The most promising themes varied across behavioral targets but 3 were consistently promising: consequences of smoking for mood, social acceptance and social popularity. Using a robust and systematic approach, this study provides campaign developers with empirical data to inform their selection of promising themes. Findings related to the campaign to prevent initiation among youth informed the development of the US Food and Drug Administration's "The Real Cost" campaign.

  17. MO-C-BRB-05: Translating NIH funding to a [potential] clinical device in breast cancer radiation therapy

    International Nuclear Information System (INIS)

    Yu, C.

    2015-01-01

    Diagnostic radiology and radiation oncology are arguably two of the most technologically advanced specialties in medicine. The imaging and radiation medicine technologies in clinical use today have been continuously improved through new advances made in the commercial and academic research arenas. This symposium explores the translational path from research through clinical implementation. Dr. Pettigrew will start this discussion by sharing his perspectives as director of the National Institute of Biomedical Imaging and Bioengineering (NIBIB). The NIBIB has focused on promoting research that is technological in nature and has high clinical impact. We are in the age of precision medicine, and the technological innovations and quantitative tools developed by engineers and physicists working with physicians are providing innovative tools that increase precision and improve outcomes in health care. NIBIB funded grants lead to a very high patenting rate (per grant dollar), and these patents have higher citation rates by other patents, suggesting greater clinical impact, as well. Two examples of clinical translation resulting from NIH-funded research will be presented, in radiation therapy and diagnostic imaging. Dr. Yu will describe a stereotactic radiotherapy device developed in his laboratory that is designed for treating breast cancer with the patient in the prone position. It uses 36 rotating Cobalt-60 sources positioned in an annular geometry to focus the radiation beam at the system’s isocenter. The radiation dose is delivered throughout the target volume in the breast by constantly moving the patient in a planned trajectory relative to the fixed isocenter. With this technique, the focal spot dynamically paints the dose distribution throughout the target volume in three dimensions. Dr. Jackson will conclude this symposium by describing the RSNA Quantitative Imaging Biomarkers Alliance (QIBA), which is funded in part by NIBIB and is a synergistic collaboration

  18. MO-C-BRB-05: Translating NIH funding to a [potential] clinical device in breast cancer radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Yu, C. [Univ Maryland School of Medicine (United States)

    2015-06-15

    Diagnostic radiology and radiation oncology are arguably two of the most technologically advanced specialties in medicine. The imaging and radiation medicine technologies in clinical use today have been continuously improved through new advances made in the commercial and academic research arenas. This symposium explores the translational path from research through clinical implementation. Dr. Pettigrew will start this discussion by sharing his perspectives as director of the National Institute of Biomedical Imaging and Bioengineering (NIBIB). The NIBIB has focused on promoting research that is technological in nature and has high clinical impact. We are in the age of precision medicine, and the technological innovations and quantitative tools developed by engineers and physicists working with physicians are providing innovative tools that increase precision and improve outcomes in health care. NIBIB funded grants lead to a very high patenting rate (per grant dollar), and these patents have higher citation rates by other patents, suggesting greater clinical impact, as well. Two examples of clinical translation resulting from NIH-funded research will be presented, in radiation therapy and diagnostic imaging. Dr. Yu will describe a stereotactic radiotherapy device developed in his laboratory that is designed for treating breast cancer with the patient in the prone position. It uses 36 rotating Cobalt-60 sources positioned in an annular geometry to focus the radiation beam at the system’s isocenter. The radiation dose is delivered throughout the target volume in the breast by constantly moving the patient in a planned trajectory relative to the fixed isocenter. With this technique, the focal spot dynamically paints the dose distribution throughout the target volume in three dimensions. Dr. Jackson will conclude this symposium by describing the RSNA Quantitative Imaging Biomarkers Alliance (QIBA), which is funded in part by NIBIB and is a synergistic collaboration

  19. Service Users perspectives in PROMISE and research.

    Science.gov (United States)

    Rae, Sarah

    2017-09-01

    Since its inception in 2013, PROMISE (PROactive Management of Integrated Services and Environments) has been supporting service users and staff at the Cambridgeshire and Peterborough NHS Foundation Trust (CPFT) on a journey to reduce reliance on force. The author's own personal experiences led to the founding of PROMISE and illustrates how individual experiences can influence a patient to lead change. Coproduction is actively embedded in PROMISE. Patients have been meaningfully involved because they are innovators and problem solvers who bring an alternative viewpoint by the very nature of their condition. A patient is more than just a person who needs to be 'fixed' they are individuals with untapped skills and added insight. There have been 2 separate Patient Advisory Groups (PAGs) since the project was first established. The first Patient Advisory Group was recruited to work with the PROMISE researchers on a study which used a participatory qualitative approach. Drawing on their lived experience and different perspectives the PAG was instrumental in shaping the qualitative study, including the research questions. Their active involvement helped to ensure that that the study was sensitively designed, methodologically robust and ethically sound. The 2 nd PAG was formed in 2016 to give the project an overall steer. Patients in this group contributed to the work on the 'No' Audit and reviewed several CPFT policies such as the Seclusion and Segregation policy which has impacted on frontline practice. They also made a significant contribution to the study design for a funding application that was submitted by the PROMISE team to the National Institute for Health Research (NIHR). Both PAGs were supported by funding from East of England Collaboration for Leadership in Applied Health Research and Care (CLAHRC EoE) and were influential in different ways. An evaluation of the 2 nd PAG which was conducted in June 2017 showed very high satisfaction levels. The free text

  20. Clinical Trials

    Medline Plus

    Full Text Available ... take part in a clinical trial. When researchers think that a trial's potential risks are greater than ... care costs for clinical trials. If you're thinking about taking part in a clinical trial, find ...

  1. ESHRE/ESGE female genital tract anomalies classification system-the potential impact of discarding arcuate uterus on clinical practice.

    Science.gov (United States)

    Knez, J; Saridogan, E; Van Den Bosch, T; Mavrelos, D; Ambler, G; Jurkovic, D

    2018-04-01

    What would be a potential impact of implementing the new ESHRE/European Society of Gynaecological Endoscopy (ESGE) female genital anomalies classification system on the management of women with previous diagnosis of arcuate uteri based on the modified American Society for Reproductive Medicine (ASRM) criteria? A significant number of women with previous diagnosis of arcuate uteri are reclassified as having partial septate uteri according to the new ESHRE/ESGE classification system which may increase the number of remedial surgical procedures. The ESHRE/ESGE classification system has defined measurement techniques, reference points and specific cut-offs to facilitate the differentiation between normal and septate uteri. These criteria have been arbitrarily defined and they rely on the measurement of uterine wall thickness and depth of distortion of uterine fundus. This was a retrospective cohort study. We searched our ultrasound clinic database from January 2011 to December 2014 to identify all women diagnosed with arcuate uterus on three-dimensional ultrasound according to the modified ASRM criteria. For each woman, the ultrasound images were stored in our clinical database and they were re-examined according to ESHRE/ESGE specifications. The presence and location of all acquired uterine anomalies, such as fibroids or adenomyosis was noted. We applied the two diagnostic approaches as specified by the ESHRE/ESGE classification: the main option (MO) and the alternative option (AO). We used the Kappa statistic to quantify the agreement between the two approaches. We also compared the number of previous miscarriages in women with normal and partial septate uteri according to the ESHRE/ESGE classification. Non-parametric Mann-Whitney and Kruskal-Wallis tests were used for the analyses and receiver-operating characteristic curves were constructed to assess the predictive values of the calculated uterine distortion indices for the detection of women at risk of suffering

  2. Natural Flavonoids as Promising Analgesic Candidates: A Systematic Review.

    Science.gov (United States)

    Xiao, Xiao; Wang, Xiaoyu; Gui, Xuan; Chen, Lu; Huang, Baokang

    2016-11-01

    Due to the chemical structural diversity and various analgesic mechanisms, an increasing number of studies indicated that some flavonoids from medicinal plants could be promising candidates for new natural analgesic drugs, which attract high interests of advanced users and academic researchers. The aim of this systematic review is to report flavonoids and its derivatives as new analgesic candidates based on the pharmacological evidences. Sixty-four papers were found concerning the potential analgesic activity of 46 flavonoids. In this case, the evidence for analgesic activity of flavonoids and total flavonoids was investigated. Meanwhile, the corresponding analgesic mechanism of flavonoids was discussed by generalizing and analyzing the current publications. Based on this review, the conclusion can be drawn that some flavonoids are promising candidates for painful conditions and deserve particular attention in further research and development. © 2016 Wiley-VHCA AG, Zurich, Switzerland.

  3. The microeconomics of personalized medicine: today's challenge and tomorrow's promise.

    Science.gov (United States)

    Davis, Jerel C; Furstenthal, Laura; Desai, Amar A; Norris, Troy; Sutaria, Saumya; Fleming, Edd; Ma, Philip

    2009-04-01

    'Personalized medicine' promises to increase the quality of clinical care and, in some cases, decrease health-care costs. Despite this, only a handful of diagnostic tests have made it to market, with mixed success. Historically, the challenges in this field were scientific. However, as discussed in this article, with the maturation of the '-omics' sciences, it now seems that the major barriers are increasingly related to economics. Overcoming the poor microeconomic alignment of incentives among key stakeholders is therefore crucial to catalysing the further development and adoption of personalized medicine, and we propose several actions that could help achieve this goal.

  4. Perpendicular recording: the promise and the problems

    International Nuclear Information System (INIS)

    Wood, Roger; Sonobe, Yoshiaki; Jin Zhen; Wilson, Bruce

    2001-01-01

    Perpendicular recording has long been advocated as a means of achieving the highest areal densities. In particular, in the context of the 'superparamagnetic limit', perpendicular recording with a soft underlayer promises several key advantages. These advantages include a higher coercivity, thicker media that should permit smaller diameter grains and higher signal-to-noise ratio. Also, the sharper edge-writing will facilitate recording at very high track densities (lower bit aspect ratio). Recent demonstrations of the technology have shown densities comparable with the highest densities reported for longitudinal recording. This paper further examines the promise that perpendicular recording will deliver an increase in areal density two to eight times higher than that achievable with longitudinal recording. There are a number of outstanding issues but the key challenge is to create a low-noise medium with a coercivity that is high and is much larger than the remanent magnetization

  5. The deepwater Gulf of Mexico : promises delivered?

    International Nuclear Information System (INIS)

    Pickering, D.R.

    1999-01-01

    A summary review of deepwater Gulf of Mexico (GOM) oil production was presented for the years 1989 to 1998. Trends and prospects in deepwater GOM production and leasing were assessed. Promises and forecasts made in the early 1990s were compared with what actually happened since then. Forecasts in the early 1990s promised deeper, faster and cheaper developments in the deepwater Gulf. Results of the comparison showed that the prognosticators were correct on all three counts. Regarding the future of the Gulf, one can be justified in being optimistic in so far as more experience, robust economics, more and cheaper rigs can be taken as reliable indicators of optimism. In contrast, there are certain negatives to consider, such as low commodity prices, budget constraints, lease expirations, technical challenges and increased competition. . 12 figs

  6. The Epidemiology, Clinical Characteristic,Transmission Potential and Control Measures of Zika Virus Infection%The Epidemiology,Clinical Characteristic,Transmission Potential and Control Measures of Zika Virus Infection

    Institute of Scientific and Technical Information of China (English)

    ALOTAIBIABDULLAHSAUDM; ALANAZIMANSOURRASHEDM; AHMADMEESAQ

    2017-01-01

    Zika virus (ZIKV) is an emerging mosquito born positive standard RNA arbovirus of Flaviviriadae family.Zika virus has been identified sporadically in human in Africa and Asia;however,clinically consequential Zika virus disease had not been documented before to the recent outbreak in the America in 2015.It is rapidly spread across the America and its devastating outcomes for pregnant women and infants.Prior to outbreak of America,Zika virus outbreaks occurred in Yap Island in Micronesia in 2007 and in French Polynesia in 2013.The World Health Organisation (WHO) declarer a Public Health Emergency of International Concern on February 1,2016.Because of the continuous geographicexpansion of both the virus and its mosquito vectors,ZIKV poses a serious threat to public health aroundthe globe.This review summarizes a fast growing body of literature on the history,epidemiology,transmission,clinical presentation and control measures to prevent the transmission of Zika virus.

  7. Melanoma Vaccines: Mixed Past, Promising Future

    Science.gov (United States)

    Ozao-Choy, Junko; Lee, Delphine J.; Faries, Mark B.

    2014-01-01

    Synopsis Cancer vaccines were one of the earliest forms of immunotherapy to be investigated. Past attempts to vaccinate against cancer, including melanoma, have mixed results, revealing the complexity of what was thought to be a simple concept. However, several recent successes and the combination of improved knowledge of tumor immunology and the advent of new immunomodulators make vaccination a promising strategy for the future. PMID:25245965

  8. Applying a soft-robotic glove as assistive device and training tool with games to support hand function after stroke: Preliminary results on feasibility and potential clinical impact.

    Science.gov (United States)

    Prange-Lasonder, Gerdienke B; Radder, Bob; Kottink, Anke I R; Melendez-Calderon, Alejandro; Buurke, Jaap H; Rietman, Johan S

    2017-07-01

    Recent technological developments regarding wearable soft-robotic devices extend beyond the current application of rehabilitation robotics and enable unobtrusive support of the arms and hands during daily activities. In this light, the HandinMind (HiM) system was developed, comprising a soft-robotic, grip supporting glove with an added computer gaming environment. The present study aims to gain first insight into the feasibility of clinical application of the HiM system and its potential impact. In order to do so, both the direct influence of the HiM system on hand function as assistive device and its therapeutic potential, of either assistive or therapeutic use, were explored. A pilot randomized clinical trial was combined with a cross-sectional measurement (comparing performance with and without glove) at baseline in 5 chronic stroke patients, to investigate both the direct assistive and potential therapeutic effects of the HiM system. Extended use of the soft-robotic glove as assistive device at home or with dedicated gaming exercises in a clinical setting was applicable and feasible. A positive assistive effect of the soft-robotic glove was proposed for pinch strength and functional task performance 'lifting full cans' in most of the five participants. A potential therapeutic impact was suggested with predominantly improved hand strength in both participants with assistive use, and faster functional task performance in both participants with therapeutic application.

  9. [Evoked potentials N200/P300 disorders and clinical phenotype in Cuban families with paranoid schizophrenia: a family-based association study].

    Science.gov (United States)

    Guerra López, Seidel; Martín Reyes, Migdyrai; Pedroso Rodríguez, María de Los Ángeles; Reyes Berazain, Adnelys; Mendoza Quiñones, Raúl; Bravo Collazo, Tania Martha; Días de Villarvilla, Thais; Machado Cano, María Julia; Bobés León, María Antonieta

    2015-04-01

    N200 and P300 event-related evoked potentials provide sensitive measurements of sensory and cognitive function and have been used to study information processing in patients with schizophrenia and their unaffected first-degree relatives. Reduced amplitude and increased latency of N200 and P300 potentials have been consistently reported in schizophrenia. Thus, event-related evoked potentials abnormalities are promising possible biological markers for genetic vulnerability to schizophrenia. To assess the association of changes in latency, amplitude and topographic distribution of potentials N200 and P300 of patients with paranoid schizophrenia and their healthy first-degree relatives, in families with schizophrenia multiplex. We measured latency and amplitude of the N200 and P300 component of evoked potentials using an auditory odd-ball paradigm in 25 schizophrenic patients (probands) from 60 families multiply affected with paranoid schizophrenia, 23 of their non-schizophrenic first-degree relatives and 25 unrelated healthy controls, through a study of family association. Schizophrenic patients and their relatives showed significant latency prolongation and amplitude reduction of the N200 and P300 waves compared to controls. Left-temporal as compared to right-temporal N200 and P300 were significantly smaller in schizophrenic patients and their non-schizophrenic first-degree relatives than in controls. Our results suggest that event-related evoked potentials abnormalities may serve as markers of genetic vulnerability in schizophrenia. Confirming results of other researchers, this present study suggests that latency prolongation and amplitude reduction of the N200 and P300 waves and an altered topography at temporal sites may be a trait “marker” of paranoid schizophrenia.

  10. The promise of telemedicine for chronic neurological disorders: the example of Parkinson's disease.

    Science.gov (United States)

    Schneider, Ruth B; Biglan, Kevin M

    2017-07-01

    Disparities in access to health care, particularly specialist care, exist worldwide. As the prevalence of chronic neurological disorders increases with ageing populations, access to neurologist care is likely to worsen in many regions if there are no changes to models of care. Telemedicine-defined here as the use of real-time, synchronous videoconferencing to deliver medical care-could be used to improve access to neurologist care for patients with a range of chronic neurological disorders. In Parkinson's disease, several studies have shown the feasibility and potential benefits of telemedicine-delivered care. Further research is needed to establish whether telemedicine can deliver on the promise of improved access to neurologist care and whether telemedicine-delivered care is comparable to in-person care in terms of clinical outcomes. Many barriers to widespread implementation of telemedicine services remain to be addressed, including reimbursement, legal considerations, and technological issues. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Promising new developments in cancer chemotherapy.

    Science.gov (United States)

    Ferrante, K; Winograd, B; Canetta, R

    1999-01-01

    attractive target for intervention in several aspects of tumor progression. Local production of MMPs with subsequent degradation of the extracellular matrix is implicated in supporting tumor growth, invasion, and angiogenesis. The development of orally active, nontoxic MMP inhibitors is critical since these compounds will likely require chronic administration in conjunction with other therapies. Oncogenes and tumor suppressor genes are appealing targets for therapy since they are thought to be responsible for a significant number of cancers. Mutations in the Ras oncogene occur with great frequency in a number of human cancers including lung, pancreas, and colon cancer. Clinical development of potent and selective inhibitors of farnesyltransferase, the Ras-processing enzyme, is ongoing. These compounds uncouple Ras activity, affect tumor growth, and have demonstrated significant antitumor activity against experimental models of human cancer. The exciting compounds and novel therapeutic approaches currently under investigation by Bristol-Myers Squibb Pharmaceutical Research Institute offer great potential as effective cancer chemotherapy agents for the near future.

  12. Potential Applications of the National Institute of Mental Health's Research Domain Criteria (RDoC) to Clinical Psychiatric Practice: How RDoC Might Be Used in Assessment, Diagnostic Processes, Case Formulation, Treatment Planning, and Clinical Notes.

    Science.gov (United States)

    Yager, Joel; Feinstein, Robert E

    2017-04-01

    Offering a new framework for understanding and studying basic dimensions of normal and abnormal human functioning and mental disorders, the National Institute of Mental Health (NIMH) has initiated the Research Domain Criteria (RDoC) project in which a series of higher order domains, representing major systems of emotion, cognition, motivation, and social behavior, and their constituent operationally defined constructs serve as organizing templates for further research and inquiry, eg, to discover validated biomarkers and endophenotypes. Cutting across traditional DSM diagnoses, the domains are defined as Negative Valence Systems, Positive Valence Systems, Cognitive Systems, Systems for Social Processes, and Arousal/Regulatory Systems. To inform educators, trainees, and practitioners about RDoC, alert them to potential practical applications, and encourage their broad exploration in clinical settings, this article reviews the RDoC domains and their subsystem constructs with regard to potential current clinical considerations and applications. We describe ways in which the RDoC domains and constructs offer transdiagnostic frameworks for complementing traditional practice; suggest clinical questions to help elucidate salient information; and, translating RDoC domains and constructs headings into clinically friendly language, offer a template for the psychiatric review of systems that can serve in clinical notes. © Copyright 2017 Physicians Postgraduate Press, Inc.

  13. Cinnamon, a promising prospect towards Alzheimer's disease.

    Science.gov (United States)

    Momtaz, Saeideh; Hassani, Shokoufeh; Khan, Fazlullah; Ziaee, Mojtaba; Abdollahi, Mohammad

    2018-04-01

    Over the last decades, an exponential increase of efforts concerning the treatment of Alzheimer's disease (AD) has been practiced. Phytochemicals preparations have a millenary background to combat various pathological conditions. Various cinnamon species and their biologically active ingredients have renewed the interest towards the treatment of patients with mild-to-moderate AD through the inhibition of tau protein aggregation and prevention of the formation and accumulation of amyloid-β peptides into the neurotoxic oligomeric inclusions, both of which are considered to be the AD trademarks. In this review, we presented comprehensive data on the interactions of a number of cinnamon polyphenols (PPs) with oxidative stress and pro-inflammatory signaling pathways in the brain. In addition, we discussed the potential association between AD and diabetes mellitus (DM), vis-à-vis the effluence of cinnamon PPs. Further, an upcoming prospect of AD epigenetic pathophysiological conditions and cinnamon has been sighted. Data was retrieved from the scientific databases such as PubMed database of the National Library of Medicine, Scopus and Google Scholar without any time limitation. The extract of cinnamon efficiently inhibits tau accumulations, Aβ aggregation and toxicity in vivo and in vitro models. Indeed, cinnamon possesses neuroprotective effects interfering multiple oxidative stress and pro-inflammatory pathways. Besides, cinnamon modulates endothelial functions and attenuates the vascular cell adhesion molecules. Cinnamon PPs may induce AD epigenetic modifications. Cinnamon and in particular, cinnamaldehyde seem to be effective and safe approaches for treatment and prevention of AD onset and/or progression. However, further molecular and translational research studies as well as prolonged clinical trials are required to establish the therapeutic safety and efficacy in different cinnamon spp. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Breath tests: principles, problems, and promise

    International Nuclear Information System (INIS)

    Lo, C.W.; Carter, E.A.; Walker, W.A.

    1982-01-01

    Breath tests rely on the measurement of gases produced in the intestine, absorbed, and expired in the breath. Carbohydrates, such as lactose and sucrose, can be administered in ysiologic doses; if malabsorbed, they will be metabolized to hydrogen by colonic bacteria. Since hydrogen is not produced by human metabolic reactions, a rise in breath hydrogen, as measured by gas chromatography, is evidence of carbohydrate malabsorption. Likewise, a rise in breath hydrogen marks the transit time of nonabsorbable carbohydrates such as lactulose through the small intestine into the colon. Simple end-expiratory interval collection into nonsiliconized vacutainer tubes has made these noninvasive tests quite convenient to perform, but various problems, including changes in stool pH intestinal motility, or metabolic rate, may influence results. Another group of breath tests uses substrates labeled with radioactive or stable isotopes of carbon. Labeled fat substrates such as trioctanoin, tripalmitin, and triolein do not produce the expected rise in labeled breath CO 2 if there is fat malabsorption. Bile acid malabsorption and small intestinal bacterial overgrowth can be measured with labeled cholylglycine or cholyltaurine. Labeled drugs such as aminopyrine, methacetin, and phenacetin can be used as an indication of drug metabolism and liver function. Radioactive substrates have been used to trace metabolic pathways and can be measured by scintillation counters. The availability of nonradioactive stable isotopes has made these ideal for use in children and pregnant women, but the cost of substrates and the mass spectrometers to measure them has so far limited their use to research centers. It is hoped that new techniques of processing and measurement will allow further realization of the exciting potential breath analysis has in a growing list of clinical applications

  15. Site selection in global clinical trials in patients hospitalized for heart failure : perceived problems and potential solutions

    NARCIS (Netherlands)

    Gheorghiade, Mihai; Vaduganathan, Muthiah; Greene, Stephen J.; Mentz, Robert J.; Adams, Kirkwood F.; Anker, Stefan D.; Arnold, Malcolm; Baschiera, Fabio; Cleland, John G. F.; Cotter, Gadi; Fonarow, Gregg C.; Giordano, Christopher; Metra, Marco; Misselwitz, Frank; Muehlhofer, Eva; Nodari, Savina; Peacock, W. Frank; Pieske, Burkert M.; Sabbah, Hani N.; Sato, Naoki; Shah, Monica R.; Stockbridge, Norman L.; Teerlink, John R.; van Veldhuisen, Dirk J.; Zalewski, Andrew; Zannad, Faiez; Butler, Javed

    There are over 1 million hospitalizations for heart failure (HF) annually in the United States alone, and a similar number has been reported in Europe. Recent clinical trials investigating novel therapies in patients with hospitalized HF (HHF) have been negative, and the post-discharge event rate

  16. Growth of self-perceived clinical competence in postgraduate training for general practice and its relation to potentially influencing factors.

    NARCIS (Netherlands)

    Kramer, A.W.M.; Zuithoff, P.; Jansen, J.J.; Tan, L.H.; Grol, R.P.T.M.; Vleuten, C.P.M. van der

    2007-01-01

    OBJECTIVE: To examine the increase in self-perceived clinical competence during a three-year postgraduate training in general practice and to explore the relation between the growth of self-perceived competence and several background variables. DESIGN: Cohort, 1995-1998. SETTING: Three-year

  17. Effect of specific or random c-DNA priming on sensitivity of tyrosinase nested RT-PCR : Potential clinical relevance

    NARCIS (Netherlands)

    Calogero, A; Hospers, GAP; Timmer-Bosscha, H; Mulder, NH; Schraffordt Koops, H.

    2000-01-01

    The reverse transcriptase polymerase chain reaction (RT-PCR) can be of clinical relevance in identifying malignant melanoma cells in blood or tissues of patients at risk for disseminated melanoma. The diagnostic value of this marker however, is still controversial. The objective of this study was to

  18. The Soil Microbiota Harbors a Diversity of Carbapenem-Hydrolyzing β-Lactamases of Potential Clinical Relevance.

    Science.gov (United States)

    Gudeta, Dereje Dadi; Bortolaia, Valeria; Amos, Greg; Wellington, Elizabeth M H; Brandt, Kristian K; Poirel, Laurent; Nielsen, Jesper Boye; Westh, Henrik; Guardabassi, Luca

    2016-01-01

    The origin of carbapenem-hydrolyzing metallo-β-lactamases (MBLs) acquired by clinical bacteria is largely unknown. We investigated the frequency, host range, diversity, and functionality of MBLs in the soil microbiota. Twenty-five soil samples of different types and geographical origins were analyzed by antimicrobial selective culture, followed by phenotypic testing and expression of MBL-encoding genes in Escherichia coli, and whole-genome sequencing of MBL-producing strains was performed. Carbapenemase activity was detected in 29 bacterial isolates from 13 soil samples, leading to identification of seven new MBLs in presumptive Pedobacter roseus (PEDO-1), Pedobacter borealis (PEDO-2), Pedobacter kyungheensis (PEDO-3), Chryseobacterium piscium (CPS-1), Epilithonimonas tenax (ESP-1), Massilia oculi (MSI-1), and Sphingomonas sp. (SPG-1). Carbapenemase production was likely an intrinsic feature in Chryseobacterium and Epilithonimonas, as it occurred in reference strains of different species within these genera. The amino acid identity to MBLs described in clinical bacteria ranged between 40 and 69%. Remarkable features of the new MBLs included prophage integration of the encoding gene (PEDO-1), an unusual amino acid residue at a key position for MBL structure and catalysis (CPS-1), and overlap with a putative OXA β-lactamase (MSI-1). Heterologous expression of PEDO-1, CPS-1, and ESP-1in E. coli significantly increased the MICs of ampicillin, ceftazidime, cefpodoxime, cefoxitin, and meropenem. Our study shows that MBL producers are widespread in soil and include four genera that were previously not known to produce MBLs. The MBLs produced by these bacteria are distantly related to MBLs identified in clinical samples but constitute resistance determinants of clinical relevance if acquired by pathogenic bacteria. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  19. PET measurements of myocardial blood flow post myocardial infarction: Relationship to invasive and cardiac magnetic resonance studies and potential clinical applications.

    Science.gov (United States)

    Gewirtz, Henry

    2017-12-01

    This review focuses on clinical studies concerning assessment of coronary microvascular and conduit vessel function primarily in the context of acute and sub acute myocardial infarction (MI). The ability of quantitative PET measurements of myocardial blood flow (MBF) to delineate underlying pathophysiology and assist in clinical decision making in this setting is discussed. Likewise, considered are physiological metrics fractional flow reserve, coronary flow reserve, index of microvascular resistance (FFR, CFR, IMR) obtained from invasive studies performed in the cardiac catheterization laboratory, typically at the time of PCI for MI. The role both of invasive studies and cardiac magnetic resonance (CMR) imaging in assessing microvascular function, a key determinant of prognosis, is reviewed. The interface between quantitative PET MBF measurements and underlying pathophysiology, as demonstrated both by invasive and CMR methodology, is discussed in the context of optimal interpretation of the quantitative PET MBF exam and its potential clinical applications.

  20. Clinical translation of stem cell therapy in traumatic brain injury: the potential of encapsulated mesenchymal cell biodelivery of glucagon-like peptide-1

    OpenAIRE

    Heile, Anna; Brinker, Thomas

    2011-01-01

    Traumatic brain injury remains a major cause of death and disability; it is estimated that annually 10 million people are affected. Preclinical studies have shown the potential therapeutic value of stem cell therapies. Neuroprotective as well as regenerative properties of stem cells have been suggested to be the mechanism of action in preclinical studies. However, up to now stem cell therapy has not been studied extensively in clinical trials. This article summarizes the current experimental ...

  1. Challenges and potential improvements in the admission process of patients with spinal cord injury in a specialized rehabilitation clinic - an interview based qualitative study of an interdisciplinary team.

    Science.gov (United States)

    Röthlisberger, Fabian; Boes, Stefan; Rubinelli, Sara; Schmitt, Klaus; Scheel-Sailer, Anke

    2017-06-26

    The admission process of patients to a hospital is the starting point for inpatient services. In order to optimize the quality of the health services provision, one needs a good understanding of the patient admission workflow in a clinic. The aim of this study was to identify challenges and potential improvements in the admission process of spinal cord injury patients at a specialized rehabilitation clinic from the perspective of an interdisciplinary team of health professionals. Semi-structured interviews with eight health professionals (medical doctors, physical therapists, occupational therapists, nurses) at the Swiss Paraplegic Centre (acute and rehabilitation clinic) were conducted based on a maximum variety purposive sampling strategy. The interviews were analyzed using a thematic analysis approach. The interviewees described the challenges and potential improvements in this admission process, focusing on five themes. First, the characteristics of the patient with his/her health condition and personality and his/her family influence different areas in the admission process. Improvements in the exchange of information between the hospital and the patient could speed up and simplify the admission process. In addition, challenges and potential improvements were found concerning the rehabilitation planning, the organization of the admission process and the interdisciplinary work. This study identified five themes of challenges and potential improvements in the admission process of spinal cord injury patients at a specialized rehabilitation clinic. When planning adaptations of process steps in one of the areas, awareness of effects in other fields is necessary. Improved pre-admission information would be a first important step to optimize the admission process. A common IT-system providing an interdisciplinary overview and possibilities for interdisciplinary exchange would support the management of the admission process. Managers of other hospitals can supplement

  2. Identification of potential neuromotor mechanisms of manual therapy in patients with musculoskeletal disablement: rationale and description of a clinical trial.

    Science.gov (United States)

    Fisher, Beth E; Davenport, Todd E; Kulig, Kornelia; Wu, Allan D

    2009-05-21

    Many health care practitioners use a variety of hands-on treatments to improve symptoms and disablement in patients with musculoskeletal pathology.Research to date indirectly suggests a potentially broad effect of manual therapy on the neuromotor processing of functional behavior within the supraspinal central nervous system (CNS) in a manner that may be independent of modification at the level of local spinal circuits. However, the effect of treatment speed, as well as the specific mechanism and locus of CNS changes, remain unclear. We developed a placebo-controlled, randomized study to test the hypothesis that manual therapy procedures directed to the talocrural joint in individuals with post-acute ankle sprain induce a change in corticospinal excitability that is relevant to improve the performance of lower extremity functional behavior. This study is designed to identify potential neuromotor changes associated with manual therapy procedures directed to the appendicular skeleton, compare the relative effect of treatment speed on potential neuromotor effects of manual therapy procedures, and determine the behavioral relevance of potential neuromotor effects of manual therapy procedures. http://www.clinicaltrials.gov identifier NCT00847769.

  3. Identification of potential neuromotor mechanisms of manual therapy in patients with musculoskeletal disablement: rationale and description of a clinical trial

    Directory of Open Access Journals (Sweden)

    Kulig Kornelia

    2009-05-01

    Full Text Available Abstract Background Many health care practitioners use a variety of hands-on treatments to improve symptoms and disablement in patients with musculoskeletal pathology. Research to date indirectly suggests a potentially broad effect of manual therapy on the neuromotor processing of functional behavior within the supraspinal central nervous system (CNS in a manner that may be independent of modification at the level of local spinal circuits. However, the effect of treatment speed, as well as the specific mechanism and locus of CNS changes, remain unclear. Methods/Design We developed a placebo-controlled, randomized study to test the hypothesis that manual therapy procedures directed to the talocrural joint in individuals with post-acute ankle sprain induce a change in corticospinal excitability that is relevant to improve the performance of lower extremity functional behavior. Discussion This study is designed to identify potential neuromotor changes associated with manual therapy procedures directed to the appendicular skeleton, compare the relative effect of treatment speed on potential neuromotor effects of manual therapy procedures, and determine the behavioral relevance of potential neuromotor effects of manual therapy procedures. Trial Registration http://www.clinicaltrials.gov identifier NCT00847769.

  4. Does environmental archaeology need an ethical promise?

    DEFF Research Database (Denmark)

    Riede, Felix; Andersen, Per; Price, Neil

    2016-01-01

    formalized ethical codes or promises that not only guide the dissemination of data but oblige scientists to relate to fundamentally political issues. This article couples a survey of the recent environmental ethics literature with two case studies of how past natural hazards have affected vulnerable...... societies in Europe?s prehistory. We ask whether cases of past calamities and their societal effects should play a greater role in public debates and whether archaeologists working with past environmental hazards should be more outspoken in their ethical considerations. We offer no firm answers, but suggest...... that archaeologists engage with debates in human?environment relations at this interface between politics, public affairs and science....

  5. Transthyretin levels: Potential biomarker for monitoring nutritional support efficacy and clinical complications risk in patients receiving parenteral nutrition.

    Science.gov (United States)

    Borges de Oliveira Nascimento Freitas, Renata Germano; Hessel, Gabriel; Junqueira Vasques, Ana Carolina; Negrão Nogueira, Roberto José

    2018-04-01

    Nutritional support is an effective strategy to restore or maintain nutritional status, to reduce clinical complications, hospitalization period and the morbidity/mortality risk of hospitalized patients. So, a good marker is important to evaluate the nutritional support. This study aims to evaluate the evolution of transthyretin levels in patients receiving parenteral nutrition (PN) during 14 days. Longitudinal study of 88 hospitalized patients. The assessments and samples were taken during the first 72 h (T0), on the 7th day (T7) and 14th day (T14) of PN. This study was approved by the Ethics Committee of the School of Medical Sciences at UNICAMP (No 538/2011). The C-reactive protein (CRP) levels were high and albumin and transthyretin levels were low at baseline. From T0 to T14, only transthyretin increased (p = 0.03). According to the receiver operation characteristic (ROC) curve, we found that the transthyretin had some improvement when the CRP levels were less than 10.4 mg/dl (T7). According to the CRP/albumin ratio, all patients classified as without risk for complications were discharged from the hospital. In addition, we observed that patients with transthyretin reduction had a concomitant higher risk for complications according to their ratio CRP/albumin (p = 0.03). CRP/albumin ratio was associated with the evolution of transthyretin levels. Transthyretin values showed significant improvement in the 14 days of PN. Especially, less inflamed patients (ie CRP less than 10.4 mg/dl) improved their transthyretin levels. So, CRP value at day 7 that predicts the transthyretin and transthyretin is a good biomarker for classification of nutritional support and clinical complications risk in patients receiving PN. Copyright © 2017 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.

  6. Clinical potential of boron neutron capture therapy for locally recurrent inoperable previously irradiated head and neck cancer

    International Nuclear Information System (INIS)

    Lim, Diana; Quah, Daniel SC; Leech, Michelle; Marignol, Laure

    2015-01-01

    This review compares the safety and efficacy of boron neutron capture therapy (BNCT) in the treatment of previously irradiated, inoperable locoregional recurrent HNC patients and compares BNCT against the standard treatment of platinum-based chemotherapy. Our analysis of published clinical trials highlights efficacy of BNCT associated with mild side effects. However, the use of BNCT should be explored in stratified randomised trials. - Highlights: • BNCT can prolong median overall survival. • BNCT can be associated with severe adverse effects. • BNCT may be comparable to chemotherapy-based regimens. • BNCT may be comparable to re-irradiation techniques regimens in patients with low performance status.

  7. Clinical proteomics identifies urinary CD14 as a potential biomarker for diagnosis of stable coronary artery disease.

    Directory of Open Access Journals (Sweden)

    Min-Yi Lee

    Full Text Available Inflammation plays a key role in coronary artery disease (CAD and other manifestations of atherosclerosis. Recently, urinary proteins were found to be useful markers for reflecting inflammation status of different organs. To identify potential biomarker for diagnosis of CAD, we performed one-dimensional SDS-gel electrophoresis followed by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS. Among the proteins differentially expressed in urine samples, monocyte antigen CD14 was found to be consistently expressed in higher amounts in the CAD patients as compared to normal controls. Using enzyme-linked immunosorbent assays to analyze the concentrations of CD14 in urine and serum, we confirmed that urinary CD14 levels were significantly higher in patients (n = 73 with multi-vessel and single vessel CAD than in normal control (n = 35 (P < 0.001. Logistic regression analysis further showed that urinary CD14 concentration level is associated with severity or number of diseased vessels and SYNTAX score after adjustment for potential confounders. Concomitantly, the proportion of CD14+ monocytes was significantly increased in CAD patients (59.7 ± 3.6% as compared with healthy controls (14.9 ± 2.1% (P < 0.001, implicating that a high level of urinary CD14 may be potentially involved in mechanism(s leading to CAD pathogenesis. By performing shotgun proteomics, we further revealed that CD14-associated inflammatory response networks may play an essential role in CAD. In conclusion, the current study has demonstrated that release of CD14 in urine coupled with more CD14+ monocytes in CAD patients is significantly correlated with severity of CAD, pointing to the potential application of urinary CD14 as a novel noninvasive biomarker for large-scale diagnostic screening of susceptible CAD patients.

  8. Reliability of sickness certificates in detecting potential sick leave reduction by modifying working conditions: a clinical epidemiology study

    Directory of Open Access Journals (Sweden)

    Johnsen Roar

    2004-03-01

    Full Text Available Abstract Background Medical sickness certificates are generally the main source for information when scrutinizing the need for aimed intervention strategies to avoid or reduce the individual and community side effects of sick leave. This study explored the value of medical sickness certificates related to daily work in Norwegian National Insurance Offices to identify sick-listed persons, where modified working conditions might reduce the ongoing sick leave. Methods The potential