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Sample records for combined neuroprotective modalities

  1. Combined modalities: chemotherapy/radiotherapy. Meeting summary

    International Nuclear Information System (INIS)

    Phillips, T.L.

    1979-01-01

    The effects of combined modalities, the standardization of terminology, the mechanisms of chemotherapeutic interactions with radiation and responses of normal and tumor systems are summarized from information presented at the Conference on Combined Modalities

  2. Combined modality treatment with radiotherapy and chemotherapy

    International Nuclear Information System (INIS)

    Tannock, I.F.; Toronto Univ., ON

    1989-01-01

    The present paper discusses some of the methodological issues which can confound the interpretation of clinical trials of combined modality treatment. It reviews some of the larger randomized trials which have evaluated combined modality treatment in cancers of the head and neck, lung, gastrointestinal tract and bladder. It concludes that adequate trials have yet to be performed in many of thses sites, but that at present, evidence for long-term benefit from adjunctivechemotherapy is meagre. Finally, it suggests some possible mechanisms which might heve limited the benefit of chemotherapy when added to radiation treatment. (Author). 87 refs.; 4 figs.; 4 tabs

  3. Spatial aspects of combined modality radiotherapy

    International Nuclear Information System (INIS)

    Bodey, Rachel K.; Evans, Phil M.; Flux, Glenn D.

    2005-01-01

    Background and purpose: A combined modality radiotherapy (CMRT) incorporates both external beam radiotherapy (EBT) and targeted radionuclide therapy (TRT) components. The spatial aspects of this combination were explored by utilising intensity modulated radiotherapy (IMRT) to provide a non-uniform EBT dose distribution. Patients and methods: Three methods of prescribing the required non-uniform distribution of EBT dose are described, based on both physical and biological criteria according to the distribution of TRT uptake. The results and consequences of these prescriptions are explored by application to three examples of patient data. Results: The planning procedure adopted allowed IMRT plans to be produced that met the prescription requirements. However, when the treatment was planned as a CMRT, compared with the use of EBT alone, more satisfactory target doses could be achieved with lower doses to normal tissues. The effects of errors in EBT delivery and in the functional data were found to cause a non-uniform prescription to tend towards the uniform case. Conclusions: The methods and results are relevant for more general biological treatment planning, in which IMRT may be used to produce dose distributions prescribed according to tumour function. The effects of delivery and dose calculation errors can have a significant impact on how such treatments should be planned

  4. Combining neuroprotectants in a model of retinal degeneration: no additive benefit.

    Directory of Open Access Journals (Sweden)

    Fabiana Di Marco

    Full Text Available The central nervous system undergoing degeneration can be stabilized, and in some models can be restored to function, by neuroprotective treatments. Photobiomodulation (PBM and dietary saffron are distinctive as neuroprotectants in that they upregulate protective mechanisms, without causing measurable tissue damage. This study reports a first attempt to combine the actions of PBM and saffron. Our working hypothesis was that the actions of PBM and saffron in protecting retinal photoreceptors, in a rat light damage model, would be additive. Results confirmed the neuroprotective potential of each used separately, but gave no evidence that their effects are additive. Detailed analysis suggests that there is actually a negative interaction between PBM and saffron when given simultaneously, with a consequent reduction of the neuroprotection. Specific testing will be required to understand the mechanisms involved and to establish whether there is clinical potential in combining neuroprotectants, to improve the quality of life of people affected by retinal pathology, such as age-related macular degeneration, the major cause of blindness and visual impairment in older adults.

  5. Biology-based combined-modality radiotherapy: workshop report

    International Nuclear Information System (INIS)

    Mason, Kathryn A.; Komaki, Ritsuko; Cox, James D.; Milas, Luka

    2001-01-01

    Purpose: The purpose of this workshop summary is to provide an overview of preclinical and clinical data on combined-modality radiotherapy. Methods and Materials: The 8th Annual Radiation Workshop at Round Top was held April 13-16, 2000 at the International Festival Institute (Round Top, TX). Results: Presentations by 30 speakers (from Germany, Netherlands, Australia, England, and France along with U.S. participants and M. D. Anderson Cancer Center faculty) formed the framework for discussions on the current status and future perspectives of biology-based combined-modality radiotherapy. Conclusion: Cellular and molecular pathways available for radiation modification by chemical and biologic agents are numerous, providing new opportunities for translational research in radiation oncology and for more effective combined-modality treatment of cancer

  6. Alternate modal combination methods in response spectrum analysis

    International Nuclear Information System (INIS)

    Wang, Y.K.; Bezler, P.

    1989-01-01

    In piping analyses using the response spectrum method Square Root of the Sum of the Squares (SRSS) with clustering between closely spaced modes is the combination procedure most commonly used to combine between the modal response components. This procedure is simple to apply and normally yields conservative estimates of the time history results. The purpose of this study is to investigate alternate methods to combine between the modal response components. These methods are mathematically based to properly account for the combination between rigid and flexible modal responses as well as closely spaced modes. The methods are those advanced by Gupta, Hadjian and Lindley-Yow to address rigid response modes and the Double Sum Combination (DSC) method and the Complete Quadratic Combination (CQC) method to account for closely spaced modes. A direct comparison between these methods as well as the SRSS procedure is made by using them to predict the response of six piping systems. For two piping systems thirty-three earthquake records were considered to account for the impact of variations in the characteristics of the excitation. The results provided by each method are compared to the corresponding time history estimates of results as well as to each other. The degree of conservatism associated with each method is characterized. 7 refs., 4 figs., 2 tabs

  7. Alternate modal combination methods in response spectrum analysis

    International Nuclear Information System (INIS)

    Bezler, P.; Curreri, J.R.; Wang, Y.K.; Gupta, A.K.

    1990-10-01

    In piping analyses using the response spectrum method Square Root of the Sum of the Squares (SRSS) with clustering between closely spaced modes is the combination procedure most commonly used to combine between the modal response components. This procedure is simple to apply and normally yields conservative estimates of the time history results. The purpose of this study is to investigate alternate methods to combine between the modal response components. These methods are mathematically based to properly account for the combination between rigid and flexible modal responses as well as closely spaced modes. The methods are those advanced by Gupta, Hadjian and Lindely-Yow to address rigid response modes and the Double Sum Combination (DSC) method and the Complete Quadratic Combination (CQC) method to account for closely spaced modes. A direct comparison between these methods as well as the SRSS procedure is made by using them to predict the response of six piping systems. The results provided by each method are compared to the corresponding time history estimates of results as well as to each other. The degree of conservatism associated with each method is characterized. 19 refs., 16 figs., 10 tabs

  8. The generalized algebraic modal combination (GAC) rule validation program

    International Nuclear Information System (INIS)

    Mertens, P.G.; Culot, M.V.; Sahgal, S.; Tinic, S.

    1991-01-01

    With R.G. 1.92 the NRC imposes to use the absolute values of the modal responses when performing Response Spectra modal combination with coupling factors derived from the current heuristic, stationary or pseudo-stationary random vibration models. This results in overly conservative calculations in the case of closely spaced modes of opposite signs, a case frequently encountered in dynamic analyses in particular when systems with close modal frequencies have a small mass ratio. A new generalised algebraic combination (GAC) formula and its associated coupling factor have been theoretically derived by the first author. It is based on a non-stationary, non-white noise random vibration model which fully accounts for all the time and frequency dependent aspects of the time histories. This should allow the conservative use of algebraic signs in the modal combination over the whole frequency range, and allow a derogation to the current NRC R.G. 1.92 practice to use absolute signs. The use of the industry wide accepted RS method with the GAC rule will result in more economical and safer NPPs through the reduction of an excessive and unrealistic number of seismic restraints and avoidance of prematurely fatigued plants. It is envisaged to use the GAC seismic response combination method for the evaluation of the seismic response of auxiliary class one lines attached to the primary coolant loop piping of the Beznau 1 and 2 nuclear power plants. Since the plant is in operation, it is imperative to use a methodology which is conservative but still as realistic as possible. The paper presents an introduction to the GAC rule and some aspects of the validation program, which will jointly be undertaken by WESI and NOK for obtaining acceptance by the Swiss Safety Authorities for a seismic qualification program. (author)

  9. Combined Modality Approaches in the Management of Adult Glioblastoma

    International Nuclear Information System (INIS)

    Shirazi, Haider A.; Grimm, Sean; Raizer, Jeffrey; Mehta, Minesh P.

    2011-01-01

    Over the past two decades, management of newly diagnosed glioblastoma has undergone significant evolution. While surgery has long been a mainstay of management for this disease, and while radiotherapy has a proven survival role, initial efforts at radiotherapy dose escalation, use of radiosurgery, brachytherapy, and altered fractionation did not improve patient survival. Recently, multiple modality therapy integrating maximal safe resection, postoperative radiation, and new systemic therapies have resulted in improved patient outcomes compared with older regimens utilizing surgery and postoperative radiation alone. Numerous trials are currently underway investigating the combination of surgery, radiation, and systemic therapy with targeted agents to find ways to further improve outcomes for adults with glioblastoma.

  10. Combined Modality Approaches in the Management of Adult Glioblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Shirazi, Haider A. [Department of Radiation Oncology, Feinberg School of Medicine, Northwestern University, Chicago, IL (United States); Grimm, Sean; Raizer, Jeffrey [Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, IL (United States); Mehta, Minesh P., E-mail: mmehta@nmff.org [Department of Radiation Oncology, Feinberg School of Medicine, Northwestern University, Chicago, IL (United States)

    2011-10-28

    Over the past two decades, management of newly diagnosed glioblastoma has undergone significant evolution. While surgery has long been a mainstay of management for this disease, and while radiotherapy has a proven survival role, initial efforts at radiotherapy dose escalation, use of radiosurgery, brachytherapy, and altered fractionation did not improve patient survival. Recently, multiple modality therapy integrating maximal safe resection, postoperative radiation, and new systemic therapies have resulted in improved patient outcomes compared with older regimens utilizing surgery and postoperative radiation alone. Numerous trials are currently underway investigating the combination of surgery, radiation, and systemic therapy with targeted agents to find ways to further improve outcomes for adults with glioblastoma.

  11. Modality

    DEFF Research Database (Denmark)

    Klinge, Alex; Müller, Henrik Høeg

    Modality: Studies in Form and Function reflects the diversity of theoretical frameworks and the heterogeneity of linguistic phenomena under the general heading of modality. Researchers in the fields of logic, philosophy and linguistics have for many years been pondering the elusive nature...... of modality and grappled with ways of capturing it. The 11 studies included here cover the span from contributions that seek to clarify controversial theoretical constructs to studies which take an empirical approach to linguistic categories and cross-linguistic typological issues. The key concepts addressed...

  12. Neuroprotective strategies for patients with acute myocardial infarction combined with hypoxic ischemic encephalopathy in the ICU

    Directory of Open Access Journals (Sweden)

    Weiwei Hu

    2017-11-01

    Full Text Available Background: We investigated neuroprotective treatment strategies for patients with acute myocardial infarction (AMI complicated with hypoxic ischemic encephalopathy (HIE in the ICU. Methods: The 83 cases diagnosed with secondary AMI were, for the first time, divided into an observation group (n = 43 and control group (n = 40. All of the patients underwent emergency or elective PCI. Patients in the control group were treated with mannitol to reduce intracranial pressure and cinepazide maleate to improve microcirculation in the brain as well as given a comprehensive treatment with oxygen inhalation, fluid infusion, acid-base imbalance correction and electrolyte disturbance. Patients in the observation group underwent conventional treatment combined with neuroprotective therapeutic strategies. The effects of the different treatment strategies were compared. Results: Consciousness recovery time, reflex recovery time, muscle tension recovery time and duration of ICU stay were significantly shorter in the observation group compared with the control group (P < 0.05. After treatment, the jugular vein oxygen saturation (SjvO2 and blood lactate (JB-LA levels of both groups were lower than before treatment and the cerebral oxygen utilization rate (O2UC increased, with a significantly higher increase in the observation group (P < 0.05. After treatment, the activities of daily living (ADL score was higher for both groups and the neural function defect (NIHS score was lower. Conclusion: The neuroprotective strategies of hypothermia and ganglioside administration assisted with hyperbaric oxygen was effective for treating AMI patients with HIE and may be worth clinical promotion. Keywords: ICU, Acute myocardial infarction, Hypoxic ischemic encephalopathy, Neural protection

  13. Neuroprotection against vascular dementia after acupuncture combined with donepezil hydrochloride: P300 event related potential

    Directory of Open Access Journals (Sweden)

    Qiang Liu

    2016-01-01

    Full Text Available Acupuncture can be used to treat various nervous system diseases. Here, 168 vascular dementia patients were orally administered donepezil hydrochloride alone (5 mg/day, once a day for 56 days, or combined with acupuncture at Shenting (DU24, Tianzhu (BL10, Sishencong (Extra, Yintang (Extra, Renzhong (DU26, Neiguan (PC6, Shenmen (HT7, Fengchi (GB20, Wangu (GB12 and Baihui (DU20 (once a day for 56 days. Compared with donepezil hydrochloride alone, P300 event related potential latency was shorter with an increased amplitude in patients treated with donepezil hydrochloride and acupuncture. Mini-Mental State Examination score was also higher. Moreover, these differences in P300 latency were identified within different infarcted regions in patients treated with donepezil hydrochloride and acupuncture. These findings indicate that acupuncture combined with donepezil hydrochloride noticeably improves cognitive function in patients with vascular dementia, and exerts neuroprotective effects against vascular dementia.

  14. Combining hypobaric hypoxia or hyperbaric oxygen postconditioning with memantine reduces neuroprotection in 7-day-old rat hypoxia-ischemia.

    Science.gov (United States)

    Gamdzyk, Marcin; Ziembowicz, Apolonia; Bratek, Ewelina; Salinska, Elzbieta

    2016-10-01

    Perinatal hypoxia-ischemia causes brain injury in neonates, but a fully successful treatment to prevent changes in the brain has yet to be developed. The aim of this study was to evaluate the effect of combining memantine treatment with HBO (2.5 ATA) or HH (0.47 ATA) on neonatal hypoxia-ischemia brain injury. 7-day old rats were subjected to hypoxia-ischemia (H-I) and treated with combination of memantine and HBO or HH. The brain damage was evaluated by examination of infarct area and the number of apoptotic cells in CA1 region of hippocampus. Additionally, the level of reactive oxygen species (ROS) was measured. Memantine, HBO or HH postconditioning applied at short time (1-6h) after H-I, and repeated for two subsequent days, resulted in significant neuroprotection. The reduction in ipsilateral hemisphere weight deficit and in the size of infarct area was observed 14days after H-I. A reduction in apoptosis and ROS level was also observed. Combining memantine with HBO or HH resulted in a loss of neuroprotection. Our results show that, combining HBO or HH postconditioning with memantine produce no additive increase in the neuroprotective effect. On the contrary, combining the treatments resulted in lower neuroprotection in comparison to the effects of memantine, HBO or HH alone. Copyright © 2016 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  15. Combining Different Modalities for 3D Imaging of Biological Objects

    CERN Document Server

    Tsyganov, E; Kulkarni, P; Mason, R; Parkey, R; Seliuonine, S; Shay, J; Soesbe, T; Zhezher, V; Zinchenko, A I

    2005-01-01

    A resolution enhanced NaI(Tl)-scintillator micro-SPECT device using pinhole collimator geometry has been built and tested with small animals. This device was constructed based on a depth-of-interaction measurement using a thick scintillator crystal and a position sensitive PMT to measure depth-dependent scintillator light profiles. Such a measurement eliminates the parallax error that degrades the high spatial resolution required for small animal imaging. This novel technique for 3D gamma-ray detection was incorporated into the micro-SPECT device and tested with a $^{57}$Co source and $^{98m}$Tc-MDP injected in mice body. To further enhance the investigating power of the tomographic imaging different imaging modalities can be combined. In particular, as proposed and shown in this paper, the optical imaging permits a 3D reconstruction of the animal's skin surface thus improving visualization and making possible depth-dependent corrections, necessary for bioluminescence 3D reconstruction in biological objects. ...

  16. Combining different modalities for 3D imaging of biological objects

    International Nuclear Information System (INIS)

    Tsyganov, Eh.; Antich, P.; Kulkarni, P.; Mason, R.; Parkey, R.; Seliuonine, S.; Shay, J.; Soesbe, T.; Zhezher, V.; Zinchenko, A.

    2005-01-01

    A resolution enhanced NaI(Tl)-scintillator micro-SPECT device using pinhole collimator geometry has been built and tested with small animals. This device was constructed based on a depth-of-interaction measurement using a thick scintillator crystal and a position sensitive PMT to measure depth-dependent scintillator light profiles. Such a measurement eliminates the parallax error that degrades the high spatial resolution required for small animal imaging. This novel technique for 3D gamma-ray detection was incorporated into the micro-SPECT device and tested with a 57 Co source and 98m Tc-MDP injected in mice body. To further enhance the investigating power of the tomographic imaging different imaging modalities can be combined. In particular, as proposed and shown, the optical imaging permits a 3D reconstruction of the animal's skin surface thus improving visualization and making possible depth-dependent corrections, necessary for bioluminescence 3D reconstruction in biological objects. This structural information can provide even more detail if the x-ray tomography is used as presented in the paper

  17. A new algebraic white-noise modal combination rule - GAC(A)

    International Nuclear Information System (INIS)

    Mertens, P.G.

    1994-01-01

    It is a well known fact that above the rigid frequency the maximum dynamic modal responses even with different multiple supports can be combined algebraically. Below the rigid frequency, and more specifically in the white-noise (amplified) region of the response spectrum, algebraic modal combination is still a matter of controversy, demonstrated e.g. by the NRC R.G. 1.92 requirement to take the absolute values of the modal responses in heuristic modal combination rules; whereas algebraic support combination is only allowed in conjunction with the envelope support response spectrum (ERS). Such regulatory requirements can lead to unrealistically high calculated responses e.g. in the coupled analysis of light secondary systems attached to heavy primary structures and in the decoupled analysis of systems when the centres of mass and stiffness do not coincide, or when the ERS is used. A new Generalised Algebraic Combination (GAC) methodology has been theoretically developed which allows practical algebraic modal and support combination over the whole frequency range of multiple support spectra. The present paper deals with the GAC-(A) i.e. the modal combination version in the white noise region of a single response spectrum and more specifically its time history integration validation, which shows that this new modal combination rule can satisfy any realistic conservatism that may be required by regulatory institutions. (orig.)

  18. Biomedical imaging modality classification using combined visual features and textual terms.

    Science.gov (United States)

    Han, Xian-Hua; Chen, Yen-Wei

    2011-01-01

    We describe an approach for the automatic modality classification in medical image retrieval task of the 2010 CLEF cross-language image retrieval campaign (ImageCLEF). This paper is focused on the process of feature extraction from medical images and fuses the different extracted visual features and textual feature for modality classification. To extract visual features from the images, we used histogram descriptor of edge, gray, or color intensity and block-based variation as global features and SIFT histogram as local feature. For textual feature of image representation, the binary histogram of some predefined vocabulary words from image captions is used. Then, we combine the different features using normalized kernel functions for SVM classification. Furthermore, for some easy misclassified modality pairs such as CT and MR or PET and NM modalities, a local classifier is used for distinguishing samples in the pair modality to improve performance. The proposed strategy is evaluated with the provided modality dataset by ImageCLEF 2010.

  19. Biomedical Imaging Modality Classification Using Combined Visual Features and Textual Terms

    Directory of Open Access Journals (Sweden)

    Xian-Hua Han

    2011-01-01

    extraction from medical images and fuses the different extracted visual features and textual feature for modality classification. To extract visual features from the images, we used histogram descriptor of edge, gray, or color intensity and block-based variation as global features and SIFT histogram as local feature. For textual feature of image representation, the binary histogram of some predefined vocabulary words from image captions is used. Then, we combine the different features using normalized kernel functions for SVM classification. Furthermore, for some easy misclassified modality pairs such as CT and MR or PET and NM modalities, a local classifier is used for distinguishing samples in the pair modality to improve performance. The proposed strategy is evaluated with the provided modality dataset by ImageCLEF 2010.

  20. Modal parameter identification based on combining transmissibility functions and blind source separation techniques

    Science.gov (United States)

    Araújo, Iván Gómez; Sánchez, Jesús Antonio García; Andersen, Palle

    2018-05-01

    Transmissibility-based operational modal analysis is a recent and alternative approach used to identify the modal parameters of structures under operational conditions. This approach is advantageous compared with traditional operational modal analysis because it does not make any assumptions about the excitation spectrum (i.e., white noise with a flat spectrum). However, common methodologies do not include a procedure to extract closely spaced modes with low signal-to-noise ratios. This issue is relevant when considering that engineering structures generally have closely spaced modes and that their measured responses present high levels of noise. Therefore, to overcome these problems, a new combined method for modal parameter identification is proposed in this work. The proposed method combines blind source separation (BSS) techniques and transmissibility-based methods. Here, BSS techniques were used to recover source signals, and transmissibility-based methods were applied to estimate modal information from the recovered source signals. To achieve this combination, a new method to define a transmissibility function was proposed. The suggested transmissibility function is based on the relationship between the power spectral density (PSD) of mixed signals and the PSD of signals from a single source. The numerical responses of a truss structure with high levels of added noise and very closely spaced modes were processed using the proposed combined method to evaluate its ability to identify modal parameters in these conditions. Colored and white noise excitations were used for the numerical example. The proposed combined method was also used to evaluate the modal parameters of an experimental test on a structure containing closely spaced modes. The results showed that the proposed combined method is capable of identifying very closely spaced modes in the presence of noise and, thus, may be potentially applied to improve the identification of damping ratios.

  1. Neuroprotective potential of curcumin in combination with piperine against 6-hydroxy dopamine induced motor deficit and neurochemical alterations in rats.

    Science.gov (United States)

    Singh, Shamsher; Kumar, Puneet

    2017-02-01

    6-hydroxy dopamine (6-OHDA) is a neurotoxin which on intranigral administration produces severe nigrostriatal damage with motor and cognitive deficit in animals. Curcumin (CMN) in combination with bioenhancer piperine (PP) in 6-hydroxydopamine-induced Parkinsonian rats was used to investigate the antioxidant, neuromodulatory and neuroprotective mechanisms. Hemi-Parkinson's rat model was developed with intranigral infusion of 6-OHDA (8 μg/2 μl, once, unilaterally), treatment with CMN (25 and 50 mg/kg) and combination of PP (2.5 mg/kg) with CMN (25 mg/kg) was given daily for 21 days starting from the 7th day after 6-OHDA infusion. The behavioral (locomotor, grip strength, and narrow beam walk) parameters were studied on weekly basis. On 22nd day, isolated brain preparations were subjected to biochemical (lipid peroxidation, glutathione, and nitrite), neuroinflammatory (IL-1β, IL-6, and TNF- α), and neurochemical (DA, NE, 5- HT, GABA, Glutamate, DOPAC, HVA, and 5-HIAA) analysis. Oral administration of CMN had significantly prevented behavioral, neuroinflammatory, and neurochemical changes and preserved the antioxidant potential of the nigrostriatum in rats treated with 6-OHDA. In the present study, PP and CMN had afforded a better neuroprotective effect compared to alone treatment on behavior, biochemical, neuroinflammatory, and neurochemical parameters in rats.

  2. Effect of Combination Therapy with Neuroprotective and Vasoprotective Agents on Cerebral Ischemia.

    Science.gov (United States)

    Yang, Jiping; Yang, Bei; Xiu, Baoxin; Qi, Jinchong; Liu, Huaijun

    2018-05-01

    Because most tested drugs are active against only one of the damaging processes associated with stroke, other mechanisms may cause cellular death. Thus, a combination of protective agents targeting different pathophysiological mechanisms may obtain better effects than a single agent. The major objective of this study was to investigate the effect of combination therapy with vascular endothelial growth factor (VEGF) and nerve growth factor (NGF) after controlled ischemic brain injury in rabbits. Animals were randomly assigned to one of the following groups: sham group, saline-treated control group or NGF+VEGF-treated group. Animals received an intracerebral microinjection of VEGF and NGF or saline at 5 or 8 hours after ischemia. The two specified time points of administration were greater than or equal to the existing therapeutic time window for monoterapy with VEGF or NGF alone (3 or 5 hours of ischemia). Infarct volume, water content, neurological deficits, neural cell apoptosis and the expression of caspase-3 and Bcl-2 were measured. Compared with saline-treated controls, the combination therapy of VEGF and NGF significantly reduced infarct volume, water content, neural cell apoptosis and the expression of caspase-3, up-regulated the expression of Bcl-2 and improved functional recovery (both ple « facteur de croissance des nerfs » (ou « NGF » en anglais). Méthodes: Les animaux ont été attribués au hasard à l'un des groupes suivants : ceux ayant reçu un traitement fictif ; ceux, du groupe témoin, ayant bénéficié d'un traitement à base de solution saline ; et finalement ceux ayant été traités au moyen des VEGF et NGF. À noter que les lapins ont reçu une micro-injection intracérébrale de VEGF et de NGF ou de solution saline 5 heures ou 8 heures à la suite de leur AVC. Ces deux délais d'administration des VEGF et NGF sont équivalents ou supérieurs aux délais actuels d'administration des VEGF ou NGF à titre de monothérapie (3 heures ou 5

  3. A comparison of the neuroprotective efficacy of individual oxime (HI-6) and combinations of oximes (HI-6+trimedoxime, HI-6+K203) in soman-poisoned rats.

    Science.gov (United States)

    Kassa, Jiri; Karasova, Jana Zdarova; Tesarova, Sandra

    2011-07-01

    The ability of two combinations of oximes (HI-6+trimedoxime, HI-6+K203) to reduce soman-induced acute neurotoxic signs and symptoms was compared with the neuroprotective efficacy of the oxime HI-6 alone, using a functional observational battery. Soman-induced neurotoxicity and the neuroprotective effects of HI-6 alone and HI-6 combined with trimedoxime or K203 in rats poisoned with soman at a sublethal dose (90 μg/kg intramuscularly, i.m.; 80% of LD₅₀ value) were monitored by the functional observational battery at 24 hours following soman administration. The results indicate that both tested oxime mixtures combined with atropine were able to allow soman-poisoned rats to survive 24 hours following soman challenge, while 4 nontreated soman-poisoned rats and 1 soman-poisoned rat treated with oxime HI-6 alone combined with atropine died within 24 hours following soman poisoning. While the oxime HI-6 alone combined with atropine treatment was able to eliminate a few soman-induced neurotoxic signs and symptoms, both oxime mixtures showed higher neuroprotective efficacy in soman-poisoned rats. Especially, the combination of HI-6 with trimedoxime was able to eliminate most soman-induced neurotoxic signs and symptoms and markedly reduce acute neurotoxicity of soman in rats. Thus, both tested mixtures of oximes combined with atropine were able to increase the neuroprotective effectiveness of antidotal treatment of acute soman poisonings, compared to the individual oxime.

  4. Combinations of ketamine and atropine are neuroprotective and reduce neuroinflammation after a toxic status epilepticus in mice

    International Nuclear Information System (INIS)

    Dhote, Franck; Carpentier, Pierre; Barbier, Laure; Peinnequin, André; Baille, Valérie; Pernot, Fabien; Testylier, Guy; Beaup, Claire; Foquin, Annie

    2012-01-01

    Epileptic seizures and status epilepticus (SE) induced by the poisoning with organophosphorus nerve agents (OP), like soman, are accompanied by neuroinflammation whose role in seizure-related brain damage (SRBD) is not clear. Antagonists of the NMDA glutamate ionotropic receptors are currently among the few compounds able to arrest seizures and provide neuroprotection even during refractory status epilepticus (RSE). Racemic ketamine (KET), in combination with atropine sulfate (AS), was previously shown to counteract seizures and SRBD in soman-poisoned guinea-pigs. In a mouse model of severe soman-induced SE, we assessed the potentials of KET/AS combinations as a treatment for SE/RSE-induced SRBD and neuroinflammation. When starting 30 min after soman challenge, a protocol involving six injections of a sub-anesthetic dose of KET (25 mg/kg) was evaluated on body weight loss, brain damage, and neuroinflammation whereas during RSE, anesthetic protocols were considered (KET 100 mg/kg). After confirming that during RSE, KET injection was to be repeated despite some iatrogenic deaths, we used these proof-of-concept protocols to study the changes in mRNA and related protein contents of some inflammatory cytokines, chemokines and adhesion molecules in cortex and hippocampus 48 h post-challenge. In both cases, the KET/AS combinations showed important neuroprotective effects, suppressed neutrophil granulocyte infiltration and partially suppressed glial activation. KET/AS could also reduce the increase in mRNA and related pro-inflammatory proteins provoked by the poisoning. In conclusion, the present study confirms that KET/AS treatment has a strong potential for SE/RSE management following OP poisoning. The mechanisms involved in the reduction of central neuroinflammation remain to be studied. -- Highlights: ► During soman-induced status epilepticus, ketamine-atropine limit brain damage. ► Molecular neuroinflammatory response is strongly decreased. ► Glial activation is

  5. Combinations of ketamine and atropine are neuroprotective and reduce neuroinflammation after a toxic status epilepticus in mice

    Energy Technology Data Exchange (ETDEWEB)

    Dhote, Franck [Département de Toxicologie et risques chimiques, Institut de Recherche Biomédicale des armées – Centre de recherches du Service de santé des armées IRBA-CRSSA, 24 avenue des Maquis du Grésivaudan, B.P. 87, 38702 La Tronche cedex (France); Carpentier, Pierre; Barbier, Laure [Département de Toxicologie et risques chimiques, Institut de Recherche Biomédicale des armées – Centre de recherches du Service de santé des armées IRBA-CRSSA, 24 avenue des Maquis du Grésivaudan, B.P. 87, 38702 La Tronche cedex (France); Peinnequin, André [Département Effets biologiques des rayonnements, Institut de Recherche Biomédicale des armées – Centre de recherches du Service de santé des armées IRBA-CRSSA, 24 avenue des Maquis du Grésivaudan, B.P. 87, 38702 La Tronche cedex (France); Baille, Valérie; Pernot, Fabien; Testylier, Guy; Beaup, Claire; Foquin, Annie [Département de Toxicologie et risques chimiques, Institut de Recherche Biomédicale des armées – Centre de recherches du Service de santé des armées IRBA-CRSSA, 24 avenue des Maquis du Grésivaudan, B.P. 87, 38702 La Tronche cedex (France); others, and

    2012-03-01

    Epileptic seizures and status epilepticus (SE) induced by the poisoning with organophosphorus nerve agents (OP), like soman, are accompanied by neuroinflammation whose role in seizure-related brain damage (SRBD) is not clear. Antagonists of the NMDA glutamate ionotropic receptors are currently among the few compounds able to arrest seizures and provide neuroprotection even during refractory status epilepticus (RSE). Racemic ketamine (KET), in combination with atropine sulfate (AS), was previously shown to counteract seizures and SRBD in soman-poisoned guinea-pigs. In a mouse model of severe soman-induced SE, we assessed the potentials of KET/AS combinations as a treatment for SE/RSE-induced SRBD and neuroinflammation. When starting 30 min after soman challenge, a protocol involving six injections of a sub-anesthetic dose of KET (25 mg/kg) was evaluated on body weight loss, brain damage, and neuroinflammation whereas during RSE, anesthetic protocols were considered (KET 100 mg/kg). After confirming that during RSE, KET injection was to be repeated despite some iatrogenic deaths, we used these proof-of-concept protocols to study the changes in mRNA and related protein contents of some inflammatory cytokines, chemokines and adhesion molecules in cortex and hippocampus 48 h post-challenge. In both cases, the KET/AS combinations showed important neuroprotective effects, suppressed neutrophil granulocyte infiltration and partially suppressed glial activation. KET/AS could also reduce the increase in mRNA and related pro-inflammatory proteins provoked by the poisoning. In conclusion, the present study confirms that KET/AS treatment has a strong potential for SE/RSE management following OP poisoning. The mechanisms involved in the reduction of central neuroinflammation remain to be studied. -- Highlights: ► During soman-induced status epilepticus, ketamine-atropine limit brain damage. ► Molecular neuroinflammatory response is strongly decreased. ► Glial activation is

  6. On nonstationarity-related errors in modal combination rules of the response spectrum method

    Science.gov (United States)

    Pathak, Shashank; Gupta, Vinay K.

    2017-10-01

    Characterization of seismic hazard via (elastic) design spectra and the estimation of linear peak response of a given structure from this characterization continue to form the basis of earthquake-resistant design philosophy in various codes of practice all over the world. Since the direct use of design spectrum ordinates is a preferred option for the practicing engineers, modal combination rules play central role in the peak response estimation. Most of the available modal combination rules are however based on the assumption that nonstationarity affects the structural response alike at the modal and overall response levels. This study considers those situations where this assumption may cause significant errors in the peak response estimation, and preliminary models are proposed for the estimation of the extents to which nonstationarity affects the modal and total system responses, when the ground acceleration process is assumed to be a stationary process. It is shown through numerical examples in the context of complete-quadratic-combination (CQC) method that the nonstationarity-related errors in the estimation of peak base shear may be significant, when strong-motion duration of the excitation is too small compared to the period of the system and/or the response is distributed comparably in several modes. It is also shown that these errors are reduced marginally with the use of the proposed nonstationarity factor models.

  7. Combining motor imagery with selective sensation toward a hybrid-modality BCI.

    Science.gov (United States)

    Yao, Lin; Meng, Jianjun; Zhang, Dingguo; Sheng, Xinjun; Zhu, Xiangyang

    2014-08-01

    A hybrid modality brain-computer interface (BCI) is proposed in this paper, which combines motor imagery with selective sensation to enhance the discrimination between left and right mental tasks, e.g., the classification between left/ right stimulation sensation and right/ left motor imagery. In this paradigm, wearable vibrotactile rings are used to stimulate both the skin on both wrists. Subjects are required to perform the mental tasks according to the randomly presented cues (i.e., left hand motor imagery, right hand motor imagery, left stimulation sensation or right stimulation sensation). Two-way ANOVA statistical analysis showed a significant group effect (F (2,20) = 7.17, p = 0.0045), and the Benferroni-corrected multiple comparison test (with α = 0.05) showed that the hybrid modality group is 11.13% higher on average than the motor imagery group, and 10.45% higher than the selective sensation group. The hybrid modality experiment exhibits potentially wider spread usage within ten subjects crossed 70% accuracy, followed by four subjects in motor imagery and five subjects in selective sensation. Six subjects showed statistically significant improvement ( Benferroni-corrected) in hybrid modality in comparison with both motor imagery and selective sensation. Furthermore, among subjects having difficulties in both motor imagery and selective sensation, the hybrid modality improves their performance to 90% accuracy. The proposed hybrid modality BCI has demonstrated clear benefits for those poorly performing BCI users. Not only does the requirement of motor and sensory anticipation in this hybrid modality provide basic function of BCI for communication and control, it also has the potential for enhancing the rehabilitation during motor recovery.

  8. Antioxidant activity of dorzolamide/timolol fixed combination in neuroprotective therapy in glaucoma

    Directory of Open Access Journals (Sweden)

    N. I. Kurysheva

    2012-01-01

    Full Text Available Purpose: to study the antioxidant activity of carbonic anhydrase inhibitors and timolol fixed combinations and to compare it with other fixed combinations.Methods: Antioxidant activity (AOA of dorzolamide/timolol (Cosopt, dorzolamide/timolol (Dorzopt Plus, latanoprost/timolol, brimonidine/timolol, travoprost/timolol and bimatoprost/timolol fixed combinations was measured in vitro using the model of oxida- tive hemolysis.Results: Dorzolamide/timolol (Cosopt AOA was higher than that of other fixed combinations and increased with the quantity of the drugs added to the model system: 40%, 52% and 75% in 30 μl, 60 μl and 90 μl respectively.Conclusion: these findings suggest that dorzolamide/timolol fixed combination has potential advantages over the other fixed combinations due to its high antioxidant activity and might be used as the neuroptotective agent for glaucoma treatment.

  9. Applying radiobiological principles to combined modality treatment of head and neck cancer--the time factor

    International Nuclear Information System (INIS)

    Peters, Lester J.; Withers, H. Rodney

    1997-01-01

    Purpose: Combined modality treatment is indicated for most advanced stage head and neck cancers. It is postulated that the efficacy of combined modality regimens could be enhanced by applying principles derived from radiotherapy fractionation studies to optimize the time factor in treatment scheduling. Methods and Materials: The premise that tumor clonogens surviving a therapeutic intervention undergo accelerated repopulation in a time-dependent fashion as their numbers are depleted is used as a model to interpret the results of various chemoradiotherapy and postsurgical radiotherapy protocols and to suggest ways in which future combined modality regimens can be more rationally designed. Results: Meta-analyses of chemoradiotherapy trials show the general superiority of concomitant vs. neoadjuvant sequential protocols. There is also emerging evidence that both the duration of postoperative radiotherapy and the delay in its instigation affect treatment outcome. These results are compatible with the hypothesis that the overall duration of the 'package deal' of combined modality treatment is an important determinant of outcome. However, a large decrease in duration of the 'package deal' does not necessarily translate into a therapeutic gain because the total dose has to be lowered to prevent intolerable acute reactions. In these circumstances tumor control will improve only if the reduced treatment time circumvents more tumor cell regeneration than the cytoreduction that could be achieved by the extra dose tolerable in a longer time period. More modest reductions in treatment time can be accomplished without dose reduction and so avoid this risk. The design of new protocols should take account of the fact that regeneration of tumor clonogens can be predicted to be nonuniform with time. Thus, the greatest therapeutic gain should be achieved by targeting periods of maximal regenerative capacity for shortening or, alternatively, for intensification of treatment. These

  10. Improved medical image modality classification using a combination of visual and textual features.

    Science.gov (United States)

    Dimitrovski, Ivica; Kocev, Dragi; Kitanovski, Ivan; Loskovska, Suzana; Džeroski, Sašo

    2015-01-01

    In this paper, we present the approach that we applied to the medical modality classification tasks at the ImageCLEF evaluation forum. More specifically, we used the modality classification databases from the ImageCLEF competitions in 2011, 2012 and 2013, described by four visual and one textual types of features, and combinations thereof. We used local binary patterns, color and edge directivity descriptors, fuzzy color and texture histogram and scale-invariant feature transform (and its variant opponentSIFT) as visual features and the standard bag-of-words textual representation coupled with TF-IDF weighting. The results from the extensive experimental evaluation identify the SIFT and opponentSIFT features as the best performing features for modality classification. Next, the low-level fusion of the visual features improves the predictive performance of the classifiers. This is because the different features are able to capture different aspects of an image, their combination offering a more complete representation of the visual content in an image. Moreover, adding textual features further increases the predictive performance. Finally, the results obtained with our approach are the best results reported on these databases so far. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Automatic vibration mode selection and excitation; combining modal filtering with autoresonance

    Science.gov (United States)

    Davis, Solomon; Bucher, Izhak

    2018-02-01

    Autoresonance is a well-known nonlinear feedback method used for automatically exciting a system at its natural frequency. Though highly effective in exciting single degree of freedom systems, in its simplest form it lacks a mechanism for choosing the mode of excitation when more than one is present. In this case a single mode will be automatically excited, but this mode cannot be chosen or changed. In this paper a new method for automatically exciting a general second-order system at any desired natural frequency using Autoresonance is proposed. The article begins by deriving a concise expression for the frequency of the limit cycle induced by an Autoresonance feedback loop enclosed on the system. The expression is based on modal decomposition, and provides valuable insight into the behavior of a system controlled in this way. With this expression, a method for selecting and exciting a desired mode naturally follows by combining Autoresonance with Modal Filtering. By taking various linear combinations of the sensor signals, by orthogonality one can "filter out" all the unwanted modes effectively. The desired mode's natural frequency is then automatically reflected in the limit cycle. In experiment the technique has proven extremely robust, even if the amplitude of the desired mode is significantly smaller than the others and the modal filters are greatly inaccurate.

  12. Does combined therapy of curcumin and epigallocatechin gallate have a synergistic neuroprotective effect against spinal cord injury?

    Directory of Open Access Journals (Sweden)

    Jiri Ruzicka

    2018-01-01

    Full Text Available Systematic inflammatory response after spinal cord injury (SCI is one of the factors leading to lesion development and a profound degree of functional loss. Anti-inflammatory compounds, such as curcumin and epigallocatechin gallate (EGCG are known for their neuroprotective effects. In this study, we investigated the effect of combined therapy of curcumin and EGCG in a rat model of acute SCI induced by balloon compression. Immediately after SCI, rats received curcumin, EGCG, curcumin + EGCG or saline [daily intraperitoneal doses (curcumin, 6 mg/kg; EGCG 17 mg/kg] and weekly intramuscular doses (curcumin, 60 mg/kg; EGCG 17 mg/kg] for 28 days. Rats were evaluated using behavioral tests (the Basso, Beattie, and Bresnahan (BBB open-field locomotor test, flat beam test. Spinal cord tissue was analyzed using histological methods (Luxol Blue-cresyl violet staining and immunohistochemistry (anti-glial fibrillary acidic protein, anti-growth associated protein 43. Cytokine levels (interleukin-1β, interleukin-4, interleukin-2, interleukin-6, macrophage inflammatory protein 1-alpha, and RANTES were measured using Luminex assay. Quantitative polymerase chain reaction was performed to determine the relative expression of genes (Sort1, Fgf2, Irf5, Mrc1, Olig2, Casp3, Gap43, Gfap, Vegf, NfκB, Cntf related to regenerative processes in injured spinal cord. We found that all treatments displayed significant behavioral recovery, with no obvious synergistic effect after combined therapy of curcumin and ECGC. Curcumin and EGCG alone or in combination increased axonal sprouting, decreased glial scar formation, and altered the levels of macrophage inflammatory protein 1-alpha, interleukin-1β, interleukin-4 and interleukin-6 cytokines. These results imply that although the expected synergistic response of this combined therapy was less obvious, aspects of tissue regeneration and immune responses in severe SCI were evident.

  13. Does combined therapy of curcumin and epigallocatechin gallate have a synergistic neuroprotective effect against spinal cord injury?

    Science.gov (United States)

    Ruzicka, Jiri; Urdzikova, Lucia Machova; Svobodova, Barbora; Amin, Anubhav G; Karova, Kristyna; Dubisova, Jana; Zaviskova, Kristyna; Kubinova, Sarka; Schmidt, Meic; Jhanwar-Uniyal, Meena; Jendelova, Pavla

    2018-01-01

    Systematic inflammatory response after spinal cord injury (SCI) is one of the factors leading to lesion development and a profound degree of functional loss. Anti-inflammatory compounds, such as curcumin and epigallocatechin gallate (EGCG) are known for their neuroprotective effects. In this study, we investigated the effect of combined therapy of curcumin and EGCG in a rat model of acute SCI induced by balloon compression. Immediately after SCI, rats received curcumin, EGCG, curcumin + EGCG or saline [daily intraperitoneal doses (curcumin, 6 mg/kg; EGCG 17 mg/kg)] and weekly intramuscular doses (curcumin, 60 mg/kg; EGCG 17 mg/kg)] for 28 days. Rats were evaluated using behavioral tests (the Basso, Beattie, and Bresnahan (BBB) open-field locomotor test, flat beam test). Spinal cord tissue was analyzed using histological methods (Luxol Blue-cresyl violet staining) and immunohistochemistry (anti-glial fibrillary acidic protein, anti-growth associated protein 43). Cytokine levels (interleukin-1β, interleukin-4, interleukin-2, interleukin-6, macrophage inflammatory protein 1-alpha, and RANTES) were measured using Luminex assay. Quantitative polymerase chain reaction was performed to determine the relative expression of genes (Sort1, Fgf2, Irf5, Mrc1, Olig2, Casp3, Gap43, Gfap, Vegf, NfκB, Cntf) related to regenerative processes in injured spinal cord. We found that all treatments displayed significant behavioral recovery, with no obvious synergistic effect after combined therapy of curcumin and ECGC. Curcumin and EGCG alone or in combination increased axonal sprouting, decreased glial scar formation, and altered the levels of macrophage inflammatory protein 1-alpha, interleukin-1β, interleukin-4 and interleukin-6 cytokines. These results imply that although the expected synergistic response of this combined therapy was less obvious, aspects of tissue regeneration and immune responses in severe SCI were evident.

  14. Acute toxicity and efficacy of postoperative combined modality therapy for adenocarcinoma of the pancreas

    International Nuclear Information System (INIS)

    Davis, Brian J.; Raben, Adam; Casper, Ephraim; Minsky, Bruce D.

    1996-01-01

    PURPOSE: To examine the acute toxicity and outcome in patients (pts) treated with combined modality therapy following resection of adenocarcinoma of the pancreas. MATERIALS AND METHODS: From 2/88 to 2/96, 34 pts (M:20, F:14) received postoperative combined modality therapy following a pancreatic resection. Tumor location included; head only: 28, head and ampulla: 1, ampulla only: 1, body and tail: 2, and tail only: 2. Postoperative stages included: stage I: 7 (21%) and stage III: 27 (79%). Pts were referred for combined modality therapy based on surgeon preference. In general, pts were treated who had one or more adverse prognostic factors. These included positive local/regional lymph nodes (79%), positive margins (50%) or disease invasive into adjacent structures (85 %). Radiation fields included the original primary tumor bed (based on preoperative CT scans) and peri-pancreatic and para-aortic lymph nodes adjacent to vertebral bodies T10 through L3. No attempt was made to include the entire pancreas in the radiation field. Patients received 5040 cGy at 180 cGy/day using a 3 or 4 field technique and CT-based treatment planning. Concurrent bolus 5-FU (375-500 mg/m 2 ) was delivered on the first three and last three days of radiation. Post-radiation maintenance bolus 5-FU was given to 7 patients for a median of 6 cycles. A toxicity assessment using the NCI toxicity criteria was performed at each weekly visit and 4 weeks following the completion of combined modality therapy. The median follow-up was 13 months (range: 2-36 months). Patterns of failure as a component of failure were assessed by radiographic criteria and, in 2 pts, by intraoperative evaluation for symptomatic progression of disease. Local/regional failure was defined as recurrence within the radiation field. Distant failure included liver, peritoneal seeding, and extra-abdominal sites. Actuarial survival was calculated from the time of surgery using the Kaplan-Meier method. RESULTS: The only grade 3

  15. Damage detection methodology on beam-like structures based on combined modal Wavelet Transform strategy

    Science.gov (United States)

    Serra, Roger; Lopez, Lautaro

    2018-05-01

    Different approaches on the detection of damages based on dynamic measurement of structures have appeared in the last decades. They were based, amongst others, on changes in natural frequencies, modal curvatures, strain energy or flexibility. Wavelet analysis has also been used to detect the abnormalities on modal shapes induced by damages. However the majority of previous work was made with non-corrupted by noise signals. Moreover, the damage influence for each mode shape was studied separately. This paper proposes a new methodology based on combined modal wavelet transform strategy to cope with noisy signals, while at the same time, able to extract the relevant information from each mode shape. The proposed methodology will be then compared with the most frequently used and wide-studied methods from the bibliography. To evaluate the performance of each method, their capacity to detect and localize damage will be analyzed in different cases. The comparison will be done by simulating the oscillations of a cantilever steel beam with and without defect as a numerical case. The proposed methodology proved to outperform classical methods in terms of noisy signals.

  16. Retrospective evaluation of combined modality treatment and prognostic factors in patients with esophageal cancer

    International Nuclear Information System (INIS)

    Neuhof, Dirk; Neumayer, Florian; Debus, Juergen; Einbeck, Wolfgang; Haschemian, Kai; Mai, Sabine K.; Wenz, Frederik; Hochhaus, Andreas; Willeke, Frank; Rudi, Jochen

    2005-01-01

    The influence of prognostic factors and combined modality treatment on survival was evaluated retrospectively for 156 patients with esophageal cancer receiving radiotherapy in different modalities between 1991 and 2001 at the Univ. of Heidelberg and the Universitaetsklinikum Mannheim. Forty-six patients (29.5%) were treated with radiotherapy alone, 74 patients (47.4%) had combined radiochemotherapy and 36 patients (23.1%) were operated on after receiving neoadjuvant radiochemotherapy. The median follow-up time was 10 months. Female patients showed a significantly better overall survival compared with male patients (p=0.031), younger patients (age 60 years) (p=0.02). Patients with hemoglobin concentration>13.4 g/dl before therapy (median hemoglobin concentration) had a significantly better overall survival than patients with lower hemoglobin concentration (p=0.044). Patients who received combined radiochemotherapy (with or without operation) had a survival advantage compared with radiotherapy alone. Overall survival after neoadjuvant treatment followed by operation was significantly better than in the two other groups, median survival times were 20 vs. 9 (RCHT) vs. 8 months (RT) (p=0.003). The data presented show for the first time that hemoglobin concentration in addition to gender and age was a prognostic factor for patients with esophageal cancer. A low hemoglobin value was a negative predictor

  17. Tolerability of Combined Modality Therapy for Rectal Cancer in Elderly Patients Aged 75 Years and Older

    International Nuclear Information System (INIS)

    Margalit, Danielle N.; Mamon, Harvey J.; Ancukiewicz, Marek; Kobayashi, Wendy; Ryan, David P.; Blaszkowsky, Lawrence S.; Clark, Jeffrey; Willett, Christopher G.; Hong, Theodore S.

    2011-01-01

    Purpose: To determine the rate of treatment deviations during combined modality therapy for rectal cancer in elderly patients aged 75 years and older. Methods and Materials: We reviewed the records of consecutively treated patients with rectal cancer aged 75 years and older treated with combined modality therapy at Massachusetts General Hospital and Brigham and Women’s Hospital from 2002 to 2007. The primary endpoint was the rate of treatment deviation, defined as a treatment break, dose reduction, early discontinuation of therapy, or hospitalization during combined modality therapy. Patient comorbidity was rated using the validated Adult Comorbidity Evaluation 27 Test (ACE-27) comorbidity index. Fisher’s exact test and the Mantel–Haenszel trend test were used to identify predictors of treatment tolerability. Results: Thirty-six eligible patients had a median age of 79.0 years (range, 75–87 years); 53% (19/36) had no or mild comorbidity and 47% (17/36) had moderate or severe comorbidity. In all, 58% of patients (21/36) were treated with preoperative chemoradiotherapy (CRT) and 33% (12/36) with postoperative CRT. Although 92% patients (33/36) completed the planned radiotherapy (RT) dose, 25% (9/36) required an RT-treatment break, 11% (4/36) were hospitalized, and 33% (12/36) had a dose reduction, break, or discontinuation of concurrent chemotherapy. In all, 39% of patients (14/36) completed ≥4 months of adjuvant chemotherapy, and 17% (6/36) completed therapy without a treatment deviation. More patients with no to mild comorbidity completed treatment than did patients with moderate to severe comorbidity (21% vs. 12%, p = 0.66). The rate of deviation did not differ between patients who had preoperative or postoperative CRT (19% vs. 17%, p = 1.0). Conclusions: The majority of elderly patients with rectal cancer in this series required early termination of treatment, treatment interruptions, or dose reductions. These data suggest that further intensification

  18. Neuroprotective Activity of Curcumin in Combination with Piperine against Quinolinic Acid Induced Neurodegeneration in Rats.

    Science.gov (United States)

    Singh, Shamsher; Kumar, Puneet

    2016-01-01

    Quinolinic acid (QA) is an excitotoxin that induces Huntington's-like symptoms in animals and humans. Curcumin (CMN) is a well-known antioxidant but the major problem is its bioavailability. Therefore, the present study was designed to investigate the effect of CMN in the presence of piperine against QA-induced excitotoxic cell death in rats. QA was administered intrastriatally at a dose of 200 nmol/2 µl saline, bilaterally. CMN (25 and 50 mg/kg/day, p.o.) and combination of CMN (25 mg/kg/day, p.o.) and with piperine (2.5 mg/kg/day, p.o.) was administered daily for the next 21 days. Body weight and behavioral parameters were observed on 1st, 7th, 14th and 21st day. On the 22nd day, animals were sacrificed and striatum was isolated for biochemical (LPO, nitrite and GSH), neuroinflammatory (interleukin (IL)-1β, IL-6 and TNF-α) and neurochemical (dopamine, norepinephrine, GABA, glutamate, 5-HT, 3,4-dihydroxyphenylacetic acid and homovanillic acid) estimation. CMN treatment showed beneficial effect against QA-induced motor deficit, biochemical and neurochemical abnormalities in rats. Combination of piperine (2.5 mg/kg/day, p.o.) with CMN (25 mg/kg/day, p.o.) significantly enhanced its protective effect as compared to treatment with CMN alone. This study has revealed that the combination of CMN and piperine showed strong antioxidant and protective effect against QA-induced behavioral and neurological alteration in rats. © 2016 S. Karger AG, Basel.

  19. Neuroprotective and cognitive-enhancing effects of the combined extract of Cyperus rotundus and Zingiber officinale.

    Science.gov (United States)

    Sutalangka, Chatchada; Wattanathorn, Jintanaporn

    2017-03-03

    Currently, food supplements to improve age-related dementia are required. Therefore, we aimed to determine the effect of the combined extract of Cyperus rotundus and Zingiber officinale (CP1) on the improvement of age-related dementia in rats with AF64A-induced memory deficits. Male Wistar rats weighing 180-200 g were orally given CP1 at doses of 100, 200 and 300 mg.kg -1 BW for a period of 14 days after bilateral intracerebroventricular administration of AF64A. Spatial memory was assessed in all rats every 7 days throughout the 14 day-experimental period. At the end of the study, neuronal density, acetylcholinesterase (AChE) activity, oxidative stress status and the activation of MAPK cascades in the hippocampus were determined. Enhanced memory, increased neuronal density, decreased AChE activity and decreased oxidative stress status together with activated pERK1/2 were observed in the hippocampus of CP1-treated rats. These results suggested that CP1 might improve memory via enhanced cholinergic function and decreased neurodegeneration and oxidative stress. CP1 is a potential novel food supplement for dementia. However, further investigations on the subchronic toxicity of CP1 and drug interactions are required.

  20. Neuroprotection in glaucoma

    Science.gov (United States)

    Vasudevan, Sushil K; Gupta, Viney; Crowston, Jonathan G

    2011-01-01

    Glaucoma is a neurodegenerative disease characterized by loss of retinal ganglion cells and their axons. Recent evidence suggests that intraocular pressure (IOP) is only one of the many risk factors for this disease. Current treatment options for this disease have been limited to the reduction of IOP; however, it is clear now that the disease progression continues in many patients despite effective lowering of IOP. In the search for newer modalities in treating this disease, much data have emerged from experimental research the world over, suggesting various pathological processes involved in this disease and newer possible strategies to treat it. This review article looks into the current understanding of the pathophysiology of glaucoma, the importance of neuroprotection, the various possible pharmacological approaches for neuroprotection and evidence of current available medications. PMID:21150020

  1. Integrated treatment modality of cathodal-transcranial direct current stimulation with peripheral sensory stimulation affords neuroprotection in a rat stroke model.

    Science.gov (United States)

    Liu, Yu-Hang; Chan, Su Jing; Pan, Han-Chi; Bandla, Aishwarya; King, Nicolas K K; Wong, Peter Tsun Hon; Chen, You-Yin; Ng, Wai Hoe; Thakor, Nitish V; Liao, Lun-De

    2017-10-01

    Cathodal-transcranial direct current stimulation induces therapeutic effects in animal ischemia models by preventing the expansion of ischemic injury during the hyperacute phase of ischemia. However, its efficacy is limited by an accompanying decrease in cerebral blood flow. On the other hand, peripheral sensory stimulation can increase blood flow to specific brain areas resulting in rescue of neurovascular functions from ischemic damage. Therefore, the two modalities appear to complement each other to form an integrated treatment modality. Our results showed that hemodynamics was improved in a photothrombotic ischemia model, as cerebral blood volume and hemoglobin oxygen saturation ([Formula: see text]) recovered to 71% and 76% of the baseline values, respectively. Furthermore, neural activities, including somatosensory-evoked potentials (110% increase), the alpha-to-delta ratio (27% increase), and the [Formula: see text] ratio (27% decrease), were also restored. Infarct volume was reduced by 50% with a 2-fold preservation in the number of neurons and a 6-fold reduction in the number of active microglia in the infarct region compared with the untreated group. Grip strength was also better preserved (28% higher) compared with the untreated group. Overall, this nonpharmacological, nonintrusive approach could be prospectively developed into a clinical treatment modality.

  2. Indications for and results of combined modality treatment of colorectal cancer

    International Nuclear Information System (INIS)

    Gunderson, L.L.

    1999-01-01

    Combined modality chemoirradiation is commonly used as a component of treatment in combination with maximum resection for both high-risk resectable and locally advanced primary or recurrent rectal cancers. With surgically resected but high-risk rectal cancers, postoperative chemoirradiation has been shown to improve both disease control (local and distant) and survival (disease-free and overall) and was recommended as standard adjuvant treatment at the 1990 National Institute of Health (NIH) Consensus Conference on Adjuvant treatment for patients with rectal and colon cancers. Subsequent intergroup trials are being conducted to help define optimal combinations of postoperative chemoirradiation for resected high-risk rectal cancers and to test sequencing issues of preoperative versus postoperative chemoirradiation. With locally unresectable primary or recurrent colorectal cancers, standard therapy with surgery, external beam irradiation (EBRT) and chemotherapy is often unsuccessful. When intraoperative electron irradiation (IOERT) is combined with standard treatment, local control and survival appear to be improved in separate analyses from the Mayo Clinic and the Massachusetts General Hospital (MGH). However, routine use of systemic therapy is also needed as a component of treatment, in view of high rates of systemic failure. (orig.)

  3. Indications for and results of combined modality treatment of colorectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Gunderson, L.L. [Mayo Medical School and Mayo Clinic, Rochester, MN (United States)

    1999-05-01

    Combined modality chemoirradiation is commonly used as a component of treatment in combination with maximum resection for both high-risk resectable and locally advanced primary or recurrent rectal cancers. With surgically resected but high-risk rectal cancers, postoperative chemoirradiation has been shown to improve both disease control (local and distant) and survival (disease-free and overall) and was recommended as standard adjuvant treatment at the 1990 National Institute of Health (NIH) Consensus Conference on Adjuvant treatment for patients with rectal and colon cancers. Subsequent intergroup trials are being conducted to help define optimal combinations of postoperative chemoirradiation for resected high-risk rectal cancers and to test sequencing issues of preoperative versus postoperative chemoirradiation. With locally unresectable primary or recurrent colorectal cancers, standard therapy with surgery, external beam irradiation (EBRT) and chemotherapy is often unsuccessful. When intraoperative electron irradiation (IOERT) is combined with standard treatment, local control and survival appear to be improved in separate analyses from the Mayo Clinic and the Massachusetts General Hospital (MGH). However, routine use of systemic therapy is also needed as a component of treatment, in view of high rates of systemic failure. (orig.)

  4. Combined modality treatment including intraoperative radiotherapy in locally advanced and recurrent rectal cancer

    International Nuclear Information System (INIS)

    Tveit, Kjell Maque; Wiig, Johan N.; Olsen, Dag Rune; Storaas, Andreas; Poulsen, Jan Peter; Giercksky, Karl-Erik

    1997-01-01

    Background: Treatment of locally advanced and recurrent rectal cancer usually has a high local recurrence rate and poor survival. Promising results have been reported by combined external radiotherapy, extensive surgery and intraoperative radiotherapy (IORT). Methods: One hundred fifteen patients with locally advanced rectal cancers fixed to the pelvic wall or locally recurrent rectal cancers underwent preoperative external radiotherapy with 46-50 Gy. Six to 8 weeks later radical pelvic surgery was attempted, and was combined with intraoperative electron beam radiotherapy (15-20 Gy) in 66 patients. The patients were followed closely to evaluate complication rate, local and distant recurrence rate and survival. Results: Surgery with no macroscopic tumour remaining was obtained in 65% of the patients with no postoperative deaths. Pelvic infection was the major complication (21%). Although the observation time is short (3-60 months), the local recurrence rate seems low (22%) and survival seems promising (about 60% at 4 years) in patients with complete tumour resection, in contrast to patients with residual tumour (none living at 4 years). Conclusions: The combined modality treatment with preoperative external radiotherapy and extensive pelvic surgery with IORT is sufficiently promising to start a randomized trial on the clinical value of IORT as a boost treatment in the multidisciplinary approach to this disease

  5. Randomized combined modality trial in small cell carcinoma of the lung

    International Nuclear Information System (INIS)

    Maurer, L.H.; Tulloh, M.; Weiss, R.B.; Blom, J.; Leone, L.; Glidewell, O.; Pajak, T.F.

    1980-01-01

    A randomized trial of combined modality therapy employing combination chemotherapy (cyclophosphamide (CTX) and methotrexate (MTX), CTX, MTX and Vincristine (VCR) and CTX, VCR, and high-dose MTX with citrovorum rescue), and radiation therapy was compared to cyclophosphamide and radiation therapy in 258 patients with pulmonary small cell carcinoma. Patients were also randomized: (1) to determine the effects of prophylactic whole brain irradiation; (2) to establish the effects of maintenance chemotherapy. Survival, frequency of response, and site of relapse were different in patients with limited disease (LD) (disease confined to lung, mediastinum, and supraclavicular lymph nodes) when compared with disease spread beyond these sites (extensive disease) (ED). No survival advantage was seen in LD when combination chemotherapy was employed, although the frequency of complete remission was greater with three drugs than with one or two drugs (48% vs 32%). In ED frequency of response was greater for three drugs than for one and two drugs (60% vs 40%), but there was no survival advantage. The median survival time for complete responders was similar for limited or extensive disease (12.1 months), but 23.8% were alive at 24 months with LD compared to none with ED. Maintenance chemotherapy significantly prolonged survival by 16.8 months with 33% alive at 24 months compared to 9% who were unmaintained. Prophylactic whole brain irradiation prevented brain metastases with only 4% developing this complication as compared to 18% of control subjects, but did not influence survival

  6. Assessment of Neuroprotective Properties of Melissa officinalis in Combination With Human Umbilical Cord Blood Stem Cells After Spinal Cord Injury

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    Seyed Ruhollah Hosseini

    2016-10-01

    Full Text Available Introduction The pathophysiology of spinal cord injury (SCI has a classically bad prognosis. It has been demonstrated that human umbilical cord blood stem cells (hUCBSCs and Melissa officinalis (MO are useful for the prevention of neurological disease. Methods Thirty-six adult male rats were randomly divided into intact, sham, control (SCI, MO, hUCBSC, and MO-hUCBSC groups. Intraperitoneal injection of MO (150 mg/kg was commenced 24 hr post-SCI and continued once a day for 14 days. Intraspinal grafting of hUCBSCs was commenced immediately in the next day. The motor and sensory functions of all animals were evaluated once a week after the commencement of SCI. Electromyography (EMG was performed in the last day in order to measure the recruitment index. Immunohistochemistry, reverse transcription-polymerase chain reaction, and transmission electron microscopy evaluations were performed to determine the level of astrogliosis and myelination. Results The results revealed that motor function (MO-hUCBSC: 15 ± 0.3, SCI: 8.2 ± 0.37, p < .001, sensory function (MO-hUCBSC: 3.57 ± 0.19, SCI: 6.38 ± 0.23, p < .001, and EMG recruitment index (MO-hUCBSC: 3.71 ± 0.18, SCI: 1.6 ± 0.1, p < .001 were significantly improved in the MO-hUCBSC group compared with SCI group. Mean cavity area (MO-hUCBSC: 0.03 ± 0.03, SCI: 0.07 ± 0.004, p < .001 was reduced and loss of lower motor neurons (MO-hUCBSC: 7.6 ± 0.43, SCI: 3 ± 0.12, p < .001 and astrogliosis density (MO-hUCBSC: 3.1 ± 0.15, SCI: 6.25 ± 1.42, p < 0.001 in the ventral horn of spinal cord were prevented in MO-hUCBSC group compared with SCI group. Conclusion The results revealed that the combination of MO and hUCBSCs in comparison with the control group has neuroprotective effects in SCI.

  7. Neuroprotection by Combined Administration with Maslinic Acid, a Natural Product from Olea europaea, and MK-801 in the Cerebral Ischemia Model

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    Yisong Qian

    2016-08-01

    Full Text Available Glutamate-mediated excitotoxicity is a major cause of ischemic brain damage. MK-801 confers neuroprotection by attenuating the activation of the N-methyl-d-aspartate (NMDA receptor, but it failed in clinical use due to the short therapeutic window. Here we aim to investigate the effects of maslinic acid, a natural product from Olea europaea, on the therapeutic time window and dose range for the neuroprotection of MK-801. Rats were administered with maslinic acid intracerebroventricularly and cerebral ischemia was induced by middle cerebral artery occlusion (MCAO followed by reperfusion. MK-801 was administered at 1 h, 2 h, 3 h and 4 h after ischemia, respectively. The cerebral infarct volume was determined by 2,3,5-Triphenyltetrazolium chloride (TTC staining, neuronal damage was assessed by Haematoxylin Eosin (H&E staining, and the expression of glial glutamate transporters and glial fibrillary acidic protein (GFAP was evaluated by immunohistochemistry and Western blot post-ischemia. Results showed that the presence of maslinic acid extended the therapeutic time window for MK-801 from 1 h to 3 h. Co-treatment of maslinic acid and MK-801 at a subthreshold dosage obviously induced neuroprotection after ischemia. The combination of these two compounds improved the outcome in ischemic rats. Moreover, maslinic acid treatment promoted the expression of GLT-1 and GFAP post-ischemia. These data suggest that the synergistic effect of maslinic acid on neurological protection might be associated with the improvement of glial function, especially with the increased expression of GLT-1. The combination therapy of maslinic acid and MK-801 may prove to be a potential strategy for treating acute ischemic stroke.

  8. Neuroprotection by Combined Administration with Maslinic Acid, a Natural Product from Olea europaea, and MK-801 in the Cerebral Ischemia Model.

    Science.gov (United States)

    Qian, Yisong; Tang, Xuzhen; Guan, Teng; Li, Yunman; Sun, Hongbin

    2016-08-19

    Glutamate-mediated excitotoxicity is a major cause of ischemic brain damage. MK-801 confers neuroprotection by attenuating the activation of the N-methyl-d-aspartate (NMDA) receptor, but it failed in clinical use due to the short therapeutic window. Here we aim to investigate the effects of maslinic acid, a natural product from Olea europaea, on the therapeutic time window and dose range for the neuroprotection of MK-801. Rats were administered with maslinic acid intracerebroventricularly and cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) followed by reperfusion. MK-801 was administered at 1 h, 2 h, 3 h and 4 h after ischemia, respectively. The cerebral infarct volume was determined by 2,3,5-Triphenyltetrazolium chloride (TTC) staining, neuronal damage was assessed by Haematoxylin Eosin (H&E) staining, and the expression of glial glutamate transporters and glial fibrillary acidic protein (GFAP) was evaluated by immunohistochemistry and Western blot post-ischemia. Results showed that the presence of maslinic acid extended the therapeutic time window for MK-801 from 1 h to 3 h. Co-treatment of maslinic acid and MK-801 at a subthreshold dosage obviously induced neuroprotection after ischemia. The combination of these two compounds improved the outcome in ischemic rats. Moreover, maslinic acid treatment promoted the expression of GLT-1 and GFAP post-ischemia. These data suggest that the synergistic effect of maslinic acid on neurological protection might be associated with the improvement of glial function, especially with the increased expression of GLT-1. The combination therapy of maslinic acid and MK-801 may prove to be a potential strategy for treating acute ischemic stroke.

  9. Feasibility of combined modality therapy for localized high-grade soft tissue sarcomas in adults

    International Nuclear Information System (INIS)

    Blum, R.H.; Greenberger, J.S.; Wilson, R.E.; Corson, J.M.

    1979-01-01

    Seventeen consecutive patients with localized, high grade soft tissue sarcomas had resection of their primary tumor, radiation therapy and chemotherapy. The soft tissue sarcoma was primary in 14 patients and regionally recurrent in 3 patients. Chemotherapy consisted of cyclophosphamide 500 mg/M 2 day 1, Adriamycin (ADR) 60 mg/M 2 day 2, and DTIC 400 mg/M 2 days 1 and 2, given every 21 days to a maximum ADR dose of 450 mg/M 2 . Cyclophosphamide and DTIC were then given to a total duration of 1 year. Radiation therapy consisted of 4000 to 5000 rad by megavoltage photons in 5 weeks, and in selected cases, an additional 1500 to 2000 rad by electron beam boost in the tumor bed delivered over 2 additional weeks. Following surgery, 12 patients were treated sequentially with an interval of chemotherapy, radiation therapy and then the completion of chemotherapy. The added morbidity of this sequential approach is minimal: one patient of 12 had delayed primary healing of her wound, 1 of 10 patients required a break in radiation therapy because of skin erythema. Four patients were treated with intensive pre-chemotherapy radiation therapy because of inadequate surgical margins. The median time on study was 18 months from onset of treatment (range, 8 to 41 months). Although there have been no local, regional or distant recurrences, the follow-up time is inadequate to assess the therapeutic benefit of this combined modality treatment

  10. The Improved Sensitivity to Crossmodal Asynchrony Caused by Voluntary Action: Comparing Combinations of Sensory Modalities

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    Norimichi Kitagawa

    2011-10-01

    Full Text Available The brain has to assess the fine temporal relationship between voluntary actions and their sensory effects to achieve precise spatiotemporal control of body movement. Recently we found that voluntary action improved the subsequent perceptual temporal discrimination between somatosensory and auditory events. In voluntary condition, participants actively pressed a button and a noise burst was presented at various onset asynchronies relative to the button press. The participants made either ‘sound-first’ or ‘touch-first’ responses. We found that the temporal order judgment performance in the voluntary condition (as indexed by just noticeable difference was significantly better than that when their finger was passively stimulated (passive condition. Temporal attention and comparable involuntary movement did not explain the improvement caused by the voluntary action. The results suggest that predicting sensory consequences via a ‘forward’ model enhances perceptual temporal resolution for precise control of the body. The present study examined whether this improved temporal sensitivity caused by the voluntary action is also observed for the other combinations of sensory modalities. We compared the effects of voluntary action on the temporal sensitivity between auditory-somatosensory, visual-somatosensory, and somatosensory-somatosensory stimulus pairs.

  11. Organ preservation in invasive bladder cancer: Brachytherapy, an alternative to cystectomy and combined modality treatment?

    International Nuclear Information System (INIS)

    Pos, Floris; Horenblas, Simon; Dom, Paul; Moonen, Luc; Bartelink, Harry

    2005-01-01

    Purpose: To evaluate our long-term results of bladder preservation with brachytherapy in the treatment of bladder cancer. Methods and materials: Between 1987 and 2000, 108 patients with T1-G3 and T2-T3a stages of bladder cancer were treated with a transurethral resection (TUR) and a course of external beam radiotherapy (30 Gy in 15 fractions) followed by brachytherapy (40 Gy). All tumors were solitary lesions with a diameter ≤5 cm. Median follow-up was 54 months (range, 1-178 months). Results: The 5-year and 10-year overall survival rates were 62% and 50%, respectively. The 5-year and 10-year disease-specific survival rates were 73% and 67%, respectively. The actuarial local control rate was 73% at 5 and 73% at 10 years, respectively. The 5-year and 10-year disease-specific survival rates for patients with a preserved bladder were 68% and 59%, respectively. Of all long-term surviving patients, 90% preserved their native bladders. The treatment was well tolerated. Acute toxicity was mild. Two patients experienced serious late toxicity: 1 patient developed a persisting vesicocutaneous fistula and the other a stricture of the urethra and ureters. Conclusion: For patients with solitary, organ confined invasive bladder cancer ≤5 cm, bladder preservation with brachytherapy is an excellent alternative to radical cystectomy and combined modality treatment

  12. Cellular recovery kinetic studies relevant to combined-modality research and therapy

    International Nuclear Information System (INIS)

    Dethlefsen, L.A.

    1979-01-01

    The relevance of cellular recovery kinetics to combined-modality therapy is evaluated within the framework of an idealized experimental flow chart and published adriamycin data. Within this context, limitations for both experimental design and data interpretations are discussed. The effects of adriamycin have been documented extensively at the molecular and cellular level and its interactions with x-irradiation have been studied, both in vitro and in vivo. The limited in vivo results suggest that the end results of a given protocol correlate with cellular recovery kinetics; however, definitive experiments simply have not been done. For example, no one has used single-dose drug and irradiation data to predict the outcome and then confirm or refute the prediction even in a relatively simple 2-dose drug + 2-dose drug + 2-dose x-ray protocol. Thus, at this time, the extent of the correlations between cellular recovery kinetics and clinical response for either normal or malignant tissues is not known and the possible relevance of such studies cannot be discounted

  13. Improved survival with combined modality treatment for Stage IV breast cancer

    International Nuclear Information System (INIS)

    Nervi, C.; Arcangeli, G.; Concolino, F.; Cortese, M.

    1979-01-01

    Between 1974 and 1977, 85 patients with breast cancer at first postmastectomy relapse were irradiated (Radiation 3500 to 6000 rad--3/5 weeks) to all clinically evident lesions. Radiation fields were properly shaped to include a maximum 40% active bone marrow. After 3 to 4 weeks rest, chemotherapy was started as adjuvant therapy for residual or subclinical disease (ADR 30 mg/M 2 Day 1 and 8, 5-FU 400 mg/M 2 Day 1 and 8, CY 100 mg/M 2 Day 1 through 14: repeated after 14 days). ADR was discontinued at 500/M 2 and substituted by MTX 30 mg/M 2 Day 1 and 8 for a total of 2 years. Irradiated sites were chest wall in 35, supraclavicular and internal mammary nodes in 22, bone in 56, single lung lesions in 12, brain in 24. Controls were 52 comparable but non-randomized patients treated with chemotherapy only. Forty days after x-irradiation 68 patients (80%) were free of disease (NED) while in 17 cases (20%) some residual was still present (RED). In 28 of 68 cases (41%) NED after x-irradiation and 13 of 17 (76%) in RED group developed second relapse after a median interval of 26 and 20 mos., respectively. Four of 52 patients (8%) in the control group had complete regression with a median interval to second relapse of 7 mos. Median survival was 30 mos., 24 mos., and 13 mos., respectively, for NED, RED and chemotherapy only. Eighteen patients (26%) are free of disease after 36 to 48 mos. in the combined modality group; none in the chemotherapy group. Combined treatment cases did not show untolerable myelodepression. In 10 long-surviving patients a marked subcutaneous and skin fibrosis developed because of drug additive effect. Stage IV breast cancers rendered clinically free of disease with x-irradiation and subsequently treated with chemotherapy survive significantly longer than with chemotherapy alone

  14. Comparing the Antiseizure and Neuroprotective Efficacy of LY293558, Diazepam, Caramiphen, and LY293558-Caramiphen Combination against Soman in a Rat Model Relevant to the Pediatric Population

    Science.gov (United States)

    Apland, James P.; Aroniadou-Anderjaska, Vassiliki; Figueiredo, Taiza H.; Pidoplichko, Volodymyr I.; Rossetti, Katia

    2018-01-01

    The currently Food and Drug Administration–approved anticonvulsant for the treatment of status epilepticus (SE) induced by nerve agents is the benzodiazepine diazepam; however, diazepam does not appear to offer neuroprotective benefits. This is of particular concern with respect to the protection of children because, in the developing brain, synaptic transmission mediated via GABAA receptors, the target of diazepam, is weak. In the present study, we exposed 21-day-old male rats to 1.2 × LD50 soman and compared the antiseizure, antilethality, and neuroprotective efficacy of diazepam (10 mg/kg), LY293558 (an AMPA/GluK1 receptor antagonist; 15 mg/kg), caramiphen (CRM, an antimuscarinic with NMDA receptor-antagonistic properties; 50 mg/kg), and LY293558 (15 mg/kg) + CRM (50 mg/kg), administered 1 hour after exposure. Diazepam, LY293558, and LY293558 + CRM, but not CRM alone, terminated SE; LY293558 + CRM treatment acted significantly faster and produced a survival rate greater than 85%. Thirty days after soman exposure, neurodegeneration in limbic regions was most severe in the CRM-treated group, minimal to severe—depending on the region—in the diazepam group, absent to moderate in the LY293558-treated group, and totally absent in the LY293558 + CRM group. Amygdala and hippocampal atrophy, a severe reduction in spontaneous inhibitory activity in the basolateral amygdala, and increased anxiety-like behavior in the open-field and acoustic startle response tests were present in the diazepam and CRM groups, whereas the LY293558 and LY293558 + CRM groups did not differ from controls. The combined administration of LY293558 and CRM, by blocking mainly AMPA, GluK1, and NMDA receptors, is a very effective anticonvulsant and neuroprotective therapy against soman in young rats. PMID:29467308

  15. Comparing the Antiseizure and Neuroprotective Efficacy of LY293558, Diazepam, Caramiphen, and LY293558-Caramiphen Combination against Soman in a Rat Model Relevant to the Pediatric Population.

    Science.gov (United States)

    Apland, James P; Aroniadou-Anderjaska, Vassiliki; Figueiredo, Taiza H; Pidoplichko, Volodymyr I; Rossetti, Katia; Braga, Maria F M

    2018-05-01

    The currently Food and Drug Administration-approved anticonvulsant for the treatment of status epilepticus (SE) induced by nerve agents is the benzodiazepine diazepam; however, diazepam does not appear to offer neuroprotective benefits. This is of particular concern with respect to the protection of children because, in the developing brain, synaptic transmission mediated via GABA A receptors, the target of diazepam, is weak. In the present study, we exposed 21-day-old male rats to 1.2 × LD 50 soman and compared the antiseizure, antilethality, and neuroprotective efficacy of diazepam (10 mg/kg), LY293558 (an AMPA/GluK1 receptor antagonist; 15 mg/kg), caramiphen (CRM, an antimuscarinic with NMDA receptor-antagonistic properties; 50 mg/kg), and LY293558 (15 mg/kg) + CRM (50 mg/kg), administered 1 hour after exposure. Diazepam, LY293558, and LY293558 + CRM, but not CRM alone, terminated SE; LY293558 + CRM treatment acted significantly faster and produced a survival rate greater than 85%. Thirty days after soman exposure, neurodegeneration in limbic regions was most severe in the CRM-treated group, minimal to severe-depending on the region-in the diazepam group, absent to moderate in the LY293558-treated group, and totally absent in the LY293558 + CRM group. Amygdala and hippocampal atrophy, a severe reduction in spontaneous inhibitory activity in the basolateral amygdala, and increased anxiety-like behavior in the open-field and acoustic startle response tests were present in the diazepam and CRM groups, whereas the LY293558 and LY293558 + CRM groups did not differ from controls. The combined administration of LY293558 and CRM, by blocking mainly AMPA, GluK1, and NMDA receptors, is a very effective anticonvulsant and neuroprotective therapy against soman in young rats. U.S. Government work not protected by U.S. copyright.

  16. Long term observations in combined modality therapy for limited stage small cell lung cancer

    International Nuclear Information System (INIS)

    Colletier, Philip J.; Komaki, Ritsuko; Schea, Randi A.; Allen, Pamela; Cox, James D.

    1997-01-01

    Purpose/Objective: With the discovery that patients with small cell lung cancer (SCLC) exhibit a high level of sensitivity to both chemotherapy and radiotherapy, the treatment of SCLC became a model for the success of combined modality treatment. In this retrospective review, we analyze the outcomes and patterns of failure when patients are treated with chemotherapy and thoracic irradiation. The relative values of sequential and concurrent chemotherapy, in conjunction with chest irradiation, are assessed. The potential benefit of prophylactic cranial irradiation is explored. The impact of prognostic factors for long term survival of SCLC patients are examined to identify pretreatment patient characteristics and treatment parameters which might predict for a favorable outcome. Materials and Methods: We identified 190 patients treated at M.D. Anderson Cancer Center from January 1985 to December 1992 with curative intent for limited stage SCLC. Prognostic factors were determined using univariate and multivariate analysis. The significant covariates for each outcome endpoint were evaluated. Probabilities of local failure, overall survival, relapse-free survival, and distant metastasis-free survival were calculated from the time of treatment using actuarial life table analysis. Results: The median age was 61, with 51% males. There were 119 patients treated sequentially, and 71 concurrently. The Karnofsky Performance Status was >= 90 in 48% of patients in the concurrent cohort, vs. 35% of the sequential group. Prophylactic cranial irradiation (PCI) was delivered in 117 cases (62%). There were 51 long term survivors, defined as survival >=36 months. The median follow-up in surviving patients was 75 months. At the time of the analysis, 166 patients (87%) had expired. The crude 2 and 3 year survival rate for the entire group was 38.4% and 26.8%, respectively. The actuarial 2-year survival was 39.9%, and at 3 years the actuarial survival was 27.8%. The median actuarial

  17. Combined Modality Management of Retroperitoneal Sarcomas: A Single-Institution Series of 121 Patients

    International Nuclear Information System (INIS)

    Bishop, Andrew J.; Zagars, Gunar K.; Torres, Keila E.; Hunt, Kelly K.; Cormier, Janice N.; Feig, Barry W.; Guadagnolo, B. Ashleigh

    2015-01-01

    Purpose: The purpose of this study was to investigate local control, survival outcomes, and complication rates of patients treated with aggressive surgery and radiation therapy (RT) for retroperitoneal sarcomas (RPS). Methods and Materials: We reviewed the medical records of 121 consecutive patients treated for RPS with surgery and RT between 1965 and 2012. The most common histology was liposarcoma (n=42; 35%). The median follow-up was 100 months (range: 20-467 months). Eighty-six patients (71%) were treated for initial presentation of RPS, and 35 patients (29%) presented with and were treated for RPS recurrence. RT was preoperative in 88 patients (73%; median dose: 50.4 Gy) and postoperative in 33 patients (27%; median dose: 55 Gy). Results: Five-year local control and overall survival rates were 56% and 57%, respectively. Two factors were associated with higher risk of any intra-abdominal recurrence at 5 years: positive or uncertain margins (58% vs 30% for negative margins, P<.001; hazard ratio [HR]: 2.7; 95% confidence interval [CI]: 1.6-4.8) and disease recurrence after previous resection (76% vs 31% for de novo RPS, P<.001; HR: 4.4; 95% CI: 2.5-7.5). The 10-year complication rate was 5%, and RT-related complications were associated with postoperative RT (P<.001) and RT dose of ≥60 Gy (P<.001). Conclusions: Intra-abdominal RPS recurrence continues to be a significant challenge despite the use of aggressive surgery and radiation therapy. Given the complications associated with postoperative radiation therapy, we recommend that preoperative radiation therapy is the preferred strategy when combined modality therapy is recommended

  18. Combined-modality therapy for patients with regional nodal metastases from melanoma

    International Nuclear Information System (INIS)

    Ballo, Matthew T.; Ross, Merrick I.; Cormier, Janice N.; Myers, Jeffrey N.; Lee, Jeffrey E.; Gershenwald, Jeffrey E.; Hwu, Patrick; Zagars, Gunar K.

    2006-01-01

    Purpose: To evaluate the outcome and patterns of failure for patients with nodal metastases from melanoma treated with combined-modality therapy. Methods and Materials: Between 1983 and 2003, 466 patients with nodal metastases from melanoma were managed with lymphadenectomy and radiation, with or without systemic therapy. Surgery was a therapeutic procedure for clinically apparent nodal disease in 434 patients (regionally advanced nodal disease). Adjuvant radiation was generally delivered with a hypofractionated regimen. Adjuvant systemic therapy was delivered to 154 patients. Results: With a median follow-up of 4.2 years, 252 patients relapsed and 203 patients died of progressive disease. The actuarial 5-year disease-specific, disease-free, and distant metastasis-free survival rates were 49%, 42%, and 44%, respectively. By multivariate analysis, increasing number of involved lymph nodes and primary ulceration were associated with an inferior 5-year actuarial disease-specific and distant metastasis-free survival. Also, the number of involved lymph nodes was associated with the development of brain metastases, whereas thickness was associated with lung metastases, and primary ulceration was associated with liver metastases. The actuarial 5-year regional (in-basin) control rate for all patients was 89%, and on multivariate analysis there were no patient or disease characteristics associated with inferior regional control. The risk of lymphedema was highest for those patients with groin lymph node metastases. Conclusions: Although regional nodal disease can be satisfactorily controlled with lymphadenectomy and radiation, the risk of distant metastases and melanoma death remains high. A management approach to these patients that accounts for the competing risks of distant metastases, regional failure, and long-term toxicity is needed

  19. Completely automated modal analysis procedure based on the combination of different OMA methods

    Science.gov (United States)

    Ripamonti, Francesco; Bussini, Alberto; Resta, Ferruccio

    2018-03-01

    In this work a completely automated output-only Modal Analysis procedure is presented and all its benefits are listed. Based on the merging of different Operational Modal Analysis methods and a statistical approach, the identification process has been improved becoming more robust and giving as results only the real natural frequencies, damping ratios and mode shapes of the system. The effect of the temperature can be taken into account as well, leading to the creation of a better tool for automated Structural Health Monitoring. The algorithm has been developed and tested on a numerical model of a scaled three-story steel building present in the laboratories of Politecnico di Milano.

  20. An improved EMD method for modal identification and a combined static-dynamic method for damage detection

    Science.gov (United States)

    Yang, Jinping; Li, Peizhen; Yang, Youfa; Xu, Dian

    2018-04-01

    Empirical mode decomposition (EMD) is a highly adaptable signal processing method. However, the EMD approach has certain drawbacks, including distortions from end effects and mode mixing. In the present study, these two problems are addressed using an end extension method based on the support vector regression machine (SVRM) and a modal decomposition method based on the characteristics of the Hilbert transform. The algorithm includes two steps: using the SVRM, the time series data are extended at both endpoints to reduce the end effects, and then, a modified EMD method using the characteristics of the Hilbert transform is performed on the resulting signal to reduce mode mixing. A new combined static-dynamic method for identifying structural damage is presented. This method combines the static and dynamic information in an equilibrium equation that can be solved using the Moore-Penrose generalized matrix inverse. The combination method uses the differences in displacements of the structure with and without damage and variations in the modal force vector. Tests on a four-story, steel-frame structure were conducted to obtain static and dynamic responses of the structure. The modal parameters are identified using data from the dynamic tests and improved EMD method. The new method is shown to be more accurate and effective than the traditional EMD method. Through tests with a shear-type test frame, the higher performance of the proposed static-dynamic damage detection approach, which can detect both single and multiple damage locations and the degree of the damage, is demonstrated. For structures with multiple damage, the combined approach is more effective than either the static or dynamic method. The proposed EMD method and static-dynamic damage detection method offer improved modal identification and damage detection, respectively, in structures.

  1. Evaluation of surgical staging prior to combined modality therapy for esophageal cancer

    International Nuclear Information System (INIS)

    Suntharalingam, M.; Vines, E.; Echo, D. van; Greenwald, B.; Krasna, M.

    1996-01-01

    OBJECTIVE: Historically, patients with esophageal cancer have had a poor outcome despite aggressive treatment approaches. Recently chemo/RT followed by surgical resection has shown a significant improvement in survival in this patient population. The success of this aggressive approach has been predicated on accurate definition of disease extent and appropriate patient selection. We have performed pre-treatment surgical staging (thoracoscopy and laparoscopy) on 38 pts. referred for management of their localized esophageal cancer. The purpose of this report is to compare the results of clinical (CT, MRI, EGD, EUS) vs. surgical staging. The data gathered prospectively will also be used to identify potential predictors for disease-free survival. METHODS: Thirty-eight pts. were treated with combined modality therapy prior to a planned surgical resection. Patients received 50.4 Gy in 1.8 Gy fractions in conjunction with 5 FU (1 Gm/m2) and Cisplatin (100 mg/m2) on days 1 and 28. Patients were evaluated 4 to 6 wks. after completion of therapy for consideration of Ivor-Lewis esophagectomy. Of the original 38 pts., 4 are awaiting surgery, 3 died prior to resection, 2 pts. progressed through chemo/RT, and 1 refused. To date, 28 pts. are available for analysis with a median follow up of 21.5 months. This group included 16 pts. with squamous cell and 12 with adenocarcinoma. RESULTS: Twenty-five of the 28 pts. taken to surgery have undergone pre treatment surgical staging (2 refused, 1 medically unfit). Evaluation of tumor status revealed noninvasive staging to be accurate 56% of the time. Five pts. were converted from T 2 to T 3 , 1 from T 3 to T 4 and 3 T 4 tumors were found to be T 3 . Using the surgical findings at time of staging, 6 pts. were found to have T 2 tumors, 16 had T 3 tumors, and 3 had T 4 tumors. Clinical lymph node status was confirmed in 15 patients (60%). Six went from N+ to N 0 and 4 pts. thought to be N 0 were N+. Eight patients had evidence of positive

  2. Combination of diagnostic medial calcaneal nerve block followed by pulsed radiofrequency for plantar fascitis pain: A new modality

    Directory of Open Access Journals (Sweden)

    Deepak Thapa

    2014-01-01

    Full Text Available Plantar fasciitis (PF is the most common cause of chronic heel pain which may be bilateral in 20 to 30% of patients. It is a very painful and disabling condition which can affect the quality of life. The management includes both pharmacological and operative procedures with no single proven effective treatment modality. In the present case series, we managed three patients with PF (one with bilateral PF. Following a diagnostic medial calcaneal nerve (MCN block at its origin, we observed reduction in verbal numerical rating scale (VNRS in all the three patients. Two patients has relapse of PF pain which was managed with MCN block followed with pulsed radio frequency (PRF. All the patients were pain-free at the time of reporting. This case series highlights the possible role of combination of diagnostic MCN block near its origin followed with PRF as a new modality in management of patients with PF.

  3. Combination of diagnostic medial calcaneal nerve block followed by pulsed radiofrequency for plantar fascitis pain: A new modality

    Science.gov (United States)

    Thapa, Deepak; Ahuja, Vanita

    2014-01-01

    Plantar fasciitis (PF) is the most common cause of chronic heel pain which may be bilateral in 20 to 30% of patients. It is a very painful and disabling condition which can affect the quality of life. The management includes both pharmacological and operative procedures with no single proven effective treatment modality. In the present case series, we managed three patients with PF (one with bilateral PF). Following a diagnostic medial calcaneal nerve (MCN) block at its origin, we observed reduction in verbal numerical rating scale (VNRS) in all the three patients. Two patients has relapse of PF pain which was managed with MCN block followed with pulsed radio frequency (PRF). All the patients were pain-free at the time of reporting. This case series highlights the possible role of combination of diagnostic MCN block near its origin followed with PRF as a new modality in management of patients with PF. PMID:24963184

  4. Neuroprotective potential of quercetin in combination with piperine against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity

    Directory of Open Access Journals (Sweden)

    Shamsher Singh

    2017-01-01

    Full Text Available 1-Methy-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP is a neurotoxin that selectively damages dopaminergic neurons in the substantia nigra pars compacta and induces Parkinson's like symptoms in rodents. Quercetin (QC is a natural polyphenolic bioflavonoid with potent antioxidant and anti-inflammatory properties but lacks of clinical attraction due to low oral bioavailability. Piperine is a well established bioavailability enhancer used pre-clinically to improve the bioavailability of antioxidants (e.g., Quercetin. Therefore, the present study was designed to evaluate the neuroprotective potential of QC together with piperine against MPTP-induced neurotoxicity in rats. MPTP (100 μg/μL/rat, bilaterally was injected intranigrally on days 1, 4 and 7 using a digital stereotaxic apparatus. QC (25 and 50 mg/kg, intragastrically and QC (25 mg/kg, intragastrically in combination with piperine (2.5 mg/kg, intragastrically were administered daily for 14 days starting from day 8 after the 3rd injection of MPTP. On day 22, animals were sacrificed and the striatum was isolated for oxidative stress parameter (thiobarbituric acid reactive substances, nitrite and glutathione, neuroinflammatory cytokine (interleukin-1β, interleukin-6, and tumor necrosis factor-α and neurotransmitter (dopamine, norepinephrine, serotonin, gamma-aminobutyric acid, glutamate, 3,4-dihydroxyphenylacetic acid, homovanillic acid, and 5-hydroxyindoleacetic acid evaluations. Bilateral infusion of MPTP into substantia nigra pars compacta led to significant motor deficits as evidenced by impairments in locomotor activity and rotarod performance in open field test and grip strength and narrow beam walk performance. Both QC (25 and 50 mg/kg and QC (25 mg/kg in combination with piperine (2.5 mg/kg, in particular the combination therapy, significantly improved MPTP-induced behavioral abnormalities in rats, reversed the abnormal alterations of neurotransmitters in the striatum, and alleviated

  5. Potential role for epidermal growth factor receptor inhibitors in combined-modality therapy for non-small-cell lung cancer

    International Nuclear Information System (INIS)

    Kim, Dong Wook; Choy, Hak

    2004-01-01

    There has been a surge of interest in the translation of discoveries in molecular biology into clinically relevant therapies in the field of hematology/oncology. The epidermal growth factor receptor (EGFR) has been a molecular target of significant interest and investigation, and preclinical and clinical studies support a role for targeted therapy in a variety of cancers, including non-small-cell lung cancer (NSCLC) via compounds that specifically inhibit EGFR. ZD1839, IMC-C225, and OSI-774 are the most clinically developed of these compounds. Interestingly, preclinical studies have demonstrated that EGFR inhibitors may have radiation-sensitizing properties, as well as increased cytotoxic activity in combination with chemotherapeutic agents, suggesting a potential role for EGFR inhibitors as an adjunct to the current combined-modality approach for therapy of Stage III NSCLC. Therefore, clinical trials have been proposed and initiated to address the issue of determining the impact of the addition of EGFR inhibitors to the standard combined-modality regimen (chemotherapy/radiation therapy ± surgery) for Stage III NSCLC. This article reviews preclinical and clinical data supporting the role for EGFR inhibitors alone or in combination with chemotherapy/radiation therapy for locally advanced NSCLC. Also, it will provide an overview of ongoing and proposed clinical studies investigating the potential role for EGFR inhibitors in Stage III NSCLC

  6. THE FIRST EXPERIENCE OF USING LOCAL HYPERTHERMIA IN COMBINED MODALITY TREATMENT OF OPERABLE NON-SMALL CELL LUNG CANCER

    Directory of Open Access Journals (Sweden)

    A. Yu. Dobrodeev

    2015-01-01

    Full Text Available The paper presents the first experience in treating 5 patients with stage II–III non-small cell lung cancer using combined modality treatment including 40 Gy preoperative hyperfractionated radiotherapy with concurrent 2 cycles of paclitaxel/carboplatin chemotherapy and local hyperthermia (10 sessions followed by radical surgery. The overal response rate to preoperative treatment was 80 %. Chemotherapy was well tolerated and hyperthermia resulted no in adverse effects. All patients underwent surgery (4 lobectomies and 1 pneumonectomy. No complications were observed in the postoperative period. The follow-up period ranged from 6 to 20 months. No evidence of disease progression and radiation-induced damages were observed.

  7. Interactive, multi-modality image registrations for combined MRI/MRSI-planned HDR prostate brachytherapy

    Directory of Open Access Journals (Sweden)

    Galen Reed

    2011-03-01

    Full Text Available Purpose: This study presents the steps and criteria involved in the series of image registrations used clinically during the planning and dose delivery of focal high dose-rate (HDR brachytherapy of the prostate. Material and methods: Three imaging modalities – Magnetic Resonance Imaging (MRI, Magnetic Resonance Spectroscopic Imaging (MRSI, and Computed Tomography (CT – were used at different steps during the process. MRSI is used for identification of dominant intraprosatic lesions (DIL. A series of rigid and nonrigid transformations were applied to the data to correct for endorectal-coil-induced deformations and for alignment with the planning CT. Mutual information was calculated as a morphing metric. An inverse planning optimization algorithm was applied to boost dose to the DIL while providing protection to the urethra, penile bulb, rectum, and bladder. Six prostate cancer patients were treated using this protocol. Results: The morphing algorithm successfully modeled the probe-induced prostatic distortion. Mutual information calculated between the morphed images and images acquired without the endorectal probe showed a significant (p = 0.0071 increase to that calculated between the unmorphed images and images acquired without the endorectal probe. Both mutual information and visual inspection serve as effective diagnostics of image morphing. The entire procedure adds less than thirty minutes to the treatment planning. Conclusion: This work demonstrates the utility of image transformations and registrations to HDR brachytherapy of prostate cancer.

  8. Combined modality therapy for locally advanced non-small cell lung carcinoma

    International Nuclear Information System (INIS)

    Recine, D.; Rowland, K.; Reddy, S.; Lee, M.S.; Bonomi, P.; Taylor, S.; Faber, L.P.; Warren, W.; Kittle, C.F.; Hendrickson, F.R.

    1990-01-01

    Multi-modality treatment consisting of cisplatin, VP-16, and 5-fluorouracil chemotherapy given concomitantly with external beam radiation was used to treat 64 patients with locally advanced Stage III non-small cell lung carcinoma. This regimen was used in a preoperative fashion for four cycles in patients considered surgically resectable and with curative intent for six cycles in the remainder of patients. The clinical response rate for the entire group was 84% and the overall local control rate was 74%. The median survival was 13 months with a median follow-up for live patients of 19 months. The actuarial 3-year survival and disease-free survival rates were 30% and 23%, respectively. Histologic complete response was 39% and appeared to predict for survival. The 3-year actuarial survival and disease-free survival rates for 23 resected patients were 69% and 45%, respectively, with the complete histologic responders having a disease-free survival of 78%. The pattern of first recurrence did not appear to differ by histology or presence of lymph nodes in this subset of patients. The actuarial 3-year survival and disease-free survival rates for inoperable patients receiving six cycles of treatment were 18% and 23%, respectively. The local control was 67% with the majority of these patients having Stage IIIB disease. The Mountain International staging system appeared to predict for operability, local recurrence, and survival. This concomitant treatment regimen is feasible, with the major toxicities being leukopenia, nausea, and vomiting

  9. Technological Advances in the Treatment of Cancer: Combining Modalities to Optimize Outcomes.

    Science.gov (United States)

    Wong, Eric T; Toms, Steven A; Ahluwalia, Manmeet S

    2015-11-01

    The anticancer treatment modality tumor treating fields (TTFields; Optune, Novocure) use the lower frequency range of the electromagnetic spectrum to destroy tumor cells during mitosis. This treatment has been evaluated in several trials of patients with glioblastoma. In these patients, TTFields are delivered through 4 transducer arrays applied to the scalp. In a phase 3 clinical trial of patients with recurrent glioblastoma, TTFields were as effective as chemotherapy, and were associated with fewer and milder systemic toxicities. Data from a phase 3 trial in newly diagnosed glioblastoma suggested that the addition of TTFields to postoperative radiation therapy and chemotherapy represents an important advance in the management of newly diagnosed glioblastoma. Ongoing clinical trials are investigating the efficacy and safety of TTFields in other tumor types, including pancreatic cancer, mesothelioma, ovarian cancer, and non–small cell lung cancer. Other recent advances in the management of cancer have been seen with immunomodulatory therapy, including immune checkpoint inhibitors. Further study will be necessary to evaluate whether TTFields will enhance or impair other established and newly emerging therapies.

  10. National Patterns of Care and Outcomes after Combined Modality Therapy for Stage IIIA Non-small Cell Lung Cancer

    Science.gov (United States)

    Patel, Aalok P.; Crabtree, Traves D.; Bell, Jennifer M.; Guthrie, Tracey J.; Robinson, Clifford G.; Morgensztern, Daniel; Colditz, Graham A.; Kreisel, Daniel; Krupnick, A. Sasha; Bradley, Jeffrey D.; Patterson, G. Alexander; Meyers, Bryan F.; Puri, Varun

    2014-01-01

    Introduction The role of surgery in addition to chemotherapy and radiation for stage IIIA non-small cell lung cancer (NSCLC) remains controversial. Since there is limited data on the benefit from surgery in this setting, we evaluated the use of combined modality therapy nationally, and explored the outcomes with and without the addition of surgery. Methods Patient variables and treatment-related outcomes were abstracted for patients with clinical stage IIIA NSCLC from the National Cancer Database. Patients receiving chemotherapy and radiation (CR) were compared to those undergoing chemotherapy, radiation, and surgery in any sequence (CRS). Results Between 1998 and 2010, 61339 patients underwent combined modality treatment for clinical stage IIIA NSCLC. Of these, 51979 (84.7%) received CR while 9360 (15.3%) underwent CRS. Patients in the CRS group were younger, more likely females and Caucasians, had smaller tumors and lower Charlson comorbidity scores. The 30-day surgical mortality was 200/8993 (2.2%). The median overall survival favored the CRS group in both unmatched (32.4 months vs. 15.7 months, p<.001) and matched analysis based on patient characteristics (34.3 months vs. 18.4months, p<.001). Conclusion There is significant heterogeneity in the treatment of stage IIIA NSCLC in the United States. Patients selected for surgery in addition to chemoradiation therapy appear to have better long-term survival. PMID:24722151

  11. Is there room for combined modality treatments? Dosimetric comparison of boost strategies for advanced head and neck and prostate cancer

    International Nuclear Information System (INIS)

    Gora, Joanna; Hopfgartner, Johannes; Kuess, Peter; Paskeviciute, Brigita; Georg, Dietmar

    2013-01-01

    The purpose of the study was to determine the dosimetric difference between three emerging treatment modalities-volumetric-modulated arc therapy (VMAT), intensity-modulated proton beam therapy (IMPT) and intensity-modulated carbon ion beam therapy (IMIT)-for two tumour sites where selective boosting of the tumour is applied. For 10 patients with locally advanced head and neck (H and N) cancer and 10 with high-risk prostate cancer (PC) a VMAT plan was generated for PTV initial that included lymph node regions, delivering 50 Gy (IsoE) for H and N and 50.4 Gy (IsoE) for PC patients. Furthermore, separate boost plans (VMAT, IMPT and IMIT) were created to boost PTV boost up to 70 Gy (IsoE) and 78 Gy (IsoE) for H and N and PC cases, respectively. Doses to brainstem, myelon, larynx and parotid glands were assessed for H and N cases. Additionally, various organs at risk (OARs) (e.g. cochlea, middle ear, masticator space) were evaluated that are currently discussed with respect to quality of life after treatment. For PC cases, bladder, rectum and femoral heads were considered as OARs. For both tumour sites target goals were easily met. Looking at OAR sparing, generally VMAT + VMAT was worst. VMAT + IMIT had the potential to spare some structures in very close target vicinity (such as cochlea, middle ear, masticator space) significantly better than VMAT + IMPT. Mean doses for rectal and bladder wall were on average 4 Gy (IsoE) and 1.5 Gy (IsoE) higher, respectively, compared to photons plus particles scenarios. Similar results were found for parotid glands and larynx. Concerning target coverage, no significant differences were observed between the three treatment concepts. Clear dosimetric benefits were observed for particle beam therapy as boost modality. However, the clinical benefit of combined modality treatments remains to be demonstrated. (author)

  12. Combined Modality Treatment for PET-Positive Non-Hodgkin Lymphoma: Favorable Outcomes of Combined Modality Treatment for Patients With Non-Hodgkin Lymphoma and Positive Interim or Postchemotherapy FDG-PET

    Energy Technology Data Exchange (ETDEWEB)

    Halasz, Lia M. [Harvard Radiation Oncology Program, Boston, Massachusetts (United States); Jacene, Heather A. [Department of Imaging, Dana-Farber Cancer Institute, and Department of Radiology, Brigham and Women' s Hospital, Boston, Massachusetts (United States); Catalano, Paul J. [Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Van den Abbeele, Annick D. [Department of Imaging, Dana-Farber Cancer Institute, and Department of Radiology, Brigham and Women' s Hospital, Boston, Massachusetts (United States); LaCasce, Ann [Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Mauch, Peter M. [Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women' s Hospital, Boston, Massachusetts (United States); Ng, Andrea K., E-mail: ang@lroc.harvard.edu [Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women' s Hospital, Boston, Massachusetts (United States)

    2012-08-01

    Purpose: To evaluate outcomes of patients treated for aggressive non-Hodgkin lymphoma (NHL) with combined modality therapy based on [{sup 18}F]fluoro-2-deoxy-2-D-glucose positron emission tomography (FDG-PET) response. Methods and Materials: We studied 59 patients with aggressive NHL, who received chemotherapy and radiation therapy (RT) from 2001 to 2008. Among them, 83% of patients had stage I/II disease. Patients with B-cell lymphoma received R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone)-based chemotherapy, and 1 patient with anaplastic lymphoma kinase-negative anaplastic T-cell lymphoma received CHOP therapy. Interim and postchemotherapy FDG-PET or FDG-PET/computed tomography (CT) scans were performed for restaging. All patients received consolidated involved-field RT. Median RT dose was 36 Gy (range, 28.8-50 Gy). Progression-free survival (PFS) and local control (LC) rates were calculated with and without a negative interim or postchemotherapy FDG-PET scan. Results: Median follow-up was 46.5 months. Thirty-nine patients had negative FDG-PET results by the end of chemotherapy, including 12 patients who had a negative interim FDG-PET scan and no postchemotherapy PET. Twenty patients were FDG-PET-positive, including 7 patients with positive interim FDG-PET and no postchemotherapy FDG-PET scans. The 3-year actuarial PFS rates for patients with negative versus positive FDG-PET scans were 97% and 90%, respectively. The 3-year actuarial LC rates for patients with negative versus positive FDG-PET scans were 100% and 90%, respectively. Conclusions: Patients who had a positive interim or postchemotherapy FDG-PET had a PFS rate of 90% at 3 years after combined modality treatment, suggesting that a large proportion of these patients can be cured with consolidated RT.

  13. A clinical study on combined modality therapy, radio-hyperthermo-chemotherapy, for pancreatic cancer

    International Nuclear Information System (INIS)

    Yamamoto, Yoshikazu

    1989-01-01

    A new multimodality therapy, radio-hyperthermo-chemotherapy, has been performed in a total of 31 pancreatic cancer patients with the purpose of improving treatment outcome. Combination of hyperthermia and chemotherapy was given as a pre-irradiation therapy in 7 resectable cancer patients. Among 24 unresectable cancer patients, 17 had irradiation in combination with hyperthermia and chemotherpay. Although both degeneration and necrosis of cancer cells were observed in all resectable cases at biopsy, these were not predictive of a better outcome. Of evaluable 17 patients with unresectable cancer, tumor regression was observed in 5 (29.4%). Although 22 patients had pain before therapy, 8 and 5 patients had remarkable and moderate pain relief, respectively, with therapy. Performance status was improved in 7 patients (29.2%). Survival rate at 12 months was still low (8.3%). However, the radio-hyperthermo-chemotherapy appears to help in increasing the quality of life in view of pain relief. (N.K.)

  14. Combined-modality treatment of solid tumors using radiotherapy and molecular targeted agents.

    Science.gov (United States)

    Ma, Brigette B Y; Bristow, Robert G; Kim, John; Siu, Lillian L

    2003-07-15

    Molecular targeted agents have been combined with radiotherapy (RT) in recent clinical trials in an effort to optimize the therapeutic index of RT. The appeal of this strategy lies in their potential target specificity and clinically acceptable toxicity. This article integrates the salient, published research findings into the underlying molecular mechanisms, preclinical efficacy, and clinical applicability of combining RT with molecular targeted agents. These agents include inhibitors of intracellular signal transduction molecules, modulators of apoptosis, inhibitors of cell cycle checkpoints control, antiangiogenic agents, and cyclo-oxygenase-2 inhibitors. Molecular targeted agents can have direct effects on the cytoprotective and cytotoxic pathways implicated in the cellular response to ionizing radiation (IR). These pathways involve cellular proliferation, DNA repair, cell cycle progression, nuclear transcription, tumor angiogenesis, and prostanoid-associated inflammation. These pathways can also converge to alter RT-induced apoptosis, terminal growth arrest, and reproductive cell death. Pharmacologic modulation of these pathways may potentially enhance tumor response to RT though inhibition of tumor repopulation, improvement of tumor oxygenation, redistribution during the cell cycle, and alteration of intrinsic tumor radiosensitivity. Combining RT and molecular targeted agents is a rational approach in the treatment of solid tumors. Translation of this approach from promising preclinical data to clinical trials is actively underway.

  15. Embolization as one modality in a combined strategy for the management of cerebral arteriovenous malformations.

    Science.gov (United States)

    Raymond, J; Iancu, D; Weill, A; Guilbert, F; Bahary, J P; Bojanowski, M; Roy, D

    2005-10-05

    We attempted to assess clinical results of management of cerebral arteriovenous malformation using a combination of endovascular, surgical and radiotherapeutic approaches. We retrospectively reviewed the angiographic and clinical data on prospectively collected consecutive patients treated by embolization from 1994 to 2004. The general philosophy was to attempt treatment by a combination of approaches only when an angiographic cure was likely or at least possible. The clinical outcome was assessed according to the modified Rankin scale. Although 404 patients were collected, complete files and follow-ups are available for 227 or 56% only. Most patients presented with hemorrhages (53%) or seizures (23%). The final management consisted in embolization alone in 34%, embolization followed by surgery in 47%, embolization and radiotherapy in 16%, and embolization, surgery and radiotherapy in 3% of patients. The embolization procedure itself could lead to an angiographic cure in only 16% of patients. When the management strategy could be completed, the cure rate increased to 66%. Complications of embolization occurred in 22.6% of patients. Overall clinical outcome was excellent (Rankin 0) in 43%, good (Rankin 1) in 38%, fair (Rankin 2) in 10%, poor (Rankin 3-5) in 2%, and the death rate was 7%. A combined strategy initially designed to provide angiographic cures cannot be completed in a significant number of patients; the total morbidity of treatment remains significant. There is no scientific evidence that cerebral arteriovenous malformations should be treated, and no clinical trial to prove that one approach is better than the other. Various treatment protocols have been proposed on empirical grounds. Small lesions can often be eradicated, with surgery when lesions are superficial, or with radiation therapy for deeper ones. There has been little controversy regarding therapeutic indications in these patients (1). The management of larger AVMs, sometimes in more eloquent

  16. Combined modality therapy for exsudative form of age-related macular degeneration

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    М. V. Budzinskaya

    2013-01-01

    Full Text Available Treatment outcomes in patients with age-related vascular degeneration due to formation of subretinal neovascular membrane (SNM of two groups: photodynamic therapy (PDT with Photosens alone (18 patients and in combination with anti-VEGF therapy with Lucentis (20 patients. For both groups Photosens was administrated i.v. in single dose of 0.05 mg/kg. The irradiation was performed on the 3rd day (the wave length 675 nm, light dose 120 J/cm2, total light dose did not exceed 500 J/cm2. The number of sessions accounted for 3 to 5 per week according to clinical manifestation of SNM. Patients with multimodality treatment had intravitreal administration of Lucensis in dose 0.05 ml (0.5 mg. The study showed that combination of PDT and anti-VEGF therapy improved vision better and with more stable effect then PDT alone. Thus vision improvement and decrease of SNM activity occurred in 50% of patients with PDT alone and in 60% of patients with multimodality treatment. For 2-year follow-up in the group of PDT alone the vision gradient gradually decreased compared with baseline vision (from 0.11 to 0.06, in the group of multimodality treatment gradual increase of vision gradient was noticed (from 0.03 to 0.155. The superior efficiency of PDT combined with anti-VEGF therapy compared with PDT alone in patients with age-related vascular degeneration was confirmed by study of vision, fundus angiography and average thickness of retina in foveola in both groups.

  17. Meaning and challenges in the practice of multiple therapeutic massage modalities: a combined methods study.

    Science.gov (United States)

    Porcino, Antony J; Boon, Heather S; Page, Stacey A; Verhoef, Marja J

    2011-09-20

    Therapeutic massage and bodywork (TMB) practitioners are predominantly trained in programs that are not uniformly standardized, and in variable combinations of therapies. To date no studies have explored this variability in training and how this affects clinical practice. Combined methods, consisting of a quantitative, population-based survey and qualitative interviews with practitioners trained in multiple therapies, were used to explore the training and practice of TMB practitioners in Alberta, Canada. Of the 5242 distributed surveys, 791 were returned (15.1%). Practitioners were predominantly female (91.7%), worked in a range of environments, primarily private (44.4%) and home clinics (35.4%), and were not significantly different from other surveyed massage therapist populations. Seventy-seven distinct TMB therapies were identified. Most practitioners were trained in two or more therapies (94.4%), with a median of 8 and range of 40 therapies. Training programs varied widely in number and type of TMB components, training length, or both. Nineteen interviews were conducted. Participants described highly variable training backgrounds, resulting in practitioners learning unique combinations of therapy techniques. All practitioners reported providing individualized patient treatment based on a responsive feedback process throughout practice that they described as being critical to appropriately address the needs of patients. They also felt that research treatment protocols were different from clinical practice because researchers do not usually sufficiently acknowledge the individualized nature of TMB care provision. The training received, the number of therapies trained in, and the practice descriptors of TMB practitioners are all highly variable. In addition, clinical experience and continuing education may further alter or enhance treatment techniques. Practitioners individualize each patient's treatment through a highly adaptive process. Therefore, treatment

  18. Combined modality treatment improves tumor control and overall survival in patients with early stage Hodgkin's lymphoma: a systematic review

    DEFF Research Database (Denmark)

    Herbst, Christine; Rehan, Fareed A; Brillant, Corinne

    2010-01-01

    as well as conference proceedings from January 1980 to February 2009 for randomized controlled trials comparing chemotherapy alone versus the same chemotherapy regimen plus radiotherapy. Progression free survival and similar outcomes were analyzed together as tumor control. Effect measures used were......Combined modality treatment (CMT) of chemotherapy followed by localized radiotherapy is standard treatment for patients with early stage Hodgkin's lymphoma. However, the role of radiotherapy has been questioned recently and some clinical study groups advocate chemotherapy only for this indication....... We thus performed a systematic review with meta-analysis of randomized controlled trials comparing chemotherapy alone with CMT in patients with early stage Hodgkin's lymphoma with respect to response rate, tumor control and overall survival (OS). We searched Medline, EMBASE and the Cochrane Library...

  19. Assessment of the quality of life of elderly with diagnosis of oral squamous cell carcinoma submitted to combined modality therapy

    Directory of Open Access Journals (Sweden)

    Erasmo Bernardo Marinho

    2017-06-01

    Full Text Available Introduction: Evaluating the quality of life allows a more accurate clinical control as well as the provision of prognostic information for specific groups. This study was designed to evaluate the quality of life of elderly diagnosed with oral squamous cell carcinoma submitted to combined modality therapy. Methods: This is a retrospective and observational study, with cross-sectional quantitative character. A total of 206 records of patients with head and neck cancer treated between April 2013 and October 2014 were analyzed. Eleven patients over six months of treatment completion were included in the study. The questionnaire of quality of life of the University of Washington (UW-QOL was applied. The data were collected regarding the social-demographic, clinical-pathological and therapeutic profiles, and the non-stimulated salivary flow was measured. Statistical analysis of quantitative data was performed by the Spearman nonlinear correlation, considering a confidence of 95%. Results: Chewing, saliva and speech showed the lowest scores (31.8; 42.3; 60.6, respectively. Statistically significant correlation was found between: shoulder and mood (r=0.787; swallowing and chewing (r=0.761; completion time of radiotherapy and recreation (r=0.659; activity and recreation (r=0.653; pain and swallowing (r=0.626; chewing and speech (r=0.607; age and speech (r=-0.617. Conclusions: Elderly with oral squamous cell carcinoma diagnosis sunmitted to combined modality therapy presented the areas related to chewing, saliva and speech as the most committed ones. Older individuals have greater impairment of speech, as well as those with longer completion of radiotherapy have better results related to the recreation area.

  20. Neuroprotective effect of bispectral index-guided fast-track anesthesia using sevoflurane combined with dexmedetomidine for intracranial aneurysm embolization

    Directory of Open Access Journals (Sweden)

    Chao-liang Tang

    2018-01-01

    Full Text Available Dexmedetomidine has sedative, anxiolytic, analgesic, anti-sympathetic, and anti-shivering effects. Dexmedetomidine might be effective in combination with sevoflurane for anesthesia, but prospective randomized controlled clinical trials with which to verify this hypothesis are lacking. In total, 120 patients who underwent embolization of an intracranial aneurysm were recruited from Anhui Provincial Hospital and Renmin Hospital of Wuhan University of China and randomly allocated to two groups. After intraoperative administration of 2% to 3% sevoflurane inhalation, one group of patients received pump-controlled intravenous injection of 1.0 μg/kg dexmedetomidine for 15 minutes followed by maintenance with 0.3 μg/kg/h until the end of surgery; the other group of patients only underwent pump-controlled infusion of saline. Bispectral index monitoring revealed that dexmedetomidine-assisted anesthesia can shorten the recovery time of spontaneous breathing, time to eye opening, and time to laryngeal mask removal. Before anesthetic induction and immediately after laryngeal mask airway removal, the glucose and lactate levels were low, the S100β and neuron-specific enolase levels were low, the perioperative blood pressure and heart rate were stable, and postoperative delirium was minimal. These findings indicate that dexmedetomidine can effectively assist sevoflurane for anesthesia during surgical embolization of intracranial aneurysms, shorten the time to consciousness and extubation, reduce the stress response and energy metabolism, stabilize hemodynamic parameters, and reduce adverse reactions, thereby reducing the damage to the central nervous system. This trial was registered at the Chinese Clinical Trial Registry (http://www.chictr.org.cn/ (registration number: ChiCTR-IPR-16008113.

  1. Prognostic factors in invasive bladder carcinoma treated by combined modality protocol (organ-sparing approach)

    International Nuclear Information System (INIS)

    Matos, Tadeja; Cufer, Tanja; Cervek, Jozica; Borstnar, Simona; Kragelj, Borut; Zumer-Pregelj, Mirjana

    2000-01-01

    Purpose: The results of bladder sparing approach for the treatment of muscle-invasive bladder cancer, using a combination of transurethral resection (TUR), chemotherapy, and radiotherapy, are encouraging. The survival of patients treated by this method is similar to the survival of patients treated by radical cystectomy. The aim of our study was to find out which pretreatment characteristics influence the survival of patients treated by organ sparing approach that would enable us to identify the patients most suitable for this type of treatment. Methods and Materials: The prognostic value of different factors, such as age, gender, performance status, hemoglobin level, clinical stage, histologic grade, presence of obstructive uropathy, and completeness of TUR, has been studied in 105 patients with invasive bladder cancer, who received a bladder sparing treatment in the period from 1988 to 1995. They were treated with a combination of TUR, followed by 2-4 cycles of methotrexate, cisplatinum, and vinblastine polychemotherapy. In complete responders the treatment was completed by radiotherapy (50 Gy to the bladder and 40 Gy to the regional lymph nodes), whereas nonresponders underwent cystectomy whenever feasible. Results: Our study has confirmed an independent prognostic value of performance status, histologic grade, and obstructive uropathy, for the disease-specific survival (DSS) of bladder cancer patients treated by a conservative approach. We believe that performance status best reflects the extent of disease and exerts significant influence on the extent and course of treatment, while obstructive uropathy is a good indicator of local spread of the disease, better than clinical T-stage. Our finding that histologic grade is one of the strongest prognostic factors shows that tumor biology also is a very important prognostic factor in patients treated by conservative approach. Conclusion: Patients with muscle-invasive bladder cancer who are most likely to benefit

  2. Combined modal split and assignment model for the multimodal transportation network of the economic circle in China

    Directory of Open Access Journals (Sweden)

    Sh. Li

    2009-09-01

    Full Text Available Economic circles have been formed and developing in China. An economic circle consists of more than one closely adjoining central cities and their influence zones. It is always the major engine for the development of one country’s economy and even for the world economy. A combined modal split and assignment model with deterministic travel demand is proposed for modelling passengers’ choices of intercity bus and train which are two main competing modes in the multimodal transportation network of the economic circle. The generalized travel cost model of highway and railway are used incorporating travel time, ticket fare and passenger’s discomfort. On the highway network, the interactions of private vehicles and intercity buses are asymmetric. Thus, a variational inequality formulation is proposed to describe the combined model. The streamlined diagonalization algorithm is presented to solve the combined model. The multimodal transportation network based on Yangtze River Delta economic circle is presented to illustrate the proposed method. The results show the efficiency of the proposed model.

  3. Results of combined modality treatment in patients with primary unresectable cancer of the oral cavity

    International Nuclear Information System (INIS)

    Kawecki, A.; Starosciak, S.; Towpik, E.; Jagielska, B.; Lenartowicz, B.; Pietras, M.; Szutkowski, Z.; Kiprian, D.

    2001-01-01

    Neoadjuvant chemotherapy may improve the results of treatment for primarily unresectable cancer of the oral cavity. The aim of this study was to estimate the tolerance and early results of neoadjuvant chemotherapy followed by surgical resection of oral cavity cancer, with immediate reconstruction and adjuvant radiotherapy. 56 patients hospitalized at the Department of Head and Neck Cancer of the Maria Sklodowska-Curie Memorial Cancer Centre - Institute of Oncology between August 1997 and June 2000 were enrolled for the purpose of the study. When tumour regresion was observed after 2-4 courses of neoadjuvant chemotherapy consisting of cisplatin, 5-fluorouracil, methotrexate, vinblastin, etoposide and leucovorin, the patients were referred for surgical resection with immediate reconstruction, followed by adjuvant radiotherapy. Regression of the primary tumor and lymph nodes of the neck was observed in 41 patients, all of whom were referred for radical surgery followed by adjuvant radiotherapy. The tolerance of combined treatment was acceptable. Complete regression was obtained in 37/56 patients. During observation 12 patients failed due to locoregional progression and 2 due to distant metastases. 23/56 patients (41 %) are alive without evidence of disease. Neoadjuvant chemotherapy allows for radical resection in a majority of patients with primarily unresectable cancer of the oral cavity. The tolerance of treatment is good. What is important, radiotherapy and chemotherapy do not impair wound healing and vascularity of musculo-cutaneous island flaps

  4. Characterising human atherosclerotic carotid plaque tissue composition and morphology using combined spectroscopic and imaging modalities.

    Science.gov (United States)

    Barrett, Hilary E; Mulvihill, John J; Cunnane, Eoghan M; Walsh, Michael T

    2015-01-01

    demonstrates the need to fully characterise the calcification structure of the plaque tissue and that a combination of FTIR and μX-CT provides the necessary information to fully understand the mechanical behaviour of the plaque tissue.

  5. Biomarkers of histone deacetylase inhibitor activity in a phase 1 combined-modality study with radiotherapy.

    Directory of Open Access Journals (Sweden)

    Anne Hansen Ree

    Full Text Available Following the demonstration that histone deacetylase inhibitors enhanced experimental radiation-induced clonogenic suppression, the Pelvic Radiation and Vorinostat (PRAVO phase 1 study, combining fractionated radiotherapy with daily vorinostat for pelvic carcinoma, was designed to evaluate both clinical and novel biomarker endpoints, the latter relating to pharmacodynamic indicators of vorinostat action in clinical radiotherapy.Potential biomarkers of vorinostat radiosensitizing action, not simultaneously manifesting molecular perturbations elicited by the radiation itself, were explored by gene expression array analysis of study patients' peripheral blood mononuclear cells (PBMC, sampled at baseline (T0 and on-treatment two and 24 hours (T2 and T24 after the patients had received vorinostat.This strategy revealed 1,600 array probes that were common for the comparisons T2 versus T0 and T24 versus T2 across all of the patients, and furthermore, that no significantly differential expression was observed between the T0 and T24 groups. Functional annotation analysis of the array data showed that a significant number of identified genes were implicated in gene regulation, the cell cycle, and chromatin biology. Gene expression was validated both in patients' PBMC and in vorinostat-treated human carcinoma xenograft models, and transient repression of MYC was consistently observed.Within the design of the PRAVO study, all of the identified genes showed rapid and transient induction or repression and therefore, in principle, fulfilled the requirement of being pharmacodynamic biomarkers of vorinostat action in fractionated radiotherapy, possibly underscoring the role of MYC in this therapeutic setting.

  6. LSPR and Interferometric Sensor Modalities Combined Using a Double-Clad Optical Fiber.

    Science.gov (United States)

    Muri, Harald Ian; Bano, Andon; Hjelme, Dag Roar

    2018-01-11

    We report on characterization of an optical fiber-based multi-parameter sensor concept combining localized surface plasmon resonance (LSPR) signal and interferometric sensing using a double-clad optical fiber. The sensor consists of a micro-Fabry-Perot in the form of a hemispherical stimuli-responsive hydrogel with immobilized gold nanorods on the facet of a cleaved double-clad optical fiber. The swelling degree of the hydrogel is measured interferometrically using the single-mode inner core, while the LSPR signal is measured using the multi-mode inner cladding. The quality of the interferometric signal is comparable to previous work on hydrogel micro-Fabry-Perot sensors despite having gold nanorods immobilized in the hydrogel. We characterize the effect of hydrogel swelling and variation of bulk solution refractive index on the LSPR peak wavelength. The results show that pH-induced hydrogel swelling causes only weak redshifts of the longitudinal LSPR mode, while increased bulk refractive index using glycerol and sucrose causes large blueshifts. The redshifts are likely due to reduced plasmon coupling of the side-by-side configuration as the interparticle distance increases with increasing swelling. The blueshifts with increasing bulk refractive index are likely due to alteration of the surface electronic structure of the gold nanorods donated by the anionic polymer network and glycerol or sucrose solutions. The recombination of biotin-streptavidin on gold nanorods in hydrogel showed a 7.6 nm redshift of the longitudinal LSPR. The LSPR response of biotin-streptavidin recombination is due to the change in local refractive index (RI), which is possible to discriminate from the LSPR response due to changes in bulk RI. In spite of the large LSPR shifts due to bulk refractive index, we show, using biotin-functionalized gold nanorods binding to streptavidin, that LSPR signal from gold nanorods embedded in the anionic hydrogel can be used for label-free biosensing. These

  7. Inclusion of molecular biotherapies with radical radiotherapy: modeling of combined modality treatment schedules

    International Nuclear Information System (INIS)

    Jones, Bleddyn; Dale, Roger G.

    1999-01-01

    tumors from the application of cytostatic therapy. There are predictions of smaller increments in TCP in heterogenous tumor populations from the application of cytostatic and radiosensitizing biotherapies in combination. Conclusions: The exercises show how the scheduling of biotherapies may critically influence tumor cure probabilities in subtle ways and give considerable insight into the interacting biological mechanisms that influence these changes. Future therapeutic developments should be guided by these principles

  8. Combined-modality treatment and organ preservation in bladder cancer. Do molecular markers predict outcome?

    International Nuclear Information System (INIS)

    Weiss, C.; Roedel, F.; Wolf, I.; Sauer, R.; Roedel, C.; Papadopoulos, T.; Engehausen, D.G.; Schrott, K.M.

    2005-01-01

    Purpose: in invasive bladder cancer, several groups have reported the value of organ preservation by a combined-treatment approach, including transurethral resection (TUR-BT) and radiochemotherapy (RCT). As more experience is acquired with this organ-sparing treatment, patient selection needs to be optimized. Clinical factors are limited in their potential to identify patients most likely to respond to RCT, thus, additional molecular markers for predicting treatment response of individual lesions are sorely needed. Patients and methods: the apoptotic index (AI) and Ki-67 index were evaluated by immunohistochemistry on pretreatment biopsies of 134 patients treated for bladder cancer by TUR-BT and RCT. Expression of each marker as well as clinicopathologic factors were then correlated with initial response, local control and cancer-specific survival with preserved bladder in univariate and multivariate analysis. Results: the median AI for all patients was 1.5% (range 0.2-7.4%). The percentage of Ki-67-positive cells in the tumors ranged from 0.2% to 85% with a median of 14.2%. A significant correlation was found for AI and tumor differentiation (G1/2: AI = 1.3% vs. G3/4: AI = 1.6%; p = 0.01). A complete response at restaging TUR-BT was achieved in 76% of patients. Factors predictive of complete response included T-category (p < 0.0001), resection status (p = 0.02), lymphovascular invasion (p = 0.01), and Ki-67 index (p = 0.02). For local control, AI (p = 0.04) and Ki-67 index (p = 0.05) as well as T-category (p = 0.005), R-status (p = 0.05), and lymphatic vessel invasion (p = 0.05) reached statistical significance. Out of the molecular markers only high Ki-67 levels were associated to cause-specific survival with preserved bladder. On multivariate analysis, T-category was the strongest independent factor for initial response, local control and cancer-specific survival with preserved bladder. Conclusion: The indices of pretreatment apoptosis and Ki-67 predict a

  9. LSPR and Interferometric Sensor Modalities Combined Using a Double-Clad Optical Fiber

    Directory of Open Access Journals (Sweden)

    Harald Ian Muri

    2018-01-01

    Full Text Available We report on characterization of an optical fiber-based multi-parameter sensor concept combining localized surface plasmon resonance (LSPR signal and interferometric sensing using a double-clad optical fiber. The sensor consists of a micro-Fabry-Perot in the form of a hemispherical stimuli-responsive hydrogel with immobilized gold nanorods on the facet of a cleaved double-clad optical fiber. The swelling degree of the hydrogel is measured interferometrically using the single-mode inner core, while the LSPR signal is measured using the multi-mode inner cladding. The quality of the interferometric signal is comparable to previous work on hydrogel micro-Fabry-Perot sensors despite having gold nanorods immobilized in the hydrogel. We characterize the effect of hydrogel swelling and variation of bulk solution refractive index on the LSPR peak wavelength. The results show that pH-induced hydrogel swelling causes only weak redshifts of the longitudinal LSPR mode, while increased bulk refractive index using glycerol and sucrose causes large blueshifts. The redshifts are likely due to reduced plasmon coupling of the side-by-side configuration as the interparticle distance increases with increasing swelling. The blueshifts with increasing bulk refractive index are likely due to alteration of the surface electronic structure of the gold nanorods donated by the anionic polymer network and glycerol or sucrose solutions. The recombination of biotin-streptavidin on gold nanorods in hydrogel showed a 7.6 nm redshift of the longitudinal LSPR. The LSPR response of biotin-streptavidin recombination is due to the change in local refractive index (RI, which is possible to discriminate from the LSPR response due to changes in bulk RI. In spite of the large LSPR shifts due to bulk refractive index, we show, using biotin-functionalized gold nanorods binding to streptavidin, that LSPR signal from gold nanorods embedded in the anionic hydrogel can be used for label

  10. Differences in Perception of Musical Stimuli among Acoustic, Electric, and Combined Modality Listeners.

    Science.gov (United States)

    Prentiss, Sandra M; Friedland, David R; Nash, John J; Runge, Christina L

    2015-05-01

    Cochlear implants have shown vast improvements in speech understanding for those with severe to profound hearing loss; however, music perception remains a challenge for electric hearing. It is unclear whether the difficulties arise from limitations of sound processing, the nature of a damaged auditory system, or a combination of both. To examine music perception performance with different acoustic and electric hearing configurations. Chord discrimination and timbre perception were tested in subjects representing four daily-use listening configurations: unilateral cochlear implant (CI), contralateral bimodal (CIHA), bilateral hearing aid (HAHA) and normal-hearing (NH) listeners. A same-different task was used for discrimination of two chords played on piano. Timbre perception was assessed using a 10-instrument forced-choice identification task. Fourteen adults were included in each group, none of whom were professional musicians. The number of correct responses was divided by the total number of presentations to calculate scores in percent correct. Data analyses were performed with Kruskal-Wallis one-way analysis of variance and linear regression. Chord discrimination showed a narrow range of performance across groups, with mean scores ranging between 72.5% (CI) and 88.9% (NH). Significant differences were seen between the NH and all hearing-impaired groups. Both the HAHA and CIHA groups performed significantly better than the CI groups, and no significant differences were observed between the HAHA and CIHA groups. Timbre perception was significantly poorer for the hearing-impaired groups (mean scores ranged from 50.3-73.9%) compared to NH (95.2%). Significantly better performance was observed in the HAHA group as compared to both groups with electric hearing (CI and CIHA). There was no significant difference in performance between the CIHA and CI groups. Timbre perception was a significantly more difficult task than chord discrimination for both the CI and CIHA

  11. Selective bladder preservation by combined modality therapy for invasive bladder cancer

    International Nuclear Information System (INIS)

    Kachnic, L. A.; Kaufman, D. S.; Zietman, A. L.; Dallow, K. C.; Griffin, P. P.; Heney, N. M.; Althausen, A. F.; Shipley, W. U.

    1995-01-01

    Purpose/Objective: To assess the success of selective organ preservation or radical cystectomy in a large group of patients with muscle-invasive bladder cancer treated with induction by combined transurethral resection (TURBT), systemic chemotherapy and radiation therapy. Materials and Methods: 106 patients (median age 68 years) were treated with induction by maximal TURBT and 2 cycles of chemotherapy (methotrexate, cisplatin, vinblastine - MCV) followed by 39.6 Gy irradiation in 1.8 Gy fractions with concomitant cisplatin. Tumor response was then evaluated by cystoscopy, rebiopsy, and urine cytology. Complete responders were consolidated with radiation to 64.8 Gy and further cisplatin. Any subsequent isolated invasive local relapse was managed by cystectomy. Patients with any less than a complete response (CR) were recommended cystectomy. Median follow-up was 4.4 years. Kaplan-Meier analysis was used to assess outcome. Results: 74 CR patients (70%) and 7 non-cystectomy candidates with less than a CR (7%) received consolidation chemotherapy and radiation. 13 incomplete responders (12%) underwent immediate cystectomy. 6 patients underwent cystectomy because they could not tolerate induction chemo-radiation. 1 complete response patient underwent radical cystectomy. 83 patients completed their planned therapy but 5 died of treatment related toxicity during induction chemotherapy. Five year actuarial overall survival and disease-specific survival were 52% and 60% respectively. For T2 patients, actuarial overall survival was 63%, and for T3-4, 45%. Five year survival with an intact functioning bladder was 43%. Five year freedom from distant metastases was 66%. Of those who had a CR after TURBT and MCV, the risk of a subsequent invasive bladder relapse was 18% at 5 years. Of those who had a CR after the completion of induction chemotherapy and 39.6 Gy, this risk was 21%. 18 patients (17%) have experienced a non-invasive bladder relapse requiring further TUR and

  12. Selective bladder preservation by combined modality therapy for invasive bladder cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kachnic, L A; Kaufman, D S; Zietman, A L; Dallow, K C; Griffin, P P; Heney, N M; Althausen, A F; Shipley, W U

    1995-07-01

    Purpose/Objective: To assess the success of selective organ preservation or radical cystectomy in a large group of patients with muscle-invasive bladder cancer treated with induction by combined transurethral resection (TURBT), systemic chemotherapy and radiation therapy. Materials and Methods: 106 patients (median age 68 years) were treated with induction by maximal TURBT and 2 cycles of chemotherapy (methotrexate, cisplatin, vinblastine - MCV) followed by 39.6 Gy irradiation in 1.8 Gy fractions with concomitant cisplatin. Tumor response was then evaluated by cystoscopy, rebiopsy, and urine cytology. Complete responders were consolidated with radiation to 64.8 Gy and further cisplatin. Any subsequent isolated invasive local relapse was managed by cystectomy. Patients with any less than a complete response (CR) were recommended cystectomy. Median follow-up was 4.4 years. Kaplan-Meier analysis was used to assess outcome. Results: 74 CR patients (70%) and 7 non-cystectomy candidates with less than a CR (7%) received consolidation chemotherapy and radiation. 13 incomplete responders (12%) underwent immediate cystectomy. 6 patients underwent cystectomy because they could not tolerate induction chemo-radiation. 1 complete response patient underwent radical cystectomy. 83 patients completed their planned therapy but 5 died of treatment related toxicity during induction chemotherapy. Five year actuarial overall survival and disease-specific survival were 52% and 60% respectively. For T2 patients, actuarial overall survival was 63%, and for T3-4, 45%. Five year survival with an intact functioning bladder was 43%. Five year freedom from distant metastases was 66%. Of those who had a CR after TURBT and MCV, the risk of a subsequent invasive bladder relapse was 18% at 5 years. Of those who had a CR after the completion of induction chemotherapy and 39.6 Gy, this risk was 21%. 18 patients (17%) have experienced a non-invasive bladder relapse requiring further TUR and

  13. Targeted Therapy of Cancer Using Photodynamic Therapy in Combination with Multi-faceted Anti-Tumor Modalities

    Directory of Open Access Journals (Sweden)

    Malini Olivo

    2010-05-01

    Full Text Available Photodynamic therapy (PDT has emerged as one of the important therapeutic options in the management of cancer and other diseases. PDT involves a tumor-localized photosensitizer (PS, which when appropriately illuminated by visible light converts oxygen into cytotoxic reactive oxygen species (ROS, that attack key structural entities within the targeted cells, ultimately resulting in necrosis or apoptosis. Though PDT is a selective modality, it can be further enhanced by combining other targeted therapeutic strategies that include the use of synthetic peptides and nanoparticles for selective delivery of photosensitizers. Another potentially promising strategy is the application of targeted therapeutics that exploit a myriad of critical pathways involved in tumorigenesis and metastasis. Vascular disrupting agents that eradicate tumor vasculature during PDT and anti-angiogenic agents that targets specific molecular pathways and prevent the formation of new blood vessels are novel therapeutic approaches that have been shown to improve treatment outcome. In addition to the well-documented mechanisms of direct cell killing and damage to the tumor vasculature, PDT can also activate the body’s immune response against tumors. Numerous pre-clinical studies and clinical observations have demonstrated the immuno-stimulatory capability of PDT. Herein, we aim to integrate the most important findings with regard to the combination of PDT and other novel targeted therapy approaches, detailing its potential in cancer photomedicine.

  14. Future directions in combined modality therapy for rectal cancer: reevaluating the role of total mesorectal excision after chemoradiotherapy

    Directory of Open Access Journals (Sweden)

    Solanki AA

    2013-08-01

    Full Text Available Abhishek A Solanki,1 Daniel T Chang,2 Stanley L Liauw11Department of Radiation and Cellular Oncology, University of Chicago, Chicago, IL, USA; 2Department of Radiation Oncology, Stanford University, Stanford, CA, USAAbstract: Most patients who develop rectal cancer present with locoregionally advanced (T3 or node-positive disease. The standard management of locoregionally advanced rectal cancer is neoadjuvant concurrent chemoradiotherapy (nCRT, followed by radical resection (low-anterior resection or abdominoperineal resection with total mesorectal excision. Approximately 15% of patients can have a pathologic complete response (pCR at the time of surgery, indicating that some patients can have no detectable residual disease after nCRT. The actual benefit of surgery in this group of patients is unclear. It is possible that omission of surgery in these patients, termed selective nonoperative management, can limit the toxicities associated with standard, multimodal combined modality therapy without compromising disease control. In this review, we discuss the clinical experiences to date using selective nonoperative management and various attempts at escalation of nCRT to improve the number of patients who have a pCR. We also explore several clinical, laboratory, imaging, histopathologic, and genetic biomarkers that have been tested as tools to predict which patients are most likely to have a pCR after nCRT.Keywords: rectal cancer, chemoradiotherapy, total mesorectal excision, nonoperative management, organ preservation

  15. Antiangiogenic agents in the treatment of recurrent or newly diagnosed glioblastoma: Analysis of single-agent and combined modality approaches

    International Nuclear Information System (INIS)

    Beal, Kathryn; Abrey, Lauren E; Gutin, Philip H

    2011-01-01

    Surgical resection followed by radiotherapy and temozolomide in newly diagnosed glioblastoma can prolong survival, but it is not curative. For patients with disease progression after frontline therapy, there is no standard of care, although further surgery, chemotherapy, and radiotherapy may be used. Antiangiogenic therapies may be appropriate for treating glioblastomas because angiogenesis is critical to tumor growth. In a large, noncomparative phase II trial, bevacizumab was evaluated alone and with irinotecan in patients with recurrent glioblastoma; combination treatment was associated with an estimated 6-month progression-free survival (PFS) rate of 50.3%, a median overall survival of 8.9 months, and a response rate of 37.8%. Single-agent bevacizumab also exceeded the predetermined threshold of activity for salvage chemotherapy (6-month PFS rate, 15%), achieving a 6-month PFS rate of 42.6% (p < 0.0001). On the basis of these results and those from another phase II trial, the US Food and Drug Administration granted accelerated approval of single-agent bevacizumab for the treatment of glioblastoma that has progressed following prior therapy. Potential antiangiogenic agents-such as cilengitide and XL184-also show evidence of single-agent activity in recurrent glioblastoma. Moreover, the use of antiangiogenic agents with radiation at disease progression may improve the therapeutic ratio of single-modality approaches. Overall, these agents appear to be well tolerated, with adverse event profiles similar to those reported in studies of other solid tumors. Further research is needed to determine the role of antiangiogenic therapy in frontline treatment and to identify the optimal schedule and partnering agents for use in combination therapy

  16. Radical Cystectomy Compared to Combined Modality Treatment for Muscle-Invasive Bladder Cancer: A Systematic Review and Meta-Analysis

    International Nuclear Information System (INIS)

    Vashistha, Vishal; Wang, Hanzhang; Mazzone, Andrew; Liss, Michael A.; Svatek, Robert S.; Schleicher, Mary; Kaushik, Dharam

    2017-01-01

    Purpose: To perform a comprehensive comparison of overall survival (OS), disease-specific survival (DSS), progression-free survival (PFS), and treatment-related complications between radical cystectomy (RC) and combined modality treatment (CMT—radiation therapy, concurrent chemotherapy, and maximal transurethral resection of bladder tumor) in the setting of muscle-invasive bladder cancer. Methods and Materials: We searched 7 databases (PubMed, Scopus, EMBASE, Proquest, CINAHL, and (ClinicalTrials.gov)) for randomized, controlled trials and prospective and retrospective studies directly comparing RC with CMT from database inception to March 2016. We conducted meta-analyses evaluating OS, DSS, and PFS with hazard ratios (HRs) and 95% confidence intervals (CIs). Results: Nineteen studies evaluating 12,380 subjects were selected. For the 8 studies encompassing 9554 subjects eligible for meta-analyses, we found no difference in OS at 5 years (HR 0.96, favoring CMT, 95% CI 0.72-1.29; P=.778) or 10 years (HR 1.02, favoring cystectomy, 95% CI 0.73-1.42; P=.905). No difference was observed in DSS at 5 years (HR 0.83, favoring radiation, 95% CI 0.54-1.28; P=.390) or 10 years (HR 1.17, favoring cystectomy, 95% CI 0.89-1.55; P=.264), or PFS at 10 years (HR 0.85, favoring CMT, 95% CI 0.43-1.67; P=.639). The cystectomy arms had higher rates of early major complications, whereas rates of minor complications were similar between the 2 treatments. Conclusion: Current meta-analysis reveals no differences in OS, DSS, or PFS between RC and CMT. Further randomized, controlled trials are necessary to identify the optimal treatment for specific patients.

  17. Radical Cystectomy Compared to Combined Modality Treatment for Muscle-Invasive Bladder Cancer: A Systematic Review and Meta-Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Vashistha, Vishal [Department of Internal Medicine, Cleveland Clinic Foundation, Cleveland, Ohio (United States); Wang, Hanzhang [Department of Urology, University of Texas Health Science Center at San Antonio, San Antonio, Texas (United States); Mazzone, Andrew [Rush Medical College, Rush University Medical Center, Chicago, Illinois (United States); Liss, Michael A.; Svatek, Robert S. [Department of Urology, University of Texas Health Science Center at San Antonio, San Antonio, Texas (United States); Schleicher, Mary [Department of Internal Medicine, Cleveland Clinic Foundation, Cleveland, Ohio (United States); Kaushik, Dharam, E-mail: Kaushik@uthscsa.edu [Department of Urology, University of Texas Health Science Center at San Antonio, San Antonio, Texas (United States)

    2017-04-01

    Purpose: To perform a comprehensive comparison of overall survival (OS), disease-specific survival (DSS), progression-free survival (PFS), and treatment-related complications between radical cystectomy (RC) and combined modality treatment (CMT—radiation therapy, concurrent chemotherapy, and maximal transurethral resection of bladder tumor) in the setting of muscle-invasive bladder cancer. Methods and Materials: We searched 7 databases (PubMed, Scopus, EMBASE, Proquest, CINAHL, and (ClinicalTrials.gov)) for randomized, controlled trials and prospective and retrospective studies directly comparing RC with CMT from database inception to March 2016. We conducted meta-analyses evaluating OS, DSS, and PFS with hazard ratios (HRs) and 95% confidence intervals (CIs). Results: Nineteen studies evaluating 12,380 subjects were selected. For the 8 studies encompassing 9554 subjects eligible for meta-analyses, we found no difference in OS at 5 years (HR 0.96, favoring CMT, 95% CI 0.72-1.29; P=.778) or 10 years (HR 1.02, favoring cystectomy, 95% CI 0.73-1.42; P=.905). No difference was observed in DSS at 5 years (HR 0.83, favoring radiation, 95% CI 0.54-1.28; P=.390) or 10 years (HR 1.17, favoring cystectomy, 95% CI 0.89-1.55; P=.264), or PFS at 10 years (HR 0.85, favoring CMT, 95% CI 0.43-1.67; P=.639). The cystectomy arms had higher rates of early major complications, whereas rates of minor complications were similar between the 2 treatments. Conclusion: Current meta-analysis reveals no differences in OS, DSS, or PFS between RC and CMT. Further randomized, controlled trials are necessary to identify the optimal treatment for specific patients.

  18. Prospective study of combined modality treatment or radiotherapy alone in the management of early-stage adult Hodgkin's disease.

    Science.gov (United States)

    Yildiz, Ferah; Zengin, Nurullah; Engin, Hüseyin; Güllü, Ibrahim; Barista, Ibrahim; Caglar, Meltem; Ozyar, Enis; Cengiz, Mustafa; Gürkaynak, Murat; Zorlu, Faruk; Caner, Biray; Atahan, I Lale; Tekuzman, Gülten

    2004-11-01

    To determine the efficacy and toxicity of combined modality treatment (CMT) or radiotherapy (RT) alone in the management of clinical Stage I-IIA adult Hodgkin's disease patients. Forty-seven patients with supradiaphragmatic clinical Stage I-IIA Hodgkin's disease without bulky mediastinal lymphadenopathy were enrolled into this prospective study between September 1997 and February 2002. Patients with very favorable criteria presenting with one or two nonbulky nodal areas involved, an erythrocyte sedimentation rate of <50 mm/h, age <40 years, and either lymphocyte predominant or nodular sclerosing histologic findings were treated by RT alone. Patients missing any of these favorable criteria were classified as the other favorable group and were treated with three courses of doxorubicin, bleomycin, vinblastine, and dacarbazine chemotherapy followed by involved-field RT. The median age was 36 years (range, 19-53 years). Of the 47 patients, 15 were women and 32 were men. Only 3 patients were classified as the most favorable group and treated with mantle RT alone; the remaining 44 were treated with CMT. The median follow-up was 51 months (range, 20-74 months). Only 2 patients developed recurrence, both out of the irradiated field, one in the contralateral neck and the other in the abdomen. The 5-year relapse-free and overall survival rate was 95.4% and 97.8%, respectively. Although none of the prognostic factors were statistically significant for relapse-free survival, a trend was noted for the response to chemotherapy (p = 0.06). Only 2 patients developed treatment-related complications. One patient treated with mantle RT alone developed severe ischemic heart disease and one in the CMT arm developed subclinical hypothyroidism. Despite the short follow-up, CMT or RT alone tailored according to the clinical prognostic factors were successful in terms of disease control in clinical Stage I-IIA Hodgkin's disease. Longer follow-up is required to make definitive conclusions.

  19. [Neuroprotective effects of curcumin].

    Science.gov (United States)

    Li, Yong; Wang, Pengwen

    2009-12-01

    Traditionally, turmeric has been put to use as a food additive and herbal medicine in Asia. Curcumin is an active principle of the perennial herb curcuma longa (commonly known as turmeric). Recent evidence suggests that curcumin has activities with potential for neuroprotective efficacy, including anti-inflammatory, antioxidant, and antiprotein-aggregate activities. In the current review, we provide the newly evidence for the potential role of curcumin in the neuroprotective effects of neurodegenerative diseases like Alzheimer's disease (AD).

  20. Improving cytotoxicity against cancer cells by chemo-photodynamic combined modalities using silver-graphene quantum dots nanocomposites

    Directory of Open Access Journals (Sweden)

    Habiba K

    2015-12-01

    Full Text Available Khaled Habiba,1,2 Joel Encarnacion-Rosado,2,3 Kenny Garcia-Pabon,2,4 Juan C Villalobos-Santos,2,5 Vladimir I Makarov,1 Javier A Avalos,2,6 Brad R Weiner,2,7,8 Gerardo Morell1,2,7 1Department of Physics, University of Puerto Rico – Rio Piedras Campus, 2Molecular Sciences Research Center, University of Puerto Rico, 3Department of Biology, 4Faculty of Education, University of Puerto Rico – Rio Piedras Campus, San Juan, 5Department of Biology, 6Department of Physics, University of Puerto Rico – Bayamon Campus, Bayamon, 7Institute for Functional Nanomaterials, University of Puerto Rico, 8Department of Chemistry, University of Puerto Rico – Rio Piedras Campus, San Juan, PR, USA Abstract: The combination of chemotherapy and photodynamic therapy has emerged as a promising strategy for cancer therapy due to its synergistic effects. In this work, PEGylated silver nanoparticles decorated with graphene quantum dots (Ag-GQDs were tested as a platform to deliver a chemotherapy drug and a photosensitizer, simultaneously, in chemo-photodynamic therapy against HeLa and DU145 cancer cells in vitro. Ag-GQDs have displayed high efficiency in delivering doxorubicin as a model chemotherapy drug to both cancer cells. The Ag-GQDs exhibited a strong antitumor activity by inducing apoptosis in cancer cells without affecting the viability of normal cells. Moreover, the Ag-GQDs exhibited a cytotoxic effect due to the generation of the reactive singlet oxygen upon 425 nm irradiation, indicating their applicability in photodynamic therapy. In comparison with chemo or photodynamic treatment alone, the combined treatment of Ag-GQDs conjugated with doxorubicin under irradiation with a 425 nm lamp significantly increased the death in DU145 and HeLa. This study suggests Ag-GQDs as a multifunctional and efficient therapeutic system for chemo-photodynamic modalities in cancer therapy. Keywords: multifunctional nanoparticles, silver nanoparticles, cancer therapy, drug

  1. Neuroprotection in glaucoma

    Directory of Open Access Journals (Sweden)

    Azadeh Doozandeh

    2016-01-01

    Full Text Available Glaucoma is a degenerative optic neuropathy characterized by retinal ganglion cell (RGC loss and visual field defects. It is known that in some glaucoma patients, death of RGCs continues despite intraocular pressure (IOP reduction. Neuroprotection in the field of glaucoma is defined as any treatment, independent of IOP reduction, which prevents RGC death. Glutamate antagonists, ginkgo biloba extract, neurotrophic factors, antioxidants, calcium channel blockers, brimonidine, glaucoma medications with blood regulatory effect and nitric oxide synthase inhibitors are among compounds with possible neuroprotective activity in preclinical studies. A few agents (such as brimonidine or memantine with neuroprotective effects in experimental studies have advanced to clinical trials; however the results of clinical trials for these agents have not been conclusive. Nevertheless, lack of compelling clinical evidence has not prevented the off-label use of some of these compounds in glaucoma practice. Stem cell transplantation has been reported to halt experimental neurodegenerative disease processes in the absence of cell replacement. It has been hypothesized that transplantation of some types of stem cells activates multiple neuroprotective pathways via secretion of various factors. The advantage of this approach is a prolonged and targeted effect. Important concerns in this field include the secretion of unwanted harmful mediators, graft survival issues and tumorigenesis. Neuroprotection in glaucoma, pharmacologically or by stem cell transplantation, is an interesting subject waiting for broad and multidisciplinary collaborative studies to better clarify its role in clinical practice.

  2. Neuroprotection of Sex Steroids

    Science.gov (United States)

    Liu, Mingyue; Kelley, Melissa H.; Herson, Paco S.; Hurn, Patricia D.

    2011-01-01

    Sex steroids are essential for reproduction and development in animals and humans, and sex steroids also play an important role in neuroprotection following brain injury. New data indicate that sex-specific responses to brain injury occur at the cellular and molecular levels. This review summarizes the current understanding of neuroprotection by sex steroids, particularly estrogen, androgen, and progesterone, based on both in vitro and in vivo studies. Better understanding of the role of sex steroids under physiological and pathological conditions will help us to develop novel effective therapeutic strategies for brain injury. PMID:20595940

  3. Neuroprotective Drug for Nerve Trauma Revealed Using Artificial Intelligence.

    Science.gov (United States)

    Romeo-Guitart, David; Forés, Joaquim; Herrando-Grabulosa, Mireia; Valls, Raquel; Leiva-Rodríguez, Tatiana; Galea, Elena; González-Pérez, Francisco; Navarro, Xavier; Petegnief, Valerie; Bosch, Assumpció; Coma, Mireia; Mas, José Manuel; Casas, Caty

    2018-01-30

    Here we used a systems biology approach and artificial intelligence to identify a neuroprotective agent for the treatment of peripheral nerve root avulsion. Based on accumulated knowledge of the neurodegenerative and neuroprotective processes that occur in motoneurons after root avulsion, we built up protein networks and converted them into mathematical models. Unbiased proteomic data from our preclinical models were used for machine learning algorithms and for restrictions to be imposed on mathematical solutions. Solutions allowed us to identify combinations of repurposed drugs as potential neuroprotective agents and we validated them in our preclinical models. The best one, NeuroHeal, neuroprotected motoneurons, exerted anti-inflammatory properties and promoted functional locomotor recovery. NeuroHeal endorsed the activation of Sirtuin 1, which was essential for its neuroprotective effect. These results support the value of network-centric approaches for drug discovery and demonstrate the efficacy of NeuroHeal as adjuvant treatment with surgical repair for nervous system trauma.

  4. Breathing, feeding, and neuroprotection

    National Research Council Canada - National Science Library

    Homma, Ikuo; Shioda, S

    2006-01-01

    ... of knowledge of brain functions and morphology. Akiyoshi Hosoyamada, M.D., Ph.D. President Showa University, Tokyo 142-8555, Japan December 2005Preface Brain research is on the march, with several advanced technical developments and new findings uncovered almost daily. Within the brain-research fields, we focus on breathing, neuroprotection, an...

  5. Morbidity of a combined modality therapy of I.A. Doxorubicin, neoadjuvant radiotherapy and surgery for locally advanced high grade Soft Tissue Sarcomas (STS) of the extremities

    International Nuclear Information System (INIS)

    Nijhuis, Paul; Pras, Betty; Sleijfer, Dirk Th.; Molenaar, Ineke M.; Schraffordt, Koops Heimen; Hoekstra, Harald J.

    1997-01-01

    Purpose/objective: In the early eighties a combined modality therapy of intra-arterial doxorubicin, neo-adjuvant radiotherapy and surgery was introduced as limb-saving treatment for 'unresectable' grade III high grade STS of the extremities. We studied short and long-term morbidity of this combined modality treatment. Materials and methods: Between 1982 and 1986 11 patients, 9 male and 2 female, median age 52 (range 24-70) years, with 'unresectable' grade III STS of the extremities were treated by preoperative i.a. infusion of doxorubicin for three consecutive days (daily dose 20 mg/m 2 ). Within 24 hours after infusion preoperative radiation of the compartment (10 x 350 cGy) was started. After chemo-radiotherapy the tumor was resected. Non-radical resections received additionally 20-30 Gy radiotherapy (9 patients). Results: No local recurrences (median follow-up 110 months); pulmonary metastases in five patients (45%). Local skin toxicity due to doxorubicin in three patients (27%). Preoperative 35 Gy radiotherapy was well tolerated. Limb-saving treatment was possible in ten patients (91%); in one patient an exarticulation of the hip had to be performed. Three of the five long-term survivors (follow-up > 10 years) developed a severe fibrosis of the affected limb (60%). Two severe long-term complications: a stress fracture of the affected femur (91 months after treatment), and a severe radiation-induced motor and sensory neuropathy of the sciatic nerve. Conclusion: The long-term results show a limb-saving rate of 91%, without increasing the risk of a local recurrence. Especially the long-term morbidity is extremely high (60%). This combination therapy should therefore no longer be advocated as a limb-saving treatment modality for these primarily 'unresectable' high grade STS of the extremities

  6. Refocusing Neuroprotection in Cerebral Reperfusion Era: New Challenges and Strategies

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    Xiao-Yi Xiong

    2018-04-01

    Full Text Available Pathophysiological processes of stroke have revealed that the damaged brain should be considered as an integral structure to be protected. However, promising neuroprotective drugs have failed when translated to clinical trials. In this review, we evaluated previous studies of neuroprotection and found that unsound patient selection and evaluation methods, single-target treatments, etc., without cerebral revascularization may be major reasons of failed neuroprotective strategies. Fortunately, this may be reversed by recent advances that provide increased revascularization with increased availability of endovascular procedures. However, the current improved effects of endovascular therapy are not able to match to the higher rate of revascularization, which may be ascribed to cerebral ischemia/reperfusion injury and lacking of neuroprotection. Accordingly, we suggest various research strategies to improve the lower therapeutic efficacy for ischemic stroke treatment: (1 multitarget neuroprotectant combinative therapy (cocktail therapy should be investigated and performed based on revascularization; (2 and more efforts should be dedicated to shifting research emphasis to establish recirculation, increasing functional collateral circulation and elucidating brain–blood barrier damage mechanisms to reduce hemorrhagic transformation. Therefore, we propose that a comprehensive neuroprotective strategy before and after the endovascular treatment may speed progress toward improving neuroprotection after stroke to protect against brain injury.

  7. Diagnostic role of (99)Tc(m)-MDP SPECT/CT combined SPECT/MRI Multi modality imaging for early and atypical bone metastases.

    Science.gov (United States)

    Chen, Xiao-Liang; Li, Qian; Cao, Lin; Jiang, Shi-Xi

    2014-01-01

    The bone metastasis appeared early before the bone imaging for most of the above patients. (99)Tc(m)-MDP ((99)Tc(m) marked methylene diphosphonate) bone imaging could diagnosis the bone metastasis with highly sensitivity, but with lower specificity. The aim of this study is to explore the diagnostic value of (99)Tc(m)-MDP SPECT/CT combined SPECT/MRI Multi modality imaging for the early period atypical bone metastases. 15 to 30 mCi (99)Tc(m)-MDP was intravenously injected to the 34 malignant patients diagnosed as doubtful early bone metastases. SPECT, CT and SPECT/CT images were captured and analyzed consequently. For the patients diagnosed as early period atypical bone metastases by SPECT/CT, combining the SPECT/CT and MRI together as the SPECT/MRI integrated image. The obtained SPECT/MRI image was analyzed and compared with the pathogenic results of patients. The results indicated that 34 early period doubtful metastatic focus, including 34 SPECT positive focus, 17 focus without special changes by using CT method, 11 bone metastases focus by using SPECT/CT method, 23 doubtful bone metastases focus, 8 doubtful bone metastases focus, 14 doubtful bone metastases focus and 2 focus without clear image. Totally, SPECT/CT combined with SPECT/MRI method diagnosed 30 bone metastatic focus and 4 doubtfully metastatic focus. In conclusion, (99)Tc(m)-MDP SPECT/CT combined SPECT/MRI Multi modality imaging shows a higher diagnostic value for the early period bone metastases, which also enhances the diagnostic accuracy rate.

  8. The potentiation of the radioprotective efficacy of two medical countermeasures, gamma-tocotrienol and amifostine, by a combination prophylactic modality

    International Nuclear Information System (INIS)

    Singh, Vijay K.; Fatanmi, Oluseyi O.; Wise, Stephen Y.; Newman, Victoria L.; Romaine, Patricia L.P.; Seed, Thomas M.

    2016-01-01

    This study was designed to evaluate the possible potentiation of survival protection afforded by relatively low-dose amifostine prophylaxis against total body irradiation in combination with a protective, less toxic agent, gamma-tocotrienol (GT3). Mice were administered amifostine and/or GT3, then exposed to 9.2 Gy 60 Co γ-irradiation and monitored for survival for 30 days. To investigate cytokine stimulation, mice were administered amifostine or GT3; serum samples were collected and analyzed for cytokines. Survival studies show single treatments of GT3 or amifostine significantly improved survival, compared to the vehicle, and combination treatments resulted in significantly higher survival compared to single treatments. In vivo studies with GT3 confirmed prior work indicating GT3 induces granulocyte colony-stimulating factor (G-CSF). This approach, the prophylactic combination of amifostine and GT3, which act through different mechanisms, shows promise and should be investigated further as a potential countermeasure for acute radiation syndrome. (authors)

  9. The Promise of Neuroprotective Agents in Parkinson’s Disease

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    Judith ePotashkin

    2011-11-01

    Full Text Available Parkinson’s Disease is characterized by loss of dopamine neurons in the substantia nigra of the brain. Since there are limited treatment options for PD, neuroprotective agents are currently being tested as a means to slow disease progression. Agents targeting oxidative stress, mitochondrial dysfunction and inflammation are prime candidates for neuroprotection. This review identifies Rasagiline, Minocycline and creatine, as the most promising neuroprotective agents for PD, and they are all currently in phase III trials. Other agents possessing protective characteristics in delaying PD include stimulants, vitamins, supplements, and other drugs. Additionally, combination therapies also show benefits in slowing PD progression. The identification of neuroprotective agents for PD provides us with therapeutic opportunities for modifying the course of disease progression and, perhaps, reducing the risk of onset when preclinical biomarkers become available.

  10. Neuroprotection in Preterm Infants

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    R. Berger

    2015-01-01

    Full Text Available Preterm infants born before the 30th week of pregnancy are especially at risk of perinatal brain damage which is usually a result of cerebral ischemia or an ascending intrauterine infection. Prevention of preterm birth and early intervention given signs of imminent intrauterine infection can reduce the incidence of perinatal cerebral injury. It has been shown that administering magnesium intravenously to women at imminent risk of a preterm birth leads to a significant reduction in the likelihood of the infant developing cerebral palsy and motor skill dysfunction. It has also been demonstrated that delayed clamping of the umbilical cord after birth reduces the rate of brain hemorrhage among preterm infants by up to 50%. In addition, mesenchymal stem cells seem to have significant neuroprotective potential in animal experiments, as they increase the rate of regeneration of the damaged cerebral area. Clinical tests of these types of therapeutic intervention measures appear to be imminent. In the last trimester of pregnancy, the serum concentrations of estradiol and progesterone increase significantly. Preterm infants are removed abruptly from this estradiol and progesterone rich environment. It has been demonstrated in animal experiments that estradiol and progesterone protect the immature brain from hypoxic-ischemic lesions. However, this neuroprotective strategy has unfortunately not yet been subject to sufficient clinical investigation.

  11. Phenobarbital Augments Hypothermic Neuroprotection

    Science.gov (United States)

    Barks, John D.; Liu, Yi-Qing; Shangguan, Yu; Silverstein, Faye S.

    2010-01-01

    Seizures are associated with adverse outcome in infants with hypoxic-ischemic encephalopathy. We hypothesized that early administration of the anticonvulsant phenobarbital after cerebral hypoxia-ischemia could enhance the neuroprotective efficacy of delayed-onset hypothermia. We tested this hypothesis in a neonatal rodent model. Seven-day-old rats (n=104) underwent right carotid ligation, followed by 90 min 8%O2 exposure; 15 min later, they received injections of phenobarbital (40 mg/kg) or saline. One or 3h later, all were treated with hypothermia (30°C, 3h). Function and neuropathology were evaluated after 7 days (“early outcomes”) or 1 month (“late outcomes”). Early outcome assessment demonstrated better sensorimotor performance and less cortical damage in phenobarbital-treated groups; there were no differences between groups in which the hypothermia delay was shortened from 3h to 1h. Late outcome assessment confirmed sustained benefits of phenobarbital+hypothermia treatment; sensorimotor performance was better (persistent attenuation of contralateral forepaw placing deficits and absence of contralateral forepaw neglect); neuropathology scores were lower (medians, phenobarbital 2, saline 8.5, pphenobarbital may augment the neuroprotective efficacy of therapeutic hypothermia. PMID:20098339

  12. [A Case of Locally Advanced Thoracic Esophageal Cancer with Larynx Preservation and Curative Resection via Combined Modality Therapy].

    Science.gov (United States)

    Iwama, Mitsuru; Kimura, Yutaka; Shiraishi, Osamu; Kato, Hiroaki; Hiraki, Yoko; Tanaka, Yumiko; Yasuda, Atsushi; Shinkai, Masayuki; Imano, Motohiro; Imamoto, Haruhiko; Yasuda, Takushi

    2017-11-01

    Prognosis of locally advanced esophageal cancer is poor. The greatest prognostic factor of locally advanced esophageal cancer is a local control. We experienced a case of T4 locally advanced thoracic esophageal cancer who was successfully resected without any combined resection after multimodality therapy. A male in 75-year-old. was diagnosed with type 3 locally advanced upper thoracic esophageal cancer whose metastatic right recurrent laryngeal lymph node invaded into the trachea. Definitive chemoradiation therapy(CRT)was performed, leading to a significant shrinkage of the main tumor, but T4 lesion remained. Next, adding DCF therapy(docetaxel, CDDP and 5-FU), a relief of T4 was finally obtained. Then, salvage surgery with subtotalesophagectomy and retrosternalesophagealreconstruction with gastric tube was performed, resulting in R0 resection without any combined resection. The postoperative course was uneventful, and the patient has been alive without recurrence for 1 year after surgery. In locally advanced cancer, focusing on T4 downstaging, it is significantly important in terms of safety, curativity and organ preservation to perform surgery after a sure sign of T4 relief by multimodality therapy.

  13. Dual-Modality Imaging of the Human Finger Joint Systems by Using Combined Multispectral Photoacoustic Computed Tomography and Ultrasound Computed Tomography

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    Yubin Liu

    2016-01-01

    Full Text Available We developed a homemade dual-modality imaging system that combines multispectral photoacoustic computed tomography and ultrasound computed tomography for reconstructing the structural and functional information of human finger joint systems. The fused multispectral photoacoustic-ultrasound computed tomography (MPAUCT system was examined by the phantom and in vivo experimental tests. The imaging results indicate that the hard tissues such as the bones and the soft tissues including the blood vessels, the tendon, the skins, and the subcutaneous tissues in the finger joints systems can be effectively recovered by using our multimodality MPAUCT system. The developed MPAUCT system is able to provide us with more comprehensive information of the human finger joints, which shows its potential for characterization and diagnosis of bone or joint diseases.

  14. Metabolic Syndrome and Neuroprotection

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    Melisa Etchegoyen

    2018-04-01

    Full Text Available Introduction: Over the years the prevalence of metabolic syndrome (MetS has drastically increased in developing countries as a major byproduct of industrialization. Many factors, such as the consumption of high-calorie diets and a sedentary lifestyle, bolster the spread of this disorder. Undoubtedly, the massive and still increasing incidence of MetS places this epidemic as an important public health issue. Hereon we revisit another outlook of MetS beyond its classical association with cardiovascular disease (CVD and Diabetes Mellitus Type 2 (DM2, for MetS also poses a risk factor for the nervous tissue and threatens neuronal function. First, we revise a few essential concepts of MetS pathophysiology. Second, we explore some neuroprotective approaches in MetS pertaining brain hypoxia. The articles chosen for this review range from the years 1989 until 2017; the selection criteria was based on those providing data and exploratory information on MetS as well as those that studied innovative therapeutic approaches.Pathophysiology: The characteristically impaired metabolic pathways of MetS lead to hyperglycemia, insulin resistance (IR, inflammation, and hypoxia, all closely associated with an overall pro-oxidative status. Oxidative stress is well-known to cause the wreckage of cellular structures and tissue architecture. Alteration of the redox homeostasis and oxidative stress alter the macromolecular array of DNA, lipids, and proteins, in turn disrupting the biochemical pathways necessary for normal cell function.Neuroprotection: Different neuroprotective strategies are discussed involving lifestyle changes, medication aimed to mitigate MetS cardinal symptoms, and treatments targeted toward reducing oxidative stress. It is well-known that the routine practice of physical exercise, aerobic activity in particular, and a complete and well-balanced nutrition are key factors to prevent MetS. Nevertheless, pharmacological control of MetS as a whole and

  15. Combined modality therapy of diffuse histology non-Hodgkin's lymphoma with cyclophosphamide, adriamycin, vincristine, prednisone (CHOP) and total body irradiation

    International Nuclear Information System (INIS)

    Weick, J.K.; Antunez, A.; Kraus, T.A.; Fabian, C.J.; Dixon, D.

    1983-01-01

    The combination of cyclophosphamide, adriamycin, vincristine, and prednisone (CHOP) alternating with total body irradiation (TBI) has been shown earlier to be effective therapy in patients with malignant lymphoma who have received prior chemotherapy and/or radiation therapy. A limited institutional pilot study was therefore done by the Southwest Oncology Group between October 1977, and November 1978 to test the benefit of this program in previously untreated persons with Stages 3 and 4 diffuse histology non-Hodgkin's lymphoma. Eleven evaluable patients with the following histologies were treated: 7 poorly differentiated, 2 with histiocytic, 1 with mixed lymphoma and 1 with well-differentiated morphology. Responses were seen in 8/11 patients (6 CR and 2 PR); 5 persons are currently alive and 6 are dead. The median duration of remission is 15 months and the median survival for all patients is 48 months. The therapy was well tolerated with a mean nadir leukocyte count of 3020 x 10 9 /μl (range 1.2 to 5.5) and a mean nadir platelet count of 188 x 10 9 /μl (range 016 to 270). As delivered, this program is capable of producing durable remissions and needs to be verified in a larger series of patients

  16. Analysis of toxicity in a group of patients treated for pancreatic cancer with combined modality 3D radiation therapy

    International Nuclear Information System (INIS)

    Fine, Robert M.; Fernandez-Vicioso, Eduardo; Higgins, Patrick; Schell, Michael; Sohn, Jason; Pelley, Robert; Walsh, R. M.; Vogt, David; Hermann, Robert

    1995-01-01

    Purpose: To evaluate the acute toxicity of a group of 37 pancreatic cancer patients treated with noncoplanar, nonopposed, conformal radiation therapy with concurrent chemotherapy (5-FU). Materials and Methods: We retrospectively evaluated a group of initially nonadvanced 37 pancreatic cancer patients treated with combined concurrent chemotherapy and 3D radiation therapy treated between 1992 until 1995. During this period we began treating the initially unresectable patients with preoperative chemo-RT (50.4 Gy) after treating an initial group of unresectable patients to a higher dose of 66.6 Gy. We also include a group of patients who received postop chemo-RT after Whipple resection (59.4 Gy). All radiation was delivered at a 1.8 Gy per fraction dose rate. The total group was made up of 37 patients of whom 21 were male (57%) and 16 female (43%). There were 22 (59%) head of pancreas lesions, 10 (27%) body of pancreas lesions, and 5 (14%) head and body of pancreas cancers. Of these 37 patients 7 (19%) were treated with chemo-RT as their only treatment, 10 patients (29%) were treated post Whipple resection, and 20 patients (54%) were treated with preoperative intent. Results: Three patients (8%) required a treatment break, one with a body and 2 with head lesions. Two of these patients stopped RT short of planned dose (32.56 and 46.8 Gy) both suffering from nausea, vomiting, and anorexia with the third, who finished a planned 66.6 Gy dose, after a 4 day rest for leukopenia. One of 20 patients (5%) preop patients underwent the planned post chemo-RT Whipple resection, while 4 of the 20 patients (20%), remained unresectable, but without disease progression and had Iodine 125 interstitial implants at exploration delivering a minimal tumor dose of 120 Gy on top or the 50.4 Gy delivered preoperatively. Four patients (11%) maintained a minimal Karnofsky score of 100, 23 patients (62%) maintained a minimal KPS of 90, 6 patients (16%) maintained a minimal KPS of 80, and 4

  17. Neuroprotective therapies for glaucoma

    Directory of Open Access Journals (Sweden)

    Song W

    2015-03-01

    Full Text Available Wei Song, Ping Huang, Chun Zhang Department of Ophthalmology, Peking University Third Hospital, Beijing, People’s Republic of China Abstract: Glaucoma is the second leading cause for blindness worldwide. It is mainly caused by glaucomatous optic neuropathy (GON characterized by retinal ganglion cell loss, which leads to visual field defect and blindness. Up to now, the main purpose of antiglaucomatous therapies has been to lower intraocular pressure (IOP through surgeries and medications. However, it has been found that progressive GON is still present in some patients with effective IOP decrease. Therefore, risk factors other than IOP elevation, like neurotrophin deprivation and excitotoxicity, contribute to progressive GON. Novel approaches of neuroprotection may be more effective for preserving the function of the optic nerve. Keywords: glaucoma, glaucomatous optic neuropathy, retinal ganglion cells, neuro­protection

  18. Involved-Node Proton Therapy in Combined Modality Therapy for Hodgkin Lymphoma: Results of a Phase 2 Study

    International Nuclear Information System (INIS)

    Hoppe, Bradford S.; Flampouri, Stella; Zaiden, Robert; Slayton, William; Sandler, Eric; Ozdemir, Savas; Dang, Nam H.; Lynch, James W.; Li, Zuofeng; Morris, Christopher G.; Mendenhall, Nancy P.

    2014-01-01

    Purpose: This study describes the early clinical outcomes of a prospective phase 2 study of consolidative involved-node proton therapy (INPT) as a component of combined-mode therapy in patients with stages I to III Hodgkin lymphoma (HL) with mediastinal involvement. Methods and Materials: Between September 2009 and June 2013, 15 patients with newly diagnosed HL received INPT after completing chemotherapy in an institutional review board-approved protocol comparing the dosimetric impact of PT with those of three-dimensional conformal radiation therapy (3DCRT) and intensity modulated RT. Based on 18 F-Fluorodeoxyglucose positron emission tomography/computed tomography ( 18 F-FDG PET/CT) response, 5 children received 15 to 25.5 cobalt Gy equivalent (CGE) of INPT after receiving 4 cycles of Adriamycin, Bleomycin, Vincristine, Etoposide, Prednisone, Cyclophosphamide or Vincristine, adriamycin, methotrexate, Prednisone chemotherapy, and 10 adults received 30.6 to 39.6 CGE of INPT after 3 to 6 cycles of Adriamycin, Bleomycine, Vinblastine, Dacarbazine. Patients were routinely evaluated for toxicity during and after treatment, using Common Terminology Criteria for Adverse Events, version 3.0, and for relapse by physical examination and routine imaging. Relapse-free survival (RFS) and event-free survival (EFS) rates were calculated using the Kaplan-Meier method from the time of diagnosis. Results: The median follow-up was 37 months (range, 26-55). Two events occurred during follow-up: 1 relapse (inside and outside the targeted field) and 1 transformation into a primary mediastinal large B cell lymphoma. The 3-year RFS rate was 93%, and the 3-year EFS rate was 87%. No acute or late grade 3 nonhematologic toxicities were observed. Conclusions: Although decades of follow-up will be needed to realize the likely benefit of PT in reducing the risk of radiation-induced late effects, PT following chemotherapy in patients with HL is well-tolerated, and disease outcomes were similar

  19. Involved-Node Proton Therapy in Combined Modality Therapy for Hodgkin Lymphoma: Results of a Phase 2 Study

    Energy Technology Data Exchange (ETDEWEB)

    Hoppe, Bradford S., E-mail: bhoppe@floridaproton.org [Radiation Oncology, University of Florida Proton Therapy Institute, Jacksonville, Florida (United States); Flampouri, Stella [Radiation Oncology, University of Florida Proton Therapy Institute, Jacksonville, Florida (United States); Zaiden, Robert [Department of Medicine, Division of Hematology and Oncology, University of Florida College of Medicine, Jacksonville, Florida (United States); Slayton, William [Department of Pediatrics, Division of Hematology and Oncology, University of Florida College of Medicine, Gainesville, Florida (United States); Sandler, Eric [Department of Pediatrics, Division of Hematology/Oncology Nemours Children' s Clinic, Jacksonville, Florida (United States); Ozdemir, Savas [Department of Radiology, Division of Functional and Molecular Imaging, University of Florida College of Medicine, Jacksonville, Florida (United States); Dang, Nam H.; Lynch, James W. [Department of Medicine, Division of Hematology and Oncology, University of Florida College of Medicine, Gainesville, Florida (United States); Li, Zuofeng; Morris, Christopher G.; Mendenhall, Nancy P. [Radiation Oncology, University of Florida Proton Therapy Institute, Jacksonville, Florida (United States)

    2014-08-01

    Purpose: This study describes the early clinical outcomes of a prospective phase 2 study of consolidative involved-node proton therapy (INPT) as a component of combined-mode therapy in patients with stages I to III Hodgkin lymphoma (HL) with mediastinal involvement. Methods and Materials: Between September 2009 and June 2013, 15 patients with newly diagnosed HL received INPT after completing chemotherapy in an institutional review board-approved protocol comparing the dosimetric impact of PT with those of three-dimensional conformal radiation therapy (3DCRT) and intensity modulated RT. Based on {sup 18}F-Fluorodeoxyglucose positron emission tomography/computed tomography ({sup 18}F-FDG PET/CT) response, 5 children received 15 to 25.5 cobalt Gy equivalent (CGE) of INPT after receiving 4 cycles of Adriamycin, Bleomycin, Vincristine, Etoposide, Prednisone, Cyclophosphamide or Vincristine, adriamycin, methotrexate, Prednisone chemotherapy, and 10 adults received 30.6 to 39.6 CGE of INPT after 3 to 6 cycles of Adriamycin, Bleomycine, Vinblastine, Dacarbazine. Patients were routinely evaluated for toxicity during and after treatment, using Common Terminology Criteria for Adverse Events, version 3.0, and for relapse by physical examination and routine imaging. Relapse-free survival (RFS) and event-free survival (EFS) rates were calculated using the Kaplan-Meier method from the time of diagnosis. Results: The median follow-up was 37 months (range, 26-55). Two events occurred during follow-up: 1 relapse (inside and outside the targeted field) and 1 transformation into a primary mediastinal large B cell lymphoma. The 3-year RFS rate was 93%, and the 3-year EFS rate was 87%. No acute or late grade 3 nonhematologic toxicities were observed. Conclusions: Although decades of follow-up will be needed to realize the likely benefit of PT in reducing the risk of radiation-induced late effects, PT following chemotherapy in patients with HL is well-tolerated, and disease outcomes

  20. First-in-human evaluation of a hybrid modality that allows combined radio- and (near-infrared) fluorescence tracing during surgery

    Energy Technology Data Exchange (ETDEWEB)

    Berg, Nynke S. van den [Leiden University Medical Center, Interventional Molecular Imaging Laboratory, Department of Radiology (Netherlands); The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Department of Urology, Amsterdam (Netherlands); Simon, Herve [Eurorad S.A., Eckbolsheim (France); Kleinjan, Gijs H. [Leiden University Medical Center, Interventional Molecular Imaging Laboratory, Department of Radiology (Netherlands); The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Department of Nuclear Medicine, Amsterdam (Netherlands); Engelen, Thijs [Leiden University Medical Center, Interventional Molecular Imaging Laboratory, Department of Radiology (Netherlands); The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Department of Head and Neck Surgery and Oncology, Amsterdam (Netherlands); Bunschoten, Anton; Welling, Mick M. [Leiden University Medical Center, Interventional Molecular Imaging Laboratory, Department of Radiology (Netherlands); Tijink, Bernard M. [The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Department of Head and Neck Surgery and Oncology, Amsterdam (Netherlands); Horenblas, Simon [The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Department of Urology, Amsterdam (Netherlands); Chambron, Jacques [The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Department of Nuclear Medicine, Amsterdam (Netherlands); Leeuwen, Fijs W.B. van [Leiden University Medical Center, Interventional Molecular Imaging Laboratory, Department of Radiology (Netherlands); The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Department of Urology, Amsterdam (Netherlands); The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Department of Head and Neck Surgery and Oncology, Amsterdam (Netherlands)

    2015-10-15

    The clinical introduction of the hybrid tracer indocyanine green (ICG)-{sup 99m}Tc-nanocolloid, composed of a radioactive and a near-infrared (NIR) fluorescence component, has created the need for surgical (imaging) modalities that allow for simultaneous detection of both signals. This study describes the first-in-human use of a prototype opto-nuclear probe during sentinel node (SN) biopsy using ICG-{sup 99m}Tc-nanocolloid. To allow for fluorescence tracing, a derivative of the conventional gamma probe technology was generated in which two optical fibers were integrated to allow for excitation (785 nm) and emission signal collection (> 810 nm). The ability of this opto-nuclear probe to detect the fluorescence signal of the hybrid tracer ICG-{sup 99m}Tc-nanocolloid was firstly determined ex vivo in (non)SNs samples obtained from 41 patients who underwent hybrid tracer-based SN biopsy in the head and neck or urogenital area. In an in vivo proof-of-concept study in nine of these 41 patients, SNs were localized using combined gamma and fluorescence tracing with the opto-nuclear probe. Fluorescence tracing was performed in a similar manner as gamma tracing and under ambient light conditions. Ex vivo, the gamma tracing option of the opto-nuclear probe correctly identified the SN in all 150 evaluated (non)SN samples. Ex vivo fluorescence tracing in the low-sensitivity mode correctly identified 71.7 % of the samples. This increased to 98.9 % when fluorescence tracing was performed in the high-sensitivity mode. In vivo fluorescence tracing (high-sensitivity mode) accurately identified the SNs in all nine patients (20 SNs evaluated; 100 %). This study demonstrates the first-in-human evaluation of a hybrid modality capable of detecting both gamma and fluorescence signals during a surgical procedure. Fluorescence tracing could be performed in ambient light. (orig.)

  1. Reduction of the treated volume to involved node radiation therapy as part of combined modality treatment for early stage aggressive non-Hodgkin’s lymphoma

    International Nuclear Information System (INIS)

    Verhappen, Marieke H.; Poortmans, Philip M.P.; Raaijmakers, Esther; Raemaekers, John M.M.

    2013-01-01

    Background and purpose: This retrospective study investigated whether focused involved node radiation therapy (INRT) can safely replace involved field RT (IFRT) in patients with early stage aggressive NHL. Patients and methods: We included 258 patients with stage I/II aggressive NHL who received combined modality treatment (87%) or primary RT alone (13%). RT consisted of a total dose of 30–40 Gy in 15–20 fractions IFRT or INRT. We compared survival, relapse pattern, radiation-related toxicity and quality of life for both RT techniques. Results: Type of RT was not related to the outcome in either the uni- or multivariate survival analysis. Relapses developed in 59 of 252 patients (23%) of which 47 (80%) were documented as distant recurrence only. Failure of the INRT technique was noted in one patient. There was no significant difference in acute radiation-related toxicity between RT-groups but IFRT showed a significantly higher incidence of higher grade toxicities. Patients treated with INRT had a significantly better physical functioning and global quality of life compared to the IFRT group. Conclusions: Given the retrospective nature of this study, no solid conclusions can be drawn. However, in view of the equivalent efficacy and more favorable toxicity profile, the replacement of IFRT by INRT in combination with chemo-(immuno)-therapy looks very attractive for patients with early stage aggressive NHL

  2. Comparative evaluation of efficacy of three treatment modalities – tetracycline fibers, scaling and root planing, and combination therapy: A clinical study

    Directory of Open Access Journals (Sweden)

    Aashima Bajaj Dang

    2016-01-01

    Full Text Available Background: Tetracycline is one of the primary antibiotics prescribed for antimicrobial therapy in periodontics. It has a broad spectrum of activity being effective against most bacteria as well as spirochetes. Due to limitations of systemic drug therapy, recent formulations of the drug for local administration in the subgingival area have been introduced, including collagen fibers impregnated with tetracycline. Aims and Objective: To compare the effectiveness of tetracycline fibers alone or in combination with scaling and root planing (SRP on clinical parameters in chronic periodontitis patients. Materials and Methods: A total of twenty patients comprising of both sexes in the age group of 35-60 years with chronic periodontitis were selected. Split-mouth design was used, and three teeth from each patient with periodontal pocket measuring > 5 mm were selected which were treated with different treatment modality. They were randomly divided into site A (SRP, site B (tetracycline fibers only, and site C (combination therapy. Clinical parameters of plaque index (PI, gingival index (GI, pocket probing depth, and clinical attachment level (CAL were recorded at 0, 30, and 45 days. The data obtained was compiled and put to statistical analysis. Results: All the three groups showed improvement in PI, GI, probing pocket depth, and CAL. Results of the study showed greater improvements in clinical parameters in Group C compared to Group A and Group B. Conclusion: The results indicate that the adjunctive use of tetracycline fibers with SRP is a clinically effective and simple nonsurgical treatment method to improve periodontal health.

  3. Neuroprotective Properties of the Marine Carotenoid Astaxanthin and Omega-3 Fatty Acids, and Perspectives for the Natural Combination of Both in Krill Oil

    Directory of Open Access Journals (Sweden)

    Marcelo P. Barros

    2014-03-01

    Full Text Available The consumption of marine fishes and general seafood has long been recommended by several medical authorities as a long-term nutritional intervention to preserve mental health, hinder neurodegenerative processes, and sustain cognitive capacities in humans. Most of the neurological benefits provided by frequent seafood consumption comes from adequate uptake of omega-3 and omega-6 polyunsaturated fatty acids, n-3/n-6 PUFAs, and antioxidants. Optimal n-3/n-6 PUFAs ratios allow efficient inflammatory responses that prevent the initiation and progression of many neurological disorders. Moreover, interesting in vivo and clinical studies with the marine antioxidant carotenoid astaxanthin (present in salmon, shrimp, and lobster have shown promising results against free radical-promoted neurodegenerative processes and cognition loss. This review presents the state-of-the-art applications of n-3/n-6 PUFAs and astaxanthin as nutraceuticals against neurodegenerative diseases associated with exacerbated oxidative stress in CNS. The fundamental “neurohormesis” principle is discussed throughout this paper. Finally, new perspectives for the application of a natural combination of the aforementioned anti-inflammatory and antioxidant agents (found in krill oil are also presented herewith.

  4. Neuroprotection by flavonoids

    Directory of Open Access Journals (Sweden)

    Dajas F.

    2003-01-01

    Full Text Available The high morbidity, high socioeconomic costs and lack of specific treatments are key factors that define the relevance of brain pathology for human health and the importance of research on neuronal protective agents. Epidemiological studies have shown beneficial effects of flavonoids on arteriosclerosis-related pathology in general and neurodegeneration in particular. Flavonoids can protect the brain by their ability to modulate intracellular signals promoting cellular survival. Quercetin and structurally related flavonoids (myricetin, fisetin, luteolin showed a marked cytoprotective capacity in in vitro experimental conditions in models of predominantly apoptotic death such as that induced by medium concentrations (200 µM of H2O2 added to PC12 cells in culture. Nevertheless, quercetin did not protect substantia nigra neurons in vivo from an oxidative insult (6-hydroxydopamine, probably due to difficulties in crossing the blood-brain barrier. On the other hand, treatment of permanent focal ischemia with a lecithin/quercetin preparation decreased lesion volume, showing that preparations that help to cross the blood-brain barrier may be critical for the expression of the effects of flavonoids on the brain. The hypothesis is advanced that a group of quercetin-related flavonoids could become lead molecules for the development of neuroprotective compounds with multitarget anti-ischemic effects.

  5. A modal characterization of Peirce algebras

    NARCIS (Netherlands)

    M. de Rijke (Maarten)

    1995-01-01

    textabstractPeirce algebras combine sets, relations and various operations linking the two in a unifying setting.This note offers a modal perspective on Peirce algebras.It uses modal logic to characterize the full Peirce algebras.

  6. Non-ablative fractional resurfacing in combination with topical tretinoin cream as a field treatment modality for multiple actinic keratosis: a pilot study and a review of other field treatment modalities.

    Science.gov (United States)

    Prens, Sebastiaan P; de Vries, Karin; Neumann, H A Martino; Prens, Errol P

    2013-06-01

    Actinic keratoses (AK) are premalignant lesions occurring mainly in sun-damaged skin. Current topical treatment options for AK and photo-damaged skin such as liquid nitrogen and electrosurgery are not suitable for field treatment. Otherwise, therapies suitable for field treatment bring along considerable patient discomfort. Non-ablative fractional resurfacing has emerged as a logical treatment option especially for field treatment of AK. To evaluate the clinical efficacy of fractional laser therapy for clearing AK and improving skin quality. To compare patient friendliness of the "fractional" therapy with those reported for other field treatment modalities. Ten patients with Fitzpatrick skin type I to III with multiple AK and extensive sun-damaged skin, received 5-10 sessions with a 4-week interval using a 1550 nm Erbium-Glass Fractionated laser (Sellas, Korea). Four weeks and 24 weeks after the last treatment the clinical results were evaluated by an independent physician. The mean degree of improvement, in terms of reduction in the number of AK and improvement of skin texture, was 54% on a 4 point PGA scale, and persisted for approximately 6 months. The biggest advantage of fractional laser treatment, besides the eradication of AK and a clear rejuvenation effect, is the absence of "downtime". Fractional non-ablative resurfacing induces significant reduction in the number of AK and improves the skin quality. Also all patients preferred fractional laser therapy above other AK treatment modalities.

  7. Interval to Biochemical Failure Predicts Clinical Outcomes in Patients With High-Risk Prostate Cancer Treated by Combined-Modality Radiation Therapy

    International Nuclear Information System (INIS)

    Shilkrut, Mark; McLaughlin, P. William; Merrick, Gregory S.; Vainshtein, Jeffrey M.; Feng, Felix Y.; Hamstra, Daniel A.

    2013-01-01

    Purpose: To validate the prognostic value of interval to biochemical failure (IBF) in patients with high-risk prostate cancer (HiRPCa) treated with combined-modality radiation therapy (CMRT) with or without androgen deprivation therapy (ADT). Methods and Materials: We conducted a retrospective review of HiRPCa (prostate-specific antigen >20 ng/mL, Gleason score [GS] 8-10, or clinical T stage T3-T4) treated with either dose-escalated external beam radiation therapy (EBRT) or CMRT. Interval to biochemical failure was classified as ≤18 or >18 months from the end of all therapy to the date of biochemical failure (BF). Kaplan-Meier methods and Cox proportional hazards regression were used to evaluate the prognostic value of IBF ≤18 months for distant metastasis (DM) and prostate cancer-specific mortality (PCSM). Results: Of 958 patients with a median follow-up of 63.2 months, 175 patients experienced BF. In those with BF, there were no differences in pretreatment clinical characteristics between the EBRT and CMRT groups, except for a higher proportion of patients with GS 8-10 in the CMRT group (70% vs 52%, P=.02). Median IBF after all therapy was 24.0 months (interquartile range 9.6-46.0) in the EBRT group and 18.9 months (interquartile range 9.2-34.5) in the CMRT group (P=.055). On univariate analysis, IBF ≤18 months was associated with increased risk of DM and PCSM in the entire cohort and the individual EBRT and CMRT groups. On multivariate analysis, only GS 9-10 and IBF ≤18 months, but not the radiation therapy regimen or ADT use, predicted DM (hazard ratio [HR] 3.7, P<.01, 95% confidence interval [CI] 1.4-10.3 for GS 9-10; HR 3.9, P<.0001, 95% CI 2.4-6.5 for IBF ≤18 months) and PCSM (HR 14.8, P<.009, 95% CI 2.0-110 for GS 9-10; HR 4.4, P<.0001, 95% CI 2.4-8.1 for IBF ≤18 months). Conclusions: Short IBF was highly prognostic for higher DM and PCSM in patients with HiRPCa. The prognostic value of IBF for DM and PCSM was not affected by the radiation

  8. General anesthetics in children: neurotoxic or neuroprotective?

    Directory of Open Access Journals (Sweden)

    Jéssica Farias Rebouças

    2017-02-01

    Full Text Available Introduction: general anesthetics are involved in neuroprotection in adults after ischemic events and cognitive impairment, thus, they also may be associated with learning disorders in children exposed to them before three years of age. Objective: Describe about the neurotoxic effects of general anesthetics in experimental animals and children. Method: This is a systematic review, performed from search in databases and on PubMed using the keywords "neurotoxicity" and "general anesthetics," and "general anesthetics," "neurotoxicity", "children", "young child "and" pediatric ". Results: The search resulted in 185 articles. Out of these, 78 met our inclusion criteria. We found that there was a significant evidence of neurotoxicity induced by general anesthetics in experimental animals that were just born, resulting in late and permanent cognitive deficits. This effect was associated with multiple exposures, exposure length of time and combination of drugs. However, some studies found cognitive impairment after a single exposure to anesthetic. Conclusion: There is insufficient evidence to state that general anesthetics are neurotoxic and have the potential to trigger learning and behavior disabilities in children. However, we suggest caution in indicating surgery in children under three years old, analyzing risk-benefit and inserting the family in the decision process.   Keywords: Neurotoxicity; Neuroprotection; Cognitive Impairment; Children; General Anesthesics

  9. Long-term outcome of combined modality therapy in retroperitoneal and deep-trunk soft-tissue sarcoma: analysis of prognostic factors

    International Nuclear Information System (INIS)

    Youssef, Emad; Fontanesi, James; Mott, Michael; Kraut, Michael; Lucas, David; Mekhael, Hany; Ben-Josef, Edgar

    2002-01-01

    Purpose: To evaluate the long-term outcome of surgery and postoperative radiotherapy (RT) in retroperitoneal and deep-trunk soft-tissue sarcoma, and to identify the prognostic factors for local control, disease-free survival, and overall survival. Methods and Materials: Between January 1980 and December 1998, 60 patients with nonmetastatic retroperitoneal and deep-trunk soft-tissue sarcoma were treated at Wayne State University using combined surgery and RT. The location was retroperitoneal in 38 patients (63%) and deep trunk in 22 (27%). Forty-six patients (76%) were treated for primary disease and 14 (24%) for recurrent disease. The resection margins were negative in 24 patients (40%), close in 3 (5%), and positive in 33 (55%; 18 microscopic and 15 macroscopic). The median tumor size was 8.6 cm (range 2-55). External beam RT (EBRT; median dose 5220 cGy) was given to 44 patients (73%) and combined EBRT (median dose 4200 cGy) and brachytherapy (median dose 1600 cGy) to 16 patients (27%). Univariate and multivariate Cox regression analyses were conducted to identify the possible associations between patient age, race, gender, tumor site, histologic features, grade, size, stage, surgical margin, RT dose, modality (EBRT vs. EBRT plus brachytherapy), and presentation (primary vs. recurrent) and disease control. Results: The actuarial 5- and 10-year disease-free survival rate was 53% and 44%, respectively. Disease-free survival was significantly associated with female gender on univariate analysis (67% for female patients and 37% for male patients at 5 years, p=0.05). On multivariate analysis, both gender and surgical margin had borderline significance (p=0.06). The actuarial local control rate was 71% and 54% at 5 and 10 years, respectively. The median time to local relapse was 10.2 months, with 75% of all failures occurring within 29 months. The surgical margin status was significantly associated with local control (78% for patients with negative or close margins vs

  10. Experimental modal analysis

    Energy Technology Data Exchange (ETDEWEB)

    Ibsen, Lars Bo; Liingaard, M.

    2006-12-15

    This technical report concerns the basic theory and principles for experimental modal analysis. The sections within the report are: Output-only modal analysis software, general digital analysis, basics of structural dynamics and modal analysis and system identification. (au)

  11. Electrical stimulation and tinnitus: neuroplasticity, neuromodulation, neuroprotection.

    Science.gov (United States)

    Abraham, Shulman; Barbara, Goldstein; Arnold, Strashun

    2013-01-01

    Neuroplasticity (NPL), neuromodulation (NM), and neuroprotection (NPT) are ongoing biophysiological processes that are linked together in sensory systems, the goal being the maintenance of a homeostasis of normal sensory function in the central nervous system. It is hypothesized that when the balance between excitatory - inhibitory action is broken in sensory systems, predominantly due to neuromodulatory activity with reduced induced inhibition and excitation predominates, sensory circuits become plastic with adaptation at synaptic levels to environmental inputs(1). Tinnitus an aberrant auditory sensation, for all clinical types, is clinically considered to reflect a failure of NPL, NM, and NPT to maintain normal auditory function at synaptic levels in sensory cortex and projected to downstream levels in the central auditory system in brain and sensorineural elements in ear. Clinically, the tinnitus sensation becomes behaviorally manifest with varying degrees of annoyance, reflecting a principle of sensory physiology that each sensation has components, i.e. sensory, affect/behavior, psychomotor and memory. Modalities of tinnitus therapies, eg instrumentation, pharmacology, surgery, target a particular component of tinnitus, with resultant activation of neuromodulators at multiple neuromodulatory centers in brain and ear. Effective neuromodulation at sensory neuronal synaptic levels results in NPL in sensory cortex, NPT and tinnitus relief. Functional brain imaging, metabolic (PET brain) and electrophysiology quantitative electroencephalography (QEEG) data in a cochlear implant soft failure patient demonstrates what is clinically considered to reflect NPL, NM, NPT. The reader is provided with a rationale for tinnitus diagnosis and treatment, with a focus on ES, reflecting the biology underlying NPL, NM, NPT.

  12. Implementation of the Scanning Laser Doppler Vibrometer Combined with a Light-Weight Pneumatic Artificial Muscle Actuator for the Modal Analysis of a Civil Structure

    Directory of Open Access Journals (Sweden)

    K. Deckers

    2012-01-01

    Full Text Available The identification of the modal parameters of bridges and other large civil constructions has become an important research issue. Different approaches have been proposed depending on the excitation used: ambient excitations (due to wind, traffic, … or artificial excitations (e.g. impact test with heavy drop weights. In practice it turns out that not all modes are well excited by the ambient forces. Hence the application of an artificial actuator is advisable. The problem is that larger constructions often require large and heavy excitation devices, which are hard to manipulate. Another difficulty encountered in performing a modal analysis on large civil constructions is the necessity for a large number of high sensitivity sensors. Consequently a large number of cables has to be installed resulting in a large setup time.

  13. Urban Modality

    Directory of Open Access Journals (Sweden)

    Jorge Gil

    2016-02-01

    Full Text Available This thesis proposes a framework for evaluating the mobility potential and performance of urban areas in the city region, as an instrument to support urban development that contributes positively to regional sustainable mobility objectives. The research takes a quantitative approach, modelling and measuring the characteristics of a city-region and of its individual urban areas, in terms of travel patterns and socioeconomic characteristics of the resident population, and in terms of built environment characteristics. It then explores how the built environment defines the affordances of urban areas for travelling by particular modes of transport, i.e. its walk-ability, cycleability, drive-ability and transit-ability, by developing a typology of what I call their ‘urban modality’. And finally the work combines this typology with the socio-economic characteristics of urban areas to determine their sustainable mobility potential and performance. It focuses on the case of the Randstad region of the Netherlands and its VINEX neighbourhoods, which are an emblematic example of new urban areas created under a policy programme with sustainable mobility objectives. A key stance in this work is the understanding that the location of an urban area in the region can be indicative of its population’s travel patterns, because the built environment (infrastructural and socio-economic characteristics are interrelated and present strong regional spatial patterns. What types of urban areas support sustainable travel patterns, and what are their spatial characteristics? How do new neighbourhoods compare to the best performing urban areas, and to other areas of the same ‘modality’ type? These are some of the questions addressed in this study. There are two main contributions of this research: the methods for building and analysing integrated multimodal network models, and the framework for contextual performance evaluation using urban area typologies. The

  14. Noise elimination algorithm for modal analysis

    Energy Technology Data Exchange (ETDEWEB)

    Bao, X. X., E-mail: baoxingxian@upc.edu.cn [Department of Naval Architecture and Ocean Engineering, China University of Petroleum (East China), Qingdao 266580 (China); Li, C. L. [Key Laboratory of Marine Geology and Environment, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071 (China); Xiong, C. B. [The First Institute of Oceanography, State Oceanic Administration, Qingdao 266061 (China)

    2015-07-27

    Modal analysis is an ongoing interdisciplinary physical issue. Modal parameters estimation is applied to determine the dynamic characteristics of structures under vibration excitation. Modal analysis is more challenging for the measured vibration response signals are contaminated with noise. This study develops a mathematical algorithm of structured low rank approximation combined with the complex exponential method to estimate the modal parameters. Physical experiments using a steel cantilever beam with ten accelerometers mounted, excited by an impulse load, demonstrate that this method can significantly eliminate noise from measured signals and accurately identify the modal frequencies and damping ratios. This study provides a fundamental mechanism of noise elimination using structured low rank approximation in physical fields.

  15. Resveratrol Neuroprotection in a Chronic Mouse Model of Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Zoe eFonseca-Kelly

    2012-05-01

    Full Text Available Resveratrol is a naturally-occurring polyphenol that activates SIRT1, an NAD-dependent deacetylase. SRT501, a pharmaceutical formulation of resveratrol with enhanced systemic absorption, prevents neuronal loss without suppressing inflammation in mice with relapsing experimental autoimmune encephalomyelitis (EAE, a model of multiple sclerosis. In contrast, resveratrol has been reported to suppress inflammation in chronic EAE, although neuroprotective effects were not evaluated. The current studies examine potential neuroprotective and immunomodulatory effects of resveratrol in chronic EAE induced by immunization with myelin oligodendroglial glycoprotein peptide in C57/Bl6 mice. Effects of two distinct formulations of resveratrol administered daily orally were compared. Resveratrol delayed the onset of EAE compared to vehicle-treated EAE mice, but did not prevent or alter the phenotype of inflammation in spinal cords or optic nerves. Significant neuroprotective effects were observed, with higher numbers of retinal ganglion cells found in eyes of resveratrol-treated EAE mice with optic nerve inflammation. Results demonstrate that resveratrol prevents neuronal loss in this chronic demyelinating disease model, similar to its effects in relapsing EAE. Differences in immunosuppression compared with prior studies suggest that immunomodulatory effects may be limited and may depend on specific immunization parameters or timing of treatment. Importantly, neuroprotective effects can occur without immunosuppression, suggesting a potential additive benefit of resveratrol in combination with anti-inflammatory therapies for multiple sclerosis.

  16. Additive Neuroprotective Effect of Borneol with Mesenchymal Stem Cells on Ischemic Stroke in Mice

    Directory of Open Access Journals (Sweden)

    Xiao-Guang Zhang

    2018-01-01

    Full Text Available Intravenous stem cell transplantation initiates neuroprotection related to the secretion of trophic factor. Borneol, a potential herbal neuroprotective agent, is a penetration enhancer. Here, we aimed to investigate whether they have additive neuroprotective effect on cerebral ischemia. Borneol was given to mice by gavage 3 days before middle cerebral artery occlusion (MCAO induction until the day when the mice were sacrificed. Mesenchymal stem cells (MSCs were intravenously injected at 24 h after MCAO induction. Neurological deficits, infarct volume, cell death, and neurogenesis were evaluated. Combined use of MSCs and borneol could more effectively reduce infarction volume and cell apoptosis, enhance neurogenesis, and improve the functional recovery than that of MSCs alone. The findings showed that combined use of borneol and stem cells provided additive neuroprotective effect on cerebral ischemia. However, the supposed effect of borneol on the improved MSC penetration still needs further direct evidence.

  17. Meditations on Metaphysical Modality

    OpenAIRE

    Willis, Edmund Lindsay James

    2011-01-01

    Although metaphysical modality has been much discussed and exploited by philosophers, its precise nature is often left unanalysed and obscure. This dissertation marks an attempt to understand it better. After examining modality in general, the specific topic is introduced through consideration of the views of Kripke and Lewis. Comparisons are then made with logical, scientific and conceptual modalities. Finally, it is argued that metaphysical modality is that variety of modality which is alet...

  18. Neuroprotective properties of GLP-1

    DEFF Research Database (Denmark)

    Holst, Jens Juul; Burcelin, Remy; Nathanson, Esther

    2011-01-01

    emptying. Furthermore, data are beginning to emerge that indicate a potential role for GLP-1 in neuroprotection. The increased risk of Alzheimer's disease, Parkinson's disease and stroke in people with type 2 diabetes suggests that shared mechanisms/pathways of cell death, possibly related to insulin...... path towards cellular dysfunction and death. This article summarizes the evidence for neuronal activity of GLP-1 and examines the limited data that currently exist on the therapeutic potential of GLP-1 in specific neurological and neurodegenerative conditions, namely Alzheimer's disease, Parkinson...

  19. Operational Modal Analysis Tutorial

    DEFF Research Database (Denmark)

    Brincker, Rune; Andersen, Palle

    of modal parameters of practical interest - including the mode shape scaling factor - with a high degree of accuracy. It is also argued that the operational technology offers the user a number of advantages over traditional modal testing. The operational modal technology allows the user to perform a modal......In this paper the basic principles in operational modal testing and analysis are presented and discussed. A brief review of the techniques for operational modal testing and identification is presented, and it is argued, that there is now a wide range of techniques for effective identification...

  20. Neither Baseline nor Changes in Serum Triiodothyronine during Levothyroxine/Liothyronine Combination Therapy Predict a Positive Response to This Treatment Modality in Hypothyroid Patients with Persistent Symptoms

    DEFF Research Database (Denmark)

    Medici, Bjarke Borregaard; la Cour, Jeppe Lerche; Michaelsson, Luba Freja

    2017-01-01

    BACKGROUND: Despite biochemical euthyroidism, some levothyroxine (L-T4)-treated hypothyroid patients report persisting symptoms and some of these patients are tentatively treated with a combination of L-T4 and liothyronine (L-T3). Combination therapy and the appropriate choice of blood tests to m...

  1. Modal Logics and Definability

    OpenAIRE

    Kuusisto, Antti

    2013-01-01

    In recent years, research into the mathematical foundations of modal logic has become increasingly popular. One of the main reasons for this is the fact that modal logic seems to adapt well to the requirements of a wide range of different fields of application. This paper is a summary of some of the author’s contributions to the understanding of modal definability theory.

  2. An investigation of developmental changes in interpretation and construction of graphic AAC symbol sequences through systematic combination of input and output modalities.

    Science.gov (United States)

    Trudeau, Natacha; Sutton, Ann; Morford, Jill P

    2014-09-01

    While research on spoken language has a long tradition of studying and contrasting language production and comprehension, the study of graphic symbol communication has focused more on production than comprehension. As a result, the relationships between the ability to construct and to interpret graphic symbol sequences are not well understood. This study explored the use of graphic symbol sequences in children without disabilities aged 3;0 to 6;11 (years; months) (n=111). Children took part in nine tasks that systematically varied input and output modalities (speech, action, and graphic symbols). Results show that in 3- and 4-year-olds, attributing meaning to a sequence of symbols was particularly difficult even when the children knew the meaning of each symbol in the sequence. Similarly, while even 3- and 4-year-olds could produce a graphic symbol sequence following a model, transposing a spoken sentence into a graphic sequence was more difficult for them. Representing an action with graphic symbols was difficult even for 5-year-olds. Finally, the ability to comprehend graphic-symbol sequences preceded the ability to produce them. These developmental patterns, as well as memory-related variables, should be taken into account in choosing intervention strategies with young children who use AAC.

  3. The Modal Dimension

    Directory of Open Access Journals (Sweden)

    Giluano Torrengo

    2018-05-01

    Full Text Available Space and time are two obvious candidates as dimensions of reality. Yet, are they the only two dimensions of reality? Famously, David Lewis maintained the doctrine of ―modal realism‖, the thesis that possible worlds exist and are entities as concrete as the actual world that we live in. In this paper, I will explore the idea that modality can be construed as a dimension along with space and time. However, although Lewis‘ modal realism is the main source of inspiration for this construal of modality, I will argue that something else is required for having a modal dimension.

  4. Unconventional neurotransmitters, neurodegeneration and neuroprotection

    Directory of Open Access Journals (Sweden)

    M. Leonelli

    2009-01-01

    Full Text Available Neurotransmitters are also involved in functions other than conventional signal transfer between nerve cells, such as development, plasticity, neurodegeneration, and neuroprotection. For example, there is a considerable amount of data indicating developmental roles for the glutamatergic, cholinergic, dopaminergic, GABA-ergic, and ATP/adenosine systems. In this review, we discuss the existing literature on these "new" functions of neurotransmitters in relation to some unconventional neurotransmitters, such as the endocannabinoids and nitric oxide. Data indicating both transcriptional and post-transcriptional modulation of endocannabinoid and nitrinergic systems after neural lesions are discussed in relation to the non-conventional roles of these neurotransmitters. Knowledge of the roles of neurotransmitters in brain functions other than information transfer is critical for a more complete understanding of the functional organization of the brain and to provide more opportunities for the development of therapeutical tools aimed at minimizing neuronal death.

  5. A combined salt-hard templating approach for synthesis of multi-modal porous carbons used for probing the simultaneous effects of porosity and electrode engineering on EDLC performance

    KAUST Repository

    Bhandari, Nidhi

    2015-06-01

    A new approach, based on a combination of salt and hard templating for producing multi-modal porous carbons is demonstrated. The hard template, silica nanoparticles, generate mesopores (∼22 nm), and in some cases borderline-macropores (∼64 nm), resulting in high pore volume (∼3.9 cm3/g) while the salt template, zinc chloride, generates borderline-mesopores (∼2 nm), thus imparting high surface area (∼2100 m2/g). The versatility of the proposed synthesis technique is demonstrated using: (i) dual salt templates with hard template resulting in magnetic, nanostructured-clay embedded (∼27% clay content), high surface area (∼1527 m2/g) bimodal carbons (∼2 and 70 nm pores), (ii) multiple hard templates with salt template resulting in tri-modal carbons (∼2, 12 and 28 nm pores), (iii) low temperature (450 °C) synthesis of bimodal carbons afforded by the presence of hygroscopic salt template, (iv) easy coupling with physical activation approaches. A selected set of thus synthesized carbons were used to evaluate, for the first time, the simultaneous effects of carbon porosity and pressure applied during electrode fabrication on EDLC performance. Electrode pressing was found to be more favorable for carbons containing hard-templated mesopores (∼87% capacitance retention at current density of 40 A/g) as compared to those without (∼54% capacitance retention). © 2015 Elsevier Ltd. All rights reserved.

  6. An Accelerated Multi-Modality Rehabilitation Protocol Combined with Botulinum Toxin-A Injection in Adult Idiopathic Toe Walking: Case Report

    Science.gov (United States)

    Yavuz, Ferdi; Balaban, Birol

    2016-01-01

    Diagnosis of Adult Idiopathic Toe Walking (AITW) is very rare in clinical practice. High quality studies regarding AITW and its treatment options have not been conducted previously. A 28-year-old male patient complaining of lower leg pain was referred to outpatient rehabilitation clinic. Physical examination revealed a gait abnormality of insufficient heel strike at initial contact. The aetiology was investigated and the patient’s walking parameters were assessed using a computerized gait analysis system. The AITW was diagnosed. Botulinum toxin-A (Dysport®) was injected to the bilateral gastrocnemius muscles. A combined 10-days rehabilitation program was designed, including a daily one-hour physiotherapist supervised exercise program, ankle dorsiflexion exercises using an EMG-biofeedback unit assisted virtual rehabilitation system (Biometrics) and virtual gait training (Rehawalk) every other day. After treatment, the patient was able to heel strike at the initiation of the stance phase of the gait. Ankle dorsiflexion range of motions increased. The most prominent improvement was seen in maximum pressure and heel force. In addition center of pressure evaluations were also improved. To the best of our knowledge this is the first case, of AITW treated with combined botulinum toxin, exercise and virtual rehabilitation systems. This short report demonstrates the rapid effect of this 10-days combined therapy. PMID:27504395

  7. Advances in Modal Logic

    DEFF Research Database (Denmark)

    Modal logic is a subject with ancient roots in the western logical tradition. Up until the last few generations, it was pursued mainly as a branch of philosophy. But in recent years, the subject has taken new directions with connections to topics in computer science and mathematics. This volume...... is the proceedings of the conference of record in its fi eld, Advances in Modal Logic. Its contributions are state-of-the-art papers. The topics include decidability and complexity results for specifi c modal logics, proof theory of modal logic, logics for reasoning about time and space, provability logic, dynamic...... epistemic logic, and the logic of evidence....

  8. Activation of endogenous p53 by combined p19Arf gene transfer and nutlin-3 drug treatment modalities in the murine cell lines B16 and C6

    Directory of Open Access Journals (Sweden)

    Zanatta Daniela B

    2010-06-01

    Full Text Available Abstract Background Reactivation of p53 by either gene transfer or pharmacologic approaches may compensate for loss of p19Arf or excess mdm2 expression, common events in melanoma and glioma. In our previous work, we constructed the pCLPG retroviral vector where transgene expression is controlled by p53 through a p53-responsive promoter. The use of this vector to introduce p19Arf into tumor cells that harbor p53wt should yield viral expression of p19Arf which, in turn, would activate the endogenous p53 and result in enhanced vector expression and tumor suppression. Since nutlin-3 can activate p53 by blocking its interaction with mdm2, we explored the possibility that the combination of p19Arf gene transfer and nutlin-3 drug treatment may provide an additive benefit in stimulating p53 function. Methods B16 (mouse melanoma and C6 (rat glioma cell lines, which harbor p53wt, were transduced with pCLPGp19 and these were additionally treated with nutlin-3 or the DNA damaging agent, doxorubicin. Viral expression was confirmed by Western, Northern and immunofluorescence assays. p53 function was assessed by reporter gene activity provided by a p53-responsive construct. Alterations in proliferation and viability were measured by colony formation, growth curve, cell cycle and MTT assays. In an animal model, B16 cells were treated with the pCLPGp19 virus and/or drugs before subcutaneous injection in C57BL/6 mice, observation of tumor progression and histopathologic analyses. Results Here we show that the functional activation of endogenous p53wt in B16 was particularly challenging, but accomplished when combined gene transfer and drug treatments were applied, resulting in increased transactivation by p53, marked cell cycle alteration and reduced viability in culture. In an animal model, B16 cells treated with both p19Arf and nutlin-3 yielded increased necrosis and decreased BrdU marking. In comparison, C6 cells were quite susceptible to either treatment, yet

  9. Activation of endogenous p53 by combined p19Arf gene transfer and nutlin-3 drug treatment modalities in the murine cell lines B16 and C6

    International Nuclear Information System (INIS)

    Merkel, Christian A; Silva Soares, Rafael B da; Carvalho, Anna Carolina V de; Zanatta, Daniela B; Bajgelman, Marcio C; Fratini, Paula; Costanzi-Strauss, Eugenia; Strauss, Bryan E

    2010-01-01

    Reactivation of p53 by either gene transfer or pharmacologic approaches may compensate for loss of p19Arf or excess mdm2 expression, common events in melanoma and glioma. In our previous work, we constructed the pCLPG retroviral vector where transgene expression is controlled by p53 through a p53-responsive promoter. The use of this vector to introduce p19Arf into tumor cells that harbor p53wt should yield viral expression of p19Arf which, in turn, would activate the endogenous p53 and result in enhanced vector expression and tumor suppression. Since nutlin-3 can activate p53 by blocking its interaction with mdm2, we explored the possibility that the combination of p19Arf gene transfer and nutlin-3 drug treatment may provide an additive benefit in stimulating p53 function. B16 (mouse melanoma) and C6 (rat glioma) cell lines, which harbor p53wt, were transduced with pCLPGp19 and these were additionally treated with nutlin-3 or the DNA damaging agent, doxorubicin. Viral expression was confirmed by Western, Northern and immunofluorescence assays. p53 function was assessed by reporter gene activity provided by a p53-responsive construct. Alterations in proliferation and viability were measured by colony formation, growth curve, cell cycle and MTT assays. In an animal model, B16 cells were treated with the pCLPGp19 virus and/or drugs before subcutaneous injection in C57BL/6 mice, observation of tumor progression and histopathologic analyses. Here we show that the functional activation of endogenous p53wt in B16 was particularly challenging, but accomplished when combined gene transfer and drug treatments were applied, resulting in increased transactivation by p53, marked cell cycle alteration and reduced viability in culture. In an animal model, B16 cells treated with both p19Arf and nutlin-3 yielded increased necrosis and decreased BrdU marking. In comparison, C6 cells were quite susceptible to either treatment, yet p53 was further activated by the combination of p19

  10. Combined stent placement and high dose PGE1 drip infusion for chronic occlusion of the superficial femoral artery as a modality to salvage chronic critical limb ischemia

    Energy Technology Data Exchange (ETDEWEB)

    Ikushima, Ichiro [Department of Radiology, Miyakonojo Medical Association Hospital, 5822-3 Oiwadacho, Miyakonojo 885-0062 (Japan)], E-mail: iku-i@fk.enjoy.ne.jp; Hirai, Toshinori [Department of Diagnostic Radiology, Graduate School of Medical Sciences, Kumamoto University (Japan); Ishii, Akihiko [Department of Radiology, Miyakonojo Medical Association Hospital, 5822-3 Oiwadacho, Miyakonojo 885-0062 (Japan); Yamashita, Yasuyuki [Department of Diagnostic Radiology, Graduate School of Medical Sciences, Kumamoto University (Japan)

    2008-04-15

    Purpose: To assess the initial effect, short-term patency, and limb salvage rates of combined stent placement and high-dose prostaglandin E-1 (PGE1) drip infusion for chronic occlusion of the superficial femoral artery (SFA). Materials and methods: A total of 15 arteriosclerotic occlusive lesions of the SFA were treated in 11 consecutive patients (mean age: 78.4 years old). All cases were of category 4 or 5, based on the criteria of the Society of Vascular Surgery and Intermittent Society for Cardiovascular Surgery (SVC/ISCVS). In all cases a self-expandable stainless steel stent was implanted. PGE1 treatment was started 3-5 days before stent placement and continued for 7-10 days after the intervention. The technical success, limb salvage outcomes, patency rates, and complications were examined. Results: In all cases, the technical success rate of the procedure was 100%. After stent implantation, the clinical status of all cases was improved by at least +2, and major amputation was not required in any cases. The 12-month primary, secondary patency rates, and limb salvage rate were 57%, 100%, and 100%, respectively. Conclusion: Combined stent placement and high-dose PGE1 drip infusion is a treatment of choice for salvaging the lower limb of a patient with chronic critical ischemia.

  11. A combined modality therapeutic approach to metastatic anal squamous cell carcinoma with systemic chemotherapy and local therapy to sites of disease: case report and review of literature.

    Science.gov (United States)

    Gnanajothy, Rosana; Warren, Graham W; Okun, Sherry; Peterson, Lindsay L

    2016-06-01

    Cases of metastatic anal carcinoma managed with a combination of systemic chemotherapy and local therapies to both solitary sites of metastases and the primary site have been reported in the literature. We present a case of a 55-year-old male with metastatic anal squamous cell carcinoma to the liver treated with induction chemotherapy with cisplatin (CDDP) and 5-fluorouracil (5FU) followed by liver resection and radiation to the anal primary with concurrent 5FU and mitomycin. This approach resulted in control of disease without evidence of recurrence, and no increased toxicities now 19 months from initial diagnosis to time of reporting. This novel approach resulted in a good treatment response as documented by imaging and symptom improvement and a long disease free interval.

  12. Modal logics are coalgebraic

    NARCIS (Netherlands)

    Cirstea, C.; Kurz, A.; Pattinson, D.; Schröder, L.; Venema, Y.

    2011-01-01

    Applications of modal logics are abundant in computer science, and a large number of structurally different modal logics have been successfully employed in a diverse spectrum of application contexts. Coalgebraic semantics, on the other hand, provides a uniform and encompassing view on the large

  13. Combined modality therapy for localized prostate carcinoma using Iridium-192 brachytherapy and external beam radiotherapy: results, morbidity, and the lack of value of surgical lymph node staging

    International Nuclear Information System (INIS)

    Baird, Michael; Ordorica, Edward; Dawson, Anne

    1997-01-01

    Purpose/Objective: (1) To quantitate the morbidity and 5 and 10 year bNED survival of Ir-192 temporary implant combined with external beam radiotherapy in the treatment of clinically localized Prostate Carcinoma. (2) To determine the need for nodal staging prior to implant. Materials and Methods: 335 consecutively treated patients seen between 8/17/84 and 8/13/93 were analyzed. All patents had retropertoneal nodal dissection and were implanted with Ir-192 using the Syed-Neblett template. Thirteen percent who completed treatment per protocol were found to have microscopically involved nodes on permanent section. 277 patients had completed the entire treatment protocol and had at least 2 years follow-up with DRE and serial serum PSAs. All patients were evaluated for morbidity using the standard RTOG morbidity scales. The bNED survival was determined using Kaplan-Meier methods with a non-rising PSA value of < 1.0 used as an indicator of disease control. All patients received 30 Gy in 50 hrs. to the implant volume, followed in two weeks by 34.2 Gy external beam (19 fx/ 25 days). The median follow up for the group is 55 months. Results: Morbidity: 69.2% of the patients experienced no reportable morbidity. Urinary morbidity was usually transient and mild (Grade 1 or 2 in 9.7%). 4.9 % experienced grade 3 urinary complaints (6.6% stress incontinence) and the incidence of grade 4 urinary complaints was 0.6%. Urinary complications were 2.5 times more common in patients who had previously undergone a TURP. Rectal complications were mild or moderate in 10.5% and usually consisted of asymptomatic rectal bleeding (6.9%). Severe rectal ulcer requiring temporary colostomy occurred in 1.4% and always healed after colostomy. Other morbidity consisted of mild, self-limited edema (2.1%). One patient had persistent edema post treatment, and there was one death from a CVA perioperatively (0.3%). 75% of patients who were potent prior to treatment maintained useful sexual function post

  14. 40 CFR 1033.520 - Alternative ramped modal cycles.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 32 2010-07-01 2010-07-01 false Alternative ramped modal cycles. 1033... cycles. (a) Locomotive testing over a ramped modal cycle is intended to improve measurement accuracy at... locomotive notch settings. Ramped modal cycles combine multiple test modes of a discrete-mode steady-state...

  15. Differential effect of IP- and IV-injected nitrogen mustard on subsequently-irradiated intestinal crypts: implications for 'dose-effect factors' predicted by experimental, combined modality therapy

    International Nuclear Information System (INIS)

    Moore, J.V.

    1984-01-01

    In experimental chemotherapy-radiotherapy, cytotoxic drugs are almost invariably injected by the intraperitoneal (IP) route. This contrasts with normal clinical practice, which is to employ the intravenous (IV) route. We have used a clonogenic assay of gastrointestinal (GI) injury in mice to show that a given administered dose of nitrogen mustard (HN 2 ), injected IP, results in a much greater reduction in the subsequent radiation dose required to achieve an isoeffect, than if the drug is injected IV. At an administered dose of 3.5 mg kg -1 of HN 2 (the animal LDsub(10/30) for IP injection), the radiation dose-reduction factor for 10% survival of intestinal crypts, was 1.94 for IP HN 2 and only 1.28 for IV HN 2 . Even the grossly-equitoxic (mouse LDsub(10/30)) dose of IV HN 2 resulted in a smaller predicted radiation dose reduction for GI injury, by a factor of 1.45. The validity of using the IP route in combined chemotherapy-radiotherapy studies designed to generate quantitative estimates of toxicity is discussed. (author)

  16. Intervention with the hypoxic tumor cell sensitizer etanidazole in the combined modality treatment of limited stage small-cell lung cancer. A one-institution study

    International Nuclear Information System (INIS)

    Urtasun, Raul C.; Palmer, Martin; Kinney, Brenda; Belch, Andrew; Hewitt, Joanne; Hanson, John

    1998-01-01

    Purpose: We report the toxicity, patterns of failure and survival of a cohort of patients with limited disease (LD) small-cell lung cancer (SCLC) treated with combined radiation and chemotherapy. During the course of thoracic irradiation, we added intravenous (i.v.) etanidazole (SR-2508, a third-generation 2-nitroimidazole) as a hypoxic cell sensitizer in an attempt to reduce the primary local failure rate and improve survival. Methods and Materials: Between July 1988 and August 1990, 30 consecutive patients with limited disease SCLC were enrolled and treated on a Phase II protocol receiving a standard combination chemotherapy regimen utilizing i.v. cisplatin 25 mg/m 2 /day x 3 days, i.v. etoposide 100 mg/m 2 /day x 3 days alternating with intravenous cyclophosphamide 1000 mg/m 2 /day, intravenous doxorubicin 15 mg/m 2 , and intravenous vincristine 2 mg (CAV) to a total of six cycles every 3 weeks. Radiotherapy and etanidazole were started after the first cycle of chemotherapy. Etanidazole was administered intravenously at a dose of 2 g/m 2 three times per week for a total of 30 g/m 2 during the course of thoracic radiation that delivered 50.00 Gy tumor dose in 25 fractions in an overall time of 6 weeks. Results: The overall response rate of the primary lesion in the thorax was 96% (CR + PR), with 64% complete responses. The median time to treatment failure was 18 months. Of the patients that have relapsed, only 18% failed in the thorax (alone or concomitant with other sites). This is a marked improvement compared to the 40-50% rate reported in the literature. The 2-year crude survival was 46%. The 3- and 5-year crude survival rate with no evidence of disease was 33 and 30%, respectively. We have observed a 10% increase in the incidence of transient etanidazole related peripheral neuropathies compared to previous etanidazole studies not utilizing systemic chemotherapy. There was no increased incidence of radiation esophagitis, pulmonary toxicity, or nephro- or

  17. Long-term results from a randomized phase II trial of neoadjuvant combined-modality therapy for locally advanced rectal cancer

    Directory of Open Access Journals (Sweden)

    Oblak Irena

    2010-09-01

    Full Text Available Abstract Background This study evaluated the effectiveness and safety of preoperative chemoradiotherapy with capecitabine in patients with locally advanced resectable rectal cancer. This report summarizes the results of the phase II study together with long-term (5-year follow-up. Methods Between June 2004 and January 2005, 57 patients with operable, clinical stage II-III adenocarcinoma of the rectum entered the study. Radiation dose was 45 Gy delivered as 25 fractions of 1.8 Gy. Concurrent chemotherapy with oral capecitabine 825 mg/m2 twice daily was administered during radiotherapy and at weekends. Surgery was scheduled 6 weeks after the completion of the chemoradiotherapy. Patients received four cycles of postoperative chemotherapy comprising either capecitabine 1250 mg/m2 bid days 1-14 every 3 weeks or bolus i.v. 5-fluorouracil 425 mg/m2/day and leucovorin 20 mg/m2/day days 1-5 every 4 weeks (choice was at the oncologist's discretion. Study endpoints included complete pathological remission, proportion of R0 resections and sphincter-sparing procedures, toxicity, survival parameters and long-term (5-year rectal and urogenital morbidity assessment. Results One patient died after receiving 27 Gy because of a pulmonary embolism. Fifty-six patients completed radiochemotherapy and had surgery. Median follow-up time was 62 months. No patients were lost to follow-up. R0 resection was achieved in 55 patients. A complete pathological response was observed in 5 patients (9.1%; T-, N- and overall downstaging rates were 40%, 52.9% and 49.1%, respectively. The 5-year overall survival rate, recurrence-free survival, and local control was 61.4% (95% CI: 48.9-73.9%, 52.4% (95% CI: 39.3-65.5%, and 87.4% (95% CI: 75.0-99.8%, respectively. In 5 patients local relapse has occurred; dissemination was observed in 19 patients and secondary malignancies have occurred in 2 patients. The most frequent side-effect of the preoperative combined therapy was dermatitis

  18. Extending Modal Transition Systems with Structured Labels

    DEFF Research Database (Denmark)

    Bauer, Sebastian S.; Juhl, Line; Larsen, Kim Guldstrand

    2012-01-01

    We introduce a novel formalism of label-structured modal transition systems that combines the classical may/must modalities on transitions with structured labels that represent quantitative aspects of the model. On the one hand, the specification formalism is general enough to include models like...... weighted modal transition systems and allows the system developers to employ more complex label refinement than in the previously studied theories. On the other hand, the formalism maintains the desirable properties required by any specification theory supporting compositional reasoning. In particular, we...

  19. Microglia and neuroprotection: implications for Alzheimer's disease.

    Science.gov (United States)

    Streit, Wolfgang J

    2005-04-01

    The first part of this paper summarizes some of the key observations from experimental work in animals that support a role of microglia as neuroprotective cells after acute neuronal injury. These studies point towards an important role of neuronal-microglial crosstalk in the facilitation of neuroprotection. Conceptually, injured neurons are thought to generate rescue signals that trigger microglial activation and, in turn, activated microglia produce trophic or other factors that help damaged neurons recover from injury. Against this background, the second part of this paper summarizes recent work from postmortem studies conducted in humans that have revealed the occurrence of senescent, or dystrophic, microglial cells in the aged and Alzheimer's disease brain. These findings suggest that microglial cells become increasingly dysfunctional with advancing age and that a loss of microglial cell function may involve a loss of neuroprotective properties that could contribute to the development of aging-related neurodegeneration.

  20. The Neuroprotection Effect of Oxygen Therapy: A Systematic Review ...

    African Journals Online (AJOL)

    2018-04-04

    Apr 4, 2018 ... investigating the neuroprotective effect of oxygen, but the outcomes as well as ...... Neuroprotective gases – Fantasy or reality for clinical use? Prog .... of oxygen on brain tissue oxygen tension in children with severe traumatic ...

  1. Normal modal preferential consequence

    CSIR Research Space (South Africa)

    Britz, K

    2012-12-01

    Full Text Available beyond the basic (propositional) KLM postulates, thereby making use of the additional expressivity provided by modal logic. In particular, we show that the additional constraints we impose on the preferential semantics ensure that the rule...

  2. Combined SPECT/CT improves detection of initial bone invasion and determination of resection margins in squamous cell carcinoma of the head and neck compared to conventional imaging modalities

    Energy Technology Data Exchange (ETDEWEB)

    Kolk, A. [Technische Universitaet Muenchen, Klinikum rechts der Isar, Department of Oral and Maxillofacial Surgery, Munich (Germany); Klinikum rechts der Isar, Technische Universitaet Muenchen, Klinik und Poliklinik fuer Mund-Kiefer und Gesichtschirurgie, Muenchen (Germany); Schuster, T. [Technische Universitaet Muenchen, Klinikum rechts der Isar, Institute of Medical Statistics and Epidemiology, Munich (Germany); Chlebowski, A.; Kesting, M.; Bissinger, O.; Weitz, J. [Technische Universitaet Muenchen, Klinikum rechts der Isar, Department of Oral and Maxillofacial Surgery, Munich (Germany); Lange, P. [Technische Universitaet Muenchen, Klinikum rechts der Isar, Department of Diagnostic Radiology, Munich (Germany); Scheidhauer, K.; Schwaiger, M.; Dinges, J. [Technische Universitaet Muenchen, Klinikum rechts der Isar, Department of Nuclear Medicine, Munich (Germany)

    2014-07-15

    Knowledge of the presence and extent of bone infiltration is crucial for planning the resection of potential bone-infiltrating squamous cell carcinomas of the head and neck (HNSCC). Routinely, plain-film radiography, multislice computed tomography (MSCT) and magnetic resonance imaging (MRI) are used for preoperative staging, but they show relatively high rates of false-positive and false-negative findings. Scintigraphy with {sup 99m}Tc-bisphosphonate has the ability to show increased metabolic bone activity. If combined with anatomical imaging (e.g. (SPECT)/CT), it facilitates the precise localization of malignant bone lesions. The aim of this study was to analyse the indications and advantages of SPECT/CT compared with standard imaging modalities and histology with regard to specificity and sensitivity A longitudinally evaluated group of 30 patients with biopsy-proven HNSCC adjacent to the mandible underwent {sup 99m}Tc-bisphosphonate SPECT/CT, MRI, MSCT and conventional radiography before partial or rim resection of the mandible was performed. Bone infiltration was first evaluated with plain films, MSCT and MRI. In a second reading, SPECT/CT data were taken into account. The results (region and certainty of bone invasion) were evaluated among the different imaging modalities and finally compared with histological specimens from surgical resection as the standard of reference. For a better evaluation of the hybrid property of SPECT/CT, a retrospectively evaluated group of 20 additional patients with tumour locations similar to those of the longitudinally examined SPECT/CT group underwent SPECT, MSCT and MRI. To assess the influence of dental foci on the specificity of the imaging modalities, all patients were separated into two subgroups depending on the presence or absence of teeth in the area of potential tumour-bone contact. Histologically proven bone infiltration was found in 17 patients (57 %) when analysed by conventional imaging modalities. SPECT/CT data

  3. Combined SPECT/CT improves detection of initial bone invasion and determination of resection margins in squamous cell carcinoma of the head and neck compared to conventional imaging modalities

    International Nuclear Information System (INIS)

    Kolk, A.; Schuster, T.; Chlebowski, A.; Kesting, M.; Bissinger, O.; Weitz, J.; Lange, P.; Scheidhauer, K.; Schwaiger, M.; Dinges, J.

    2014-01-01

    Knowledge of the presence and extent of bone infiltration is crucial for planning the resection of potential bone-infiltrating squamous cell carcinomas of the head and neck (HNSCC). Routinely, plain-film radiography, multislice computed tomography (MSCT) and magnetic resonance imaging (MRI) are used for preoperative staging, but they show relatively high rates of false-positive and false-negative findings. Scintigraphy with 99m Tc-bisphosphonate has the ability to show increased metabolic bone activity. If combined with anatomical imaging (e.g. (SPECT)/CT), it facilitates the precise localization of malignant bone lesions. The aim of this study was to analyse the indications and advantages of SPECT/CT compared with standard imaging modalities and histology with regard to specificity and sensitivity A longitudinally evaluated group of 30 patients with biopsy-proven HNSCC adjacent to the mandible underwent 99m Tc-bisphosphonate SPECT/CT, MRI, MSCT and conventional radiography before partial or rim resection of the mandible was performed. Bone infiltration was first evaluated with plain films, MSCT and MRI. In a second reading, SPECT/CT data were taken into account. The results (region and certainty of bone invasion) were evaluated among the different imaging modalities and finally compared with histological specimens from surgical resection as the standard of reference. For a better evaluation of the hybrid property of SPECT/CT, a retrospectively evaluated group of 20 additional patients with tumour locations similar to those of the longitudinally examined SPECT/CT group underwent SPECT, MSCT and MRI. To assess the influence of dental foci on the specificity of the imaging modalities, all patients were separated into two subgroups depending on the presence or absence of teeth in the area of potential tumour-bone contact. Histologically proven bone infiltration was found in 17 patients (57 %) when analysed by conventional imaging modalities. SPECT/CT data revealed

  4. Wine polyphenols: potential agents in neuroprotection.

    Science.gov (United States)

    Basli, Abdelkader; Soulet, Stéphanie; Chaher, Nassima; Mérillon, Jean-Michel; Chibane, Mohamed; Monti, Jean-Pierre; Richard, Tristan

    2012-01-01

    There are numerous studies indicating that a moderate consumption of red wine provides certain health benefits, such as the protection against neurodegenerative diseases. This protective effect is most likely due to the presence of phenolic compounds in wine. Wine polyphenolic compounds are well known for the antioxidant properties. Oxidative stress is involved in many forms of cellular and molecular deterioration. This damage can lead to cell death and various neurodegenerative disorders, such as Parkinson's or Alzheimer's diseases. Extensive investigations have been undertaken to determine the neuroprotective effects of wine-related polyphenols. In this review we present the neuroprotective abilities of the major classes of wine-related polyphenols.

  5. Epigenetics and Therapeutic Targets Mediating Neuroprotection

    Science.gov (United States)

    Qureshi, Irfan A.; Mehler, Mark F.

    2015-01-01

    The rapidly evolving science of epigenetics is transforming our understanding of the nervous system in health and disease and holds great promise for the development of novel diagnostic and therapeutic approaches targeting neurological diseases. Increasing evidence suggests that epigenetic factors and mechanisms serve as important mediators of the pathogenic processes that lead to irrevocable neural injury and of countervailing homeostatic and regenerative responses. Epigenetics is, therefore, of considerable translational significance to the field of neuroprotection. In this brief review, we provide an overview of epigenetic mechanisms and highlight the emerging roles played by epigenetic processes in neural cell dysfunction and death and in resultant neuroprotective responses. PMID:26236020

  6. Wine Polyphenols: Potential Agents in Neuroprotection

    Science.gov (United States)

    Basli, Abdelkader; Soulet, Stéphanie; Chaher, Nassima; Mérillon, Jean-Michel; Chibane, Mohamed; Monti, Jean-Pierre; Richard, Tristan

    2012-01-01

    There are numerous studies indicating that a moderate consumption of red wine provides certain health benefits, such as the protection against neurodegenerative diseases. This protective effect is most likely due to the presence of phenolic compounds in wine. Wine polyphenolic compounds are well known for the antioxidant properties. Oxidative stress is involved in many forms of cellular and molecular deterioration. This damage can lead to cell death and various neurodegenerative disorders, such as Parkinson's or Alzheimer's diseases. Extensive investigations have been undertaken to determine the neuroprotective effects of wine-related polyphenols. In this review we present the neuroprotective abilities of the major classes of wine-related polyphenols. PMID:22829964

  7. Radiotherapy versus combined modality in early stages

    DEFF Research Database (Denmark)

    Specht, L.; Carde, P.; Mauch, P.

    1992-01-01

    be reduced, and that the stress of experiencing a relapse is avoided in many patients. The major argument against the use of chemotherapy up front is: that by careful staging and selection of patients and by careful radiotherapy techniques the number of patients exposed to potentially toxic chemotherapy may...... metaanalysis of these trials indicate that we still do not definitively know whether or not the addition of prophylactic chemotherapy up front improves survival. Arguments in favour of the addition of chemotherapy up front are: that laparotomy may be avoided, that radiation fields and doses may perhaps...

  8. Radiotherapy versus combined modality in early stages

    DEFF Research Database (Denmark)

    Specht, L; Carde, P; Mauch, P

    1992-01-01

    metaanalysis of these trials indicate that we still do not definitively know whether or not the addition of prophylactic chemotherapy up front improves survival. Arguments in favour of the addition of chemotherapy up front are: that laparotomy may be avoided, that radiation fields and doses may perhaps...... be reduced, and that the stress of experiencing a relapse is avoided in many patients. The major argument against the use of chemotherapy up front is: that by careful staging and selection of patients and by careful radiotherapy techniques the number of patients exposed to potentially toxic chemotherapy may...

  9. Modality effects in implicit artificial grammar learning: An EEG study.

    Science.gov (United States)

    Silva, Susana; Folia, Vasiliki; Inácio, Filomena; Castro, São Luís; Petersson, Karl Magnus

    2018-05-15

    Recently, it has been proposed that sequence learning engages a combination of modality-specific operating networks and modality-independent computational principles. In the present study, we compared the behavioural and EEG outcomes of implicit artificial grammar learning in the visual vs. auditory modality. We controlled for the influence of surface characteristics of sequences (Associative Chunk Strength), thus focusing on the strictly structural aspects of sequence learning, and we adapted the paradigms to compensate for known frailties of the visual modality compared to audition (temporal presentation, fast presentation rate). The behavioural outcomes were similar across modalities. Favouring the idea of modality-specificity, ERPs in response to grammar violations differed in topography and latency (earlier and more anterior component in the visual modality), and ERPs in response to surface features emerged only in the auditory modality. In favour of modality-independence, we observed three common functional properties in the late ERPs of the two grammars: both were free of interactions between structural and surface influences, both were more extended in a grammaticality classification test than in a preference classification test, and both correlated positively and strongly with theta event-related-synchronization during baseline testing. Our findings support the idea of modality-specificity combined with modality-independence, and suggest that memory for visual vs. auditory sequences may largely contribute to cross-modal differences. Copyright © 2018 Elsevier B.V. All rights reserved.

  10. Toward predicate approaches to modality

    CERN Document Server

    Stern, Johannes

    2016-01-01

    In this volume, the author investigates and argues for, a particular answer to the question: What is the right way to logically analyze modalities from natural language within formal languages? The answer is: by formalizing modal expressions in terms of predicates. But, as in the case of truth, the most intuitive modal principles lead to paradox once the modal notions are conceived as predicates. The book discusses the philosophical interpretation of these modal paradoxes and argues that any satisfactory approach to modality will have to face the paradoxes independently of the grammatical category of the modal notion. By systematizing modal principles with respect to their joint consistency and inconsistency, Stern provides an overview of the options and limitations of the predicate approach to modality that may serve as a useful starting point for future work on predicate approaches to modality. Stern also develops a general strategy for constructing philosophically attractive theories of modal notions conce...

  11. Neuroprotective effect of paeonol against isofluraneinduced ...

    African Journals Online (AJOL)

    Purpose: To investigate whether paeonol affords neuroprotection against isoflurane-induced neurotoxicity. Methods: Separate groups of neonatal rat pups were administered paeonol (20, 40 or 80 mg/kg) from post-natal day 3 (P3) to post-natal day 15. On post-natal day 7, the pups were exposed to 6 h of isoflurane (0.75 ...

  12. Proliferative Activity and Neuroprotective Effect of Ligustrazene ...

    African Journals Online (AJOL)

    Proliferative Activity and Neuroprotective Effect of. Ligustrazene Derivative by Irritation of Vascular. Endothelial Growth Factor Expression in Middle Cerebral. Artery Occlusion Rats. Zhang Huazheng1, Wang Penglong2, Ren Liwei1, Wang Xiaobo2, Li Guoliang2,. Wang Mina1, Chu Fuhao2, Gong Yan2, Xu Bing2, Bi Siling1, ...

  13. The modal study

    International Nuclear Information System (INIS)

    Cook, J.R.

    1988-01-01

    The term ''Modal Study'' refers to a research program conducted for the Nuclear Regulatory Commission (NRC) on the level of protection provided by NRC-certified packages during the shipment of spent nuclear fuel form U.S. power reactors. The objective of the study was to examine the response of the packages to actual highway and railway accident conditions. The Modal Study results show that NRC-certified spent fuel casks would perform their safety functions under severe, actual accident conditions. The study also explains how NRC's cask design conditions, which are expressed in engineering terms, relate to actual accident conditions, with which the public is more familiar. The Modal Study, along with other transportation studies, physical testing of casks, and the spent fuel shipment safety record confirm the view that casks provide a high level of public safety during spent fuel transport

  14. Human neuron-astrocyte 3D co-culture-based assay for evaluation of neuroprotective compounds.

    Science.gov (United States)

    Terrasso, Ana Paula; Silva, Ana Carina; Filipe, Augusto; Pedroso, Pedro; Ferreira, Ana Lúcia; Alves, Paula Marques; Brito, Catarina

    Central nervous system drug development has registered high attrition rates, mainly due to the lack of efficacy of drug candidates, highlighting the low reliability of the models used in early-stage drug development and the need for new in vitro human cell-based models and assays to accurately identify and validate drug candidates. 3D human cell models can include different tissue cell types and represent the spatiotemporal context of the original tissue (co-cultures), allowing the establishment of biologically-relevant cell-cell and cell-extracellular matrix interactions. Nevertheless, exploitation of these 3D models for neuroprotection assessment has been limited due to the lack of data to validate such 3D co-culture approaches. In this work we combined a 3D human neuron-astrocyte co-culture with a cell viability endpoint for the implementation of a novel in vitro neuroprotection assay, over an oxidative insult. Neuroprotection assay robustness and specificity, and the applicability of Presto Blue, MTT and CytoTox-Glo viability assays to the 3D co-culture were evaluated. Presto Blue was the adequate endpoint as it is non-destructive and is a simpler and reliable assay. Semi-automation of the cell viability endpoint was performed, indicating that the assay setup is amenable to be transferred to automated screening platforms. Finally, the neuroprotection assay setup was applied to a series of 36 test compounds and several candidates with higher neuroprotective effect than the positive control, Idebenone, were identified. The robustness and simplicity of the implemented neuroprotection assay with the cell viability endpoint enables the use of more complex and reliable 3D in vitro cell models to identify and validate drug candidates. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Parametric modal transition systems

    DEFF Research Database (Denmark)

    Beneš, Nikola; Křetínský, Jan; Larsen, Kim Guldstrand

    2011-01-01

    Modal transition systems (MTS) is a well-studied specification formalism of reactive systems supporting a step-wise refinement methodology. Despite its many advantages, the formalism as well as its currently known extensions are incapable of expressing some practically needed aspects in the refin......Modal transition systems (MTS) is a well-studied specification formalism of reactive systems supporting a step-wise refinement methodology. Despite its many advantages, the formalism as well as its currently known extensions are incapable of expressing some practically needed aspects...

  16. Tense, aspect, and modality

    NARCIS (Netherlands)

    Pfau, R.; Steinbach, M.; Woll, B.; Pfau, R.; Steinbach, M.; Woll, B.

    2012-01-01

    Cross-linguistically, the grammatical categories tense, aspect, and modality - when they are overtly expressed - are generally realized by free morphemes (such as adverbials and auxiliaries) or by bound inflectional markers. The discussion in this chapter will make clear that this generalization

  17. A Modality Called 'Negation'

    NARCIS (Netherlands)

    Berto, F.

    2015-01-01

    I propose a comprehensive account of negation as a modal operator, vindicating a moderate logical pluralism. Negation is taken as a quantifier on worlds, restricted by an accessibility relation encoding the basic concept of compatibility. This latter captures the core meaning of the operator. While

  18. Novel Neuroprotective Strategies in Ischemic Retinal Lesions

    Directory of Open Access Journals (Sweden)

    Robert Gabriel

    2010-02-01

    Full Text Available Retinal ischemia can be effectively modeled by permanent bilateral common carotid artery occlusion, which leads to chronic hypoperfusion-induced degeneration in the entire rat retina. The complex pathways leading to retinal cell death offer a complex approach of neuroprotective strategies. In the present review we summarize recent findings with different neuroprotective candidate molecules. We describe the protective effects of intravitreal treatment with: (i urocortin 2; (ii a mitochondrial ATP-sensitive K+ channel opener, diazoxide; (iii a neurotrophic factor, pituitary adenylate cyclase activating polypeptide; and (iv a novel poly(ADP-ribose polymerase inhibitor (HO3089. The retinoprotective effects are demonstrated with morphological description and effects on apoptotic pathways using molecular biological techniques.

  19. Putative neuroprotective agents in neuropsychiatric disorders.

    Science.gov (United States)

    Dodd, Seetal; Maes, Michael; Anderson, George; Dean, Olivia M; Moylan, Steven; Berk, Michael

    2013-04-05

    In many individuals with major neuropsychiatric disorders including depression, bipolar disorder and schizophrenia, their disease characteristics are consistent with a neuroprogressive illness. This includes progressive structural brain changes, cognitive and functional decline, poorer treatment response and an increasing vulnerability to relapse with chronicity. The underlying molecular mechanisms of neuroprogression are thought to include neurotrophins and regulation of neurogenesis and apoptosis, neurotransmitters, inflammatory, oxidative and nitrosative stress, mitochondrial dysfunction, cortisol and the hypothalamic-pituitary-adrenal axis, and epigenetic influences. Knowledge of the involvement of each of these pathways implies that specific agents that act on some or multiple of these pathways may thus block this cascade and have neuroprotective properties. This paper reviews the potential of the most promising of these agents, including lithium and other known psychotropics, aspirin, minocycline, statins, N-acetylcysteine, leptin and melatonin. These agents are putative neuroprotective agents for schizophrenia and mood disorders. Copyright © 2012 Elsevier Inc. All rights reserved.

  20. Wine Polyphenols: Potential Agents in Neuroprotection

    Directory of Open Access Journals (Sweden)

    Abdelkader Basli

    2012-01-01

    Full Text Available There are numerous studies indicating that a moderate consumption of red wine provides certain health benefits, such as the protection against neurodegenerative diseases. This protective effect is most likely due to the presence of phenolic compounds in wine. Wine polyphenolic compounds are well known for the antioxidant properties. Oxidative stress is involved in many forms of cellular and molecular deterioration. This damage can lead to cell death and various neurodegenerative disorders, such as Parkinson’s or Alzheimer’s diseases. Extensive investigations have been undertaken to determine the neuroprotective effects of wine-related polyphenols. In this review we present the neuroprotective abilities of the major classes of wine-related polyphenols.

  1. ASTROCYTES IN THE NEUROPROTECTION AFTER BRAIN STROKE

    Directory of Open Access Journals (Sweden)

    Gloria Patricia Cardona Gomez

    2015-03-01

    Full Text Available Astrocytes are specialized glial cells of the nervous system, which have multiple homeostatic functions for the survival and maintenance of the neurovascular unit. It has been shown that astrocytes have critical role in the dynamics pro survival conferring neuroprotective, angiogenic, immunomodulatory, neurogenic, antioxidants and regulatory synapse functions (Shen et al 2012; Gimsa et al 2013; Proschel et al 2014; making them excellent candidates as the source of neuroprotection and neurorestauration of tissue affected by events ischemia and / or reperfusion. However, these cells also may be involved in negative responses such as reactive astrocytes and glial scar under chronic excitotoxic responses generated by these events. To know what are the key points in the pro and anti-survival responses of astrocytes, would allow use them as targets in cellular therapies. This review has aim to study the mechanisms for neuroprotection in these cells (Posada-Duque et al submitted, which would make them targets of cell therapy, through of inducing regeneration, such as vehicle for corrective molecular systems and trigger endogenous cellular events that can recover the tissue homeostasis, which is lost after progressive damage.

  2. The modality effect and echoic persistence.

    Science.gov (United States)

    Watkins, O C; Watkins, M J

    1980-09-01

    The modality effect refers to the higher level of recall of the last few items of a list when presentation is auditory as opposed to visual. It is usually attributed to echoic memory. The effect may be sharply reduced by an ostensibly irrelevant auditory item appended to the end of the list. Previous research suggests that this "suffix effect" arises only when the suffix item occurs within 2 sec of the last list item. This finding strengthens the widely held assumption that echoic information decays within 2 sec, and has led to the assumption that if echoic information is to be useful in serial recall it must first be encoded into a more durable modality-independent form. Both assumptions conflict with the research reported here. The first two experiments demonstrate substantial suffix effects with suffix delays of 2 and 4 sec, indicating that echoic information lasts at least 4 sec. This finding implies that echoic information may aid recall directly, an implication that was supported in Experiments 3 and 4. In Experiment 3 serial recall was interrupted with a brief distractor task. The modality effect was smaller when this task was auditory than when it was visual, suggesting that echoic information was still available immediately prior to recency recall. In Experiment 4 list presentation was broken by a 4-sec pause; the modalities of the list halves were combined factorially. Interest focused on the recency positions of the first half. A modality effect was found at these positions when the second half was visual but not when it was auditory. This is contrary to the hypothesis that echoic information is encoded before recall, but is consistent with the hypothesis that echoic information is encoded before recall, but is consistent with the alternative hypothesis that echoic information is used directly at recall. The final two experiments concern the modality effect found when a delay is interpolated between list presentation and recall. Experiment 5 showed that

  3. Modal Logics with Counting

    Science.gov (United States)

    Areces, Carlos; Hoffmann, Guillaume; Denis, Alexandre

    We present a modal language that includes explicit operators to count the number of elements that a model might include in the extension of a formula, and we discuss how this logic has been previously investigated under different guises. We show that the language is related to graded modalities and to hybrid logics. We illustrate a possible application of the language to the treatment of plural objects and queries in natural language. We investigate the expressive power of this logic via bisimulations, discuss the complexity of its satisfiability problem, define a new reasoning task that retrieves the cardinality bound of the extension of a given input formula, and provide an algorithm to solve it.

  4. Constructions, pragmatics and modality

    Directory of Open Access Journals (Sweden)

    Antonio Fortin

    2013-05-01

    Full Text Available This paper rejects the commonplace view that the semantics of certain modal deverbal adjectives (MDAs, which have traditionally been assumed to be non-compositional, require complex lexical or syntactic encoding (cf. e.g. Riehemann 1994 and 1998, Booij 2007 and 2010a. Instead, it shows that productive MDA formation is semantically compositional, and that the prima facie idiosyncratic meanings are, in fact, conversational implicatures.

  5. The Neuroprotective Disease-Modifying Potential of Psychotropics in Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    Edward C. Lauterbach

    2012-01-01

    Full Text Available Neuroprotective treatments in Parkinson's disease (PD have remained elusive. Psychotropics are commonly prescribed in PD without regard to their pathobiological effects. The authors investigated the effects of psychotropics on pathobiological proteins, proteasomal activity, mitochondrial functions, apoptosis, neuroinflammation, trophic factors, stem cells, and neurogenesis. Only findings replicated in at least 2 studies were considered for these actions. Additionally, PD-related gene transcription, animal model, and human neuroprotective clinical trial data were reviewed. Results indicate that, from a PD pathobiology perspective, the safest drugs (i.e., drugs least likely to promote cellular neurodegenerative mechanisms balanced against their likelihood of promoting neuroprotective mechanisms include pramipexole, valproate, lithium, desipramine, escitalopram, and dextromethorphan. Fluoxetine favorably affects transcription of multiple genes (e.g., MAPT, GBA, CCDC62, HIP1R, although it and desipramine reduced MPTP mouse survival. Haloperidol is best avoided. The most promising neuroprotective investigative priorities will involve disease-modifying trials of the safest agents alone or in combination to capture salutary effects on H3 histone deacetylase, gene transcription, glycogen synthase kinase-3, α-synuclein, reactive oxygen species (ROS, reactive nitrogen species (RNS, apoptosis, inflammation, and trophic factors including GDNF and BDNF.

  6. First-order modal logic theorem proving and standard PROLOG

    OpenAIRE

    Nonnengart, A.

    1992-01-01

    Many attempts have been started to combine logic programming and modal logics. Most of them however, do not use classical PROLOG, but extend the PROLOG idea in order to cope with modal logic formulae directly. These approaches have the disadvantage that for each logic new logic programming systems are to be developed and the knowledge and experience gathered from PROLOG can hardly be utilized. Modal logics based on Kripke-style relational semantics, however, allow a direct translation from mo...

  7. Dual modality densitometry

    International Nuclear Information System (INIS)

    Tjugum, Stein-Arild

    2003-01-01

    Different measurement principles and design issues for gamma-ray densitometry for pipe flow are investigated. The dual modality densitometry (DMD) principle for salinity measurement and flow regime identification by multibeam densitometry are tested and verified. The measurement principles are implemented in a compact instrument design with low energy source and compact detectors. The DMD principle is experimentally verified for 3 inch and 2 inch pipes. These measurements are done on homogenous brine/gas mixtures. Both salinity independent GVF measurements and salinity measurements are obtained. The standard deviation of the salinity measurements are about 2 percent. This measurement inaccuracy is mainly caused by inhomogeneity in the liquid/gas distribution, and measurements are thus sensitive to changes in the flow regime. Models for the generation of scattered radiation are developed, and these have been used in the data-analysis and for producing special sensitivity maps for the generation of scattered radiation. The models are a useful tool for further development of the DMD principle. The work on multibeam gamma-ray densitometry has shown that flow regimes can be identified with as few as two detectors. This is verified in the flow-loop tests. Unambiguous flow regime identification will often require that the multibeam measurements are combined with other flow measurements. With a higher number of detectors more detailed information is found, and from the 9-beam measurements with the University of Bergen (UoB) gamma-ray tomography different flow regimes could clearly be identified from time series plots of the data. A laboratory prototype compact gamma-ray densitometer, the MiniGamma, has been built up and tested. Both the DMD measurement principle and the multibeam arrangement for flow regime identification are implemented in the instrument, and are successfully tested. The detector-types tested are CdZnTe semiconductor detectors, a miniature scintillation

  8. Preferential reasoning for modal logics

    CSIR Research Space (South Africa)

    Britz, K

    2011-11-01

    Full Text Available Modal logic is the foundation for a versatile and well-established class of knowledge representation formalisms in artificial intelligence. Enriching modal logics with non-monotonic reasoning capabilities such as preferential reasoning as developed...

  9. Neuroprotective effects of estrogen in CNS injuries: insights from animal models

    Directory of Open Access Journals (Sweden)

    Raghava N

    2017-07-01

    the treatment of CNS injuries due to the controversies surrounding it, the neuroprotective effects of its metabolite and derivative or combination of E2 with another therapeutic agent are showing significant impacts in animal models that can potentially shape the new treatment strategies for these CNS injuries in humans. Keywords: estrogen, neuroprotection, spinal cord injury, traumatic brain injury, ischemic brain injury

  10. Effects of auditory and visual modalities in recall of words.

    Science.gov (United States)

    Gadzella, B M; Whitehead, D A

    1975-02-01

    Ten experimental conditions were used to study the effects of auditory and visual (printed words, uncolored and colored pictures) modalities and their various combinations with college students. A recall paradigm was employed in which subjects responded in a written test. Analysis of data showed the auditory modality was superior to visual (pictures) ones but was not significantly different from visual (printed words) modality. In visual modalities, printed words were superior to colored pictures. Generally, conditions with multiple modes of representation of stimuli were significantly higher than for conditions with single modes. Multiple modalities, consisting of two or three modes, did not differ significantly from each other. It was concluded that any two modalities of the stimuli presented simultaneously were just as effective as three in recall of stimulus words.

  11. Advances of operational modal identification

    International Nuclear Information System (INIS)

    Zhang, L.

    2001-01-01

    Operational modal analysis has shown many advantages compared to the traditional one. In this paper, the development of ambient modal identification in time domain is summarized. The mathematical models for modal identification have been presented as unified framework for time domain (TD) System realization algorithms, such as polyrefence (PRCE), extended Ibrahim time domain (EITD) and eigensystem realization algorithm (ERA), etc., and recently developed Stochastic subspace technique (SST). The latest technique named as frequency domain decomposition (FDD) is introduced for operational modal identification, which has many advantages as a frequency domain (FD) technique. Applications of the operational modal analysis in civil and mechanical engineering have shown the success and accuracy of the advanced operational modal identification algorithms- FDD and SST techniques. The major issues of TD and FD operational modal identification are also discussed. (author)

  12. On modal cross-coupling in the asymptotic modal limit

    Science.gov (United States)

    Culver, Dean; Dowell, Earl

    2018-03-01

    The conditions under which significant modal cross-coupling occurs in dynamical systems responding to high-frequency, broadband forcing that excites many modes is studied. The modal overlap factor plays a key role in the analysis of these systems as the modal density (the ratio of number of modes to the frequency bandwidth) becomes large. The modal overlap factor is effectively the ratio of the width of a resonant peak (the damping ratio times the resonant frequency) to the average frequency interval between resonant peaks (or rather, the inverse of the modal density). It is shown that this parameter largely determines whether substantial modal cross-coupling occurs in a given system's response. Here, two prototypical systems are considered. The first is a simple rectangular plate whose significant modal cross-coupling is the exception rather than the norm. The second is a pair of rectangular plates attached at a point where significant modal cross-coupling is more likely to occur. We show that, for certain cases of modal density and damping, non-negligible cross coupling occurs in both systems. Under similar circumstances, the constraint force between the two plates in the latter system becomes broadband. The implications of this for using Asymptotic Modal Analysis (AMA) in multi-component systems are discussed.

  13. Cerium and yttrium oxide nanoparticles are neuroprotective

    International Nuclear Information System (INIS)

    Schubert, David; Dargusch, Richard; Raitano, Joan; Chan, S.-W.

    2006-01-01

    The responses of cells exposed to nanoparticles have been studied with regard to toxicity, but very little attention has been paid to the possibility that some types of particles can protect cells from various forms of lethal stress. It is shown here that nanoparticles composed of cerium oxide or yttrium oxide protect nerve cells from oxidative stress and that the neuroprotection is independent of particle size. The ceria and yttria nanoparticles act as direct antioxidants to limit the amount of reactive oxygen species required to kill the cells. It follows that this group of nanoparticles could be used to modulate oxidative stress in biological systems

  14. Effects of dimethyl fumarate on neuroprotection and immunomodulation

    Directory of Open Access Journals (Sweden)

    Albrecht Philipp

    2012-07-01

    Full Text Available Abstract Background Neuronal degeneration in multiple sclerosis has been linked to oxidative stress. Dimethyl fumarate is a promising novel oral therapeutic option shown to reduce disease activity and progression in patients with relapsing-remitting multiple sclerosis. These effects are presumed to originate from a combination of immunomodulatory and neuroprotective mechanisms. We aimed to clarify whether neuroprotective concentrations of dimethyl fumarate have immunomodulatory effects. Findings We determined time- and concentration-dependent effects of dimethyl fumarate and its metabolite monomethyl fumarate on viability in a model of endogenous neuronal oxidative stress and clarified the mechanism of action by quantitating cellular glutathione content and recycling, nuclear translocation of transcription factors, and the expression of antioxidant genes. We compared this with changes in the cytokine profiles released by stimulated splenocytes measured by ELISPOT technology and analyzed the interactions between neuronal and immune cells and neuronal function and viability in cell death assays and multi-electrode arrays. Our observations show that dimethyl fumarate causes short-lived oxidative stress, which leads to increased levels and nuclear localization of the transcription factor nuclear factor erythroid 2-related factor 2 and a subsequent increase in glutathione synthesis and recycling in neuronal cells. Concentrations that were cytoprotective in neuronal cells had no negative effects on viability of splenocytes but suppressed the production of proinflammatory cytokines in cultures from C57BL/6 and SJL mice and had no effects on neuronal activity in multi-electrode arrays. Conclusions These results suggest that immunomodulatory concentrations of dimethyl fumarate can reduce oxidative stress without altering neuronal network activity.

  15. Short-Term Memory in Mathematics-Proficient and Mathematics-Disabled Students as a Function of Input-Modality/Output-Modality Pairings.

    Science.gov (United States)

    Webster, Raymond E.

    1980-01-01

    A significant two-way input modality by output modality interaction suggested that short term memory capacity among the groups differed as a function of the modality used to present the items in combination with the output response required. (Author/CL)

  16. Clinical trials for neuroprotection in ALS.

    Science.gov (United States)

    Siciliano, G; Carlesi, C; Pasquali, L; Piazza, S; Pietracupa, S; Fornai, F; Ruggieri, S; Murri, L

    2010-07-01

    Owing to uncertainty on the pathogenic mechanisms underlying motor neuron degeneration in amyotrophic lateral sclerosis (ALS) riluzole remains the only available therapy, with only marginal effects on disease survival. Here we review some of the recent advances in the search for disease-modifying drugs for ALS based on their putative neuroprotective effetcs. A number of more or less established agents have recently been investigated also in ALS for their potential role in neuroprotection and relying on antiglutamatergic, antioxidant or antiapoptotic strategies. Among them Talampanel, beta-lactam antibiotics, Coenzyme Q10, and minocycline have been investigated. Progress has also been made in exploiting growth factors for the treatment of ALS, partly due to advances in developing effective delivery systems to the central nervous system. A number of new therapies have also been identified, including a novel class of compounds, such as heat-shock protein co-inducers, which upregulate cell stress responses, and agents promoting autophagy and mitochondriogenesis, such as lithium and rapamycin. More recently, alterations of mRNA processing were described as a pathogenic mechanism in genetically defined forms of ALS, as those related to TDP-43 and FUS-TLS gene mutations. This knowledge is expected to improve our understanding of the pathogenetic mechanism in ALS and developing more effective therapies.

  17. Nutraceutical Antioxidants as Novel Neuroprotective Agents

    Directory of Open Access Journals (Sweden)

    Daniel A. Linseman

    2010-11-01

    Full Text Available A variety of antioxidant compounds derived from natural products (nutraceuticals have demonstrated neuroprotective activity in either in vitro or in vivo models of neuronal cell death or neurodegeneration, respectively. These natural antioxidants fall into several distinct groups based on their chemical structures: (1 flavonoid polyphenols like epigallocatechin 3-gallate (EGCG from green tea and quercetin from apples; (2 non-flavonoid polyphenols such as curcumin from tumeric and resveratrol from grapes; (3 phenolic acids or phenolic diterpenes such as rosmarinic acid or carnosic acid, respectively, both from rosemary; and (4 organosulfur compounds including the isothiocyanate, L-sulforaphane, from broccoli and the thiosulfonate allicin, from garlic. All of these compounds are generally considered to be antioxidants. They may be classified this way either because they directly scavenge free radicals or they indirectly increase endogenous cellular antioxidant defenses, for example, via activation of the nuclear factor erythroid-derived 2-related factor 2 (Nrf2 transcription factor pathway. Alternative mechanisms of action have also been suggested for the neuroprotective effects of these compounds such as modulation of signal transduction cascades or effects on gene expression. Here, we review the literature pertaining to these various classes of nutraceutical antioxidants and discuss their potential therapeutic value in neurodegenerative diseases.

  18. Metaphysical Modality, Modality of Predicate and the Theory of

    Directory of Open Access Journals (Sweden)

    l nabavi

    2010-05-01

    This paper discusses the historical overview of the metaphysical modality firstly and then shows that the theory of "Decisive Necessity” is true and justified in a model of modal logic with equivalent accessibility relation and homogeneous possible world view (fixed domain.

  19. Treatment modalities of palatal impacted canines

    OpenAIRE

    Dimova, Cena; Papakoca, Kiro; Ristoska, Sonja; Kovacevska, Ivona

    2012-01-01

    Introduction: The orthodontic treatment of impacted maxillary canine remains a challenge to today’s clinicians. The treatment of this clinical entity usually involves surgical exposure of the impacted tooth, followed by orthodontic traction to guide and align it into the dental arch. The impacted palatal canine requires a combination of both treatment modalities: orthodontic management and oral surgical treatment. Two types of approach are commonly used: simple exposure, or exposure with brac...

  20. Brain aromatase: roles in reproduction and neuroprotection.

    Science.gov (United States)

    Roselli, Charles F

    2007-01-01

    It is well established that aromatization constitutes an essential part of testosterone's signaling pathway in brain and that estrogen metabolites, often together with testosterone, organize and activate masculine neural circuits. This paper summarizes the current understanding regarding the distribution, regulation and function of brain aromatase in mammals. Data from our laboratory are presented that highlight the important function of aromatase in the regulation of androgen feedback sensitivity in non-human primates and the possible role that aromatase plays in determining the brain structure and sexual partner preferences of rams. In addition, new data is presented indicating that the capacity for aromatization in cortical astrocytes is associated with cell survival and may be important for neuroprotection. It is anticipated that a better appreciation of the physiological and pathophysiological functions of aromatase will lead to important clinical insights.

  1. Therapeutic neuroprotective agents for amyotrophic lateral sclerosis

    Science.gov (United States)

    Pandya, Rachna S.; Zhu, Haining; Li, Wei; Bowser, Robert; Friedlander, Robert M.

    2014-01-01

    Amyotrophic lateral sclerosis (ALS) is a fatal chronic neurodegenerative disease whose hallmark is proteinaceous, ubiquitinated, cytoplasmic inclusions in motor neurons and surrounding cells. Multiple mechanisms proposed as responsible for ALS pathogenesis include dysfunction of protein degradation, glutamate excitotoxicity, mitochondrial dysfunction, apoptosis, oxidative stress, and inflammation. It is therefore essential to gain a better understanding of the underlying disease etiology and search for neuroprotective agents that might delay disease onset, slow progression, prolong survival, and ultimately reduce the burden of disease. Because riluzole, the only Food and Drug Administration (FDA)-approved treatment, prolongs the ALS patient’s life by only 3 months, new therapeutic agents are urgently needed. In this review, we focus on studies of various small pharmacological compounds targeting the proposed pathogenic mechanisms of ALS and discuss their impact on disease progression. PMID:23864030

  2. The emerging role of retromer in neuroprotection.

    Science.gov (United States)

    McMillan, Kirsty J; Korswagen, Hendrick C; Cullen, Peter J

    2017-08-01

    Efficient sorting and transportation of integral membrane proteins, such as ion channels, nutrient transporters, signalling receptors, cell-cell and cell-matrix adhesion molecules is essential for the function of cellular organelles and hence organism development and physiology. Retromer is a master controller of integral membrane protein sorting and transport through one of the major sorting station within eukaryotic cells, the endosomal network. Subtle de-regulation of retromer is an emerging theme in the pathoetiology of Parkinson's disease. Here we summarise recent advances in defining the neuroprotective role of retromer and how its de-regulation may contribute to Parkinson's disease by interfering with: lysosomal health and protein degradation, association with accessory proteins including the WASH complex and mitochondrial health. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  3. Anesthetic Preconditioning as Endogenous Neuroprotection in Glaucoma

    Directory of Open Access Journals (Sweden)

    Tsung-Han Chou

    2018-01-01

    Full Text Available Blindness in glaucoma is the result of death of Retinal Ganglion Cells (RGCs and their axons. RGC death is generally preceded by a stage of reversible dysfunction and structural remodeling. Current treatments aimed at reducing intraocular pressure (IOP are ineffective or incompletely effective in management of the disease. IOP-independent neuroprotection or neuroprotection as adjuvant to IOP lowering in glaucoma remains a challenge as effective agents without side effects have not been identified yet. We show in DBA/2J mice with spontaneous IOP elevation and glaucoma that the lifespan of functional RGCs can be extended by preconditioning RGCs with retrobulbar lidocaine in one eye at four months of age that temporary blocks RGC axonal transport. The contralateral, PBS-injected eye served as control. Lidocaine-induced impairment of axonal transport to superior colliculi was assessed by intravitreal injection of cholera toxin B. Long-term (nine months effect of lidocaine were assessed on RGC electrical responsiveness (PERG, IOP, expression of relevant protein (BDNF, TrkB, PSD95, GFAP, Synaptophysin, and GAPDH and RGC density. While lidocaine treatment did not alter the age-related increase of IOP, TrkB expression was elevated, GFAP expression was decreased, RGC survival was improved by 35%, and PERG function was preserved. Results suggest that the lifespan of functional RGCs in mouse glaucoma can be extended by preconditioning RGCs in early stages of the disease using a minimally invasive treatment with retrobulbar lidocaine, a common ophthalmologic procedure. Lidocaine is inexpensive, safe and is approved by Food and Drug Administration (FDA to be administered intravenously.

  4. On Modal Refinement and Consistency

    DEFF Research Database (Denmark)

    Nyman, Ulrik; Larsen, Kim Guldstrand; Wasowski, Andrzej

    2007-01-01

    Almost 20 years after the original conception, we revisit several fundamental question about modal transition systems. First, we demonstrate the incompleteness of the standard modal refinement using a counterexample due to Hüttel. Deciding any refinement, complete with respect to the standard...

  5. Krull dimension in modal logic

    NARCIS (Netherlands)

    Bezhanishvili, G.; Bezhanishvili, N.; Lucero-Bryan, J.; van Mill, J.

    2017-01-01

    We develop the theory of Krull dimension for S4-algebras and Heyting algebras. This leads to the concept of modal Krull dimension for topological spaces. We compare modal Krull dimension to other well-known dimension functions, and show that it can detect differences between topological spaces that

  6. Modal Logics for Cryptographic Processes

    DEFF Research Database (Denmark)

    Frendrup, U.; Huttel, Hans; Jensen, N. J.

    2002-01-01

    We present three modal logics for the spi-calculus and show that they capture strong versions of the environment sensitive bisimulation introduced by Boreale et al. Our logics differ from conventional modal logics for process calculi in that they allow us to describe the knowledge of an attacker ...

  7. Load Estimation from Modal Parameters

    DEFF Research Database (Denmark)

    Aenlle, Manuel López; Brincker, Rune; Fernández, Pelayo Fernández

    2007-01-01

    In Natural Input Modal Analysis the modal parameters are estimated just from the responses while the loading is not recorded. However, engineers are sometimes interested in knowing some features of the loading acting on a structure. In this paper, a procedure to determine the loading from a FRF m...

  8. Neuroprotection for treatment of glaucoma in adults.

    Science.gov (United States)

    Sena, Dayse F; Lindsley, Kristina

    2017-01-25

    Glaucoma is a heterogeneous group of conditions involving progressive damage to the optic nerve, deterioration of retinal ganglion cells, and ultimately visual field loss. It is a leading cause of blindness worldwide. Open angle glaucoma (OAG), the most common form of glaucoma, is a chronic condition that may or may not present with increased intraocular pressure (IOP). Neuroprotection for glaucoma refers to any intervention intended to prevent optic nerve damage or cell death. The objective of this review was to systematically examine the evidence regarding the effectiveness of neuroprotective agents for slowing the progression of OAG in adults compared with no neuroprotective agent, placebo, or other glaucoma treatment. We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2016, Issue 7), Ovid MEDLINE, Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Ovid MEDLINE Daily (January 1946 to August 2016), Embase (January 1980 to August 2016), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to August 2016), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov), and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 16 August 2016. We included randomised controlled trials (RCTs) in which topical or oral treatments were used for neuroprotection in adults with OAG. Minimum follow-up time was four years. Two review authors independently reviewed titles and abstracts from the literature searches. We obtained full-text copies of potentially relevant studies and re-evaluated for inclusion. Two review authors independently extracted data related to study characteristics, risk of bias, and outcomes. We identified one trial for this review, thus we

  9. Differential effects of synthetic progestagens on neuron survival and estrogen neuroprotection in cultured neurons.

    Science.gov (United States)

    Jayaraman, Anusha; Pike, Christian J

    2014-03-25

    Progesterone and other progestagens are used in combination with estrogens for clinical purposes, including contraception and postmenopausal hormone therapy. Progesterone and estrogens have interactive effects in brain, however interactions between synthetic progestagens and 17β-estradiol (E2) in neurons are not well understood. In this study, we investigated the effects of seven clinically relevant progestagens on estrogen receptor (ER) mRNA expression, E2-induced neuroprotection, and E2-induced BDNF mRNA expression. We found that medroxyprogesterone acetate decreased both ERα and ERβ expression and blocked E2-mediated neuroprotection and BDNF expression. Conversely, levonorgestrel and nesterone increased ERα and or ERβ expression, were neuroprotective, and failed to attenuate E2-mediated increases in neuron survival and BDNF expression. Other progestagens tested, including norethindrone, norethindrone acetate, norethynodrel, and norgestimate, had variable effects on the measured endpoints. Our results demonstrate a range of qualitatively different actions of progestagens in cultured neurons, suggesting significant variability in the neural effects of clinically utilized progestagens. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  10. Bumetanide augments the neuroprotective efficacy of phenobarbital plus hypothermia in a neonatal hypoxia-ischemia model

    Science.gov (United States)

    Liu, YiQing; Shangguan, Yu; Barks, John D.E.; Silverstein, Faye S.

    2014-01-01

    The NaKCl cotransporter NKCC1 facilitates intraneuronal chloride accumulation in the developing brain. Bumetanide, a clinically available diuretic, inhibits this chloride transporter, and augments the antiepileptic effects of phenobarbital in neonatal rodents. In a neonatal cerebral hypoxia-ischemia (HI) model, elicited by right carotid ligation, followed by 90 min 8% O2 exposure in 7-day-old(P7) rats, phenobarbital(PB) increases the neuroprotective efficacy of hypothermia. We evaluated whether bumetanide influenced the neuroprotective efficacy of combination treatment with PB and hypothermia(HT). P7 rats underwent HI lesioning; 15 min later, all received PB (30 mg/kg). 10 min later, half received bumetanide (10 mg/kg, PB-HT+BUM) and half received saline (PB-HT+SAL). One hour after HI, all were cooled (30°C, 3h). Contralateral forepaw sensorimotor function and brain damage were evaluated 1 to 4 weeks later. Forepaw functional measures were close to normal in the PB-HT+BUM group, while deficits persisted in PB-HT+SAL controls; there were corresponding reductions in right cerebral hemisphere damage (at P35, % damage: PB-HT+BUM, 21±16 versus 38±20 in controls). These results provide evidence that NKCC1 inhibition amplifies phenobarbital bioactivity in the immature brain, and suggest that co-administration of phenobarbital and bumetanide may represent a clinically feasible therapy to augment the neuroprotective efficacy of therapeutic hypothermia in asphyxiated neonates. PMID:22398701

  11. Neuroprotection against oxidative stress by serum from heat acclimated rats.

    Science.gov (United States)

    Beit-Yannai, E; Trembovler, V; Horowitz, M; Lazarovici, P; Kohen, R; Shohami, E

    1998-09-25

    Exposure of PC12 cells, to 1% serum derived from normothermic (CON) rats resulted in 79% cell death. Sister cultures treated with 1% serum derived from heat acclimated (ACC) rats, were neuroprotected and expressed a significant reduction in cell death. In PC12 cells exposed to a free radical generator causing an oxidative stress, 90% cell death was measured in CON serum treated cultures, while ACC serum treated cultures were neuroprotected. Xanthine oxidase activity and uric acid (UA) levels were lower in ACC serum compared to CON. Addition of UA to both sera abolished the difference in cell viability, and toxicity of ACC serum reached that of CON. These findings suggest a causal relationship between the lower levels of UA in ACC and the neuroprotective effect observed. The present study proposes heat acclimation as an experimental and/or clinical tool for the achievement of neuroprotection.

  12. Neuroprotective Treatment of Laser-Induced Retinal Injuries

    National Research Council Canada - National Science Library

    Rosner, Mordechai

    2001-01-01

    .... It is not possible to prevent all these injuries and there is no treatment. This study was designed to evaluate the neuroprotective effect of dextromethorphan, memantine and brimonidine in our rat model of laser- induced retinal-lesions Methods...

  13. Neuroprotection as initial therapy in acute stroke. Third Report of an Ad Hoc Consensus Group Meeting. The European Ad Hoc Consensus Group.

    Science.gov (United States)

    1998-01-01

    treatment of acute stroke should aim to maintain these physiological variables as close to normal as possible, and certainly within strictly defined limits. THE PLACE OF NEUROPROTECTANTS IN ACUTE STROKE MANAGEMENT: Stroke patients are a very heterogeneous group with respect to stroke mechanisms and severity, general condition, age and co-morbidities. At the present time, the only firm guideline than can be proposed for patient selection is the need for early admission to enable neuroprotectant and/or thrombolytic treatment to be started as soon as possible within the therapeutic window. The severity of potential side-effects will largely determine who should assess a patient with suspected stroke and initiate treatment. There is little information on which to base the duration of neuroprotectant therapy, and more experimental data are needed. Even if prehospital treatment proves to be feasible, it should not replace comprehensive stroke management in a specialist hospital unit. Clinical trials of neuroprotectants should only be performed in stroke units. The combined approach of restoring blood flow and providing neuroprotection may be the most productive in human stroke, but current clinical trial design will have to change in order to test combination therapy. Important side-effects are those that interfere with any possible benefit or increase mortality. PHARMACO-ECONOMIC ASPECTS OF NEUROPROTECTANTS: The early increase in hospital cost associated with neuroprotectant therapy may be balanced by the shorter length of hospital stay and lesser degree of disability of the surviving patients. The overall direct financial cost is highly dependent on the number of patients eligible for neuroprotectant therapy, which is itself dependent on the length of the therapeutic window and the severity of potential side-effects. A treatment that achieves a good functional outcome is the most cost-effective approach.

  14. Neuroprotective Drug for Nerve Trauma Revealed Using Artificial Intelligence

    OpenAIRE

    Romeo-Guitart, David; Forés, Joaquim; Herrando-Grabulosa, Mireia; Valls, Raquel; Leiva-Rodríguez, Tatiana; Galea, Elena; González-Pérez, Francisco; Navarro, Xavier; Petegnief, Valerie; Bosch, Assumpció; Coma, Mireia; Mas, José Manuel; Casas, Caty

    2018-01-01

    Here we used a systems biology approach and artificial intelligence to identify a neuroprotective agent for the treatment of peripheral nerve root avulsion. Based on accumulated knowledge of the neurodegenerative and neuroprotective processes that occur in motoneurons after root avulsion, we built up protein networks and converted them into mathematical models. Unbiased proteomic data from our preclinical models were used for machine learning algorithms and for restrictions to be imposed on m...

  15. Operational Modal Analysis of the Cablestayed Footbridge

    Directory of Open Access Journals (Sweden)

    Kortiš Ján

    2017-12-01

    Full Text Available Modern architecture leads to design subtle bridge structures that are more sensitive to increased dynamic loading than the massive ones. This phenomenon can be especially observed on lightweight steel structures such as suspended footbridges. As a result, it is necessary to know precisely its dynamic characteristics, such as natural frequencies, natural shapes and damping of construction. This information can be used for further analysis such as damage detection, system identification, health monitoring, etc. or also for the design of new types of construction. For this purpose, classical modal analysis using trigger load or harmonic vibration exciter in combination with acceleration sensors is used in practice. However, there are many situations where it is not possible to stop the traffic or operation of the bridge. The article presents an experimental measurement of the dynamic parameters of the structure at the operating load using the operational modal analysis.

  16. Operational Modal Analysis of the Cablestayed Footbridge

    Science.gov (United States)

    Kortiš, Ján; Daniel, Ľuboš; Farbák, Matúš; Maliar, Lukáš; Škarupa, Milan

    2017-12-01

    Modern architecture leads to design subtle bridge structures that are more sensitive to increased dynamic loading than the massive ones. This phenomenon can be especially observed on lightweight steel structures such as suspended footbridges. As a result, it is necessary to know precisely its dynamic characteristics, such as natural frequencies, natural shapes and damping of construction. This information can be used for further analysis such as damage detection, system identification, health monitoring, etc. or also for the design of new types of construction. For this purpose, classical modal analysis using trigger load or harmonic vibration exciter in combination with acceleration sensors is used in practice. However, there are many situations where it is not possible to stop the traffic or operation of the bridge. The article presents an experimental measurement of the dynamic parameters of the structure at the operating load using the operational modal analysis.

  17. Small Molecule Anticonvulsant Agents with Potent In Vitro Neuroprotection

    Science.gov (United States)

    Smith, Garry R.; Zhang, Yan; Du, Yanming; Kondaveeti, Sandeep K.; Zdilla, Michael J.; Reitz, Allen B.

    2012-01-01

    Severe seizure activity is associated with recurring cycles of excitotoxicity and oxidative stress that result in progressive neuronal damage and death. Intervention to halt these pathological processes is a compelling disease-modifying strategy for the treatment of seizure disorders. In the present study, a core small molecule with anticonvulsant activity has been structurally optimized for neuroprotection. Phenotypic screening of rat hippocampal cultures with nutrient medium depleted of antioxidants was utilized as a disease model. Increased cell death and decreased neuronal viability produced by acute treatment with glutamate or hydrogen peroxide were prevented by our novel molecules. The neuroprotection associated with this chemical series has marked structure activity relationships that focus on modification of the benzylic position of a 2-phenyl-2-hydroxyethyl sulfamide core structure. Complete separation between anticonvulsant activity and neuroprotective action was dependent on substitution at the benzylic carbon. Chiral selectivity was evident in that the S-enantiomer of the benzylic hydroxy group had neither neuroprotective nor anticonvulsant activity, while the R-enantiomer of the lead compound had full neuroprotective action at ≤40 nM and antiseizure activity in three animal models. These studies indicate that potent, multifunctional neuroprotective anticonvulsants are feasible within a single molecular entity. PMID:22535312

  18. Neuroprotective potential of high-dose biotin.

    Science.gov (United States)

    McCarty, Mark F; DiNicolantonio, James J

    2017-11-01

    A recent controlled trial has established that high-dose biotin supplementation - 100 mg, three times daily - has a stabilizing effect on progression of multiple sclerosis (MS). Although this effect has been attributed to an optimization of biotin's essential cofactor role in the brain, a case can be made that direct stimulation of soluble guanylate cyclase (sGC) by pharmacological concentrations of biotin plays a key role in this regard. The utility of high-dose biotin in MS might reflect an anti-inflammatory effect of cGMP on the cerebral microvasculature, as well on oligodendrocyte differentiation and on Schwann cell production of neurotrophic factors thought to have potential for managing MS. But biotin's ability to boost cGMP synthesis in the brain may have broader neuroprotective potential. In many types of neurons and neural cells, cGMP exerts neurotrophic-mimetic effects - entailing activation of the PI3K-Akt and Ras-ERK pathways - that promote neuron survival and plasticity. Hippocampal long term potentiation requires nitric oxide synthesis, which in turn promotes an activating phosphorylation of CREB via a pathway involving cGMP and protein kinase G (PKG). In Alzheimer's disease (AD), amyloid beta suppresses this mechanism by inhibiting sGC activity; agents which exert a countervailing effect by boosting cGMP levels tend to restore effective long-term potentiation in rodent models of AD. Moreover, NO/cGMP suppresses amyloid beta production within the brain by inhibiting expression of amyloid precursor protein and BACE1. In conjunction with cGMP's ability to oppose neuron apoptosis, these effects suggest that high-dose biotin might have potential for the prevention and management of AD. cGMP also promotes neurogenesis, and may lessen stroke risk by impeding atherogenesis and hypertrophic remodeling in the cerebral vasculature. The neuroprotective potential of high-dose biotin likely could be boosted by concurrent administration of brain

  19. Mobile Education: Towards Affective Bi-modal Interaction for Adaptivity

    Directory of Open Access Journals (Sweden)

    Efthymios Alepis

    2009-04-01

    Full Text Available One important field where mobile technology can make significant contributions is education. However one criticism in mobile education is that students receive impersonal teaching. Affective computing may give a solution to this problem. In this paper we describe an affective bi-modal educational system for mobile devices. In our research we describe a novel approach of combining information from two modalities namely the keyboard and the microphone through a multi-criteria decision making theory.

  20. Distributed Graphs for Solving Co-modal Transport Problems

    OpenAIRE

    Karama , Jeribi; Hinda , Mejri; Hayfa , Zgaya; Slim , Hammadi

    2011-01-01

    International audience; The paper presents a new approach based on a special distributed graphs in order to solve co-modal transport problems. The co-modal transport system consists on combining different transport modes effectively in terms of economic, environmental, service and financial efficiency, etc. However, the problem is that these systems must deal with different distributed information sources stored in different locations and provided by different public and private companies. In...

  1. Many-dimensional modal logics theory and applications

    CERN Document Server

    Gabbay, D M; Wolter, F; Zakharyaschev, M

    2003-01-01

    Modal logics, originally conceived in philosophy, have recently found many applications in computer science, artificial intelligence, the foundations of mathematics, linguistics and other disciplines. Celebrated for their good computational behaviour, modal logics are used as effective formalisms for talking about time, space, knowledge, beliefs, actions, obligations, provability, etc. However, the nice computational properties can drastically change if we combine some of these formalisms into a many-dimensional system, say, to reason about knowledge bases developing in time or moving objects.

  2. A Causal Theory of Modality

    Directory of Open Access Journals (Sweden)

    José Tomás Alvarado

    2009-08-01

    Full Text Available This work presents a causal conception of metaphysical modality in which a state of affairs is metaphysically possible if and only if it can be caused (in the past, the present or the future by current entities. The conception is contrasted with what is called the “combinatorial” conception of modality, in which everything can co-exist with anything else. This work explains how the notion of ‘causality’ should be construed in the causal theory, what difference exists between modalities thus defined from nomological modality, how accessibility relations between possible worlds should be interpreted, and what is the relation between the causal conception and the necessity of origin.

  3. Blood Glutamate Scavenging: Insight into Neuroprotection

    Directory of Open Access Journals (Sweden)

    Alexander Zlotnik

    2012-08-01

    Full Text Available Brain insults are characterized by a multitude of complex processes, of which glutamate release plays a major role. Deleterious excess of glutamate in the brain’s extracellular fluids stimulates glutamate receptors, which in turn lead to cell swelling, apoptosis, and neuronal death. These exacerbate neurological outcome. Approaches aimed at antagonizing the astrocytic and glial glutamate receptors have failed to demonstrate clinical benefit. Alternatively, eliminating excess glutamate from brain interstitial fluids by making use of the naturally occurring brain-to-blood glutamate efflux has been shown to be effective in various animal studies. This is facilitated by gradient driven transport across brain capillary endothelial glutamate transporters. Blood glutamate scavengers enhance this naturally occurring mechanism by reducing the blood glutamate concentration, thus increasing the rate at which excess glutamate is cleared. Blood glutamate scavenging is achieved by several mechanisms including: catalyzation of the enzymatic process involved in glutamate metabolism, redistribution of glutamate into tissue, and acute stress response. Regardless of the mechanism involved, decreased blood glutamate concentration is associated with improved neurological outcome. This review focuses on the physiological, mechanistic and clinical roles of blood glutamate scavenging, particularly in the context of acute and chronic CNS injury. We discuss the details of brain-to-blood glutamate efflux, auto-regulation mechanisms of blood glutamate, natural and exogenous blood glutamate scavenging systems, and redistribution of glutamate. We then propose different applied methodologies to reduce blood and brain glutamate concentrations and discuss the neuroprotective role of blood glutamate scavenging.

  4. The research progress of dual-modality probes for molecular imaging

    International Nuclear Information System (INIS)

    Cao Feng; Chen Yue

    2010-01-01

    Various imaging modalities have been exploited to investigate the anatomic or functional dissemination of tissues in the body. However, no single imaging modality allows overall structural, functional, and molecular information as each imaging modality has its own unique strengths and weaknesses. The combination of two imaging modalities that investigates the strengths of different methods might offer the prospect of improved diagnostic abilities. As more and more dual-modality imaging system have become clinically adopted, significant progress has been made toward the creation of dual-modality imaging probes, which can be used as novel tools for future multimodality systems. These all-in-one probes take full advantage of two different imaging modalities and could provide comprehensive information for clinical diagnostics. This review discusses the advantages and challenges in developing dual-modality imaging probes. (authors)

  5. Integration of Multi-Modal Biomedical Data to Predict Cancer Grade and Patient Survival.

    Science.gov (United States)

    Phan, John H; Hoffman, Ryan; Kothari, Sonal; Wu, Po-Yen; Wang, May D

    2016-02-01

    The Big Data era in Biomedical research has resulted in large-cohort data repositories such as The Cancer Genome Atlas (TCGA). These repositories routinely contain hundreds of matched patient samples for genomic, proteomic, imaging, and clinical data modalities, enabling holistic and multi-modal integrative analysis of human disease. Using TCGA renal and ovarian cancer data, we conducted a novel investigation of multi-modal data integration by combining histopathological image and RNA-seq data. We compared the performances of two integrative prediction methods: majority vote and stacked generalization. Results indicate that integration of multiple data modalities improves prediction of cancer grade and outcome. Specifically, stacked generalization, a method that integrates multiple data modalities to produce a single prediction result, outperforms both single-data-modality prediction and majority vote. Moreover, stacked generalization reveals the contribution of each data modality (and specific features within each data modality) to the final prediction result and may provide biological insights to explain prediction performance.

  6. Quantitative multi-modal NDT data analysis

    International Nuclear Information System (INIS)

    Heideklang, René; Shokouhi, Parisa

    2014-01-01

    A single NDT technique is often not adequate to provide assessments about the integrity of test objects with the required coverage or accuracy. In such situations, it is often resorted to multi-modal testing, where complementary and overlapping information from different NDT techniques are combined for a more comprehensive evaluation. Multi-modal material and defect characterization is an interesting task which involves several diverse fields of research, including signal and image processing, statistics and data mining. The fusion of different modalities may improve quantitative nondestructive evaluation by effectively exploiting the augmented set of multi-sensor information about the material. It is the redundant information in particular, whose quantification is expected to lead to increased reliability and robustness of the inspection results. There are different systematic approaches to data fusion, each with its specific advantages and drawbacks. In our contribution, these will be discussed in the context of nondestructive materials testing. A practical study adopting a high-level scheme for the fusion of Eddy Current, GMR and Thermography measurements on a reference metallic specimen with built-in grooves will be presented. Results show that fusion is able to outperform the best single sensor regarding detection specificity, while retaining the same level of sensitivity

  7. Edaravone offers neuroprotection for acute diabetic stroke patients.

    Science.gov (United States)

    Zheng, J; Chen, X

    2016-11-01

    Edaravone, a novel free-radical scavenger, has been shown to alleviate cerebral ischemic injury and protect against vascular endothelial dysfunction. However, the effects of edaravone in acute diabetic stroke patients remain undetermined. A randomized, double-blind, placebo-controlled study was performed to prospectively evaluate the effects of edaravone on acute diabetic stroke patients admitted to our hospital within 24 h of stroke onset. The edaravone group received edaravone (30 mg twice per day) diluted with 100 ml of saline combined with antiplatelet drug aspirin and atorvastatin for 14 days. The non-edaravone group was treated only with 100 ml of saline twice per day combined with aspirin and atorvastatin. Upon admission, and on days 7, 14 post-stroke onset, neurological deficits and activities of daily living were assessed using the National Institutes of Health Stroke Scale (NIHSS) and the Barthel Index (BI), respectively. The occurrence of hemorrhage transformation, pulmonary infection, progressive stroke and epilepsy was also evaluated on day 14 post-treatment. A total of 65 consecutive acute diabetic stroke patients were enrolled, of whom 35 were allocated to the edaravone group and 30 to the non-edaravone group. There was no significant group difference in baseline clinical characteristics, but mean NIHSS scores were lower (60 %), and BI scores were 1.7-fold higher, in edaravone-treated patients vs. controls on day 14. Furthermore, the incidence of hemorrhage transformation, pulmonary infection, progressive stroke and epilepsy was markedly reduced in the edaravone vs. non-edaravone group. Edaravone represents a promising neuroprotectant against cerebral ischemic injury in diabetic patients.

  8. Neuroprotección en la encefalopatia hipóxico isquémica perinatal: Tratamientos con eficacia clínica demostrada y perspectivas futuras Neuroprotection in perinatal hypoxic-ischemic encephalopathy: Effective treatment and future perspectives

    Directory of Open Access Journals (Sweden)

    Agustín Legido

    2007-01-01

    present the future perspectives of other clinical and basic research investigations. Therapies with demonstrated clinical efficacy: Allopurinol: It blocks the production of free radicals following hypoxia-ischemia. In a recent study, infants with hypoplastic left heart syndrome treated with allopurinol, but not those with other congenital cardiopathies, had significantly less number of complications than controls, including death, seizures, coma or cardiac events. Opioids: In another recent study, newborns with HIE treated with morphine or phentanyl, had less severe brain damage on MRI and a better neurological outcome. Hypothermia: Both local (head cooling or systemic (whole body hypothermia have a neuroprotective effect in selected newborns with HIE, Future perspectives: Antiepileptic drugs. They have multiple mechanisms of action that can block the biochemical cascade of neuronal damage in HIE. Other therapeutic modalities. Among them the following should be emphasized: combined neuroprotective treatments, growth factors, genetic therapies, stem cell transplant, and neuroprotective immunization. In conclusión, a better knowledge of the molecular mechanisms of HIE pathogenesis and better clinical studies of neuroprotective therapies will open new possibilities aplicable to clinical practice. These advances will undoubtedly improve the prognosis of newborns with HIE.

  9. Neurodegeneration and Neuroprotection in Diabetic Retinopathy

    Directory of Open Access Journals (Sweden)

    Abdullah S. Alhomida

    2013-01-01

    Full Text Available Diabetic retinopathy is widely considered to be a neurovascular disease. This is in contrast to its previous identity as solely a vascular disease. Early in the disease progression of diabetes, the major cells in the neuronal component of the retina consist of retinal ganglion cells and glial cells, both of which have been found to be compromised. A number of retinal function tests also indicated a functional deficit in diabetic retina, which further supports dysfunction of neuronal cells. As an endocrinological disorder, diabetes alters metabolism both systemically and locally in several body organs, including the retina. A growing body of evidences indicates increased levels of excitotoxic metabolites, including glutamate, branched chain amino acids and homocysteine in cases of diabetic retinopathy. Also present, early in the disease, are decreased levels of folic acid and vitamin-B12, which are potential metabolites capable of damaging neurons. These altered levels of metabolites are found to activate several metabolic pathways, leading to increases in oxidative stress and decreases in the level of neurotrophic factors. As a consequence, they may damage retinal neurons in diabetic patients. In this review, we have discussed those potential excitotoxic metabolites and their implications in neuronal damage. Possible therapeutic targets to protect neurons are also discussed. However, further research is needed to understand the exact molecular mechanism of neurodegeneration so that effective neuroprotection strategies can be developed. By protecting retinal neurons early in diabetic retinopathy cases, damage of retinal vessels can be protected, thereby helping to ameliorate the progression of diabetic retinopathy, a leading cause of blindness worldwide.

  10. CM-2 Environmental/Modal Testing of SPACEHAB Racks

    Science.gov (United States)

    McNelis, Mark E.; Goodnight, Thomas W.

    2001-01-01

    Combined environmental/modal vibration testing has been implemented at the NASA Glenn Research Center's Structural Dynamics Laboratory. The benefits of combined vibration testing are that it facilitates test article modal characterization and vibration qualification testing. The Combustion Module-2 (CM-2) is a space experiment that will launch on shuttle mission STS-107 in the SPACEHAB Research Double Module. The CM-2 flight hardware is integrated into a SPACEHAB single and double rack. CM-2 rack-level combined vibration testing was recently completed on a shaker table to characterize the structure's modal response and verify the random vibration response. Control accelerometers and limit force gauges, located between the fixture and rack interface, were used to verify the input excitation. Results of the testing were used to verify the loads and environments for flight on the shuttles.

  11. Medical management of Parkinson's disease: focus on neuroprotection.

    Science.gov (United States)

    Boll, Marie-Catherine; Alcaraz-Zubeldia, Mireya; Rios, Camilo

    2011-06-01

    Neuroprotection refers to the protection of neurons from excitotoxicity, oxidative stress and apoptosis as principal mechanisms of cell loss in a variety of diseases of the central nervous system. Our interest in Parkinson's disease (PD) treatment is focused on drugs with neuroprotective properties in preclinical experiments and evidence-based efficacy in human subjects. To this date, neuroprotection has never been solidly proven in clinical trials but recent adequate markers and/or strategies to study and promote this important goal are described. A myriad of compounds with protective properties in cell cultures and animal models yield to few treatments in clinical practice. At present, markers of neuronal vitality, disease modifying effects and long term clinical stability are the elements searched for in clinical trials. This review highlights new strategies to monitor patients with PD. Currently, neuroprotection in subjects has not been solidly achieved for selegiline and pramipexole; however, a recent rasagiline trial design is showing new indications of disease course modifying effects. In neurological practice, it is of utmost importance to take into account the potential neuroprotection exerted by a treatment in conjunction with its symptomatic efficacy.

  12. Inhalation gases or gaseous mediators as neuroprotectants for cerebral ischaemia.

    Science.gov (United States)

    Sutherland, Brad A; Harrison, Joanne C; Nair, Shiva M; Sammut, Ivan A

    2013-01-01

    Ischaemic stroke is one of the leading causes of morbidity and mortality worldwide. While recombinant tissue plasminogen activator can be administered to produce thrombolysis and restore blood flow to the ischaemic brain, therapeutic benefit is only achieved in a fraction of the subset of patients eligible for fibrinolytic intervention. Neuroprotective therapies attempting to restrict the extent of brain injury following cerebral ischaemia have not been successfully translated into the clinic despite overwhelming pre-clinical evidence of neuroprotection. Therefore, an adequate treatment for the majority of acute ischaemic stroke patients remains elusive. In the stroke literature, the use of therapeutic gases has received relatively little attention. Gases such as hyperbaric and normobaric oxygen, xenon, hydrogen, helium and argon all possess biological effects that have shown to be neuroprotective in pre-clinical models of ischaemic stroke. There are significant advantages to using gases including their relative abundance, low cost and feasibility for administration, all of which make them ideal candidates for a translational therapy for stroke. In addition, modulating cellular gaseous mediators including nitric oxide, carbon monoxide, and hydrogen sulphide may be an attractive option for ischaemic stroke therapy. Inhalation of these gaseous mediators can also produce neuroprotection, but this strategy remains to be confirmed as a viable therapy for ischaemic stroke. This review highlights the neuroprotective potential of therapeutic gas therapy and modulation of gaseous mediators for ischaemic stroke. The therapeutic advantages of gaseous therapy offer new promising directions in breaking the translational barrier for ischaemic stroke.

  13. Neuroprotective and Cognitive Enhancement Potentials of Baicalin: A Review

    Directory of Open Access Journals (Sweden)

    Kandhasamy Sowndhararajan

    2018-06-01

    Full Text Available Neurodegenerative diseases are a heterogeneous group of disorders that are characterized by the gradual loss of neurons. The development of effective neuroprotective agents to prevent and control neurodegenerative diseases is specifically important. Recently, there has been an increasing interest in selecting flavonoid compounds as potential neuroprotective agents, owing to their high effectiveness with low side effects. Baicalin is one of the important flavonoid compounds, which is mainly isolated from the root of Scutellaria baicalensis Georgi (an important Chinese medicinal herb. In recent years, a number of studies have shown that baicalin has a potent neuroprotective effect in various in vitro and in vivo models of neuronal injury. In particular, baicalin effectively prevents neurodegenerative diseases through various pharmacological mechanisms, including antioxidative stress, anti-excitotoxicity, anti-apoptotic, anti-inflammatory, stimulating neurogenesis, promoting the expression of neuronal protective factors, etc. This review mainly focuses on the neuroprotective and cognitive enhancement effects of baicalin. The aim of the present review is to compile all information in relation to the neuroprotective and cognitive enhancement effects of baicalin and its molecular mechanisms of action in various in vitro and in vivo experimental models.

  14. Neuroprotection for Stroke: Current Status and Future Perspectives

    Directory of Open Access Journals (Sweden)

    Christoph Kleinschnitz

    2012-09-01

    Full Text Available Neuroprotection aims to prevent salvageable neurons from dying. Despite showing efficacy in experimental stroke studies, the concept of neuroprotection has failed in clinical trials. Reasons for the translational difficulties include a lack of methodological agreement between preclinical and clinical studies and the heterogeneity of stroke in humans compared to homogeneous strokes in animal models. Even when the international recommendations for preclinical stroke research, the Stroke Academic Industry Roundtable (STAIR criteria, were followed, we have still seen limited success in the clinic, examples being NXY-059 and haematopoietic growth factors which fulfilled nearly all the STAIR criteria. However, there are a number of neuroprotective treatments under investigation in clinical trials such as hypothermia and ebselen. Moreover, promising neuroprotective treatments based on a deeper understanding of the complex pathophysiology of ischemic stroke such as inhibitors of NADPH oxidases and PSD-95 are currently evaluated in preclinical studies. Further concepts to improve translation include the investigation of neuroprotectants in multicenter preclinical Phase III-type studies, improved animal models, and close alignment between clinical trial and preclinical methodologies. Future successful translation will require both new concepts for preclinical testing and innovative approaches based on mechanistic insights into the ischemic cascade.

  15. The Neuroprotective Functions of Transforming Growth Factor Beta Proteins

    Directory of Open Access Journals (Sweden)

    Gábor Lovas

    2012-07-01

    Full Text Available Transforming growth factor beta (TGF-β proteins are multifunctional cytokines whose neural functions are increasingly recognized. The machinery of TGF-β signaling, including the serine kinase type transmembrane receptors, is present in the central nervous system. However, the 3 mammalian TGF-β subtypes have distinct distributions in the brain suggesting different neural functions. Evidence of their involvement in the development and plasticity of the nervous system as well as their functions in peripheral organs suggested that they also exhibit neuroprotective functions. Indeed, TGF-β expression is induced following a variety of types of brain tissue injury. The neuroprotective function of TGF-βs is most established following brain ischemia. Damage in experimental animal models of global and focal ischemia was shown to be attenuated by TGF-βs. In addition, support for their neuroprotective actions following trauma, sclerosis multiplex, neurodegenerative diseases, infections, and brain tumors is also accumulating. The review will also describe the potential mechanisms of neuroprotection exerted by TGF-βs including anti-inflammatory, -apoptotic, -excitotoxic actions as well as the promotion of scar formation, angiogenesis, and neuroregeneration. The participation of these mechanisms in the neuroprotective effects of TGF-βs during different brain lesions will also be discussed.

  16. The measurement of the modal strain fields using digital shearography

    Directory of Open Access Journals (Sweden)

    Gomes J.M.

    2010-06-01

    Full Text Available This work presents a Michelson shearography interferometer configuration associated with stroboscopic double illumination technique for the measurement of modal rotation fields and their strain fields on a clamped circular aluminium plate. The speckle pattern is frozen by the synchronization between the LASER illumination and the modal vibration of the object. The quantitative evaluation is performed for each digital shearogram using a time modulation technique. The setup of double illumination LASER with out-of-plane opposite sensitivity allows the two phase maps measurement of the modal spatial gradient. The modal rotation and strain fields are extracted by the combination of this two digital phase maps. Image processing techniques are applied on the phase maps to obtain full-field measurements using a dedicated post-processing algorithm. Finally, is presented a comparison between the experimental measurement and the numerical solution.

  17. Modalities in homotopy type theory

    DEFF Research Database (Denmark)

    Rijke, Egbert; Shulman, Michael; Spitters, Bas

    2017-01-01

    Univalent homotopy type theory (HoTT) may be seen as a language for the category of ∞-groupoids. It is being developed as a new foundation for mathematics and as an internal language for (elementary) higher toposes. We develop the theory of factorization systems, reflective subuniverses......, and modalities in homotopy type theory, including their construction using a "localization" higher inductive type. This produces in particular the (n-connected, n-truncated) factorization system as well as internal presentations of subtoposes, through lex modalities. We also develop the semantics...

  18. Linear contextual modal type theory

    DEFF Research Database (Denmark)

    Schack-Nielsen, Anders; Schürmann, Carsten

    Abstract. When one implements a logical framework based on linear type theory, for example the Celf system [?], one is immediately con- fronted with questions about their equational theory and how to deal with logic variables. In this paper, we propose linear contextual modal type theory that gives...... a mathematical account of the nature of logic variables. Our type theory is conservative over intuitionistic contextual modal type theory proposed by Nanevski, Pfenning, and Pientka. Our main contributions include a mechanically checked proof of soundness and a working implementation....

  19. Vocabulary acquisition in aphasia: Modality can matter.

    Science.gov (United States)

    Tuomiranta, Leena; Grönroos, Ann-Mari; Martin, Nadine; Laine, Matti

    2014-11-01

    The present case study investigated modality-specific aspects of novel word acquisition in aphasia. It was prompted by recent aphasia case studies indicating great interindividual variability in the ability to learn and maintain novel words in aphasia. Moreover, two previous case studies revealed a striking effect of input modality by showing effective word learning and re-learning via visual input only (Kohen, Sola, Tuomiranta, Laine, & Martin, 2012; Tuomiranta et al., 2014). The present participant TS with chronic nonfluent aphasia and post-semantic anomia was administered novel word-referent learning tasks. In the first experiment, the learning phase included simultaneous phonological and orthographic input, while the follow-up was probed separately for spoken and written responses. In the second experiment, we studied the effect of four different input and output modality combinations on her ability to learn to name the novel items. In the first experiment, TS's spoken naming performance during the learning phase was just within the range of healthy controls. Maintenance declined and remained outside that range during the whole 6-month follow-up. However, TS maintained the learned words better in written than in spoken naming throughout the follow-up, and in written naming, her maintenance stayed within the control's range up to 8 weeks post-training. The second experiment indicated that the best learning outcome was achieved with orthographic input. Orthographic input combined with orthographic output resulted in fast and accurate learning of the novel words. Interestingly, TS's test profile was opposite to her learning profile, as she repeated better than she read aloud in the linguistic background assessment. The results from the present case highlight the importance of multiple learning channels for word acquisition in individuals with aphasia. Probing the functionality of different input and output channels for learning may also prove valuable in tailoring

  20. Using lithium as a neuroprotective agent in patients with cancer

    Directory of Open Access Journals (Sweden)

    Khasraw Mustafa

    2012-11-01

    Full Text Available Abstract Neurocognitive impairment is being increasingly recognized as an important issue in patients with cancer who develop cognitive difficulties either as part of direct or indirect involvement of the nervous system or as a consequence of either chemotherapy-related or radiotherapy-related complications. Brain radiotherapy in particular can lead to significant cognitive defects. Neurocognitive decline adversely affects quality of life, meaningful employment, and even simple daily activities. Neuroprotection may be a viable and realistic goal in preventing neurocognitive sequelae in these patients, especially in the setting of cranial irradiation. Lithium is an agent that has been in use for psychiatric disorders for decades, but recently there has been emerging evidence that it can have a neuroprotective effect. This review discusses neurocognitive impairment in patients with cancer and the potential for investigating the use of lithium as a neuroprotectant in such patients.

  1. Neuroprotective effects of anticonvulsants in rat hippocampal slice cultures exposed to oxygen/glucose deprivation

    DEFF Research Database (Denmark)

    Rekling, Jens C

    2003-01-01

    cell death induced by OGD. The newer anticonvulsants carbamazepine, felbamate, lamotrigine, tiagabine, and oxcarbazepine also had significant neuroprotective effects, but gabapentin, valproic acid (10 mM), levetiracetam and retigabine were not neuroprotective at a concentration up to 300 micro...

  2. Melatonin-Based Therapeutics for Neuroprotection in Stroke

    Directory of Open Access Journals (Sweden)

    Cesar V. Borlongan

    2013-04-01

    Full Text Available The present review paper supports the approach to deliver melatonin and to target melatonin receptors for neuroprotection in stroke. We discuss laboratory evidence demonstrating neuroprotective effects of exogenous melatonin treatment and transplantation of melatonin-secreting cells in stroke. In addition, we describe a novel mechanism of action underlying the therapeutic benefits of stem cell therapy in stroke, implicating the role of melatonin receptors. As we envision the clinical entry of melatonin-based therapeutics, we discuss translational experiments that warrant consideration to reveal an optimal melatonin treatment strategy that is safe and effective for human application.

  3. The modal logic of forcing

    NARCIS (Netherlands)

    Hamkins, J.D.; Löwe, B.

    2008-01-01

    A set theoretical assertion psi is forceable or possible, written lozenge psi, if psi holds in some forcing extension, and necessary, written square psi, if psi holds in all forcing extensions. In this forcing interpretation of modal logic, we establish that if ZFC is consistent, then the

  4. Neuroprotection trek--the next generation: the measurement is the message.

    Science.gov (United States)

    Andrews, Russell J

    2005-08-01

    Animal trials of many pharmacological neuroprotective agents have been quite successful, whereas trials in humans have been uniformly disappointing. A major difference between laboratory research in animals and clinical research in humans is the amount and/or quality of data obtained. The goal of this presentation is to argue that when clinical studies consist of more valid, objective data--that is, as our measurement capabilities in clinical research become as robust as they are in laboratory research--we are likely to gain new insights into both (1) injury to the nervous system and (2) neuroprotective treatment strategies. Technological advances (in data acquisition and analysis)--often novel even in the laboratory--will be the "scale" that will enable progress in measurement. As examples of such technological advances, two projects initiated at NASA Ames Research Center are cited. The NASA Smart Probe Project, with the goal of combining multiple microsensors and neural networks for real-time tissue identification (e.g., for tumor detection), has recently moved into the clinical realm, with a prototype being used to diagnose breast cancer in women "on the spot". The NASA Nanoelectrode Array Project has fabricated nanoscale devices that can simultaneously monitor electrical activity and neurotransmitter concentrations, while providing electrical stimulation focally and precisely (and potentially in a closed-loop fashion based on the input from the nanosensors). The large amounts of data that such techniques can acquire and analyze--separated spatially and temporally throughout the nervous system, if necessary--will provide insights not only into neuroprotective strategies, but also into the workings of the nervous system itself.

  5. Fetal Neuroprotection by Magnesium Sulfate: From Translational Research to Clinical Application

    Directory of Open Access Journals (Sweden)

    Clément Chollat

    2018-04-01

    Full Text Available Despite improvements in perinatal care, preterm birth still occurs regularly and the associated brain injury and adverse neurological outcomes remain a persistent challenge. Antenatal magnesium sulfate administration is an intervention with demonstrated neuroprotective effects for preterm births before 32 weeks of gestation (WG. Owing to its biological properties, including its action as an N-methyl-d-aspartate receptor blocker and its anti-inflammatory effects, magnesium is a good candidate for neuroprotection. In hypoxia models, including hypoxia-ischemia, inflammation, and excitotoxicity in various species (mice, rats, pigs, magnesium sulfate preconditioning decreased the induced lesions’ sizes and inflammatory cytokine levels, prevented cell death, and improved long-term behavior. In humans, some observational studies have demonstrated reduced risks of cerebral palsy after antenatal magnesium sulfate therapy. Meta-analyses of five randomized controlled trials using magnesium sulfate as a neuroprotectant showed amelioration of cerebral palsy at 2 years. A meta-analysis of individual participant data from these trials showed an equally strong decrease in cerebral palsy and the combined risk of fetal/infant death and cerebral palsy at 2 years. The benefit remained similar regardless of gestational age, cause of prematurity, and total dose received. These data support the use of a minimal dose (e.g., 4 g loading dose ± 1 g/h maintenance dose over 12 h to avoid potential deleterious effects. Antenatal magnesium sulfate is now recommended by the World Health Organization and many pediatric and obstetrical societies, and it is requisite to maximize its administration among women at risk of preterm delivery before 32 WG.

  6. Novel tactics for neuroprotection in Parkinson's disease: Role of antibiotics, polyphenols and neuropeptides.

    Science.gov (United States)

    Reglodi, Dora; Renaud, Justine; Tamas, Andrea; Tizabi, Yousef; Socías, Sergio B; Del-Bel, Elaine; Raisman-Vozari, Rita

    2017-08-01

    Parkinson's disease is a progressive neurodegenerative disorder characterized by the degeneration of midbrain nigral dopaminergic neurons. Although its etiology remains unknown, the pathological role of several factors has been highlighted, namely oxidative stress, neuroinflammation, protein misfolding, and mitochondrial dysfunction, in addition to genetic predispositions. The current therapy is mainly symptomatic with l-DOPA aiming to replace dopamine. Novel therapeutic approaches are being investigated with the intention of influencing pathways leading to neuronal death and dysfunction. The present review summarizes three novel approaches, the use of which is promising in pre-clinical studies. Polyphenols have been shown to possess neuroprotective properties on account of their well-established antioxidative and anti-inflammatory actions but also due to their influence on protein misfolding and mitochondrial homeostasis. Within the amazing ancillary effects of antibiotics, their neuroprotective properties against neurodegenerative and neuroinflammatory processes are of great interest for the development of effective therapies against Parkinson's disease. Experimental evidence supports the potential of antibiotics as neuroprotective agents, being useful not only to prevent the formation of toxic α-synuclein oligomers but also to ameliorate mitochondrial dysfunction and neuroinflammation. Neuropeptides offer another approach with their diverse effects in the nervous system. Among them, pituitary adenylate cyclase-activating polypeptide, a member of the secretin/glucagon superfamily, has several advantageous effects in models of neurodegeneration, namely anti-apoptotic, anti-inflammatory and antioxidant actions, the combination of which offers a potent protective effect in dopaminergic neurons. Owing to their pleiotropic modes of action, these novel therapeutic candidates have potential in tackling the multidimensional features of Parkinson's disease. Copyright

  7. Parallel pathways for cross-modal memory retrieval in Drosophila.

    Science.gov (United States)

    Zhang, Xiaonan; Ren, Qingzhong; Guo, Aike

    2013-05-15

    Memory-retrieval processing of cross-modal sensory preconditioning is vital for understanding the plasticity underlying the interactions between modalities. As part of the sensory preconditioning paradigm, it has been hypothesized that the conditioned response to an unreinforced cue depends on the memory of the reinforced cue via a sensory link between the two cues. To test this hypothesis, we studied cross-modal memory-retrieval processing in a genetically tractable model organism, Drosophila melanogaster. By expressing the dominant temperature-sensitive shibire(ts1) (shi(ts1)) transgene, which blocks synaptic vesicle recycling of specific neural subsets with the Gal4/UAS system at the restrictive temperature, we specifically blocked visual and olfactory memory retrieval, either alone or in combination; memory acquisition remained intact for these modalities. Blocking the memory retrieval of the reinforced olfactory cues did not impair the conditioned response to the unreinforced visual cues or vice versa, in contrast to the canonical memory-retrieval processing of sensory preconditioning. In addition, these conditioned responses can be abolished by blocking the memory retrieval of the two modalities simultaneously. In sum, our results indicated that a conditioned response to an unreinforced cue in cross-modal sensory preconditioning can be recalled through parallel pathways.

  8. Phase II Trial of Combined Modality Therapy With Concurrent Topotecan Plus Radiotherapy Followed by Consolidation Chemotherapy for Unresectable Stage III and Selected Stage IV Non-Small-Lung Cancer

    International Nuclear Information System (INIS)

    Seung, Steven K.; Ross, Helen J.

    2009-01-01

    Purpose: The optimal combination of chemotherapy and radiotherapy (RT) and the role of consolidation chemotherapy in patients with locally advanced non-small-cell lung cancer (NSCLC) are unknown. Topotecan is active against NSCLC, can safely be combined with RT at effective systemic doses, and can be given by continuous infusion, making it an attractive study agent against locally advanced NSCLC. Methods and Materials: In this pilot study, 20 patients were treated with infusion topotecan 0.4 mg/m 2 /d with three-dimensional conformal RT to 63 Gy both delivered Monday through Friday for 7 weeks. Patients without progression underwent consolidation chemotherapy with etoposide and a platinum agent for one cycle followed by two cycles of docetaxel. The study endpoints were treatment response, time to progression, survival, and toxicity. Results: Of the 20 patients, 19 completed induction chemoradiotherapy and 13 completed consolidation. Of the 20 patients, 18 had a partial response and 1 had stable disease after induction chemoradiotherapy. The 3-year overall survival rate was 32% (median, 18 months). The local and distant progression-free survival rate was 30% (median, 21 months) and 58% (median, not reached), respectively. Three patients developed central nervous system metastases, 1 within 228 days, 1 within 252 days, and 1 within 588 days. Three patients had pulmonary emboli. Therapy was well tolerated with 1 of 20 developing Grade 4 lymphopenia. Grade 3 hematologic toxicity was seen in 17 of 20 patients but was not clinically significant. Other Grade 3 toxicities included esophagitis in 3, esophageal stricture in 2, fatigue in 8, and weight loss in 1. Grade 3 pneumonitis occurred in 6 of 20 patients. Conclusion: Continuous infusion topotecan with RT was well tolerated and active in the treatment of poor-risk patients with unresectable Stage III NSCLC

  9. Neuroprotective potential of Citrullus lanatus seed extract and ...

    African Journals Online (AJOL)

    Mercury chloride toxicity continues to be relevant in the advent of increased interest in mining activity in Nigeria. The neuroprotective potential of Citrullus lanatus seed extract (CLSE) (Watermelon seed) and vitamin E (VIT E) on mercury chloride intoxication on the frontal cerebral cortex of male rats was investigated.

  10. Neuroprotective therapies in glaucoma: II. Genetic nanotechnology tools.

    Science.gov (United States)

    Nafissi, Nafiseh; Foldvari, Marianna

    2015-01-01

    Neurotrophic factor genome engineering could have many potential applications not only in the deeper understanding of neurodegenerative disorders but also in improved therapeutics. The fields of nanomedicine, regenerative medicine, and gene/cell-based therapy have been revolutionized by the development of safer and efficient non-viral technologies for gene delivery and genome editing with modern techniques for insertion of the neurotrophic factors into clinically relevant cells for a more sustained pharmaceutical effect. It has been suggested that the long-term expression of neurotrophic factors is the ultimate approach to prevent and/or treat neurodegenerative disorders such as glaucoma in patients who do not respond to available treatments or are at the progressive stage of the disease. Recent preclinical research suggests that novel neuroprotective gene and cell therapeutics could be promising approaches for both non-invasive neuroprotection and regenerative functions in the eye. Several progenitor and retinal cell types have been investigated as potential candidates for glaucoma neurotrophin therapy either as targets for gene therapy, options for cell replacement therapy, or as vehicles for gene delivery. Therefore, in parallel with deeper understanding of the specific protective effects of different neurotrophic factors and the potential therapeutic cell candidates for glaucoma neuroprotection, the development of non-invasive and highly specific gene delivery methods with safe and effective technologies to modify cell candidates for life-long neuroprotection in the eye is essential before investing in this field.

  11. Multiple sclerosis: Neuroprotective alliance of estrogen-progesterone and gender

    NARCIS (Netherlands)

    Kipp, M.; Amor, S.; Kraut, R.; Beyer, C.

    2012-01-01

    The potential of 17β-estradiol and progesterone as neuroprotective factors is well-recognized. Persuasive data comes from in vitro and animal models reflecting a wide range of CNS disorders. These studies have endeavored to translate findings into human therapies. Nonetheless, few human studies show

  12. Neuroprotective effect of creatine against propionic acid toxicity in ...

    African Journals Online (AJOL)

    With sufficient research and clinical trials in future, this could prove to be successful in treatment or management of autism as a neurodevelopmental disorder recently related to PA neurotoxicity. Keywords: Propionic acid, creatine, SH-SY5Y, comet assay, DNA fragmentation assay, apoptosis, neuroprotection. African Journal ...

  13. Neuroprotective effects of α-lipoic acid against hypoxic– ischemic ...

    African Journals Online (AJOL)

    Purpose: To explore the neuroprotective efficacy of α-lipoic acid (ALA) against hypoxic-ischemic encephalopathy (HIE) in neonatal rats. Methods: Forty-eight rats (P7-pups) were randomly assigned to one of four groups: group I received saline; group II (HI) underwent unilateral carotid artery ligation and hypoxia (92 % N2 ...

  14. Putative neuroprotective actions of N-acyl-ethanolamines

    DEFF Research Database (Denmark)

    Hansen, Harald S.; Moesgaard, B.; Petersen, G.

    2002-01-01

    when other phospholipids are subjected to rapid degradation. This is an important biosynthetic aspect of NAPE and NAE, as NAEs may be neuroprotective by a number of different mechanisms involving both receptor activation and non-receptor-mediated effects, e.g. by binding to cannabinoid receptors...

  15. Neuroprotective effects of Ellagic acid on Neonatal Hypoxic Brain ...

    African Journals Online (AJOL)

    Purpose: To investigate if ellagic acid exerts neuroprotective effects in hypoxic ischemic (HI) brain injury by inhibiting apoptosis and inflammatory responses. Methods: Separate groups of rat pups from post-natal day 4 (D4) were administered with ellagic acid (10, 20 or 40 mg/kg body weight) orally till post- natal day 10 ...

  16. Neuroprotective effect of creatine against propionic acid toxicity in ...

    African Journals Online (AJOL)

    edoja

    2013-07-31

    Jul 31, 2013 ... Full Length Research Paper. Neuroprotective effect of creatine against propionic acid toxicity in neuroblastoma SH-SY5Y cells in culture. Afaf El-Ansary*, Ghada Abu-Shmais and Abeer Al-Dbass. Biochemistry Department, College of Science, King Saud University, P.O. Box 22452, Zip code 11495, Riyadh, ...

  17. Neuroprotection as a Therapeutic Target for Diabetic Retinopathy

    Science.gov (United States)

    Hernández, Cristina; Simó, Rafael

    2016-01-01

    Diabetic retinopathy (DR) is a multifactorial progressive disease of the retina and a leading cause of vision loss. DR has long been regarded as a vascular disorder, although neuronal death and visual impairment appear before vascular lesions, suggesting an important role played by neurodegeneration in DR and the appropriateness of neuroprotective strategies. Upregulation of vascular endothelial growth factor (VEGF), the main target of current therapies, is likely to be one of the first responses to retinal hyperglycemic stress and VEGF may represent an important survival factor in early phases of DR. Of central importance for clinical trials is the detection of retinal neurodegeneration in the clinical setting, and spectral domain optical coherence tomography seems the most indicated technique. Many substances have been tested in animal studies for their neuroprotective properties and for possible use in humans. Perhaps, the most intriguing perspective is the use of endogenous neuroprotective substances or nutraceuticals. Together, the data point to the central role of neurodegeneration in the pathogenesis of DR and indicate neuroprotection as an effective strategy for treating this disease. However, clinical trials to determine not only the effectiveness and safety but also the compliance of a noninvasive route of drug administration are needed. PMID:27123463

  18. Neuroprotection as a Therapeutic Target for Diabetic Retinopathy

    Directory of Open Access Journals (Sweden)

    Cristina Hernández

    2016-01-01

    Full Text Available Diabetic retinopathy (DR is a multifactorial progressive disease of the retina and a leading cause of vision loss. DR has long been regarded as a vascular disorder, although neuronal death and visual impairment appear before vascular lesions, suggesting an important role played by neurodegeneration in DR and the appropriateness of neuroprotective strategies. Upregulation of vascular endothelial growth factor (VEGF, the main target of current therapies, is likely to be one of the first responses to retinal hyperglycemic stress and VEGF may represent an important survival factor in early phases of DR. Of central importance for clinical trials is the detection of retinal neurodegeneration in the clinical setting, and spectral domain optical coherence tomography seems the most indicated technique. Many substances have been tested in animal studies for their neuroprotective properties and for possible use in humans. Perhaps, the most intriguing perspective is the use of endogenous neuroprotective substances or nutraceuticals. Together, the data point to the central role of neurodegeneration in the pathogenesis of DR and indicate neuroprotection as an effective strategy for treating this disease. However, clinical trials to determine not only the effectiveness and safety but also the compliance of a noninvasive route of drug administration are needed.

  19. NEUROPROTECTIVE THERAPIES IN GLAUCOMA: II. GENETIC NANOTECHNOLOGY TOOLS

    Directory of Open Access Journals (Sweden)

    Nafiseh eNafissi

    2015-10-01

    Full Text Available Neurotrophic factor genome engineering could have many potential applications not only in the deeper understanding of neurodegenerative disorders but also in improved therapeutics. The field of nanomedicine, regenerative medicine, and gene/cell-based therapy have been revolutionized by the development of safer and efficient non-viral technologies for gene delivery and genome editing with modern techniques for insertion of the neurotrophic factors into clinically relevant cells for a more sustained pharmaceutical effect. It has been suggested that the long-term expression of neurotrophic factors is the ultimate approach to prevent and/or treat neurodegenerative disorders such as glaucoma in patients who do not respond to available treatments or are at the progressive stage of the disease. Recent preclinical research suggests that novel neuroprotective gene and cell therapeutics could be promising approaches for both non-invasive neuroprotection and regenerative functions in the eye. Several progenitor and retinal cell types have been investigated as potential candidates for glaucoma neurotrophin therapy either as targets for gene therapy, options for cell replacement therapy, or as vehicles for gene delivery. Therefore, in parallel with deeper understanding of the specific protective effects of different neurotrophic factors and the potential therapeutic cell candidates for glaucoma neuroprotection, the development of non-invasive and highly specific gene delivery methods with safe and effective technologies to modify cell candidates for life-long neuroprotection in the eye is essential before investing in this field.

  20. The Neuroprotective Effect Of Electro-Acupuncture Against Ischemic ...

    African Journals Online (AJOL)

    The Neuroprotective Effect Of Electro-Acupuncture Against Ischemic Stroke In Animal Model: A Review. ... Conclusion: An awareness of the benefits of acupuncture might lead more patients into accepting acupuncture therapy for the management of patients with ischemic stroke and patients with high risk of ischemic stroke.

  1. Neuroprotective effect corilagin in spinal cord injury rat model by ...

    African Journals Online (AJOL)

    Background: Neurological functions get altered in a patient suffering from spinal cord injury (SCI). Present study evaluates the neuroprotective effect of corilagin in spinal cord injury rats by inhibiting nuclear factor-kappa B (NF-κB), inflammatory mediators and apoptosis. Materials and method: Spinal cord injury was ...

  2. Neuroprotective effect of Terminalia chebula extracts and ellagic ...

    African Journals Online (AJOL)

    Background: Alzheimer's disease (AD) is one of the common neurodegenerative disorders among elderly. The purpose of this study was to determine the neuroprotective effect and mechanisms of action underlying the Terminalia chebula extracts and ellagic acid by using beta-amyloid25-35 (Aβ25-35)-induced cell toxicity ...

  3. Melatonin for women in pregnancy for neuroprotection of the fetus.

    Science.gov (United States)

    Wilkinson, Dominic; Shepherd, Emily; Wallace, Euan M

    2016-03-29

    Melatonin is an antioxidant with anti-inflammatory and anti-apoptotic effects. Animal studies have supported a fetal neuroprotective role for melatonin when administered maternally. It is important to assess whether melatonin, given to the mother, can reduce the risk of neurosensory disabilities (including cerebral palsy) and death, associated with fetal brain injury, for the preterm or term compromised fetus. To assess the effects of melatonin when used for neuroprotection of the fetus. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 January 2016). We planned to include randomised controlled trials and quasi-randomised controlled trials comparing melatonin given to women in pregnancy (regardless of the route, timing, dose and duration of administration) for fetal neuroprotection with placebo, no treatment, or with an alternative agent aimed at providing fetal neuroprotection. We also planned to include comparisons of different regimens for administration of melatonin. Two review authors planned to independently assess trial eligibility, trial quality and extract the data. We found no randomised trials for inclusion in this review. One study is ongoing. As we did not identify any randomised trials for inclusion in this review, we are unable to comment on implications for practice at this stage.Although evidence from animals studies has supported a fetal neuroprotective role for melatonin when administered to the mother during pregnancy, no trials assessing melatonin for fetal neuroprotection in pregnant women have been completed to date. However, there is currently one ongoing randomised controlled trial (with an estimated enrolment target of 60 pregnant women) which examines the dose of melatonin, administered to women at risk of imminent very preterm birth (less than 28 weeks' gestation) required to reduce brain damage in the white matter of the babies that were born very preterm.Further high-quality research is needed and research

  4. Quantum supports and modal logic

    International Nuclear Information System (INIS)

    Svetlichny, G.

    1986-01-01

    Recently Foulis, Piron, and Randall introduced a new interpretation of empirical and quantum logics which substitute for the notion of a probabilistic weight a combinatorial notion called a support. The informal use of the notion of ''possible outcomes of experiments'' suggests that this interpretation can be related to corresponding formal notions as treated by modal logic. The purpose of this paper is to prove that in fact supports are in one-to-one correspondence with the sets of possibly true elementary propositions in Kripke models of a set of modal formulas associated to the empirical or quantum logic. This hopefully provides a sufficiently detailed link between the two rather distinct logical systems to shed useful light on both

  5. Modal abstractions of concurrent behavior

    DEFF Research Database (Denmark)

    Nielson, Flemming; Nanz, Sebastian; Nielson, Hanne Riis

    2011-01-01

    We present an effective algorithm for the automatic construction of finite modal transition systems as abstractions of potentially infinite concurrent processes. Modal transition systems are recognized as valuable abstractions for model checking because they allow for the validation as well...... as refutation of safety and liveness properties. However, the algorithmic construction of finite abstractions from potentially infinite concurrent processes is a missing link that prevents their more widespread usage for model checking of concurrent systems. Our algorithm is a worklist algorithm using concepts...... from abstract interpretation and operating upon mappings from sets to intervals in order to express simultaneous over- and underapprox-imations of the multisets of process actions available in a particular state. We obtain a finite abstraction that is 3-valued in both states and transitions...

  6. Imaging Modalities for Cervical Spondylotic Stenosis and Myelopathy

    Directory of Open Access Journals (Sweden)

    C. Green

    2012-01-01

    Full Text Available Cervical spondylosis is a spectrum of pathology presenting as neck pain, radiculopathy, and myelopathy or all in combination. Diagnostic imaging is essential to diagnosis and preoperative planning. We discuss the modalities of imaging in common practice. We examine the use of imaging to differentiate among central, subarticular, and lateral stenosis and in the assessment of myelopathy.

  7. Tetrahydrocannabinolic acid is a potent PPARγ agonist with neuroprotective activity.

    Science.gov (United States)

    Nadal, Xavier; Del Río, Carmen; Casano, Salvatore; Palomares, Belén; Ferreiro-Vera, Carlos; Navarrete, Carmen; Sánchez-Carnerero, Carolina; Cantarero, Irene; Bellido, Maria Luz; Meyer, Stefan; Morello, Gaetano; Appendino, Giovanni; Muñoz, Eduardo

    2017-12-01

    Phytocannabinoids are produced in Cannabis sativa L. in acidic form and are decarboxylated upon heating, processing and storage. While the biological effects of decarboxylated cannabinoids such as Δ 9 -tetrahydrocannabinol have been extensively investigated, the bioactivity of Δ 9 -tetahydrocannabinol acid (Δ 9 -THCA) is largely unknown, despite its occurrence in different Cannabis preparations. Here we have assessed possible neuroprotective actions of Δ 9 -THCA through modulation of PPARγ pathways. The effects of six phytocannabinoids on PPARγ binding and transcriptional activity were investigated. The effect of Δ 9 -THCA on mitochondrial biogenesis and PPARγ coactivator 1-α expression was investigated in Neuro-2a (N2a) cells. The neuroprotective effect was analysed in STHdh Q111/Q111 cells expressing a mutated form of the huntingtin protein and in N2a cells infected with an adenovirus carrying human huntingtin containing 94 polyQ repeats (mHtt-q94). The in vivo neuroprotective activity of Δ 9 -THCA was investigated in mice intoxicated with the mitochondrial toxin 3-nitropropionic acid (3-NPA). Cannabinoid acids bind and activate PPARγ with higher potency than their decarboxylated products. Δ 9 -THCA increased mitochondrial mass in neuroblastoma N2a cells and prevented cytotoxicity induced by serum deprivation in STHdh Q111/Q111 cells and by mutHtt-q94 in N2a cells. Δ 9 -THCA, through a PPARγ-dependent pathway, was neuroprotective in mice treated with 3-NPA, improving motor deficits and preventing striatal degeneration. In addition, Δ 9 -THCA attenuated microgliosis, astrogliosis and up-regulation of proinflammatory markers induced by 3-NPA. Δ 9 -THCA shows potent neuroprotective activity, which is worth considering for the treatment of Huntington's disease and possibly other neurodegenerative and neuroinflammatory diseases. © 2017 The British Pharmacological Society.

  8. Neuroprotection with hypothermia and allopurinol in an animal model of hypoxic-ischemic injury: Is it a gender question?

    Directory of Open Access Journals (Sweden)

    Javier Rodríguez-Fanjul

    Full Text Available Hypoxic-ischemic encephalopathy (HIE is one of the most important causes of neonatal brain injury. Therapeutic hypothermia (TH is the standard treatment for term newborns after perinatal hypoxic ischemic injury (HI. Despite this, TH does not provide complete neuroprotection. Allopurinol seems to be a good neuroprotector in several animal studies, but it has never been tested in combination with hypothermia. Clinical findings show that male infants with (HI fare more poorly than matched females in cognitive outcomes. However, there are few studies about neuroprotection taking gender into account in the results. The aim of the present study was to evaluate the potential additive neuroprotective effect of allopurinol when administrated in association with TH in a rodent model of moderate HI. Gender differences in neuroprotection were also evaluated.P10 male and female rat pups were subjected to HI (Vannucci model and randomized into five groups: sham intervention (Control, no treatment (HI, hypothermia (HIH, allopurinol (HIA, and dual therapy (hypothermia and allopurinol (HIHA. To evaluate a treatment's neuroprotective efficiency, 24 hours after the HI event caspase3 activation was measured. Damaged area and hippocampal volume were also measured 72 hours after the HI event. Negative geotaxis test was performed to evaluate early neurobehavioral reflexes. Learning and spatial memory were assessed via Morris Water Maze (MWM test at 25 days of life.Damaged area and hippocampal volume were different among treatment groups (p = 0.001. The largest tissue lesion was observed in the HI group, followed by HIA. There were no differences between control, HIH, and HIHA. When learning process was analyzed, no differences were found. Females from the HIA group had similar results to the HIH and HIHA groups. Cleaved caspase 3 expression was increased in both HI and HIA. Despite this, in females cleaved caspase-3 was only differently increased in the HI group. All

  9. Mechanism of action of shoulder-modifying anoxic radiosensitizers and their use in combination with other treatment modalities. Coordinated programme on improvement in radiotherapy of cancer using modifiers of radiosensitivity of cells

    International Nuclear Information System (INIS)

    Harris, J.W.

    1982-01-01

    Research during the period of the Research Agreement has focused on four approaches to increased killing of tumor cells: hypoxic sensitizers, protective agents, hyperthermia and chemotherapeutic drugs. Various considerations have been examined, both in vitro and, to a lesser extent, in vivo, but the chief emphasis has been on the basic mechanisms involved. Results have been published in more than twenty publications and may be summarized as follows. Chemical sensitization: Results with the glutathione-oxidant ''diamide'' confirmed the importance of cellular GSH in the oxygen effect. Moreover, the possibility of combining agents like diamide with the nitroimidazole agents (e.g. misonidazole) was examined. Perhaps the most fundamental observation was the decrease in survival curve shoulder seen, for hypoxic cells, when irradiation was done in the presence of diamide. Chemical protection: The thio-phosphate WR2721, with respect to protection of various tissues and to the basis for its differential protection of normal tissues vs tumors was tested. Other studies have examined the mechanism(s) by which thiols protect against X-ray damage and the effects of certain chemotherapy drugs (e.g. Cis-platinum). Hyperthermia: Heat has been studied in conjunction with neutron irradiation (there is no differential effect on hypoxic cells) and at lower temperatures (40 0 ). The latter treatment (40 0 C for 2 hrs) removes the shoulder from the euoxic X-ray survival curve. Chemotherapy agents: These studies have explored the effects of clinically-used drugs on euoxic and hypoxic cells. No differences in efficiency are seen for acutely hypoxic cells. A system has been developed for chronic hypoxic in vitro and here different drug effects may be seen. Of particular interest is the decrease in OER observed in chronically hypoxic cells, possibly due to a decreased cellular content of glutathione. The damage due to Cis-platinum can be protected against, in large measure, by cysteamine

  10. Anesthetic neuroprotection: antecedents and an appraisal of preclinical and clinical data quality.

    Science.gov (United States)

    Ishida, Kazuyoshi; Berger, Miles; Nadler, Jacob; Warner, David S

    2014-01-01

    Anesthetics have been studied for nearly fifty years as potential neuroprotective compounds in both perioperative and resuscitation medicine. Although anesthetics present pharmacologic properties consistent with preservation of brain viability in the context of an ischemic insult, no anesthetic has been proven efficacious for neuroprotection in humans. After such effort, it could be concluded that anesthetics are simply not neuroprotective in humans. Moreover, pharmacologic neuroprotection with non-anesthetic drugs has also repeatedly failed to be demonstrated in human acute brain injury. Recent focus has been on rectification of promising preclinical neuroprotection data and subsequent failed clinical trials. This has led to consensus guidelines for the process of transferring purported therapeutics from bench to bedside. In this review we first examined the history of anesthetic neuroprotection research. Then, a systematic review was performed to identify major clinical trials of anesthetic neuroprotection. Both the preclinical neuroprotection portfolio cited to justify a clinical trial and the design and conduct of that clinical trial were evaluated using modern standards that include the Stroke Therapy Academic Industry Roundtable (STAIR) and Consolidated Standards of Reporting Trials (CONSORT) guidelines. In publications intended to define anesthetic neuroprotection, we found overall poor quality of both preclinical efficacy analysis portfolios and clinical trial designs and conduct. Hence, using current translational research standards, it was not possible to conclude from existing data whether anesthetics ameliorate perioperative ischemic brain injury. Incorporation of advances in translational neuroprotection research conduct may provide a basis for more definitive and potentially successful clinical trials of anesthetics as neuroprotectants.

  11. IMPACT (Imaging and Molecular Markers for Patients with Lung Cancer: Approaches with Molecular Targets and Complementary, Innovative and Therapeutic Modalities)

    National Research Council Canada - National Science Library

    Hong, Waun Ki; Herbst, Roy

    2006-01-01

    .... These projects combine targeted approaches using molecular and imaging techniques to validate activity against a target and monitor response using imaging modalities specific to the receptor using...

  12. IMPACT (Imaging and Molecular Markers for Patients with Lung Cancer: Approaches with Molecular Targets and Complementary, Innovative and Therapeutic Modalities)

    National Research Council Canada - National Science Library

    Hong, Waun K; Herbst, Roy

    2008-01-01

    .... These projects combine targeted approaches using molecular and imaging techniques to validate activity against a target and monitor response using imaging modalities specific to the receptor using...

  13. IMPACT (Imaging and Molecular Markers for Patients with Lung Cancer: Approaches with Molecular Targets and Complementary, Innovative and Therapeutic Modalities)

    National Research Council Canada - National Science Library

    Hong, Waun K; Herbst, Roy

    2007-01-01

    .... These projects combine targeted approaches using molecular and imaging techniques to validate activity against a target and monitor response using imaging modalities specific to the receptor using...

  14. Don Cossack Army Charters of the Mid 18th Century Via the Category of Modality

    Directory of Open Access Journals (Sweden)

    Elena Mihaylovna Sheptukhina

    2015-12-01

    Full Text Available The article deals with the language means of modality in the texts of military charters of the mid 18th cent. from the "Mikhailovsky stanitza hetman" archive (State Achieve of Volgograd Region. Military charters used to be major documents of legislation within Don Cossack Host, as being at that time an administrative unit in the territory of Russian Empire. The results of the contextual analysis verify the following facts: the charter texts are mainly characterized by an imperative tone of regulation that is caused by coordination between dominant meanings of a propositional (situational modality of necessity and pragmatic modality of volition, that are thought to be interrelated in utterances. The modal meaning of necessity is marked by the verbal construction with an independent infinitive or the combinations of modal verbs (imet' / possess; nadlezhat' / be to, modal predicatives with a dependent infinitive (dolzhen, nadobno, etc. / must (have to. Modality of volition is presented with a set of lexical units that possess the meanings of ordering, permission, offers, verbal forms that are used as performatives, or point to the status of a subject, etc. The texts under study represent some other modal meanings: possibility (with the words moch' / be able to; mozhno / could / may combined with an infinitive, in subordinate clauses with a particle li (if / wether, etc. in an interrogative clauses. In complex sentences with subordination combinations of various modal meanings are observed.

  15. The effects of a protein enriched diet with lean red meat combined with a multi-modal exercise program on muscle and cognitive health and function in older adults: study protocol for a randomised controlled trial.

    Science.gov (United States)

    Daly, Robin M; Gianoudis, Jenny; Prosser, Melissa; Kidgell, Dawson; Ellis, Kathryn A; O'Connell, Stella; Nowson, Caryl A

    2015-08-08

    Age-related muscle wasting has been strongly implicated with falls and fractures in the elderly, but it has also been associated with cognitive decline and dementia. Progressive resistance training (PRT) and adequate dietary protein are recognised as important contributors to the maintenance of muscle health and function in older adults. However, both factors also have the potential to improve brain function and prevent cognitive decline via several pathways, including the regulation of various growth and neurotrophic factors [insulin-like growth factor-1 (IGF-1)]; brain-derived growth factor (BDNF)] and/or the modulation of systemic inflammation. The primary aim of this study is to investigate whether a modest increase in dietary protein achieved through the consumption of lean red meat three days per week, when combined with PRT, can enhance muscle mass, size and strength and cognitive function in community-dwelling older people. The study design is a 48-week randomised controlled trial consisting of a 24-week intervention with a 24-week follow-up. Men and women (n=152) aged 65 years and over residing in the community will be randomly allocated to: 1) PRT and provided with 220 g (raw weight) of lean red meat to be cooked and divided into two 80 g servings on each of the three days that they complete their exercise session, or 2) control PRT in which participants will be provided with and advised to consume ≥1 serving (~1/2 cup) of rice and/or pasta or 1 medium potato on each of the three training days. The primary outcome measures will be muscle mass, size and strength and cognitive function. Secondary outcomes will include changes in: muscle function, neural health (corticospinal excitability and inhibition and voluntary activation), serum IGF-1 and BDNF, adipokines and inflammatory markers, fat mass and inter-/intra-muscular fat, blood pressure, lipids and health-related quality of life. All outcome measures will be assessed at baseline and 24 weeks, with the

  16. The neuroprotective effect of lovastatin on MPP(+)-induced neurotoxicity is not mediated by PON2.

    Science.gov (United States)

    Aguirre-Vidal, Yoshajandith; Montes, Sergio; Tristan-López, Luis; Anaya-Ramos, Laura; Teiber, John; Ríos, Camilo; Baron-Flores, Verónica; Monroy-Noyola, Antonio

    2015-05-01

    Parkinson's disease (PD) is a neurodegenerative disorder characterized by loss of the pigmented dopaminergic neurons in the substantia nigra pars compacta with subsequent striatal dopamine (DA) deficiency and increased lipid peroxidation. The etiology of the disease is still unclear and it is thought that PD may be caused by a combination of genetic and environmental factors. In the search of new pharmacological options, statins have been recognized for their potential application to treat PD, due to their antioxidant effect. The aim of this work is to contribute in the characterization of the neuroprotective effect of lovastatin in a model of PD induced by 1-methyl-4-phenylpyridinium (MPP(+)). Male Wistar rats (200-250 g) were randomly allocated into 4 groups and administered for 7 days with different pharmacological treatments. Lovastatin administration (5 mg/kg) diminished 40% of the apomorphine-induced circling behavior, prevented the striatal DA depletion and lipid peroxides formation by MPP(+) intrastriatal injection, as compared to the group of animals treated only with MPP(+). Lovastatin produced no change in paraoxonase-2 (PON2) activity. It is evident that lovastatin conferred neuroprotection against MPP(+)-induced protection but this effect was not associated with the induction of PON2 in the rat striatum. Copyright © 2015. Published by Elsevier B.V.

  17. Novel Neuroprotective Multicomponent Therapy for Amyotrophic Lateral Sclerosis Designed by Networked Systems.

    Directory of Open Access Journals (Sweden)

    Mireia Herrando-Grabulosa

    Full Text Available Amyotrophic Lateral Sclerosis is a fatal, progressive neurodegenerative disease characterized by loss of motor neuron function for which there is no effective treatment. One of the main difficulties in developing new therapies lies on the multiple events that contribute to motor neuron death in amyotrophic lateral sclerosis. Several pathological mechanisms have been identified as underlying events of the disease process, including excitotoxicity, mitochondrial dysfunction, oxidative stress, altered axonal transport, proteasome dysfunction, synaptic deficits, glial cell contribution, and disrupted clearance of misfolded proteins. Our approach in this study was based on a holistic vision of these mechanisms and the use of computational tools to identify polypharmacology for targeting multiple etiopathogenic pathways. By using a repositioning analysis based on systems biology approach (TPMS technology, we identified and validated the neuroprotective potential of two new drug combinations: Aliretinoin and Pranlukast, and Aliretinoin and Mefloquine. In addition, we estimated their molecular mechanisms of action in silico and validated some of these results in a well-established in vitro model of amyotrophic lateral sclerosis based on cultured spinal cord slices. The results verified that Aliretinoin and Pranlukast, and Aliretinoin and Mefloquine promote neuroprotection of motor neurons and reduce microgliosis.

  18. Direct calculation of modal contributions to thermal conductivity via Green–Kubo modal analysis

    International Nuclear Information System (INIS)

    Lv, Wei; Henry, Asegun

    2016-01-01

    We derived a new method for direct calculation of the modal contributions to thermal conductivity, which is termed Green–Kubo modal analysis (GKMA). The GKMA method combines the lattice dynamics formalism with the Green–Kubo formula for thermal conductivity, such that the thermal conductivity becomes a direct summation of modal contributions, where one need not define the phonon velocity. As a result, the GKMA method can be applied to any material/group of atoms, where the atoms vibrate around stable equilibrium positions, which includes non-stoichiometric compounds, random alloys, amorphous materials and even rigid molecules. By using molecular dynamics simulations to obtain the time history of each mode’s contribution to the heat current, one naturally includes anharmonicity to full order and can obtain insight into the interactions between different modes through the cross-correlations. As an example, we applied the GMKA method to crystalline and amorphous silicon. The modal contributions at each frequency result from the analysis and thereby allow one to apply a quantum correction to the mode heat capacity to determine the temperature dependence of thermal conductivity. The predicted temperature dependent thermal conductivity for amorphous silicon shows the best agreement with experiments to date. The GKMA method provides new insight into the nature of phonon transport, as it casts the problem in terms of mode–mode correlation instead of scattering, and provides a general unified formalism that can be used to understand phonon–phonon interactions in essentially any class of materials or structures where the atoms vibrate around stable equilibrium sites. (paper)

  19. Sensory stimulation for lowering intraocular pressure, improving blood flow to the optic nerve and neuroprotection in primary open-angle glaucoma.

    Science.gov (United States)

    Rom, Edith

    2013-12-01

    Primary open-angle glaucoma is a group of optic neuropathies that can lead to irreversible blindness. Sensory stimulation in the form of acupuncture or ear acupressure may contribute to protecting patients from blindness when used as a complementary method to orthodox treatment in the form of drops, laser or surgery. The objective of this article is to provide a narrative overview of the available literature up to July 2012. It summarises reported evidence on the potential beneficial effects of sensory stimulation for glaucoma. Sensory stimulation appears to significantly enhance the pressure-lowering effect of orthodox treatments. Studies suggest that it may also improve blood flow to the eye and optic nerve head. Furthermore, it may play a role in neuroprotection through regulating nerve growth factor and brain-derived neurotrophic factor and their receptors, thereby encouraging the survival pathway in contrast to the pathway to apoptosis. Blood flow and neuroprotection are areas that are not directly influenced by orthodox treatment modalities. Numerous different treatment protocols were used to investigate the effect of sensory stimulation on intraocular pressure, blood flow or neuroprotection of the retina and optic nerve in the animal model and human pilot studies. Objective outcomes were reported to have been evaluated with Goldmann tonometry, Doppler ultrasound techniques and electrophysiology (pattern electroretinography, visually evoked potentials), and supported with histological studies in the animal model. Taken together, reported evidence from these studies strongly suggests that sensory stimulation is worthy of further research.

  20. Tailoring distributed modal sensors for in-plane modal filtering

    International Nuclear Information System (INIS)

    Donoso, A; Bellido, J C

    2009-01-01

    In this note we deal with finding the shape of distributed piezoelectric modal sensors for isolating the in-plane mode shapes of plates. The problem is treated by an optimization approach, in which a binary function is used to model the design variable: the polarization profile of the piezoelectric layer. The numerical procedure proposed here allows us to find polarization profiles which take on two values only, i.e. either positive or negative polarization, that make it possible to isolate particular vibration modes in the frequency domain. (technical note)

  1. Valproic acid potentiates curcumin-mediated neuroprotection in Lipopolysaccharide induced rats

    Directory of Open Access Journals (Sweden)

    Amira eZaky

    2014-10-01

    Full Text Available The etiology of neuroinflammation is complex and comprises multifactorial, involving both genetic and environmental factors during which diverse genetic and epigenetic modulations are implicated. Curcumin (Cur, and valproic acid (VPA, histone deacetylase 1 inhibitor, have neuroprotective effects. The present study was designed with an aim to investigate the ability of co-treatment of both compounds (Cur or VPA (200mg/kg for four weeks to augment neuroprotection and enhance brain recovery from intra-peritoneal (IP injection of (250 µg/kg lipopolysaccharide (LPS-stimulated neuroinflammatory condition on rat brain cortex. Cortex activation and the effects of combined treatment and production of proinflammatory mediators, COX-2, APE1 and nitric oxide/iNOS were investigated. Neuroinflammation development was assessed by histological analyses and by investigating associated indices (BACE1, APP, PSEN-1 and PSEN-2. Furthermore we measured the expression profile of let-7 miRNAs members a, b, c, e and f in all groups, a highly abundant regulator of gene expression in the CNS. Protein and mRNA levels of neuroinflammation markers COX-2, BACE1, APP and iNOS were also attenuated by combined therapy. On the other hand, assessment of the indicated five let-7 members, showed distinct expression profile pattern in the different groups. Let-7 a, b and c disappeared in the induced group, an effect that was partially suppressed by co-addition of either Cur or VPA. These data suggest that the combined treatment induced significantly the expression of the five members when compared to rats treated with Cur or VPA only as well as to self-recovery group, which indicates a possible benefit from the synergistic effect of Cur-VPA combination as therapeutic agents for neuroinflammation and its associated disorders. The mechanism elucidated here highlights the particular drug-induced expression profile of let-7 family as new targets for future pharmacological development.

  2. Modal intersection types, two-level languages, and staged synthesis

    DEFF Research Database (Denmark)

    Henglein, Fritz; Rehof, Jakob

    2016-01-01

    -linguistic framework for staged program synthesis, where metaprograms are automatically synthesized which, when executed, generate code in a target language. We survey the basic theory of staged synthesis and illustrate by example how a two-level language theory specialized from λ∩ ⎕ can be used to understand......A typed λ-calculus, λ∩ ⎕, is introduced, combining intersection types and modal types. We develop the metatheory of λ∩ ⎕, with particular emphasis on the theory of subtyping and distributivity of the modal and intersection type operators. We describe how a stratification of λ∩ ⎕ leads to a multi...... the process of staged synthesis....

  3. Bimodal extinction without cross-modal extinction.

    OpenAIRE

    Inhoff, A W; Rafal, R D; Posner, M J

    1992-01-01

    Three patients with unilateral neurological injury were clinically examined. All showed consistent unilateral extinction in the tactile and visual modalities on simultaneous intramodal stimulation. There was virtually no evidence for cross-modal extinction, however, so that contralateral stimulation of one modality would have extinguished perception of ipsilateral stimuli in the other modality. It is concluded that the attentional system controlling the encoding of tactile and visual stimuli ...

  4. Modular sequent calculi for classical modal logics

    NARCIS (Netherlands)

    Gilbert, David; Maffezioli, Paolo

    This paper develops sequent calculi for several classical modal logics. Utilizing a polymodal translation of the standard modal language, we are able to establish a base system for the minimal classical modal logic E from which we generate extensions (to include M, C, and N) in a modular manner. Our

  5. Completeness for flat modal fixpoint logics

    NARCIS (Netherlands)

    Santocanale, L.; Venema, Y.

    2010-01-01

    This paper exhibits a general and uniform method to prove axiomatic completeness for certain modal fixpoint logics. Given a set Γ of modal formulas of the form γ(x,p1,…,pn), where x occurs only positively in γ, we obtain the flat modal fixpoint language L♯(Γ) by adding to the language of polymodal

  6. MR microscopy as a research modality

    International Nuclear Information System (INIS)

    Kang, Heung Sik; Kim, Seung Hyup; Han, Man Chung; Lee, Sang Hoon; Lee, Yoon Seong; Yi, Jung Han; Cho, Zang Hee

    1988-01-01

    A combination of high gradient (0.46mT/cm) and small radiofrequency coils (8cm diameter) was used to obtain images with effective thickness of 2.0mm and pixel dimensions as small as 196 μ in the live chick embryo and surgically resected human femoral head with avascular necrosis. The signal-to-noise ratio was sufficient to allow identification of major anatomical structures of live chick embryo and delineation of osteonecrotic segment in femoral head. The changes of signal intensity in necrotic femoral head was well correlated with histopathologic findings. MR microscopy is considered as a good research modality in the field of embryology, teratology and MR tissue characterization

  7. MR microscopy as a research modality

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Heung Sik; Kim, Seung Hyup; Han, Man Chung; Lee, Sang Hoon; Lee, Yoon Seong [College of Medicine, Seoul National University, Seoul (Korea, Republic of); Yi, Jung Han; Cho, Zang Hee [Korea Advanced insititute of Science, Taejon (Korea, Republic of)

    1988-02-15

    A combination of high gradient (0.46mT/cm) and small radiofrequency coils (8cm diameter) was used to obtain images with effective thickness of 2.0mm and pixel dimensions as small as 196 {mu} in the live chick embryo and surgically resected human femoral head with avascular necrosis. The signal-to-noise ratio was sufficient to allow identification of major anatomical structures of live chick embryo and delineation of osteonecrotic segment in femoral head. The changes of signal intensity in necrotic femoral head was well correlated with histopathologic findings. MR microscopy is considered as a good research modality in the field of embryology, teratology and MR tissue characterization.

  8. Physical modalities in chronic pain management.

    Science.gov (United States)

    Rakel, Barbara; Barr, John O

    2003-09-01

    The following conclusions can be made based on review of the evidence: There is limited but positive evidence that select physical modalities are effective in managing chronic pain associated with specific conditions experienced by adults and older individuals. Overall, studies have provided the most support for the modality of therapeutic exercise. Different physical modalities have similar magnitudes of effects on chronic pain. Therefore, selection of the most appropriate physical modality may depend on the desired functional outcome for the patient, the underlying impairment, and the patient's preference or prior experience with the modality. Certain patient characteristics may decrease the effectiveness of physical modalities, as has been seen with TENS. These characteristics include depression, high trait anxiety, a powerful others locus of control, obesity, narcotic use, and neuroticism. The effect on pain by various modalities is generally strongest in the short-term period immediately after the intervention series, but effects can last as long as 1 year after treatment (e.g., with massage). Most research has tested the effect of physical modalities on chronic low back pain and knee OA. The effectiveness of physical modalities for other chronic pain conditions needs to be evaluated more completely. Older and younger adults often experience similar effects on their perception of pain from treatment with physical modalities. Therefore, use of these modalities for chronic pain in older adults is appropriate, but special precautions need to be taken. Practitioners applying physical modalities need formal training that includes the risks and precautions for these modalities. If practitioners lack formal training in the use of physical modalities, or if modality use is not within their scope of practice, it is important to consult with and refer patients to members of the team who have this specialized training. Use of a multidisciplinary approach to chronic pain

  9. Detecting Pedestrian Flocks by Fusion of Multi-Modal Sensors in Mobile Phones

    DEFF Research Database (Denmark)

    Kjærgaard, Mikkel Baun; Wirz, Martin; Roggen, Daniel

    2012-01-01

    derived from multiple sensor modalities of modern smartphones. Automatic detection of flocks has several important applications, including evacuation management and socially aware computing. The novelty of this paper is, firstly, to use data fusion techniques to combine several sensor modalities (WiFi...

  10. Load Estimation from Natural input Modal Analysis

    DEFF Research Database (Denmark)

    Aenlle, Manuel López; Brincker, Rune; Canteli, Alfonso Fernández

    2005-01-01

    One application of Natural Input Modal Analysis consists in estimating the unknown load acting on structures such as wind loads, wave loads, traffic loads, etc. In this paper, a procedure to determine loading from a truncated modal model, as well as the results of an experimental testing programme...... estimation. In the experimental program a small structure subjected to vibration was used to estimate the loading from the measurements and the experimental modal space. The modal parameters were estimated by Natural Input Modal Analysis and the scaling factors of the mode shapes obtained by the mass change...

  11. Modality and Task Switching Interactions using Bi-Modal and Bivalent Stimuli

    Science.gov (United States)

    Sandhu, Rajwant; Dyson, Benjamin J.

    2013-01-01

    Investigations of concurrent task and modality switching effects have to date been studied under conditions of uni-modal stimulus presentation. As such, it is difficult to directly compare resultant task and modality switching effects, as the stimuli afford both tasks on each trial, but only one modality. The current study investigated task and…

  12. MINERVA - a multi-modal radiation treatment planning system

    Energy Technology Data Exchange (ETDEWEB)

    Wemple, C.A. E-mail: cew@enel.gov; Wessol, D.E.; Nigg, D.W.; Cogliati, J.J.; Milvich, M.L.; Frederickson, C.; Perkins, M.; Harkin, G.J

    2004-11-01

    Researchers at the Idaho National Engineering and Environmental Laboratory and Montana State University have undertaken development of MINERVA, a patient-centric, multi-modal, radiation treatment planning system. This system can be used for planning and analyzing several radiotherapy modalities, either singly or combined, using common modality independent image and geometry construction and dose reporting and guiding. It employs an integrated, lightweight plugin architecture to accommodate multi-modal treatment planning using standard interface components. The MINERVA design also facilitates the future integration of improved planning technologies. The code is being developed with the Java Virtual Machine for interoperability. A full computation path has been established for molecular targeted radiotherapy treatment planning, with the associated transport plugin developed by researchers at the Lawrence Livermore National Laboratory. Development of the neutron transport plugin module is proceeding rapidly, with completion expected later this year. Future development efforts will include development of deformable registration methods, improved segmentation methods for patient model definition, and three-dimensional visualization of the patient images, geometry, and dose data. Transport and source plugins will be created for additional treatment modalities, including brachytherapy, external beam proton radiotherapy, and the EGSnrc/BEAMnrc codes for external beam photon and electron radiotherapy.

  13. Dual ant colony operational modal analysis parameter estimation method

    Science.gov (United States)

    Sitarz, Piotr; Powałka, Bartosz

    2018-01-01

    Operational Modal Analysis (OMA) is a common technique used to examine the dynamic properties of a system. Contrary to experimental modal analysis, the input signal is generated in object ambient environment. Operational modal analysis mainly aims at determining the number of pole pairs and at estimating modal parameters. Many methods are used for parameter identification. Some methods operate in time while others in frequency domain. The former use correlation functions, the latter - spectral density functions. However, while some methods require the user to select poles from a stabilisation diagram, others try to automate the selection process. Dual ant colony operational modal analysis parameter estimation method (DAC-OMA) presents a new approach to the problem, avoiding issues involved in the stabilisation diagram. The presented algorithm is fully automated. It uses deterministic methods to define the interval of estimated parameters, thus reducing the problem to optimisation task which is conducted with dedicated software based on ant colony optimisation algorithm. The combination of deterministic methods restricting parameter intervals and artificial intelligence yields very good results, also for closely spaced modes and significantly varied mode shapes within one measurement point.

  14. Neuroprotective mechanism of losartan and its interaction with nimesulide against chronic fatigue stress.

    Science.gov (United States)

    Kumar, Anil; Singh, Barinder; Mishra, Jitendriya; Sah, Sangeeta Pilkhwal; Pottabathini, Raghavender

    2015-12-01

    Potential role of angiotensin-II and cyclooxygenase have been suggested in the pathophysiology of chronic fatigue stress. The present study has been designed to evaluate the neuroprotective effect of losartan and its interaction with nimesulide against chronic fatigue stress and related complications in mice. In the present study, male Laca mice (20-30 g) were subjected to running wheel activity test session (RWATS) for 6 min daily for 21 days. Losartan, nimesulide and their combinations were administered daily for 21 days, 45 min before being subjected to RWATS. Various behavioral and biochemical and neuroinflammatory mediators were assessed subsequently. 21 days RWATS treatment significantly decreased number of wheel rotations/6 min indicating fatigue stress like behaviors as compared to naive group. 21 days treatment with losartan (10 and 20 mg/kg, ip), nimesulide (5 and 10 mg/kg, po) and their combinations significantly improved behavior [increased number of wheel rotations, reversal of post-exercise fatigue, locomotor activity, antianxiety-like behavior (number of entries, latency to enter and time spent in mirror chamber), and memory performance (transfer latency in plus-maze performance task)], biochemical parameters (reduced serum corticosterone, brain lipid peroxidation, nitrite concentration, acetylcholinesterase activity, restored reduced glutathione levels and catalase activity) as compared to RWATS control. Besides, TNF-α, CRP levels were significantly attenuated by these drugs and their combinations as compared to control. The present study highlights the role of cyclooxygenase modulation in the neuroprotective effect of losartan against chronic fatigue stress-induced behavioral, biochemical and cellular alterations in mice.

  15. Modality and Perceptual-Motor Experience Influence the Detection of Temporal Deviations in Tap Dance Sequences

    Directory of Open Access Journals (Sweden)

    Mauro Murgia

    2017-08-01

    Full Text Available Accurate temporal information processing is critically important in many motor activities within disciplines such as dance, music, and sport. However, it is still unclear how temporal information related to biological motion is processed by expert and non-expert performers. It is well-known that the auditory modality dominates the visual modality in processing temporal information of simple stimuli, and that experts outperform non-experts in biological motion perception. In the present study, we combined these two areas of research; we investigated how experts and non-experts detected temporal deviations in tap dance sequences, in the auditory modality compared to the visual modality. We found that temporal deviations were better detected in the auditory modality compared to the visual modality, and by experts compared to non-experts. However, post hoc analyses indicated that these effects were mainly due to performances obtained by experts in the auditory modality. The results suggest that the experience advantage is not equally distributed across the modalities, and that tap dance experience enhances the effectiveness of the auditory modality but not the visual modality when processing temporal information. The present results and their potential implications are discussed in both temporal information processing and biological motion perception frameworks.

  16. Resveratrol Neuroprotection in Stroke and Traumatic CNS injury

    Science.gov (United States)

    Lopez, Mary; Dempsey, Robert J; Vemuganti, Raghu

    2015-01-01

    Resveratrol, a stilbene formed in many plants in response to various stressors, elicits multiple beneficial effects in vertebrates. Particularly, resveratrol was shown to have therapeutic properties in cancer, atherosclerosis and neurodegeneration. Resveratrol-induced benefits are modulated by multiple synergistic pathways that control oxidative stress, inflammation and cell death. Despite the lack of a definitive mechanism, both in vivo and in vitro studies suggest that resveratrol can induce a neuroprotective state when administered acutely or prior to experimental injury to the CNS. In this review, we discuss the neuroprotective potential of resveratrol in stroke, traumatic brain injury and spinal cord injury, with a focus on the molecular pathways responsible for this protection. PMID:26277384

  17. Neuroprotective Compound from an Endophytic Fungus, Colletotrichum sp. JS-0367.

    Science.gov (United States)

    Song, Ji Hoon; Lee, Changyeol; Lee, Dahae; Kim, Soonok; Bang, Sunghee; Shin, Myoung-Sook; Lee, Jun; Kang, Ki Sung; Shim, Sang Hee

    2018-05-23

    Colletotrichum sp. JS-0367 was isolated from Morus alba (mulberry), identified, and cultured on a large scale for chemical investigation. One new anthraquinone (1) and three known anthraquinones (2-4) were isolated and identified using spectroscopic methods including 1D/2D-NMR and HRESIMS. Although the neuroprotective effects of some anthraquinones have been reported, the biological activities of the four anthraquinones isolated in this study have not been reported. Therefore, the neuroprotective effects of these compounds were determined against murine hippocampal HT22 cell death induced by glutamate. Compound 4, evariquinone, showed strong protective effects against HT22 cell death induced by glutamate by the inhibition of intracellular ROS accumulation and Ca 2+ influx triggered by glutamate. Immunoblot analysis revealed that compound 4 reduced the phosphorylation of MAPKs (JNK, ERK1/2, and p38) induced by glutamate. Furthermore, compound 4 strongly attenuated glutamate-mediated apoptotic cell death.

  18. Neuroprotective effects of Resveratrol in Alzheimer Disease Pathology

    Directory of Open Access Journals (Sweden)

    Shraddha D Rege

    2014-09-01

    Full Text Available Alzheimer’s disease (AD is a chronic neurodegenerative disorder characterized by a progressive loss of cognitive and behavioral abilities. Extracellular senile plaques and intracellular neurofibrillary tangles are hallmarks of AD. Researchers aim to analyze the molecular mechanisms underlying AD pathogenesis; however, the therapeutic options available to treat this disease are inadequate. In the past few years, several studies have reported interesting insights about the neuroprotective properties of the polyphenolic compound resveratrol (3, 5, 4’-trihydroxy-trans-stilbene when used with in vitro and in vivo models of AD. The aim of this review is to focus on the neuroprotective and antioxidant effects of resveratrol on AD and its multiple potential mechanisms of action. In addition, because the naturally occurring forms of resveratrol have a very limited half-life in plasma, a description of potential analogues aimed at increasing bioavailability in plasma is also discussed.

  19. Astaxanthin as a Potential Neuroprotective Agent for Neurological Diseases

    Directory of Open Access Journals (Sweden)

    Haijian Wu

    2015-09-01

    Full Text Available Neurological diseases, which consist of acute injuries and chronic neurodegeneration, are the leading causes of human death and disability. However, the pathophysiology of these diseases have not been fully elucidated, and effective treatments are still lacking. Astaxanthin, a member of the xanthophyll group, is a red-orange carotenoid with unique cell membrane actions and diverse biological activities. More importantly, there is evidence demonstrating that astaxanthin confers neuroprotective effects in experimental models of acute injuries, chronic neurodegenerative disorders, and neurological diseases. The beneficial effects of astaxanthin are linked to its oxidative, anti-inflammatory, and anti-apoptotic characteristics. In this review, we will focus on the neuroprotective properties of astaxanthin and explore the underlying mechanisms in the setting of neurological diseases.

  20. [Similarity of cycloprolylglycine to piracetam in antihypoxic and neuroprotective effects].

    Science.gov (United States)

    Kolisnikova, K N; Gudasheva, T A; Nazarova, G A; Antipov, T A; Voronina, T A; Seredenin, S B

    2012-01-01

    The antihypoxic activity of the endogenous cyclic dipeptide cycloprolylglycine (CPG) has been studied on a model of normobaric hypoxia with hypercapnia and its neuroprotective activity has been studied on a model of human neuroblastoma SH-SY5Y cell damage by 6-hydroxydopamine. It is established that CPG exhibits the antihypoxic activity at doses of 0.5 and 1.0 mg/kg (i.p.) on outbred and BALB/c mice, but not on C57B1/6 mice. The neuroprotective activity of CPG was detected in 10(-5) - 10(-8) M concentration range only when the treatment was carried out 24h before toxin introduction. The obtained data confirm the hypothesis that piracetam is a mimetic of the endogenous CPG neuropeptide.

  1. Chemical Modification of the Multi-Target Neuroprotective Compound Fisetin

    OpenAIRE

    Chiruta, Chandramouli; Schubert, David; Dargusch, Richard; Maher, Pamela

    2011-01-01

    Many factors are implicated in age-related CNS disorders making it unlikely that modulating only a single factor will provide effective treatment. Perhaps a better approach is to identify small molecules that have multiple biological activities relevant to the maintenance of brain function. Recently, we identified an orally active, neuroprotective and cognition-enhancing molecule, the flavonoid fisetin, that is effective in several animal models of CNS disorders. Fisetin has direct antioxidan...

  2. Targeted proteins involved in the neuroprotective effects of lithium citrate

    OpenAIRE

    I. Yu. Torshin; O. A. Gromova; L. A. Mayorova; A. Yu. Volkov

    2017-01-01

    Preparations based on organic lithium salts are promising neuroprotective agents that are effective just in the micromolar concentration range and, at the same time, have high safety (Toxicity Class V).Objective: to elucidate more detailed mechanisms responsible for the biological and pharmacological effects of lithium citrate, by analyzing the possible interactions of lithium ion with human proteome proteins that are also represented in the rat proteome.Material and methods. The targets of l...

  3. Neuroprotective 2-(2-phenylethyl)chromones of Imperata cylindrica.

    Science.gov (United States)

    Yoon, Jeong Seon; Lee, Mi Kyeong; Sung, Sang Hyun; Kim, Young Choong

    2006-02-01

    Bioactivity-guided fractionation of the methanolic extract of the rhizomes of Imperata cylindrica afforded a new compound, 5-hydroxy-2-(2-phenylethyl)chromone (1), together with three known compounds, 5-hydroxy-2-[2-(2-hydroxyphenyl)ethyl]chromone (2), flidersiachromone (3), and 5-hydroxy-2-styrylchromone (4). Among these four compounds, 1 and 2 showed significant neuroprotective activity against glutamate-induced neurotoxicity in primary cultures of rat cortical cells.

  4. Locally advanced cervix carcinoma - innovation in combined modality therapy

    International Nuclear Information System (INIS)

    Swift, Patrick S.

    1996-01-01

    Locally advanced cervical carcinoma continues to be a challenge to the clinician due to local failure as well as systemic metastases. Standard intracavitary and external beam techniques result in local control rates of only 35-65%, with long term survival rates of 25-60% in patients with state IIIA-IVA disease, indicating the need to identify new treatment strategies. Optimization programs for remote-afterloading interstitial brachytherapy allow the delivery of higher local doses of radiation to volumes that more closely approximate tumor target volumes as identified on MR scans, leading to improved therapeutic ratios. Identification of subsets of patients more likely to fail standard therapy, either locally or systemically, may be possible through such techniques as in vivo measurements of hypoxia with Eppendorf oxygen electrodes, interstitial fluid pressure measurements, the Comet assay, and nitroimidazole binding methods. Traditional chemotherapies, administered in either a neoadjuvant role or concomitantly with radiation have been disappointing in prospective trials. A variety of new agents are being investigated to determine if they can increase the frequency or duration of complete response. The taxanes, with response rates of 17-23% by themselves, are being assessed as potential radiosensitizers. The camptotheicin CRT-11 (Irinotecan) has demonstrated activity in platinum resistant cervix cancer, with response rates of 24%. Bioradiotherapeutic approaches, using 13-cis-retinoic acid and interferon-2a, are undergoing phase II studies. Neoangiogenesis inhibitors and vaccines against HPV are also being examined. The aggressive pursuit of techniques that help identify those patients most likely to fail, that allow the delivery of higher radiation doses more safely to the target volume, and that incorporate the use of more effective systemic therapies is necessary to improve the outcome for this disease

  5. Hypoxia as a target for combined modality treatments

    NARCIS (Netherlands)

    Wouters, B G; Weppler, S A; Koritzinsky, M; Landuyt, W; Nuyts, S; Theys, J; Chiu, R K; Lambin, P

    There is overwhelming evidence that solid human tumours grow within a unique micro-environment. This environment is characterised by an abnormal vasculature, which leads to an insufficient supply of oxygen and nutrients to the tumour cells. These characteristics of the environment limit the

  6. Progressive ototoxicity after combined modality treatment of medulloblastoma

    International Nuclear Information System (INIS)

    Dutton, S.C.; Neault, M.; Billett, A.E.; LaVally, B.; Scott, R.M.; Sallan, S.E.; Tarbell, N.J.

    1996-01-01

    Objective: Prospective study to evaluate the response rate, survival and toxicity of pre-irradiation chemotherapy in the treatment of children with seeding CNS tumors. Materials and Methods: Forty-two patients with medulloblastoma were enrolled on a prospective pre-irradiation chemotherapy protocol between 1984 and 1990. Patients (Median age 9.5 years; 29 males, 13 females) received post-operative chemotherapy [cisplatinum 100 mg/m2 q 3 weeks) and vincristine (1.5 mg/m2 weekly) for 9 weeks. Infants (4 patients) received nitrogen mustard (6 mg/m2), procarbazine (100 mg/m2) and vincristine (1.5 mg/m2) until age two followed by craniospinal radiation (CSI). Forty-one patients received CSI with ≥ 50 Gy to the posterior fossa (PF). The median doses to the whole brain, PF, and spine were 33.8 Gy, 55.3 Gy, 27.8 Gy, respectively. Results: Five-year overall survival was 86% and event-free survival was 65% (median follow-up for survivors, 61 months). Thirteen of 15 patients with complete surgical resection documented by post-operative imaging remained free of disease during chemotherapy (CT), and were considered unevaluable for response to CT. The response rate (complete plus partial) to pre-irradiation CT was 45% ((13(29))). Ten patients had stable disease and 6 had progressive disease (PD). Three of 6 patients with PD were long-term survivors after CSI. Thirteen patients relapsed with a median time to failure of 14.5 months. Sites of failure were PF (5 pts), spinal cord (3 pts), CNS/meninges (3 pts), PF/spinal cord (1 pt), and bone metastasis (1 pt). Ototoxicity analysis was performed using 24 patients who had normal hearing in the better ear before chemotherapy and at least one follow-up audiogram for comparison after therapy. 17 patients had an audiogram immediately after CT, and 71% of pts ((12(17))) had high frequency hearing impairment beginning in 3000-8000 Hz range. 18% ((3(17))) had hearing loss in the 500-2000 Hz range necessitating a hearing aid post-CT. 22 patients were tested 1-18 months post-CSI, and showed similar hearing profiles compared to post-CT audiograms ((4(22)) pts required hearing aids). 14 patients were tested from 2.5-10 years post-CSI. (11(14)) patients with long-term follow-up audiograms showed progressive hearing loss with more severe deficits compared to the prior audiogram performed between 1-18 months post-CSI. 93% ((13(14))) of these patients had at least high frequency hearing loss. 57% ((8(14))) had deficits requiring a hearing aid. Conclusion: We conclude that pre-irradiation chemotherapy with cisplatinum and vincristine and low dose craniospinal irradiation is effective post-operative therapy for medulloblastoma. However, this regimen is associated with clinically significant hearing loss which is progressive over time. Serial audiograms should be part of routine follow-up care of children with medulloblastoma in order to evaluate and treat the long-term sequelae of successful treatment

  7. Stem Cell-Based Neuroprotective and Neurorestorative Strategies

    Directory of Open Access Journals (Sweden)

    Chia-Wei Hung

    2010-05-01

    Full Text Available Stem cells, a special subset of cells derived from embryo or adult tissues, are known to present the characteristics of self-renewal, multiple lineages of differentiation, high plastic capability, and long-term maintenance. Recent reports have further suggested that neural stem cells (NSCs derived from the adult hippocampal and subventricular regions possess the utilizing potential to develop the transplantation strategies and to screen the candidate agents for neurogenesis, neuroprotection, and neuroplasticity in neurodegenerative diseases. In this article, we review the roles of NSCs and other stem cells in neuroprotective and neurorestorative therapies for neurological and psychiatric diseases. We show the evidences that NSCs play the key roles involved in the pathogenesis of several neurodegenerative disorders, including depression, stroke and Parkinson’s disease. Moreover, the potential and possible utilities of induced pluripotent stem cells (iPS, reprogramming from adult fibroblasts with ectopic expression of four embryonic genes, are also reviewed and further discussed. An understanding of the biophysiology of stem cells could help us elucidate the pathogenicity and develop new treatments for neurodegenerative disorders. In contrast to cell transplantation therapies, the application of stem cells can further provide a platform for drug discovery and small molecular testing, including Chinese herbal medicines. In addition, the high-throughput stem cell-based systems can be used to elucidate the mechanisms of neuroprotective candidates in translation medical research for neurodegenerative diseases.

  8. Docosahexaenoic acid confers enduring neuroprotection in experimental stroke.

    Science.gov (United States)

    Hong, Sung-Ha; Belayev, Ludmila; Khoutorova, Larissa; Obenaus, Andre; Bazan, Nicolas G

    2014-03-15

    Recently we demonstrated that docosahexaenoic acid (DHA) is highly neuroprotective when animals were allowed to survive during one week. This study was conducted to establish whether the neuroprotection induced by DHA persists with chronic survival. Sprague-Dawley rats underwent 2h of middle cerebral artery occlusion (MCAo) and treated with DHA or saline at 3h after MCAo. Animals received neurobehavioral examination (composite neuroscore, rota-rod, beam walking and Y maze tests) followed by ex vivo magnetic resonance imaging and histopathology at 3 weeks. DHA improved composite neurologic score beginning on day 1 by 20%, which persisted throughout weeks 1-3 by 24-41% compared to the saline-treated group. DHA prolonged the latency in rota-rod on weeks 2-3 by 162-178%, enhanced balance performance in the beam walking test on weeks 1 and 2 by 42-51%, and decreased the number of entries in the Y maze test by 51% and spontaneous alteration by 53% on week 2 compared to the saline-treated group. DHA treatment reduced tissue loss (computed from T2-weighted images) by 24% and total and cortical infarct volumes by 46% and 54% compared to the saline-treated group. These results show that DHA confers enduring ischemic neuroprotection. Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.

  9. Neurotropic and neuroprotective activities of the earthworm peptide Lumbricusin

    International Nuclear Information System (INIS)

    Kim, Dae Hong; Lee, Ik Hwan; Nam, Seung Taek; Hong, Ji; Zhang, Peng; Hwang, Jae Sam; Seok, Heon; Choi, Hyemin; Lee, Dong Gun; Kim, Jae Il; Kim, Ho

    2014-01-01

    Highlights: • 11-mer peptide Lumbricusin, a defensin like peptide, is isolated from earthworm. • We here demonstrated that Lumbricusin has neurotropic and neuroprotective effects. • p27 degradation by Lumbricusin mediates effects of Lumbricusin on neuronal cells. - Abstract: We recently isolated a polypeptide from the earthworm Lumbricus terrestris that is structurally similar to defensin, a well-known antibacterial peptide. An 11-mer antibacterial peptide (NH 2 -RNRRWCIDQQA), designated Lumbricusin, was synthesized based on the amino acid sequence of the isolated polypeptide. Since we previously reported that CopA3, a dung beetle peptide, enhanced neuronal cell proliferation, we here examined whether Lumbricusin exerted neurotropic and/or neuroprotective effects. Lumbricusin treatment induced a time-dependent increase (∼51%) in the proliferation of human neuroblastoma SH-SY5Y cells. Lumbricusin also significantly inhibited the apoptosis and decreased viability induced by treatment with 6-hydroxy dopamine, a Parkinson’s disease-mimicking agent. Immunoblot analyses revealed that Lumbricusin treatment increased ubiquitination of p27 Kip1 protein, a negative regulator of cell-cycle progression, in SH-SY5Y cells, and markedly promoted its degradation. Notably, adenoviral-mediated over-expression of p27 Kip1 significantly blocked the antiapoptotic effect of Lumbricusin in 6-hydroxy dopamine-treated SH-SY5Y cells. These results suggest that promotion of p27 Kip1 degradation may be the main mechanism underlying the neuroprotective and neurotropic effects of Lumbricusin

  10. Neuroprotection and its molecular mechanism following spinal cord injury☆

    Science.gov (United States)

    Liu, Nai-Kui; Xu, Xiao-Ming

    2012-01-01

    Acute spinal cord injury initiates a complex cascade of molecular events termed ‘secondary injury’, which leads to progressive degeneration ranging from early neuronal apoptosis at the lesion site to delayed degeneration of intact white matter tracts, and, ultimately, expansion of the initial injury. These secondary injury processes include, but are not limited to, inflammation, free radical-induced cell death, glutamate excitotoxicity, phospholipase A2 activation, and induction of extrinsic and intrinsic apoptotic pathways, which are important targets in developing neuroprotective strategies for treatment of spinal cord injury. Recently, a number of studies have shown promising results on neuroprotection and recovery of function in rodent models of spinal cord injury using treatments that target secondary injury processes including inflammation, phospholipase A2 activation, and manipulation of the PTEN-Akt/mTOR signaling pathway. The present review outlines our ongoing research on the molecular mechanisms of neuroprotection in experimental spinal cord injury and briefly summarizes our earlier findings on the therapeutic potential of pharmacological treatments in spinal cord injury. PMID:25624837

  11. Curcumin: a potential neuroprotective agent in Parkinson's disease.

    Science.gov (United States)

    Mythri, R B; Bharath, M M Srinivas

    2012-01-01

    Parkinson's disease (PD) is an age-associated neurodegenerative disease clinically characterized as a movement disorder. The motor symptoms in PD arise due to selective degeneration of dopaminergic neurons in the substantia nigra of the ventral midbrain thereby depleting the dopamine levels in the striatum. Most of the current pharmacotherapeutic approaches in PD are aimed at replenishing the striatal dopamine. Although these drugs provide symptomatic relief during early PD, many patients develop motor complications with long-term treatment. Further, PD medications do not effectively tackle tremor, postural instability and cognitive deficits. Most importantly, most of these drugs do not exhibit neuroprotective effects in patients. Consequently, novel therapies involving natural antioxidants and plant products/molecules with neuroprotective properties are being exploited for adjunctive therapy. Curcumin is a polyphenol and an active component of turmeric (Curcuma longa), a dietary spice used in Indian cuisine and medicine. Curcumin exhibits antioxidant, anti-inflammatory and anti-cancer properties, crosses the blood-brain barrier and is neuroprotective in neurological disorders. Several studies in different experimental models of PD strongly support the clinical application of curcumin in PD. The current review explores the therapeutic potential of curcumin in PD.

  12. Molecular Basis for Certain Neuroprotective Effects of Thyroid Hormone

    Directory of Open Access Journals (Sweden)

    Paul eDavis

    2011-10-01

    Full Text Available The pathophysiology of brain damage that is common to ischemia-reperfusion inury and brain trauma includes disordered neuronal and glial cell energetics, intracellular acidosis, calcium toxicity, extracellular excitotoxic glutamate accumulation and dysfunction of the cytoskeleton and endoplasmic reticulum. Thyroid hormone isoforms, 3, 5, 3'-triiodo-L-thyronine (T3 and L-thyroxine (T4, have nongenomic and genomic actions that are relevant to repair of certain features of the pathophysiology of brain damage. Thyroid hormone can nongenomically repair intracullar H+ accumulation by stimulation of the Na+/H+ exchanger and can support desirably low [Ca2+]i.c. by activation of plasma membrane Ca2+-ATPase. Thyroid hormone nongenomically stimulates astrocyte glutamate uptake, an action that protects both glial cells and neurons. The hormone supports the integrity of the cytoskeleton by its effect on actin. Several proteins linked to thyroid hormone action are also neuroprotective. For example, the hormone stimulates expression of the seladin-1 gene whose gene product is anti-apoptotic and is potentially protection in the setting of neurodegeneration. Transthyretin (TTR is a serum transport protein for T4 that is important to blood-brain barrier transfer of the hormone and TTR has also been found to be neuroprotective in the setting of ischemia. Finally, the interesting thyronamine derivatives of T4 have been shown to protect against ischemic brain damage through their ability to induce hypothermia in the intact organism. Thus, thyroid hromone or hormone derivatives have experimental promise as neuroprotective agents.

  13. Neuroprotective effects of female sex steroids in cerebral ischemia

    Directory of Open Access Journals (Sweden)

    Drača Sanja

    2013-03-01

    Full Text Available The central and peripheral nervous system are important targets of sex steroids. Sex steroids affect the brain development and differentiation, and influence neuronal functions. Recent evidence emphasizes a striking sex-linked difference in brain damage after experimental stroke, as well as the efficacy of hormones in treating cerebral stroke injury. Several different models of cerebral ischemia have been utilized for hormone neuroprotection studies, including transient or permanent middle cerebral artery occlusion, transient global ischemia, and transient forebrain ischemia. Extensive experimental studies have shown that female sex steroids such as progesterone and 176-estradiol exert neuroprotective effects in the experimental models of stroke, although deleterious effects have also been reported. Also, a significance of numerous factors, including gender and age of experimental animals, localization of brain lesion, duration of ischemia and precise dose of steroids has been pointed out. There are multiple potential mechanisms that might be invoked to explain the beneficial effects of female sex steroids in brain injury, involving neuroprotection, anti-inflammatory properties, effects on vasculature and altered transcriptional regulation. A several clinical trials on the effects of sex hormones to traumatic brain injury have been performed, suggesting that hormone therapy may represent a new therapeutic tool to combat certain diseases, such as traumatic brain injury. Further basic science studies and randomized clinical trials are necessary to reveal a potential application of these molecules as a new therapeutic strategy.

  14. Neurotropic and neuroprotective activities of the earthworm peptide Lumbricusin

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Dae Hong; Lee, Ik Hwan; Nam, Seung Taek; Hong, Ji; Zhang, Peng [Department of Life Science, College of Natural Science, Daejin University, Pocheon, Gyeonggido 487-711 (Korea, Republic of); Hwang, Jae Sam [Department of Agricultural Biology, National Academy of Agricultural Science, RDA, Suwon 441-707 (Korea, Republic of); Seok, Heon [Department of Biomedical Engineering, Jungwon University, Goesan, Chungcheongbukdo 367-700 (Korea, Republic of); Choi, Hyemin; Lee, Dong Gun [School of Life Sciences, KNU Creative Bioresearch Group (BK21 Plus Program), College of Natural Sciences, Kyungpook National University, Daehak-ro 80, Buk-gu, Daegu 702-701 (Korea, Republic of); Kim, Jae Il [School of Life Sciences, Gwangju Institute of Science and Technology, Oryong-dong, Buk-gu, Gwangju 500-712 (Korea, Republic of); Kim, Ho, E-mail: hokim@daejin.ac.kr [Department of Life Science, College of Natural Science, Daejin University, Pocheon, Gyeonggido 487-711 (Korea, Republic of)

    2014-06-06

    Highlights: • 11-mer peptide Lumbricusin, a defensin like peptide, is isolated from earthworm. • We here demonstrated that Lumbricusin has neurotropic and neuroprotective effects. • p27 degradation by Lumbricusin mediates effects of Lumbricusin on neuronal cells. - Abstract: We recently isolated a polypeptide from the earthworm Lumbricus terrestris that is structurally similar to defensin, a well-known antibacterial peptide. An 11-mer antibacterial peptide (NH{sub 2}-RNRRWCIDQQA), designated Lumbricusin, was synthesized based on the amino acid sequence of the isolated polypeptide. Since we previously reported that CopA3, a dung beetle peptide, enhanced neuronal cell proliferation, we here examined whether Lumbricusin exerted neurotropic and/or neuroprotective effects. Lumbricusin treatment induced a time-dependent increase (∼51%) in the proliferation of human neuroblastoma SH-SY5Y cells. Lumbricusin also significantly inhibited the apoptosis and decreased viability induced by treatment with 6-hydroxy dopamine, a Parkinson’s disease-mimicking agent. Immunoblot analyses revealed that Lumbricusin treatment increased ubiquitination of p27{sup Kip1} protein, a negative regulator of cell-cycle progression, in SH-SY5Y cells, and markedly promoted its degradation. Notably, adenoviral-mediated over-expression of p27{sup Kip1} significantly blocked the antiapoptotic effect of Lumbricusin in 6-hydroxy dopamine-treated SH-SY5Y cells. These results suggest that promotion of p27{sup Kip1} degradation may be the main mechanism underlying the neuroprotective and neurotropic effects of Lumbricusin.

  15. Graphical representation of covariant-contravariant modal formulae

    Directory of Open Access Journals (Sweden)

    Miguel Palomino

    2011-08-01

    Full Text Available Covariant-contravariant simulation is a combination of standard (covariant simulation, its contravariant counterpart and bisimulation. We have previously studied its logical characterization by means of the covariant-contravariant modal logic. Moreover, we have investigated the relationships between this model and that of modal transition systems, where two kinds of transitions (the so-called may and must transitions were combined in order to obtain a simple framework to express a notion of refinement over state-transition models. In a classic paper, Boudol and Larsen established a precise connection between the graphical approach, by means of modal transition systems, and the logical approach, based on Hennessy-Milner logic without negation, to system specification. They obtained a (graphical representation theorem proving that a formula can be represented by a term if, and only if, it is consistent and prime. We show in this paper that the formulae from the covariant-contravariant modal logic that admit a "graphical" representation by means of processes, modulo the covariant-contravariant simulation preorder, are also the consistent and prime ones. In order to obtain the desired graphical representation result, we first restrict ourselves to the case of covariant-contravariant systems without bivariant actions. Bivariant actions can be incorporated later by means of an encoding that splits each bivariant action into its covariant and its contravariant parts.

  16. Neuroprotective effects of testosterone metabolites and dependency on receptor action on the morphology of somatic motoneurons following the death of neighboring motoneurons.

    Science.gov (United States)

    Cai, Yi; Chew, Cory; Muñoz, Fernando; Sengelaub, Dale R

    2017-06-01

    Partial depletion of spinal motoneuron populations induces dendritic atrophy in neighboring motoneurons, and treatment with testosterone is neuroprotective, attenuating induced dendritic atrophy. In this study we examined whether the protective effects of testosterone could be mediated via its androgenic or estrogenic metabolites. Furthermore, to assess whether these neuroprotective effects were mediated through steroid hormone receptors, we used receptor antagonists to attempt to prevent the neuroprotective effects of hormones after partial motoneuron depletion. Motoneurons innervating the vastus medialis muscles of adult male rats were selectively killed by intramuscular injection of cholera toxin-conjugated saporin. Simultaneously, some saporin-injected rats were treated with either dihydrotestosterone or estradiol, alone or in combination with their respective receptor antagonists, or left untreated. Four weeks later, motoneurons innervating the ipsilateral vastus lateralis muscle were labeled with cholera toxin-conjugated horseradish peroxidase, and dendritic arbors were reconstructed in three dimensions. Compared with intact normal animals, partial motoneuron depletion resulted in decreased dendritic length in remaining quadriceps motoneurons. Dendritic atrophy was attenuated with both dihydrotestosterone and estradiol treatment to a degree similar to that seen with testosterone, and attenuation of atrophy was prevented by receptor blockade. Together, these findings suggest that neuroprotective effects on motoneurons can be mediated by either androgenic or estrogenic hormones and require action via steroid hormone receptors, further supporting a role for hormones as neurotherapeutic agents in the injured nervous system. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 691-707, 2017. © 2016 Wiley Periodicals, Inc.

  17. Cell therapy centered on IL-1Ra is neuroprotective in experimental stroke

    DEFF Research Database (Denmark)

    Clausen, Bettina Hjelm; Lambertsen, Kate Lykke; Dagnæs-Hansen, Frederik

    2016-01-01

    ), a known neuroprotectant in stroke, can promote neuroprotection, by modulating the detrimental inflammatory response in the tissue at risk. We show by the use of IL-1Ra-overexpressing and IL-1Ra-deficient mice that IL-1Ra is neuroprotective in stroke. Characterization of the cellular and spatiotemporal...... irradiated mice with IL-1Ra-producing bone marrow cells is associated with neuroprotection and recruitment of IL-1Ra-producing leukocytes after stroke. Neuroprotection is also achieved by therapeutic injection of IL-1Ra-producing bone marrow cells 30 min after stroke onset, additionally improving...... by demonstration of IL-1Ra-producing cells in the human cortex early after ischemic stroke. Taken together, our results attribute distinct neuroprotective or neurotoxic functions to segregated subsets of microglia and suggest that treatment strategies increasing the production of IL-1Ra by infiltrating leukocytes...

  18. Neuroprotective effects of electro acupuncture on hypoxic-ischemic encephalopathy in newborn rats Ass.

    Science.gov (United States)

    Xu, Tao; Li, Wenjie; Liang, Yiqun; Yang, Zhonghua; Liu, Jingdong; Wang, Yejun; Su, Nailun

    2014-11-01

    Hypoxic-ischemic encephalopathy (HIE) is a common and potentially devastating condition in the neonate, associated with high mortality and morbidity. Effective treatment options are limited and therefore alternative therapies such as acupuncture are increasingly used. Previous studies have shown that electro acupuncture promoted proliferation of neural progenitor cell and increased expression of neurotrophic factor in HIE. However, effects of electro acupuncture on downstream signaling pathways have been rarely researched. So, in the present study, we aimed to evaluate the neuroprotective effects of electro acupuncture on HIE and to further investigate the role of GDNF family receptor member RET and its key downstream PI3-K/Akt pathway in the process. A rat HIE model was constructed by the left common carotid artery (LCCA) ligation method in combination with hypoxic treatment. Considering that Baihui (GV20), Dazhui (GV14), Quchi (LI11) and Yongquan (KI1) are commonly used in clinics for stroke treatment and are easy to locate, we chose the above four acupoints as the combination for electro acupuncture treatment which was performed once a day for different time periods. Hematoxylin-eosin (HE) staining and transmission electron microscopy results showed that electro acupuncture could ameliorate neurologic damage and alleviate the degenerative changes of ultra structure of cortical neurons in rats subjected to HIE. And the longer acupuncture treatment lasted, the better its therapeutic effect would be. This was accompanied by gradually increased expression of GDNF family receptor RET at the mRNA level and its downstream signaling Akt at the protein level in the ischemic cortex. These findings suggest that electro acupuncture shows neuroprotective effects in HIE, which at least in part is attributed to activation of PI3-K/Akt signaling pathway.

  19. Ghrelin-AMPK Signaling Mediates the Neuroprotective Effects of Calorie Restriction in Parkinson's Disease

    Science.gov (United States)

    Bayliss, Jacqueline A.; Lemus, Moyra B.; Stark, Romana; Santos, Vanessa V.; Thompson, Aiysha; Rees, Daniel J.; Galic, Sandra; Elsworth, John D.; Kemp, Bruce E.; Davies, Jeffrey S.

    2016-01-01

    Calorie restriction (CR) is neuroprotective in Parkinson's disease (PD) although the mechanisms are unknown. In this study we hypothesized that elevated ghrelin, a gut hormone with neuroprotective properties, during CR prevents neurodegeneration in an 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD. CR attenuated the MPTP-induced loss of substantia nigra (SN) dopamine neurons and striatal dopamine turnover in ghrelin WT but not KO mice, demonstrating that ghrelin mediates CR's neuroprotective effect. CR elevated phosphorylated AMPK and ACC levels in the striatum of WT but not KO mice suggesting that AMPK is a target for ghrelin-induced neuroprotection. Indeed, exogenous ghrelin significantly increased pAMPK in the SN. Genetic deletion of AMPKβ1 and 2 subunits only in dopamine neurons prevented ghrelin-induced AMPK phosphorylation and neuroprotection. Hence, ghrelin signaling through AMPK in SN dopamine neurons mediates CR's neuroprotective effects. We consider targeting AMPK in dopamine neurons may recapitulate neuroprotective effects of CR without requiring dietary intervention. SIGNIFICANCE STATEMENT The neuroprotective mechanisms of calorie restriction (CR) in Parkinson's disease are unknown. Indeed, the difficulty to adhere to CR necessitates an alternative method to recapitulate the neuroprotective benefits of CR while bypassing dietary constraints. Here we show that CR increases plasma ghrelin, which targets substantia nigra dopamine to maintain neuronal survival. Selective deletion on AMPK beta1 and beta2 subunits only in DAT cre-expressing neurons shows that the ghrelin-induced neuroprotection requires activation of AMPK in substantia nigra dopamine neurons. We have discovered ghrelin as a key metabolic signal, and AMPK in dopamine neurons as its target, which links calorie restriction with neuroprotection in Parkinson's disease. Thus, targeting AMPK in dopamine neurons may provide novel neuroprotective benefits in Parkinson's disease. PMID

  20. Training Modalities to Increase Sensorimotor Adaptability

    Science.gov (United States)

    Bloomberg, J. J.; Mulavara, A. P.; Peters, B. T.; Brady, R.; Audas, C.; Cohen, H. S.

    2009-01-01

    During the acute phase of adaptation to novel gravitational environments, sensorimotor disturbances have the potential to disrupt the ability of astronauts to perform required mission tasks. The goal of our current series of studies is develop a sensorimotor adaptability (SA) training program designed to facilitate recovery of functional capabilities when astronauts transition to different gravitational environments. The project has conducted a series of studies investigating the efficacy of treadmill training combined with a variety of sensory challenges (incongruent visual input, support surface instability) designed to increase adaptability. SA training using a treadmill combined with exposure to altered visual input was effective in producing increased adaptability in a more complex over-ground ambulatory task on an obstacle course. This confirms that for a complex task like walking, treadmill training contains enough of the critical features of overground walking to be an effective training modality. SA training can be optimized by using a periodized training schedule. Test sessions that each contain short-duration exposures to multiple perturbation stimuli allows subjects to acquire a greater ability to rapidly reorganize appropriate response strategies when encountering a novel sensory environment. Using a treadmill mounted on top of a six degree-of-freedom motion base platform we investigated locomotor training responses produced by subjects introduced to a dynamic walking surface combined with alterations in visual flow. Subjects who received this training had improved locomotor performance and faster reaction times when exposed to the novel sensory stimuli compared to control subjects. Results also demonstrate that individual sensory biases (i.e. increased visual dependency) can predict adaptive responses to novel sensory environments suggesting that individual training prescription can be developed to enhance adaptability. These data indicate that SA

  1. Neuroprotection and secondary damage following spinal cord injury: concepts and methods.

    Science.gov (United States)

    Hilton, Brett J; Moulson, Aaron J; Tetzlaff, Wolfram

    2017-06-23

    Neuroprotection refers to the attenuation of pathophysiological processes triggered by acute injury to minimize secondary damage. The development of neuroprotective treatments represents a major goal in the field of spinal cord injury (SCI) research. In this review, we discuss the strengths and limitations of the methodologies employed to assess secondary damage and neuroprotection in preclinical models of traumatic SCI. We also discuss modelling issues and how new tools might be exploited to study secondary damage and neuroprotection. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  2. Experienced Sensory Modalities in Dream Recall

    OpenAIRE

    岡田, 斉

    2000-01-01

    The purpose of the present study is to survey the frequency of visual, auditory, kinaesthetic, cutaneous, organic, gustatory, and olfactory experience in dream recall. A total of 1267 undergraduate students completed a dream recall frequency questionnaire, which contained a question about dream recall frequency and about recall frequency of seven sensory modalities. Results showed that seven sensory modalities were divided into two groups; normally perceived sensory modalities in dreaming, wh...

  3. Pathological histone acetylation in Parkinson's disease: Neuroprotection and inhibition of microglial activation through SIRT 2 inhibition.

    Science.gov (United States)

    Harrison, Ian F; Smith, Andrew D; Dexter, David T

    2018-02-14

    Parkinson's disease (PD) is associated with degeneration of nigrostriatal neurons due to intracytoplasmic inclusions composed predominantly of a synaptic protein called α-synuclein. Accumulations of α-synuclein are thought to 'mask' acetylation sites on histone proteins, inhibiting the action of histone acetyltransferase (HAT) enzymes in their equilibrium with histone deacetylases (HDACs), thus deregulating the dynamic control of gene transcription. It is therefore hypothesised that the misbalance in the actions of HATs/HDACs in neurodegeneration can be rectified with the use of HDAC inhibitors, limiting the deregulation of transcription and aiding neuronal homeostasis and neuroprotection in disorders such as PD. Here we quantify histone acetylation in the Substantia Nigra pars compacta (SNpc) in the brains of control, early and late stage PD cases to determine if histone acetylation is a function of disease progression. PD development is associated with Braak-dependent increases in histone acetylation. Concurrently, we show that as expected disease progression is associated with reduced markers of dopaminergic neurons and increased markers of activated microglia. We go on to demonstrate that in vitro, degenerating dopaminergic neurons exhibit histone hypoacetylation whereas activated microglia exhibit histone hyperacetylation. This suggests that the disease-dependent increase in histone acetylation observed in human PD cases is likely a combination of the contributions of both degenerating dopaminergic neurons and infiltrating activated microglia. The HDAC SIRT 2 has become increasingly implicated as a novel target for mediation of neuroprotection in PD: the neuronal and microglial specific effects of its inhibition however remain unclear. We demonstrate that SIRT 2 expression in the SNpc of PD brains remains relatively unchanged from controls and that SIRT 2 inhibition, via AGK2 treatment of neuronal and microglial cultures, results in neuroprotection of

  4. A study of exercise modality and physical self-esteem in breast cancer survivors.

    Science.gov (United States)

    Musanti, Rita

    2012-02-01

    This study, theoretically based on the Exercise Self-Esteem Model, EXSEM, examined effects of exercise modality on physical and global self-esteem (PSE, GSE) in breast cancer survivors. The EXSEM posits GSE at the apex with PSE feeding into GSE. PSE has three subdomains: physical condition (PC), attractive body (AB), and physical strength (PS). The goals were to compare the effect of combination modality versus single-modality exercise on PSE and GSE and to explore the relationship between exercise modality and the subdomains of PSE. Survivors were randomly allocated to flexibility (F), aerobic (A), resistance (R), or aerobic plus resistance (AR), 12-wk, individualized, home-based exercise program. Pre/posttesting included submaximal treadmill test, six-repetition maximum chest press and leg press, YMCA bench press, shoulder/hip flexibility, and bioelectric impedance analysis body composition. Esteem measures were the Physical Self-Perception Profile and the Rosenberg Self-Esteem Scale. Forty-two women completed the study (F = 12, A = 10, R = 9, and AR = 11). Fitness improvements congruent with exercise modality were seen in all groups. PSE and GSE outcomes did not reveal a greater effect from the combination modality program, AR, compared with the single-modality programs A and R. The relationships between the single-modality groups and the subdomains of PC, PS, and AB were supported in the R group (PS and AB increased) and were partially supported in the A group (PC, not AB, increased). A single-modality R program significantly improved all domains of PSE, and participation in the A program improved the PC subdomain. The combination exercise program did not enhance PSE greater than the single-modality programs. EXSEM was a useful framework for exploring esteem in breast cancer survivors.

  5. Modalities of hemodialysis: Quality improvement

    Directory of Open Access Journals (Sweden)

    Ayman Karkar

    2012-01-01

    Full Text Available Hemodialysis (HD treatment had, over many years, improved the survival rate of patients with end-stage renal disease. However, standard or conventional HD prescription is far from being optimal in replacing the function of normal kidneys. Its unphysiologic clearance pattern and inability to remove all types and sizes of uremic toxins results in inter- and intra-dialysis complications and an unacceptably high rate of cardiovascular morbidity and mortality. Efficiency of HD can be improved by increasing blood and dialysate flow rates, dialyzer size and surface area and duration and frequency of dialysis sessions. Home HD, where short daily or long slow nocturnal HD sessions can conveniently be performed, provides an excellent option for quality of life improvement and reduction in morbidity and mortality. Recent innovations in the specifications of HD machines and improvement in dialysis membranes characteristics and water treatment technology paved the way for achieving quality HD. These advancements have resulted in efficient implementation of adsorption, diffusion and/or convection principles using adsorption HD, hemofiltration, hemodiafiltration (HDF and online HDF modalities in order to achieve optimum HD. Implementation of these innovations resulted in better quality care achievements in clinical practice and reduction in morbidity and mortality rates among HD patients.

  6. Preemptive analgesia I: physiological pathways and pharmacological modalities.

    LENUS (Irish Health Repository)

    Kelly, D J

    2012-02-03

    PURPOSE: This two-part review summarizes the current knowledge of physiological mechanisms, pharmacological modalities and controversial issues surrounding preemptive analgesia. SOURCE: Articles from 1966 to present were obtained from the MEDLINE databases. Search terms included: analgesia, preemptive; neurotransmitters; pain, postoperative; hyperalgesia; sensitization, central nervous system; pathways, nociception; anesthetic techniques; analgesics, agents. Principal findings: The physiological basis of preemptive analgesia is complex and involves modification of the pain pathways. The pharmacological modalities available may modify the physiological responses at various levels. Effective preemptive analgesic techniques require multi-modal interception of nociceptive input, increasing threshold for nociception, and blocking or decreasing nociceptor receptor activation. Although the literature is controversial regarding the effectiveness of preemptive analgesia, some general recommendations can be helpful in guiding clinical care. Regional anesthesia induced prior to surgical trauma and continued well into the postoperative period is effective in attenuating peripheral and central sensitization. Pharmacologic agents such as NSAIDs (non-steroidal anti-inflammatory drugs) opioids, and NMDA (N-methyl-D-aspartate) - and alpha-2-receptor antagonists, especially when used in combination, act synergistically to decrease postoperative pain. CONCLUSION: The variable patient characteristics and timing of preemptive analgesia in relation to surgical noxious input requires individualization of the technique(s) chosen. Multi-modal analgesic techniques appear most effective.

  7. MIDA - Optimizing control room performance through multi-modal design

    International Nuclear Information System (INIS)

    Ronan, A. M.

    2006-01-01

    Multi-modal interfaces can support the integration of humans with information processing systems and computational devices to maximize the unique qualities that comprise a complex system. In a dynamic environment, such as a nuclear power plant control room, multi-modal interfaces, if designed correctly, can provide complementary interaction between the human operator and the system which can improve overall performance while reducing human error. Developing such interfaces can be difficult for a designer without explicit knowledge of Human Factors Engineering principles. The Multi-modal Interface Design Advisor (MIDA) was developed as a support tool for system designers and developers. It provides design recommendations based upon a combination of Human Factors principles, a knowledge base of historical research, and current interface technologies. MIDA's primary objective is to optimize available multi-modal technologies within a human computer interface in order to balance operator workload with efficient operator performance. The purpose of this paper is to demonstrate MIDA and illustrate its value as a design evaluation tool within the nuclear power industry. (authors)

  8. Multi-modal locomotion: from animal to application

    International Nuclear Information System (INIS)

    Lock, R J; Burgess, S C; Vaidyanathan, R

    2014-01-01

    The majority of robotic vehicles that can be found today are bound to operations within a single media (i.e. land, air or water). This is very rarely the case when considering locomotive capabilities in natural systems. Utility for small robots often reflects the exact same problem domain as small animals, hence providing numerous avenues for biological inspiration. This paper begins to investigate the various modes of locomotion adopted by different genus groups in multiple media as an initial attempt to determine the compromise in ability adopted by the animals when achieving multi-modal locomotion. A review of current biologically inspired multi-modal robots is also presented. The primary aim of this research is to lay the foundation for a generation of vehicles capable of multi-modal locomotion, allowing ambulatory abilities in more than one media, surpassing current capabilities. By identifying and understanding when natural systems use specific locomotion mechanisms, when they opt for disparate mechanisms for each mode of locomotion rather than using a synergized singular mechanism, and how this affects their capability in each medium, similar combinations can be used as inspiration for future multi-modal biologically inspired robotic platforms. (topical review)

  9. Focal ischemia of the brain after neuroprotected carotid artery stenting.

    Science.gov (United States)

    Schlüter, Michael; Tübler, Thilo; Steffens, Johann C; Mathey, Detlef G; Schofer, Joachim

    2003-09-17

    This study sought to assess the incidence of cerebral ischemia in nonselected patients undergoing neuroprotected carotid angioplasty and stenting (CAS) without preceding multiple-vessel diagnostic angiography. Protection devices to prevent distal embolization during CAS are presently under clinical investigation. Diffusion-weighted magnetic resonance imaging (MRI) visualizes recent ischemia of the brain and may aid in assessing the efficacy of protection devices. Elective CAS was performed in 42 consecutive patients (15 female, 27 male; mean age, 67 +/- 9 years) using six different types of cerebral protection systems. All patients underwent MRI of the brain before and after a total of 44 interventions. Placement and retrieval of the devices and stent deployment was achieved in all procedures. New ischemic foci were seen on postinterventional MRI in 10 cases (22.7%). One patient had sustained a major stroke, whereas no adverse neurological sequelae were associated with the other nine procedures. In the latter, one to three foci (maximum area 43.0 mm(2)) were detected in cerebral regions subtended by the ipsilateral carotid artery in eight cases and by the contralateral carotid artery in one case. In the stroke patient, 12 ischemic foci (maximum area 84.5 mm(2)) were exclusively located in the contralateral hemisphere. Follow-up MRI at 4.1 months (median, n = 7) identified residuals of cerebral ischemia only in this patient. Neuroprotected CAS is associated in about 25% of cases with predominantly silent cerebral ischemia. Our findings suggest manipulation of endoluminal equipment in the supraaortic vessels to be a major risk factor for cerebral embolism during neuroprotected CAS.

  10. Food, nutrigenomics, and neurodegeneration--neuroprotection by what you eat!

    Science.gov (United States)

    Virmani, Ashraf; Pinto, Luigi; Binienda, Zbigniew; Ali, Syed

    2013-10-01

    Diet in human health is no longer simple nutrition, but in light of recent research, especially nutrigenomics, it is linked via evolution and genetics to cell health status capable of modulating apoptosis, detoxification, and appropriate gene response. Nutritional deficiency and disease especially lack of vitamins and minerals is well known, but more recently, epidemiological studies suggest a role of fruits and vegetables, as well as essential fatty acids and even red wine (French paradox), in protection against disease. In the early 1990s, various research groups started considering the use of antioxidants (e.g., melatonin, resveratrol, green tea, lipoic acid) and metabolic compounds (e.g., nicotinamide, acetyl-L-carnitine, creatine, coenzyme Q10) as possible candidates in neuroprotection. They were of course considered on par with snake oil salesman (women) at the time. The positive actions of nutritional supplements, minerals, and plant extracts in disease prevention are now mainstream and commercial health claims being made are subject to regulation in most countries. Apart from efficacy and finding, the right dosages, the safety, and especially the level of purification and lack of contamination are all issues that are important as their use becomes widespread. From the mechanistic point of view, most of the time these substances replenish the body's deficiency and restore normal function. However, they also exert actions that are not sensu stricto nutritive and could be considered pharmacological especially that, at times, higher intake than recommended (RDA) is needed to see these effects. Free radicals and neuroinflammation processes underlie many neurodegenerative conditions, even Parkinson's disease and Alzheimer's disease. Curcumin, carotenoids, acetyl-L-carnitine, coenzyme Q10, vitamin D, and polyphenols and other nutraceuticals have the potential to target multiple pathways in these conditions. In summary, augmenting neuroprotective pathways using

  11. Encapsulation of curcumin in polyelectrolyte nanocapsules and their neuroprotective activity

    Science.gov (United States)

    Szczepanowicz, Krzysztof; Jantas, Danuta; Piotrowski, Marek; Staroń, Jakub; Leśkiewicz, Monika; Regulska, Magdalena; Lasoń, Władysław; Warszyński, Piotr

    2016-09-01

    Poor water solubility and low bioavailability of lipophilic drugs can be potentially improved with the use of delivery systems. In this study, encapsulation of nanoemulsion droplets was utilized to prepare curcumin nanocarriers. Nanosize droplets containing the drug were encapsulated in polyelectrolyte shells formed by the layer-by-layer (LbL) adsorption of biocompatible polyelectrolytes: poly-L-lysine (PLL) and poly-L-glutamic acid (PGA). The size of synthesized nanocapsules was around 100 nm. Their biocompatibility and neuroprotective effects were evaluated on the SH-SY5Y human neuroblastoma cell line using cell viability/toxicity assays (MTT reduction, LDH release). Statistically significant toxic effect was clearly observed for PLL coated nanocapsules (reduction in cell viability about 20%-60%), while nanocapsules with PLL/PGA coating did not evoke any detrimental effects on SH-SY5Y cells. Curcumin encapsulated in PLL/PGA showed similar neuroprotective activity against hydrogen peroxide (H2O2)-induced cell damage, as did 5 μM curcumin pre-dissolved in DMSO (about 16% of protection). Determination of concentration of curcumin in cell lysate confirmed that curcumin in nanocapsules has cell protective effect in lower concentrations (at least 20 times) than when given alone. Intracellular mechanisms of encapsulated curcumin-mediated protection engaged the prevention of the H2O2-induced decrease in mitochondrial membrane potential (MMP) but did not attenuate Reactive Oxygen Species (ROS) formation. The obtained results indicate the utility of PLL/PGA shell nanocapsules as a promising, alternative way of curcumin delivery for neuroprotective purposes with improved efficiency and reduced toxicity.

  12. A New Triterpene from Buddleja lindleyana with Neuroprotective Effect

    Directory of Open Access Journals (Sweden)

    Ya-Shuo Ren

    2017-07-01

    Full Text Available In the phytochemical investigation of Buddleja lindleyana , a new 3-acetyl substituted triterpene, 13, 28-epoxy-23-hydroxy-3β-acetoxy-olean-11-ene (1, together with four same skeleton type known compounds (2-5 were isolated. The structure of 1 was elucidated by means of extensive spectroscopic analysis. Their neuroprotective effect against 1-methyl-4 -phenylpyridinium ion-induced (MPP +-induced neurotoxicity in SH-SY5Y cells were evaluated. The structure activity relationship of compounds 1-5 has been discussed preliminarily.

  13. Ketogenic Diet Provides Neuroprotective Effects against Ischemic Stroke Neuronal Damages

    Directory of Open Access Journals (Sweden)

    Sheida Shaafi

    2014-12-01

    Full Text Available Ischemic stroke is a leading cause of death and disability in the world. Many mechanisms contribute in cell death in ischemic stroke. Ketogenic diet which has been successfully used in the drug-resistant epilepsy has been shown to be effective in many other neurologic disorders. The mechanisms underlying of its effects are not well studied, but it seems that its neuroprotective ability is mediated at least through alleviation of excitotoxicity, oxidative stress and apoptosis events. On the basis of these mechanisms, it is postulated that ketogenic diet could provide benefits to treatment of cerebral ischemic injuries.

  14. Neuroprotection and Anti-Epileptogenesis with Mitochondria-Targeted Antioxidant

    Science.gov (United States)

    2016-06-01

    Nissl , Fluoro-jade C (FJ), NeuN and heat shock protein 70-72 (HSP). Nissl , FJ and NeuN stains were used to assess neuroprotection. HSP was used to...days after SE. The brains were removed and sectioned on a vibratome (50µm) throughout the dorsal hippocampus. Sections were stained for Nissl ...2.5mg/kg (n=2). Nissl - stained sections from the left hemisphere of each brain were evaluated for damage and scored using the following scale: 1

  15. Top-down (Prior Knowledge) and Bottom-up (Perceptual Modality) Influences on Spontaneous Interpersonal Synchronization.

    Science.gov (United States)

    Gipson, Christina L; Gorman, Jamie C; Hessler, Eric E

    2016-04-01

    Coordination with others is such a fundamental part of human activity that it can happen unintentionally. This unintentional coordination can manifest as synchronization and is observed in physical and human systems alike. We investigated the role of top-down influences (prior knowledge of the perceptual modality their partner is using) and bottom-up factors (perceptual modality combination) on spontaneous interpersonal synchronization. We examine this phenomena with respect to two different theoretical perspectives that differently emphasize top-down and bottom-up factors in interpersonal synchronization: joint-action/shared cognition theories and ecological-interactive theories. In an empirical study twelve dyads performed a finger oscillation task while attending to each other's movements through either visual, auditory, or visual and auditory perceptual modalities. Half of the participants were given prior knowledge of their partner's perceptual capabilities for coordinating across these different perceptual modality combinations. We found that the effect of top-down influence depends on the perceptual modality combination between two individuals. When people used the same perceptual modalities, top-down influence resulted in less synchronization and when people used different perceptual modalities, top-down influence resulted in more synchronization. Furthermore, persistence in the change in behavior as a result of having perceptual information about each other ('social memory') was stronger when this top-down influence was present.

  16. Cross-modal decoupling in temporal attention.

    Science.gov (United States)

    Mühlberg, Stefanie; Oriolo, Giovanni; Soto-Faraco, Salvador

    2014-06-01

    Prior studies have repeatedly reported behavioural benefits to events occurring at attended, compared to unattended, points in time. It has been suggested that, as for spatial orienting, temporal orienting of attention spreads across sensory modalities in a synergistic fashion. However, the consequences of cross-modal temporal orienting of attention remain poorly understood. One challenge is that the passage of time leads to an increase in event predictability throughout a trial, thus making it difficult to interpret possible effects (or lack thereof). Here we used a design that avoids complete temporal predictability to investigate whether attending to a sensory modality (vision or touch) at a point in time confers beneficial access to events in the other, non-attended, sensory modality (touch or vision, respectively). In contrast to previous studies and to what happens with spatial attention, we found that events in one (unattended) modality do not automatically benefit from happening at the time point when another modality is expected. Instead, it seems that attention can be deployed in time with relative independence for different sensory modalities. Based on these findings, we argue that temporal orienting of attention can be cross-modally decoupled in order to flexibly react according to the environmental demands, and that the efficiency of this selective decoupling unfolds in time. © 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  17. History of Civil Engineering Modal Analysis

    DEFF Research Database (Denmark)

    Brincker, Rune

    2008-01-01

    techniques are available for civil engineering modal analysis. The testing of civil structures defers from the traditional modal testing in the sense, that very often it is difficult, or sometimes impossible, to artificially excite a large civil engineering structure. Also, many times, even though...

  18. Three-valued logics in modal logic

    NARCIS (Netherlands)

    Kooi, Barteld; Tamminga, Allard

    2013-01-01

    Every truth-functional three-valued propositional logic can be conservatively translated into the modal logic S5. We prove this claim constructively in two steps. First, we define a Translation Manual that converts any propositional formula of any three-valued logic into a modal formula. Second, we

  19. Neuroprotection in Parkinson's disease: A systematic review of the preclinical data

    NARCIS (Netherlands)

    Douna, H.; Bavelaar, B.M.; Pellikaan, H.; Olivier, B.; Pieters, T.

    2012-01-01

    Aim: This study aimed to systematically review the preclinical data of neuroprotective agents for Parkinson's disease (PD) to support the translation of these compounds. Methods: The study consisted of two phases. In phase I, Pubmed and Scopus were systematically searched for neuroprotective agents

  20. Magnesium sulphate for women at risk of preterm birth for neuroprotection of the fetus

    NARCIS (Netherlands)

    Doyle, Lex W.; Crowther, Caroline A.; Middleton, Philippa; Marret, Stephane; Rouse, Dwight

    2009-01-01

    Background Epidemiological and basic science evidence suggests that magnesium sulphate before birth may be neuroprotective for the fetus. Objectives To assess the effects of magnesium sulphate as a neuroprotective agent when given to women considered at risk of preterm birth. Search strategy We

  1. Neuroprotection as initial therapy in acute stroke - Third report of an Ad Hoc Consensus Group Meeting

    NARCIS (Netherlands)

    Bogousslavsky, J; De Keyser, J; Diener, HC; Fieschi, C; Hacke, W; Kaste, M; Orgogozo, JM; Pulsinelli, W; Wahlgren, NG

    1998-01-01

    Although a considerable body of scientific data is now available on neuroprotection in acute ischaemic stroke, this field is not yet established in clinical practice. At its third meeting, the European Ad Hoc Consensus Group considered the potential for neuroprotection in acute stroke and the

  2. Imaging modalities of abdominal tumors in children

    International Nuclear Information System (INIS)

    Reither, M.

    1993-01-01

    Further technological progress in cross-sectional imaging modalities, accumuting experience with increasingly refined hardware and software and accumulating specific contrast media allow new algorithms for the assessment of abdominal tumors in children. However, ultrasound remains the diagnostic method of choice: Conventional roentgenology with or without contrast media is decreasing, but often reveals further differential diagnostic details. MRI is becoming more prominent and is often performed immediately after ultrasound. The inauguration of gradient echo sequences and consequent shorter examination times combined with the elimination of pulsation and motion artefacts extends the diagnostic spectrum of the upper and middle abdomen. The application of oral or rectal contrast agents for imaging of the GI tract ameliorates the differentiation of pathologic processes. Recently volumetric CT/ultrafast CT has been gaining in importance for abdominal examinations in the pediatric age group. CT especially is helpful if there are bony structures in the region being examined. CT, however, involves ionizing radiation and timely administration of oral and intravenous contrast material. Moreover, as pediatric radiologists, we must strongly withstand tendencies to perform CT more often because it is less expensive, rather than avoiding ionizing radiation by using MRI. (orig.) [de

  3. Antrodia camphorata Potentiates Neuroprotection against Cerebral Ischemia in Rats via Downregulation of iNOS/HO-1/Bax and Activated Caspase-3 and Inhibition of Hydroxyl Radical Formation

    Directory of Open Access Journals (Sweden)

    Po-Sheng Yang

    2015-01-01

    Full Text Available Antrodia camphorata (A. camphorata is a fungus generally used in Chinese folk medicine for treatment of viral hepatitis and cancer. Our previous study found A. camphorata has neuroprotective properties and could reduce stroke injury in cerebral ischemia animal models. In this study, we sought to investigate the molecular mechanisms of neuroprotective effects of A. camphorata in middle cerebral artery occlusion (MCAO rats. A selective occlusion of the middle cerebral artery (MCA with whole blood clots was used to induce ischemic stroke in rats and they were orally treated with A. camphorata (0.25 and 0.75 g/kg/day alone or combined with aspirin (5 mg/kg/day. To provide insight into the functions of A. camphorata mediated neuroprotection, the expression of Bax, inducible nitric oxide synthase (iNOS, haem oxygenase-1 (HO-1, and activated caspase-3 was determined by Western blot assay. Treatment of aspirin alone significantly reduced the expressions of HO-1 (P<0.001, iNOS (P<0.001, and Bax (P<0.01 in ischemic regions. The reduction of these expressions was more potentiated when rats treated by aspirin combined with A. camphorata (0.75 g/kg/day. Combination treatment also reduced apoptosis as measured by a significant reduction in active caspase-3 expression in the ischemic brain compared to MCAO group (P<0.01. Moreover, treatment of A. camphorata significantly (P<0.05 reduced fenton reaction-induced hydroxyl radical (OH• formation at a dose of 40 mg/mL. Taken together, A. camphorata has shown neuroprotective effects in embolic rats, and the molecular mechanisms may correlate with the downregulation of Bax, iNOS, HO-1, and activated caspase-3 and the inhibition of OH• signals.

  4. Gene expression in cerebral ischemia: a new approach for neuroprotection.

    Science.gov (United States)

    Millán, Mónica; Arenillas, Juan

    2006-01-01

    Cerebral ischemia is one of the strongest stimuli for gene induction in the brain. Hundreds of genes have been found to be induced by brain ischemia. Many genes are involved in neurodestructive functions such as excitotoxicity, inflammatory response and neuronal apoptosis. However, cerebral ischemia is also a powerful reformatting and reprogramming stimulus for the brain through neuroprotective gene expression. Several genes may participate in both cellular responses. Thus, isolation of candidate genes for neuroprotection strategies and interpretation of expression changes have been proven difficult. Nevertheless, many studies are being carried out to improve the knowledge of the gene activation and protein expression following ischemic stroke, as well as in the development of new therapies that modify biochemical, molecular and genetic changes underlying cerebral ischemia. Owing to the complexity of the process involving numerous critical genes expressed differentially in time, space and concentration, ongoing therapeutic efforts should be based on multiple interventions at different levels. By modification of the acute gene expression induced by ischemia or the apoptotic gene program, gene therapy is a promising treatment but is still in a very experimental phase. Some hurdles will have to be overcome before these therapies can be introduced into human clinical stroke trials. Copyright 2006 S. Karger AG, Basel.

  5. Targeting AMPK Signaling as a Neuroprotective Strategy in Parkinson's Disease.

    Science.gov (United States)

    Curry, Daniel W; Stutz, Bernardo; Andrews, Zane B; Elsworth, John D

    2018-03-26

    Parkinson's disease (PD) is the second most common neurodegenerative disorder. It is characterized by the accumulation of intracellular α-synuclein aggregates and the degeneration of nigrostriatal dopaminergic neurons. While no treatment strategy has been proven to slow or halt the progression of the disease, there is mounting evidence from preclinical PD models that activation of 5'-AMP-activated protein kinase (AMPK) may have broad neuroprotective effects. Numerous dietary supplements and pharmaceuticals (e.g., metformin) that increase AMPK activity are available for use in humans, but clinical studies of their effects in PD patients are limited. AMPK is an evolutionarily conserved serine/threonine kinase that is activated by falling energy levels and functions to restore cellular energy balance. However, in response to certain cellular stressors, AMPK activation may exacerbate neuronal atrophy and cell death. This review describes the regulation and functions of AMPK, evaluates the controversies in the field, and assesses the potential of targeting AMPK signaling as a neuroprotective treatment for PD.

  6. Neuroprotective effects of testosterone treatment in men with multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Florian Kurth

    2014-01-01

    Full Text Available Multiple sclerosis (MS is an inflammatory and neurodegenerative disease of the central nervous system. While current medication reduces relapses and inflammatory activity, it has only a modest effect on long-term disability and gray matter atrophy. Here, we have characterized the potential neuroprotective effects of testosterone on cerebral gray matter in a pilot clinical trial. Ten men with relapsing–remitting MS were included in this open-label phase II trial. Subjects were observed without treatment for 6 months, followed by testosterone treatment for another 12 months. Focal gray matter loss as a marker for neurodegeneration was assessed using voxel-based morphometry. During the non-treatment phase, significant voxel-wise gray matter decreases were widespread (p≤ 0.05 corrected. However, during testosterone treatment, gray matter loss was no longer evident. In fact, a significant gray matter increase in the right frontal cortex was observed (p≤ 0.05 corrected. These observations support the potential of testosterone treatment to stall (and perhaps even reverse neurodegeneration associated with MS. Furthermore, they warrant the investigation of testosterone's neuroprotective effects in larger, placebo controlled MS trials as well as in other neurodegenerative diseases. This is the first report of gray matter increase as the result of treatment in MS.

  7. Phytoceramide Shows Neuroprotection and Ameliorates Scopolamine-Induced Memory Impairment

    Directory of Open Access Journals (Sweden)

    Seikwan Oh

    2011-10-01

    Full Text Available The function and the role phytoceramide (PCER and phytosphingosine (PSO in the central nervous system has not been well studied. This study was aimed at investigating the possible roles of PCER and PSO in glutamate-induced neurotoxicity in cultured neuronal cells and memory function in mice. Phytoceramide showed neuro-protective activity in the glutamate-induced toxicity in cultured cortical neuronal cells. Neither phytosphingosine nor tetraacetylphytosphingosine (TAPS showed neuroproective effects in neuronal cells. PCER (50 mg/kg, p.o. recovered the scopolamine-induced reduction in step-through latency in the passive avoidance test; however, PSO did not modulate memory function on this task. The ameliorating effects of PCER on spatial memory were confirmed by the Morris water maze test. In conclusion, through behavioral and neurochemical experimental results, it was demonstrated that central administration of PCER produces amelioration of memory impairment. These results suggest that PCER plays an important role in neuroprotection and memory enhancement and PCER could be a potential new therapeutic agent for the treatment of neurodegenerative diseases such as Alzheimer’s disease.

  8. Neuroprotective Effects of Psychotropic Drugs in Huntington’s Disease

    Directory of Open Access Journals (Sweden)

    Edward C. Lauterbach

    2013-11-01

    Full Text Available Psychotropics (antipsychotics, mood stabilizers, antidepressants, anxiolytics, etc. are commonly prescribed to treat Huntington’s disease (HD. In HD preclinical models, while no psychotropic has convincingly affected huntingtin gene, HD modifying gene, or huntingtin protein expression, psychotropic neuroprotective effects include upregulated huntingtin autophagy (lithium, histone acetylation (lithium, valproate, lamotrigine, miR-222 (lithium-plus-valproate, mitochondrial protection (haloperidol, trifluoperazine, imipramine, desipramine, nortriptyline, maprotiline, trazodone, sertraline, venlafaxine, melatonin, neurogenesis (lithium, valproate, fluoxetine, sertraline, and BDNF (lithium, valproate, sertraline and downregulated AP-1 DNA binding (lithium, p53 (lithium, huntingtin aggregation (antipsychotics, lithium, and apoptosis (trifluoperazine, loxapine, lithium, desipramine, nortriptyline, maprotiline, cyproheptadine, melatonin. In HD live mouse models, delayed disease onset (nortriptyline, melatonin, striatal preservation (haloperidol, tetrabenazine, lithium, sertraline, memory preservation (imipramine, trazodone, fluoxetine, sertraline, venlafaxine, motor improvement (tetrabenazine, lithium, valproate, imipramine, nortriptyline, trazodone, sertraline, venlafaxine, and extended survival (lithium, valproate, sertraline, melatonin have been documented. Upregulated CREB binding protein (CBP; valproate, dextromethorphan and downregulated histone deacetylase (HDAC; valproate await demonstration in HD models. Most preclinical findings await replication and their limitations are reviewed. The most promising findings involve replicated striatal neuroprotection and phenotypic disease modification in transgenic mice for tetrabenazine and for sertraline. Clinical data consist of an uncontrolled lithium case series (n = 3 suggesting non-progression and a primarily negative double-blind, placebo-controlled clinical trial of lamotrigine.

  9. Astrocytes, therapeutic targets for neuroprotection and neurorestoration in ischemic stroke

    Science.gov (United States)

    Liu, Zhongwu; Chopp, Michael

    2015-01-01

    Astrocytes are the most abundant cell type within the central nervous system. They play essential roles in maintaining normal brain function, as they are a critical structural and functional part of the tripartite synapses and the neurovascular unit, and communicate with neurons, oligodendrocytes and endothelial cells. After an ischemic stroke, astrocytes perform multiple functions both detrimental and beneficial, for neuronal survival during the acute phase. Aspects of the astrocytic inflammatory response to stroke may aggravate the ischemic lesion, but astrocytes also provide benefit for neuroprotection, by limiting lesion extension via anti-excitotoxicity effects and releasing neurotrophins. Similarly, during the late recovery phase after stroke, the glial scar may obstruct axonal regeneration and subsequently reduce the functional outcome; however, astrocytes also contribute to angiogenesis, neurogenesis, synaptogenesis, and axonal remodeling, and thereby promote neurological recovery. Thus, the pivotal involvement of astrocytes in normal brain function and responses to an ischemic lesion designates them as excellent therapeutic targets to improve functional outcome following stroke. In this review, we will focus on functions of astrocytes and astrocyte-mediated events during stroke and recovery. We will provide an overview of approaches on how to reduce the detrimental effects and amplify the beneficial effects of astrocytes on neuroprotection and on neurorestoration post stroke, which may lead to novel and clinically relevant therapies for stroke. PMID:26455456

  10. Conceptual structure within and between modalities

    Directory of Open Access Journals (Sweden)

    Katia eDilkina

    2013-01-01

    Full Text Available Current views of semantic memory share the assumption that conceptual representations are based on multi-modal experience, which activates distinct modality-specific brain regions. This proposition is widely accepted, yet little is known about how each modality contributes to conceptual knowledge and how the structure of this contribution varies across these multiple information sources. We used verbal feature lists, features from drawings and verbal co-occurrence statistics from latent semantic analysis to examine the informational structure in four domains of knowledge: perceptual, functional, encyclopedic and verbal. The goals of the analysis were three-fold: (1 to assess the structure within individual modalities; (2 to compare structures between modalities; and (3 to assess the degree to which concepts organize categorically or randomly.Our results indicated significant and unique structure in all four modalities: perceptually, concepts organize based on prominent features such as shape, size, color and parts; functionally, they group based on use and interaction; encyclopedically, they arrange based on commonality in location or behavior; and verbally, they group associatively or relationally. Visual/perceptual knowledge gives rise to the strongest hierarchical organization and is closest to classic taxonomic structure. Information is organized somewhat similarly in the perceptual and encyclopedic domains, which differs significantly from the structure in the functional and verbal domains. Notably, the verbal modality has the most unique organization, which is not at all categorical but also not random. The idiosyncrasy and complexity of conceptual structure across modalities begs the question of how all of these modality-specific experiences are fused together into coherent, multi-faceted yet unified concepts. Accordingly, both methodological and theoretical implications of the present findings are discussed.

  11. NIF Periscope Wall Modal Study Comparison of Results for 2 FEA Models with 2 Modal Tests

    International Nuclear Information System (INIS)

    Eli, M W; Gerhard, M A; Lee, C L; Sommer, S C; Woehrle, T G

    2000-01-01

    This report summarizes experimentally and numerically determined modal properties for one of the reinforced concrete end walls of the NIF Periscope Support Structure in Laser Bay 1. Two methods were used to determine these modal properties: (1) Computational finite-element analyses (modal extraction process); and (2) Experimental modal analysis based on measured test data. This report also includes experimentally determined modal properties for a prototype LM3/Polarizer line-replaceable unit (LRU) and a prototype PEPC LRU. Two important parameters, used during the design phase, are validated through testing [ref 1]. These parameters are the natural frequencies and modal damping (of the system in question) for the first several global modes of vibration. Experimental modal testing provides these modal values, along with the corresponding mode shapes. Another important parameter, the input excitation (expected during normal operation of the NIF laser system) [ref 1], can be verified by performing a series of ambient vibration measurements in the vicinity of the particular system (or subsystem) of interest. The topic of ambient input excitation will be covered in a separate report. Due to the large mass of the Periscope Pedestal, it is difficult to excite the entire series of Periscope Pedestal Walls all at once. It was decided that the experimental modal tests would be performed on just one Periscope End Wall in Laser Bay 1. Experimental modal properties for the Periscope End Wall have been used to validate and update the FE analyses. Results from the analyses and modal tests support the conclusion that the Periscope Pedestal will not exceed the stability budget, which is described in reference 1. The results of the modal tests for the Periscope End Wall in Laser Bay 1 have provided examples of modal properties that can be derived from future modal tests of the entire Periscope Assembly (excluding the LRU's). This next series of larger modal tests can be performed

  12. Mechanisms of cannabidiol neuroprotection in hypoxic-ischemic newborn pigs: role of 5HT(1A) and CB2 receptors.

    Science.gov (United States)

    Pazos, M Ruth; Mohammed, Nagat; Lafuente, Hector; Santos, Martin; Martínez-Pinilla, Eva; Moreno, Estefania; Valdizan, Elsa; Romero, Julián; Pazos, Angel; Franco, Rafael; Hillard, Cecilia J; Alvarez, Francisco J; Martínez-Orgado, Jose

    2013-08-01

    The mechanisms underlying the neuroprotective effects of cannabidiol (CBD) were studied in vivo using a hypoxic-ischemic (HI) brain injury model in newborn pigs. One- to two-day-old piglets were exposed to HI for 30 min by interrupting carotid blood flow and reducing the fraction of inspired oxygen to 10%. Thirty minutes after HI, the piglets were treated with vehicle (HV) or 1 mg/kg CBD, alone (HC) or in combination with 1 mg/kg of a CB₂ receptor antagonist (AM630) or a serotonin 5HT(1A) receptor antagonist (WAY100635). HI decreased the number of viable neurons and affected the amplitude-integrated EEG background activity as well as different prognostic proton-magnetic-resonance-spectroscopy (H(±)-MRS)-detectable biomarkers (lactate/N-acetylaspartate and N-acetylaspartate/choline ratios). HI brain damage was also associated with increases in excitotoxicity (increased glutamate/N-acetylaspartate ratio), oxidative stress (decreased glutathione/creatine ratio and increased protein carbonylation) and inflammation (increased brain IL-1 levels). CBD administration after HI prevented all these alterations, although this CBD-mediated neuroprotection was reversed by co-administration of either WAY100635 or AM630, suggesting the involvement of CB₂ and 5HT(1A) receptors. The involvement of CB₂ receptors was not dependent on a CBD-mediated increase in endocannabinoids. Finally, bioluminescence resonance energy transfer studies indicated that CB₂ and 5HT(1A) receptors may form heteromers in living HEK-293T cells. In conclusion, our findings demonstrate that CBD exerts robust neuroprotective effects in vivo in HI piglets, modulating excitotoxicity, oxidative stress and inflammation, and that both CB₂ and 5HT(1A) receptors are implicated in these effects. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. Neuroprotective properties of cannabigerol in Huntington's disease: studies in R6/2 mice and 3-nitropropionate-lesioned mice.

    Science.gov (United States)

    Valdeolivas, Sara; Navarrete, Carmen; Cantarero, Irene; Bellido, María L; Muñoz, Eduardo; Sagredo, Onintza

    2015-01-01

    Different plant-derived and synthetic cannabinoids have shown to be neuroprotective in experimental models of Huntington's disease (HD) through cannabinoid receptor-dependent and/or independent mechanisms. Herein, we studied the effects of cannabigerol (CBG), a nonpsychotropic phytocannabinoid, in 2 different in vivo models of HD. CBG was extremely active as neuroprotectant in mice intoxicated with 3-nitropropionate (3NP), improving motor deficits and preserving striatal neurons against 3NP toxicity. In addition, CBG attenuated the reactive microgliosis and the upregulation of proinflammatory markers induced by 3NP, and improved the levels of antioxidant defenses that were also significantly reduced by 3NP. We also investigated the neuroprotective properties of CBG in R6/2 mice. Treatment with this phytocannabinoid produced a much lower, but significant, recovery in the deteriorated rotarod performance typical of R6/2 mice. Using HD array analysis, we were able to identify a series of genes linked to this disease (e.g., symplekin, Sin3a, Rcor1, histone deacetylase 2, huntingtin-associated protein 1, δ subunit of the gamma-aminobutyric acid-A receptor (GABA-A), and hippocalcin), whose expression was altered in R6/2 mice but partially normalized by CBG treatment. We also observed a modest improvement in the gene expression for brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1), and peroxisome proliferator-activated receptor-γ (PPARγ), which is altered in these mice, as well as a small, but significant, reduction in the aggregation of mutant huntingtin in the striatal parenchyma in CBG-treated animals. In conclusion, our results open new research avenues for the use of CBG, alone or in combination with other phytocannabinoids or therapies, for the treatment of neurodegenerative diseases such as HD.

  14. Social networking sites: an adjunctive treatment modality for psychological problems.

    Science.gov (United States)

    Menon, Indu S; Sharma, Manoj Kumar; Chandra, Prabha S; Thennarasu, K

    2014-07-01

    Social networking is seen as a way to enhance social support and feeling of well-being. The present work explores the potentials of social networking sites as an adjunctive treatment modality for initiating treatment contact as well as for managing psychological problems. Interview schedule, Facebook intensity questionnaire were administered on 28 subjects with a combination of 18 males and 10 females. They were taken from the in-patient and out-patient psychiatry setting of the hospital. Facebook was the most popular sites and used to seek emotional support on the basis of the frequent updates of emotional content that users put in their profile; reconciliations, escape from the problems or to manage the loneliness; getting information about illness and its treatment and interaction with experts and also manifested as problematic use. It has implications for developing social networking based adjunctive treatment modality for psychological problems.

  15. The contribution of cutaneous and kinesthetic sensory modalities in haptic perception of orientation.

    Science.gov (United States)

    Frisoli, Antonio; Solazzi, Massimiliano; Reiner, Miriam; Bergamasco, Massimo

    2011-06-30

    The aim of this study was to understand the integration of cutaneous and kinesthetic sensory modalities in haptic perception of shape orientation. A specific robotic apparatus was employed to simulate the exploration of virtual surfaces by active touch with two fingers, with kinesthetic only, cutaneous only and combined sensory feedback. The cutaneous feedback was capable of displaying the local surface orientation at the contact point, through a small plate indenting the fingerpad at contact. A psychophysics test was conducted with SDT methodology on 6 subjects to assess the discrimination threshold of angle perception between two parallel surfaces, with three sensory modalities and two shape sizes. Results show that the cutaneous sensor modality is not affected by size of shape, but kinesthetic performance is decreasing with smaller size. Cutaneous and kinesthetic sensory cues are integrated according to a Bayesian model, so that the combined sensory stimulation always performs better than single modalities alone. Copyright © 2010 Elsevier Inc. All rights reserved.

  16. Multi-Modality Medical Image Fusion Based on Wavelet Analysis and Quality Evaluation

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Multi-modality medical image fusion has more and more important applications in medical image analysisand understanding. In this paper, we develop and apply a multi-resolution method based on wavelet pyramid to fusemedical images from different modalities such as PET-MRI and CT-MRI. In particular, we evaluate the different fusionresults when applying different selection rules and obtain optimum combination of fusion parameters.

  17. Cross-modal versus within-modal recall: differences in behavioral and brain responses.

    Science.gov (United States)

    Butler, Andrew J; James, Karin H

    2011-10-31

    Although human experience is multisensory in nature, previous research has focused predominantly on memory for unisensory as opposed to multisensory information. In this work, we sought to investigate behavioral and neural differences between the cued recall of cross-modal audiovisual associations versus within-modal visual or auditory associations. Participants were presented with cue-target associations comprised of pairs of nonsense objects, pairs of nonsense sounds, objects paired with sounds, and sounds paired with objects. Subsequently, they were required to recall the modality of the target given the cue while behavioral accuracy, reaction time, and blood oxygenation level dependent (BOLD) activation were measured. Successful within-modal recall was associated with modality-specific reactivation in primary perceptual regions, and was more accurate than cross-modal retrieval. When auditory targets were correctly or incorrectly recalled using a cross-modal visual cue, there was re-activation in auditory association cortex, and recall of information from cross-modal associations activated the hippocampus to a greater degree than within-modal associations. Findings support theories that propose an overlap between regions active during perception and memory, and show that behavioral and neural differences exist between within- and cross-modal associations. Overall the current study highlights the importance of the role of multisensory information in memory. Copyright © 2011 Elsevier B.V. All rights reserved.

  18. DICOM versus HL7 for modality interfacing

    OpenAIRE

    Oosterwijk, Herman

    1998-01-01

    Digital modalities such as CT, MRI, Ultrasound and Computerized Radiography systems, generating softcopy images to be used by a Picture Archiving and Communication System (PACS), need to identify the images properly in order to retrieve and manage them. In many cases, a technologist re-enters patient demographic and study related information at the modality, even although it is usually already present somewhere in the hospital Information System (IS). In order to achieve a higher level of eff...

  19. Models of galaxies - The modal approach

    International Nuclear Information System (INIS)

    Lin, C.C.; Lowe, S.A.

    1990-01-01

    The general viability of the modal approach to the spiral structure in normal spirals and the barlike structure in certain barred spirals is discussed. The usefulness of the modal approach in the construction of models of such galaxies is examined, emphasizing the adoption of a model appropriate to observational data for both the spiral structure of a galaxy and its basic mass distribution. 44 refs

  20. Eigenvectors phase correction in inverse modal problem

    Science.gov (United States)

    Qiao, Guandong; Rahmatalla, Salam

    2017-12-01

    The solution of the inverse modal problem for the spatial parameters of mechanical and structural systems is heavily dependent on the quality of the modal parameters obtained from the experiments. While experimental and environmental noises will always exist during modal testing, the resulting modal parameters are expected to be corrupted with different levels of noise. A novel methodology is presented in this work to mitigate the errors in the eigenvectors when solving the inverse modal problem for the spatial parameters. The phases of the eigenvector component were utilized as design variables within an optimization problem that minimizes the difference between the calculated and experimental transfer functions. The equation of motion in terms of the modal and spatial parameters was used as a constraint in the optimization problem. Constraints that reserve the positive and semi-positive definiteness and the inter-connectivity of the spatial matrices were implemented using semi-definite programming. Numerical examples utilizing noisy eigenvectors with augmented Gaussian white noise of 1%, 5%, and 10% were used to demonstrate the efficacy of the proposed method. The results showed that the proposed method is superior when compared with a known method in the literature.

  1. From Sensory Signals to Modality-Independent Conceptual Representations: A Probabilistic Language of Thought Approach.

    Directory of Open Access Journals (Sweden)

    Goker Erdogan

    2015-11-01

    Full Text Available People learn modality-independent, conceptual representations from modality-specific sensory signals. Here, we hypothesize that any system that accomplishes this feat will include three components: a representational language for characterizing modality-independent representations, a set of sensory-specific forward models for mapping from modality-independent representations to sensory signals, and an inference algorithm for inverting forward models-that is, an algorithm for using sensory signals to infer modality-independent representations. To evaluate this hypothesis, we instantiate it in the form of a computational model that learns object shape representations from visual and/or haptic signals. The model uses a probabilistic grammar to characterize modality-independent representations of object shape, uses a computer graphics toolkit and a human hand simulator to map from object representations to visual and haptic features, respectively, and uses a Bayesian inference algorithm to infer modality-independent object representations from visual and/or haptic signals. Simulation results show that the model infers identical object representations when an object is viewed, grasped, or both. That is, the model's percepts are modality invariant. We also report the results of an experiment in which different subjects rated the similarity of pairs of objects in different sensory conditions, and show that the model provides a very accurate account of subjects' ratings. Conceptually, this research significantly contributes to our understanding of modality invariance, an important type of perceptual constancy, by demonstrating how modality-independent representations can be acquired and used. Methodologically, it provides an important contribution to cognitive modeling, particularly an emerging probabilistic language-of-thought approach, by showing how symbolic and statistical approaches can be combined in order to understand aspects of human perception.

  2. Neuroprotective properties of nitric oxide and S-nitrosoglutathione

    International Nuclear Information System (INIS)

    Rauhala, Pekka; Andoh, Tsugunobu; Chiueh, C.C.

    2005-01-01

    Oxidative stress and apoptosis may play an important role in the neurodegeneration. The present paper outlines antioxidative and antiapototic mechanisms of nitric oxide and S-nitrosothiols, which could mediate neuroprotection. Nitric oxide generated by nitric oxide synthase or released from an endogenous S-nitrosothiol, S-nitrosoglutathione may up-regulate antioxidative thioredoxin system and antiapototic Bcl-2 protein through a cGMP-dependent mechanism. Moreover, nitric oxide radicals have been shown to have direct antioxidant effect through their reaction with free radicals and iron-oxygen complexes. In addition to serving as a stabilizer and carrier of nitric oxide, S-nitrosoglutathione may have protective effect through transnitrosylation reactions. Based on these new findings, a hypothesis arises that the homeostasis of nitric oxide, S-nitrosothiols, glutathione, and thioredoxin systems is important for protection against oxidative stress, apoptosis, and related neurodegenerative disorders

  3. Gene expression analysis to identify molecular correlates of pre- and post-conditioning derived neuroprotection.

    Science.gov (United States)

    Prasad, Shiv S; Russell, Marsha; Nowakowska, Margeryta; Williams, Andrew; Yauk, Carole

    2012-06-01

    Mild ischaemic exposures before or after severe injurious ischaemia that elicit neuroprotective responses are referred to as preconditioning and post-conditioning. The corresponding molecular mechanisms of neuroprotection are not completely understood. Identification of the genes and associated pathways of corresponding neuroprotection would provide insight into neuronal survival, potential therapeutic approaches and assessments of therapies for stroke. The objectives of this study were to use global gene expression approach to infer the molecular mechanisms in pre- and post-conditioning-derived neuroprotection in cortical neurons following oxygen and glucose deprivation (OGD) in vitro and then to apply these findings to predict corresponding functional pathways. To this end, microarray analysis was applied to rat cortical neurons with or without the pre- and post-conditioning treatments at 3-h post-reperfusion, and differentially expressed transcripts were subjected to statistical, hierarchical clustering and pathway analyses. The expression patterns of 3,431 genes altered under all conditions of ischaemia (with and without pre- or post-conditioning). We identified 1,595 genes that were commonly regulated within both the pre- and post-conditioning treatments. Cluster analysis revealed that transcription profiles clustered tightly within controls, non-conditioned OGD and neuroprotected groups. Two clusters defining neuroprotective conditions associated with up- and downregulated genes were evident. The five most upregulated genes within the neuroprotective clusters were Tagln, Nes, Ptrf, Vim and Adamts9, and the five most downregulated genes were Slc7a3, Bex1, Brunol4, Nrxn3 and Cpne4. Pathway analysis revealed that the intracellular and second messenger signalling pathways in addition to cell death were predominantly associated with downregulated pre- and post-conditioning associated genes, suggesting that modulation of cell death and signal transduction pathways

  4. Neuroprotection by Caffeine in Hyperoxia-Induced Neonatal Brain Injury

    Directory of Open Access Journals (Sweden)

    Stefanie Endesfelder

    2017-01-01

    Full Text Available Sequelae of prematurity triggered by oxidative stress and free radical-mediated tissue damage have coined the term “oxygen radical disease of prematurity”. Caffeine, a potent free radical scavenger and adenosine receptor antagonist, reduces rates of brain damage in preterm infants. In the present study, we investigated the effects of caffeine on oxidative stress markers, anti-oxidative response, inflammation, redox-sensitive transcription factors, apoptosis, and extracellular matrix following the induction of hyperoxia in neonatal rats. The brain of a rat pups at postnatal Day 6 (P6 corresponds to that of a human fetal brain at 28–32 weeks gestation and the neonatal rat is an ideal model in which to investigate effects of oxidative stress and neuroprotection of caffeine on the developing brain. Six-day-old Wistar rats were pre-treated with caffeine and exposed to 80% oxygen for 24 and 48 h. Caffeine reduced oxidative stress marker (heme oxygenase-1, lipid peroxidation, hydrogen peroxide, and glutamate-cysteine ligase catalytic subunit (GCLC, promoted anti-oxidative response (superoxide dismutase, peroxiredoxin 1, and sulfiredoxin 1, down-regulated pro-inflammatory cytokines, modulated redox-sensitive transcription factor expression (Nrf2/Keap1, and NFκB, reduced pro-apoptotic effectors (poly (ADP-ribose polymerase-1 (PARP-1, apoptosis inducing factor (AIF, and caspase-3, and diminished extracellular matrix degeneration (matrix metalloproteinases (MMP 2, and inhibitor of metalloproteinase (TIMP 1/2. Our study affirms that caffeine is a pleiotropic neuroprotective drug in the developing brain due to its anti-oxidant, anti-inflammatory, and anti-apoptotic properties.

  5. Pharmacological preconditioning with GYKI 52466: a prophylactic approach to neuroprotection

    Directory of Open Access Journals (Sweden)

    Chelsea S Goulton

    2010-08-01

    Full Text Available Some toxins and drugs can trigger lasting neuroprotective mechanisms that enable neurons to resist a subsequent severe insult. This ‘pharmacological preconditioning’ has far-reaching implications for conditions in which blood flow to the brain is interrupted. We have previously shown that in vitro preconditioning with the AMPA receptor antagonist GYKI 52466 induces tolerance to kainic acid (KA toxicity in hippocampus. This effect persists well after washout of the drug and may be mediated via inverse agonism of G protein linked receptors. Given the amplifying nature of metabotropic modulation, we hypothesised that GYKI 52466 may be effective in reducing seizure severity at doses well below those normally associated with adverse side effects. Here we report that pharmacological preconditioning with low-dose GYKI imparts a significant protection against KA-induced seizures in vivo. GYKI (3 mg/kg, s.c., 90 to 180 min. prior to high-dose KA, markedly reduced seizure scores, virtually abolished all level 3 and level 4 seizures, and completely suppressed KA-induced hippocampal cFOS expression. In addition, preconditioned animals exhibited significant reductions in high frequency/high amplitude spiking and ECoG power in the delta, theta, alpha and beta bands during KA. Adverse behaviours often associated with higher doses of GYKI were not evident during preconditioning. The fact that GYKI is effective at doses well-below, and at pre-administration intervals well-beyond previous studies, suggests that a classical blockade of ionotropic AMPA receptors does not underlie anticonvulsant effects. Low-dose GYKI preconditioning may represent a novel, prophylactic strategy for neuroprotection in a field almost completely devoid of effective pharmaceuticals.

  6. Altered network communication following a neuroprotective drug treatment.

    Directory of Open Access Journals (Sweden)

    Kathleen Vincent

    Full Text Available Preconditioning is defined as a range of stimuli that allow cells to withstand subsequent anaerobic and other deleterious conditions. While cell protection under preconditioning is well established, this paper investigates the influence of neuroprotective preconditioning drugs, 4-aminopyridine and bicuculline (4-AP/bic, on synaptic communication across a broad network of in vitro rat cortical neurons. Using a permutation test, we evaluated cross-correlations of extracellular spiking activity across all pairs of recording electrodes on a 64-channel multielectrode array. The resulting functional connectivity maps were analyzed in terms of their graph-theoretic properties. A small-world effect was found, characterized by a functional network with high clustering coefficient and short average path length. Twenty-four hours after exposure to 4-AP/bic, small-world properties were comparable to control cultures that were not treated with the drug. Four hours following drug washout, however, the density of functional connections increased, while path length decreased and clustering coefficient increased. These alterations in functional connectivity were maintained at four days post-washout, suggesting that 4-AP/bic preconditioning leads to long-term effects on functional networks of cortical neurons. Because of their influence on communication efficiency in neuronal networks, alterations in small-world properties hold implications for information processing in brain systems. The observed relationship between density, path length, and clustering coefficient is captured by a phenomenological model where connections are added randomly within a spatially-embedded network. Taken together, results provide information regarding functional consequences of drug therapies that are overlooked in traditional viability studies and present the first investigation of functional networks under neuroprotective preconditioning.

  7. Meta-Analysis of Creatine for Neuroprotection Against Parkinson's Disease.

    Science.gov (United States)

    Attia; Ahmed, Hussien; Gadelkarim, Mohamed; Morsi, Mahmoud; Awad, Kamal; Elnenny, Mohamed; Ghanem, Esraa; El-Jaafary, Shaimaa; Negida, Ahmed

    2017-01-01

    Creatine is an antioxidant agent that showed neuroprotective effects in animal models of Parkinson's disease (PD). Creatine was selected by the National Institute of Neurological Disorders and Stroke as a possible disease modifying agent for Parkinson's disease. Therefore, many clinical trials evaluated the efficacy of creatine for patients with PD. The aim of this systematic review and meta-analysis is to synthesize evidence from published randomized controlled trials (RCTs) about the efficacy of Creatine for patients with PD. We followed PRISMA statement guidelines during the preparation of this systematic review and meta-analysis. A computer literature search for PubMed, EBSCO, web of science and Ovid Midline was carried out. We included RCTs comparing creatine with placebo in terms of motor functions and quality of life. Outcomes of total Unified Parkinson's Disease Rating Scale (UPDRS), UPDRS I, UPDRS II, and UPDRS III were pooled as mean difference (MD) between two groups from baseline to the endpoint. Statistical heterogeneity was assessed by visual inspection of the forest plot and measured by chi-square and I square tests. Three RCTs (n=1935) were included in this study. The overall effect did not favor either of the two groups in terms of: UPDRS total score (MD 1.07, 95% CI [3.38 to 1.25], UPDRS III (MD 0.62, 95% CI [2.27 to 1.02]), UPDRS II (MD 0.03, 95% CI [0.81 to 0.86], or UPDRS I (MD 0.03, 95% CI [0.33 to 0.28]). Current evidence does not support the use of creatine for neuroprotection against PD. Future well-designed, randomized controlled trials are needed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  8. Status epilepticus and cardiopulmonary arrest in a patient with carbon monoxide poisoning with full recovery after using a neuroprotective strategy: a case report

    Directory of Open Access Journals (Sweden)

    Abdulaziz Salman

    2012-12-01

    Full Text Available Abstract Introduction Carbon monoxide poisoning can be associated with life-threatening complications, including significant and disabling cardiovascular and neurological sequelae. Case presentation We report a case of carbon monoxide poisoning in a 25-year-old Saudi woman who presented to our facility with status epilepticus and cardiopulmonary arrest. Her carboxyhemoglobin level was 21.4 percent. She made a full recovery after we utilized a neuroprotective strategy and normobaric oxygen therapy, with no delayed neurological sequelae. Conclusions Brain protective modalities are very important for the treatment of complicated cases of carbon monoxide poisoning when they present with neurological toxicities or cardiac arrest. They can be adjunctive to normobaric oxygen therapy when the use of hyperbaric oxygen is not feasible.

  9. Mixed-Modality Stimulation to Evoke Two Modalities Simultaneously in One Channel for Electrocutaneous Sensory Feedback.

    Science.gov (United States)

    Choi, Kyunghwan; Kim, Pyungkang; Kim, Kyung-Soo; Kim, Soohyun

    2017-12-01

    One of the long-standing challenges in upper limb prosthetics is restoring the sensory feedback that is missing due to amputation. Two approaches have previously been presented to provide various types of sensory information to users, namely, multi-modality sensory feedback and using an array of single-modality stimulators. However, the feedback systems used in these approaches were too bulky to be embedded in prosthesis sockets. In this paper, we propose an electrocutaneous sensory feedback method that is capable of conveying two modalities simultaneously with only one electrode. The stimulation method, which we call mixed-modality stimulation, utilizes the phenomenon in which the superposition of two electric pulse trains of different frequencies is able to evoke two different modalities (i.e., pressure and tapping) at the same time. We conducted psychophysical experiments in which healthy subjects were required to recognize the intensity of pressure or the frequency of tapping from mixed-modality or two-channel stimulations. The results demonstrated that the subjects were able to discriminate the features of the two modalities in one electrode during mixed-modality stimulation and that the accuracies of successful recognitions (mean ± standard deviation) for the two feedback variables were 84.3 ± 7% for mixed-modality stimulation and 89.5 ± 6% for two-channel dual-modality stimulation, showing no statistically significant difference. Therefore, mixed-modality stimulation is an attractive method for modulating two modalities independently with only one electrode, and it could be used for implementing a compact sensory feedback system that is able to provide two different types of sensory information from prosthetics.

  10. Does the intrathecal propofol have a neuroprotective effect on spinal cord ischemia?

    Science.gov (United States)

    Sahin, Murat; Gullu, Huriye; Peker, Kemal; Sayar, Ilyas; Binici, Orhan; Yildiz, Huseyin

    2015-11-01

    The neuroprotective effects of propofol have been confirmed. However, it remains unclear whether intrathecal administration of propofol exhibits neuroprotective effects on spinal cord ischemia. At 1 hour prior to spinal cord ischemia, propofol (100 and 300 µg) was intrathecally administered in rats with spinal cord ischemia. Propofol pre-treatment greatly improved rat pathological changes and neurological function deficits at 24 hours after spinal cord ischemia. These results suggest that intrathecal administration of propofol exhibits neuroprotective effects on spinal cord structural and functional damage caused by ischemia.

  11. Does the intrathecal propofol have a neuroprotective effect on spinal cord ischemia?

    Directory of Open Access Journals (Sweden)

    Murat Sahin

    2015-01-01

    Full Text Available The neuroprotective effects of propofol have been confirmed. However, it remains unclear whether intrathecal administration of propofol exhibits neuroprotective effects on spinal cord ischemia. At 1 hour prior to spinal cord ischemia, propofol (100 and 300 µg was intrathecally administered in rats with spinal cord ischemia. Propofol pre-treatment greatly improved rat pathological changes and neurological function deficits at 24 hours after spinal cord ischemia. These results suggest that intrathecal administration of propofol exhibits neuroprotective effects on spinal cord structural and functional damage caused by ischemia.

  12. The Neuroprotective Properties of Hericium erinaceus in Glutamate-Damaged Differentiated PC12 Cells and an Alzheimer's Disease Mouse Model.

    Science.gov (United States)

    Zhang, Junrong; An, Shengshu; Hu, Wenji; Teng, Meiyu; Wang, Xue; Qu, Yidi; Liu, Yang; Yuan, Ye; Wang, Di

    2016-11-01

    Hericium erinaceus , an edible and medicinal mushroom, displays various pharmacological activities in the prevention of dementia in conditions such as Parkinson's and Alzheimer's disease. The present study explored the neuroprotective effects of H. erinaceus mycelium polysaccharide-enriched aqueous extract (HE) on an l-glutamic acid (l-Glu)-induced differentiated PC12 (DPC12) cellular apoptosis model and an AlCl₃ combined with d-galactose-induced Alzheimer's disease mouse model. The data revealed that HE successfully induced PC12 cell differentiation. A 3 h HE incubation at doses of 50 and 100 µg/mL before 25 mM of l-Glu effectively reversed the reduction of cell viability and the enhancement of the nuclear apoptosis rate in DPC12 cells. Compared with l-Glu-damaged cells, in PC12 cells, HE suppressed intracellular reactive oxygen species accumulation, blocked Ca 2+ overload and prevented mitochondrial membrane potential (MMP) depolarization. In the Alzheimer's disease mouse model, HE administration enhanced the horizontal and vertical movements in the autonomic activity test, improved the endurance time in the rotarod test, and decreased the escape latency time in the water maze test. It also improved the central cholinergic system function in the Alzheimer's mice, demonstrated by the fact that it dose-dependently enhanced the acetylcholine (Ach) and choline acetyltransferase (ChAT) concentrations in both the serum and the hypothalamus. Our findings provide experimental evidence that HE may provide neuroprotective candidates for treating or preventing neurodegenerative diseases.

  13. Comparative analysis of success of psoriasis treatment with standard therapeutic modalities and balneotherapy.

    Science.gov (United States)

    Baros, Duka Ninković; Gajanin, Vesna S; Gajanin, Radoslav B; Zrnić, Bogdan

    2014-01-01

    Psoriasis is a chronic, inflammatory, immune-mediated skin disease. In addition to standard therapeutic modalities (antibiotics, cytostatics, phototherapy, photochemotherapy and retinoids), nonstandard methods can be used in the treatment of psoriasis. This includes balneotherapy which is most commonly used in combination with therapeutic resources. The aim of this research was to determine the length of remission of psoriasis in patients treated with standard therapeutic modalities, balneotherapy, and combined treatment (standard therapeutic modalities and balneotherapy). The study analyzed 60 adult patients, of both sexes, with different clinical forms of psoriasis, who were divided into three groups according to the applied therapeutic modalities: the first group (treated with standard therapeutic modalities), the second group (treated with balneotherapy) and the third group (treated with combined therapy-standard methods therapy and balneotherapy). The Psoriasis Area and Severity Index was determined in first, third and sixth week of treatment for all patients. The following laboratory analysis were performed and monitored: C reactive protein, iron with total iron binding capacity, unsaturated iron binding capacity and ferritin, uric acid, rheumatoid factors and antibodies to streptolysin O in the first and sixth week of treatment. The average length of remission in patients treated with standard therapeutic modalities and in those treated with balneotherapy was 1.77 +/- 0.951 months and 1.79 +/- 0.918 months, respectively. There was a statistically significant difference in the duration of remission between the patients treated with combination therapy and patients treated with standard therapeutic modalities (p = 0.019) and balneotherapy (p = 0.032). The best results have been achieved when the combination therapy was administered.

  14. Metaphysical Modality, Modality of Predicate and the Theory of "Decisive Necessity”

    Directory of Open Access Journals (Sweden)

    L. Nabavi

    2010-01-01

    Full Text Available Aristotle in the Organon (1949: 9,30 a ,15-19 explicitly states that in a categorical syllogism when the minor premise is absolute (without modality operator and the major is necessary, the conclusion will be necessary too. This Aristotle's view has been the source of many conflicts and disputes in the history of logic. The famous logicians and historians of logic in the twentieth century as "Nicholas Rescher" and "Becker" believe that Aristotle's view is justifiable and defensible (at least compared to the first figure only if, the modality of major premise is considered as the property of predicate (modality de re. Today, we know very well that the modality of predicate is closely linked to Metaphysical and philosophical Modality. “Shihab al-Din al- Suhrawardi” in the theory of "Decisive (Battateh Necessity” by accepting this base, explicitly states that, in the beginning, the modality must be mentioned as a part of the predicate and then the modality of relation or copula is summarized and reduced to necessity. The modern formalization of the most important part of this theory is as follows: ("x (àAx É à Bx º ("x □ (àAx É à BxThis paper discusses the historical overview of the metaphysical modality firstly and then shows that the theory of "Decisive Necessity” is true and justified in a model of modal logic with equivalent accessibility relation and homogeneous possible world view (fixed domain.

  15. Modality-specific effects on crosstalk in task switching: evidence from modality compatibility using bimodal stimulation.

    Science.gov (United States)

    Stephan, Denise Nadine; Koch, Iring

    2016-11-01

    The present study was aimed at examining modality-specific influences in task switching. To this end, participants switched either between modality compatible tasks (auditory-vocal and visual-manual) or incompatible spatial discrimination tasks (auditory-manual and visual-vocal). In addition, auditory and visual stimuli were presented simultaneously (i.e., bimodally) in each trial, so that selective attention was required to process the task-relevant stimulus. The inclusion of bimodal stimuli enabled us to assess congruence effects as a converging measure of increased between-task interference. The tasks followed a pre-instructed sequence of double alternations (AABB), so that no explicit task cues were required. The results show that switching between two modality incompatible tasks increases both switch costs and congruence effects compared to switching between two modality compatible tasks. The finding of increased congruence effects in modality incompatible tasks supports our explanation in terms of ideomotor "backward" linkages between anticipated response effects and the stimuli that called for this response in the first place. According to this generalized ideomotor idea, the modality match between response effects and stimuli would prime selection of a response in the compatible modality. This priming would cause increased difficulties to ignore the competing stimulus and hence increases the congruence effect. Moreover, performance would be hindered when switching between modality incompatible tasks and facilitated when switching between modality compatible tasks.

  16. Decentralized modal identification using sparse blind source separation

    International Nuclear Information System (INIS)

    Sadhu, A; Hazra, B; Narasimhan, S; Pandey, M D

    2011-01-01

    Popular ambient vibration-based system identification methods process information collected from a dense array of sensors centrally to yield the modal properties. In such methods, the need for a centralized processing unit capable of satisfying large memory and processing demands is unavoidable. With the advent of wireless smart sensor networks, it is now possible to process information locally at the sensor level, instead. The information at the individual sensor level can then be concatenated to obtain the global structure characteristics. A novel decentralized algorithm based on wavelet transforms to infer global structure mode information using measurements obtained using a small group of sensors at a time is proposed in this paper. The focus of the paper is on algorithmic development, while the actual hardware and software implementation is not pursued here. The problem of identification is cast within the framework of under-determined blind source separation invoking transformations of measurements to the time–frequency domain resulting in a sparse representation. The partial mode shape coefficients so identified are then combined to yield complete modal information. The transformations are undertaken using stationary wavelet packet transform (SWPT), yielding a sparse representation in the wavelet domain. Principal component analysis (PCA) is then performed on the resulting wavelet coefficients, yielding the partial mixing matrix coefficients from a few measurement channels at a time. This process is repeated using measurements obtained from multiple sensor groups, and the results so obtained from each group are concatenated to obtain the global modal characteristics of the structure

  17. Decentralized modal identification using sparse blind source separation

    Science.gov (United States)

    Sadhu, A.; Hazra, B.; Narasimhan, S.; Pandey, M. D.

    2011-12-01

    Popular ambient vibration-based system identification methods process information collected from a dense array of sensors centrally to yield the modal properties. In such methods, the need for a centralized processing unit capable of satisfying large memory and processing demands is unavoidable. With the advent of wireless smart sensor networks, it is now possible to process information locally at the sensor level, instead. The information at the individual sensor level can then be concatenated to obtain the global structure characteristics. A novel decentralized algorithm based on wavelet transforms to infer global structure mode information using measurements obtained using a small group of sensors at a time is proposed in this paper. The focus of the paper is on algorithmic development, while the actual hardware and software implementation is not pursued here. The problem of identification is cast within the framework of under-determined blind source separation invoking transformations of measurements to the time-frequency domain resulting in a sparse representation. The partial mode shape coefficients so identified are then combined to yield complete modal information. The transformations are undertaken using stationary wavelet packet transform (SWPT), yielding a sparse representation in the wavelet domain. Principal component analysis (PCA) is then performed on the resulting wavelet coefficients, yielding the partial mixing matrix coefficients from a few measurement channels at a time. This process is repeated using measurements obtained from multiple sensor groups, and the results so obtained from each group are concatenated to obtain the global modal characteristics of the structure.

  18. Working memory resources are shared across sensory modalities.

    Science.gov (United States)

    Salmela, V R; Moisala, M; Alho, K

    2014-10-01

    A common assumption in the working memory literature is that the visual and auditory modalities have separate and independent memory stores. Recent evidence on visual working memory has suggested that resources are shared between representations, and that the precision of representations sets the limit for memory performance. We tested whether memory resources are also shared across sensory modalities. Memory precision for two visual (spatial frequency and orientation) and two auditory (pitch and tone duration) features was measured separately for each feature and for all possible feature combinations. Thus, only the memory load was varied, from one to four features, while keeping the stimuli similar. In Experiment 1, two gratings and two tones-both containing two varying features-were presented simultaneously. In Experiment 2, two gratings and two tones-each containing only one varying feature-were presented sequentially. The memory precision (delayed discrimination threshold) for a single feature was close to the perceptual threshold. However, as the number of features to be remembered was increased, the discrimination thresholds increased more than twofold. Importantly, the decrease in memory precision did not depend on the modality of the other feature(s), or on whether the features were in the same or in separate objects. Hence, simultaneously storing one visual and one auditory feature had an effect on memory precision equal to those of simultaneously storing two visual or two auditory features. The results show that working memory is limited by the precision of the stored representations, and that working memory can be described as a resource pool that is shared across modalities.

  19. Evaluation of the neurotoxic/neuroprotective role of organoselenides using differentiated human neuroblastoma SH-SY5Y cell line challenged with 6-hydroxydopamine.

    Science.gov (United States)

    Lopes, Fernanda Martins; Londero, Giovana Ferreira; de Medeiros, Liana Marengo; da Motta, Leonardo Lisbôa; Behr, Guilherme Antônio; de Oliveira, Valeska Aguiar; Ibrahim, Mohammad; Moreira, José Cláudio Fonseca; Porciúncula, Lisiane de Oliveira; da Rocha, João Batista Teixeira; Klamt, Fábio

    2012-08-01

    It is well established that oxidative stress plays a major role in several neurodegenerative conditions, like Parkinson disease (PD). Hence, there is an enormous effort for the development of new antioxidants compounds with therapeutic potential for the management of PD, such as synthetic organoselenides molecules. In this study, we selected between nine different synthetic organoselenides the most eligible ones for further neuroprotection assays, using the differentiated human neuroblastoma SH-SY5Y cell line as in vitro model. Neuronal differentiation of exponentially growing human neuroblastoma SH-SY5Y cells was triggered by cultivating cells with DMEM/F12 medium with 1% of fetal bovine serum (FBS) with the combination of 10 μM retinoic acid for 7 days. Differentiated cells were further incubated with different concentrations of nine organoselenides (0.1, 0.3, 3, 10, and 30 μM) for 24 h and cell viability, neurites densities and the immunocontent of neuronal markers were evaluated. Peroxyl radical scavenging potential of each compound was determined with TRAP assay. Three organoselenides tested presented low cytotoxicity and high antioxidant properties. Pre-treatment of cells with those compounds for 24 h lead to a significantly neuroprotection against 6-hydroxydopamine (6-OHDA) toxicity, which were directly related to their antioxidant properties. Neuroprotective activity of all three organoselenides was compared to diphenyl diselenide (PhSe)₂, the simplest of the diaryl diselenides tested. Our results demonstrate that differentiated human SH-SY5Y cells are suitable cellular model to evaluate neuroprotective/neurotoxic role of compounds, and support further evaluation of selected organoselenium molecules as potential pharmacological and therapeutic drugs in the treatment of PD.

  20. Different patterns of modality dominance across development.

    Science.gov (United States)

    Barnhart, Wesley R; Rivera, Samuel; Robinson, Christopher W

    2018-01-01

    The present study sought to better understand how children, young adults, and older adults attend and respond to multisensory information. In Experiment 1, young adults were presented with two spoken words, two pictures, or two word-picture pairings and they had to determine if the two stimuli/pairings were exactly the same or different. Pairing the words and pictures together slowed down visual but not auditory response times and delayed the latency of first fixations, both of which are consistent with a proposed mechanism underlying auditory dominance. Experiment 2 examined the development of modality dominance in children, young adults, and older adults. Cross-modal presentation attenuated visual accuracy and slowed down visual response times in children, whereas older adults showed the opposite pattern, with cross-modal presentation attenuating auditory accuracy and slowing down auditory response times. Cross-modal presentation also delayed first fixations in children and young adults. Mechanisms underlying modality dominance and multisensory processing are discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Multilayer modal actuator-based piezoelectric transformers.

    Science.gov (United States)

    Huang, Yao-Tien; Wu, Wen-Jong; Wang, Yen-Chieh; Lee, Chih-Kung

    2007-02-01

    An innovative, multilayer piezoelectric transformer equipped with a full modal filtering input electrode is reported herein. This modal-shaped electrode, based on the orthogonal property of structural vibration modes, is characterized by full modal filtering to ensure that only the desired vibration mode is excited during operation. The newly developed piezoelectric transformer is comprised of three layers: a multilayered input layer, an insulation layer, and a single output layer. The electrode shape of the input layer is derived from its structural vibration modal shape, which takes advantage of the orthogonal property of the vibration modes to achieve a full modal filtering effect. The insulation layer possesses two functions: first, to couple the mechanical vibration energy between the input and output, and second, to provide electrical insulation between the two layers. To meet the two functions, a low temperature, co-fired ceramic (LTCC) was used to provide the high mechanical rigidity and high electrical insulation. It can be shown that this newly developed piezoelectric transformer has the advantage of possessing a more efficient energy transfer and a wider optimal working frequency range when compared to traditional piezoelectric transformers. A multilayer piezoelectric, transformer-based inverter applicable for use in LCD monitors or portable displays is presented as well.

  2. The metaphysics of quantum mechanics: Modal interpretations

    Science.gov (United States)

    Gluck, Stuart Murray

    2004-11-01

    This dissertation begins with the argument that a preferred way of doing metaphysics is through philosophy of physics. An understanding of quantum physics is vital to answering questions such as: What counts as an individual object in physical ontology? Is the universe fundamentally indeterministic? Are indiscernibles identical? This study explores how the various modal interpretations of quantum mechanics answer these sorts of questions; modal accounts are one of the two classes of interpretations along with so-called collapse accounts. This study suggests a new alternative within the class of modal views that yields a more plausible ontology, one in which the Principle of the Identity of Indisceribles is necessarily true. Next, it shows that modal interpretations can consistently deny that the universe must be fundamentally indeterministic so long as they accept certain other metaphysical commitments: either a perfect initial distribution of states in the universe or some form of primitive dispositional properties. Finally, the study sketches out a future research project for modal interpretations based on developing quantified quantum logic.

  3. Neuroprotective Effect of Insulin-like Growth Factor-II on 1- Methyl-4 ...

    African Journals Online (AJOL)

    Tropical Journal of Pharmaceutical Research July 2015; 14 (7): 1191-1197 ... Abstract. Purpose: To evaluate the receptor-mediated neuroprotective effect of insulin-like growth factor-II (IGF- ... catecholamines, reduces levels of dopamine and.

  4. Sparse multivariate measures of similarity between intra-modal neuroimaging datasets

    Directory of Open Access Journals (Sweden)

    Maria J. Rosa

    2015-10-01

    Full Text Available An increasing number of neuroimaging studies are now based on either combining more than one data modality (inter-modal or combining more than one measurement from the same modality (intra-modal. To date, most intra-modal studies using multivariate statistics have focused on differences between datasets, for instance relying on classifiers to differentiate between effects in the data. However, to fully characterize these effects, multivariate methods able to measure similarities between datasets are needed. One classical technique for estimating the relationship between two datasets is canonical correlation analysis (CCA. However, in the context of high-dimensional data the application of CCA is extremely challenging. A recent extension of CCA, sparse CCA (SCCA, overcomes this limitation, by regularizing the model parameters while yielding a sparse solution. In this work, we modify SCCA with the aim of facilitating its application to high-dimensional neuroimaging data and finding meaningful multivariate image-to-image correspondences in intra-modal studies. In particular, we show how the optimal subset of variables can be estimated independently and we look at the information encoded in more than one set of SCCA transformations. We illustrate our framework using Arterial Spin Labelling data to investigate multivariate similarities between the effects of two antipsychotic drugs on cerebral blood flow.

  5. Pre- and Post-Conditions Expressed in Variants of the Modal µ-Calculus

    Science.gov (United States)

    Tanabe, Yoshinori; Sekizawa, Toshifusa; Yuasa, Yoshifumi; Takahashi, Koichi

    Properties of Kripke structures can be expressed by formulas of the modal µ-calculus. Despite its strong expressive power, the validity problem of the modal µ-calculus is decidable, and so are some of its variants enriched by inverse programs, graded modalities, and nominals. In this study, we show that the pre- and post-conditions of transformations of Kripke structures, such as addition/deletion of states and edges, can be expressed using variants of the modal µ-calculus. Combined with decision procedures we have developed for those variants, the properties of sequences of transformations on Kripke structures can be deduced. We show that these techniques can be used to verify the properties of pointer-manipulating programs.

  6. Automated Modal Parameter Estimation for Operational Modal Analysis of Large Systems

    DEFF Research Database (Denmark)

    Andersen, Palle; Brincker, Rune; Goursat, Maurice

    2007-01-01

    In this paper the problems of doing automatic modal parameter extraction and how to account for large number of data to process are considered. Two different approaches for obtaining the modal parameters automatically using OMA are presented: The Frequency Domain Decomposition (FDD) technique and...

  7. The Long Run: Neuroprotective Effects of Physical Exercise on Adult Neurogenesis from Youth to Old Age

    OpenAIRE

    Saraulli, Daniele; Costanzi, Marco; Mastrorilli, Valentina; Farioli-Vecchioli, Stefano

    2017-01-01

    Background The rapid lengthening of life expectancy has raised the problem of providing social programs to counteract the age-related cognitive decline in a growing number of older people. Physical activity stands among the most promising interventions aimed at brain wellbeing, because of its effective neuroprotective action and low social cost. The purpose of this review is to describe the neuroprotective role exerted by physical activity in different life stages. In particular, we focus on ...

  8. Fatty Acid Methyl Esters and Solutol HS 15 Confer Neuroprotection After Focal and Global Cerebral Ischemia

    OpenAIRE

    Lin, Hung Wen; Saul, Isabel; Gresia, Victoria L.; Neumann, Jake T.; Dave, Kunjan R.; Perez-Pinzon, Miguel A.

    2013-01-01

    We previously showed that palmitic methyl ester (PAME) and stearic acid methyl ester (SAME) are simultaneously released from the sympathetic ganglion and PAME possesses potent vasodilatory properties which may be important in cerebral ischemia. Since PAME is a potent vasodilator simultaneously released with SAME, our hypothesis was that PAME/SAME confers neuroprotection in rat models of focal/global cerebral ischemia. We also examined the neuroprotective properties of Soluto...

  9. Affirmation Modality in Bulgarian, Macedonian and Serbian

    Directory of Open Access Journals (Sweden)

    Marcin Grygiel

    2015-06-01

    Full Text Available Affirmation Modality in Bulgarian, Macedonian and Serbian In the case of affirmation modality the speakers transform their utterances by stressing or attributing a positive value as an additional component added to the semantic structure of a proposition. This type of affirmative polarization is triggered in opposition to negation or hypothetically negative contexts. The goal of the present paper is twofold: on the one hand to compare and contrast affirmative periphrastic constructions in Bulgarian, Macedonian and Serbian and, on the other hand, to ascertain what these constructions reveal regarding the organization of grammatical categories in general and the status of affirmation modality as a coherent and homogenous category with a linguistic validity.

  10. Complete proof systems for weighted modal logic

    DEFF Research Database (Denmark)

    Larsen, Kim G.; Mardare, Radu

    2014-01-01

    (WML) is a multi-modal logic that expresses qualitative and quantitative properties of WTSs. While WML has been studied in various contexts and for various application domains, no proof system has been developed for it. In this paper we solve this open problem and propose both weak-complete and strong......The weighted transition systems (WTS) considered in this paper are transition systems having both states and transitions labeled with real numbers: the state labels denote quantitative resources, while the transition labels denote costs of transitions in terms of resources. Weighted Modal Logic....... This work emphasizes a series of similarities between WML and the probabilistic/stochastic modal logics for Markov processes and Harsanyi type spaces, such as the use of particular infinitary rules to guarantee the strong-completeness....

  11. Comparison of particle-radiation-therapy modalities

    International Nuclear Information System (INIS)

    Fairchild, R.G.; Bond, V.P.

    1981-01-01

    The characteristics of dose distribution, beam alignment, and radiobiological advantages accorded to high LET radiation were reviewed and compared for various particle beam radiotherapeutic modalities (neutron, Auger electrons, p, π - , He, C, Ne, and Ar ions). Merit factors were evaluated on the basis of effective dose to tumor relative to normal tissue, linear energy transfer (LET), and dose localization, at depths of 1, 4, and 10 cm. In general, it was found that neutron capture therapy using an epithermal neutron beam provided the best merit factors available for depths up to 8 cm. The position of fast neutron therapy on the Merit Factor Tables was consistently lower than that of other particle modalities, and above only 60 Co. The largest body of clinical data exists for fast neutron therapy; results are considered by some to be encouraging. It then follows that if benefits with fast neutron therapy are real, additional gains are within reach with other modalities

  12. Tumour Debulking for Esophageal Cancer - Thermal Modalities

    Directory of Open Access Journals (Sweden)

    David Fleischer

    1992-01-01

    Full Text Available Esophageal cancer usually is discovered at a late stage and curative therapy seldom is possible. The prognosis is poor and most therapy is palliative. Endoscopic therapy commonly is employed; two common treatments involve thermal modalities. The Nd:YAG laser has been employed for 10 years and is effective in relieving obstruction in approximately 90% of cases. Re-ohstruction usually occurs in two to three months and repeat treatment may be necessary. Limitations to laser use include the fact that equipment is expensive and there are technical restrictions. An alternative thermal modality is the bipolar coagulation tumour probe which employs bipolar electrocoagulation. It is less expensive and, if the tumour is circumferential, tends to be easier to use. (It should not be used if the cancer is noncircumferential. The advantages and limitations of each modality are addressed.

  13. Applied modal analysis of wind turbine blades

    DEFF Research Database (Denmark)

    Pedersen, H.B.; Kristensen, O.J.D.

    2003-01-01

    In this project modal analysis has been used to determine the natural frequencies, damping and the mode shapes for wind turbine blades. Different methods to measure the position and adjust the direction of the measuring points are discussed. Differentequipment for mounting the accelerometers...... is investigated by repeated measurement on the same wind turbine blade. Furthermore the flexibility of the test set-up is investigated, by use ofaccelerometers mounted on the flexible adapter plate during the measurement campaign. One experimental campaign investigated the results obtained from a loaded...... and unloaded wind turbine blade. During this campaign the modal analysis are performed on ablade mounted in a horizontal and a vertical position respectively. Finally the results obtained from modal analysis carried out on a wind turbine blade are compared with results obtained from the Stig Øyes blade_EV1...

  14. Complex harmonic modal analysis of rotor systems

    International Nuclear Information System (INIS)

    Han, Dong Ju

    2015-01-01

    Complex harmonic analysis for rotor systems has been proposed from the strict complex modal analysis based upon Floquet theory. In this process the harmonic balance method is adopted, effectively associated with conventional eigenvalue analysis. Also, the harmonic coefficients equivalent to dFRFs in harmonic mode has been derived in practice. The modes are classified from identifying the modal characteristics, and the adaptation of harmonic balance method has been proven by comparing the results of the stability analyses from Floque theory and the eigen analysis. The modal features of each critical speed are depicted in quantitatively and qualitatively by showing that the strengths of each component of the harmonic coefficients are estimated from the order of magnitude analysis according to their harmonic patterns. This effectiveness has been verified by comparing with the numerical solutions

  15. Cross-modal links among vision, audition, and touch in complex environments.

    Science.gov (United States)

    Ferris, Thomas K; Sarter, Nadine B

    2008-02-01

    This study sought to determine whether performance effects of cross-modal spatial links that were observed in earlier laboratory studies scale to more complex environments and need to be considered in multimodal interface design. It also revisits the unresolved issue of cross-modal cuing asymmetries. Previous laboratory studies employing simple cues, tasks, and/or targets have demonstrated that the efficiency of processing visual, auditory, and tactile stimuli is affected by the modality, lateralization, and timing of surrounding cues. Very few studies have investigated these cross-modal constraints in the context of more complex environments to determine whether they scale and how complexity affects the nature of cross-modal cuing asymmetries. Amicroworld simulation of battlefield operations with a complex task set and meaningful visual, auditory, and tactile stimuli was used to investigate cuing effects for all cross-modal pairings. Significant asymmetric performance effects of cross-modal spatial links were observed. Auditory cues shortened response latencies for collocated visual targets but visual cues did not do the same for collocated auditory targets. Responses to contralateral (rather than ipsilateral) targets were faster for tactually cued auditory targets and each visual-tactile cue-target combination, suggesting an inhibition-of-return effect. The spatial relationships between multimodal cues and targets significantly affect target response times in complex environments. The performance effects of cross-modal links and the observed cross-modal cuing asymmetries need to be examined in more detail and considered in future interface design. The findings from this study have implications for the design of multimodal and adaptive interfaces and for supporting attention management in complex, data-rich domains.

  16. Artificial Vision, New Visual Modalities and Neuroadaptation

    Directory of Open Access Journals (Sweden)

    Hilmi Or

    2012-01-01

    Full Text Available To study the descriptions from which artificial vision derives, to explore the new visual modalities resulting from eye surgeries and diseases, and to gain awareness of the use of machine vision systems for both enhancement of visual perception and better understanding of neuroadaptation. Science could not define until today what vision is. However, some optical-based systems and definitions have been established considering some factors for the formation of seeing. The best known system includes Gabor filter and Gabor patch which work on edge perception, describing the visual perception in the best known way. These systems are used today in industry and technology of machines, robots and computers to provide their "seeing". These definitions are used beyond the machinery in humans for neuroadaptation in new visual modalities after some eye surgeries or to improve the quality of some already known visual modalities. Beside this, “the blindsight” -which was not known to exist until 35 years ago - can be stimulated with visual exercises. Gabor system is a description of visual perception definable in machine vision as well as in human visual perception. This system is used today in robotic vision. There are new visual modalities which arise after some eye surgeries or with the use of some visual optical devices. Also, blindsight is a different visual modality starting to be defined even though the exact etiology is not known. In all the new visual modalities, new vision stimulating therapies using the Gabor systems can be applied. (Turk J Oph thal mol 2012; 42: 61-5

  17. Fas/CD95 regulatory protein Faim2 is neuroprotective after transient brain ischemia.

    Science.gov (United States)

    Reich, Arno; Spering, Christopher; Gertz, Karen; Harms, Christoph; Gerhardt, Ellen; Kronenberg, Golo; Nave, Klaus A; Schwab, Markus; Tauber, Simone C; Drinkut, Anja; Harms, Kristian; Beier, Chrstioph P; Voigt, Aaron; Göbbels, Sandra; Endres, Matthias; Schulz, Jörg B

    2011-01-05

    Death receptor (DR) signaling has a major impact on the outcome of numerous neurological diseases, including ischemic stroke. DRs mediate not only cell death signals, but also proinflammatory responses and cell proliferation. Identification of regulatory proteins that control the switch between apoptotic and alternative DR signaling opens new therapeutic opportunities. Fas apoptotic inhibitory molecule 2 (Faim2) is an evolutionary conserved, neuron-specific inhibitor of Fas/CD95-mediated apoptosis. To investigate its role during development and in disease models, we generated Faim2-deficient mice. The ubiquitous null mutation displayed a viable and fertile phenotype without overt deficiencies. However, lack of Faim2 caused an increase in susceptibility to combined oxygen-glucose deprivation in primary neurons in vitro as well as in caspase-associated cell death, stroke volume, and neurological impairment after cerebral ischemia in vivo. These processes were rescued by lentiviral Faim2 gene transfer. In summary, we provide evidence that Faim2 is a novel neuroprotective molecule in the context of cerebral ischemia.

  18. Established rheumatoid arthritis - new imaging modalities

    DEFF Research Database (Denmark)

    McQueen, Fiona M; Østergaard, Mikkel

    2007-01-01

    in real-time and facilitates diagnostic and therapeutic interventions such as joint aspiration and injection. Exciting experimental modalities are also being developed with the potential to provide not just morphological but functional imaging. Techniques such as positron emission tomography (PET......) and high-resolution computerized tomography. Erosions are very clearly depicted using these modalities and MRI also allows imaging of soft tissues with assessment of joint inflammation. High-resolution ultrasound is a convenient clinical technique for the assessment of erosions, synovitis and tenosynovitis...

  19. Nonoperative modalities to treat symptomatic cervical spondylosis.

    LENUS (Irish Health Repository)

    Hirpara, Kieran Michael

    2012-01-01

    Cervical spondylosis is a common and disabling condition. It is generally felt that the initial management should be nonoperative, and these modalities include physiotherapy, analgesia and selective nerve root injections. Surgery should be reserved for moderate to severe myelopathy patients who have failed a period of conservative treatment and patients whose symptoms are not adequately controlled by nonoperative means. A review of the literature supporting various modalities of conservative management is presented, and it is concluded that although effective, nonoperative treatment is labour intensive, requiring regular review and careful selection of medications and physical therapy on a case by case basis.

  20. Dorsal and ventral streams across sensory modalities

    Institute of Scientific and Technical Information of China (English)

    Anna Sedda; Federica Scarpina

    2012-01-01

    In this review,we describe the current models of dorsal and ventral streams in vision,audition and touch.Available theories take their first steps from the model of Milner and Goodale,which was developed to explain how human actions can be efficiently carried out using visual information.Since then,similar concepts have also been applied to other sensory modalities.We propose that advances in the knowledge of brain functioning can be achieved through models explaining action and perception patterns independently from sensory modalities.

  1. Response Modality Variations Affect Determinations of Children's Learning Styles.

    Science.gov (United States)

    Janowitz, Jeffrey M.

    The Swassing-Barbe Modality Index (SBMI) uses visual, auditory, and tactile inputs, but only reconstructed output, to measure children's modality strengths. In this experiment, the SBMI's three input modalities were crossed with two output modalities (spoken and drawn) in addition to the reconstructed standard to result in nine treatment…

  2. The Modality-Match Effect in Recognition Memory

    Science.gov (United States)

    Mulligan, Neil W.; Osborn, Katherine

    2009-01-01

    The modality-match effect in recognition refers to superior memory for words presented in the same modality at study and test. Prior research on this effect is ambiguous and inconsistent. The present study demonstrates that the modality-match effect is found when modality is rendered salient at either encoding or retrieval. Specifically, in…

  3. Mechanism of neuroprotective mitochondrial remodeling by PKA/AKAP1.

    Directory of Open Access Journals (Sweden)

    Ronald A Merrill

    2011-04-01

    Full Text Available Mitochondrial shape is determined by fission and fusion reactions catalyzed by large GTPases of the dynamin family, mutation of which can cause neurological dysfunction. While fission-inducing protein phosphatases have been identified, the identity of opposing kinase signaling complexes has remained elusive. We report here that in both neurons and non-neuronal cells, cAMP elevation and expression of an outer-mitochondrial membrane (OMM targeted form of the protein kinase A (PKA catalytic subunit reshapes mitochondria into an interconnected network. Conversely, OMM-targeting of the PKA inhibitor PKI promotes mitochondrial fragmentation upstream of neuronal death. RNAi and overexpression approaches identify mitochondria-localized A kinase anchoring protein 1 (AKAP1 as a neuroprotective and mitochondria-stabilizing factor in vitro and in vivo. According to epistasis studies with phosphorylation site-mutant dynamin-related protein 1 (Drp1, inhibition of the mitochondrial fission enzyme through a conserved PKA site is the principal mechanism by which cAMP and PKA/AKAP1 promote both mitochondrial elongation and neuronal survival. Phenocopied by a mutation that slows GTP hydrolysis, Drp1 phosphorylation inhibits the disassembly step of its catalytic cycle, accumulating large, slowly recycling Drp1 oligomers at the OMM. Unopposed fusion then promotes formation of a mitochondrial reticulum, which protects neurons from diverse insults.

  4. Neuroprotective effects of statins against amyloid β-induced neurotoxicity

    Directory of Open Access Journals (Sweden)

    Hsin-Hua Li

    2018-01-01

    Full Text Available A growing body of evidence suggests that disruption of the homeostasis of lipid metabolism affects the pathogenesis of Alzheimer's disease (AD. In particular, dysregulation of cholesterol homeostasis in the brain has been reported to considerably increase the risk of developing AD. Thus, dysregulation of lipid homeostasis may increase the amyloid β (Aβ levels by affecting amyloid precursor protein (APP cleavage, which is the most important risk factor involved in the pathogenesis of AD. Previous research demonstrated that Aβ can trigger neuronal insulin resistance, which plays an important role in response to Aβ-induced neurotoxicity in AD. Epidemiological studies also suggested that statin use is associated with a decreased incidence of AD. Therefore, statins are believed to be a good candidate for conferring neuroprotective effects against AD. Statins may play a beneficial role in reducing Aβ-induced neurotoxicity. Their effect involves a putative mechanism beyond its cholesterol-lowering effects in preventing Aβ-induced neurotoxicity. However, the underlying molecular mechanisms of the protective effect of statins have not been clearly determined in Aβ-induced neurotoxicity. Given that statins may provide benefits beyond the inhibition of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA reductase, these drugs may also improve the brain. Thus, statins may have beneficial effects on impaired insulin signaling by activating AMP-activated protein kinase (AMPK in neuronal cells. They play a potential therapeutic role in targeting Aβ-mediated neurotoxicity.

  5. Neuroprotective effects of phytochemicals on dopaminergic neuron cultures.

    Science.gov (United States)

    Sandoval-Avila, S; Diaz, N F; Gómez-Pinedo, U; Canales-Aguirre, A A; Gutiérrez-Mercado, Y K; Padilla-Camberos, E; Marquez-Aguirre, A L; Díaz-Martínez, N E

    2016-06-21

    Parkinson's disease is a progressive neurodegenerative disorder characterised by a loss of dopaminergic neurons in the substantia nigra pars compacta, which results in a significant decrease in dopamine levels and consequent functional motor impairment. Although its aetiology is not fully understood, several pathogenic mechanisms, including oxidative stress, have been proposed. Current therapeutic approaches are based on dopamine replacement drugs; these agents, however, are not able to stop or even slow disease progression. Novel therapeutic approaches aimed at acting on the pathways leading to neuronal dysfunction and death are under investigation. In recent years, such natural molecules as polyphenols, alkaloids, and saponins have been shown to have a neuroprotective effect due to their antioxidant and anti-inflammatory properties. The aim of our review is to analyse the most relevant studies worldwide addressing the benefits of some phytochemicals used in in vitro models of Parkinson's disease. Copyright © 2016 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.

  6. Cell type-specific neuroprotective activity of untranslocated prion protein.

    Directory of Open Access Journals (Sweden)

    Elena Restelli

    2010-10-01

    Full Text Available A key pathogenic role in prion diseases was proposed for a cytosolic form of the prion protein (PrP. However, it is not clear how cytosolic PrP localization influences neuronal viability, with either cytotoxic or anti-apoptotic effects reported in different studies. The cellular mechanism by which PrP is delivered to the cytosol of neurons is also debated, and either retrograde transport from the endoplasmic reticulum or inefficient translocation during biosynthesis has been proposed. We investigated cytosolic PrP biogenesis and effect on cell viability in primary neuronal cultures from different mouse brain regions.Mild proteasome inhibition induced accumulation of an untranslocated form of cytosolic PrP in cortical and hippocampal cells, but not in cerebellar granules. A cyclopeptolide that interferes with the correct insertion of the PrP signal sequence into the translocon increased the amount of untranslocated PrP in cortical and hippocampal cells, and induced its synthesis in cerebellar neurons. Untranslocated PrP boosted the resistance of cortical and hippocampal neurons to apoptotic insults but had no effect on cerebellar cells.These results indicate cell type-dependent differences in the efficiency of PrP translocation, and argue that cytosolic PrP targeting might serve a physiological neuroprotective function.

  7. Quercetin, not caffeine, is a major neuroprotective component in coffee.

    Science.gov (United States)

    Lee, Moonhee; McGeer, Edith G; McGeer, Patrick L

    2016-10-01

    Epidemiologic studies indicate that coffee consumption reduces the risk of Parkinson's disease and Alzheimer's disease. To determine the factors involved, we examined the protective effects of coffee components. The test involved prevention of neurotoxicity to SH-SY5Y cells that was induced by lipopolysaccharide plus interferon-γ or interferon-γ released from activated microglia and astrocytes. We found that quercetin, flavones, chlorogenic acid, and caffeine protected SH-SY5Y cells from these toxins. They also reduced the release of tumor necrosis factor-α and interleukin-6 from the activated microglia and astrocytes and attenuated the activation of proteins from P38 mitogen-activated protein kinase (MAPK) and nuclear factor kappa light chain enhancer of activated B cells (NFκB). After exposure to toxin containing glial-stimulated conditioned medium, we also found that quercetin reduced oxidative/nitrative damage to DNA, as well as to the lipids and proteins of SH-SY5Y cells. There was a resultant increase in [GSH]i in SH-SY5Y cells. The data indicate that quercetin is the major neuroprotective component in coffee against Parkinson's disease and Alzheimer's disease. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Neuroprotective function for ramified microglia in hippocampal excitotoxicity

    Directory of Open Access Journals (Sweden)

    Vinet Jonathan

    2012-01-01

    Full Text Available Abstract Background Most of the known functions of microglia, including neurotoxic and neuroprotective properties, are attributed to morphologically-activated microglia. Resting, ramified microglia are suggested to primarily monitor their environment including synapses. Here, we show an active protective role of ramified microglia in excitotoxicity-induced neurodegeneration. Methods Mouse organotypic hippocampal slice cultures were treated with N-methyl-D-aspartic acid (NMDA to induce excitotoxic neuronal cell death. This procedure was performed in slices containing resting microglia or slices that were chemically or genetically depleted of their endogenous microglia. Results Treatment of mouse organotypic hippocampal slice cultures with 10-50 μM N-methyl-D-aspartic acid (NMDA induced region-specific excitotoxic neuronal cell death with CA1 neurons being most vulnerable, whereas CA3 and DG neurons were affected less. Ablation of ramified microglia severely enhanced NMDA-induced neuronal cell death in the CA3 and DG region rendering them almost as sensitive as CA1 neurons. Replenishment of microglia-free slices with microglia restored the original resistance of CA3 and DG neurons towards NMDA. Conclusions Our data strongly suggest that ramified microglia not only screen their microenvironment but additionally protect hippocampal neurons under pathological conditions. Morphological activation of ramified microglia is thus not required to influence neuronal survival.

  9. Estrone is neuroprotective in rats after traumatic brain injury.

    Science.gov (United States)

    Gatson, Joshua W; Liu, Ming-Mei; Abdelfattah, Kareem; Wigginton, Jane G; Smith, Scott; Wolf, Steven; Simpkins, James W; Minei, Joseph P

    2012-08-10

    In various animal and human studies, early administration of 17β-estradiol, a strong antioxidant, anti-inflammatory, and anti-apoptotic agent, significantly decreases the severity of injury in the brain associated with cell death. Estrone, the predominant estrogen in postmenopausal women, has been shown to be a promising neuroprotective agent. The overall goal of this project was to determine if estrone mitigates secondary injury following traumatic brain injury (TBI) in rats. Male rats were given either placebo (corn oil) or estrone (0.5 mg/kg) at 30 min after severe TBI. Using a controlled cortical impact device in rats that underwent a craniotomy, the right parietal cortex was injured using the impactor tip. Non-injured control and sham animals were also included. At 72 h following injury, the animals were perfused intracardially with 0.9% saline followed by 10% phosphate-buffered formalin. The whole brain was removed, sliced, and stained for TUNEL-positive cells. Estrone decreased cortical lesion volume (pcerebral cortical levels of TUNEL-positive staining (pprotective pathways such as the ERK1/2 and BDNF pathways, decreases ischemic secondary injury, and decreases apoptotic-mediated cell death. These results suggest that estrone may afford protection to those suffering from TBI.

  10. Transthyretin neuroprotection in Alzheimer's disease is dependent on proteolysis.

    Science.gov (United States)

    Silva, Catarina S; Eira, Jessica; Ribeiro, Carlos A; Oliveira, Ângela; Sousa, Mónica M; Cardoso, Isabel; Liz, Márcia A

    2017-11-01

    The deposition of amyloid β peptide (Aβ) in the hippocampus is one of the major hallmarks of Alzheimer's disease, a neurodegenerative disorder characterized by memory loss and cognitive impairment. The modulation of Aβ levels in the brain results from an equilibrium between its production from the amyloid precursor protein and removal by amyloid clearance proteins, which might occur via enzymatic (Aβ-degrading enzymes) or nonenzymatic (binding/transport proteins) reactions. Transthyretin (TTR) is one of the major Aβ-binding proteins acting as a neuroprotector in AD. In addition, TTR cleaves Aβ peptide in vitro. In this work, we show that proteolytically active TTR, and not the inactive form of the protein, impacts on Aβ fibrillogenesis, degrades neuronal-secreted Aβ, and reduces Aβ-induced toxicity in hippocampal neurons. Our data demonstrate that TTR proteolytic activity is required for the neuroprotective effect of the protein constituting a putative novel therapeutic target for AD. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Refinement Checking on Parametric Modal Transition Systems

    DEFF Research Database (Denmark)

    Benes, Nikola; Kretínsky, Jan; Larsen, Kim Guldstrand

    2015-01-01

    Modal transition systems (MTS) is a well-studied specification formalism of reactive systems supporting a step-wise refinement methodology. Despite its many advantages, the formalism as well as its currently known extensions are incapable of expressing some practically needed aspects in the refin...

  12. Dynamic analysis of pipings by Modal Synthesis

    International Nuclear Information System (INIS)

    Augusto, O.B.; Mattar Neto, M.

    1986-01-01

    A Modal Synthesis method, the component modes, and its implementation as a post-processor of finite element program is presented. Examples of calculations of stationary and transient vibrations for monitoring pipelines of nuclear power plants are analysed. (M.C.K.) [pt

  13. Established rheumatoid arthritis - new imaging modalities

    DEFF Research Database (Denmark)

    McQueen, Fiona M; Østergaard, Mikkel

    2007-01-01

    New imaging modalities are assuming an increasingly important role in the investigation and management of rheumatoid arthritis. It is now possible to obtain information about all tissues within the joint in three dimensions using tomographic techniques such as magnetic resonance imaging (MRI...

  14. Nanomaterials Toxicity and Cell Death Modalities

    Directory of Open Access Journals (Sweden)

    Daniela De Stefano

    2012-01-01

    Full Text Available In the last decade, the nanotechnology advancement has developed a plethora of novel and intriguing nanomaterial application in many sectors, including research and medicine. However, many risks have been highlighted in their use, particularly related to their unexpected toxicity in vitro and in vivo experimental models. This paper proposes an overview concerning the cell death modalities induced by the major nanomaterials.

  15. Dual-Modality Breast Tomosynthesis1

    OpenAIRE

    Williams, Mark B.; Judy, Patricia G.; Gunn, Spencer; Majewski, Stanislaw

    2010-01-01

    Pilot clinical evaluation of this dual-modality tomosynthesis system suggests that it is a feasible and accurate method with which to detect and diagnose breast cancer and that specificity and positive predictive value can be improved by adding molecular breast imaging tomosynthesis to x-ray tomosynthesis.

  16. Sensor Placement for Modal Parameter Subset Estimation

    DEFF Research Database (Denmark)

    Ulriksen, Martin Dalgaard; Bernal, Dionisio; Damkilde, Lars

    2016-01-01

    The present paper proposes an approach for deciding on sensor placements in the context of modal parameter estimation from vibration measurements. The approach is based on placing sensors, of which the amount is determined a priori, such that the minimum Fisher information that the frequency resp...

  17. Learning Modalities--Should They Be Considered?

    Science.gov (United States)

    Jones, John Paul

    The author summarizes and reviews seven research studies which seek to determine the role of individual modal preference as related to learning to read. The seven studies are by Bateman (1968); Robinson (1968); Jones (1970); Bruininks (1968); Cripe (1966); de Hirsh, Jansky, and Langford (1966); and Bursuk (1971). Of these studies, only Bursuk…

  18. The Fourier modal method for aperiodic structures

    NARCIS (Netherlands)

    Pisarenco, M.; Maubach, J.M.L.; Setija, I.D.; Mattheij, R.M.M.

    2010-01-01

    This paper extends the area of application of the Fourier modal method from periodic structures to non-periodic ones illuminated under arbitrary angles. This is achieved by placing perfectly matched layers at the lateral boundaries and reformulating the problem in terms of a contrast field.

  19. Current diagnostic modalities for vulnerable plaque detection

    NARCIS (Netherlands)

    J.A. Schaar (Johannes); F. Mastik (Frits); E.S. Regar (Eveline); C.A. den Uil (Corstiaan); F.J.H. Gijsen (Frank); J.J. Wentzel (Jolanda); P.W.J.C. Serruys (Patrick); A.F.W. van der Steen (Ton)

    2007-01-01

    textabstractRupture of vulnerable plaques is the main cause of acute coronary syndrome and myocardial infarction. Identification of vulnerable plaques is therefore essential to enable the development of treatment modalities to stabilize such plaques. Several diagnostic methods are currently tested

  20. Computing modal dispersion characteristics of radially Asymmetric ...

    African Journals Online (AJOL)

    We developed a matrix theory that applies to with non-circular/circular but concentric layers fibers. And we compute the dispersion characteristics of radially unconventional fiber, known as Asymmetric Bragg fiber. An attempt has been made to determine how the modal characteristics change as circular Bragg fiber is ...

  1. PENGARUH GOOD CORPORATE GOVERNANCE, KINERJA KEUANGAN, MODAL INTELEKTUAL TERHADAP PENGUNGKAPAN MODAL INTELEKTUAL

    Directory of Open Access Journals (Sweden)

    Gilang Anies Saendy

    2015-10-01

    Full Text Available Dampak perkembangan globalisasi membutuhkan informasi lebih lanjut, terutama informasi tentang modal intelektual perusahaan. Tapi, dalam kondisi nyata informasi modal intelektual masih rendah, yakni sekitar 27-35%. Objek penelitian ini adalah perbankan yang terdapat dalam direktori Pasar Modal Indonesia (ICMD 2010-2013. Jumlah populasi adalah 36 perbankan dan 17 sampel dengan menggunakan purposive sampling. Metode yang digunakan adalah analisis jalur. Hasil penelitian ini menunjukkan bahwa tidak pengaruh antara pelaksanaan GCG untuk pengungkapan modal intelektual dan kinerja keuangan. Selain itu, ada pengaruh positif antara kinerja modal intelektual terhadap kinerja keuangan dan kinerja keuangan untuk pengungkapan modal intelektual. Selanjutnya, hasil penelitian menunjukkan bahwa tidak efek mediasi melalui kinerja keuangan perusahaan antara implementasi GCG dalam pengungkapan modal intelektual. Hasilnya juga mengatakan ada efek mediasi antara pelaksanaan GCG untuk pengungkapan modal intelektual pikir kinerja modal intelektual. The development due to the increase of globalization gives impact to the need of having more information. One of them is the need to have information on company’s intellectual capital. But, in real condition, intellectual capital information is still low. It is about 27-35%. The objects of this research are banks organized in Indonesian Capital Market Directory (ICMD from 2010-2013. Total populations were 36 banks, and finally 17 samples were selected by using purposive sampling. The method used is path analysis. The results of this research show that there is no influence between GCG’s implementation on intellectual capital disclosure and financial performance. However, there are  positive influences of intellectual capital performance on the financial performance, and financial performance on the disclosure of intellectual capital. Besides, this research said that there is no effect of mediation through the company

  2. MODALITIES OF TRAINING PARAMETER ALTERNATION IN NOWADAYS STRENGTH TRAINING PRACTICE

    Directory of Open Access Journals (Sweden)

    RANISAVLJEV IGOR

    2010-12-01

    Full Text Available Large number of variables could be alternated during the process of planning and programming in sports training. Superior training results in majority of sports are achieved by optimally manipulating training parameters in appropriate sequences and combinations. Additionally, in some sports they might be the result of appropriate periodization pattern. Today's tendency in strength training practice is training movements instead of training muscles. Exercise classification according to the dominant movement types, allows creating new modalities in training alternation. Additional variations in volume, intensity, rest brakes, repetition velocity andinter-repetition rest can be the important part of functional strength training program. Alternation and combination of different training parameters makes appropriate training stimulus for strength increase in the most of nowadays sports. Optimal alternation of basic training parameters should be the first part in the processof planning and programming. As a result, majority of athletes might not need advanced periodization patterns for optimal improvement in muscle strength and power

  3. Evidentiality, Epistemic Modality, and Epistemic Status

    Directory of Open Access Journals (Sweden)

    Rezeda Dilshatovna Shakirova

    2016-09-01

    Full Text Available The article discusses the interaction of evidentiality categories, typical of many Turkic, Finno-Ugric, Samoyed, certain Slavic, and other languages with the categories of epistemic modality, which is widely represented particularly in Germanic languages. The methodological framework of this study consists of the general philosophic, general scientific and private levels. The general philosophic methodology is based on the analytic philosophy, under the linguistic trend of which the language study was carried out to solve philosophic problems. The general scientific methodological bases of the study are related to the principle of identifying similarities and differences of the categories analyzed and the systematicity of description, whereas the descriptive method and techniques thereof are used primarily as the private-linguistic methods. In contrast to evidentiality, indicating the source of information, the epistemic modality marks different level of the information reliability. In the modern German language, the categories studied have a zone of intersection in terms of community within the means of expression, to which modal words and modal verbs as well as the verb scheinen can be primarily related. However, in the modern German language, there is no question of the category of evidentiality in the plane, within which it is currently being studied basing on the material of those languages, to the fragment of the grammatical system of which it is primarily inherent. As a rule, the semantics of evidentiality in these languages provides no information on the degree of reliability of the source of knowledge. To overcome the contradiction of such nature, this work suggests paying attention to the category of epistemic status of an utterance, the semantic structure of which is wider than evidentiality and epistemic modality and includes the level of reliability of the source of knowledge along with the designation thereof. In today's German

  4. Conflict when making decisions about dialysis modality.

    Science.gov (United States)

    Chen, Nien-Hsin; Lin, Yu-Ping; Liang, Shu-Yuan; Tung, Heng-Hsin; Tsay, Shiow-Luan; Wang, Tsae-Jyy

    2018-01-01

    To explore decisional conflict and its influencing factors on choosing dialysis modality in patients with end-stage renal diseases. The influencing factors investigated include demographics, predialysis education, dialysis knowledge, decision self-efficacy and social support. Making dialysis modality decisions can be challenging for patients with end-stage renal diseases; there are pros and cons to both haemodialysis and peritoneal dialysis. Patients are often uncertain as to which one will be the best alternative for them. This decisional conflict increases the likelihood of making a decision that is not based on the patient's values or preferences and may result in undesirable postdecisional consequences. Addressing factors predisposing patients to decisional conflict helps to facilitate informed decision-making and then to improve healthcare quality. A predictive correlational cross-sectional study design was used. Seventy patients were recruited from the outpatient dialysis clinics of two general hospitals in Taiwan. Data were collected with study questionnaires, including questions on demographics, dialysis modality and predialysis education, the Dialysis Knowledge Scale, the Decision Self-Efficacy scale, the Social Support Scale, and the Decisional Conflict Scale. The mean score on the Decisional Conflict Scale was 29.26 (SD = 22.18). Decision self-efficacy, dialysis modality, predialysis education, professional support and dialysis knowledge together explained 76.4% of the variance in decisional conflict. Individuals who had lower decision self-efficacy, did not receive predialysis education on both haemodialysis and peritoneal dialysis, had lower dialysis knowledge and perceived lower professional support reported higher decisional conflict on choosing dialysis modality. When providing decisional support to predialysis stage patients, practitioners need to increase patients' decision self-efficacy, provide both haemodialysis and peritoneal dialysis

  5. Neuroprotective effect of a new variant of Epo nonhematopoietic against oxidative stress

    Directory of Open Access Journals (Sweden)

    C. Castillo

    2018-04-01

    Full Text Available Human erythropoietin is mainly recognized for its hematopoietic function; however, by binding to its receptor (EpoR, it can activate different signaling pathways as STAT, PI3K, MAPK and RAS to increase cellular differentiation or provide neuroprotective effects, among others. A recombinant human erythropoietin variant with low glycosylation and without hematopoietic effect (EpoL was purified from skimmed goat milk. Recombinant human erythropoietin (Epo was obtained from CHO cell line and used as control to compare EpoL effects. Neuroprotection studies were performed in PC12 cells and rat hippocampal slices. Cells were pretreated during 1 h with EpoL or Epo and exposed to oxidative agents (H2O2 or FCCP; cell viability was assayed at the end of the experiment by the MTT method. Hippocampal slices were exposed to 15 min of oxygen and glucose deprivation (OGD and the neuroprotective drugs EpoL or Epo were incubated for 2 h post-OGD in re-oxygenated medium. Cell cultures stressed with oxidative agents, and pretreated with EpoL, showed neuroprotective effects of 30% at a concentration 10 times lower than that of Epo. Moreover, similar differences were observed in OGD ex vivo assays. Neuroprotection elicited by EpoL was lost when an antibody against EpoR was present, indicating that its effect is EpoR-dependent. In conclusion, our results suggest that EpoL has a more potent neuroprotective profile than Epo against oxidative stress, mediated by activation of EpoR, thus EpoL represents an important target to develop a potential biopharmaceutical to treat different central nervous system pathologies related to oxidative stress such as stroke or neurodegenerative diseases. Keywords: Erythropoietin, Erythropoietin receptor, Neuroprotection, Oxidative stress

  6. Neuroprotective "agents" in surgery. Secret "agent" man, or common "agent" machine?

    Science.gov (United States)

    Andrews, R. J.

    1999-01-01

    The search for clinically-effective neuroprotective agents has received enormous support in recent years--an estimated $200 million by pharmaceutical companies on clinical trials for traumatic brain injury alone. At the same time, the pathophysiology of brain injury has proved increasingly complex, rendering the likelihood of a single agent "magic bullet" even more remote. On the other hand, great progress continues with technology that makes surgery less invasive and less risky. One example is the application of endovascular techniques to treat coronary artery stenosis, where both the invasiveness of sternotomy and the significant neurological complication rate (due to microemboli showering the cerebral vasculature) can be eliminated. In this paper we review aspects of intraoperative neuroprotection both present and future. Explanations for the slow progress on pharmacologic neuroprotection during surgery are presented. Examples of technical advances that have had great impact on neuroprotection during surgery are given both from coronary artery stenosis surgery and from surgery for Parkinson's disease. To date, the progress in neuroprotection resulting from such technical advances is an order of magnitude greater than that resulting from pharmacologic agents used during surgery. The progress over the last 20 years in guidance during surgery (CT and MRI image-guidance) and in surgical access (endoscopic and endovascular techniques) will soon be complemented by advances in our ability to evaluate biological tissue intraoperatively in real-time. As an example of such technology, the NASA Smart Probe project is considered. In the long run (i.e., in 10 years or more), pharmacologic "agents" aimed at the complex pathophysiology of nervous system injury in man will be the key to true intraoperative neuroprotection. In the near term, however, it is more likely that mundane "agents" based on computers, microsensors, and microeffectors will be the major impetus to improved

  7. Automatic selective attention as a function of sensory modality in aging.

    Science.gov (United States)

    Guerreiro, Maria J S; Adam, Jos J; Van Gerven, Pascal W M

    2012-03-01

    It was recently hypothesized that age-related differences in selective attention depend on sensory modality (Guerreiro, M. J. S., Murphy, D. R., & Van Gerven, P. W. M. (2010). The role of sensory modality in age-related distraction: A critical review and a renewed view. Psychological Bulletin, 136, 975-1022. doi:10.1037/a0020731). So far, this hypothesis has not been tested in automatic selective attention. The current study addressed this issue by investigating age-related differences in automatic spatial cueing effects (i.e., facilitation and inhibition of return [IOR]) across sensory modalities. Thirty younger (mean age = 22.4 years) and 25 older adults (mean age = 68.8 years) performed 4 left-right target localization tasks, involving all combinations of visual and auditory cues and targets. We used stimulus onset asynchronies (SOAs) of 100, 500, 1,000, and 1,500 ms between cue and target. The results showed facilitation (shorter reaction times with valid relative to invalid cues at shorter SOAs) in the unimodal auditory and in both cross-modal tasks but not in the unimodal visual task. In contrast, there was IOR (longer reaction times with valid relative to invalid cues at longer SOAs) in both unimodal tasks but not in either of the cross-modal tasks. Most important, these spatial cueing effects were independent of age. The results suggest that the modality hypothesis of age-related differences in selective attention does not extend into the realm of automatic selective attention.

  8. Supervised Cross-Modal Factor Analysis for Multiple Modal Data Classification

    KAUST Repository

    Wang, Jingbin

    2015-10-09

    In this paper we study the problem of learning from multiple modal data for purpose of document classification. In this problem, each document is composed two different modals of data, i.e., An image and a text. Cross-modal factor analysis (CFA) has been proposed to project the two different modals of data to a shared data space, so that the classification of a image or a text can be performed directly in this space. A disadvantage of CFA is that it has ignored the supervision information. In this paper, we improve CFA by incorporating the supervision information to represent and classify both image and text modals of documents. We project both image and text data to a shared data space by factor analysis, and then train a class label predictor in the shared space to use the class label information. The factor analysis parameter and the predictor parameter are learned jointly by solving one single objective function. With this objective function, we minimize the distance between the projections of image and text of the same document, and the classification error of the projection measured by hinge loss function. The objective function is optimized by an alternate optimization strategy in an iterative algorithm. Experiments in two different multiple modal document data sets show the advantage of the proposed algorithm over other CFA methods.

  9. Taurine Provides Neuroprotection against Retinal Ganglion Cell Degeneration

    Science.gov (United States)

    Froger, Nicolas; Cadetti, Lucia; Lorach, Henri; Martins, Joao; Bemelmans, Alexis-Pierre; Dubus, Elisabeth; Degardin, Julie; Pain, Dorothée; Forster, Valérie; Chicaud, Laurent; Ivkovic, Ivana; Simonutti, Manuel; Fouquet, Stéphane; Jammoul, Firas; Léveillard, Thierry; Benosman, Ryad; Sahel, José-Alain; Picaud, Serge

    2012-01-01

    Retinal ganglion cell (RGC) degeneration occurs in numerous retinal diseases leading to blindness, either as a primary process like in glaucoma, or secondary to photoreceptor loss. However, no commercial drug is yet directly targeting RGCs for their neuroprotection. In the 70s, taurine, a small sulfonic acid provided by nutrition, was found to be essential for the survival of photoreceptors, but this dependence was not related to any retinal disease. More recently, taurine deprivation was incriminated in the retinal toxicity of an antiepileptic drug. We demonstrate here that taurine can improve RGC survival in culture or in different animal models of RGC degeneration. Taurine effect on RGC survival was assessed in vitro on primary pure RCG cultures under serum-deprivation conditions, and on NMDA-treated retinal explants from adult rats. In vivo, taurine was administered through the drinking water in two glaucomatous animal models (DBA/2J mice and rats with vein occlusion) and in a model of Retinitis pigmentosa with secondary RGC degeneration (P23H rats). After a 6-day incubation, 1 mM taurine significantly enhanced RGCs survival (+68%), whereas control RGCs were cultured in a taurine-free medium, containing all natural amino-acids. This effect was found to rely on taurine-uptake by RGCs. Furthermore taurine (1 mM) partly prevented NMDA-induced RGC excitotoxicity. Finally, taurine supplementation increased RGC densities both in DBA/2J mice, in rats with vein occlusion and in P23H rats by contrast to controls drinking taurine-free water. This study indicates that enriched taurine nutrition can directly promote RGC survival through RGC intracellular pathways. It provides evidence that taurine can positively interfere with retinal degenerative diseases. PMID:23115615

  10. Cytochrome C is tyrosine 97 phosphorylated by neuroprotective insulin treatment.

    Directory of Open Access Journals (Sweden)

    Thomas H Sanderson

    Full Text Available Recent advancements in isolation techniques for cytochrome c (Cytc have allowed us to discover post-translational modifications of this protein. We previously identified two distinct tyrosine phosphorylated residues on Cytc in mammalian liver and heart that alter its electron transfer kinetics and the ability to induce apoptosis. Here we investigated the phosphorylation status of Cytc in ischemic brain and sought to determine if insulin-induced neuroprotection and inhibition of Cytc release was associated with phosphorylation of Cytc. Using an animal model of global brain ischemia, we found a ∼50% decrease in neuronal death in the CA1 hippocampal region with post-ischemic insulin administration. This insulin-mediated increase in neuronal survival was associated with inhibition of Cytc release at 24 hours of reperfusion. To investigate possible changes in the phosphorylation state of Cytc we first isolated the protein from ischemic pig brain and brain that was treated with insulin. Ischemic brains demonstrated no detectable tyrosine phosphorylation. In contrast Cytc isolated from brains treated with insulin showed robust phosphorylation of Cytc, and the phosphorylation site was unambiguously identified as Tyr97 by immobilized metal affinity chromatography/nano-liquid chromatography/electrospray ionization mass spectrometry. We next confirmed these results in rats by in vivo application of insulin in the absence or presence of global brain ischemia and determined that Cytc Tyr97-phosphorylation is strongly induced under both conditions but cannot be detected in untreated controls. These data suggest a mechanism whereby Cytc is targeted for phosphorylation by insulin signaling, which may prevent its release from the mitochondria and the induction of apoptosis.

  11. Erythropoietin's Beta Common Receptor Mediates Neuroprotection in Spinal Cord Neurons.

    Science.gov (United States)

    Foley, Lisa S; Fullerton, David A; Mares, Joshua; Sungelo, Mitchell; Weyant, Michael J; Cleveland, Joseph C; Reece, T Brett

    2017-12-01

    Paraplegia from spinal cord ischemia-reperfusion (SCIR) remains an elusive and devastating complication of complex aortic operations. Erythropoietin (EPO) attenuates this injury in models of SCIR. Upregulation of the EPO beta common receptor (βcR) is associated with reduced damage in models of neural injury. The purpose of this study was to examine whether EPO-mediated neuroprotection was dependent on βcR expression. We hypothesized that spinal cord neurons subjected to oxygen-glucose deprivation would mimic SCIR injury in aortic surgery and EPO treatment attenuates this injury in a βcR-dependent fashion. Lentiviral vectors with βcR knockdown sequences were tested on neuron cell cultures. The virus with greatest βcR knockdown was selected. Spinal cord neurons from perinatal wild-type mice were harvested and cultured to maturity. They were treated with knockdown or nonsense virus and transduced cells were selected. Three groups (βcR knockdown virus, nonsense control virus, no virus control; n = 8 each) were subjected to 1 hour of oxygen-glucose deprivation. Viability was assessed. βcR expression was quantified by immunoblot. EPO preserved neuronal viability after oxygen-glucose deprivation (0.82 ± 0.04 versus 0.61 ± 0.01; p neuron preservation was similar in the nonsense virus and control mice (0.82 ± 0.04 versus 0.80 ± 0.05; p = 0.77). EPO neuron preservation was lost in βcR knockdown mice compared with nonsense control mice (0.46 ± 0.03 versus 0.80 ± 0.05; p neuronal loss after oxygen-glucose deprivation in a βcR-dependent fashion. This receptor holds immense clinical promise as a target for pharmacotherapies treating spinal cord ischemic injury. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  12. The administration of hydrogen sulphide prior to ischemic reperfusion has neuroprotective effects in an acute stroke model.

    Directory of Open Access Journals (Sweden)

    Chul-Woong Woo

    Full Text Available Emerging evidence has suggested that hydrogen sulfide (H2S may alleviate the cellular damage associated with cerebral ischemia/reperfusion (I/R injury. In this study, we assessed using 1H-magnetic resonance imaging/magnetic resonance spectroscopy (1H-MRI/MRS and histologic analysis whether H2S administration prior to reperfusion has neuroprotective effects. We also evaluated for differences in the effects of H2S treatment at 2 time points. 1H-MRI/MRS data were obtained at baseline, and at 3, 9, and 24 h after ischemia from 4 groups: sham, control (I/R injury, sodium hydrosulfide (NaHS-30 and NaHS-1 (NaHS delivery at 30 and 1 min before reperfusion, respectively. The total infarct volume and the midline shift at 24 h post-ischemia were lowest in the NaHS-1, followed by the NaHS-30 and control groups. Peri-infarct volume was significantly lower in the NaHS-1 compared to NaHS-30 and control animals. The relative apparent diffusion coefficient (ADC in the peri-infarct region showed that the NaHS-1 group had significantly lower values compared to the NaHS-30 and control animals and that NaHS-1 rats showed significantly higher relative T2 values in the peri-infarct region compared to the controls. The relative ADC value, relative T2 value, levels of N-acetyl-L-aspartate (NAA, and the NAA, glutamate, and taurine combination score (NGT in the ischemic core region at 24 h post-ischemia did not differ significantly between the 2 NaHS groups and the control except that the NAA and NGT values were higher in the peri-infarct region of the NaHS-1 animals at 9 h post-ischemia. In the ischemic core and peri-infarct regions, the apoptosis rate was lowest in the NaHS-1 group, followed by the NaHS-30 and control groups. Our results suggest that H2S treatment has neuroprotective effects on the peri-infarct region during the evolution of I/R injury. Furthermore, our findings indicate that the administration of H2S immediately prior to reperfusion produces the

  13. Modal Testing of Mechanical Structures subject to Operational Excitation Forces

    DEFF Research Database (Denmark)

    Møller, N.; Brincker, Rune; Herlufsen, H.

    2001-01-01

    Operational Modal Analysis also known as Output Only Modal Analysis has in the recent years been used for extracting modal parameters of civil engineering structures and is now becoming popular for mechanical structures. The advantage of the method is that no artificial excitation need to be appl......Operational Modal Analysis also known as Output Only Modal Analysis has in the recent years been used for extracting modal parameters of civil engineering structures and is now becoming popular for mechanical structures. The advantage of the method is that no artificial excitation need...

  14. Morphological functional criteria of neuroprotective therapy efficacy in glaucomatous optic neuropathy

    Directory of Open Access Journals (Sweden)

    Tszin Dan

    2015-01-01

    Full Text Available Electrophysiological tests may be used to detect early glaucomatous changes and glaucoma progression risk and to monitor treatment efficacy. Most important pathogenic aspects of glaucomatous process, pathogenesis and multifactorial nature of glaucomatous optic neuropathy are described. Major triggers of glaucomatous optic neuropathy are mechanical and vascular. Principles of neuroprotective therapy, neuroprotective drugs, and mechanisms of action of direct and indirect neuroprotective agents are presented. IOPcc is a basis for neuroprotective therapy selection and its efficacy monitoring. Amongst neuroprotective drugs, NMDA agonists, antioxidants, peptides, and calcium channel blockers are of special importance. Structural damage and functional deficiency (e.g., visual field loss in glaucoma and the most informative and accurate methods of their detection are characterized. Confocal laser microscopy, optical coherence tomography, and scanning laser polarimetry are compared. These techniques are used to study optic nerve head and retinal nerve fiber layer. They are proposed as diagnostic and monitoring tools for glaucoma, glaucoma suspicion, and ocular hypertension. The most sensitive and specific electrophysiological tests for glaucomatous optic neuropathy are pattern electroretinography, multfocal electroretinography, and multifocal visually evoked potentials. 

  15. Progranulin and Its Related MicroRNAs after Status Epilepticus: Possible Mechanisms of Neuroprotection.

    Science.gov (United States)

    Körtvelyessy, Peter; Huchtemann, Tessa; Heinze, Hans-Jochen; Bittner, Daniel M

    2017-02-24

    The current knowledge about neuroprotective mechanisms in humans after status epilepticus is scarce. One reason is the difficulty to measure possible mediators of these neuroprotective mechanisms. The dawn of microRNA detection in the cerebrospinal fluid (CSF) and the recent advancements in measuring proteins in the CSF such as progranulin, which is, e.g., responsible for neurite outgrowth and limiting exceeding neuroinflammatory responses, have given us new insights into putative neuroprotective mechanisms following status epilepticus. This should complement the animal data. In this review, we cover what is known about the role of progranulin as well as the links between microRNA changes and the progranulin pathway following status epilepticus in humans and animals hypothesizing neuroprotective and neurorehabilitative effects. Progranulin has also been found to feature prominently in the neuroprotective processes under hypoxic conditions and initiating neurorehabilitative processes. These properties may be used therapeutically, e.g., through drugs that raise the progranulin levels and therefore the cerebral progranulin levels as well with the goal of improving the outcome after status epilepticus.

  16. Progranulin and Its Related MicroRNAs after Status Epilepticus: Possible Mechanisms of Neuroprotection

    Directory of Open Access Journals (Sweden)

    Peter Körtvelyessy

    2017-02-01

    Full Text Available The current knowledge about neuroprotective mechanisms in humans after status epilepticus is scarce. One reason is the difficulty to measure possible mediators of these neuroprotective mechanisms. The dawn of microRNA detection in the cerebrospinal fluid (CSF and the recent advancements in measuring proteins in the CSF such as progranulin, which is, e.g., responsible for neurite outgrowth and limiting exceeding neuroinflammatory responses, have given us new insights into putative neuroprotective mechanisms following status epilepticus. This should complement the animal data. In this review, we cover what is known about the role of progranulin as well as the links between microRNA changes and the progranulin pathway following status epilepticus in humans and animals hypothesizing neuroprotective and neurorehabilitative effects. Progranulin has also been found to feature prominently in the neuroprotective processes under hypoxic conditions and initiating neurorehabilitative processes. These properties may be used therapeutically, e.g., through drugs that raise the progranulin levels and therefore the cerebral progranulin levels as well with the goal of improving the outcome after status epilepticus.

  17. Model Design of Piezoelectric Micromachined Modal Gyroscope

    Directory of Open Access Journals (Sweden)

    Xiaojun Hu

    2011-01-01

    Full Text Available This paper reports a novel kind of solid-state microgyroscope, which is called piezoelectric micromachined modal gyroscope (PMMG. PMMG has large stiffness and robust resistance to shake and strike because there is no evident mass-spring component in its structure. This work focused on quantitative optimization of the gyroscope, which is still blank for such gyroscope. The modal analysis by the finite element method (FEM was firstly conducted. A set of quantitative indicators were developed to optimize the operation mode. By FEM, the harmonic analysis was conducted to find the way to efficiently actuate the operational mode needed. The optimal configuration of driving electrodes was obtained. At last, the Coriolis analysis was conducted to show the relation between angular velocity and differential output voltage by the Coriolis force under working condition. The results obtained in this paper provide theoretical basis for realizing this novel kind of micromachined gyroscope.

  18. Modality shift effects mimic multisensory interactions

    DEFF Research Database (Denmark)

    Gondan, Matthias; Vorberg, D.; Greenlee, M.W.

    2007-01-01

    be avoided using an additional tactile stimulus (T) and evaluating the ERP difference (T + TAV) - (TA + TV). A second possible confound is the modality shift effect (MSE): for example, the auditory N1 is increased if an auditory stimulus follows a visual stimulus, whereas it is smaller if the modality......A frequent approach to study interactions of the auditory and the visual system is to measure event-related potentials (ERPs) to auditory, visual, and auditory-visual stimuli (A, V, AV). A nonzero result of the AV - (A + V) comparison indicates that the sensory systems interact at a specific...... processing stage. Two possible biases weaken the conclusions drawn by this approach: first, subtracting two ERPs from one requires that A, V, and AV do not share any common activity. We have shown before (Gondan and Röder in Brain Res 1073-1074:389-397, 2006) that the problem of common activity can...

  19. Kinetic Study of Curcumin on Modal Fabric

    Directory of Open Access Journals (Sweden)

    Abu Naser Md. Ahsanul Haque

    2018-03-01

    Full Text Available A kinetic study of curcumin on modal fabric was carried out using an initial dye concentration of 1 g/L at three different temperatures, 70 °C, 85 °C and 100 °C, at pH 7 and an material to liquor ratio of 1:20. Pseudo first-order and pseudo second-order kinetics were applied, and it was found that the adsorption kinetics of curcumin on modal fabric matched the pseudo second-order kinetic model. The activation energy was found to be equal to 71.14 kJ/mol, while the enthalpy and entropy of activation were 68.16 kJ/mol and –66.02 J/molK respectively.

  20. MOSFET dosimetry on modern radiation oncology modalities

    International Nuclear Information System (INIS)

    Rosenfeld, A.B.

    2002-01-01

    The development of MOSFET dosimetry is presented with an emphasis on the development of a scanning MOSFET dosimetry system for modern radiation oncology modalities. Fundamental aspects of MOSFETs in relation to their use as dosemeters are briefly discussed. The performance of MOSFET dosemeters in conformal radiotherapy, hadron therapy, intensity-modulated radiotherapy and microbeam radiation therapy is compared with other dosimetric techniques. In particular the application of MOSFET dosemeters in the characterisation and quality assurance of the steep dose gradients associated with the penumbra of some modern radiation oncology modalities is investigated. A new in vivo, on-line, scanning MOSFET read out system is also presented. The system has the ability to read out multiple MOSFET dosemeters with excellent spatial resolution and temperature stability and minimal slow border trapping effects. (author)

  1. The life trajectories modality of oral history

    Directory of Open Access Journals (Sweden)

    Rita de Cássia Gonçalves

    2007-05-01

    Full Text Available This article seeks to explore the potential of qualitative research. It presents the life trajectory modality of the oral history method, to discuss the possibility of its utilization in scientific research in the Social Work profession. The epistemological foundations of oral history are discussed to establish its scientific character. The life trajectories modality is presented as a historic and social construction that utilizes different interview techniques to give voice to previously invisible subjects, indicating the principal phases of the methodological procedures used in this approach. The conclusions highlight the importance of the construction of this model and its projection as a research proposal that implies a process of understanding and analyzing the social universes that are contextualized and interconnected, considering the realities of the life trajectories of the subjects studied.

  2. Deception Detection, Transmission, & Modality in Age & Sex

    Directory of Open Access Journals (Sweden)

    Charlotte Dorothy Sweeney

    2014-06-01

    Full Text Available This study is the first to create and use spontaneous (i.e. unrehearsed pro-social lies in an ecological setting. Creation of the stimuli involved fifty-one older adult and forty-four college student senders who lied authentically in that their lies were spontaneous in the service of protecting a research assistant. In the main study, seventy-seven older adult and eighty-four college raters attempted to detect lies in the older adult and college senders in three modalities: audio, visual, and audiovisual. Raters of both age groups were best at detecting lies in the audiovisual and worst in the visual modalities. Overall, college students were better detectors than older adults. There was an age-matching effect for college students but not for older adults. Older adult males were the hardest to detect. The older the adult was the worse the ability to detect deception.

  3. Breast Cancer Screening, Mammography, and Other Modalities.

    Science.gov (United States)

    Fiorica, James V

    2016-12-01

    This article is an overview of the modalities available for breast cancer screening. The modalities discussed include digital mammography, digital breast tomosynthesis, breast ultrasonography, magnetic resonance imaging, and clinical breast examination. There is a review of pertinent randomized controlled trials, studies and meta-analyses which contributed to the evolution of screening guidelines. Ultimately, 5 major medical organizations formulated the current screening guidelines in the United States. The lack of consensus in these guidelines represents an ongoing controversy about the optimal timing and method for breast cancer screening in women. For mammography screening, the Breast Imaging Reporting and Data System lexicon is explained which corresponds with recommended clinical management. The presentation and discussion of the data in this article are designed to help the clinician individualize breast cancer screening for each patient.

  4. Modal instability of rod fiber amplifiers: a semi-analytic approach

    DEFF Research Database (Denmark)

    Jørgensen, Mette Marie; Hansen, Kristian Rymann; Laurila, Marko

    2013-01-01

    The modal instability (MI) threshold is estimated for four rod fiber designs by combining a semi-analytic model with the finite element method. The thermal load due to the quantum defect is calculated and used to numerically determine the mode distributions on which the expression for the onset o...

  5. Trait modality distribution of aquatic macrofauna communities as explained by pesticides and water chemistry

    OpenAIRE

    Ieromina, O.; Musters, C. J. M.; Bodegom, P. M.; Peijnenburg, W. J. G. M.; Vijver, M. G.

    2016-01-01

    Analyzing functional species? characteristics (species traits) that represent physiological, life history and morphological characteristics of species help understanding the impacts of various stressors on aquatic communities at field conditions. This research aimed to study the combined effects of pesticides and other environmental factors (temperature, dissolved oxygen, dissolved organic carbon, floating macrophytes cover, phosphate, nitrite, and nitrate) on the trait modality distribution ...

  6. Dual-modality PET/CT instrumentation-today and tomorrow

    DEFF Research Database (Denmark)

    Lonsdale, Markus Nowak; Beyer, Thomas

    2010-01-01

    Positron emission tomography (PET) has proven to be a clinically valuable imaging modality, particularly for oncology staging and therapy follow-up. The introduction of combined PET/CT imaging has helped address challenging imaging situations when anatomical information on PET-only was inadequate...

  7. Focus of Attention and Choice of Text Modality in Multimedia Learning

    Science.gov (United States)

    Schnotz, Wolfgang; Mengelkamp, Christoph; Baadte, Christiane; Hauck, Georg

    2014-01-01

    The term "modality effect" in multimedia learning means that students learn better from pictures combined with spoken rather than written text. The most prominent explanations refer to the split attention between visual text reading and picture observation which could affect transfer of information into working memory, maintenance of…

  8. Extended feature-fusion guidelines to improve image-based multi-modal biometrics

    CSIR Research Space (South Africa)

    Brown, Dane

    2016-09-01

    Full Text Available The feature-level, unlike the match score-level, lacks multi-modal fusion guidelines. This work demonstrates a practical approach for improved image-based biometric feature-fusion. The approach extracts and combines the face, fingerprint...

  9. Open-geometry Fourier modal method: modeling nanophotonic structures in infinite domains

    DEFF Research Database (Denmark)

    Häyrynen, Teppo; de Lasson, Jakob Rosenkrantz; Gregersen, Niels

    2016-01-01

    We present an open-geometry Fourier modal method based on a new combination of open boundary conditions and an efficient k-space discretization. The open boundary of the computational domain is obtained using basis functions that expand the whole space, and the integrals subsequently appearing due...

  10. Multi-Modal Obstacle Detection in Unstructured Environments with Conditional Random Fields

    DEFF Research Database (Denmark)

    Kragh, Mikkel; Underwood, James

    modality. Geometrically, tall grass, fallen leaves, or terrain roughness can mistakenly be perceived as non-traversable or might even obscure actual obstacles. Likewise, traversable grass or dirt roads and obstacles such as trees and bushes might be visually ambiguous. In this paper, we combine appearance...

  11. Modeling open nanophotonic systems using the Fourier modal method: Generalization to 3D Cartesian coordinates

    DEFF Research Database (Denmark)

    Häyrynen, Teppo; Østerkryger, Andreas Dyhl; de Lasson, Jakob Rosenkrantz

    2017-01-01

    Recently, an open geometry Fourier modal method based on a new combination ofan open boundary condition and a non-uniform $k$-space discretization wasintroduced for rotationally symmetric structures providing a more efficientapproach for modeling nanowires and micropillar cavities [J. Opt. Soc. A...... moreaccurate and efficient modeling of open 3D nanophotonic structures....

  12. Focused labeled proof systems for modal logic

    OpenAIRE

    Miller , Dale; Volpe , Marco

    2015-01-01

    International audience; Focused proofs are sequent calculus proofs that group inference rules into alternating positive and negative phases. These phases can then be used to define macro-level inference rules from Gentzen's original and tiny introduction and structural rules. We show here that the inference rules of labeled proof systems for modal logics can similarly be described as pairs of such phases within the LKF focused proof system for first-order classical logic. We consider the syst...

  13. A Transgenic Tri-Modality Reporter Mouse

    OpenAIRE

    Yan, Xinrui; Ray, Pritha; Paulmurugan, Ramasamy; Tong, Ricky; Gong, Yongquan; Sathirachinda, Ataya; Wu, Joseph C.; Gambhir, Sanjiv S.

    2013-01-01

    Transgenic mouse with a stably integrated reporter gene(s) can be a valuable resource for obtaining uniformly labeled stem cells, tissues, and organs for various applications. We have generated a transgenic mouse model that ubiquitously expresses a tri-fusion reporter gene (fluc2-tdTomato-ttk) driven by a constitutive chicken β-actin promoter. This "Tri-Modality Reporter Mouse" system allows one to isolate most cells from this donor mouse and image them for bioluminescent (fluc2), fluorescent...

  14. Multi modal child-to-child interaction

    DEFF Research Database (Denmark)

    Fisker, Tine Basse

    In this presentation the interaction and relation of three boys is analyzed using multi modal analysis. The analysis clearly, and surprisingly demonstrates that the boys interact via different modes and that they are able to handle several interaction partners at the same time. They co......-construct interaction in rather complex and unexpected ways using verbal as well as non-verbal modes in interaction....

  15. A method for experimental modal separation

    Science.gov (United States)

    Hallauer, W. L., Jr.

    1977-01-01

    A method is described for the numerical simulation of multiple-shaker modal survey testing using simulated experimental data to optimize the shaker force-amplitude distribution for the purpose of isolating individual modes of vibration. Inertia, damping, stiffness, and model data are stored on magnetic disks, available by direct access to the interactive FORTRAN programs which perform all computations required by this relative force amplitude distribution method.

  16. Modality-specificity of Selective Attention Networks

    OpenAIRE

    Stewart, Hannah J.; Amitay, Sygal

    2015-01-01

    Objective: To establish the modality specificity and generality of selective attention networks. Method: Forty-eight young adults completed a battery of four auditory and visual selective attention tests based upon the Attention Network framework: the visual and auditory Attention Network Tests (vANT, aANT), the Test of Everyday Attention (TEA), and the Test of Attention in Listening (TAiL). These provided independent measures for auditory and visual alerting, orienting, and conflict resoluti...

  17. Non-modal analysis in plasmas

    International Nuclear Information System (INIS)

    Mahajan, S.M.; Rogava, A.D.; Berezhiani, V.

    1996-01-01

    The techniques of non-modal analysis are applied to investigate the time evolution of a variety of plasma flows with velocity shear. It is shown that large transient amplifications may result for appropriate initial perturbations. The role of this amplification in determining the nonlinear dynamics of these systems (when all the normal modes are stable) is discussed. Examples are taken from Laboratory, astrophysical and cosmic plasmas

  18. Imaging Breast Density: Established and Emerging Modalities

    Directory of Open Access Journals (Sweden)

    Jeon-Hor Chen

    2015-12-01

    Full Text Available Mammographic density has been proven as an independent risk factor for breast cancer. Women with dense breast tissue visible on a mammogram have a much higher cancer risk than women with little density. A great research effort has been devoted to incorporate breast density into risk prediction models to better estimate each individual’s cancer risk. In recent years, the passage of breast density notification legislation in many states in USA requires that every mammography report should provide information regarding the patient’s breast density. Accurate definition and measurement of breast density are thus important, which may allow all the potential clinical applications of breast density to be implemented. Because the two-dimensional mammography-based measurement is subject to tissue overlapping and thus not able to provide volumetric information, there is an urgent need to develop reliable quantitative measurements of breast density. Various new imaging technologies are being developed. Among these new modalities, volumetric mammographic density methods and three-dimensional magnetic resonance imaging are the most well studied. Besides, emerging modalities, including different x-ray–based, optical imaging, and ultrasound-based methods, have also been investigated. All these modalities may either overcome some fundamental problems related to mammographic density or provide additional density and/or compositional information. The present review article aimed to summarize the current established and emerging imaging techniques for the measurement of breast density and the evidence of the clinical use of these density methods from the literature.

  19. Applied modal analysis of wind turbine blades

    Energy Technology Data Exchange (ETDEWEB)

    Broen Pedersen, H.; Dahl Kristensen, O.J.

    2003-02-01

    In this project modal analysis has been used to determine the natural frequencies, damping and the mode shapes for wind turbine blades. Different methods to measure the position and adjust the direction of the measuring points are discussed. Different equipment for mounting the accelerometers are investigated and the most suitable are chosen. Different excitation techniques are tried during experimental campaigns. After a discussion the pendulum hammer were chosen, and a new improved hammer was manufactured. Some measurement errors are investigated. The ability to repeat the measured results is investigated by repeated measurement on the same wind turbine blade. Furthermore the flexibility of the test set-up is investigated, by use of accelerometers mounted on the flexible adapter plate during the measurement campaign. One experimental campaign investigated the results obtained from a loaded and unloaded wind turbine blade. During this campaign the modal analysis are performed on a blade mounted in a horizontal and a vertical position respectively. Finally the results obtained from modal analysis carried out on a wind turbine blade are compared with results obtained from the Stig Oeyes blade{sub E}V1 program. (au)

  20. TESS Lens-Bezel Assembly Modal Testing

    Science.gov (United States)

    Dilworth, Brandon J.; Karlicek, Alexandra

    2017-01-01

    The Transiting Exoplanet Survey Satellite (TESS) program, led by the Kavli Institute for Astrophysics and Space Research at the Massachusetts Institute of Technology (MIT) will be the first-ever spaceborne all-sky transit survey. MIT Lincoln Laboratory is responsible for the cameras, including the lens assemblies, detector assemblies, lens hoods, and camera mounts. TESS is scheduled to be launched in August of 2017 with the primary goal to detect small planets with bright host starts in the solar neighborhood, so that detailed characterizations of the planets and their atmospheres can be performed. The TESS payload consists of four identical cameras and a data handling unit. Each camera consists of a lens assembly with seven optical elements and a detector assembly with four charge-coupled devices (CCDs) including their associated electronics. The optical prescription requires that several of the lenses are in close proximity to a neighboring element. A finite element model (FEM) was developed to estimate the relative deflections between each lens-bezel assembly under launch loads to predict that there are adequate clearances preventing the lenses from making contact. Modal tests using non-contact response measurements were conducted to experimentally estimate the modal parameters of the lens-bezel assembly, and used to validate the initial FEM assumptions. Key Words Non-contact measurements, modal analysis, model validation

  1. The metastasis-promoting S100A4 protein confers neuroprotection in brain injury

    DEFF Research Database (Denmark)

    Dmytriyeva, Oksana; Pankratova, Stanislava; Owczarek, Sylwia

    2012-01-01

    and downregulating the neuroprotective protein metallothionein I+II. We identify two neurotrophic motifs in S100A4 and show that these motifs are neuroprotective in animal models of brain trauma. Finally, we find that S100A4 rescues neurons via the Janus kinase/STAT pathway and, partially, the interleukin-10......Identification of novel pro-survival factors in the brain is paramount for developing neuroprotective therapies. The multifunctional S100 family proteins have important roles in many human diseases and are also upregulated by brain injury. However, S100 functions in the nervous system remain...... unclear. Here we show that the S100A4 protein, mostly studied in cancer, is overexpressed in the damaged human and rodent brain and released from stressed astrocytes. Genetic deletion of S100A4 exacerbates neuronal loss after brain trauma or excitotoxicity, increasing oxidative cell damage...

  2. Angiotensin II Type 2 Receptor Agonist Experts Sustained Neuroprotective Effects In Aged Rats

    DEFF Research Database (Denmark)

    Sumners, Colin; Isenberg, Jacob; Harmel, Allison

    2016-01-01

    OBJECTIVE: The renin angiotensin system is a promising target for stroke neuroprotection and therapy through activation of angiotensin type II receptors (AT2R). The selective non-peptide AT2R agonist, Compound 21 (C21), has been shown to exhibit neuroprotection and improve stroke outcomes...... in preclinical studies, effects that likely involve neurotropic actions. However, these beneficial actions of C21 have not been demonstrated to occur beyond 1 week post stroke. The objective of this study was to determine if systemic administration of C21 would exert sustained neuroprotective effects in aged...... min), 24 h, and 48 h after stroke. Infarct size was assessed by magnetic resonance imaging at 21 days post MCAO. Animals received blinded neurological exams at 4 h, 24 h, 72 h, 7d, 14d, and 21d post-MCAO. RESULTS: Systemic treatment with C21 after stroke significantly improved neurological function...

  3. Use of a wire extender during neuroprotected vertebral artery angioplasty and stenting.

    Science.gov (United States)

    Lesley, Walter S; Kumar, Ravi; Rangaswamy, Rajesh

    2010-09-01

    The off-label use of an extender wire during vertebral artery stenting and angioplasty with or with neuroprotection has not been previously reported. Retrospective, single-patient, technical report. After monorail balloon angioplasty was performed on a proximal left vertebral artery stenosis, the 190 cm long Accunet neuroprotection filter device was not long enough for delivery of an over-the-wire stent. After mating a 145 cm long, 0.014 inch extension wire to the filter device, a balloon-mounted Liberté stent was implanted with good angiographic and clinical results. The off-label use of an extender wire permits successful over-the-wire stenting on a monorail neuroprotection device for vertebral artery endosurgery.

  4. Automated Modal Parameter Estimation of Civil Engineering Structures

    DEFF Research Database (Denmark)

    Andersen, Palle; Brincker, Rune; Goursat, Maurice

    In this paper the problems of doing automatic modal parameter extraction of ambient excited civil engineering structures is considered. Two different approaches for obtaining the modal parameters automatically are presented: The Frequency Domain Decomposition (FDD) technique and a correlation...

  5. Nanomedicine-Based Neuroprotective Strategies in Patient Specific-iPSC and Personalized Medicine

    Directory of Open Access Journals (Sweden)

    Shih-Fan Jang

    2014-03-01

    Full Text Available In recent decades, nanotechnology has attracted major interests in view of drug delivery systems and therapies against diseases, such as cancer, neurodegenerative diseases, and many others. Nanotechnology provides the opportunity for nanoscale particles or molecules (so called “Nanomedicine” to be delivered to the targeted sites, thereby, reducing toxicity (or side effects and improving drug bioavailability. Nowadays, a great deal of nano-structured particles/vehicles has been discovered, including polymeric nanoparticles, lipid-based nanoparticles, and mesoporous silica nanoparticles. Nanomedical utilizations have already been well developed in many different aspects, including disease treatment, diagnostic, medical devices designing, and visualization (i.e., cell trafficking. However, while quite a few successful progressions on chemotherapy using nanotechnology have been developed, the implementations of nanoparticles on stem cell research are still sparsely populated. Stem cell applications and therapies are being considered to offer an outstanding potential in the treatment for numbers of maladies. Human induced pluripotent stem cells (iPSCs are adult cells that have been genetically reprogrammed to an embryonic stem cell-like state. Although the exact mechanisms underlying are still unclear, iPSCs are already being considered as useful tools for drug development/screening and modeling of diseases. Recently, personalized medicines have drawn great attentions in biological and pharmaceutical studies. Generally speaking, personalized medicine is a therapeutic model that offers a customized healthcare/cure being tailored to a specific patient based on his own genetic information. Consequently, the combination of nanomedicine and iPSCs could actually be the potent arms for remedies in transplantation medicine and personalized medicine. This review will focus on current use of nanoparticles on therapeutical applications, nanomedicine

  6. Magnesium sulphate for fetal neuroprotection: benefits and challenges of a systematic knowledge translation project in Canada.

    Science.gov (United States)

    Teela, Katherine C; De Silva, Dane A; Chapman, Katie; Synnes, Anne R; Sawchuck, Diane; Basso, Melanie; Liston, Robert M; von Dadelszen, Peter; Magee, Laura A

    2015-12-22

    Administration of magnesium sulphate (MgSO4) to women with imminent preterm birth at e-learning module available to all SOGC members, and at MAG-CP participating sites, on-site educational rounds and focus group discussions, and circulation of an anonymous 'Barriers and Facilitators' survey for the systematic identification of facilitators and barriers for uptake of practice change. We compared these strategies according to: (i) breadth of respondents reached; (ii) rates and richness of identified barriers, facilitators, and knowledge needed; and (iii) cost. No individual KT method was superior to the others by all criteria, and in combination, they provided richer information than any individual method. The e-learning module reached the most diverse audience of health care providers, the site visits provided opportunity for iterative dialogue, and the survey was the least expensive. Although the site visits provided the most detailed information around individual and organizational barriers, the 'Barriers and Facilitators' survey provided more detail regarding social-level barriers. The facilitators identified varied by KT method. The type of knowledge needed was further defined by the e-learning module and surveys. Our findings suggest that a multifaceted approach to KT is optimal for translating national obstetric guidelines into clinical practice. As audit and feedback are essential parts of the process by which evidence to practice gaps are closed, MAG-CP is continuing the iterative KT process described in this paper concurrent with tracking of MgSO4 use for fetal neuroprotection and maternal and child outcomes until September 2015; results are anticipated in 2016.

  7. C60-based ebselen derivative: synthesis by bingel cyclopropanation and enhanced antioxidative and neuroprotective activity

    International Nuclear Information System (INIS)

    Xufeng Liu; Wenchao Guan; Wengshan Ke

    2007-01-01

    C 60 -based ebselen derivative 3 was synthesized through Bingel cyclopropanation of C 60 with the ebselen malonate 2. Compound 3 was obtained in 42% yield (based on consumed C 60 ) in a three-step synthesis starting from 2-(chloroseleno)benzoyl chloride and 2-(2aminoethoxy)ethanol. Its structure was confirmed by 1H NMR, 13 C NMR, IR, UV and FAB-MS spectroscopy analyses. In order to verify the enhanced antioxidative and neuroprotective activity of 3, a C 60 derivative (4), an ebselen derivative (2), and their mixture (4 plus 2 in equimolar ratio) were employed to treat cortical neuronal cells, following the same procedure used with 3 and at the same final concentration (30 μmol L -1 ). Cell viabilities of the four treated groups were estimated by LDH (lactic dehydrogenase) leakage and MTT (3-(4, 5-dimethylthiazole-2yl)-2,5-diphenyl-tetrazolium bromide) assays. Results showed that the antioxidative and protective activities of C 60 -based ebselen derivative 3 against H 2 O 2 -mediated neuronal injury (MTT(OD) 0.364 ± 0.028; LDH release (UL -1 ) 4.66 ± 0.28) were significantly higher than those of C 6 )0 derivative 4 (MTT(OD) 0.324 ± 0.025; LDH release (UL -1 ) 5.39 ± 0.17), ebselen derivative 2 (MTT(OD) 0.294 ± 0.021; LDH release (UL -1 ) 5.71 ± 0.27), and the mixture of 4 and 2 (MTT(OD) 0.310 ± 0.018; LDH release (UL -1 ) 5.54 ±0.39). These findings demonstrated that the combination of two molecular units with similar biological activities (C 60 and ebselen) may be a desirable way of obtaining new and more biologically effective C 60 -based compounds. (author)

  8. Stability and time-domain analysis of the dispersive tristability in microresonators under modal coupling

    Science.gov (United States)

    Dumeige, Yannick; Féron, Patrice

    2011-10-01

    Coupled nonlinear resonators have potential applications for the integration of multistable photonic devices. The dynamic properties of two coupled-mode nonlinear microcavities made of Kerr material are studied by linear stability analysis. Using a suitable combination of the modal coupling rate and the frequency detuning, it is possible to obtain configurations where a hysteresis loop is included inside other bistable cycles. We show that a single resonator with two modes both linearly and nonlinearly coupled via the cross-Kerr effect can have a multistable behavior. This could be implemented in semiconductor nonlinear whispering-gallery-mode microresonators under modal coupling for all optical signal processing or ternary optical logic applications.

  9. Stability and time-domain analysis of the dispersive tristability in microresonators under modal coupling

    International Nuclear Information System (INIS)

    Dumeige, Yannick; Feron, Patrice

    2011-01-01

    Coupled nonlinear resonators have potential applications for the integration of multistable photonic devices. The dynamic properties of two coupled-mode nonlinear microcavities made of Kerr material are studied by linear stability analysis. Using a suitable combination of the modal coupling rate and the frequency detuning, it is possible to obtain configurations where a hysteresis loop is included inside other bistable cycles. We show that a single resonator with two modes both linearly and nonlinearly coupled via the cross-Kerr effect can have a multistable behavior. This could be implemented in semiconductor nonlinear whispering-gallery-mode microresonators under modal coupling for all optical signal processing or ternary optical logic applications.

  10. Paracrine effect of carbon monoxide - astrocytes promote neuroprotection through purinergic signaling in mice.

    Science.gov (United States)

    Queiroga, Cláudia S F; Alves, Raquel M A; Conde, Sílvia V; Alves, Paula M; Vieira, Helena L A

    2016-08-15

    The neuroprotective role of carbon monoxide (CO) has been studied in a cell-autonomous mode. Herein, a new concept is disclosed - CO affects astrocyte-neuron communication in a paracrine manner to promote neuroprotection. Neuronal survival was assessed when co-cultured with astrocytes that had been pre-treated or not with CO. The CO-pre-treated astrocytes reduced neuronal cell death, and the cellular mechanisms were investigated, focusing on purinergic signaling. CO modulates astrocytic metabolism and extracellular ATP content in the co-culture medium. Moreover, several antagonists of P1 adenosine and P2 ATP receptors partially reverted CO-induced neuroprotection through astrocytes. Likewise, knocking down expression of the neuronal P1 adenosine receptor A2A-R (encoded by Adora2a) reverted the neuroprotective effects of CO-exposed astrocytes. The neuroprotection of CO-treated astrocytes also decreased following prevention of ATP or adenosine release from astrocytic cells and inhibition of extracellular ATP metabolism into adenosine. Finally, the neuronal downstream event involves TrkB (also known as NTRK2) receptors and BDNF. Pharmacological and genetic inhibition of TrkB receptors reverts neuroprotection triggered by CO-treated astrocytes. Furthermore, the neuronal ratio of BDNF to pro-BDNF increased in the presence of CO-treated astrocytes and decreased whenever A2A-R expression was silenced. In summary, CO prevents neuronal cell death in a paracrine manner by targeting astrocytic metabolism through purinergic signaling. © 2016. Published by The Company of Biologists Ltd.

  11. The contribution to the modal analysis using an infrared camera

    Directory of Open Access Journals (Sweden)

    Dekys Vladimír

    2018-01-01

    Full Text Available The paper deals with modal analysis using an infrared camera. The test objects were excited by the modal exciter with narrowband noise and the response was registered as a frame sequence by the high speed infrared camera FLIR SC7500. The resonant frequencies and the modal shapes were determined from the infrared spectrum recordings. Lock-in technology has also been used. The experimental results were compared with calculated natural frequencies and modal shapes.

  12. Comparison of sine dwell and broadband methods for modal testing

    Science.gov (United States)

    Chen, Jay-Chung

    1989-01-01

    The objectives of modal tests for large complex spacecraft structural systems are outlined. The comparison criteria for the modal test methods, namely, the broadband excitation and the sine dwell methods, are established. Using the Galileo spacecraft modal test and the Centaur G Prime upper stage vehicle modal test as examples, the relative advantage or disadvantage of each method is examined. The usefulness or shortcomings of the methods are given from a practical engineering viewpoint.

  13. On sine dwell or broadband methods for modal testing

    Science.gov (United States)

    Chen, Jay-Chung; Wada, Ben K.

    1987-01-01

    For large, complex spacecraft structural systems, the objectives of the modal test are outlined. Based on these objectives, the comparison criteria for the modal test methods, namely, the broadband excitation and the sine dwell methods are established. Using the Galileo spacecraft modal test and the Centaur G Prime upper stage vehicle modal test as examples, the relative advantages or disadvantages of each method are examined. The usefulness or shortcoming of the methods are given from a practicing engineer's view point.

  14. Converging modalities ground abstract categories: the case of politics.

    Science.gov (United States)

    Farias, Ana Rita; Garrido, Margarida V; Semin, Gün R

    2013-01-01

    Three studies are reported examining the grounding of abstract concepts across two modalities (visual and auditory) and their symbolic representation. A comparison of the outcomes across these studies reveals that the symbolic representation of political concepts and their visual and auditory modalities is convergent. In other words, the spatial relationships between specific instances of the political categories are highly overlapping across the symbolic, visual and auditory modalities. These findings suggest that abstract categories display redundancy across modal and amodal representations, and are multimodal.

  15. Neuroprotective effects of riluzole in early phase Parkinson's disease on clinically relevant parameters in the marmoset MPTP model

    NARCIS (Netherlands)

    Verhave, P.S.; Jongsma, M.J.; Berg, R.M. van den; Vanwersch, R.A.P.; Smit, A.B.; Philippens, I.H.C.H.M.

    2012-01-01

    The present study evaluates neuroprotection in a marmoset MPTP (1-methyl-1,2,3,6-tetrahydropyridine) model representing early Parkinson's disease (PD). The anti-glutamatergic compound riluzole is used as a model compound for neuroprotection. The compound is one of the few protective compounds used

  16. The modality effect of ego depletion: Auditory task modality reduces ego depletion.

    Science.gov (United States)

    Li, Qiong; Wang, Zhenhong

    2016-08-01

    An initial act of self-control that impairs subsequent acts of self-control is called ego depletion. The ego depletion phenomenon has been observed consistently. The modality effect refers to the effect of the presentation modality on the processing of stimuli. The modality effect was also robustly found in a large body of research. However, no study to date has examined the modality effects of ego depletion. This issue was addressed in the current study. In Experiment 1, after all participants completed a handgrip task, one group's participants completed a visual attention regulation task and the other group's participants completed an auditory attention regulation task, and then all participants again completed a handgrip task. The ego depletion phenomenon was observed in both the visual and the auditory attention regulation task. Moreover, participants who completed the visual task performed worse on the handgrip task than participants who completed the auditory task, which indicated that there was high ego depletion in the visual task condition. In Experiment 2, participants completed an initial task that either did or did not deplete self-control resources, and then they completed a second visual or auditory attention control task. The results indicated that depleted participants performed better on the auditory attention control task than the visual attention control task. These findings suggest that altering task modality may reduce ego depletion. © 2016 Scandinavian Psychological Associations and John Wiley & Sons Ltd.

  17. Evidence for a supra-modal representation of emotion from cross-modal adaptation.

    Science.gov (United States)

    Pye, Annie; Bestelmeyer, Patricia E G

    2015-01-01

    Successful social interaction hinges on accurate perception of emotional signals. These signals are typically conveyed multi-modally by the face and voice. Previous research has demonstrated uni-modal contrastive aftereffects for emotionally expressive faces or voices. Here we were interested in whether these aftereffects transfer across modality as theoretical models predict. We show that adaptation to facial expressions elicits significant auditory aftereffects. Adaptation to angry facial expressions caused ambiguous vocal stimuli drawn from an anger-fear morphed continuum to be perceived as less angry and more fearful relative to adaptation to fearful faces. In a second experiment, we demonstrate that these aftereffects are not dependent on learned face-voice congruence, i.e. adaptation to one facial identity transferred to an unmatched voice identity. Taken together, our findings provide support for a supra-modal representation of emotion and suggest further that identity and emotion may be processed independently from one another, at least at the supra-modal level of the processing hierarchy. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Dantrolene is neuroprotective in Huntington's disease transgenic mouse model

    Directory of Open Access Journals (Sweden)

    Chen Xi

    2011-11-01

    Full Text Available Abstract Background Huntington's disease (HD is a progressive neurodegenerative disorder caused by a polyglutamine expansion in the Huntingtin protein which results in the selective degeneration of striatal medium spiny neurons (MSNs. Our group has previously demonstrated that calcium (Ca2+ signaling is abnormal in MSNs from the yeast artificial chromosome transgenic mouse model of HD (YAC128. Moreover, we demonstrated that deranged intracellular Ca2+ signaling sensitizes YAC128 MSNs to glutamate-induced excitotoxicity when compared to wild type (WT MSNs. In previous studies we also observed abnormal neuronal Ca2+ signaling in neurons from spinocerebellar ataxia 2 (SCA2 and spinocerebellar ataxia 3 (SCA3 mouse models and demonstrated that treatment with dantrolene, a ryanodine receptor antagonist and clinically relevant Ca2+ signaling stabilizer, was neuroprotective in experiments with these mouse models. The aim of the current study was to evaluate potential beneficial effects of dantrolene in experiments with YAC128 HD mouse model. Results The application of caffeine and glutamate resulted in increased Ca2+ release from intracellular stores in YAC128 MSN cultures when compared to WT MSN cultures. Pre-treatment with dantrolene protected YAC128 MSNs from glutamate excitotoxicty, with an effective concentration of 100 nM and above. Feeding dantrolene (5 mg/kg twice a week to YAC128 mice between 2 months and 11.5 months of age resulted in significantly improved performance in the beam-walking and gait-walking assays. Neuropathological analysis revealed that long-term dantrolene feeding to YAC128 mice significantly reduced the loss of NeuN-positive striatal neurons and reduced formation of Httexp nuclear aggregates. Conclusions Our results support the hypothesis that deranged Ca2+ signaling plays an important role in HD pathology. Our data also implicate the RyanRs as a potential therapeutic target for the treatment of HD and demonstrate that Ryan

  19. Dantrolene is neuroprotective in Huntington's disease transgenic mouse model.

    Science.gov (United States)

    Chen, Xi; Wu, Jun; Lvovskaya, Svetlana; Herndon, Emily; Supnet, Charlene; Bezprozvanny, Ilya

    2011-11-25

    Huntington's disease (HD) is a progressive neurodegenerative disorder caused by a polyglutamine expansion in the Huntingtin protein which results in the selective degeneration of striatal medium spiny neurons (MSNs). Our group has previously demonstrated that calcium (Ca2+) signaling is abnormal in MSNs from the yeast artificial chromosome transgenic mouse model of HD (YAC128). Moreover, we demonstrated that deranged intracellular Ca2+ signaling sensitizes YAC128 MSNs to glutamate-induced excitotoxicity when compared to wild type (WT) MSNs. In previous studies we also observed abnormal neuronal Ca2+ signaling in neurons from spinocerebellar ataxia 2 (SCA2) and spinocerebellar ataxia 3 (SCA3) mouse models and demonstrated that treatment with dantrolene, a ryanodine receptor antagonist and clinically relevant Ca2+ signaling stabilizer, was neuroprotective in experiments with these mouse models. The aim of the current study was to evaluate potential beneficial effects of dantrolene in experiments with YAC128 HD mouse model. The application of caffeine and glutamate resulted in increased Ca2+ release from intracellular stores in YAC128 MSN cultures when compared to WT MSN cultures. Pre-treatment with dantrolene protected YAC128 MSNs from glutamate excitotoxicty, with an effective concentration of 100 nM and above. Feeding dantrolene (5 mg/kg) twice a week to YAC128 mice between 2 months and 11.5 months of age resulted in significantly improved performance in the beam-walking and gait-walking assays. Neuropathological analysis revealed that long-term dantrolene feeding to YAC128 mice significantly reduced the loss of NeuN-positive striatal neurons and reduced formation of Httexp nuclear aggregates. Our results support the hypothesis that deranged Ca2+ signaling plays an important role in HD pathology. Our data also implicate the RyanRs as a potential therapeutic target for the treatment of HD and demonstrate that RyanR inhibitors and Ca2+ signaling stabilizers such as

  20. Fuzzy Reasoning Based on First-Order Modal Logic,

    NARCIS (Netherlands)

    Zhang, Xiaoru; Zhang, Z.; Sui, Y.; Huang, Z.

    2008-01-01

    As an extension of traditional modal logics, this paper proposes a fuzzy first-order modal logic based on believable degree, and gives out a description of the fuzzy first-order modal logic based on constant domain semantics. In order to make the reasoning procedure between the fuzzy assertions

  1. The Perceptual Basis of the Modality Effect in Multimedia Learning

    Science.gov (United States)

    Rummer, Ralf; Schweppe, Judith; Furstenberg, Anne; Scheiter, Katharina; Zindler, Antje

    2011-01-01

    Various studies have demonstrated an advantage of auditory over visual text modality when learning with texts and pictures. To explain this modality effect, two complementary assumptions are proposed by cognitive theories of multimedia learning: first, the visuospatial load hypothesis, which explains the modality effect in terms of visuospatial…

  2. Asialoerythropoietin is a nonerythropoietic cytokine with broad neuroprotective activity in vivo

    DEFF Research Database (Denmark)

    Erbayraktar, Serhat; Grasso, Giovanni; Sfacteria, Alessandra

    2003-01-01

    Erythropoietin (EPO) is a tissue-protective cytokine preventing vascular spasm, apoptosis, and inflammatory responses. Although best known for its role in hematopoietic lineages, EPO also affects other tissues, including those of the nervous system. Enthusiasm for recombinant human erythropoietin...... importantly, asialoEPO exhibits a broad spectrum of neuroprotective activities, as demonstrated in models of cerebral ischemia, spinal cord compression, and sciatic nerve crush. These data suggest that nonerythropoietic variants of rhEPO can cross the blood-brain barrier and provide neuroprotection....

  3. Neuroprotective properties of a novel, non-haematopoietic agonist of the erythropoietin receptor

    DEFF Research Database (Denmark)

    Pankratova, Stanislava; Kiryushko, Dar'Ya; Sonn, Katrin

    2010-01-01

    they are involved in tissue protection. However, the use of erythropoietin as a neuroprotective agent may be hampered by its erythropoietic activity. Therefore, developing non-haematopoietic erythropoietin mimetics is important. Based on the crystal structure of the complex of erythropoietin and its receptor, we...... attenuated seizures, decreased mortality and reduced neurodegeneration in an in vivo model of kainic acid-induced neurotoxicity. In contrast to erythropoietin, Epotris did not stimulate erythropoiesis upon chronic administration. Thus, Epotris is a novel neuroprotective non-haematopoietic erythropoietin...

  4. Dual-modal photoacoustic and ultrasound imaging of dental implants

    Science.gov (United States)

    Lee, Donghyun; Park, Sungjo; Kim, Chulhong

    2018-02-01

    Dental implants are common method to replace decayed or broken tooth. As the implant treatment procedures varies according to the patients' jawbone, bone ridge, and sinus structure, appropriate examinations are necessary for successful treatment. Currently, radiographic examinations including periapical radiology, panoramic X-ray, and computed tomography are commonly used for diagnosing and monitoring. However, these radiographic examinations have limitations in that patients and operators are exposed to radioactivity and multiple examinations are performed during the treatment. In this study, we demonstrated photoacoustic (PA) and ultrasound (US) combined imaging of dental implant that can lower the total amount of absorbed radiation dose in dental implant treatment. An acoustic resolution PA macroscopy and a clinical PA/US system was used for dental implant imaging. The acquired dual modal PA/US imaging results support that the proposed photoacoustic imaging strategy can reduce the radiation dose rate during dental implant treatment.

  5. Knowledge Engineering Aspects of Affective Bi-Modal Educational Applications

    Science.gov (United States)

    Alepis, Efthymios; Virvou, Maria; Kabassi, Katerina

    This paper analyses the knowledge and software engineering aspects of educational applications that provide affective bi-modal human-computer interaction. For this purpose, a system that provides affective interaction based on evidence from two different modes has been developed. More specifically, the system's inferences about students' emotions are based on user input evidence from the keyboard and the microphone. Evidence from these two modes is combined by a user modelling component that incorporates user stereotypes as well as a multi criteria decision making theory. The mechanism that integrates the inferences from the two modes has been based on the results of two empirical studies that were conducted in the context of knowledge engineering of the system. The evaluation of the developed system showed significant improvements in the recognition of the emotional states of users.

  6. Can Medical Herbs Stimulate Regeneration or Neuroprotection and Treat Neuropathic Pain in Chemotherapy-Induced Peripheral Neuropathy?

    Directory of Open Access Journals (Sweden)

    Sven Schröder

    2013-01-01

    Full Text Available Chemotherapy-induced neuropathy (CIPN has a relevant impact on the quality of life of cancer patients. There are no curative conventional treatments, so further options have to be investigated. We conducted a systematic review in English and Chinese language databases to illuminate the role of medical herbs. 26 relevant studies on 5 single herbs, one extract, one receptor-agonist, and 8 combinations of herbs were identified focusing on the single herbs Acorus calamus rhizoma, Cannabis sativa fructus, Chamomilla matricaria, Ginkgo biloba, Salvia officinalis, Sweet bee venom, Fritillaria cirrhosae bulbus, and the herbal combinations Bu Yang Huan Wu, modified Bu Yang Huan Wu plus Liuwei Di Huang, modified Chai Hu Long Gu Mu Li Wan, Geranii herba plus Aconiti lateralis praeparata radix , Niu Che Sen Qi Wan (Goshajinkigan, Gui Zhi Jia Shu Fu Tang (Keishikajutsubuto, Huang Qi Wu Wu Tang (Ogikeishigomotsuto, and Shao Yao Gan Cao Tang (Shakuyakukanzoto. The knowledge of mechanism of action is still limited, the quality of clinical trials needs further improvement, and studies have not yielded enough evidence to establish a standard practice, but a lot of promising substances have been identified. While CIPN has multiple mechanisms of neuronal degeneration, a combination of herbs or substances might deal with multiple targets for the aim of neuroprotection or neuroregeneration in CIPN.

  7. Comparing Image Perception of Bladder Tumors in Four Different Storz Professional Image Enhancement System Modalities Using the íSPIES App

    NARCIS (Netherlands)

    Kamphuis, Guido M.; de Bruin, D. Martijn; Brandt, Martin J.; Knoll, Thomas; Conort, Pierre; Lapini, Alberto; Dominguez-Escrig, Jose L.; de La Rosette, Jean J. M. C. H.

    2016-01-01

    To evaluate the variation of interpretation of the same bladder urothelium image in different Storz Professional Image Enhancement System (SPIES) modalities. SPIES contains a White light (WL), Spectra A (SA), Spectra B (SB), and Clara and Chroma combined (CC) modality. An App for the iPAD retina was

  8. Does Modality Matter? The Effects of Reading, Listening, and Dual Modality on Comprehension

    Directory of Open Access Journals (Sweden)

    Beth A. Rogowsky

    2016-09-01

    Full Text Available With advancing technology, there is increasing interest in differences between listening versus reading comprehension or doing both simultaneously. Ninety-one participants were randomly assigned to one of three groups that received the same instructional material (the preface and a chapter from a non-fiction book, but each in a different input modality (digital audiobook, e-text, dual modality. After completing the material, participants took the same comprehension test in written form to establish both immediate comprehension (Time 1 and 2-week retention (Time 2. No statistically significant differences were found for any analyses pertaining to effects of the three different instructional conditions on comprehension at Time 1 or Time 2. Additional analyses showed that both males and females in each condition recalled an equal amount of information, regardless of whether they listened to an audiobook, read from an electronic tablet, or both listened and read simultaneously (dual modality.

  9. Perception of Scenes in Different Sensory Modalities: A Result of Modal Completion.

    Science.gov (United States)

    Gruber, Ronald R; Block, Richard A

    2017-01-01

    Dynamic perception includes amodal and modal completion, along with apparent movement. It fills temporal gaps for single objects. In 2 experiments, using 6 stimulus presentation conditions involving 3 sensory modalities, participants experienced 8-10 sequential stimuli (200 ms each) with interstimulus intervals (ISIs) of 0.25-7.0 s. Experiments focused on spatiotemporal completion (walking), featural completion (object changing), auditory, completion (falling bomb), and haptic changes (insect crawling). After each trial, participants judged whether they experienced the process of "happening " or whether they simply knew that the process must have occurred. The phenomenon was frequency independent, being reported at short ISIs but not at long ISIs. The phenomenon involves dynamic modal completion and possibly also conceptual processes.

  10. Modality-specificity of Selective Attention Networks.

    Science.gov (United States)

    Stewart, Hannah J; Amitay, Sygal

    2015-01-01

    To establish the modality specificity and generality of selective attention networks. Forty-eight young adults completed a battery of four auditory and visual selective attention tests based upon the Attention Network framework: the visual and auditory Attention Network Tests (vANT, aANT), the Test of Everyday Attention (TEA), and the Test of Attention in Listening (TAiL). These provided independent measures for auditory and visual alerting, orienting, and conflict resolution networks. The measures were subjected to an exploratory factor analysis to assess underlying attention constructs. The analysis yielded a four-component solution. The first component comprised of a range of measures from the TEA and was labeled "general attention." The third component was labeled "auditory attention," as it only contained measures from the TAiL using pitch as the attended stimulus feature. The second and fourth components were labeled as "spatial orienting" and "spatial conflict," respectively-they were comprised of orienting and conflict resolution measures from the vANT, aANT, and TAiL attend-location task-all tasks based upon spatial judgments (e.g., the direction of a target arrow or sound location). These results do not support our a-priori hypothesis that attention networks are either modality specific or supramodal. Auditory attention separated into selectively attending to spatial and non-spatial features, with the auditory spatial attention loading onto the same factor as visual spatial attention, suggesting spatial attention is supramodal. However, since our study did not include a non-spatial measure of visual attention, further research will be required to ascertain whether non-spatial attention is modality-specific.

  11. Modality-specificity of selective attention networks

    Directory of Open Access Journals (Sweden)

    Hannah Jamieson Stewart

    2015-11-01

    Full Text Available Objective: To establish the modality specificity and generality of selective attention networks. Method: Forty-eight young adults completed a battery of four auditory and visual selective attention tests based upon the Attention Network framework: the visual and auditory Attention Network Tests (vANT, aANT, the Test of Everyday Attention (TEA, and the Test of Attention in Listening (TAiL. These provided independent measures for auditory and visual alerting, orienting, and conflict resolution networks. The measures were subjected to an exploratory factor analysis to assess underlying attention constructs. Results: The analysis yielded a four-component solution. The first component comprised of a range of measures from the TEA and was labeled ‘general attention’. The third component was labeled ‘auditory attention’, as it only contained measures from the TAiL using pitch as the attended stimulus feature. The second and fourth components were labeled as ‘spatial orienting’ and ‘spatial conflict’, respectively – they were comprised of orienting and conflict resolution measures from the vANT, aANT and TAiL attend-location task – all tasks based upon spatial judgments (e.g., the direction of a target arrow or sound location. Conclusions: These results do not support our a-priori hypothesis that attention networks are either modality specific or supramodal. Auditory attention separated into selectively attending to spatial and non-spatial features, with the auditory spatial attention loading onto the same factor as visual spatial attention, suggesting spatial attention is supramodal. However, since our study did not include a non-spatial measure of visual attention, further research will be required to ascertain whether non-spatial attention is modality-specific.

  12. Water as an Independent Taste Modality

    Directory of Open Access Journals (Sweden)

    Andrew M Rosen

    2010-10-01

    Full Text Available To qualify as a basic taste quality or modality, defined as a group of chemicals that taste alike, three empirical benchmarks have commonly been used. The first is that a candidate group of tastants must have a dedicated transduction mechanism in the peripheral nervous system. The second is that the tastants evoke physiological responses in dedicated afferent taste nerves innervating the oropharyngeal cavity. Last, the taste stimuli evoke activity in central gustatory neurons, some of which may respond only to that group of tastants. Here we argue that water may also be an independent taste modality. This argument is based on the identification of a water dedicated transduction mechanism in the peripheral nervous system, water responsive fibers of the peripheral taste nerves and the observation of water responsive neurons in all gustatory regions within the central nervous system. We have described electrophysiological responses from single neurons in nucleus of the solitary tract (NTS and parabrachial nucleus of the pons (PbN, respectively the first two central relay nuclei in the rodent brainstem, to water presented as a taste stimulus in anesthetized rats. Responses to water were in some cases as robust as responses to other taste qualities and sometimes occurred in the absence of responses to other tastants. Both excitatory and inhibitory responses were observed. Also, the temporal features of the water response resembled those of other taste responses. We argue that water may constitute an independent taste modality that is processed by dedicated neural channels at all levels of the gustatory neuraxis. Water-dedicated neurons in the brainstem may constitute key elements in the regulatory system for fluid in the body, i.e. thirst, and as part of the swallowing reflex circuitry.

  13. Man versus machine: the preferred modality.

    Science.gov (United States)

    Sanko, Jill; Shekhter, Ilya; Rosen, Lisa; Arheart, Kristopher; Birnbach, David

    2012-12-01

    When learning objectives do not specifically dictate the use of one simulation modality over another, we sought to answer the question of which modality is preferred. We also assessed the impact of debriefing, and the frequency of participants asserting their leadership, as well as self-reported comfort and competence, and the ability to generate differential diagnoses when either a standardised patient (SP) or high-technology simulator (HTS) was used. One hundred and forty medical students participated in a simulation-based activity focusing on teamwork, task delegation, role clarity and effective communication. Two similar clinical scenarios were presented, and either an HTS or an SP was used. Following each scenario, participants were surveyed on the realism of the simulation and the patient, and also on their self-assessed comfort and competence. They were also asked to indicate which role they played, to list possible differential diagnoses for the case and, following the second scenario, which modality they preferred. The surveys indicated that 91 per cent (127) of students preferred the SP. The perceived realism of the simulation was higher for the second scenario than for the first. Scenarios with an SP were found to be significantly more realistic than the scenarios where the HTS was used. Comfort and competence scores were higher following the second scenario. No differences in the ability of participants to generate a list of differentials were found, and nearly twice as many participants reported taking the leadership role during their second simulation. We have found low and high technology to have similar effectiveness for achieving learning objectives and for the demonstration of skills; however, students clearly preferred the SPs. © Blackwell Publishing Ltd 2012.

  14. Deep Multimodal Pain Recognition: A Database and Comparison of Spatio-Temporal Visual Modalities

    DEFF Research Database (Denmark)

    Haque, Mohammad Ahsanul; Nasrollahi, Kamal; Moeslund, Thomas B.

    2018-01-01

    , exploiting both spatial and temporal information of the face to assess pain level, and second, incorporating multiple visual modalities to capture complementary face information related to pain. Most works in the literature focus on merely exploiting spatial information on chromatic (RGB) video data......PAIN)' database, for RGBDT pain level recognition in sequences. We provide a first baseline results including 5 pain levels recognition by analyzing independent visual modalities and their fusion with CNN and LSTM models. From the experimental evaluation we observe that fusion of modalities helps to enhance...... recognition performance of pain levels in comparison to isolated ones. In particular, the combination of RGB, D, and T in an early fusion fashion achieved the best recognition rate....

  15. Systematic Verification of the Modal Logic Cube in Isabelle/HOL

    Directory of Open Access Journals (Sweden)

    Christoph Benzmüller

    2015-07-01

    Full Text Available We present an automated verification of the well-known modal logic cube in Isabelle/HOL, in which we prove the inclusion relations between the cube's logics using automated reasoning tools. Prior work addresses this problem but without restriction to the modal logic cube, and using encodings in first-order logic in combination with first-order automated theorem provers. In contrast, our solution is more elegant, transparent and effective. It employs an embedding of quantified modal logic in classical higher-order logic. Automated reasoning tools, such as Sledgehammer with LEO-II, Satallax and CVC4, Metis and Nitpick, are employed to achieve full automation. Though successful, the experiments also motivate some technical improvements in the Isabelle/HOL tool.

  16. Application of a bi-modal PBR nuclear propulsion and power system to military missions

    Science.gov (United States)

    Venetoklis, Peter S.

    1995-01-01

    The rapid proliferation of arms technology and space access combined with current economic realities in the United States are creating ever greater demands for more capable space-based military assets. The paper illustrates that bi-modal nuclear propulsion and power based on the Particle Bed Reactor (PBR) is a high-leverage tehcnology that can maximize utility while minimizing cost. Mission benefits offered by the bi-modal PBR, including enhanced maneuverability, lifetime, survivability, payload power, and operational flexibility, are discussed. The ability to deliver desired payloads on smaller boosters is also illustrated. System descriptions and parameters for 10 kWe and 100 kWe power output levels are summarized. It is demonstrated via design exercise that bi-modal PBR dramtically enhances performance of a military satellite in geosynchronous orbit, increasing payload mass, payload power, and maneuverability.

  17. A Modal Logic for Termgraph Rewriting

    OpenAIRE

    Balbiani, Ph.; Echahed, R.; Herzig, A.

    2010-01-01

    We propose a modal logic tailored to describe graph transformations and discuss some of its properties. We focus on a particular class of graphs called termgraphs. They are first-order terms augmented with sharing and cycles. Termgraphs allow one to describe classical data-structures (possibly with pointers) such as doubly-linked lists, circular lists etc. We show how the proposed logic can faithfully describe (i) termgraphs as well as (ii) the application of a termgraph rewrite rule (i.e. ma...

  18. Modal decomposition without a priori scale information

    CSIR Research Space (South Africa)

    Schulze, C

    2012-12-01

    Full Text Available , and A. Friberg, ?Transverse laser mode structure determination from spatial coherence measurements: Experimental results,? Appl. Phys. B. 49, 409?414 (1989). 4. A. Cutolo, T. Isernia, I. Izzo, R. Pierri, and L. Zeni, ?Transverse mode analysis of a... laser beam by near-and far-field intensity measurements,? Appl. Opt. 34, 7974?7978 (1995). 5. M. Santarsiero, F. Gori, R. Borghi, and G. Guattari, ?Evaluation of the modal structure of light beams composed of incoherent mixtures of hermite...

  19. On Determinism in Modal Transition Systems

    DEFF Research Database (Denmark)

    Benes, Nikola; Kretinsky, Jan; Larsen, Kim Guldstrand

    2009-01-01

    Modal transition systems (MTS) is a formalism which extends the classical notion of labelled transition systems by introducing transitions of two types: must transitions that have to be present in any implementation of the MTS and may transitions that are allowed but not required. The MTS framewo....... In the present article, we provide a comprehensive account of the MTS framework in the deterministic setting. We study a number of problems previously considered on MTS and point out to what extend we can expect better results under the restriction of determinism....

  20. Shoulder distention arthrography as a treatment modality

    International Nuclear Information System (INIS)

    Kang, Heung Sik; Park, Chan Sup; Kim, Jin Ho; Kim, Sang Bum

    1987-01-01

    18 patients with painful stiff shoulder joint were underwent shoulder distension arthrography as a treatment modality, followed by physical therapy. Range of motion of shoulder joint was evaluated at 1 week and 4 weeks after arthrography. The results were as follows; 1. Arthrographic findings were decreased volume of joint cavity, obliteration of axillary recess, small subscapularis bursa, serrated capsular margin and non-filling of biceps tendon sheath. In 3 cases, rotator cuff tear was found. 2. Range of motion of shoulder joint was improved after distension arthrography. 3. In 3 patients have rotator cuff tear, range of motion was not improved