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Sample records for stn 50-488 stn

  1. ISLSCP II River Routing Data (STN-30p)

    National Aeronautics and Space Administration — The Simulated Topological Network (STN-30p) data set provides the large-scale hydrological modeling community an accurate representation of the global river system...

  2. ISLSCP II River Routing Data (STN-30p)

    National Aeronautics and Space Administration — ABSTRACT: The Simulated Topological Network (STN-30p) data set provides the large-scale hydrological modeling community an accurate representation of the global...

  3. Perkins Nuclear Station, Units 1, 2, and 3: Final environmental statement (Docket Nos. STN 50-488, STN 50-489, and STN 50-490

    1975-10-01

    The proposed action is the issuance of a construction permit to the Duke Power Company for the construction of the Perkins Nuclear Station (PNS) Units 1, 2, and 3 located in Davie County, North Carolina. A total of 2402 acres will be used for the PNS site; another 1401 acres will be used for the Carter Creek Impoundment. Construction-related activities on the primary site will disturb about 617 acres. Approximately 631 acres of land will be required for transmission line right-of-way, and a railroad spur will affect 77 acres. This constitutes a minor local impact. The heat dissipation system will require a maximum water makeup of 55,816 gpm, of which 50,514 gpm will be consumed due to drift and evaporative losses. This amount represents 4% of the mean monthly flow of the Yadkin River. The cooling tower blowdown and chemical effluents from the station will increase the dissolved solids concentration in the Yadkin River by a maximum of 18 ppm. The thermal alterations and increases in total dissolved solids concentration will not significantly affect the aquatic productivity of the Yadkin River. 26 figs., 51 tabs

  4. Stimulation site within the MRI-defined STN predicts postoperative motor outcome.

    Wodarg, Fritz; Herzog, Jan; Reese, René; Falk, Daniela; Pinsker, Markus O; Steigerwald, Frank; Jansen, Olav; Deuschl, Günther; Mehdorn, H Maximillian; Volkmann, Jens

    2012-06-01

    High-frequency stimulation of the subthalamic nucleus (STN-HFS) is highly effective in treating motor symptoms in Parkinson's disease (PD) and medication side effects as well as in improving quality of life. Despite preoperative screening for patients as eligible candidates for this treatment, electrode position may furthermore influence treatment quality. Here, we investigated the relationship between the anatomical site of stimulation within the MRI-defined STN and the outcome of PD patients after STN-HFS. In 30 PD patients with bilateral STN stimulation, we retrospectively defined the boundaries of the STN within the axial target plane of the stereotactic T2-weighted MRI and determined the position of the active electrode contact in relation to the border of the STN. The position of the active contact within the STN was the only variable to predict the outcome of STN stimulation. In contrast, covariates such as age, disease duration, symptom severity, and response to levodopa had no effect. The lateral position of the stimulation contact within the STN led to significantly better clinical improvement, lower stimulation parameters, and less need for postoperative dopaminergic medication. The outcome of patients with stimulation contacts within the medial region of the STN was significantly worse. Precise targeting of the lateral region of the STN is essential for achieving sufficient stimulation efficacy. Preoperative T2-weighted MRI might be a useful component of the targeting procedure to improve the outcome of PD patients. Copyright © 2012 Movement Disorder Society.

  5. Comparison of weight changes following unilateral and staged bilateral STN DBS for advanced PD.

    Lee, Eric M; Kurundkar, Ashish; Cutter, Gary R; Huang, He; Guthrie, Barton L; Watts, Ray L; Walker, Harrison C

    2011-09-01

    Unilateral and bilateral subthalamic nucleus deep brain stimulation (STN DBS) in Parkinson's disease (PD) result in weight gain in the initial postoperative months, but little is known about the changes in weight following unilateral and staged bilateral STN DBS over longer time intervals. A case-control comparison evaluated weight changes over 2 years in 43 consecutive unilateral STN DBS patients, among whom 25 elected to undergo staged bilateral STN DBS, and 21 age-matched and disease severity matched PD controls without DBS. Regression analyses incorporating age, gender, and baseline weight in case or control were conducted to assess weight changes 2 years after the initial unilateral surgery. Unilateral STN DBS and staged bilateral STN DBS patients gained 3.9 ± 2.0 kg and 5.6 ± 2.1 kg versus their preoperative baseline weight (P < 0.001, respectively) while PD controls without DBS lost 0.8 ± 1.1 kg. Although bilateral STN DBS patients gained 1.7 kg more than unilateral STN DBS patients at 2 years, this difference was not statistically significant (P = 0.885). Although there was a trend toward greater weight gain in staged bilateral STN DBS patients versus unilateral patients, we found no evidence for an equivalent or synergistic increase in body weight following placement of the second DBS electrode.

  6. Status report on nuclear power - information from STN databases

    Prinz, H.

    1995-01-01

    The worldwide future of nuclear power as seen about 25 years ago is presented based on a literature search in the INIS database. The role of nuclear power today, after TMI and Chernobyl, in energy supplies and in combating the greehouse effect is evaluated by literature searches in STN databases (e.g. INIS, ETDE, COMPENDEX, CA, ULIDAT, INSPEC). An evaluation is given of the different information contents of bibliographic databases such as INIS and pure information databases such as NLDB. (orig./HP)

  7. STN-stimulation in Parkinson's disease restores striatal inhibition of thalamocortical projection

    Geday, Jacob; Østergaard, Karen; Johnsen, Erik

    2009-01-01

    To test the hypothesis that deep brain stimulation of the subthalamic nucleus (STN) restores the inhibitory output to the striatothalamocortical loop in Parkinson's disease, we obtained functional brain images of blood flow in 10 STN-stimulated patients with Parkinson's disease. Patients were...... in the STN and in the left nucleus lentiformis. Conversely, flow declined in the left supplementary motor area (BA 6), ventrolateral nucleus of the left thalamus, and right cerebellum. Activation of the basal ganglia and deactivation of supplementary motor area and thalamus were both correlated...... with the improvement of motor function. The result is consistent with the explanation that stimulation in resting patients raises output from the STN with activation of the inhibitory basal ganglia output nuclei and subsequent deactivation of the thalamic anteroventral and ventrolateral nuclei and the supplementary...

  8. Inhibition of Serratia marcescens Smj-11 biofilm formation by Alcaligenes faecalis STN17 crude extract

    Lutfi, Zainal; Ahmad, Asmat; Usup, Gires

    2014-01-01

    Serratia marcescens biofilms are formed when they are bound to surfaces in aqueous environments. S. marcescens utilizes N-acylhomoserine lactone (AHL) as its quorum sensing signal molecule. The accumulation of AHL indicates the bacteria to produce matrices to form biofilms. Prodigiosin (2-methyl-3-pentyl-6-methoxyprodigiosin), which causes red pigmentation in the colonies, are also produced when the AHL reaches a certain threshold. The Alcaligenes faecalis STN17 crude extract is believed to inhibit quorum sensing in the S. marcescens Smj-11 and, thus, impedes its biofilm formation ability. A. faecalis STN17 was grown in marine broth, and ethyl acetate extraction was carried out. The crude compound of A. faecalis STN17 was diluted at high concentration (0.2-6.4 mg/mL) and was taken to confirm anti-biofilm activity through the crystal violet method in 96-wells plate. Then, the crude extract underwent purification using simple solvents partitioning test to discern the respective compounds that had the anti-biofilm activity under the crystal violet method. The crystal violet test showed that the crude did have anti-biofilm activity on S. marcescens Smj-11, but did not kill the cells. This finding signifies that the suppression of biofilm formation in S. marcescens by A. faecalis STN17 has a strong correlation. The partitioning test showed that A. faecalis STN17 crude extract has several compounds and only the compound(s) in chloroform showed activities. In conclusion, the crude extract of A. faecalis STN17 has the ability to inhibit S. marcescens Smj-11 biofilm formation

  9. Inhibition of Serratia marcescens Smj-11 biofilm formation by Alcaligenes faecalis STN17 crude extract

    Lutfi, Zainal; Ahmad, Asmat [School of Biosciences and Biotechnology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia (UKM), 43600 Bangi, Selangor (Malaysia); Usup, Gires [School of Environmental and Natural Resources Sciences, Faculty of Science and Technology, Universiti Kebangsaan Malaysia (UKM), 43600 Bangi, Selangor (Malaysia)

    2014-09-03

    Serratia marcescens biofilms are formed when they are bound to surfaces in aqueous environments. S. marcescens utilizes N-acylhomoserine lactone (AHL) as its quorum sensing signal molecule. The accumulation of AHL indicates the bacteria to produce matrices to form biofilms. Prodigiosin (2-methyl-3-pentyl-6-methoxyprodigiosin), which causes red pigmentation in the colonies, are also produced when the AHL reaches a certain threshold. The Alcaligenes faecalis STN17 crude extract is believed to inhibit quorum sensing in the S. marcescens Smj-11 and, thus, impedes its biofilm formation ability. A. faecalis STN17 was grown in marine broth, and ethyl acetate extraction was carried out. The crude compound of A. faecalis STN17 was diluted at high concentration (0.2-6.4 mg/mL) and was taken to confirm anti-biofilm activity through the crystal violet method in 96-wells plate. Then, the crude extract underwent purification using simple solvents partitioning test to discern the respective compounds that had the anti-biofilm activity under the crystal violet method. The crystal violet test showed that the crude did have anti-biofilm activity on S. marcescens Smj-11, but did not kill the cells. This finding signifies that the suppression of biofilm formation in S. marcescens by A. faecalis STN17 has a strong correlation. The partitioning test showed that A. faecalis STN17 crude extract has several compounds and only the compound(s) in chloroform showed activities. In conclusion, the crude extract of A. faecalis STN17 has the ability to inhibit S. marcescens Smj-11 biofilm formation.

  10. Neuropsychological effects of bilateral STN stimulation in Parkinson disease - A controlled study

    Smeding, HMM; Koning-Haanstra, M; Schuurman, PR; Nijssen, P; van Laar, T; Schmand, B; Speelman, J.D.

    2006-01-01

    Objective: To evaluate the cognitive and behavioral effects of bilateral subthalamic nucleus (STN) stimulation in patients with Parkinson disease (PD). Methods: The authors included 103 patients; 99 patients were evaluated 6 months after surgery. A control group of 39 patients with PD was formed and

  11. CTC1-STN1 coordinates G- and C-strand synthesis to regulate telomere length.

    Gu, Peili; Jia, Shuting; Takasugi, Taylor; Smith, Eric; Nandakumar, Jayakrishnan; Hendrickson, Eric; Chang, Sandy

    2018-05-17

    Coats plus (CP) is a rare autosomal recessive disorder caused by mutations in CTC1, a component of the CST (CTC1, STN1, and TEN1) complex important for telomere length maintenance. The molecular basis of how CP mutations impact upon telomere length remains unclear. The CP CTC1 L1142H mutation has been previously shown to disrupt telomere maintenance. In this study, we used CRISPR/Cas9 to engineer this mutation into both alleles of HCT116 and RPE cells to demonstrate that CTC1:STN1 interaction is required to repress telomerase activity. CTC1 L1142H interacts poorly with STN1, leading to telomerase-mediated telomere elongation. Impaired interaction between CTC1 L1142H :STN1 and DNA Pol-α results in increased telomerase recruitment to telomeres and further telomere elongation, revealing that C:S binding to DNA Pol-α is required to fully repress telomerase activity. CP CTC1 mutants that fail to interact with DNA Pol-α resulted in loss of C-strand maintenance and catastrophic telomere shortening. Our findings place the CST complex as an important regulator of both G-strand extensions by telomerase and C-strand synthesis by DNA Pol-α. © 2018 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  12. Safety Evaluation Report related to the operation of Palo Verde Nuclear Generating Station, Units 1, 2, and 3 (Docket Nos. STN 50-528, STN 50-529, and STN 50-530)

    1984-10-01

    Supplement No. 6 to the Safety Evaluation Report for the application filed by Arizona Public Service Company, et al., for licenses to operate the Palo Verde Nuclear Generating Station, Units 1, 2, and 3 (Docket Nos. STN 50-528/529/530), located in Maricopa County, Arizona, has been prepared by the Office of Nuclear Reactor Regulation of the Nuclear Regulatory Commission. The purpose of this supplement is to update the Safety Evaluation Report by providing an evaluation of (1) additional information submitted by the applicant since Supplement No. 5 was issued and (2) matters that the staff had under review when Supplement No. 5 was issued

  13. Safety Evaluation Report related to the operation of Palo Verde Nuclear Generating Station, Units 1, 2, and 3 (Docket Nos. STN 50-528, STN 50-529, and STN 50-530). Supplement No. 7

    1984-12-01

    Supplement No. 7 to the Safety Evaluation Report for the application filed by Arizona Public Service Company et al. for licenses to operate the Palo Verde Nuclear Generating Station, Units 1, 2, and 3 (Docket Nos. STN 50-528/529/530), located in Maricopa County, Arizona, has been prepared by the Office of Nuclear Reactor Regulation of the Nuclear Regulatory Commission. The purpose of this supplement is to update the Safety Evaluation Report by providing an evaluation of: (1) additional information submitted by the applicant since Supplement No. 6 was issued; and (2) matters that the staff had under review when Supplement No. 6 was issued

  14. Effects of STN and GPi deep brain stimulation on impulse control disorders and dopamine dysregulation syndrome.

    Sarah J Moum

    Full Text Available Impulse control disorders (ICDs and dopamine dysregulation syndrome (DDS are important behavioral problems that affect a subpopulation of patients with Parkinson's disease (PD and typically result in markedly diminished quality of life for patients and their caregivers. We aimed to investigate the effects of subthalamic nucleus (STN and internal globus pallidus (GPi deep brain stimulation (DBS on ICD/DDS frequency and dopaminergic medication usage.A retrospective chart review was performed on 159 individuals who underwent unilateral or bilateral PD DBS surgery in either STN or GPi. According to published criteria, pre- and post-operative records were reviewed to categorize patients both pre- and post-operatively as having ICD, DDS, both ICD and DDS, or neither ICD nor DDS. Group differences in patient demographics, clinical presentations, levodopa equivalent dose (LED, and change in diagnosis following unilateral/bilateral by brain target (STN or GPi DBS placement were examined.28 patients met diagnostic criteria for ICD or DDS pre- or post-operatively. ICD or DDS classification did not differ by GPi or STN target stimulation. There was no change in DDS diagnosis after unilateral or bilateral stimulation. For ICD, diagnosis resolved in 2 of 7 individuals after unilateral or bilateral DBS. Post-operative development of these syndromes was significant; 17 patients developed ICD diagnoses post-operatively with 2 patients with pre-operative ICD developing DDS post-operatively.Unilateral or bilateral DBS did not significantly treat DDS or ICD in our sample, even though a few cases of ICD resolved post-operatively. Rather, our study provides preliminary evidence that DDS and ICD diagnoses may emerge following DBS surgery.

  15. Coordinated reset stimulation in a large-scale model of the STN-GPe circuit

    Martin eEbert

    2014-11-01

    Full Text Available Synchronization of populations of neurons is a hallmark of several brain diseases. Coordinated reset (CR stimulation is a model-based stimulation technique which specifically counteracts abnormal synchrony by desynchronization. Electrical CR stimulation, e.g. for the treatment of Parkinson’s disease (PD, is administered via depth electrodes. In order to get a deeper understanding of this technique, we extended the top-down approach of previous studies and constructed a large-scale computational model of the respective brain areas. Furthermore, we took into account the spatial anatomical properties of the simulated brain structures and incor- porated a detailed numerical representation of 2·104 simulated neurons. We simulated the subthalamic nucleus (STN and the globus pallidus externus (GPe. Connections within the STN were governed by spike-timing dependent plasticity (STDP. In this way, we modeled the physiological and pathological activity of the considered brain structures. In particular, we investigated how plasticity could be exploited and how the model could be shifted from strongly synchronized (pathological activity to strongly desynchronized (healthy activity of the neuronal populations via CR stimulation of the STN neurons. Furthermore, we investigated the impact of specific stimulation parameters especially the electrode position on the stimulation outcome. Our model provides a step forward towards a biophysically realistic model of the brain areas relevant to the emergence of pathological neuronal activity in PD. Furthermore, our model constitutes a test bench for the optimization of both stimulation parameters and novel electrode geometries for efficient CR stimulation.

  16. MDS-UPDRS to assess non-motor symptoms after STN DBS for Parkinson's disease.

    Jafari, Nickey; Pahwa, Rajesh; Nazzaro, Jules M; Arnold, Paul M; Lyons, Kelly E

    2016-01-01

    To determine if the non-motor sections of the Movement Disorder Society's (MDS) version of the Unified Parkinson's Disease Rating Scale (UPDRS) could supplement the original UPDRS as a patient completed assessment of changes in non-motor symptoms in Parkinson's disease (PD) patients after bilateral subthalamic nucleus (STN) deep brain stimulation (DBS). Thirty PD patients who underwent bilateral STN DBS were assessed using the total UPDRS and the non-motor sections of the MDS-UPDRS prior to surgery and one year following surgery. This study focuses on non-motor symptoms as assessed by Part I of the UPDRS and Part 1A and 1B of the MDS-UPDRS. One year following surgery, no individual non-motor symptoms or the total mentation score of the UPDRS were significantly changed. In comparison, the MDS-UPDRS showed significant improvements in sleep and urinary problems and a trend towards improvement in anxiety, constipation, daytime sleepiness, fatigue and pain. This study provides evidence that the MDS-UPDRS non-motor sections, when completed by the patients, can supplement the original version of the UPDRS as an effective method of measuring changes in non-motor symptoms after DBS. It also reinforces the benefits of bilateral STN DBS on non-motor symptoms of PD.

  17. Safety Evaluation Report related to the operation of Palo Verde Nuclear Generating Station, Units 1, 2, and 3 (Dockets Nos. STN 50-528, STN 50-529, and STN 50-530)

    1987-03-01

    Supplement No. 11 to the Safety Evaluation Report for the application filed by Arizona Public Service Company et al. for licenses to operate the Palo Verde Nuclear Generating Station, Units 1, 2, and 3 (Docket Nos. STN 50-528/529/530), located in Maricopa County, Arizone, has been prepared by the Office of Nuclear Reactor Regulation of the Nuclear Regulatory Commission. The purpose of this supplement is to update the Safety Evaluation Report by providing an evaluation of (1) additional information submitted by the applicant since Supplement No. 10 was issued and (2) other matters requiring staff review since Supplenent No. 10 was issued, specifically those issues that required resolution before Unit 3 low-power licensing

  18. Safety Evaluation Report related to the operation of Palo Verde Nuclear Generating Station, Units 1, 2, and 3 (Docket Nos. STN 50-528, STN 50-529, and STN 50-530). Supplement No. 9

    1985-12-01

    Supplement No. 9 to the Safety Evaluation Report for the application filed by Arizona Public Service Company et al. for licenses to operate the Palo Verde Nuclear Generating Station, Units 1, 2 and 3 (Docket Nos. STN 50-528/529/530), located in Maricopa County, Arizona, has been prepared by the Office of Nuclear Reactor Regulation of the Nuclear Regulatory Commission. The purpose of this supplement is to update the Safety Evaluation Report by providing an evaluation of: (1) additional information submitted by the applicant since Supplement No. 8 was issued; and (2) matters that the staff had under review when Supplement No. 8 was issued, specifically those issues which required resolution prior to Unit 2 fuel loading and testing up to 5% of full power

  19. What is dorso-lateral in the subthalamic Nucleus (STN)?--a topographic and anatomical consideration on the ambiguous description of today's primary target for deep brain stimulation (DBS) surgery.

    Coenen, Volker A; Prescher, Andreas; Schmidt, Thorsten; Picozzi, Piero; Gielen, Frans L H

    2008-11-01

    The most frequently used target for DBS in advanced Parkinson Disease (PD) is the sensorimotor subthalamic nucleus (STN), anatomically referred to as dorso-lateral STN [3]. Ambiguities arise, regarding the true meaning of this description in the STN. Does "dorsal" indicate posterior or superior? At its best, this definition assigns two directions in space to a three-dimensional structure. This paper evaluates the ambiguity and describes the sensorimotor part of the STN in stereotactic space.

  20. Does early verbal fluency decline after STN implantation predict long-term cognitive outcome after STN-DBS in Parkinson's disease?

    Borden, Alaina; Wallon, David; Lefaucheur, Romain; Derrey, Stéphane; Fetter, Damien; Verin, Marc; Maltête, David

    2014-11-15

    An early and transient verbal fluency (VF) decline and impairment in frontal executive function, suggesting a cognitive microlesion effect may influence the cognitive repercussions related to subthalamic nucleus deep brain stimulation (STN-DBS). Neuropsychological tests including semantic and phonemic verbal fluency were administered both before surgery (baseline), the third day after surgery (T3), at six months (T180), and at an endpoint multiple years after surgery (Tyears). Twenty-four patients (mean age, 63.5 ± 9.5 years; mean disease duration, 12 ± 5.8 years) were included. Both semantic and phonemic VF decreased significantly in the acute post-operative period (44.4 ± 28.2% and 34.3 ± 33.4%, respectively) and remained low at 6 months compared to pre-operative levels (decrease of 3.4 ± 47.8% and 10.8 ± 32.1%) (P < 0.05). Regression analysis showed phonemic VF to be an independent factor of decreased phonemic VF at six months. Age was the only independent predictive factor for incident Parkinson's disease dementia (PDD) (F (4,19)=3.4, P<0.03). An acute post-operative decline in phonemic VF can be predictive of a long-term phonemic VF deficit. The severity of this cognitive lesion effect does not predict the development of dementia which appears to be disease-related. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Does unilateral basal ganglia activity functionally influence the contralateral side? What we can learn from STN stimulation in patients with Parkinson's disease.

    Brun, Yohann; Karachi, Carine; Fernandez-Vidal, Sara; Jodoin, Nicolas; Grabli, David; Bardinet, Eric; Mallet, Luc; Agid, Yves; Yelnik, Jerome; Welter, Marie-Laure

    2012-09-01

    In humans, the control of voluntary movement, in which the corticobasal ganglia (BG) circuitry participates, is mainly lateralized. However, several studies have suggested that both the contralateral and ipsilateral BG systems are implicated during unilateral movement. Bilateral improvement of motor signs in patients with Parkinson's disease (PD) has been reported with unilateral lesion or high-frequency stimulation (HFS) of the internal part of the globus pallidus or the subthalamic nucleus (STN-HFS). To decipher the mechanisms of production of ipsilateral movements induced by the modulation of unilateral BG circuitry activity, we recorded left STN neuronal activity during right STN-HFS in PD patients operated for bilateral deep brain stimulation. Left STN single cells were recorded in the operating room during right STN-HFS while patients experienced, or did not experience, right stimulation-induced dyskinesias. Most of the left-side STN neurons (64%) associated with the presence of right dyskinesias were inhibited, with a significant decrease in burst and intraburst frequencies. In contrast, left STN neurons not associated with right dyskinesias were mainly activated (48%), with a predominant increase 4-5 ms after the stimulation pulse and a decrease in oscillatory activity. This suggests that unilateral neuronal STN modulation is associated with changes in the activity of the contralateral STN. The fact that one side of the BG system can influence the functioning of the other could explain the occurrence of bilateral dyskinesias and motor improvement observed in PD patients during unilateral STN-HFS, as a result of a bilateral disruption of the pathological activity in the corticosubcortical circuitry.

  2. A inter-relação das sialomucinas (antígenos Tn e Stn com o adenocarcinoma no esôfago de Barrett Relationship of the sialomucins (Tn and Stn antigens with adenocarcinoma in Barrett's esophagus

    Plínio Conte de Faria Júnior

    2007-08-01

    Full Text Available OBJETIVO: O esôfago de Barrett (EB é conseqüência do refluxo gastroesofágico crônico e considerado fator de risco para o desenvolvimento de adenocarcinoma. Estudos do muco, em especial das mucinas ácidas representadas pelas sialomucinas presentes nas células caliciformes, mostraram que na metaplasia do tipo intestinal, o epitélio do órgão pode expressar antígenos denominados Tn e Stn. Estes antígenos já foram analisados em tumores gástricos e colônicos, porém não foram encontradas referências à sua utilização no EB. Este trabalho objetivou analisar estes antígenos em doentes com EB e em adenocarcinoma associado ao EB. MÉTODOS: Foram estudados, utilizando testes imunohistoquímicos, os antígenos Tn e Stn, nas biópsias endoscópicas de 29 doentes com EB, sete com adenocarcinoma no EB, além de oito indivíduos com epitélio esofágico normal. RESULTADOS: Nas células caliciformes, foi observada positividade para Stn em 100% dos casos e para Tn em 48% dos casos. Nas células colunares, o Stn foi sempre negativo, enquanto o Tn foi positivo em 100% dos casos. Entretanto, nos doentes com adenocarcinoma no EB, a positividade para ambos os antígenos foi de 100%. Nos indivíduos normais, houve positividade para o antígeno Tn e negatividade para Stn em todos os casos (100%. CONCLUSÃO: É provável que nos doentes com EB a positividade para o Tn, à semelhança do ocorrido quanto à positividade do mesmo antígeno nos portadores de adenocarcinoma, possa significar maior suscetibilidade para ocorrência futura de câncer. Assim, a pesquisa das sialomucinas poderá ser rotineiramente utilizada, contribuindo como fator prognóstico para desenvolvimento de adenocarcinoma no EB.OBJECIVE: Barrett's esophagus (BE is a consequence of chronic gastroesophageal reflux and is considered a risk factor for adenocarcinoma. The study of the mucus, especially acid mucins, such as the sialomucins in the goblet cells which characterize BE, showed

  3. The human CTC1/STN1/TEN1 complex regulates telomere maintenance in ALT cancer cells

    Huang, Chenhui; Jia, Pingping; Chastain, Megan; Shiva, Olga; Chai, Weihang, E-mail: wchai@wsu.edu

    2017-06-15

    Maintaining functional telomeres is important for long-term proliferation of cells. About 15% of cancer cells are telomerase-negative and activate the alternative-lengthening of telomeres (ALT) pathway to maintain their telomeres. Recent studies have shown that the human CTC1/STN1/TEN1 complex (CST) plays a multi-faceted role in telomere maintenance in telomerase-expressing cancer cells. However, the role of CST in telomere maintenance in ALT cells is unclear. Here, we report that human CST forms a functional complex localizing in the ALT-associated PML bodies (APBs) in ALT cells throughout the cell cycle. Suppression of CST induces telomere instabilities including telomere fragility and elevates telomeric DNA recombination, leading to telomere dysfunction. In addition, CST deficiency significantly diminishes the abundance of extrachromosomal circular telomere DNA known as C-circles and t-circles. Suppression of CST also results in multinucleation in ALT cells and impairs cell proliferation. Our findings imply that the CST complex plays an important role in regulating telomere maintenance in ALT cells. - Highlights: • CST localizes at telomeres and ALT-associated PML bodies in ALT cells throughout the cell cycle. • CST is important for promoting telomeric DNA replication in ALT cells. • CST deficiency decreases ECTR formation and increases T-SCE. • CST deficiency impairs ALT cell proliferation and results in multinucleation.

  4. Cognitive and Psychiatric Effects of STN versus GPi Deep Brain Stimulation in Parkinson's Disease: A Meta-Analysis of Randomized Controlled Trials.

    Jia-Wei Wang

    Full Text Available Deep brain stimulation (DBS of either the subthalamic nucleus (STN or the globus pallidus interna (GPi can reduce motor symptoms in patients with Parkinson's disease (PD and improve their quality of life. However, the effects of STN DBS and GPi DBS on cognitive functions and their psychiatric effects remain controversial. The present meta-analysis was therefore performed to clarify these issues.We searched the PUBMED, EMBASE, and the Cochrane Central Register of Controlled Trials databases. Other sources, including internet-based clinical trial registries and grey literature sources, were also searched. After searching the literature, two investigators independently performed literature screens to assess the quality of the included trials and to extract the data. The outcomes included the effects of STN DBS and GPi DBS on multiple cognitive domains, depression, anxiety, and quality of life.Seven articles related to four randomized controlled trials that included 521 participants were incorporated into the present meta-analysis. Compared with GPi DBS, STN DBS was associated with declines in selected cognitive domains after surgery, including attention, working memory and processing speed, phonemic fluency, learning and memory, and global cognition. However, there were no significant differences in terms of quality of life or psychiatric effects, such as depression and anxiety, between the two groups.A selective decline in frontal-subcortical cognitive functions is observed after STN DBS in comparison with GPi DBS, which should not be ignored in the target selection for DBS treatment in PD patients. In addition, compared to GPi DBS, STN DBS does not affect depression, anxiety, and quality of life.

  5. Cognitive and Psychiatric Effects of STN versus GPi Deep Brain Stimulation in Parkinson's Disease: A Meta-Analysis of Randomized Controlled Trials.

    Wang, Jia-Wei; Zhang, Yu-Qing; Zhang, Xiao-Hua; Wang, Yun-Peng; Li, Ji-Ping; Li, Yong-Jie

    2016-01-01

    Deep brain stimulation (DBS) of either the subthalamic nucleus (STN) or the globus pallidus interna (GPi) can reduce motor symptoms in patients with Parkinson's disease (PD) and improve their quality of life. However, the effects of STN DBS and GPi DBS on cognitive functions and their psychiatric effects remain controversial. The present meta-analysis was therefore performed to clarify these issues. We searched the PUBMED, EMBASE, and the Cochrane Central Register of Controlled Trials databases. Other sources, including internet-based clinical trial registries and grey literature sources, were also searched. After searching the literature, two investigators independently performed literature screens to assess the quality of the included trials and to extract the data. The outcomes included the effects of STN DBS and GPi DBS on multiple cognitive domains, depression, anxiety, and quality of life. Seven articles related to four randomized controlled trials that included 521 participants were incorporated into the present meta-analysis. Compared with GPi DBS, STN DBS was associated with declines in selected cognitive domains after surgery, including attention, working memory and processing speed, phonemic fluency, learning and memory, and global cognition. However, there were no significant differences in terms of quality of life or psychiatric effects, such as depression and anxiety, between the two groups. A selective decline in frontal-subcortical cognitive functions is observed after STN DBS in comparison with GPi DBS, which should not be ignored in the target selection for DBS treatment in PD patients. In addition, compared to GPi DBS, STN DBS does not affect depression, anxiety, and quality of life.

  6. Application value of combined measurement of serum sTn, CA242, CA19-9 and CEA in the diagnosis of gastroenterological neoplasm

    Zhang Wanzhong; Chen Zhizhou; Fan Zhenfu

    2007-01-01

    To determine the application value of four serum tumor markers sTn, CA242, CA 19-9 and CEA in the diagnosis of gastroenterological neoplasm, the serum sTn, CA242, CA19-9 and CEA in 30 normal adult controls and 60 patients with gastroenterological neoplasm were measured by IRMA. The results showed that the serum sTn, CA242, CA19-9 and CEA levels in patients with gastric carcinoma or colorectal carcinoma were much higher than those in control group (P<0.01). The serum CEA, CA19-9 and CA242 levels in patients with colorectal carcinoma were significantly higher than those in patients with gastric carcinoma (P<0.01), but the serum sTn level in the former was markedly lower (P<0.01) than that in the latter. The sensitivity of tumor marker increased with the progress of clinical stages, with a considerably higher sensitivity for stage IV compared with stage I-II (P<0.01). The combined test of four tumor markers could be more sensitive than single test in detecting gastric carcinoma and colorectal carcinoma (P<0.05). Four tumor markers are useful for diagnosing gastroenterological neoplasm, and the combined measurement of 4 tumor markers could increase the sensitivity of detecting gastric carcinoma. (authors)

  7. Návrh IS pro Místní knihovnu města Jevišovice

    Vašíček, Daniel

    2010-01-01

    Bakalářská práce pojednává o návrhu vytvoření databáze pro místní knihovnu města Jevišovice. Práce obsahuje vlastní návrh databáze a její vytvoření v programu Microsoft Access. Dále obsahuje vytvoření pracovního rozhraní pomocí VBA. The thesis deals with the concept of the Jevisovice city Local Library database creating. The thesis contains the concept of the database and its creation in the Microsoft Access software. Further, the work includes the creation of the VBA comunication interfac...

  8. Draft environmental statement related to the proposed manufacture of floating nuclear power plants (Docket No. STN 50-437)

    1976-10-01

    The proposed action is the issuance of a manufacturing license to Offshore Power Systems for the startup and operation of a proposed manufacturing facility located at Blount Island, Jacksonville, Florida (Docket No. STN 50-436). No nuclear fuel will be handled or stored at the manufacturing site. The plants will be fueled after they have been towed to and moored within breadwaters at specific offshore locations designated by the purchaser and after an operating license has been issued by the Nuclear Regulatory Commision. Each nuclear generating plant, mounted on a floating platform, has a net capacity of 1150 MWe. This energy is provided by a pressurized water reactor steam supply system consisting of a Westinghouse four-loop 3425 MWt unit with an ice-condenser containment system. When one or more of these units is located within a single breakwater, the installation is designated an offshore power station. 3 figs., 1 tab

  9. Comparison of imaging modalities and source-localization algorithms in locating the induced activity during deep brain stimulation of the STN.

    Mideksa, K G; Singh, A; Hoogenboom, N; Hellriegel, H; Krause, H; Schnitzler, A; Deuschl, G; Raethjen, J; Schmidt, G; Muthuraman, M

    2016-08-01

    One of the most commonly used therapy to treat patients with Parkinson's disease (PD) is deep brain stimulation (DBS) of the subthalamic nucleus (STN). Identifying the most optimal target area for the placement of the DBS electrodes have become one of the intensive research area. In this study, the first aim is to investigate the capabilities of different source-analysis techniques in detecting deep sources located at the sub-cortical level and validating it using the a-priori information about the location of the source, that is, the STN. Secondly, we aim at an investigation of whether EEG or MEG is best suited in mapping the DBS-induced brain activity. To do this, simultaneous EEG and MEG measurement were used to record the DBS-induced electromagnetic potentials and fields. The boundary-element method (BEM) have been used to solve the forward problem. The position of the DBS electrodes was then estimated using the dipole (moving, rotating, and fixed MUSIC), and current-density-reconstruction (CDR) (minimum-norm and sLORETA) approaches. The source-localization results from the dipole approaches demonstrated that the fixed MUSIC algorithm best localizes deep focal sources, whereas the moving dipole detects not only the region of interest but also neighboring regions that are affected by stimulating the STN. The results from the CDR approaches validated the capability of sLORETA in detecting the STN compared to minimum-norm. Moreover, the source-localization results using the EEG modality outperformed that of the MEG by locating the DBS-induced activity in the STN.

  10. r-CBF brain SPET before surgery and during subthalamic nuclei (STN) high frequency stimulation (DBS) in Parkinson's Disease

    Gerundini, P.; Benti, R.; De Notaris, A.; Ferrari, M.; Raimondi, A.; Mariani, C.; Antonini, A.; Pezzoli, G.; Gaini, S.M.

    2002-01-01

    Deep brain stimulation (DBS) of the subthalamic nuclei (STN) can improve motor symptoms and reduces the need for medical therapy in severe Parkinson's Disease (PD). Moreover, DBS can affect, as the medical treatment, cerebral perfusion/metabolism even in cortical/subcortical areas not primarily involved in PD motor symptoms. Aim of the study was the assessment of r-CBF changes by mean of brain SPECT in severe PD .before surgery and during DBS of the STN. Methods. 14 PD patients (duration 15.2±5.1 ys; H and Y off-score 3.6±0.7) underwent STN electrode implantation. Residual motor dysfunction was assessed by UPDRS score up to one year after surgery. SPECT was performed after i.v. injection of Tc-99m ECD (740 MBq) in PD group before and 6-9 months after surgery and in 13 age matched normals. Standardized ROIs templates were applied in brain sections to generate perfusion ratios in the cerebral cortex and basal ganglia. Statistical Parametric Mapping (SPM) analysis of SPET studies was also obtained. Results: 6 months after surgery the mean UPDRS score improvement was 48.8±26.1% (DBS on) vs pre surgery. 8 patients (R+) had UPDRS improvement >50% (mean 67.7±8.8%); 6 patients (R-) had score improvement <50% (mean 22.9±18.9%). Before surgery, motor dysfunction during therapy was similar in R+ and R- groups (mean UPDRS 19.8±8.2 vs. 21.3±9.6). During BDS, UPDRS mean score without medical therapy was lower in R+ (15.6±5.6) vs. R- (35.0±12.4; p<0.001). ROIs and SPM analysis of pre-surgery SPET studies showed significant hypoperfusion (p<0.01) in the occipital gyri of PD vs control groups. No significant differences were found by comparing pre/post surgery SPECT patterns in whole PD group. However, in R- group SPECT showed significant hypoperfusion in pre-frontal areas, parietal and occipital gyri vs R+ patients (p<0.02) and controls (p<0.01). Before surgery, R+ group had borderline occipital hypoperfusion (p=0.04) and mild increase of putaminal perfusion (p=0.03) vs

  11. Freestanding rGO-SWNT-STN Composite Film as an Anode for Li Ion Batteries with High Energy and Power Densities

    Taeseup Song

    2015-12-01

    Full Text Available Freestanding Si-Ti-Ni alloy particles/reduced graphene oxide/single wall carbon nanotube composites have been prepared as an anode for lithium ion batteries via a simple filtration method. This composite electrode showed a 9% increase in reversible capacity, a two-fold higher cycle retention at 50 cycles and a two-fold higher rate capability at 2 C compared to pristine Si-Ti-Ni (STN alloy electrodes. These improvements were attributed to the suppression of the pulverization of the STN active material by the excellent mechanical properties of the reduced graphene oxide-single wall carbon nanotube networks and the enhanced kinetics associated with both electron and Li ion transport.

  12. Stratifying Parkinson's Patients With STN-DBS Into High-Frequency or 60 Hz-Frequency Modulation Using a Computational Model.

    Khojandi, Anahita; Shylo, Oleg; Mannini, Lucia; Kopell, Brian H; Ramdhani, Ritesh A

    2017-07-01

    High frequency stimulation (HFS) of the subthalamic nucleus (STN) is a well-established therapy for Parkinson's disease (PD), particularly the cardinal motor symptoms and levodopa induced motor complications. Recent studies have suggested the possible role of 60 Hz stimulation in STN-deep brain stimulation (DBS) for patients with gait disorder. The objective of this study was to develop a computational model, which stratifies patients a priori based on symptomatology into different frequency settings (i.e., high frequency or 60 Hz). We retrospectively analyzed preoperative MDS-Unified Parkinson's Disease Rating Scale III scores (32 indicators) collected from 20 PD patients implanted with STN-DBS at Mount Sinai Medical Center on either 60 Hz stimulation (ten patients) or HFS (130-185 Hz) (ten patients) for an average of 12 months. Predictive models using the Random Forest classification algorithm were built to associate patient/disease characteristics at surgery to the stimulation frequency. These models were evaluated objectively using leave-one-out cross-validation approach. The computational models produced, stratified patients into 60 Hz or HFS (130-185 Hz) with 95% accuracy. The best models relied on two or three predictors out of the 32 analyzed for classification. Across all predictors, gait and rest tremor of the right hand were consistently the most important. Computational models were developed using preoperative clinical indicators in PD patients treated with STN-DBS. These models were able to accurately stratify PD patients into 60 Hz stimulation or HFS (130-185 Hz) groups a priori, offering a unique potential to enhance the utilization of this therapy based on clinical subtypes. © 2017 International Neuromodulation Society.

  13. Motor and non-motor circuitry activation induced by subthalamic nucleus deep brain stimulation (STN DBS) in Parkinson’s disease patients: Intraoperative fMRI for DBS

    Knight, Emily J.; Testini, Paola; Min, Hoon-Ki; Gibson, William S.; Gorny, Krzysztof R.; Favazza, Christopher P.; Felmlee, Joel P.; Kim, Inyong; Welker, Kirk M.; Clayton, Daniel A.; Klassen, Bryan T.; Chang, Su-youne; Lee, Kendall H.

    2015-01-01

    Objective To test the hypothesis suggested by previous studies that subthalamic nucleus (STN) deep brain stimulation (DBS) in patients with PD would affect the activity of both motor and non-motor networks, we applied intraoperative fMRI to patients receiving DBS. Patients and Methods Ten patients receiving STN DBS for PD underwent intraoperative 1.5T fMRI during high frequency stimulation delivered via an external pulse generator. The study was conducted between the dates of January 1, 2013 and September 30, 2014. Results We observed blood oxygen level dependent (BOLD) signal changes (FDR<.001) in the motor circuitry, including primary motor, premotor, and supplementary motor cortices, thalamus, pedunculopontine nucleus (PPN), and cerebellum, as well as in the limbic circuitry, including cingulate and insular cortices. Activation of the motor network was observed also after applying a Bonferroni correction (p<.001) to our dataset, suggesting that, across subjects, BOLD changes in the motor circuitry are more consistent compared to those occurring in the non-motor network. Conclusions These findings support the modulatory role of STN DBS on the activity of motor and non-motor networks, and suggest complex mechanisms at the basis of the efficacy of this treatment modality. Furthermore, these results suggest that, across subjects, BOLD changes in the motor circuitry are more consistent compared to those occurring in the non-motor network. With further studies combining the use of real time intraoperative fMRI with clinical outcomes in patients treated with DBS, functional imaging techniques have the potential not only to elucidate the mechanisms of DBS functioning, but also to guide and assist in the surgical treatment of patients affected by movement and neuropsychiatric disorders. PMID:26046412

  14. Safety-evaluation report related to the final design of the Standard Nuclear Steam Supply Reference System - CESSAR System 80. Docket No. STN 50-470

    1983-03-01

    Supplement No. 1 to the Safety Evaluation Report for the application filed by Combustion Engineering, Inc. for a Final Design Approval for the Combustion Engineering Standard Safety Analysis Report (STN 50-470) has been prepared by the Office of Nuclear Reactor Regulation of the Nuclear Regulatory Commission. The purpose of this supplement is to update the Safety Evaluation by providing: (1) the evaluation of additional information submitted by the applicant since the Safety Evaluation Report was issued, (2) the evaluation of the matters the staff had under review when the Safety Evaluation Report was issued, and (3) the response to comments made by the Advisory Committee on Reactor Safeguards

  15. Safety Evaluation Report related to the operation of Wolf Creek Generating Station, Unit No. 1 (Docket No. STN 50-482). Supplement No. 6

    1985-06-01

    This report supplements the Safety Evaluation Report (SER) for the application filed by the Kansas Gas and Electric Company, as applicant and agent for the owners, for a license to operate the Wolf Creek Generating Station, Unit 1 (Docket No. STN 50-482). The facility is located in Coffey County, Kansas. This supplement provides recent information regarding resolution of the license conditions identified in the SER. Because of the favorable resolution of the items discussed in this report, the staff concludes that the facility can be operated by the licensee at power levels greater than 5% without endangering the health and safety of the public

  16. Safety Evaluation Report related to the operation of Wolf Creek Generating Station, Unit No. 1 (Docket No. STN 50-482). Supplement No. 5

    1985-03-01

    This report supplements the Safety Evaluation Report (SER) for the application filed by the Kansas Gas and Electric Company, as applicant and agent for the owners, for a license to operate the Wolf Creek Generating Station, Unit 1 (Docket No. STN 50-482). The facility is located in Coffey County, Kansas. This supplement has been prepared by the Office of Nuclear Reactor Regulation of the US Nuclear Regulatory Commission and provides recent information regarding resolution of the open items identified in the SER. Because of the favorable resolution of the items discussed in this report, the staff concludes that the facility can be operated by the applicant without endangering the health and safety of the public

  17. Safety evaluation report related to the preliminary design of the Standard Nuclear Steam Supply Reference System, RESAR SP/90 (Docket No. STN 50-601)

    1991-04-01

    On October 24, 1983, the Westinghouse Electric Corporation tendered its application for a preliminary design approval of the advanced pressurized-water reactor design for the SP/90 reactor. The Westinghouse Reference Safety Analysis Report (RESAR SP/90, Docket No. STN 50-601), describing the design of the facility, was submitted from October 24, 1983 through March 9, 1987. Staff of the US Nuclear Regulatory Commission, Office of Nuclear Reactor Regulation, has prepared this safety evaluation report of the RESAR SP/90 on the basis of its review. Because of the stage of the design, there are open issues that have not been resolved. These issues are discussed in detail throughout this report, and a summary is provided in Section 1.6 of this report. The applicant will be required to address these and any additional such concerns that may be raised during the course of the staff's review of advanced light-water reactors in support of a final design approval application. This report shall not constitute a commitment to issue a permit or license or in any way affect the authority of the Commission, its adjudicatory boards, and other presiding officers in any proceeding under Subpart G of Title 10 of the Code of Federal Regulations, Part 2

  18. Final environmental statement related to the proposed manufacture of floating nuclear power plants: (Docket No. STN 50-437): Part 2, A generic environmental statement considering the siting and operation of floating nuclear power plants

    1976-09-01

    The proposed action is the issuance of a manufacturing license to Offshore Power Systems for the startup and operation of a proposed manufacturing facility located at Blount Island, Jacksonville, Florida (Docket No. STN 50-437). No nuclear fuel will be handled or stored at the manufacturing site. The plants will be fueled after they have been towed to and moored within protected basins at specific locations designated by the purchaser and after an operating license has been issued by the Nuclear Regulatory Commission. Each nuclear generating plant, mounted on a floating platform, has a net capacity of 1150 MWe. This energy is provided by a pressurized water reactor steam supply system consisting of a Westinghouse four-loop 3425-MWt unit with an ice-condenser containment system. When one or more of these units is located within a single breakwater, the installation is designated an offshore power station. 226 figs., 95 tabs

  19. The androgen receptor controls expression of the cancer-associated sTn antigen and cell adhesion through induction of ST6GalNAc1 in prostate cancer

    Munkley, Jennifer; Oltean, Sebastian; Vodák, Daniel; Wilson, Brian T.; Livermore, Karen E.; Zhou, Yan; Star, Eleanor; Floros, Vasileios I.; Johannessen, Bjarne; Knight, Bridget; McCullagh, Paul; McGrath, John; Crundwell, Malcolm; Skotheim, Rolf I.; Robson, Craig N.; Leung, Hing Y.; Harries, Lorna W.; Rajan, Prabhakar; Mills, Ian G.; Elliott, David J.

    2015-01-01

    Patterns of glycosylation are important in cancer, but the molecular mechanisms that drive changes are often poorly understood. The androgen receptor drives prostate cancer (PCa) development and progression to lethal metastatic castration-resistant disease. Here we used RNA-Seq coupled with bioinformatic analyses of androgen-receptor (AR) binding sites and clinical PCa expression array data to identify ST6GalNAc1 as a direct and rapidly activated target gene of the AR in PCa cells. ST6GalNAc1 encodes a sialytransferase that catalyses formation of the cancer-associated sialyl-Tn antigen (sTn), which we find is also induced by androgen exposure. Androgens induce expression of a novel splice variant of the ST6GalNAc1 protein in PCa cells. This splice variant encodes a shorter protein isoform that is still fully functional as a sialyltransferase and able to induce expression of the sTn-antigen. Surprisingly, given its high expression in tumours, stable expression of ST6GalNAc1 in PCa cells reduced formation of stable tumours in mice, reduced cell adhesion and induced a switch towards a more mesenchymal-like cell phenotype in vitro. ST6GalNAc1 has a dynamic expression pattern in clinical datasets, being significantly up-regulated in primary prostate carcinoma but relatively down-regulated in established metastatic tissue. ST6GalNAc1 is frequently upregulated concurrently with another important glycosylation enzyme GCNT1 previously associated with prostate cancer progression and implicated in Sialyl Lewis X antigen synthesis. Together our data establishes an androgen-dependent mechanism for sTn antigen expression in PCa, and are consistent with a general role for the androgen receptor in driving important coordinate changes to the glycoproteome during PCa progression. PMID:26452038

  20. OS IMPACTOS NO ATIVO IMOBILIZADO DA UNIVERSIDADE FEDERAL DE JUIZ DE FORA (UFJF E SUAS DECORRÊNCIAS PARA O CONTROLE GERENCIAL INSTITUCIONAL A PARTIR DA IMPLANTAÇÃO DA PORTARIA CONJUNTA SPU-STN N. 703/2014

    Maria Simoni Nascimento Soncin

    2017-01-01

    Full Text Available A atualização do valor contábil dos imóveis ao valor de mercado busca evidenciar a capacidade destes ativos em gerar benefícios econômicos e de prestar serviços de qualidade à sociedade. Objetivou-se com essa pesquisa apresentar a atualização, proposta na Portaria Conjunta SPU/STN N. 703/2014, dos bens imóveis de uso educacional, do campus da Universidade Federal de Juiz de Fora, para averiguar os impactos desse procedimento no subgrupo do ativo Imobilizado e suas decorrências para o controle gerencial. O método utilizado como estratégia de pesquisa foi o estudo de caso, realizado na UFJF, por meio de atualizações dos valores registrados no SPIUnet e de análises horizontal e vertical, no balanço patrimonial, nos anos de 2014 e 2015. Os resultados da pesquisa demonstraram que o impacto no imobilizado é relevante, representando um acréscimo real de 34,36% no patrimônio imobiliário desta Universidade. E, que este procedimento poderá auxiliar o controle gerencial, pois fortalece a credibilidade da informação e a transparência dos atos da gestão pública.   The updating of the book value of real estate to market value seeks to highlight the ability of these assets to generate economic benefits and to provide quality services to society. The objective of this research was to present the update, proposed in Joint Ordinance SPU / STN No. 703/2014, of real estate for educational use, at the campus of the Federal University of Juiz de Fora, to investigate the impacts of this procedure on the subgroup of assets Fixed assets and their consequences for management control. The method used as a research strategy was the case study carried out at the UFJF, through updates of the values recorded in SPIUnet and of horizontal and vertical analyzes in the balance sheet, in the years 2014 and 2015. The results of the research demonstrated that The impact on property, plant and equipment is significant, representing a real increase of 34

  1. Final environmental statement related to the proposed manufacture of floating nuclear power plants by Offshore Power Systems: (Docket No. STN 50-437): Part 2, A generic environmental statement considering the siting and operation of floating nuclear power plants

    1976-09-01

    The proposed action is the issuance of a manufacturing license to Offshore Power Systems for the startup and operation of a proposed manufacturing facility located at Blount Island, Jacksonville, Florida (Docket No. STN 50-437). No nuclear fuel will be handled or stored at the manufacturing site. The plants will be fueled after they have been towed to and moored within protected basins at specific locations designated by the purchaser and after an operating license has been issued by the Nuclear Regulatory Commission. Each nuclear generating plant, mounted on a floating platform, has a net capacity of 1150 MWe. This energy is provided by a pressurized water reactor steam supply system consisting of a Westinghouse four-loop 3425-MWt unit with an ice-condenser containment system. When one or more of these units is located within a single breakwater, the installation is designated an offshore power station. Volume 2 contains the siting criteria, regulations, effects of construction, effects of operation, and a safety analysis. 2 figs., 2 tabs

  2. Mediation by the serotonergic system of U-50,488H-induced antinociception and tolerance

    Ho, Begonia Yeeman.

    1989-01-01

    The antinociceptive action of U-50,488H, a selective {kappa}-opioid receptor agonist, was attenuated by serotonergic but not by noradrenergic receptor antagonists. Intracerebroventricularly (i.c.v.) administered U-50,488H was antagonized by more than two fold by i.c.v. administered pindolol, methysergide, mianserin, ketanserin, pirenperone or ICS-205,930. A similar degree of antagonism of U-50,488H (i.c.v.) was found after intrathecal (i.t.) treatments with pindolol, methysergide or ICS-205,930 but not with mianserin, ketanserin or pirenperone. When U-50,488H and the antagonists were both given i.t., its antinociceptive action was attenuated by pindolol or methysergide, potentiated by mianserin, ketanserin or pirenperone and not affected by ICS-205,930. The release of serotonin was further studied directly by using a superfusion system. A naloxone reversible, concentration- and Ca{sup 2+}- dependent enhancement of release of ({sup 3}H)serotonin by U-50,488H was observed in spinal and brain tissues. Tolerance to the antinociceptive action of U-50,488H was induced in mice using slow release preparations of U-50,488H. Serotonergic receptor antagonists (pindolol or ketanserin) were co-administered with U-50,488H to test for their effects on the development of tolerance to U-50,488H.

  3. stní Agenda 21

    CENIA, česká informační agentura životního prostředí

    2013-01-01

    Veletrh Česká příroda, kterým Ministerstvo životního prostředí současně zahájilo celoroční kampaň se stejným názvem, se uskutečnil v pátek 19. a sobotu 20. dubna 2013 od 10 do 18 hodin v prostorách pražského Národního domu na Vinohradech. Veletrh podpořil svou návštěvou v sobotu 20. dubna 2013 ministr životního prostředí Tomáš Chalupa, který zároveň pokřtil knihu Nejkrásnější výlety do chráněných krajinných oblastí ČR. Bohatý doprovodný program probíhal souběžně na několika místech Národního ...

  4. Synthesis of tritium-labelled (-)-U50,488, a selective kappa opioid agonist

    Thurkauf, A.; Costa, B. de; Rice, K.C.

    1989-01-01

    The preparation of 3 H labelled (-)-trans-3,4-dichloro-N-methyl-N[2-(1-pyrrolidinyl) cyclohexyl]benzeneacetamide (U50,488) in four steps from N-methylcyclohexylaziridine is described. The synthesis of the pharmacologically active (-) isomer of U50, 488 was accomplished through the resolution of the intermediate 2-[1-(3-pyrrolinyl)]-N-methylcyclohexylamine using (+)-mandelic acid. (Author)

  5. Palo Verde Nuclear Generating Station, Units 1, 2 and 3 (Docket Nos. STN 50-528, STN 50-529 and STN 50-530): Final environmental statement

    1975-09-01

    The proposed action is the issuance of construction permits to the Arizona public Service Company for the construction of the Palo Verde Nuclear Generating Station, Units 1, 2, and 3. Preparation of the 3800-acre site will involve the clearing of up to 2500 acres of land, 1500 of which will be prominently devoted to station facilities. An additional 1200- to 1300-acre evaporation pond will ultimately be developed during the lifetime of the station. About 2200 site acres, previously devoted to agriculture, will be excluded from this land use. Soil disturbance during construction of the station, transmission lines, and water conveyance pipeline will tend to promote erosion and increase siltation in local ephemeral water courses. Stringent measures will be taken to minimize these effects. The total radiation dose to construction workers is estimated to be 15 man-rem. This dose is a small fraction of the approximately 470 man-rem which will be received by the construction force over the same period from natural background radiation. Station, transmission line, and water pipeline construction will kill, remove, displace, or otherwise disturb involved flora and fauna, and will eliminate varying amounts of wildlife breeding, nesting, and forage habitat. These will not be important permanent impacts to the population stability and structure of the involved local ecosystems of the Sonoran desert; however, measures will be taken to minimize such effects as do result form the proposed action

  6. Palo Verde Nuclear Generating Station, Units 1, 2, and 3 (Docket Nos. STN 50-528, STN 50-529, and STN 50-530): Final environmental statement

    1982-02-01

    The proposed action is the issuance of operating licenses to the Arizona Public Service Company (APS, applicant) for the startup and operation of PVNGS, Units 1, 2, and 3, located in Maricopa County, about 24 km (15 mi) west of Buckeye, Arizona. The information in this statement represents the second assessment of the environmental impact associated with PVNGS Units 1, 2, and 3 pursuant to the guidelines of the National Environmental Policy Act of 1969 (NEPA) and Title 10 of the Code of Federal Regulations (10 CFR) Part 51 of the Commissions's Regulations. After receiving an application in July 1974 to construct this station, the staff carried out a review of impacts that would occur during its construction and operation. That evaluation was issued as a Final Environmental Statement/emdash/Construction Phase (FES-CP). After this environmental review, a safety review, an evaluation by the Advisory Committee on Reactor Safeguards, and public hearings in Phoenix, Arizona, the US Nuclear Regulatory Commission issued Construction Permits Nos. CPPR-141, CPPR-142, and CPPR-143 for the construction of PVNGS Units 1, 2, and 3. As of September 1981, the construction of Unit 1 was about 92 percent complete, Unit 2 was 68 percent complete, and Unit 3 was 26 percent complete. 11 figs., 21 tabs

  7. Callaway Plant Units 1 and 2: Final environmental statement (Docket Nos. STN 50-483 and STN 50-486)

    1975-03-01

    The proposed action is the issuance of a construction permit to the Union Electric company for the construction of the Callaway Plant Units 1 and 2. The Callaway Plant, located 5 m north of the Missouri River in Callaway County, Missouri, will employ a pressurized water reactor to produce up to 3425 megawatts thermal (MWt) from each unit. A steam turbine-generator will use the heat to provide 1120 MWe (net) of electrical power capacity. A stretch power level of 3579 MWt (1160 MWe) is anticipated at a future date and is considered in the assessments contained in this statement. The exhaust steam will be cooled in a closed cycle mode, with water from the Missouri River. Constructing the plant and adjacent facilities will disturb an area of about 600 acres, of which less than 300 acres will be occupied by the operating plant and road and rail access to it. The land presently consists of cropland, pasture and forest. About 1140 acres will be required for the transmission line routes. The land presently consists of forest, pasture and cropland. No unique land usage is involved. Siltation and erosion during construction generally will have minor adverse effects, based upon the extent of protection measures the applicant plans to impose. The effect on Logan Creek is expected to be minor, but further assessment is needed, including possible additional precautions. About 14% of the benthic invertebrate population will be lost in the rectangular area defined by the river width and the length of the area to be dredged for shoreline structures. 28 figs., 53 tabs

  8. Present attitudes of physical education students towards future employment in their profession [Současné názory studentů tělesné výchovy na jejich budoucí zaměstnání v této profesi

    Magdalena Majer

    2010-06-01

    Full Text Available OBJECTIVE: The aim of the research was to examine empirically the attitudes of physical education students towards their future profession in physical culture and some of their considerations about the choice of their field of study and their opinion about the course of studies. METHODS: The research embraced physical education students studying at the Academy of Physical Education in Cracow. The research took place in two stages (May 2005 and 2008. The first part involved first year students (N = 162, the second the same students then being fourth year students, but only those, who passed all semesters on time (N = 103. The students' attitudes towards their future profession were examined by means of a questionnaire worked out by Grabowski and Skrzypiec. RESULTS: For 45.6% of our respondents the choice of their field of study and prospective profession was determined by positive factors. More than half of the tested students (51.6% chose physical education as their field of study because of their interests and passion. Salary, stability and terms of work are also significant factors. More than half of the respondents declare their willingness to work in their profession after graduation. CONCLUSIONS: From among the values preferred while choosing the physical educator's profession, passion was the main choice of the respondents, regardless of gender. The fact that their studies' positive influence on the respondents' attitudes towards their future profession decrease clearly between the first and the last year of studies, is alarming. It would be advisable to do more detailed research in other schools to verify the educational system and the practical preparation of prospective physical education teachers.[CÍLE: Cílem výzkumu bylo empiricky posoudit názory studentů tělesné výchovy na jejich budoucí zaměstnání v tělesné výchově a některé z důvodů, proč si vybrali tento studijní obor, a jejich názory na průběh studia

  9. Determination of sites of U50,488H-promoted phosphorylation of the mouse κ opioid receptor (KOPR): disconnect between KOPR phosphorylation and internalization.

    Chen, Chongguang; Chiu, Yi-Ting; Wu, Wenman; Huang, Peng; Mann, Anika; Schulz, Stefan; Liu-Chen, Lee-Yuan

    2016-02-15

    Phosphorylation sites of KOPR (κ opioid receptor) following treatment with the selective agonist U50,488H {(-)(trans)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidiny)cyclo-hexyl]benzeneacetamide} were identified after affinity purification, SDS/PAGE, in-gel digestion with Glu-C and HPLC-MS/MS. Single- and double-phosphorylated peptides were identified containing phosphorylated Ser(356), Thr(357), Thr(363) and Ser(369) in the C-terminal domain. Antibodies were generated against three phosphopeptides containing pSer(356)/pThr(357), pThr(363) and pSer(369) respectively, and affinity-purified antibodies were found to be highly specific for phospho-KOPR. U50,488H markedly enhanced staining of the KOPR by pThr(363)-, pSer(369)- and pSer(356)/pThr(357)-specific antibodies in immunoblotting, which was blocked by the selective KOPR antagonist norbinaltorphimine. Ser(369) phosphorylation affected Thr(363) phosphorylation and vice versa, and Thr(363) or Ser(369) phosphorylation was important for Ser(356)/Thr(357) phosphorylation, revealing a phosphorylation hierarchy. U50,488H, but not etorphine, promoted robust KOPR internalization, although both were full agonists. U50,488H induced higher degrees of phosphorylation than etorphine at Ser(356)/Thr(357), Thr(363) and Ser(369) as determined by immunoblotting. Using SILAC (stable isotope labelling by amino acids in cell culture) and HPLC-MS/MS, we found that, compared with control (C), U50,488H (U) and etorphine (E) KOPR promoted single phosphorylation primarily at Thr(363) and Ser(369) with U/E ratios of 2.5 and 2 respectively. Both induced double phosphorylation at Thr(363)+Ser(369) and Thr(357)+Ser(369) with U/E ratios of 3.3 and 3.4 respectively. Only U50,488H induced triple phosphorylation at Ser(356)+Thr(357)+Ser(369). An unphosphorylated KOPR-(354-372) fragment containing all of the phosphorylation sites was detected with a C/E/U ratio of 1/0.7/0.4, indicating that ∼60% and ∼30% of the mouse KOPR are phosphorylated

  10. Leisure time, occupational, domestic, and commuting physical activity of inhabitants of the Czech Republic aged 55-69: Influence of socio-demographic and environmental factors [Pohybová aktivita obyvatel České republiky ve věku 55-69 let prováděná v rámci volného času, zaměstnání, v domácnosti a při přesunech: Vliv socio-demografických a environmentálních faktorů

    Jana Pelclová

    2009-09-01

    domácnosti, v zaměstnání a při přesunech u obyvatel České republiky ve věku 55–69 let a za druhé zjistit, které socio-demografické a environmentální faktory mohou mít vliv na plnění doporučení k pohybové aktivitě prováděné ve volném čase, v domácnosti, v zaměstnání a při přesunech. METODIKA: Dlouhá verze mezinárodního dotazníku k pohybové aktivitě (IPAQ byla využita pro zjištění pohybové aktivity u 320 náhodně vybraných obyvatel České republiky ve věku 55–69 let. Respondenti také zodpověděli doplňkové otázky vztahující se k socio-demografickým a environmentálním faktorům. VÝSLEDKY: Plnění doporučení k středně zatěžující pohybové aktivitě bylo spojeno se základním vzděláním, věkem 55–59 let (při srovnání s věkem 65-69, bydlením v rodinném domku a nekuřáctvím, zatímco významným faktorem pro plnění doporučení k chůzi byl pouze faktor zaměstnání. Odlišné socio-demografické a environmentální faktory významně ovlivňují plnění doporučení k pohybové aktivitě při zkoumání pohybové aktivity ve volném čase, v domácnosti, v zaměstnání a při přesunech. ZÁVĚRY: Tato zjištění je potřeba brát v úvahu, zejména pokud by měla být, s ohledem na česká specifika, vytvořena úspěšná strategie na podporu pohybové aktivity u lidí předdůchodového a důchodového věku.

  11. Safety evaluation report related to the operation of Palo Verde Nuclear Generating Station, Units, 1, 2, and 3: Docket Nos. STN 50-528, STN 50-529, and STN 50-530

    1983-03-01

    Information is presented concerning site characteristics; mechanical systems and components; reactor coolant system; engineered safety systems; reactor instrumentation; reactor operations; and quality assurance

  12. Final environmental statement related to construction of Cherokee Nuclear Station, Units 1, 2, and 3: (Docket Nos. STN 50-491, STN 50-492, and STN 50-493)

    1975-10-01

    The proposed action is the issuance of a construction permit to the Duke Power Company for the construction of the Cherokee Nuclear Station (CNS) Units 1, 2, and 3 located in Cherokee County, South Carolina. A total of 2263 acres will be removed from public use for the CNS site. Construction-related activities on the site will disturb about 751 acres. Approximately 654 acres of land will be required for transmission line right-of-way, and a railroad spur will affect 83 acres. This constitutes a minor regional impact. No significant environmental impacts are anticipated from normal operational releases of radioactive materials. The total annual dose to the US population (total body plus thyroid) from operation of the plant is 210 man-rems which is less than the normal fluctuations in the background dose this population would receive. The occupational dose is approximately 1400 man-rems/year. The heat dissipation system will require a maximum water makeup of 55,814 gpm, of which 50,514 gpm will be consumed due to drift and evaporative losses. This amount represents 4.5% of the mean monthly flow and 23.8% of the low flow of the Broad River. The cooling tower blowdown and chemical effluents from the station will increase the dissolved solids concentration in the river by a maximum of 44 ppM. The thermal alterations and increases in total dissolved solids concentration will not significantly affect the aquatic productivity of the river. 114 refs., 25 figs., 46 tabs

  13. Final supplement to the final environmental statement related to construction of Palo Verde Nuclear Generating Station Units 1, 2 and 3 (Docket Nos. STN 50-528, STN 50-529, and STN 50-530)

    1976-02-01

    The proposed action is the issuance of construction permits to the Arizona Public Service Company for the construction of the Palo Verde Nuclear Generating Station, Units 1, 2, and 3. Preparation of the 3800-acre site will involve the clearing of up to 2500 acres of land, 1500 of which will ultimately be developed during the lifetime of the station. About 2200 site acres, previously devoted to agriculture, will be excluded from this land use. Soil disturbance during construction of the station, transmission lines, and water conveyance pipeline will tend to promote erosion and increase siltation local ephemeral water courses. Stringent measures will be taken to minimize these effects (Sec. 4.5). Station, transmission line, and water pipeline construction will kill, remove, displace, or otherwise disturb involved flora and fauna, and will eliminate varying amounts of wildlife breeding, nesting, and forage habitat. These will not be important permanent impacts to the population stability and structure of the involved local ecosystems of the Sonoran desert; however, measures will be taken to minimize such effects as do results from the proposed action. 26 refs., 1 fig., 20 tabs

  14. Safety evaluation report related to the operation of Palo Verde nuclear generating station, Units 1, 2, and 3. Docket Nos. STN 50-528, STN 50-529, and STN 50-530, Arizona Public Service Company

    1982-05-01

    On November 13, 1981, the Nuclear Regulatory Commission (NRC) staff issued its Safety Evaluation Report (SER) relating to the application for licenses to operate the Palo Verde Nuclear Generating Station, Unit Nos. 1, 2 and 3 (PVNGS 1-3); Supplement No. 1 to the SER was issued on February 4, 1982. In the SER and Supplement No. 1, the staff identified certain issues where either further information was required of the applicant or additional staff effort was necessary to complete the review of the application. The purpose of this supplement is to update the SER by providing (1) the evaluation of additional information submitted by the applicant since Supplement No. 1 to the SER was issued, and (2) the evaluation of the matters that the staff had under review and Supplement No. 1 was issued

  15. Palo Verde Nuclear Generating Station, Units 1, 2 and 3 (Docket Nos. STN 50-528, STN 50-529 and STN 50-530): Draft supplement to the Final environmental satement

    1975-11-01

    The proposed action is the issuance of construction permits to the Arizona Public Service Company for the construction of the Palo Verde Nuclear Generating Station, Units 1, 2, and 3. Preparation of the 3800-acre site will involve the clearing of up to 2500 acres of land, 1500 of which will be permanently devoted to station facilities. An additional 1200- to 1300-acre evaporation pond will ultimately be developed during the lifetime of the station. About 2200 site acres, previously devoted to agriculture, will be excluded from this land use. Soil disturbance during construction of the station, transmission lines, and water conveyance pipeline will tend to promote erosion and increase siltation in local ephemeral water courses. Stringent measures will be taken to minimize these effects. Station, transmission line, and water pipeline construction will kill, remove, displace, or otherwise disturb involved flora and fauna, and will eliminate varying amounts of wildlife breeding, nesting, and forage habitat. These will not be important permanent impacts to the population stability and structure of the involved local ecosystems of the Sonoran desert; however, measures will be taken to minimize such effects as do result from the proposed action. The pumping of groundwater will cause a local drawdown of about 1 ft/yr, less than that currently occurring; hence, the impact is considered acceptable. 1 fig., 20 tabs

  16. Safety evaluation report related to the operation of Palo Verde Nuclear Generating Station, Units 1, 2, and 3: Docket Nos. STN 50-528, STN 50-529, and STN 50-530

    1982-09-01

    Additional information is presented concerning site characteristics; inservice testing of pumps and valves; reactor coolant system; engineered safety systems; electric power systems; auxiliary systems; and quality assurance

  17. Safety Evaluation Report related to the operation of Palo Verde Nuclear Generating Station, Units 1, 2, and 3 (Docket Nos. STN 50-528, STN 50-529, and STN 50-530). Supplement No. 8

    1985-05-01

    Purpose of this supplement is to update the Safety Evaluation Report by providing an evaluation of additional information submitted by the applicant since Supplement No. 7 was issued and matters that the staff had under review when Supplement No. 7 was issued, specifically those issues which required resolution prior to plant operation of Unit 1 above 5% full power

  18. Safety Evaluation Report related to the operation of Byron Station, Units 1 and 2 (Docket Nos. STN 50-454 and STN 50-455). Supplement No. 7

    1986-11-01

    Supplement No. 7 to the Safety Evaluation Report related to Commonwealth Edison Company's application for licenses to operate the Byron Station, Units 1 and 2, located in Rockvale Township, Ogle County, Illinois, has been prepared by the Office of Nuclear Reactor Regulation of the US Nuclear Regulatory Commission. This supplement provides additional information supporting the license for initial criticality and power ascension to full-power operation for Unit 2

  19. Technical Specifications, Braidwood Station, Unit Nos. 1 and 2 (Docket Nos. STN 50-456 and STN 50-457). Appendix ''A'' to License No. NPF-59

    1986-10-01

    Information is presented for Braidwood Station Unit Nos. 1 and 2 in the areas of: safety limits and limiting safety system settings; limiting conditions for operation and surveillance requirements; design features; and administrative controls

  20. Technical Specifications, Byron Station, Unit Nos. 1 and 2 (Docket Nos. STN 50-454 and STN 50-455). Appendix A to license No. NPF-37

    1985-02-01

    The Byron Station, Unit No. 1 and Unit No. 2 Technical Specifications were prepared by the US Nuclear Regulatory Commission to set forth the limits, operating conditions, and other requirements applicable to a nuclear reactor facility as set forth in Section 50.36 of 10 CFR Part 50 for the protection of the health and safety of the public. Specifications are presented for limiting conditions for operation for the reactor control system, power distribution limits, instrumentation, primary coolant circuit, ECCS, containment systems, plant systems, electrical power systems, refueling operations, radioactive effluents, and radiological environmental monitoring

  1. Marble Hill Nuclear Generating Station, Units 1 and 2: Final environmental statement (Docket Nos. STN 50-546 and STN 50-547)

    1976-09-01

    The proposed action is the issuance of construction permits to the Public Service Company of Indiana, Inc., Northern Indiana Public Service Company, Inc., East Kentucky Power Cooperative, Inc., and Wabash Valley Power Association for the construction of the Marble Hill Nuclear Generating Station, Units 1 and 2 (MH 1and2). The 987-acre site is predominately forest and cropland. Construction-related activities on the site would disturb about 250 acres. The portion of this land not be used for the plant facilities, parking lots, roads, etc., will be restored by seeding and landscaping. The temporary removal of vegetation will tend to promote erosion. Increased siltation and turbidity can be expected in local streams during construction, but measures will be taken to minimize these effects. A maximum of 69 cfs of cooling water will be withdrawn from the Ohio River of which cfs will be returned to the river via pipeline with the dissolved solids concentration increased by a factor of about 6. About cfs will be evaporated to the atmosphere by the cooling towers. The volume of discharge (9 cfs) is very small compared with the river flow (annual mean is about 110,000 cfs) and the thermal effect on the river ecosystem is not expected to be significant. Chemical discharges from the plant will be diluted to concentrations below those which might adversely affect aquatic biota. The risk associated with accidental radiation exposure will be very low. 43 figs., 115 tabs

  2. Safety Evaluation Report related to the operation of Byron Station, Units 1 and 2 (Dockets Nos. STN 50-454 and STN 50-455)

    1984-10-01

    Supplement No. 5 to the Safety Evaluation Report related to Commonwealth Edison Company's application for licenses to operate the Byron Station, Units 1 and 2, located in Rockvale Township, Ogle County, Illinois, has been prepared by the Office of Nuclear Reactor Regulation of the US Nuclear Regulatory Commission. This supplement reports the status of certain items that had not been resolved at the time of publication of the Safety Evaluation Report. Because of the favorable resolution of the items discussed in this report, the staff concludes that there is reasonable assurance that the facility can be operated by the applicant without endangering the health and safety of the public

  3. Final environmental statement related to the operation of Byron Station, Units 1 and 2 (Docket Nos. STN 50-454 and STN 50-455)

    1982-04-01

    The proposed action is the issuance of an operating license to Commonwealth Edison Company (CECo) of Chicago, Illinois, for startup and operation of the Byron Station, Units 1 and 2 on a 710-ha (1754-acre) site in Ogle County 6 km (4 miles) south-southwest of Byron, Illinois, and 3 km (2 miles) east of the Rock River. Each of the two generating units consists of a pressurized-water reactor, four steam generators, one steam turbine generator, a heat-dissipation system, and associated auxiliary and engineered safeguards. Information is presented under the following topics: purpose and need for the action; alternatives to the proposed action; project description and affected environment; environmental consequences and mitigating actions; evaluation of the proposed action; list of contributors; list of agencies and organizations requested to comment on the draft environmental statement; and responses to comments on the Draft Environmental Statement

  4. Draft environmental statement related to the operation of Braidwood Station, Units 1 and 2 (Docket Nos. STN 50-456 and STN 50-457)

    1983-12-01

    The Draft Environment Statement contains the second assessment of the environmental impact associated with the operation of Braidwood Station, Units 1 and 2, pursuant to the National Environmental Policy Act of 1969 (NEPA) and Title 10 of the Code of Federal Regulations, Part 51, as amended, of the Nuclear Regulatory Commission regulations. This statement examines the environment, environmental consequences and mitigating actions, and environmental and economic benefits and costs. Land use and terrestrial and aquatic ecological impacts will be small. Operational impacts to historic and archeologic sites will be negligible. The effects of routine operations, energy transmission, and periodic maintenance of rights of way and transmission facilities should not jeopardize any populations of endangered or threatened species. No significant impacts are anticipated from normal operational releases of radioactivity. The risk of radiation exposure associated with accidental release of radioactivity is very low. The net socioeconomi effects of the project will be beneficial. On the basis of the analysis and evaluation set forth in this environmental statement, it is concluded that the action called for under NEPA and 10 CFR 51 is the issuance of operating licenses for Braidwood Station, Units 1 and 2

  5. Technical specifications, Braidwood Station, Unit Nos. 1 and 2 (Docket Nos. STN 50-456 and STN 50-457): Appendix ''A'' to License No. NPF-70

    1987-05-01

    The Braidwood Station, Unit Nos. 1 and 2, Technical Specifications were prepared by the US Nuclear Regulatory Commission to set forth the limits, operating conditions, and other requirements applicable to a nuclear reactor facility as set forth in Section 50.36 of 10 CFR Part 50 for the protection of the health and safety of the public. 18 figs., 55 tabs

  6. Draft environmental statement related to the proposed Jamesport Nuclear Power Station, Units 1 and 2: (Docket Nos. STN-50-516 and STN-50-517)

    1975-02-01

    The proposed action is the issuance of construction permits to the Long Island Lighting Company for the construction of the Jamesport Nuclear Power Station, Units 1 and 2, located on Long Island Sound in the Town of Riverhead, New York. Operation of the proposed once-through cooling system will result in the heating of 4180 cfs of water by 18/degree/F. Phytoplankton, zooplankton, and ichthyoplankton will be entrained by the cooling system. The organisms in approximately 40 /times/ 10 9 ft 3 of water per year will suffer direct mortality due to chlorination and heat shock. The risk associated with accidental radiation exposure will be very low. A bottom area of some 105.5 acres will be affected by dredging and jetty construction. Of this total, 4.35 acres will be permanently replaced by jetties, and 101.15 acres will be temporarily (a total of four years) disrupted by dredging. This impact will be temporary, since the dredged areas will be recolonized by the benthic community upon completion of work. There is a potential for substantial impingement loss of fishes on the intake screens which will require additional data to quantify. Approximately 39 miles of transmission lines will be constructed. Ninety-two percent of the total routings utilize existing rights-of-way, railroad rights-of-way, or new rights-of-way immediately adjacent to railroad rights-of-way. The rights-of-way will require approximately 621 acres. 65 refs., 64 tabs

  7. Final environmental statement related to the operation of Braidwood Station, Units 1 and 2 (Docket Nos. STN 50-456 and STN 50-457)

    1984-06-01

    This Final Environmental Statement contains the second assessment of the environmental impact associated with the operation of Braidwood Station, Units 1 and 2, pursuant to the National Environmental Policy Act of 1969 (NEPA) and Title 10 of the Code of Federal Regulations, Part 51, as amended, of the Nuclear Regulatory Commission regulations. This statement examines the environment, environmental consequences and mitigating actions, and environmental and economic benefits and costs. Land use and terrestrial and aquatic ecological impacts will be small. Operational impacts to historic and archeologic sites will be moderate. The effects of routine operations, energy transmission, and periodic maintenance of rights of way and transmission facilities should not jeopardize any populations of endangered or threatened species. No significant impacts are anticipated from normal operational releases of radioactivity. The risk of radiation exposure associated with accidental release of radioactivity is very low. The net socioeconomic effects of the project will be beneficial. On the basis of the analysis and evaluation set forth in this environmental statement, it is concluded that the action called for under NEPA and 10 CFR 51 is the issuance of operating licenses for Braidwood Station, Units 1 and 2. 27 figures, 23 tables

  8. Revised draft environmental statement related to construction of Atlantic Generating Station Units 1 and 2 (Docket Nos. STN 50-477 and STN 50-478)

    1976-10-01

    The proposed action is the issuance of a construction permit to Public Service Electric and Gas Company (PDE and G) for the construction of the Atlantic Generating Station (AGS), Units 1 and 2. The AGS is the first nuclear power station in the United States proposed for construction in the offshore waters on the continental shelf. The AHS will be located in the Atlantic Ocean 2.8 miles offshore of Atlantic and Ocean countries. New Jersey, 11 miles northeast of Atlantic City, and will consist of two floating nuclear power plants enclosed in a protective rubble-mound breakwater. Both plants will be identical, of standardized design, and will employ pressurized water reactors to produce up to approximately 3425 megawatts thermal (MWt) each. Steam turbine generators will use this heat to produce up to approximately 1150 megawatts of electrical power (MWe) per unit. The main condensers will be cooled by the flow of seawater drawn from within the breakwater and discharged shoreward and external to the breakwater. This statement identifies various environmental aspects and potential adverse effects associated with the construction and operation of the AGS. Based upon an approximate two-year review period which included a multidisciplined assessment of extensive survey and modeling data, these effects are considered by the staff to be of a generally acceptable nature. Breakwater construction will result in the destruction of 100 acres of benthic infauna (burrowing animals) and the development of a reef-type community on the breakwater. The production of new biomass (standing crop) by the reef community is expected to compensate for the infaunal biomass destroyed by dredging and will contribute mainly to the local sport fishery. 93 figs., 110 tabs

  9. Final Environmental Statement related to the operation of Shearon Harris Nuclear Power Plant, Units 1 and 2 (Docket Nos. STN 50-400 and STN 50-401)

    1983-10-01

    This Final Environmental Statement contains the second assessment of the environmental impact associated with the operation of the Shoran Harris Nuclear Power Plant, Units 1 and 2, pursuant to the National Environmental Policy Act of 1969 (NEPA) and 10 CFR 51, as amended, of the NRC regulations. This statement examines the environment, environmental consequences and mitigating actions, and environmental economic benefits and costs. Land use and terrestrial and aquatic-ecological impacts will be small. Operational impacts to historic and archaeological sites will be negligible. The effects of routine operations, energy transmission, and periodic maintenance of rights-of-way and transmission facilities should not jeopardize any populations of endangered or threatened species. No significant impacts are anticipated from normal operational releases of radioactivity. The risk of radiation exposure associated with accidental release of radioactivity is very low. The net socioeconomic effects of the project will be beneficial. 19 figs., 21 tabs

  10. Safety Evaluation Report, related to the operation of Byron Station, Units 1 and 2 (Docket Nos. STN 50-454 and STN 50-455)

    1983-11-01

    Supplement No. 3 to the Safety Evaluation Report related to Commonwealth Edison Company's application for licenses to operate the Byron Station, Units 1 and 2, located in Rockvale Township, Ogle County, Illinois, has been prepared by the Office of Nuclear Reactor Regulation of the US Nuclear Regulatory Commission. This supplement reports the status of certain items that had not been resolved at the time of publication of the Safety Evaluation Report

  11. Draft environmental statement related to the operation of Shearon Harris Nuclear Power Plant, Units 1 and 2. Docket Nos. STN 50-400 and STN 50-401

    1983-04-01

    This Draft Environmental Statement contains the second assessment of the environmental impact associated with the operation of the Shearon Harris Nuclear Power Plant, Units 1 and 2, pursuant to the National Environmental Policy Act of 1979 (NEPA) and 10 CFR 51, as amended, of the NRC regulations. This statement examines the environment, environmental consequences and mitigating actions, and environmental and economic benefits and costs. Land use and terrestrial and aquatic-ecological impacts will be small. Operational impacts to historic and archeological sites will be negligible. The effects of routine operations, energy transmission, and periodic maintenance of rights-of-way and transmission facilities should not jeopardize any populations of endangered or threatened species. No significant impacts are anticipated from normal operational releases of radioactivity. The risk of radiation exposure associated with accidental release of radioactivity is very low. The net socio-economic effects of the project will be beneficial. The action called for is the issuance of an operating license for Shearon Harris PLant, Units 1 and 2

  12. Safety evaluation report related to the operation of Shearon Harris Nuclear Power Plant, Units 1 and 2. Docket Nos. STN 50-400 and STN 50-401

    1983-11-01

    The Safety Evaluation Report for the application filed by the Carolina Power and Light Company, as applicant and owner, for licenses to operate the Shearon Harris Nuclear Power Plant Units 1 and 2 (Docket Nos. 50-400 and 50-401) has been prepared by the Office of Nuclear Reactor Regulation of US Nuclear Regulatory Commission. The facility is located near Raleigh, North Carolina. Subject to favorable resolution of the items discussed in this report, the NRC staff concludes that the facility can be operated by the applicant without endangering the health and safety of the public

  13. Safety evaluation report related to the operation of Byron Station, Units 1 and 2. Docket Nos. STN 50-454 and STN 50-455

    1983-01-01

    Supplement No. 2 to the Safety Evaluation Report related to Commonwealth Edison Company's application for licenses to operate the Byron Station, Units 1 and 2, located in Rockvale Township, Ogle County, Illinois, has been prepared by the Office of Nuclear Reactor Regulation of the US Nuclear Regulatory Commission. This supplement reports the status of certain items that had not been resolved at the time of publication of the Safety Evaluation Report

  14. Safety Evaluation Report related to the operation of Byron Station, Units 1 and 2 (Docket Nos. STN 50-454 and STN 50-455)

    1984-05-01

    Supplement No. 4 to the Safety Evaluation Report related to Commonwealth Edison Company's application for licenses to operate the Byron Station, Units 1 and 2, located in Rockvale Township, Ogle County, Illinois, has been prepared by the Office of Nuclear Reactor Regulation of the US Nuclear Regulatory Commission. This supplement reports the status of certain items that had not been resolved at the time of publication of the Safety Evaluation Report

  15. Safety Evaluation Report related to the operation of Braidwood Station, Units 1 and 2 (Docket Nos. STN 50-456 and STN 50-457)

    1988-06-01

    In November 1983, the staff of the Nuclear Regulatory Commission issued its Safety Evaluation Report (NUREG-1002) regarding the application filed by the Commonwealth Edison Company, as applicant and owner, for a license to operate Braidwood Station, Units 1 and 2 (Docket Nos. 50-456 and 50-457). The first supplement to NUREG-1002 was issued in September 1986; the second supplement was issued in October 1986; the third supplement was issued in May 1987; the fourth supplement was issued in July 1987 in support of the full power license for Unit 1; the fifth supplement was issued in December 1987 in support of the low power license for Unit 2. This sixth supplement to NUREG-1002 is in support of the full-power license for Unit 2 and provides the status of items that remained unresolved at the time Supplement 5 was published. The facility is located in Reed Township, Will County, Illinois

  16. Draft environmental statement related to construction of Erie Nuclear Plant, Units 1 and 2: (Docket Nos. STN 50-580 and STN 50-581)

    1977-11-01

    The proposed action is the issuance of construction permits to the Ohio Edison Company, acting on behalf of itself, the Cleveland Electric Illuminating Company, Duquesne Light Company, Pennsylvania Power Company, and the Toledo Edison Company, for the construction of the Erie Nuclear Plant Units 1 and 2, located in Erie County, Ohio. A total of 704 hectares (ha) (1740 acres) will be used for the Erie plant site. Construction-related activities on the primary site will disturb about 223 ha (551 acres). Approximately 641 ha (1584 acres) will be required for transmission line rights-of-way. The 3.86-km (2.4-mile) intake and discharge pipeline land corridor will involve alteration of approximately 13 ha (32 acres) of corridor and 1 ha (2.5 acres) for shore facilities. Also, 3.9 ha (9.6 acres) of lake bottom will be disturbed to provide 15-m-wide (50-ft-wide) trenches and an additional 15-m-wide (50-ft-wide) area for storage of excavated material for subsequent backfill for the 701-m (2300-ft) intake and 579-m (1900-ft) discharge lines. Plant construction will involve some community impacts. No residents will be displaced from the site property. Traffic on local roads will increase due to construction and commuting activities. The influx of construction workers' families (a peak work force of about 2700) is expected to cause no major housing or school problems. It is assumed that aquatic organisms entrained in the circulating water system will be killed due to thermal and mechanical shock. The maximum impact based on the population densities of phytoplankton and zooplankton organisms in the adjacent lake area will be the destruction of 0.1% of the entrainable organisms from the lake water. The entrainment of fish larvae will not constitute a significant impact on the lake fishery. 62 figs., 32 tabs

  17. Safety Evaluation report related to the operation of Braidwood Station, Units 1 and 2 (Docket Nos. STN 50-456 and STN 50-457)

    1987-07-01

    In November 1983, the staff of the Nuclear Regulatory Commission issued its Safety Evaluation Report (NUREG-1002) regarding the application filed by the Commonwealth Edison Company, as applicant and owner, for a license to operate Braidwood Station, Units 1 and 2 (Docket Nos. 50-456 and 50-457). The first supplement to NUREG-1002 was issued in September 1986; the second supplement to NUREG-1002 was issued in October 1986; the third supplement to NUREG-1002 was issued in May 1987. This fourth supplement to NUREG-1002 reports the status of certain items that remained unresolved at the time Supplement 3 was published. The facility is located in Reed Township, Will County, Illinois

  18. Safety evaluation report related to the operation of Byron Station, Units 1 and 2 (Docket Nos. STN 50-454 and STN 50-455)

    1987-03-01

    Supplement No. 8 to the Safety Evaluation Report related to Commonwealth Edison Company's application for licenses to operate the Byron Station, Units 1 and 2, located in Rockvale Township, Ogle County, Illinois, has been prepared by th Office of Nuclear Reactor Regulation of the US Nuclear Regulatory Commission. This supplement provides recent information regarding resolution of the license conditions identified in the SER. Because of the favorable resolution of the items discussed in this report, the staff concludes that the Byron Station, Unit 2 can be operated by the licensee at power levels greater than 5% without endangering the health and safety of the public

  19. Draft environmental statement related to construction of Yellow Creek Nuclear Plant, Units 1 and 2: (Docket Nos. STN 50-566 and STN 50-567)

    1977-06-01

    The proposed action is the issuance of construction permits to the Tennessee Valley Authority for the construction of the Yellow Creek Nuclear Plant Units 1 and 2. The 470-hectare site is predominantly wooded. Construction-related activities on the site would disturb about 59 hectares. The portion of this land not to be used for plant facilities, parking lots, roads, etc., will be restored by seeding and landscaping. The temporary removal of vegetation will tend to promote erosion. Increased siltation and turbidity can be expected in the Yellow Creek embayment during construction, but measures will be taken to minimize these effects. A maximum of 237.6 m 3 /min of make-up water will be withdrawn from the Yellow Creek embayment, of which 106 m 3 /min will be returned to Pickwick Lake via a pipeline with the dissolved solids concentration increased by a factor of about two. About 106 m 3 /min will be evaporated to the atmosphere by the cooling towers. The volume of thermal discharge (106 m 3 /min) is small compared with the flow in Pickwick Lake (minimum daily average flow of 7812 m 3 /min) and the effect on the Pickwick Lake ecosystem is not expected to be significant. During periods of average flow the plant could use about 24% of the flow through Yellow Creek embayment. Chemical discharges (with the possible exception of copper) from the plant will be diluted to concentrations below those which might adversely affect aquatic biota. The risk associated with accidental radiation exposure will be very low. 42 figs., 100 tabs

  20. Performance of Electrolyte Supported Solid Oxide Fuel Cells with STN Anodes

    Veltzé, Sune; Reddy Sudireddy, Bhaskar; Jørgensen, Peter Stanley

    2013-01-01

    In order to replace the state of the art Ni-cermet as SOFC anode, electrolyte supported cells comprising CGO/Ni infiltrated Nbdoped SrTiO3 anodes, and LSM/YSZ cathodes have been developed and tested as single 5 x 5 cm2 cells. The initial performance reached 0.4 W/cm2 at 850 C. Further tests under...

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    Konečná, Hana

    2010-01-01

    Roč. 51, č. 1 (2010), s. 269-298 ISSN 1211-4413 R&D Projects: GA ČR GA405/08/0703 Institutional research plan: CEZ:AV0Z90610518 Keywords : anoikonyms * Jemnice * Lhotice * survey Subject RIV: AI - Linguistics

  2. Psychologické problémy odchodu ze zaměstnání

    Plecháčková, Veronika

    2008-01-01

    Bachelor thesis "Psychological problems related to leaving one's job" considers negative impacts related to leaving one's job, job loss, change of job status, change of status from employed to unemployed. The thesis theoretically summarizes existing problems in five chapters. It defines basic facts, informs about basic researches of unemployment impact on individua and family. The main part of the thesis describes psychological and psycho-sociological impact of unemployment. Its impact on phy...

  3. Technical specifications, Braidwood Station Unit Nos. 1 and 2 (Docket Nos. STN 50-456 and STN 50-457): Appendix ''A'' to License No. NPF-72, [October 1986-July 1987

    1987-07-01

    The Braidwood Station, Units 1 and 2, technical specifications were prepared by the US Nuclear Regulatory Commission to set forth the limits, operating conditions, and other requirements applicable to a nuclear reactor facility as set forth in Section 50.36 of 10 CFR Part 50 for the protection of the health and safety of the public

  4. Final supplement to the final environmental statement related to construction of Skagit Nuclear Power Project, Units 1 and 2: (Docket Nos. STN 50-522 and STN 50-523)

    1977-04-01

    The proposed action is the issuance of construction permits to the Puget Sound Power and Light Company, Pacific Power and Light Company, Washington Water Power Company and the Portland General Electric Company, for the construction of Skagit Nuclear Power Projects Units 1 and 2 in Skagit County, Washington (about 64 miles north of Seattle and 6 miles ENE of Sedro Woolley). These units are scheduled for commercial service in 1984 and 1986, respectively. The exhaust steam from the turbine-generators will be cooled in condensers which will utilize one hyperbolic-type natural-draft cooling tower per unit to dissipate heat to the atmosphere. Water (106 cfs max.) for the cooling tower makeup (82.4 cfs) and other plant uses will be withdrawn from the Skagit River through Ranney Collectors embedded in the north bank of the river and pumped to the plant through a pipeline about 35,000 ft. long. Cooling tower blowdown (7 cfs max.) from the project and dilution water (20 cfs max.) will flow through a pipeline back to the river where it will be discharged through a diffuser. Approximately 1750 acres of forested and agricultural land will be removed from harvesting for the life of the power plant; 360 acres of this land will be diverted to industrial use. This will affect less than 0.5% of standing forest in Skagit County and 16 acres in cultivated crops and pasturage. Increased siltation of onsite creeks and the Skagit River from construction work and the small amounts of heat and chemicals discharged to the river during plant operation will have insignificant impacts on water quality and aquatic biota due to erosion control efforts and dilution by the large river flow. (16,200 cfs average; 4740 cfs 7-day, 10-yr low). 18 figs

  5. Pomístní jména a jejich zpracování ve Slovníku pomístních jmen na Moravě a ve Slezsku

    Šipková, Milena

    2010-01-01

    Roč. 51, č. 1 (2010), s. 48-78 ISSN 1211-4413 R&D Projects: GA ČR GA405/08/0703 Institutional research plan: CEZ:AV0Z90610518 Keywords : anoikonyms * dictionary * dialects * onymic maps * anoikonyms area * Dictionary of Moravian and Sikesian anoikonyms / minor place names Subject RIV: AI - Linguistics

  6. Pomístní jména na území obce Otročiněves

    Klimtová, Barbora

    2012-01-01

    Roč. 53, č. 1 (2012), s. 149-161 ISSN 1211-4413 Institutional support: RVO:68378092 Keywords : minor place names * age group * direct research * Central Bohemia * communication * maps Subject RIV: AI - Linguistics

  7. Perceived Changes in Communication as an Effect of STN Surgery in Parkinson's Disease: A Qualitative Interview Study

    Emilia Ahlberg

    2011-01-01

    Full Text Available The aim of the present study was to explore four individuals' perspective of the way their speech and communication changed as a result of subthalamic nucleus deep brain stimulation treatment for Parkinson's disease. Interviews of two men and two women were analyzed using qualitative content analysis. Three themes emerged as a result of the analysis. The first theme included sub-themes describing both increased and unexpected communication difficulties such as a more vulnerable speech function, re-emerging stuttering and cognitive difficulties affecting communication. The second theme comprised strategies to improve communication, using different speech techniques and communicative support, as well as trying to achieve changes in medical and stimulation parameters. The third theme included descriptions of mixed feelings surrounding the surgery. Participants described the surgery as an unavoidable dramatic change, associated both with improved quality of life but also uncertainty and lack of information, particularly regarding speech and communication changes. Despite negative effects on speech, the individuals were generally very pleased with the surgical outcome. More information before surgery regarding possible side effects on speech, meeting with a previously treated patient and possibly voice and speech therapy before or after surgery are suggested to facilitate the adjustment to the new speech conditions.

  8. Technical specifications: Byron Station Unit No. 1 (Docket No. STN 50-454). Appendix A to License No. NPF-23

    1984-10-01

    Specifications are presented concerning safety limits; reactor control systems; instrumentation; coolant circuits; emergency core cooling systems; containment systems; plant systems; electrical power systems; refueling operations; radioactive effluents; radiological environmental monitoring; design features; and administrative controls

  9. Technical specifications, Callaway Plant, Unit No. 1. Appendix A to license No. NPF-25 (Docket No. STN 50-483)

    Anderson, F.D.

    1984-06-01

    Technical specifications are presented for the limiting conditions for operation and surveillance requirements for the reactor core, reactivity control systems, power distribution limits, instrumentation, reactor coolant system, emergency core cooling systems, containment systems, plant systems, electrical power systems, refueling operations, special test exceptions, radioactive effluents, radiological environmental monitoring; design features of the site, containment, core, coolant system, and fuel storage; and plant staff organization

  10. Spokojenost se životem a zaměstnáním v České republice

    Mysíková, Martina; Večerník, Jiří

    2016-01-01

    Roč. 64, č. 7 (2016), s. 851-866 ISSN 0032-3233 R&D Projects: GA ČR(CZ) GA14-15008S Institutional support: RVO:68378025 Keywords : life satisfaction * job satisfaction * subjective well-being * Czech Republic Subject RIV: AH - Economics Impact factor: 0.589, year: 2016

  11. Sufix -na v pomístních jménech v Čechách

    Štěpán, Pavel

    2015-01-01

    Roč. 98, č. 2 (2015), s. 79-90 ISSN 0027-8203 R&D Projects: GA ČR GPP406/12/P600 Institutional support: RVO:68378092 Keywords : minor place names * functions of suffixes * sufix -na * suffixation Subject RIV: AI - Linguistics

  12. Kámen v pomístních jménech Moravy a Slezska

    Štefková, Marta

    2012-01-01

    Roč. 53, č. 1 (2012), s. 282-294 ISSN 1211-4413 R&D Projects: GA ČR GAP406/11/1786 Keywords : anoikonyms * minor place names * structure type * motivation * stone * rock Subject RIV: AI - Linguistics

  13. Dialektologie a Slovník pomístních jmen na Moravě a ve Slezsku

    Čižmárová, Libuše

    -, - (2011), s. 6-6. ISBN 978-80-86496-49-8. [Čeština v pohledu synchronním a diachronním. 01.06.2011-03.06.2011, Praha] Institutional research plan: CEZ:AV0Z90610518 Keywords : minor place names * dialectology * onomastics * dialect dictionary * interactive electronic dictionary * dialect development * comparative maps Subject RIV: AI - Linguistics

  14. stní měny: Alternativa pro chudé a zelené regiony?

    Kaisner, Jakub

    2010-01-01

    Do local currency initiatives rise in poorer regions with preference of green politics? That's one of the questions, that paper focused on regional currencies in Germany tried to answer. Analysis was performed on the sample of 29 districts, where the local currency project has been attempted. Research revealed the uneven concentration of projects in the country in favor of the wealthier areas with lower unemployment rates, a result opposite to that of similar research in the U.S. The assumpti...

  15. Význam rodiny a její kombinace se zaměstnáním

    Urbanová, Lucie

    2011-01-01

    This bachelor thesis considers the importance of a family and the question of harmonization of family and work life.It defines a family and work as very significant parts of a human life and points at some main attitudes towards the issues of putting family life and work together. Some transformations in terms of the relationship between a family and work in the past are suggested. There are also stated some basic measures of the state, which support a family. This thesis also considers the p...

  16. Safety-Evaluation Report related to the operation of Wolf Creek Generating Station, Unit No. 1. Docket No. STN 50-482. Supplement No. 2

    1983-06-01

    Additional information is presented concerning design criteria for structures, systems, and components; fuel elements; pressure vessel; instrumentation and control; emergency plans; quality assurance; and requirements related to the Three Mile Island-2 reactor accident

  17. Effect of Ru/CGO versus Ni/CGO Co- Infiltration on the Performance and Stability of STN-Based SOFCs

    Ramos, Tania; Veltzé, Sune; Sudireddy, Bhaskar Reddy

    2014-01-01

    /CGO infiltrated cell reached ∼0.7 W cm–2 at 850 °C, 4% H2O/H2, whereas the Ni/CGO infiltrated cell reached ∼0.3 W cm–2, with the current morphologies and loadings. Operation at 0.125 A cm–2, 850 °C, feeding 50% H2O/H2 to the anode and air to the cathode, for a period >300 h, showed superior stability for the Ru....../CGO infiltrated cell, with ∼0.04 mV h–1 degradation rate, when compared to the Ni/CGO infiltrated cell (∼0.5 mV h–1). For the Ni/CGO case, the observed degradation has been tentatively linked to initial changes in the electrochemical active area and longterm detrimental interactions between components....

  18. Prefixálně-sufixální adjektiva v pomístních jménech v Čechách

    Štěpán, Pavel

    2011-01-01

    Roč. 94, č. 4 (2011), s. 194-203 ISSN 0027-8203 Institutional research plan: CEZ:AV0Z90610518 Keywords : minor place-names * adjectives * prefixal-suffixal formation * word-formation Subject RIV: AI - Linguistics

  19. Title list of documents made publicly available. Documents from October-December 1978 for Dockets 50-334 through STN 50-597

    1978-01-01

    This special edition of the Title List contains Docket 50 material from 1978 that has not appeared in previous issues of the Title List. The documents in this supplement are indexed by personal author, corporate source, and report number. The listings of this material on the domestic licensing of production and utilization facilities, divided into the categories used for filing and searching in the NRC Public Document Room, are presented

  20. Final Environmental Statement related to the operation of Wolf Creek Generating Station, Unit No. 1. Docket No. STN 50-482, Kansas Gas and Electric Company, et al

    1982-06-01

    This final environmental statement contains the second assessment of the environmental impact associated with operation of Wolf Creek Generating Station Unit 1 pursuant to the National Environmental Policy Act of 1969 (NEPA) and 10 CFR Part 51, as amended, of the NRC's regulations. This statement examines: the affected environment, environmental consequences and mitigating actions, and environmental and economic benefits and costs. Land use and terrestrial- and aquatic-ecological impacts will be small. Air-quality impacts will also be small. However, steam fog from the station's cooling lake has the potential for reducing visibility over nearby roads and bridges. A fog-monitoring program for roads and bridges near the lake has been recommended. Impacts to historic and prehistoric sites will be negligible. Chemical discharges to the Neosho River are expected to have no appreciable impacts on water quality under normal conditions and will be required to meet conditions of the station's NPDES permit. The effects of routine operations, energy transmission, and periodic maintenance of rights-of-way and transmission line facilities should not jeopardize any populations of endangered or threatened species. No significant impacts are anticipated from normal operational releases of radioactivity. The risk associated with accidental radiation exposure is very low. The net socioeconomic effects of the project will be beneficial. The action called for is the issuance of an operating license for the Wolf Creek Generating Station Unit 1

  1. Pomístní jména, jejich stabilita a vztah k historii krajiny. Na příkladu Bernartic u Milevska

    Dohnal, Martin

    2016-01-01

    Roč. 42, č. 1 (2016), s. 43-82 ISSN 0323-0988 Institutional support: RVO:68378076 Keywords : local names * historical landscape * Early Modern history * 1600-2000 * Bernartice (district of Písek) Subject RIV: AC - Archeology, Anthropology, Ethnology

  2. Safety evaluation report related to the operation of Wolf Creek Generating Staton, Unit No. 1, (Docket No. STN 50-482). Supplement No. 4

    1983-12-01

    Supplement No. 4 to the Safety Evaluation Report related to the operation of the Wolf Creek Generating Station, Unit No. 1 updates the information contained in the Safety Evaluation Report, dated April 1982 and Supplements 1, 2, and 3, dated August 1982, June 1983 and August, 1983, respectively. Supplement No. 4 addresses open issues, confirmatory items and addresses Board Notifications. The Safety Evaluation and its supplements pertain to the application for a license to operate the Wolf Creek Generating Station, Unit No. 1 filed by Kansas Gas and Electric Company on February 19, 1980. The Construction Permit No. CPPR-147 was issued on May 17, 1977

  3. Konfrontace znalosti pomístních jmen v Jemnici, Rosicích a ve Lhoticích

    Ireinová, Martina; Konečná, Hana

    2010-01-01

    Roč. 51, č. 1 (2010), s. 299-304 ISSN 1211-4413 R&D Projects: GA ČR GA405/08/0703 Institutional research plan: CEZ:AV0Z90610518 Keywords : anoikonyms * Rosice * Jemnice * Lhotice * confrontation Subject RIV: AI - Linguistics

  4. Safety Evaluation Report related to the operation of Wolf Creek Generating Station, Unit No. 1. Docket No. STN 50-482. Kansas Gas and Electric Company, et al

    1982-08-01

    Information is presented concerning site characteristics; design criteria for structures, systems, and components; engineered safety features; instrumentation and controls; conduct of operations; accident analysis; report of the Advisory Committee on Reactor Safeguards; and TMI-2 requirements

  5. stní klimatické zóny a jejich význam ve městech České republiky

    Lehnert, M.; Geletič, Jan

    2017-01-01

    Roč. 20, č. 2 (2017), s. 9-16 ISSN 1212-0855 Institutional support: RVO:86652079 Keywords : local climate zones * air temperature * urban heat island Subject RIV: DG - Athmosphere Sciences, Meteorology OBOR OECD: Climatic research http://www.uur.cz/images/5-publikacni-cinnost-a-knihovna/casopis/2017/2017-02/04-mistni.pdf

  6. Effects of STN DBS and auditory cueing on the performance of sequential movements and the occurrence of action tremor in Parkinson’s disease

    Heida, Tjitske; Wentink, E.C.; Zhao, Yan; Marani, Enrico

    2014-01-01

    Background: Parkinson’s disease (PD) patients show a higher ability to perform repetitive movements when they are cued by external stimuli, suggesting that rhythmic synchronization with an auditory timekeeper can be achieved in the absence of intact basal ganglia function. Deep brain stimulation

  7. Dialektologické aspekty Slovníku pomístních jmen na Moravě a ve Slezsku

    Čižmárová, Libuše

    2012-01-01

    Roč. 6, č. 1 (2012), s. 117-130. ISBN 978-83-7654-182-2. ISSN 1898-9276. [Aktualne problemy dialektologii słowiańskiej. Poznań-Obrzycko, 12.05.2010-15.05.2010] R&D Projects: GA ČR GA405/08/0703 Keywords : dialect ology * onomastics * anoikonyms * dictionary of minor place names Subject RIV: AI - Linguistics

  8. Safety evaluation report in the matter of Offshore Power Systems Floating Nuclear Plants (1-8). Docket No. STN 50-437

    1980-02-01

    The staff has performed an evaluation of a refractory sacrificial bed, called a core ladle, proposed by Offshore Power Systems (OPS) to be installed in Floating Nuclear Plants (FNPs) to delay the melt-through penetration of molten core debris in the unlikely event of a core meltdown accident. The core ladle design as proposed by OPS is in response to the staff's manufacturing license Condition 4 given in the Final Environmental Statement, Part III, NUREG-0502, dated December 1978 (FES-III). This condition requires that a pad constructed of magnesium oxide, or other equivalent refractory material, be installed in the FNP structure within the lower reactor cavity. The material must provide increased resistance to melt-through by the molten reactor core, must not react with core debris to form a large volume of gases, and must not have any deleterious effects on safety

  9. Safety Evaluation Report related to the operation of Shearon Harris Nuclear Power Plant, Unit No. 1 (Docket No. STN 50-400). Supplement No. 4

    1986-10-01

    This report, Supplement No. 4 to the Safety Evaluation Report for the application filed by the Carolina Power and Light Company and North Carolina Eastern Municipal Power Agency (the applicants) for a license to operate the Shearon Harris Nuclear Power Plant Unit 1 (Docket No. 50-400), has been prepared by the Office of Nuclear Reactor Regulation of the US Nuclear Regulatory Commission. This supplement reports the status of certain items that had not been resolved at the time of publication of the Safety Evaluation Report and Supplement Nos. 1, 2, and 3

  10. Palo Verde Nuclear Generating Station Units 1, 2, and 3: Draft environmental statement (Docket Nos. STN 50-528, 529, and 530)

    1975-04-01

    The proposed action is the issuance of construction permits to the Arizona Public Service Corporation for the construction of the Palo Verde Nuclear Generating Station, Units 1, 2 and 3. Preparation of the 3880-acre site will involve the clearing of up to 2500 acres of land, 1500 of which will be permanently devoted to station facilities. An additional 1200- to 1300-acre evaporation pond will ultimately be developed during the lifetime of the station. About 2200 site acres, previously devoted to agriculture, will be excluded from this land use (Sec. 4. 1). Soil disturbance during construction of the station, transmission lines, and water conveyance pipeline will tend to promote erosion and increase siltation in local ephemeral water courses. Stringent measures will be taken to minimize these effects (Sec. 4.5). Station, transmission line, and water pipeline construction will kill, remove displace, or otherwise disturb involved flora and fauna, and will eliminate varying amounts of wildlife breeding, nesting, and forage habitat. These will not be important impacts to the population stability and structure of the involved local ecosystems of the Sonoran desert; however, measures will be taken to minimize such effects (Sec. 4.3 and 4.5). Approximately 60 acres of agricultural land will be temporarily affected by construction in transmission corridors. The great majority can be returned to that use upon completion of construction, thus the impact is considered minor. Similarly, most grazing lands affected along these corridors, as well as along the water pipeline corridor, can eventually be returned to that use. New archaeological resources could be discovered along the path of final transmission corridor alignments. The applicant will take measures to locate and protect such resources if they exist. 75 refs., 24 figs., 65 tabs

  11. Final environmental statement. Final addendum to Part II: Manufacture of floating nuclear power plants by Offshore Power Systems. DOCKET-STN--50-437

    1978-06-01

    This Addendum to Part II of the Final Environmental Statement related to manufacture of floating nuclear power plants by Offshore Power Systems (OPS), NUREG-0056, issued September 1976, was prepared by the U.S. Nuclear Regulatory Commission (NRC), Office of Nuclear Reactor Regulation. The staff's basic evaluation is presented in NUREG-0056. The current Addendum provides further consideration of a number of topics discussed in NUREG-0056, particularly additional consideration of shore zone siting at estuarine and ocean regions. This Summary and Conclusions recapitulates and is cumulative for Part II of the FES and the current Addendum. Augmentations to the Summary and Conclusions presented in Part II of the FES and arising from the evaluations contained in this Addendum are italicized

  12. Washington Public Power Supply System Nuclear Projects 3 and 5 (Docket Nos. STN 50-508 and 50-509): Final environmental statement

    1975-06-01

    The proposed action is the issuance of construction permits to the Washington Public Power Supply System for the construction of the Washington Nuclear Projects 3 and 5 (WNP 3 and 5). The 2170-acre site is predominately forest. Construction-related activities on the site would disturb about 300 acres. The portion of this land not to be used for the plant facilities, parking lots, roads, etc., will be restored by seeding and landscaping. The temporary removal of vegetation will tend to promote erosion. Increased siltation and turbidity can be expected in local rivers and streams during construction, but stringent measures will be undertaken to minimize these effects. A maximum of 72.5 cfs of cooling water will be withdrawn from the Chehalis River of which 12.5 cfs will be returned to the river via pipeline with the dissolved solids concentration increased by a factor of about 6. About 60 cfs will be evaporated to the atmosphere by the cooling towers. Minor and temporary impacts to the biota of the river and its south bank will result from construction activities. The volume of thermal discharge (12.5 cfs) is small compared with the river flow (annual mean is about 6600 cfs) and the effect on the river ecosystem is not expected to be significant. Chemical discharges from the plant, including chlorine, will be diluted to concentrations below those which might adversely affect aquatic biota. The risk associated with accidental radiation exposure will be very low. 37 figs., 58 tabs

  13. Technical specifications: Callaway Plant, Unit No. 1 (Docket No. STN 50-483). Appendix A to License No. NPF-30. Revision 1

    1984-10-01

    Revised specifications are presented concerning limiting safety system settings for control systems, power distribution, instrumentation, coolant system, emergency core cooling system, containment systems, plant systems, electrical systems, refueling operations, radioactive effluents, and radiation environmental monitoring

  14. Tvorba elektronického Slovníku pomístních jmen na Moravě a ve Slezsku

    Čižmárová, Libuše

    2010-01-01

    Roč. 51, č. 1 (2010), s. 79-93 ISSN 1211-4413 R&D Projects: GA ČR GA405/08/0703 Institutional research plan: CEZ:AV0Z90610518 Keywords : Dictionary of Moravian and Silesian Anoikonyms * electronic dictionary * digital database * generating maps Subject RIV: AI - Linguistics

  15. Pomístní jména na Moravě a ve Slezsku a jejich zpracování

    Šipková, Milena

    2010-01-01

    Roč. 20, č. 1 (2010), s. 73-74 ISSN 0862-8351 R&D Projects: GA ČR GA405/08/0703 Institutional research plan: CEZ:AV0Z90610518 Keywords : minor place names * Dictionary of Moravian and Silesian anoikonyms * pople’s religiousness * dialect * history of settlement * local history Subject RIV: AI - Linguistics

  16. Safety evaluation report related to the operation of Shearon Harris Nuclear Power Plant, Unit No. 1 (Docket No. STN 50-400). Supplement No. 1

    1984-06-01

    This report, Supplement No. 1 to the Safety Evaluation Report for the application filed by the Carolina Power and Light Company and North Carolina Eastern Municipal Power Agency (the applicant) for license to operate the Shearon Harris Nuclear Power Plant Unit 1 (Docket No. 50-400), has been prepared by the Office of Nuclear Reactor Regulation of the U.S. Nuclear Regulatory Commission. This supplement reports the status of certain items that had not been resolved at the time of publication of the Safety Evaluation Report

  17. Safety Evaluation Report related to the operation of Shearon Harris Nuclear Power Plant, Unit No. 1 (Docket No. STN 50-400). Supplement No. 2

    1985-06-01

    This report, Supplement No. 2 to the Safety Evaluation Report for the application filed by the Carolina Power and Light Company and North Carolina Eastern Municipal Power Agency (the applicants) for a license to operate the Shearon Harris Nuclear Power Plant Unit 1 (Docket No. 50-400), has been prepared by the Office of Nuclear Reactor Regulation of the US Nuclear Regulatory Commission. This supplement reports the status of certain items that had not been resolved at the time of publication of the Safety Evaluation Report and Supplement No. 1

  18. Safety Evaluation Report related to the operation of Shearon Harris Nuclear Power Plant, Unit No. 1 (Docket No. STN 50-400). Supplement No. 3

    1986-05-01

    This report, Supplement No. 3 to the Safety Evaluation Report for the application filed by the Carolina Power and Light Company and North Carolina Eastern Municipal Power Agency (the applicants) for a license to operate the Shearon Harris Nuclear Power Plant Unit 1 (Docket No. 50-400), has been prepared by the Office of Nuclear Reactor Regulation of the US Nuclear Regulatory Commission. This supplement reports the status of certain items that had not been resolved at the time of publication of the Safety Evaluation Report and Supplement Nos. 1 and 2

  19. Chemoenzymatically synthesized multimeric Tn/STn MUC1 glycopeptides elicit cancer-specific anti-MUC1 antibody responses and override tolerance

    Sørensen, Anne Louise; Reis, Celso A; Tarp, Mads A

    2005-01-01

    The MUC1 mucin represents a prime target antigen for cancer immunotherapy because it is abundantly expressed and aberrantly glycosylated in carcinomas. Attempts to generate strong humoral immunity to MUC1 by immunization with peptides have generally failed partly because of tolerance. In this stu...

  20. Safety evaluation report related to the construction of Skagit/Hanford Nuclear Project, Units 1 and 2. Docket Nos. STN 50-522 and 50-523

    1982-12-01

    Supplement 3 to the Safety Evaluation Report for the application filed by Puget Sound Power and Light Company on behalf of itself, the Pacific Power and Light Company, The Washington Water Power Company, and the Portland General Electric Company for construction permits to build the Skagit/Hanford Nuclear Project has been issued by the Office of Nuclear Reactor Regulation of the United States Nuclear Regulatory Commission. This supplement is an evaluation of the site relocation amendment to the Preliminary Safety Analysis Report. The proposed site has been relocated from Skagit County, Washington, to the Department of Energy's Hanford Reservation

  1. Základ býk- v pomístních jménech na Moravě a ve Slezsku

    Konečná, Hana

    2010-01-01

    Roč. 51, č. 1 (2010), s. 189-201 ISSN 1211-4413 R&D Projects: GA ČR GA405/08/0703 Institutional research plan: CEZ:AV0Z90610518 Keywords : anoikonyms * Moravia, * Silesia * word basis býk -/býč- * motivation * word-formation Subject RIV: AI - Linguistics

  2. Proměny časování a způsobu návratu matek do zaměstnání

    Hašková, Hana

    2011-01-01

    Roč. 12, č. 2 (2011), s. 40-52 ISSN 1213-0028 R&D Projects: GA ČR GAP404/10/0021 Institutional research plan: CEZ:AV0Z70280505 Keywords : capabilities for work - life balance * refamilization Subject RIV: AO - Sociology, Demography www.genderonline.cz

  3. Doba dojíždění do zaměstnání a pracovní úrazy

    ŘEŽÁBKOVÁ, Jana

    2010-01-01

    Commuting is regular travelling between one?s place of residence and the place of work. A lot of us surely remember our grandmothers and grandfathers talking keenly how they used to go to work to a farm, weaving factory, distillery and further facilities. It used to be usual that people had jobs at distances they could walk. On the other hand nowadays it is quite normal that some people have their places of work tens of kilometres from their homes and they have to commute by various means of ...

  4. The effects of unilateral versus bilateral subthalamic nucleus deep brain stimulation on prosaccades and antisaccades in Parkinson's disease.

    Goelz, Lisa C; David, Fabian J; Sweeney, John A; Vaillancourt, David E; Poizner, Howard; Metman, Leonard Verhagen; Corcos, Daniel M

    2017-02-01

    Unilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) in patients with Parkinson's disease improves skeletomotor function assessed clinically, and bilateral STN DBS improves motor function to a significantly greater extent. It is unknown whether unilateral STN DBS improves oculomotor function and whether bilateral STN DBS improves it to a greater extent. Further, it has also been shown that bilateral, but not unilateral, STN DBS is associated with some impaired cognitive-motor functions. The current study compared the effect of unilateral and bilateral STN DBS on sensorimotor and cognitive aspects of oculomotor control. Patients performed prosaccade and antisaccade tasks during no stimulation, unilateral stimulation, and bilateral stimulation. There were three sets of findings. First, for the prosaccade task, unilateral STN DBS had no effect on prosaccade latency and it reduced prosaccade gain; bilateral STN DBS reduced prosaccade latency and increased prosaccade gain. Second, for the antisaccade task, neither unilateral nor bilateral stimulation had an effect on antisaccade latency, unilateral STN DBS increased antisaccade gain, and bilateral STN DBS increased antisaccade gain to a greater extent. Third, bilateral STN DBS induced an increase in prosaccade errors in the antisaccade task. These findings suggest that while bilateral STN DBS benefits spatiotemporal aspects of oculomotor control, it may not be as beneficial for more complex cognitive aspects of oculomotor control. Our findings are discussed considering the strategic role the STN plays in modulating information in the basal ganglia oculomotor circuit.

  5. Bariéry v zaměstnávání bývalých uživatelů drog a jejich uplatnitelnost na trhu práce

    Jakešová, Ivana

    2011-01-01

    This thesis deals with the reintegration of persons recovering from drug addiction and their return to the labour market. The reintegration model is chosen by social company, Café Therapy, one of the first social enterprises to focus specifically on the re-employment of individuals. The main goal of this work is to analyse how successful the company has been, in terms of social effectiveness and self-sufficiency and whether or not the funds invested return by way of the tax system. The object...

  6. Příspěvek automobilové dopravy k místnímu znečištění ovzduší

    Smolík, Jiří; Bízek, V.; Schwarz, Jaroslav; Ždímal, Vladimír; Ondráček, Jakub; Džumbová, Lucie; Mašková, Ludmila

    21/41/, č. 3 (2009), s. 21-26 ISSN 1211-0337 Institutional research plan: CEZ:AV0Z40720504 Keywords : aerosol particles * traffic emissions * size distributor number Subject RIV: CF - Physical ; Theoretical Chemistry

  7. Pomístní jména na území českého národního jazyka jako (historický) pramen

    Spinková, Stanislava

    XVIII, č. 1 (2014), s. 133-139 ISSN 1803-5663 R&D Projects: GA ČR GAP406/11/1786 Keywords : anoikonym * dialectology * onomastics * minor place names * vanished settlement * cattle * emigration * minning * processing of minerals Subject RIV: AI - Linguistics

  8. Po stopách dobytka a drůbeže v materiálu Slovníku pomístních jmen na Moravě a ve Slezsku

    Spinková, Stanislava

    2010-01-01

    Roč. 51, č. 1 (2010), s. 202-226 ISSN 1211-4413 R&D Projects: GA ČR GA405/08/0703 Institutional research plan: CEZ:AV0Z90610518 Keywords : anoikonyms * cattle * sheep and poultry * pasture * common land * wet ground Subject RIV: AI - Linguistics

  9. Podporované zaměstnávání a pracovní uplatnění lidí s mentálním postižením

    Matoušková, Jana

    2010-01-01

    Theoretical part of my thesis deals with the problems connected with employment of persons with mild and moderate form of mental retardation, especially from the perspective of their psychical characters and specific education. The thesis describes the system of social services that are provided to mentally affected persons too. It contains legislative determinants of integration and determinants of labor market related to the employment of mentally affected persons. This thesis defines the t...

  10. Návrh strategie destinačního managementu města Olomouce ke studentům místních vysokých škol

    Karlová, Edita

    2015-01-01

    Karlová E., Proposal of strategy to destination management to students of universities in Olomouc. Bachelor thesis. Brno: Mendel University in Brno, 2015. Bachelor thesis is focused on analysis of tourism in Olomouc, attitude to tourism and spending spare time by students. First part of the thesis is aimed on describing theory of tourism, tourism management, tourist behaviour, destination management, spare time and travelling of youth. Analysis of tourist trade in Olomouc was made from the st...

  11. stní akční skupina jako iniciátor řešení lokálních problémů venkova

    Trávníček, Tomáš

    2015-01-01

    Topic of this diploma thesis is "The Local Action Group as an initiator of solving local problems in the countryside". Thesis describes action groups in a conception in programme LEADER and its reflection in their goals and activites. The main goal of this thesis is to present latest news of action group and evaluate its contribution to that region. Analyses requirements of progress in new Local Action Groups and suggests great solutions in specific region for which could LAG make new strateg...

  12. Disease progression continues in patients with advanced Parkinson's disease and effective subthalamic nucleus stimulation

    Hilker, R; Portman, AT; Voges, J; Staal, MJ; Burghaus, L; van Laar, T; Koulousakis, A; Maguire, RP; Pruim, J; de Jong, BM; Herholz, K; Sturm, [No Value; Heiss, WD; Leenders, KL

    Objectives: Glutamate mediated excitotoxicity of the hyperactive subthalamic nucleus (STN) has been reported to contribute to nigral degeneration in Parkinson's disease (PD). Deep brain stimulation of the STN (STN DBS), in its role as a highly effective treatment of severe PD motor complications,

  13. 75 FR 13606 - Arizona Public Service Company, Palo Verde Nuclear Generating Station, Units 1, 2, and 3...

    2010-03-22

    ... NUCLEAR REGULATORY COMMISSION [Docket Nos. STN 50-528, STN 50-529, and STN 50-530; NRC-2010-0114] Arizona Public Service Company, Palo Verde Nuclear Generating Station, Units 1, 2, and 3; Environmental...-74, issued to Arizona Public Service Company (APS, the licensee), for operation of the Palo Verde...

  14. Possibility of improvement of potentiodynamic method for monitoring ...

    Unknown

    For the preparation of mortars, Portland cement. CEM I 42⋅5 according to standard STN P ENV 197-1 (table. 1), and silica sand according to standard STN 72 1208 were used. For the preparation of corrosion sensors con- struction steel according to standard STN 41 0425 was used. Calcium chloride used was chemically ...

  15. Facilitating effects of deep brain stimulation on feedback learning in Parkinson's disease.

    Meissner, Sarah Nadine; Südmeyer, Martin; Keitel, Ariane; Pollok, Bettina; Bellebaum, Christian

    2016-10-15

    Deep brain stimulation (DBS) of the subthalamic nucleus (STN) provides an effective treatment for Parkinson's disease (PD) motor symptoms. However, findings of effects on cognitive function such as feedback learning remain controversial and rare. The aim of the present study was to gain a better understanding of cognitive alterations associated with STN-DBS. Therefore, we investigated effects of STN-DBS on active and observational feedback learning in PD. 18 PD patients with STN-DBS and 18 matched healthy controls completed active and observational feedback learning tasks. Patients were investigated ON and OFF STN-DBS. Tasks consisted of learning (with feedback) and test phases (without feedback). STN-DBS improved active learning during feedback trials and PD patients ON (but not OFF) STN-DBS showed comparable performance patterns as healthy controls. No STN-DBS effect was found when assessing performance during active test trials without feedback. In this case, however, STN-DBS effects were found to depend on symptom severity. While more impaired patients benefited from STN-DBS, stimulation had no facilitating effect on patients with less severe symptoms. Along similar lines, the severity of motor symptoms tended to be significantly correlated with differences in active test performance due to STN-DBS. For observational feedback learning, there was a tendency for a positive STN-DBS effect with patients reaching the performance level of healthy controls only ON STN-DBS. The present data suggest that STN-DBS facilitates active feedback learning in PD patients. Furthermore, they provide first evidence that STN-DBS might not only affect learning from own but also from observed actions and outcomes. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Stereotactic localization and visualization of the subthalamic nucleus

    SHEN Wei-gao; WANG Hai-yang; LIN Zhi-guo; SHEN Hong; CHEN Xiao-guang; FU Yi-li; GAO Wen-peng

    2009-01-01

    Background The subthalamic nucleus (STN) is widely recognized as one of the most important and commonly targeted nuclei in stereotactic and functional neurosurgery. The success of STN surgery depends on accuracy in target determination. Construction of a digitalized atlas of STN based on stereotactic MRI will play an instrumental role in the accuracy of anatomical localization. The aim of this study was to investigate the three-dimensional (3D) target location of STN in stereotactic space and construct a digitalized atlas of STN to accomplish the visualization of the STN on stereotactic MRI, thus providing clinical guidance on the precise anatomical localization of STN.Methods One hundred and twenty healthy people volunteered to be scanned by 1.5 Tesla MRI scanning with 1-mm-thick slice in the standard stereotactic space between 2005 and 2006. One adult male was selected for 3D reconstruction of STN. The precess of 3D reconstruction included identification, manual segmentation, extraction,conservation and reconstruction.Results There was a significant correlation between the coordinates and age (P <0.05). The volume of left STN was significantly larger than the right STN, and there was a significant negative correlation between volume and age (P <0.05).The surface of the STN nucleus after 3D reconstruction appeared smooth, natural and realistic. The morphological feature of STN on the individual brain could be visualized directly in 3D. The 3D reconstructed STN could be rotated,zoomed and displayed at any direction in the stereotactic space. The anteroposterior diameter of the STN nucleus was longer than the vertical and transverse diameters in 3D space. The 3D reconstruction of STN manifested typical structure of the "dual lens".Conclusions The visualization of individual brain atlas based on stereotactic MRI is feasible. However, software for automated segmentation, extraction and registration of MR images need to be further developed.

  17. Sialyl-Tn vaccine induces antibody-mediated tumour protection in a relevant murine model

    Julien, S; Picco, G; Sewell, R

    2009-01-01

    challenge. We show that synthetic STn coupled to keyhole limpet haemocyanin (Theratope), induced antibodies to STn that recognised the glycan carried on a number of glycoproteins and in these mice a significant delay in tumour growth was observed. The protection was dependent on STn being expressed...... by the tumour and was antibody mediated. Affinity chromatography of the STn-expressing tumour cell line, followed by mass spectrometry, identified osteopontin as a novel STn-carrying glycoprotein which was highly expressed by the tumours. These results suggest that if antibodies can be induced to a number...

  18. Primary productivity in Mandovi-Zuari estuaries in Goa

    KrishnaKumari, L.; Bhattathiri, P.M.A.; Matondkar, S.G.P.; John, J.

    , chlorophyll a ranged from 0.07- 2.68 mg/m³ at the coastal station at off Cabo (Stn 1); 0.01-4.33 mg/m³ at Mandovi (Stn 2) and 0.16 to 3.95 mg/m³ at Zuari (Stn 3). PP varied from 0.5 - 54.69 mgC/m³/hr at Stn 1, 0.19-67.69 mgC/m³/hr at Stn 2 and 0.17-63.24 mg...

  19. Subthalamic stimulation differentially modulates declarative and nondeclarative memory.

    Hälbig, Thomas D; Gruber, Doreen; Kopp, Ute A; Scherer, Peter; Schneider, Gerd-Helge; Trottenberg, Thomas; Arnold, Guy; Kupsch, Andreas

    2004-03-01

    Declarative memory has been reported to rely on the medial temporal lobe system, whereas non-declarative memory depends on basal ganglia structures. We investigated the functional role of the subthalamic nucleus (STN), a structure closely connected with the basal ganglia for both types of memory. Via deep brain high frequency stimulation (DBS) we manipulated neural activity of the STN in humans. We found that DBS-STN differentially modulated memory performance: declarative memory was impaired, whereas non-declarative memory was improved in the presence of STN-DBS indicating a specific role of the STN in the activation of memory systems. Copyright 2004 Lippincott Williams & Wilkins

  20. Asymmetric right/left encoding of emotions in the human subthalamic nucleus

    Renana eEitan

    2013-10-01

    Full Text Available Emotional processing is lateralized to the non-dominant brain hemisphere. However, there is no clear spatial model for lateralization of emotional domains in the basal ganglia. The subthalamic nucleus (STN, an input structure in the basal ganglia network, plays a major role in the pathophysiology of Parkinson’s disease (PD. This role is probably not limited only to the motor deficits of PD, but may also span the emotional and cognitive deficits commonly observed in PD patients. Beta oscillations (12-30Hz, the electrophysiological signature of PD, are restricted to the dorsolateral part of the STN that corresponds to the anatomically defined sensorimotor STN. The more medial, more anterior and more ventral parts of the STN are thought to correspond to the anatomically defined limbic and associative territories of the STN. Surprisingly, little is known about the electrophysiological properties of the non-motor domains of the STN, nor about electrophysiological differences between right and left STNs.In this study, microelectrodes were utilized to record the STN spontaneous spiking activity and responses to vocal non-verbal emotional stimuli during deep brain stimulation (DBS surgeries in human PD patients. The oscillation properties of the STN neurons were used to map the dorsal oscillatory and the ventral non-oscillatory regions of the STN. Emotive auditory stimulation evoked activity in the ventral non-oscillatory region of the right STN. These responses were not observed in the left ventral STN or in the dorsal regions of either the right or left STN. Therefore, our results suggest that the ventral non-oscillatory regions are asymmetrically associated with non-motor functions, with the right ventral STN associated with emotional processing. These results suggest that DBS of the right ventral STN may be associated with beneficial or adverse emotional effects observed in PD patients and may relieve mental symptoms in other neurological and

  1. Subthalamic nucleus stimulation affects limbic and associative circuits: a PET study

    Le Jeune, Florence; Peron, Julie; Grandjean, Didier; Drapier, Sophie; Verin, Marc; Haegelen, Claire; Garin, Etienne; Millet, Bruno

    2010-01-01

    Although high-frequency deep brain stimulation of the subthalamic nucleus (STN DBS) improves motor symptoms in advanced Parkinson's disease (PD), clinical studies have reported cognitive, motivational and emotional changes. These results suggest that the STN forms part of a broadly distributed neural network encompassing the associative and limbic circuits. We sought to pinpoint the cortical and subcortical brain areas modulated by STN DBS, in order to assess the STN's functional role and explain neuropsychological modifications following STN DBS in PD. We studied resting state glucose metabolism in 20 PD patients before and after STN DBS and 13 age-matched healthy controls using 18 F-FDG PET. We used statistical analysis (SPM2) first to compare pre-stimulation metabolism in PD patients with metabolism in healthy controls, then to study metabolic modifications in PD patients following STN DBS. The first analysis revealed no pre-stimulation metabolic abnormalities in associative or limbic circuitry. After STN DBS, metabolic modifications were found in several regions known for their involvement in the limbic and associative circuits. These metabolic results confirm the STN's central role in associative and limbic basal ganglia circuits. They will provide information for working hypotheses for future studies investigating neuropsychological changes and metabolic modifications related to STN DBS, with a view to improving our knowledge of this structure's functional role. (orig.)

  2. Subthalamic nucleus stimulation affects limbic and associative circuits: a PET study

    Le Jeune, Florence [Centre Eugene Marquis, Service de Medecine Nucleaire, Rennes (France); Universite Rennes 1, Hopital Pontchaillou, CHU de Rennes, Unite de Recherche Universitaire ' ' Comportement et Noyaux Gris Centraux' ' , Rennes (France); Centre Eugene Marquis, Service Medecine Nucleaire, Rennes (France); Peron, Julie [Universite Rennes 1, Hopital Pontchaillou, CHU de Rennes, Unite de Recherche Universitaire ' ' Comportement et Noyaux Gris Centraux' ' , Rennes (France); Hopital Pontchaillou, CHU de Rennes, Clinique Neurologique, Rennes (France); University of Geneva, Neuroscience of Emotion and Affective Dynamics, Department of Psychology and Swiss Center for Affective Sciences, Geneva (Switzerland); Grandjean, Didier [University of Geneva, Neuroscience of Emotion and Affective Dynamics, Department of Psychology and Swiss Center for Affective Sciences, Geneva (Switzerland); Drapier, Sophie; Verin, Marc [Universite Rennes 1, Hopital Pontchaillou, CHU de Rennes, Unite de Recherche Universitaire ' ' Comportement et Noyaux Gris Centraux' ' , Rennes (France); Hopital Pontchaillou, CHU de Rennes, Clinique Neurologique, Rennes (France); Haegelen, Claire [Universite Rennes 1, Hopital Pontchaillou, CHU de Rennes, Unite de Recherche Universitaire ' ' Comportement et Noyaux Gris Centraux' ' , Rennes (France); Hopital Pontchaillou, CHU de Rennes, Service de Neurochirurgie, Rennes (France); Garin, Etienne [Centre Eugene Marquis, Service de Medecine Nucleaire, Rennes (France); Millet, Bruno [Universite Rennes 1, Hopital Pontchaillou, CHU de Rennes, Unite de Recherche Universitaire ' ' Comportement et Noyaux Gris Centraux' ' , Rennes (France); S.H.U. Psychiatrie Adulte, CH Guillaume Regnier, Rennes (France)

    2010-08-15

    Although high-frequency deep brain stimulation of the subthalamic nucleus (STN DBS) improves motor symptoms in advanced Parkinson's disease (PD), clinical studies have reported cognitive, motivational and emotional changes. These results suggest that the STN forms part of a broadly distributed neural network encompassing the associative and limbic circuits. We sought to pinpoint the cortical and subcortical brain areas modulated by STN DBS, in order to assess the STN's functional role and explain neuropsychological modifications following STN DBS in PD. We studied resting state glucose metabolism in 20 PD patients before and after STN DBS and 13 age-matched healthy controls using {sup 18}F-FDG PET. We used statistical analysis (SPM2) first to compare pre-stimulation metabolism in PD patients with metabolism in healthy controls, then to study metabolic modifications in PD patients following STN DBS. The first analysis revealed no pre-stimulation metabolic abnormalities in associative or limbic circuitry. After STN DBS, metabolic modifications were found in several regions known for their involvement in the limbic and associative circuits. These metabolic results confirm the STN's central role in associative and limbic basal ganglia circuits. They will provide information for working hypotheses for future studies investigating neuropsychological changes and metabolic modifications related to STN DBS, with a view to improving our knowledge of this structure's functional role. (orig.)

  3. Targeting the subthalamic nucleus in a preclinical model of alcohol use disorder.

    Pelloux, Yann; Baunez, Christelle

    2017-07-01

    The subthalamic nucleus (STN) has only recently been considered to have a role in reward processing. In rats, inactivation of the STN by lesion or high-frequency stimulation (HFS) decreases motivation for cocaine but increases motivation for sucrose. For ethanol, the effect of STN lesion depends on the individual's baseline intake; decreasing motivation for ethanol in rats with lower ethanol intake, while increasing motivation for ethanol in rats with higher-but still limited-ethanol intake. However, the involvement of the STN in behaviour more closely resembling some aspects of alcohol use disorder has not been assessed. This study aimed to determine the effect of STN lesions on the escalation of ethanol intake, subsequent increases in the motivation to "work" for ethanol and the choice of ethanol over a non-drug alternative. We found that STN lesion prevented increases in ethanol intake observed during intermittent ethanol access and after a long period of ethanol privation. STN lesion also decreased the motivation to work for ethanol after escalated intake. Surprisingly, STN lesion increased the choice of alcohol over saccharin. This was associated with a blunting of the hedonic responses to the taste of the reinforcement alternatives. These results evidence the involvement of the STN in different ethanol-motivated behaviours and therefore position the STN as an interesting target for the treatment of alcohol use disorders.

  4. Impaired glutamatergic projection from the motor cortex to the subthalamic nucleus in 6-hydroxydopamine-lesioned hemi-parkinsonian rats.

    Wang, Yan-Yan; Wang, Yong; Jiang, Hai-Fei; Liu, Jun-Hua; Jia, Jun; Wang, Ke; Zhao, Fei; Luo, Min-Hua; Luo, Min-Min; Wang, Xiao-Min

    2018-02-01

    The glutamatergic projection from the motor cortex to the subthalamic nucleus (STN) constitutes the cortico-basal ganglia circuit and plays a critical role in the control of movement. Emerging evidence shows that the cortico-STN pathway is susceptible to dopamine depletion. Specifically in Parkinson's disease (PD), abnormal electrophysiological activities were observed in the motor cortex and STN, while the STN serves as a key target of deep brain stimulation for PD therapy. However, direct morphological changes in the cortico-STN connectivity in response to PD progress are poorly understood at present. In the present study, we used a trans-synaptic anterograde tracing method with herpes simplex virus-green fluorescent protein (HSV-GFP) to monitor the cortico-STN connectivity in a rat model of PD. We found that the connectivity from the primary motor cortex (M1) to the STN was impaired in parkinsonian rats as manifested by a marked decrease in trans-synaptic infection of HSV-GFP from M1 neurons to STN neurons in unilateral 6-hydroxydopamine (6-OHDA)-lesioned rats. Ultrastructural analysis with electron microscopy revealed that excitatory synapses in the STN were also impaired in parkinsonian rats. Glutamatergic terminals identified by a specific marker (vesicular glutamate transporter 1) were reduced in the STN, while glutamatergic neurons showed an insignificant change in their total number in both the M1 and STN regions. These results indicate that the M1-STN glutamatergic connectivity is downregulated in parkinsonian rats. This downregulation is mediated probably via a mechanism involving the impairments of excitatory terminals and synapses in the STN. Copyright © 2017. Published by Elsevier Inc.

  5. Subthalamic Neural Activity Patterns Anticipate Economic Risk Decisions in Gambling

    Rosa, M.; Carpaneto, J.; Priori, A.

    2018-01-01

    Abstract Economic decision-making is disrupted in individuals with gambling disorder, an addictive behavior observed in Parkinson’s disease (PD) patients receiving dopaminergic therapy. The subthalamic nucleus (STN) is involved in the inhibition of impulsive behaviors; however, its role in impulse control disorders and addiction is still unclear. Here, we recorded STN local field potentials (LFPs) in PD patients with and without gambling disorder during an economic decision-making task. Reaction times analysis showed that for all patients, the decision whether to risk preceded task onset. We compared then for both groups the STN LFP preceding high- and low-risk economic decisions. We found that risk avoidance in gamblers correlated with larger STN LFP low-frequency (gambling disorder were instead not correlated with pretask STN LFP. Our results suggest that STN activity preceding task onset affects risk decisions by preemptively inhibiting attraction to high but unlikely rewards in favor of a long-term payoff. PMID:29445770

  6. Frontosubthalamic Circuits for Control of Action and Cognition

    Herz, Damian M.; Brown, Peter; Forstmann, Birte U.; Zaghloul, Kareem

    2016-01-01

    The subthalamic nucleus (STN) of the basal ganglia appears to have a potent role in action and cognition. Anatomical and imaging studies show that different frontal cortical areas directly project to the STN via so-called hyperdirect pathways. This review reports some of the latest findings about such circuits, including simultaneous recordings from cortex and the STN in humans, single-unit recordings in humans, high-resolution fMRI, and neurocomputational modeling. We argue that a major function of the STN is to broadly pause behavior and cognition when stop signals, conflict signals, or surprise signals occur, and that the fronto-STN circuits for doing this, at least for stopping and conflict, are dissociable anatomically and in terms of their spectral reactivity. We also highlight recent evidence for synchronization of oscillations between prefrontal cortex and the STN, which may provide a preferential “window in time” for single neuron communication via long-range connections. PMID:27911752

  7. Deep brain stimulation of the subthalamic nucleus alters frontal activity during spatial working memory maintenance of patients with Parkinson's disease.

    Mayer, Jutta S; Neimat, Joseph; Folley, Bradley S; Bourne, Sarah K; Konrad, Peter E; Charles, David; Park, Sohee

    2016-08-01

    Deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves the motor symptoms of Parkinson's disease (PD). The STN may represent an important relay station not only in the motor but also the associative cortico-striato-thalamocortical pathway. Therefore, STN stimulation may alter cognitive functions, such as working memory (WM). We examined cortical effects of STN-DBS on WM in early PD patients using functional near-infrared spectroscopy. The effects of dopaminergic medication on WM were also examined. Lateral frontal activity during WM maintenance was greater when patients were taking dopaminergic medication. STN-DBS led to a trend-level worsening of WM performance, accompanied by increased lateral frontal activity during WM maintenance. These findings suggest that STN-DBS in PD might lead to functional modifications of the basal ganglia-thalamocortical pathway during WM maintenance.

  8. Subthalamic Neural Activity Patterns Anticipate Economic Risk Decisions in Gambling.

    Mazzoni, A; Rosa, M; Carpaneto, J; Romito, L M; Priori, A; Micera, S

    2018-01-01

    Economic decision-making is disrupted in individuals with gambling disorder, an addictive behavior observed in Parkinson's disease (PD) patients receiving dopaminergic therapy. The subthalamic nucleus (STN) is involved in the inhibition of impulsive behaviors; however, its role in impulse control disorders and addiction is still unclear. Here, we recorded STN local field potentials (LFPs) in PD patients with and without gambling disorder during an economic decision-making task. Reaction times analysis showed that for all patients, the decision whether to risk preceded task onset. We compared then for both groups the STN LFP preceding high- and low-risk economic decisions. We found that risk avoidance in gamblers correlated with larger STN LFP low-frequency (gambling disorder were instead not correlated with pretask STN LFP. Our results suggest that STN activity preceding task onset affects risk decisions by preemptively inhibiting attraction to high but unlikely rewards in favor of a long-term payoff.

  9. Role of dysphagia in evaluating Parkinson patients for subthalamic nucleus stimulation: a case report.

    Allert, Niels; Kelm, Daniela; Spottke, Annika; Coenen, Volker A

    2011-09-01

    In the selection of Parkinson patients for deep brain stimulation (DBS) of the subthalamic nucleus (STN) a risk-benefit-analysis is performed regarding symptoms that commonly improve and symptoms that may deteriorate. Speech is among the symptoms that may deteriorate. In contrast, the differential effects of STN-DBS on swallowing are less clear. Here, we present a Parkinson patient with dysphagia from concomitant oculo-pharyngeal muscle dystrophy successfully treated by STN-DBS. The role of dysphagia in evaluating Parkinson patients for STN-DBS is discussed.

  10. Subthalamic nucleus stimulation impairs emotional conflict adaptation in Parkinson's disease.

    Irmen, Friederike; Huebl, Julius; Schroll, Henning; Brücke, Christof; Schneider, Gerd-Helge; Hamker, Fred H; Kühn, Andrea A

    2017-10-01

    The subthalamic nucleus (STN) occupies a strategic position in the motor network, slowing down responses in situations with conflicting perceptual input. Recent evidence suggests a role of the STN in emotion processing through strong connections with emotion recognition structures. As deep brain stimulation (DBS) of the STN in patients with Parkinson's disease (PD) inhibits monitoring of perceptual and value-based conflict, STN DBS may also interfere with emotional conflict processing. To assess a possible interference of STN DBS with emotional conflict processing, we used an emotional Stroop paradigm. Subjects categorized face stimuli according to their emotional expression while ignoring emotionally congruent or incongruent superimposed word labels. Eleven PD patients ON and OFF STN DBS and eleven age-matched healthy subjects conducted the task. We found conflict-induced response slowing in healthy controls and PD patients OFF DBS, but not ON DBS, suggesting STN DBS to decrease adaptation to within-trial conflict. OFF DBS, patients showed more conflict-induced slowing for negative conflict stimuli, which was diminished by STN DBS. Computational modelling of STN influence on conflict adaptation disclosed DBS to interfere via increased baseline activity. © The Author (2017). Published by Oxford University Press.

  11. Different populations of subthalamic neurons encode cocaine vs. sucrose reward and predict future error.

    Lardeux, Sylvie; Paleressompoulle, Dany; Pernaud, Remy; Cador, Martine; Baunez, Christelle

    2013-10-01

    The search for treatment of cocaine addiction raises the challenge to find a way to diminish motivation for the drug without decreasing it for natural rewards. Subthalamic nucleus (STN) inactivation decreases motivation for cocaine while increasing motivation for food, suggesting that STN can dissociate different rewards. Here, we investigated how rat STN neurons respond to cues predicting cocaine or sucrose and to reward delivery while rats are performing a discriminative stimuli task. We show that different neuronal populations of STN neurons encode cocaine and sucrose. In addition, we show that STN activity at the cue onset predicts future error. When changing the reward predicted unexpectedly, STN neurons show capacities of adaptation, suggesting a role in reward-prediction error. Furthermore, some STN neurons show a response to executive error (i.e., "oops neurons") that is specific to the missed reward. These results position the STN as a nexus where natural rewards and drugs of abuse are coded differentially and can influence the performance. Therefore, STN can be viewed as a structure where action could be taken for the treatment of cocaine addiction.

  12. Immune responses of mice and human breast cancer patients following immunization with synthetic sialyl-Tn conjugated to KLH plus detox adjuvant.

    Longenecker, B M; Reddish, M; Koganty, R; MacLean, G D

    1993-08-12

    We generated a synthetic epitope, NANA alpha(2-6) GalNAc alpha-O-Crotyl (STn-crotyl), designed to "mimic" the natural O-linked epitope expressed on human carcinoma cells, NANA alpha(2-6)GalNAc alpha-O-Serine (STn-serine). STn-crotyl was conjugated to the carrier protein KLH through the crotyl linker arm, and a "vaccine" containing STn-KLH plus DETOX adjuvant was formulated. The immunogenicity of the vaccine was evaluated preclinically in CAF1 mice and subsequently in patients with metastatic breast cancer. The specificity and titers of IgG antibodies were evaluated by kinetic ELISA on synthetic STn-HSA and on ovine submaxillary mucin (OSM) solid phases. Ovine submaxillary mucin is a convenient source of repeating, natural O-linked STn-serine structures. Mice immunized three times with as little as 0.25 micrograms of STn-KLH produced IgG titers ranging from 1:10(4) to 1:10(5) when tested on solid phase OSM. Anti-OSM IgG, both polyclonal and monoclonal antibodies, generated from these mice were completely inhibited in their binding to solid phase OSM equally well by STn-serine and STn-crotyl synthetic haptens but not by several other closely related synthetic haptens. These monoclonal antibodies also bound to STn determinants on human tumor cell surfaces. Breast cancer patients immunized with 100 micrograms of the same vaccine produced median peak IgG titers 1:1280 measured on STn-HSA and 1:160 on OSM. Hapten inhibition experiments with the human sera demonstrated the specificities of the IgG antibodies for STn-crotyl and STn-serine, but not against several other related synthetic haptens. We found little evidence that the artificial linker arm (crotyl linker) contributed substantially to either the titer or affinity of the antibodies generated in either mice or human breast cancer patients. This suggests that the antibodies recognized the cancer-associated disaccharide NANA alpha(2-->6)-GalNAc. Small but not large doses of STn-KLH immunogen induced anti-STn DTH

  13. Subthalamic nucleus high-frequency stimulation modulates neuronal reactivity to cocaine within the reward circuit.

    Hachem-Delaunay, Sabira; Fournier, Marie-Line; Cohen, Candie; Bonneau, Nicolas; Cador, Martine; Baunez, Christelle; Le Moine, Catherine

    2015-08-01

    The subthalamic nucleus (STN) is a critical component of a complex network controlling motor, associative and limbic functions. High-frequency stimulation (HFS) of the STN is an effective therapy for motor symptoms in Parkinsonian patients and can also reduce their treatment-induced addictive behaviors. Preclinical studies have shown that STN HFS decreases motivation for cocaine while increasing that for food, highlighting its influence on rewarding and motivational circuits. However, the cellular substrates of these effects remain unknown. Our objectives were to characterize the cellular consequences of STN HFS with a special focus on limbic structures and to elucidate how STN HFS may interfere with acute cocaine effects in these brain areas. Male Long-Evans rats were subjected to STN HFS (130 Hz, 60 μs, 50-150 μA) for 30 min before an acute cocaine injection (15 mg/kg) and sacrificed 10 min following the injection. Neuronal reactivity was analyzed through the expression of two immediate early genes (Arc and c-Fos) to decipher cellular responses to STN HFS and cocaine. STN HFS only activated c-Fos in the globus pallidus and the basolateral amygdala, highlighting a possible role on emotional processes via the amygdala, with a limited effect by itself in other structures. Interestingly, and despite some differential effects on Arc and c-Fos expression, STN HFS diminished the c-Fos response induced by acute cocaine in the striatum. By preventing the cellular effect of cocaine in the striatum, STN HFS might thus decrease the reinforcing properties of the drug, which is in line with the inhibitory effect of STN HFS on the rewarding and reinforcing properties of cocaine. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Synthesis by spark plasma sintering of a novel protonic/electronic conductor composite: BaCe0.2Zr0.7Y0.1O3−δ /Sr0.95Ti0.9Nb0.1O3−δ (BCZY27/STN95)

    Fish, Jason; Ricote, Sandrine; Lenrick, Filip

    2013-01-01

    and sintered conventionally (CS) at 1350–1500 °C, as well as by spark plasma sintering (SPS) at 1300–1350 °C. CS samples were porous and exhibited high degrees of inter-phase reaction. Nickel oxide sintering aids did not improve CS sample density. In contrast, samples made by SPS were significantly denser (>95...... of these regions with high-resolution transmission electron microscopy and selective area electron diffraction. We thus suggest that these phases are present as independent grains in the bulk. It is believed these secondary phases inhibit electronic conductivity in the composite....

  15. Politika odvolání jako inovativní nástroj prosazování transparentnosti a občanské účasti ve slovenské a polské místní samosprávě

    Smith, Michael

    2011-01-01

    Roč. 43, č. 4 (2011), s. 338-361 ISSN 0049-1225 R&D Projects: GA MV VG20102013029 Institutional research plan: CEZ:AV0Z70280505 Keywords : local recall * recall referendum * local government Subject RIV: AO - Sociology, Demography Impact factor: 0.191, year: 2011 http://www.sav.sk/journals/uploads/08240943Smith%20-%20OK.pdf

  16. Používání menšinových jazyků v úředním styku pohledem národnostních menšin a orgánů místní samosprávy

    Sulitka, Andrej

    2015-01-01

    Roč. 61, č. 4 (2015), s. 109-113 ISSN 0323-0619 Institutional support: RVO:68378076 Keywords : national minorities * minority languages * self-government Subject RIV: AC - Archeology, Anthropology, Ethnology

  17. Česká nářečí a pomístní jména aneb jak rytíř (?) Močihuba získal a opět pozbyl své jméno

    Čižmárová, Libuše

    2016-01-01

    Roč. 56, č. 1 (2016), s. 52-61 ISSN 1211-4413 R&D Projects: GA ČR GAP406/11/1786 Institutional support: RVO:68378092 Keywords : Czech dialects * minor place-names * anthroponyms * Močihuba * Mlčí huba * Rácov Subject RIV: AI - Linguistics

  18. Pohybová náročnost vybraných pracovních profesí, sestavení vhodného kompenzačního programu pro profese se sedavým typem zaměstnání

    FRÖSTLOVÁ, Daniela

    2017-01-01

    The main theme of my work is finding the locomotive load in selected professions and build a compensation program for professionals with a sedentary job. When selecting this topic for me was the decisive topicality of the selected topic, I see especially in the ever-growing problems with musculoskeletal system of persons employed in sedentary occupations, which are one of the consequences of their employment. The first theoretical part of the thesis includes a detailed analysis of the issues ...

  19. Selectively stimulating neural populations in the subthalamic region using a novel deep brain stimulation lead design

    van Dijk, Kees Joab; Verhagen, R.; Bour, L.J.; Heida, Tjitske

    2013-01-01

    Deep brain stimulation (DBS) of the Subthalamic Nucleus (STN) is widely used in advanced stages of Parkinson's disease(PD) and has proven to be an effective treatment of the various motor symptoms. The therapy involves implanting a lead consisting of multiple electrodes in the STN through which

  20. 7T MRI subthalamic nucleus atlas for use with 3T MRI.

    Milchenko, Mikhail; Norris, Scott A; Poston, Kathleen; Campbell, Meghan C; Ushe, Mwiza; Perlmutter, Joel S; Snyder, Abraham Z

    2018-01-01

    Deep brain stimulation (DBS) of the subthalamic nucleus (STN) reduces motor symptoms in most patients with Parkinson disease (PD), yet may produce untoward effects. Investigation of DBS effects requires accurate localization of the STN, which can be difficult to identify on magnetic resonance images collected with clinically available 3T scanners. The goal of this study is to develop a high-quality STN atlas that can be applied to standard 3T images. We created a high-definition STN atlas derived from seven older participants imaged at 7T. This atlas was nonlinearly registered to a standard template representing 56 patients with PD imaged at 3T. This process required development of methodology for nonlinear multimodal image registration. We demonstrate mm-scale STN localization accuracy by comparison of our 3T atlas with a publicly available 7T atlas. We also demonstrate less agreement with an earlier histological atlas. STN localization error in the 56 patients imaged at 3T was less than 1 mm on average. Our methodology enables accurate STN localization in individuals imaged at 3T. The STN atlas and underlying 3T average template in MNI space are freely available to the research community. The image registration methodology developed in the course of this work may be generally applicable to other datasets.

  1. Effect of subthalamic nucleus or globus pallidus interna stimulation on oculomotor function in patients with Parkinson's disease.

    Fridley, Jared; Adams, Gareth; Sun, Ping; York, Michelle; Atassi, Farah; Lai, Eugene; Simpson, Richard; Viswanathan, Ashwin; Yoshor, Daniel

    2013-01-01

    Deep brain stimulation (DBS) of either the globus pallidus interna (GPi) or subthalamic nucleus (STN) is similarly effective for treating somatomotor manifestations of Parkinson's disease (PD), but differences in how stimulation of each target affects oculomotor function are poorly understood. We sought to determine if stimulation of the STN, but not the GPi, affects oculomotor function in PD patients. Nineteen PD patients with DBS implants (8 bilateral GPi, 9 bilateral STN and 2 unilateral STN) were studied. Testing was performed with stimulation on, then off. Somatomotor function was tested using the Unified Parkinson's Disease Rating Scale (UPDRS) motor exam. For oculomotor testing, patients performed pro- and antisaccade tasks while monitored with an infrared eye tracker. Saccadic latency, saccadic intrusions, and square-wave jerks (SWJs) were measured for each trial. As expected, UPDRS motor scores improved with both GPi and STN stimulation. With GPi stimulation, there was no significant difference in oculomotor function with stimulation on or off. However, with STN stimulation on, there was a significant increase in the mean number of SWJs/s, as well as a significant decrease in latency for both pro- and antisaccade tasks. Stimulation of either GPi or STN had similar effects on somatomotor function, but only STN stimulation significantly altered oculomotor function. Copyright © 2013 S. Karger AG, Basel.

  2. Subthalamic Nucleus Deep Brain Stimulation Changes Velopharyngeal Control in Parkinson's Disease

    Hammer, Michael J.; Barlow, Steven M.; Lyons, Kelly E.; Pahwa, Rajesh

    2011-01-01

    Purpose: Adequate velopharyngeal control is essential for speech, but may be impaired in Parkinson's disease (PD). Bilateral subthalamic nucleus deep brain stimulation (STN DBS) improves limb function in PD, but the effects on velopharyngeal control remain unknown. We tested whether STN DBS would change aerodynamic measures of velopharyngeal…

  3. 75 FR 4111 - Biweekly Notice; Applications and Amendments to Facility Operating Licenses Involving No...

    2010-01-26

    ... value for all steam generators, both hot and cold legs, in Table RA124-2. Specifically, for the... possibility of a new or different kind of accident from any accident previously evaluated; or (3) involve a...-mail to [email protected] . Arizona Public Service Company, et al., Docket Nos. STN 50-528, STN 50...

  4. Network effects of subthalamic deep brain stimulation drive a unique mixture of responses in basal ganglia output.

    Humphries, Mark D; Gurney, Kevin

    2012-07-01

    Deep brain stimulation (DBS) is a remarkably successful treatment for the motor symptoms of Parkinson's disease. High-frequency stimulation of the subthalamic nucleus (STN) within the basal ganglia is a main clinical target, but the physiological mechanisms of therapeutic STN DBS at the cellular and network level are unclear. We set out to begin to address the hypothesis that a mixture of responses in the basal ganglia output nuclei, combining regularized firing and inhibition, is a key contributor to the effectiveness of STN DBS. We used our computational model of the complete basal ganglia circuit to show how such a mixture of responses in basal ganglia output naturally arises from the network effects of STN DBS. We replicated the diversification of responses recorded in a primate STN DBS study to show that the model's predicted mixture of responses is consistent with therapeutic STN DBS. We then showed how this 'mixture of response' perspective suggests new ideas for DBS mechanisms: first, that the therapeutic frequency of STN DBS is above 100 Hz because the diversification of responses exhibits a step change above this frequency; and second, that optogenetic models of direct STN stimulation during DBS have proven therapeutically ineffective because they do not replicate the mixture of basal ganglia output responses evoked by electrical DBS. © 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  5. Strontium Titanate-based Composite Anodes for Solid Oxide Fuel Cells

    Blennow Tullmar, Peter; Kammer Hansen, Kent; Wallenberg, L.R.

    2008-01-01

    Surfactant-assisted infiltration of Gd-doped ceria (CGO) in Nb-doped SrTiO3 (STN) was investigated as a potential fuel electrode for solid oxide fuel cells (SOFC). An electronically conductive backbone structure of STN was first fabricated at high temperatures and then combined with the mixed con...

  6. Deep brain stimulation of the subthalamic nucleus improves reward-based decision-learning in Parkinson's disease

    van Wouwe, N.C.; Ridderinkhof, K.R.; van den Wildenberg, W.P.M.; Band, G.P.H.; Abisogun, A.; Elias, W.J.; Frysinger, R.; Wylie, S.A.

    2011-01-01

    Recently, the subthalamic nucleus (STN) has been shown to be critically involved in decision-making, action selection, and motor control. Here we investigate the effect of deep brain stimulation (DBS) of the STN on reward-based decision-learning in patients diagnosed with Parkinson's disease (PD).

  7. Deep brain stimulation of the subthalamic nucleus improves reward-based decision-learning in Parkinson’s disease

    Wouwe, N.C. van; Ridderinkhof, K.R.; Wildenberg, W.P.M. van den; Band, G.P.H.; Abisogun, A.; Elias, W.J.; Frysinger, R.; Wylie, S.A.

    2011-01-01

    Recently, the subthalamic nucleus (STN) has been shown to be critically involved in decision-making, action selection, and motor control. Here we investigate the effect of deep brain stimulation (DBS) of the STN on reward-based decision-learning in patients diagnosed with Parkinson’s disease (PD).

  8. Anatomy of the Human Subthalamic Nucleus: A Combined Morphometric Study

    Ioannis Mavridis

    2013-01-01

    Full Text Available Purpose. Our purpose was to provide a combined clinically oriented study focused on the detailed anatomy of the human STN, with great respect to its targeting. Methods. For our imaging study, we used cerebral magnetic resonance images (MRIs from 26 neurosurgical patients and for our anatomic study 32 cerebral hemispheres from 18 normal brains from cadaver donors. We measured and analyzed the STN dimensions (based on its stereotactic coordinates. Results. At stereotactic level Z=-4, the STN length was 7.7 mm on MRIs and 8.1 mm in anatomic specimens. Its width was 6 mm on MRIs and 6.3 mm in anatomic specimens. The STN was averagely visible in 3.2 transverse MRI slices and its maximum dimension was 8.5 mm. The intercommissural distance was 26.3 mm on MRIs and 27.3 mm in anatomic specimens. We found statistically significant difference of the STN width and length between individuals <60 and ≥60 years old. Conclusion. The identification of the STN limits was easier in anatomic specimens than on MRIs and easier on T2 compared to T1-weighted MRIs sections. STN dimensions appear slightly smaller on MRIs. Younger people have wider and longer STN.

  9. Deep brain stimulation modulates synchrony within spatially and spectrally distinct resting state networks in Parkinson's disease

    Oswal, Ashwini; Beudel, Martijn; Zrinzo, Ludvic; Limousin, Patricia; Hariz, Marwan; Foltynie, Tom; Litvak, Vladimir; Brown, Peter

    2016-01-01

    Oswal et al. characterise the effect of deep brain stimulation (DBS) on STN-cortical synchronisation in Parkinson-s disease. They propose that cortical driving of the STN in beta frequencies is subdivided anatomically and spectrally, corresponding to the hyperdirect and indirect pathways. DBS

  10. Deep Brain Stimulation of the Subthalamic Nucleus Parameter Optimization for Vowel Acoustics and Speech Intelligibility in Parkinson's Disease

    Knowles, Thea; Adams, Scott; Abeyesekera, Anita; Mancinelli, Cynthia; Gilmore, Greydon; Jog, Mandar

    2018-01-01

    Purpose: The settings of 3 electrical stimulation parameters were adjusted in 12 speakers with Parkinson's disease (PD) with deep brain stimulation of the subthalamic nucleus (STN-DBS) to examine their effects on vowel acoustics and speech intelligibility. Method: Participants were tested under permutations of low, mid, and high STN-DBS frequency,…

  11. A novel lead design enables selective deep brain stimulation of neural populations in the subthalamic region

    van Dijk, Kees J.; Verhagen, Rens; Chaturvedi, Ashutosh; McIntyre, Cameron C.; Bour, Lo J.; Heida, Ciska; Veltink, Peter H.

    2015-01-01

    The clinical effects of deep brain stimulation (DBS) of the subthalamic nucleus (STN-DBS) as a treatment for Parkinson's disease are sensitive to the location of the DBS lead within the STN. New high density (HD) lead designs have been created which are hypothesized to provide additional degrees of

  12. A novel lead design enables selective deep brain stimulation of neural populations in the subthalamic region

    van Dijk, Kees J.; Verhagen, Rens; Chaturvedi, Ashutosh; McIntyre, Cameron C.; Bour, Lo J.; Heida, Tjitske; Veltink, Peter H.

    2015-01-01

    Objective. The clinical effects of deep brain stimulation (DBS) of the subthalamic nucleus (STN-DBS) as a treatment for Parkinson's disease are sensitive to the location of the DBS lead within the STN. New high density (HD) lead designs have been created which are hypothesized to provide additional

  13. Seasonal variation in the proximate composition of rock oyster Saccostrea cucullata from Bombay coast

    Krishnakumari, L.; Nair, V.R.

    Changes in proximate composition of soft tissue of rock oyster Saccostrea cucullata inhabiting a polluted station at Bandra (stn. B) and a relatively clean area at Mudh Island (stn. M) were studied. An average protein content of 48.88 + or - 3...

  14. Mechanisms Underlying Decision-Making as Revealed by Deep-Brain Stimulation in Patients with Parkinson's Disease.

    Herz, Damian M; Little, Simon; Pedrosa, David J; Tinkhauser, Gerd; Cheeran, Binith; Foltynie, Tom; Bogacz, Rafal; Brown, Peter

    2018-04-23

    To optimally balance opposing demands of speed and accuracy during decision-making, we must flexibly adapt how much evidence we require before making a choice. Such adjustments in decision thresholds have been linked to the subthalamic nucleus (STN), and therapeutic STN deep-brain stimulation (DBS) has been shown to interfere with this function. Here, we performed continuous as well as closed-loop DBS of the STN while Parkinson's disease patients performed a perceptual decision-making task. Closed-loop STN DBS allowed temporally patterned STN stimulation and simultaneous recordings of STN activity. This revealed that DBS only affected patients' ability to adjust decision thresholds if applied in a specific temporally confined time window during deliberation. Only stimulation in that window diminished the normal slowing of response times that occurred on difficult trials when DBS was turned off. Furthermore, DBS eliminated a relative, time-specific increase in STN beta oscillations and compromised its functional relationship with trial-by-trial adjustments in decision thresholds. Together, these results provide causal evidence that the STN is involved in adjusting decision thresholds in distinct, time-limited processing windows during deliberation. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  15. Topographic organization of the human and non-human primate subthalamic nucleus

    Alkemade, A.; Schnitzler, A.; Forstmann, B.U.

    2015-01-01

    Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is used to relieve motor symptoms of Parkinson's disease. A tripartite system of STN subdivisions serving motoric, associative, and limbic functions was proposed, mainly based on tracing studies, which are limited by low numbers of

  16. The frequency of carcinoma in solitary thyroid nodules and in ...

    Muhimbili Medical Centre, Dar es Salaam was made to determine the frequency of malignancy in patients with solitary non-toxic thyroid nodule (STN) and in those with multinodular goitre (MNG). There were 60 cases of STN and. 178 with MNG. Nodular goitre was found to be predominantly a disease of females with sex.

  17. Effect of unilateral versus bilateral electrostimulation in subthalamic nucleus on speech in Parkinsons disease

    Wang, Emily; Verhagen Metman, Leo; Bakay, Roy; Arzbaecher, Jean; Bernard, Bryan

    2004-05-01

    Previously, it was found that 16 right-handed patients with idiopathic Parkinsons disease who underwent unilateral implantation of deep brain stimulator in subthalamic nucleus (STN) showed significant improvement in their nonspeech motor functions. Eight of the 16 patients had stimulator in the left STN and eight in the right STN. In contrast, their speech function showed very mild improvement that was limited to the respiratory/phonotory subsystems. Further, there seemed a trend that the patients with right STN stimulation did better than those with left STN stimulation. It was speculated that the difference might be due to a micro lesion caused by the surgical procedure to the corticobulbar fibers run in the left internal capsule. This paper reports speech changes associated with bilateral DBS in STN in four of the 16 subjects who elected to have deep brain stimulator implanted in STN on the opposite side of the brain at a later time. Results show negative changes in speech after bilateral DBS in STN. The changes were not limited to the micro lesion effect due to the surgery itself, but also related to the active stimulation on the dominant hemisphere for speech processing. [Work supported by NIH.

  18. Shade changing effectiveness of plasdone and blue covarine-based whitening toothpaste on teeth stained with chlorhexidine and black tea.

    Bergesch, Vania; Baggio Aguiar, Flávio Henrique; Turssi, Cecilia Pedroso; Gomes França, Fabiana Mantovani; Basting, Roberta Tarkany; Botelho Amaral, Flávia Lucisano

    2017-01-01

    This study evaluated the effectiveness of toothbrushing with whitening toothpaste in altering the shade of stained human enamel. Thirty fragments of human enamel, stained with chlorhexidine/black tea underwent 1000 and 5000 brushing cycles (BC) with ( n = 10): PLS (Gel Dental Day, Bitufo), Close Up White Now, Unilever (COVB) and regular (Gel Dental Night, Bitufo) toothpaste. Images were taken before staining (baseline), after staining (STN) and following 1000 and 5000 BC and were analyzed using the CIELAB parameters (ΔE, Δb and ΔL). Data were submitted to two-way ANOVA (α = 0.05). ΔE was higher from STN to baseline; 1000 BC to STN and 5000 BC to STN ( P < 0.001). Significant differences in Δb values were found from 1000 BC to STN and 5000 BC to STN. For COVB, greater ΔL was observed from 1000 BC to STN, what differed statistically from the regular toothpaste ( P < 0.05). There was no difference between toothpaste when ΔL was calculated from 5000 CB to STN. Toothpaste containing COVB or PLS in association with 5000 BCs showed similar effectiveness in changing enamel shade; but after the first 1000 toothbrushing cycles, the use of COVB toothpaste promoted higher lightness in stained enamel.

  19. Localisation of the subthalamic nucleus in Parkinson's disease with neural beta and gamma activity of local field potentials

    Verhagen, R.; Zwartjes - de Klerk, D.G.M; Heida, Tjitske; Contarino, M.F.; de Bie, R.M.A.; van den Munckhof, P; Schuurman, P.R.; Martens, H.C.F.; Veltink, Petrus H.; Bour, L.J.

    2013-01-01

    To evaluate the nature of oscillatory activity in the subthalamic nucleus (STN) by means of intraoperative local field potential (LFP) recordings, its relationship with microelectrode recordings (MER) and its potential use to locate the STN and its sensorimotor sub-area in patients with Parkinson’s

  20. Effects of Medication and Subthalamic Nucleus Deep Brain Stimulation on Tongue Movements in Speakers with Parkinson's Disease Using Electropalatography: A Pilot Study

    Hartinger, Mariam; Tripoliti, Elina; Hardcastle, William J.; Limousin, Patricia

    2011-01-01

    Parkinson's disease (PD) affects speech in the majority of patients. Subthalamic nucleus deep brain stimulation (STN-DBS) is particularly effective in reducing tremor and rigidity. However, its effect on speech is variable. The aim of this pilot study was to quantify the effects of bilateral STN-DBS and medication on articulation, using…

  1. Psychiatric and social outcome after deep brain stimulation for advanced Parkinson's disease

    Boel, Judith A.; Odekerken, Vincent J. J.; Geurtsen, Gert J.; Schmand, Ben A.; Cath, Danielle C.; Figee, Martijn; van den Munckhof, Pepijn; de Haan, Rob J.; Schuurman, P. Richard; de Bie, Rob M. A.; van Laar, Teus; van Dijk, J. Marc C.; Mosch, Arne; Hoffmann, Carel F. E.; Nijssen, Peter C. G.; Beute, Guus N.; van Vugt, Jeroen P. P.; Lenders, Mathieu W. P. M.; Contarino, M. Fiorella; Bour, Lo J.

    2016-01-01

    The aim of this study was to assess psychiatric and social outcome 12 months after bilateral deep brain stimulation (DBS) of the globus pallidus pars interna (GPi) and subthalamic nucleus (STN) for advanced Parkinson's disease (PD). We randomly assigned patients to receive GPi DBS (n = 65) or STN

  2. Two and three dimensional electron backscattered diffraction analysis of solid oxide cells materials

    Saowadee, Nath

    in solid oxide fuel cell and electrolysis cell. Conductivity of STN is one of the important properties that researchers desire to improve. Grin boundary conductivity contributes to the overall conductivity of the STN. Grain boundary density controlled by mainly grain growth in material processing. Grain......There are two main technique were developed in this work: a technique to calculate grain boundary energy and pressure and a technique to measure lattice constant from EBSD. The techniques were applied to Nb-doped Strontium titanate (STN) and yttria stabilized zirconia (YSZ) which are commonly used...... boundary migration in grain growth involves grain boundary mobility and net pressure on it. Thus grain boundary energy and pressure of STN were calculated in this work. Secondary phase is undesired in STN and YSZ synthesis. The secondary phase in ceramics with the same compounds can have different lattice...

  3. Dynamic stereotypic responses of basal ganglia neurons to subthalamic nucleus high frequency stimulation in the parkinsonian primate

    Anan eMoran

    2011-04-01

    Full Text Available Deep brain stimulation in the subthalamic nucleus (STN is a well-established therapy for patients with severe Parkinson‟s disease (PD; however, its mechanism of action is still unclear. In this study we explored static and dynamic activation patterns in the basal ganglia during high frequency macro-stimulation of the STN. Extracellular multi-electrode recordings were performed in primates rendered parkinsonian using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Recordings were preformed simultaneously in the STN and the globus pallidus externus and internus. Single units were recorded preceding and during the stimulation. During the stimulation, STN mean firing rate dropped significantly, while pallidal mean firing rates did not change significantly. The vast majority of neurons across all three nuclei displayed stimulation driven modulations, which were stereotypic within each nucleus but differed across nuclei. The predominant response pattern of STN neurons was somatic inhibition. However, most pallidal neurons demonstrated synaptic activation patterns. A minority of neurons across all nuclei displayed axonal activation. Temporal dynamics were observed in the response to stimulation over the first 10 seconds in the STN and over the first 30 seconds in the pallidum. In both pallidal segments, the synaptic activation response patterns underwent delay and decay of the magnitude of the peak response due to short term synaptic depression. We suggest that during STN macro stimulation the STN goes through a functional ablation as its upper bound on information transmission drops significantly. This notion is further supported by the evident dissociation between the stimulation driven pre-synaptic STN somatic inhibition and the post-synaptic axonal activation of its downstream targets. Thus, basal ganglia output maintains its firing rate while losing the deleterious effect of the STN. This may be a part of the mechanism leading to the beneficial

  4. Treatment of ovarian cancer by targeting the tumor stem cell-associated carbohydrate antigen, Sialyl-Thomsen-nouveau.

    Starbuck, Kristen; Al-Alem, Linah; Eavarone, David A; Hernandez, Silvia Fatima; Bellio, Chiara; Prendergast, Jillian M; Stein, Jenna; Dransfield, Daniel T; Zarrella, Bianca; Growdon, Whitfield B; Behrens, Jeff; Foster, Rosemary; Rueda, Bo R

    2018-05-01

    Recurrent ovarian cancer (OvCa) is thought to result in part from the inability to eliminate rare quiescent cancer stem cells (CSCs) that survive cytotoxic chemotherapy and drive tumor resurgence. The Sialyl-Thomsen-nouveau antigen (STn) is a carbohydrate moiety present on protein markers of CSCs in pancreatic, colon, and gastric malignancies. We have demonstrated that human OvCa cell lines contain varying levels of cells that independently express either STn or the ovarian CSC marker CD133. Here we determine co-expression of STn and CD133 in a subset of human OvCa cell lines. Analyses of colony and sphere forming capacity and of response to standard-of-care cytotoxic therapy suggest a subset of OvCa STn + cells display some CSC features. The effect of the anti-STn antibody-drug conjugates (ADCs) S3F-CL-MMAE and 2G12-2B2-CL-MMAE on OvCa cell viability in vitro and in vivo was also assessed. Treatment with S3F-CL-MMAE reduced the viability of two of three OvCa cell lines in vitro and exposure to either S3F-CL-MMAE or 2G12-2B2-CL-MMAE reduced OVCAR3-derived xenograft volume in vivo , depleting STn + tumor cells. In summary, STn + cells demonstrate some stem-like properties and specific therapeutic targeting of STn in ovarian tumors may be an effective clinical strategy to eliminate both STn + CSC and STn + non-CSC populations.

  5. The subthalamic nucleus keeps you high on emotion: behavioral consequences of its inactivation

    Yann ePelloux

    2014-12-01

    Full Text Available The subthalamic nucleus (STN belongs to the basal ganglia and is the current target for the surgical treatment of neurological and psychiatric disorders such as Parkinson’s Disease (PD and obsessive compulsive disorders, but also a proposed site for the treatment of addiction. It is therefore very important to understand its functions in order to anticipate and prevent possible side-effects in the patients. Although the involvement of the STN is well documented in motor, cognitive and motivational processes, less is known regarding emotional processes. Here we have investigated the direct consequences of STN inactivation by excitotoxic lesions on emotional processing and reinforcement in the rat. We have used various behavioral procedures to assess affect for neutral, positive and negative reinforcers in STN lesioned rats. STN lesions reduced affective responses for positive (sweet solutions and negative (electric foot shock, Lithium Chloride-induced sickness reinforcers while they had no effect on responses for a more neutral reinforcer (novelty induced place preference. Furthermore, when given the choice between saccharine, a sweet but non caloric solution, and glucose, a more bland but caloric solution, in contrast to sham animals that preferred saccharine, STN lesioned animals preferred glucose over saccharine. Taken altogether these results reveal that STN plays a critical role in emotional processing. These results, in line with some clinical observations in PD patients subjected to STN surgery, suggest possible emotional side-effects of treatments targeting the STN. They also suggest that the increased motivation for sucrose previously reported cannot be due to increased pleasure, but could be responsible for the decreased motivation for cocaine reported after STN inactivation.

  6. Deep brain stimulation for Parkinson's disease: defining the optimal location within the subthalamic nucleus.

    Bot, Maarten; Schuurman, P Richard; Odekerken, Vincent J J; Verhagen, Rens; Contarino, Fiorella Maria; De Bie, Rob M A; van den Munckhof, Pepijn

    2018-05-01

    Individual motor improvement after deep brain stimulation (DBS) of the subthalamic nucleus (STN) for Parkinson's disease (PD) varies considerably. Stereotactic targeting of the dorsolateral sensorimotor part of the STN is considered paramount for maximising effectiveness, but studies employing the midcommissural point (MCP) as anatomical reference failed to show correlation between DBS location and motor improvement. The medial border of the STN as reference may provide better insight in the relationship between DBS location and clinical outcome. Motor improvement after 12 months of 65 STN DBS electrodes was categorised into non-responding, responding and optimally responding body-sides. Stereotactic coordinates of optimal electrode contacts relative to both medial STN border and MCP served to define theoretic DBS 'hotspots'. Using the medial STN border as reference, significant negative correlation (Pearson's correlation -0.52, P<0.01) was found between the Euclidean distance from the centre of stimulation to this DBS hotspot and motor improvement. This hotspot was located at 2.8 mm lateral, 1.7 mm anterior and 2.5 mm superior relative to the medial STN border. Using MCP as reference, no correlation was found. The medial STN border proved superior compared with MCP as anatomical reference for correlation of DBS location and motor improvement, and enabled defining an optimal DBS location within the nucleus. We therefore propose the medial STN border as a better individual reference point than the currently used MCP on preoperative stereotactic imaging, in order to obtain optimal and thus less variable motor improvement for individual patients with PD following STN DBS. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  7. High frequency deep brain stimulation attenuates subthalamic and cortical rhythms in Parkinson’s disease

    Diane eWhitmer

    2012-06-01

    Full Text Available Parkinson’s disease (PD is marked by excessive synchronous activity in the beta (8-35 Hz band throughout the cortico-basal ganglia network. The optimal location of high frequency deep brain stimulation (HF DBS within the subthalamic nucleus (STN region and the location of maximal beta hypersynchrony are currently matters of debate. Additionally, the effect of STN HF DBS on neural synchrony in functionally connected regions of motor cortex is unknown and of great interest. Scalp EEG studies demonstrated that stimulation of the STN can activate motor cortex antidromically, but the spatial specificity of this effect has not been examined. The present study examined the effect of STN HF DBS on neural synchrony within the cortico-basal ganglia network in patients with PD. We measured local field potentials dorsal to and within the STN of PD patients, and additionally in the motor cortex in a subset of these patients. We used diffusion tensor imaging (DTI to guide the placement of subdural cortical surface electrodes over the DTI-identified origin of the hyperdirect pathway between motor cortex and the STN. The results demonstrated that local beta power was attenuated during HF DBS both dorsal to and within the STN. The degree of attenuation was monotonic with increased DBS voltages in both locations, but this voltage-dependent effect was greater in the central STN than dorsal to the STN (p < 0.05. Cortical signals over the estimated origin of the hyperdirect pathway also demonstrated attenuation of beta hypersynchrony during DBS dorsal to or within STN, whereas signals from non-specific regions of motor cortex were not attenuated. The spatially specific suppression of beta synchrony in the motor cortex support the hypothesis that DBS may treat Parkinsonism by reducing excessive synchrony in the functionally connected sensorimotor network.

  8. Dynamic stereotypic responses of Basal Ganglia neurons to subthalamic nucleus high-frequency stimulation in the parkinsonian primate.

    Moran, Anan; Stein, Edward; Tischler, Hadass; Belelovsky, Katya; Bar-Gad, Izhar

    2011-01-01

    Deep brain stimulation (DBS) in the subthalamic nucleus (STN) is a well-established therapy for patients with severe Parkinson's disease (PD); however, its mechanism of action is still unclear. In this study we explored static and dynamic activation patterns in the basal ganglia (BG) during high-frequency macro-stimulation of the STN. Extracellular multi-electrode recordings were performed in primates rendered parkinsonian using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Recordings were preformed simultaneously in the STN and the globus pallidus externus and internus. Single units were recorded preceding and during the stimulation. During the stimulation, STN mean firing rate dropped significantly, while pallidal mean firing rates did not change significantly. The vast majority of neurons across all three nuclei displayed stimulation driven modulations, which were stereotypic within each nucleus but differed across nuclei. The predominant response pattern of STN neurons was somatic inhibition. However, most pallidal neurons demonstrated synaptic activation patterns. A minority of neurons across all nuclei displayed axonal activation. Temporal dynamics were observed in the response to stimulation over the first 10 seconds in the STN and over the first 30 seconds in the pallidum. In both pallidal segments, the synaptic activation response patterns underwent delay and decay of the magnitude of the peak response due to short term synaptic depression. We suggest that during STN macro-stimulation the STN goes through a functional ablation as its upper bound on information transmission drops significantly. This notion is further supported by the evident dissociation between the stimulation driven pre-synaptic STN somatic inhibition and the post-synaptic axonal activation of its downstream targets. Thus, BG output maintains its firing rate while losing the deleterious effect of the STN. This may be a part of the mechanism leading to the beneficial effect of DBS in PD.

  9. Acute changes in mood induced by subthalamic deep brain stimulation in Parkinson disease are modulated by psychiatric diagnosis.

    Eisenstein, Sarah A; Dewispelaere, William B; Campbell, Meghan C; Lugar, Heather M; Perlmutter, Joel S; Black, Kevin J; Hershey, Tamara

    2014-01-01

    Deep brain stimulation of the subthalamic nucleus (STN DBS) reduces Parkinson disease (PD) motor symptoms but has unexplained, variable effects on mood. The study tested the hypothesis that pre-existing mood and/or anxiety disorders or increased symptom severity negatively affects mood response to STN DBS. Thirty-eight PD participants with bilateral STN DBS and on PD medications were interviewed with Structured Clinical Interview for DSM-IV-TR Axis I Disorders (SCID) and completed Beck Depression Inventory (BDI) and Spielberger State Anxiety Inventory (SSAI) self-reports. Subsequently, during OFF and optimal ON (clinical settings) STN DBS conditions and while off PD medications, motor function was assessed with the United Parkinson Disease Rating Scale (UPDRS, part III), and participants rated their mood with Visual Analogue Scales (VAS), and again completed SSAI. VAS mood variables included anxiety, apathy, valence and emotional arousal. STN DBS improved UPDRS scores and mood. Unexpectedly, PD participants diagnosed with current anxiety or mood disorders experienced greater STN DBS-induced improvement in mood than those diagnosed with remitted disorders or who were deemed as having never met threshold criteria for diagnosis. BDI and SSAI scores did not modulate mood response to STN DBS, indicating that clinical categorical diagnosis better differentiates mood response to STN DBS than self-rated symptom severity. SCID diagnosis, BDI and SSAI scores did not modulate motor response to STN DBS. PD participants diagnosed with current mood or anxiety disorders are more sensitive to STN DBS-induced effects on mood, possibly indicating altered basal ganglia circuitry in this group. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Load-Dependent Interference of Deep Brain Stimulation of the Subthalamic Nucleus with Switching from Automatic to Controlled Processing During Random Number Generation in Parkinson's Disease.

    Williams, Isobel Anne; Wilkinson, Leonora; Limousin, Patricia; Jahanshahi, Marjan

    2015-01-01

    Deep brain stimulation of the subthalamic nucleus (STN DBS) ameliorates the motor symptoms of Parkinson's disease (PD). However, some aspects of executive control are impaired with STN DBS. We tested the prediction that (i) STN DBS interferes with switching from automatic to controlled processing during fast-paced random number generation (RNG) (ii) STN DBS-induced cognitive control changes are load-dependent. Fifteen PD patients with bilateral STN DBS performed paced-RNG, under three levels of cognitive load synchronised with a pacing stimulus presented at 1, 0.5 and 0.33 Hz (faster rates require greater cognitive control), with DBS on or off. Measures of output randomness were calculated. Countscore 1 (CS1) indicates habitual counting in steps of one (CS1). Countscore 2 (CS2) indicates a more controlled strategy of counting in twos. The fastest rate was associated with an increased CS1 score with STN DBS on compared to off. At the slowest rate, patients had higher CS2 scores with DBS off than on, such that the differences between CS1 and CS2 scores disappeared. We provide evidence for a load-dependent effect of STN DBS on paced RNG in PD. Patients could switch to more controlled RNG strategies during conditions of low cognitive load at slower rates only when the STN stimulators were off, but when STN stimulation was on, they engaged in more automatic habitual counting under increased cognitive load. These findings are consistent with the proposal that the STN implements a switch signal from the medial frontal cortex which enables a shift from automatic to controlled processing.

  11. Subthalamic nucleus long-range synchronization—an independent hallmark of human Parkinson's disease

    Moshel, Shay; Shamir, Reuben R.; Raz, Aeyal; de Noriega, Fernando R.; Eitan, Renana; Bergman, Hagai; Israel, Zvi

    2013-01-01

    Beta-band synchronous oscillations in the dorsolateral region of the subthalamic nucleus (STN) of human patients with Parkinson's disease (PD) have been frequently reported. However, the correlation between STN oscillations and synchronization has not been thoroughly explored. The simultaneous recordings of 2390 multi-unit pairs recorded by two parallel microelectrodes (separated by fixed distance of 2 mm, n = 72 trajectories with two electrode tracks >4 mm STN span) in 57 PD patients undergoing STN deep brain stimulation surgery were analyzed. Automatic procedures were utilized to divide the STN into dorsolateral oscillatory and ventromedial non-oscillatory regions, and to quantify the intensity of STN oscillations and synchronicity. Finally, the synchronicity of simultaneously vs. non-simultaneously recorded pairs were compared using a shuffling procedure. Synchronization was observed predominately in the beta range and only between multi-unit pairs in the dorsolateral oscillatory region (n = 615). In paired recordings between sites in the dorsolateral and ventromedial (n = 548) and ventromedial-ventromedial region pairs (n = 1227), no synchronization was observed. Oscillation and synchronicity intensity decline along the STN dorsolateral-ventromedial axis suggesting a fuzzy border between the STN regions. Synchronization strength was significantly correlated to the oscillation power, but synchronization was no longer observed following shuffling. We conclude that STN long-range beta oscillatory synchronization is due to increased neuronal coupling in the Parkinsonian brain and does not merely reflect the outcome of oscillations at similar frequency. The neural synchronization in the dorsolateral (probably the motor domain) STN probably augments the pathological changes in firing rate and patterns of subthalamic neurons in PD patients. PMID:24312018

  12. Glycine: an alternative transmitter candidate of the pallidosubthalamic projection neurons in the rat

    Takada, M.; Hattori, T.

    1987-01-01

    Autoradiographic retrograde tracing techniques with radioactive transmitters were used to analyse the identity of a putative transmitter in the rat pallidosubthalamic (GP-STN) pathway. One to 2 hours after the stereotaxic injection of 3 H-glycine restricted to the STN, a large number of neuronal somata were radiolabeled in the GP. No comparable labeling was observed following the injection of 3 H-gamma-aminobutyric acid ( 3 H-GABA) into the same nucleus even with survival times as long as 6 hours. Specifically, no significant somatic labeling was detected either in the GP or in the caudoputamen (CPU). Only when 3 H-GABA was injected into the substantia nigra did CPU and GP neurons become labeled. On the contrary, STN neuronal somata were invariably labeled 6 hours after the intrapallidal injection of 3 H-GABA, whereas no perikaryal labeling was observed in the STN after 3 H-glycine injection into the GP. The perikaryal labeling was prevented in all cases by intraventricular administration of colchicine 1 day before the isotope injections. The observations suggest that 3 H-glycine was preferentially transported retrogradely through the GP-STN pathway, and 3 H-GABA through the STN-GP projection. In view of the recent controversy on the role of GABA as a putative transmitter of the GP-STN projection, we now propose glycine as an alternative transmitter candidate of these critically situated neurons in the basal ganglia

  13. Cognitive outcome and reliable change indices two years following bilateral subthalamic nucleus deep brain stimulation.

    Williams, Amy E; Arzola, Gladys Marina; Strutt, Adriana M; Simpson, Richard; Jankovic, Joseph; York, Michele K

    2011-06-01

    Subthalamic nucleus deep brain stimulation (STN-DBS) is currently the treatment of choice for medication-resistant levodopa-related motor complications in patients with Parkinson's disease (PD). While STN-DBS often results in meaningful motor improvements, consensus regarding long-term neuropsychological outcome continues to be debated. We assessed the cognitive outcomes of 19 STN-DBS patients compared to a group of 18 medically-managed PD patients on a comprehensive neuropsychological battery at baseline and two years post-surgery. Patients did not demonstrate changes in global cognitive functioning on screening measures. However, neuropsychological results revealed impairments in nonverbal recall, oral information processing speed, and lexical and semantic fluency in STN-DBS patients compared to PD controls 2 years post-surgery in these preliminary analyses. Additionally, reliable change indices revealed that approximately 50% of STN-DBS patients demonstrated significant declines in nonverbal memory and oral information processing speed compared to 25-30% of PD controls, and 26% of STN-DBS patients declined on lexical fluency compared to 11% of PD patients. Approximately 30% of both groups declined on semantic fluency. The number of STN-DBS patients who converted to dementia 2 years following surgery was not significantly different from the PD participants (32% versus 16%, respectively). Our results suggest that neuropsychological evaluations may identify possible mild cognitive changes following surgery. Copyright © 2011 Elsevier Ltd. All rights reserved.

  14. Risk factors for malignancy in patients with solitary thyroid nodules and their impact on the management

    Jun D Tai

    2012-01-01

    Full Text Available Background: Presently it is difficult to differentiate malignancy for thyroid nodules by palpation, ultrasonography and fine-needle aspiration cytology (FNAC at the outpatient department, especially for solitary thyroid nodule (STN. So a great emphasis should be placed on the STN. AIms: The objective of this study was to investigate the predictive clinicopathological risk factors for malignancy in patients with STN and further to provide an appropriate clinical management. Materials and Methods: The records were reviewed from 265 patients with STN who had undergone thyroidectomy in our hospital. All cases were classified as two independent groups in terms of the final pathological results to assess the independent risk factors using a multinomial logistic regression analysis. Results: A multinomial logistic analysis revealed that the male gender, microcalcification and cervical lymphadenopathy were independent risk factors related to malignancy in patients with STN. The incidence of malignancy in patients with 0,1,2,3 risks was 10.71%, 26.6%, 61.43%, and 100%, respectively. Conclusions: Male gender, microcalcification and lymphadenopathy were independent risk factors for predicting the malignancy in patients with STN. Patients with more than two of those risk factors should be subjected to further examination or thyroidectomy. The findings may provide a simple and reasonable management for the STN.

  15. The impact of Parkinson's disease and subthalamic deep brain stimulation on reward processing.

    Evens, Ricarda; Stankevich, Yuliya; Dshemuchadse, Maja; Storch, Alexander; Wolz, Martin; Reichmann, Heinz; Schlaepfer, Thomas E; Goschke, Thomas; Lueken, Ulrike

    2015-08-01

    Due to its position in cortico-subthalamic and cortico-striatal pathways, the subthalamic nucleus (STN) is considered to play a crucial role not only in motor, but also in cognitive and motivational functions. In the present study we aimed to characterize how different aspects of reward processing are affected by disease and deep brain stimulation of the STN (DBS-STN) in patients with idiopathic Parkinson's disease (PD). We compared 33 PD patients treated with DBS-STN under best medical treatment (DBS-on, medication-on) to 33 PD patients without DBS, but optimized pharmacological treatment and 34 age-matched healthy controls. We then investigated DBS-STN effects using a postoperative stimulation-on/ -off design. The task set included a delay discounting task, a task to assess changes in incentive salience attribution, and the Iowa Gambling Task. The presence of PD was associated with increased incentive salience attribution and devaluation of delayed rewards. Acute DBS-STN increased risky choices in the Iowa Gambling Task under DBS-on condition, but did not further affect incentive salience attribution or the evaluation of delayed rewards. Findings indicate that acute DBS-STN affects specific aspects of reward processing, including the weighting of gains and losses, while larger-scale effects of disease or medication are predominant in others reward-related functions. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Deep brain stimulation of the subthalamic nucleus modulates reward processing and action selection in Parkinson patients.

    Wagenbreth, Caroline; Zaehle, Tino; Galazky, Imke; Voges, Jürgen; Guitart-Masip, Marc; Heinze, Hans-Jochen; Düzel, Emrah

    2015-06-01

    Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for motor impairments in Parkinson's disease (PD) but its effect on the motivational regulation of action control is still not fully understood. We investigated whether DBS of the STN influences the ability of PD patients to act for anticipated reward or loss, or whether DBS improves action execution independent of motivational valence. 16 PD patients (12 male, mean age = 58.5 ± 10.17 years) treated with bilateral STN-DBS and an age- and gender-matched group of healthy controls (HC) performed a go/no-go task whose contingencies explicitly decouple valence and action. Patients were tested with (ON) and without (OFF) active STN stimulation. For HC, there was a benefit in performing rewarded actions when compared to actions that avoided punishment. PD patients showed such a benefit reliably only when STN stimulation was ON. In fact, the relative behavioral benefit for go for reward over go to avoid losing was stronger in the PD patients under DBS ON than in HC. In PD patients, rather than generally improving motor functions independent of motivational valence, modulation of the STN by DBS improves action execution specifically when rewards are anticipated. Thus, STN-DBS establishes a reliable congruency between action and reward ("Pavlovian congruency") and remarkably enhances it over the level observed in HC.

  17. Bilateral stimulation of the subthalamic nucleus has differential effects on reactive and proactive inhibition and conflict-induced slowing in Parkinson's disease.

    Obeso, Ignacio; Wilkinson, Leonora; Rodríguez-Oroz, Maria-Cruz; Obeso, Jose A; Jahanshahi, Marjan

    2013-05-01

    It has been proposed that the subthalamic nucleus (STN) mediates response inhibition and conflict resolution through the fronto-basal ganglia pathways. Our aim was to compare the effects of deep brain stimulation (DBS) of the STN on reactive and proactive inhibition and conflict resolution in Parkinson's disease using a single task. We used the conditional Stop signal reaction time task that provides the Stop signal reaction time (SSRT) as a measure of reactive inhibition, the response delay effect (RDE) as a measure of proactive inhibition and conflict-induced slowing (CIS) as a measure of conflict resolution. DBS of the STN significantly prolonged SSRT relative to stimulation off. However, while the RDE measure of proactive inhibition was not significantly altered by DBS of the STN, relative to healthy controls, RDE was significantly lower with DBS off but not DBS on. DBS of the STN did not alter the mean CIS but produced a significant differential effect on the slowest and fastest RTs on conflict trials, further prolonging the slowest RTs on the conflict trials relative to DBS off and to controls. These results are the first demonstration, using a single task in the same patient sample, that DBS of the STN produces differential effects on reactive and proactive inhibition and on conflict resolution, suggesting that these effects are likely to be mediated through the impact of STN stimulation on different fronto-basal ganglia pathways: hyperdirect, direct and indirect.

  18. Self-Reported Executive Functioning in Everyday Life in Parkinson's Disease after Three Months of Subthalamic Deep Brain Stimulation.

    Pham, Uyen Ha Gia; Andersson, Stein; Toft, Mathias; Pripp, Are Hugo; Konglund, Ane Eidahl; Dietrichs, Espen; Malt, Ulrik Fredrik; Skogseid, Inger Marie; Haraldsen, Ira Ronit Hebolt; Solbakk, Anne-Kristin

    2015-01-01

    Objective. Studies on the effect of subthalamic deep brain stimulation (STN-DBS) on executive functioning in Parkinson's disease (PD) are still controversial. In this study we compared self-reported daily executive functioning in PD patients before and after three months of STN-DBS. We also examined whether executive functioning in everyday life was associated with motor symptoms, apathy, and psychiatric symptoms. Method. 40 PD patients were examined with the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A), the Symptom Checklist 90-Revised (SCL-90-R), and the Apathy Evaluation Scale (AES-S). Results. PD patients reported significant improvement in daily life executive functioning after 3 months of STN-DBS. Anxiety scores significantly declined, while other psychiatric symptoms remained unchanged. The improvement of self-reported executive functioning did not correlate with motor improvement after STN-DBS. Apathy scores remained unchanged after surgery. Only preoperative depressed mood had predictive value to the improvement of executive function and appears to prevent potentially favorable outcomes from STN-DBS on some aspects of executive function. Conclusion. PD patients being screened for STN-DBS surgery should be evaluated with regard to self-reported executive functioning. Depressive symptoms in presurgical PD patients should be treated. Complementary information about daily life executive functioning in PD patients might enhance further treatment planning of STN-DBS.

  19. An examination of the effects of subthalamic nucleus inhibition or μ-opioid receptor stimulation on food-directed motivation in the non-deprived rat

    Pratt, Wayne E.; Choi, Eugene; Guy, Elizabeth G.

    2012-01-01

    The subthalamic nucleus (STN) serves important functions in regulating movement, cognition, and motivation and is connected with cortical and basal ganglia circuits that process reward and reinforcement. In order to further examine the role of the STN on motivation toward food in non-deprived rats, these experiments studied the effects of pharmacological inhibition or μ-opioid receptor stimulation of the STN on the 2-hr intake of a sweetened fat diet, the amount of work exerted to earn sucrose on a progressive ratio 2 (PR-2) schedule of reinforcement, and performance on a differential reinforcement of low-rate responding (DRL) schedule for sucrose reward. Separate behavioral groups (N = 6–9) were tested following bilateral inhibition of the STN with the GABAA receptor agonist muscimol (at 0–5 ng/0.5 μl/side) or following μ-opioid receptor stimulation with the agonist D-Ala2, N-MePhe4, Gly-ol-enkephalin (DAMGO; at 0, 0.025 or 0.25 μg/0.5 μl/side). Although STN inhibition increased ambulatory behavior during 2-hr feeding sessions, it did not significantly alter intake of the sweetened fat diet. STN inhibition also did not affect the breakpoint for sucrose pellets during a 1-hr PR-2 reinforcement schedule or impact the number of reinforcers earned on a 1-hr DRL-20 sec reinforcement schedule in non-deprived rats. In contrast, STN μ-opioid receptor stimulation significantly increased feeding on the palatable diet and reduced the reinforcers earned on a DRL-20 schedule, although DAMGO microinfusions had no effect on PR-2 performance. These data suggest that STN inhibition does not enhance incentive motivation for food in the absence of food restriction and that STN μ-opioid receptors play an important and unique role in motivational processes. PMID:22391117

  20. Posterolateral Trajectories Favor a Longer Motor Domain in Subthalamic Nucleus Deep Brain Stimulation for Parkinson Disease.

    Tamir, Idit; Marmor-Levin, Odeya; Eitan, Renana; Bergman, Hagai; Israel, Zvi

    2017-10-01

    The clinical outcome of patients with Parkinson disease (PD) who undergo subthalamic nucleus (STN) deep brain stimulation (DBS) is, in part, determined by the length of the electrode trajectory through the motor STN domain, the dorsolateral oscillatory region (DLOR). Trajectory length has been found to correlate with the stimulation-related improvement in patients' motor function (estimated by part III of the United Parkinson's Disease Rating Scale [UPDRS]). Therefore, it seems that ideally trajectories should have maximal DLOR length. We retrospectively studied the influence of various anatomic aspects of the brains of patients with PD and the geometry of trajectories planned on the length of the DLOR and STN recorded during DBS surgery. We examined 212 trajectories and 424 microelectrode recording tracks in 115 patients operated on in our center between 2010 and 2015. We found a strong correlation between the length of the recorded DLOR and STN. Trajectories that were more lateral and/or posterior in orientation had a longer STN and DLOR pass, although the DLOR/STN fraction length remained constant. The STN target was more lateral when the third ventricle was wider, and the latter correlated with older age and male gender. Trajectory angles correlate with the recorded STN and DLOR lengths, and should be altered toward a more posterolateral angle in older patients and atrophied brains to compensate for the changes in STN location and geometry. These fine adjustments should yield a longer motor domain pass, thereby improving the patient's predicted outcome. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Is the carbohydrate sialosyl-Tn a marker for altered, non-malignant activity in squamous epithelium in the head and neck region?

    Bryne, M.; Gravdahl, C.; Koppang, H.S.

    1995-01-01

    on basal cells in some lesions with epithelial hyperplasia and dysplasia. The aim of this study was to carry out a systematic investigation of STn expression on epithelial basal cells in hyperplastic, 'borderline' malignant, and malignant head and neck lesions, to see if the expression of STn is associated...... with basal cells in other locations. The most highly differentiated lesions, such as focal epithelial hyperplasia and verrucous hyperplasia, revealed a high percentage (86 per cent in both cases) of STn reactivity. The least-differentiated verrucous carcinomas (VCs) and keratoacanthomas (KAs) did not express...

  2. Effects of dopaminergic and subthalamic stimulation on musical performance.

    van Vugt, Floris T; Schüpbach, Michael; Altenmüller, Eckart; Bardinet, Eric; Yelnik, Jérôme; Hälbig, Thomas D

    2013-05-01

    Although subthalamic-deep brain stimulation (STN-DBS) is an efficient treatment for Parkinson's disease (PD), its effects on fine motor functions are not clear. We present the case of a professional violinist with PD treated with STN-DBS. DBS improved musical articulation, intonation and emotional expression and worsened timing relative to a timekeeper (metronome). The same effects were found for dopaminergic treatment. These results suggest that STN-DBS, mimicking the effects of dopaminergic stimulation, improves fine-tuned motor behaviour whilst impairing timing precision.

  3. Long-term Efficacy of Subthalamic Nucleus Deep Brain Stimulation in Parkinson′s Disease: A 5-year Follow-up Study in China

    Lu-Lu Jiang

    2015-01-01

    Conclusions: STN DBS is an effective intervention for PD, although associated with a slightly diminished efficacy after 5 years. Compared with other studies, patients in our study required lower voltage and medication for satisfactory symptom control.

  4. Deep Brain Stimulation Target Selection in an Advanced Parkinson's Disease Patient with Significant Tremor and Comorbid Depression

    Amar S. Patel

    2017-04-01

    Full Text Available Clinical Vignette: A 67-year-old female with advanced Parkinson's disease (PD, medically refractory tremor, and a history of significant depression presents for evaluation of deep brain stimulation (DBS candidacy.  Clinical Dilemma: Traditionally, stimulation of the subthalamic nucleus (STN has been the preferred target for patients with significant PD tremor. However, STN stimulation is avoided in patients with a significant pre-surgical history of mood disorder.  Clinical Solution: Bilateral DBS of the globus pallidus interna led to significant short term improvement in PD motor symptoms, including significant tremor reduction.  Gap in Knowledge: There is insufficient evidence to support or refute clinicians' traditional preference for STN stimulation in treating refractory PD tremor. Similarly, the available evidence for risk of worsening depression and/or suicidality after STN DBS is mixed. Both questions require further clarification to guide patient and clinician decision-making.

  5. Resistance to freezing and thawing of mortar specimens made from ...

    Unknown

    2000-06-03

    Jun 3, 2000 ... Portland cement (PC) production is markedly dependent on a relatively high ... under the attack of various media is still insufficiently verified (Beretka et al ..... cement of higher quality. (IV) The ... Chemical Industry) p. 1. STN 72 ...

  6. Deep brain stimulation of the subthalamic nucleus improves pain in Parkinson's disease.

    Pellaprat, Jean; Ory-Magne, Fabienne; Canivet, Cindy; Simonetta-Moreau, Marion; Lotterie, Jean-Albert; Radji, Fatai; Arbus, Christophe; Gerdelat, Angélique; Chaynes, Patrick; Brefel-Courbon, Christine

    2014-06-01

    In Parkinson's disease (PD), chronic pain is a common symptom which markedly affects the quality of life. Some physiological arguments proposed that Deep Brain Stimulation of the Subthalamic Nucleus (STN-DBS) could improve pain in PD. We investigated in 58 PD patients the effect of STN-DBS on pain using the short McGill Pain Questionnaire and other pain parameters such as the Bodily discomfort subscore of the Parkinson's disease Questionnaire 39 and the Unified Parkinson's Disease Rating Scale section II (UPDRS II) item 17. All pain scores were significantly improved 12 months after STN-DBS. This improvement was not correlated with motor improvement, depression scores or L-Dopa reduction. STN-DBS induced a substantial beneficial effect on pain in PD, independently of its motor effects and mood status of patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. The Mathematics of Dispatchability Revisited

    Morris, Paul

    2016-01-01

    Dispatchability is an important property for the efficient execution of temporal plans where the temporal constraints are represented as a Simple Temporal Network (STN). It has been shown that every STN may be reformulated as a dispatchable STN, and dispatchability ensures that the temporal constraints need only be satisfied locally during execution. Recently it has also been shown that Simple Temporal Networks with Uncertainty, augmented with wait edges, are Dynamically Controllable provided every projection is dispatchable. Thus, the dispatchability property has both theoretical and practical interest. One thing that hampers further work in this area is the underdeveloped theory. The existing definitions are expressed in terms of algorithms, and are less suitable for mathematical proofs. In this paper, we develop a new formal theory of dispatchability in terms of execution sequences. We exploit this to prove a characterization of dispatchability involving the structural properties of the STN graph. This facilitates the potential application of the theory to uncertainty reasoning.

  8. FDG-PET study of the bilateral subthalamic nucleus stimulation effects on the regional cerebral metabolism in advanced Parkinson disease

    Li, D.; Shen, J.; Zan, S.; Sun, B.; Zuo, C.; Guan, Y.; Zhao, Y.

    2006-01-01

    The aim of the study was to evaluate the changes in regional cerebral metabolic rate of glucose (rCMRGIu) induced by bilateral subthalamic nucleus (STN) stimulation in advanced Parkinson's disease (PD). 18 F-Fluorodeoxyglucose (FDG) PET data obtained before and one month after stimulation were analyzed with statistical parametric mapping (SPM). As a result of clinically effective bilateral STN stimulation, rCMRGIu increased in lateral globus pallidus (GP), upper brain stem, dorsolateral prefrontal cortex (DLPFC) and posterior parietal-occipital cortex, and decreased in the orbital frontal cortex and parahippocampus gyrus (p <0.001). We conclude that the alleviation of clinical symptoms in advanced PD by bilateral STN stimulation may be the result of activation of both ascending and descending pathways from STN and of restoration of the impaired higher-order cortex functions. (author)

  9. Deep brain stimulation of the subthalamic nucleus: effectiveness in advanced Parkinson's disease patients previously reliant on apomorphine

    Varma, T; Fox, S; Eldridge, P; Littlechild, P; Byrne, P; Forster, A; Marshall, A; Cameron, H; McIver, K; Fletcher, N; Steiger, M

    2003-01-01

    Objectives: To assess the efficacy of bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) in patients with advanced Parkinson's disease previously reliant on apomorphine as their main antiparkinsonian medication.

  10. Association of heart rate variability with clinical outcome in Parkinsonian patients after subthalamic deep brain stimulation: A retrospective cohort study

    Shin-Yuan Chen

    2011-09-01

    Conclusion: Our study showed an improvement in autonomic cardiovascular regulation in Parkinsonian patients with >50% improvement in rating scale after STN-DBS, which implied morbidity reduction in nonmotor symptoms among such patients.

  11. The Dominant-Subthalamic Nucleus Phenomenon in Bilateral Deep Brain Stimulation for Parkinson’s Disease: Evidence from a Gait Analysis Study

    Mario Giorgio Rizzone

    2017-10-01

    Full Text Available BackgroundIt has been suggested that parkinsonian [Parkinson’s disease (PD] patients might have a “dominant” (DOM subthalamic nucleus (STN, whose unilateral electrical stimulation [deep brain stimulation (DBS] could lead to an improvement in PD symptoms similar to bilateral STN-DBS.ObjectivesSince disability in PD patients is often related to gait problems, in this study, we wanted to investigate in a group of patients bilaterally implanted for STN-DBS: (1 if it was possible to identify a subgroup of subjects with a dominant STN; (2 in the case, if the unilateral stimulation of the dominant STN was capable to improve gait abnormalities, as assessed by instrumented multifactorial gait analysis, similarly to what observed with bilateral stimulation.MethodsWe studied 10 PD patients with bilateral STN-DBS. A clinical evaluation and a kinematic, kinetic, and electromyographic (EMG analysis of overground walking were performed—off medication—in four conditions: without stimulation, with bilateral stimulation, with unilateral right or left STN-DBS. Through a hierarchical agglomerative cluster analysis based on motor Unified Parkinson’s Disease Rating Scale scores, it was possible to separate patients into two groups, based on the presence (six patients, DOM group or absence (four patients, NDOM group of a dominant STN.ResultsIn the DOM group, both bilateral and unilateral stimulation of the dominant STN significantly increased gait speed, stride length, range of motion of lower limb joints, and peaks of moment and power at the ankle joint; moreover, the EMG activation pattern of distal leg muscles was improved. The unilateral stimulation of the non-dominant STN did not produce any significant effect. In the NDOM group, only bilateral stimulation determined a significant improvement of gait parameters.ConclusionIn the DOM group, the effect of unilateral stimulation of the dominant STN determined an improvement of gait parameters similar to

  12. Basal ganglia dysfunction in OCD: subthalamic neuronal activity correlates with symptoms severity and predicts high-frequency stimulation efficacy.

    Welter, M-L; Burbaud, P; Fernandez-Vidal, S; Bardinet, E; Coste, J; Piallat, B; Borg, M; Besnard, S; Sauleau, P; Devaux, B; Pidoux, B; Chaynes, P; Tézenas du Montcel, S; Bastian, A; Langbour, N; Teillant, A; Haynes, W; Yelnik, J; Karachi, C; Mallet, L

    2011-05-03

    Functional and connectivity changes in corticostriatal systems have been reported in the brains of patients with obsessive-compulsive disorder (OCD); however, the relationship between basal ganglia activity and OCD severity has never been adequately established. We recently showed that deep brain stimulation of the subthalamic nucleus (STN), a central basal ganglia nucleus, improves OCD. Here, single-unit subthalamic neuronal activity was analysed in 12 OCD patients, in relation to the severity of obsessions and compulsions and response to STN stimulation, and compared with that obtained in 12 patients with Parkinson's disease (PD). STN neurons in OCD patients had lower discharge frequency than those in PD patients, with a similar proportion of burst-type activity (69 vs 67%). Oscillatory activity was present in 46 and 68% of neurons in OCD and PD patients, respectively, predominantly in the low-frequency band (1-8 Hz). In OCD patients, the bursty and oscillatory subthalamic neuronal activity was mainly located in the associative-limbic part. Both OCD severity and clinical improvement following STN stimulation were related to the STN neuronal activity. In patients with the most severe OCD, STN neurons exhibited bursts with shorter duration and interburst interval, but higher intraburst frequency, and more oscillations in the low-frequency bands. In patients with best clinical outcome with STN stimulation, STN neurons displayed higher mean discharge, burst and intraburst frequencies, and lower interburst interval. These findings are consistent with the hypothesis of a dysfunction in the associative-limbic subdivision of the basal ganglia circuitry in OCD's pathophysiology.

  13. Adaptive grip force is modulated by subthalamic beta activity in Parkinson's disease patients

    Lukas L. Imbach

    2015-01-01

    Conclusion: The time-locked suppression of beta oscillatory activity in the STN is in line with previous reports of beta ERD prior to voluntary movements. Our results show that the STN is involved in anticipatory grip force control in PD patients. The difference in the phasic beta ERD between the two tasks and the reduction of cortico-subthalamic synchronization suggests that qualitatively different neuronal network states are involved in different grip force control tasks.

  14. Network effects of subthalamic deep brain stimulation drive a unique mixture of responses in basal ganglia output

    Humphries, Mark D.; Gurney, Kevin

    2012-01-01

    Deep brain stimulation (DBS) is a remarkably successful treatment for the motor symptoms of Parkinson's disease. High-frequency stimulation of the subthalamic nucleus (STN) within the basal ganglia is a main clinical target, but the physiological mechanisms of therapeutic STN DBS at the cellular and network level are unclear. We set out to begin to address the hypothesis that a mixture of responses in the basal ganglia output nuclei, combining regularized firing and inhibition, is a key contr...

  15. Review of selected contributions of the conference 'Integrated quality management systems in completion of units 3 and 4 Mochovce'

    2009-04-01

    There were 14 contributions presented of the conference focused on the integrated quality management systems in completion EMO34. Contributions were focused both on theoretical problems from the project management area and on the applications in practice in management systems implementation in accordance with the standards: STN EN ISO 9001:2000, STN EN ISO 14 001:2005, and OHSAS 18 001:1999 at the completion of the Nuclear Power Plant Mochovce of units 3 and 4

  16. The effects of bilateral stimulation of the subthalamic nucleus on heart rate variability in patients with Parkinson's disease.

    Liu, Kang-Du; Shan, Din-E; Kuo, Terry B J; Yang, Cheryl C H

    2013-07-01

    The beneficial effects of subthalamic nucleus deep brain stimulation (STN-DBS) on motor symptoms and quality of life in Parkinson's disease (PD) are well known, but little is known of the effects on autonomic function. Diffusion of current during stimulation of the STN may simultaneously involve the motor and nonmotor, limbic and associative areas of the STN. The aims of this study were to examine whether STN stimulation affects functions of the autonomic nervous system and, if so, to correlate the effects with the active contacts of electrodes in the STN. Eight PD patients with good motor control and quality of sleep after STN-DBS surgery were recruited. All patients had two days of recordings with portable polysomnography (PSG) (first night with stimulation "on" and second night "off"). From the PSG data, the first sleep cycle of each recording night was defined. Heart rate variability (HRV) was analyzed between the same uninterrupted periods of the two sleep nights. In addition, the optimal electrode positions were defined from postoperative MRI studies, and the coordinates of active contacts were confirmed. HRV spectral analysis showed that only low-frequency (LF)/high-frequency (HF) power was significantly activated in the stimulation "on" groups (P = 0.011). There was a significant negative correlation between power change of LF/HF and electrode position lateral to the midcommissural point (ρ = 0.857, P = 0.007) These results demonstrate that STN-DBS can enhance sympathetic regulation; the autonomic response may be due to electrical signals being distributed to limbic components of the STN or descending sympathetic pathways in the zona incerta.

  17. Subthalamic deep brain stimulation improves auditory sensory gating deficit in Parkinson's disease.

    Gulberti, A; Hamel, W; Buhmann, C; Boelmans, K; Zittel, S; Gerloff, C; Westphal, M; Engel, A K; Schneider, T R; Moll, C K E

    2015-03-01

    While motor effects of dopaminergic medication and subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson's disease (PD) patients are well explored, their effects on sensory processing are less well understood. Here, we studied the impact of levodopa and STN-DBS on auditory processing. Rhythmic auditory stimulation (RAS) was presented at frequencies between 1 and 6Hz in a passive listening paradigm. High-density EEG-recordings were obtained before (levodopa ON/OFF) and 5months following STN-surgery (ON/OFF STN-DBS). We compared auditory evoked potentials (AEPs) elicited by RAS in 12 PD patients to those in age-matched controls. Tempo-dependent amplitude suppression of the auditory P1/N1-complex was used as an indicator of auditory gating. Parkinsonian patients showed significantly larger AEP-amplitudes (P1, N1) and longer AEP-latencies (N1) compared to controls. Neither interruption of dopaminergic medication nor of STN-DBS had an immediate effect on these AEPs. However, chronic STN-DBS had a significant effect on abnormal auditory gating characteristics of parkinsonian patients and restored a physiological P1/N1-amplitude attenuation profile in response to RAS with increasing stimulus rates. This differential treatment effect suggests a divergent mode of action of levodopa and STN-DBS on auditory processing. STN-DBS may improve early attentive filtering processes of redundant auditory stimuli, possibly at the level of the frontal cortex. Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  18. Movement-related changes in local and long-range synchronization in Parkinson’s disease revealed by simultaneous magnetoencephalography and intracranial recordings

    Litvak, Vladimir; Eusebio, Alexandre; Jha, Ashwani; Oostenveld, Robert; Barnes, Gareth; Foltynie, Tom; Limousin, Patricia; Zrinzo, Ludvic; Hariz, Marwan I.; Friston, Karl; Brown, Peter

    2012-01-01

    Functional neurosurgery has afforded the opportunity to assess interactions between populations of neurons in the human cerebral cortex and basal ganglia in patients with Parkinson’s disease (PD). Interactions occur over a wide range of frequencies, and the functional significance of those above 30 Hz is particularly unclear. Do they improve movement and, if so, in what way? We acquired simultaneously magnetoencephalography (MEG) and direct recordings from the subthalamic nucleus (STN) in 17 PD patients. We examined the effect of synchronous and sequential finger movements and of the dopamine prodrug levodopa on induced power in the contralateral primary motor cortex (M1) and STN and on the coherence between the two structures. We observed discrete peaks in M1 and STN power over 60-90 Hz and 300-400 Hz. All these power peaks increased with movement and levodopa treatment. Only STN activity over 60-90 Hz was coherent with activity in M1. Directionality analysis showed that STN gamma activity at 60-90 Hz tended to drive gamma activity in M1. The effects of levodopa on both local and distant synchronisation over 60-90 Hz correlated with the degree of improvement in bradykinesia-rigidity, as did local STN activity at 300-400 Hz. Despite this, there were no effects of movement type, nor interactions between movement type and levodopa in the STN, nor in the coherence between STN and M1. We conclude that synchronisation over 60-90 Hz in the basal ganglia cortical network is prokinetic, but likely through a modulatory effect rather than any involvement in explicit motor processing. PMID:22855804

  19. The Subthalamic Nucleus, Limbic Function, and Impulse Control.

    Rossi, P Justin; Gunduz, Aysegul; Okun, Michael S

    2015-12-01

    It has been well documented that deep brain stimulation (DBS) of the subthalamic nucleus (STN) to address some of the disabling motor symptoms of Parkinson's disease (PD) can evoke unintended effects, especially on non-motor behavior. This observation has catalyzed more than a decade of research concentrated on establishing trends and identifying potential mechanisms for these non-motor effects. While many issues remain unresolved, the collective result of many research studies and clinical observations has been a general recognition of the role of the STN in mediating limbic function. In particular, the STN has been implicated in impulse control and the related construct of valence processing. A better understanding of STN involvement in these phenomena could have important implications for treating impulse control disorders (ICDs). ICDs affect up to 40% of PD patients on dopamine agonist therapy and approximately 15% of PD patients overall. ICDs have been reported to be associated with STN DBS. In this paper we will focus on impulse control and review pre-clinical, clinical, behavioral, imaging, and electrophysiological studies pertaining to the limbic function of the STN.

  20. Deep Brain Stimulation of the Subthalamic Nucleus Improves Lexical Switching in Parkinsons Disease Patients.

    Vonberg, Isabelle; Ehlen, Felicitas; Fromm, Ortwin; Kühn, Andrea A; Klostermann, Fabian

    2016-01-01

    Reduced verbal fluency (VF) has been reported in patients with Parkinson's disease (PD), especially those treated by Deep Brain Stimulation of the subthalamic nucleus (STN DBS). To delineate the nature of this dysfunction we aimed at identifying the particular VF-related operations modified by STN DBS. Eleven PD patients performed VF tasks in their STN DBS ON and OFF condition. To differentiate VF-components modulated by the stimulation, a temporal cluster analysis was performed, separating production spurts (i.e., 'clusters' as correlates of automatic activation spread within lexical fields) from slower cluster transitions (i.e., 'switches' reflecting set-shifting towards new lexical fields). The results were compared to those of eleven healthy control subjects. PD patients produced significantly more switches accompanied by shorter switch times in the STN DBS ON compared to the STN DBS OFF condition. The number of clusters and time intervals between words within clusters were not affected by the treatment state. Although switch behavior in patients with DBS ON improved, their task performance was still lower compared to that of healthy controls. Beyond impacting on motor symptoms, STN DBS seems to influence the dynamics of cognitive procedures. Specifically, the results are in line with basal ganglia roles for cognitive switching, in the particular case of VF, from prevailing lexical concepts to new ones.

  1. Deep Brain Stimulation of the Subthalamic Nucleus Improves Lexical Switching in Parkinsons Disease Patients.

    Isabelle Vonberg

    Full Text Available Reduced verbal fluency (VF has been reported in patients with Parkinson's disease (PD, especially those treated by Deep Brain Stimulation of the subthalamic nucleus (STN DBS. To delineate the nature of this dysfunction we aimed at identifying the particular VF-related operations modified by STN DBS.Eleven PD patients performed VF tasks in their STN DBS ON and OFF condition. To differentiate VF-components modulated by the stimulation, a temporal cluster analysis was performed, separating production spurts (i.e., 'clusters' as correlates of automatic activation spread within lexical fields from slower cluster transitions (i.e., 'switches' reflecting set-shifting towards new lexical fields. The results were compared to those of eleven healthy control subjects.PD patients produced significantly more switches accompanied by shorter switch times in the STN DBS ON compared to the STN DBS OFF condition. The number of clusters and time intervals between words within clusters were not affected by the treatment state. Although switch behavior in patients with DBS ON improved, their task performance was still lower compared to that of healthy controls.Beyond impacting on motor symptoms, STN DBS seems to influence the dynamics of cognitive procedures. Specifically, the results are in line with basal ganglia roles for cognitive switching, in the particular case of VF, from prevailing lexical concepts to new ones.

  2. Optimal MRI methods for direct stereotactic targeting of the subthalamic nucleus and globus pallidus

    O'Gorman, Ruth L.; Shmueli, Karin; Ashkan, Keyoumars; Selway, Richard P.; Samuel, Michael; Lythgoe, David J.; Shahidiani, Asal; Wastling, Stephen J.; Footman, Michelle; Jarosz, Jozef

    2011-01-01

    Reliable identification of the subthalamic nucleus (STN) and globus pallidus interna (GPi) is critical for deep brain stimulation (DBS) of these structures. The purpose of this study was to compare the visibility of the STN and GPi with various MRI techniques and to assess the suitability of each technique for direct stereotactic targeting. MR images were acquired from nine volunteers with T2- and proton density-weighted (PD-W) fast spin echo, susceptibility-weighted imaging (SWI), phase-sensitive inversion recovery and quantitative T1, T2 and T2 * mapping sequences. Contrast-to-noise ratios (CNR) for the STN and GPi were calculated for all sequences. Targeting errors on SWI were evaluated on magnetic susceptibility maps. The sequences demonstrating the best conspicuity of DBS target structures (SWI and T2*) were then applied to ten patients with movement disorders, and the CNRs for these techniques were assessed. SWI offers the highest CNR for the STN, but standard PD-W images provide the best CNR for the pallidum. Susceptibility maps indicated that the GPi margins may be shifted slightly on SWI, although no shifts were seen for the STN. SWI may improve the visibility of the STN on pre-operative MRI, potentially improving the accuracy of direct stereotactic targeting. (orig.)

  3. [Mental competence in the context of deep brain stimulation].

    Berghmans, R L P; De Wert, G M W R

    2004-07-10

    In a case of Parkinson's disease, the patient was treated with deep brain stimulation of the subthalamic nucleus (STN-DBS). STN-DBS affected the mental competence of the patient and ethical questions were raised about the decision as to the direction of further treatment. The patient was asked for his opinion on the therapeutic options during a phase of non-stimulation and chose to be stimulated and admitted to a psychiatric hospital because of mental incompetence rather than remaining unstimulated, mentally competent but bedridden. Developments in the neurosciences (including STN-DBS) raise a number of different fundamental (theoretical and philosophical) as well as practical questions. STN-DBS can have various unintended (behavioural) effects. In the case presented, more weight was rightly given to the mental competence of the unstimulated patient, although comments can be made with regard to his decision making, as his choice was made in a phase of serious distress. Attention is paid to the relevance of a so-called self-binding directive. STN-DBS is not morally neutral and the case involves a tragic dilemma: a conflict between irreconcilable duties for the physician. The further development and proliferation of STN-DBS requires caution and moral deliberation. It remains important to search for alternative treatment strategies with less undesirable side effects.

  4. Syncope Associated with Subthalamic Nucleus Deep Brain Stimulation in a Patient with Parkinson’s Disease

    Dursun Aygun

    2013-01-01

    Full Text Available In advanced Parkinson's disease (PD, deep brain stimulation (DBS may be an alternative option for the treatment of motor symptoms. Side effects associated with subthalamic nucleus (STN DBS in patients with PD are emerging as the most frequent sensory and motor symptoms. DBS-related syncope is reported as extremely rare. We wanted to discuss the mechanisms of syncope associated with STN DBS in a patient with Parkinson's disease. Case report. Sixty-three-year-old female patient is followed up with diagnosis of idiopathic Parkinson's disease for 6 years in our clinic. The patient has undergone STN DBS due to painful dystonia and drug resistant tremor. During the operation, when the left STN was stimulated at 5 milliampere (mAmp, the patient developed presyncopal symptoms. However, when the stimulation was stopped symptoms improved. During the early period after the operation, when the right STN was stimulated at 1.3 millivolts (mV, she developed the pre-yncopal symptoms and then syncope. Our case shows that STN DBS may lead to directly autonomic symptoms resulting in syncope during stimulation-on (stim-on.

  5. 18F-FDG PET imaging on the neuronal network of Parkinson's disease patients following deep brain stimulation of bilateral subthalamic nucleus

    Zuo Chuantao; Huang Zhemin; Zhao Jun; Guan Yihui; Lin Xiangtong; Li Dianyou; Sun Bomin

    2007-01-01

    Objective: There is evidence that the cause and progression of Parkinson's disease (PD) may be attributed to subthalamic nucleus (STN) dysfunction and that external electrical stimulation of the STN may improve the underlying neuronal network. This study aimed at using 18 F-FDG PET to monitor the functional status of the neuronal network of advanced PD patients following deep brain stimulation (DBS) of bilateral STN. Methods: Five PD patients in advanced stage, rated according to unified PD rat- ing scale (UPDRS) motion score, underwent bilateral STN DBS implantation. Six months after the implantation, each patient was studied with 18 F-FDG PET scans under stimulation turned 'on' and 'off' conditions. Statistical parametric mapping 2 (SPM2) was applied for data analyses. Results: Bilateral STN DBS reduced glucose utilization in lentiform nucleus (globus pallidus), bilateral thalamus, cerebellum, as well as the distal parietal cortex. However, glucose utilization in midbrain and pons was increased. The PD-related pattern (PDRP) scores were significantly different during the 'on' status (2.12 ± 15.24) and 'off' status (4.93 ± 13.01), which corresponded to the clinical improvement of PD symptoms as PDRP scores decreased. Conclusion: 18 F-FDG PET may be useful in monitoring and mapping the metabolism of the neuronal network during bilateral STN DBS, thus supporting its therapeutic impact on PD patients. (authors)

  6. Investigation of a novel protonic/electronic ceramic composite material as a candidate for hydrogen separation membranes

    Fish, Jason S.

    A novel ceramic protonic/electronic conductor composite BaCe 0.2Zr0.7Y0.1O3-delta / Sr0.95 Ti0.9Nb0.1O3-delta (BCZY27/STN95: BS27) has been synthesized, and its electrical properties and hydrogen permeability have been investigated. The volume ratio of the STN95 phase was varied from 50 - 70 % to test the effects on conductivity and hydrogen permeability. BCZY27 and STN95 powders were prepared by solid-state reaction, and membrane samples were fabricated through conventional and spark plasma sintering techniques. The phase composition, density, and microstructure were compared between the sintering methodologies. Total conductivities of 0.01 - 0.06 S·cm -1 were obtained in wet (+1 % H2O) dilute H2/(N 2, He, Ar) from 600 - 800 °C for 50 volume % STN95. With increasing STN content (60 and 70 volume %), conductivity generally increased, though remained lower than predicted by standard effective medium models, even at 70 volume % STN95. A new effective medium model was proposed, which accounted for an interfacial resistance term associated with the heterojunctions formed between the BCZY27 and STN95 phases. Better fits for the measured data were achieved with this new method, although some effects remain unexplained. Discrepancies between the model and experiment were attributed to space charge effects, grain boundary resistances, and insulating impurity phase formation during synthesis. Dense BS27 samples were tested for high-temperature hydrogen permeation and a measured flux of 0.006 mumol·cm-2·s -1 was recorded for a 50 volume % STN95 sample at 700 °C, using dry argon as a sweep gas. This value represents a modest improvement on other ceramic composite membranes, but remains short of targets for commercialization. Persistent leaks in the flux experiments generated a shallower hydrogen gradient across the samples, although this p(H2) on the sweep side simultaneously decreased the oxygen partial pressure gradient across the sample and preserved the reduced state

  7. The effects of high frequency subthalamic stimulation on balance performance and fear of falling in patients with Parkinson's disease

    Jarnlo Gun-Britt

    2009-04-01

    Full Text Available Abstract Background Balance impairment is one of the most distressing symptoms in Parkinson's disease (PD even with pharmacological treatment (levodopa. A complementary treatment is high frequency stimulation in the subthalamic nucleus (STN. Whether STN stimulation improves postural control is under debate. The aim of this study was to explore the effects of STN stimulation alone on balance performance as assessed with clinical performance tests, subjective ratings of fear of falling and posturography. Methods Ten patients (median age 66, range 59–69 years with bilateral STN stimulation for a minimum of one year, had their anti-PD medications withdrawn overnight. Assessments were done both with the STN stimulation turned OFF and ON (start randomized. In both test conditions, the following were assessed: motor symptoms (descriptive purposes, clinical performance tests, fear of falling ratings, and posturography with and without vibratory proprioceptive disturbance. Results STN stimulation alone significantly (p = 0.002 increased the scores of the Berg balance scale, and the median increase was 6 points. The results of all timed performance tests, except for sharpened Romberg, were significantly (p ≤ 0.016 improved. The patients rated their fear of falling as less severe, and the total score of the Falls-Efficacy Scale(S increased (p = 0.002 in median with 54 points. All patients completed posturography when the STN stimulation was turned ON, but three patients were unable to do so when it was turned OFF. The seven patients with complete data showed no statistical significant difference (p values ≥ 0.109 in torque variance values when comparing the two test situations. This applied both during quiet stance and during the periods with vibratory stimulation, and it was irrespective of visual input and sway direction. Conclusion In this sample, STN stimulation alone significantly improved the results of the clinical performance tests that mimic

  8. Late Consequential Surgical Bed Soft Tissue Necrosis in Advanced Oropharyngeal Squamous Cell Carcinomas Treated With Transoral Robotic Surgery and Postoperative Radiation Therapy

    Lukens, J. Nicholas; Lin, Alexander; Gamerman, Victoria; Mitra, Nandita; Grover, Surbhi; McMenamin, Erin M.; Weinstein, Gregory S.; O'Malley, Bert W.; Cohen, Roger B.; Orisamolu, Abimbola; Ahn, Peter H.; Quon, Harry

    2014-01-01

    Purpose: A subset of patients with oropharyngeal squamous cell carcinoma (OP-SCC) managed with transoral robotic surgery (TORS) and postoperative radiation therapy (PORT) developed soft tissue necrosis (STN) in the surgical bed months after completion of PORT. We investigated the frequency and risk factors. Materials and Methods: This retrospective analysis included 170 consecutive OP-SCC patients treated with TORS and PORT between 2006 and 2012, with >6 months' of follow-up. STN was defined as ulceration of the surgical bed >6 weeks after completion of PORT, requiring opioids, biopsy, or hyperbaric oxygen therapy. Results: A total of 47 of 170 patients (28%) had a diagnosis of STN. Tonsillar patients were more susceptible than base-of-tongue (BOT) patients, 39% (41 of 104) versus 9% (6 of 66), respectively. For patients with STN, median tumor size was 3.0 cm (range 1.0-5.6 cm), and depth of resection was 2.2 cm (range 1.0-5.1 cm). Median radiation dose and dose of fraction to the surgical bed were 6600 cGy and 220 cGy, respectively. Thirty-one patients (66%) received concurrent chemotherapy. Median time to STN was 2.5 months after PORT. All patients had resolution of STN after a median of 3.7 months. Multivariate analysis identified tonsillar primary (odds ratio [OR] 4.73, P=.01), depth of resection (OR 3.12, P=.001), total radiation dose to the resection bed (OR 1.51 per Gy, P<.01), and grade 3 acute mucositis (OR 3.47, P=.02) as risk factors for STN. Beginning May 2011, after implementing aggressive avoidance of delivering >2 Gy/day to the resection bed mucosa, only 8% (2 of 26 patients) experienced STN (all grade 2). Conclusions: A subset of OP-SCC patients treated with TORS and PORT are at risk for developing late consequential surgical bed STN. Risk factors include tonsillar location, depth of resection, radiation dose to the surgical bed, and severe mucositis. STN risk is significantly decreased with carefully avoiding a radiation dosage of >2 Gy/day to

  9. Three-dimensional fluid-attenuated inversion recovery sequence for visualisation of subthalamic nucleus for deep brain stimulation in Parkinson's disease

    Heo, Young Jin [University of Ulsan College of Medicine, Asan Medical Center, Department of Radiology, Research Institute of Radiology, Seoul (Korea, Republic of); Inje University, Department of Radiology, Busan Paik Hospital, Busan (Korea, Republic of); Kim, Sang Joon; Kim, Ho Sung; Choi, Choong Gon; Jung, Seung Chai [University of Ulsan College of Medicine, Asan Medical Center, Department of Radiology, Research Institute of Radiology, Seoul (Korea, Republic of); Lee, Jung Kyo [University of Ulsan College of Medicine, Asan Medical Center, Department of Neurosurgery, Seoul (Korea, Republic of); Lee, Chong Sik; Chung, Sun J. [University of Ulsan College of Medicine, Asan Medical Center, Department of Neurology, Seoul (Korea, Republic of); Cho, So Hyun [Department of Radiology, Busan (Korea, Republic of); Lee, Gyoung Ro [Philips HealthCare Korea, Seoul (Korea, Republic of)

    2015-09-15

    Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an accepted treatment for advanced Parkinson's disease (PD). However, targeting the STN is difficult due to its relatively small size and variable location. The purpose of this study was to assess which of the following sequences obtained with the 3.0 T MR system can accurately delineate the STN: coronal 3D fluid-attenuated inversion recovery (FLAIR), 2D T2*-weighted fast-field echo (T2*-FFE) and 2D T2-weighted turbo spin-echo (TSE) sequences. We included 20 consecutive patients with PD who underwent 3.0 T MR for DBS targeting. 3D FLAIR, 2D T2*-FFE and T2-TSE images were obtained for all study patients. Image quality and demarcation of the STN were analysed using 4-point scales, and contrast ratio (CR) of the STN and normal white matter was calculated. The Friedman test was used to compare the three sequences. In qualitative analysis, the 2D T2*-FFE image showed more artefacts than 3D FLAIR or 2D T2-TSE, but the difference did not reach statistical significance. 3D FLAIR images showed significantly superior demarcation of the STN compared with 2D T2*-FFE and T2-TSE images (P < 0.001, respectively). The CR of 3D FLAIR was significantly higher than that of 2D T2*-FFE or T2-TSE images in multiple comparison correction (P < 0.001), but there was no significant difference in the CR between 2D T2*-FFE and T2-TSE images. Coronal 3D FLAIR images showed the most accurate demarcation of the STN for DBS targeting among coronal 3D FLAIR, 2D T2*-FFE and T2-TSE images. (orig.)

  10. Cognition and Depression Following Deep Brain Stimulation of the Subthalamic Nucleus and Globus Pallidus Pars Internus in Parkinson's Disease: A Meta-Analysis.

    Combs, Hannah L; Folley, Bradley S; Berry, David T R; Segerstrom, Suzanne C; Han, Dong Y; Anderson-Mooney, Amelia J; Walls, Brittany D; van Horne, Craig

    2015-12-01

    Parkinson's disease (PD) is a common, degenerative disorder of the central nervous system. Individuals experience predominantly extrapyramidal symptoms including resting tremor, rigidity, bradykinesia, gait abnormalities, cognitive impairment, depression, and neurobehavioral concerns. Cognitive impairments associated with PD are diverse, including difficulty with attention, processing speed, executive functioning, memory recall, visuospatial functions, word-retrieval, and naming. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) or globus pallidus internus (GPi) is FDA approved and has been shown to be effective in reducing motor symptoms of PD. Studies have found that stimulating STN and GPi are equally effective at improving motor symptoms and dyskinesias; however, there has been discrepancy as to whether the cognitive, behavioral, and mood symptoms are affected differently between the two targets. The present study used random-effects meta-analytic models along with a novel p-curve analytic procedure to compare the potential cognitive and emotional impairments associated with STN-DBS in the current literature to those associated with GPi-DBS. Forty-one articles were reviewed with an aggregated sample size of 1622 patients. Following STN-DBS, small declines were found in psychomotor speed, memory, attention, executive functions, and overall cognition; and moderate declines were found in both semantic and phonemic fluency. However, GPi-DBS resulted in fewer neurocognitive declines than STN-DBS (small declines in attention and small-moderate declines in verbal fluency). With regards to its effect on depression symptomatology, both GPi-DBS and STN-DBS resulted in lower levels of depressive symptoms post-surgery. From a neurocognitive standpoint, both GPi-DBS and STN-DBS produce subtle cognitive declines but appears to be relatively well tolerated.

  11. Immunization of breast cancer patients using a synthetic sialyl-Tn glycoconjugate plus Detox adjuvant.

    MacLean, G D; Reddish, M; Koganty, R R; Wong, T; Gandhi, S; Smolenski, M; Samuel, J; Nabholtz, J M; Longenecker, B M

    1993-01-01

    We have synthesized various formulations that have potential for active specific immunotherapy (ASI) of human cancers. Sialyl-Tn (STn) is a potentially important target structure for ASI because its expression on mucins is a strong, independent predictor of poor prognosis, suggesting that it may have functional significance in the metastatic process. In this first pilot study of synthetic sialyl-Tn hapten conjugated to keyhole limpet hemocyanin (STn-KLH), with Detox adjuvant, toxicity and humoral immunogenicity were assessed in 12 patients with metastatic breast cancer. Toxicity was minimal, restricted to local cutaneous reactions (apart from transient nausea and vomiting following single low-dose cyclophosphamide treatment). Using STn-conjugated human serum albumin in a solid-phase enzyme-linked immunosorbent assay, it was shown that all patients developed IgM and IgG specific for the synthetic STn hapten. Following immunization, most patients were shown to develop increased titres of complement-mediated cytotoxic antibodies, partially inhibited by synthetic STn hapten, but not by the related TF hapten. We also detected IgM and IgG antibodies reactive with natural STn determinants expressed on ovine submaxillary mucin, the STn specificity of this reactivity being confirmed by hapten inhibition. Evaluation of clinical efficacy in a small pilot study is difficult. Five patients are alive 12 or more months after entry, and another 4 patients are alive 6 or more months after entry into the study. All 3 patients with known widespread bulky disease progressed despite ASI, 2 having died from widespread cancer. Two patients had partial responses, each lasting 6 months. While several patients had disease stability for 3-10 months, 1 patient with pulmonary metastases remains stable 15 months after entry into the program.

  12. Three-dimensional fluid-attenuated inversion recovery sequence for visualisation of subthalamic nucleus for deep brain stimulation in Parkinson's disease

    Heo, Young Jin; Kim, Sang Joon; Kim, Ho Sung; Choi, Choong Gon; Jung, Seung Chai; Lee, Jung Kyo; Lee, Chong Sik; Chung, Sun J.; Cho, So Hyun; Lee, Gyoung Ro

    2015-01-01

    Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an accepted treatment for advanced Parkinson's disease (PD). However, targeting the STN is difficult due to its relatively small size and variable location. The purpose of this study was to assess which of the following sequences obtained with the 3.0 T MR system can accurately delineate the STN: coronal 3D fluid-attenuated inversion recovery (FLAIR), 2D T2*-weighted fast-field echo (T2*-FFE) and 2D T2-weighted turbo spin-echo (TSE) sequences. We included 20 consecutive patients with PD who underwent 3.0 T MR for DBS targeting. 3D FLAIR, 2D T2*-FFE and T2-TSE images were obtained for all study patients. Image quality and demarcation of the STN were analysed using 4-point scales, and contrast ratio (CR) of the STN and normal white matter was calculated. The Friedman test was used to compare the three sequences. In qualitative analysis, the 2D T2*-FFE image showed more artefacts than 3D FLAIR or 2D T2-TSE, but the difference did not reach statistical significance. 3D FLAIR images showed significantly superior demarcation of the STN compared with 2D T2*-FFE and T2-TSE images (P < 0.001, respectively). The CR of 3D FLAIR was significantly higher than that of 2D T2*-FFE or T2-TSE images in multiple comparison correction (P < 0.001), but there was no significant difference in the CR between 2D T2*-FFE and T2-TSE images. Coronal 3D FLAIR images showed the most accurate demarcation of the STN for DBS targeting among coronal 3D FLAIR, 2D T2*-FFE and T2-TSE images. (orig.)

  13. A systematic review of studies on anatomical position of electrode contacts used for chronic subthalamic stimulation in Parkinson's disease.

    Caire, François; Ranoux, Danièle; Guehl, Dominique; Burbaud, Pierre; Cuny, Emmanuel

    2013-09-01

    The dorso-lateral part of the subthalamic nucleus (STN) is considered as the usual target of deep brain stimulation for Parkinson's disease. Nevertheless, the exact anatomical location of the electrode contacts used for chronic stimulation is still a matter of debate. The aim of this study was to perform a systematic review of the existing literature on this issue. We searched for studies on the anatomical location of active contacts published until December 2012. We identified 13 studies, published between 2002 and 2010, including 260 patients and 466 electrodes. One hundred and sixty-four active contacts (35 %) were identified within the STN, 117 (25 %) at the interface between STN and the surrounding structures, 184 (40 %) above the STN and one within the substantia nigra. We observed great discrepancies between the different series. The contra-lateral improvement was between 37 and 78.5 % for contacts located within the STN, between 48.6 and 73 % outside the STN, between 65.3 and 66 % at the interface. The authors report no clear correlation between anatomical location and stimulation parameters. Post-operative analysis of the anatomical location of active contacts is difficult, and all the methods used are debatable. The relationship between the anatomical location of active contacts and the clinical effectiveness of stimulation is unclear. It would be necessary to take into account the volume of the electrode contacts and the diffusion of the stimulation. We can nevertheless assume that the interface between dorso-lateral STN, zona incerta and Forel's fields could be directly involved in the effects of stimulation.

  14. High-Frequency Stimulation of the Subthalamic Nucleus Activates Motor Cortex Pyramidal Tract Neurons by a Process Involving Local Glutamate, GABA and Dopamine Receptors in Hemi-Parkinsonian Rats.

    Chuang, Chi-Fen; Wu, Chen-Wei; Weng, Ying; Hu, Pei-San; Yeh, Shin-Rung; Chang, Yen-Chung

    2018-04-30

    Deep brain stimulation (DBS) is widely used to treat advanced Parkinson’s disease (PD). Here, we investigated how DBS applied on the subthalamic nucleus (STN) influenced the neural activity in the motor cortex. Rats, which had the midbrain dopaminergic neurons partially depleted unilaterally, called the hemi-Parkinsonian rats, were used as a study model. c-Fos expression in the neurons was used as an indicator of neural activity. Application of high-frequency stimulation (HFS) upon the STN was used to mimic the DBS treatment. The motor cortices in the two hemispheres of hemi-Parkinsonian rats were found to contain unequal densities of c-Fos-positive (Fos+) cells, and STN-HFS rectified this bilateral imbalance. In addition, STN-HFS led to the intense c-Fos expression in a group of motor cortical neurons which exhibited biochemical and anatomical characteristics resembling those of the pyramidal tract (PT) neurons sending efferent projections to the STN. The number of PT neurons expressing high levels of c-Fos was significantly reduced by local application of the antagonists of non-N-methyl-D-aspartate (non-NMDA) glutamate receptors, gammaaminobutyric acid A (GABAA) receptors and dopamine receptors in the upper layers of the motor cortex. The results indicate that the coincident activations of synapses and dopamine receptors in the motor cortex during STN-HFS trigger the intense expression of c-Fos of the PT neurons. The implications of the results on the cellular mechanism underlying the therapeutic effects of STN-DBS on the movement disorders of PD are also discussed.

  15. Cortical Plasticity Induction by Pairing Subthalamic Nucleus Deep-Brain Stimulation and Primary Motor Cortical Transcranial Magnetic Stimulation in Parkinson's Disease.

    Udupa, Kaviraja; Bahl, Nina; Ni, Zhen; Gunraj, Carolyn; Mazzella, Filomena; Moro, Elena; Hodaie, Mojgan; Lozano, Andres M; Lang, Anthony E; Chen, Robert

    2016-01-13

    Noninvasive brain stimulation studies have shown abnormal motor cortical plasticity in Parkinson's disease (PD). These studies used peripheral nerve stimulation paired with transcranial magnetic stimulation (TMS) to primary motor cortex (M1) at specific intervals to induce plasticity. Induction of cortical plasticity through stimulation of the basal ganglia (BG)-M1 connections has not been studied. In the present study, we used a novel technique of plasticity induction by repeated pairing of deep-brain stimulation (DBS) of the BG with M1 stimulation using TMS. We hypothesize that repeated pairing of subthalamic nucleus (STN)-DBS and M1-TMS at specific time intervals will lead to plasticity in the M1. Ten PD human patients with STN-DBS were studied in the on-medication state with DBS set to 3 Hz. The interstimulus intervals (ISIs) between STN-DBS and TMS that produced cortical facilitation were determined individually for each patient. Three plasticity induction conditions with repeated pairings (180 times) at specific ISIs (∼ 3 and ∼ 23 ms) that produced cortical facilitation and a control ISI of 167 ms were tested in random order. Repeated pairing of STN-DBS and M1-TMS at short (∼ 3 ms) and medium (∼ 23 ms) latencies increased M1 excitability that lasted for at least 45 min, whereas the control condition (fixed ISI of 167 ms) had no effect. There were no specific changes in motor thresholds, intracortical circuits, or recruitment curves. Our results indicate that paired-associative cortical plasticity can be induced by repeated STN and M1 stimulation at specific intervals. These results show that STN-DBS can modulate cortical plasticity. We introduced a new experimental paradigm to test the hypothesis that pairing subthalamic nucleus deep-brain stimulation (STN-DBS) with motor cortical transcranial magnetic stimulation (M1-TMS) at specific times can induce cortical plasticity in patients with Parkinson's disease (PD). We found that repeated pairing of STN

  16. Impulse control behaviors and subthalamic deep brain stimulation in Parkinson disease.

    Merola, Aristide; Romagnolo, Alberto; Rizzi, Laura; Rizzone, Mario Giorgio; Zibetti, Maurizio; Lanotte, Michele; Mandybur, George; Duker, Andrew P; Espay, Alberto J; Lopiano, Leonardo

    2017-01-01

    To determine the clinical and demographic correlates of persistent, remitting, and new-onset impulse control behaviors (ICBs) before and after subthalamic deep brain stimulation (STN-DBS) in Parkinson's disease (PD). We compared the pre- and post-surgical prevalence of ICBs, classified as impulse control disorders (ICD), dopamine dysregulation syndrome (DDS), and punding in 150 consecutive PD STN-DBS-treated patients and determined the association with motor, cognitive, neuropsychological, and neuropsychiatric endpoints. At baseline (before STN-DBS), ICBs were associated with younger age (p = 0.045) and male gender (85 %; p = 0.001). Over an average follow-up of 4.3 ± 2.1 years of chronic STN-DBS there was an overall trend for reduction in ICBs (from 17.3 to 12.7 %; p = 0.095) with significant improvement in hypersexuality (12-8.0 %; p = 0.047), gambling (10.7-5.3 %; p = 0.033), and DDS (4.7-0 %; p disorders; persistent ICB in those with obsessive-compulsive traits. PD-related ICBs exhibit a complex outcome after STN-DBS, with a tendency for overall reduction but with age, gender, dopaminergic therapy, and neuropsychiatric features exerting independent effects.

  17. Deep Brain Stimulation of Caudal Zona Incerta and Subthalamic Nucleus in Patients with Parkinson's Disease: Effects on Voice Intensity

    Sofie Lundgren

    2011-01-01

    Full Text Available Deep brain stimulation of the subthalamic nucleus (STN-DBS in patients with Parkinson's disease (PD affects speech inconsistently. Recently, stimulation of the caudal zona incerta (cZi-DBS has shown superior motor outcomes for PD patients, but effects on speech have not been systematically investigated. The aim of this study was to compare the effects of cZi-DBS and STN-DBS on voice intensity in PD patients. Mean intensity during reading and intensity decay during rapid syllable repetition were measured for STN-DBS and cZi-DBS patients (eight patients per group, before- and 12 months after-surgery on- and off-stimulation. For mean intensity, there were small significant differences on- versus off-stimulation in each group: 74.2 (2.0 dB contra 72.1 (2.2 dB (=.002 for STN-DBS, and 71.6 (4.1 dB contra 72.8 (3.4 dB (=.03 for cZi-DBS, with significant interaction (<.001. Intensity decay showed no significant changes. The subtle differences found for mean intensity suggest that STN-DBS and cZi-DBS may influence voice intensity differently.

  18. Personality Changes after Deep Brain Stimulation in Parkinson’s Disease

    Uyen Pham

    2015-01-01

    Full Text Available Objectives. Deep brain stimulation of the subthalamic nucleus (STN-DBS is a recognized therapy that improves motor symptoms in advanced Parkinson’s disease (PD. However, little is known about its impact on personality. To address this topic, we have assessed personality traits before and after STN-DBS in PD patients. Methods. Forty patients with advanced PD were assessed with the Temperament and Character Inventory (TCI: the Urgency, Premeditation, Perseverance, Sensation Seeking impulsive behaviour scale (UPPS, and the Neuroticism and Lie subscales of the Eysenck Personality Questionnaire (EPQ-N, EPQ-L before surgery and after three months of STN-DBS. Collateral information obtained from the UPPS was also reported. Results. Despite improvement in motor function and reduction in dopaminergic dosage patients reported lower score on the TCI Persistence and Self-Transcendence scales, after three months of STN-DBS, compared to baseline (P=0.006; P=0.024. Relatives reported significantly increased scores on the UPPS Lack of Premeditation scale at follow-up (P=0.027. Conclusion. STN-DBS in PD patients is associated with personality changes in the direction of increased impulsivity.

  19. High and low frequency stimulation of the subthalamic nucleus induce prolonged changes in subthalamic and globus pallidus neurons

    Hagar eLavian

    2013-12-01

    Full Text Available High frequency stimulation (HFS of the subthalamic nucleus (STN is widely used to treat the symptoms of Parkinson’s disease but the mechanism of this therapy is unclear. Using a rat brain slice preparation maintaining the connectivity between the STN and one of its target nuclei, the globus pallidus (GP, we investigated the effects of high and low frequency stimulation (HFS 100 Hz, LFS 10 Hz on activity of single neurons in the STN and GP. Both HFS and LFS caused changes in firing frequency and pattern of subthalamic and pallidal neurons. These changes were of synaptic origin, as they were abolished by glutamate and GABA antagonists. Both HFS and LFS also induced a long-lasting reduction in firing frequency in STN neurons possibly contending a direct causal link between HFS and the outcome DBS. In the GP both HFS and LFS induced either a long-lasting depression, or less frequently, a long-lasting excitation. Thus, in addition to the intrinsic activation of the stimulated neurons, long-lasting stimulation of the STN may trigger prolonged biochemical processes.

  20. CLINICOPATHOLOGICAL CHARACTERISTICS OF SOLITARY NODULE OF THYROID- A CROSS-SECTIONAL STUDY IN A TERTIARY CENTER

    T. V. Haridas

    2017-04-01

    Full Text Available BACKGROUND Solitary Thyroid Nodules (STN occur in 4-7% of the adult population. Owing to increasing incidence of malignancy, it is necessary to differentiate patients with benign STN from malignant ones for early intervention and better patient management. The aim of the study is to study the clinicopathological characteristics of STN for better diagnosis, evaluation and management; evaluate the efficacy of FNAC in preoperative diagnostics of solitary thyroid nodules. MATERIALS AND METHODS The study was conducted over a period of one year at a tertiary healthcare institution in South India. One hundred patients with solitary nodule of thyroid were studied by taking detailed history and conducting clinical examination, thyroid hormone assay, ultrasonogram, FNAC and histopathological examination. The chances of malignancy and age, sex and site distribution were also analysed. RESULTS Solitary thyroid nodule cases showed female preponderance (81%, presented mostly as neck swelling followed by dysphagia (11%. Most common FNAC report was of colloid nodule (61%, followed by follicular neoplasm (20% and papillary carcinoma (9%. Final HPR showed 53% as colloid nodule and 27% as papillary carcinoma. CONCLUSION Differentiating between benign and malignant lesions and their comprehensive management are the challenges presented by STN. Fine Needle Aspiration Cytology (FNAC is the diagnostic tool of choice for the initial evaluation of STN.

  1. Decline in verbal fluency after subthalamic nucleus deep brain stimulation in Parkinson's disease: a microlesion effect of the electrode trajectory?

    Le Goff, Floriane; Derrey, Stéphane; Lefaucheur, Romain; Borden, Alaina; Fetter, Damien; Jan, Maryvonne; Wallon, David; Maltête, David

    2015-01-01

    Decline in verbal fluency (VF) is frequently reported after chronic deep brain stimulation (DBS) of the subthalamic nucleus (STN) in Parkinson disease (PD). We investigated whether the trajectory of the implanted electrode correlate with the VF decline 6 months after surgery. We retrospectively analysed 59 PD patients (mean age, 61.9 ± 7; mean disease duration, 13 ± 4.6) who underwent bilateral STN-DBS. The percentage of VF decline 6 months after STN-DBS in the on-drug/on-stimulation condition was determined in respect of the preoperative on-drug condition. The patients were categorised into two groups (decline and stable) for each VF. Cortical entry angles, intersection with deep grey nuclei (caudate, thalamic or pallidum), and anatomical extent of the STN affected by the electrode pathway, were compared between groups. A significant decline of both semantic and phonemic VF was found after surgery, respectively 14.9% ± 22.1 (P < 0.05) and 14.2% ± 30.3 (P < 0.05). Patients who declined in semantic VF (n = 44) had a left trajectory with a more anterior cortical entry point (56 ± 53 versus 60 ± 55 degree, P = 0.01) passing less frequently trough the thalamus (P = 0.03). Microlesion of left brain regions may contribute to subtle cognitive impairment following STN-DBS in PD.

  2. Ethical safety of deep brain stimulation: A study on moral decision-making in Parkinson's disease.

    Fumagalli, Manuela; Marceglia, Sara; Cogiamanian, Filippo; Ardolino, Gianluca; Picascia, Marta; Barbieri, Sergio; Pravettoni, Gabriella; Pacchetti, Claudio; Priori, Alberto

    2015-07-01

    The possibility that deep brain stimulation (DBS) in Parkinson's disease (PD) alters patients' decisions and actions, even temporarily, raises important clinical, ethical and legal questions. Abnormal moral decision-making can lead to ethical rules violations. Previous experiments demonstrated the subthalamic (STN) activation during moral decision-making. Here we aim to study whether STN DBS can affect moral decision-making in PD patients. Eleven patients with PD and bilateral STN DBS implant performed a computerized moral task in ON and OFF stimulation conditions. A control group of PD patients without DBS implant performed the same experimental protocol. All patients underwent motor, cognitive and psychological assessments. STN stimulation was not able to modify neither reaction times nor responses to moral task both when we compared the ON and the OFF state in the same patient (reaction times, p = .416) and when we compared DBS patients with those treated only with the best medical treatment (reaction times: p = .408, responses: p = .776). Moral judgment is the result of a complex process, requiring cognitive executive functions, problem-solving, anticipations of consequences of an action, conflict processing, emotional evaluation of context and of possible outcomes, and involving different brain areas and neural circuits. Our data show that STN DBS leaves unaffected moral decisions thus implying relevant clinical and ethical implications for DBS consequences on patients' behavior, on decision-making and on judgment ability. In conclusion, the technique can be considered safe on moral behavior. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Increased extracellular dopamine and 5-hydroxytryptamine levels contribute to enhanced subthalamic nucleus neural activity during exhausting exercise

    Y Hu

    2015-09-01

    Full Text Available The purpose of the study was to explore the mechanism underlying the enhanced subthalamic nucleus (STN neural activity during exhausting exercise from the perspective of monoamine neurotransmitters and changes of their corresponding receptors. Rats were randomly divided into microdialysis and immunohistochemistry study groups. For microdialysis study, extracellular fluid of the STN was continuously collected with a microdialysis probe before, during and 90 min after one bout of exhausting exercise. Dopamine (DA and 5-hydroxytryptamine (5-HT levels were subsequently detected with high-performance liquid chromatography (HPLC. For immunohistochemistry study, the expression of DRD 2 and HT 2C receptors in the STN, before, immediately after and 90 min after exhaustion was detected through immunohistochemistry technique. Microdialysis study results showed that the extracellular DA and 5-HT neurotransmitters increased significantly throughout the procedure of exhausting exercise and the recovery period (P0.05. Our results suggest that the increased extracellular DA and 5-HT in the STN might be one important factor leading to the enhanced STN neural activity and the development of fatigue during exhausting exercise. This study may essentially offer useful evidence for better understanding of the mechanism of the central type of exercise-induced fatigue.

  4. The atypical subthalamic nucleus--an anatomical variant relevant for stereotactic targeting.

    Reese, René; Pinsker, Markus O; Herzog, Jan; Wodarg, Fritz; Steigerwald, Frank; Pötter-Nerger, Monika; Falk, Daniela; Deuschl, Günther; Mehdorn, H Maximilian; Volkmann, Jens

    2012-04-01

    The improvement of PD motor symptoms by DBS of the STN depends on exact targeting. A combination of MRI and multitrajectory microrecordings was used for localization of the STN in a group of 228 consecutive PD patients. In 1% of our cases, the STN was consistently shifted in the anterior (3.3 ± 0.8mm) and medial (3.0 ± 0.9 mm) direction within the target plane, compared to controls. Adjustment of the original target coordinates after intraoperative reevaluation of the MRI and confirmation by typical subthalamic neuronal recordings along the deviant trajectory allowed the implantation of clinically effective electrodes in all cases. The relative improvement of the motor UPDRS at 6-months follow-up in patients with an atypical and typical STN was comparable. An atypical position of the STN does not need to complicate DBS surgery, if detected by a combination of MRI-based targeting and electrophysiological guidance. Copyright © 2012 Movement Disorder Society.

  5. Novel anti-Sialyl-Tn monoclonal antibodies and antibody-drug conjugates demonstrate tumor specificity and anti-tumor activity.

    Prendergast, Jillian M; Galvao da Silva, Ana Paula; Eavarone, David A; Ghaderi, Darius; Zhang, Mai; Brady, Dane; Wicks, Joan; DeSander, Julie; Behrens, Jeff; Rueda, Bo R

    Targeted therapeutics that can differentiate between normal and malignant tumor cells represent the ideal standard for the development of a successful anti-cancer strategy. The Sialyl-Thomsen-nouveau antigen (STn or Sialyl-Tn, also known as CD175s) is rarely seen in normal adult tissues, but it is abundantly expressed in many types of human epithelial cancers. We have identified novel antibodies that specifically target with high affinity the STn glycan independent of its carrier protein, affording the potential to recognize a wider array of cancer-specific sialylated proteins. A panel of murine monoclonal anti-STn therapeutic antibodies were generated and their binding specificity and efficacy were characterized in vitro and in in vivo murine cancer models. A subset of these antibodies were conjugated to monomethyl auristatin E (MMAE) to generate antibody-drug conjugates (ADCs). These ADCs demonstrated in vitro efficacy in STn-expressing cell lines and significant tumor growth inhibition in STn-expressing tumor xenograft cancer models with no evidence of overt toxicity.

  6. Behavioral and electrophysiological evidence for early and automatic detection of phonological equivalence in variable speech inputs.

    Kharlamov, Viktor; Campbell, Kenneth; Kazanina, Nina

    2011-11-01

    Speech sounds are not always perceived in accordance with their acoustic-phonetic content. For example, an early and automatic process of perceptual repair, which ensures conformity of speech inputs to the listener's native language phonology, applies to individual input segments that do not exist in the native inventory or to sound sequences that are illicit according to the native phonotactic restrictions on sound co-occurrences. The present study with Russian and Canadian English speakers shows that listeners may perceive phonetically distinct and licit sound sequences as equivalent when the native language system provides robust evidence for mapping multiple phonetic forms onto a single phonological representation. In Russian, due to an optional but productive t-deletion process that affects /stn/ clusters, the surface forms [sn] and [stn] may be phonologically equivalent and map to a single phonological form /stn/. In contrast, [sn] and [stn] clusters are usually phonologically distinct in (Canadian) English. Behavioral data from identification and discrimination tasks indicated that [sn] and [stn] clusters were more confusable for Russian than for English speakers. The EEG experiment employed an oddball paradigm with nonwords [asna] and [astna] used as the standard and deviant stimuli. A reliable mismatch negativity response was elicited approximately 100 msec postchange in the English group but not in the Russian group. These findings point to a perceptual repair mechanism that is engaged automatically at a prelexical level to ensure immediate encoding of speech inputs in phonological terms, which in turn enables efficient access to the meaning of a spoken utterance.

  7. Choreatic Side Effects of Deep Brain Stimulation of the Anteromedial Subthalamic Nucleus for Treatment-Resistant Obsessive-Compulsive disorder.

    Mulders, Anne E P; Leentjens, Albert F G; Schruers, Koen; Duits, Annelien; Ackermans, Linda; Temel, Yasin

    2017-08-01

    Patients with treatment-resistant obsessive-compulsive disorder (OCD) are potential candidates for deep brain stimulation (DBS). The anteromedial subthalamic nucleus (STN) is among the most commonly used targets for DBS in OCD. We present a patient with a 30-year history of treatment-resistant OCD who underwent anteromedial STN-DBS. Despite a clear mood-enhancing effect, stimulation caused motor side effects, including bilateral hyperkinesia, dyskinesias, and sudden large amplitude choreatic movements of arms and legs when stimulating at voltages greater than approximately 1.5 V. DBS at lower amplitudes and at other contact points failed to result in a significant reduction of obsessions and compulsions without inducing motor side effects. Because of this limitation in programming options, we decided to reoperate and target the ventral capsule/ventral striatum (VC/VS), which resulted in a substantial reduction in key obsessive and compulsive symptoms without serious side effects. Choreatic movements and hemiballismus have previously been linked to STN dysfunction and have been incidentally reported as side effects of DBS of the dorsolateral STN in Parkinson disease (PD). However, in PD, these side effects were usually transient, and they rarely interfered with DBS programming. In our patient, the motor side effects were persistent, and they made optimal DBS programming impossible. To our knowledge, such severe and persistent motor side effects have not been described previously for anteromedial STN-DBS. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Patients' expectations in subthalamic nucleus deep brain stimulation surgery for Parkinson disease.

    Hasegawa, Harutomo; Samuel, Michael; Douiri, Abdel; Ashkan, Keyoumars

    2014-12-01

    Subthalamic nucleus (STN) deep brain stimulation (DBS) is an established treatment for patients with advanced Parkinson disease. However, some patients feel less satisfied with the outcome of surgery. We sought to study the relationship between expectations, satisfaction, and outcome in STN DBS for Parkinson disease. Twenty-two consecutive patients undergoing STN DBS completed a modified 39-item Parkinson disease questionnaire (PDQ-39) preoperatively and 6 months postoperatively. A satisfaction questionnaire accompanied the postoperative questionnaire. Patients expected a significant improvement from surgery preoperatively: preoperative score (median PDQ-39 summary score [interquartile range]): 37.0 (9.5), expected postoperative score: 13.0 (8.0), P Parkinson disease. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Hemiballismus, Hyperphagia, and Behavioral Changes following Subthalamic Infarct

    Masoud Etemadifar

    2012-01-01

    Full Text Available The function of subthalamic nucleus (STN which is a part of the basal ganglia system is not clear, but it is hypothesized that this component might be involved in action selection. Unilateral damage to STN, which can commonly occur due to the small vessel stroke mainly, causes hemiballismus and sometimes hemichorea-hemiballismus. This paper deals with a 60-year-old patient with sudden onset of abnormal movements in his right limbs. He had increased appetite and hyperphagia and also developed mood and behavioral changes (aggressiveness, irritability, anxiety, and sometimes obscene speech. The magnetic resonance imaging revealed infarct area in left subthalamus. In our case, hemiballismus is caused by infarction in left subthalamic area. Occurrence of irritability, anxiety, and some behavioral changes such as aggressiveness and obscene speech can be explained by impairment of STN role in nonmotor behavior and cognitive function as a result of infarct.

  10. Glycoproteomic analysis of serum from patients with gastric precancerous lesions

    Gomes, Catarina; Almeida, Andreia; Ferreira, José Alexandre

    2013-01-01

    Gastric cancer is preceded by a carcinogenesis pathway that includes gastritis caused by Helicobacter pylori infection, chronic atrophic gastritis that may progress to intestinal metaplasia (IM), dysplasia, and ultimately gastric carcinoma of the more common intestinal subtype. The identification...... of glycosylation changes in circulating serum proteins in patients with precursor lesions of gastric cancer is of high interest and represents a source of putative new biomarkers for early diagnosis and intervention. This study applies a glycoproteomic approach to identify altered glycoproteins expressing...... the simple mucin-type carbohydrate antigens T and STn in the serum of patients with gastritis, IM (complete and incomplete subtypes), and control healthy individuals. The immunohistochemistry analysis of the gastric mucosa of these patients showed expression of T and STn antigens in gastric lesions, with STn...

  11. IMPACT STRENGTH AND FAILURE ANALYSIS OF WELDED DAMASCUS STEEL

    Rastislav Mintách

    2012-01-01

    Full Text Available The aim of this work was the experimental research of damascus steel from point of view of the structural analyze, impact strength and failure analyzes. The damascus steel was produced by method of forged welding from STN 41 4260 spring steel and STN 41 9312 tool steel. The damascus steel consisted of both 84 and 168 layers. The impact strength was experimentally determined for original steels and damascus steels after heat treatment in dependence on temperature in the range from -60 to 160 °C. It has been found that the impact strength of experimental steels decreased with decreasing temperature behind with correlated change of damage mode. In the case of experimental tests performed at high temperature ductile fracture was revealed and with decreasing temperature proportion of cleavage facets increased. Only the STN 41 9312 steel did not show considerable difference in values of the impact strength with changing temperature.

  12. Therapeutic deep brain stimulation in Parkinsonian rats directly influences motor cortex.

    Li, Qian; Ke, Ya; Chan, Danny C W; Qian, Zhong-Ming; Yung, Ken K L; Ko, Ho; Arbuthnott, Gordon W; Yung, Wing-Ho

    2012-12-06

    Much recent discussion about the origin of Parkinsonian symptoms has centered around the idea that they arise with the increase of beta frequency waves in the EEG. This activity may be closely related to an oscillation between subthalamic nucleus (STN) and globus pallidus. Since STN is the target of deep brain stimulation, it had been assumed that its action is on the nucleus itself. By means of simultaneous recordings of the firing activities from populations of neurons and the local field potentials in the motor cortex of freely moving Parkinsonian rats, this study casts doubt on this assumption. Instead, we found evidence that the corrective action is upon the cortex, where stochastic antidromic spikes originating from the STN directly modify the firing probability of the corticofugal projection neurons, destroy the dominance of beta rhythm, and thus restore motor control to the subjects, be they patients or rodents. Copyright © 2012 Elsevier Inc. All rights reserved.

  13. The effect of low frequency stimulation of the pedunculopontine tegmental nucleus on basal ganglia in a rat model of Parkinson's disease.

    Park, Eunkyoung; Song, Inho; Jang, Dong Pyo; Kim, In Young

    2014-08-08

    The pedunculopontine nucleus (PPN) has recently been introduced as an alternative target to the subthalamic nucleus (STN) or globus pallidus internus (GPi) for the treatment of advanced Parkinson's disease with severe and medically intractable axial symptoms such as gait and postural impairment. However, it is little known about how electrical stimulation of the PPN affects control of neuronal activities between the PPN and basal ganglia. We examined how low frequency stimulation of the pedunculopontine tegmental nucleus (PPTg) affects control of neuronal activities between the PPN and basal ganglia in 6-OHDA lesioned rats. In order to identify the effect of low frequency stimulation on the PPTg, neuronal activity in both the STN and substantia nigra par reticulata (SNr) were recorded and subjected to quantitative analysis, including analysis of firing rates and firing patterns. In this study, we found that the firing rates of the STN and SNr were suppressed during low frequency stimulation of the PPTg. However, the firing pattern, in contrast to the firing rate, did not exhibit significant changes in either the STN or SNr of 6-OHDA lesioned rats during low frequency stimulation of the PPTg. In addition, we also found that the firing rate of STN and SNr neurons displaying burst and random pattern were decreased by low frequency stimulation of PPTg, while the neurons displaying regular pattern were not affected. These results indicate that low frequency stimulation of the PPTg affects neuronal activity in both the STN and SNr, and may represent electrophysiological efficacy of low frequency PPN stimulation. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  14. High-frequency stimulation of the subthalamic nucleus modifies the expression of vesicular glutamate transporters in basal ganglia in a rat model of Parkinson's disease.

    Favier, Mathieu; Carcenac, Carole; Drui, Guillaume; Boulet, Sabrina; El Mestikawy, Salah; Savasta, Marc

    2013-12-05

    It has been suggested that glutamatergic system hyperactivity may be related to the pathogenesis of Parkinson's disease (PD). Vesicular glutamate transporters (VGLUT1-3) import glutamate into synaptic vesicles and are key anatomical and functional markers of glutamatergic excitatory transmission. Both VGLUT1 and VGLUT2 have been identified as definitive markers of glutamatergic neurons, but VGLUT 3 is also expressed by non glutamatergic neurons. VGLUT1 and VGLUT2 are thought to be expressed in a complementary manner in the cortex and the thalamus (VL/VM), in glutamatergic neurons involved in different physiological functions. Chronic high-frequency stimulation (HFS) of the subthalamic nucleus (STN) is the neurosurgical therapy of choice for the management of motor deficits in patients with advanced PD. STN-HFS is highly effective, but its mechanisms of action remain unclear. This study examines the effect of STN-HFS on VGLUT1-3 expression in different brain nuclei involved in motor circuits, namely the basal ganglia (BG) network, in normal and 6-hydroxydopamine (6-OHDA) lesioned rats. Here we report that: 1) Dopamine(DA)-depletion did not affect VGLUT1 and VGLUT3 expression but significantly decreased that of VGLUT2 in almost all BG structures studied; 2) STN-HFS did not change VGLUT1-3 expression in the different brain areas of normal rats while, on the contrary, it systematically induced a significant increase of their expression in DA-depleted rats and 3) STN-HFS reversed the decrease in VGLUT2 expression induced by the DA-depletion. These results show for the first time a comparative analysis of changes of expression for the three VGLUTs induced by STN-HFS in the BG network of normal and hemiparkinsonian rats. They provide evidence for the involvement of VGLUT2 in the modulation of BG cicuits and in particular that of thalamostriatal and thalamocortical pathways suggesting their key role in its therapeutic effects for alleviating PD motor symptoms.

  15. External pallidal stimulation improves parkinsonian motor signs and modulates neuronal activity throughout the basal ganglia thalamic network.

    Vitek, Jerrold L; Zhang, Jianyu; Hashimoto, Takao; Russo, Gary S; Baker, Kenneth B

    2012-01-01

    Deep brain stimulation (DBS) of the internal segment of the globus pallidus (GPi) and the subthalamic nucleus (STN) are effective for the treatment of advanced Parkinson's disease (PD). We have shown previously that DBS of the external segment of the globus pallidus (GPe) is associated with improvements in parkinsonian motor signs; however, the mechanism of this effect is not known. In this study, we extend our findings on the effect of STN and GPi DBS on neuronal activity in the basal ganglia thalamic network to include GPe DBS using the 1-methyl-4-phenyl-1.2.3.6-tetrahydropyridine (MPTP) monkey model. Stimulation parameters that improved bradykinesia were associated with changes in the pattern and mean discharge rate of neuronal activity in the GPi, STN, and the pallidal [ventralis lateralis pars oralis (VLo) and ventralis anterior (VA)] and cerebellar [ventralis lateralis posterior pars oralis (VPLo)] receiving areas of the motor thalamus. Population post-stimulation time histograms revealed a complex pattern of stimulation-related inhibition and excitation for the GPi and VA/VLo, with a more consistent pattern of inhibition in STN and excitation in VPLo. Mean discharge rate was reduced in the GPi and STN and increased in the VPLo. Effective GPe DBS also reduced bursting in the STN and GPi. These data support the hypothesis that therapeutic DBS activates output from the stimulated structure and changes the temporal pattern of neuronal activity throughout the basal ganglia thalamic network and provide further support for GPe as a potential therapeutic target for DBS in the treatment of PD. Copyright © 2011 Elsevier Inc. All rights reserved.

  16. Emotion recognition impairment and apathy after subthalamic nucleus stimulation in Parkinson's disease have separate neural substrates.

    Drapier, D; Péron, J; Leray, E; Sauleau, P; Biseul, I; Drapier, S; Le Jeune, F; Travers, D; Bourguignon, A; Haegelen, C; Millet, B; Vérin, M

    2008-09-01

    To test the hypothesis that emotion recognition and apathy share the same functional circuit involving the subthalamic nucleus (STN). A consecutive series of 17 patients with advanced Parkinson's disease (PD) was assessed 3 months before (M-3) and 3 months (M+3) after STN deep brain stimulation (DBS). Mean (+/-S.D.) age at surgery was 56.9 (8.7) years. Mean disease duration at surgery was 11.8 (2.6) years. Apathy was measured using the Apathy Evaluation Scale (AES) at both M-3 and M3. Patients were also assessed using a computerised paradigm of facial emotion recognition [Ekman, P., & Friesen, W. V. (1976). Pictures of facial affect. Palo Alto: Consulting Psychologist Press] before and after STN DBS. Prior to this, the Benton Facial Recognition Test was used to check that the ability to perceive faces was intact. Apathy had significantly worsened at M3 (42.5+/-8.9, p=0.006) after STN-DBS, in relation to the preoperative assessment (37.2+/-5.5). There was also a significant reduction in recognition percentages for facial expressions of fear (43.1%+/-22.9 vs. 61.6%+/-21.4, p=0.022) and sadness (52.7%+/-19.1 vs. 67.6%+/-22.8, p=0.031) after STN DBS. However, the postoperative worsening of apathy and emotion recognition impairment were not correlated. Our results confirm that the STN is involved in both the apathy and emotion recognition networks. However, the absence of any correlation between apathy and emotion recognition impairment suggests that the worsening of apathy following surgery could not be explained by a lack of facial emotion recognition and that its behavioural and cognitive components should therefore also be taken into consideration.

  17. Dynamics of human subthalamic neuron phase-locking to motor and sensory cortical oscillations during movement.

    Lipski, Witold J; Wozny, Thomas A; Alhourani, Ahmad; Kondylis, Efstathios D; Turner, Robert S; Crammond, Donald J; Richardson, Robert Mark

    2017-09-01

    Coupled oscillatory activity recorded between sensorimotor regions of the basal ganglia-thalamocortical loop is thought to reflect information transfer relevant to movement. A neuronal firing-rate model of basal ganglia-thalamocortical circuitry, however, has dominated thinking about basal ganglia function for the past three decades, without knowledge of the relationship between basal ganglia single neuron firing and cortical population activity during movement itself. We recorded activity from 34 subthalamic nucleus (STN) neurons, simultaneously with cortical local field potentials and motor output, in 11 subjects with Parkinson's disease (PD) undergoing awake deep brain stimulator lead placement. STN firing demonstrated phase synchronization to both low- and high-beta-frequency cortical oscillations, and to the amplitude envelope of gamma oscillations, in motor cortex. We found that during movement, the magnitude of this synchronization was dynamically modulated in a phase-frequency-specific manner. Importantly, we found that phase synchronization was not correlated with changes in neuronal firing rate. Furthermore, we found that these relationships were not exclusive to motor cortex, because STN firing also demonstrated phase synchronization to both premotor and sensory cortex. The data indicate that models of basal ganglia function ultimately will need to account for the activity of populations of STN neurons that are bound in distinct functional networks with both motor and sensory cortices and code for movement parameters independent of changes in firing rate. NEW & NOTEWORTHY Current models of basal ganglia-thalamocortical networks do not adequately explain simple motor functions, let alone dysfunction in movement disorders. Our findings provide data that inform models of human basal ganglia function by demonstrating how movement is encoded by networks of subthalamic nucleus (STN) neurons via dynamic phase synchronization with cortex. The data also

  18. Use of intraoperative local field potential spectral analysis to differentiate basal ganglia structures in Parkinson's disease patients.

    Kolb, Rachel; Abosch, Aviva; Felsen, Gidon; Thompson, John A

    2017-06-01

    Identification of brain structures traversed during implantation of deep brain-stimulating (DBS) electrodes into the subthalamic nucleus (STN-DBS) for the treatment of Parkinson's disease (PD) frequently relies on subjective correspondence between kinesthetic response and multiunit activity. However, recent work suggests that local field potentials (LFP) could be used as a more robust signal to objectively differentiate subcortical structures. The goal of this study was to analyze the spectral properties of LFP collected during STN-DBS in order to objectively identify commonly traversed brain regions and improve our understanding of aberrant oscillations in the PD-related pathophysiological cortico-basal ganglia network. In 21 PD patients, LFP were collected and analyzed during STN-DBS implantation surgery. Spectral power for delta-, theta-, alpha-, low-beta-, and high-beta-frequency bands was assessed at multiple depths throughout the subcortical structures traversed on the trajectory to the ventral border of STN. Similar to previous findings, beta-band oscillations had an increased magnitude within the borders of the motor-related area of STN, however, across several subjects, we also observed increased high-beta magnitude within the borders of thalamus. Comparing across all patients using relative power, we observed a gradual increase in the magnitude of both low- and high-beta-frequency bands as the electrode descended from striatum to STN. These results were also compared with frequency bands below beta, and similar trends were observed. Our results suggest that LFP signals recorded during the implantation of a DBS electrode evince distinct oscillatory signatures that distinguish subcortical structures. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

  19. Potential mechanisms for imperfect synchronization in parkinsonian basal ganglia.

    Choongseok Park

    Full Text Available Neural activity in the brain of parkinsonian patients is characterized by the intermittently synchronized oscillatory dynamics. This imperfect synchronization, observed in the beta frequency band, is believed to be related to the hypokinetic motor symptoms of the disorder. Our study explores potential mechanisms behind this intermittent synchrony. We study the response of a bursting pallidal neuron to different patterns of synaptic input from subthalamic nucleus (STN neuron. We show how external globus pallidus (GPe neuron is sensitive to the phase of the input from the STN cell and can exhibit intermittent phase-locking with the input in the beta band. The temporal properties of this intermittent phase-locking show similarities to the intermittent synchronization observed in experiments. We also study the synchronization of GPe cells to synaptic input from the STN cell with dependence on the dopamine-modulated parameters. Earlier studies showed how the strengthening of dopamine-modulated coupling may lead to transitions from non-synchronized to partially synchronized dynamics, typical in Parkinson's disease. However, dopamine also affects the cellular properties of neurons. We show how the changes in firing patterns of STN neuron due to the lack of dopamine may lead to transition from a lower to a higher coherent state, roughly matching the synchrony levels observed in basal ganglia in normal and parkinsonian states. The intermittent nature of the neural beta band synchrony in Parkinson's disease is achieved in the model due to the interplay of the timing of STN input to pallidum and pallidal neuronal dynamics, resulting in sensitivity of pallidal output to the phase of the arriving STN input. Thus the mechanism considered here (the change in firing pattern of subthalamic neurons through the dopamine-induced change of membrane properties may be one of the potential mechanisms responsible for the generation of the intermittent synchronization

  20. Modulation of Human Time Processing by Subthalamic Deep Brain Stimulation

    Timmermann, Lars; Reck, Christiane; Maarouf, Mohammad; Jörgens, Silke; Ploner, Markus; Südmeyer, Martin; Groiss, Stefan Jun; Sturm, Volker; Niedeggen, Michael; Schnitzler, Alfons

    2011-01-01

    Timing in the range of seconds referred to as interval timing is crucial for cognitive operations and conscious time processing. According to recent models of interval timing basal ganglia (BG) oscillatory loops are involved in time interval recognition. Parkinsońs disease (PD) is a typical disease of the basal ganglia that shows distortions in interval timing. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a powerful treatment of PD which modulates motor and cognitive functions depending on stimulation frequency by affecting subcortical-cortical oscillatory loops. Thus, for the understanding of BG-involvement in interval timing it is of interest whether STN-DBS can modulate timing in a frequency dependent manner by interference with oscillatory time recognition processes. We examined production and reproduction of 5 and 15 second intervals and millisecond timing in a double blind, randomised, within-subject repeated-measures design of 12 PD-patients applying no, 10-Hz- and ≥130-Hz-STN-DBS compared to healthy controls. We found under(re-)production of the 15-second interval and a significant enhancement of this under(re-)production by 10-Hz-stimulation compared to no stimulation, ≥130-Hz-STN-DBS and controls. Milliseconds timing was not affected. We provide first evidence for a frequency-specific modulatory effect of STN-DBS on interval timing. Our results corroborate the involvement of BG in general and of the STN in particular in the cognitive representation of time intervals in the range of multiple seconds. PMID:21931767

  1. Effect of low-frequency deep brain stimulation on sensory thresholds in Parkinson's disease.

    Belasen, Abigail; Rizvi, Khizer; Gee, Lucy E; Yeung, Philip; Prusik, Julia; Ramirez-Zamora, Adolfo; Hanspal, Era; Paiva, Priscilla; Durphy, Jennifer; Argoff, Charles E; Pilitsis, Julie G

    2017-02-01

    OBJECTIVE Chronic pain is a major distressing symptom of Parkinson's disease (PD) that is often undertreated. Subthalamic nucleus (STN) deep brain stimulation (DBS) delivers high-frequency stimulation (HFS) to patients with PD and has been effective in pain relief in a subset of these patients. However, up to 74% of patients develop new pain concerns while receiving STN DBS. Here the authors explore whether altering the frequency of STN DBS changes pain perception as measured through quantitative sensory testing (QST). METHODS Using QST, the authors measured thermal and mechanical detection and pain thresholds in 19 patients undergoing DBS via HFS, low-frequency stimulation (LFS), and off conditions in a randomized order. Testing was performed in the region of the body with the most pain and in the lower back in patients without chronic pain. RESULTS In the patients with chronic pain, LFS significantly reduced heat detection thresholds as compared with thresholds following HFS (p = 0.029) and in the off state (p = 0.010). Moreover, LFS resulted in increased detection thresholds for mechanical pressure (p = 0.020) and vibration (p = 0.040) compared with these thresholds following HFS. Neither LFS nor HFS led to changes in other mechanical thresholds. In patients without chronic pain, LFS significantly increased mechanical pain thresholds in response to the 40-g pinprick compared with thresholds following HFS (p = 0.032). CONCLUSIONS Recent literature has suggested that STN LFS can be useful in treating nonmotor symptoms of PD. Here the authors demonstrated that LFS modulates thermal and mechanical detection to a greater extent than HFS. Low-frequency stimulation is an innovative means of modulating chronic pain in PD patients receiving STN DBS. The authors suggest that STN LFS may be a future option to consider when treating Parkinson's patients in whom pain remains the predominant complaint.

  2. Modulation of human time processing by subthalamic deep brain stimulation.

    Wojtecki, Lars; Elben, Saskia; Timmermann, Lars; Reck, Christiane; Maarouf, Mohammad; Jörgens, Silke; Ploner, Markus; Südmeyer, Martin; Groiss, Stefan Jun; Sturm, Volker; Niedeggen, Michael; Schnitzler, Alfons

    2011-01-01

    Timing in the range of seconds referred to as interval timing is crucial for cognitive operations and conscious time processing. According to recent models of interval timing basal ganglia (BG) oscillatory loops are involved in time interval recognition. Parkinsońs disease (PD) is a typical disease of the basal ganglia that shows distortions in interval timing. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a powerful treatment of PD which modulates motor and cognitive functions depending on stimulation frequency by affecting subcortical-cortical oscillatory loops. Thus, for the understanding of BG-involvement in interval timing it is of interest whether STN-DBS can modulate timing in a frequency dependent manner by interference with oscillatory time recognition processes. We examined production and reproduction of 5 and 15 second intervals and millisecond timing in a double blind, randomised, within-subject repeated-measures design of 12 PD-patients applying no, 10-Hz- and ≥ 130-Hz-STN-DBS compared to healthy controls. We found under(re-)production of the 15-second interval and a significant enhancement of this under(re-)production by 10-Hz-stimulation compared to no stimulation, ≥ 130-Hz-STN-DBS and controls. Milliseconds timing was not affected. We provide first evidence for a frequency-specific modulatory effect of STN-DBS on interval timing. Our results corroborate the involvement of BG in general and of the STN in particular in the cognitive representation of time intervals in the range of multiple seconds.

  3. The Breast Cancer-Associated Glycoforms of MUC1, MUC1-Tn and sialyl-Tn, Are Expressed in COSMC Wild-Type Cells and Bind the C-Type Lectin MGL.

    Richard Beatson

    Full Text Available Aberrant glycosylation occurs in the majority of human cancers and changes in mucin-type O-glycosylation are key events that play a role in the induction of invasion and metastases. These changes generate novel cancer-specific glyco-antigens that can interact with cells of the immune system through carbohydrate binding lectins. Two glyco-epitopes that are found expressed by many carcinomas are Tn (GalNAc-Ser/Thr and STn (NeuAcα2,6GalNAc-Ser/Thr. These glycans can be carried on many mucin-type glycoproteins including MUC1. We show that the majority of breast cancers carry Tn within the same cell and in close proximity to extended glycan T (Galβ1,3GalNAc the addition of Gal to the GalNAc being catalysed by the T synthase. The presence of active T synthase suggests that loss of the private chaperone for T synthase, COSMC, does not explain the expression of Tn and STn in breast cancer cells. We show that MUC1 carrying both Tn or STn can bind to the C-type lectin MGL and using atomic force microscopy show that they bind to MGL with a similar dead adhesion force. Tumour associated STn is associated with poor prognosis and resistance to chemotherapy in breast carcinomas, inhibition of DC maturation, DC apoptosis and inhibition of NK activity. As engagement of MGL in the absence of TLR triggering may lead to anergy, the binding of MUC1-STn to MGL may be in part responsible for some of the characteristics of STn expressing tumours.

  4. High-Frequency Stimulation at the Subthalamic Nucleus Suppresses Excessive Self-Grooming in Autism-Like Mouse Models.

    Chang, Andrew D; Berges, Victoria A; Chung, Sunho J; Fridman, Gene Y; Baraban, Jay M; Reti, Irving M

    2016-06-01

    Approximately one quarter of individuals with an autism spectrum disorder (ASD) display self-injurious behavior (SIB) ranging from head banging to self-directed biting and punching. Sometimes, these behaviors are extreme and unresponsive to pharmacological and behavioral therapies. We have found electroconvulsive therapy (ECT) can produce life-changing results, with more than 90% suppression of SIB frequency. However, these patients typically require frequent maintenance ECT (mECT), as often as every 5 days, to sustain the improvement gained during the acute course. Long-term consequences of such frequent mECT started as early as childhood in some cases are unknown. Accordingly, there is a need for alternative forms of chronic stimulation for these patients. To explore the feasibility of deep brain stimulation (DBS) for intractable SIB seen in some patients with an ASD, we utilized two genetically distinct mouse models demonstrating excessive self-grooming, namely the Viaat-Mecp2(-/y) and Shank3B(-/-) lines, and administered high-frequency stimulation (HFS) via implanted electrodes at the subthalamic nucleus (STN-HFS). We found that STN-HFS significantly suppressed excessive self-grooming in both genetic lines. Suppression occurs both acutely when stimulation is switched on, and persists for several days after HFS is stopped. This effect was not explained by a change in locomotor activity, which was unaffected by STN-HFS. Likewise, social interaction deficits were not corrected by STN-HFS. Our data show STN-HFS suppresses excessive self-grooming in two autism-like mouse models, raising the possibility DBS might be used to treat intractable SIB associated with ASDs. Further studies are required to explore the circuitry engaged by STN-HFS, as well as other potential stimulation sites. Such studies might also yield clues about pathways, which could be modulated by non-invasive stimulatory techniques.

  5. Region Based CNN for Foreign Object Debris Detection on Airfield Pavement.

    Cao, Xiaoguang; Wang, Peng; Meng, Cai; Bai, Xiangzhi; Gong, Guoping; Liu, Miaoming; Qi, Jun

    2018-03-01

    In this paper, a novel algorithm based on convolutional neural network (CNN) is proposed to detect foreign object debris (FOD) based on optical imaging sensors. It contains two modules, the improved region proposal network (RPN) and spatial transformer network (STN) based CNN classifier. In the improved RPN, some extra select rules are designed and deployed to generate high quality candidates with fewer numbers. Moreover, the efficiency of CNN detector is significantly improved by introducing STN layer. Compared to faster R-CNN and single shot multiBox detector (SSD), the proposed algorithm achieves better result for FOD detection on airfield pavement in the experiment.

  6. Simple mucin-type carbohydrates in normal and malignant human endometrium

    Ravn, V; Mandel, U; Svenstrup, B

    1995-01-01

    The simple mucin-type carbohydrate antigens, Tn, sialosyl-Tn, and T, are tumor-associated antigens of adenocarcinomas. We evaluated by immunohistochemistry the expression of Tn, sialosyl-Tn (s-Tn), T, and sialosyl-T (s-T) antigens in normal nonsecretory, early gestational, and malignant human...... and malignant endometrium, and the expression of s-T antigen was positively correlated with E2 levels in serum. Our findings suggest a hormonal influence on expression of simple mucin-type carbohydrates in human endometrium. However, the accumulation of Tn and s-Tn antigens in malignant endometrial cells seem...

  7. The Role of 3T Magnetic Resonance Imaging for Targeting the Human Subthalamic Nucleus in Deep Brain Stimulation for Parkinson Disease.

    Longhi, Michele; Ricciardi, Giuseppe; Tommasi, Giorgio; Nicolato, Antonio; Foroni, Roberto; Bertolasi, Laura; Beltramello, Alberto; Moretto, Giuseppe; Tinazzi, Michele; Gerosa, Massimo

    2015-05-01

    Chronic stimulation of the human subthalamic nucleus (STN) is gradually becoming accepted as a long-term therapeutic option for patients with advanced Parkinson disease (PD). 3Tesla (T) magnetic resonance imaging (MRI) improves contrast resolution in basal ganglia nuclei containing high levels of iron, because of magnetic susceptibility effects that increase significantly as the magnetic field gets higher. This phenomenon can be used for better visualization of the STN and may reduce the time necessary for detailed microrecording (MER) mapping, increasing surgery efficacy and lowering morbidity. The objective of this retrospective study is to analyze a population of 20 deep brain stimulation (DBS) electrode implanted patients with PD divided into two groups in which different targeting methods were used. Mean age was 56 years (range 37 to 69 years). Mean disease duration was 11.6 years. Mean follow-up was 12 months (range 6 to 36 months). Patients were divided into two groups: Group A contained 6 patients who underwent STN targeting using 1T stereotactic (T1w + T2w) MRI plus STN indirect atlas derived targeting. Group B consisted of 14 patients who underwent STN targeting using 3T nonstereotactic (T2w) MRI fused with 1T T1w stereotactic MRI and STN direct targeting. For statistical analysis, we compared (five different parameters in both (matched) groups: Unified Parkinson's disease rating scale (UPDRS) score reduction (medication off before surgery against stimulation on/medication off after surgery), postoperative drug reduction, duration of surgery, the "central preoperative track" chosen as final implantation track during surgery, and correspondence between the targeted STN and the intraoperative neurophysiologic data. Mean UPDRS III score reduction (medication off/stimulation on versus preoperative medication off) was 69% in Group A and 74% in Group B (p = 0.015, log-rank test) respectively. Postoperatively, antiparkinsonian treatment was reduced by 66

  8. Safety evaluation report related to the operation of Braidwood Station, Units 1 and 2 (Docket Nos. 50-456 and 50-457)

    1983-11-01

    The Safety Evaluation Report for the application filed by the Commonwealth Edison Company, as applicant and owner, for a license to operate Braidwood Station, Units 1 and 2 (Docket Nos. STN 50-456 and STN 50-457), has been prepared by the Office of Nuclear Reactor Regulation of the US Nuclear Regulatory Commission. The facility is located in Reed Township, Will County, Illinois. Subject to favorable resolution of the items discussed in this report, the staff concludes that the facility can be operated by the applicant without endangering the health and safety of the public

  9. Motivational Tuning of Fronto-Subthalamic Connectivity Facilitates Control of Action Impulses

    Herz, Damian M.; Christensen, Mark S.; Bruggemann, Norbert

    2014-01-01

    It is critical for survival to quickly respond to environmental stimuli with the most appropriate action. This task becomes most challenging when response tendencies induced by relevant and irrelevant stimulus features are in conflict, and have to be resolved in real time. Inputs from the pre...... for fast and accurate responses. These effects were mediated by enhanced activation and connectivity of the IFG–STN pathway. These results provide causal evidence for a pivotal role of the IFG–STN pathway during action control. Additionally, they suggest a parallel rather than hierarchical organization...

  10. Safety Evaluation Report related to the operation of Braidwood Station, Units 1 and 2 (Docket Nos. 50-456 and 50-457). Supplement No. 1

    1986-09-01

    In November 1983 the staff of the Nuclear Regulatory Commission issued its Safety Evaluation Report (NUREG-1002) regarding the application filed by the Commonwealth Edison Company, as applicant and owner, for a license to operate Braidwood Station, Units 1 and 2 (Docket Nos. STN 50-456 and STN 50-457). The facility is located in Reed Township, Will County, Illinois. This first supplement to NUREG-1002 reports the status of certain items that remained unresolved at the time the Safety Evaluation Report was published

  11. Safety evaluation report: related to the operation of Seabrook Station, Units 1 and 2, Docket Nos. 50-443 and 50-444, Public Service Company of New Hampshire, et al

    1983-03-01

    The Safety Evaluation Report for the application filed by the Public Service Company of New Hampshire, et al., for licenses to operate Seabrook Station, Units 1 and 2 (Docket Nos. STN 50-443 and STN 50-444), has been prepared by the Office of Nuclear Reactor Regulation of the US Nuclear Regulatory Commission. The facility is located in Seabrook, New Hampshire. Subject to favorable resolution of the items discussed in this report, the staff concludes that the facility can be operated by the applicant without endangering the health and safety of the public

  12. Congress of Neurological Surgeons Systematic Review and Evidence-Based Guideline on Subthalamic Nucleus and Globus Pallidus Internus Deep Brain Stimulation for the Treatment of Patients With Parkinson's Disease: Executive Summary.

    Rughani, Anand; Schwalb, Jason M; Sidiropoulos, Christos; Pilitsis, Julie; Ramirez-Zamora, Adolfo; Sweet, Jennifer A; Mittal, Sandeep; Espay, Alberto J; Martinez, Jorge Gonzalez; Abosch, Aviva; Eskandar, Emad; Gross, Robert; Alterman, Ron; Hamani, Clement

    2018-06-01

    Is bilateral subthalamic nucleus deep brain stimulation (STN DBS) more, less, or as effective as bilateral globus pallidus internus deep brain stimulation (GPi DBS) in treating motor symptoms of Parkinson's disease, as measured by improvements in Unified Parkinson's Disease Rating Scale, part III (UPDRS-III) scores? Given that bilateral STN DBS is at least as effective as bilateral GPi DBS in treating motor symptoms of Parkinson's disease (as measured by improvements in UPDRS-III scores), consideration can be given to the selection of either target in patients undergoing surgery to treat motor symptoms. (Level I). Is bilateral STN DBS more, less, or as effective as bilateral GPi DBS in allowing reduction of dopaminergic medication in Parkinson's disease? When the main goal of surgery is reduction of dopaminergic medications in a patient with Parkinson's disease, then bilateral STN DBS should be performed instead of GPi DBS. (Level I). Is bilateral STN DBS more, less, or as effective as bilateral GPi DBS in treating dyskinesias associated with Parkinson's disease? There is insufficient evidence to make a generalizable recommendation regarding the target selection for reduction of dyskinesias. However, when the reduction of medication is not anticipated and there is a goal to reduce the severity of "on" medication dyskinesias, the GPi should be targeted. (Level I). Is bilateral STN DBS more, less, or as effective as bilateral GPi DBS in improving quality of life measures in Parkinson's disease? When considering improvements in quality of life in a patient undergoing DBS for Parkinson's disease, there is no basis to recommend bilateral DBS in 1 target over the other. (Level I). Is bilateral STN DBS associated with greater, lesser, or a similar impact on neurocognitive function than bilateral GPi DBS in Parkinson disease? If there is significant concern about cognitive decline, particularly in regards to processing speed and working memory in a patient undergoing DBS

  13. Bilateral high frequency subthalamic stimulation in Parkinson's disease: long-term neurological follow-up

    Romito, L. M.; Scerrati, M.; Contarino, M. F.; Iacoangeli, M.; Bentivoglio, A. R.; Albanese, A.

    2003-01-01

    AIM: High frequency stimulation of the subthalamic nucleus (STN) is gaining recognition as a new symptomatic treatment for Parkinson's disease (PD). The first available long-term observations show the stability of the efficacy of this procedure in time. METHODS: Quadripolar leads were implanted

  14. Free-living energy expenditure reduced after deep brain stimulation surgery for Parkinson's disease

    Jørgensen, Hans Ulrik; Werdelin, Lene; Lokkegaard, Annemette

    2012-01-01

    with deep brain stimulation in the subthalamic nucleus (STN-DBS) is now considered the gold standard in fluctuating PD. Many patients experience a gain of weight following the surgery. The aim of this study was to identify possible mechanisms, which may contribute to body weight gain in patients with PD...

  15. Impulse control behaviours in patients with Parkinson's disease after subthalamic deep brain stimulation: de novo cases and 3-year follow-up.

    Amami, P; Dekker, I; Piacentini, S; Ferré, F; Romito, L M; Franzini, A; Foncke, E M J; Albanese, A

    2015-05-01

    To document the occurrence of impulse control behaviours (ICBs) in patients with Parkinson's disease after 3 years of continuous deep brain stimulation (DBS) of the subthalamic nucleus (STN). Detailed neurological and ICB assessments were performed before STN DBS and up to 3 years after implant. 13 out of 56 patients (23.2%) had ICBs at baseline; they took higher doses of dopamine agonists (DAA). Three years after implant 11 had fully remitted with a 60.8% reduction of DAA medication; the remaining two, who had a similar medication reduction, had only compulsive eating, having recovered from hypersexuality. Six of the 43 patients without ICBs at baseline (14%) developed transient de novo ICBs after implant; none of them had ICBs at the 3-year observation. ICBs were abolished in patients 3 years after STN DBS and DAA dosages were lowered. New ICBs may occur after implant and are transient in most cases. Compulsive eating may be specifically related to STN stimulation. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  16. Effects of stereotactic neurosurgery on postural instability and gait in Parkinson's disease

    Bakker, Maaike; Esselink, Rianne A. J.; Munneke, Marten; Limousin-Dowsey, Patricia; Speelman, Hans D.; Bloem, Bastiaan R.

    2004-01-01

    Postural instability and gait disability (PIGD) are disabling signs of Parkinson's disease. Stereotactic surgery aimed at the internal globus pallidus (GPi) or subthalamic nucleus (STN) might improve PIGD, but the precise effects remain unclear. We performed a systematic review of studies that

  17. Subthalamic deep brain stimulation modulates conscious perception of sensory function in Parkinson's disease.

    Cury, Rubens G; Galhardoni, Ricardo; Teixeira, Manoel J; Dos Santos Ghilardi, Maria G; Silva, Valquiria; Myczkowski, Martin L; Marcolin, Marco A; Barbosa, Egberto R; Fonoff, Erich T; Ciampi de Andrade, Daniel

    2016-12-01

    Subthalamic deep brain stimulation (STN-DBS) is used to treat refractory motor complications in Parkinson disease (PD), but its effects on nonmotor symptoms remain uncertain. Up to 80% of patients with PD may have pain relief after STN-DBS, but it is unknown whether its analgesic properties are related to potential effects on sensory thresholds or secondary to motor improvement. We have previously reported significant and long-lasting pain relief after DBS, which did not correlate with motor symptomatic control. Here we present secondary data exploring the effects of DBS on sensory thresholds in a controlled way and have explored the relationship between these changes and clinical pain and motor improvement after surgery. Thirty-seven patients were prospectively evaluated before STN-DBS and 12 months after the procedure compared with healthy controls. Compared with baseline, patients with PD showed lower thermal and mechanical detection and higher cold pain thresholds after surgery. There were no changes in heat and mechanical pain thresholds. Compared with baseline values in healthy controls, patients with PD had higher thermal and mechanical detection thresholds, which decreased after surgery toward normalization. These sensory changes had no correlation with motor or clinical pain improvement after surgery. These data confirm the existence of sensory abnormalities in PD and suggest that STN-DBS mainly influenced the detection thresholds rather than painful sensations. However, these changes may depend on the specific effects of DBS on somatosensory loops with no correlation to motor or clinical pain improvement.

  18. Intensive Voice Treatment (LSVT[R]LOUD) for Parkinson's Disease Following Deep Brain Stimulation of the Subthalamic Nucleus

    Spielman, Jennifer; Mahler, Leslie; Halpern, Angela; Gilley, Phllip; Klepitskaya, Olga; Ramig, Lorraine

    2011-01-01

    Purpose: Intensive voice therapy (LSVT[R]LOUD) can effectively manage voice and speech symptoms associated with idiopathic Parkinson disease (PD). This small-group study evaluated voice and speech in individuals with and without deep brain stimulation of the subthalamic nucleus (STN-DBS) before and after LSVT LOUD, to determine whether outcomes…

  19. Pitch Variability in Patients with Parkinson's Disease: Effects of Deep Brain Stimulation of Caudal Zona Incerta and Subthalamic Nucleus

    Karlsson, Fredrik; Olofsson, Katarina; Blomstedt, Patric; Linder, Jan; van Doorn, Jan

    2013-01-01

    Purpose: The purpose of the present study was to examine the effect of deep brain stimulation (DBS) of the subthalamic nucleus (STN) and the caudal zona incerta (cZi) pitch characteristics of connected speech in patients with Parkinson's disease (PD). Method: The authors evaluated 16 patients preoperatively and 12 months after DBS surgery. Eight…

  20. Articulatory Closure Proficiency in Patients with Parkinson's Disease Following Deep Brain Stimulation of the Subthalamic Nucleus and Caudal Zona Incerta

    Karlsson, Fredrik; Olofsson, Katarina; Blomstedt, Patric; Linder, Jan; Nordh, Erik; van Doorn, Jan

    2014-01-01

    Purpose: The present study aimed at comparing the effects of deep brain stimulation (DBS) treatment of the subthalamic nucleus (STN) and the caudal zona incerta (cZi) on the proficiency in achieving oral closure and release during plosive production of people with Parkinson's disease. Method: Nineteen patients participated preoperatively and…

  1. Deep Brain Stimulation of Caudal Zona Incerta and Subthalamic Nucleus in Patients with Parkinson's Disease: Effects on Diadochokinetic Rate

    Fredrik Karlsson

    2011-01-01

    Full Text Available The hypokinetic dysarthria observed in Parkinson's disease (PD affects the range, speed, and accuracy of articulatory gestures in patients, reducing the perceived quality of speech acoustic output in continuous speech. Deep brain stimulation (DBS of the subthalamic nucleus (STN-DBS and of the caudal zona incerta (cZi-DBS are current surgical treatment options for PD. This study aimed at investigating the outcome of STN-DBS (7 patients and cZi-DBS (7 patients in two articulatory diadochokinesis tasks (AMR and SMR using measurements of articulation rate and quality of the plosive consonants (using the percent measurable VOT metric. The results indicate that patients receiving STN-DBS increased in articulation rate in the Stim-ON condition in the AMR task only, with no effect on production quality. Patients receiving cZi-DBS decreased in articulation rate in the Stim-ON condition and further showed a reduction in production quality. The data therefore suggest that cZi-DBS is more detrimental for extended articulatory movements than STN-DBS.

  2. Subthalamic deep brain stimulation reduces pathological information transmission to the thalamus in a rat model of parkinsonism

    Collin James Anderson

    2015-07-01

    Full Text Available The degeneration of dopaminergic neurons in the substantia nigra pars compacta leads to parkinsonian motor symptoms via changes in electrophysiological activity throughout the basal ganglia. High-frequency deep brain stimulation (DBS partially treats these symptoms, but the mechanisms are unclear. We hypothesize that motor symptoms of Parkinson's disease are associated with increased information transmission from basal ganglia output neurons to motor thalamus input neurons, and that therapeutic DBS of the subthalamic nucleus (STN treats these symptoms by reducing this extraneous information transmission. We tested these hypotheses in a unilateral, 6-hydroxydopamine-lesioned rodent model of hemiparkinsonism. Information transfer between basal ganglia output neurons and motor thalamus input neurons increased in both the orthodromic and antidromic directions with hemiparkinsonian onset, and these changes were reversed by behaviorally therapeutic STN-DBS. Omnidirectional information increases in the parkinsonian state underscore the detrimental nature of that pathological information, and suggest a loss of information channel independence. Therapeutic STN-DBS reduced that pathological information, suggesting an effective increase in the number of independent information channels. We interpret these data with a model in which pathological information and fewer information channels diminishes the scope of possible motor activities, driving parkinsonian symptoms. In this model, STN-DBS restores information-channel independence by eliminating or masking the parkinsonism-associated information, and thus enlarges the scope of possible motor activities, alleviating parkinsonian symptoms.

  3. Neural activity in the rat basal ganglia

    Zhao, Yan; Stegenga, J.; Heida, Tjitske; van Wezel, Richard Jack Anton

    2013-01-01

    Objectives: Pathological oscillations in the beta frequencies (8-30Hz) have been found in the local field potentials of Parkinson's disease (PD) patients and non-human primate models of PD1. In particular, these synchronizations appear in the subthalamic nucleus (STN), a common target for deep brain

  4. The impact of multichannel microelectrode recording (MER) in deep brain stimulation of the basal ganglia.

    Kinfe, Thomas M; Vesper, Jan

    2013-01-01

    Deep brain stimulation (DBS) of the basal ganglia (Ncl. subthalamicus, Ncl. ventralis intermedius thalami, globus pallidus internus) has become an evidence-based and well-established treatment option in otherwise refractory movement disorders. The Ncl. subthalamicus (STN) is the target of choice in Parkinson's disease.However, a considerable discussion is currently ongoing with regard to the necessity for micro-electrode recording (MER) in DBS surgery.The present review provides an overview on deep brain stimulation and (MER) of the STN in patients with Parkinson's disease. Detailed description is given concerning the multichannel MER systems nowadays available for DBS of the basal ganglia, especially of the STN, as a useful tool for target refinement. Furthermore, an overview is given of the historical aspects, spatial mapping of the STN by MER, and its impact for accuracy and precision in current functional stereotactic neurosurgery.The pros concerning target refinement by MER means on the one hand, and cons including increased bleeding risk, increased operation time, local or general anesthesia, and single versus multichannel microelectrode recording are discussed in detail. Finally, the authors favor the use of MER with intraoperative testing combined with imaging to achieve a more precise electrode placement, aiming to ameliorate clinical outcome in therapy-resistant movement disorders.

  5. Subthalamic nucleus stimulation does not influence basal glucose metabolism or insulin sensitivity in patients with Parkinson's disease

    Lammers, Nicolette M.; Sondermeijer, Brigitte M.; Twickler, Th B. Marcel; de Bie, Rob M.; Ackermans, Mariëtte T.; Fliers, Eric; Schuurman, P. Richard; la Fleur, Susanne E.; Serlie, Mireille J.

    2014-01-01

    Animal studies have shown that central dopamine signaling influences glucose metabolism. As a first step to show this association in an experimental setting in humans, we studied whether deep brain stimulation (DBS) of the subthalamic nucleus (STN), which modulates the basal ganglia circuitry,

  6. Effects of focused ion beam milling on electron backscatter diffraction patterns in strontium titanate and stabilized zirconia

    Saowadee, Nath; Agersted, Karsten; Bowen, Jacob R.

    2012-01-01

    This study investigates the effect of focused ion beam (FIB) current and accelerating voltage on electron backscatter diffraction pattern quality of yttria‐stabilized zirconia (YSZ) and Nb‐doped strontium titanate (STN) to optimize data quality and acquisition time for 3D‐EBSD experiments by FIB...

  7. Effective improvement of interface modified strontium titanate based solid oxide fuel cell anodes by infiltration with nano-sized palladium and gadolinium-doped cerium oxide

    Abdul Jabbar, Mohammed Hussain; Høgh, Jens Valdemar Thorvald; Zhang, Wei

    2013-01-01

    The development of low temperature solid oxide fuel cell (SOFC) anodes by infiltration of Pd/Gd-doped cerium oxide (CGO) electrocatalysts in Nb-doped SrTiO3 (STN) backbones has been investigated. Modification of the electrode/electrolyte interface by thin layer of spin-coated CGO (400-500 nm) con...

  8. Influence of composted dairy manure and perennial forage on soil carbon and nitrogen fractions during transition into organic management

    Composted dairy manure (CDM) is among the management practices used in transitioning from a conventional to an organic agricultural system. The objectives of this study are to evaluate the impact of several organic nitrogen (N) sources on: (i) soil organic C (SOC) and soil total N (STN) content; (ii...

  9. The effect of deep brain stimulation of the subthalamic nucleus on executive functions: impaired verbal fluency and intact updating, planning and conflict resolution in Parkinson's disease.

    Demeter, Gyula; Valálik, István; Pajkossy, Péter; Szőllősi, Ágnes; Lukács, Ágnes; Kemény, Ferenc; Racsmány, Mihály

    2017-04-24

    Although the improvement of motor symptoms in Parkinson's disease (PD) after deep brain stimulation (DBS) of the subthalamic nucleus (STN) is well documented, there are open questions regarding its impact on cognitive functions. The aim of this study was to assess the effect of bilateral DBS of the STN on executive functions in PD patients using a DBS wait-listed PD control group. Ten PD patients with DBS implantation (DBS group) and ten PD wait-listed patients (Clinical control group) participated in the study. Neuropsychological tasks were used to assess general mental ability and various executive functions. Each task was administered twice to each participant: before and after surgery (with the stimulators on) in the DBS group and with a matched delay between the two task administration points in the control group. There was no significant difference between the DBS and the control groups' performance in tasks measuring the updating of verbal, spatial or visual information (Digit span, Corsi and N-back tasks), planning and shifting (Trail Making B), and conflict resolution (Stroop task). However, the DBS group showed a significant decline on the semantic verbal fluency task after surgery compared to the control group, which is in line with findings of previous studies. Our results provide support for the relative cognitive safety of the STN DBS using a wait-listed PD control group. Differential effects of the STN DBS on frontostriatal networks are discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Levodopa Effect on Basal Ganglia Motor Circuit in Parkinson's Disease.

    Gao, Lin-Lin; Zhang, Jia-Rong; Chan, Piu; Wu, Tao

    2017-01-01

    To investigate the effects of levodopa on the basal ganglia motor circuit (BGMC) in Parkinson's disease (PD). Thirty PD patients with asymmetrical bradykinesia and 30 control subjects were scanned using resting-state functional MRI. Functional connectivity of the BGMC was measured and compared before and after levodopa administration in patients with PD. The correlation between improvements in bradykinesia and changes in BGMC connectivity was examined. In the PD-off state (before medication), the posterior putamen and internal globus pallidus (GPi) had decreased connectivity while the subthalamic nucleus (STN) had enhanced connectivity within the BGMC relative to control subjects. Levodopa administration increased the connectivity of posterior putamen- and GPi-related networks but decreased the connectivity of STN-related networks. Improvements in bradykinesia were correlated with enhanced connectivity of the posterior putamen-cortical motor pathway and with decreased connectivity of the STN-thalamo-cortical motor pathway. In PD patients with asymmetrical bradykinesia, levodopa can partially normalize the connectivity of the BGMC with a larger effect on the more severely affected side. Moreover, the beneficial effect of levodopa on bradykinesia is associated with normalization of the striato-thalamo-cortical motor and STN-cortical motor pathways. Our findings inform the neural mechanism of levodopa treatment in PD. © 2016 John Wiley & Sons Ltd.

  11. Pallidotomy suppresses beta power in the subthalamic nucleus of Parkinson's disease patients

    Contarino, Maria Fiorella; Bour, Lo J.; Bot, Maarten; van den Munckhof, Pepijn; Speelman, Johannes D.; Schuurman, P. Richard; de Bie, Rob M. A.

    2011-01-01

    Parkinsonian patients, who have had a unilateral pallidotomy, may require bilateral deep brain stimulation of the subthalamic nucleus (STN), due to disease progression. The current model of the basal ganglia circuitry does not predict a direct effect of pallidotomy on the neuronal activity of the

  12. Surgical Treatment of Dyskinesia in Parkinson’s Disease

    Renato Puppi Munhoz

    2014-04-01

    Full Text Available One of the main indications for stereotactic surgery in Parkinson’s disease (PD is the control of levodopa induced dyskinesia. This can be achieved by by pallidotomy and globus pallidus internus (GPi deep brain stimulation (DBS or by subthalamotomy and subthalamic nucleus (STN DBS, which usually allow for a cut down in the dosage of levodopa. DBS has assumed a pivotal role in stereotactic surgical treatment of PD and, in fact, ablative procedures are currently considered surrogates, particularly when bilateral procedures are required, as DBS does not produce a brain lesion and the stimulator can be programmed to induce better therapeutic effects while minimizing adverse effects. Interventions in either the STN and the GPi seem to be similar in controlling most of the other motor aspects of PD, nonetheless, GPi surgery seems to induce a more particular and direct effect on dyskinesia, while the antidyskinetic effect of STN interventions is mostly dependent on a reduction of dopaminergic drug dosages. Hence, the si ne qua non condition for a reduction of dyskinesia when STN interventions are intended is their ability to allow for a reduction of levodopa dosage. Pallidal surgery is indicated when dyskinesia is a dose-limiting factor for maintaining or introducing higher adequate levels of dopaminergic therapy. Also medications used for the treatment of PD may be useful for the improvement of several non-motor aspects of the disease, including sleep, psychiatric, and cognitive domains, therefore, dose reduction of medication withdrawal are not always a fruitful objective.

  13. Factors predicting the instant effect of motor function after subthalamic nucleus deep brain stimulation in Parkinson's disease.

    Su, Xin-Ling; Luo, Xiao-Guang; Lv, Hong; Wang, Jun; Ren, Yan; He, Zhi-Yi

    2017-01-01

    Subthalamic nucleus deep brain stimulation (STN-DBS) is an effective treatment for Parkinson's disease (PD), the predictive effect of levodopa responsiveness on surgical outcomes was confirmed by some studies, however there were different conclusions about that through long- and short-term follow-ups. We aimed to investigate the factors which influence the predictive value of levodopa responsiveness, and discover more predictive factors of surgical outcomes. Twenty-three PD patients underwent bilateral STN-DBS and completed our follow-up. Clinical evaluations were performed 1 week before and 3 months after surgery. STN-DBS significantly improved motor function of PD patients after 3 months; preoperative levodopa responsiveness and disease subtype predicted the effect of DBS on motor function; gender, disease duration and duration of motor fluctuations modified the predictive effect of levodopa responsiveness on motor improvement; the duration of motor fluctuations and severity of preoperative motor symptoms modified the predictive effect of disease subtype on motor improvement. The intensity of levodopa responsiveness served as a predictor of motor improvement more accurately in female patients, patients with shorter disease duration or shorter motor fluctuations; PD patients with dominant axial symptoms benefit less from STN-DBS compared to those with limb-predominant symptoms, especially in their later disease stage.

  14. 75 FR 53985 - Arizona Public Service Company, et al., Palo Verde Nuclear Generating Station, Unit 3; Temporary...

    2010-09-02

    ... NUCLEAR REGULATORY COMMISSION [Docket No. STN 50-530; NRC-2010-0281] Arizona Public Service Company, et al., Palo Verde Nuclear Generating Station, Unit 3; Temporary Exemption 1.0 Background Arizona Public Service Company (APS, the licensee) is the holder of Facility Operating License No. NPF-74, which...

  15. Einfluss der Lage des aktiven Kontaktes innerhalb des Nucleus subthalamicus auf den Effekt der tiefen Hirnstimulation bei Parkinson Patienten- Eine MRT-basierte Untersuchung

    Wodarg, Fritz

    2013-01-01

    Anhand Prä- und postoperativer MRT-Bilder wird die Lage der Elektroden zur Hochfrequenzstimulation innerhalb des N. subthalamicus bestimmt und mit dem klinischen Ergebnis der Stimulation bei 30 Parkinson Patienten korreliert. Eine Stimulation in lateralen Anteilen des STN bringt signifikant bessere klinische Ergebnisse.

  16. The Parkinsonian Subthalamic Network: Measures of Power, Linear, and Non-linear Synchronization and their Relationship to L-DOPA Treatment and OFF State Motor Severity.

    West, Timothy; Farmer, Simon; Berthouze, Luc; Jha, Ashwani; Beudel, Martijn; Foltynie, Thomas; Limousin, Patricia; Zrinzo, Ludvic; Brown, Peter; Litvak, Vladimir

    2016-01-01

    In this paper we investigated the dopaminergic modulation of neuronal interactions occurring in the subthalamic nucleus (STN) during Parkinson's disease (PD). We utilized linear measures of local and long range synchrony such as power and coherence, as well as Detrended Fluctuation Analysis for Phase Synchrony (DFA-PS)- a recently developed non-linear method that computes the extent of long tailed autocorrelations present in the phase interactions between two coupled signals. Through analysis of local field potentials (LFPs) taken from the STN we seek to determine changes in the neurodynamics that may underpin the pathophysiology of PD in a group of 12 patients who had undergone surgery for deep brain stimulation. We demonstrate up modulation of alpha-theta (5-12 Hz) band power in response to L-DOPA treatment, whilst low beta band power (15-20 Hz) band-power is suppressed. We also find evidence for significant local connectivity within the region surrounding STN although there was evidence for its modulation via administration of L-DOPA. Further to this we present evidence for a positive correlation between the phase ordering of bilateral STN interactions and the severity of bradykinetic and rigidity symptoms in PD. Although, the ability of non-linear measures to predict clinical state did not exceed standard measures such as beta power, these measures may help identify the connections which play a role in pathological dynamics.

  17. Simple mucins (T, sialosyl-T, Tn and sialosyl-Tn) are not diagnostic for malignant breast lesions

    Reed, W.; Bryne, M.; Clausen, Henrik

    1994-01-01

    positive for T antigen, 82% for s-T antigen, 66% for Tn antigen and 22% for s-Tn antigen. The staining pattern was nearly identical for carcinomas with and without lymph node metastases. In conclusion, immunostaining for simple mucins does not permit a clear distinction between benign and malignant breast...

  18. Changes in the expression of N- and O-glycopeptides in patients with colorectal cancer and hepatocellular carcinoma quantified by full-MS scan FT-ICR and multiple reaction monitoring

    Darebná, P.; Novák, Petr; Kučera, R.; Topolčan, O.; Sanda, M.; Goldman, R.; Pompach, Petr

    2017-01-01

    Roč. 153, SI (2017), s. 44-52 ISSN 1874-3919 Grant - others:Ministerstvo pro místní rozvoj(CZ) CZ2.16./3.1.00/24023 Institutional support: RVO:61388971 Keywords : Mass spectrometry * Glycomics * FT-ICR Subject RIV: EE - Microbiology, Virology OBOR OECD: Microbiology Impact factor: 3.914, year: 2016

  19. Improved ceramic anodes for SOFCs with modified electrode/electrolyte interface

    Abdul Jabbar, Mohammed Hussain; Høgh, Jens Valdemar Thorvald; Zhang, Wei

    2012-01-01

    The electrode performance of solid oxide fuel cell anode with Pd nanoparticles at the interface of ScYSZ electrolyte and Sr0.94Ti0.9Nb0.1O3 (STN) electrode introduced in the form of metal functional layer have been investigated at temperatures below 600 °C. A metal functional layer consisting of Pd...... was deposited by magnetron sputtering. Effecting from heat treatments, Pd nanoparticles with particle sizes in the range of 5–20 nm were distributed at the interface, and throughout the backbone. The polarization resistance of the modified STN reduced to 30 Ωcm2 at 600 °C, which is three times less than...... an unmodified STN backbone. In order to improve the anode performance further, Pd and Gd-doped CeO2 electrocatalysts were infiltrated into the STN backbone. The modified interface with Pd nanoparticles in combination with nanostructured electrocatalyst by infiltration resulted in polarisation resistances of 0...

  20. Reference: 636 [Arabidopsis Phenome Database[Archive

    Full Text Available plasts, a process known as retrograde signaling. We have identified CHLOROPLAST RNA BINDING (CRB), a putativ...s affecting STN7, GUN1, and GUN5, unrelated nuclear-encoded chloroplast proteins known to be involved in retrograde

  1. Subthalamic nucleus stimulation reverses mediofrontal influence over decision threshold

    Cavanagh, J.F.; Wiecki, T.V.; Cohen, M.X.; Figueroa, C.M.; Samanta, J.; Sherman, S.J.; Frank, M.J.

    2011-01-01

    It takes effort and time to tame one's impulses. Although medial prefrontal cortex (mPFC) is broadly implicated in effortful control over behavior, the subthalamic nucleus (STN) is specifically thought to contribute by acting as a brake on cortico-striatal function during decision conflict, buying

  2. Hitting the right target : noninvasive localization of the subthalamic nucleus motor part for specific deep brain stimulation

    Brunenberg, E.J.L.

    2011-01-01

    Deep brain stimulation of the subthalamic nucleus (STN) has gained momentum as a therapy for advanced Parkinson’s disease. The stimulation effectively alleviates the patients’ typical motor symptoms on a long term, but can give rise to cognitive and psychiatric adverse effects as well. Based on

  3. Insect pests and their natural enemies on spring oilseed rape in Estonia : impact of cropping systems

    E. VEROMANN

    2008-12-01

    Full Text Available To investigate the impact of different cropping systems, the pests, their hymenopteran parasitoids and predatory ground beetles present in two spring rape crops in Estonia, in 2003, were compared. One crop was grown under a standard (STN cropping system and the other under a minimised (MIN system. The STN system plants had more flowers than those in the MIN system, and these attracted significantly more Meligethes aeneus, the only abundant and real pest in Estonia. Meligethes aeneus had two population peaks: the first during opening of the first flowers and the second, the new generation, during ripening of the pods. The number of new generation M. aeneus was almost four times greater in the STN than in the MIN crop. More carabids were caught in the MIN than in STN crop. The maximum abundance of carabids occurred two weeks before that of the new generation of M. aeneus, at the time when M. aeneus larvae were dropping to the soil for pupation and hence were vulnerable to predation by carabids.

  4. A randomized double-blind crossover trial comparing subthalamic and pallidal deep brain stimulation for dystonia

    Schjerling, Lisbeth; Hjermind, Lena E; Jespersen, Bo

    2013-01-01

    Object The authors' aim was to compare the subthalamic nucleus (STN) with the globus pallidus internus (GPi) as a stimulation target for deep brain stimulation (DBS) for medically refractory dystonia. Methods In a prospective double-blind crossover study, electrodes were bilaterally implanted in ...

  5. Long-term effects of pallidal or subthalamic deep brain stimulation on quality of life in Parkinson's disease

    Volkmann, Jens; Albanese, Alberto; Kulisevsky, Jaime; Tornqvist, Aana-Lena; Houeto, Jean-Luc; Pidoux, Bernard; Bonnet, Anne-Marie; Mendes, Alexandre; Benabid, Alim-Louis; Fraix, Valerie; van Blercom, Nadege; Xie, Jing; Obeso, José; Rodriguez-Oroz, Maria Cruz; Guridi, Jurge; Schnitzler, Alfons; Timmermann, Lars; Gironell, Alexandre A.; Molet, Juan; Pascual-Sedano, Benta; Rehncrona, Stig; Moro, Elena; Lang, Anthony C.; Lozano, Andres M.; Bentivoglio, Anna Rita; Scerrati, Massimo; Contarino, Maria Fiorella; Romito, Luigi; Janssens, Marc; Agid, Yves

    2009-01-01

    We assessed the effects of deep brain stimulation of the subthalamic nucleus (STN-DBS) or internal pallidum (GPi-DBS) on health-related quality of life (HrQoL) in patients with advanced Parkinson's disease participating in a previously reported multicenter trial. Sickness Impact Profile (SIP)

  6. Adaptation of Flux-Corrected Transport Algorithms for Modeling Dusty Flows.

    1983-12-20

    Defense Comunications Agency Olcy Attn XLA Washington, DC 20305 01cy Attn nTW-2 (ADR CNW D I: Attn Code 240 for) Olcy Attn NL-STN O Library Olcy Attn...Library Olcy Attn TIC-Library Olcy Attn R Welch Olcy Attn M Johnson Los Alamos National Scientific Lab. Mail Station 5000 Information Science, Inc. P

  7. MRI anatomical mapping and direct stereotactic targeting in the subthalamic region: functional and anatomical correspondence in Parkinson's disease

    Lemaire, Jean-Jacques; Coste, Jerome; Ouchchane, Lemlih; Hemm, Simone; Derost, Philippe; Ulla, Miguel; Durif, Franck; Siadoux, Severine; Gabrillargues, Jean; Chazal, Jean

    2007-01-01

    Object Relationships between clinical effects, anatomy, and electrophysiology are not fully understood in DBS of the subthalamic region in Parkinson's disease. We proposed an anatomic study based on direct image-guided stereotactic surgery with a multiple source data analysis. Materials and Methods A manual anatomic mapping was realized on coronal 1.5-Tesla MRI of 15 patients. Biological data were collected under local anesthesia: the spontaneous neuron activities and the clinical efficiency and the appearance of adverse effects. They were related to relevant current values (mA), the benefit threshold (bt, minimal current leading an clear efficiency), the adverse effect threshold (at, minimal current leading an adverse effect) and the stimulation margin (sm = at - bt); they were matched with anatomy. Results We found consistent relationships between anatomy and biological data. The optimal stimulation parameters (low bt + high sm) were noted in the dorsolateral STN. The highest spontaneous neuron activity was found in the ventromedial STN. Dorsolateral (sensorimotor) STN seems the main DBS effector. The highest spontaneous neuron activity seems related to the anterior (rostral) ventromedial (limbic) STN. Conclusion 1.5 Tesla images provide sufficiently detailed subthalamic anatomy for image-guided stereotactic surgery and may aid in understanding DBS mechanisms. (orig.)

  8. Effects of Subthalamic and Nigral Stimulation on Gait Kinematics in Parkinson’s Disease

    Marlieke Scholten

    2017-10-01

    Full Text Available Conventional subthalamic deep brain stimulation for Parkinson’s disease (PD presumably modulates the spatial component of gait. However, temporal dysregulation of gait is one of the factors that is tightly associated with freezing of gait (FOG. Temporal locomotor integration may be modulated differentially at distinct levels of the basal ganglia. Owing to its specific descending brainstem projections, stimulation of the substantia nigra pars reticulata (SNr area might modulate spatial and temporal parameters of gait differentially compared to standard subthalamic nucleus (STN stimulation. Here, we aimed to characterize the differential effect of STN or SNr stimulation on kinematic gait parameters. We analyzed biomechanical parameters during unconstrained over ground walking in 12 PD patients with subthalamic deep brain stimulation and FOG. Patients performed walking in three therapeutic conditions: (i Off stimulation, (ii STN stimulation (alone, and (iii SNr stimulation (alone. SNr stimulation was achieved by stimulating the most caudal contact of the electrode. We recorded gait using three sensors (each containing a tri-axial accelerometer, gyroscope, and magnetometer attached on both left and right ankle, and to the lumbar spine. STN stimulation improved both the spatial features (stride length, stride length variability and the temporal parameters of gait. SNr stimulation improved temporal parameters of gait (swing time asymmetry. Correlation analysis suggested that patients with more medial localization of the SNr contact associated with a stronger regularization of gait. These results suggest that SNr stimulation might support temporal regularization of gait integration.

  9. Weight gain after subthalamic nucleus deep brain stimulation in Parkinson's disease is influenced by dyskinesias' reduction and electrodes' position.

    Balestrino, Roberta; Baroncini, Damiano; Fichera, Mario; Donofrio, Carmine Antonio; Franzin, Alberto; Mortini, Pietro; Comi, Giancarlo; Volontè, Maria Antonietta

    2017-12-01

    Parkinson's disease is a common neurodegenerative disease that can be treated with pharmacological or surgical therapy. Subthalamic nucleus (STN) deep brain stimulation is a commonly used surgical option. A reported side effect of STN-DBS is weight gain: the aim of our study was to find those factors that determine weight gain, through one year-long observation of 32 patients that underwent surgery in our centre. During the follow-up, we considered: anthropometric features, hormonal levels, motor outcome, neuropsychological and quality of life outcomes, therapeutic parameters and electrodes position. The majority (84%) of our patients gained weight (6.7 kg in 12 months); more than a half of the cohort became overweight. At 12th month, weight gain showed a correlation with dyskinesias reduction, electrodes voltage and distance on the lateral axis. In the multivariate regression analysis, the determinants of weight gain were dyskinesias reduction and electrodes position. In this study, we identified dyskinesias reduction and distance between the active electrodes and the third ventricle as determining factors of weight gain after STN-DBS implantation in PD patients. The first finding could be linked to a decrease in energy consumption, while the second one could be due to a lower stimulation of the lateral hypothalamic area, known for its important role in metabolism and body weight control. Weight gain is a common finding after STN-DBS implantation, and it should be carefully monitored given the potential harmful consequences of overweight.

  10. General Anesthesia versus Local Anesthesia in StereotaXY (GALAXY) for Parkinson's disease: study protocol for a randomized controlled trial

    Holewijn, R. A.; Verbaan, D.; de Bie, R. M. A.; Schuurman, P. R.

    2017-01-01

    Background: The aim of the study is to investigate if deep brain stimulation (DBS) in the subthalamic nucleus (STN) for Parkinson's disease (PD) under general anesthesia further improves outcome by lessening postoperative cognitive, mood, and behavioral adverse effects; shorten surgical time and

  11. Microstructural and electrical characterization of Nb-doped SrTiO3–YSZ composites for solid oxide cell electrodes

    Reddy Sudireddy, Bhaskar; Blennow Tullmar, Peter; Nielsen, Karsten Agersted

    2012-01-01

    phases. However, microstructural analysis revealed segregation and formation of Nb enriched particles in the 50 vol.% 8YSZ composite. Chemical analysis by energy dispersive spectroscopy (EDS) also showed the inter-diffusion of elements (especially Ti from STN and Zr from 8YSZ) from both phases on small...

  12. Mental Health-Related Healthcare Use Following Bilateral Deep Brain Stimulation For Parkinson's Disease.

    Westbay, Lauren C; Cao, Lishan; Burnett-Zeigler, Inger; Reizine, Natalie; Barton, Brandon; Ippolito, Dolores; Weaver, Frances M; Stroupe, Kevin T

    2015-01-01

    The subthalamic nucleus (STN) and the globus pallidus internus (GPi) are both effective targets for deep brain stimulation (DBS) to relieve motor symptoms of Parkinson's disease. However, studies have reported varied effects on mental health-related adverse events and depressed mood following DBS. The current observational study sought to compare mental health healthcare utilization and costs for three years following STN or GPi DBS. For a cohort of Veterans (n = 161) with Parkinson's disease who participated in a larger multi-site randomized trial, we compared mental health outpatient visits, medication use, inpatient admissions, and associated costs by DBS target site (STN vs. GPi). Neither group nor time differences were significant for mental health outpatient or inpatient utilization following DBS. Overall costs associated with mental health visits and medications did not differ by time or by group. However, the percentage of patients with mental health medication use increased in the 6-month and 6 to 12 month periods post-surgery. The STN group had significantly greater increase in medication use at 6 to 12 months post-surgery compared to the GPi group (p use following surgery, this study suggests that mental health healthcare use and costs are stable over time and similar between DBS targets. Prior research findings of mental health-related adverse events and mood following DBS did not translate to greater mental health service utilization in our cohort. The changes seen in the year following surgery may reflect temporary adjustments with stabilization over time.

  13. Effects of Stimulation of the Subthalamic Nucleus on Naming and Reading Nouns and Verbs in Parkinson's Disease

    Silveri, Maria Caterina; Ciccarelli, Nicoletta; Baldonero, Eleonora; Piano, Carla; Zinno, Massimiliano; Soleti, Francesco; Bentivoglio, Anna Rita; Albanese, Alberto; Daniele, Antonio

    2012-01-01

    An impairment for verbs has been described in patients with Parkinson's disease (PD), suggesting that a disruption of frontal-subcortical circuits may result in dysfunction of the neural systems involved in action-verb processing. A previous study suggested that deep brain stimulation (DBS) of the subthalamic nucleus (STN) during verb generation…

  14. Serotonergic projections from the raphe nuclei to the subthalamic nucleus; a retrograde- and anterograde neuronal tracing study

    Reznitsky, Martin; Plenge, Per; Hay-Schmidt, Anders

    2016-01-01

    the 5-HT1A and 5-HT2A not were present. Retrograde tracer FluoroGold or Choleratoxin subunit B were iontophoretically delivered in the STN and combined with immunohistochemistry for 5-HT in order to map the topographic organization in the dorsal raphe system. The study showed that approximately 320...

  15. Psychiatric and social outcome after deep brain stimulation for advanced Parkinson's disease

    Boel, Judith A.; Odekerken, Vincent J. J.; Geurtsen, Gert J.; Schmand, Ben A.; Cath, Danielle C.; Figee, Martijn; van den Munckhof, Pepijn; de Haan, Rob J.; Schuurman, P. Richard; de Bie, Rob M. A.; van Dijk, J. Marc C.; Staal, Michael

    BackgroundThe aim of this study was to assess psychiatric and social outcome 12 months after bilateral deep brain stimulation (DBS) of the globus pallidus pars interna (GPi) and subthalamic nucleus (STN) for advanced Parkinson's disease (PD). MethodsWe randomly assigned patients to receive GPi DBS

  16. Psychiatric and social outcome after deep brain stimulation for advanced Parkinson's disease

    Boel, J.A.; Odekerken, V.J.J.; Geurtsen, G.J.; Schmand, B.A.; Cath, D.C.; Figee, M.; van den Munckhof, P.; de Haan, R.J.; Schuurman, P.R.; de Bie, R.M.A.

    BACKGROUND: The aim of this study was to assess psychiatric and social outcome 12 months after bilateral deep brain stimulation (DBS) of the globus pallidus pars interna (GPi) and subthalamic nucleus (STN) for advanced Parkinson's disease (PD). METHODS: We randomly assigned patients to receive GPi

  17. Psychiatric and social outcome after deep brain stimulation for advanced Parkinson's disease

    Boel, Judith A; Odekerken, Vincent J J; Geurtsen, Gert J; Schmand, Ben A; Cath, Danielle C; Figee, Martijn; van den Munckhof, Pepijn; de Haan, Rob J; Schuurman, P Richard; de Bie, Rob M A

    2016-01-01

    BACKGROUND: The aim of this study was to assess psychiatric and social outcome 12 months after bilateral deep brain stimulation (DBS) of the globus pallidus pars interna (GPi) and subthalamic nucleus (STN) for advanced Parkinson's disease (PD). METHODS: We randomly assigned patients to receive GPi

  18. Meta-analysis comparing deep brain stimulation of the globus pallidus and subthalamic nucleus to treat advanced Parkinson disease.

    Liu, Yi; Li, Weina; Tan, Changhong; Liu, Xi; Wang, Xin; Gui, Yuejiang; Qin, Lu; Deng, Fen; Hu, Changlin; Chen, Lifen

    2014-09-01

    Deep brain stimulation (DBS) is the surgical procedure of choice for patients with advanced Parkinson disease (PD). The globus pallidus internus (GPi) and the subthalamic nucleus (STN) are commonly targeted by this procedure. The purpose of this meta-analysis was to compare the efficacy of DBS in each region. MEDLINE/PubMed, EMBASE, Web of Knowledge, and the Cochrane Library were searched for English-language studies published before April 2013. of studies investigating the efficacy and clinical outcomes of DBS of the GPi and STN for PD were analyzed. Six eligible trials containing a total of 563 patients were included in the analysis. Deep brain stimulation of the GPi or STN equally improved motor function, measured by the Unified Parkinson's Disease Rating Scale Section III (UPDRSIII) (motor section, for patients in on- and off-medication phases), within 1 year postsurgery. The change score for the on-medication phase was 0.68 (95% CI - 2.12 to 3.47, p > 0.05; 5 studies, 518 patients) and for the off-medication phase was 1.83 (95% CI - 3.12 to 6.77, p > 0.05; 5 studies, 518 patients). The UPDRS Section II (activities of daily living) scores for patients on medication improved equally in both DBS groups (p = 0.97). STN DBS allowed medication dosages to be reduced more than GPi DBS (95% CI 129.27-316.64, p < 0.00001; 5 studies, 540 patients). Psychiatric symptoms, measured by Beck Depression Inventory, 2nd edition scores, showed greater improvement from baseline after GPi DBS than after STN DBS (standardized mean difference -2.28, 95% CI -3.73 to -0.84, p = 0.002; 3 studies, 382 patients). GPi and STN DBS improve motor function and activities of daily living for PD patients. Differences in therapeutic efficacy for PD were not observed between the 2 procedures. STN DBS allowed greater reduction in medication for patients, whereas GPi DBS provided greater relief from psychiatric symptoms. An understanding of other symptomatic aspects of targeting each region and long

  19. Deep Brain Stimulation of the Subthalamic Nucleus Does Not Affect the Decrease of Decision Threshold during the Choice Process When There Is No Conflict, Time Pressure, or Reward.

    Leimbach, Friederike; Georgiev, Dejan; Litvak, Vladimir; Antoniades, Chrystalina; Limousin, Patricia; Jahanshahi, Marjan; Bogacz, Rafal

    2018-06-01

    During a decision process, the evidence supporting alternative options is integrated over time, and the choice is made when the accumulated evidence for one of the options reaches a decision threshold. Humans and animals have an ability to control the decision threshold, that is, the amount of evidence that needs to be gathered to commit to a choice, and it has been proposed that the subthalamic nucleus (STN) is important for this control. Recent behavioral and neurophysiological data suggest that, in some circumstances, the decision threshold decreases with time during choice trials, allowing overcoming of indecision during difficult choices. Here we asked whether this within-trial decrease of the decision threshold is mediated by the STN and if it is affected by disrupting information processing in the STN through deep brain stimulation (DBS). We assessed 13 patients with Parkinson disease receiving bilateral STN DBS six or more months after the surgery, 11 age-matched controls, and 12 young healthy controls. All participants completed a series of decision trials, in which the evidence was presented in discrete time points, which allowed more direct estimation of the decision threshold. The participants differed widely in the slope of their decision threshold, ranging from constant threshold within a trial to steeply decreasing. However, the slope of the decision threshold did not depend on whether STN DBS was switched on or off and did not differ between the patients and controls. Furthermore, there was no difference in accuracy and RT between the patients in the on and off stimulation conditions and healthy controls. Previous studies that have reported modulation of the decision threshold by STN DBS or unilateral subthalamotomy in Parkinson disease have involved either fast decision-making under conflict or time pressure or in anticipation of high reward. Our findings suggest that, in the absence of reward, decision conflict, or time pressure for decision

  20. Impact of Combined Subthalamic Nucleus and Substantia Nigra Stimulation on Neuropsychiatric Symptoms in Parkinson’s Disease Patients

    U. Hidding

    2017-01-01

    Full Text Available The goal of the study was to compare the tolerability and the effects of conventional subthalamic nucleus (STN and combined subthalamic nucleus and substantia nigra (STN+SNr high-frequency stimulation in regard to neuropsychiatric symptoms in Parkinson’s disease patients. In this single center, randomized, double-blind, cross-over clinical trial, twelve patients with advanced Parkinson’s disease (1 female; age: 61.3±7.3 years; disease duration: 12.3±5.4 years; Hoehn and Yahr stage: 2.2±0.39 were included. Apathy, fatigue, depression, and impulse control disorder were assessed using a comprehensive set of standardized rating scales and questionnaires such as the Lille Apathy Rating Scale (LARS, Modified Fatigue Impact Scale (MFIS, Becks Depression Inventory (BDI-I, Questionnaire for Impulsive-Compulsive Disorders in Parkinson’s Disease Rating Scale (QUIP-RS, and Parkinson’s Disease Questionnaire (PDQ-39. Three patients that were initially assigned to the STN+SNr stimulation mode withdrew from the study within the first week due to discomfort. Statistical comparison of data retrieved from patients who completed the study revealed no significant differences between both stimulation conditions in terms of mean scores of scales measuring apathy, fatigue, depression, impulse control disorder, and quality of life. Individual cases showed an improvement of apathy under combined STN+SNr stimulation. In general, combined STN+SNr stimulation seems to be safe in terms of neuropsychiatric side effects, although careful patient selection and monitoring in the short-term period after changing stimulation settings are recommended.

  1. Lesions to the subthalamic nucleus decrease impulsive choice but impair autoshaping in rats: the importance of the basal ganglia in Pavlovian conditioning and impulse control.

    Winstanley, Catharine A; Baunez, Christelle; Theobald, David E H; Robbins, Trevor W

    2005-06-01

    Although the subthalamic nucleus (STN) is involved in regulating motor function, and inactivation of this structure relieves the motor symptoms in Parkinsonian patients, recent data indicate that corticosubthalamic connections are involved in both the regulation of attention and the ability to withhold from responding. Considerable evidence suggests that the neural circuitry underlying such behavioural disinhibition or impulsive action can be at least partially dissociated from that implicated in impulsive decision-making and it has been suggested that the tendency to choose impulsively is related to the ability to form and use Pavlovian associations. To explore these hypotheses further, STN-lesioned rats were tested on the delay-discounting model of impulsive choice, where impulsivity is defined as the selection of a small immediate over a larger delayed reward, as well as in a rodent autoshaping paradigm. In contrast to previous reports of increased impulsive action, STN lesions decreased impulsive choice but dramatically impaired the acquisition of the autoshaping response. When the STN was lesioned after the establishment of autoshaping behaviour, lesioned subjects were more sensitive to the omission of reward, indicative of a reduction in the use of Pavlovian associations to control autoshaping performance. These results emphasize the importance of the STN in permitting conditioned stimulus-unconditioned stimulus associations to regulate goal-seeking, a function which may relate to the alterations in impulsive choice observed in the delay-discounting task. These data bear a striking similarity to those observed after lesions of the orbitofrontal cortex and are suggestive of an important role for corticosubthalamic connections in complex cognitive behaviour.

  2. Right Fronto-Subcortical White Matter Microstructure Predicts Cognitive Control Ability on the Go/No-go Task in a Community Sample.

    Hinton, Kendra E; Lahey, Benjamin B; Villalta-Gil, Victoria; Boyd, Brian D; Yvernault, Benjamin C; Werts, Katherine B; Plassard, Andrew J; Applegate, Brooks; Woodward, Neil D; Landman, Bennett A; Zald, David H

    2018-01-01

    Go/no-go tasks are widely used to index cognitive control. This construct has been linked to white matter microstructure in a circuit connecting the right inferior frontal gyrus (IFG), subthalamic nucleus (STN), and pre-supplementary motor area. However, the specificity of this association has not been tested. A general factor of white matter has been identified that is related to processing speed. Given the strong processing speed component in successful performance on the go/no-go task, this general factor could contribute to task performance, but the general factor has often not been accounted for in past studies of cognitive control. Further, studies on cognitive control have generally employed small unrepresentative case-control designs. The present study examined the relationship between go/no-go performance and white matter microstructure in a large community sample of 378 subjects that included participants with a range of both clinical and subclinical nonpsychotic psychopathology. We found that white matter microstructure properties in the right IFG-STN tract significantly predicted task performance, and remained significant after controlling for dimensional psychopathology. The general factor of white matter only reached statistical significance when controlling for dimensional psychopathology. Although the IFG-STN and general factor tracts were highly correlated, when both were included in the model, only the IFG-STN remained a significant predictor of performance. Overall, these findings suggest that while a general factor of white matter can be identified in a young community sample, white matter microstructure properties in the right IFG-STN tract show a specific relationship to cognitive control. The findings highlight the importance of examining both specific and general correlates of cognition, especially in tasks with a speeded component.

  3. Raclopride or high-frequency stimulation of the subthalamic nucleus stops cocaine-induced motor stereotypy and restores related alterations in prefrontal basal ganglia circuits.

    Aliane, Verena; Pérez, Sylvie; Deniau, Jean-Michel; Kemel, Marie-Louise

    2012-11-01

    Motor stereotypy is a key symptom of various neurological or neuropsychiatric disorders. Neuroleptics or the promising treatment using deep brain stimulation stops stereotypies but the mechanisms underlying their actions are unclear. In rat, motor stereotypies are linked to an imbalance between prefrontal and sensorimotor cortico-basal ganglia circuits. Indeed, cortico-nigral transmission was reduced in the prefrontal but not sensorimotor basal ganglia circuits and dopamine and acetylcholine release was altered in the prefrontal but not sensorimotor territory of the dorsal striatum. Furthermore, cholinergic transmission in the prefrontal territory of the dorsal striatum plays a crucial role in the arrest of motor stereotypy. Here we found that, as previously observed for raclopride, high-frequency stimulation of the subthalamic nucleus (HFS STN) rapidly stopped cocaine-induced motor stereotypies in rat. Importantly, raclopride and HFS STN exerted a strong effect on cocaine-induced alterations in prefrontal basal ganglia circuits. Raclopride restored the cholinergic transmission in the prefrontal territory of the dorsal striatum and the cortico-nigral information transmissions in the prefrontal basal ganglia circuits. HFS STN also restored the N-methyl-d-aspartic-acid-evoked release of acetylcholine and dopamine in the prefrontal territory of the dorsal striatum. However, in contrast to raclopride, HFS STN did not restore the cortico-substantia nigra pars reticulata transmissions but exerted strong inhibitory and excitatory effects on neuronal activity in the prefrontal subdivision of the substantia nigra pars reticulata. Thus, both raclopride and HFS STN stop cocaine-induced motor stereotypy, but exert different effects on the related alterations in the prefrontal basal ganglia circuits. © 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  4. A biophysical model of the cortex-basal ganglia-thalamus network in the 6-OHDA lesioned rat model of Parkinson's disease.

    Kumaravelu, Karthik; Brocker, David T; Grill, Warren M

    2016-04-01

    Electrical stimulation of sub-cortical brain regions (the basal ganglia), known as deep brain stimulation (DBS), is an effective treatment for Parkinson's disease (PD). Chronic high frequency (HF) DBS in the subthalamic nucleus (STN) or globus pallidus interna (GPi) reduces motor symptoms including bradykinesia and tremor in patients with PD, but the therapeutic mechanisms of DBS are not fully understood. We developed a biophysical network model comprising of the closed loop cortical-basal ganglia-thalamus circuit representing the healthy and parkinsonian rat brain. The network properties of the model were validated by comparing responses evoked in basal ganglia (BG) nuclei by cortical (CTX) stimulation to published experimental results. A key emergent property of the model was generation of low-frequency network oscillations. Consistent with their putative pathological role, low-frequency oscillations in model BG neurons were exaggerated in the parkinsonian state compared to the healthy condition. We used the model to quantify the effectiveness of STN DBS at different frequencies in suppressing low-frequency oscillatory activity in GPi. Frequencies less than 40 Hz were ineffective, low-frequency oscillatory power decreased gradually for frequencies between 50 Hz and 130 Hz, and saturated at frequencies higher than 150 Hz. HF STN DBS suppressed pathological oscillations in GPe/GPi both by exciting and inhibiting the firing in GPe/GPi neurons, and the number of GPe/GPi neurons influenced was greater for HF stimulation than low-frequency stimulation. Similar to the frequency dependent suppression of pathological oscillations, STN DBS also normalized the abnormal GPi spiking activity evoked by CTX stimulation in a frequency dependent fashion with HF being the most effective. Therefore, therapeutic HF STN DBS effectively suppresses pathological activity by influencing the activity of a greater proportion of neurons in the output nucleus of the BG.

  5. Predictive timing functions of cortical beta oscillations are impaired in Parkinson's disease and influenced by L-DOPA and deep brain stimulation of the subthalamic nucleus

    A. Gulberti

    2015-01-01

    Full Text Available Cortex-basal ganglia circuits participate in motor timing and temporal perception, and are important for the dynamic configuration of sensorimotor networks in response to exogenous demands. In Parkinson's disease (PD patients, rhythmic auditory stimulation (RAS induces motor performance benefits. Hitherto, little is known concerning contributions of the basal ganglia to sensory facilitation and cortical responses to RAS in PD. Therefore, we conducted an EEG study in 12 PD patients before and after surgery for subthalamic nucleus deep brain stimulation (STN-DBS and in 12 age-matched controls. Here we investigated the effects of levodopa and STN-DBS on resting-state EEG and on the cortical-response profile to slow and fast RAS in a passive-listening paradigm focusing on beta-band oscillations, which are important for auditory–motor coupling. The beta-modulation profile to RAS in healthy participants was characterized by local peaks preceding and following auditory stimuli. In PD patients RAS failed to induce pre-stimulus beta increases. The absence of pre-stimulus beta-band modulation may contribute to impaired rhythm perception in PD. Moreover, post-stimulus beta-band responses were highly abnormal during fast RAS in PD patients. Treatment with levodopa and STN-DBS reinstated a post-stimulus beta-modulation profile similar to controls, while STN-DBS reduced beta-band power in the resting-state. The treatment-sensitivity of beta oscillations suggests that STN-DBS may specifically improve timekeeping functions of cortical beta oscillations during fast auditory pacing.

  6. A network analysis of ¹⁵O-H₂O PET reveals deep brain stimulation effects on brain network of Parkinson's disease.

    Park, Hae-Jeong; Park, Bumhee; Kim, Hae Yu; Oh, Maeng-Keun; Kim, Joong Il; Yoon, Misun; Lee, Jong Doo; Chang, Jin Woo

    2015-05-01

    As Parkinson's disease (PD) can be considered a network abnormality, the effects of deep brain stimulation (DBS) need to be investigated in the aspect of networks. This study aimed to examine how DBS of the bilateral subthalamic nucleus (STN) affects the motor networks of patients with idiopathic PD during motor performance and to show the feasibility of the network analysis using cross-sectional positron emission tomography (PET) images in DBS studies. We obtained [¹⁵O]H₂O PET images from ten patients with PD during a sequential finger-to-thumb opposition task and during the resting state, with DBS-On and DBS-Off at STN. To identify the alteration of motor networks in PD and their changes due to STN-DBS, we applied independent component analysis (ICA) to all the cross-sectional PET images. We analysed the strength of each component according to DBS effects, task effects and interaction effects. ICA blindly decomposed components of functionally associated distributed clusters, which were comparable to the results of univariate statistical parametric mapping. ICA further revealed that STN-DBS modifies usage-strengths of components corresponding to the basal ganglia-thalamo-cortical circuits in PD patients by increasing the hypoactive basal ganglia and by suppressing the hyperactive cortical motor areas, ventrolateral thalamus and cerebellum. Our results suggest that STN-DBS may affect not only the abnormal local activity, but also alter brain networks in patients with PD. This study also demonstrated the usefulness of ICA for cross-sectional PET data to reveal network modifications due to DBS, which was not observable using the subtraction method.

  7. Subthalamic nucleus deep brain stimulation impacts language in early Parkinson's disease.

    Lara Phillips

    Full Text Available Although deep brain stimulation (DBS of the basal ganglia improves motor outcomes in Parkinson's disease (PD, its effects on cognition, including language, remain unclear. This study examined the impact of subthalamic nucleus (STN DBS on two fundamental capacities of language, grammatical and lexical functions. These functions were tested with the production of regular and irregular past-tenses, which contrast aspects of grammatical (regulars and lexical (irregulars processing while controlling for multiple potentially confounding factors. Aspects of the motor system were tested by contrasting the naming of manipulated (motor and non-manipulated (non-motor objects. Performance was compared between healthy controls and early-stage PD patients treated with either DBS/medications or medications alone. Patients were assessed on and off treatment, with controls following a parallel testing schedule. STN-DBS improved naming of manipulated (motor but not non-manipulated (non-motor objects, as compared to both controls and patients with just medications, who did not differ from each other across assessment sessions. In contrast, STN-DBS led to worse performance at regulars (grammar but not irregulars (lexicon, as compared to the other two subject groups, who again did not differ. The results suggest that STN-DBS negatively impacts language in early PD, but may be specific in depressing aspects of grammatical and not lexical processing. The finding that STN-DBS affects both motor and grammar (but not lexical functions strengthens the view that both depend on basal ganglia circuitry, although the mechanisms for its differential impact on the two (improved motor, impaired grammar remain to be elucidated.

  8. Predictive timing functions of cortical beta oscillations are impaired in Parkinson's disease and influenced by L-DOPA and deep brain stimulation of the subthalamic nucleus.

    Gulberti, A; Moll, C K E; Hamel, W; Buhmann, C; Koeppen, J A; Boelmans, K; Zittel, S; Gerloff, C; Westphal, M; Schneider, T R; Engel, A K

    2015-01-01

    Cortex-basal ganglia circuits participate in motor timing and temporal perception, and are important for the dynamic configuration of sensorimotor networks in response to exogenous demands. In Parkinson's disease (PD) patients, rhythmic auditory stimulation (RAS) induces motor performance benefits. Hitherto, little is known concerning contributions of the basal ganglia to sensory facilitation and cortical responses to RAS in PD. Therefore, we conducted an EEG study in 12 PD patients before and after surgery for subthalamic nucleus deep brain stimulation (STN-DBS) and in 12 age-matched controls. Here we investigated the effects of levodopa and STN-DBS on resting-state EEG and on the cortical-response profile to slow and fast RAS in a passive-listening paradigm focusing on beta-band oscillations, which are important for auditory-motor coupling. The beta-modulation profile to RAS in healthy participants was characterized by local peaks preceding and following auditory stimuli. In PD patients RAS failed to induce pre-stimulus beta increases. The absence of pre-stimulus beta-band modulation may contribute to impaired rhythm perception in PD. Moreover, post-stimulus beta-band responses were highly abnormal during fast RAS in PD patients. Treatment with levodopa and STN-DBS reinstated a post-stimulus beta-modulation profile similar to controls, while STN-DBS reduced beta-band power in the resting-state. The treatment-sensitivity of beta oscillations suggests that STN-DBS may specifically improve timekeeping functions of cortical beta oscillations during fast auditory pacing.

  9. A randomised phase II study of sialyl-Tn and DETOX-B adjuvant with or without cyclophosphamide pretreatment for the active specific immunotherapy of breast cancer.

    Miles, D W; Towlson, K E; Graham, R; Reddish, M; Longenecker, B M; Taylor-Papadimitriou, J; Rubens, R D

    1996-10-01

    Studies in animal models of mouse mammary carcinoma have shown that ovine submaxillary mucin, which carries multiple sialyl-Tn (STn) epitopes, is effective in stimulating an immune response and inhibiting tumour growth. In similar studies using carbohydrate antigens, pretreatment with low-dose cyclophosphamide has been shown to be important in modulating the immune response to antigen possibly by inhibiting suppresser T-cell activity. In a clinical trial assessing the efficacy and toxicity of synthetic STn, patients with metastatic breast cancer were randomised to receive 100 micrograms STn linked to keyhole limpet haemocyanin (KLH) with DETOX-B adjuvant given by subcutaneous injection at weeks 0, 2, 5 and 9 with or without low-dose cyclophosphamide (CTX, 300 mg m-2) pretreatment, 3 days before the start of immunotherapy. Patients with responding or stable disease after the first four injections were eligible to receive STn-KLH at 4 week intervals. The main toxicity noted was the development of subcutaneous granulomata at injection sites. Of 23 patients randomised, 18 received four injections, 5 patients having developed progressive disease during the initial 12 week period. Two minor responses were noted in the 18 patients who received four active specific immunotherapy (ASI) injections and a further five patients had stable disease. Six patients continued ASI at 4 week intervals and a partial response was noted in a patient who had previously had stable disease. All patients developed IgG and IgM responses to sialyl-Tn and levels of IgM antibodies were significantly higher in those patients who were pretreated with CTX. Measurable tumour responses have been recorded following ASI with STn-KLH plus DETOX and the immunomodulatory properties of low-dose CTX have been confirmed.

  10. Non-motor outcomes of subthalamic stimulation in Parkinson's disease depend on location of active contacts.

    Dafsari, Haidar Salimi; Petry-Schmelzer, Jan Niklas; Ray-Chaudhuri, K; Ashkan, Keyoumars; Weis, Luca; Dembek, Till A; Samuel, Michael; Rizos, Alexandra; Silverdale, Monty; Barbe, Michael T; Fink, Gereon R; Evans, Julian; Martinez-Martin, Pablo; Antonini, Angelo; Visser-Vandewalle, Veerle; Timmermann, Lars

    2018-03-16

    Subthalamic nucleus (STN) deep brain stimulation (DBS) improves quality of life (QoL), motor, and non-motor symptoms (NMS) in Parkinson's disease (PD). Few studies have investigated the influence of the location of neurostimulation on NMS. To investigate the impact of active contact location on NMS in STN-DBS in PD. In this prospective, open-label, multicenter study including 50 PD patients undergoing bilateral STN-DBS, we collected NMSScale (NMSS), NMSQuestionnaire (NMSQ), Hospital Anxiety and Depression Scale (anxiety/depression, HADS-A/-D), PDQuestionnaire-8 (PDQ-8), Scales for Outcomes in PD-motor examination, motor complications, activities of daily living (ADL), and levodopa equivalent daily dose (LEDD) preoperatively and at 6 months follow-up. Changes were analyzed with Wilcoxon signed-rank/t-test and Bonferroni-correction for multiple comparisons. Although the STN was targeted visually, we employed an atlas-based approach to explore the relationship between active contact locations and DBS outcomes. Based on fused MRI/CT-images, we identified Cartesian coordinates of active contacts with patient-specific Mai-atlas standardization. We computed linear mixed-effects models with x-/y-/z-coordinates as independent, hemispheres as within-subject, and test change scores as dependent variables. NMSS, NMSQ, PDQ-8, motor examination, complications, and LEDD significantly improved at follow-up. Linear mixed-effect models showed that NMS and QoL improvement significantly depended on more medial (HADS-D, NMSS), anterior (HADS-D, NMSQ, PDQ-8), and ventral (HADS-A/-D, NMSS, PDQ-8) neurostimulation. ADL improved more in posterior, LEDD in lateral neurostimulation locations. No relationship was observed for motor examination and complications scores. Our study provides evidence that more anterior, medial, and ventral STN-DBS is significantly related to more beneficial non-motor outcomes. Copyright © 2018. Published by Elsevier Inc.

  11. Seasonal changes in nutrients, chlorophyll a and the phytoplankton assemblage of the western subarctic gyre in the Pacific Ocean

    Mochizuki, Mamiko; Shiga, Naonobu; Saito, Masaru; Imai, Keiri; Nojiri, Yukihiro

    The standing stock and species composition of phytoplankton (>10 μm) were studied using monthly water samples collected at Stn KNOT (Kyodo North Pacific Ocean Time Series; 44°N, 155°E) in the western subarctic gyre in the Pacific Ocean through June 1998 to June 1999 (except for January-April 1999) and January-February 2000. One-liter water samples were preserved in 1% neutrally buffered formalin. Identification and enumeration of phytoplankton were made with an inverted microscope. Nutrients did not appear to be depleted for phytoplakton growth during any season. The vertical distribution of phytoplankton was primarily restricted by the pycnocline, and the bulk of phytoplankton assemblage existed within the surface mixed layer. In July, however, some senescent cells were observed at 200 m. Phytoplankton abundance clearly showed a spring maximum (i.e. spring bloom) in May. The seasonal change in cell numbers, however, did not coincide closely with the change in chlorophyll a concentration. Centric diatoms, which were composed of Thalassiosira, Chaetoceros, and Coscinodiscus, dominated all year round, and showed temporal succession. Pennate diatoms (mostly Neodenticula seminae and Fragilariopsis) increased only during the spring bloom. Dinoflagellates (mostly Gymnodinium and Prorocentrum) were low in abundance, although they increased in summer when the phytoplankton standing stock was low. Silicoflagellate abundance was extremely low. Comparing the annual species composition of phytoplankton between Stn KNOT and Stn P (50°N, 145°W) in the Alaskan Gyre, there was a remarkable difference between the two sites. The phytoplankton assemblage at Stn P is characterized by a high abundance of Rhizosolenia alata and low abundance of Thalassiosira. In contrast, Thalassiosira dominates at Stn KNOT during most seasons.

  12. Processing of emotional information in the human subthalamic nucleus.

    Buot, Anne; Welter, Marie-Laure; Karachi, Carine; Pochon, Jean-Baptiste; Bardinet, Eric; Yelnik, Jérôme; Mallet, Luc

    2013-12-01

    The subthalamic nucleus (STN) is an efficient target for treating patients with Parkinson's disease as well as patients with obsessive-compulsive disorder (OCD) using high frequency stimulation (HFS). In both Parkinson's disease and OCD patients, STN-HFS can trigger abnormal behaviours, such as hypomania and impulsivity. To investigate if this structure processes emotional information, and whether it depends on motor demands, we recorded subthalamic local field potentials in 16 patients with Parkinson's disease using deep brain stimulation electrodes. Recordings were made with and without dopaminergic treatment while patients performed an emotional categorisation paradigm in which the response varied according to stimulus valence (pleasant, unpleasant and neutral) and to the instruction given (motor, non-motor and passive). Pleasant, unpleasant and neutral stimuli evoked an event related potential (ERP). Without dopamine medication, ERP amplitudes were significantly larger for unpleasant compared with neutral pictures, whatever the response triggered by the stimuli; and the magnitude of this effect was maximal in the ventral part of the STN. No significant difference in ERP amplitude was observed for pleasant pictures. With dopamine medication, ERP amplitudes were significantly increased for pleasant compared with neutral pictures whatever the response triggered by the stimuli, while ERP amplitudes to unpleasant pictures were not modified. These results demonstrate that the ventral part of the STN processes the emotional valence of stimuli independently of the motor context and that dopamine enhances processing of pleasant information. These findings confirm the specific involvement of the STN in emotional processes in human, which may underlie the behavioural changes observed in patients with deep brain stimulation.

  13. Long telomeres produced by telomerase-resistant recombination are established from a single source and are subject to extreme sequence scrambling.

    Jianing Xu

    Full Text Available Considerable evidence now supports the idea that the moderate telomere lengthening produced by recombinational telomere elongation (RTE in a Kluyveromyces lactis telomerase deletion mutant occurs through a roll-and-spread mechanism. However, it is unclear whether this mechanism can account for other forms of RTE that produce much longer telomeres such as are seen in human alternative lengthening of telomere (ALT cells or in the telomerase-resistant type IIR "runaway" RTE such as occurs in the K. lactis stn1-M1 mutant. In this study we have used mutationally tagged telomeres to examine the mechanism of RTE in an stn1-M1 mutant both with and without telomerase. Our results suggest that the establishment stage of the mutant state in newly generated stn1-M1 ter1-Δ mutants surprisingly involves a first stage of sudden telomere shortening. Our data also show that, as predicted by the roll-and-spread mechanism, all lengthened telomeres in a newly established mutant cell commonly emerge from a single telomere source. However, in sharp contrast to the RTE of telomerase deletion survivors, we show that the RTE of stn1-M1 ter1-Δ cells produces telomeres whose sequences undergo continuous intense scrambling via recombination. While telomerase was not necessary for the long telomeres in stn1-M1 cells, its presence during their establishment was seen to interfere with the amplification of repeats via recombination, a result consistent with telomerase retaining its ability to add repeats during active RTE. Finally, we observed that the presence of active mismatch repair or telomerase had important influences on telomeric amplification and/or instability.

  14. Releasing metal catalysts via phase transition: (NiO)0.05-(SrTi0.8Nb0.2O3)0.95 as a redox stable anode material for solid oxide fuel cells.

    Xiao, Guoliang; Wang, Siwei; Lin, Ye; Zhang, Yanxiang; An, Ke; Chen, Fanglin

    2014-11-26

    Donor-doped perovskite-type SrTiO3 experiences stoichiometric changes at high temperatures in different Po2 involving the formation of Sr or Ti-rich impurities. NiO is incorporated into the stoichiometric strontium titanate, SrTi0.8Nb0.2O3-δ (STN), to form an A-site deficient perovskite material, (NiO)0.05-(SrTi0.8Nb0.2O3)0.95 (Ni-STN), for balancing the phase transition. Metallic Ni nanoparticles can be released upon reduction instead of forming undesired secondary phases. This material design introduces a simple catalytic modification method with good compositional control of the ceramic backbones, by which transport property and durability of solid oxide fuel cell anodes are largely determined. Using Ni-STN as anodes for solid oxide fuel cells, enhanced catalytic activity and remarkable stability in redox cycling have been achieved. Electrolyte-supported cells with the cell configuration of Ni-STN-SDC anode, La0.8Sr0.2Ga0.87Mg0.13O3 (LSGM) electrolyte, and La0.6Sr0.4Co0.2Fe0.8O3 (LSCF) cathode produce peak power densities of 612, 794, and 922 mW cm(-2) at 800, 850, and 900 °C, respectively, using H2 as the fuel and air as the oxidant. Minor degradation in fuel cell performance resulted from redox cycling can be recovered upon operating the fuel cells in H2. Such property makes Ni-STN a promising regenerative anode candidate for solid oxide fuel cells.

  15. Deep brain stimulation for Parkinson's disease: meta-analysis of results of randomized trials at varying lengths of follow-up.

    Mansouri, Alireza; Taslimi, Shervin; Badhiwala, Jetan H; Witiw, Christopher D; Nassiri, Farshad; Odekerken, Vincent J J; De Bie, Rob M A; Kalia, Suneil K; Hodaie, Mojgan; Munhoz, Renato P; Fasano, Alfonso; Lozano, Andres M

    2018-04-01

    OBJECTIVE Deep brain stimulation (DBS) is effective in the management of patients with advanced Parkinson's disease (PD). While both the globus pallidus pars interna (GPi) and the subthalamic nucleus (STN) are accepted targets, their relative efficacy in randomized controlled trials (RCTs) has not been established beyond 12 months. The objective of this study was to conduct a meta-analysis of RCTs to compare outcomes among adults with PD undergoing DBS of GPi or STN at various time points, including 36 months of follow-up. METHODS The MEDLINE, Embase, CENTRAL, Web of Science, and CINAHL databases were searched. Registries for clinical trials, selected conference proceedings, and the table of contents for selected journals were also searched. Screens were conducted independently and in duplicate. Among the 623 studies initially identified (615 through database search, 7 through manual review of bibliographies, and 1 through a repeat screen of literature prior to submission), 19 underwent full-text review; 13 of these were included in the quantitative meta-analysis. Data were extracted independently and in duplicate. The Cochrane Collaboration tool was used to assess the risk of bias. The GRADE evidence profile tool was used to assess the quality of the evidence. Motor scores, medication dosage reduction, activities of daily living, depression, dyskinesias, and adverse events were compared. The influence of disease duration (a priori) and the proportion of male patients within a study (post hoc) were explored as potential subgroups. RESULTS Thirteen studies (6 original cohorts) were identified. No difference in motor scores or activities of daily living was identified at 36 months. Medications were significantly reduced with STN stimulation (5 studies, weighted mean difference [WMD] -365.46, 95% CI -599.48 to -131.44, p = 0.002). Beck Depression Inventory scores were significantly better with GPi stimulation (3 studies; WMD 2.53, 95% CI 0.99-4.06 p = 0.001). The

  16. A Preliminary Report on Disordered Speech with Deep Brain Stimulation in Individuals with Parkinson's Disease

    Christopher Dromey

    2011-01-01

    Full Text Available Deep brain stimulation (DBS of the subthalamic nucleus (STN has proven effective in treating the major motor symptoms of advanced Parkinson's disease (PD. The aim of this study was to learn which laryngeal and articulatory acoustic features changed in patients who were reported to have worse speech with stimulation. Six volunteers with PD who had bilateral STN electrodes were recorded with DBS turned on or off. Perceptual ratings reflected poorer speech performance with DBS on. Acoustic measures of articulation (corner vowel formants, diphthong slopes, and a spirantization index and phonation (perturbation, long-term average spectrum as well as verbal fluency scores showed mixed results with DBS. Some speakers improved while others became worse on individual measures. The magnitude of DBS effects was not predictable based on the patients' demographic characteristics. Future research involving adjustments to stimulator settings or electrode placement may be beneficial in limiting the negative effects of DBS on speech.

  17. Safety evaluation report related to the operation of Seabrook Station, Units 1 and 2. Docket Nos. 50-443 and 50-444. Suppl. 1

    1983-04-01

    This report supplements the Safety Evaluation Report (NUREG-0896, March 1983) for the application filed by the Public Service Company of New Hampshire, et. al., for licenses to operate Seabrook Station, Units 1 and 2 (Docket Nos. STN 50-443 and STN 50-444). It has been prepared by the Office of Nuclear Reactor Regulation of the US Nuclear Regulatory Commission and provides recent information on open items identified in the SER. The facility is located in Seabrook, New Hampshire. Subject to favorable resolution of the items discussed in this report, the staff concludes that the facility can be operated by the applicant without endangering the health and safety of the public

  18. Safety Evaluation Report related to the operation of Seabrook Station, Units 1 and 2 (Docket Nos. 50-443 and 50-444)

    1989-05-01

    This report is Supplement No. 8 to the Safety Evaluation Report (SER) (NUREG-0896, March 1983) for the application filed by the Public Service Company of New Hampshire, et al., for licenses to operate Seabrook Station, Units 1 and 2 (Docket Nos. STN 50-443 and STN 50-444). It has been prepared by the Office of Nuclear Reactor Regulation of the US Nuclear Regulatory Commission and provides recent information on open items identified in the SER. The facility is located in Seabrook, New Hampshire. Subject to favorable resolution of the items discussed in this report, the staff concludes that the facility can be operated by the applicant without endangering the health and safety of the public. 2 figs., 1 tab

  19. Safety Evaluation Report related to the operation of Seabrook Station, Units 1 and 2 (Docket Nos. 50-443 and 50-444). Supplement No. 5

    1986-07-01

    This report is Supplement No. 5 to the Safety Evaluation Report (NUREG-0896, March 1983) for the application filed by the Public Service Company of New Hampshire, et al., for licenses to operate Seabrook Station, Units 1 and 2 Docket Nos. STN 50-443 and STN 50-444). It has been prepared by the Office of Nuclear Reactor Regulation of the US Nuclear Regulatory Commission and provides recent information on open items identified in the SER. The facility is located in Seabrook, New Hampshire. Subject to favorable resolution of the items discussed in this report, the staff concludes that the facility can be operated by the applicant without endangering the health and safety of the public

  20. Differential Effect of Solution Conditions on the Conformation of the Actinoporins Sticholysin II and Equinatoxin II

    EDSON V.F. FAUTH

    2014-12-01

    Full Text Available Actinoporins are a family of pore-forming proteins with hemolytic activity. The structural basis for such activity appears to depend on their correct folding. Such folding encompasses a phosphocholine binding site, a tryptophan-rich region and the activity-related N-terminus segment. Additionally, different solution conditions are known to be able to influence the pore formation by actinoporins, as for Sticholysin II (StnII and Equinatoxin II (EqtxII. In this context, the current work intends to characterize the influence of distinct solution conditions in the conformational behavior of these proteins through molecular dynamics (MD simulations. The obtained data offer structural insights into actinoporins dynamics in solution, characterizing its conformational behavior at the atomic level, in accordance with previous experimental data on StnII and EqtxII hemolytic activities.

  1. Effects of DBS, premotor rTMS, and levodopa on motor function and silent period in advanced Parkinson's disease

    Bäumer, Tobias; Hidding, Ute; Hamel, Wolfgang

    2009-01-01

    Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a widely used and highly effective treatment for patients with advanced Parkinson's disease (PD). Repetitive TMS (rTMS) applied to motor cortical areas has also been shown to improve symptoms in PD and modulate motor cortical...... excitability. Here, we compared clinical and neurophysiological effects of STN stimulation with those of 1 Hz rTMS given to the dorsal premotor cortex (PMd) and those following intake of levodopa in a group of PD patients with advanced disease. Ten PD patients were studied on 2 consecutive days before...... and after surgery. Clinical effects were determined using the UPDRS motor score. Motor thresholds, motor-evoked potential (MEP) amplitudes during slight voluntary contraction, and the cortical silent periods (SP) were measured using TMS. Before surgery effects of levodopa and 1 Hz PMd rTMS and after surgery...

  2. Safety evaluation report related to the operation of Seabrook Station, Units 1 and 2 (Docket Nos. 50-443 and 50-444)

    1986-05-01

    This report is Supplement 4 to the Safety Evaluation Report (SER, NUREG-0896, March 1983) for the application filed by the Public Service Company of New Hampshire, et al., for licenses to operate Seabrook Station, Units 1 and 2 (Docket Nos. STN 50-443 and STN 50-444). It has been prepared by the Office of Nuclear Reactor Regulation of the US Nuclear Regulatory Commission and provides recent information on open items identified in the SER. The facility is located in Seabrook, New Hamphsire. Subject to favorable resolution of the items discussed in this report, the staff concludes that the facility can be operated by the applicant without endangering the health and safety of the public

  3. Probing the O-glycoproteome of Gastric Cancer Cell Lines for Biomarker Discovery

    Vieira Campos, Diana Alexandra; Freitas, Daniela; Gomes, Joana

    2015-01-01

    biomarker assays. However, the current knowledge of secreted and circulating O-glycoproteins is limited. Here, we used the COSMC KO "SimpleCell" (SC) strategy to characterize the O-glycoproteome of two gastric cancer SC lines (AGS, MKN45) as well as a gastric cell line (KATO III) which naturally expresses...... at least partially truncated O-glycans. Overall we identified 499 O-glycoproteins and 1,236 O-glycosites in gastric cancer SCs, and a total 47 O-glycoproteins and 73 O-glycosites in the KATO III cell line. We next modified the glycoproteomic strategy to apply it to pools of sera from gastric cancer...... with the STn glycoform were further validated as being expressed in gastric cancer tissue. A proximity ligation assay was used to demonstrate that CD44 was expressed with the STn glycoform in gastric cancer tissues. The study provides a discovery strategy for aberrantly glycosylated O-glycoproteins and a set...

  4. Safety evaluation report related to the operation of Seabrook Station, Units 1 and 2 (Docket Nos. 50-443 and 50-444)

    1987-10-01

    This report is Supplement No. 7 to the Safety Evaluation Report (NUREG-0896, March 1983) for the application filed by the Public Service Company of New Hampshire, et al. for licenses to operate Seabrook Station, Units 1 and 2 (Docket Nos. STN 50-443 and STN 50-444). It has been prepared by the Office of Nuclear Reactor Regulation of the US Nuclear Regulatory Commission and provides recent information on open items identified in the SER. The facility is located in Seabrook, New Hampshire. Subject to favorable resolution of the items discussed in this report, the staff concludes that the facility can be operated by the applicant without endangering the health and safety of the public

  5. A revisit to vityaz transform fault area, Central Indian Ridge: Isotopic evidence of probable hydrothermal activity.

    Shirodkar, P.V.; Banerjee, R.; Xiao, Y.K.

    at the Institute of Salt Lakes, China by +ve thermal ionisation mass spectrometry of Cs2BO4+ and Cs2Cl+ ions respectively, using a VG 354 model TIMS [14]. The measured isotopic ratios were expressed as del values relative to their standard reference materials.... 37.5 38 38.5 39 39.5 40 Del 11B 2000 1600 1200 800 400 0 W at er d ep th (m ) -0.2 0 0.2 0.4 0.6 0.8 Del 37Cl 2000 1600 1200 800 400 0 Figure 2: Vertical profiles of δ11B and δ37Cl in water column at Stn.VM3 in the CIR. Stn. No. Latitude Longitude...

  6. Temperature dependence of the deformation behavior of 316 stainless steel after low temperature neutron irradiation

    Pawel-Robertson, J.E.; Rowcliffe, A.F.; Grossbeck, M.L. [Oak Ridge National Lab., TN (United States)] [and others

    1996-10-01

    The effects of low temperature neutron irradiation on the tensile behavior of 316 stainless steel have been investigated. A single heat of solution annealed 316 was irradiated to 7 and 18 dpa at 60, 200, 330, and 400{degrees}C. The tensile properties as a function of dose and as a function of temperature were examined. Large changes in yield strength, deformation mode, strain to necking, and strain hardening capacity were seen in this irradiation experiment. The magnitudes of the changes are dependent on both irradiation temperature and neutron dose. Irradiation can more than triple the yield strength over the unirradiated value and decrease the strain to necking (STN) to less than 0.5% under certain conditions. A maximum increase in yield strength and a minimum in the STN occur after irradiation at 330{degrees}C but the failure mode remains ductile.

  7. Review of selected contributions of the conference 'Project control in quality management systems'

    2008-04-01

    There were 12 contributions presented of the conference focused on the project management in quality management systems. Contributions were focused both on theoretical problems from the project management area and on the applications in practice in management systems implementation in accordance with the standards: STN EN ISO 9001:2000, STN EN ISO 14 001:2005, and OHSAS 18 001:1999. One contribution was focused on the project management in the project of preparation of finishing of the building of the Nuclear Power Plant Mochovce of 3. and 4. block and one contribution was focused on the amendment of the Atomic Act or on the preparation of the new Atomic Act with regard to duty of transposition of the Directive of the Council 2006/117/Euratom on control and supervision of the overseas transportations of radioactive waste and nuclear fuel burnt-up into legislation of the Slovak Republic

  8. Safety-evaluation report related to the operation of Seabrook Station, Units 1 and 2. Docket Nos. 50-443 and 50-444

    1983-06-01

    This report is Supplement 2 to the Safety Evaluation Report (NUREG-0896, March 1983) for the application filed by the Public Service Company of New Hampshire, et al., for licenses to operate Seabrook Station, Units 1 and 2 (Docket Nos. STN 50-443 and STN 50-444). It has been prepared by the Office of Nuclear Reactor Regulation of the US Nuclear Regulatory Commission and provides recent information on open items identified in the SER. The facility is located in Seabrook, New Hampshire. Subject to favorable resolution of the items discussed in this report, the staff concludes that the facility can be operated by the applicant without endangering the health and safety of the public

  9. Effects of Subthalamic Stimulation on Olfactory Function in Parkinson Disease.

    Cury, Rubens Gisbert; Carvalho, Margarete de Jesus; Lasteros, Fernando Jeyson Lopez; Dias, Alice Estevo; Dos Santos Ghilardi, Maria Gabriela; Paiva, Anderson Rodrigues Brandão; Coutinho, Artur Martins; Buchpiguel, Carlos Alberto; Teixeira, Manoel J; Barbosa, Egberto Reis; Fonoff, Erich Talamoni

    2018-06-01

    Olfactory dysfunction is a nonmotor symptom of Parkinson disease (PD) associated with reduction in quality of life. There is no evidence on whether improvements in olfaction after subthalamic deep brain stimulation (STN-DBS) may be directly attributable to motor improvement or whether this reflects a direct effect of DBS on olfactory brain areas. The aim of the present study was to evaluate the effect of DBS on olfactory function in PD, as well as to explore the correlation between these changes and changes in motor symptoms and brain metabolism. Thirty-two patients with PD were screened for STN-DBS. Patients were evaluated before and 1 year after surgery. Primary outcome was the change in olfactory function (Sniffin' Sticks odor-identification test [SST]) after surgery among the patients with hyposmia at baseline. Secondary outcomes included the relationship between motor outcomes and olfactory changes and [ 18 F]fluorodeoxyglucose-positron emission tomography analysis between subgroups with improvement versus no improvement of smell. STN-DBS improved SST after surgery (preoperative SST, median 7.3 ± 2.4 vs. postoperative SST, median 8.2 ± 2.1; P = 0.045) in a subset of patients among 29 of 32 patients who presented with hyposmia at baseline. The improvement in SST was correlated with DBS response (r = 0.424; P = 0.035). There was also an increase in glucose metabolism in the midbrain, cerebellum, and right frontal lobe in patients with SST improvement (P < 0.001). STN-DBS improves odor identification in a subset of patients with PD. Motor improvement together with changes in the brain metabolism may be linked to this improvement. Copyright © 2018 Elsevier Inc. All rights reserved.

  10. Palo Verde Generating Station, Units 4 and 5. License application, general information

    1978-01-01

    A license application for two more Palo Verde reactors, Units 4 and 5, is presented. The two PWR reactors have a nominal net generating power each of 1,270 MW(e). Containments are steel-lined prestressed cylindrical structures with hemispherical domes. The reactors are replicas of Palo Verde 1, 2 and 3 (see DOCKETS 50528, 50529 and 50530) using the standard Combustion Engineering System 80 (see DOCKET-STN-50470)

  11. Cerebral Activations Related to Ballistic, Stepwise Interrupted and Gradually Modulated Movements in Parkinson Patients

    Toxopeus, Carolien M.; Maurits, Natasha M.; Valsan, Gopal; Conway, Bernard A.; Leenders, Klaus L.; de Jong, Bauke M.

    2012-01-01

    Patients with Parkinson’s disease (PD) experience impaired initiation and inhibition of movements such as difficulty to start/stop walking. At single-joint level this is accompanied by reduced inhibition of antagonist muscle activity. While normal basal ganglia (BG) contributions to motor control include selecting appropriate muscles by inhibiting others, it is unclear how PD-related changes in BG function cause impaired movement initiation and inhibition at single-joint level. To further elucidate these changes we studied 4 right-hand movement tasks with fMRI, by dissociating activations related to abrupt movement initiation, inhibition and gradual movement modulation. Initiation and inhibition were inferred from ballistic and stepwise interrupted movement, respectively, while smooth wrist circumduction enabled the assessment of gradually modulated movement. Task-related activations were compared between PD patients (N = 12) and healthy subjects (N = 18). In healthy subjects, movement initiation was characterized by antero-ventral striatum, substantia nigra (SN) and premotor activations while inhibition was dominated by subthalamic nucleus (STN) and pallidal activations, in line with the known role of these areas in simple movement. Gradual movement mainly involved antero-dorsal putamen and pallidum. Compared to healthy subjects, patients showed reduced striatal/SN and increased pallidal activation for initiation, whereas for inhibition STN activation was reduced and striatal-thalamo-cortical activation increased. For gradual movement patients showed reduced pallidal and increased thalamo-cortical activation. We conclude that PD-related changes during movement initiation fit the (rather static) model of alterations in direct and indirect BG pathways. Reduced STN activation and regional cortical increased activation in PD during inhibition and gradual movement modulation are better explained by a dynamic model that also takes into account enhanced

  12. Epidemiological characterization of Acinetobacter baumannii bloodstream isolates from a Chinese Burn Institute: A three-year study.

    Huang, Guangtao; Yin, Supeng; Xiang, Lijuan; Gong, Yali; Sun, Kedai; Luo, Xiaoqiang; Zhang, Cheng; Yang, Zichen; Deng, Liuyang; Jiang, Bei; Jin, Shouguang; Chen, Jing; Peng, Yizhi

    2016-11-01

    Acinetobacter baumannii infection is a serious threat to burn patients. Bacteremia due to A. baumannii is becoming the most common cause of mortality following burn. However, the epidemiology of A. baumannii causing burn-related bloodstream infections has rarely been reported. We retrospectively collected 81 A. baumannii isolates from the bloodstream of burn patients over a three-year period. Antibiotic susceptibility tests, the prevalence of antibiotic-resistant genes and sequence typing (ST) were conducted to characterize these strains. Most of the isolates showed an extensive drug-resistant phenotype. The resistance frequencies to imipenem and meropenem were 94% and 91%, respectively. The blaOXA-23-like gene, AmpC, IS-AmpC, PER and SIM are the five most prevalent resistant genes, and their prevalence rates are 93% (75/81), 86% (70/81), 73% (59/81), 73% (59/81) and 52% (42/81), respectively. The 81 isolates were grouped into 10 known and 18 unknown ST types, with ST368 (38%) being the most prevalent. Except for ST457 and four new types (STn2, STn6, STn11 and STn14), the remaining 23 ST types belonged to one clonal complex 92, which is most common among clinical isolate in China. The above results indicated that ST368 isolates possessing both the blaOXA-23-like gene and ampC gene were the main culprits of the increasing nosocomial A. baumannii infection in this study. More attention should be paid to monitoring the molecular epidemiology of A. baumannii isolates from burn patients to prevent further distribution. Such information may help clinicians with therapeutic decisions and infection control in the Burns Institute. Copyright © 2016. Published by Elsevier Ltd.

  13. Mismatch negativity-like potential (MMN-like) in the subthalamic nuclei in Parkinson’s disease patients

    Minks, E.; Jurák, Pavel; Chládek, Jan; Chrastina, J.; Halámek, Josef; Shaw, D. J.; Bareš, M.

    2014-01-01

    Roč. 121, č. 12 (2014), s. 1507-1522 ISSN 0300-9564 R&D Projects: GA ČR GAP103/11/0933; GA MŠk ED0017/01/01; GA MŠk(CZ) LO1212 Institutional support: RVO:68081731 Keywords : Mismatch negativity * MMN * MMN-like * Subthalamic nucleus * STN * Intracranial electrodes Subject RIV: BD - Theory of Information Impact factor: 2.402, year: 2014

  14. ERÜ 1993 : kroonika / Reet Olevsoo

    Olevsoo, Reet, 1956-

    1994-01-01

    8. veebr. : [taotlus ETARi direktorile personaalpalga määramiseks]; 15. veebr.-12. märts : [T. Reimo stažeeris Göttingeni Ülikooli Rmtk-s]; 25. märts : [kohvikuõhtu ETARis. A. Normak rääkis Potsdami Ülikooli STN Koolituskeskuse seminarist]; 1.-15. juuni : [M. Triipan õppereisil Saksamaal]; 29. okt. : [lahtiste uste päevad ETARis]; 3. nov. : [A. Valmas esitati Eesti Kultuurifondi aastapreemia saamiseks

  15. The Evaluation of the Effect of Multiwall Carbon Nano Tube (MWCNT) on In Vitro Proliferation and Shoot Tip Necrosis of Pistachio Rootstock UCB-1 (Pistacia integrima × P. atlantica)

    Shahrzad Aghasi Kermani; Hossein Hokmabadi; Marzieh Ghanbari Jahromi

    2017-01-01

    UCB-1 (Pistacia atlantica × P. integrima) is a commercial rootstock for pistachio in some pistachio plantations across the world. This rootstock is very new in Iran and recently, it has been used commercially in some plantations due to its high growth. Propagation of this rootstock by tissue culture results in many limitations such as shoot tip necrosis (STN) and a low proliferation rate. Therefore, any process that leads to improve the proliferation rate and feature will be used in commercia...

  16. Validation of Passive Sampling Devices for Monitoring of Munitions Constituents in Underwater Environments

    2017-09-01

    TNT TOC TSS Low Order Detonation Munitions constituents Munitions Debris Method Detection Limit Munitions and explosives of concern Mean low...Total organic carbon ( TOC ) and grain size distribution from stations A1, T10, T11, and T12 at BSS...16 syringes/stn) TNT, ADNTs, DNTs, RDX 4 locations in BSS based on positive POCIS results Sediment 5 TOC , grain size 4, co-located with sediment

  17. Influence of basal ganglia on upper limb locomotor synergies. Evidence from deep brain stimulation and L-DOPA treatment in Parkinson's disease.

    Crenna, P; Carpinella, I; Lopiano, L; Marzegan, A; Rabuffetti, M; Rizzone, M; Lanotte, M; Ferrarin, M

    2008-12-01

    Clinical evidence of impaired arm swing while walking in patients with Parkinson's disease suggests that basal ganglia and related systems play an important part in the control of upper limb locomotor automatism. To gain more information on this supraspinal influence, we measured arm and thigh kinematics during walking in 10 Parkinson's disease patients, under four conditions: (i) baseline (no treatment), (ii) therapeutic stimulation of the subthalamic nucleus (STN), (iii)L-DOPA medication and (iv) combined STN stimulation and L-DOPA. Ten age-matched controls provided reference data. Under baseline conditions the range of patients' arm motion was severely restricted, with no correlation with the excursion of the thigh. In addition, the arm swing was abnormally coupled in time with oscillation of the ipsilateral thigh. STN stimulation significantly increased the gait speed and improved the spatio-temporal parameters of arm and thigh motion. The kinematic changes as a function of gait speed changes, however, were significantly smaller for the upper than the lower limb, in contrast to healthy controls. Arm motion was also less responsive after L-DOPA. Simultaneous deep brain stimulation and L-DOPA had additive effects on thigh motion, but not on arm motion and arm-thigh coupling. The evidence that locomotor automatisms of the upper and lower limbs display uncorrelated impairment upon dysfunction of the basal ganglia, as well as different susceptibility to electrophysiological and pharmacological interventions, points to the presence of heterogeneously distributed, possibly partially independent, supraspinal control channels, whereby STN and dopaminergic systems have relatively weaker influence on the executive structures involved in the arm swing and preferential action on those for lower limb movements. These findings might be considered in the light of phylogenetic changes in supraspinal control of limb motion related to primate bipedalism.

  18. VERIFICATION OF THE FOOD SAFETY MANAGEMENT SYSTEM IN DEEP FROZEN FOOD PRODUCTION PLANT

    Peter Zajác

    2010-07-01

    Full Text Available In work is presented verification of food safety management system of deep frozen food. Main emphasis is on creating set of verification questions within articles of standard STN EN ISO 22000:2006 and on searching of effectiveness in food safety management system. Information were acquired from scientific literature sources and they pointed out importance of implementation and upkeep of effective food safety management system. doi:10.5219/28

  19. Electrical properties and flux performance of composite ceramic hydrogen separation membranes

    Fish, J.S.; Ricote, Sandrine; O'Hayre, R.

    2015-01-01

    The electrical properties and hydrogen permeation flux behavior of the all-ceramic protonic/electronic conductor composite BaCe0.2Zr0.7Y0.1O3-δ/Sr0.95Ti0.9Nb0.1O3-δ (BCZY27/STN95: BS27) are evaluated. Conductivity and hydrogen permeability are examined as a function of phase volume ratios. Total ...

  20. Cerebral activations related to ballistic, stepwise interrupted and gradually modulated movements in Parkinson patients.

    Carolien M Toxopeus

    Full Text Available Patients with Parkinson's disease (PD experience impaired initiation and inhibition of movements such as difficulty to start/stop walking. At single-joint level this is accompanied by reduced inhibition of antagonist muscle activity. While normal basal ganglia (BG contributions to motor control include selecting appropriate muscles by inhibiting others, it is unclear how PD-related changes in BG function cause impaired movement initiation and inhibition at single-joint level. To further elucidate these changes we studied 4 right-hand movement tasks with fMRI, by dissociating activations related to abrupt movement initiation, inhibition and gradual movement modulation. Initiation and inhibition were inferred from ballistic and stepwise interrupted movement, respectively, while smooth wrist circumduction enabled the assessment of gradually modulated movement. Task-related activations were compared between PD patients (N = 12 and healthy subjects (N = 18. In healthy subjects, movement initiation was characterized by antero-ventral striatum, substantia nigra (SN and premotor activations while inhibition was dominated by subthalamic nucleus (STN and pallidal activations, in line with the known role of these areas in simple movement. Gradual movement mainly involved antero-dorsal putamen and pallidum. Compared to healthy subjects, patients showed reduced striatal/SN and increased pallidal activation for initiation, whereas for inhibition STN activation was reduced and striatal-thalamo-cortical activation increased. For gradual movement patients showed reduced pallidal and increased thalamo-cortical activation. We conclude that PD-related changes during movement initiation fit the (rather static model of alterations in direct and indirect BG pathways. Reduced STN activation and regional cortical increased activation in PD during inhibition and gradual movement modulation are better explained by a dynamic model that also takes into account

  1. Computational Models Describing Possible Mechanisms for Generation of Excessive Beta Oscillations in Parkinson's Disease.

    Alex Pavlides

    2015-12-01

    Full Text Available In Parkinson's disease, an increase in beta oscillations within the basal ganglia nuclei has been shown to be associated with difficulty in movement initiation. An important role in the generation of these oscillations is thought to be played by the motor cortex and by a network composed of the subthalamic nucleus (STN and the external segment of globus pallidus (GPe. Several alternative models have been proposed to describe the mechanisms for generation of the Parkinsonian beta oscillations. However, a recent experimental study of Tachibana and colleagues yielded results which are challenging for all published computational models of beta generation. That study investigated how the presence of beta oscillations in a primate model of Parkinson's disease is affected by blocking different connections of the STN-GPe circuit. Due to a large number of experimental conditions, the study provides strong constraints that any mechanistic model of beta generation should satisfy. In this paper we present two models consistent with the data of Tachibana et al. The first model assumes that Parkinsonian beta oscillation are generated in the cortex and the STN-GPe circuits resonates at this frequency. The second model additionally assumes that the feedback from STN-GPe circuit to cortex is important for maintaining the oscillations in the network. Predictions are made about experimental evidence that is required to differentiate between the two models, both of which are able to reproduce firing rates, oscillation frequency and effects of lesions carried out by Tachibana and colleagues. Furthermore, an analysis of the models reveals how the amplitude and frequency of the generated oscillations depend on parameters.

  2. Effect of Deep Brain Stimulation on Speech Performance in Parkinson's Disease

    Skodda, Sabine

    2012-01-01

    Deep brain stimulation (DBS) has been reported to be successful in relieving the core motor symptoms of Parkinson's disease (PD) and motor fluctuations in the more advanced stages of the disease. However, data on the effects of DBS on speech performance are inconsistent. While there are some series of patients documenting that speech function was relatively unaffected by DBS of the nucleus subthalamicus (STN), other investigators reported on improvements of distinct parameters of oral control...

  3. EUROBASES

    Glaeser, K.

    1993-01-01

    Data available via Eurobases are not disseminated exclusively, for in a free information market monopolies have become anachronistic. Thus over 30 organizations disseminate our EC databases or parts of them, among them well-known players in the online market such as Data Star, STN, MDC, JURIS, FT Profile, to name but a few. The SESAME database is listing a series of projects in radiation protection and decommissioning of nuclear installations. (orig./DG)

  4. Preparation of CIGS thin films by HiPIMS or DC sputtering and various selenization processes

    Olejníček, Jiří; Hubička, Zdeněk; Kšírová, Petra; Kment, Štěpán; Brunclíková, Michaela; Kohout, Michal; Čada, Martin; Darveau, S.A.; Exstrom, C.L.

    2013-01-01

    Roč. 16, č. 2 (2013), s. 314-319 ISSN 1203-8407 R&D Projects: GA MŠk LH12045 Institutional support: RVO:68378271 Keywords : CIGS * HIPIMS * selenization * nanocrystals * solar energy * sputtering * thin films Subject RIV: BL - Plasma and Gas Discharge Physics Impact factor: 1.106, year: 2013 http://www.ingentaconnect.com/content/stn/jaots/2013/00000016/00000002/art00015

  5. Altered neuronal firing pattern of the basal ganglia nucleus plays a role in levodopa-induced dyskinesia in patients with Parkinson's disease

    Xiaoyu eLi

    2015-11-01

    Full Text Available Background: Levodopa therapy alleviates the symptoms of Parkinson's disease (PD, but long-term treatment often leads to motor complications such as levodopa-induced dyskinesia (LID. Aim: To explore the neuronal activity in the basal ganglia nuclei in patients with PD and LID. Methods: Thirty patients with idiopathic PD (age, 55.1±11.0 years; disease duration, 8.7±5.6 years were enrolled between August 2006 and August 2013 at the Xuanwu Hospital, Capital Medical University, China. Their Hoehn and Yahr scores ranged from 2 to 4 and their UPDRS III scores were 28.5±5.2. Fifteen of them had severe LID (UPDRS IV scores of 6.7±1.6. Microelectrode recording was performed in the globus pallidus internus (GPi and subthalamic nucleus (STN during pallidotomy (n=12 or STN deep brain stimulation (DBS; bilateral, n=12; unilateral, n=6. The firing patterns and frequencies of various cell types were analyzed by assessing single cell interspike intervals (ISIs and the corresponding coefficient of variation (CV. Results: A total of 295 neurons were identified from the GPi (n=12 and STN (n=18. These included 26 (8.8% highly grouped discharge, 30 (10.2% low frequency firing, 78 (26.4% rapid tonic discharge, 103 (34.9% irregular activity, and 58 (19.7% tremor-related activity. There were significant differences between the two groups (P<0.05 for neurons with irregular firing, highly irregular cluster-like firing, and low-frequency firing. Conclusion: Altered neuronal activity was observed in the basal ganglia nucleus of GPi and STN, and may play important roles in the pathophysiology of PD and LID.

  6. [Effects of slopes on nitrogen transport along with runoff from sloping plots on a lateritic red soil amended with sewage sludge].

    Chen, Yan-Hui; Chen, Ming-Hua; Wang, Guo; Chen, Wen-Xiang; Yang, Shun-Cheng; Chai, Peng

    2010-10-01

    The effects of different slopes on nitrogen transport along with runoff from sloping plots amended with sewage sludge on a lateritic red soil were studied under simulated rainfall conditions. When the sludge was broadcasted and mixed with surface soils (BM), the MTN (total nitrogen of mixing sample), STN (total nitrogen of settled sample), TPN (total particulate nitrogen), TSN (total suspended nitrogen), TDN (total dissolved nitrogen) and NH4(+) -N concentrations and nitrogen loss amounts in runoff of all treatments were highest at 1 day or 18 days after application. The highest concentrations and the loss amounts of MTN and STN in the slope runoff for the BM treatment increased with slope degree, showing increasing pollution risks to the surface waters. The STN concentration and loss amounts from the 25 degrees plots were 126.1 mg x L(-1) and 1788.6 mg x m(-2), respectively, being 4.6 times and 5.8 times of the corresponding values from the 10 degrees plots, respectively. Then the concentrations and the loss amounts of nitrogen (except NO3(-) -N) from the BM plots diminished rapidly first and then tended to be stable with dwindling differences between the slopes. The loss of MTN and STN in early runoff (1 day and 18 days) accounted for 68.6% -73.4% and 62.3% -66.7% of the cumulative loss amounts during the experimental period for all the broadcasted treatments. Runoff loss coefficients of MTN increased in the order of 20 degrees > 25 degrees > 15 degrees > 10 degrees. Nitrogen was largely lost in dissolved species while large portion of NH4(+) -N was lost with particulates.

  7. Task Specific Inter-Hemispheric Coupling in Human Subthalamic Nuclei

    Felix eDarvas

    2014-09-01

    Full Text Available Cortical networks and quantitative measures of connectivity are integral to the study of brain function. Despite lack of direct connections between left and right subthalamic nuclei (STN, there are apparent physiological connections. During clinical examination of patients with Parkinson’s Disease (PD, this connectivity is exploited to enhance signs of PD, yet our understanding of this connectivity is limited. We hypothesized that movement leads to synchronization of neural oscillations in bilateral STN, and we implemented phase coherence, a measure of phase-locking between cortical sites in a narrow frequency band, to demonstrate this synchronization. We analyzed task specific phase synchronization and causality between left and right STN local field potentials (LFP recorded from both hemispheres simultaneously during a cued movement task in four subjects with PD who underwent Deep Brain Stimulation (DBS surgery. We used a data driven approach to determine inter-hemispheric channel pairs and frequencies with a task specific increase in phase locking.We found significant phase locking between hemispheres in alpha frequency (8-12 Hz in all subjects concurrent with movement of either hand. In all subjects, phase synchronization increased over baseline upon or prior to hand movement onset and lasted until the motion ceased. Left and right hand movement showed similar patterns. Granger causality at the phase-locking frequencies between synchronized electrodes revealed a unidirectional causality from right to left STN regardless of which side was moved.Phase synchronization across hemispheres between basal ganglia supports existence of a bilateral network having lateralized regions of specialization for motor processing. Our results suggest this bilateral network is activated by a unilateral motor program. Understanding phase synchronization in natural brain functions is critical to development of future DBS systems that augment goal directed

  8. Subthalamic nucleus stimulation affects theory of mind network: a PET study in Parkinson's disease.

    Péron, Julie; Le Jeune, Florence; Haegelen, Claire; Dondaine, Thibaut; Drapier, Dominique; Sauleau, Paul; Reymann, Jean-Michel; Drapier, Sophie; Rouaud, Tiphaine; Millet, Bruno; Vérin, Marc

    2010-03-29

    There appears to be an overlap between the limbic system, which is modulated by subthalamic nucleus (STN) deep brain stimulation (DBS) in Parkinson's disease (PD), and the brain network that mediates theory of mind (ToM). Accordingly, the aim of the present study was to investigate the effects of STN DBS on ToM of PD patients and to correlate ToM modifications with changes in glucose metabolism. To this end, we conducted (18)FDG-PET scans in 13 PD patients in pre- and post-STN DBS conditions and correlated changes in their glucose metabolism with modified performances on the Eyes test, a visual ToM task requiring them to describe thoughts or feelings conveyed by photographs of the eye region. Postoperative PD performances on this emotion recognition task were significantly worse than either preoperative PD performances or those of healthy controls (HC), whereas there was no significant difference between preoperative PD and HC. Conversely, PD patients in the postoperative condition performed within the normal range on the gender attribution task included in the Eyes test. As far as the metabolic results are concerned, there were correlations between decreased cerebral glucose metabolism and impaired ToM in several cortical areas: the bilateral cingulate gyrus (BA 31), right middle frontal gyrus (BA 8, 9 and 10), left middle frontal gyrus (BA 6), temporal lobe (fusiform gyrus, BA 20), bilateral parietal lobe (right BA 3 and right and left BA 7) and bilateral occipital lobe (BA 19). There were also correlations between increased cerebral glucose metabolism and impaired ToM in the left superior temporal gyrus (BA 22), left inferior frontal gyrus (BA 13 and BA 47) and right inferior frontal gyrus (BA 47). All these structures overlap with the brain network that mediates ToM. These results seem to confirm that STN DBS hinders the ability to infer the mental states of others and modulates a distributed network known to subtend ToM.

  9. The confirmation audit in Mochovce nuclear power plant

    Andlova, Z.

    2004-01-01

    Mochovce NPP, as the first plant of the Slovenske elektrarne, a. s., has obtained certificate for the environmental management system (EMS) in September 2002, which was established according to the standard STN ISO 14 001:1996. The Audit EMS was executed by the Det Norske Veritas. Mochovce NPP has obtained the EMS Certificate after compliance of process requests and it is valid for three years. After expire of this period the certification process must be repeated. (author)

  10. Inhibition of JAK3 and PKC via Immunosuppressive Drugs Tofacitinib and Sotrastaurin Inhibits Proliferation of Human B Lymphocytes In Vitro.

    Martina, M N; Ramirez Bajo, M J; Bañon-Maneus, E; Moya Rull, D; Hierro-Garcia, N; Revuelta, I; Campistol, J M; Rovira, J; Diekmann, F

    2016-11-01

    Antibody-mediated response in solid organ transplantation is critical for graft dysfunction and loss. The use of immunosuppressive agents partially inhibits the B-lymphocyte response leading to a risk of acute and chronic antibody-mediated rejection. This study evaluated the impact of JAK3 and PKC inhibitors tofacitinib (Tofa) and sotrastaurin (STN), respectively, on B-cell proliferation, apoptosis, and activation in vitro. Human B cells isolated from peripheral blood of healthy volunteers were cocultured with CD40 ligand-transfected fibroblasts as feeder cells in the presence of interleukin (IL) 2, IL-10, and IL-21. The cocultures were treated with immunosuppressants Tofa, STN, and rapamycin (as a control), to analyze the proliferation and apoptosis of B cells by means of Cyquant and flow cytometry, respectively. CD27 and IgG staining were applied to evaluate whether treatments modified the activation of B cells. Tofa and STN were able to inhibit B-cell proliferation to the same extent as rapamycin, without inducing cell apoptosis. After 6 days in coculture with feeder cells, all B cells showed CD27 memory B-cell phenotype. None of the immunosuppressive treatments modified the proportion between class-switched and non-class-switched memory B cells observed in nontreated cultures. The high predominance of CD27 + CD24 + phenotype was not modified by any immunosuppressive treatment. Our results show that Tofa and STN can suppress B-cell antibody responses to an extent similar to rapamycin, in vitro; therefore these compounds may be a useful therapy against antibody-mediated rejection in transplantation. Copyright © 2016. Published by Elsevier Inc.

  11. VP1, the major capsid protein of the mouse polyomavirus, binds microtubules, promotes their acetylation and blocks the host cell cycle

    Horníková, L.; Fraiberk, M.; Man, Petr; Janovec, V.; Forstová, J.

    2017-01-01

    Roč. 284, č. 2 (2017), s. 301-323 E-ISSN 1742-4658 R&D Projects: GA MŠk(CZ) ED1.1.00/02.0109; GA MŠk(CZ) LO1509 Grant - others:Ministerstvo pro místní rozvoj(CZ) CZ.2.16./3.1.00/24023 Institutional support: RVO:61388971 Keywords : cell cycle arrest * chaperone Hsp90 * microtubules Subject RIV: EE - Microbiology, Virology OBOR OECD: Microbiology

  12. Komunikace ve vybrané organizaci

    HRUBÁ, Jana

    2017-01-01

    The aim of my bachelor work is to analyze communication in a chosen company and suggest possible changes to improve it. Literary research explain communication in general and then it focuses on the communication with the customers. Practical part was based on questionnaire, which tries to find out how customer perceive communication with the chosen company and how company perceive communication with customers. This research was done in a company STN-ESOX spol. s r.o.

  13. The potential anticonvulsant activity of the ethanolic extracts of Achillea nobilis and Momordica charantia in rats

    Gamal A. Soliman

    2016-06-01

    Full Text Available Context: Currently available antiepileptic drugs have debilitating adverse effects. Natural products and plants already used in traditional medicine can be a good place to start in the search for safer and more effective options. Aims: To investigate the anticonvulsant potential of Achillea nobilis and Momordica charantia extracts in maximal electroshock (MES, as well as pentylenetetrazole (PTZ- and strychnine nitrate (STN- induced seizure models in rats. Methods: For each model, eight groups of 21-day-old male Albino rats were used. The 1st group was kept as control, 2nd as standard (diazepam, 7.5 mg/kg; 3rd – 5th treated with A. nobilis (100, 200 and 300 mg/kg; and 6th – 8th administered M. charantia (100, 200 and 300 mg/kg. After 30 min, rats were exposed to a shock of 150 mA by a convulsiometer, via ear electrodes for 2 s (in MES test or sc injection of PTZ (85 mg/kg or STN (2.5 mg/kg. Results: A. nobilis and M. charantia extracts (200 and 300 mg/kg demonstrated dose-dependent anticonvulsant effect against MES-induced seizures. In the PTZ induced convulsion, A. nobilis and M. charantia (200 and 300 mg/kg significantly slowed the commencement of convulsions and minimized the duration of seizures. A. nobilis (300 mg/kg showed 60% protection in rats against STN induced seizures. In contrast, A. nobilis (100 and 200 mg/kg and M. charantia (100, 200 and 300 mg/kg showed no significant protection against STN-induced seizures in rats. Conclusions: The results of the present study suggest that both extracts exhibited marked anticonvulsant activities.

  14. The network of causal interactions for beta oscillations in the pedunculopontine nucleus, primary motor cortex, and subthalamic nucleus of walking parkinsonian rats.

    Li, Min; Zhou, Ming; Wen, Peng; Wang, Qiang; Yang, Yong; Xiao, Hu; Xie, Zhengyuan; Li, Xing; Wang, Ning; Wang, Jinyan; Luo, Fei; Chang, Jingyu; Zhang, Wangming

    2016-08-01

    Oscillatory activity has been well-studied in many structures within cortico-basal ganglia circuits, but it is not well understood within the pedunculopontine nucleus (PPN), which was recently introduced as a potential target for the treatment of gait and postural impairments in advanced stages of Parkinson's disease (PD). To investigate oscillatory activity in the PPN and its relationship with oscillatory activity in cortico-basal ganglia circuits, we simultaneously recorded local field potentials in the PPN, primary motor cortex (M1), and subthalamic nucleus (STN) of 6-hydroxydopamine (6-OHDA)-induced hemiparkinsonian rats during resting and walking. After analysis of power spectral density, coherence, and partial Granger causality, three major findings emerged: 1) after 6-OHDA lesions, beta band oscillations were enhanced in all three regions during walking; 2) the direction of information flow for beta oscillations among the three structures was STN→M1, STN→PPN, and PPN→M1; 3) after the treatment of levodopa, beta activity in the three regions was reduced significantly and the flow of beta band was also abrogated. Our results suggest that beta activity in the PPN is transmitted from the basal ganglia and probably comes from the STN, and the STN plays a dominant role in the network of causal interactions for beta activity. Thus, the STN may be a potential source of aberrant beta band oscillations in PD. Levodopa can inhibit beta activity in the PPN of parkinsonian rats but cannot relieve parkinsonian patients' axial symptoms clinically. Therefore, beta oscillations may not be the major cause of axial symptoms. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Toward relating the subthalamic nucleus spiking activity to the local field potentials acquired intranuclearly

    Michmizos, K P; Nikita, K S; Sakas, D

    2011-01-01

    Studies on neurophysiological correlates of the functional magnetic resonance imaging (fMRI) signals reveal a strong relationship between the local field potential (LFP) acquired invasively and metabolic signal changes in fMRI experiments. Most of these studies failed to reveal an analogous relationship between metabolic signals and the spiking activity. That would allow for the prediction of the neural activity exclusively from the fMRI signals. However, the relationship between fMRI signals and spiking activity can be inferred indirectly provided that the LFPs can be used to predict the spiking activity of the area. Until now, only the LFP–spike relationship in cortical areas has been examined. Herein, we show that the spiking activity can be predicted by the LFPs acquired in a deep nucleus, namely the subthalamic nucleus (STN), using a nonlinear cascade model. The model can reproduce the spike patterns inside the motor area of the STN that represent information about the motor plans. Our findings expand the possibility of further recruiting non-invasive neuroimaging techniques to understand the activity of the STN and predict or even control movement

  16. Subthalamic nucleus stimulation does not influence basal glucose metabolism or insulin sensitivity in patients with Parkinson's disease.

    Lammers, Nicolette M; Sondermeijer, Brigitte M; Twickler, Th B Marcel; de Bie, Rob M; Ackermans, Mariëtte T; Fliers, Eric; Schuurman, P Richard; La Fleur, Susanne E; Serlie, Mireille J

    2014-01-01

    Animal studies have shown that central dopamine signaling influences glucose metabolism. As a first step to show this association in an experimental setting in humans, we studied whether deep brain stimulation (DBS) of the subthalamic nucleus (STN), which modulates the basal ganglia circuitry, alters basal endogenous glucose production (EGP) or insulin sensitivity in patients with Parkinson's disease (PD). We studied 8 patients with PD treated with DBS STN, in the basal state and during a hyperinsulinemic euglycemic clamp using a stable glucose isotope, in the stimulated and non-stimulated condition. We measured EGP, hepatic insulin sensitivity, peripheral insulin sensitivity (Rd), resting energy expenditure (REE), glucoregulatory hormones, and Parkinson symptoms, using the Unified Parkinson's Disease Rating Scale (UPDRS). Basal plasma glucose and EGP did not differ between the stimulated and non-stimulated condition. Hepatic insulin sensitivity was similar in both conditions and there were no significant differences in Rd and plasma glucoregulatory hormones between DBS on and DBS off. UPDRS was significantly higher in the non-stimulated condition. DBS of the STN in patients with PD does not influence basal EGP or insulin sensitivity. These results suggest that acute modulation of the motor basal ganglia circuitry does not affect glucose metabolism in humans.

  17. Investigating Synchronous Oscillation and Deep Brain Stimulation Treatment in A Model of Cortico-Basal Ganglia Network.

    Lu, Meili; Wei, Xile; Loparo, Kenneth A

    2017-11-01

    Altered firing properties and increased pathological oscillations in the basal ganglia have been proven to be hallmarks of Parkinson's disease (PD). Increasing evidence suggests that abnormal synchronous oscillations and suppression in the cortex may also play a critical role in the pathogenic process and treatment of PD. In this paper, a new closed-loop network including the cortex and basal ganglia using the Izhikevich models is proposed to investigate the synchrony and pathological oscillations in motor circuits and their modulation by deep brain stimulation (DBS). Results show that more coherent dynamics in the cortex may cause stronger effects on the synchrony and pathological oscillations of the subthalamic nucleus (STN). The pathological beta oscillations of the STN can both be efficiently suppressed with DBS applied directly to the STN or to cortical neurons, respectively, but the underlying mechanisms by which DBS suppresses the beta oscillations are different. This research helps to understand the dynamics of pathological oscillations in PD-related motor regions and supports the therapeutic potential of stimulation of cortical neurons.

  18. Effect of Deep Brain Stimulation on Parkinson's Nonmotor Symptoms following Unilateral DBS: A Pilot Study

    Nelson Hwynn

    2011-01-01

    Full Text Available Parkinson’s disease (PD management has traditionally focused largely on motor symptoms. Deep brain stimulation (DBS of the subthalamic nucleus (STN and globus pallidus internus (GPi are effective treatments for motor symptoms. Nonmotor symptoms (NMSs may also profoundly affect the quality of life. The purpose of this pilot study was to evaluate NMS changes pre- and post-DBS utilizing two recently developed questionnaires. Methods. NMS-Q (questionnaire and NMS-S (scale were administered to PD patients before/after unilateral DBS (STN/GPi targets. Results. Ten PD patients (9 STN implants, 1 GPi implant were included. The three most frequent NMS symptoms identified utilizing NMS-Q in pre-surgical patients were gastrointestinal (100%, sleep (100%, and urinary (90%. NMS sleep subscore significantly decreased (−1.6 points ± 1.8, =0.03. The three most frequent NMS symptoms identified in pre-surgical patients using NMS-S were gastrointestinal (90%, mood (80%, and cardiovascular (80%. The largest mean decrease of NMS scores was seen in miscellaneous symptoms (pain, anosmia, weight change, and sweating (−7 points ± 8.7, and cardiovascular/falls (−1.9, =0.02. Conclusion. Non-motor symptoms improved on two separate questionnaires following unilateral DBS for PD. Future studies are needed to confirm these findings and determine their clinical significance as well as to examine the strengths/weaknesses of each questionnaire/scale.

  19. A polypeptide-DNA hybrid with selective linking capability applied to single molecule nano-mechanical measurements using optical tweezers.

    Fatemeh Moayed

    Full Text Available Many applications in biosensing, biomaterial engineering and single molecule biophysics require multiple non-covalent linkages between DNA, protein molecules, and surfaces that are specific yet strong. Here, we present a novel method to join proteins and dsDNA molecule at their ends, in an efficient, rapid and specific manner, based on the recently developed linkage between the protein StrepTactin (STN and the peptide StrepTag II (ST. We introduce a two-step approach, in which we first construct a hybrid between DNA and a tandem of two STs peptides (tST. In a second step, this hybrid is linked to polystyrene bead surfaces and Maltose Binding Protein (MBP using STN. Furthermore, we show the STN-tST linkage is more stable against forces applied by optical tweezers than the commonly used biotin-Streptavidin (STV linkage. It can be used in conjunction with Neutravidin (NTV-biotin linkages to form DNA tethers that can sustain applied forces above 65 pN for tens of minutes in a quarter of the cases. The method is general and can be applied to construct other surface-DNA and protein-DNA hybrids. The reversibility, high mechanical stability and specificity provided by this linking procedure make it highly suitable for single molecule mechanical studies, as well as biosensing and lab on chip applications.

  20. Effects of deep brain stimulation on balance and gait in patients with Parkinson's disease: A systematic neurophysiological review.

    Collomb-Clerc, A; Welter, M-L

    2015-11-01

    Deep brain stimulation (DBS) of the subthalamic nucleus (STN) and internal globus pallidus (GPi) deep brain stimulation (DBS) provides an efficient treatment for the alleviation of motor signs in patients with Parkinson's disease. The effects of DBS on gait and balance disorders are less successful and may even lead to an aggravation of freezing of gait and imbalance. The identification of a substantia nigra pars reticulata (SNr)-mesencephalic locomotor region (MLR) network in the control of locomotion and postural control and of its dysfunction/lesion in PD patients with gait and balance disorders led to suggestion that DBS should be targeting the SNr and the pedunculopontine nucleus (part of the MLR) for PD patients with these disabling axial motor signs. However, the clinical results to date have been disappointing. In this review, we discuss the effects of DBS of these basal ganglia and brainstem structures on the neurophysiological parameters of gait and balance control in PD patients. Overall, the data suggest that both STN and GPi-DBS improve gait parameters and quiet standing postural control in PD patients, but have no effect or may even aggravate dynamic postural control, in particular with STN-DBS. Conversely, DBS of the SNr and PPN has no effect on gait parameters but improves anticipatory postural adjustments and gait postural control. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  1. Subthalamic deep brain stimulation and dopaminergic medication in Parkinson's disease: Impact on inter-limb coupling.

    Daneault, Jean-François; Carignan, Benoit; Sadikot, Abbas F; Duval, Christian

    2016-10-29

    Patients with Parkinson's disease (PD) often present with bimanual coordination deficits whose exact origins remain unclear. One aspect of bimanual coordination is inter-limb coupling. This is characterized by the harmonization of movement parameters between limbs. We assessed different aspects of bimanual coordination in patients with PD, including inter-limb coupling, and determined whether they are altered by subthalamic (STN) deep brain stimulation (DBS) or dopaminergic medication. Twenty PD patients were tested before STN DBS surgery; with and without medication. Post- surgery, patients were tested with their stimulators on and off as well as with and without medication. Patients were asked to perform a unimanual and bimanual rapid repetitive diadochokinesis task. The difference in mean amplitude and mean duration of cycles between hands was computed in order to assess inter-limb coupling. Also, mean angular velocity of both hands and structural coupling were computed for the bimanual task. There was a positive effect of medication and stimulation on mean angular velocity, which relates to clinical improvement. PD patients exhibited temporal inter-limb coupling that was not altered by either medication or STN stimulation. However, PD patients did not exhibit spatial inter-limb coupling. Again, this was not altered by medication or stimulation. Collectively, the results suggest that structures independent of the dopaminergic system and basal ganglia may mediate temporal and spatial inter-limb coupling. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  2. Outcomes of Interventional-MRI Versus Microelectrode Recording-Guided Subthalamic Deep Brain Stimulation

    Philip S. Lee

    2018-04-01

    Full Text Available In deep brain stimulation (DBS of the subthalamic nucleus (STN for Parkinson’s disease (PD, there is debate concerning the use of neuroimaging alone to confirm correct anatomic placement of the DBS lead into the STN, versus the use of microelectrode recording (MER to confirm functional placement. We performed a retrospective study of a contemporaneous cohort of 45 consecutive patients who underwent either interventional-MRI (iMRI or MER-guided DBS lead implantation. We compared radial lead error, motor and sensory side effect, and clinical benefit programming thresholds, and pre- and post-operative unified PD rating scale scores, and levodopa equivalent dosages. MER-guided surgery was associated with greater radial error compared to the intended target. In general, side effect thresholds during initial programming were slightly lower in the MER group, but clinical benefit thresholds were similar. No significant difference in the reduction of clinical symptoms or medication dosage was observed. In summary, iMRI lead implantation occurred with greater anatomic accuracy, in locations demonstrated to be the appropriate functional region of the STN, based on the observation of similar programming side effect and benefit thresholds obtained with MER. The production of equivalent clinical outcomes suggests that surgeon and patient preference can be used to guide the decision of whether to recommend iMRI or MER-guided DBS lead implantation to appropriate patients with PD.

  3. Apathy following Bilateral Deep Brain Stimulation of Subthalamic Nucleus in Parkinson’s Disease: A Meta-Analysis

    Ying Wang

    2018-01-01

    Full Text Available Bilateral deep brain stimulation of subthalamic nucleus (STN-DBS has proven effective in improving motor symptoms in Parkinson’s disease (PD patients. However, psychiatric changes after surgery are controversial. In this study, we specifically analyzed apathy following bilateral STN-DBS in PD patients using a meta-analysis. Relevant articles utilized for this study were obtained through literature search on PubMed, ScienceDirect, and Embase databases. The articles included were those contained both pre- and postsurgery apathy data acquired using the Starkstein Apathy Scale or Apathy Evaluation Scale with patient follow-up of at least three months. A total of 9 out of 86 articles were included in our study through this strict screening process. Standardized mean difference (SMD, that is, Cohen’s d, with a 95% confidence interval (CI was calculated to show the change. We found a significant difference between the presurgery stage and the postsurgery stage scores (SMD = 0.35, 95% CI: 0.17∼0.52, P<0.001. STN-DBS seems to relatively worsen the condition of apathy, which may result from both the surgery target (subthalamic nucleus and the reduction of dopaminergic medication. Further studies should focus on the exact mechanisms of possible postoperative apathy in the future.

  4. Apathy following Bilateral Deep Brain Stimulation of Subthalamic Nucleus in Parkinson's Disease: A Meta-Analysis

    Zhang, Xiaona

    2018-01-01

    Bilateral deep brain stimulation of subthalamic nucleus (STN-DBS) has proven effective in improving motor symptoms in Parkinson's disease (PD) patients. However, psychiatric changes after surgery are controversial. In this study, we specifically analyzed apathy following bilateral STN-DBS in PD patients using a meta-analysis. Relevant articles utilized for this study were obtained through literature search on PubMed, ScienceDirect, and Embase databases. The articles included were those contained both pre- and postsurgery apathy data acquired using the Starkstein Apathy Scale or Apathy Evaluation Scale with patient follow-up of at least three months. A total of 9 out of 86 articles were included in our study through this strict screening process. Standardized mean difference (SMD), that is, Cohen's d, with a 95% confidence interval (CI) was calculated to show the change. We found a significant difference between the presurgery stage and the postsurgery stage scores (SMD = 0.35, 95% CI: 0.17∼0.52, P < 0.001). STN-DBS seems to relatively worsen the condition of apathy, which may result from both the surgery target (subthalamic nucleus) and the reduction of dopaminergic medication. Further studies should focus on the exact mechanisms of possible postoperative apathy in the future.

  5. Inclusion of Cocoa as a Dietary Supplement Represses Expression of Inflammatory Proteins in Spinal Trigeminal Nucleus in Response to Chronic Trigeminal Nerve Stimulation

    Cady, Ryan J.; Denson, Jennifer E.; Durham, Paul L.

    2013-01-01

    Scope Central sensitization is implicated in the pathology of temporomandibular joint disorder (TMD) and other types of orofacial pain. We investigated the effects of dietary cocoa on expression of proteins involved in the development of central sensitization in the spinal trigeminal nucleus (STN) in response to inflammatory stimulation of trigeminal nerves. Methods and results Male Sprague Dawley rats were fed either a control diet or an isocaloric diet consisting of 10% cocoa powder 14 days prior to bilateral injection of complete Freund’s adjuvant (CFA) into the temporomandibular joint to promote prolonged activation of trigeminal ganglion neurons and glia. While dietary cocoa stimulated basal expression of GLAST and MKP-1 when compared to animals on a normal diet, cocoa suppressed basal calcitonin gene-related peptide levels in the STN. CFA-stimulated levels of protein kinase A, P2X3, P-p38, GFAP, and OX-42, whose elevated levels in the STN are implicated in central sensitization, were repressed to near control levels in animals on a cocoa enriched diet. Similarly, dietary cocoa repressed CFA-stimulated inflammatory cytokine expression. Conclusion Based on our findings, we speculate that cocoa enriched diets could be beneficial as a natural therapeutic option for TMD and other chronic orofacial pain conditions. PMID:23576361

  6. Subthalamic Nucleus Deep Brain Stimulation Alters Prefrontal Correlates of Emotion Induction.

    Bick, Sarah K B; Folley, Bradley S; Mayer, Jutta S; Park, Sohee; Charles, P David; Camalier, Corrie R; Pallavaram, Srivatsan; Konrad, Peter E; Neimat, Joseph S

    2017-04-01

    Deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves motor symptoms in advanced Parkinson's disease. STN DBS may also affect emotion, possibly by impacting a parallel limbic cortico-striatal circuit. The objective of this study was to investigate changes in prefrontal cortical activity related to DBS during an emotion induction task. We used near infrared spectroscopy to monitor prefrontal cortex hemodynamic changes during an emotion induction task. Seven DBS patients were tested sequentially in the stimulation-on and stimulation-off states while on dopaminergic medication. Patients watched a series of positive, negative, and neutral videos. The general linear model was used to compare prefrontal oxygenated hemoglobin concentration between DBS states. Deep brain stimulation was correlated with prefrontal oxygenated hemoglobin changes relative to the stimulation off state in response to both positive and negative videos. These changes were specific to emotional stimuli and were not seen during neutral stimuli. These results suggest that STN stimulation influences the prefrontal cortical representation of positive and negative emotion induction. © 2016 International Neuromodulation Society.

  7. Distinct populations of neurons respond to emotional valence and arousal in the human subthalamic nucleus.

    Sieger, Tomáš; Serranová, Tereza; Růžička, Filip; Vostatek, Pavel; Wild, Jiří; Štastná, Daniela; Bonnet, Cecilia; Novák, Daniel; Růžička, Evžen; Urgošík, Dušan; Jech, Robert

    2015-03-10

    Both animal studies and studies using deep brain stimulation in humans have demonstrated the involvement of the subthalamic nucleus (STN) in motivational and emotional processes; however, participation of this nucleus in processing human emotion has not been investigated directly at the single-neuron level. We analyzed the relationship between the neuronal firing from intraoperative microrecordings from the STN during affective picture presentation in patients with Parkinson's disease (PD) and the affective ratings of emotional valence and arousal performed subsequently. We observed that 17% of neurons responded to emotional valence and arousal of visual stimuli according to individual ratings. The activity of some neurons was related to emotional valence, whereas different neurons responded to arousal. In addition, 14% of neurons responded to visual stimuli. Our results suggest the existence of neurons involved in processing or transmission of visual and emotional information in the human STN, and provide evidence of separate processing of the affective dimensions of valence and arousal at the level of single neurons as well.

  8. Assessing the direct effects of deep brain stimulation using embedded axon models

    Sotiropoulos, Stamatios N.; Steinmetz, Peter N.

    2007-06-01

    To better understand the spatial extent of the direct effects of deep brain stimulation (DBS) on neurons, we implemented a geometrically realistic finite element electrical model incorporating anisotropic and inhomogenous conductivities. The model included the subthalamic nucleus (STN), substantia nigra (SN), zona incerta (ZI), fields of Forel H2 (FF), internal capsule (IC) and Medtronic 3387/3389 electrode. To quantify the effects of stimulation, we extended previous studies by using multi-compartment axon models with geometry and orientation consistent with anatomical features of the brain regions of interest. Simulation of axonal firing produced a map of relative changes in axonal activation. Voltage-controlled stimulation, with clinically typical parameters at the dorso-lateral STN, caused axon activation up to 4 mm from the target. This activation occurred within the FF, IC, SN and ZI with current intensities close to the average injected during DBS (3 mA). A sensitivity analysis of model parameters (fiber size, fiber orientation, degree of inhomogeneity, degree of anisotropy, electrode configuration) revealed that the FF and IC were consistently activated. Direct activation of axons outside the STN suggests that other brain regions may be involved in the beneficial effects of DBS when treating Parkinsonian symptoms.

  9. Study of organic sulphur compounds (DMS, DMSP and CS2) in lagoon ecosystems: the case of the Venice lagoon.

    Gambaro, Andrea; Moret, Ivo; Piazza, Rossano; Andreoli, Carlo; Corami, Fabiana; Turetta, Clara; Cescon, Paolo

    2003-03-01

    This study of the origin and fate of dimethyl sulphide (DMS) in a particular and complex lagoon ecosystem such as that of the Venice lagoon focuses on the temporal evolutions of DMS concentrations in surface water together with those of dimethylsulphoniopropionate (DMSP), carbon disulphide (CS2), nutrients (nitrate, nitrite, ammonium, phosphate, silicate), sulphate, chlorophyll a, chlorinity, water temperature and phytoplankton (composition and density). Measurements were made from 3 March 1997 to 23 July 1998 at three stations in the central part of the Venice lagoon. The temporal trends of DMS concentration showed an absolute maximum concentration in winter (65 nmol S/l, 19/2/1998, Stn. 1; 119 nmol S/l, 19/2/1998, Stn. 2; 29 nmol S/l, 17/2/1998, Stn. 3) and two relative maxima in the spring-summer period. The spring-summer secondary maxima of DMS concentration were related to the maxima of DMSP and chlorophyll a concentrations and consequently to phytoplanktonic abundance while the winter DMS maximum showed no relation to DMSP or to chlorophyll a suggesting that the production and the fate of DMS could be different for the two periods. According to previous studies the CS2 concentration increased in the spring, achieved its maximum in summer, decreased in autumn and fell to its minimum in winter.

  10. Existence of Lipschitz selections of the Steiner map

    Bednov, B. B.; Borodin, P. A.; Chesnokova, K. V.

    2018-02-01

    This paper is concerned with the problem of the existence of Lipschitz selections of the Steiner map {St}_n, which associates with n points of a Banach space X the set of their Steiner points. The answer to this problem depends on the geometric properties of the unit sphere S(X) of X, its dimension, and the number n. For n≥slant 4 general conditions are obtained on the space X under which {St}_n admits no Lipschitz selection. When X is finite dimensional it is shown that, if n≥slant 4 is even, the map {St}_n has a Lipschitz selection if and only if S(X) is a finite polytope; this is not true if n≥slant 3 is odd. For n=3 the (single-valued) map {St}_3 is shown to be Lipschitz continuous in any smooth strictly-convex two-dimensional space; this ceases to be true in three-dimensional spaces. Bibliography: 21 titles.

  11. Neuropsychological and quality of life assessment in patients with Parkinson's disease submitted to bilateral deep brain stimulation in the subthalamic nucleus

    Alessandra Shenandoa Heluani

    Full Text Available ABSTRACT Deep brain stimulation (DBS has been widely used to control motor symptoms and improve quality of life in patients with Parkinsons disease (PD. Recently, DBS in the subthalamic nucleus (STN has become the preferred target for patients with mixed motor symptoms. Despite resultant motor and quality of life improvements, the procedure has been associated with cognitive decline, mainly in language skills, and also with psychiatric symptoms. Objective: To evaluate the influence of DBS in the STN on cognition, mood and quality of life. Methods: We studied 20 patients with PD submitted to DBS in the STN from May 2008 to June 2012 with an extensive battery of cognitive tests including memory, language, praxis, executive functions and attention assessments; the Parkinson's Disease Quality of Life Questionnaire (PDQ-39; and the Hospital Anxiety and Depression Scale (HAD, were applied both before and after the surgery. Data was analyzed using SPSS version 17.0 and results compared using the paired Student's t test. Results: A total of 20 patients with pre and post-operative assessments were included. A statistically significant improvement was found in total score and on subscales of mobility, activities of daily living and emotional well-being from the PDQ-39 (P=0.009, 0.025, 0.001 and 0.034, respectively. No significant difference was found on the cognitive battery or mood scale. Conclusion: DBS in the SNT improved quality of life in PD with no negative impact on cognitive skills and mood.

  12. Deep Multi-Task Learning for Tree Genera Classification

    Ko, C.; Kang, J.; Sohn, G.

    2018-05-01

    The goal for our paper is to classify tree genera using airborne Light Detection and Ranging (LiDAR) data with Convolution Neural Network (CNN) - Multi-task Network (MTN) implementation. Unlike Single-task Network (STN) where only one task is assigned to the learning outcome, MTN is a deep learning architect for learning a main task (classification of tree genera) with other tasks (in our study, classification of coniferous and deciduous) simultaneously, with shared classification features. The main contribution of this paper is to improve classification accuracy from CNN-STN to CNN-MTN. This is achieved by introducing a concurrence loss (Lcd) to the designed MTN. This term regulates the overall network performance by minimizing the inconsistencies between the two tasks. Results show that we can increase the classification accuracy from 88.7 % to 91.0 % (from STN to MTN). The second goal of this paper is to solve the problem of small training sample size by multiple-view data generation. The motivation of this goal is to address one of the most common problems in implementing deep learning architecture, the insufficient number of training data. We address this problem by simulating training dataset with multiple-view approach. The promising results from this paper are providing a basis for classifying a larger number of dataset and number of classes in the future.

  13. Camel as a transboundary vector for emerging exotic Salmonella serovars.

    Ghoneim, Nahed H; Abdel-Moein, Khaled A; Zaher, Hala

    2017-05-01

    The current study was conducted to shed light on the role of imported camels as a transboundary vector for emerging exotic Salmonella serovars. Fecal samples were collected from 206 camels directly after slaughtering including 25 local camels and 181 imported ones as well as stool specimens were obtained from 50 slaughterhouse workers at the same abattoir. The obtained samples were cultured while Salmonella serovars were identified through Gram's stain films, biochemical tests and serotyping with antisera kit. Moreover, the obtained Salmonella serovars were examined by PCR for the presence of invA and stn genes. The overall prevalence of Salmonella serovars among the examined camels was 8.3%. Stn gene was detected in the vast majority of exotic strains (11/14) 78.6% including emerging serovars such as Salmonella Saintpaul, S. Chester, S. Typhimurium whereas only one isolate from local camels carried stn gene (1/3) 33.3%. On the other hand, none of the examined humans yielded positive result. Our findings highlight the potential role of imported camels as a transboundary vector for exotic emerging Salomenella serovars.

  14. Human CST Facilitates Genome-wide RAD51 Recruitment to GC-Rich Repetitive Sequences in Response to Replication Stress.

    Chastain, Megan; Zhou, Qing; Shiva, Olga; Fadri-Moskwik, Maria; Whitmore, Leanne; Jia, Pingping; Dai, Xueyu; Huang, Chenhui; Ye, Ping; Chai, Weihang

    2016-08-02

    The telomeric CTC1/STN1/TEN1 (CST) complex has been implicated in promoting replication recovery under replication stress at genomic regions, yet its precise role is unclear. Here, we report that STN1 is enriched at GC-rich repetitive sequences genome-wide in response to hydroxyurea (HU)-induced replication stress. STN1 deficiency exacerbates the fragility of these sequences under replication stress, resulting in chromosome fragmentation. We find that upon fork stalling, CST proteins form distinct nuclear foci that colocalize with RAD51. Furthermore, replication stress induces physical association of CST with RAD51 in an ATR-dependent manner. Strikingly, CST deficiency diminishes HU-induced RAD51 foci formation and reduces RAD51 recruitment to telomeres and non-telomeric GC-rich fragile sequences. Collectively, our findings establish that CST promotes RAD51 recruitment to GC-rich repetitive sequences in response to replication stress to facilitate replication restart, thereby providing insights into the mechanism underlying genome stability maintenance. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  15. Properties of Neurons in External Globus Pallidus Can Support Optimal Action Selection

    Bogacz, Rafal; Martin Moraud, Eduardo; Abdi, Azzedine; Magill, Peter J.; Baufreton, Jérôme

    2016-01-01

    The external globus pallidus (GPe) is a key nucleus within basal ganglia circuits that are thought to be involved in action selection. A class of computational models assumes that, during action selection, the basal ganglia compute for all actions available in a given context the probabilities that they should be selected. These models suggest that a network of GPe and subthalamic nucleus (STN) neurons computes the normalization term in Bayes’ equation. In order to perform such computation, the GPe needs to send feedback to the STN equal to a particular function of the activity of STN neurons. However, the complex form of this function makes it unlikely that individual GPe neurons, or even a single GPe cell type, could compute it. Here, we demonstrate how this function could be computed within a network containing two types of GABAergic GPe projection neuron, so-called ‘prototypic’ and ‘arkypallidal’ neurons, that have different response properties in vivo and distinct connections. We compare our model predictions with the experimentally-reported connectivity and input-output functions (f-I curves) of the two populations of GPe neurons. We show that, together, these dichotomous cell types fulfil the requirements necessary to compute the function needed for optimal action selection. We conclude that, by virtue of their distinct response properties and connectivities, a network of arkypallidal and prototypic GPe neurons comprises a neural substrate capable of supporting the computation of the posterior probabilities of actions. PMID:27389780

  16. Evaluation of deep brain stimulation for Parkinson's disease by using FDG PET

    Guan, Y.H.; Zuo, C.T.; Zhao, J.; Lin, X.T.; Sun, B.M.

    2002-01-01

    Objective: Patients are effectively treated with medication in their initial phases of Parkinson's disease. However, the drugs become less effective and the adverse effects revealed. Recent years, the chronic deep brain stimulation is becoming an important treatment for patients with patients with Parkinson's disease. It has shown that the Parkinson's state is characterized by pathological neural activity in the motor system including the internal segment of the globus pallidus (GPi) and the subthalamic nucleus (STN). The chronic deep brain stimulation can make benefits in the patients by intermediate the pathological neural activity. It needs an external method to evaluate the mechanism of therapy and to monitor the effect of treatment. The objective of our study is to observe the regional glucose metabolism changes in the motor loops and demonstrate the mechanism of therapy and how to monitor the treatment. Patients and Methods: Employing FDG PET, we had studied 7 patients who suffered from Parkinson's disease all the patients were failing medical therapy.the electrodes were implanted in the brain by the direction of MRI.The target of DBS is STN. Resting FDG PET were performed on and off STN stimulation. Metabolic changes with DBS were correlated with clinical improvement as measured by changes in Unified Parkinson's Disease Rating Scale (UPDRS) motor ratings off medication. PET imaging was read by visual interpretation in blind method and calculated by semi-quantitative analysis. The statistic data was analysis after FDG PET imaging. Results: Through the research, regional cerebral glucose metabolic changes with DBS on and off were correlated with clinical improvement as measured by changes in Unified Parkinson's Disease Rating Scale (UPDRS) motor ratings. STN DBS improved UPDRS motor ratings (33%, P<0.001) and significantly increased regional glucose metabolism in the frontal lobe, temporal lobe, Parietal lobe cortex ipsilateral to stimulation. The heighten

  17. Local field potential recordings in a non-human primate model of Parkinsons disease using the Activa PC + S neurostimulator

    Connolly, Allison T; Muralidharan, Abirami; Hendrix, Claudia; Johnson, Luke; Gupta, Rahul; Stanslaski, Scott; Denison, Tim; Baker, Kenneth B; Vitek, Jerrold L; Johnson, Matthew D

    2016-01-01

    Objective Using the Medtronic Activa® PC + S system, this study investigated how passive joint manipulation, reaching behavior, and deep brain stimulation (DBS) modulate local field potential (LFP) activity in the subthalamic nucleus (STN) and globus pallidus (GP). Approach Five non-human primates were implanted unilaterally with one or more DBS leads. LFPs were collected in montage recordings during resting state conditions and during motor tasks that facilitate the expression of parkinsonian motor signs. These recordings were made in the naïve state in one subject, in the parkinsonian state in two subjects, and in both naïve and parkinsonian states in two subjects. Main results LFPs measured at rest were consistent over time for a given recording location and parkinsonian state in a given subject; however, LFPs were highly variable between subjects, between and within recording locations, and across parkinsonian states. LFPs in both naïve and parkinsonian states across all recorded nuclei contained a spectral peak in the beta band (10–30 Hz). Moreover, the spectral content of recorded LFPs was modulated by passive and active movement of the subjects’ limbs. LFPs recorded during a cued-reaching task displayed task-related beta desynchronization in STN and GP. The bidirectional capabilities of the Activa® PC + S also allowed for recording LFPs while delivering DBS. The therapeutic effect of STN DBS on parkinsonian rigidity outlasted stimulation for 30–60 s, but there was no correlation with beta band power. Significance This study emphasizes (1) the variability in spontaneous LFPs amongst subjects and (2) the value of using the Activa® PC + S system to record neural data in the context of behavioral tasks that allow one to evaluate a subject’s symptomatology. PMID:26469737

  18. Non-stationary discharge patterns in motor cortex under subthalamic nucleus deep brain stimulation.

    Santaniello, Sabato; Montgomery, Erwin B; Gale, John T; Sarma, Sridevi V

    2012-01-01

    Deep brain stimulation (DBS) of the subthalamic nucleus (STN) directly modulates the basal ganglia (BG), but how such stimulation impacts the cortex upstream is largely unknown. There is evidence of cortical activation in 6-hydroxydopamine (OHDA)-lesioned rodents and facilitation of motor evoked potentials in Parkinson's disease (PD) patients, but the impact of the DBS settings on the cortical activity in normal vs. Parkinsonian conditions is still debated. We use point process models to analyze non-stationary activation patterns and inter-neuronal dependencies in the motor and sensory cortices of two non-human primates during STN DBS. These features are enhanced after treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which causes a consistent PD-like motor impairment, while high-frequency (HF) DBS (i.e., ≥100 Hz) strongly reduces the short-term patterns (period: 3-7 ms) both before and after MPTP treatment, and elicits a short-latency post-stimulus activation. Low-frequency DBS (i.e., ≤50 Hz), instead, has negligible effects on the non-stationary features. Finally, by using tools from the information theory [i.e., receiver operating characteristic (ROC) curve and information rate (IR)], we show that the predictive power of these models is dependent on the DBS settings, i.e., the probability of spiking of the cortical neurons (which is captured by the point process models) is significantly conditioned on the timely delivery of the DBS input. This dependency increases with the DBS frequency and is significantly larger for high- vs. low-frequency DBS. Overall, the selective suppression of non-stationary features and the increased modulation of the spike probability suggest that HF STN DBS enhances the neuronal activation in motor and sensory cortices, presumably because of reinforcement mechanisms, which perhaps involve the overlap between feedback antidromic and feed-forward orthodromic responses along the BG-thalamo-cortical loop.

  19. A common optimization principle for motor execution in healthy subjects and parkinsonian patients.

    Baraduc, Pierre; Thobois, Stéphane; Gan, Jing; Broussolle, Emmanuel; Desmurget, Michel

    2013-01-09

    Recent research on Parkinson's disease (PD) has emphasized that parkinsonian movement, although bradykinetic, shares many attributes with healthy behavior. This observation led to the suggestion that bradykinesia in PD could be due to a reduction in motor motivation. This hypothesis can be tested in the framework of optimal control theory, which accounts for many characteristics of healthy human movement while providing a link between the motor behavior and a cost/benefit trade-off. This approach offers the opportunity to interpret movement deficits of PD patients in the light of a computational theory of normal motor control. We studied 14 PD patients with bilateral subthalamic nucleus (STN) stimulation and 16 age-matched healthy controls, and tested whether reaching movements were governed by similar rules in these two groups. A single optimal control model accounted for the reaching movements of healthy subjects and PD patients, whatever the condition of STN stimulation (on or off). The choice of movement speed was explained in all subjects by the existence of a preset dynamic range for the motor signals. This range was idiosyncratic and applied to all movements regardless of their amplitude. In PD patients this dynamic range was abnormally narrow and correlated with bradykinesia. STN stimulation reduced bradykinesia and widened this range in all patients, but did not restore it to a normal value. These results, consistent with the motor motivation hypothesis, suggest that constrained optimization of motor effort is the main determinant of movement planning (choice of speed) and movement production, in both healthy and PD subjects.

  20. Practice Parameter: treatment of Parkinson disease with motor fluctuations and dyskinesia (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology.

    Pahwa, R; Factor, S A; Lyons, K E; Ondo, W G; Gronseth, G; Bronte-Stewart, H; Hallett, M; Miyasaki, J; Stevens, J; Weiner, W J

    2006-04-11

    To make evidence-based treatment recommendations for the medical and surgical treatment of patients with Parkinson disease (PD) with levodopa-induced motor fluctuations and dyskinesia. To that end, five questions were addressed. 1. Which medications reduce off time? 2. What is the relative efficacy of medications in reducing off time? 3. Which medications reduce dyskinesia? 4. Does deep brain stimulation (DBS) of the subthalamic nucleus (STN), globus pallidus interna (GPi), or ventral intermediate (VIM) nucleus of the thalamus reduce off time, dyskinesia, and antiparkinsonian medication usage and improve motor function? 5. Which factors predict improvement after DBS? A 10-member committee including movement disorder specialists and general neurologists evaluated the available evidence based on a structured literature review including MEDLINE, EMBASE, and Ovid databases from 1965 through June 2004. 1. Entacapone and rasagiline should be offered to reduce off time (Level A). Pergolide, pramipexole, ropinirole, and tolcapone should be considered to reduce off time (Level B). Apomorphine, cabergoline, and selegiline may be considered to reduce off time (Level C). 2. The available evidence does not establish superiority of one medicine over another in reducing off time (Level B). Sustained release carbidopa/levodopa and bromocriptine may be disregarded to reduce off time (Level C). 3. Amantadine may be considered to reduce dyskinesia (Level C). 4. Deep brain stimulation of the STN may be considered to improve motor function and reduce off time, dyskinesia, and medication usage (Level C). There is insufficient evidence to support or refute the efficacy of DBS of the GPi or VIM nucleus of the thalamus in reducing off time, dyskinesia, or medication usage, or to improve motor function. 5. Preoperative response to levodopa predicts better outcome after DBS of the STN (Level B).

  1. Target Selection Recommendations Based on Impact of Deep Brain Stimulation Surgeries on Nonmotor Symptoms of Parkinson′s Disease

    Xiao-Hong Wang

    2015-01-01

    Full Text Available Objective: This review examines the evidence that deep brain stimulation (DBS has extensive impact on nonmotor symptoms (NMSs of patients with Parkinson′s disease (PD. Data Sources: We retrieved information from the PubMed database up to September, 2015, using various search terms and their combinations including PD, NMSs, DBS, globus pallidus internus (GPi, subthalamic nucleus (STN, and ventral intermediate thalamic nucleus. Study Selection: We included data from peer-reviewed journals on impacts of DBS on neuropsychological profiles, sensory function, autonomic symptoms, weight changes, and sleep disturbances. For psychological symptoms and cognitive impairment, we tried to use more reliable proofs: Random, control, multicenter, large sample sizes, and long period follow-up clinical studies. We categorized the NMSs into four groups: those that would improve definitively following DBS; those that are not significantly affected by DBS; those that remain controversial on their surgical benefit; and those that can be worsened by DBS. Results: In general, it seems to be an overall beneficial effect of DBS on NMSs, such as sensory, sleep, gastrointestinal, sweating, cardiovascular, odor, urological symptoms, and sexual dysfunction, GPi-DBS may produce similar results; Both STN and Gpi-DBS are safe with regard to cognition and psychology over long-term follow-up, though verbal fluency decline is related to DBS; The impact of DBS on behavioral addictions and dysphagia is still uncertain. Conclusions: As the motor effects of STN-DBS and GPi-DBS are similar, NMSs may determine the target choice in surgery of future patients.

  2. Tackling psychosocial maladjustment in Parkinson's disease patients following subthalamic deep-brain stimulation: A randomised clinical trial.

    Joao Flores Alves Dos Santos

    Full Text Available Subthalamic nucleus deep brain stimulation (STN-DBS is an effective treatment for the motor and non-motor signs of Parkinson's disease (PD, however, psychological disorders and social maladjustment have been reported in about one third of patients after STN-DBS. We propose here a perioperative psychoeducation programme to limit such social and familial disruption.Nineteen PD patients and carers were included in a randomised single blind study. Social adjustment scale (SAS scores from patients and carers that received the psychoeducation programme (n = 9 were compared, both 1 and 2 years after surgery, with patients and carers with usual care (n = 10. Depression, anxiety, cognitive status, apathy, coping, parkinsonian disability, quality-of-life, carers' anxiety and burden were also analysed.Seventeen patients completed the study, 2 were excluded from the final analysis because of adverse events. At 1 year, 2/7 patients with psychoeducation and 8/10 with usual care had an aggravation in at least one domain of the SAS (p = .058. At 2 years, only 1 patient with psychoeducation suffered persistent aggravated social adjustment as compared to 8 patients with usual care (p = .015. At 1 year, anxiety, depression and instrumental coping ratings improved more in the psychoeducation than in the usual care group (p = .038, p = .050 and p = .050, respectively. No significant differences were found between groups for quality of life, cognitive status, apathy or motor disability.Our results suggest that a perioperative psychoeducation programme prevents social maladjustment in PD patients following STN-DBS and improves anxiety and depression compared to usual care. These preliminary data need to be confirmed in larger studies.

  3. Optimized programming algorithm for cylindrical and directional deep brain stimulation electrodes.

    Anderson, Daria Nesterovich; Osting, Braxton; Vorwerk, Johannes; Dorval, Alan D; Butson, Christopher R

    2018-04-01

    Deep brain stimulation (DBS) is a growing treatment option for movement and psychiatric disorders. As DBS technology moves toward directional leads with increased numbers of smaller electrode contacts, trial-and-error methods of manual DBS programming are becoming too time-consuming for clinical feasibility. We propose an algorithm to automate DBS programming in near real-time for a wide range of DBS lead designs. Magnetic resonance imaging and diffusion tensor imaging are used to build finite element models that include anisotropic conductivity. The algorithm maximizes activation of target tissue and utilizes the Hessian matrix of the electric potential to approximate activation of neurons in all directions. We demonstrate our algorithm's ability in an example programming case that targets the subthalamic nucleus (STN) for the treatment of Parkinson's disease for three lead designs: the Medtronic 3389 (four cylindrical contacts), the direct STNAcute (two cylindrical contacts, six directional contacts), and the Medtronic-Sapiens lead (40 directional contacts). The optimization algorithm returns patient-specific contact configurations in near real-time-less than 10 s for even the most complex leads. When the lead was placed centrally in the target STN, the directional leads were able to activate over 50% of the region, whereas the Medtronic 3389 could activate only 40%. When the lead was placed 2 mm lateral to the target, the directional leads performed as well as they did in the central position, but the Medtronic 3389 activated only 2.9% of the STN. This DBS programming algorithm can be applied to cylindrical electrodes as well as novel directional leads that are too complex with modern technology to be manually programmed. This algorithm may reduce clinical programming time and encourage the use of directional leads, since they activate a larger volume of the target area than cylindrical electrodes in central and off-target lead placements.

  4. Molecular fingerprinting of Cryptosporidium oocysts isolated during water monitoring.

    Nichols, Rosely A B; Campbell, Brian M; Smith, Huw V

    2006-08-01

    We developed and validated a PCR-based method for identifying Cryptosporidium species and/or genotypes present on oocyst-positive microscope slides. The method involves removing coverslips and oocysts from previously examined slides followed by DNA extraction. We tested four loci, the 18S rRNA gene (N18SDIAG and N18SXIAO), the Cryptosporidium oocyst wall protein (COWP) gene (STN-COWP), and the dihydrofolate reductase (dhfr) gene (by multiplex allele-specific PCR), for amplifying DNA from low densities of Cryptosporidium parvum oocysts experimentally seeded onto microscope slides. The N18SDIAG locus performed consistently better than the other three tested. Purified oocysts from humans infected with C. felis, C. hominis, and C. parvum and commercially purchased C. muris were used to determine the sensitivities of three loci (N18SDIAG, STN-COWP, and N18SXIAO) to detect low oocyst densities. The N18SDIAG primers provided the greatest number of positive results, followed by the N18SXIAO primers and then the STN-COWP primers. Some oocyst-positive slides failed to generate a PCR product at any of the loci tested, but the limit of sensitivity is not entirely based on oocyst number. Sixteen of 33 environmental water monitoring Cryptosporidium slides tested (oocyst numbers ranging from 1 to 130) contained mixed Cryptosporidium species. The species/genotypes most commonly found were C. muris or C. andersoni, C. hominis or C. parvum, and C. meleagridis or Cryptosporidium sp. cervine, ferret, and mouse genotypes. Oocysts on one slide contained Cryptosporidium muskrat genotype II DNA.

  5. Motor and Nonmotor Circuitry Activation Induced by Subthalamic Nucleus Deep Brain Stimulation in Patients With Parkinson Disease: Intraoperative Functional Magnetic Resonance Imaging for Deep Brain Stimulation.

    Knight, Emily J; Testini, Paola; Min, Hoon-Ki; Gibson, William S; Gorny, Krzysztof R; Favazza, Christopher P; Felmlee, Joel P; Kim, Inyong; Welker, Kirk M; Clayton, Daniel A; Klassen, Bryan T; Chang, Su-youne; Lee, Kendall H

    2015-06-01

    To test the hypothesis suggested by previous studies that subthalamic nucleus (STN) deep brain stimulation (DBS) in patients with Parkinson disease would affect the activity of motor and nonmotor networks, we applied intraoperative functional magnetic resonance imaging (fMRI) to patients receiving DBS. Ten patients receiving STN DBS for Parkinson disease underwent intraoperative 1.5-T fMRI during high-frequency stimulation delivered via an external pulse generator. The study was conducted between January 1, 2013, and September 30, 2014. We observed blood oxygen level-dependent (BOLD) signal changes (false discovery rate <0.001) in the motor circuitry (including the primary motor, premotor, and supplementary motor cortices; thalamus; pedunculopontine nucleus; and cerebellum) and in the limbic circuitry (including the cingulate and insular cortices). Activation of the motor network was observed also after applying a Bonferroni correction (P<.001) to the data set, suggesting that across patients, BOLD changes in the motor circuitry are more consistent compared with those occurring in the nonmotor network. These findings support the modulatory role of STN DBS on the activity of motor and nonmotor networks and suggest complex mechanisms as the basis of the efficacy of this treatment modality. Furthermore, these results suggest that across patients, BOLD changes in the motor circuitry are more consistent than those in the nonmotor network. With further studies combining the use of real-time intraoperative fMRI with clinical outcomes in patients treated with DBS, functional imaging techniques have the potential not only to elucidate the mechanisms of DBS functioning but also to guide and assist in the surgical treatment of patients affected by movement and neuropsychiatric disorders. clinicaltrials.gov Identifier: NCT01809613. Copyright © 2015 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

  6. Subthalamic nucleus electrical stimulation modulates calcium activity of nigral astrocytes.

    Elodie Barat

    Full Text Available The substantia nigra pars reticulata (SNr is a major output nucleus of the basal ganglia, delivering inhibitory efferents to the relay nuclei of the thalamus. Pathological hyperactivity of SNr neurons is known to be responsible for some motor disorders e.g. in Parkinson's disease. One way to restore this pathological activity is to electrically stimulate one of the SNr input, the excitatory subthalamic nucleus (STN, which has emerged as an effective treatment for parkinsonian patients. The neuronal network and signal processing of the basal ganglia are well known but, paradoxically, the role of astrocytes in the regulation of SNr activity has never been studied.In this work, we developed a rat brain slice model to study the influence of spontaneous and induced excitability of afferent nuclei on SNr astrocytes calcium activity. Astrocytes represent the main cellular population in the SNr and display spontaneous calcium activities in basal conditions. Half of this activity is autonomous (i.e. independent of synaptic activity while the other half is dependent on spontaneous glutamate and GABA release, probably controlled by the pace-maker activity of the pallido-nigral and subthalamo-nigral loops. Modification of the activity of the loops by STN electrical stimulation disrupted this astrocytic calcium excitability through an increase of glutamate and GABA releases. Astrocytic AMPA, mGlu and GABA(A receptors were involved in this effect.Astrocytes are now viewed as active components of neural networks but their role depends on the brain structure concerned. In the SNr, evoked activity prevails and autonomous calcium activity is lower than in the cortex or hippocampus. Our data therefore reflect a specific role of SNr astrocytes in sensing the STN-GPe-SNr loops activity and suggest that SNr astrocytes could potentially feedback on SNr neuronal activity. These findings have major implications given the position of SNr in the basal ganglia network.

  7. Local field potential recordings in a non-human primate model of Parkinsons disease using the Activa PC + S neurostimulator

    Connolly, Allison T.; Muralidharan, Abirami; Hendrix, Claudia; Johnson, Luke; Gupta, Rahul; Stanslaski, Scott; Denison, Tim; Baker, Kenneth B.; Vitek, Jerrold L.; Johnson, Matthew D.

    2015-12-01

    Objective. Using the Medtronic Activa® PC + S system, this study investigated how passive joint manipulation, reaching behavior, and deep brain stimulation (DBS) modulate local field potential (LFP) activity in the subthalamic nucleus (STN) and globus pallidus (GP). Approach. Five non-human primates were implanted unilaterally with one or more DBS leads. LFPs were collected in montage recordings during resting state conditions and during motor tasks that facilitate the expression of parkinsonian motor signs. These recordings were made in the naïve state in one subject, in the parkinsonian state in two subjects, and in both naïve and parkinsonian states in two subjects. Main results. LFPs measured at rest were consistent over time for a given recording location and parkinsonian state in a given subject; however, LFPs were highly variable between subjects, between and within recording locations, and across parkinsonian states. LFPs in both naïve and parkinsonian states across all recorded nuclei contained a spectral peak in the beta band (10-30 Hz). Moreover, the spectral content of recorded LFPs was modulated by passive and active movement of the subjects’ limbs. LFPs recorded during a cued-reaching task displayed task-related beta desynchronization in STN and GP. The bidirectional capabilities of the Activa® PC + S also allowed for recording LFPs while delivering DBS. The therapeutic effect of STN DBS on parkinsonian rigidity outlasted stimulation for 30-60 s, but there was no correlation with beta band power. Significance. This study emphasizes (1) the variability in spontaneous LFPs amongst subjects and (2) the value of using the Activa® PC + S system to record neural data in the context of behavioral tasks that allow one to evaluate a subject’s symptomatology.

  8. Motor outcome and electrode location in deep brain stimulation in Parkinson's disease.

    Koivu, Maija; Huotarinen, Antti; Scheperjans, Filip; Laakso, Aki; Kivisaari, Riku; Pekkonen, Eero

    2018-05-30

    To evaluate the efficacy and adverse effects of subthalamic deep brain stimulation (STN-DBS) in patients with advanced Parkinson's disease (PD) and the possible correlation between electrode location and clinical outcome. We retrospectively reviewed 87 PD-related STN-DBS operations at Helsinki University Hospital (HUH) from 2007 to 2014. The changes of Unified Parkinson's Disease Rating Scale (UPDRS) part III score, Hoehn & Yahr stage, antiparkinson medication, and adverse effects were studied. We estimated the active electrode location in three different coordinate systems: direct visual analysis of MRI correlated to brain atlas, location in relation to the nucleus borders and location in relation to the midcommisural point. At 6 months after operation, both levodopa equivalent doses (LEDs; 35%, Wilcoxon signed-rank test = 0.000) and UPDRS part III scores significantly decreased (38%, Wilcoxon signed-rank test = 0.000). Four patients (5%) suffered from moderate DBS-related dysarthria. The generator and electrodes had to be removed in one patient due to infection (1%). Electrode coordinates in the three coordinate systems correlated well with each other. On the left side, more ventral location of the active contact was associated with greater LED decrease. STN-DBS improves motor function and enables the reduction in antiparkinson medication with an acceptable adverse effect profile. More ventral location of the active contact may allow stronger LED reduction. Further research on the correlation between contact location, clinical outcome, and LED reduction is warranted. © 2018 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.

  9. Quality of life outcome after subthalamic stimulation in Parkinson's disease depends on age.

    Dafsari, Haidar S; Reker, Paul; Stalinski, Lisa; Silverdale, Monty; Rizos, Alexandra; Ashkan, Keyoumars; Barbe, Michael T; Fink, Gereon R; Evans, Julian; Steffen, Julia; Samuel, Michael; Dembek, Till A; Visser-Vandewalle, Veerle; Antonini, Angelo; Ray-Chaudhuri, K; Martinez-Martin, Pablo; Timmermann, Lars

    2018-01-01

    The purpose of this study was to investigate how quality of life outcome after bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) in Parkinson's disease (PD) depends on age. In this prospective, open-label, multicenter study including 120 PD patients undergoing bilateral STN-DBS, we investigated the PDQuestionnaire-8 (PDQ-8), Unified PD Rating Scale-III, Scales for Outcomes in PD-motor examination, complications, activities of daily living, and levodopa equivalent daily dose preoperatively and at 5 months follow-up. Significant changes at follow-up were analyzed with Wilcoxon signed-rank test and Bonferroni correction for multiple comparisons. To explore the influence of age post hoc, the patients were classified into 3 age groups (≤59, 60-69, ≥70 years). Intragroup changes were analyzed with Wilcoxon signed-rank and intergroup differences with Kruskal-Wallis tests. The strength of clinical responses was evaluated using effect size. The PDQuestionnaire-8, Scales for Outcomes in PD-motor complications, activities of daily living, and levodopa equivalent daily dose significantly improved in the overall cohort and all age groups with no significant intergroup differences. However, PDQuestionnaire-8 effect sizes for age groups ≤59, 60 to 69, and ≥70 years, respectively, were strong, moderate, and small. Furthermore, PDQuestionnaire-8 domain analyses revealed that all domains except cognition and emotional well-being significantly improved in patients aged ≤59 years, whereas only communication, activities of daily living, and stigma improved in patients aged 60-69 years, and activities of daily living and stigma in patients aged ≥70 years. Although quality of life, motor complications, and activities of daily living significantly improved in all age groups after bilateral STN-DBS, the beneficial effect on overall quality of life was more pronounced and affected a wider range of quality of life domains in younger patients. © 2017 International

  10. Lead intoxication induces noradrenaline depletion, motor nonmotor disabilities, and changes in the firing pattern of subthalamic nucleus neurons.

    Sabbar, M; Delaville, C; De Deurwaerdère, P; Benazzouz, A; Lakhdar-Ghazal, N

    2012-05-17

    Lead intoxication has been suggested as a high risk factor for the development of Parkinson disease. However, its impact on motor and nonmotor functions and the mechanism by which it can be involved in the disease are still unclear. In the present study, we studied the effects of lead intoxication on the following: (1) locomotor activity using an open field actimeter and motor coordination using the rotarod test, (2) anxiety behavior using the elevated plus maze, (3) "depression-like" behavior using sucrose preference test, and (4) subthalamic nucleus (STN) neuronal activity using extracellular single unit recordings. Male Sprague-Dawley rats were treated once a day with lead acetate or sodium acetate (20 mg/kg/d i.p.) during 3 weeks. The tissue content of monoamines was used to determine alteration of these systems at the end of experiments. Results show that lead significantly reduced exploratory activity, locomotor activity and the time spent on the rotarod bar. Furthermore, lead induced anxiety but not "depressive-like" behavior. The electrophysiological results show that lead altered the discharge pattern of STN neurons with an increase in the number of bursting and irregular cells without affecting the firing rate. Moreover, lead intoxication resulted in a decrease of tissue noradrenaline content without any change in the levels of dopamine and serotonin. Together, these results show for the first time that lead intoxication resulted in motor and nonmotor behavioral changes paralleled by noradrenaline depletion and changes in the firing activity of STN neurons, providing evidence consistent with the induction of atypical parkinsonian-like deficits. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

  11. The Impact of Subthalamic Deep Brain Stimulation on Sleep-Wake Behavior: A Prospective Electrophysiological Study in 50 Parkinson Patients.

    Baumann-Vogel, Heide; Imbach, Lukas L; Sürücü, Oguzkan; Stieglitz, Lennart; Waldvogel, Daniel; Baumann, Christian R; Werth, Esther

    2017-05-01

    This prospective observational study was designed to systematically examine the effect of subthalamic deep brain stimulation (DBS) on subjective and objective sleep-wake parameters in Parkinson patients. In 50 consecutive Parkinson patients undergoing subthalamic DBS, we assessed motor symptoms, medication, the position of DBS electrodes within the subthalamic nucleus (STN), subjective sleep-wake parameters, 2-week actigraphy, video-polysomnography studies, and sleep electroencepahalogram frequency and dynamics analyses before and 6 months after surgery. Subthalamic DBS improved not only motor symptoms and reduced daily intake of dopaminergic agents but also enhanced subjective sleep quality and reduced sleepiness (Epworth Sleepiness Scale: -2.1 ± 3.8, p sleep efficiency (+5.2 ± 17.6%, p = .005) and deep sleep (+11.2 ± 32.2 min, p = .017) and increased accumulation of slow-wave activity over the night (+41.0 ± 80.0%, p = .005). Rapid eye movement sleep features were refractory to subthalamic DBS, and the dynamics of sleep as assessed by state space analyses did not normalize. Increased sleep efficiency was associated with active electrode contact localization more distant from the ventral margin of the left subthalamic nucleus. Subthalamic DBS deepens and consolidates nocturnal sleep and improves daytime wakefulness in Parkinson patients, but several outcomes suggest that it does not normalize sleep. It remains elusive whether modulated activity in the STN directly contributes to changes in sleep-wake behavior, but dorsal positioning of electrodes within the STN is linked to improved sleep-wake outcomes. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

  12. Are there adaptive changes in the human brain of patients with Parkinson's disease treated with long-term deep brain stimulation of the subthalamic nucleus? A 4-year follow-up study with regional cerebral blood flow SPECT

    Sestini, Stelvio; Castagnoli, Antonio [Ospedale Misericordia e Dolce, Department of Diagnostic Imaging, Nuclear Medicine Unit, Prato (Italy); Pupi, Alberto [University of Florence, Department of Clinical Physiopathology, Nuclear Medicine Unit, Florence (Italy); Ammannati, Franco; Silvia, Ramat; Sorbi, Sandro [University of Florence, Department of Neurological and Psychiatric Sciences, Florence (Italy)

    2007-10-15

    The aim of this follow-up study was to assess persistent motor and regional cerebral blood flow (rCBF) changes in patients with Parkinson's disease (PD) treated with high-frequency deep brain stimulation (DBS) of the subthalamic nucleus (STN). Ten PD patients with STN-DBS underwent three rCBF SPECT studies at rest, once preoperatively in the off-drug condition (T{sub 0}), and twice postoperatively in the off-drug/off-stimulation conditions at 5 {+-} 2 (T{sub 1}) and 42 {+-} 7 months (T{sub 2}). Patients were assessed using the UPDRS, H and Y and S and E scales. SPM was used to investigate baseline rCBF changes from the preoperative condition to the postoperative conditions and the relationship between rCBF and UPDRS scores used as covariate of interest. Parkinsonian patients showed a clinical improvement which was significant only on follow-up at 42 months. The main effect of treatment from T{sub 0} to T{sub 1} was to produce baseline rCBF increases in the pre-supplementary motor area (pre-SMA), premotor cortex and somatosensory association cortex. From T{sub 1} to T{sub 2} a further baseline rCBF increase was detected in the pre-SMA (p < 0.0001). A correlation was detected between the slight improvement in motor scores and the rCBF increase in the pre-SMA (p < 0.0001), which is known to play a crucial role in clinical progression. Our study suggests the presence of adaptive functional changes in the human brain of PD patients treated with long-term STN-DBS. Such adaptive processes seem to occur in the pre-SMA and to play only a slightly beneficial role in terms of functional compensation of motor impairment. (orig.)

  13. The emergence of two anti-phase oscillatory neural populations in a computational model of the Parkinsonian globus pallidus

    Robert John Merrison-Hort

    2013-12-01

    Full Text Available Experiments in rodent models of Parkinson's Disease have demonstrated a prominent increase of oscillatory firing patterns in neurons within the Parkinsonian globus pallidus (GP which may underlie some of the motor symptoms of the disease. There are two main pathways from the cortex to GP: via the striatum and via the subthalamic nucleus (STN, but it is not known how these inputs sculpt the pathological pallidal firing patterns. To study this we developed a novel neural network model of conductance-based spiking pallidal neurons with cortex-modulated input from STN neurons. Our results support the hypothesis that entrainment occurs primarily via the subthalamic pathway. We find that as a result of the interplay between excitatory input from the STN and mutual inhibitory coupling between GP neurons, a homogeneous population of GP neurons demonstrates a self-organising dynamical behaviour where two groups of neurons emerge: one spiking in-phase with the cortical rhythm and the other in anti-phase. This finding mirrors what is seen in recordings from the GP of rodents that have had Parkinsonism induced via brain lesions. Our model also includes downregulation of Hyperpolarization-activated Cyclic Nucleotide-gated (HCN channels in response to burst firing of GP neurons, since this has been suggested as a possible mechanism for the emergence of Parkinsonian activity. We found that the downregulation of HCN channels provides even better correspondence with experimental data but that it is not essential in order for the two groups of oscillatory neurons to appear. We discuss how the influence of inhibitory striatal input will strengthen our results.

  14. Subthalamic nucleus electrical stimulation modulates calcium activity of nigral astrocytes.

    Barat, Elodie; Boisseau, Sylvie; Bouyssières, Céline; Appaix, Florence; Savasta, Marc; Albrieux, Mireille

    2012-01-01

    The substantia nigra pars reticulata (SNr) is a major output nucleus of the basal ganglia, delivering inhibitory efferents to the relay nuclei of the thalamus. Pathological hyperactivity of SNr neurons is known to be responsible for some motor disorders e.g. in Parkinson's disease. One way to restore this pathological activity is to electrically stimulate one of the SNr input, the excitatory subthalamic nucleus (STN), which has emerged as an effective treatment for parkinsonian patients. The neuronal network and signal processing of the basal ganglia are well known but, paradoxically, the role of astrocytes in the regulation of SNr activity has never been studied. In this work, we developed a rat brain slice model to study the influence of spontaneous and induced excitability of afferent nuclei on SNr astrocytes calcium activity. Astrocytes represent the main cellular population in the SNr and display spontaneous calcium activities in basal conditions. Half of this activity is autonomous (i.e. independent of synaptic activity) while the other half is dependent on spontaneous glutamate and GABA release, probably controlled by the pace-maker activity of the pallido-nigral and subthalamo-nigral loops. Modification of the activity of the loops by STN electrical stimulation disrupted this astrocytic calcium excitability through an increase of glutamate and GABA releases. Astrocytic AMPA, mGlu and GABA(A) receptors were involved in this effect. Astrocytes are now viewed as active components of neural networks but their role depends on the brain structure concerned. In the SNr, evoked activity prevails and autonomous calcium activity is lower than in the cortex or hippocampus. Our data therefore reflect a specific role of SNr astrocytes in sensing the STN-GPe-SNr loops activity and suggest that SNr astrocytes could potentially feedback on SNr neuronal activity. These findings have major implications given the position of SNr in the basal ganglia network.

  15. Local Fields in Human Subthalamic Nucleus Track the Lead-up to Impulsive Choices

    John M. Pearson

    2017-11-01

    Full Text Available The ability to adaptively minimize not only motor but cognitive symptoms of neurological diseases, such as Parkinson's Disease (PD and obsessive-compulsive disorder (OCD, is a primary goal of next-generation deep brain stimulation (DBS devices. On the basis of studies demonstrating a link between beta-band synchronization and severity of motor symptoms in PD, the minimization of beta band activity has been proposed as a potential training target for closed-loop DBS. At present, no comparable signal is known for the impulsive side effects of PD, though multiple studies have implicated theta band activity within the subthalamic nucleus (STN, the site of DBS treatment, in processes of conflict monitoring and countermanding. Here, we address this challenge by recording from multiple independent channels within the STN in a self-paced decision task to test whether these signals carry information sufficient to predict stopping behavior on a trial-by-trial basis. As in previous studies, we found that local field potentials (LFPs exhibited modulations preceding self-initiated movements, with power ramping across multiple frequencies during the deliberation period. In addition, signals showed phasic changes in power around the time of decision. However, a prospective model that attempted to use these signals to predict decision times showed effects of risk level did not improve with the addition of LFPs as regressors. These findings suggest information tracking the lead-up to impulsive choices is distributed across multiple frequency scales in STN, though current techniques may not possess sufficient signal-to-noise ratios to predict—and thus curb—impulsive behavior on a moment-to-moment basis.

  16. Avoiding Internal Capsule Stimulation With a New Eight-Channel Steering Deep Brain Stimulation Lead.

    van Dijk, Kees J; Verhagen, Rens; Bour, Lo J; Heida, Ciska; Veltink, Peter H

    2017-10-15

    Novel deep brain stimulation (DBS) lead designs are currently entering the market, which are hypothesized to provide a way to steer the stimulation field away from neural populations responsible for side effects and towards populations responsible for beneficial effects. The objective of this study is to assess the performances of a new eight channel steering-DBS lead and compare this with a conventional cylindrical contact (CC) lead. The two leads were evaluated in a finite element electric field model combined with multicompartment neuron and axon models, representing the internal capsule (IC) fibers and subthalamic nucleus (STN) cells. We defined the optimal stimulation setting as the configuration that activated the highest percentage of STN cells, without activating any IC fibers. With this criterion, we compared monopolar stimulation using a single contact of the steering-DBS lead and CC lead, on three locations and four orientations of the lead. In addition, we performed a current steering test case by dividing the current over two contacts with the steering-DBS lead in its worst-case orientation. In most cases, the steering-DBS lead is able to stimulate a significantly higher percentage of STN cells compared to the CC lead using single contact stimulation or using a two contact current steering protocol when there is approximately a 1 mm displacement of the CC lead. The results also show that correct placement and orientation of the lead in the target remains an important aspect in achieving the optimal stimulation outcome. Currently, clinical trials are set up in Europe with a similar design as the steering-DBS lead. Our results illustrate the importance of the orientation of the new steering-DBS lead in avoiding side effects induced by stimulation of IC fibers. Therefore, in clinical trials sufficient attention should be paid to implanting the steering DBS-lead in the most effective orientation. © 2017 International Neuromodulation Society.

  17. Simulating the Effects of Short-Term Synaptic Plasticity on Postsynaptic Dynamics in the Globus Pallidus

    Moran eBrody

    2013-08-01

    Full Text Available The rat globus pallidus (GP is one of the nuclei of the basal ganglia and plays an important role in a variety of motor and cognitive processes. In vivo studies have shown that repetitive stimulation evokes complex modulations of GP activity. In vitro and computational studies have suggested that short-term synaptic plasticity (STP could be one of the underlying mechanisms. The current study used simplified single compartment modeling to explore the possible effect of STP on the activity of GP neurons during low and high frequency stimulation. To do this we constructed a model of a GP neuron connected to a small network of neurons from the three major input sources to GP neurons: striatum (Str, subthalamic nucleus (STN and GP collaterals. All synapses were implemented with a kinetic model of STP. The in vitro recordings of responses to low frequency repetitive stimulation were highly reconstructed, including rate changes and locking to the stimulus. Mainly involved were fast forms of plasticity which have been found at these synapses. . The simulations were qualitatively compared to a data set previously recorded in vitro in our lab. Reconstructions of experimental responses to high frequency stimulation required adding slower forms of plasticity to the STN and GP collateral synapses, as well as adding metabotropic receptors to the STN-GP synapses. These finding suggest the existence of as yet unreported slower short-term dynamics in the GP. The computational model made additional predictions about GP activity during low and high frequency stimulation that may further our understanding of the mechanisms underlying repetative stimulation of the GP.

  18. Non-amidated and amidated members of the C-type allatostatin (AST-C) family are differentially distributed in the stomatogastric nervous system of the American lobster, Homarus americanus.

    Christie, Andrew E; Miller, Alexandra; Fernandez, Rebecca; Dickinson, Evyn S; Jordan, Audrey; Kohn, Jessica; Youn, Mina C; Dickinson, Patsy S

    2018-01-13

    The crustacean stomatogastric nervous system (STNS) is a well-known model for investigating neuropeptidergic control of rhythmic behavior. Among the peptides known to modulate the STNS are the C-type allatostatins (AST-Cs). In the lobster, Homarus americanus, three AST-Cs are known. Two of these, pQIRYHQCYFNPISCF (AST-C I) and GNGDGRLYWRCYFNAVSCF (AST-C III), have non-amidated C-termini, while the third, SYWKQCAFNAVSCFamide (AST-C II), is C-terminally amidated. Here, antibodies were generated against one of the non-amidated peptides (AST-C I) and against the amidated isoform (AST-C II). Specificity tests show that the AST-C I antibody cross-reacts with both AST-C I and AST-C III, but not AST-C II; the AST-C II antibody does not cross-react with either non-amidated peptide. Wholemount immunohistochemistry shows that both subclasses (non-amidated and amidated) of AST-C are distributed throughout the lobster STNS. Specifically, the antibody that cross-reacts with the two non-amidated peptides labels neuropil in the CoGs and the stomatogastric ganglion (STG), axons in the superior esophageal (son) and stomatogastric (stn) nerves, and ~ 14 somata in each commissural ganglion (CoG). The AST-C II-specific antibody labels neuropil in the CoGs, STG and at the junction of the sons and stn, axons in the sons and stn, ~ 42 somata in each CoG, and two somata in the STG. Double immunolabeling shows that, except for one soma in each CoG, the non-amidated and amidated peptides are present in distinct sets of neuronal profiles. The differential distributions of the two AST-C subclasses suggest that the two peptide groups are likely to serve different modulatory roles in the lobster STNS.

  19. Análise do encaminhamento das contas dos municípios brasileiros do ano de 2008 = Analysis of referral of the brazilian municipalities of accounts for the year 2008

    José Dionísio Gomes da Silva

    2010-05-01

    Full Text Available A consolidação das contas anuais dos municípios e estados que constituem a República Federativado Brasil é um instrumento que possibilita a sociedade à observação global das informaçõesconsolidadas de todos os entes da federação. Esta pesquisa tem como objetivo geral analisar se osmunicípios brasileiros encaminharam os dados de suas contas, no ano de 2008, no prazo determinadopelo Art. 51 da LRF (30 de abril. Foram utilizadas as pesquisas descritiva, bibliográfica, documental equalitativa. A coleta de dados foi realizada no sítio do Instituto Brasileiro de Geografia e Estatística(IBGE para identificar a quantidade de municípios e sua distribuição pelas regiões, e no sítio daSecretaria do Tesouro Nacional (STN, a fim de obter as datas de encaminhamento das contas dessesmunicípios. Os resultados revelaram que dos 5.563 municípios brasileiros apenas 76,54% entregaramas suas contas anuais no prazo estabelecido no Art. 51 da LRF, 19,29% enviaram depois do prazo, e,por fim, 4,17% ainda não tinham encaminhado essas informações para a Secretaria do TesouroNacional (STN, até o dia de emissão do relatório utilizado para a coleta de dados da pesquisa.The consolidation of accounts of municipalities and states that constitute the Federal Republic of Brazilis an instrument that enables the company to the global observation of the consolidated information ofall the states. This research aims at analyzing whether the municipalities forwarded data from itsaccounts in 2008, the deadline established by Article 51 of the LRF (April 30. We used descriptiveresearch, literature, documentary and qualitative. Data collection was performed at the site of theBrazilian Institute of Geography and Statistics (IBGE to identify the number of municipalities and theirdistribution by regions, and the site of the National Treasury Secretariat (STN to obtain the dates ofreferral accounts of those municipalities. The results showed that from 5563 only 76

  20. Calculation of Selected Emissions from Transport Services in Road Public Transport

    Konečný Vladimír

    2017-01-01

    Full Text Available The article deals with road public transport and its impact on the environment. According to the methodology given in EN 16258, CO2 emission value has been calculated. The input data for the calculation and the results are shown in the tables. The declaration is created according to STN CEN / TR 14310, which contains recommendations for compiling environmental reports. Finally, the comparison of the environmental impact of a bus and a passenger car, when converted to one passenger, bus has a lower CO2 emission than a passenger car in that section.

  1. The Passenger Satisfaction Survey in the Regional Integrated Public Transport System

    Martina Valaskova

    2008-11-01

    Full Text Available This article describes the Quality criteria Method of the Servicesin the Integrated Public Transport System in Slovak Republic.The proposed method is based on the detailed list of theQuality criteria of the Services in Public Transport from theview of passengers. The criteria are determined based on theSlovak Technical Norm STN EN 138 16 which is related toquality of transport. The method has been applied in RegionalIntegrated Public Transport System of Zilina (ZRIDS in theform of Passenger Quality Satisfaction Survey.

  2. Problems Related to Use of Some Terms in System Reliability Analysis

    Nadezda Hanusova

    2004-01-01

    Full Text Available The paper deals with problems of using dependability terms, defined in actual standard STN IEC 50 (191: International electrotechnical dictionary, chap. 191: Dependability and quality of service (1993, in a technical systems dependability analysis. The goal of the paper is to find a relation between terms introduced in the mentioned standard and used in the technical systems dependability analysis and rules and practices used in a system analysis of the system theory. Description of a part of the system life cycle related to reliability is used as a starting point. The part of a system life cycle is described by the state diagram and reliability relevant therms are assigned.

  3. Comparative evaluation of the impact of WRF/NMM and WRF/ARW meteorology on CMAQ simulations for PM2.5 and its related precursors during the 2006 TexAQS/GoMACCS study

    S. T. Rao

    2012-05-01

    Full Text Available This study presents a comparative evaluation of the impact of WRF-NMM and WRF-ARW meteorology on CMAQ simulations of PM2.5, its composition and related precursors over the eastern United States with the intensive observations obtained by aircraft (NOAA WP-3, ship and surface monitoring networks (AIRNow, IMPROVE, CASTNet and STN during the 2006 TexAQS/GoMACCS study. The results at the AIRNow surface sites show that both ARW-CMAQ and NMM-CMAQ reproduced day-to-day variations of observed PM2.5 and captured the majority of observed PM2.5 within a factor of 2 with a NMB value of −0.4% for ARW-CMAQ and −18% for NMM-CMAQ. Both models performed much better at the urban sites than at the rural sites, with greater underpredictions at the rural sites. Both models consistently underestimated the observed PM2.5 at the rural IMPROVE sites by −1% for the ARW-CMAQ and −19% for the NMM-CMAQ. The greater underestimations of SO42−, OC and EC by the NMM-CMAQ contributed to increased underestimation of PM2.5 at the IMPROVE sites. The NMB values for PM2.5 at the STN urban sites are 15% and −16% for the ARW-CMAQ and NMM-CMAQ, respectively. The underestimation of PM2.5 at the STN sites by the NMM-CMAQ mainly results from the underestimations of the SO42−, NH4+ and TCM components, whereas the overestimation of PM2.5 at the STN sites by the ARW-CMAQ results from the overestimations of SO42−, NO3−, and NH4+. The Comparison with WP-3 aircraft measurements reveals that both ARW-CMAQ and NMM-CMAQ have very similar model performance for vertical profiles for PM2.5 chemical components (SO42−, NH4+ and related gaseous species (HNO3, SO2, NH3, isoprene, toluene, terpenes as both models used the same chemical mechanisms and emissions. The results of ship along the coast of southeastern Texas over the Gulf of Mexico show that both models captured the temporal variations and broad synoptic change seen in the observed HCHO and acetaldehyde with the means NMB 2.

  4. Abrasion Resistance of as-Cast High-Chromium Cast Iron

    Pokusová Marcela

    2014-12-01

    Full Text Available High chromium cast irons are widely used as abrasion resistant materials. Their properties and wear resistance depend on carbides and on the nature of the matrix supporting these carbides. The paper presents test results of irons which contain (in wt.% 18-22 Cr and 2-5 C, and is alloyed by 1.7 Mo + 5 Ni + 2 Mn to improve the toughness. Tests showed as-cast irons with mostly austenitic matrix achieved hardness 36-53 HRC but their relative abrasion-resistance was higher than the tool steel STN 19436 heat treated on hardness 60 HRC.

  5. Subthalamic nucleus stimulation affects theory of mind network: a PET study in Parkinson's disease.

    Julie Péron

    Full Text Available BACKGROUND: There appears to be an overlap between the limbic system, which is modulated by subthalamic nucleus (STN deep brain stimulation (DBS in Parkinson's disease (PD, and the brain network that mediates theory of mind (ToM. Accordingly, the aim of the present study was to investigate the effects of STN DBS on ToM of PD patients and to correlate ToM modifications with changes in glucose metabolism. METHODOLOGY/PRINCIPAL FINDINGS: To this end, we conducted (18FDG-PET scans in 13 PD patients in pre- and post-STN DBS conditions and correlated changes in their glucose metabolism with modified performances on the Eyes test, a visual ToM task requiring them to describe thoughts or feelings conveyed by photographs of the eye region. Postoperative PD performances on this emotion recognition task were significantly worse than either preoperative PD performances or those of healthy controls (HC, whereas there was no significant difference between preoperative PD and HC. Conversely, PD patients in the postoperative condition performed within the normal range on the gender attribution task included in the Eyes test. As far as the metabolic results are concerned, there were correlations between decreased cerebral glucose metabolism and impaired ToM in several cortical areas: the bilateral cingulate gyrus (BA 31, right middle frontal gyrus (BA 8, 9 and 10, left middle frontal gyrus (BA 6, temporal lobe (fusiform gyrus, BA 20, bilateral parietal lobe (right BA 3 and right and left BA 7 and bilateral occipital lobe (BA 19. There were also correlations between increased cerebral glucose metabolism and impaired ToM in the left superior temporal gyrus (BA 22, left inferior frontal gyrus (BA 13 and BA 47 and right inferior frontal gyrus (BA 47. All these structures overlap with the brain network that mediates ToM. CONCLUSION/SIGNIFICANCE: These results seem to confirm that STN DBS hinders the ability to infer the mental states of others and modulates a

  6. Dual orexin receptor antagonist 12 inhibits expression of proteins in neurons and glia implicated in peripheral and central sensitization.

    Cady, R J; Denson, J E; Sullivan, L Q; Durham, P L

    2014-06-06

    Sensitization and activation of trigeminal nociceptors is implicated in prevalent and debilitating orofacial pain conditions including temporomandibular joint (TMJ) disorders. Orexins are excitatory neuropeptides that function to regulate many physiological processes and are reported to modulate nociception. To determine the role of orexins in an inflammatory model of trigeminal activation, the effects of a dual orexin receptor antagonist (DORA-12) on levels of proteins that promote peripheral and central sensitization and changes in nocifensive responses were investigated. In adult male Sprague-Dawley rats, mRNA for orexin receptor 1 (OX₁R) and receptor 2 (OX₂R) were detected in trigeminal ganglia and spinal trigeminal nucleus (STN). OX₁R immunoreactivity was localized primarily in neuronal cell bodies in the V3 region of the ganglion and in laminas I-II of the STN. Animals injected bilaterally with complete Freund's adjuvant (CFA) in the TMJ capsule exhibited increased expression of P-p38, P-ERK, and lba1 in trigeminal ganglia and P-ERK and lba1 in the STN at 2 days post injection. However, levels of each of these proteins in rats receiving daily oral DORA-12 were inhibited to near basal levels. Similarly, administration of DORA-12 on days 3 and 4 post CFA injection in the TMJ effectively inhibited the prolonged stimulated expression of protein kinase A, NFkB, and Iba1 in the STN on day 5 post injection. While injection of CFA mediated a nocifensive response to mechanical stimulation of the orofacial region at 2h and 3 and 5 days post injection, treatment with DORA-12 suppressed the nocifensive response on day 5. Somewhat surprisingly, nocifensive responses were again observed on day 10 post CFA stimulation in the absence of daily DORA-12 administration. Our results provide evidence that DORA-12 can inhibit CFA-induced stimulation of trigeminal sensory neurons by inhibiting expression of proteins associated with sensitization of peripheral and central

  7. Expressão de sulfomucinas e de carboidratos de mucinas simples no esôfago de Barrett Expression of sulphomucins and simple-mucin type carbohydrate in Barrett's esophagus

    Frederico Henrique C. Melo

    2007-04-01

    Full Text Available INTRODUÇÃO: A expressão de mucinas sulfatadas e de antígenos de carboidratos simples de mucinas tem sido relacionada com o risco de transformação maligna no trato gastrintestinal. OBJETIVOS: Avaliar a expressão de mucinas sulfatadas e dos antígenos Tn, sTn, T e sT no esôfago de Barrett (EB. MATERIAL E MÉTODO: Estudaram-se 50 biópsias de EB. As amostras foram processadas rotineiramente para exame histológico (hematoxilina e eosina [HE] e ácido periódico de Schiff [PAS]/azul de alcião. Cortes adicionais foram corados para detecção de mucinas sulfatadas (diamina férrica e dos antígenos Tn, sTn, T e sT por imuno-histoquímica. O EB foi classificado quanto aos subtipos de metaplasia intestinal e sua extensão nas amostras. A expressão de Tn, sTn, T e sT no EB foi discriminada quanto à positividade em células caliciformes e colunares. RESULTADOS: Detectou-se metaplasia intestinal incompleta com secreção de sulfomucinas em 47 casos; em três não se identificou a lesão nos cortes realizados para a histoquímica. Observou-se metaplasia intestinal tipo III em 44 dos 47 casos analisados (93,6% e do tipo II isoladamente em três casos (6,4%. Não se detectou metaplasia intestinal do tipo I. Tn expressou-se fortemente em células colunares em 94% dos casos e foi focal/negativo nas caliciformes; sTn exibiu forte marcação nas células caliciformes em 88% dos casos. Os demais marcadores foram negativos na maior parte dos casos (T negativo em 82% e sT em 87,8%. CONCLUSÕES: A expressão de sulfomucinas e de antígenos de carboidratos simples de mucinas foi homogênea no EB. A lesão caracterizou-se por metaplasia intestinal incompleta com extenso componente de tipo III e expressão de Tn e sTn. Esses dados sugerem que os marcadores testados não permitem discriminar lesões com diferentes potenciais de transformação maligna.BACKGROUND: The expression of sulphomucins and simple-mucin type carbohydrate antigens has been used as marker

  8. Interaction of Reinforced Elastomeric Bearings in Bridge Construction

    Nittmannová Ľubica

    2016-03-01

    Full Text Available The aim of this paper is to demonstrate the behavior of reinforced elastomeric bearings under various loads. They are made of special types of bearings. The experimental verification of these special bearings has been tested on various types of loading. The results of the experimental measurements are compared with the results of the numerical modeling and calculations according to the standard assumptions in STN EN 1337-3. In the conclusion, the results are summarized for the selected types of bearings.

  9. Case study of a physiotherapy treatment of patient with Arthritis of the wrist joints

    Liapis, Achilleas

    2016-01-01

    Title: Case study of a physiotherapy treatment of patient with Arthritis of the wrist joints. Název: Kazuistika fyzioterapeutické péče o pacienta s diagnózou artróza zápěstních kloubů Aim The aim of my bachelor thesis is to analyze the diagnosis of my patient and find a proper therapeutic plan for his health care and to prevent any further complication. Moreover I will be able to understand the function and the structure of wrist joint. Summary My bachelor thesis is divided into two main part...

  10. The deep stimulation of the sub-thalamus nucleus affects the limbic and associative circuits: a study in {sup 18}F-F.D.G. -PET in the Parkinson disease;La stimulation profonde du noyau sous thalamique affecte les circuits limbique et associatif: une etude en 18FDG-TEP dans la maladie de Parkinson

    Le Jeune, F.; Garin, E. [Centre Eugene-Marquis, Servive de medecine nucleaire, 35 - Rennes (France); Le Jeune, F.; Peron, J.; Grandjean, D.; Drapier, S.; Haegelen, C.; Garin, E.; Millet, B.; Verin, M. [Universite de Rennes-1, URU comportement et noyaux gris centraux, 35 - Rennes (France); Peron, J.; Drapier, S.; Haegelen, C.; Verin, M. [CHU Pontchaillou, service de neurologie, 35 - Rennes (France); Grandjean, D. [University of Genova, Swiss Center for Affective Sciences, Geneve (Switzerland); Millet, B. [Centre hospitalier Guillaume-Regnier, service de psychiatrie adulte, 35 - Rennes (France)

    2010-05-15

    The purpose of this study is to highlight the changes in brain metabolism in {sup 18}F.D.G.-PET to improve understanding of the non-motor functional role .This study confirms the non-motor functional role of the sub thalamic nucleus (S.T.N.) in limbic and associative circuits in humans.These results provide working hypotheses to study the correlations between neuropsychological alterations clinically diagnosed and cerebral metabolism in order to identify the neural circuits involved. (N.C.)

  11. The factors influencing microstructure and mechanical properties of ADI

    A. Vaško

    2009-01-01

    Full Text Available The paper deals with the influence of different conditions of isothermal heat treatment on microstructure and mechanical properties of austempered ductile iron (ADI. Different temperature of isothermal transformation of austenite and different holding time at this temperature were used for heat treatment of specimens. The microstructure of specimens after casting and after heat treatment was evaluated by STN EN ISO 945 and by image analysis (using Lucia software. Mechanical properties were evaluated by the tensile test, the Rockwell hardness test and fatigue tests.

  12. Tenth anniversary of CAS ONLINE service : What CAS services should be in the new era of chemical information

    Kostakos, Charles N.

    Chemical Abstracts Service celebrated 10th anniversary of CAS online information service in 1990. A speech given on the occasion reviewed history of the CAS ONLINE, in relation to its most important benefits for scientists and engineers. The development of STN international, the network through which CAS ONLINE is accessible around the world, was also discussed in the speech. The CAS ONLINE now contains a wide variety of files relating to chemical field including CA file, Registry file. CA previews,. CASREACT, CIN. MARPAT, etc for supplying chemical information worldwide.

  13. Consolidação das contas públicas: análise do cumprimento do art. 51 da LRF pelos municípios do Estado do Rio Grande do Norte = Public account consolidation: an analysis of the enforcement of LRF art. 51 by the municipalities in the State of Rio Grande do Norte

    Mauricio Corrêa da Silva

    2011-11-01

    Full Text Available A consolidação das contas tem por objetivo apresentar demonstrações financeiras de duas ou mais sociedades, como se fossem uma única entidade. As sociedades consolidadas continuam existindo juridicamente, sendo a consolidação efetuada apenas extracontabilmente. O objetivo geral desta pesquisa é analisar a situação dos municípios do Estado do Rio Grande do Norte quanto a cumprir o encaminhamento de suas contas, conforme determinado pelo Art. 51 da LRF, no período de 2000 a 2008. Para tal, foram utilizadas as pesquisas descritiva, documental, bibliográfica e qualitativa. Os dados da pesquisa foram extraídos do sítio eletrônico da Secretaria do Tesouro Nacional (STN - www.stn.fazenda.gov.br. Na pesquisa foi utilizada uma amostra intencional dos 167 municípios do Estado do Rio Grande do Norte, agrupados em quatro Mesorregiões. Os resultados revelaram que dos 167 municípios do Estado do Rio Grande do Norte, 20 municípios se encontram pendentes, em determinado ano, de encaminhar os dados de suas contas para a consolidação das contas públicas nacionais, e que a grande maioria dos municípios potiguares remeteu seus dados com atraso (após 30 de abril. Account consolidation has as its objective to present financial statements of two or more organizations, as if they were one. The consolidated organizations continue to exist from a legal perspective, with the consolidation being performed only outside an accounting viewpoint. The general objective of this research is to analyze the situation of the municipalities in the State of Rio Grande do Norte as to the enforcement on the forwarding of their accounts, determined by Art. 51 of LRF from 2000 to 2008. For such, a descriptive, documental, bibliographical and qualitative research has been used. The research data were extracted from the electronic website of the National Treasury Secretary (STN - www.stn.fazenda.gov.br. An intentional sample of the 167 municipalities of the State of

  14. Integrated Management System in construction company-effective tool of quality, environment and safety level improving

    Gašparík, Jozef

    2009-01-01

    Contribution Presents the struCture of integrated M anageMent systeM ( iMs) according to international standards ISO 9001:2008, ISO 14001:2004 and STN OHSAS 18001:2009, which consists of 3 management systems focused to quality, environment and safety of building processes. The purpose of paper is to describe basic steps concerning the development of IMS. Paper analises basic processes of IMS like company vision, IMS planning, implementing, monitoring, revive and improving. The paper presents ...

  15. Glycan elongation beyond the mucin associated Tn antigen protects tumor cells from immune-mediated killing

    Madsen, Caroline B; Lavrsen, Kirstine; Steentoft, Catharina

    2013-01-01

    are recognized as cancer associated truncated glycans, and are expressed in many adenocarcinomas, e.g. breast- and pancreatic cancer cells. To investigate the role of the cancer associated glycan truncations in immune-mediated killing we created glyco-engineered breast- and pancreatic cancer cells expressing...... only the shortest possible mucin-like glycans (Tn and STn). Glyco-engineering was performed by zinc finger nuclease (ZFN) knockout (KO) of the Core 1 enzyme chaperone COSMC, thereby preventing glycan elongation beyond the initial GalNAc residue in O-linked glycans. We find that COSMC KO in the breast...

  16. Cancer-associated autoantibodies to MUC1 and MUC4--a blinded case–control study of colorectal cancer in UK collaborative trial of ovarian cancer screening

    Pedersen, Johannes W; Gentry-Maharaj, Aleksandra; Nøstdal, Alexander

    2014-01-01

    of colorectal cancer diagnosis and healthy controls. Subsequently, the selected biomarkers were evaluated in a blinded nested case–control study using stored serum samples from among the 50,640 women randomized to the multimodal arm of the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS), where......, at 95% specificity. IgA to MUC4 glycoforms were unable to discriminate between cases and controls in the UKCTOCS sera. Additional analysis was undertaken by combining the data of MUC1-STn and MUC1-Core3 with previously generated data on autoantibodies to p53 peptides, which increased the sensitivity...

  17. Spectroscopic databases - A tool for structure elucidation

    Luksch, P [Fachinformationszentrum Karlsruhe, Gesellschaft fuer Wissenschaftlich-Technische Information mbH, Eggenstein-Leopoldshafen (Germany)

    1990-05-01

    Spectroscopic databases have developed to useful tools in the process of structure elucidation. Besides the conventional library searches, new intelligent programs have been added, that are able to predict structural features from measured spectra or to simulate for a given structure. The example of the C13NMR/IR database developed at BASF and available on STN is used to illustrate the present capabilities of online database. New developments in the field of spectrum simulation and methods for the prediction of complete structures from spectroscopic information are reviewed. (author). 10 refs, 5 figs.

  18. Deep brain stimulation for movement disorders. Considerations on 276 consecutive patients.

    Franzini, Angelo; Cordella, Roberto; Messina, Giuseppe; Marras, Carlo Efisio; Romito, Luigi Michele; Carella, Francesco; Albanese, Alberto; Rizzi, Michele; Nardocci, Nardo; Zorzi, Giovanna; Zekay, Edvin; Broggi, Giovanni

    2011-10-01

    The links between Stn DBS and advanced Parkinson disease, and between GPi DBS and dystonia are nearly universally accepted by the neurologists and neurosurgeons. Nevertheless, in some conditions, targets such as the ventral thalamus and the Zona Incerta may be considered to optimize the results and avoid the side effects. Positive and negative aspects of current DBS treatments justify the research of new targets, new stimulation programs and new hardware. Since 1993, at the Istituto Nazionale Neurologico "Carlo Besta" in Milan, 580 deep brain electrodes were implanted in 332 patients. 276 patients were affected by movement disorders. The DBS targets included Stn, GPi, Voa, Vop, Vim, CM-pf, cZi, IC. The long-term follow-up is reported and related to the chosen target. DBS gave a new therapeutic option to patients affected by severe movement disorders, and in some cases resolved life-threatening pathological conditions that would otherwise result in the death of the patient, such as in status dystonicus, and post-stroke hemiballismus. Nevertheless, the potential occurrence of severe complications still limit a wider use of DBS. At today, the use of DBS in severe movement disorders is strongly positive even if further investigations and studies are needed to unveil potential new applications, and to refine the selection criteria for the actual indications and targets. The experience of different targets may be useful to guide and tailor the target choice to the individual clinical condition.

  19. Legislation

    1996-01-01

    Nuclear Regulatory Authority of the Slovak Republic (NRA SR) developed a methodology and the NRA SR Chairman's Regulation that sets out a uniform administration procedure in collecting administration fees, for the purpose of applying the Act of the National council of the Slovak Republic on Administration Fees. Pursuant to the Act on Czech-Slovak technical standards, NRA SR has a function of an uneglectable participant in commenting on draft Slovak technical standards (STN). A total of 101 drafts were reviewed. The standard drafts in most cases concerned taking European standards and international standards over into the STN system, with respect to the Slovak Republic integration into the European Union. Coordination of technical standardization is assessed by the Council for Technical Standardization that is established at the Slovak Institute of Technical Standardization. The NRA SR's staff member takes part at meetings of the Council. In the third year of their existence, NRA SR started to issue their own publications that should provide legal and qualified information about peaceful use of nuclear power. NRA SR in co-operation with VUJE a.s. Trnava issued the first publication 'Selected legal documents on peaceful use of nuclear power (general binding legal regulations)'. The publication contains texts or extracts from 21 regulations

  20. Fission yeast shelterin regulates DNA polymerases and Rad3(ATR kinase to limit telomere extension.

    Ya-Ting Chang

    2013-11-01

    Full Text Available Studies in fission yeast have previously identified evolutionarily conserved shelterin and Stn1-Ten1 complexes, and established Rad3(ATR/Tel1(ATM-dependent phosphorylation of the shelterin subunit Ccq1 at Thr93 as the critical post-translational modification for telomerase recruitment to telomeres. Furthermore, shelterin subunits Poz1, Rap1 and Taz1 have been identified as negative regulators of Thr93 phosphorylation and telomerase recruitment. However, it remained unclear how telomere maintenance is dynamically regulated during the cell cycle. Thus, we investigated how loss of Poz1, Rap1 and Taz1 affects cell cycle regulation of Ccq1 Thr93 phosphorylation and telomere association of telomerase (Trt1(TERT, DNA polymerases, Replication Protein A (RPA complex, Rad3(ATR-Rad26(ATRIP checkpoint kinase complex, Tel1(ATM kinase, shelterin subunits (Tpz1, Ccq1 and Poz1 and Stn1. We further investigated how telomere shortening, caused by trt1Δ or catalytically dead Trt1-D743A, affects cell cycle-regulated telomere association of telomerase and DNA polymerases. These analyses established that fission yeast shelterin maintains telomere length homeostasis by coordinating the differential arrival of leading (Polε and lagging (Polα strand DNA polymerases at telomeres to modulate Rad3(ATR association, Ccq1 Thr93 phosphorylation and telomerase recruitment.

  1. Identification of the DNA-Binding Domains of Human Replication Protein A That Recognize G-Quadruplex DNA

    Aishwarya Prakash

    2011-01-01

    Full Text Available Replication protein A (RPA, a key player in DNA metabolism, has 6 single-stranded DNA-(ssDNA- binding domains (DBDs A-F. SELEX experiments with the DBDs-C, -D, and -E retrieve a 20-nt G-quadruplex forming sequence. Binding studies show that RPA-DE binds preferentially to the G-quadruplex DNA, a unique preference not observed with other RPA constructs. Circular dichroism experiments show that RPA-CDE-core can unfold the G-quadruplex while RPA-DE stabilizes it. Binding studies show that RPA-C binds pyrimidine- and purine-rich sequences similarly. This difference between RPA-C and RPA-DE binding was also indicated by the inability of RPA-CDE-core to unfold an oligonucleotide containing a TC-region 5′ to the G-quadruplex. Molecular modeling studies of RPA-DE and telomere-binding proteins Pot1 and Stn1 reveal structural similarities between the proteins and illuminate potential DNA-binding sites for RPA-DE and Stn1. These data indicate that DBDs of RPA have different ssDNA recognition properties.

  2. Toward defining deep brain stimulation targets in MNI space: A subcortical atlas based on multimodal MRI, histology and structural connectivity.

    Ewert, Siobhan; Plettig, Philip; Li, Ningfei; Chakravarty, M Mallar; Collins, D Louis; Herrington, Todd M; Kühn, Andrea A; Horn, Andreas

    2018-04-15

    Three-dimensional atlases of subcortical brain structures are valuable tools to reference anatomy in neuroscience and neurology. For instance, they can be used to study the position and shape of the three most common deep brain stimulation (DBS) targets, the subthalamic nucleus (STN), internal part of the pallidum (GPi) and ventral intermediate nucleus of the thalamus (VIM) in spatial relationship to DBS electrodes. Here, we present a composite atlas based on manual segmentations of a multimodal high resolution brain template, histology and structural connectivity. In a first step, four key structures were defined on the template itself using a combination of multispectral image analysis and manual segmentation. Second, these structures were used as anchor points to coregister a detailed histological atlas into standard space. Results show that this approach significantly improved coregistration accuracy over previously published methods. Finally, a sub-segmentation of STN and GPi into functional zones was achieved based on structural connectivity. The result is a composite atlas that defines key nuclei on the template itself, fills the gaps between them using histology and further subdivides them using structural connectivity. We show that the atlas can be used to segment DBS targets in single subjects, yielding more accurate results compared to priorly published atlases. The atlas will be made publicly available and constitutes a resource to study DBS electrode localizations in combination with modern neuroimaging methods. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Beta oscillations in freely moving Parkinson's subjects are attenuated during deep brain stimulation.

    Quinn, Emma J; Blumenfeld, Zack; Velisar, Anca; Koop, Mandy Miller; Shreve, Lauren A; Trager, Megan H; Hill, Bruce C; Kilbane, Camilla; Henderson, Jaimie M; Brontë-Stewart, Helen

    2015-11-01

    Investigations into the effect of deep brain stimulation (DBS) on subthalamic (STN) beta (13-30 Hz) oscillations have been performed in the perioperative period with the subject tethered to equipment. Using an embedded sensing neurostimulator, this study investigated whether beta power was similar in different resting postures and during forward walking in freely moving subjects with Parkinson's disease (PD) and whether STN DBS attenuated beta power in a voltage-dependent manner. Subthalamic local field potentials were recorded from the DBS lead, using a sensing neurostimulator (Activa(®) PC+S, Medtronic, Inc., Food and Drug Administration- Investigational Device Exemption (IDE)-, institutional review board-approved) from 15 PD subjects (30 STNs) off medication during lying, sitting, and standing, during forward walking, and during randomized periods of 140 Hz DBS at 0 V, 1 V, and 2.5/3 V. Continuous video, limb angular velocity, and forearm electromyography recordings were synchronized with neural recordings. Data were parsed to avoid any movement or electrical artifact during resting states. Beta power was similar during lying, sitting, and standing (P = 0.077, n = 28) and during forward walking compared with the averaged resting state (P = 0.466, n = 24), although akinetic rigid PD subjects tended to exhibit decreased beta power when walking. Deep brain stimulation at 3 V and at 1 V attenuated beta power compared with 0 V (P closed-loop DBS. © 2015 International Parkinson and Movement Disorder Society.

  4. OPTIMAL REPRESENTATION OF MER SIGNALS APPLIED TO THE IDENTIFICATION OF BRAIN STRUCTURES DURING DEEP BRAIN STIMULATION

    Hernán Darío Vargas Cardona

    2015-07-01

    Full Text Available Identification of brain signals from microelectrode recordings (MER is a key procedure during deep brain stimulation (DBS applied in Parkinson’s disease patients. The main purpose of this research work is to identify with high accuracy a brain structure called subthalamic nucleus (STN, since it is the target structure where the DBS achieves the best therapeutic results. To do this, we present an approach for optimal representation of MER signals through method of frames. We obtain coefficients that minimize the Euclidean norm of order two. From optimal coefficients, we extract some features from signals combining the wavelet packet and cosine dictionaries. For a comparison frame with the state of the art, we also process the signals using the discrete wavelet transform (DWT with several mother functions. We validate the proposed methodology in a real data base. We employ simple supervised machine learning algorithms, as the K-Nearest Neighbors classifier (K-NN, a linear Bayesian classifier (LDC and a quadratic Bayesian classifier (QDC. Classification results obtained with the proposed method improves significantly the performance of the DWT. We achieve a positive identification of the STN superior to 97,6%. Identification outcomes achieved by the MOF are highly accurate, as we can potentially get a false positive rate of less than 2% during the DBS.

  5. Early hypersynchrony in juvenile PINK1-/- motor cortex is rescued by antidromic stimulation

    Romain eCARRON

    2014-05-01

    Full Text Available In Parkinson’s disease, cortical networks show enhanced synchronized activity but whether this precedes motor signs is unknown. We investigated this question in PINK1-/- mice, a genetic rodent model of the PARK6 variant of familial Parkinson’s disease which shows impaired spontaneous locomotion at 16 months. We used two-photon calcium imaging and whole-cell patch clamp in slices from juvenile (P14-P21 wild-type or PINK1-/- mice. We designed a horizontal tilted cortico-subthalamic slice where the only connection between cortex and subthalamic nucleus (STN is the hyperdirect cortico-subthalamic pathway. We report excessive correlation and synchronization in PINK1-/- M1 cortical networks 15 months before motor impairment. The percentage of correlated pairs of neurons and their strength of correlation were higher in the PINK1-/- M1 than in the wild type network and the synchronized network events involved a higher percentage of neurons. Both features were independent of thalamo-cortical pathways, insensitive to chronic levodopa treatment of pups, but totally reversed by antidromic invasion of M1 pyramidal neurons by axonal spikes evoked by high frequency stimulation (HFS of the STN. Our study describes an early excess of synchronization in the PINK1-/- cortex and suggests a potential role of antidromic activation of cortical interneurons in network desynchronization. Such backward effect on interneurons activity may be of importance for HFS-induced network desynchronization.

  6. Verbal Memory Decline following DBS for Parkinson's Disease: Structural Volumetric MRI Relationships.

    Geevarghese, Ruben; Lumsden, Daniel E; Costello, Angela; Hulse, Natasha; Ayis, Salma; Samuel, Michael; Ashkan, Keyoumars

    2016-01-01

    Parkinson's disease is a chronic degenerative movement disorder. The mainstay of treatment is medical. In certain patients Deep Brain Stimulation (DBS) may be offered. However, DBS has been associated with post-operative neuropsychology changes, especially in verbal memory. Firstly, to determine if pre-surgical thalamic and hippocampal volumes were related to verbal memory changes following DBS. Secondly, to determine if clinical factors such as age, duration of symptoms or motor severity (UPDRS Part III score) were related to verbal memory changes. A consecutive group of 40 patients undergoing bilateral Subthalamic Nucleus (STN)-DBS for PD were selected. Brain MRI data was acquired, pre-processed and structural volumetric data was extracted using FSL. Verbal memory test scores for pre- and post-STN-DBS surgery were recorded. Linear regression was used to investigate the relationship between score change and structural volumetric data. A significant relationship was demonstrated between change in List Learning test score and thalamic (left, p = 0.02) and hippocampal (left, p = 0.02 and right p = 0.03) volumes. Duration of symptoms was also associated with List Learning score change (p = 0.02 to 0.03). Verbal memory score changes appear to have a relationship to pre-surgical MRI structural volumetric data. The findings of this study provide a basis for further research into the use of pre-surgical MRI to counsel PD patients regarding post-surgical verbal memory changes.

  7. Swallowing and deep brain stimulation in Parkinson’s disease: A systematic review

    Troche, Michelle S.; Brandimore, Alexandra E.; Foote, Kelly D.; Okun, Michael S.

    2013-01-01

    The purpose of this review is to assess the current state of the literature on the topic of deep brain stimulation (DBS) and its effects on swallowing function in Parkinson’s disease (PD). Pubmed, Cochrane review, and web of science searches were completed on all articles addressing DBS that contained a swallowing outcome measure. Outcome measures included the penetration/aspiration scale, pharyngeal transit time, oropharyngeal residue, drooling, aspiration pneumonia, death, hyolaryngeal excursion, epiglottic inversion, UPDRS scores, and presence of coughing/throat clearing during meals. The search identified 13 studies specifically addressing the effects of DBS on swallowing. Critical assessment of the 13 identified peer-reviewed publications revealed nine studies employing an experimental design, (e.g. “on” vs. “off”, pre- vs. post-DBS) and four case reports. None of the nine experimental studies were found to identify clinically significant improvement or decline in swallowing function with DBS. Despite these findings, several common threads were identified across experimental studies and will be examined in this review. Additionally, available data demonstrate that, although subthalamic nucleus (STN) stimulation has been considered to cause more impairment to swallowing function than globus pallidus internus (GPi) stimulation, there are no experimental studies directly comparing swallowing function in STN vs. GPi. Moreover, there has been no comparison of unilateral vs. bilateral DBS surgery and the coincident effects on swallowing function. This review includes a critical analysis of all experimental studies and discusses methodological issues that should be addressed in future studies. PMID:23726461

  8. Microwave modulation characteristics of twisted liquid crystals with chiral dopant

    Rui Yuan

    2017-01-01

    Full Text Available Adding a chiral dopant in twisted nematic (TN liquid crystal cell can stabilize the orientation of liquid crystal molecules, particularly in high TN (HTN or super TN (STN liquid crystal cells. The difference in pitches in liquid crystal is induced by the chiral dopant, and these different pitches affect the orientation of liquid crystal director under an external applied voltage and influence the characteristics of microwave modulation. To illustrate this point, the microwave phase shift per unit length (MPSL versus voltage is calculated on the basis of the elastic theory of liquid crystal and the finite-difference iterative method. Enhancing the pitch induced by the chiral dopant in liquid crystal increases the MPSLs, but the stability of the twisted structures is decreased. Thus, appropriate pitches of 100d, 4d, and 2d can be applied in TN, HTN, and STN cells with cell gap d to enhance the characteristics of microwave modulation and stabilize the structures in twisted cell. This method can improve the characteristics of liquid crystal microwave modulators such that the operating voltage and the size of such phase shifters can be decreased.

  9. The Evaluation of the Effect of Multiwall Carbon Nano Tube (MWCNT on In Vitro Proliferation and Shoot Tip Necrosis of Pistachio Rootstock UCB-1 (Pistacia integrima × P. atlantica

    Shahrzad Aghasi Kermani

    2017-05-01

    Full Text Available UCB-1 (Pistacia atlantica × P. integrima is a commercial rootstock for pistachio in some pistachio plantations across the world. This rootstock is very new in Iran and recently, it has been used commercially in some plantations due to its high growth. Propagation of this rootstock by tissue culture results in many limitations such as shoot tip necrosis (STN and a low proliferation rate. Therefore, any process that leads to improve the proliferation rate and feature will be used in commercial propagation of this rootstock. Nanotubes are widely used in in vitro cultures. For this reason, we used different concentrations of carbon nanotubes (0, 50, 100, 150, 200 µg/l and benzyladenine (0, 0.5, 1, 1.5 and 2 mg/l to improve the proliferation rate and qualitative indices. The results showed that using carbon nanotubes concentration of 200 µg/l with 2mg/l of benzyladenine (BA led to maximum proliferation (4 microshoots per explant, maximum shoot length (3.68 cm and minimum STN (8% and vitrification (this isn’t a word? (0 % percentage.

  10. CDX2 homeoprotein is involved in the regulation of ST6GalNAc-I gene in intestinal metaplasia

    Pinto, Rita; Barros, Rita; Pereira-Castro, Isabel

    2015-01-01

    lesions and in the intestine, CDX2 homeobox transcription factor is co-expressed with STn and ST6GalNAc-I. We therefore hypothesized that CDX2 might induce STn expression by positive regulation of ST6GalNAc-I. We showed that ST6GalNAc-I transcript levels and CDX2 have a coordinated expression upon Caco-2...... in vitro differentiation, and overexpression of CDX2 in MKN45 gastric cells increases ST6GalNAc-I transcript levels. Nine putative CDX-binding sites in the ST6GalNAc-I-regulatory sequence were identified and analyzed by chromatin immunoprecipitation in Caco-2 cells and in IM. The results showed that CDX2...... protein is recruited to all regions, being the most proximal sites preferentially occupied in vivo. Luciferase assays demonstrated that CDX2 is able to transactivate ST6GalNac-I-regulatory region. The induction was stronger for the regions mapped in the neighbourhood of ATG start codon and site...

  11. Interaction of oscillations, and their suppression via deep brain stimulation, in a model of the cortico-basal ganglia network.

    Kang, Guiyeom; Lowery, Madeleine M

    2013-03-01

    Growing evidence suggests that synchronized neural oscillations in the cortico-basal ganglia network may play a critical role in the pathophysiology of Parkinson's disease. In this study, a new model of the closed loop network is used to explore the generation and interaction of network oscillations and their suppression through deep brain stimulation (DBS). Under simulated dopamine depletion conditions, increased gain through the hyperdirect pathway resulted in the interaction of neural oscillations at different frequencies in the cortex and subthalamic nucleus (STN), leading to the emergence of synchronized oscillations at a new intermediate frequency. Further increases in synaptic gain resulted in the cortex driving synchronous oscillatory activity throughout the network. When DBS was added to the model a progressive reduction in STN power at the tremor and beta frequencies was observed as the frequency of stimulation was increased, with resonance effects occurring for low frequency DBS (40 Hz) in agreement with experimental observations. The results provide new insights into the mechanisms by which synchronous oscillations can arise within the network and how DBS may suppress unwanted oscillatory activity.

  12. Stimulation sites in the subthalamic nucleus projected onto a mean 3-D atlas of the thalamus and basal ganglia.

    Sarnthein, Johannes; Péus, Dominik; Baumann-Vogel, Heide; Baumann, Christian R; Sürücü, Oguzkan

    2013-09-01

    In patients with severe forms of Parkinson's disease (PD), deep brain stimulation (DBS) commonly targets the subthalamic nucleus (STN). Recently, the mean 3-D Morel-Atlas of the basal ganglia and the thalamus was introduced. It combines information contained in histological data from ten post-mortem brains. We were interested whether the Morel-Atlas is applicable for the visualization of stimulation sites. In a consecutive PD patient series, we documented preoperative MRI planning, intraoperative target adjustment based on electrophysiological and neurological testing, and perioperative CT target reconstruction. The localization of the DBS electrodes and the optimal stimulation sites were projected onto the Morel-Atlas. We included 20 patients (median age 62 years). The active contact had mean coordinates Xlat = ±12.1 mm, Yap = -1.8 mm, Zvert = -3.2 mm. There was a significant difference between the initially planned site and the coordinates of the postoperative active contact site (median 2.2 mm). The stimulation site was, on average, more anterior and more dorsal. The electrode contact used for optimal stimulation was found within the STN of the atlas in 38/40 (95 %) of implantations. The cluster of stimulation sites in individual patients-as deduced from preoperative MR, intraoperative electrophysiology and neurological testing-showed a high degree of congruence with the atlas. The mean 3D Morel Atlas is thus a useful tool for postoperative target visualization. This represents the first clinical evaluation of the recently created atlas.

  13. Tractographical model of the cortico-basal ganglia and corticothalamic connections: Improving Our Understanding of Deep Brain Stimulation.

    Avecillas-Chasin, Josué M; Rascón-Ramírez, Fernando; Barcia, Juan A

    2016-05-01

    The cortico-basal ganglia and corticothalamic projections have been extensively studied in the context of neurological and psychiatric disorders. Deep brain stimulation (DBS) is known to modulate many of these pathways to produce the desired clinical effect. The aim of this work is to describe the anatomy of the main circuits of the basal ganglia using tractography in a surgical planning station. We used imaging studies of 20 patients who underwent DBS for movement and psychiatric disorders. We segmented the putamen, caudate nucleus (CN), thalamus, and subthalamic nucleus (STN), and we also segmented the cortical areas connected with these subcortical areas. We used tractography to define the subdivisions of the basal ganglia and thalamus through the generation of fibers from the cortical areas to the subcortical structures. We were able to generate the corticostriatal and corticothalamic connections involved in the motor, associative and limbic circuits. Furthermore, we were able to reconstruct the hyperdirect pathway through the corticosubthalamic connections and we found subregions in the STN. Finally, we reconstructed the cortico-subcortical connections of the ventral intermediate nucleus, the nucleus accumbens and the CN. We identified a feasible delineation of the basal ganglia and thalamus connections using tractography. These results could be potentially useful in DBS if the parcellations are used as targets during surgery. © 2016 Wiley Periodicals, Inc.

  14. Deficits in inhibitory control and conflict resolution on cognitive and motor tasks in Parkinson's disease.

    Obeso, Ignacio; Wilkinson, Leonora; Casabona, Enrique; Bringas, Maria Luisa; Álvarez, Mario; Álvarez, Lázaro; Pavón, Nancy; Rodríguez-Oroz, Maria-Cruz; Macías, Raúl; Obeso, Jose A; Jahanshahi, Marjan

    2011-07-01

    Recent imaging studies in healthy controls with a conditional stop signal reaction time (RT) task have implicated the subthalamic nucleus (STN) in response inhibition and the pre-supplementary motor area (pre-SMA) in conflict resolution. Parkinson's disease (PD) is characterized by striatal dopamine deficiency and overactivity of the STN and underactivation of the pre-SMA during movement. We used the conditional stop signal RT task to investigate whether PD produced similar or dissociable effects on response initiation, response inhibition and response initiation under conflict. In addition, we also examined inhibition of prepotent responses on three cognitive tasks: the Stroop, random number generation and Hayling sentence completion. PD patients were impaired on the conditional stop signal reaction time task, with response initiation both in situations with or without conflict and response inhibition all being significantly delayed, and had significantly greater difficulty in suppressing prepotent or habitual responses on the Stroop, Hayling and random number generation tasks relative to controls. These results demonstrate the existence of a generalized inhibitory deficit in PD, which suggest that PD is a disorder of inhibition as well as activation and that in situations of conflict, executive control over responses is compromised.

  15. Detection of cell surface hydrophobicity, biofilm and fimbirae genes in salmonella isolated from tunisian clinical and poultry meat.

    Ben Abdallah, Fethi; Lagha, Rihab; Said, Khaled; Kallel, Héla; Gharbi, Jawhar

    2014-04-01

    The aim of this study was to evaluate the ability of 15 serotypes of Salmonella to form biofilm on polystyrene, polyvinyl chloride (PVC) and glass surfaces. . Initially slime production was assessed on CRA agar and hydrophobicity of 20 Salmonella strains isolated from poultry and human and two Salmonella enterica serovar Typhimurium references strains was achieved by microbial adhesion to n-hexadecane. In addition, biofilm formation on polystyrene, PVC and glass surfaces was also investigated by using MTT and XTT colorimetric assay. Further, distribution of Salmonella enterotoxin (stn), Salmonella Enteritidis fimbrial (sef) and plasmid encoded fimbrial (pef) genes among tested strains was achieved by PCR. Salmonella strains developed red and white colonies on CRA and they are considered as hydrophilic with affinity values to n-hexadecane ranged between 0.29% and 29.55%. Quantitative biofilm assays showed that bacteria are able to form biofilm on polystyrene with different degrees and 54.54% of strains produce a strong biofilm on glass. In addition, all the strains form only a moderate (54.54%) and weak (40.91%) biofilm on PVC. PCR detection showed that only S. Enteritidis harbour Sef gene, whereas Pef and stn genes were detected in S. Kentucky, S. Amsterdam, S. Hadar, S. Enteritidis and S. Typhimurium. Salmonella serotypes are able to form biofilm on hydrophobic and hydrophilic industrial surfaces. Biofilm formation of Salmonella on these surfaces has an increased potential to compromise food safety and potentiate public health risk.

  16. Complex repetitive behavior: punding after bilateral subthalamic nucleus stimulation in Parkinson's disease.

    Pallanti, Stefano; Bernardi, Silvia; Raglione, Laura Maria; Marini, Paolo; Ammannati, Franco; Sorbi, Sandro; Ramat, Silvia

    2010-07-01

    "Punding" is the term used to describe a stereotyped motor behavior characterized by an intense fascination with repetitive purposeless movements, such as taking apart mechanical objects, handling common objects as if they were new and entertaining, constantly picking at oneself, etc. As a phenomenon with both impulsive and compulsive features, the phenomenology of punding is currently being questioned. In order to investigate the pathophysiology of this phenomenon, we screened a population of Parkinson's disease (PD) outpatients who underwent subthalamic nucleus deep brain stimulation (STN DBS). We conducted a patient-and-relative-completed survey with 24 consecutive patients in an academic outpatient care center, using a modified version of a structured interview. Patients were administered the Unified Parkinson's Disease Rating Scale (UPDRS), the Obsessive-Compulsive Inventory and the Sheehan Disability Scale. Five (20.8%) of the 24 subjects were identified as punders, including three men (60%) and two women. The punders were comparable to the non-punders in terms of clinical and demographic factors. The punder and non-punder groups only differed statistically with regard to the length of time from DBS implantation. Those findings suggest that punding might be induced by STN DBS, and its rate of occurrence in DBS population seems to be more common than previously suspected. Copyright 2010 Elsevier Ltd. All rights reserved.

  17. DOPAMINE AND THE BIOLOGY OF CREATIVITY: LESSONS FROM PARKINSON’S DISEASE

    Eugénie eLhommée

    2014-04-01

    Full Text Available BACKGROUND: Parkinson’s disease (PD is characterized by reduced flexibility, conceptualization and visuo-spatial abilities. Although these are essential to creativity, case studies show emergence of creativity during PD. Knowledge about the role of dopamine in creativity so far only stems from a few case reports. We aim at demonstrating that creativity can be induced by dopaminergic treatments in PD, and tends to disappear after withdrawal of dopamine agonists. METHODS: 11 consecutive creative PD patients were selected from candidates for subthalamic deep brain stimulation (STN DBS surgery, and compared to 22 non-creative control PD patients. Motor disability (UPDRS III, cognition (Frontal Score, Mattis scale and behaviour (Ardouin scale were assessed before surgery and one year after. RESULTS: Before surgery, whereas cognitive and motor assessments where similar between groups, dopamine agonist (but not levodopa dosages were higher in creative patients (p=0.01. The Ardouin scale revealed also a specific psycho-behavioural profile of creative patients which had higher scores for mania (pCONCLUSION: Creativity in PD is linked to dopamine agonist therapy, and tends to disappear after STN DBS in parallel to reduction of dopamine agonists, which are relatively selective for the mesolimbic D3 dopamine receptors

  18. A neural mass model of basal ganglia nuclei simulates pathological beta rhythm in Parkinson's disease

    Liu, Fei; Wang, Jiang; Liu, Chen; Li, Huiyan; Deng, Bin; Fietkiewicz, Chris; Loparo, Kenneth A.

    2016-12-01

    An increase in beta oscillations within the basal ganglia nuclei has been shown to be associated with movement disorder, such as Parkinson's disease. The motor cortex and an excitatory-inhibitory neuronal network composed of the subthalamic nucleus (STN) and the external globus pallidus (GPe) are thought to play an important role in the generation of these oscillations. In this paper, we propose a neuron mass model of the basal ganglia on the population level that reproduces the Parkinsonian oscillations in a reciprocal excitatory-inhibitory network. Moreover, it is shown that the generation and frequency of these pathological beta oscillations are varied by the coupling strength and the intrinsic characteristics of the basal ganglia. Simulation results reveal that increase of the coupling strength induces the generation of the beta oscillation, as well as enhances the oscillation frequency. However, for the intrinsic properties of each nucleus in the excitatory-inhibitory network, the STN primarily influences the generation of the beta oscillation while the GPe mainly determines its frequency. Interestingly, describing function analysis applied on this model theoretically explains the mechanism of pathological beta oscillations.

  19. Electrocorticography reveals beta desynchronization in the basal ganglia-cortical loop during rest tremor in Parkinson's disease.

    Qasim, Salman E; de Hemptinne, Coralie; Swann, Nicole C; Miocinovic, Svjetlana; Ostrem, Jill L; Starr, Philip A

    2016-02-01

    The pathophysiology of rest tremor in Parkinson's disease (PD) is not well understood, and its severity does not correlate with the severity of other cardinal signs of PD. We hypothesized that tremor-related oscillatory activity in the basal-ganglia-thalamocortical loop might serve as a compensatory mechanism for the excessive beta band synchronization associated with the parkinsonian state. We recorded electrocorticography (ECoG) from the sensorimotor cortex and local field potentials (LFP) from the subthalamic nucleus (STN) in patients undergoing lead implantation for deep brain stimulation (DBS). We analyzed differences in measures of network synchronization during epochs of spontaneous rest tremor, versus epochs without rest tremor, occurring in the same subjects. The presence of tremor was associated with reduced beta power in the cortex and STN. Cortico-cortical coherence and phase-amplitude coupling (PAC) decreased during rest tremor, as did basal ganglia-cortical coherence in the same frequency band. Cortical broadband gamma power was not increased by tremor onset, in contrast to the movement-related gamma increase typically observed at the onset of voluntary movement. These findings suggest that the cortical representation of rest tremor is distinct from that of voluntary movement, and support a model in which tremor acts to decrease beta band synchronization within the basal ganglia-cortical loop. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Interaction of synchronized dynamics in cortex and basal ganglia in Parkinson's disease.

    Ahn, Sungwoo; Zauber, S Elizabeth; Worth, Robert M; Witt, Thomas; Rubchinsky, Leonid L

    2015-09-01

    Parkinson's disease pathophysiology is marked by increased oscillatory and synchronous activity in the beta frequency band in cortical and basal ganglia circuits. This study explores the functional connections between synchronized dynamics of cortical areas and synchronized dynamics of subcortical areas in Parkinson's disease. We simultaneously recorded neuronal units (spikes) and local field potentials (LFP) from subthalamic nucleus (STN) and electroencephalograms (EEGs) from the scalp in parkinsonian patients, and analysed the correlation between the time courses of the spike-LFP synchronization and inter-electrode EEG synchronization. We found the (non-invasively obtained) time course of the synchrony strength between EEG electrodes and the (invasively obtained) time course of the synchrony between spiking units and LFP in STN to be weakly, but significantly, correlated with each other. This correlation is largest for the bilateral motor EEG synchronization, followed by bilateral frontal EEG synchronization. Our observations suggest that there may be multiple functional modes by which the cortical and basal ganglia circuits interact with each other in Parkinson's disease: not only may synchronization be observed between some areas in cortex and the basal ganglia, but also synchronization within cortex and within basal ganglia may be related, suggesting potentially a more global functional interaction. More coherent dynamics in one brain region may modulate or activate the dynamics of another brain region in a more powerful way, causing correlations between changes in synchrony strength in the two regions. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  1. Restoring the basal ganglia in Parkinson's disease to normal via multi-input phase-shifted deep brain stimulation.

    Agarwal, Rahul; Sarma, Sridevi V

    2010-01-01

    Deep brain stimulation (DBS) injects a high frequency current that effectively disables the diseased basal ganglia (BG) circuit in Parkinson's disease (PD) patients, leading to a reversal of motor symptoms. Though therapeutic, high frequency stimulation consumes significant power forcing frequent surgical battery replacements and causing widespread influence into other brain areas which may lead to adverse side effects. In this paper, we conducted a rigorous study to assess whether low frequency signals can restore behavior in PD patients by restoring neural activity in the BG to the normal state. We used a biophysical-based model of BG nuclei and motor thalamus whose parameters can be set to simulate the normal state and the PD state with and without DBS. We administered pulse train DBS waveforms to the subthalamic nucleus (STN) with frequencies ranging from 1-150Hz. For each DBS frequency, we computed statistics on the simulated neural activity to assess whether it is restored to the normal state. In particular, we searched for DBS waveforms that suppress pathological bursting, oscillations, correlations and synchronization prevalent in the PD state and that enable thalamic cells to relay cortical inputs reliably. We found that none of the tested waveforms restores neural activity to the normal state. However, our simulations led us to construct a novel DBS strategy involving low frequency multi-input phaseshifted DBS to be administered into the STN. This strategy successfully suppressed all pathological symptoms in the BG in addition to enabling thalamic cells to relay cortical inputs reliably.

  2. Effect of Deep Brain Stimulation on Speech Performance in Parkinson's Disease

    Sabine Skodda

    2012-01-01

    Full Text Available Deep brain stimulation (DBS has been reported to be successful in relieving the core motor symptoms of Parkinson's disease (PD and motor fluctuations in the more advanced stages of the disease. However, data on the effects of DBS on speech performance are inconsistent. While there are some series of patients documenting that speech function was relatively unaffected by DBS of the nucleus subthalamicus (STN, other investigators reported on improvements of distinct parameters of oral control and voice. Though, these ameliorations of single speech modalities were not always accompanied by an improvement of overall speech intelligibility. On the other hand, there are also indications for an induction of dysarthria as an adverse effect of STN-DBS occurring at least in some patients with PD. Since a deterioration of speech function has more often been observed under high stimulation amplitudes, this phenomenon has been ascribed to a spread of current-to-adjacent pathways which might also be the reason for the sporadic observation of an onset of dysarthria under DBS of other basal ganglia targets (e.g., globus pallidus internus/GPi or thalamus/Vim. The aim of this paper is to review and evaluate reports in the literature on the effects of DBS on speech function in PD.

  3. The Antiparkinsonian and Antidyskinetic Mechanisms of Mucuna pruriens in the MPTP-Treated Nonhuman Primate

    Christopher A. Lieu

    2012-01-01

    Full Text Available Chronic treatment with levodopa (LD in Parkinson's disease (PD can cause drug induced dyskinesias. Mucuna pruriens endocarp powder (MPEP contains several compounds including natural LD and has been reported to not cause drug-induced dyskinesias. We evaluated the effects of Mucuna pruriens to determine if its underlying mechanistic actions are exclusively due to LD. We first compared MPEP with and without carbidopa (CD, and LD+CD in hemiparkinsonian (HP monkeys. Each treatment ameliorated parkinsonism. We then compared the neuronal firing properties of the substantia nigra reticulata (SNR and subthalamic nucleus (STN in HP monkeys with MPEP+CD and LD+CD to evaluate basal ganglia circuitry alterations. Both treatments decreased SNR firing rate compared to HP state. However, LD+CD treatments significantly increased SNR bursting firing patterns that were not seen with MPEP+CD treatments. No significant changes were seen in STN firing properties. We then evaluated the effects of a water extract of MPEP. Oral MPWE ameliorated parkinsonism without causing drug-induced dyskinesias. The distinctive neurophysiological findings in the basal ganglia and the ability to ameliorate parkinsonism without causing dyskinesias strongly suggest that Mucuna pruriens acts through a novel mechanism that is different from that of LD.

  4. The Antiparkinsonian and Antidyskinetic Mechanisms of Mucuna pruriens in the MPTP-Treated Nonhuman Primate.

    Lieu, Christopher A; Venkiteswaran, Kala; Gilmour, Timothy P; Rao, Anand N; Petticoffer, Andrew C; Gilbert, Erin V; Deogaonkar, Milind; Manyam, Bala V; Subramanian, Thyagarajan

    2012-01-01

    Chronic treatment with levodopa (LD) in Parkinson's disease (PD) can cause drug induced dyskinesias. Mucuna pruriens endocarp powder (MPEP) contains several compounds including natural LD and has been reported to not cause drug-induced dyskinesias. We evaluated the effects of Mucuna pruriens to determine if its underlying mechanistic actions are exclusively due to LD. We first compared MPEP with and without carbidopa (CD), and LD+CD in hemiparkinsonian (HP) monkeys. Each treatment ameliorated parkinsonism. We then compared the neuronal firing properties of the substantia nigra reticulata (SNR) and subthalamic nucleus (STN) in HP monkeys with MPEP+CD and LD+CD to evaluate basal ganglia circuitry alterations. Both treatments decreased SNR firing rate compared to HP state. However, LD+CD treatments significantly increased SNR bursting firing patterns that were not seen with MPEP+CD treatments. No significant changes were seen in STN firing properties. We then evaluated the effects of a water extract of MPEP. Oral MPWE ameliorated parkinsonism without causing drug-induced dyskinesias. The distinctive neurophysiological findings in the basal ganglia and the ability to ameliorate parkinsonism without causing dyskinesias strongly suggest that Mucuna pruriens acts through a novel mechanism that is different from that of LD.

  5. Sensory contribution to vocal emotion deficit in Parkinson's disease after subthalamic stimulation.

    Péron, Julie; Cekic, Sezen; Haegelen, Claire; Sauleau, Paul; Patel, Sona; Drapier, Dominique; Vérin, Marc; Grandjean, Didier

    2015-02-01

    Subthalamic nucleus (STN) deep brain stimulation in Parkinson's disease induces modifications in the recognition of emotion from voices (or emotional prosody). Nevertheless, the underlying mechanisms are still only poorly understood, and the role of acoustic features in these deficits has yet to be elucidated. Our aim was to identify the influence of acoustic features on changes in emotional prosody recognition following STN stimulation in Parkinson's disease. To this end, we analysed the performances of patients on vocal emotion recognition in pre-versus post-operative groups, as well as of matched controls, entering the acoustic features of the stimuli into our statistical models. Analyses revealed that the post-operative biased ratings on the Fear scale when patients listened to happy stimuli were correlated with loudness, while the biased ratings on the Sadness scale when they listened to happiness were correlated with fundamental frequency (F0). Furthermore, disturbed ratings on the Happiness scale when the post-operative patients listened to sadness were found to be correlated with F0. These results suggest that inadequate use of acoustic features following subthalamic stimulation has a significant impact on emotional prosody recognition in patients with Parkinson's disease, affecting the extraction and integration of acoustic cues during emotion perception. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Predictive potential of pre-operative functional neuroimaging in patients treated with subthalamic stimulation

    Sestini, Stelvio; Castagnoli, Antonio; Pupi, Alberto; Sciagra, Roberto; Ammannati, Franco; Ramat, Silvia; Sorbi, Sandro; Mansi, Luigi

    2010-01-01

    The aim of this study was to investigate the predictive potential of pre-operative regional cerebral blood flow (rCBF) in the pre-supplementary motor area (pre-SMA) and clinical factors in Parkinson's disease (PD) patients treated with subthalamic nucleus (STN) stimulation. Ten patients underwent rCBF SPECT and motor Unified Parkinson's Disease Rating Scale (UPDRS) pre- and post-operatively during stimulation at 5 and 42 months. Statistical parametric mapping (SPM) was used to extract rCBF values in the pre-SMA because it is related with motor improvement. Post-operative outcomes included motor response to stimulation and percent improvement in UPDRS. Pre-operative predictors were explored by correlation test, linear regression and multivariate analyses. Higher pre-operative rCBF in the pre-SMA and younger age were associated with favourable outcomes at 5 and 42 months. Pre-operative rCBF results were significantly associated with baseline clinical factors. This study shows that PD patients with younger age have higher rCBF values in the pre-SMA and better outcome, thus giving the rationale to the hypothesis that STN stimulation could be considered early in the course of disease. (orig.)

  7. Selective left, right and bilateral stimulation of subthalamic nuclei in Parkinson's disease: differential effects on motor, speech and language function.

    Schulz, Geralyn M; Hosey, Lara A; Bradberry, Trent J; Stager, Sheila V; Lee, Li-Ching; Pawha, Rajesh; Lyons, Kelly E; Metman, Leo Verhagen; Braun, Allen R

    2012-01-01

    Deep brain stimulation (DBS) of the subthalamic nucleus improves the motor symptoms of Parkinson's disease, but may produce a worsening of speech and language performance at rates and amplitudes typically selected in clinical practice. The possibility that these dissociated effects might be modulated by selective stimulation of left and right STN has never been systematically investigated. To address this issue, we analyzed motor, speech and language functions of 12 patients implanted with bilateral stimulators configured for optimal motor responses. Behavioral responses were quantified under four stimulator conditions: bilateral DBS, right-only DBS, left-only DBS and no DBS. Under bilateral and left-only DBS conditions, our results exhibited a significant improvement in motor symptoms but worsening of speech and language. These findings contribute to the growing body of literature demonstrating that bilateral STN DBS compromises speech and language function and suggests that these negative effects may be principally due to left-sided stimulation. These findings may have practical clinical consequences, suggesting that clinicians might optimize motor, speech and language functions by carefully adjusting left- and right-sided stimulation parameters.

  8. Subthalamic nucleus detects unnatural android movement.

    Ikeda, Takashi; Hirata, Masayuki; Kasaki, Masashi; Alimardani, Maryam; Matsushita, Kojiro; Yamamoto, Tomoyuki; Nishio, Shuichi; Ishiguro, Hiroshi

    2017-12-19

    An android, i.e., a realistic humanoid robot with human-like capabilities, may induce an uncanny feeling in human observers. The uncanny feeling about an android has two main causes: its appearance and movement. The uncanny feeling about an android increases when its appearance is almost human-like but its movement is not fully natural or comparable to human movement. Even if an android has human-like flexible joints, its slightly jerky movements cause a human observer to detect subtle unnaturalness in them. However, the neural mechanism underlying the detection of unnatural movements remains unclear. We conducted an fMRI experiment to compare the observation of an android and the observation of a human on which the android is modelled, and we found differences in the activation pattern of the brain regions that are responsible for the production of smooth and natural movement. More specifically, we found that the visual observation of the android, compared with that of the human model, caused greater activation in the subthalamic nucleus (STN). When the android's slightly jerky movements are visually observed, the STN detects their subtle unnaturalness. This finding suggests that the detection of unnatural movements is attributed to an error signal resulting from a mismatch between a visual input and an internal model for smooth movement.

  9. Predictive potential of pre-operative functional neuroimaging in patients treated with subthalamic stimulation

    Sestini, Stelvio; Castagnoli, Antonio [Ospedale Misericordia e Dolce, Department of Diagnostic Imaging, Nuclear Medicine Unit, Prato (Italy); Pupi, Alberto; Sciagra, Roberto [University of Florence, Department of Clinical Physiopathology, Nuclear Medicine Unit, Florence (Italy); Ammannati, Franco; Ramat, Silvia; Sorbi, Sandro [University of Florence, Department of Neurological and Psychiatric Sciences, Florence (Italy); Mansi, Luigi [University II Naples, Department of Diagnostic Imaging, Nuclear Medicine Unit, Naples (Italy)

    2010-01-15

    The aim of this study was to investigate the predictive potential of pre-operative regional cerebral blood flow (rCBF) in the pre-supplementary motor area (pre-SMA) and clinical factors in Parkinson's disease (PD) patients treated with subthalamic nucleus (STN) stimulation. Ten patients underwent rCBF SPECT and motor Unified Parkinson's Disease Rating Scale (UPDRS) pre- and post-operatively during stimulation at 5 and 42 months. Statistical parametric mapping (SPM) was used to extract rCBF values in the pre-SMA because it is related with motor improvement. Post-operative outcomes included motor response to stimulation and percent improvement in UPDRS. Pre-operative predictors were explored by correlation test, linear regression and multivariate analyses. Higher pre-operative rCBF in the pre-SMA and younger age were associated with favourable outcomes at 5 and 42 months. Pre-operative rCBF results were significantly associated with baseline clinical factors. This study shows that PD patients with younger age have higher rCBF values in the pre-SMA and better outcome, thus giving the rationale to the hypothesis that STN stimulation could be considered early in the course of disease. (orig.)

  10. Subthalamic hGAD65 Gene Therapy and Striatum TH Gene Transfer in a Parkinson’s Disease Rat Model

    Zheng, Deyu; Jiang, Xiaohua; Zhao, Junpeng; Duan, Deyi; Zhao, Huanying; Xu, Qunyuan

    2013-01-01

    The aim of the present study is to detect a combination method to utilize gene therapy for the treatment of Parkinson’s disease (PD). Here, a PD rat model is used for the in vivo gene therapy of a recombinant adeno-associated virus (AAV2) containing a human glutamic acid decarboxylase 65 (rAAV2-hGAD65) gene delivered to the subthalamic nucleus (STN). This is combined with the ex vivo gene delivery of tyrosine hydroxylase (TH) by fibroblasts injected into the striatum. After the treatment, the rotation behavior was improved with the greatest efficacy in the combination group. The results of immunohistochemistry showed that hGAD65 gene delivery by AAV2 successfully led to phenotypic changes of neurons in STN. And the levels of glutamic acid and GABA in the internal segment of the globus pallidus (GPi) and substantia nigra pars reticulata (SNr) were obviously lower than the control groups. However, hGAD65 gene transfer did not effectively protect surviving dopaminergic neurons in the SNc and VTA. This study suggests that subthalamic hGAD65 gene therapy and combined with TH gene therapy can alleviate symptoms of the PD model rats, independent of the protection the DA neurons from death. PMID:23738148

  11. Technical Case Report of Deep Brain Stimulation: Is it Possible Single Electrode Reach to Both of Subthalamic Nucleus and Ventral Intermediate Nucleus in One Stage?

    Kaptan, Hülagu; Çakmur, Raif

    2018-04-15

    The primary target of this operation is Ventral Intermediate Nucleus (VIM); however VIM - Subthalamic Nucleus (STN) were tried to be reached with one electrode, adjusting the angle well, the coronal section; medial of VIM can partially reach the STN. Using the properties of the electrode; we believe we could act on a wide area. An analysis was performed on one patient who underwent VIM Deep Brain Stimulation (DBS) in 3 periods (pre - peri - post-operation). A 53 - year - old woman diagnosed with Parkinson's disease 8 years earlier including symptoms of severe tremor on the right than left underwent bilateral DBS VIM. Obtaining a satisfactory improvement of tremor, the patient did well, and postoperative complications were not observed. The patient was discharged from hospital on postoperative thirty day. It is certain that more research and experience are needed. However, we believe that the two targets can reach the same point and the second operations for another target can be avoided.We believe that this initiative is advantageous and promising regarding patient and cost.

  12. Identifying footprints of directional and balancing selection in marine and freshwater three-spined stickleback (Gasterosteus aculeatus) populations.

    Mäkinen, H S; Cano, J M; Merilä, J

    2008-08-01

    Natural selection is expected to leave an imprint on the neutral polymorphisms at the adjacent genomic regions of a selected gene. While directional selection tends to reduce within-population genetic diversity and increase among-population differentiation, the reverse is expected under balancing selection. To identify targets of natural selection in the three-spined stickleback (Gasterosteus aculeatus) genome, 103 microsatellite and two indel markers including expressed sequence tags (EST) and quantitative trait loci (QTL)-associated loci, were genotyped in four freshwater and three marine populations. The results indicated that a high proportion of loci (14.7%) might be affected by balancing selection and a lower proportion (2.8%) by directional selection. The strongest signatures of directional selection were detected in a microsatellite locus and two indel markers located in the intronic regions of the Eda-gene coding for the number of lateral plates. Yet, other microsatellite loci previously found to be informative in QTL-mapping studies revealed no signatures of selection. Two novel microsatellite loci (Stn12 and Stn90) located in chromosomes I and VIII, respectively, showed signals of directional selection and might be linked to genomic regions containing gene(s) important for adaptive divergence. Although the coverage of the total genomic content was relatively low, the predominance of balancing selection signals is in agreement with the contention that balancing, rather than directional selection is the predominant mode of selection in the wild.

  13. Patterns of Cell Activity in the Subthalamic Region Associated with the Neuroprotective Action of Near-Infrared Light Treatment in MPTP-Treated Mice

    Victoria E. Shaw

    2012-01-01

    Full Text Available We have shown previously that near-infrared light (NIr treatment or photobiomodulation neuroprotects dopaminergic cells in substantia nigra pars compacta (SNc from degeneration induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP in mice. The present study explores whether NIr treatment changes the patterns of Fos expression in the subthalamic region, namely, the subthalamic nucleus (STN and zona incerta (ZI; both cell groups have abnormally overactive cells in parkinsonian cases. BALB/c mice were treated with MPTP (100–250 mg/kg or saline either over 30 hours followed by either a two-hour or six-day survival period (acute model or over five weeks followed by a three-week survival period (chronic model. NIr and MPTP were applied simultaneously. Brains were processed for Fos immunochemistry, and cell number was estimated using stereology. Our major finding was that NIr treatment reduced (30–45% the increase in Fos+ cell number evident in the STN and ZI after MPTP insult. This reduction was concurrent with the neuroprotection of dopaminergic SNc cells shown previously and was evident in both MPTP models (except for the 2 hours survival period which showed no changes in cell number. In summary, our results indicated that NIr had long lasting effects on the activity of cells located deep in the brain and had repaired partially the abnormal activity generated by the parkinsonian toxin.

  14. Shifting from constant-voltage to constant-current in Parkinson's disease patients with chronic stimulation.

    Amami, P; Mascia, M M; Franzini, A; Saba, F; Albanese, A

    2017-08-01

    The study aimed to evaluate safety and efficacy of shifting stimulation settings from constant-voltage (CV) to constant-current (CC) programming in patients with Parkinson's disease (PD) and chronic subthalamic nucleus deep brain stimulation (STN DBS). Twenty PD patients with chronic STN DBS set in CV programming were shifted to CC and followed for 3 months; the other stimulation settings and the medication regimen remained unchanged. Side effects, motor, non-motor, executive functions, and impedance were assessed at baseline and during follow-up. No adverse events were observed at time of shifting or during CC stimulation. Motor and non-motor measures remained unchanged at follow-up despite impedance decreased. Compared to baseline, inhibition processes improved at follow-up. The shifting strategy was well tolerated and the clinical outcome was maintained with no need to adjust stimulation settings or medications notwithstanding a decrease of impedance. Improvement of inhibition processes is a finding which needed further investigation.

  15. Exploring risk factors for stuttering development in Parkinson disease after deep brain stimulation.

    Picillo, Marina; Vincos, Gustavo B; Sammartino, Francesco; Lozano, Andres M; Fasano, Alfonso

    2017-05-01

    Stuttering is a speech disorder with disruption of verbal fluency, occasionally present in Parkinson's disease (PD). PD co-incident stuttering may either worsen or improve after Deep Brain Stimulation (DBS). Sixteen out of 453 PD patients (3.5%) exhibited stuttering after DBS (PD-S) and were compared with a group of patients without stuttering (PD-NS) using non-parametric statistics. After DBS, stuttering worsened in 3 out of 4 patients with co-incidental stuttering. Most PD-S underwent subthalamic (STN) DBS, but 4 were implanted in the globus pallidus (GPi). Nine out of 16 PD-S (56.3%) reported a positive familial history for stuttering compared to none of the PD-NS. PD-S were mainly male (81.3%) with slight worse motor features compared to PD-NS. Herein, we describe a group of PD patients developing stuttering after DBS and report the presence of a positive familial history for stuttering as the most relevant risk factor, suggesting a possible underlying genetic cause. The fact that stuttering occurred after either STN or GPi DBS is an argument against the impact of medication reduction on stuttering. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. The Genome-Scale Integrated Networks in Microorganisms

    Tong Hao

    2018-02-01

    Full Text Available The genome-scale cellular network has become a necessary tool in the systematic analysis of microbes. In a cell, there are several layers (i.e., types of the molecular networks, for example, genome-scale metabolic network (GMN, transcriptional regulatory network (TRN, and signal transduction network (STN. It has been realized that the limitation and inaccuracy of the prediction exist just using only a single-layer network. Therefore, the integrated network constructed based on the networks of the three types attracts more interests. The function of a biological process in living cells is usually performed by the interaction of biological components. Therefore, it is necessary to integrate and analyze all the related components at the systems level for the comprehensively and correctly realizing the physiological function in living organisms. In this review, we discussed three representative genome-scale cellular networks: GMN, TRN, and STN, representing different levels (i.e., metabolism, gene regulation, and cellular signaling of a cell’s activities. Furthermore, we discussed the integration of the networks of the three types. With more understanding on the complexity of microbial cells, the development of integrated network has become an inevitable trend in analyzing genome-scale cellular networks of microorganisms.

  17. Unusual uptake of prostate specific tracer {sup 68}Ga-PSMA-HBED-CC in a benign thyroid nodule

    Tripathi, Madhavi; Chakraborty, Partha Sarathi; Sahoo, Manas Kumar; Bal, Chandrasekhar; Aggarwal, Shipra; Arora, Geetanjali; Kumar, Praveen; Kumar, Rajeev; Gupta, Ravikant [A.I.I.M.S, New Delhi (India)

    2016-12-15

    {sup 68}Ga-Prostate specific membrane antigen- N,N′-bis[2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine-N,N′-diacetic acid- positron emission tomography/computed tomography or 68 Ga- HBED-CC-PSMA PET/CT, popularly known as PSMA PET/CT, is able to detect a small volume of recurrent prostate carcinoma (PC) when there is a prostate specific antigen (PSA) rise on follow-up after prostatectomy or other definitive treatment for PC. The use of PSMA PET/CT in the initial staging in PC is uncertain at this time. Clinical studies are underway to define its exact role in the management of the disease. At the same time it is important to be aware of unexpected sites of uptake of this ligand. We present here the case of a 62-year-old male patient who underwent prostatectomy for adenocarcinoma prostate. He also had a long-standing left solitary thyroid nodule (STN). Four months after surgery, he had a rising trend in serum PSA levels on three occasions, but the absolute value was less than 4 at all times. He underwent a {sup 68}Ga-PSMA-HBED-CC PET/CT, but it did not reveal any recurrent/metastatic site of disease. However, there was increased tracer uptake in the left STN. Fine needle aspiration cytology revealed features of atypia of undetermined significance, Bethesda category III. The patient underwent a left hemithyroidectomy and the histopathology showed features of a follicular adenoma.

  18. Constant Current versus Constant Voltage Subthalamic Nucleus Deep Brain Stimulation in Parkinson's Disease.

    Ramirez de Noriega, Fernando; Eitan, Renana; Marmor, Odeya; Lavi, Adi; Linetzky, Eduard; Bergman, Hagai; Israel, Zvi

    2015-02-18

    Background: Subthalamic nucleus (STN) deep brain stimulation (DBS) is an established therapy for advanced Parkinson's disease (PD). Motor efficacy and safety have been established for constant voltage (CV) devices and more recently for constant current (CC) devices. CC devices adjust output voltage to provide CC stimulation irrespective of impedance fluctuation, while the current applied by CV stimulation depends on the impedance that may change over time. No study has directly compared the clinical effects of these two stimulation modalities. Objective: To compare the safety and clinical impact of CC STN DBS to CV STN DBS in patients with advanced PD 2 years after surgery. Methods: Patients were eligible for inclusion if they had undergone STN DBS surgery for idiopathic PD, had been implanted with a Medtronic Activa PC and if their stimulation program and medication had been stable for at least 1 year. This single-center trial was designed as a double-blind, randomized, prospective study with crossover after 2 weeks. Motor equivalence of the 2 modalities was confirmed utilizing part III of the Unified Parkinson's Disease Rating Scale (UPDRS). PD diaries and multiple subjective and objective evaluations of quality of life, depression, cognition and emotional processing were evaluated on both CV and on CC stimulation. Analysis using the paired t test with Bonferroni correction for multiple comparisons was performed to identify any significant difference between the stimulation modalities. Results: 8 patients were recruited (6 men, 2 women); 1 patient did not complete the study. The average age at surgery was 56.7 years (range 47-63). Disease duration at the time of surgery was 7.5 years (range 3-12). Patients were recruited 23.8 months (range 22.5-24) after surgery. At the postoperative study baseline, this patient group showed an average motor improvement of 69% (range 51-97) as measured by the change in UPDRS part III with stimulation alone. Levodopa equivalent

  19. Variations in speciated emissions from spark-ignition and compression-ignition motor vehicles in California's south coast air basin.

    Fujita, Eric M; Zielinska, Barbara; Campbell, David E; Arnott, W Patrick; Sagebiel, John C; Mazzoleni, Lynn; Chow, Judith C; Gabele, Peter A; Crews, William; Snow, Richard; Clark, Nigel N; Wayne, W Scott; Lawson, Douglas R

    2007-06-01

    The U.S. Department of Energy Gasoline/Diesel PM Split Study examined the sources of uncertainties in using an organic compound-based chemical mass balance receptor model to quantify the contributions of spark-ignition (SI) and compression-ignition (CI) engine exhaust to ambient fine particulate matter (PM2.5). This paper presents the chemical composition profiles of SI and CI engine exhaust from the vehicle-testing portion of the study. Chemical analysis of source samples consisted of gravimetric mass, elements, ions, organic carbon (OC), and elemental carbon (EC) by the Interagency Monitoring of Protected Visual Environments (IMPROVE) and Speciation Trends Network (STN) thermal/optical methods, polycyclic aromatic hydrocarbons (PAHs), hopanes, steranes, alkanes, and polar organic compounds. More than half of the mass of carbonaceous particles emitted by heavy-duty diesel trucks was EC (IMPROVE) and emissions from SI vehicles contained predominantly OC. Although total carbon (TC) by the IMPROVE and STN protocols agreed well for all of the samples, the STN/IMPROVE ratios for EC from SI exhaust decreased with decreasing sample loading. SI vehicles, whether low or high emitters, emitted greater amounts of high-molecular-weight particulate PAHs (benzo[ghi]perylene, indeno[1,2,3-cd]pyrene, and coronene) than did CI vehicles. Diesel emissions contained higher abundances of two- to four-ring semivolatile PAHs. Diacids were emitted by CI vehicles but are also prevalent in secondary organic aerosols, so they cannot be considered unique tracers. Hopanes and steranes were present in lubricating oil with similar composition for both gasoline and diesel vehicles and were negligible in gasoline or diesel fuels. CI vehicles emitted greater total amounts of hopanes and steranes on a mass per mile basis, but abundances were comparable to SI exhaust normalized to TC emissions within measurement uncertainty. The combustion-produced high-molecular-weight PAHs were found in used

  20. Early spawning of Antarctic krill in the Scotia Sea is fuelled by “superfluous” feeding on non-ice associated phytoplankton blooms

    Schmidt, Katrin; Atkinson, Angus; Venables, Hugh J.; Pond, David W.

    2012-01-01

    The spawning success of Antarctic krill ( Euphausia superba) is generally assumed to depend on substantial winter sea ice extent, as ice biota can serve as a food source during winter/spring and the seasonal ice melt conditions the upper water column for extensive phytoplankton blooms. However, direct observations during spring are rare. Here we studied krill body condition and maturity stage in relation to feeding (i.e. stomach fullness, diet, absorption of individual fatty acids and defecation rate) across the Scotia Sea in November 2006. The phytoplankton concentrations were low at the marginal ice zone (MIZ) in the southern Scotia Sea (Stn. 1, 2, and 3), high in open waters of the Southern Antarctic Circumpolar Current Front (SACCF) in the central Scotia Sea (Stn. 5), and moderate further north (Stn. 6 and 7). Krill had low lipid reserves (˜6.5% of dry mass, DM), low mass:length ratios (˜1.7 mg DM mm -1), and small digestive glands (˜7% of total DM) near the ice edge. The stomachs contained lithogenic particles, diatom debris, and bacterial fatty acids, but low proportions of diatom-indicating fatty acids, which suggest that these krill were feeding on detritus rather than on fresh ice algae. In the SACCF, krill had higher lipid reserves (˜10% of DM), high mass:length ratios (˜2.2 mg DM mm -1), and large digestive glands (˜16% of total DM). Stomach content and tissue composition indicate feeding on diatoms. In the north, moderate food concentrations co-occurred with low lipid reserves in krill, and moderate mass:length ratios and digestive gland sizes. Only in the phytoplankton bloom in the SACCF had the mating season already started and some females were about to spawn. Based on the way krill processed their food at the different stations, we indicate two mechanisms that can lead to fast regeneration of body reserves and oocyte maturation in E. superba. One is "superfluous" feeding at high food concentrations, which maximises the overall nutrient gain

  1. Successful in vivo hyperthermal therapy toward breast cancer by Chinese medicine shikonin-loaded thermosensitive micelle

    Su Y

    2017-05-01

    Full Text Available Yonghua Su,1,* Nian Huang,1,* Di Chen,2,* Li Zhang,2,* Xia Dong,2 Yun Sun,2 Xiandi Zhu,2 Fulei Zhang,2 Jie Gao,2 Ying Wang,2 Kexing Fan,2 Puichi Lo,3 Wei Li,2 Changquan Ling1 1Department of Integrative Oncology, Changhai Hospital of Traditional Chinese Medicine, 2International Joint Cancer Institute, The Second Military Medical University, Shanghai, 3Department of Biomedical Sciences, City University of Hong Kong, Kowloon Tong, Hong Kong, China *These authors contributed equally to this work Abstract: The Chinese traditional medicine Shikonin is an ideal drug due to its multiple targets to tumor cells. But in clinics, improving its aqueous solubility and tumor accumulation is still a challenge. Herein, a copolymer with tunable poly(N-isopropylacrymaide and polylactic acid block lengths is designed, synthesized, and characterized in nuclear magnetic resonance. The corresponding thermosensitive nanomicelle (TN with well-defined core-shell structure is then assembled in an aqueous solution. For promoting the therapeutic index, the physical-chemistry properties of TNs including narrow size, low critical micellar concentration, high serum stability, tunable volume phase transition temperature (VPTT, high drug-loading capacity, and temperature-controlled drug release are systematically investigated and regulated through the fine self-assembly. The shikonin is then entrapped in a degradable inner core resulting in a shikonin-loaded thermosensitive nanomicelle (STN with a VPTT of ~40°C. Compared with small-molecular shikonin, the in vitro cellular internalization and cytotoxicity of STN against breast cancer cells (Michigan Cancer Foundation-7 are obviously enhanced. In addition, the therapeutic effect is further enhanced by the programmed cell death (PCD specifically evoked by shikonin. Interestingly, both the proliferation inhibition and PCD are synergistically promoted as T > VPTT, namely the temperature-regulated passive targeting. Consequently, as

  2. Atlas-based identification of targets for functional radiosurgery

    Stancanello, Joseph; Romanelli, Pantaleo; Modugno, Nicola; Cerveri, Pietro; Ferrigno, Giancarlo; Uggeri, Fulvio; Cantore, Giampaolo

    2006-01-01

    Functional disorders of the brain, such as Parkinson's disease, dystonia, epilepsy, and neuropathic pain, may exhibit poor response to medical therapy. In such cases, surgical intervention may become necessary. Modern surgical approaches to such disorders include radio-frequency lesioning and deep brain stimulation (DBS). The subthalamic nucleus (STN) is one of the most useful stereotactic targets available: STN DBS is known to induce substantial improvement in patients with end-stage Parkinson's disease. Other targets include the Globus Pallidus pars interna (GPi) for dystonia and Parkinson's disease, and the centromedian nucleus of the thalamus (CMN) for neuropathic pain. Radiosurgery is an attractive noninvasive alternative to treat some functional brain disorders. The main technical limitation to radiosurgery is that the target can be selected only on the basis of magnetic resonance anatomy without electrophysiological confirmation. The aim of this work is to provide a method for the correct atlas-based identification of the target to be used in functional neurosurgery treatment planning. The coordinates of STN, CMN, and GPi were identified in the Talairach and Tournoux atlas and transformed to the corresponding regions of the Montreal Neurological Institute (MNI) electronic atlas. Binary masks describing the target nuclei were created. The MNI electronic atlas was deformed onto the patient magnetic resonance imaging-T1 scan by applying an affine transformation followed by a local nonrigid registration. The first transformation was based on normalized cross correlation and the second on optimization of a two-part objective function consisting of similarity criteria and weighted regularization. The obtained deformation field was then applied to the target masks. The minimum distance between the surface of an implanted electrode and the surface of the deformed mask was calculated. The validation of the method consisted of comparing the electrode-mask distance to

  3. Optimal control of directional deep brain stimulation in the parkinsonian neuronal network

    Fan, Denggui; Wang, Zhihui; Wang, Qingyun

    2016-07-01

    The effect of conventional deep brain stimulation (DBS) on debilitating symptoms of Parkinson's disease can be limited because it can only yield the spherical field. And, some side effects are clearly induced with influencing their adjacent ganglia. Recent experimental evidence for patients with Parkinson's disease has shown that a novel DBS electrode with 32 independent stimulation source contacts can effectively optimize the clinical therapy by enlarging the therapeutic windows, when it is applied on the subthalamic nucleus (STN). This is due to the selective activation in clusters of various stimulation contacts which can be steered directionally and accurately on the targeted regions of interest. In addition, because of the serious damage to the neural tissues, the charge-unbalanced stimulation is not typically indicated and the real DBS utilizes charge-balanced bi-phasic (CBBP) pulses. Inspired by this, we computationally investigate the optimal control of directional CBBP-DBS from the proposed parkinsonian neuronal network of basal ganglia-thalamocortical circuit. By appropriately tuning stimulation for different neuronal populations, it can be found that directional steering CBBP-DBS paradigms are superior to the spherical case in improving parkinsonian dynamical properties including the synchronization of neuronal populations and the reliability of thalamus relaying the information from cortex, which is in a good agreement with the physiological experiments. Furthermore, it can be found that directional steering stimulations can increase the optimal stimulation intensity of desynchronization by more than 1 mA compared to the spherical case. This is consistent with the experimental result with showing that there exists at least one steering direction that can allow increasing the threshold of side effects by 1 mA. In addition, we also simulate the local field potential (LFP) and dominant frequency (DF) of the STN neuronal population induced by the activation

  4. La/Yb and Th/Sc in settling particles: vertical and horizontal transport of lithogenic material in the western North Pacific

    Otosaka, Shigeyoshi; Noriki, Shinichiro; Honda, Makio C.

    2004-01-01

    In order to understand the origins and transport processes of lithogenic aluminosilicate in the western North Pacific, time-series traps were deployed at Stn. KNOT at 44degN 155degE (water depth: 5320 m). Annual mean content of aluminum (Al) which is a proxy of lithogenic material in settling particles was 0.38% at 1 km depth, 0.78% at 3 km depth and 1.14% at 5 km depth, respectively. Mass fluxes were corrected by 230 Th and 231 Pa activities in particles and seawater. Annual mean corrected Al fluxes at 1, 3 and 5 km depths were calculated to 0.45, 0.46 and 0.33 g/m 2 /year, respectively. Lanthanum/ytterbium (La/Yb) and thorium/scandium (Th/Sc) ratios were used as proxies for estimating the origin of lithogenic aluminosilicate in settling particles. Both La/Yb and Th/Sc ratios in settling particles increased with depth, and the seasonal variation was the smallest at 5 km depth. It was considered that variations of La/Yb and Th/Sc ratios in settling particles reflected the change of source material of lithogenic aluminosilicates. Origins of lithogenic materials in the settling particles were summarized using two end-members, loess from central Asian continent (AL) and basalts from the Kurile-Kamchatka Islands (KEK). Contributions of end-members in settling particles were estimated from the La/Yb and Th/Sc ratios. The contribution of KK particles in lithogenic materials was calculated to be 84% at 1 km depth, and 61% at 3 and 5 km depths, respectively. Although the KK material was the dominant constituent of the terrigenous component in settling particles at Stn. KNOT, the KK flux decreased with depth. On the other hand, the AL flux increased with depth and the significant increase of the AL flux was presumably due to the lateral import of AL particles to the deep layer at Stn. KNOT. From these results we conclude that the distribution of lithogenic materials recorded in sediments in the western North Pacific are influenced by the northward transport of AL within the

  5. Complementary roles of different oscillatory activities in the subthalamic nucleus in coding motor effort in Parkinsonism.

    Tan, Huiling; Pogosyan, Alek; Anzak, Anam; Ashkan, Keyoumars; Bogdanovic, Marko; Green, Alexander L; Aziz, Tipu; Foltynie, Thomas; Limousin, Patricia; Zrinzo, Ludvic; Brown, Peter

    2013-10-01

    The basal ganglia may play an important role in the control of motor scaling or effort. Recently local field potential (LFP) recordings from patients with deep brain stimulation electrodes in the basal ganglia have suggested that local increases in the synchronisation of neurons in the gamma frequency band may correlate with force or effort. Whether this feature uniquely codes for effort and whether such a coding mechanism holds true over a range of efforts is unclear. Here we investigated the relationship between frequency-specific oscillatory activities in the subthalamic nucleus (STN) and manual grips made with different efforts. The latter were self-rated using the 10 level Borg scale ranging from 0 (no effort) to 10 (maximal effort). STN LFP activities were recorded in patients with Parkinson's Disease (PD) who had undergone functional surgery. Patients were studied while motor performance was improved by dopaminergic medication. In line with previous studies we observed power increase in the theta/alpha band (4-12 Hz), power suppression in the beta band (13-30 Hz) and power increase in the gamma band (55-90 Hz) and high frequency band (101-375 Hz) during voluntary grips. Beta suppression deepened, and then reached a floor level as effort increased. Conversely, gamma and high frequency power increases were enhanced during grips made with greater effort. Multiple regression models incorporating the four different spectral changes confirmed that the modulation of power in the beta band was the only independent predictor of effort during grips made with efforts rated <5. In contrast, increases in gamma band activity were the only independent predictor of effort during grips made with efforts ≥5. Accordingly, the difference between power changes in the gamma and beta bands correlated with effort across all effort levels. These findings suggest complementary roles for changes in beta and gamma band activities in the STN in motor effort coding. The latter function

  6. Glycan elongation beyond the mucin associated Tn antigen protects tumor cells from immune-mediated killing.

    Caroline B Madsen

    Full Text Available Membrane bound mucins are up-regulated and aberrantly glycosylated during malignant transformation in many cancer cells. This results in a negatively charged glycoprotein coat which may protect cancer cells from immune surveillance. However, only limited data have so far demonstrated the critical steps in glycan elongation that make aberrantly glycosylated mucins affect the interaction between cancer cells and cytotoxic effector cells of the immune system. Tn (GalNAc-Ser/Thr, STn (NeuAcα2-6GalNAc-Ser/Thr, T (Galβ1-3GalNAc-Ser/Thr, and ST (NeuAcα2-6Galβ1-3GalNAc-Ser/Thr antigens are recognized as cancer associated truncated glycans, and are expressed in many adenocarcinomas, e.g. breast- and pancreatic cancer cells. To investigate the role of the cancer associated glycan truncations in immune-mediated killing we created glyco-engineered breast- and pancreatic cancer cells expressing only the shortest possible mucin-like glycans (Tn and STn. Glyco-engineering was performed by zinc finger nuclease (ZFN knockout (KO of the Core 1 enzyme chaperone COSMC, thereby preventing glycan elongation beyond the initial GalNAc residue in O-linked glycans. We find that COSMC KO in the breast and pancreatic cancer cell lines T47D and Capan-1 increases sensitivity to both NK cell mediated antibody-dependent cellular-cytotoxicity (ADCC and cytotoxic T lymphocyte (CTL-mediated killing. In addition, we investigated the association between total cell surface expression of MUC1/MUC16 and NK or CTL mediated killing, and observed an inverse correlation between MUC16/MUC1 expression and the sensitivity to ADCC and CTL-mediated killing. Together, these data suggest that up-regulation of membrane bound mucins protects cells from immune mediated killing, and that particular glycosylation steps, as demonstrated for glycan elongation beyond Tn and STn, can be important for fine tuning of the immune escape mechanisms in cancer cells.

  7. Lead-Induced Atypical Parkinsonism in Rats: Behavioral, Electrophysiological, and Neurochemical Evidence for a Role of Noradrenaline Depletion

    Mariam Sabbar

    2018-03-01

    Full Text Available Background: Lead neurotoxicity is a major health problem known as a risk factor for neurodegenerative diseases, including the manifestation of parkinsonism-like disorder. While lead is known to preferentially accumulate in basal ganglia, the mechanisms underlying behavioral disorders remain unknown. Here, we investigated the neurophysiological and biochemical correlates of motor deficits induced by sub-chronic injections of lead.Methods: Sprague Dawely rats were exposed to sub-chronic injections of lead (10 mg/kg, i.p. or to a single i.p. injection of 50 mg/kg N-(2-chloroethyl-N-ethyl-2-bromobenzylamine hydrochloride (DSP-4, a drug known to induce selective depletion of noradrenaline. Rats were submitted to a battery of behavioral tests, including the open field for locomotor activity and rotarod for motor coordination. Electrophysiological recordings were carried out in three major basal ganglia nuclei, the subthalamic nucleus (STN, globus pallidus (GP, and substantia nigra pars reticulata (SNr. At the end of experiments, post-mortem tissue level of the three monoamines (dopamine, noradrenaline, and serotonin and their metabolites has been determined using HPLC.Results: Lead intoxication significantly impaired exploratory and locomotor activity as well as motor coordination. It resulted in a significant reduction in the level of noradrenaline in the cortex and dopamine and its metabolites, DOPAC, and HVA, in the striatum. The tissue level of serotonin and its metabolite 5-HIAA was not affected in the two structures. Similarly, DSP-4, which induced a selective depletion of noradrenaline, significantly decreased exploratory, and locomotor activity as well as motor coordination. L-DOPA treatment did not improve motor deficits induced by lead and DSP-4 in the two animal groups. Electrophysiological recordings showed that both lead and DSP-4 did not change the firing rate but resulted in a switch from the regular normal firing to irregular and

  8. Microstructural evolution of nanosized Ce0.8Gd0.2O1.9/Ni infiltrate in a Zr0.84Y0.16O1.92-Sr0.94Ti0.9Nb0.1O3-δ based SOFC anode under electrochemical evaluation

    Zhang, Wei; Kuhn, Luise Theil; Ramos, Tania

    are of paramount importance for performance and performance stability. Therefore an accurate understanding of the microstructure evolution during electrochemical operation will facilitate evaluating performances of SOFC anodes, and in turn optimize its design. Here we report a wealth of microstructural...... investigations of Ce0.8Gd0.2O1.9/Ni (hereafter CGO/Ni)-infiltrated Zr0.84Y0.16O1.92 composited Sr0.94Ti0.9Nb0.1O3-δ (STN94/8YSZ) anode in a symmetric cell design under a short electrochemical evaluation test (fingerprint test), applying electrochemical impedance spectroscopy (EIS) at mild 3% H2O/H2 and harsh 50...

  9. Application of dry separative methods for decreasing content the residues unburned coal and separation Fe from black coal flies ash

    František Kaľavský

    2008-06-01

    Full Text Available Main obstacle using of fly ashes in building, that is its main consumer, is the residue of unburned coal; it is expressed of loss onignition - LOI. In present, the valid STN and EU standard limits the content of LOI to 3 – 5 %, in national conditions maximum 7 %.Application of processing technologies also has to assure utilization of fly ash that provides a possibility of complex utilizationof individual products obtained by modification.By means of corona separation, based on different conductivity of individual fly ash elements, it is possible to separate unburnedcoal particles. The fly ash sample from black coal burning in melting boiler that was deposited on fly ash deposit, content of LOIof dielectric particle 6,45 % at 61 % weight yield was achieved. In the samples taken from dry taking of fly ash the non-conductingproduct contained 7,72 % of LOI at 73 % of weight yield.

  10. Infiltrated SrTiO3:FeCr-based anodes for metalsupported SOFC

    Blennow Tullmar, Peter; Persson, Åsa Helen; Nielsen, Jimmi

    2012-01-01

    The concept of using highly electronically conducting backbones with subsequent infiltration of electrocatalytic active materials, has recently been used to develop an alternative SOFC design based on a ferritic stainless steel support. The metal-supported SOFC is comprised of porous and highly e...... changes occurring in the anode layer during testing. The results indicate that the STN component in the anode seems to have a positive effect on the corrosion stability of the FeCr-particles in the anode layer.......) and FeCr. Electrochemical characterization and post test SEM analysis have been used to get an insight into the possible degradation mechanisms of this novel electrode infiltrated with Gd-doped CeO2 and Ni. Accelerated oxidation/corrosion experiments have been conducted to evaluate the microstructural...

  11. Deep Brain Stimulation in Parkinson’s Disease: New and Emerging Targets for Refractory Motor and Nonmotor Symptoms

    Dustin Anderson

    2017-01-01

    Full Text Available Parkinson’s disease (PD is a progressive neurodegenerative condition characterized by bradykinesia, tremor, rigidity, and postural instability (PI, in addition to numerous nonmotor manifestations. Many pharmacological therapies now exist to successfully treat PD motor symptoms; however, as the disease progresses, it often becomes challenging to treat with medications alone. Deep brain stimulation (DBS has become a crucial player in PD treatment, particularly for patients who have disabling motor complications from medical treatment. Well-established DBS targets include the subthalamic nucleus (STN, the globus pallidus pars interna (GPi, and to a lesser degree the ventral intermediate nucleus (VIM of the thalamus. Studies of alternative DBS targets for PD are ongoing, the majority of which have shown some clinical benefit; however, more carefully designed and controlled studies are needed. In the present review, we discuss the role of these new and emerging DBS targets in treating refractory axial motor symptoms and other motor and nonmotor symptoms (NMS.

  12. Proceedings of the USAF Structural Integrity Program Conference Held in 11-13 December 1990 in San Antonio, Texas

    1991-08-01

    z o wIx 2W WCOZ F-om 0 0 . zu C, 0a <o-z - w c0 -0 CL-cr. a: QI 0~~ Wo I. _ Oo () cr cr. 0< Oz30 i-1*CC0 *lW 0 w a. Cf461 aI~ ɘ w0 WLJW CfOz 0ɘ wwW...in the rotor bore, the sec- ond, a surface crack at the cone- web junction. Typical florescent--penetrate-inspection capability (FPI) is finding a 35 by...this reason, automatic or web , wing ctr. section, stn. eveni computer controlled shot 1000" carry the following peer ing is to be preferred "Repair

  13. Metodología de evaluación de confiabilidad para estudios de planeamiento del sistema de transmisión colombiano

    Fernández Ramírez, César Augusto

    2014-01-01

    Resumen: Este trabajo busca presentar una propuesta de criterios y metodología que permita unificar la evaluación de la confiabilidad del Sistema de Transmisión Nacional, para ser aplicada en el desarrollo de los estudios de planeamiento de la transmisión de energía eléctrica en Colombia, y en la evaluación de proyectos individuales de conexión al STN. Con este propósito se realizó el análisis de las metodologías y de los criterios empleados por la Unidad de Planeación Minero-Energética, como...

  14. Erie Nuclear Plant, Units 1 and 2. License application, preliminary safety analysis report, volume 1: chapter 1

    1977-01-01

    Erie 1 and 2 reactors will be located on a site consisting of 1,740 acres in Berlin Township about 2.4 miles south of Lake Erie and 8.9 miles southeast of Sandusky, Ohio. Lake Erie will provide makeup water. The ultimate heat sink will be a 40 acre cooling reservoir shared by both units. Each unit has a proposed core thermal power level of 3,760 MW(t) and a nominal net capacity of about 1282 MW(e). Unit 1 is scheduled for commercial operation by 4/1/84 and Unit 2 by 4/1/86. Fuel will be Zircaloy-4 clad tubes containing cylindrical fuel pellets of UO 2 . B and W pressurized water reactor units to be employed are described in DOCKET-STN-50561

  15. COMPARISON OF THE QUALITY OF VEGETABLE OILS DESIGNED FOR THE FRYING FOOD

    Ladislav Mura

    2012-12-01

    Full Text Available The object of the research was to investigate the quality of vegetable oils for cooking food. The analysis used two types of oils - oil Fritol and Promienna. Both oils were purchased commercially. Oil changes were observed at frying French fries. At the same changes were observed oil stored at room temperature and the temperature in the refrigerator. The determined parameters included the measurement of polar materials in oil with electronic device Testo 265 for measuring the quality of cooking oil. Determination of change in the texture of oil during the oil deterioration by device Texturometer TA.XT Plus and determination the peroxide value by STN EN ISO 3960:2007. The work is also evaluating the results of the studied parameters. In all compared cases based on the content of the TPM showed higher heat resistance oil Fritol and sample of oil stored in the refrigerator.doi:10.5219/210

  16. Pilot study of a heptavalent vaccine-keyhole limpet hemocyanin conjugate plus QS21 in patients with epithelial ovarian, fallopian tube, or peritoneal cancer

    Sabbatini, Paul J; Ragupathi, Govind; Hood, Chandra

    2007-01-01

    PURPOSE: To characterize the safety and immunogenicity of a heptavalent antigen-keyhole limpet hemocyanin (KLH) plus QS21 vaccine construct in patients with epithelial ovarian, fallopian tube, or peritoneal cancer in second or greater complete clinical remission. EXPERIMENTAL DESIGN: Eleven......). RESULTS: Eleven patients were included in the safety analysis; 9 of 11 patients remained on study for at least 2 weeks past fourth vaccination and were included in the immunologic analysis (two withdrew, disease progression). The vaccine was well tolerated. Self-limited and mild fatigue (maximum grade 2...... patients in this pilot trial received a heptavalent vaccine s.c. containing GM2 (10 microg), Globo-H (10 microg), Lewis Y (10 microg), Tn(c) (3 microg), STn(c) (3 microg), TF(c) (3 microg), and Tn-MUC1 (3 microg) individually conjugated to KLH and mixed with adjuvant QS21(100 microg). Vaccinations were...

  17. Anodes for Solid Oxide Fuel Cells Operating at Low Temperatures

    Abdul Jabbar, Mohammed Hussain

    An important issue that has limited the potential of Solid Oxide Fuel Cells (SOFCs) for portable applications is its high operating temperatures (800-1000 ºC). Lowering the operating temperature of SOFCs to 400-600 ºC enable a wider material selection, reduced degradation and increased lifetime....... On the other hand, low-temperature operation poses serious challenges to the electrode performance. Effective catalysts, redox stable electrodes with improved microstructures are the prime requisite for the development of efficient SOFC anodes. The performance of Nb-doped SrT iO3 (STN) ceramic anodes...... at 400ºC. The potential of using WO3 ceramic as an alternative anode materials has been explored. The relatively high electrode polarization resistance obtained, 11 Ohm cm2 at 600 ºC, proved the inadequate catalytic activity of this system for hydrogen oxidation. At the end of this thesis...

  18. Characterization of an immunodominant cancer-specific O-glycopeptide epitope in murine podoplanin (OTS8)

    Steentoft, Catharina; Schjoldager, Katrine T; Cló, Emiliano

    2010-01-01

    antibody 237, developed to a spontaneous murine fibrosarcoma, was shown to be directed to murine podoplanin (OTS8) with truncated Tn O-glycans. Our understanding of such cancer-specific auto-antibodies to truncated glycoforms of glycoproteins is limited. Here we have investigated immunogenicity...... of a chemoenzymatically produced Tn-glycopeptide derived from the putative murine podoplanin O-glycopeptide epitope. We found that the Tn O-glycopeptide was highly immunogenic in mice and produced a Tn-glycoform specific response with no reactivity against unglycosylated peptides or the O-glycopeptide with extended O......-glycan (STn and T glycoforms). The immunodominant epitope was strictly dependent on the peptide sequence, required Tn at a specific single Thr residue (Thr(77)), and antibodies to the epitope were not found in naive mice. We further tested a Tn O-glycopeptide library derived from human podoplanin...

  19. Identification and evaluation of nextgeneration PTM-specific antibodies

    Persson, Nina Emilia

    -chain fragment variable (scFv)clones. Two different analyses are performed on the same microarray. There is no need for anypurification or enrichment before screening. In the first analysis, the ability of the individualscFv clone to bind to the soluble form of the antigens is evaluated. Favouring selection....... Including antibodies target several different categories of antigens suchas proteins, glycoproteins and glycolipids. Glycoproteins have become highlighted in cancerresearch since they are frequently involved in the initiation and spreading of cancer. One form ofglycosylation of proteins is the O...... for the patients. Severalmonoclonal antibodies have been generated against the Tn- and STn-antigens, but none has yetreached approval for therapeutic or diagnostic use. Indicating the need for a new generation ofantibodies against this type aberrant glycosylation.The two major techniques used for the production...

  20. Promotion of Tumor Invasion by Cooperation of Granulocytes and Macrophages Activated by Anti-tumor Antibodies

    Emilio Barbera-Guillem

    1999-11-01

    Full Text Available We investigated the potential role of anti-tumor antibodies and tumor antigens in the formation of immune complexes which promote matrix degradation and angiogenesis. B-cell deficient or B-cell depleted mice showed a reduction in tumor invasion and metastasis. In vitro invasion assays and in vivo models of metastasis showed that anti-sTn antibodies and sTn tumor antigens form complexes which induce granulocytes and macrophages together to mediate tumor invasion and metastasis by processes including extracellular matrix degradation and angiogenesis. These results suggest the existence of a tumor promoting role of a B-cell immune response induced by shed tumor associated antigens of solid, nonlymphoid tumors.