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Sample records for repeated phencyclidine treatment

  1. alpha(7) Nicotinic acetylcholine receptor activation prevents behavioral and molecular changes induced by repeated phencyclidine treatment

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    Thomsen, Morten Skøtt; Christensen, Ditte Z; Hansen, Henrik H;

    2009-01-01

    , and administration of the NMDA-antagonist phencyclidine (PCP) in rodents is a well validated model of such cognitive deficits. Here we show that repeated PCP treatment (10 mg/kg/day for 10 days) decreased the expression of parvalbumin and synaptophysin mRNA in the mouse PFC, which corresponds to changes seen...... in patients with schizophrenia. In addition, PCP increased the basal mRNA expression in the PFC of the activity-regulated cytoskeleton-associated protein (Arc), a molecule involved in synaptic plasticity. These molecular changes produced by PCP were accompanied by a behavioral impairment as determined...... in a modified Y-maze test. Polymorphisms in the alpha(7) nicotinic acetylcholine receptor (nAChR) gene have been linked to schizophrenia. Here we demonstrate that acute administration of the selective alpha(7) nAChR partial agonist SSR180711 dose-dependently reversed the behavioral impairment induced by PCP...

  2. Automation of the social interaction test by a video-tracking system: behavioural effects of repeated phencyclidine treatment.

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    Sams-Dodd, F

    1995-07-01

    The social interaction test is a valuable behavioural model for testing anxiolytic and neuroleptic drugs. The test quantifies the level of social behaviour between pairs of rats and it is usually based on manual analysis of behaviour. Advances in computer technology have made it possible to track the movements of pairs of rats in an arena, and the present paper describes the automation of the social interaction test by the commercial video-tracking programme, the EthoVision system. The ability of the automated system to correctly measure the social behaviour of rats is demonstrated by determining a dose-response relationship in the social interaction test for phencyclidine, a psychotomimetic drug that reduces social behaviour between pairs of rats. These data are subsequently analysed by the manual and automated data-acquisition methods and the results are compared. The study shows that the automated data-acquisition method best describes the behavioural effects of phencyclidine in the social interaction test by the locomotor activity of the rats, how much time the rats spend in different sections of the testing arena, and the level of social behaviour. Correlation analysis of the results from the manual and automated data-acquisition methods shows that the social behaviour measured by the automated system corresponds correctly to the social behaviour measured by the manual analysis. The present study has shown that the automated data-acquisition method can quantify locomotor activity, how rats use a testing arena and the level of social behaviour between rats in the social interaction test. The system cannot distinguish between social and aggressive behaviours, and therefore the rats should be tested in an unfamiliar arena to reduce territorial behaviour. Taking this limitation into consideration, the social interaction test can be automated by this computer-based video-tracking system and can be used as a routine test for quantifying the effects of drugs on the

  3. Repeated potentiation of the metabotropic glutamate receptor 5 and the alpha 7 nicotinic acetylcholine receptor modulates behavioural and GABAergic deficits induced by early postnatal phencyclidine (PCP) treatment

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    Kjaerby, Celia; Bundgaard, Christoffer; Fejgin, Kim;

    2013-01-01

    treatment, pyramidal neurons displayed a reduced mIPSC frequency and up-regulation of extrasynaptic THIP-induced current. ADX47273 treatment restored this up-regulation of THIP-induced current. Reduced receptor function seems to be the underlying cause of the reported changes, since repeated treatment...

  4. Phencyclidine Induced Oculogyric Crisis Responding Well to Conventional Treatment

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    Hassan Tahir

    2015-01-01

    Full Text Available Background. Oculogyric crisis is a form of acute dystonic reaction characterized by involuntary upward deviation of eye ball. Its causes are broad with antipsychotics and antiemetics as the most common causes. Case Presentation. A 25-year-old man with the past medical history of marijuana use presented to ED with involuntary upward deviation of eye 1 day after using phencyclidine (PCP for the first time. He did not have any other symptoms and was hemodynamically stable. All laboratory investigations were normal except urine drug screen which was positive for PCP. Patient was treated with IV diphenhydramine which improved his symptoms. Conclusion. Illicit drug abuse is a growing problem in our society with increasingly more patients presenting to ED with its complications. The differential diagnosis of acute dystonic reactions should be extended to include illicit drugs as the potential cause of reversible acute dystonias especially in high risk patients.

  5. Acute phencyclidine treatment induces extensive and distinct protein phosphorylation in rat frontal cortex

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    Palmowski, Pawel; Rogowska-Wrzesinska, Adelina; Williamson, James

    2014-01-01

    assessment of the regulated proteins biological function revealed that PCP perturbs key processes in the frontal cortex including calcium homeostasis, organization of cytoskeleton, endo/exocytosis, and energy metabolism. This study on acute PCP treatment provides the largest proteomics and phosphoproteomics......Phencyclidine (PCP), a noncompetitive N-methyl-d-aspartate receptor antagonist, induces psychotomimetic effects in humans and animals. Administration of PCP to rodents is used as a preclinical model for schizophrenia; however, the molecular mechanisms underlying the symptoms remain largely unknown....... Acute PCP treatment rapidly induces behavioral and cognitive deficits; therefore, post-translational regulation of protein activity is expected to play a role at early time points. We performed mass-spectrometry- driven quantitative analysis of rat frontal cortex 15, 30, or 240 min after...

  6. A schizophrenia rat model induced by early postnatal phencyclidine treatment and characterized by Magnetic Resonance Imaging

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    Broberg, Brian V; Madsen, Kristoffer H; Plath, Niels

    2013-01-01

    administration of phencyclidine (PCP) induces schizophrenia-like symptoms in healthy volunteers and exacerbates symptoms in patients with schizophrenia. In this study, pharmacological Magnetic Resonance Imaging (phMRI) was used to evaluate if rats treated with 20mg/kg PCP on postnatal days 7, 9, and 11 (neoPCP......), compared to saline (neoVeh), were hypersensitive to acute PCP administration in adulthood (acutePCP). Intravenous administration of 0.5mg/kg acutePCP produced robust and sustained relative cerebral blood volume (rCBV) increase in discrete frontal, neocortical, hippocampal, thalamic, and limbic brain...... structures in both neoPCP:acutePCP and neoVeh:acutePCP rats compared to acute saline treatment (Vehicle control group). AcutePCP injection significantly increased the rCBV response in the medial prefrontal cortex and nucleus accumbens compared to the Vehicle control group, without distinguishing neoPCP...

  7. Acute phencyclidine treatment induces extensive and distinct protein phosphorylation in rat frontal cortex

    DEFF Research Database (Denmark)

    Palmowski, Pawel; Rogowska-Wrzesinska, Adelina; Williamson, James

    2014-01-01

    Phencyclidine (PCP), a noncompetitive N-methyl-d-aspartate receptor antagonist, induces psychotomimetic effects in humans and animals. Administration of PCP to rodents is used as a preclinical model for schizophrenia; however, the molecular mechanisms underlying the symptoms remain largely unknown....... Acute PCP treatment rapidly induces behavioral and cognitive deficits; therefore, post-translational regulation of protein activity is expected to play a role at early time points. We performed mass-spectrometry- driven quantitative analysis of rat frontal cortex 15, 30, or 240 min after...... the administration of PCP (10 mg/kg). We identified and quantified 23 548 peptides, including 4749 phosphopeptides, corresponding to 2604 proteins. A total of 352 proteins exhibited altered phosphorylation levels, indicating that protein phosphorylation is involved in the acute response to PCP. Computational...

  8. Effect of an NCAM mimetic peptide FGL on impairment in spatial learning and memory after neonatal phencyclidine treatment in rats

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    Secher, Thomas; Berezin, Vladimir; Bock, Elisabeth

    2008-01-01

    The FGL peptide is a neural cell adhesion molecule-derived fibroblast growth factor receptor agonist. FGL has both neurotrophic and memory enhancing properties. Neonatal phencyclidine (PCP) treatment on postnatal days 7, 9, and 11 has been shown to result in long-lasting behavioral abnormalities......, including cognitive impairment relevant to schizophrenia. The present study investigated the effect of FGL on spatial learning and memory deficits induced by neonatal PCP treatment. Rat pups were treated with 30mg/kg PCP on postnatal days 7, 9, and 11. Additionally, the rats were subjected to a chronic FGL...... treatment regimen where FGL was administered throughout development. Rats were tested as adults for spatial reference memory, reversal learning, and working memory in the Morris water maze. The PCP-treated rats demonstrated a robust impairment in working memory and reversal learning. However, the long...

  9. Changes in dopamine D2 and GluR-1 glutamate receptor mRNAs in the rat brain after treatment with phencyclidine.

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    Tomita,Hiroaki

    1995-04-01

    Full Text Available In situ hybridization of slide-mounted brain sections from rats subjected to acute and chronic phencyclidine treatment was carried out using synthetic oligonucleotides complementary to dopamine D2-receptor and non-N-methyl-D-aspartate (NMDA glutamate-receptor-subunit (GluR-1 mRNAs. There was no significant difference in either the D2-receptor or the GluR-1 mRNA levels in any brain region of the acute phencyclidine (10 mg/kg-treated and control groups. However, chronic administration of phencyclidine (10 mg/kg/day, 14 days significantly decreased the dopamine D2-receptor mRNA level in the caudate-putamen (by 27%, P < 0.01 and significantly increased the GluR-1 mRNA level in the prefrontal cortex (by 29%, P < 0.001. These results suggest that the chronic pharmaco-behavioral effects of phencyclidine may involve expression of both dopamine- and non-NMDA glutamate-receptor mRNAs.

  10. Effects of subchronic phencyclidine (PCP treatment on social behaviors, and operant discrimination and reversal learning in C57BL/6J mice

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    Jonathan L Brigman

    2009-02-01

    Full Text Available Subchronic treatment with the psychotomimetic phencyclidine (PCP has been proposed as a rodent model of the negative and cognitive/executive symptoms of schizophrenia. There has, however, been a paucity of studies on this model in mice, despite the growing use of the mouse as a subject in genetic and molecular studies of schizophrenia. In the present study, we evaluated the effects of subchronic PCP treatment (5 mg/kg twice daily x 7 days, followed by 7 days withdrawal in C57BL/6J mice on 1 social behaviors using a sociability/social novelty-preference paradigm, and 2 pairwise visual discrimination and reversal learning using a touchscreen-based operant system. Results showed that mice subchronically treated with PCP made more visits to (but did not spend more time with a social stimulus relative to an inanimate one, and made more visits and spent more time investigating a novel social stimulus over a familiar one. Subchronic PCP treatment did not significantly affect behavior in either the discrimination or reversal learning tasks. These data encourage further analysis of the potential utility of mouse subchronic PCP treatment for modeling the social withdrawal component of schizophrenia. They also indicate that the treatment regimen employed was insufficient to impair our measures of discrimination and reversal learning in the C57BL/6J strain. Further work will be needed to identify alternative methods (e.g., repeated cycles of subchronic PCP treatment, use of different mouse strains that produce discrimination and/or reversal impairment, as well as other cognitive/executive measures that are sensitive to chronic PCP treatment in mice.

  11. Metabolism of phencyclidine

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    Hoag, M.K.P.

    1987-01-01

    Phencyclidine (PCP) is a drug of abuse which may produce, in some users, a persistent schizophreniform psychosis. The possibility that long term effects of PCP are mediated by metabolic activation of the parent compound to reactive species is consistent with the demonstration of metabolism-dependent covalent binding of radiolabeled PCP in vivo and in vitro to macromolecules in rodent lung, liver, and kidney. Formation of the electrophilic iminium ion metabolite of PCP is believed to be critical for covalent binding since binding was inhibited by cyanide ion at concentrations which did not inhibit metabolism of PCP but did trap the iminium ion to form the corresponding alpha-aminonitrile. The present studies were designed to characterize further the biological fate of PCP by identifying possible macromolecular targets of the reactive metabolite(s).

  12. Enhancement of social novelty discrimination by positive allosteric modulators at metabotropic glutamate 5 receptors: adolescent administration prevents adult-onset deficits induced by neonatal treatment with phencyclidine.

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    Clifton, Nicholas E; Morisot, Nadège; Girardon, Sylvie; Millan, Mark J; Loiseau, Florence

    2013-02-01

    Metabotropic glutamate-5 receptors (mGluR5), which physically and functionally interact with N-methyl-D-Aspartate (NMDA) receptors, likewise control cognitive processes and have been proposed as targets for novel classes of antipsychotic agent. Since social cognition is impaired in schizophrenia and disrupted by NMDA receptor antagonists like dizocilpine, we evaluated its potential modulation by mGluR5. Acute administration (0.63-40 mg/kg) of the mGluR5 positive allosteric modulators (PAMs), 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide (CDPPB) and ADX47273, reversed a delay-induced impairment in social novelty discrimination (SND) in adult rats. The action of CDPPB was blocked by the mGluR5 antagonist, 2-methyl-6-(phenylethynyl)-pyridine (2.5-10 mg/kg), and was also expressed upon microinjection into frontal cortex (0.63-10 μg/side), but not striatum. Supporting an interrelationship between mGluR5 and NMDA receptors, enhancement of SND by CDPPB was blocked by dizocilpine (0.08 mg/kg) while, reciprocally, dizocilpine-induced impairment in SND was attenuated by CDPPB (10 mg/kg). The SND deficit elicited by post-natal administration of phencyclidine (10 mg/kg, days 7-11) was reversed by CDPPB or ADX47273 in adults at week 8. This phencyclidine-induced impairment in cognition emerged in adult rats from week 7 on, and chronic, pre-symptomatic treatment of adolescent rats with CDPPB over weeks 5-6 (10 mg/kg per day) prevented the appearance of SND deficits in adults until at least week 13. In conclusion, as evaluated by a SND procedure, mGluR5 PAMs promote social cognition via actions expressed in interaction with NMDA receptors and exerted in frontal cortex. MGluR5 PAMs not only reverse but also (when given during adolescence) prevent the emergence of cognitive impairment associated with a developmental model of schizophrenia.

  13. Potential of repeated polymer well treatments

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    Lakatos, I.; Lakatos-Szabo, J. (Hungarian Academy of Sciences, Budapest (Hungary)); Munkacsi, I.; Troemboeczki, S.

    1993-11-01

    This paper analyzes field results obtained by routine application of a polymer/silicate well treatment technique at the Algyo-2 field in Hungary. First, the reservoir is described briefly; then, the basic concept of the method is outlined. Reference is made to the multifunctioning chemical mechanism of gelation and the favorable rheological properties of the treating fluids that jointly result in a highly selective placement and an efficient permeability reduction in the target reservoir space. Application of the method 17 times in 16 producing wells yielded more than 90,000 Mg of incremental oil production. Typical well behaviors also are illustrated. Finally, the potential of repeated treatments is discussed, taking laboratory and field results into account.

  14. Phencyclidine prevents spatial navigation and passive avoidance deficits in ibotenate lesioned rats.

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    O'Connell, A; Earley, B; Leonard, B E

    1994-09-01

    The potential neuroprotective effects of phencyclidine (5 mg/kg i.p.) were assessed in rats which had been treated with the excitotoxin, ibotenic acid (IBO) (0.015 M) to lesion the nucleus basalis magnocellularis. IBO treated rats showed a significant impairment in 13 of the 25 test trials in the spatial navigation Morris water maze task and deficits in passive avoidance learning. Phencyclidine was found to prevent the IBO-induced impairment in 4 of the 13 test trials in which the IBO Morris maze deficit was observed and also successfully prevented the passive avoidance learning deficits. Neurochemically, IBO was shown to reduce the levels of gamma amino-n-butyric acid (GABA) in the cortex. This effect of IBO on the inhibitory GABAergic system may contribute to the direct toxic effects of IBO which is mediated through excitatory amino acid receptors. Phencyclidine had no effect on the changes in GABA produced by IBO. The effect of phencyclidine treatment on IBO behavioural toxicity observed in this study demonstrates that antagonism of the phencyclidine receptor site on the N-methyl-D-aspartate receptor complex may be partially protective against the excitotoxic damage induced by IBO.

  15. Hippocampal serotonin depletion unmasks differences in the hyperlocomotor effects of phencyclidine and MK-801: quantitative versus qualitative analyses

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    Wendy K Adams

    2013-08-01

    Full Text Available Antagonism of N-methyl-D-aspartate (NMDA receptors by phencyclidine is thought to underlie its ability to induce a schizophrenia-like syndrome in humans, yet evidence indicates it has a broader pharmacological profile. Our previous lesion studies highlighted a role for serotonergic projections from the median, but not dorsal, raphe nucleus in mediating the hyperlocomotor effects of phencyclidine, without changing the action of the more selective NMDA receptor antagonist, MK-801. Here we compared locomotor responses to phencyclidine and MK 801 in rats that were administered 5,7 dihydroxytryptamine (5,7-DHT into either the dorsal or ventral hippocampus, which are preferentially innervated by median and dorsal raphe, respectively. Dorsal hippocampus lesions potentiated phencyclidine-induced hyperlocomotion (0.5, 2.5 mg/kg, but not the effect of MK-801 (0.1 mg/kg. Ventral hippocampus lesions did not alter the hyperlocomotion elicited by either compound. Given that phencyclidine and MK-801 may induce different spatiotemporal patterns of locomotor behavior, together with the known role of the dorsal hippocampus in spatial processing, we also assessed whether the 5,7-DHT-lesions caused any qualitative differences in locomotor responses. Treatment with phencyclidine or MK-801 increased the smoothness of the path travelled (reduced spatial d and decreased the predictability of locomotor patterns within the chambers (increased entropy. 5,7-DHT-lesions of the dorsal hippocampus did not alter the effects of phencyclidine on spatial d or entropy—despite potentiating total distance moved—but caused a slight reduction in levels of MK-801-induced entropy. Taken together, serotonergic lesions targeting the dorsal hippocampus unmask a functional differentiation of the hyperlocomotor effects of phencyclidine and MK 801. These findings have implications for studies utilising NMDA receptor antagonists in modeling glutamatergic dysfunction in schizophrenia.

  16. Investigating the long-term effect of subchronic phencyclidine-treatment on novel object recognition and the association between the gut microbiota and behavior in the animal model of schizophrenia.

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    Pyndt Jørgensen, B; Krych, L; Pedersen, T B; Plath, N; Redrobe, J P; Hansen, A K; Nielsen, D S; Pedersen, C S; Larsen, C; Sørensen, D B

    2015-03-15

    Subchronic phencyclidine (subPCP) treatment induces schizophrenic-like behavior in rodents, including cognitive deficits and increased locomotor sensitivity towards acute administration of PCP. Evidence is accumulating that the gut microbiota (GM) influences behavior through modulation of the microbiota-gut-brain axis, and hence, part of the variation within this animal model may derive from variation in the GM. The aims of this study was to investigate first, the duration of subPCP-induced cognitive impairment in the novel object recognition test, and second, the possible effect of subchronic PCP-treatment on the GM, and the association between the GM and the behavioral parameters. The association was further investigated by antibiotic reduction of the GM. Male Lister Hooded rats were dosed twice daily i.p. with either 5mg/kg PCP or sterile isotonic saline for seven days followed by a seven-day washout period. Rats were tested in the novel object recognition and the locomotor activity assays immediately after, three weeks after, or six weeks after washout, and the fecal GM was analyzed by high throughput sequencing. Antibiotic- and control-treated rats were tested in the same manner following washout. In conclusion, subPCP-treatment impaired novel object recognition up to three weeks after washout, whereas locomotor sensitivity was increased for at least six weeks after washout. Differences in the core gut microbiome immediately after washout suggested subPCP treatment to alter the GM. GM profiles correlated to memory performance. Administration of ampicillin abolished the subPCP-induced memory deficit. It thus seems reasonable to speculate that the GM influences memory performance, contributing to variation within the model.

  17. Translational aspects of the novel object recognition task in rats abstinent following sub-chronic treatment with phencyclidine (PCP: effects of modafinil and relevance to cognitive deficits in schizophrenia?

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    John P Redrobe

    2010-11-01

    Full Text Available Phencyclidine (PCP induces a behavioural syndrome in rodents that bears remarkable similarities to some of the core symptoms observed in schizophrenic patients, among those cognitive deficits. The successful alleviation of cognitive impairments associated with schizophrenia (CIAS has become a major focus of research efforts as they remain largely untreated. The aim of the present study was to investigate the effects of selected antipsychotic and cognition enhancing drugs, namely haloperidol, risperidone, donepezil, and modafinil in an animal model widely used in preclinical schizophrenia research. To this end, the novel object recognition (NOR task was applied to rats abstinent following sub-chronic treatment with PCP. Rats were administered either PCP (5 mg/kg, i.p. or vehicle twice a day for 7 days, followed by a 7-day washout period, before testing in NOR. Upon testing, vehicle-treated rats successfully discriminated between novel and familiar objects, an effect abolished in rats that had previously been exposed to PCP-treatment. Acute treatment with modafinil (64 mg/kg, p.o. ameliorated the PCP-induced deficit in novel object exploration, whereas haloperidol (0.1 mg/kg, s.c., risperidone (0.2 mg/kg, i.p. and donepezil (3 mg/kg, p.o. were without significant effect. Given the negligible efficacy of haloperidol and risperidone, and the contradictory data with donepezil to treat CIAS in the clinic, together with the promising preliminary pro-cognitive effects of modafinil in certain subsets of schizophrenic patients, the sub-chronic PCP-NOR abstinence paradigm may represent an attractive option for the identification of potential novel treatments for CIAS.

  18. Repeated treatments of drooling with botulinum toxin B in neurology

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    Møller, Eigild; Daugaard, Dorthe; Holm, Ole

    2015-01-01

    OBJECTIVES: To investigate efficacy, saliva flow, and composition in repeated BoNT-B treatments of drooling. MATERIALS AND METHODS: Seventeen neurological patients (median 66 years), referred for treatment of drooling participated in this observational study. Median total doses of 4000 units...

  19. Repeated morphine treatment influences operant and spatial learning differentially

    Institute of Scientific and Technical Information of China (English)

    Mei-Na WANG; Zhi-Fang DONG; Jun CAO; Lin XU

    2006-01-01

    Objective To investigate whether repeated morphine exposure or prolonged withdrawal could influence operant and spatial learning differentially. Methods Animals were chronically treated with morphine or subjected to morphine withdrawal. Then, they were subjected to two kinds of learning: operant conditioning and spatial learning.Results The acquisition of both simple appetitive and cued operant learning was impaired after repeated morphine treatment. Withdrawal for 5 weeks alleviated the impairments. Single morphine exposure disrupted the retrieval of operant memory but had no effect on rats after 5-week withdrawal. Contrarily, neither chronic morphine exposure nor 5-week withdrawal influenced spatial learning task of the Morris water maze. Nevertheless, the retrieval of spatial memory was impaired by repeated morphine exposure but not by 5-week withdrawal. Conclusion These observations suggest that repeated morphine exposure can influence different types of learning at different aspects, implicating that the formation of opiate addiction may usurp memory mechanisms differentially.

  20. Differential expression of parvalbumin in neonatal phencyclidine-treated rats and socially isolated rats.

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    Kaalund, Sanne S; Riise, Jesper; Broberg, Brian V; Fabricius, Katrine; Karlsen, Anna S; Secher, Thomas; Plath, Niels; Pakkenberg, Bente

    2013-02-01

    Decreased parvalbumin expression is a hallmark of the pathophysiology of schizophrenia and has been associated with abnormal cognitive processing and decreased network specificity. It is not known whether this decrease is due to reduced expression of the parvalbumin protein or degeneration of parvalbumin-positive interneurons (PV(+) interneurons). In this study, we examined PV(+) expression in two rat models of cognitive dysfunction in schizophrenia: the environmental social isolation (SI) and pharmacological neonatal phencyclidine (neoPCP) models. Using a stereological method, the optical fractionator, we counted neurons, PV(+) interneurons, and glial cells in the medial prefrontal cortex (mPFC) and hippocampus (HPC). In addition, we quantified the mRNA level of parvalbumin in the mPFC. There was a statistically significant reduction in the number of PV(+) interneurons (p = 0.021) and glial cells (p = 0.024) in the mPFC of neonatal phencyclidine rats, but not in SI rats. We observed no alterations in the total number of neurons, hippocampal PV(+) interneurons, parvalbumin mRNA expression or volume of the mPFC or HPC in the two models. Thus, as the total number of neurons remains unchanged following phencyclidine (PCP) treatment, we suggest that the decreased number of counted PV(+) interneurons represents a reduced parvalbumin protein expression below immunohistochemical detection limit rather than a true cell loss. Furthermore, these results indicate that the effect of neonatal PCP treatment is not limited to neuronal populations.

  1. Tetrahydrocannabinol interactions with phencyclidine and methaqualone

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    Lame, M.W.

    1983-01-01

    To determine the effects of ..delta../sup 9/-tetrahydrocannabinol (THC) on the pharmacokinetics and metabolism of phencyclidine (PCP) or methaqualone (MTQ), both in vivo and in vitro studies were conducted using Sprague Dawley rats. In the in vivo studies, plasma levels of /sup 3/H-PCP.HCl equivalents were significantly altered by the administration of THC, with the test curve elevated and parallel to the control. Tissue data followed the same pattern as plasma. The urinary, fecal, and biliary excretion of /sup 3/H-PCP.HCl equivalents for the most part did not show significant perturbation with the coadministration of THC. With respect of MTQ, plasma studies indicated that THC could significantly elevate /sup 14/C-MTQ equivalents for the first 4.5 hours, reduce these levels from approximately 6.5 to 16.5 hours, and again elevate the levels above controls for the period from 19.5 to 22.5 hours. All significant changes in tissue levels mirrored plasma value differences seen between test and control animals. Biliary excretion data indicated that THC showed a trend towards altering the active excretion of /sup 14/C-MTQ equivalents. In vitro microsomal metabolism studies indicated that THC production of phenylcyclohexylamine, 1-(1-phenyl-4-hydroxycyclohexyl)piperidine, and 1-(1-phenylcyclohexyl)-4-hydroxypiperidine. Similar studies conducted with MTQ revealed that THC at the 0.05, 0.025, and 0.0125 mM levels also inhibited the metabolism of this compound.

  2. PTSD among a treatment sample of repeat DUI offenders.

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    Peller, Allyson J; Najavits, Lisa M; Nelson, Sarah E; LaBrie, Richard A; Shaffer, Howard J

    2010-08-01

    Recent studies indicate that posttraumatic stress disorder (PTSD) is one of the most common psychiatric comorbidities among driving-under-the-influence (DUI) offenders in treatment. Investigation of DUI offenders' PTSD and clinical characteristics could have important implications for prevention and treatment. This prospective study examined the demographic and clinical characteristics of repeat DUI offenders with PTSD symptoms at baseline and 1-year follow-up. Seven hundred twenty-nine DUI offenders admitted to a 2-week inpatient program participated in the study. Participants with PTSD evidenced more severe psychiatric comorbidity and reported a higher DUI recidivism rate at 1-year than those without PTSD. This study suggests a need to address PTSD among DUI offenders, as well as to further develop methodologies for accurately reporting DUI recidivism.

  3. Simulation of psychosis by continuous delivery of phencyclidine from controlled-release polymer implants.

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    Schroeder, U; Schroeder, H; Darius, J; Grecksch, G; Sabel, B A

    1998-12-01

    To simulate psychosis in rats we have developed a method for the continuous delivery of phencyclidine (PCP) using implantable controlled-release polymers. PCP polymer implants produced deficits in latent inhibition which do not occur after repeated bolus injections. PCP implanted rats were also devoid of any anxiogenic signs, motoric hyperactivity and learning acquisition which can be seen in rats receiving daily bolus injections of a comparable PCP dose. This behavioral double-dissociation of the two modes of PCP application was accompanied by respective neurochemical changes. PCP binding sites were reduced in both striatum and hippocampus, but in the hippocampus, loss of PCP binding sites was more severe following pulsatile PCP administration. Morphological assessment revealed a significant shrinkage of the CA3 region in hippocampus in both groups. Pharmacokinetic analysis showed that the maximum PCP concentration in the brain after bolus injections was 10-fold above the PCP implants.

  4. Ketamine and phencyclidine: the good, the bad and the unexpected

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    Lodge, D; Mercier, M S

    2015-01-01

    The history of ketamine and phencyclidine from their development as potential clinical anaesthetics through drugs of abuse and animal models of schizophrenia to potential rapidly acting antidepressants is reviewed. The discovery in 1983 of the NMDA receptor antagonist property of ketamine and phencyclidine was a key step to understanding their pharmacology, including their psychotomimetic effects in man. This review describes the historical context and the course of that discovery and its expansion into other hallucinatory drugs. The relevance of these findings to modern hypotheses of schizophrenia and the implications for drug discovery are reviewed. The findings of the rapidly acting antidepressant effects of ketamine in man are discussed in relation to other glutamatergic mechanisms. PMID:26075331

  5. Compressed air massage: repeated treatment causes less muscle oedema than a single treatment

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    M. A. Gregory

    2007-02-01

    Full Text Available Compressed air massage is a new treatment modality that has been shown to cause skeletal muscle capillary dilation for up to 24 hours after a single treatment and significantly hastens healing of diabetic ulcers. This study compares the effect of one treatment of a single muscle group, with repeated treatments of several muscle groups. Methods: Four vervet monkeys underwent one, 15 min, treatment of compressed air massage at 1 Bar, to the tibialis anterior muscle and four animals received similar treatment to the whole lower leg on three consecutive days. The tibialis anterior of the treated and untreated limbs was biopsied immediately after the final treatment. Muscle fibre diameters were measured from 1µm thick toluidine blue stained resin embedded sections using light microscopy and computerized image analysis software. Results: For treatment of the whole lower limb, the mean fibre diameter increased by 6.0% from 47.31±13.4µm(95%CI:46.47-48.16 in control biopsies to 50.14±13.93µm (95%CI:49.26-51.02 in treated muscle (p<0.001.Treatment of a single muscle showed an increase in diameter of 11.3%, from 48.21±12.68µm (95%CI:47.31-49.11 to53.63+14.29µm (95%CI:52.61-54.66 (p<0.001. Treatment of a single muscle caused significantly more oedema thantreatment of the whole limb (p<0.001. Conclusions: Repeated treatment causes skeletal muscle oedema, and this appears to be dose related. Skeletal muscleoedema after three treatments is less than after a single treatment. Further studies on the use of compressed air massage on injured muscle are warranted.

  6. Impaired GABAergic Inhibition in the Prefrontal Cortex of Early Postnatal Phencyclidine (PCP)-Treated Rats

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    Kjaerby, Celia; Broberg, Brian V; Kristiansen, Uffe

    2014-01-01

    in adulthood. The present study examines prefrontal GABAergic transmission in adult rats administered with the NMDA receptor channel blocker, phencyclidine (PCP), for 3 days during the second postnatal week. Whole-cell patch-clamp recordings from pyramidal cells in PCP-treated rats showed a 22% reduction...... in the frequency of miniature inhibitory postsynaptic currents in layer II/III, but not in layer V pyramidal neurons of the prefrontal cortex. Furthermore, early postnatal PCP treatment caused insensitivity toward effects of the GABA transporter 1 (GAT-1) inhibitor, 1,2,5,6-tetrahydro-1-[2-[[(diphenyl...... postnatal PCP-treated rats and support the hypothesis that PCP administration during neurodevelopment affects the functionality of interneurons in later life....

  7. Phencyclidine in the social interaction test: an animal model of schizophrenia with face and predictive validity.

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    Sams-Dodd, F

    1999-01-01

    Phencyclidine (PCP) is a hallucinogenic drug that can mimic several aspects of the schizophrenic symptomatology in healthy volunteers. In a series of studies PCP was administered to rats to determine whether it was possible to develop an animal model of the positive and negative symptoms of schizophrenia. The rats were tested in the social interaction test and it was found that PCP dose-dependently induces stereotyped behaviour and social withdrawal, which may correspond to certain aspects of the positive and negative symptoms, respectively. The effects of PCP could be reduced selectively by antipsychotic drug treatment, whereas drugs lacking antipsychotic effects did not alleviate the PCP-induced behaviours. Together these findings indicate that PCP effects in the rat social interaction test may be a model of the positive and negative symptoms of schizophrenia with face and predictive validity and that it may be useful for the evaluation of novel antipsychotic compounds.

  8. Decrease in adverse reactions after repeated ivermectin treatment in onchocerciasis.

    Science.gov (United States)

    Van der Lelij, A; Rothova, A; Klaassen-Broekema, N; Wilson, W R; Barbe, R F; Stilma, J S

    1990-10-01

    We assessed the side-effects after multiple single-dose treatment with ivermectin (150 micrograms/kg) in onchocerciasis patients form a hyperendemic area in Sierra Leone, in order to investigate whether medical surveillance was always necessary. After initial treatment 87 onchocerciasis patients were examined for adverse reactions. Fourty-four of these 87 patients (51%) received a second dose of ivermectin 5 months later and thirty-five (40%) received a third dose one year later. The side-effects after the second and third doses were significantly diminished, when compared with the initial dose of ivermectin in the treatment of onchocerciasis (chi2 test p less than 0.005, resp. p less than 0.008). Side-effects requiring therapy were observed in 32% of patients after the first dose, in 18% after the second dose and in 11% after the third dose of ivermectin. Severe side-effects (9%) were only seen after the initial ivermectin dose. All the severe adverse reactions appeared within 48 hours. In view of our findings, it seems necessary that the first treatment with ivermectin should take place under strict medical supervision during at least two days. Five months after treatment with a single dose of ivermectin 29 out of 44 patients (66%) still had a positive skin-snip test. Seven months after the second dose 15 of 35 patients (43%) had a positive skin-snip count. Since almost half of the patients had a positive skin-snip test despite two treatments with ivermectin, it could be argued that in hyperendemic areas treatment should consist of at least two doses in the first year.

  9. Cardiac actions of phencyclidine in isolated guinea pig and rat heart: possible involvement of slow channels

    Energy Technology Data Exchange (ETDEWEB)

    Temma, K.; Akera, T.; Ng, Y.C.

    1985-03-01

    The mechanisms responsible for the positive inotropic effect of phencyclidine were studied in isolated preparations of guinea pig and rat heart. In electrically paced left atrial muscle preparations, phencyclidine increased the force of contraction; rat heart muscle preparations were more sensitive than guinea pig heart muscle preparations. The positive inotropic effect of phencyclidine was not significantly reduced by a combination of phentolamine and nadolol; however, the effect was competitively blocked by verapamil in the presence of phentolamine and nadolol. Inhibition of the outward K+ current by tetraethylammonium chloride also produced a positive inotropic effect; however, the effect of tetraethylammonium was reduced by phentolamine and nadolol, and was almost insensitive to verapamil. The inotropic effect of phencyclidine was associated with a marked prolongation of the action potential duration and a decrease in maximal upstroke velocity of the action potential, with no change in the resting membrane potential. The specific (/sup 3/H)phencyclidine binding observed with membrane preparations from guinea pig ventricular muscle was saturable with a single class of high-affinity binding site. This binding was inhibited by verapamil, diltiazem, or nitrendipine, but not by ryanodine or tetrodotoxin. These results suggest that the positive inotropic effect of phencyclidine results from enhanced Ca/sup 2 +/ influx via slow channels, either by stimulation of the channels or secondary to inhibition of outward K/sup +/ currents.

  10. Assessing small-volume spinal cord dose for repeat spinal stereotactic body radiotherapy treatments

    Science.gov (United States)

    Ma, Lijun; Kirby, Neil; Korol, Renee; Larson, David A.; Sahgal, Arjun

    2012-12-01

    Spinal cord biologically effective dose (BED) limits are critical to safe spine stereotactic body radiotherapy (SBRT) delivery. In particular, when repeating SBRT to the same site, the problem of adding non-uniform BED distributions within small volumes of spinal cord has yet to be solved. We report a probability-based generalized BED (gBED) model to guide repeat spine SBRT treatment planning. The gBED was formulated by considering the sequential damaging probabilities of repeat spine SBRT treatments. Parameters from the standard linear-quadratic model, such as α/β = 2 Gy for the spinal cord, were applied. We tested the model based on SBRT specific spinal cord tolerance using a simulated and ten clinical repeat SBRT cases. The gBED provides a consistent solution for superimposing non-uniform dose distributions from different fractionation schemes, analogous to the BED for uniform dose distributions. Based on ten clinical cases, the gBED was observed to eliminate discrepancies in the cumulative BED of approximately 5% to 20% within small volumes (e.g. 0.1-2.0 cc) of spinal cord, as compared to a conventional calculation method. When assessing spinal cord tolerance for repeat spinal SBRT treatments, caution should be exercised when applying conventional BED calculations for small volumes of spinal cord irradiated, and the gBED potentially provides more conservative and consistently derived dose surrogates to guide safe treatment planning and treatment outcome modeling.

  11. a7 nicotinic receptor agonism mitigates phencyclidine-induced changes in synaptophysin and Arc gene expression in the mouse prefrontal cortex

    DEFF Research Database (Denmark)

    Thomsen, Morten S; Hansen, Henrik H; Mikkelsen, Jens D

    2010-01-01

    Repeated phencyclidine (PCP) administration in mice reproduces several histopathological features of schizophrenia, such as reduced synaptophysin and parvalbumin mRNA expression in the frontal cortex. These changes can be prevented by co-administering the a7 nicotinic acetylcholine receptor (n......AChR) agonist SSR180711 with PCP, but it is not known to what extent PCP-induced changes can be normalized once they have already occurred. Here we use semi-quantitative in situ hybridization to show that repeated administration of SSR180711 (3 mg/kg b.i.d. for 5 days) subsequent to repeated PCP administration...... (10 mg/kg/day for 10 days) is able to mitigate the reduction of synaptophysin mRNA expression induced by PCP in two prefrontal cortical regions, the medial prefrontal cortex (mPFC) and the ventrolateral orbitofrontal cortex (VLO). This effect is accompanied by a normalization of the PCP...

  12. α7 nicotinic receptor agonism mitigates phencyclidine-induced changes in synaptophysin and Arc gene expression in the mouse prefrontal cortex

    DEFF Research Database (Denmark)

    Thomsen, Morten S; Hansen, Henrik H; Mikkelsen, Jens D

    2010-01-01

    Repeated phencyclidine (PCP) administration in mice reproduces several histopathological features of schizophrenia, such as reduced synaptophysin and parvalbumin mRNA expression in the frontal cortex. These changes can be prevented by co-administering the α7 nicotinic acetylcholine receptor (n......AChR) agonist SSR180711 with PCP, but it is not known to what extent PCP-induced changes can be normalized once they have already occurred. Here we use semi-quantitative in situ hybridization to show that repeated administration of SSR180711 (3 mg/kg b.i.d. for 5 days) subsequent to repeated PCP administration...... (10 mg/kg/day for 10 days) is able to mitigate the reduction of synaptophysin mRNA expression induced by PCP in two prefrontal cortical regions, the medial prefrontal cortex (mPFC) and the ventrolateral orbitofrontal cortex (VLO). This effect is accompanied by a normalization of the PCP...

  13. Contact transcleral ciliary body photodynamic therapy with verteporfin in pigmented rabbits: effect of repeated treatments.

    Science.gov (United States)

    Charisis, Spyridon K; Naoumidi, Irene I; Ginis, Harilaos S; Detorakis, Efstathios T; Tsilimbaris, Miltiadis K

    2010-01-01

    We studied the effect on the intraocular pressure (IOP) and the ciliary body (CB) morphology after four consecutive contact transcleral photodynamic treatments of the ciliary body (CB-PDT) with verteporfin in pigmented rabbits. Twenty-two pigmented rabbits underwent CB-PDT (study group), performed once (six rabbits) or repeated for up to four times (16 rabbits). Six additional rabbits received only laser treatment without photosensitizer administration (control group). CB-PDT was performed in one eye in rabbits of the study group, with the fellow eye serving as internal control. Verteporfin dosage was 1 mg kg(-1) as bolus injection and laser settings were 40 mW (600 microm core optical fiber) for 1.5 min per spot, for 10 spots. In repeated CB-PDT, treatments were performed in 4-day intervals. Daily IOP measurements were recorded. Histological studies were performed at selected time points. An IOP reduction, more sustained following repeated treatments, was detected in all treated eyes but not in fellow eyes or in the control group. On the average, the IOP was restored to pretreatment levels 4 days after the last treatment. No serious adverse events were observed and the CB architecture was intact at the end of the experiment. Repeated CB-PDT is safe and results in a short-term reduction of IOP. Induced CB alterations are reversible.

  14. Repeated ketamine treatment induces sex-specific behavioral and neurochemical effects in mice.

    Science.gov (United States)

    Thelen, Connor; Sens, Jonathon; Mauch, Joseph; Pandit, Radhika; Pitychoutis, Pothitos M

    2016-10-01

    One of the most striking discoveries in the treatment of major depression was the finding that infusion of a single sub-anesthetic dose of ketamine induces rapid and sustained antidepressant effects in treatment-resistant depressed patients. However, ketamine's antidepressant-like actions are transient and can only be sustained by repeated drug treatment. Despite the fact that women experience major depression at roughly twice the rate of men, research regarding the neurobiological antidepressant-relevant effects of ketamine has focused almost exclusively on the male sex. Importantly, knowledge regarding the sex-differentiated effects, the frequency and the dose on which repeated ketamine administration stops being beneficial, is limited. In the current study, we investigated the behavioral, neurochemical and synaptic molecular effects of repeated ketamine treatment (10mg/kg; 21days) in male and female C57BL/6J mice. We report that ketamine induced beneficial antidepressant-like effects in male mice, but induced both anxiety-like (i.e., decreased time spent in the center of the open field arena) and depressive-like effects (i.e., enhanced immobility duration in the forced swim test; FST) in their female counterparts. Moreover, repeated ketamine treatment induced sustained sex-differentiated neurochemical and molecular effects, as it enhanced hippocampal synapsin protein levels and serotonin turnover in males, but attenuated glutamate and aspartate levels in female mice. Taken together, our findings indicate that repeated ketamine treatment induces opposite behavioral effects in male and female mice, and thus, present data have far-reaching implications for the sex-oriented use of ketamine in both experimental and clinical research settings.

  15. Safety and Efficacy of Repeated-Dose Intravenous Ketamine for Treatment-Resistant Depression

    NARCIS (Netherlands)

    aan het Rot, Marije; Collins, Katherine A.; Murrough, James W.; Perez, Andrew M.; Reich, David L.; Charney, Dennis S.; Mathew, Sanjay J.

    2010-01-01

    Background: A single subanesthetic (intravenous) IV dose of ketamine might have rapid but transient antidepressant effects in patients with treatment-resistant depression (TRD). Here we tested the tolerability, safety, and efficacy of repeated-dose open-label IV ketamine (six infusions over 12 days)

  16. Identification and quantification of phencyclidine pyrolysis products formed during smoking

    Energy Technology Data Exchange (ETDEWEB)

    Lue, L.P.; Scimeca, J.A.; Thomas, B.F.; Martin, B.R.

    As a result of frequent phencyclidine (PCP) abuse, pyrolysis studies were conducted to further investigate its fate during smoking. Marijuana placebo cigarettes were impregnated with /sup 3/H-PCP HCl and burned under conditions simulating smoking. Mainstream smoke was passed through glass wool filters as well as acidic and basic traps. Approximately 90% of the starting material could be accounted for in the first glass wool trap and cigarette holder. HPLC and GC/MS analysis of methanol extracts of these glass wool traps revealed the presence of 1-phenyl-1-cyclohexene (47% of the starting material) > PCP (40%) > piperidine (15%) > N-acetylpiperidine (9%). It was not possible to fully account for the remainder of the piperidine moiety. It has been reported that at high temperatures PCP is converted to numerous polynuclear aromatic compounds which include styrene, ..cap alpha..-methylstyrene, naphthalene, 2-methyl-naphthalene, 1-methylnaphthalene, biphenyl, cyclohexylbenzene, acenaphthene, phenanthrene, and anthracene. These compounds were not formed from PCP under smoking conditions.

  17. Impaired GABAergic inhibition in the prefrontal cortex of early postnatal phencyclidine (PCP)-treated rats.

    Science.gov (United States)

    Kjaerby, Celia; Broberg, Brian V; Kristiansen, Uffe; Dalby, Nils Ole

    2014-09-01

    A compromised γ-aminobutyric acid (GABA)ergic system is hypothesized to be part of the underlying pathophysiology of schizophrenia. N-methyl-D-aspartate (NMDA) receptor hypofunction during neurodevelopment is proposed to disrupt maturation of interneurons causing an impaired GABAergic transmission in adulthood. The present study examines prefrontal GABAergic transmission in adult rats administered with the NMDA receptor channel blocker, phencyclidine (PCP), for 3 days during the second postnatal week. Whole-cell patch-clamp recordings from pyramidal cells in PCP-treated rats showed a 22% reduction in the frequency of miniature inhibitory postsynaptic currents in layer II/III, but not in layer V pyramidal neurons of the prefrontal cortex. Furthermore, early postnatal PCP treatment caused insensitivity toward effects of the GABA transporter 1 (GAT-1) inhibitor, 1,2,5,6-tetrahydro-1-[2-[[(diphenyl-methylene)amino]oxy]ethyl]-3-pyridinecarboxylic acid, and also diminished currents passed by δ-subunit-containing GABAA receptors in layer II/III pyramidal neurons. The observed impairments in GABAergic function are compatible with the alteration of GABAergic markers as well as cognitive dysfunction observed in early postnatal PCP-treated rats and support the hypothesis that PCP administration during neurodevelopment affects the functionality of interneurons in later life. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  18. Differential expression of parvalbumin interneurons in neonatal phencyclidine treated rats and socially isolated rats

    DEFF Research Database (Denmark)

    Kaalund, Sanne Simone; Riise, Jesper; Broberg, Brian

    2013-01-01

    of parvalbumin-positive interneurons (PV(+) interneurons). In this study we examined PV(+) expression in two rat models of cognitive dysfunction in schizophrenia, the environmental social isolation (SI) and pharmacological neonatal phencyclidine (neoPCP) models. Using a stereological method, the optical...... cells (p = 0.024) in the mPFC of neonatal phencyclidine rats. We observed no alterations in the total number of neurons, hippocampal PV(+) interneurons, parvalbumin mRNA expression or volume of the mPFC or HPC in the two models. Thus, as the total number of neurons remains unchanged following...

  19. Changes in pathological pattern and treatment regimens based on repeat renal biopsy in lupus nephritis

    Institute of Scientific and Technical Information of China (English)

    WANG Guo-bao; XU Zheng-jin; LIU Hong-fa; ZHOU Qiu-gen; ZHOU Zhan-mei; JIA Nan

    2012-01-01

    Background Relapses occur frequently in patients with lupus nephritis.Renal biopsy is the gold standard for assessing renal activity and hence guiding the treatment.Whether repeat renal biopsy is helpful during flares of lupus nephritis remains inconclusive.In the present study,we retrospectively reviewed the patients with lupus nephritis who had more than one renal biopsy with the hope to find the clinical value of repeat biopsy.Methods Patients who had a diagnosis of lupus nephritis and two or more renal biopsies were selected from the database of the patient pathology registration at this renal division.Renal biopsy was evaluated according to the International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification of lupus nephritis.The pathological patterns and treatment regimens were analyzed after a repeat biopsy.Results We identified 44 systemic lupus erythematosus patients with serial renal biopsies.In total,there were 94 renal biopsies.Overall,the pathological transition occurred in 64% instances according to the ISN/RPS class.When the transition was analyzed according to proliferative,membranous or mix lesions,it showed different profile:35% in patients with proliferative lesion,23.5% patients with mix lesions,100% in patients with pure membranous lesion.The pathological transition could not be predicted by any clinical characteristics.After the repeat renal biopsy,34% of patients had a change in their treatment regimens.Conclusions The pathological conversion was very prevalent in patients with lupus nephritis.However,the transitions became less prevalent when they were analyzed according to pure membranous,proliferative,and mix lesion.Repeat biopsy might be helpful to avoid unnecessary increased immunosuppression therapy.

  20. Intracranial aneurysms that repeatedly reopen over time after coiling: imaging characteristics and treatment outcome

    Energy Technology Data Exchange (ETDEWEB)

    Rooij, Willem J. van; Sprengers, Marieke E.; Sluzewski, Menno [St Elisabeth Ziekenhuis, Department of Radiology, Tilburg (Netherlands); Beute, Guus N. [St Elisabeth Ziekenhuis, Department of Neurosurgery, Tilburg (Netherlands)

    2007-04-15

    We report imaging and clinical characteristics of patients with aneurysms that repeatedly reopened over time and were coiled three times or more during a follow-up period of 2-11 years. At angiographic follow-up of 624 of 827 aneurysms coiled between 1995 and 2005, 74 aneurysms (8.9%) reopened and were additionally coiled. During an extended follow-up, 12 aneurysms (1.5%) in 12 patients repeatedly reopened and were repeatedly coiled. Initial aneurysm sizes ranged from 15 to 30 mm. Four aneurysms contained intraluminal thrombus. Eight aneurysms were associated with subarachnoid hemorrhage and two with a mass effect, and two were incidentally discovered. The locations of aneurysms were basilar artery (eight), carotid artery (two), anterior communicating artery (one) and middle cerebral artery (one). Altogether, 49 coil treatments were performed in the 12 aneurysms, ranging from three to six coil treatments per aneurysm. Of the 49 coil treatments, 20 (41%) were performed with a supporting device. There were no procedural complications (0%, 97.5% CI 0-5.7%). The mean clinical follow-up period was 70.6 months (median 60, range 25-135 months). All 12 patients are neurologically doing well (GOS 5). Reopening was by compaction in nine aneurysms and by migration of coils into intraluminal thrombus in three aneurysms. In two aneurysms, late regrowth became apparent at 76 and 95 months after the previous coiling. Aneurysms that reopen over time and need to be coiled for a second time should be imaged at regular intervals to detect repeated reopening or regrowth. The treatment strategy of regular follow-up and additional treatments when necessary is effective and safe. (orig.)

  1. Inmate responses to prison-based drug treatment: a repeated measures analysis.

    Science.gov (United States)

    Welsh, Wayne N

    2010-06-01

    Using a sample of 347 prison inmates and general linear modeling (GLM) repeated measures analyses, this paper examined during-treatment responses (e.g., changes in psychological and social functioning) to prison-based TC drug treatment. These effects have rarely been examined in previous studies, and never with a fully multivariate model accounting for within-subjects effects (changes over time), between-subjects effects (e.g., levels of risk and motivation), and within/between-subjects interactions (timexriskxmotivation). The results provide evidence of positive inmate change in response to prison TC treatment, but the patterns of results varied depending upon: (a) specific indicators of psychological and social functioning, motivation, and treatment process; (b) the time periods examined (1, 6, and 12 months during treatment); and (c) baseline levels of risk and motivation. Significant interactions between time and type of inmate suggest important new directions for research, theory, and practice in offender-based substance abuse treatment.

  2. Disposition of phencyclidine in mice after smoke exposure

    Energy Technology Data Exchange (ETDEWEB)

    Freeman, A.S.; Martin, B.R.

    Mice were exposed to the smoke from placebo marihuana cigarettes treated with phencyclidine hydrochloride (PCP . HCl). A dose-related decrement in motor performance was observed after exposure to the smoke from cigarettes containing 10-15 mg of PCP . HCl. Tissue levels of /sup 3/H-PCP, /sup 3/H-PC (pyrolysis product), and /sup 3/H-metabolites were measured in several tissues up to 7 days after exposure to 50 mg of /sup 3/H-PCP . HCl. /sup 3/H-PCP levels were highest in liver followed by lung, brain, fat, and plasma for the first 10 min after exposure. The /sup 3/H-PCP concentration in all tissues, except fat, declined during the subsequent 50 min. Liver and lung contained the highest levels of /sup 3/H-metabolites during this hour, followed by plasma, fat, and brain. Brain levels of /sup 3/H-PCP correlated well with the magnitude and duration of behavioral effects observed (r . 0.98). /sup 3/H-PC was also well absorbed from smoke as evidenced by initial tissue levels comparable to those of /sup 3/H-PCP, but they declined more rapidly than /sup 3/H-PCP levels. Excellent correlations were obtained between /sup 3/H-PCP and /sup 3/H-PC concentrations in plasma and those in liver, lung, and brain. /sup 3/H-PCP was not detected in any tissue 3 days after smoke exposure. At 1 and 3 days, radioactivity corresponding to metabolites persisted in liver and lung, but had largely disappeared by 7 days.

  3. Synthesis and characterization of phencyclidine and his derivatives

    Directory of Open Access Journals (Sweden)

    Ilić Nataša C.

    2010-01-01

    Full Text Available Phencyclidine (PCP or 1-phenyl-cyclohexylpiperidine is the best known representative drug from the compound class of arylcyclohexylamines. On an account of pharmacological activities it belongs to the family of drugs known as a dissociative anesthetics. In recent years, great attention has been paid to the investigation of the substances that have been abused, including PCP. PCP is the synthetic drug with stimulant and hallucinogens effects (street name “angel dust” and it's situated on the Schedule Substances List, in Serbia and worldwide. In the beginning, PCP has been sold in pharmacies as local anesthetic, but very quickly it was pulled from sale because of the unwanted effects on consumer´s health causing psychoactive addiction. Taking into the account that today a great attention has been given to the substances that are subject of abuse, in this paper, biological and pharmacological effect of PCP and it's derivative is described. It is shown that PCP is antagonist of N-methyl-D-aspartate (NMDA and that it causes antiglutamateric hallucinations. Unlike BTCP which agonist is NMDA receptor and is obtained by modifying the structure of PCP. This paper presents a PCP metabolism and provides an overview of the methods for their identification and quantification in the biological samples. Immunological tests of PCP in the biological samples can provide a quick but wrong result because of the possible interference with the other substances of abuse as opposed to instrumental methods. Based on the presented method and the results it was concluded that the method of choice for the examinations of biological samples for the presence of PCP is gas chromatography in combination with mass spectroscopy.

  4. Hydrogen production by anaerobic microbial communities exposed to repeated heat treatments.

    Science.gov (United States)

    Duangmanee, T; Padmasiri, S I; Simmons, J J; Raskin, L; Sung, S

    2007-09-01

    Biological hydrogen production by anaerobic mixed communities was studied in laboratory-scale bioreactors using sucrose as the substrate. A bioreactor in which a fraction of the return sludge was exposed to repeated heat treatments performed better than a control bioreactor without repeated heat treatment of return sludge and produced a yield of 2.15 moles of hydrogen per mole of sucrose, with 50% hydrogen in the biogas. Terminal restriction fragment length polymorphism analysis showed that two different Clostridium groups (comprised of one or more species) were dominant during hydrogen production. The relative abundance of two other non-Clostridium groups increased during periods of decreased hydrogen production. The first group consisted of Bifidobacterium thermophilum, and the second group included one or more of Bacillus, Melissococcus, Spirochaeta, and Spiroplasma spp.

  5. Positive association of phencyclidine-responsive genes, PDE4A and PLAT, with schizophrenia.

    Science.gov (United States)

    Deng, Xiangdong; Takaki, Hiromi; Wang, Lixiang; Kuroki, Tosihide; Nakahara, Tatsuo; Hashimoto, Kijiro; Ninomiya, Hideaki; Arinami, Tadao; Inada, Toshiya; Ujike, Hiroshi; Itokawa, Masanari; Tochigi, Mamoru; Watanabe, Yuichiro; Someya, Toshiyuki; Kunugi, Hiroshi; Iwata, Nakao; Ozaki, Norio; Shibata, Hiroki; Fukumaki, Yasuyuki

    2011-12-01

    As schizophrenia-like symptoms are produced by administration of phencyclidine (PCP), a noncompetitive antagonist of N-methyl-D-aspartate (NMDA) receptors, PCP-responsive genes could be involved in the pathophysiology of schizophrenia. We injected PCP to Wistar rats and isolated five different parts of the brain in 1 and 4 hr after the injection. We analyzed the gene expression induced by the PCP treatment of these tissues using the AGILENT rat cDNA microarray system. We observed changes in expression level in 90 genes and 21 ESTs after the treatment. Out of the 10 genes showing >2-fold expressional change evaluated by qRT-PCR, we selected 7 genes as subjects for the locus-wide association study to identify susceptibility genes for schizophrenia in the Japanese population. In haplotype analysis, significant associations were detected in combinations of two SNPs of BTG2 (P = 1.4 × 10(-6) ), PDE4A (P = 1.4 × 10(-6) ), and PLAT (P = 1 × 10(-3) ), after false discovery rate (FDR) correction. Additionally, we not only successfully replicated the haplotype associations in PDE4A (P = 6.8 × 10(-12) ) and PLAT (P = 0.015), but also detected single-point associations of one SNP in PDE4A (P = 0.0068) and two SNPs in PLAT (P = 0.0260 and 0.0104) in another larger sample set consisting of 2,224 cases and 2,250 controls. These results indicate that PDE4A and PLAT may be susceptibility genes for schizophrenia in the Japanese population.

  6. Multiple treatment comparisons in a series of anti-malarial trials with an ordinal primary outcome and repeated treatment evaluations

    Directory of Open Access Journals (Sweden)

    Youdom Solange

    2012-05-01

    Full Text Available Abstract Background Artemisinin-based combination therapies (ACT are widely used in African countries, including Cameroon. Between 2005 and 2007, five randomized studies comparing different treatment arms among artesunate-amodiaquine and other ACT were conducted in Cameroonian children aged two to 60 months who had uncomplicated Plasmodium falciparum malaria. In these studies, the categorical criterion proposed by the World Health Organization (WHO to assess the relative effectiveness of anti-malarial drugs was repeatedly evaluated on Days 14, 21 and 28 after treatment initiation. The aim of the present study was to compare the effects of different treatments on this repeated ordinal outcome, hence using the fully available information. Methods The quantitative synthesis was based on individual patient data. Due to the incomplete block design concerning treatment arms between different trials, a mixed treatment comparison (MTC meta-analysis approach was adopted. The repeated ordinal outcome was modelled through a latent variable, as a proportional odds mixed model with trial, period and treatment arms as covariates. The model was further complexified to account for the variance heterogeneity, and the individual log-residual variance was modelled as a linear mixed model, as well. The effects of individual covariates at inclusion, such as parasitaemia, fever, gender and weight, were also tested. Model parameters were estimated using a Bayesian approach via the WinBUGS software. After selecting the best model using Deviance Information Criterion (DIC, mixed treatment comparisons were based on the estimated treatment effects. Results Modeling the residual variance improved the model ability to adjust the data. The results showed that, compared to artesunate-amodiaquine (ASAQ, dihydroartemisinin-piperaquine (DHPP was significantly more efficacious. Artesunate-chlorproguanil-dapsone (ASCD was less efficacious than artesunate

  7. Treatment of bacterial brain abscess by repeated aspiration. Follow up by serial computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Yamamoto, Masaaki; Fukushima, Takeo; Hirakawa, Katsuyuki; Kimura, Hideo; Tomonaga, Masamichi [Fukuoka Univ. (Japan). School of Medicine

    2000-02-01

    Bacterial brain abscess often requires repeated aspiration before the abscess finally resolves. However, there are no guidelines for treatment by aspiration; for example, when should the abscess be tapped again, or when can an abscess be treated by antibiotics alone without further aspiration. Eleven patients with bacterial brain abscess treated by aspiration were evaluated to establish treatment guidelines for brain abscess, in particular the abscess size on serial computed tomography (CT) after aspiration. CT was performed about 24 hours after aspiration to evaluate the size of the abscess, and almost weekly during follow up. The diameter of the brain abscess before and after the initial and last aspirations were reviewed. In eight of the 11 patients, abscesses were aspirated repeatedly: two to three times in most patients. The diameter of the abscesses was 2.5-4.5 cm (mean 3.5 cm) before the last aspiration, and 1.4-3.4 cm (mean 2.3 cm) after the last aspiration, or when continuous drainage was discontinued. Perifocal edema was moderately decreased within 3 weeks after the last aspiration by medical treatment alone, with a concomitant decrease in the volume of the abscess. There were no deaths, and most patients had a favorable outcome. These results suggest that after the diameter of the abscess becomes less than 2 to 3 cm and does not increase anymore on serial CT, medical treatment alone can be anticipated to give satisfactory results without further aspiration. (author)

  8. Botulinum toxin type A in the treatment of bilateral primary axillary hyperhidrosis: efficacy and duration with repeated treatments.

    Science.gov (United States)

    Lowe, Phillipa L; Cerdan-Sanz, Suzanne; Lowe, Nicholas J

    2003-05-01

    Botulinum toxin type A (BTX-A) has been shown to be effective for the temporary reduction of local hyperhidrosis. To investigate the duration of efficacy of BTX-A with repeat treatments for axillary hyperhidrosis. Patients who completed a prior randomized, controlled, parallel-group study comparing BTX-A with vehicle for bilateral primary axillary hyperhidrosis were eligible for this 18-month, open-label, noncomparative, follow-up study. Patients had to request further treatment, fulfill the preceding study inclusion/exclusion criteria, and have spontaneous sweat production that was more than 50% of the baseline value of the previous study. Patients received up to four treatments of intradermal BTX-A (2 mL, 50 U). All of the 12 patients who were enrolled completed the study. Two of the 12 patients (17%) were previously treated with placebo. In the 18 months of study and follow-up, five patients (42%) required a total of two active injections. Three patients (25%) required a total of three active injections, and four patients (33%) required a total of four active injections. The response rate was 83% (10 of 12) at 4 weeks after the first treatment. The mean percentage change from baseline in overall sweat production was approximately 80% at Week 4. The mean time between the first and second treatment in this study was just over 29 weeks, with a range of 17.8 to 57.5 weeks. BTX-A is an effective repeat treatment for axillary hyperhidrosis giving variable but clinically helpful remission. No clinically relevant changes in vital signs or safety parameters were noted.

  9. Brain catechol-O-methyltransferase (COMT) inhibition by tolcapone counteracts recognition memory deficits in normal and chronic phencyclidine-treated rats and in COMT-Val transgenic mice.

    Science.gov (United States)

    Detrait, Eric R; Carr, Greg V; Weinberger, Daniel R; Lamberty, Yves

    2016-08-01

    The critical involvement of dopamine in cognitive processes has been well established, suggesting that therapies targeting dopamine metabolism may alleviate cognitive dysfunction. Catechol-O-methyl transferase (COMT) is a catecholamine-degrading enzyme, the substrates of which include dopamine, epinephrine, and norepinephrine. The present work illustrates the potential therapeutic efficacy of COMT inhibition in alleviating cognitive impairment. A brain-penetrant COMT inhibitor, tolcapone, was tested in normal and phencyclidine-treated rats and COMT-Val transgenic mice. In a novel object recognition procedure, tolcapone counteracted a 24-h-dependent forgetting of a familiar object as well as phencyclidine-induced recognition deficits in the rats at doses ranging from 7.5 to 30 mg/kg. In contrast, entacapone, a COMT inhibitor that does not readily cross the blood-brain barrier, failed to show efficacy at doses up to 30 mg/kg. Tolcapone at a dose of 30 mg/kg also improved novel object recognition performance in transgenic mice, which showed clear recognition deficits. Complementing earlier studies, our results indicate that central inhibition of COMT positively impacts recognition memory processes and might constitute an appealing treatment for cognitive dysfunction related to neuropsychiatric disorders.

  10. The Effect of Phencyclidine New Derivatives on Anxiety Behaviors in Rats

    Directory of Open Access Journals (Sweden)

    Ramin Hajkhani

    2010-04-01

    Full Text Available Objective(s Anxiety is a common disorder which afflicts many people in any society and is often accompanied by physiological sensations such as tachycardia, chest pain, shortness of breath, insensitivity, etc. The purpose of present study was to evaluate the putative anxiolytic-like effects of phencyclidine (1-(1-phenylcyclohexyl piperidine, CAS 956-90-1, PCP, I and its methyl and methoxy hydroxyl derivatives (II, III using elevated plus maze test of anxiety. Materials and Methods Phencyclidine as well as its methyl and methoxy hydroxyl derivatives (I, II, III (hydrochloride, 1, 2, 5 mg/kg were synthesized and administrated intraperitoneally (IP on adult male Wistar rats.ResultsThe results of this study demonstrated that, intraperitoneal (IP administration of PCP analogues (I, II, III hydrochloride (1, 2, 5 mg/kg increases the percentage of open arm time (OAT% and percentage of open arm entries (OAE%.ConclusionThis study revealed that both derivatives of phencyclidine (II, III were more effective than PCP (I itself in modulation of anxiety behavior in rats.

  11. Repeated dexamphetamine treatment alters the dopaminergic system and increases the phMRI response to methylphenidate

    Science.gov (United States)

    Schrantee, Anouk; Tremoleda, Jordi L.; Wylezinska-Arridge, Marzena; Bouet, Valentine; Hesseling, Peter; Meerhoff, Gideon F.; de Bruin, Kora M.; Koeleman, Jan; Freret, Thomas; Boulouard, Michel; Desfosses, Emilie; Galineau, Laurent; Gozzi, Alessandro; Dauphin, François; Gsell, Willy; Booij, Jan; Lucassen, Paul J.; Reneman, Liesbeth

    2017-01-01

    Dexamphetamine (AMPH) is a psychostimulant drug that is used both recreationally and as medication for attention deficit hyperactivity disorder. Preclinical studies have demonstrated that repeated exposure to AMPH can induce damage to nerve terminals of dopamine (DA) neurons. We here assessed the underlying neurobiological changes in the DA system following repeated AMPH exposure and pre-treated rats with AMPH or saline (4 times 5 mg/kg s.c., 2 hours apart), followed by a 1-week washout period. We then used pharmacological MRI (phMRI) with a methylphenidate (MPH) challenge, as a sensitive and non-invasive in-vivo measure of DAergic function. We subsequently validated the DA-ergic changes post-mortem, using a.o. high-performance liquid chromatography (HPLC) and autoradiography. In the AMPH pre-treated group, we observed a significantly larger BOLD response to the MPH challenge, particularly in DA-ergic brain areas and their downstream projections. Subsequent autoradiography studies showed that AMPH pre-treatment significantly reduced DA transporter (DAT) density in the caudate-putamen (CPu) and nucleus accumbens, whereas HPLC analysis revealed increases in the DA metabolite homovanillic acid in the CPu. Our results suggest that AMPH pre-treatment alters DAergic responsivity, a change that can be detected with phMRI in rats. These phMRI changes likely reflect increased DA release together with reduced DAT binding. The ability to assess subtle synaptic changes using phMRI is promising for both preclinical studies of drug discovery, and for clinical studies where phMRI can be a useful tool to non-invasively investigate DA abnormalities, e.g. in neuropsychiatric disorders. PMID:28241065

  12. Postnatal Phencyclidine (PCP) as a Neurodevelopmental Animal Model of Schizophrenia Pathophysiology and Symptomatology: A Review.

    Science.gov (United States)

    Grayson, B; Barnes, S A; Markou, A; Piercy, C; Podda, G; Neill, J C

    Cognitive dysfunction and negative symptoms of schizophrenia remain an unmet clinical need. Therefore, it is essential that new treatments and approaches are developed to recover the cognitive and social impairments that are seen in patients with schizophrenia. These may only be discovered through the use of carefully validated, aetiologically relevant and translational animal models. With recent renewed interest in the neurodevelopmental hypothesis of schizophrenia, postnatal administration of N-methyl-D-aspartate receptor (NMDAR) antagonists such as phencyclidine (PCP) has been proposed as a model that can mimic aspects of schizophrenia pathophysiology. The purpose of the current review is to examine the validity of this model and compare it with the adult subchronic PCP model. We review the ability of postnatal PCP administration to produce behaviours (specifically cognitive deficits) and neuropathology of relevance to schizophrenia and their subsequent reversal by pharmacological treatments. We review studies investigating effects of postnatal PCP on cognitive domains in schizophrenia in rats. Morris water maze and delayed spontaneous alternation tasks have been used for working memory, attentional set-shifting for executive function, social novelty discrimination for selective attention and prepulse inhibition of acoustic startle for sensorimotor gating. In addition, we review studies on locomotor activity and neuropathology. We also include two studies using dual hit models incorporating postnatal PCP and two studies on social behaviour deficits following postnatal PCP. Overall, the evidence we provide supports the use of postnatal PCP to model cognitive and neuropathological disturbances of relevance to schizophrenia. To date, there is a lack of evidence to support a significant advantage of postnatal PCP over the adult subchronic PCP model and full advantage has not been taken of its neurodevelopmental component. When thoroughly characterised, it is likely

  13. Cardiometabolic treatment decisions in patients with type 2 diabetes : the role of repeated measurements and medication burden

    NARCIS (Netherlands)

    Voorham, J.; Haaijer-Ruskamp, F. M.; Wolffenbuttel, B. H. R.; Stolk, R. P.; Denig, P.

    2010-01-01

    Purpose Clinical guidelines for cardiometabolic risk management indicate a simple threshold-based strategy for treatment, but physicians and their patients may be reluctant to modify drug treatment after a single elevated measurement. We determined how repeated measurements of blood pressure, choles

  14. Cardiometabolic treatment decisions in patients with type 2 diabetes : the role of repeated measurements and medication burden

    NARCIS (Netherlands)

    Voorham, J.; Haaijer-Ruskamp, F. M.; Wolffenbuttel, B. H. R.; Stolk, R. P.; Denig, P.

    2010-01-01

    Purpose Clinical guidelines for cardiometabolic risk management indicate a simple threshold-based strategy for treatment, but physicians and their patients may be reluctant to modify drug treatment after a single elevated measurement. We determined how repeated measurements of blood pressure,

  15. Anticonvulsant effects of acute treatment with cyane-carvone at repeated oral doses in epilepsy models.

    Science.gov (United States)

    Marques, Thiago Henrique Costa; Marques, Maria Leonildes Boavista Gomes Castelo Branco; Medeiros, Jand-Venes Rolim; Lima, Tamires Cardoso; de Sousa, Damião Pergentino; de Freitas, Rivelilson Mendes

    2014-09-01

    Epilepsy affects about 40 million people worldwide. Many drugs block seizures, but have little effect in preventing or curing this disease. So the search for new drugs for epilepsy treatment using animal models prior to testing in humans is important. Increasingly pharmaceutical industries invest in the Re​search & Drug Development area to seek safe and effective new therapeutic alternatives to the currently available epilepsy treatment. In this perspective, natural compounds have been investigated in epilepsy models, particularly the monoterpenes obtained from medicinal plants. In our study we investigated the effects of cyane-carvone (CC), a synthetic substance prepared from natural a monoterpene, carvone, against pilocarpine- (PILO), pentylenetetrazole- (PTZ) and picrotoxine (PTX)-induced seizures in mice after acute treatment with repeated oral doses (CC 25, 50 and 75 mg/kg) for 14 days. CC in all doses tested showed increase in latency to first seizure, decrease in percentages of seizuring animals as well as reduction percentages of dead animals (pepilepsy models. In addition, our data suggest that CC could act in an allosteric site of GABAA, which would be different from the site in which BDZ acts, since flumazenil was not able to reverse any of CC effects on the modulation of seizure parameters related with epilepsy models investigated. New studies should be conducted to investigate CC effects in other neurotransmitter systems. Nevertheless, our study reinforces the hypothesis that CC could be used, after further research, as a new pharmaceutical formulation and a promising alternative for epilepsy treatment, since it showed anticonvulsant effects. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Quantitative aspects of spermatogenesis in rats and dogs after repeated hexachlorophene treatment.

    Science.gov (United States)

    James, R W; Heywood, R; Crook, D

    1980-05-01

    Hexachlorophene was administered orally, at subneurotoxic doses, to rats (5 mg/kg/day) and dogs (3 mg/kg/day) for 9 weeks: some of the rats and dogs were observed for a further 13 weeks. The serum concentrations of pituitary gonadotrophin and testosterone were unaffected in either species. No changes were induced in the testicular dimensions or semen characteristics of dogs and no macroscopic post mortem abnormalities, organ weight differences or lesions detectable by conventional light microscopy were found in their testes, pituitaries or secondary sex organs. A transient reduction in the number of germ cells counted in cross-sections of seminiferous tubules was seen in rats after 4 weeks treatment. After 9 weeks treatment, reduced spermatogonial counts were recorded in canine seminiferous tubules; in other respects spermatogenesis was proceeding normally. No delayed effects were apparent in eith species. It is concluded that repeated administration of hexachlorophene at subneurotoxic levels did not induce significant impairment of spermatogenesis in rats or dogs.

  17. Live-Birth Rate Associated With Repeat In Vitro Fertilization Treatment Cycles.

    Science.gov (United States)

    Smith, Andrew D A C; Tilling, Kate; Nelson, Scott M; Lawlor, Debbie A

    The likelihood of achieving a live birth with repeat in vitro fertilization (IVF) is unclear, yet treatment is commonly limited to 3 or 4 embryo transfers. To determine the live-birth rate per initiated ovarian stimulation IVF cycle and with repeated cycles. Prospective study of 156,947 UK women who received 257,398 IVF ovarian stimulation cycles between 2003 and 2010 and were followed up until June 2012. In vitro fertilization, with a cycle defined as an episode of ovarian stimulation and all subsequent separate fresh and frozen embryo transfers. Live-birth rate per IVF cycle and the cumulative live-birth rates across all cycles in all women and by age and treatment type. Optimal, prognosis-adjusted, and conservative cumulative live-birth rates were estimated, reflecting 0%, 30%, and 100%, respectively, of women who discontinued due to poor prognosis and having a live-birth rate of 0 had they continued. Among the 156,947 women, the median age at start of treatment was 35 years (interquartile range, 32-38; range, 18-55), and the median duration of infertility for all 257,398 cycles was 4 years (interquartile range, 2-6; range, live-birth rate for the first cycle was 29.5% (95% CI, 29.3%-29.7%). This remained above 20% up to and including the fourth cycle. The cumulative prognosis-adjusted live-birth rate across all cycles continued to increase up to the ninth cycle, with 65.3% (95% CI, 64.8%-65.8%) of women achieving a live birth by the sixth cycle. In women younger than 40 years using their own oocytes, the live-birth rate for the first cycle was 32.3% (95% CI, 32.0%-32.5%) and remained above 20% up to and including the fourth cycle. Six cycles achieved a cumulative prognosis-adjusted live-birth rate of 68.4% (95% CI, 67.8%-68.9%). For women aged 40 to 42 years, the live-birth rate for the first cycle was 12.3% (95% CI, 11.8%-12.8%), with 6 cycles achieving a cumulative prognosis-adjusted live-birth rate of 31.5% (95% CI, 29.7%-33.3%). For women older than 42

  18. Brief exposure to methamphetamine (METH) and phencyclidine (PCP) during late development leads to long-term learning deficits in rats.

    Science.gov (United States)

    White, Ilsun M; Minamoto, Takehiro; Odell, Joseph R; Mayhorn, Joseph; White, Wesley

    2009-04-17

    Exposure to methamphetamine (METH) and phencyclidine (PCP) during early development is thought to produce later behavioral deficits. We postulated that exposure to METH and PCP during later development would produce similar behavioral deficits, particularly learning deficits in adulthood. Wistar rats were treated with METH (9 mg/kg), PCP (9 mg/kg), or saline during later development, postnatal days (PD) 50-51, and subsequent behavioral changes were examined including: locomotor activity during the acute drug state (PD 50-51) and the post-drug phase (PD 50-80); social interaction on PD 54-80; and spatial discrimination and reversal in adulthood (after PD 90). METH and PCP differentially affected locomotion during the acute state, but not during the post-drug phase. METH decreased social interaction throughout tests two weeks after drug treatment, whereas PCP decreased social interaction only during the first 8 min of tests. Neither METH nor PCP impaired initial acquisition of spatial discrimination. However, reversal was significantly impaired by PCP, whereas METH produced a mild deficit, compared to controls. Our data provide evidence that exposure to PCP and METH during later development lead to enduring cognitive deficits in adulthood. Selective impairment of reversal may reflect neurological damage in the prefrontal cortex due to early exposure to drugs.

  19. Aroma improvement by repeated freeze-thaw treatment during Tuber melanosporum fermentation

    Science.gov (United States)

    Xiao, Deng-Rong; Liu, Rui-Sang; He, Long; Li, Hong-Mei; Tang, Ya-Ling; Liang, Xin-Hua; Chen, Tao; Tang, Ya-Jie

    2015-01-01

    The aroma attributes of sulfurous, mushroom and earthy are the most important characteristics of the aroma of Tuber melanosporum. However, these three aroma attributes are absent in the T. melanosporum fermentation system. To improve the quality of the aroma, repeated freeze-thaw treatment (RFTT) was adopted to affect the interplay of volatile organic compounds (VOCs). Using RFTT, not only was the score on the hedonic scale of the aroma increased from the “liked slightly” to the “liked moderately” grade, but the aroma attributes of sulfurous, mushroom and earthy could also be smelled in the T. melanosporum fermentation system for the first time. A total of 29 VOCs were identified, and 9 compounds were identified as the key discriminative volatiles affected by RFTT. Amino acid analysis revealed that methionine, valine, serine, phenylalanine, isoleucine and threonine were the key substrates associated with the biosynthesis of the 9 key discriminative VOCs. This study noted that amino acid metabolism played an important role in the regulation of the aroma of the T. melanosporum fermentation system. PMID:26607288

  20. Aroma improvement by repeated freeze-thaw treatment during Tuber melanosporum fermentation.

    Science.gov (United States)

    Xiao, Deng-Rong; Liu, Rui-Sang; He, Long; Li, Hong-Mei; Tang, Ya-Ling; Liang, Xin-Hua; Chen, Tao; Tang, Ya-Jie

    2015-11-26

    The aroma attributes of sulfurous, mushroom and earthy are the most important characteristics of the aroma of Tuber melanosporum. However, these three aroma attributes are absent in the T. melanosporum fermentation system. To improve the quality of the aroma, repeated freeze-thaw treatment (RFTT) was adopted to affect the interplay of volatile organic compounds (VOCs). Using RFTT, not only was the score on the hedonic scale of the aroma increased from the "liked slightly" to the "liked moderately" grade, but the aroma attributes of sulfurous, mushroom and earthy could also be smelled in the T. melanosporum fermentation system for the first time. A total of 29 VOCs were identified, and 9 compounds were identified as the key discriminative volatiles affected by RFTT. Amino acid analysis revealed that methionine, valine, serine, phenylalanine, isoleucine and threonine were the key substrates associated with the biosynthesis of the 9 key discriminative VOCs. This study noted that amino acid metabolism played an important role in the regulation of the aroma of the T. melanosporum fermentation system.

  1. Acute withdrawal from repeated cocaine treatment enhances latent inhibition of a conditioned fear response.

    Science.gov (United States)

    Murphy, C A; Heidbreder, C; Feldon, J

    2001-02-01

    Psychostimulant-induced locomotor sensitization and disrupted latent inhibition (LI) of a classically conditioned association are two paradigms that have been widely studied as animal behavioural models of psychosis. In this study we assessed the effects of withdrawal from the repeated intermittent administration of cocaine on LI of a conditioned fear response. Animals which were either preexposed (PE) to a tone conditioned stimulus (CS) or naive to the tone (i.e. non-preexposed: NPE) subsequently experienced 10 pairings of the tone CS with footshock. Afterwards, both groups received five daily injections of cocaine (20 mg/kg, i.p.) or saline. After 3 days of withdrawal from drug treatment, animals were tested for conditioned freezing to the context of the footshock chamber, and 1 day later, for conditioned freezing to the tone CS. Cocaine-sensitized animals exhibited markedly enhanced LI compared to saline-treated animals, due to the fact that NPE-cocaine animals spent more time freezing during the tone CS than NPE-saline animals, whereas PE-cocaine animals showed a tendency toward reduced freezing compared to the saline groups. While these results suggest the presence of increased anxiety in cocaine-withdrawn NPE animals, the absence of this effect in cocaine-withdrawn PE rats indicates that cocaine withdrawal also influences the retrieval of previously learned information.

  2. Live-birth rate associated with repeat in vitro fertilisation treatment cycles

    Science.gov (United States)

    Smith, Andrew D.A.C.; Tilling, Kate

    2016-01-01

    Importance The likelihood of achieving a live-birth with repeat in-vitro fertilisation (IVF) is unclear, yet treatment is commonly limited to three or four embryo transfers. Objective To determine the live-birth rate per initiated IVF cycle and with repeated cycles. Design, Setting and Participants Prospective study of 156,947 UK women who received 257,398 IVF ovarian stimulation cycles between 2003 and 2010 and were followed until June 2012. Main exposure IVF, with a cycle defined as an episode of ovarian stimulation and all subsequent separate fresh and frozen embryo transfers. Main Outcome(s) Live-birth rate per IVF cycle and the cumulative live-birth rates across all cycles in all women and by age and treatment type. Optimal, prognosis-adjusted and conservative cumulative live-birth rates were estimated, reflecting 0%, 30% and 100% of women discontinuing due to poor prognosis and having a live-birth rate of zero had they continued. Results In all women the live-birth rate for the first cycle was 29.5% (95%CI: 29.3, 29.7). This remained above 20% up to and including the fourth cycle. The cumulative prognosis-adjusted live-birth rate across all cycles continued to increase up to the ninth, with 65.3% (64.8, 65.8) of women achieving a live-birth by the sixth cycle. In women younger than 40 using their own oocytes, the live-birth rate for the first cycle was 32.3% (32.0, 32.5), and remained above 20% up to and including the fourth cycle. Six cycles achieved a cumulative prognosis-adjusted live-birth rate of 68.4% (67.8, 68.9). For women aged 40-42, the live-birth rate for the first cycle was 12.3% (95%CI: 11.8, 12.8), with six cycles achieving a cumulative prognosis-adjusted live-birth rate of 31.5% (29.7, 33.3). For women older than 42 years all rates within each cycle were less than 4%. No age differential was observed among women using donor oocytes. Rates were lower in those with untreated male factor infertility compared to those with any other cause, but

  3. [Safety of repeat median sternotomy in the palliative treatment of patients with univentricular heart].

    Science.gov (United States)

    Díliz-Nava, Héctor; Meléndez-Sagaón, Isis; Tamaríz-Cruz, Orlando; García-Benitez, Luis; Araujo-Martínez, Aric; Palacios-Macedo, Alexis

    2017-01-13

    Establish the morbidity and mortality of patients with univentricular hearts who underwent repeat median sternotomy at the Instituto Nacional de Pediatría METHOD: We retrospectively review the clinical charts of all patient who underwent repeat median sternotomy from 2001 to 2016. Sixty-five patients underwent 76 surgeries through repeat median sternotomy. Fifty-nine patients had a first repeat median sternotomy with a mean age of 36months (range 4-176months) and a mean weight of 12.2kg (range 3.2-21.5kg). Forty patients had a Glenn procedure and 19 patients had a Fontan procedure. There were 17 patients with second repeat median sternotomy, mean age of 89months (range 48-156months) and mean weight of 22.7kg (14.4-41kg). In all 17 patients a Fontan procedure was done. Section of the right coronary artery with electrocardiographic changes and a right atrium tear that caused hypotension, occurred during first repeat sternotomy. An aortic tear occurred during a second repeat sternotomy with massive bleeding and consequent death. This represents a 3.9% of reentry injury. We conclude that repeat median sternotomy is a safe procedure. Copyright © 2016 Instituto Nacional de Cardiología Ignacio Chávez. Publicado por Masson Doyma México S.A. All rights reserved.

  4. Efficacy and Safety of Repeated Courses of rTMS Treatment in Patients with Chronic Subjective Tinnitus

    Science.gov (United States)

    Lehner, Astrid; Schecklmann, Martin; Poeppl, Timm B.; Kreuzer, Peter M.; Peytard, Juliette; Frank, Elmar; Langguth, Berthold

    2015-01-01

    Background. Repetitive transcranial magnetic stimulation (rTMS) has shown promising effects in the treatment of chronic subjective tinnitus. However, little is known about maintenance treatment in order to achieve long-lasting improvements. Objective. This study addresses the questions whether the repeated application of rTMS treatment can contribute to the maintenance or enhancement of treatment effects and if so in which cases repetitive treatment courses are beneficial. Methods. 55 patients with chronic tinnitus were treated with two rTMS treatment courses with ten treatment sessions each. The mean intertreatment interval was 20.65 ± 18.56 months. Tinnitus severity was assessed before and after each treatment course. Results. Both treatments were well tolerated and caused significant improvement of tinnitus severity. The main predictor for the outcome of the second treatment was the development of tinnitus distress in the phase between both treatment courses: the more patients worsened in this interval, the more they improved during the second treatment course. Conclusion. Repeated application of rTMS seems to be useful in tinnitus management and should preferentially be offered to patients who experience a worsening of their tinnitus during the intertreatment interval, irrespective of their response to the first treatment course. PMID:26583152

  5. Efficacy and Safety of Repeated Courses of rTMS Treatment in Patients with Chronic Subjective Tinnitus

    Directory of Open Access Journals (Sweden)

    Astrid Lehner

    2015-01-01

    Full Text Available Background. Repetitive transcranial magnetic stimulation (rTMS has shown promising effects in the treatment of chronic subjective tinnitus. However, little is known about maintenance treatment in order to achieve long-lasting improvements. Objective. This study addresses the questions whether the repeated application of rTMS treatment can contribute to the maintenance or enhancement of treatment effects and if so in which cases repetitive treatment courses are beneficial. Methods. 55 patients with chronic tinnitus were treated with two rTMS treatment courses with ten treatment sessions each. The mean intertreatment interval was 20.65 ± 18.56 months. Tinnitus severity was assessed before and after each treatment course. Results. Both treatments were well tolerated and caused significant improvement of tinnitus severity. The main predictor for the outcome of the second treatment was the development of tinnitus distress in the phase between both treatment courses: the more patients worsened in this interval, the more they improved during the second treatment course. Conclusion. Repeated application of rTMS seems to be useful in tinnitus management and should preferentially be offered to patients who experience a worsening of their tinnitus during the intertreatment interval, irrespective of their response to the first treatment course.

  6. The Effect of Repeated Ketamine Infusion Over Facial Emotion Recognition in Treatment-Resistant Depression: A Preliminary Report.

    Science.gov (United States)

    Shiroma, Paulo R; Albott, C Sophia; Johns, Brian; Thuras, Paul; Wels, Joseph; Lim, Kelvin O

    2015-01-01

    In contrast to improvement in emotion recognition bias by traditional antidepressants, the authors report preliminary findings that changes in facial emotion recognition are not associated with response of depressive symptoms after repeated ketamine infusions or relapse during follow-up in treatment-resistant depression.

  7. Effect of Repeated Anthelminthic Treatment on Malaria in School Children in Kenya: A Randomized, Open-Label, Equivalence Trial.

    Science.gov (United States)

    Kepha, Stella; Nuwaha, Fred; Nikolay, Birgit; Gichuki, Paul; Mwandawiro, Charles S; Mwinzi, Pauline N; Odiere, Maurice R; Edwards, Tansy; Allen, Elizabeth; Brooker, Simon J

    2016-01-15

    School children living in the tropics are often concurrently infected with plasmodium and helminth parasites. It has been hypothesized that immune responses evoked by helminths may modify malaria-specific immune responses and increase the risk of malaria. We performed a randomized, open-label, equivalence trial among 2436 school children in western Kenya. Eligible children were randomized to receive either 4 repeated doses or a single dose of albendazole and were followed up during 13 months to assess the incidence of clinical malaria. Secondary outcomes were Plasmodium prevalence and density, assessed by repeat cross-sectional surveys over 15 months. Analysis was conducted on an intention-to-treat basis with a prespecified equivalence range of 20%. During 13 months of follow-up, the incidence rate of malaria was 0.27 episodes/person-year in the repeated treatment group and 0.26 episodes/person-year in the annual treatment group (incidence difference, 0.01; 95% confidence interval, -.03 to .06). The prevalence and density of malaria parasitemia did not differ by treatment group at any of the cross-sectional surveys. Our findings suggest that repeated deworming does not alter risks of clinical malaria or malaria parasitemia among school children and that school-based deworming in Africa may have no adverse consequences for malaria. NCT01658774. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America.

  8. Selective serotonin re-uptake inhibitors potentiate gene blunting induced by repeated methylphenidate treatment: Zif268 versus Homer1a.

    Science.gov (United States)

    Van Waes, Vincent; Vandrevala, Malcolm; Beverley, Joel; Steiner, Heinz

    2014-11-01

    There is a growing use of psychostimulants, such as methylphenidate (Ritalin; dopamine re-uptake inhibitor), for medical treatments and as cognitive enhancers in the healthy. Methylphenidate is known to produce some addiction-related gene regulation. Recent findings in animal models show that selective serotonin re-uptake inhibitors (SSRIs), including fluoxetine, can potentiate acute induction of gene expression by methylphenidate, thus indicating an acute facilitatory role for serotonin in dopamine-induced gene regulation. We investigated whether repeated exposure to fluoxetine, in conjunction with methylphenidate, in adolescent rats facilitated a gene regulation effect well established for repeated exposure to illicit psychostimulants such as cocaine-blunting (repression) of gene inducibility. We measured, by in situ hybridization histochemistry, the effects of a 5-day repeated treatment with methylphenidate (5 mg/kg), fluoxetine (5 mg/kg) or a combination on the inducibility (by cocaine) of neuroplasticity-related genes (Zif268, Homer1a) in the striatum. Repeated methylphenidate treatment alone produced minimal gene blunting, while fluoxetine alone had no effect. In contrast, fluoxetine added to methylphenidate robustly potentiated methylphenidate-induced blunting for both genes. This potentiation was widespread throughout the striatum, but was most robust in the lateral, sensorimotor striatum, thus mimicking cocaine effects. For illicit psychostimulants, blunting of gene expression is considered part of the molecular basis of addiction. Our results thus suggest that SSRIs, such as fluoxetine, may increase the addiction liability of methylphenidate.

  9. Massive venlafaxine overdose resulted in a false positive Abbott AxSYM (R) urine immunoassay for phencyclidine

    NARCIS (Netherlands)

    Bond, GR; Steele, PE; Uges, DRA

    2003-01-01

    Case report: A 13-yr-old girl overdosed on 48 x 150 mg venlafaxine (Effexor XR(R)). She was taking venlafaxine regularly for depression. Her only other medications included topical Benzamycin and pyridoxine 50 mg daily for acne. The Abbott AxSYM(R) assay was positive only for phencyclidine, but GC/M

  10. Repeatability and Reproducibility of Quantitative Corneal Shape Analysis after Orthokeratology Treatment Using Image-Pro Plus Software

    Science.gov (United States)

    Mei, Ying; Tang, Zhiping

    2016-01-01

    Purpose. To evaluate the repeatability and reproducibility of quantitative analysis of the morphological corneal changes after orthokeratology treatment using “Image-Pro Plus 6.0” software (IPP). Methods. Three sets of measurements were obtained: two sets by examiner 1 with 5 days apart and one set by examiner 2 on the same day. Parameters of the eccentric distance, eccentric angle, area, and roundness of the corneal treatment zone were measured using IPP. The intraclass correlation coefficient (ICC) and repetitive coefficient (COR) were used to calculate the repeatability and reproducibility of these three sets of measurements. Results. ICC analysis suggested “excellent” reliability of more than 0.885 for all variables, and COR values were less than 10% for all variables within the same examiner. ICC analysis suggested “excellent” reliability for all variables of more than 0.90, and COR values were less than 10% for all variables between different examiners. All extreme values of the eccentric distance and area of the treatment zone pointed to the same material number in three sets of measurements. Conclusions. IPP could be used to acquire the exact data of the characteristic morphological corneal changes after orthokeratology treatment with good repeatability and reproducibility. This trial is registered with trial registration number: ChiCTR-IPR-14005505.

  11. Repeatability and Reproducibility of Quantitative Corneal Shape Analysis after Orthokeratology Treatment Using Image-Pro Plus Software

    Directory of Open Access Journals (Sweden)

    Ying Mei

    2016-01-01

    Full Text Available Purpose. To evaluate the repeatability and reproducibility of quantitative analysis of the morphological corneal changes after orthokeratology treatment using “Image-Pro Plus 6.0” software (IPP. Methods. Three sets of measurements were obtained: two sets by examiner 1 with 5 days apart and one set by examiner 2 on the same day. Parameters of the eccentric distance, eccentric angle, area, and roundness of the corneal treatment zone were measured using IPP. The intraclass correlation coefficient (ICC and repetitive coefficient (COR were used to calculate the repeatability and reproducibility of these three sets of measurements. Results. ICC analysis suggested “excellent” reliability of more than 0.885 for all variables, and COR values were less than 10% for all variables within the same examiner. ICC analysis suggested “excellent” reliability for all variables of more than 0.90, and COR values were less than 10% for all variables between different examiners. All extreme values of the eccentric distance and area of the treatment zone pointed to the same material number in three sets of measurements. Conclusions. IPP could be used to acquire the exact data of the characteristic morphological corneal changes after orthokeratology treatment with good repeatability and reproducibility. This trial is registered with trial registration number: ChiCTR-IPR-14005505.

  12. Polymicrobial Gardnerella biofilm resists repeated intravaginal antiseptic treatment in a subset of women with bacterial vaginosis: a preliminary report.

    Science.gov (United States)

    Swidsinski, Alexander; Loening-Baucke, Vera; Swidsinski, Sonja; Verstraelen, Hans

    2015-03-01

    Bacterial vaginosis is a recalcitrant polymicrobial biofilm infection that often resists standard antibiotic treatment. We therefore considered repeated treatment with octenidine, a local antiseptic that has previously been shown to be highly effective in several biofilm-associated infections. Twenty-four patients with recurrent BV were treated with a 7-day course of octenidine (octenidine dihydrochloride spray application with the commercial product Octenisept). In case of treatment failure or relapse within 6 months, patients were re-treated with a 28-day course of octenidine. In case of recurrence within 6 months after the second treatment course, patients were treated again with a 28-day course followed by weekly applications for 2 months. Treatment effect was evaluated by assessment of the presence of the biofilm on voided vaginal epithelial cells through fluorescence in situ hybridisation. The initial cure rate following a 7-day course of octenidine was as high as 87.5%. The 6-month relapse rate was, however, as high as 66.6%. Repeated treatment for 28 days led to an overall cure rate of 75.0%; however, it was also associated with emergence of complete resistance to octenidine in a subset of women. The overall cure rate after three treatment courses with 1-year follow-up was 62.5 %, with 37.5 % of the patients showing complete resistance to octenidine. Our preliminary results showed that octenidine dihydrochloride was initially highly effective, but the efficacy of repeated and prolonged treatment dropped quickly as challenge with the antiseptic rapidly led to bacterial resistance in a considerable subset of women.

  13. Identification and quantitation of amphetamines, cocaine, opiates, and phencyclidine in oral fluid by liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Fritch, Dean; Blum, Kristen; Nonnemacher, Sheena; Haggerty, Brenda J; Sullivan, Matthew P; Cone, Edward J

    2009-01-01

    Analytical methods for measuring multiple licit and illicit drugs and metabolites in oral fluid require high sensitivity, specificity, and accuracy. With the limited volume available for testing, comprehensive methodology is needed for simultaneous measurement of multiple analytes in a single aliquot. This report describes the validation of a semi-automated method for the simultaneous extraction, identification, and quantitation of 21 analytes in a single oral fluid aliquot. The target compounds included are amphetamine, methamphetamine, 3,4-methylenedioxymethamphetamine, 3,4-methylenedioxy-amphetamine, 3,4-methylenedioxyethylamphetamine, pseudoephedrine, cocaine, benzoylecgonine, codeine, norcodeine, 6-acetylcodeine, morphine, 6-acetylmorphine, hydrocodone, norhydrocodone, dihydrocodeine, hydromorphone, oxycodone, noroxycodone, oxymorphone, and phencyclidine. Oral fluid specimens were collected with the Intercept device and extracted by solid-phase extraction (SPE). Drug recovery from the Intercept device averaged 84.3%, and SPE extraction efficiency averaged 91.2% for the 21 analytes. Drug analysis was performed by liquid chromatography-tandem mass spectrometry in the positive electrospray mode using ratios of qualifying product ions within +/-25% of calibration standards. Matrix ion suppression ranged from -57 to 8%. The limit of quantitation ranged from 0.4 to 5 ng/mL using 0.2 mL of diluted oral fluid sample. Application of the method was demonstrated by testing oral fluid specimens from drug abuse treatment patients. Thirty-nine patients tested positive for various combinations of licit and illicit drugs and metabolites. In conclusion, this validated method is suitable for simultaneous measurement of 21 licit and illicit drugs and metabolites in oral fluid.

  14. Short- and long-term behavioral analysis of social interaction, ultrasonic vocalizations and social motivation in a chronic phencyclidine model.

    Science.gov (United States)

    Peters, Suzanne M; Tuffnell, Joe A; Pinter, Ilona J; van der Harst, Johanneke E; Spruijt, Berry M

    2017-05-15

    Phencyclidine (PCP) has been suggested to induce symptoms of schizophrenia. However, animal models using PCP administration have produced ambiguous results thus far. It seems that acute effects are similar to symptoms of schizophrenia, however, it is not clear if PCP can induce permanent behavioral changes that reflect schizophrenic-like symptoms. Therefore, we assessed the ability of chronic PCP administration (3mg/kg, 14 days) to induce short or long lasting behavioral changes in rats. Social behavior, including ultrasonic vocalizations and motivation for social contact were investigated at different time points, up to 29-36 days, after cessation of PCP treatment. During a social separation test, performed at 5 and 36 days, PCP treated rats spent less time near the divider that separates them from their familiar cage mate compared with saline (SAL) treated rats. Further, at short term, PCP was able to induce a decrease in social behavior. In contrast, at long-term, PCP treated animals spent more time in contact when exposed to an unfamiliar partner as compared to SAL treated rats. But, this difference was not observed when exposed to a familiar partner. We did not find any difference in ultrasonic vocalizations at all time points. The results of our study indicate that PCP is unable to induce overt long term deficits in social interaction behavior. Rather, it seems that PCP diminishes motivation for social contact. The long-term consequences of chronic PCP administration on social behavior in rodent models remain complex, and future studies addressing this are still needed. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Effect of novel antipsychotic drugs on phencyclidine-induced stereotyped behaviour and social isolation in the rat social interaction test.

    Science.gov (United States)

    Sams-Dodd, F

    1997-06-01

    Phencyclidine (PCP) induces stereotyped behaviour and social isolation in rats; comparisons with clinical observations have suggested that these behaviours may mimic certain aspects of the positive and the negative symptoms, respectively, of an acute schizophrenic episode. Novel antipsychotics are effective in treating the positive symptoms in schizophrenic patients and have also shown some promise in treating the negative symptoms. In the present study the effects of the novel antipsychotics remoxipride (2.5-20 mg/kg), risperidone (0.02-0.63 mg/kg), sertindole (0.01-2.5 mg/kg), olanzapine (0.16-2.5 mg/kg) and quetiapine (0.16-10 mg/kg) on PCP-induced behaviours were determined. The drugs were administered daily for 3 or 21 days in combination with vehicle or 2.0 mg/kg of PCP for the last 3 days of the administration regime, and the rats were tested using the social interaction test. The antipsychotic drugs all reliably reduced the level of PCP-induced stereotyped behaviour and had distinct effects on PCP-induced social isolation. Comparison with clinical findings suggests that the PCP-induced behaviours respond to treatment with antipsychotic drugs in a manner that correlates well with clinical observations, and that this animal model of schizophrenia may be useful for evaluating novel drug candidates. However, the study also showed that additional experiments are required to determine the specificity by which antipsychotic drugs alleviate PCP-induced behaviours because most of the drugs also affected considerably the behaviour of the control animals.

  16. Repeated treatment with (-)-sulpiride plus a low dose of SCH 23390 displays wider neuroleptic activity without inducing dopaminergic supersensitivity.

    Science.gov (United States)

    Dall'Olio, R; Gandolfi, O; Roncada, P; Vaccheri, A; Montanaro, N

    1990-01-01

    Combined treatment with (-)-sulpiride plus a low dose of the D1 receptor antagonist SCH 23390, unlike (-)-sulpiride given alone, blocked rat striatal dopaminergic transmission. Five days after the withdrawal of 21-day repeated administration of the combined treatment, no increase in apomorphine-induced stereotyped behaviour was observed. The results suggest that the combination of a D2 blocker and a low dose of a D1 blocker produces a wider spectrum of neuroleptic activity without an overt risk of inducing dopaminergic behavioural supersensitivity.

  17. [Anxiogenic and anxiolytic effects of lithium chloride under preventive and therapeutic treatments of male mice with repeated experience of aggression].

    Science.gov (United States)

    Smagin, D A; Kudryavtseva, N N

    2014-01-01

    Repeated experience of aggression in daily agonistic interactions is accompanied by development of changes in behaviors and psychoemotional states indicating the development of the psychopathology of aggressive behavior, which are difficult to correct by drugs used for decrease of aggression in the clinics. In this paper the influence of lithium chloride on the behavior of aggressive males in different tests assessing anxiety, communication and exploratory activity (elevated plus maze test, social interaction test, partition test), as well as aggressiveness (agonistic interaction test) were studied. Lithium chloride (Sigma-Aldrich Co, 100 mg/kg/day, i.p.) was administered preventively to male in ranging from the 7th day of agonistic interactions, as well as therapeutically to males with 21 days of aggression experience during the period without agonistic interactions. Also the effects of chronic lithium chloride treatment on behaviors of animals without agonistic interactions (intact mice) were studied. Period of drug and saline (as the controls) treatment--14 days. It has been shown that preventive lithium chloride treatment of male mice with repeated experience of aggression induced pronounced anxiogenic effect, under therapeutic treatment--nxiolytic effects. Anxiolytic effect was also observed in intact males. There is no effect of lithium chloride on aggression. Differences in the effects of lithium chloride under preveitive and therapeutic treatments, as well as the causes of individual sensitivity to the drug in male mice in one group were discussed.

  18. Repeat transsphenoidal surgery for the treatment of remaining or recurring pituitary tumors in acromegaly.

    Science.gov (United States)

    Yamada, Shozo; Fukuhara, Noriaki; Oyama, Kenichi; Takeshita, Akira; Takeuchi, Yasuharu

    2010-10-01

    Acromegaly is a disorder characterized by hypersecretion of growth hormone caused by a growth hormone-secreting pituitary adenoma. To evaluate the long-term efficacy and safety of repeat transsphenoidal surgery for persistent or recurrent acromegaly. We retrospectively reviewed records for 53 acromegalic patients who underwent repeat transsphenoidal surgery for persistent or progressive acromegaly at Toranomon Hospital between 1987 and 2006. Multivariate logistic regression was performed to evaluate preoperative factors influencing the surgical outcome. Thirty-one patients (58.5%) met the criteria for cure on long-term follow-up endocrine findings. Furthermore, 17 patients were well controlled with normal insulin-like growth factor I levels without (2 patients) or with medication (15 patients), whereas insulin-like growth factor I levels were still above normal in 5 patients after postoperative adjuvant therapy. Only 1 patient was undergoing additional hormonal replacement after surgery, although transient cerebrospinal fluid leak, transient abducens nerve palsy, severe nasal bleeding, and pituitary abscess occurred in each patient, respectively. Multivariate analysis clarified that a favorable surgical outcome was achieved in patients without cavernous sinus invasion (hazard ratio 12.56), tumor segmentation (hazard ratio 5.82), or in those older than 40 years old (hazard ratio 3.21). Repeat surgery can be performed safely with an approximately 60% long-term cure rate in this series. Reoperation should therefore be considered for persistent or recurrent disease in acromegalic patients in whom adjuvant therapy is not effective enough or cannot be accepted. The careful study of initial or preoperative magnetic resonance imaging and the use of micro-Doppler, endoscope, and eye movement monitoring device during surgery can help increase cure rate with a lower complication rate.

  19. Repeatability of dose painting by numbers treatment planning in prostate cancer radiotherapy based on multiparametric magnetic resonance imaging

    Science.gov (United States)

    van Schie, Marcel A.; Steenbergen, Peter; Viet Dinh, Cuong; Ghobadi, Ghazaleh; van Houdt, Petra J.; Pos, Floris J.; Heijmink, Stijn W. T. J. P.; van der Poel, Henk G.; Renisch, Steffen; Vik, Torbjørn; van der Heide, Uulke A.

    2017-07-01

    Dose painting by numbers (DPBN) refers to a voxel-wise prescription of radiation dose modelled from functional image characteristics, in contrast to dose painting by contours which requires delineations to define the target for dose escalation. The direct relation between functional imaging characteristics and DPBN implies that random variations in images may propagate into the dose distribution. The stability of MR-only prostate cancer treatment planning based on DPBN with respect to these variations is as yet unknown. We conducted a test-retest study to investigate the stability of DPBN for prostate cancer in a semi-automated MR-only treatment planning workflow. Twelve patients received a multiparametric MRI on two separate days prior to prostatectomy. The tumor probability (TP) within the prostate was derived from image features with a logistic regression model. Dose mapping functions were applied to acquire a DPBN prescription map that served to generate an intensity modulated radiation therapy (IMRT) treatment plan. Dose calculations were done on a pseudo-CT derived from the MRI. The TP and DPBN map and the IMRT dose distribution were compared between both MRI sessions, using the intraclass correlation coefficient (ICC) to quantify repeatability of the planning pipeline. The quality of each treatment plan was measured with a quality factor (QF). Median ICC values for the TP and DPBN map and the IMRT dose distribution were 0.82, 0.82 and 0.88, respectively, for linear dose mapping and 0.82, 0.84 and 0.94 for square root dose mapping. A median QF of 3.4% was found among all treatment plans. We demonstrated the stability of DPBN radiotherapy treatment planning in prostate cancer, with excellent overall repeatability and acceptable treatment plan quality. Using validated tumor probability modelling and simple dose mapping techniques it was shown that despite day-to-day variations in imaging data still consistent treatment plans were obtained.

  20. Enhanced prefrontal serotonin 2A receptor signaling in the subchronic phencyclidine mouse model of schizophrenia

    DEFF Research Database (Denmark)

    Santini, Martin A; Ratner, Cecilia Friis; Aznar, Susana

    2013-01-01

    -like psychosis in humans. Subchronic phencyclidine (PCP) administration is a well-established model for schizophrenia-like symptoms in rodents. The aim of the present study was to investigate whether subchronic PCP administration changes expression, binding, or functionality of cortical 5-HT2A Rs. As a measure......) in the frontal cortex. Mice were treated with PCP (10 mg/kg) or saline for 10 days, followed by a 5-day washout period. The PCP pretreatment increased the overall induction of HTR and frontal cortex IEG mRNA expression following a single challenge with DOI. These functional changes were not associated...... with changes in 5-HT2A R binding. Also, binding of the 5-HT1A R and the 5-HT transporter was unaffected. Finally, basal mRNA level of Arc was increased in the prefrontal cortex after subchronic PCP administration as revealed with in situ hybridization. Together these findings indicate that PCP administration...

  1. Effect of repeated pulsed electric field treatment on the quality of hot-boned beef loins and topsides.

    Science.gov (United States)

    Bekhit, Alaa El-Din A; Suwandy, Via; Carne, Alan; van de Ven, Remy; Hopkins, David L

    2016-01-01

    The effects of repeated (1×, 2×, 3×) pulsed electric field (PEF) treatment (10 kV, 90 Hz, 20 μs) on the quality of beef loins and topsides were evaluated, including the tenderness, purge loss, cooking loss, myofibrillar protein profile and post-mortem proteolysis. Both muscle types were obtained from each of 12 steers and were processed within 6h. After PEF treatment samples of both muscle types were subjected to 3, 7, 14 and 21 days ageing. The 1× and 2× PEF treatments had no effect on the tenderisation of hot-boned beef Musculus longissimus lumborum muscle for all ageing treatment times, while the 3× treatment reduced the tenderness. The opposite effect was observed in hot-boned beef Musculus semimembranosus muscles where the 3× treatment produced meat with lowest shear force at 3 days post-treatment time, but this beneficial effect disappeared with longer ageing times. An increase in proteolysis of troponin T was seen to the largest extent with 1× PEF treatment and decreased with every extra application of treatment.

  2. Transitory FGF treatment results in the long-lasting suppression of the proliferative response to repeated FGF stimulation.

    Science.gov (United States)

    Poole, Ashleigh; Knowland, Nicholas; Cooper, Emily; Cole, Rebecca; Wang, Hongchuan; Booth, Lucas; Kacer, Doreen; Tarantini, Francesca; Friesel, Robert; Prudovsky, Igor

    2014-05-01

    FGF applied as a single growth factor to quiescent mouse fibroblasts induces a round of DNA replication, however continuous stimulation results in arrest in the G1 phase of the next cell cycle. We hypothesized that FGF stimulation induces the establishment of cell memory, which prevents the proliferative response to repeated or continuous FGF application. When a 2-5 days quiescence period was introduced between primary and repeated FGF treatments, fibroblasts failed to efficiently replicate in response to secondary FGF application. The establishment of "FGF memory" during the first FGF stimulation did not require DNA synthesis, but was dependent on the activity of FGF receptors, MEK, p38 MAPK and NFκB signaling, and protein synthesis. While secondary stimulation resulted in strongly decreased replication rate, we did not observe any attenuation of morphological changes, Erk1/2 phosphorylation and cyclin D1 induction. However, secondary FGF stimulation failed to induce the expression of cyclin A, which is critical for the progression from G1 to S phase. Treatment of cells with a broad range histone deacetylase inhibitor during the primary FGF stimulation rescued the proliferative response to the secondary FGF treatment suggesting that the establishment of "FGF memory" may be based on epigenetic changes. We suggest that "FGF memory" can prevent the hyperplastic response to cell damage and inflammation, which are associated with an enhanced FGF production and secretion. "FGF memory" may present a natural obstacle to the efficient application of recombinant FGFs for the treatment of ulcers, ischemias, and wounds.

  3. Omeprazole versus ranitidine in the medical treatment of acute upper gastrointestinal bleeding: assessment by early repeat endoscopy.

    Science.gov (United States)

    Fasseas, P; Leybishkis, B; Rocca, G

    2001-12-01

    The purpose of this study was to assess the effects of acid suppression in patients with upper gastrointestinal bleeding using early repeat endoscopy. Ninety-two patients with the diagnosis of acute upper gastrointestinal bleeding (endoscopically verified), entered a single-blind, randomised study comparing two treatment groups: omeprazole (40 mg orally daily) to ranitidine (50 mg intravenously four times daily). The lesions considered were gastric ulcers, duodenal ulcers and erosive gastritis. All patients were candidates for medical treatment. The parameters assessed included: 1) stabilisation of the lesion by repeat endoscopy at 7.0 +/- 3.0 days, 2) bleeding recurrence, 3) duration of stay in the intermediate medical care unit. For erosive gastritis only parameters 2 and 3 were considered. The study was limited to the hospitalisation period. Endoscopic stabilisation rate at 7.0 +/- 3.0 days for duodenal lesions was higher in the omeprazole group (71% vs 37%, p=0.03), but there was no significant difference for gastric lesions (50% vs 54%, NS). The overall bleeding recurrence rate (0% vs 17%, p=0.013) and the duration of stay (3.9 vs 6.4 days, p<0.01) were significantly lower in the omeprazole group. Our study suggests that omeprazole is more effective than ranitidine in the pharmacological treatment of acute upper gastrointestinal bleeding.

  4. Differential effects of subchronic phencyclidine on anxiety in the light-enhanced startle-, light/dark exploration- and open field tests.

    Science.gov (United States)

    Enkel, Thomas; Thomas, Mara; Bartsch, Dusan

    2013-04-15

    Subchronic treatment with the N-methyl-d-aspartate receptor antagonist phencyclidine (PCP) is a valuable approach to model the symptomatology of schizophrenia, a multi-facetted psychiatric disorder, in rodents. We addressed the question whether subchronic PCP (scPCP) treatment (5 mg/kg bidaily for 7 days) would affect anxiety in rats, since contradictory findings have been reported so far. Anxiety-like behaviour was assessed using the light-enhanced startle paradigm (LES), a method which measures the effect of the natural aversion to light on the startle reflex and does not depend on motivated behaviour or exploratory drive. For comparison, anxiety-like behaviour was measured in the light-dark exploration test (LDT) and in an open field environment (OFT). The scPCP-treatment did not affect baseline startle reactivity or light-enhanced startle, suggesting normal anxiety levels in treated animals. Further, normal anxiety-like behaviour was also found in the OFT. In the LDT, scPCP treated rats displayed shorter latencies to enter the lit compartment and shuttled more between the dark and lit compartments, behaviours indicative of decreased anxiety and/or increased exploratory activity. Our findings therefore suggest that the effects of scPCP-treatment on anxiety-like behaviour are task-dependent and recommend the additional use of tests independent from exploratory drive or other motivated behaviours, such as the LES paradigm.

  5. Neonatal administration of phencyclidine decreases the number of putative inhibitory interneurons and increases neural excitability to auditory paired clicks in the hippocampal CA3 region of freely moving adult mice.

    Science.gov (United States)

    Okamoto, M; Katayama, T; Suzuki, Y; Hoshino, K-Y; Yamada, H; Matsuoka, N; Jodo, E

    2012-11-08

    Animals exposed to phencyclidine (PCP) during the neonatal period have fewer GABAergic interneurons in the corticolimbic area, including the hippocampus, and exhibit abnormal behaviors after attaining maturation that correspond with schizophrenic symptoms. Since a lack of inhibitory interneurons in the hippocampus has also been reported in postmortem studies of patients with schizophrenia, the deficit may induce abnormal activity of hippocampal neurons that underlies pathological states in schizophrenia. However, it remains unclear how PCP treatment during the neonatal period affects the discharge activity of hippocampal neurons in adulthood. In the current study, single unit responses of hippocampal CA3 neurons to paired auditory clicks were recorded in freely moving mice repeatedly injected with PCP or saline during the neonatal period. The recorded neurons were classified into two subpopulations, narrow-spike neurons and broad-spike neurons, based on the spike width. The spontaneous discharge rate was higher in the narrow-spike neurons than in the broad-spike neurons, indicating that the narrow-spike neurons correspond with hippocampal inhibitory neurons. The proportion of narrow-spike neurons was significantly smaller in neonatally PCP-treated mice than in saline-treated mice. The broad-spike neurons that exhibited a response magnitude to the second click as large as that to the first click (E/E-type response) showed longer response duration to the paired clicks in PCP-treated mice than in the saline-treated mice. Further, the number of neurons with E/E-type response was higher in the PCP-treated mice than in the saline-treated mice. Finally, the attenuation of an auditory-evoked potential component, N40, to the second click (sensory gating) was blunted in the PCP-treated mice when compared with that in the saline-treated mice. These results suggest that the neonatal administration of PCP induced a deficit of inhibitory interneurons and altered discharge

  6. Effects of repeat fenbendazole treatment in dairy calves with giardiosis on cyst excretion, clinical signs and production.

    Science.gov (United States)

    O'Handley, R M; Cockwill, C; Jelinski, M; McAllister, T A; Olson, M E

    2000-04-28

    In this 90-day study, 60 male Holstein dairy calves were experimentally infected with Giardia duodenalis. Calves were randomly blocked by weight into treatment (N=30) and placebo (N=30) groups. Beginning on study Day 0, calves in the treatment group were administered an oral dose of 5mg/kg of fenbendazole once daily for three consecutive days. Calves in the placebo group received a daily oral treatment of 5 ml of saline for 3 days. These treatments were repeated on Days 30 and 60 of the study. Fecal samples were collected from calves once per week and examined for the presence of Giardia cysts. Calves were monitored daily for clinical signs of intestinal disease and all episodes of diarrhea recorded. Calves were weighed once per week and total feed intake, on a dry matter basis, was calculated daily. Following each treatment, the number of calves shedding Giardia cysts in the fenbendazole group was reduced (pfenbendazole group had fewer cysts (pfenbendazole had fewer total days with diarrhea (pfenbendazole is an effective treatment for giardiosis, resulting in a clinical benefit and reducing the number of infective cysts shed by calves. However, this treatment regime had no impact on production parameters and reinfection occurred rapidly in these calves.

  7. ErbB signaling antagonist ameliorates behavioral deficit induced by phencyclidine (PCP) in mice, without affecting metabolic syndrome markers.

    Science.gov (United States)

    Tadmor, Hagar; Golani, Idit; Doron, Ravid; Kremer, Ilana; Shamir, Alon

    2017-08-14

    Schizophrenia is a severe syndrome that affects about 1% of the world population. Since the mid-1950s, antipsychotics have been used to treat schizophrenia with preference for treating positive symptoms; however, their tolerance level is low, there are numerous side effects, and only some patients respond to the treatment. Antipsychotic medications that are more effective, better tolerated, and with fewer adverse effects are urgently needed. Given the accumulating evidence of the role filled by the ErbB signaling network in the biology of the dopamine, GABA, and glutamate systems, and in the etiology of schizophrenia, we hypothesized that the ErbB network is a candidate for development of a novel agent through which various symptoms of schizophrenia and other psychiatric disorders might be treated. Herein, we studied, in mice, the capability of blocking the ErbB signaling, in comparison with the atypical antipsychotic drug clozapine, to counter schizophrenia-like behavior induced by acute and sub-chronic phencyclidine (PCP), and determined whether inhibition of the ErbB networks induced weight gain and affected social and exploratory behavior, and metabolic syndrome markers. We demonstrated that administration of the pan-ErbB inhibitor JNJ28871063 (JNJ) reduced the level of activity in the open field induced by an acute injection of PCP. Moreover, the ability of JNJ to attenuate the effect of PCP is as effective as clozapine. In addition and like clozapine, JNJ normalized social behavior impairment induced by sub-chronic PCP and stress. Adult JNJ-treated mice displayed normal sociability and exploratory behavior, and their serum cholesterol, LDL, and HDL levels were lower than in the saline-treated mice. Sub-chronic treatment did not affect weight gain, glucose levels, and the activity of hepatic enzymes catalase and SOD. These data suggest that treatment with JNJ attenuates abnormal behaviors induced by PCP, and has similar effects as the antipsychotic drug

  8. Comparative Genomic Hybridization Selection of Blastocysts for Repeated Implantation Failure Treatment: A Pilot Study

    Science.gov (United States)

    Greco, Ermanno; Bono, Sara; Ruberti, Alessandra; Lobascio, Anna Maria; Greco, Pierfrancesco; Biricik, Anil; Spizzichino, Letizia; Greco, Alessia; Tesarik, Jan; Minasi, Maria Giulia; Fiorentino, Francesco

    2014-01-01

    The aim of this study is to determine if the use of preimplantation genetic screening (PGS) by array comparative genomic hybridization (array CGH) and transfer of a single euploid blastocyst in patients with repeated implantation failure (RIF) can improve clinical results. Three patient groups are compared: 43 couples with RIF for whom embryos were selected by array CGH (group RIF-PGS), 33 couples with the same history for whom array CGH was not performed (group RIF NO PGS), and 45 good prognosis infertile couples with array CGH selected embryos (group NO RIF PGS). A single euploid blastocyst was transferred in groups RIF-PGS and NO RIF PGS. Array CGH was not performed in group RIF NO PGS in which 1-2 blastocysts were transferred. One monoembryonic sac with heartbeat was found in 28 patients of group RIF PGS and 31 patients of group NO RIF PGS showing similar clinical pregnancy and implantation rates (68.3% and 70.5%, resp.). In contrast, an embryonic sac with heartbeat was only detected in 7 (21.2%) patients of group RIF NO PGS. In conclusion, PGS by array CGH with single euploid blastocyst transfer appears to be a successful strategy for patients with multiple failed IVF attempts. PMID:24779011

  9. Repeated superovulation using a simplified FSH/eCG treatment for in vivo embryo production in sheep.

    Science.gov (United States)

    Forcada, F; Ait Amer-Meziane, M; Abecia, J A; Maurel, M C; Cebrián-Pérez, J A; Muiño-Blanco, T; Asenjo, B; Vázquez, M I; Casao, A

    2011-03-01

    This study investigated the efficacy of a simplified repeated superovulation treatment (eCG plus FSH in a single dose, rather than the usual protocol of six decreasing doses of FSH) in the in vivo embryo production in Ojalada donor ewes during the breeding season. In vitro viability after vitrification and warming of embryos recovered from both treatments was also assessed. In addition, the study examined the effects of the concentration of anti-eCG antibodies before each eCG/FSH treatment on in vivo embryo production. Thirty-eight females at the end of their reproductive lives were given the decreasing (n = 19) or simplified (n = 19) superovulatory treatment up to three times at intervals of ≥ 50 d. The onset of estrus was 5 h earlier (P < 0.05) among ewes that received the eCG/FSH protocol (25.2 ± 0.80 h) than it was among those that received the decreasing superovulatory treatment (30.1 ± 1.0 h), but the two treatments did not differ significantly in ovulation rates or the number and viability of embryos recovered. Both of the superovulatory protocols were significantly (P < 0.05 to P < 0.01) less effective after the first application. After three superovulatory treatments, the average number of viable embryos per ewe was 14.1 ± 2.3 and 13.7 ± 2.5 in the decreasing and simplified protocols, respectively. High anti-eCG antibody concentrations just before the superovulatory treatment with eCG/FSH were associated with a significant decrease (P < 0.05) in the rates of fertilization, viability, and freezability, especially in the second and third recoveries. Repeated superovulatory treatments with eCG/FSH can provide an efficient means of producing high quality embryos in the ewes of endangered breeds at the end of their reproductive lives, although further studies are needed to characterize the response associated with high concentrations of anti-eCG antibodies. Copyright © 2011 Elsevier Inc. All rights reserved.

  10. Are There Linguistic Markers of Suicidal Writing That Can Predict the Course of Treatment? A Repeated Measures Longitudinal Analysis.

    Science.gov (United States)

    Brancu, Mira; Jobes, David; Wagner, Barry M; Greene, Jeffrey A; Fratto, Timothy A

    2016-07-02

    The purpose of this pilot study was to predict resolution of suicidal ideation and risk over the course of therapy among suicidal outpatients (N = 144) using a novel method for analyzing Self- verses Relationally oriented qualitative written responses to the Suicide Status Form (SSF). A content analysis software program was used to extract word counts and a repeated measures longitudinal design was implemented to assess improvement over time. Patients with primarily Relationally focused word counts were more likely to have a quicker suicide risk resolution than those with more Self-focused word counts (6-7 sessions versus 17-18 sessions). Implications of these data are discussed, including the potential for enhancing treatment outcomes using this method with individuals entering treatment.

  11. Utility of repeated praziquantel dosing in the treatment of schistosomiasis in high-risk communities in Africa: a systematic review.

    Directory of Open Access Journals (Sweden)

    Charles H King

    2011-09-01

    Full Text Available Controversy persists about the optimal approach to drug-based control of schistosomiasis in high-risk communities. In a systematic review of published studies, we examined evidence for incremental benefits from repeated praziquantel dosing, given 2 to 8 weeks after an initial dose, in Schistosoma-endemic areas of Africa.We performed systematic searches of electronic databases PubMed and EMBASE for relevant data using search terms 'schistosomiasis', 'dosing' and 'praziquantel' and hand searches of personal collections and bibliographies of recovered articles. In 10 reports meeting study criteria, improvements in parasitological treatment outcomes after two doses of praziquantel were greater for S. mansoni infection than for S. haematobium infection. Observed cure rates (positive to negative conversion in egg detection assays were, for S. mansoni, 69-91% cure after two doses vs. 42-79% after one dose and, for S. haematobium, 46-99% cure after two doses vs. 37-93% after a single dose. Treatment benefits in terms of reduction in intensity (mean egg count were also different for the two species-for S. mansoni, the 2-dose regimen yielded an weighted average 89% reduction in standardized egg counts compared to a 83% reduction after one dose; for S. haematobium, two doses gave a 93% reduction compared to a 94% reduction with a single dose. Cost-effectiveness analysis was performed based on Markov life path modeling.Although schedules for repeated treatment with praziquantel require greater inputs in terms of direct costs and community participation, there are incremental benefits to this approach at an estimated cost of $153 (S. mansoni-$211 (S. haematobium per additional lifetime QALY gained by double treatment in school-based programs. More rapid reduction of infection-related disease may improve program adherence, and if, as an externality of the program, transmission can be reduced through more effective coverage, significant additional benefits are

  12. The role of 5-HT1A receptors in phencyclidine (PCP)-induced novel object recognition (NOR) deficit in rats.

    Science.gov (United States)

    Horiguchi, M; Meltzer, H Y

    2012-05-01

    Atypical antipsychotic drugs (APDs), many of which are direct or indirect serotonin (5-HT)(1A) agonists, and tandospirone, a 5-HT(1A) partial agonist, have been reported to improve cognition in schizophrenia. We tested the effect of 5-HT(1A) agonism, alone, and in combination with other psychotropic agents, including the atypical APD, lurasidone, in reversing the deficit in novel object recognition (NOR) induced by subchronic treatment with the non-competitive NMDA receptor antagonist, phencyclidine (PCP) (2 mg/kg, b.i.d., for 7 days). Subchronic treatment with PCP induced a persistent NOR deficit. Lurasidone (0.1 mg/kg), a potent 5-HT(1A) partial agonist, 5-HT(2A) antagonist, and weaker D(2) antagonist, tandospirone (0.6 mg/kg), and the selective post-synaptic 5-HT(1A) agonist, F15599 (0.16 mg/kg), ameliorated the subchronic PCP-induced-NOR deficit. The 5-HT(1A) antagonist, WAY100635 (0.6 mg/kg), blocked the ameliorating effects of tandospirone and lurasidone. The combination of sub-effective doses of tandospirone (0.2 mg/kg) and lurasidone (0.03 mg/kg) also reversed the PCP-induced NOR-deficit. Buspirone, a less potent partial 5-HT(1A) agonist than tandospirone, was less effective. Co-administration of tandospirone (0.2 mg/kg) and pimavanserin (3 mg/kg), a relatively selective 5-HT(2A) receptor inverse agonist, did not reverse the effect of sub-chronic PCP on NOR. The D(2) antagonist, haloperidol, blocked the ameliorating effect of tandospirone on the PCP-induced deficit in NOR. These results indicate that 5-HT(1A) agonism is adequate to ameliorate the PCP-induced impairment in NOR and suggest further study of utilizing the combination of a 5-HT(1A) agonist and an atypical APD to ameliorate some types of cognitive impairment in schizophrenia.

  13. Community treatment orders in the UK 5 years on: a repeat national survey of psychiatrists

    Science.gov (United States)

    DeRidder, Ritz; Molodynski, Andrew; Manning, Catherine; McCusker, Pearse; Rugkåsa, Jorun

    2016-01-01

    Aims and method Community treatment orders (CTOs) are increasingly embedded into UK practice and their use continues to rise. However, they remain highly controversial. We surveyed psychiatrists to establish their experiences and current opinions of using CTOs and to compare findings with our previous survey conducted in 2010. Results The opinions of psychiatrists in the UK have not changed since 2010 in spite of recent evidence questioning the effectiveness of CTOs. Clinical factors (the need for engagement and treatment adherence, and the achievement of adherence and improved insight) remain the most important considerations in initiating and discharging a CTO. Clinical implications Given the accumulating evidence from research and clinical practice that CTOs do not improve outcomes, it is concerning that psychiatrists' opinions have not altered in response, particularly given the implications for patient care. PMID:27280030

  14. Effects of repeated quetiapine treatment on conditioned avoidance responding in rats.

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    Gao, Jun; Feng, Min; Swalve, Natashia; Davis, Collin; Sui, Nan; Li, Ming

    2015-12-15

    The present study characterized the behavioral mechanisms of avoidance-disruptive effect of quetiapine in the conditioned avoidance response test under two behavioral testing (2 warning signals vs. 1 warning signal) and two drug administration conditions (subcutaneous vs. intravenous). In Experiments 1 and 2, well-trained adult male Sprague-Dawley rats were tested under the subcutaneous (s.c.) quetiapine treatment (5.0, 15.0, 25.0, 50.0mg/kg) for 7 days in a novel procedure consisting of two conditioned stimuli (CS) (white noise serving as CS1 and pure tone as CS2). Only the highest dose (50.0mg/kg) produced a persistent suppression of the avoidance response without impairing the escape response. The magnitude of suppression of the CS1 avoidance was similar to that of CS2 avoidance. No significant group difference was found in the quetiapine (15.0mg/kg, s.c.) challenge test, indicating a lack of a long-term quetiapine effect. In Experiment 3, well-trained rats were tested under the intravenous (i.v.) quetiapine treatment (3.0, 9.0, 15.0mg/kg) for 5 days and challenged with quetiapine (6.0mg/kg, i.v. followed by 9.0mg/kg, s.c.). Only the white noise was used as the CS. Similar to what was being observed in Experiments 1 and 2, intravenously administered quetiapine dose-dependently suppressed avoidance responding during the drug test days, but did not alter drug sensitivity in the challenge days. Thus, quetiapine does not appear to show a preferential inhibition of the avoidance response to a less salient stimulus; and prior quetiapine treatment (s.c. and i.v.) does not cause a sensitization or tolerance to quetiapine.

  15. Repeated Treatments with Chitosan in Combination with Antibiotics Completely Eradicate Uropathogenic Escherichia coli From Infected Mouse Urinary Bladders.

    Science.gov (United States)

    Erman, Andreja; Hergouth, Veronika Križan; Blango, Matthew G; Kos, Mojca Kerec; Mulvey, Matthew A; Veranic, Peter

    2017-08-01

    Uropathogenic Escherichia coli (UPEC), the primary causative agents of urinary tract infections, colonize and invade the epithelial cells of the bladder urothelium. Infection of immature urothelial cells can result in the formation of persistent intracellular reservoirs that are refractory to antibiotic treatments. Previously, we defined a novel therapeutic strategy that used the bladder cell exfoliant chitosan to deplete UPEC reservoirs. However, although a single treatment of chitosan followed by ciprofloxacin administration had a marked effect on reducing UPEC titers within the bladder, this treatment failed to prevent relapsing bacteriuria. We show here that repeated use of chitosan in conjunction with the antibiotic ciprofloxacin completely eradicates UPEC from the urinary tract and prevents the development of relapsing bouts of bacteriuria. In addition, microscopy revealed rapid restoration of bladder integrity following chitosan treatment, indicating that chitosan can be used to effectively combat recalcitrant bladder infections without causing lasting harm to the urothelium. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  16. In vitro kinetics of amiodarone and its major metabolite in two human liver cell models after acute and repeated treatments.

    Science.gov (United States)

    Pomponio, Giuliana; Savary, Camille C; Parmentier, Céline; Bois, Frederic; Guillouzo, André; Romanelli, Luca; Richert, Lysiane; Di Consiglio, Emma; Testai, Emanuela

    2015-12-25

    The limited value of in vitro toxicity data for the in vivo extrapolation has been often attributed to the lack of kinetic data. Here the in vitro kinetics of amiodarone (AMI) and its mono-N-desethyl (MDEA) metabolite was determined and modelled in primary human hepatocytes (PHH) and HepaRG cells, after single and repeated administration of clinically relevant concentrations. AMI bioavailability was influenced by adsorption to the plastic and the presence of protein in the medium (e.g. 10% serum protein reduced the uptake by half in HepaRG cells). The cell uptake was quick (within 3h), AMI metabolism was efficient and a dynamic equilibrium was reached in about a week after multiple dosing. In HepaRG cells the metabolic clearance was higher than in PHH and increased over time, as well as CYP3A4. The interindividual variability in MDEA production in PHHs was not proportional to the differences in CYP3A4 activities, suggesting the involvement of other CYPs and/or AMI-related CYP inhibition. After repeated treatment AMI showed a slight potential for bioaccumulation, whereas much higher intracellular MDEA levels accumulated over time, especially in the HepaRG cells, associated with occurrence of phospholipidosis. The knowledge of in vitro biokinetics is important to transform an actual in vitro concentration-effect into an in vivo dose-effect relationship by using appropriate modelling, thus improving the in vitro-to-in vivo extrapolation.

  17. Cysteine Metabolism and Oxidative Processes in the Rat Liver and Kidney after Acute and Repeated Cocaine Treatment.

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    Danuta Kowalczyk-Pachel

    Full Text Available The role of cocaine in modulating the metabolism of sulfur-containing compounds in the peripheral tissues is poorly understood. In the present study we addressed the question about the effects of acute and repeated (5 days cocaine (10 mg/kg i.p. administration on the total cysteine (Cys metabolism and on the oxidative processes in the rat liver and kidney. The whole pool of sulfane sulfur, its bound fraction and hydrogen sulfide (H2S were considered as markers of anaerobic Cys metabolism while the sulfate as a measure of its aerobic metabolism. The total-, non-protein- and protein- SH group levels were assayed as indicators of the redox status of thiols. Additionally, the activities of enzymes involved in H2S formation (cystathionine γ-lyase, CSE; 3-mercaptopyruvate sulfurtransferase, 3-MST and GSH metabolism (γ-glutamyl transpeptidase, γ-GT; glutathione S-transferase, GST were determined. Finally, we assayed the concentrations of reactive oxygen species (ROS and malondialdehyde (MDA as markers of oxidative stress and lipid peroxidation, respectively. In the liver, acute cocaine treatment, did not change concentrations of the whole pool of sulfane sulfur, its bound fraction, H2S or sulfate but markedly decreased levels of non-protein SH groups (NPSH, ROS and GST activity while γ-GT was unaffected. In the kidney, acute cocaine significantly increased concentration of the whole pool of sulfane sulfur, reduced the content of its bound fraction but H2S, sulfate and NPSH levels were unchanged while ROS and activities of GST and γ-GT were reduced. Acute cocaine enhanced activity of the CSE and 3-MST in the liver and kidney, respectively. Repeatedly administered cocaine enhanced the whole pool of sulfane sulfur and reduced H2S level simultaneously increasing sulfate content both in the liver and kidney. After repeated cocaine, a significant decrease in ROS was still observed in the liver while in the kidney, despite unchanged ROS content, a marked

  18. Cysteine Metabolism and Oxidative Processes in the Rat Liver and Kidney after Acute and Repeated Cocaine Treatment.

    Science.gov (United States)

    Kowalczyk-Pachel, Danuta; Iciek, Małgorzata; Wydra, Karolina; Nowak, Ewa; Górny, Magdalena; Filip, Małgorzata; Włodek, Lidia; Lorenc-Koci, Elżbieta

    2016-01-01

    The role of cocaine in modulating the metabolism of sulfur-containing compounds in the peripheral tissues is poorly understood. In the present study we addressed the question about the effects of acute and repeated (5 days) cocaine (10 mg/kg i.p.) administration on the total cysteine (Cys) metabolism and on the oxidative processes in the rat liver and kidney. The whole pool of sulfane sulfur, its bound fraction and hydrogen sulfide (H2S) were considered as markers of anaerobic Cys metabolism while the sulfate as a measure of its aerobic metabolism. The total-, non-protein- and protein- SH group levels were assayed as indicators of the redox status of thiols. Additionally, the activities of enzymes involved in H2S formation (cystathionine γ-lyase, CSE; 3-mercaptopyruvate sulfurtransferase, 3-MST) and GSH metabolism (γ-glutamyl transpeptidase, γ-GT; glutathione S-transferase, GST) were determined. Finally, we assayed the concentrations of reactive oxygen species (ROS) and malondialdehyde (MDA) as markers of oxidative stress and lipid peroxidation, respectively. In the liver, acute cocaine treatment, did not change concentrations of the whole pool of sulfane sulfur, its bound fraction, H2S or sulfate but markedly decreased levels of non-protein SH groups (NPSH), ROS and GST activity while γ-GT was unaffected. In the kidney, acute cocaine significantly increased concentration of the whole pool of sulfane sulfur, reduced the content of its bound fraction but H2S, sulfate and NPSH levels were unchanged while ROS and activities of GST and γ-GT were reduced. Acute cocaine enhanced activity of the CSE and 3-MST in the liver and kidney, respectively. Repeatedly administered cocaine enhanced the whole pool of sulfane sulfur and reduced H2S level simultaneously increasing sulfate content both in the liver and kidney. After repeated cocaine, a significant decrease in ROS was still observed in the liver while in the kidney, despite unchanged ROS content, a marked increase

  19. Treatment and functional result of desmoplastic fibroma with repeated recurrences in the forearm: A case report

    Science.gov (United States)

    RUI, JING; GUAN, WENJIE; GU, YUDONG; LAO, JIE

    2016-01-01

    Desmoplastic fibroma, alternatively known as aggressive fibromatosis or desmoid tumors, occurs in the form of benign locally aggressive tumors that possess a high rate of recurrence. The forearm bones are rarely involved. The current study presents a case of desmoplastic fibroma in the distal forearm of a 23-year-old man. The tumor was widely resected, and the bone defect was reconstructed using an autologous vascularized fibular graft during the resection procedure. The patient experienced recurrence three times and underwent four resections during the subsequent 3 years following the initial resection. After 10 years of follow-up, the patient's functional recovery remains positive. Despite the implication that surgical resection may be involved in the development of aggressive fibromatosis, surgical wide local excision and functional reconstruction were recommended for the treatment of the present patient. PMID:26893769

  20. Repeated Insulin-like Growth Factor 1 (IGF1 treatment in a patient with Rett Syndrome: a single case study

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    Giorgio ePini

    2014-06-01

    Full Text Available Rett syndrome (RTT is a devastating neurodevelopmental disorder that has no cure. Patients show regression of acquired skills, motor and speech impairment, cardio-respiratory distress, microcephaly and stereotyped hand movements. The majority of RTT patients display mutations in the gene that codes for the Methyl-CpG binding protein 2 (MeCP2, which is involved in the development of the central nervous system, especially synaptic and circuit maturation. Thus, agents that promote brain development and synaptic function are good candidates for ameliorating the symptoms of RTT. In particular, Insulin-like growth Factor 1 (IGF1 and its active peptide (1-3IGF1 cross the Blood Brain Barrier, and therefore are ideal treatments for RTT Indeed, both (1-3IGF1 and IGF1 treatment significantly ameliorates RTT symptoms in a mouse model of the disease In a previous study we established that IGF1 is safe and well tolerated on Rett patients. In this open label clinical case study, we assess the safety and tolerability of IGF1 administration in two cycles of the treatment. Before and after each cycle we monitored the clinical and blood parameters, autonomic function and social and cognitive abilities, and we found that IGF1 was well tolerated each time and did not induce any side effect, nor it interfered with the other treatments that the patient was undergoing. We noticed a moderate improvement in the cognitive, social and autonomic abilities of the patient after each cycle but the benefits were not retained between the two cycles, consistent with the preclinical observation that treatments for RTT should be administered through life. We find that repeated IGF1 treatment is safe and well tolerated in Rett patients but observed effects are not retained between cycles. These results have applications to other pathologies considering that IGF1 has been shown to be effective in other disorders of the autism spectrum.

  1. Repeated insulin-like growth factor 1 treatment in a patient with rett syndrome: a single case study.

    Science.gov (United States)

    Pini, Giorgio; Scusa, M Flora; Benincasa, Alberto; Bottiglioni, Ilaria; Congiu, Laura; Vadhatpour, Cyrus; Romanelli, Anna Maria; Gemo, Ilaria; Puccetti, Chetti; McNamara, Rachel; O'Leary, Seán; Corvin, Aiden; Gill, Michael; Tropea, Daniela

    2014-01-01

    Rett syndrome (RTT) is a devastating neurodevelopmental disorder that has no cure. Patients show regression of acquired skills, motor, and speech impairment, cardio-respiratory distress, microcephaly, and stereotyped hand movements. The majority of RTT patients display mutations in the gene that codes for the Methyl-CpG binding protein 2 (MeCP2), which is involved in the development of the central nervous system, especially synaptic and circuit maturation. Thus, agents that promote brain development and synaptic function are good candidates for ameliorating the symptoms of RTT. In particular, insulin-like growth factor 1 (IGF1) and its active peptide (1-3) IGF1 cross the Blood Brain Barrier, and therefore are ideal treatments for RTT Indeed, both (1-3) IGF1 and IGF1 treatment significantly ameliorates RTT symptoms in a mouse model of the disease In a previous study, we established that IGF1 is safe and well tolerated on Rett patients. In this open label clinical case study, we assess the safety and tolerability of IGF1 administration in two cycles of the treatment. Before and after each cycle, we monitored the clinical and blood parameters, autonomic function, and social and cognitive abilities, and we found that IGF1 was well tolerated each time and did not induce any side effect, nor it interfered with the other treatments that the patient was undergoing. We noticed a moderate improvement in the cognitive, social, and autonomic abilities of the patient after each cycle but the benefits were not retained between the two cycles, consistent with the pre-clinical observation that treatments for RTT should be administered through life. We find that repeated IGF1 treatment is safe and well tolerated in Rett patients but observed effects are not retained between cycles. These results have applications to other pathologies considering that IGF1 has been shown to be effective in other disorders of the autism spectrum.

  2. Is it important to repeat the positioning maneuver after the treatment for benign paroxysmal positional vertigo?

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    Alexandra Kolontai de Sousa Oliveira

    2015-04-01

    Full Text Available INTRODUCTION: Benign paroxysmal positional vertigo (BPPV is the most common cause of peripheral vestibular dysfunction.OBJECTIVE: To assess whether the performance of the Dix-Hallpike maneuver after the Epley positioning maneuver has prognostic value in the evolution of unilateral ductolithiasis of posterior semicircular canal.METHODS: A prospective cohort study in monitored patients at otoneurology ambulatory with a diagnosis of BPPV; they were submitted to the therapeutic maneuver and then to a retest in order to evaluate the treatment effectiveness; all cases were reassessed one week later and the retest prognostic value was evaluated.RESULTS: A sample of 64 patients which 47 belonging to negative retest group and 17 belonging to positive retest. Performed the maneuver in all patients, the retest presented 51.85% sensitivity, 91.89% specificity, 82.35% positive predictive value and 72.34% negative predictive value.CONCLUSION: The study shows that doing the retest after repositioning maneuver of particles in BPPV is effectual, since it has high specificity.

  3. Repeated BCG treatment of mouse bladder selectively stimulates small GTPases and HLA antigens and inhibits single-spanning uroplakins

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    O'Donnell Michael A

    2007-11-01

    Full Text Available Abstract Background Despite being a mainstay for treating superficial bladder carcinoma and a promising agent for interstitial cystitis, the precise mechanism of Bacillus Calmette-Guerin (BCG remains poorly understood. It is particularly unclear whether BCG is capable of altering gene expression beyond its well-recognized pro-inflammatory effects and how this relates to its therapeutic efficacy. The objective of this study was to determine differentially expressed genes in the mouse bladder following repeated intravesical BCG therapy. Methods Mice were transurethrally instilled with BCG or pyrogen-free on days 1, 7, 14, and 21. Seven days after the last instillation, urothelia along with the submucosa was removed and amplified ds-DNA was prepared from control- and BCG-treated bladder mucosa and used to generate suppression subtractive hybridization (SSH. Plasmids from control- and BCG-specific differentially expressed clones and confirmed by Virtual Northern were then purified and the inserts were sequenced and annotated. Finally, chromatin immune precipitation combined with real-time polymerase chain reaction assay (ChIP/Q-PCR was used to validate SSH-selected transcripts. Results Repeated intravesical BCG treatment induced an up regulation of genes associated with antigen presentation (B2M, HLA-A, HLA-DQA1, HLA-DQB2, HLA-E, HLA-G, IGHG, and IGH and representatives of two IFNγ-induced small GTPase families: the GBPs (GBP1, GBP2, and GBP5 and the p47GTPases (IIGTP1, IIGTP2, and TGTP. Genes expressed in saline-treated bladders but down-regulated by BCG included: the single-spanning uroplakins (UPK3a and UPK2, SPRR2G, GSTM5, and RSP 19. Conclusion Here we introduced a hypothesis-generator approach to determine key genes involved in the urothelium/sumbmucosa responses to BCG therapy. Urinary bladder responds to repeated BCG treatment by up-regulating not only antigen presentation-related genes, but also GBP and p47 small GTPases, both potentially

  4. Relation between hippocampal gamma waves and behavioral disturbances induced by phencyclidine and methamphetamine.

    Science.gov (United States)

    Ma, J; Leung, L S

    2000-06-15

    The relationship between hippocampal electrical activity and behavioral hyperactivity induced by either phencyclidine (PCP) or methamphetamine (MAP) was examined in freely behaving rats. The EEGs at the hippocampal CA1 region were simultaneously recorded with the animal's behavior for 2 h after administration of either PCP or MAP. PCP (10 mg/kg, intraperitoneal (i.p.)) significantly increased locomotor activity including rearing, walking, head-weaving and circling. Spectral analysis of the EEG showed that hippocampal gamma waves (30-70 Hz), but not other frequency bands, were significantly increased from 5 to 120 min after systemic injection of PCP. Inactivation of the medial septum with muscimol, a gamma-aminobutyric acid receptor A agonist, 15 min prior to injection of PCP, suppressed both hippocampal gamma waves and locomotor activity. MAP (1.5 mg/kg, i.p.) also increased locomotor activity for longer than 2 h. During the behavioral hyperactivity induced by MAP, hippocampal EEG showed θ and gamma rhythms that were not significantly different from those during walking before MAP. However, MAP-induced behavioral activity was suppressed by pre-injection of muscimol in the medial septum, which also decreased hippocampal gamma activity. It is suggested that the medial septum plays a role in mediating behavioral disturbances induced by both PCP and MAP through control of the hippocampal electrical activity, and that hippocampal gamma waves may play a permissible role in the expression of behaviors.

  5. Application of solvent microextraction to the analysis of amphetamines and phencyclidine in urine.

    Science.gov (United States)

    Casari, C; Andrews, A R

    2001-09-01

    A fast and simple method to detect some commonly abused illicit drugs, amphetamine, methamphetamine, 3,4-methylendioxy-amphetamine (MDA), 3,4-methylendioxy-methamphetamine (MDMA), 3,4-methylendioxy-N-ethylamphetamine (MDEA) and phencyclidine (PCP) in urine using solvent microextraction (SME) combined with gas chromatography (GC) analysis has been developed. The extraction is conducted by suspending a 2 microl drop of chloroform in a 2 ml urine sample. Following 8 min of extraction, the organic solvent is withdrawn into the syringe and injected into a GC with a pulsed discharge helium ionization detector (PDHID). The effects of different extraction solvents and times, pH and sample preparation were studied. The optimized method was capable of detecting drugs in urine at concentrations below Substance Abuse and Mental Health Services Administration (SAMHSA) established cut-off values for preliminary testing. Good linearity and reproducibility of extraction were obtained. The limits of detection were 0.5 microg/ml for amphetamine, 0.1 microg/ml for methamphetamine and MDA, 0.05 microg/ml for MDMA, 0.025 microg/ml for MDEA and 0.015 microg/ml for PCP. Relative standard deviation (R.S.D.) values ranged between 5 and 20% for the studied drugs.

  6. Effects of hallucinogenic agents mescaline and phencyclidine on zebrafish behavior and physiology.

    Science.gov (United States)

    Kyzar, Evan J; Collins, Christopher; Gaikwad, Siddharth; Green, Jeremy; Roth, Andrew; Monnig, Louie; El-Ounsi, Mohamed; Davis, Ari; Freeman, Andrew; Capezio, Nicholas; Stewart, Adam Michael; Kalueff, Allan V

    2012-04-27

    Mescaline and phencyclidine (PCP) are potent hallucinogenic agents affecting human and animal behavior. As their psychotropic effects remain poorly understood, further research is necessary to characterize phenotypes they evoke in various animal models. Zebrafish (Danio rerio) are rapidly emerging as a new model organism for neuroscience research. Here, we examine the effects of mescaline (5-20mg/l) and PCP (0.5-3mg/l) in several zebrafish paradigms, including the novel tank, open field and shoaling tests. Mescaline and PCP dose-dependently increased top activity in the novel tank test, also reducing immobility and disrupting the patterning of zebrafish swimming, as assessed by ethograms. PCP, but not mescaline, evoked circling behavior in the open field test. At the highest doses tested, mescaline markedly increased, while PCP did not affect, zebrafish shoaling behavior. Finally, 20mg/l mescaline did not alter, and 3mg/l PCP elevated, whole-body cortisol levels. Overall, our studies indicate high sensitivity of zebrafish models to hallucinogenic compounds with complex behavioral and physiological effects.

  7. Repeated cisplatin treatment can lead to a multiresistant tumor cell population with stem cell features and sensitivity to 3-bromopyruvate.

    Science.gov (United States)

    Wintzell, My; Löfstedt, Lina; Johansson, Joel; Pedersen, Anne B; Fuxe, Jonas; Shoshan, Maria

    2012-12-01

    Cisplatin is used in treatment of several types of cancer, including epithelial ovarian carcinoma (EOC). In order to mimic clinical treatment and to investigate longterm effects of cisplatin in surviving cancer cells, two EOC cell lines were repeatedly treated with low doses. In the SKOV-3 cell line originating from malignant ascites, but not in A2780 cells from a primary tumor, this led to emergence of a stable population (SKOV-3-R) which in the absence of cisplatin showed increased motility, epithelial-mesenchymal transition (EMT) and expression of cancer stem cell markers CD117, CD44 and ALDH1. Accordingly, the cells formed self-renewing spheres in serum-free stem cell medium. Despite upregulation of mitochondrial mass and cytochrome c, and no upregulation of Bcl-2/Bcl-xL, SKOV-3-R were multiresistant to antineoplastic drugs. Cancer stem cells, or tumor-initiating cells (TICs) are highly chemoresistant and are believed to cause relapse into disseminated and resistant EOC. Our second aim was therefore to target resistance in these TIC-like cells. Resistance could be correlated with upregulation of hexokinase-II and VDAC, which are known to form a survival-promoting mitochondrial complex. The cells were thus sensitive to 3-bromopyruvate, which dissociates hexokinase-II from this complex, and were particularly sensitive to combination treatment with cisplatin at doses down to 0.1 x IC 50. 3-bromopyruvate might thus be of use in targeting the especially aggressive TIC populations.

  8. Impact monitoring of the national scale up of zinc treatment for childhood diarrhea in Bangladesh: repeat ecologic surveys.

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    Charles P Larson

    2009-11-01

    Full Text Available BACKGROUND: Zinc treatment of childhood diarrhea has the potential to save 400,000 under-five lives per year in lesser developed countries. In 2004 the World Health Organization (WHO/UNICEF revised their clinical management of childhood diarrhea guidelines to include zinc. The aim of this study was to monitor the impact of the first national campaign to scale up zinc treatment of childhood diarrhea in Bangladesh. METHODS/FINDINGS: Between September 2006 to October 2008 seven repeated ecologic surveys were carried out in four representative population strata: mega-city urban slum and urban nonslum, municipal, and rural. Households of approximately 3,200 children with an active or recent case of diarrhea were enrolled in each survey round. Caretaker awareness of zinc as a treatment for childhood diarrhea by 10 mo following the mass media launch was attained in 90%, 74%, 66%, and 50% of urban nonslum, municipal, urban slum, and rural populations, respectively. By 23 mo into the campaign, approximately 25% of urban nonslum, 20% of municipal and urban slum, and 10% of rural under-five children were receiving zinc for the treatment of diarrhea. The scale-up campaign had no adverse effect on the use of oral rehydration salt (ORS. CONCLUSIONS: Long-term monitoring of scale-up programs identifies important gaps in coverage and provides the information necessary to document that intended outcomes are being attained and unintended consequences avoided. The scale-up of zinc treatment of childhood diarrhea rapidly attained widespread awareness, but actual use has lagged behind. Disparities in zinc coverage favoring higher income, urban households were identified, but these were gradually diminished over the two years of follow-up monitoring. The scale up campaign has not had any adverse effect on the use of ORS. Please see later in the article for the Editors' Summary.

  9. Dietary Intake of Sulforaphane-Rich Broccoli Sprout Extracts during Juvenile and Adolescence Can Prevent Phencyclidine-Induced Cognitive Deficits at Adulthood.

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    Yumi Shirai

    Full Text Available Oxidative stress and inflammation play a role in cognitive impairment, which is a core symptom of schizophrenia. Furthermore, a hallmark of the pathophysiology of this disease is the dysfunction of cortical inhibitory γ-aminobutyric acid (GABA neurons expressing parvalbumin (PV, which is also involved in cognitive impairment. Sulforaphane (SFN, an isothiocyanate derived from broccoli, is a potent activator of the transcription factor Nrf2, which plays a central role in the inducible expressions of many cytoprotective genes in response to oxidative stress. Keap1 is a cytoplasmic protein that is essential for the regulation of Nrf2 activity. Here, we found that pretreatment with SFN attenuated cognitive deficits, the increase in 8-oxo-dG-positive cells, and the decrease in PV-positive cells in the medial prefrontal cortex and hippocampus after repeated administration of phencyclidine (PCP. Furthermore, PCP-induced cognitive deficits were improved by the subsequent subchronic administration of SFN. Interestingly, the dietary intake of glucoraphanin (a glucosinolate precursor of SFN during the juvenile and adolescence prevented the onset of PCP-induced cognitive deficits as well as the increase in 8-oxo-dG-positive cells and the decrease in PV-positive cells in the brain at adulthood. Moreover, the NRF2 gene and the KEAP1 gene had an epistatic effect on cognitive impairment (e.g., working memory and processing speed in patients with schizophrenia. These findings suggest that SFN may have prophylactic and therapeutic effects on cognitive impairment in schizophrenia. Therefore, the dietary intake of SFN-rich broccoli sprouts during the juvenile and adolescence may prevent the onset of psychosis at adulthood.

  10. Repeated quick hot-and-chilling treatments for the inactivation of Escherichia coli O157:H7 in mung bean and radish seeds.

    Science.gov (United States)

    Bari, Md Latiful; Sugiyama, Jun; Kawamoto, Shinnichi

    2009-01-01

    The majority of the seed sprout-related outbreaks have been associated with Escherichia coli O157:H7. Therefore, it is necessary to find an effective method to inactivate these organisms on the seeds prior to sprouting. This study was conducted to assess the effectiveness of repeated quick hot-and-chilling treatments with various chemicals to inactivate E. coli O157:H7 populations inoculated onto mung bean and radish seeds intended for sprout production and to determine the effect of these treatments on seed germination. The treatment time was 20 sec for quick hot and 20 sec for quick chilling in one repeat. Likewise up to five repeats were done throughout the experiments. The chemicals used for this study were electrolyzed acidic (EO) water, phytic acid (0.05%), oxalic acid (3%), surfcera(R), and alpha-torino water(R), and distilled water was used as control. The quick hot treatment was done with 75 degrees C, 70 degrees C, and 60 degrees C, and the chilling temperature was 0 degrees C. The treated seeds were then assessed for the efficacy of this treatment in reducing populations of the pathogens and the effects of repeated quick hot-and-chilling treatments on germination yield. It was found that repeating treatment at 75 degrees C for two or three repeats with phytic acid and oxalic acid could reduce 4.38-log colony-forming unit (CFU)/g of E. coli O157:H7 in mung bean seeds. EO water and distilled water were found equally effective at 75 degrees C for four or five repeats to inactivate E. coli O157:H7 in mung bean seeds. However, alpha-torino water(R) and surfcera(R) were not found effective in comparison to other sanitizers used in this experiment. Irrespective of sanitizer used, the germination yield of the mung bean seed was not affected significantly. On the other hand, distilled water, EO water, and alpha-torino water(R) at 75 degrees C for five repeats were found effective in reducing 5.80-log CFU/g of E. coli O157:H7 in radish seeds; however, the

  11. Effect of repeated sauna treatment on exercise tolerance and endothelial function in patients with chronic heart failure.

    Science.gov (United States)

    Ohori, Takashi; Nozawa, Takashi; Ihori, Hiroyuki; Shida, Takuya; Sobajima, Mitsuo; Matsuki, Akira; Yasumura, Satoshi; Inoue, Hiroshi

    2012-01-01

    Repeated sauna treatment, known as Waon therapy, has been shown to improve cardiac function as well as exercise tolerance in patients with chronic heart failure. However, the underlying mechanisms of this therapy regarding these improvements remain to be elucidated. Forty-one patients with chronic heart failure (mean age 68.3 ± 13.5 years old) underwent Waon therapy 5 times a week for 3 weeks. Before and after treatment, a number of assessments were performed in all subjects: 6-minute walk test, echocardiography, determination of neurohumoral factors and number of circulating CD34(+) cells, and a flow-mediated dilation (FMD) test of endothelial function. Cardiopulmonary exercise testing was also performed in 20 patients. Waon therapy increased the left ventricular ejection fraction (from 30.4 ± 12.6% to 32.5% ± 12.8%, p = 0.023) and reduced plasma levels of norepinephrine (from 400 ± 258 to 300 ± 187 pg/ml, p = 0.015) and brain natriuretic peptide (from 550 ± 510 to 416 ± 431 pg/ml, p = 0.035). Waon therapy increased the 6-minute walk distance (from 337 ± 120 to 379 ± 126 m, p sauna therapy in patients with chronic heart failure improves exercise tolerance in association with improvement in endothelial function.

  12. Prolonged reversal of the phencyclidine-induced impairment in novel object recognition by a serotonin (5-HT)1A-dependent mechanism.

    Science.gov (United States)

    Horiguchi, Masakuni; Miyauchi, Masanori; Neugebauer, Nichole M; Oyamada, Yoshihiro; Meltzer, Herbert Y

    2016-03-15

    Many acute treatments transiently reverse the deficit in novel object recognition (NOR) produced by subchronic treatment with the N-methyl-d-aspartate receptor non-competitive antagonist, phencyclidine (PCP), in rodents. Treatments which restore NOR for prolonged periods after subchronic PCP treatment may have greater relevance for treating the cognitive impairment in schizophrenia than those which restore NOR transiently. We examined the ability of post-PCP subchronic lurasidone, an atypical APD with potent serotonin (5-HT)1A partial agonism and subchronic tandospirone, a selective 5-HT1A partial agonist, to enable prolonged reversal of the subchronic PCP-induced NOR deficit. Rats treated with subchronic PCP (2mg/kg, twice daily for 7 days) or vehicle, followed by a 7day washout period were subsequently administered lurasidone or tandospirone twice daily for 7 days (day 15-21), and tested for NOR weekly for up to two additional weeks. Subchronic lurasidone (1, but not 0.1mg/kg) or tandospirone (5, but not 0.6mg/kg) significantly reversed the PCP-induced NOR deficit at 24h and 7days after the last injection, respectively. The effect of lurasidone persisted for one more week (day 36, 14 days after the last lurasidone dose), while tandospirone-treated rats were able to perform NOR at 7, but not 14, days after the last tandospirone dose. Co-administration of WAY100635 (0.6mg/kg), a 5-HT1A antagonist, with lurasidone, blocked the ability of lurasidone to restore NOR, suggesting that 5-HT1A receptor stimulation is necessary for lurasidone to reverse the effects of PCP. The role of dopamine, GABA and the MAPK/ERK signalling pathway in the persistent, but not indefinite, restoration of NOR is discussed.

  13. Hexanucleotide Repeat Expansion in C9ORF72 Is Not Detected in the Treatment-Resistant Schizophrenia Patients of Chinese Han.

    Science.gov (United States)

    Xu, Xijia; Xie, Shiping; Shi, Xiaomeng; Lv, Jie; Tang, Xiaowei; Wang, Xiaolan; Lu, Shuiping; Wang, Mingzhong; Zhang, Xiaobing; Sun, Jing; Yao, Hui

    2015-01-01

    Hexanucleotide (GGGGCC) repeat expansion in C9ORF72 (HRE) causes frontotemporal lobar degeneration, frontotemporal dementia-amyotrophic lateral sclerosis, and amyotrophic lateral sclerosis. HRE was also seen in the genomes of patients suffering from several other degenerative diseases. However, whether it is present in the treatment-resistant schizophrenia patients remains unknown. Genotyping 386 patients suffering from treatment-resistant schizophrenia using the method of Repeat-Primed PCR, we reported here that no HRE was detected in the patients of Chinese Han.

  14. Phencyclidine (PCP) produces sexually dimorphic effects on voluntary sucrose consumption and elevated plus maze behavior.

    Science.gov (United States)

    Turgeon, Sarah M; Anderson, Nicole; O'Loughlin, Kerry

    2010-04-01

    Previous research in our laboratory indicates that the psychotomimetic drug phencyclidine (PCP) reduces voluntary sucrose consumption in male rats, potentially modeling the schizophrenic symptom of anhedonia. Given reports from the clinical literature that schizophrenia has a later age of onset and more favorable outcome in females, PCP might be expected to have sexually dimorphic effects in animal models of schizophrenia such as PCP-induced decreases in voluntary sucrose consumption. Young adult (66 days old) and adult (109 days old) male and female rats were trained to drink sucrose during a 30 min/day presentation protocol. On the day prior to the test day, animals were treated with PCP (15 mg/kg) or saline four hours after the onset of the sucrose presentation (20 h prior to the sucrose on the test day). PCP decreased sucrose consumption on the test day similarly in adult males and females, although females also showed decreased water consumption. In young animals, PCP decreased sucrose consumption in males but not in females. These results are consistent with the prediction that females will be less sensitive to the schizophrenia-like behavioral effects of PCP. In a separate study, the same animals were tested in an elevated plus maze one to two months after testing for voluntary sucrose consumption. Significant sex x drug interaction effects on a number of measures in the elevated plus maze indicated that prior exposure to PCP had an anxiolytic effect in females and an anxiogenic effect in males. While unexpected, this finding indicates an additional sexually dimorphic effect of PCP on behavior and its potential relevance to the PCP model of schizophrenia is discussed. 2010 Elsevier Inc. All rights reserved.

  15. Budd-Chiari syndrome and heparin-induced thrombocytopenia in polycythemia vera: Successful treatment with repeated TIPS and interferon alpha

    Directory of Open Access Journals (Sweden)

    Akoum Riad

    2009-01-01

    Full Text Available Polycythemia vera (PV is a common cause of Budd-Chiari syndrome (BCS and portal vein thrombosis (PVT. The postpartum period is a precipitating cofactor. An additional heparin-induced thrombocytopenia/thrombosis (HIT/T leads to a life-threatening condition in which transjugular intrahepatic portosystemic shunting (TIPS seems to be the only life-saving procedure. We describe the case of a subacute BCS and PVT in the late postpartum period. The diagnosis was established using CT scan, MRI, and Doppler ultrasonography of abdominal vessels and the laboratory findings were compatible with PV. After a successful creation of TIPS, a HIT/T worsened the hemorrhagic and thrombotic picture. TIPS procedure was successfully repeated and heparin was replaced with Fondaparinux and then vitamin K antagonist. The treatment with interferon alpha-2A, started after the normalization of liver functions, resulted in a complete remission within 6 months. The JAK2 V617F mutation clone remained undetectable after 2 years′ follow-up.

  16. Cocaine and phencyclidine inhibition of the acetylcholine receptor: analysis of the mechanisms of action based on measurements of ion flux in the millisecond-to-minute time region.

    Science.gov (United States)

    Karpen, J W; Aoshima, H; Abood, L G; Hess, G P

    1982-01-01

    The effects of cocaine and of phencyclidine and procaine on acetylcholine receptor-controlled ion flux were measured in the millisecond-to-minute time region. Chemical kinetic measurements of ion flux were made in membrane vesicles prepared from the electric organ of Electrophorus electricus and in PC-12 cells, a sympathetic neuronal cell line. A quench-flow technique was used to measure ion flux in the millisecond-to-second range in membrane vesicles. Cocaine and phencyclidine both inhibit acetylcholine receptor-controlled ion flux, but by different mechanisms. Both compounds decrease the initial rate of ion flux, an effect observed with the local anesthetic procaine. This inhibition cannot be prevented by saturating concentrations of acetylcholine (1 mM). These results from chemical kinetic experiments are consistent with electrophysiological measurements which indicate that local anesthetics act by interfering with the movement of ions through receptor-formed channels. The chemical kinetic experiments, however, give additional information about the action of phencyclidine. They indicate that phencyclidine also increases the rate of receptor inactivation (desensitization) and changes the equilibrium between active and inactive receptor conformations, effects not observed in the presence of cocaine or procaine. PMID:6953408

  17. Bacopa monnieri (Brahmi) improved novel object recognition task and increased cerebral vesicular glutamate transporter type 3 in sub-chronic phencyclidine rat model of schizophrenia.

    Science.gov (United States)

    Piyabhan, Pritsana; Wannasiri, Supaporn; Naowaboot, Jarinyaporn

    2016-12-01

    Reduced vesicular glutamate transporter 1 (VGLUT1) and 2 (VGLUT2) indicate glutamatergic hypofunction leading to cognitive impairment in schizophrenia. However, VGLUT3 involvement in cognitive dysfunction has not been reported in schizophrenia. Brahmi (Bacopa monnieri) might be a new treatment and prevention for cognitive deficits in schizophrenia by acting on cerebral VGLUT3 density. We aimed to study cognitive enhancement- and neuroprotective-effects of Brahmi on novel object recognition and cerebral VGLUT3 immunodensity in sub-chronic (2 mg/kg, Bid, ip) phencyclidine (PCP) rat model of schizophrenia. Rats were assigned to three groups for cognitive enhancement effect study: Group 1, Control; Group 2, PCP administration; Group 3, PCP+Brahmi. A neuroprotective-effect study was also carried out. Rats were again assigned to three groups: Group 1, Control; Group 2, PCP administration; Group 3, Brahmi+PCP. Discrimination ratio (DR) representing cognitive ability was obtained from a novel object recognition task. VGLUT3 immunodensity was measured in the prefrontal cortex, striatum and cornu ammonis fields 1-3 (CA1-3) using immunohistochemistry. We found reduced DR in the PCP group, which occurred alongside VGLUT3 reduction in all brain areas. PCP+Brahmi showed higher DR score with increased VGLUT3 immunodensity in the prefrontal cortex and striatum. Brahmi+PCP group showed a higher DR score with increased VGLUT3 immunodensity in the prefrontal cortex, striatum and CA1-3. We concluded that reduced cerebral VGLUT3 was involved in cognitive deficit in PCP-administrated rats. Receiving Brahmi after PCP restored cognitive deficit by increasing VGLUT3 in the prefrontal cortex and striatum. Receiving Brahmi before PCP prevented cognitive impairment by elevating VGLUT3 in prefrontal cortex, striatum and CA1-3. Therefore, Brahmi could be a new frontier of restoration and prevention of cognitive deficit in schizophrenia. © 2016 John Wiley & Sons Australia, Ltd.

  18. The Effect of Age and Initial Central Retinal Thickness on Earlier Need of Repeat Ozurdex Treatment for Macular Edema Due to Retinal Vein Occlusion: A Retrospective Case Series.

    Science.gov (United States)

    Lin, Chun-Ju; Chen, Huan-Sheng; Su, Cheng-Wen; Tien, Peng-Tai; Lin, Jane-Ming; Chen, Wen-Lu; Kuo, Chung-Yuan; Lai, Chun-Ting; Tsai, Yi-Yu

    2017-09-26

    To evaluate the effects of dexamethasone intravitreal implant (Ozurdex) and identify risk factors for repeated treatment in patients with macula edema due to branch retinal vein occlusion (BRVO) or central retinal vein occlusion (CRVO). Patients followed up for at least 6 months were enrolled from 2013 to 2016. Dexamethasone intravitreal implant was given as the baseline treatment. For evaluation of dexamethasone intravitreal implant effects and complications, the demographics, medical history, best-corrected visual acuity (BCVA), intraocular pressure, and central retinal thickness (CRT) were recorded. Multivariate Cox proportional hazard model and logistic regression were used to identify factors for repeated treatment. Twenty-three BRVO and 11 CRVO patients were enrolled. There were 15 males and 19 females. Fifteen (44.12%) patients needed only one dexamethasone intravitreal implant. The peak CRT and BCVA significantly improved. Comparing single-injection with multiple-injection group, age and initial CRT more than 400 μm were significantly higher in the multiple-injection group. From multivariate logistic regression and Cox proportional hazards analysis, patients with age older than 55 years and initial CRT more than 400 μm had higher risk for multiple injections. Patients receiving as-needed schedule of dexamethasone intravitreal implant had significant peak CRT and BCVA improvement. Age older than 55 years and initial CRT more than 400 μm were significant risk factors associated with repeated dexamethasone intravitreal implant treatment.

  19. Effect of Repeated Stress Treatments During the Follicular Phase and Early Pregnancy on Reproductive Performance of Gilts

    NARCIS (Netherlands)

    Soede, N.M.; Roelofs, J.B.; Verheijen, R.J.E.; Schouten, W.G.P.; Hazeleger, W.; Kemp, B.

    2007-01-01

    In pig husbandry, stress is being considered an important cause of impaired reproductive performance. Therefore, an experiment was performed to quantify effects of repeated stressors during the follicular phase and/or during early pregnancy on reproductive performance of gilts. Eighty-one cyclic

  20. Risk Factors of Repeated Infectious Disease Incidence among Substance Dependent Girls and Boys Court-Referred to Treatment

    Science.gov (United States)

    Pagano, Maria E.; Maietti, Candice M.; Levine, Alan D.

    2015-01-01

    A small portion of Americans account for a disproportionate amount of the incidences of sexually transmitted infection observed over a short period of time. Studies with adults have begun to characterize this population, yet there is very little data on adolescent sexually transmitted infection repeaters (STIR). This study explores characteristics…

  1. Treatment of neuroblastoma in congenital central hypoventilation syndrome with a PHOX2B polyalanine repeat expansion mutation: New twist on a neurocristopathy syndrome.

    Science.gov (United States)

    Armstrong, Amy E; Weese-Mayer, Debra E; Mian, Amir; Maris, John M; Batra, Vandana; Gosiengfiao, Yasmin; Reichek, Jennifer; Madonna, Mary Beth; Bush, Jonathan W; Shore, Richard M; Walterhouse, David O

    2015-11-01

    Neuroblastoma in patients with congenital central hypoventilation syndrome (CCHS) as part of a neurocristopathy syndrome is a rare finding and has only been associated with paired-like homeobox 2b (PHOX2B) non-polyalanine-repeat-expansion mutations. To the best of our knowledge, we report the first case of a child with CCHS and Hirschsprung disease who had a PHOX2B polyalanine-repeat-expansion mutation (PARM) (genotype 20/33) and developed high-risk neuroblastoma. We further describe his treatment including chemotherapy and therapeutic I(131) -metaiodobenzylguanidine. This case highlights the need to consider neuroblastoma in patients with CCHS and the longest PHOX2B PARMs and to individualize treatment based on co-morbidities.

  2. In-vitro cervical mucus-sperm penetration tests and outcome of infertility treatments in couples with repeatedly negative post-coital tests.

    Science.gov (United States)

    Farhi, J; Valentine, A; Bahadur, G; Shenfield, F; Steele, S J; Jacobs, H S

    1995-01-01

    The results of in-vitro cervical mucus-sperm penetration tests and cross-hostility tests in 178 couples with repeatedly negative post-coital tests were recorded. Using a protocol of three cycles with intra-uterine inseminations (IUI) followed by three cycles with ovulation induction + IUI, the association between the cause of infertility, results of the in-vitro tests and the outcome of infertility treatment was investigated. We found that repeatedly negative post-coital tests are a good indicator of a cervical mucus-sperm penetration problem. The cross-hostility test clearly differentiates the abnormal factor in this interaction, and a good performance of the donors' spermatozoa in the cervical mucus correlates with increased pregnancy rate. In male factor infertility, failure of the husbands' spermatozoa to penetrate cervical mucus was not indicative of a deficient fertilization potential in vivo. In these patients a serious attempt should therefore be made to reverse the infertility by treatment with IUI or ovulation induction + IUI before attempting assisted reproduction. Women with polycystic ovaries and repeatedly negative post-coital tests should be investigated for sperm receptivity of the cervical mucus. Low receptivity of the cervical mucus may imply that endometrial receptivity and oocyte quality are also low. Ovulation induction and not IUI alone should therefore be used as the preferred mode of treatment to improve pregnancy rate.

  3. Efficacy and safety of fixed-dose artesunate-amodiaquine vs. artemether-lumefantrine for repeated treatment of uncomplicated malaria in Ugandan children.

    Directory of Open Access Journals (Sweden)

    Adoke Yeka

    Full Text Available The safety and efficacy of the two most widely used fixed-dose artemisinin-based combination therapies (ACT, artesunate-amodiaquine (ASAQ and artemether-lumefantrine (AL are well established for single episodes of uncomplicated Plasmodium falciparum malaria, but the effects of repeated, long-term use are not well documented. We conducted a 2-year randomized, open-label, longitudinal, phase IV clinical trial comparing the efficacy and safety of fixed-dose ASAQ and AL for repeated treatment of uncomplicated malaria in children under 5 years at Nagongera Health Centre, Uganda. Participants were randomized to ASAQ or AL and all subsequent malaria episodes were treated with the same regimen. 413 children were enrolled and experienced a total of 6027 malaria episodes (mean 15; range, 1-26. For the first malaria episode, the PCR-corrected-cure rate for ASAQ (97.5% was non-inferior to that for AL (97.0%; 95% CI [-0.028; 0.037]. PCR-corrected cure rates for subsequent malaria episodes that had over 100 cases (episodes 2-18, ranged from 88.1% to 98.9% per episode, with no clear difference between the treatment arms. Parasites were completely cleared by day 3 for all malaria episodes and gametocyte carriage was less than 1% by day 21. Fever clearance was faster in the ASAQ group for the first episode. Treatment compliance for subsequent episodes (only first dose administration observed was close to 100%. Adverse events though common were similar between treatment arms and mostly related to the disease. Serious adverse events were uncommon, comparable between treatment arms and resolved spontaneously. Anemia and neutropenia occurred in <0.5% of cases per episode, abnormal liver function tests occurred in 0.3% to 1.4% of cases. Both regimens were safe and effective for repeated treatment of malaria.Current Controlled Trials NCT00699920.

  4. Deployment Repeatability

    Science.gov (United States)

    2016-04-01

    controlled to great precision, but in a Cubesat , there may be no attitude determination at all. Such a Cubesat might treat sun angle and tumbling rates as...could be sensitive to small differences in motor controller timing. In these cases, the analyst might choose to model the entire deployment path, with...knowledge of the material damage model or motor controller timing precision. On the other hand, if many repeated and environmentally representative

  5. Biological wastewater treatment by a bioreactor with repeated coupling of aerobes and anaerobes aiming at on-site reduction of excess sludge.

    Science.gov (United States)

    Yu, Anfeng; Feng, Quan; Liu, Zehua; Zhou, Yunan; Xing, Xin-Hui

    2006-01-01

    Activated sludge has been widely used in wastewater treatment throughout the world. However, the biggest disadvantage of this method is the by-production of excess sludge in a large amount, resulting in difficulties in operation and high costs for wastewater treatment. Technological innovations for wastewater treatment capable of reducing excess sludge have thus become research topics of interest in recent years. In our present research, we developed a new biological wastewater treatment process by repeated coupling of aerobes and anaerobes (rCAA) to reduce the excess sludge during the treatment of wastewater. During 460-day continuous running, COD (300-700 mg/L) and TOC (100-350 mg/L) were effectively removed, of which the removal rate was above 80 and 90%, respectively. SS in the effluent was 13 mg/L on average in the rCAA bioreactor without a settling tank. The on-site reduction of the excess sludge in the rCAA might be contributed by several mechanisms. The degradation of the grown aerobes after moving into the anaerobic regions was considered to be one of the most important factors. Besides, the repeatedly coupling of aerobes and anaerobes could also result in a complex microbial community with more metazoans and decoupling of the microbial anabolism and catabolism.

  6. Repeated maternal dexamethasone treatments in late gestation increases 11beta-hydroxysteroid dehydrogenase type 1 expression in the hippocampus of the newborn rat.

    Science.gov (United States)

    Wan, Shunlun; Hao, Rusong; Sun, Kang

    This study was designed to investigate the effect of repeated maternal injections of dexamethasone in late gestation on the expression of newborn hippocampal 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1), the enzyme amplifying glucocorticoids' action by converting biologically inactive 11-ketone metabolites into active glucocorticoids. Daily dexamethasone treatments (0.10 mg/kg body weight) in the last week of gestation were carried out in the pregnant rat. The expression of 11beta-HSD1 in the newborn hippocampal tissue was analyzed with Western blot and real-time polymerase chain reaction (PCR). The effect of corticosterone on the expression of 11beta-HSD1 was studied in cultured hippocampal neurons derived from newborn offspring received prenatal dexamethasone treatments. Both body and brain weights of the offspring were reduced significantly by repeated dexamethasone treatments in the last week of gestation. Western blot and real-time PCR analysis showed that both 11beta-HSD1 protein and mRNA expressions were increased significantly in the hippocampus of the newborn offspring on the first and seventh days after birth. Corticosterone could induce 11beta-HSD1 expression in cultured hippocampal neurons prepared from newborns received prenatal dexamethasone treatments, which was blocked by glucocorticoid receptor antagonist RU38486. The above findings suggest that repeated prenatal dexamethasone treatments at the end of gestation increase 11beta-HSD1 expression in the hippocampal tissue of the offspring, which may trigger a positive feedback pathway for the generation of biologically active glucocorticoids in the hippocampal tissue of the newborns.

  7. Inhibition of the tyrosine phosphatase STEP61 restores BDNF expression and reverses motor and cognitive deficits in phencyclidine-treated mice

    OpenAIRE

    Xu, Jian; Kurup, Pradeep; Baguley, Tyler D.; Foscue, Ethan; Ellman, Jonathan A.; Nairn, Angus C.; Lombroso, Paul J.

    2015-01-01

    Brain-derived neurotrophic factor (BDNF) and STriatal-Enriched protein tyrosine Phosphatase 61 (STEP61) have opposing functions in the brain, with BDNF supporting and STEP61 opposing synaptic strengthening. BDNF and STEP61 also exhibit an inverse pattern of expression in a number of brain disorders, including schizophrenia (SZ). NMDAR antagonists such as phencyclidine (PCP) elicit SZ-like symptoms in rodent models and unaffected individuals, and exacerbate psychotic episodes in SZ. Here we ch...

  8. Soil microarthropods are only weakly impacted after 13 years of repeated drought treatment in wet and dry heathland soils

    DEFF Research Database (Denmark)

    Holmstrup, Martin; Sørensen, Jesper G.; Schmidt, Inger Kappel

    2013-01-01

    Studies of biological responses in the terrestrial environment to rapid changes in climate have mostly been concerned with aboveground biota, whereas less is known of belowground organisms. The present study focuses on mites and springtails of heathland ecosystems and how the microarthropod...... and frequency of drought had only weak persistent effects on springtail species composition, but practically no effect on major mite groups (Oribatida, Prostigmata or Mesostigmata) suggesting that ecosystem functions of microarthropods may only be transiently impacted by repeated spring or summer drought....

  9. The involvement of noradrenergic transmission in the morphine-induced locomotor hyperactivity in mice withdrawn from repeated morphine treatment

    OpenAIRE

    Airio, Juha; Ahtee, Liisa

    1999-01-01

    Our previous studies suggest that in addition to the cerebral dopaminergic systems the noradrenergic ones have a crucial role in the morphine-induced behavioural sensitization in mice. Therefore the effects of α2-adrenoceptor antagonist, idazoxan (1 and 3 mg kg−1, i.p.) on morphine-induced locomotor hyperactivity as well as on morphine-induced changes in cerebral noradrenaline (NA) and striatal dopamine (DA) metabolism were studied in mice withdrawn for 3 days from 5 day repeated morphine tre...

  10. Effects of 7-day repeated treatment with the 5-HT2A inverse agonist/antagonist pimavanserin on methamphetamine vs. food choice in male rhesus monkeys.

    Science.gov (United States)

    Banks, Matthew L

    2016-08-01

    Preclinical drug vs. food choice is an emerging group of drug self-administration procedures that have shown predictive validity to clinical drug addiction. Emerging data suggest that serotonin (5-HT)2A receptors modulate mesolimbic dopamine function, such that 5-HT2A antagonists blunt the abuse-related neurochemical effects of monoamine transporter substrates, such as amphetamine or methamphetamine. Whether subchronic 5-HT2A antagonist treatment attenuates methamphetamine reinforcement in any preclinical drug self-administration procedure is unknown. The study aim was therefore to determine 7-day treatment effects with the 5-HT2A inverse agonist/antagonist pimavanserin on methamphetamine vs. food choice in monkeys. Behavior was maintained under a concurrent schedule of food delivery (1g pellets, fixed-ratio 100 schedule) and intravenous methamphetamine injections (0-0.32 mg/kg/injection, fixed-ratio 10 schedule) in male rhesus monkeys (n=3). Methamphetamine choice dose-effect functions were determined daily before and during 7-day repeated pimavanserin (1.0-10mg/kg/day, intramuscular) treatment periods. Under control conditions, increasing methamphetamine doses resulted in a corresponding increase in methamphetamine vs. food choice. Repeated pimavanserin administration failed to attenuate methamphetamine choice and produce a reciprocal increase in food choice in any monkey up to doses (3.2-10mg/kg) that suppressed rates of operant responding primarily during components where behavior was maintained by food pellets. Repeated 5-HT2A receptor inverse agonist/antagonist treatment did not attenuate methamphetamine reinforcement under a concurrent schedule of intravenous methamphetamine and food presentation in nonhuman primates. Overall, these results do not support the therapeutic potential of 5-HT2A inverse agonists/antagonists as candidate medications for methamphetamine addiction. Copyright © 2016 The Author(s). Published by Elsevier Ireland Ltd.. All rights

  11. Repeated 100 Hz TENS for the Treatment of Chronic Inflammatory Hyperalgesia and Suppression of Spinal Release of Substance P in Monoarthritic Rats

    Directory of Open Access Journals (Sweden)

    Hong-Xiang Liu

    2007-01-01

    Full Text Available Transcutaneous electrical nerve stimulation (TENS has been shown to be an effective measure for pain relief. The aim of the present study was to determine the optimal intensity and interval of repeated 100 Hz TENS for the treatment of chronic inflammatory hyperalgesia in a monoarthritic pain model of the rat, and to assess the changes of the spinal substance P (SP release in response to TENS treatment. A reliable, reproducible chronic monoarthritic pain model was produced by intra-articular injection of complete Freund's adjuvant (CFA at single ankle joint. The efficacy of 100 Hz TENS treatments with different frequencies and intensities was compared. In the acute period (within 3 weeks of monoarthritis, twice-a-week schedule of TENS reduced the swelling of the inflamed ankle significantly. In the stable period (4–9 weeks, however, once-a-week schedule produced a significantly better therapeutic effect on both inflammation and arthritic hyperalgesia than that of twice- or five-times-a-week schedule. Using three levels of intensity of TENS, we found that the weaker (1-1-2 mA stimulation produced significantly better therapeutic effects. Repeated TENS produced a reduction of SP content in spinal perfusate in parallel with the progressive reduction of the arthritic pain scores. Our results suggest that (i consecutive TENS treatments produced cumulative effect for chronic hyperalgesia, (ii for chronic inflammatory hyperalgesia, a weaker intensity and more sparsely arranged treatment schedule may produce better therapeutic effect and (iii a decrease in SP release may serve as one of the possible neurochemical mechanisms underlying the therapeutic effects of multiple TENS treatments on chronic inflammatory hyperalgesia.

  12. Effects of repeated high-dose methamphetamine and ceftriaxone post-treatments on tissue content of dopamine and serotonin as well as glutamate and glutamine.

    Science.gov (United States)

    Althobaiti, Yusuf S; Almalki, Atiah H; Das, Sujan C; Alshehri, Fahad S; Sari, Youssef

    2016-11-10

    Repeated exposure to high doses of methamphetamine (METH) is known to alter several neurotransmitters in certain brain regions. Little is known about the effects of ceftriaxone (CEF), a β-lactam antibiotic, known to upregulate glutamate transporter subtype 1, post-treatment on METH-induced depletion of dopamine and serotonin (5-HT) tissue content in brain reward regions. Moreover, the effects of METH and CEF post-treatment on glutamate and glutamine tissue content are not well understood. In this study, Wistar rats were used to investigate the effects of METH and CEF post-treatment on tissue content of dopamine/5-HT and glutamate/glutamine in the nucleus accumbens (NAc) and prefrontal cortex (PFC). Rats received either saline or METH (10mg/kg, i.p. every 2h×4) followed by either saline or CEF (200mg/kg, i.p, every day×3) post-treatment. METH induced a significant depletion of dopamine and 5-HT in the NAc and PFC. Importantly, dopamine tissue content was completely restored in the NAc following CEF post-treatment. Additionally, METH caused a significant decrease in glutamate and glutamine tissue content in PFC, and this effect was attenuated by CEF post-treatment. These findings demonstrate for the first time the attenuating effects of CEF post-treatment on METH induced alterations in the tissue contents of dopamine, glutamate, and glutamine. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  13. Blonanserin reverses the phencyclidine (PCP)-induced impairment in novel object recognition (NOR) in rats: role of indirect 5-HT(1A) partial agonism.

    Science.gov (United States)

    Horiguchi, M; Meltzer, H Y

    2013-06-15

    Blonanserin is an atypical antipsychotic drug (APD) which, compared to other atypical APDs, is a relatively selective serotonin (5-HT)2A and dopamine D2 antagonist. Comparing blonanserin with more broadly acting atypical APDs could be useful to test the contributions of actions at other monoamine receptors, e.g. 5-HT1A receptors, to the reversal of PCP-induced novel object recognition (NOR) deficit. In this study, we tested the effect of blonanserin alone, and in combination with 5-HT1A agents, on NOR deficit induced by subchronic treatment with the N-methyl-D-aspartate (NMDA) receptor antagonist, phencyclidine (PCP; 2 mg/kg), b.i.d., for 7 days. Blonanserin, 1mg/kg, but not 0.3mg/kg, improved the PCP-induced NOR deficit. However, at 1mg/kg, object exploration was diminished. Co-administration of sub-effective doses of blonanserin (0.3 mg/kg) and the 5-HT1A partial agonist, tandospirone (0.2 mg/kg), significantly reversed the NOR deficit without diminishing activity during the acquisition or retention periods. The combination of WAY100635 (0.6 mg/kg), a 5-HT1A antagonist, and blonanserin (1 mg/kg), also diminished object exploration which prevented assessment of the effect of this combination on NOR. WAY100635 (0.6 mg/kg) blocked the ameliorating effect of risperidone (0.1 mg/kg), another atypical APD with low affinity for 5-HT1A receptors, but did not impair exploration. These results suggest that blonansein and risperidone, atypical APDs which lack a direct action on 5-HT1A receptors require 5-HT1A receptor stimulation to reverse the subchronic PCP-induced NOR deficit and provide a support for clinical trial of blonanserin in combination with tandospirone to ameliorate cognitive impairment in schizophrenia and to have fewer side effects. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. Prevalence of apical periodontitis relative to endodontic treatment in an adult Dutch population: a repeated cross-sectional study

    NARCIS (Netherlands)

    Peters, L.B.; Lindeboom, J.A.; Elst, M.E.; Wesselink, P.R.

    2011-01-01

    We aimed to compare an Amsterdam subpopulation's current prevalence of root canal fillings and associated periapical radiolucencies with a similar patient sample from 1988. An Amsterdam subpopulation was evaluated for missing teeth, restorations, quality of endodontic treatment, and periapical

  15. Are repeated assisted reproductive technology treatments and an unsuccessful outcome risk factors for unipolar depression in infertile women?

    DEFF Research Database (Denmark)

    Sejbaek, Camilla S; Pinborg, Anja; Hageman, Ida

    2015-01-01

    INTRODUCTION: Previous studies have shown conflicting results whether unsuccessful medically assisted reproduction is a risk factor for depression among women. This study therefore investigated if women with no live birth after assisted reproductive technology (ART) treatment had a higher risk...... of unipolar depression compared with women with a live birth after ART treatment. MATERIAL AND METHODS: The Danish National ART-Couple (DANAC) Cohort is a national register-based cohort study that consists of women who received ART treatment from 1 January 1994 to 30 September 2009, in Denmark (n = 41 050......). Information on unipolar depression was obtained from the Danish Psychiatric Central Research Register. The analyses were conducted in Cox regression analysis. RESULTS: During the 308 494 person-years of follow up, 552 women were diagnosed with unipolar depression. A Cox proportional hazards model showed...

  16. Alterations in brain-derived neurotrophic factor in the mouse hippocampus following acute but not repeated benzodiazepine treatment.

    Directory of Open Access Journals (Sweden)

    Stephanie C Licata

    Full Text Available Benzodiazepines (BZs are safe drugs for treating anxiety, sleep, and seizure disorders, but their use also results in unwanted effects including memory impairment, abuse, and dependence. The present study aimed to reveal the molecular mechanisms that may contribute to the effects of BZs in the hippocampus (HIP, an area involved in drug-related plasticity, by investigating the regulation of immediate early genes following BZ administration. Previous studies have demonstrated that both brain derived neurotrophic factor (BDNF and c-Fos contribute to memory- and abuse-related processes that occur within the HIP, and their expression is altered in response to BZ exposure. In the current study, mice received acute or repeated administration of BZs and HIP tissue was analyzed for alterations in BDNF and c-Fos expression. Although no significant changes in BDNF or c-Fos were observed in response to twice-daily intraperitoneal (i.p. injections of diazepam (10 mg/kg + 5 mg/kg or zolpidem (ZP; 2.5 mg/kg + 2.5 mg/kg, acute i.p. administration of both triazolam (0.03 mg/kg and ZP (1.0 mg/kg decreased BDNF protein levels within the HIP relative to vehicle, without any effect on c-Fos. ZP specifically reduced exon IV-containing BDNF transcripts with a concomitant increase in the association of methyl-CpG binding protein 2 (MeCP2 with BDNF promoter IV, suggesting that MeCP2 activity at this promoter may represent a ZP-specific mechanism for reducing BDNF expression. ZP also increased the association of phosphorylated cAMP response element binding protein (pCREB with BDNF promoter I. Future work should examine the interaction between ZP and DNA as the cause for altered gene expression in the HIP, given that BZs can enter the nucleus and intercalate into DNA directly.

  17. Rapid and Longer-Term Antidepressant Effects of Repeated Ketamine Infusions in Treatment-Resistant Major Depression

    NARCIS (Netherlands)

    Murrough, James W.; Perez, Andrew M.; Pillemer, Sarah; Stern, Jessica; Parides, Michael K.; aan het Rot, Marije; Collins, Katherine A.; Mathew, Sanjay J.; Charney, Dennis S.; Iosifescu, Dan V.

    2013-01-01

    Background: Ketamine is reported to have rapid antidepressant effects; however, there is limited understanding of the time-course of ketamine effects beyond a single infusion. A previous report including 10 participants with treatment-resistant major depression (TRD) found that six ketamine

  18. Rapid and Longer-Term Antidepressant Effects of Repeated Ketamine Infusions in Treatment-Resistant Major Depression

    NARCIS (Netherlands)

    Murrough, James W.; Perez, Andrew M.; Pillemer, Sarah; Stern, Jessica; Parides, Michael K.; aan het Rot, Marije; Collins, Katherine A.; Mathew, Sanjay J.; Charney, Dennis S.; Iosifescu, Dan V.

    2013-01-01

    Background: Ketamine is reported to have rapid antidepressant effects; however, there is limited understanding of the time-course of ketamine effects beyond a single infusion. A previous report including 10 participants with treatment-resistant major depression (TRD) found that six ketamine infusion

  19. Phencyclidine (PCP)-induced disruption in cognitive performance is gender-specific and associated with a reduction in brain-derived neurotrophic factor (BDNF) in specific regions of the female rat brain.

    Science.gov (United States)

    Snigdha, Shikha; Neill, Joanna C; McLean, Samantha L; Shemar, Gaurav K; Cruise, Leonie; Shahid, Mohammed; Henry, Brian

    2011-03-01

    Phencyclidine (PCP), used to mimic certain aspects of schizophrenia, induces sexually dimorphic, cognitive deficits in rats. In this study, the effects of sub-chronic PCP on expression of brain-derived neurotrophic factor (BDNF), a neurotrophic factor implicated in the pathogenesis of schizophrenia, have been evaluated in male and female rats. Male and female hooded-Lister rats received vehicle or PCP (n=8 per group; 2 mg/kg i.p. twice daily for 7 days) and were tested in the attentional set shifting task prior to being sacrificed (6 weeks post-treatment). Levels of BDNF mRNA were measured in specific brain regions using in situ hybridisation. Male rats were less sensitive to PCP-induced deficits in the extra-dimensional shift stage of the attentional set shifting task compared to female rats. Quantitative analysis of brain regions demonstrated reduced BDNF levels in the medial prefrontal cortex (pPCP-treated rats compared with controls. In contrast, BDNF was significantly reduced only in the orbital cortex and central amygdaloid region of male rats (pPCP administration has a long-lasting down-regulatory effect on BDNF mRNA expression in the female rat brain which may underlie some of the behavioural deficits observed post PCP administration.

  20. Nutrient and toxic element soil concentrations during repeated mineral and compost fertilization treatments in a Mediterranean agricultural soil.

    Science.gov (United States)

    Baldantoni, Daniela; Morra, Luigi; Saviello, Giovanni; Alfani, Anna

    2016-12-01

    Agricultural soils of semi-arid Mediterranean areas are often subjected to depletion of their chemical, physical, and biological properties. In this context, organic fertilization, in addition to providing nutrients for a longer time in respect to mineral fertilization, improves many other characteristics related to soil fertility. Moreover, the combined use of organic and mineral fertilizers may promote a more sustainable crop production. However, a concern on the long-term use of organic fertilizers arises in relation to the possible accumulation of toxic elements in soil and their transfer to human beings. For this reason, a long-term study on nutrient and toxic element total concentrations and availabilities during fertilization treatments was carried out. In particular, mineral NPK fertilized soils, soils amended with biowaste compost, soils amended with biowaste compost plus mineral nitrogen, and unfertilized soils were analyzed for 11 chemical elements. The results highlighted that temporal variations in total and bioavailable concentrations of both nutrients and toxic elements, occurring also in unfertilized soils, are wider than those related to fertilization treatments. Anyway, soil amendments with biowaste compost, alone or in combination with mineral fertilizers, reduce Cu bioavailability but improve K, Fe, Mn, and Zn availabilities, excluding at the same time a long-term accumulation in soil. Total and bioavailable toxic element concentrations (apart from available Cd) do not vary in relation to fertilization treatments.

  1. Variation in target and rectum dose due to prostate deformation: an assessment by repeated MR imaging and treatment planning

    Energy Technology Data Exchange (ETDEWEB)

    Kerkhof, E M; Put, R W van der; Raaymakers, B W; Heide, U A van der; Vulpen, M van; Lagendijk, J J W [Department of Radiotherapy, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht (Netherlands)], E-mail: E.Kerkhof@umcutrecht.nl

    2008-10-21

    In daily clinical practice, implanted fiducial markers are used to correct for prostate motion, but not for prostate deformation. The aim of this study is to investigate the variation in target and rectum dose due to the deformation of the prostate gland (without seminal vesicles). Therefore, we performed five to six MRI scans of eight healthy volunteers that exhibited large variation in rectal volume and thus prostate deformation. Prostate motion was corrected by a mask-based rigid registration which uses the delineation as well as the internal structures of the prostate gland. Per MRI scan, one IMRT plan with a PTV margin of 4 mm was created, resulting in 41 IMRT plans. The dose distribution of the IMRT plan based on the MRI scan with the minimum rectal volume was applied to the other rigidly registered MRI scans to evaluate the impact of prostate deformation. In conclusion, pre-treatment planning on the minimum rectal volume can cause a fraction dose increase (up to 15%) to the rectum due to prostate deformation. The impact on the total dose increase to the rectum depends on the intrapatient rectum variation during treatment, but is negligible with the currently used PTV margins in a fractionated treatment.

  2. Variation in target and rectum dose due to prostate deformation: an assessment by repeated MR imaging and treatment planning

    Science.gov (United States)

    Kerkhof, E. M.; van der Put, R. W.; Raaymakers, B. W.; van der Heide, U. A.; van Vulpen, M.; Lagendijk, J. J. W.

    2008-10-01

    In daily clinical practice, implanted fiducial markers are used to correct for prostate motion, but not for prostate deformation. The aim of this study is to investigate the variation in target and rectum dose due to the deformation of the prostate gland (without seminal vesicles). Therefore, we performed five to six MRI scans of eight healthy volunteers that exhibited large variation in rectal volume and thus prostate deformation. Prostate motion was corrected by a mask-based rigid registration which uses the delineation as well as the internal structures of the prostate gland. Per MRI scan, one IMRT plan with a PTV margin of 4 mm was created, resulting in 41 IMRT plans. The dose distribution of the IMRT plan based on the MRI scan with the minimum rectal volume was applied to the other rigidly registered MRI scans to evaluate the impact of prostate deformation. In conclusion, pre-treatment planning on the minimum rectal volume can cause a fraction dose increase (up to 15%) to the rectum due to prostate deformation. The impact on the total dose increase to the rectum depends on the intrapatient rectum variation during treatment, but is negligible with the currently used PTV margins in a fractionated treatment.

  3. Variation in target and rectum dose due to prostate deformation: an assessment by repeated MR imaging and treatment planning.

    Science.gov (United States)

    Kerkhof, E M; van der Put, R W; Raaymakers, B W; van der Heide, U A; van Vulpen, M; Lagendijk, J J W

    2008-10-21

    In daily clinical practice, implanted fiducial markers are used to correct for prostate motion, but not for prostate deformation. The aim of this study is to investigate the variation in target and rectum dose due to the deformation of the prostate gland (without seminal vesicles). Therefore, we performed five to six MRI scans of eight healthy volunteers that exhibited large variation in rectal volume and thus prostate deformation. Prostate motion was corrected by a mask-based rigid registration which uses the delineation as well as the internal structures of the prostate gland. Per MRI scan, one IMRT plan with a PTV margin of 4 mm was created, resulting in 41 IMRT plans. The dose distribution of the IMRT plan based on the MRI scan with the minimum rectal volume was applied to the other rigidly registered MRI scans to evaluate the impact of prostate deformation. In conclusion, pre-treatment planning on the minimum rectal volume can cause a fraction dose increase (up to 15%) to the rectum due to prostate deformation. The impact on the total dose increase to the rectum depends on the intrapatient rectum variation during treatment, but is negligible with the currently used PTV margins in a fractionated treatment.

  4. Prognostic value of repeated {sup 123}I-metaiodobenzylguanidine imaging in patients with dilated cardiomyopathy with congestive heart failure before and after optimized treatments. Comparison with neurohumoral factors

    Energy Technology Data Exchange (ETDEWEB)

    Matsui, Toshiki; Tsutamoto, Takayoshi; Maeda, Keiko; Kusukawa, Junya; Kinoshita, Masahiko [Shiga Univ. of Medical Science, Otsu (Japan)

    2002-06-01

    The present study was undertaken to assess whether repeated measurement of cardiac {sup 123}I-metaiodobenzylguanidine (MIBG) imaging parameters before and after optimized treatments is useful for predicting the prognosis of patients with congestive heart failure (CHF) resulting from dilated cardiomyopathy (DCM). The subjects were 85 consecutive patients with DCM who had a left ventricular ejection fraction (LVEF) of less than 45%. The MIBG and the concentrations of neurohumoral factors were measured at baseline and after 6 months of optimized treatments. Cox proportional hazards analysis was performed to assess the various parameters before and after treatment. Twenty-three patients had a cardiac event (12 died; 11 hospitalized) during a mean follow-up period of 2 years. Although there was no difference between the baseline heart to mediastinum (H/M) ratio measured by MIBG between survivors and nonsurvivors, the H/M ratio was significantly decreased in nonsurvivors after 6 months. Multivariate analysis revealed that a high plasma concentration of brain natriuretic peptide level after 6 months (p=0.0049) and absolute changes in the H/M ratio (p=0.0046) were independent predictors of mortality. Comparison of the H/M ratio on MIBG imaging before and after optimized additional treatment provided useful information for predicting mortality and was independent of clinical and neurohumoral factors previously shown to be associated with poor prognosis in patients with DCM. (author)

  5. 胚胎反复植入失败的母体因素及应对策略%Mothers’ Factors and Treatment of Repeated Implantation Failure

    Institute of Scientific and Technical Information of China (English)

    张伟伟; 张云山

    2014-01-01

    胚胎反复植入失败(repeated implantation failure, RIF)是在经过多次IVF-ET后,移植的胚胎没有着床。胚胎植入失败与母体或胚胎因素有关,其中母体因素包括宫腔病理学、血栓形成倾向和免疫因素等。近年来许多方法用于改善和治疗引起RIF的母体因素,如宫腔内灌注β-hCG、阴道用西地那非和静脉输注英脱利匹特注射液等。临床医生应积极探寻导致RIF的病因,并采取积极有效的措施改善RIF患者的妊娠结局。%[ABSTRACT]Repeated implantation failure (RIF) is determined when transferred embryos fail to implant after several IVF treatment attempts. Implantation failure is related to either maternal factors or embryonic causes. Maternal factors include uterine anatomic abnormalities, thrombophilia and immunological factors. In recent years, many methods are used to improve and treat the maternal factors, such as intrauterine administration of hCG, vaginal sildenafil and administer intralipid solution. Clinicans should explore the reasons for RIF and take effective measures to improve the outcome of these patients.

  6. Repeated treatments with ingenol mebutate for prophylaxis of UV-induced squamous cell carcinoma in hairless mice

    DEFF Research Database (Denmark)

    Erlendsson, Andrés M; Thaysen-Petersen, Daniel; Bay, Christiane

    2016-01-01

    of a corticosteroid would reduce IngMeb-induced local skin responses (LSRs) without affecting tumor postponement. METHODS: Hairless mice (n=150; 6 groups á 25 mice) were irradiated with solar simulated ultraviolet radiation (UVR) until SCC developed. During UV-irradiation and before tumor development, five single......, 1-, 2-, 3-, 4-, 5-, 6-, and 7days after each IngMeb treatment. RESULTS: IngMeb significantly delayed tumor development compared to UVR alone (UVR day 168 vs. UVR+IngMeb day 189; p=0.025). LSR included erythema, flaking, crusting, bleeding, vesiculation, and ulceration. The composite LSR-scores were...... of moderate intensity in non-UV irradiated skin (max LSR IngMeb Tx 1-5: 1.5-2.5) and more pronounced in photodamaged skin (max LSR Tx 5; IngMeb 1.5 vs. UVR+IngMeb 1.8; p

  7. Diverse action of repeated corticosterone treatment on synaptic transmission, neuronal plasticity, and morphology in superficial and deep layers of the rat motor cortex.

    Science.gov (United States)

    Kula, Joanna; Gugula, Anna; Blasiak, Anna; Bobula, Bartosz; Danielewicz, Joanna; Kania, Alan; Tylko, Grzegorz; Hess, Grzegorz

    2017-07-27

    One of the adverse effects of prolonged stress in rats is impaired performance of skilled reaching and walking tasks. The mechanisms that lead to these abnormalities are incompletely understood. Therefore, we compared the effects of twice daily repeated corticosterone injections for 7 days on miniature excitatory postsynaptic currents (mEPSCs), as well as on synaptic plasticity and morphology of layers II/III and V pyramidal neurons of the primary motor cortex (M1) of male Wistar rats. Corticosterone treatment resulted in increased frequency, but not amplitude, of mEPSCs in layer II/III neurons accompanied by increased complexity of the apical part of their dendritic tree, with no changes in the density of dendritic spines. The frequency and amplitude of mEPSCs as well as the parameters characterizing the complexity of the dendritic tree were not changed in layer V cells; however, their dendritic spine density was increased. While corticosterone treatment resulted in an increase in the amplitude of field potentials evoked in intralaminar connections within layer II/III, it did not influence field responses in layer V intralaminar connections, as well as the extent of chemically induced layer V long-term potentiation (chemLTP) by the application of tetraethylammonium (TEA, 25 mM). However, chemLTP induction in layer II/III was impaired in slices prepared from corticosterone-treated animals. These data indicate that repeated 7-day administration of exogenous corticosterone induces structural and functional plasticity in the M1, which occurs mainly in layer II/III pyramidal neurons. These findings shed light on potential sites of action and mechanisms underlying stress-induced impairment of motor functions.

  8. Validation of analysis of amphetamines, opiates, phencyclidine, cocaine, and benzoylecgonine in oral fluids by liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Kala, Subbarao V; Harris, Steve E; Freijo, Tom D; Gerlich, Stan

    2008-10-01

    The aim of the present study was to develop and validate a method for the detection and quantitation of drugs of abuse in oral fluids. Fortified oral fluid samples (made in-house) and samples from donors collected with Quantasil oral fluid collection kits from Immunalysis were screened on an Olympus 5400 using reagents purchased from Immunalysis. Amphetamines (AMPs), opiates, phencyclidine (PCP), and cocaine and its metabolite benzoylecgonine (BE) in oral fluids were quantitated by an Applied Biosystems 3200 QTRAP liquid chromatograph-tandem mass spectrometer (LC-MS-MS). AMPs, opiates, PCP, cocaine, and BE were extracted from samples using liquid-liquid or solid-phase extractions and the extracts were separated on a Shimadzu high-performance liquid chromatograph prior to the MS-MS analysis. For each drug, two multiple reaction mode transitions were monitored using positive electrospray ionization coupled to an MS-MS detector. Corresponding d3, d5, d6, and d11 internal standards were used to quantitate the results. The limit of detection/quantitation for AMPs, opiates, PCP, cocaine, and its metabolite BE were 10, 10, 2, 2, and 2 ng/mL of oral fluid, respectively, on a signal-to-noise ratio > 4. This corresponded to 25, 25, 5, 5, and 5 pg on column. The method was verified by participating in the North America Oral Fluid Proficiency Testing administered by Research Triangle Institute and by analyzing real samples from donors. In conclusion, LC-MS-MS provided a simple way to analyze and quantitate drugs of abuse in oral fluids.

  9. Phencyclidine affects firing activity of ventral tegmental area neurons that are related to reward and social behaviors in rats.

    Science.gov (United States)

    Katayama, T; Okamoto, M; Suzuki, Y; Hoshino, K-Y; Jodo, E

    2013-06-14

    Patients with schizophrenia exhibit deficits in motivation and affect, which suggests an impairment in the reward system. The psychotomimetic drug, phencyclidine (PCP), also induces schizophrenia-like negative symptoms, such as reduced motivation, blunted affect, and social withdrawal in both humans and animals. Previous studies have indicated that the dopaminergic neurons in the ventral tegmental area (VTA) play a pivotal role in the development of reward-associated learning and motivation. However, how PCP affects the activity of VTA neurons during performance of a reward-related task and social interaction with others in unanesthetized animals remains unclear. Here, we recorded the unit activity of VTA neurons in freely moving rats before and after systemic administration of PCP in a classical conditioning paradigm, and during social interaction with an unfamiliar partner. In the classical conditioning task, two different tones were sequentially presented, one of which accompanied electrical stimulation of the medial forebrain bundle as an unconditioned stimulus. After identifying the response properties of recorded neurons in the classical conditioning task and social interaction, animals received an intraperitoneal injection of PCP. Our study demonstrated that most VTA neurons responsive to reward-associated stimuli were also activated during social interaction. Such activation of neurons was considerably suppressed by systemic administration of PCP, thus, PCP may affect the firing activity of VTA neurons that are involved in motivation, learning, and social interaction. Disruption of the response of VTA neurons to reward stimuli and socially interactive situations may be involved in PCP-induced impairments similar to the negative symptoms of schizophrenia.

  10. The results of surgical treatment of 14 patients underwent repeated tricuspid valve operations%三尖瓣再次手术14例

    Institute of Scientific and Technical Information of China (English)

    周明阳; 张健群; 孟旭; 李温斌; 孔晴宇

    2008-01-01

    目的 总结三尖瓣再次手术的治疗效果及经验.方法 2002年至2006年,收治14例三尖瓣再次手术病人,其中三尖瓣成形术后再次出现关闭不全12例,三尖瓣置换术后人工瓣膜功能障碍2例.结果 再次实施三尖瓣成形术5例,三尖瓣置换术9例.死亡2例,余者治愈出院.10例随访2~40个月,1例心功能Ⅲ级,余者均为Ⅰ~Ⅱ级.结论 再次三尖瓣手术治疗效果确切,手术死亡与手术方式的选择以及围术期心、肾功能衰竭有关.%Objective To evaluate the results and surgical treatment of the repeated tricuspid valve operations. Methods The hospital records was reviewed for 14 patients who underwent repeated tricuspid valve operations between 2003 and 2006, including 12 patients with tricuspid regurgitation received first tricuspid valve repair and 2 patients, with prosthetic valve dysfunction. Results Reoperations of tricuspid valve included 5 tricuspid valve repair and 9 tricuspid valve replacement. There were two postoperative deaths. Post-operative heart function (NYHA) was improved significantly, 1 case in Ⅲ and 9 in Ⅰ-Ⅱ. Ten survivors were followed up for 2 - 40 months. Conclusion Tricuspid valve reoperations may be performed with acceptable operative mortality. Perioperative death was associated with surgical methods and heart or renal function failure.

  11. The ketamine analogue methoxetamine and 3- and 4-methoxy analogues of phencyclidine are high affinity and selective ligands for the glutamate NMDA receptor.

    Directory of Open Access Journals (Sweden)

    Bryan L Roth

    Full Text Available In this paper we determined the pharmacological profiles of novel ketamine and phencyclidine analogues currently used as 'designer drugs' and compared them to the parent substances via the resources of the National Institute of Mental Health Psychoactive Drug Screening Program. The ketamine analogues methoxetamine ((RS-2-(ethylamino-2-(3-methoxyphenylcyclohexanone and 3-MeO-PCE (N-ethyl-1-(3-methoxyphenylcyclohexanamine and the 3- and 4-methoxy analogues of phencyclidine, (1-[1-(3-methoxyphenylcyclohexyl]piperidine and 1-[1-(4-methoxyphenylcyclohexyl]piperidine, were all high affinity ligands for the PCP-site on the glutamate NMDA receptor. In addition methoxetamine and PCP and its analogues displayed appreciable affinities for the serotonin transporter, whilst the PCP analogues exhibited high affinities for sigma receptors. Antagonism of the NMDA receptor is thought to be the key pharmacological feature underlying the actions of dissociative anaesthetics. The novel ketamine and PCP analogues had significant affinities for the NMDA receptor in radioligand binding assays, which may explain their psychotomimetic effects in human users. Additional actions on other targets could be important for delineating side-effects.

  12. Repeat-until-success quantum repeaters

    Science.gov (United States)

    Bruschi, David Edward; Barlow, Thomas M.; Razavi, Mohsen; Beige, Almut

    2014-09-01

    We propose a repeat-until-success protocol to improve the performance of probabilistic quantum repeaters. Conventionally, these rely on passive static linear-optics elements and photodetectors to perform Bell-state measurements (BSMs) with a maximum success rate of 50%. This is a strong impediment for entanglement swapping between distant quantum memories. Every time a BSM fails, entanglement needs to be redistributed between the corresponding memories in the repeater link. The key ingredients of our scheme are repeatable BSMs. Under ideal conditions, these turn probabilistic quantum repeaters into deterministic ones. Under realistic conditions, our protocol too might fail. However, using additional threshold detectors now allows us to improve the entanglement generation rate by almost orders of magnitude, at a nominal distance of 1000 km, compared to schemes that rely on conventional BSMs. This improvement is sufficient to make the performance of our scheme comparable to the expected performance of some deterministic quantum repeaters.

  13. Anxiolytic effects of repeated treatment with an essential oil from Lippia alba and (R-(--carvone in the elevated T-maze

    Directory of Open Access Journals (Sweden)

    V.Y. Hatano

    2012-03-01

    Full Text Available Lippia alba (Mill. N.E. Brown (Verbenaceae is widely used in different regions of Central and South America as a tranquilizer. The plant’s anxiolytic properties, however, merit investigation. The present study evaluated the effects of repeated daily (14 days intraperitoneal (ip treatment with an essential oil (EO from a chemotype of L. alba (LA, chemotype II, 12.5 and 25 mg/kg; N = 6-8 and (R-(--carvone (25 mg/kg; N = 8-12, the main constituent of this chemotype, on male Wistar rats (weighing 250 g at the beginning of the experiments submitted to the elevated T-maze (ETM. The ETM allows the measurement of two defensive responses: inhibitory avoidance and one-way escape. In terms of psychopathology, these responses have been related to generalized anxiety and panic disorder, respectively. Treatment with the EO impaired ETM avoidance latencies, without altering escape, in a way similar to the reference drug diazepam (P < 0.05 (avoidance 2: control = 84.6 ± 35.2; EO 12.5 mg/kg = 11.8 ± 3.8; EO 25 mg/kg = 14.6 ± 2.7; diazepam = 7 ± 2.1. (R-(--carvone also significantly altered this same response (P < 0.05; avoidance 1: control = 91.9 ± 31.5; carvone = 11.6 ± 1.8; diazepam = 8.1 ± 3.3. These results were not due to motor changes since no significant effects were detected in an open field. These observations suggest that LA exerts anxiolytic-like effects on a specific subset of defensive behaviors that have been implicated in generalized anxiety disorder, and suggest that carvone is one of the constituents of LA responsible for its action as a tranquilizer.

  14. Anxiolytic effects of repeated treatment with an essential oil from Lippia alba and (R)-(-)-carvone in the elevated T-maze

    Energy Technology Data Exchange (ETDEWEB)

    Hatano, V.Y.; Torricelli, A.S. [Departamento de Biociências, Universidade Federal de São Paulo, Santos, SP (Brazil); Giassi, A.C.C. [Cellular and Molecular Medicine, University of Ottawa, Ottawa (Canada); Coslope, L.A. [Parque Nacional da Chapada Diamantina, Chapada Diamantina, BA (Brazil); Viana, M.B. [Departamento de Biociências, Universidade Federal de São Paulo, Santos, SP (Brazil)

    2012-02-27

    Lippia alba (Mill.) N.E. Brown (Verbenaceae) is widely used in different regions of Central and South America as a tranquilizer. The plant's anxiolytic properties, however, merit investigation. The present study evaluated the effects of repeated daily (14 days) intraperitoneal (ip) treatment with an essential oil (EO) from a chemotype of L. alba (LA, chemotype II, 12.5 and 25 mg/kg; N = 6-8) and (R)-(-)-carvone (25 mg/kg; N = 8-12), the main constituent of this chemotype, on male Wistar rats (weighing 250 g at the beginning of the experiments) submitted to the elevated T-maze (ETM). The ETM allows the measurement of two defensive responses: inhibitory avoidance and one-way escape. In terms of psychopathology, these responses have been related to generalized anxiety and panic disorder, respectively. Treatment with the EO impaired ETM avoidance latencies, without altering escape, in a way similar to the reference drug diazepam (P < 0.05) (avoidance 2: control = 84.6 ± 35.2; EO 12.5 mg/kg = 11.8 ± 3.8; EO 25 mg/kg = 14.6 ± 2.7; diazepam = 7 ± 2.1). (R)-(-)-carvone also significantly altered this same response (P < 0.05; avoidance 1: control = 91.9 ± 31.5; carvone = 11.6 ± 1.8; diazepam = 8.1 ± 3.3). These results were not due to motor changes since no significant effects were detected in an open field. These observations suggest that LA exerts anxiolytic-like effects on a specific subset of defensive behaviors that have been implicated in generalized anxiety disorder, and suggest that carvone is one of the constituents of LA responsible for its action as a tranquilizer.

  15. Anxiolytic effects of repeated treatment with an essential oil from Lippia alba and (R)-(-)-carvone in the elevated T-maze.

    Science.gov (United States)

    Hatano, V Y; Torricelli, A S; Giassi, A C C; Coslope, L A; Viana, M B

    2012-03-01

    Lippia alba (Mill.) N.E. Brown (Verbenaceae) is widely used in different regions of Central and South America as a tranquilizer. The plant's anxiolytic properties, however, merit investigation. The present study evaluated the effects of repeated daily (14 days) intraperitoneal (ip) treatment with an essential oil (EO) from a chemotype of L. alba (LA, chemotype II, 12.5 and 25 mg/kg; N = 6-8) and (R)-(-)-carvone (25 mg/kg; N = 8-12), the main constituent of this chemotype, on male Wistar rats (weighing 250 g at the beginning of the experiments) submitted to the elevated T-maze (ETM). The ETM allows the measurement of two defensive responses: inhibitory avoidance and one-way escape. In terms of psychopathology, these responses have been related to generalized anxiety and panic disorder, respectively. Treatment with the EO impaired ETM avoidance latencies, without altering escape, in a way similar to the reference drug diazepam (P < 0.05) (avoidance 2: control = 84.6 ± 35.2; EO 12.5 mg/kg = 11.8 ± 3.8; EO 25 mg/kg = 14.6 ± 2.7; diazepam = 7 ± 2.1). (R)-(-)-carvone also significantly altered this same response (P < 0.05; avoidance 1: control = 91.9 ± 31.5; carvone = 11.6 ± 1.8; diazepam = 8.1 ± 3.3). These results were not due to motor changes since no significant effects were detected in an open field. These observations suggest that LA exerts anxiolytic-like effects on a specific subset of defensive behaviors that have been implicated in generalized anxiety disorder, and suggest that carvone is one of the constituents of LA responsible for its action as a tranquilizer.

  16. Sensitivity and Specificity of Multiple Kato-Katz Thick Smears and a Circulating Cathodic Antigen Test for Schistosoma mansoni Diagnosis Pre- and Post-repeated-Praziquantel Treatment

    Science.gov (United States)

    Lamberton, Poppy H. L.; Kabatereine, Narcis B.; Oguttu, David W.; Fenwick, Alan; Webster, Joanne P.

    2014-01-01

    Background Two Kato-Katz thick smears (Kato-Katzs) from a single stool are currently recommended for diagnosing Schistosoma mansoni infections to map areas for intervention. This ‘gold standard’ has low sensitivity at low infection intensities. The urine point-of-care circulating cathodic antigen test (POC-CCA) is potentially more sensitive but how accurately they detect S. mansoni after repeated praziquantel treatments, their suitability for measuring drug efficacy and their correlation with egg counts remain to be fully understood. We compared the accuracies of one to six Kato-Katzs and one POC-CCA for the diagnosis of S. mansoni in primary-school children who have received zero to ten praziquantel treatments. We determined the impact each diagnostic approach may have on monitoring and evaluation (M&E) and drug-efficacy findings. Method/Principle Findings In a high S. mansoni endemic area of Uganda, three days of consecutive stool samples were collected from primary school-aged children (six - 12 years) at five time-points in year one: baseline, one-week-post-, four-weeks-post-, six-months-post-, and six-months-one-week-post-praziquantel and three time-points in years two and three: pre-, one-week-post- and four-weeks-post-praziquantel-treatment/retreatment (n = 1065). Two Kato-Katzs were performed on each stool. In parallel, one urine sample was collected and a single POC-CCA evaluated per child at each time-point in year one (n = 367). At baseline, diagnosis by two Kato-Katzs (sensitivity = 98.6%) or one POC-CCA (sensitivity = 91.7%, specificity = 75.0%) accurately predicted S. mansoni infections. However, one year later, a minimum of three Kato-Katzs, and two years later, five Kato-Katzs were required for accurate diagnosis (sensitivity >90%) and drug-efficacy evaluation. The POC-CCA was as sensitive as six Kato-Katzs four-weeks-post and six-months-post-treatment, if trace readings were classified as positive. Conclusions

  17. Sensitivity and specificity of multiple Kato-Katz thick smears and a circulating cathodic antigen test for Schistosoma mansoni diagnosis pre- and post-repeated-praziquantel treatment.

    Directory of Open Access Journals (Sweden)

    Poppy H L Lamberton

    2014-09-01

    Full Text Available Two Kato-Katz thick smears (Kato-Katzs from a single stool are currently recommended for diagnosing Schistosoma mansoni infections to map areas for intervention. This 'gold standard' has low sensitivity at low infection intensities. The urine point-of-care circulating cathodic antigen test (POC-CCA is potentially more sensitive but how accurately they detect S. mansoni after repeated praziquantel treatments, their suitability for measuring drug efficacy and their correlation with egg counts remain to be fully understood. We compared the accuracies of one to six Kato-Katzs and one POC-CCA for the diagnosis of S. mansoni in primary-school children who have received zero to ten praziquantel treatments. We determined the impact each diagnostic approach may have on monitoring and evaluation (M&E and drug-efficacy findings.In a high S. mansoni endemic area of Uganda, three days of consecutive stool samples were collected from primary school-aged children (six - 12 years at five time-points in year one: baseline, one-week-post-, four-weeks-post-, six-months-post-, and six-months-one-week-post-praziquantel and three time-points in years two and three: pre-, one-week-post- and four-weeks-post-praziquantel-treatment/retreatment (n = 1065. Two Kato-Katzs were performed on each stool. In parallel, one urine sample was collected and a single POC-CCA evaluated per child at each time-point in year one (n = 367. At baseline, diagnosis by two Kato-Katzs (sensitivity = 98.6% or one POC-CCA (sensitivity = 91.7%, specificity = 75.0% accurately predicted S. mansoni infections. However, one year later, a minimum of three Kato-Katzs, and two years later, five Kato-Katzs were required for accurate diagnosis (sensitivity >90% and drug-efficacy evaluation. The POC-CCA was as sensitive as six Kato-Katzs four-weeks-post and six-months-post-treatment, if trace readings were classified as positive.Six Kato-Katzs (two/stool from three stools and/or one POC-CCA are required

  18. Repeated morphine treatment alters polysialylated neural cell adhesion molecule, glutamate decarboxylase-67 expression and cell proliferation in the adult rat hippocampus.

    Science.gov (United States)

    Kahn, Laëtitia; Alonso, Gérard; Normand, Elisabeth; Manzoni, Olivier J

    2005-01-01

    Altered synaptic transmission and plasticity in brain areas involved in reward and learning are thought to underlie the long-lasting effects of addictive drugs. In support of this idea, opiates reduce neurogenesis [A.J. Eisch et al. (2000) Proceedings of the National Academy of Sciences USA, 97, 7579-7584] and enhance long-term potentiation in adult rodent hippocampus [J.M. Harrison et al. (2002) Journal of Neurophysiology, 87, 2464-2470], a key structure of learning and memory processes. Here we studied how repeated morphine treatment and withdrawal affect cell proliferation and neuronal phenotypes in the dentate gyrus-CA3 region of the adult rat hippocampus. Our data showed a strong reduction of cellular proliferation in morphine-dependent animals (54% of control) that was followed by a rebound increase after 1 week withdrawal and a return to normal after 2 weeks withdrawal. Morphine dependence was also associated with a drastic reduction in the expression levels of the polysialylated form of neural cell adhesion molecule (68% of control), an adhesion molecule expressed by newly generated neurons and involved in cell migration and structural plasticity. Polysialylated neural cell adhesion molecule levels quickly returned to normal following withdrawal. In morphine-dependent rats, we found a significant increase of glutamate decarboxylase-67 mRNA transcription (170% of control) in dentate gyrus granular cells which was followed by a marked rebound decrease after 1 week withdrawal and a return to normal after 4 weeks withdrawal. Together, the results show, for the first time, that, in addition to reducing cell proliferation and neurogenesis, chronic exposure to morphine dramatically alters neuronal phenotypes in the dentate gyrus-CA3 region of the adult rat hippocampus.

  19. Repeated PTZ treatment at 25-day intervals leads to a highly efficient accumulation of doublecortin in the dorsal hippocampus of rats.

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    Ana-Maria Buga

    Full Text Available BACKGROUND: Neurogenesis persists throughout life in the adult mammalian brain. Because neurogenesis can only be assessed in postmortem tissue, its functional significance remains undetermined, and identifying an in vivo correlate of neurogenesis has become an important goal. By studying pentylenetetrazole-induced brain stimulation in a rat model of kindling we accidentally discovered that 25±1 days periodic stimulation of Sprague-Dawley rats led to a highly efficient increase in seizure susceptibility. METHODOLOGY/PRINCIPAL FINDINGS: By EEG, RT-PCR, western blotting and immunohistochemistry, we show that repeated convulsive seizures with a periodicity of 25±1 days led to an enrichment of newly generated neurons, that were BrdU-positive in the dentate gyrus at day 25±1 post-seizure. At the same time, there was a massive increase in the number of neurons expressing the migratory marker, doublecortin, at the boundary between the granule cell layer and the polymorphic layer in the dorsal hippocampus. Some of these migrating neurons were also positive for NeuN, a marker for adult neurons. CONCLUSION/SIGNIFICANCE: Our results suggest that the increased susceptibility to seizure at day 25±1 post-treatment is coincident with a critical time required for newborn neurons to differentiate and integrate into the existing hippocampal network, and outlines the importance of the dorsal hippocampus for seizure-related neurogenesis. This model can be used as an in vivo correlate of neurogenesis to study basic questions related to neurogenesis and to the neurogenic mechanisms that contribute to the development of epilepsy.

  20. Selective involvement of kappa opioid and phencyclidine receptors in the analgesic and motor effects of dynorphin-A-(1-13)-Tyr-Leu-Phe-Asn-Gly-Pro.

    Science.gov (United States)

    Shukla, V K; Bansinath, M; Dumont, M; Lemaire, S

    1992-09-18

    Dynorphin A-(1-13)-Tyr-Leu-Phe-Asn-Gly-Pro (Dyn Ia; 1-8 nmol) injected intracerebroventricularly in the mouse produces two independent behavioral effects: (1) a norbinaltorphimine (kappa opioid antagonist)-reversible analgesia in the acetic acid-induced writhing test and (2) motor dysfunction characterized by wild running, pop-corn jumping, hindlimb jerking and barrel rolling and antagonized by the irreversible phencyclidine (PCP) and sigma (sigma) receptor antagonist, metaphit and the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonists, dextromethorphan and ketamine. The specific involvement of the PCP receptor in the motor effects of Dyn Ia is supported by the direct competitive interaction of the peptide with the binding of [3H]MK-801 (Ki: 0.63 microM) and [3H]TCP (Ki: 4.6 microM) to mouse brain membrane preparations.

  1. Exploring metabolic pathway disruption in the subchronic phencyclidine model of schizophrenia with the Generalized Singular Value Decomposition

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    Morris Brian J

    2011-05-01

    Full Text Available Abstract Background The quantification of experimentally-induced alterations in biological pathways remains a major challenge in systems biology. One example of this is the quantitative characterization of alterations in defined, established metabolic pathways from complex metabolomic data. At present, the disruption of a given metabolic pathway is inferred from metabolomic data by observing an alteration in the level of one or more individual metabolites present within that pathway. Not only is this approach open to subjectivity, as metabolites participate in multiple pathways, but it also ignores useful information available through the pairwise correlations between metabolites. This extra information may be incorporated using a higher-level approach that looks for alterations between a pair of correlation networks. In this way experimentally-induced alterations in metabolic pathways can be quantitatively defined by characterizing group differences in metabolite clustering. Taking this approach increases the objectivity of interpreting alterations in metabolic pathways from metabolomic data. Results We present and justify a new technique for comparing pairs of networks--in our case these networks are based on the same set of nodes and there are two distinct types of weighted edges. The algorithm is based on the Generalized Singular Value Decomposition (GSVD, which may be regarded as an extension of Principle Components Analysis to the case of two data sets. We show how the GSVD can be interpreted as a technique for reordering the two networks in order to reveal clusters that are exclusive to only one. Here we apply this algorithm to a new set of metabolomic data from the prefrontal cortex (PFC of a translational model relevant to schizophrenia, rats treated subchronically with the N-methyl-D-Aspartic acid (NMDA receptor antagonist phencyclidine (PCP. This provides us with a means to quantify which predefined metabolic pathways (Kyoto

  2. Substance use -- phencyclidine (PCP)

    Science.gov (United States)

    ... peace pill, rocket fuel, super grass, wack. PCP's Effects on Your Brain PCP is a mind-altering drug. This means ... not seeing friends who are still using PCP. Exercise and eat healthy foods . Taking care of your body helps it heal from the harmful effects of PCP. You will feel better, too. Avoid ...

  3. Long-term changes in brain following continuous phencyclidine administration: An autoradiographic study using flunitrazepam, ketanserin, mazindol, quinuclidinyl benzilate, piperidyl-3,4-{sup 3}H(N)-TCP, and AMPA receptor ligands

    Energy Technology Data Exchange (ETDEWEB)

    Ellison, Gaylord; Keys, Alan; Noguchi, Kevin [Univ. of California Los Angeles, Dept. of Psychology, Los Angeles, CA (United States)

    1999-05-01

    Phencyclidine induces a model psychosis which can persist for prolonged periods and presents a strong drug model of schizophrenia. When given continuously for several days to rats, phencyclidine and other N-methyl-D-aspartate (NMDA) antagonists induce neural degeneration in a variety of limbic structures, including retrosplenial cortex, hippocampus, septohippocampal projections, and piriform cortex. In an attempt to further clarify the mechanisms underlying these degeneration patterns, autoradiographic studies using a variety of receptor ligands were conducted in animals 21 days after an identical dosage of the continuous phencyclidine administration employed in the previous degeneration studies. The results indicated enduring alterations in a number of receptors: these included decreased piperidyl-3,4-{sup 3}H(N)-TCP (TCP), flunitrazepam, and mazindol binding in many of the limbic regions in which degeneration has been reported previously. Quinuclidinyl benzilate and (AMPA) binding were decreased in anterior cingulate and piriform cortex, and in accumbens and striatum. Piperidyl-3,4-{sup 3}H(N)-TCP binding was decreased in most hippocampal regions. Many of these long-term alterations would not have been predicted by prior studies of the neurotoxic effects of continuous phencyclidine, and these results do not suggest a unitary source for the neurotoxicity. Whereas retrosplenial cortex, the structure which degenerates earliest, showed minimal alterations, some of the most consistent, long term alterations were in structures which evidence no immediate signs of neural degeneration, such as anterior cingulate cortex and caudate nucleus. In these structures, some of the receptor changes appeared to develop gradually (they were not present immediately after cessation of drug administration), and thus were perhaps due to changed input from regions evidencing neurotoxicity. Some of these findings, particularly in anterior cingulate, may have implications for models of

  4. O retratamento da tuberculose no município do Recife, 1997: uma abordagem epidemiológica Repeated treatment of tuberculosis in the city of Recife, 1997: an epidemiological approach

    Directory of Open Access Journals (Sweden)

    HERMIRA MARIA AMORIM CAMPOS

    2000-09-01

    Full Text Available Objetivo: Este estudo descreve as características e analisa o acompanhamento de casos de retratamento ocorridos em residentes no município do Recife, no ano de 1997, com o objetivo de avaliar a importância deste grupo de doentes para a vigilância da tuberculose nos sistemas locais de saúde. Casuística e métodos: Foi realizado um estudo transversal com uma amostra de 240 casos de retratamento que representaram 16,2% dos casos de tuberculose notificados à Secretaria Estadual de Saúde do Estado de Pernambuco, em 1997. Resultados: O abandono do tratamento anterior foi o principal motivo para o retratamento (55,8%, seguido por casos de recidiva da doença (39,2%. Os doentes eram predominantemente do sexo masculino, com idade entre 30 e 49 anos, com baixa ou nenhuma escolaridade, e apresentavam um predomínio da forma pulmonar. Chama a atenção que 42,7% dos casos de retratamento tinham história de dois ou mais tratamentos anteriores. Em relação ao desfecho do retratamento, 52,5% dos casos apresentaram resultado desfavorável. Entre estes, 44,2% dos indivíduos abandonaram o esquema terapêutico e 39,6% deles fizeram-no até o primeiro mês. Os casos que voltaram a tratar-se após recidiva apresentaram maior percentual de desfecho favorável de retratamento (64% quando comparados com os casos que voltaram a tratar-se após falência ou abandono do tratamento anterior e esta diferença foi estatisticamente significante (chi² = 19,55; p Objectives: This study describes the epidemiological profile of cases of repeated treatment of tuberculosis occurring among residents of the city of Recife in the year of 1997. Material and methods: A cross-sectional study was performed and 240 cases of repeated treatment were studied, representing 16.2% of all cases of tuberculosis. Results: Interruption of previous treatment was the principal reason for repeated treatments (55.8%, followed by cases of recurrence of the disease (39.2%. Patients undergoing

  5. Quantum repeated games revisited

    CERN Document Server

    Frackiewicz, Piotr

    2011-01-01

    We present a scheme for playing quantum repeated 2x2 games based on the Marinatto and Weber's approach to quantum games. As a potential application, we study twice repeated Prisoner's Dilemma game. We show that results not available in classical game can be obtained when the game is played in the quantum way. Before we present our idea, we comment on the previous scheme of playing quantum repeated games.

  6. Increasing Belief in the Effectiveness of HIV Treatment as Prevention : Results of Repeated, National Surveys of Australian Gay and Bisexual Men, 2013-15

    NARCIS (Netherlands)

    Holt, Martin; Lea, Toby; Schmidt, Heather-Marie; Murphy, Dean; Rosengarten, Marsha; Crawford, David; Ellard, Jeanne; Kolstee, Johann; de Wit, John

    2016-01-01

    We surveyed Australian gay and bisexual men, assessing belief in HIV treatment as prevention (TasP) and support for early treatment. We identified the characteristics of participants who believed in TasP and supported early treatment using multivariate logistic regression. In 2013, 1316 men particip

  7. Bioavailability of gallic acid and catechins from grape seed polyphenol extract is improved by repeated dosing in rats: implications for treatment in Alzheimer's disease.

    Science.gov (United States)

    Ferruzzi, Mario G; Lobo, Jessica K; Janle, Elsa M; Cooper, Bruce; Simon, James E; Wu, Qing-Li; Welch, Cara; Ho, Lap; Weaver, Connie; Pasinetti, Giulio M

    2009-01-01

    The present study explored the bioavailability and brain deposition of a grape seed polyphenolic extract (GSPE) previously found to attenuate cognitive deterioration in a mouse model of Alzheimer's disease (AD). Plasma pharmacokinetic response of major GSPE phenolic components was measured following intragastric gavage of 50, 100, and 150 mg GSPE per kg body weight. Liquid chromatography-mass spectrometry (LC-MS) analysis identified gallic acid (GA), catechin (C), and epicatechin (EC) in plasma of rats gavaged acutely with GSPE. Additionally, 4-methylgallic acid (4-OMeGA), 3'-methylcatechin (3'-OMeC), and 3'-methylepicatechin (3'-OMeEC) were identified as circulating metabolites of GSPE phenolic constituents. Cmax for individual GSPE constituents and their metabolites increased in a dose-dependent fashion (with increasing GSPE oral dose). Repeated daily exposure to GSPE was found to significantly increase bioavailability (defined as plasma AUC0-8h) of GA, C, and EC by 198, 253, and 282% relative to animals receiving only a single acute GSPE dose. EC and C were not detectable in brain tissues of rats receiving a single GSPE dose but reached levels of 290.7 +/-45.9 and 576.7 +/- 227.7 pg/g in brain tissues from rats administered GSPE for 10 days. This study suggests that brain deposition of GA, C, and EC is affected by repeated dosing of GSPE.

  8. Inhibition of the tyrosine phosphatase STEP61 restores BDNF expression and reverses motor and cognitive deficits in phencyclidine-treated mice.

    Science.gov (United States)

    Xu, Jian; Kurup, Pradeep; Baguley, Tyler D; Foscue, Ethan; Ellman, Jonathan A; Nairn, Angus C; Lombroso, Paul J

    2016-04-01

    Brain-derived neurotrophic factor (BDNF) and STriatal-Enriched protein tyrosine Phosphatase 61 (STEP61) have opposing functions in the brain, with BDNF supporting and STEP61 opposing synaptic strengthening. BDNF and STEP61 also exhibit an inverse pattern of expression in a number of brain disorders, including schizophrenia (SZ). NMDAR antagonists such as phencyclidine (PCP) elicit SZ-like symptoms in rodent models and unaffected individuals, and exacerbate psychotic episodes in SZ. Here we characterize the regulation of BDNF expression by STEP61, utilizing PCP-treated cortical culture and PCP-treated mice. PCP-treated cortical neurons showed both an increase in STEP61 levels and a decrease in BDNF expression. The reduction in BDNF expression was prevented by STEP61 knockdown or use of the STEP inhibitor, TC-2153. The PCP-induced increase in STEP61 expression was associated with the inhibition of CREB-dependent BDNF transcription. Similarly, both genetic and pharmacologic inhibition of STEP prevented the PCP-induced reduction in BDNF expression in vivo and normalized PCP-induced hyperlocomotion and cognitive deficits. These results suggest a mechanism by which STEP61 regulates BDNF expression, with implications for cognitive functioning in CNS disorders.

  9. Reconfigurable multiport EPON repeater

    Science.gov (United States)

    Oishi, Masayuki; Inohara, Ryo; Agata, Akira; Horiuchi, Yukio

    2009-11-01

    An extended reach EPON repeater is one of the solutions to effectively expand FTTH service areas. In this paper, we propose a reconfigurable multi-port EPON repeater for effective accommodation of multiple ODNs with a single OLT line card. The proposed repeater, which has multi-ports in both OLT and ODN sides, consists of TRs, BTRs with the CDR function and a reconfigurable electrical matrix switch, can accommodate multiple ODNs to a single OLT line card by controlling the connection of the matrix switch. Although conventional EPON repeaters require full OLT line cards to accommodate subscribers from the initial installation stage, the proposed repeater can dramatically reduce the number of required line cards especially when the number of subscribers is less than a half of the maximum registerable users per OLT. Numerical calculation results show that the extended reach EPON system with the proposed EPON repeater can save 17.5% of the initial installation cost compared with a conventional repeater, and can be less expensive than conventional systems up to the maximum subscribers especially when the percentage of ODNs in lightly-populated areas is higher.

  10. Revisiting the TALE repeat.

    Science.gov (United States)

    Deng, Dong; Yan, Chuangye; Wu, Jianping; Pan, Xiaojing; Yan, Nieng

    2014-04-01

    Transcription activator-like (TAL) effectors specifically bind to double stranded (ds) DNA through a central domain of tandem repeats. Each TAL effector (TALE) repeat comprises 33-35 amino acids and recognizes one specific DNA base through a highly variable residue at a fixed position in the repeat. Structural studies have revealed the molecular basis of DNA recognition by TALE repeats. Examination of the overall structure reveals that the basic building block of TALE protein, namely a helical hairpin, is one-helix shifted from the previously defined TALE motif. Here we wish to suggest a structure-based re-demarcation of the TALE repeat which starts with the residues that bind to the DNA backbone phosphate and concludes with the base-recognition hyper-variable residue. This new numbering system is consistent with the α-solenoid superfamily to which TALE belongs, and reflects the structural integrity of TAL effectors. In addition, it confers integral number of TALE repeats that matches the number of bound DNA bases. We then present fifteen crystal structures of engineered dHax3 variants in complex with target DNA molecules, which elucidate the structural basis for the recognition of bases adenine (A) and guanine (G) by reported or uncharacterized TALE codes. Finally, we analyzed the sequence-structure correlation of the amino acid residues within a TALE repeat. The structural analyses reported here may advance the mechanistic understanding of TALE proteins and facilitate the design of TALEN with improved affinity and specificity.

  11. Successful Treatment of Hemifacial Myokymia and Dystonia Associated to Linear Scleroderma “En Coup de Sabre” with Repeated Botox Injections

    Directory of Open Access Journals (Sweden)

    Carlos A. Cañas

    2012-01-01

    Full Text Available Linear scleroderma “en coup de sabre” (LSCS is a form of localized scleroderma presents as band-like sclerotic lesions of the frontoparietal area. It has been reported in association with diverse neurological manifestations like seizures, migraine, neuromyotonia, dystonia and abnormalities in MRI and CT studies as cerebral atrophy, white matter lesions, intraparenchymal calcification, meningeocortical alterations, and skull atrophy. We describe a patient with LSCS associated with two abnormal movements: permanent myokimia of right masseter muscle and recurrent spasmodic retraction of right cigomatic and depressor labii inferioris muscles. He was initially treated with methotrexate and steroids without response, so later on he underwent repeated Botox injections with remarkable improvement.

  12. Recursive quantum repeater networks

    CERN Document Server

    Van Meter, Rodney; Horsman, Clare

    2011-01-01

    Internet-scale quantum repeater networks will be heterogeneous in physical technology, repeater functionality, and management. The classical control necessary to use the network will therefore face similar issues as Internet data transmission. Many scalability and management problems that arose during the development of the Internet might have been solved in a more uniform fashion, improving flexibility and reducing redundant engineering effort. Quantum repeater network development is currently at the stage where we risk similar duplication when separate systems are combined. We propose a unifying framework that can be used with all existing repeater designs. We introduce the notion of a Quantum Recursive Network Architecture, developed from the emerging classical concept of 'recursive networks', extending recursive mechanisms from a focus on data forwarding to a more general distributed computing request framework. Recursion abstracts independent transit networks as single relay nodes, unifies software layer...

  13. Increasing Belief in the Effectiveness of HIV Treatment as Prevention: Results of Repeated, National Surveys of Australian Gay and Bisexual Men, 2013-15.

    Science.gov (United States)

    Holt, Martin; Lea, Toby; Schmidt, Heather-Marie; Murphy, Dean; Rosengarten, Marsha; Crawford, David; Ellard, Jeanne; Kolstee, Johann; de Wit, John

    2016-07-01

    We surveyed Australian gay and bisexual men, assessing belief in HIV treatment as prevention (TasP) and support for early treatment. We identified the characteristics of participants who believed in TasP and supported early treatment using multivariate logistic regression. In 2013, 1316 men participated; 1251 participated in 2015. Belief in TasP increased from 2.6 % in 2013 to 13.1 % in 2015 (p HIV treatment was associated with being younger, living in New South Wales and being in paid employment. We recommend continued monitoring of the growing gap in belief about TasP between HIV-positive men and HIV-negative/untested men.

  14. Investigation of Repeat Client Drop-Out and Re-Enrolment Cycles in Fourteen Methadone Maintenance Treatment Clinics in Guangdong, China.

    Science.gov (United States)

    Zhang, Lei; Zou, Xia; Zhang, Di; Li, Xiaoling; Zhao, Peizhen; Ling, Li

    2015-01-01

    Client adherence is vital for effective methadone maintenance treatment (MMT). This study explores the pattern and associated factors of client adherence, drop-out and re-enrolment in the Chinese MMT programme over the period of 2006-2013. This retrospective study was conducted in 14 MMT clinics in Guangdong Province, China. We employed Kaplan-Meier survival analysis to estimate the rates of drop-out and re-enrolment of MMT clients and multivariate Cox regression to identify associated factors. Among 1,512 study participants, 79% have experienced 'drop-out' during the 7-year study period. However, 82% 'dropped-out' clients resumed treatment at a later time. Low education level (junior high or below versus otherwise, HR = 1.21, 1.05-1.40), low methadone dosage in the first treatment episode (drop-outs of the participants. Among the 'dropped-out' clients, being female (HR = 1.40, 1.23-1.60), being married (HR = 1.19, 1.09-1.30), and having a higher proportion of positive urine tests in the first treatment episode (≥50% versusdrop-out out of clients in MMT programmes is common. Insufficient dosage and higher proportion of positive urine samples in the first treatment episode are the key determinants for subsequent client drop-out and re-enrolment. Interventions should target clients in their early stage of treatment to improve retention in the long term.

  15. Optimal and safe treatment of spider leg veins measuring less than 1.5 mm on skin type IV patients, using repeated low-fluence Nd:YAG laser pulses after polidocanol injection.

    Science.gov (United States)

    Moreno-Moraga, Javier; Hernández, Esteban; Royo, Josefina; Alcolea, Justo; Isarría, M Jose; Pascu, Mihail Lucian; Smarandache, Adriana; Trelles, Mario

    2013-05-01

    Treatment of micro-veins of less than 1.5 mm with laser and with chemical sclerosis is technically challenging because of their difficulty to remedy. Laser treatment is even more difficult when dark phototypes are involved.Three groups of 30 patients each, skin type IV, and vessels measuring less than 1.5 mm in diameter, were enrolled for two treatment sessions 8 weeks apart: group A, polidocanol (POL) micro-foam injection; group B, Nd:YAG laser alone; and group C, laser after POL injection. Repeated 8-Hz low-fluence pulses, moving the hand piece over a 3-cm vein segment with an average of five laser passes maximum and with a total time irradiation of 1 s were used. Sixteen weeks after the second treatment, statistically, degree of clearance after examining photographs and patients satisfaction index, plotted on a visual analogue scale and comparing results of all three groups, results were significantly better for group C (p<0.0001). No significant differences in complications were noticed between the three groups. Efficacy of combining POL and laser proved safe and satisfactory in 96 % of patients using low-fluence laser pulses with a total cumulative energy in the 3 cm venous segment, lower than that of conventional treatment. Very few and transient complications were observed. POL foam injection followed by laser pulses is safe and efficient for vein treatment in dark-skinned patients.

  16. Phencyclidine analog use in Sweden--intoxication cases involving 3-MeO-PCP and 4-MeO-PCP from the STRIDA project.

    Science.gov (United States)

    Bäckberg, Matilda; Beck, Olof; Helander, Anders

    2015-11-01

    3-Methoxy-phencyclidine (3-MeO-PCP) and 4-methoxy-phencyclidine (4-MeO-PCP) are analogs of and drug substitutes for the dissociative substance PCP ("Angel dust"), a recreational drug that was most popular in the 1970s. In Sweden, use of methoxylated PCP analogs was noted starting in mid-2013, according to statistics from the Poisons Information Centre. The objective of this case series was to present clinical and bioanalytical data from analytically confirmed non-fatal intoxications associated with 3-MeO-PCP and/or 4-MeO-PCP within the STRIDA project. Observational case series of consecutive patients with self-reported or suspected exposure to new psychoactive substances (NPS) and who require hospital care. Blood and urine samples were collected from intoxicated patients presenting at emergency departments (ED) or intensive care units (ICU) all over Sweden. NPS analysis was performed by multicomponent liquid chromatographic-tandem mass spectrometric (LC-MS/MS) and LC-high-resolution MS (LC-HRMS) methods. Data on clinical features were collected during Poisons Information Centre consultations and retrieved from medical records. The Poisons Information Centre registered its first call related to methoxylated PCP analogs in July 2013, while analytically confirmed cases first appeared in October 2013. From July 2013 to March 2015, 1243 cases of suspected NPS intoxication originating from ED or ICU were enrolled in the STRIDA project. During the 21-month period, 56 (4.5%) patients tested positive for 3-MeO-PCP and 11 (0.9%) for 4-MeO-PCP; 8 of these cases involved both substances. The 59 patients were aged 14-55 (median: 26) years and 51 (86%) were men. Co-exposure to other NPSs and/or classical drugs of abuse was common with only 7 cases (12%) indicated to be 3-MeO-PCP single-substance intoxications; prominent clinical signs seen in the latter cases were hypertension (systolic blood pressure ≥ 140 mmHg; 7 cases), tachycardia (≥ 100/min; 5 cases), and altered mental

  17. The child accident repeater: a review.

    Science.gov (United States)

    Jones, J G

    1980-04-01

    The child accident repeater is defined as one who has at least three accidents that come to medical attention within a year. The accident situation has features in common with those of the child who has a single accident through simple "bad luck", but other factors predispose him to repeated injury. In the child who has a susceptible personality, a tendency for accident repetition may be due to a breakdown in adjustment to a stressful environment. Prevention of repeat accidents should involve the usual measures considered appropriate for all children as well as an attempt to provide treatment of significant maladjustment and modification of a stressful environment.

  18. PCP-based mice models of schizophrenia: differential behavioral, neurochemical and cellular effects of acute and subchronic treatments.

    Science.gov (United States)

    Castañé, Anna; Santana, Noemí; Artigas, Francesc

    2015-11-01

    N-methyl-D-aspartate receptor (NMDA-R) hypofunction has been proposed to account for the pathophysiology of schizophrenia. Thus, NMDA-R blockade has been used to model schizophrenia in experimental animals. Acute and repeated treatments have been successfully tested; however, long-term exposure to NMDA-R antagonists more likely resembles the core symptoms of the illness. To explore whether schizophrenia-related behaviors are differentially induced by acute and subchronic phencyclidine (PCP) treatment in mice and to examine the neurobiological bases of these differences. Subchronic PCP induced a sensitization of acute locomotor effects. Spontaneous alternation in a T-maze and novel object recognition performance were impaired after subchronic but not acute PCP, suggesting a deficit in working memory. On the contrary, reversal learning and immobility in the tail suspension test were unaffected. Subchronic PCP significantly reduced basal dopamine but not serotonin output in medial prefrontal cortex (mPFC) and markedly decreased the expression of tyrosine hydroxylase in the ventral tegmental area. Finally, acute and subchronic PCP treatments evoked a different pattern of c-fos expression. At 1 h post-treatment, acute PCP increased c-fos expression in many cortical regions, striatum, thalamus, hippocampus, and dorsal raphe. However, the increased c-fos expression produced by subchronic PCP was restricted to the retrosplenial cortex, thalamus, hippocampus, and supramammillary nucleus. Four days after the last PCP injection, c-fos expression was still increased in the hippocampus of subchronic PCP-treated mice. Acute and subchronic PCP administration differently affects neuronal activity in brain regions relevant to schizophrenia, which could account for their different behavioral effects.

  19. The Pentapeptide Repeat Proteins

    Energy Technology Data Exchange (ETDEWEB)

    Vetting,M.; Hegde, S.; Fajardo, J.; Fiser, A.; Roderick, S.; Takiff, H.; Blanchard, J.

    2006-01-01

    The Pentapeptide Repeat Protein (PRP) family has over 500 members in the prokaryotic and eukaryotic kingdoms. These proteins are composed of, or contain domains composed of, tandemly repeated amino acid sequences with a consensus sequence of [S, T,A, V][D, N][L, F]-[S, T,R][G]. The biochemical function of the vast majority of PRP family members is unknown. The three-dimensional structure of the first member of the PRP family was determined for the fluoroquinolone resistance protein (MfpA) from Mycobacterium tuberculosis. The structure revealed that the pentapeptide repeats encode the folding of a novel right-handed quadrilateral {beta}-helix. MfpA binds to DNA gyrase and inhibits its activity. The rod-shaped, dimeric protein exhibits remarkable size, shape and electrostatic similarity to DNA.

  20. Differential effects of repeated low dose treatment with the cannabinoid agonist WIN 55,212-2 in experimental models of bone cancer pain and neuropathic pain

    DEFF Research Database (Denmark)

    Hald, Andreas; Ding, Ming; Egerod, Kristoffer Lihme;

    2008-01-01

    . Furthermore, this treatment strategy was not found to induce measurable CNS related side effects or tolerance. Cancer cell viability assays and bone volume fraction assessed by micro computed tomography (microCT) demonstrated that these effects were not due to changes in cancer progression. The difference...

  1. The impact of repeated treatment with praziquantel of schistosomiasis in children under six years of age living in an endemic area for Schistosoma haematobium infection

    Directory of Open Access Journals (Sweden)

    T Mduluza

    2001-09-01

    Full Text Available Praziquantel was given every eight weeks for two years to children aged under six years of age, living in a Schistosoma haematobium endemic area. Infection with S. haematobium and haematuria were examined in urine and antibody profiles (IgA, IgE, IgM, IgG1, IgG2, IgG3, and IgG4 against S. haematobium adult worm and egg antigens were determined from sera collected before each treatment. Chemotherapy reduced infection prevalence and mean intensity from 51.8% and 110 eggs per 10 ml urine, respectively, before starting re-treatment programme to very low levels thereafter. Praziquantel is not accumulated after periodic administration in children. Immunoglobulin levels change during the course of treatment with a shift towards 'protective' mechanisms. The significant changes noted in some individuals were the drop in 'blocking' IgG2 and IgG4 whereas the 'protecting' IgA and IgG1 levels increased. The antibody profiles in the rest of the children remained generally unchanged throughout the study and no haematuria was observed after the second treatment. The removal of worms before production of large number of eggs, prevented the children from developing morbidity.

  2. Effect of a Mind-Body Therapeutic Program for Infertile Women Repeating In Vitro Fertilization Treatment on Uncertainty, Anxiety, and Implantation Rate

    Directory of Open Access Journals (Sweden)

    Miok Kim, PhD

    2014-03-01

    Conclusion: This study is meaningful as the first intervention program for alleviating uncertainty and anxiety provided during the IVF treatment process. The positive effects of the mind-body therapeutic program in alleviating both uncertainty and anxiety have direct meaning for clinical applications.

  3. Impact of ivermectin on onchocerciasis transmission: Assessing the empirical evidence that repeated ivermectin mass treatments may lead to elimination/eradication in West-Africa

    NARCIS (Netherlands)

    G.J.J.M. Borsboom (Gerard); B.A. Boatin (Boakye); N.J.D. Nagelkerke (Nico); H. Agoua (Hyacinthe); K.L.B. Akpoboua (Komlan); E.W. Soumbey Alley (E. William); Y. Bissan (Yeriba); A. Renz (Anna); L. Yameogo (Laurent); J.H.F. Remme (Jan); J.D.F. Habbema (Dik)

    2003-01-01

    markdownabstract__Background:__ The Onchocerciasis Control Program (OCP) in West Africa has been closed down at the end of 2002. All subsequent control will be transferred to the participating countries and will almost entirely be based on periodic mass treatment with ivermectin. This makes the ques

  4. Authors' reply to comment on "Are repeated assisted reproductive technology treatments and an unsuccessful outcome risk factors for unipolar depression in infertile women?"

    DEFF Research Database (Denmark)

    Sejbaek, Camilla S.; Pinborg, Anja; Hageman, Ida

    2016-01-01

    The aim of our national register-based study (1) was to investigate the risk of a new episode of unipolar depression among women treated with assisted reproductive technology (ART) in regards to whether they had achieved a live birth (as a result of treatment or spontaneous conception) or not. He...

  5. Repeating the Past

    Science.gov (United States)

    Moore, John W.

    1998-05-01

    As part of the celebration of the Journal 's 75th year, we are scanning each Journal issue from 25, 50, and 74 years ago. Many of the ideas and practices described are so similar to present-day "innovations" that George Santayana's adage (1) "Those who cannot remember the past are condemned to repeat it" comes to mind. But perhaps "condemned" is too strong - sometimes it may be valuable to repeat something that was done long ago. One example comes from the earliest days of the Division of Chemical Education and of the Journal.

  6. Burnout as a risk factor for antidepressant treatment - a repeated measures time-to-event analysis of 2936 Danish human service workers

    DEFF Research Database (Denmark)

    Madsen, Ida E H; Lange, Theis; Borritz, Marianne

    2015-01-01

    Burnout is a state of emotional exhaustion, feelings of reduced personal accomplishment, and withdrawal from work thought to occur as a consequence of prolonged occupational stress. The condition is not included in the diagnostic classifications, but is considered likely to develop into depressive...... disorder in some cases. We examined the prospective association between burnout and antidepressant treatment, as an indicator of clinically significant mental disorder. We further investigated potential effect-modifiers of the association, to identify factors that may prevent this progression of burnout...... modeling, examining the risk of entering antidepressant treatment in relation to the level of work-related burnout measured by the Copenhagen Burnout inventory. As effect-modifiers we examined both sociodemographic factors and a range of psychosocial work environment factors. The level of burnout predicted...

  7. Post-traumatic Stress Disorder Symptoms in a Female Patient Following Repeated Teasing: Treatment with Gabapentin and Lamotrigine and the Possible Role of Sensitization

    OpenAIRE

    Kishimoto, Akira; Goto, Yurie; Hashimoto, Kenji

    2014-01-01

    Post-traumatic stress disorder (PTSD) is a pathological response to trauma characterized by frequent recollections, recurrent nightmares, and flashbacks of the traumatic event(s). To date, the precise mechanisms underlying the development of PTSD remain unknown. Several studies have suggested that antiepileptic drugs, such as gabapentin and lamotrigine, may be effective in the treatment of PTSD symptoms. We report on a 15-year-old Japanese female junior high school student who developed PTSD ...

  8. Prefrontal cortical and striatal transcriptional responses to the reinforcing effect of repeated methylphenidate treatment in the spontaneously hypertensive rat, animal model of attention-deficit/hyperactivity disorder (ADHD)

    OpenAIRE

    dela Peña, Ike; Kim, Hee Jin; Sohn, Aeree; Kim, Bung-Nyun; Han, Doug Hyun; Ryu, Jong Hoon; Shin, Chan Young; Noh, Minsoo; Cheong, Jae Hoon

    2014-01-01

    Background Methylphenidate is the most commonly used stimulant drug for the treatment of attention-deficit/hyperactivity disorder (ADHD). Research has found that methylphenidate is a “reinforcer” and that individuals with ADHD also abuse this medication. Nevertheless, the molecular consequences of long-term recreational methylphenidate use or abuse in individuals with ADHD are not yet fully known. Methods Spontaneously hypertensive rats (SHR), the most validated and widely used ADHD animal mo...

  9. Treatment with an anti-CD11d integrin antibody reduces neuroinflammation and improves outcome in a rat model of repeated concussion

    OpenAIRE

    2013-01-01

    Background Concussions account for the majority of traumatic brain injuries (TBI) and can result in cumulative damage, neurodegeneration, and chronic neurological abnormalities. The underlying mechanisms of these detrimental effects remain poorly understood and there are presently no specific treatments for concussions. Neuroinflammation is a major contributor to secondary damage following more severe TBI, and recent findings from our laboratory suggest it may be involved in the cumulative pr...

  10. All-optical repeater.

    Science.gov (United States)

    Silberberg, Y

    1986-06-01

    An all-optical device containing saturable gain, saturable loss, and unsaturable loss is shown to transform weak, distorted optical pulses into uniform standard-shape pulses. The proposed device performs thresholding, amplification, and pulse shaping as required from an optical repeater. It is shown that such a device could be realized by existing semiconductor technology.

  11. Bidirectional Manchester repeater

    Science.gov (United States)

    Ferguson, J.

    1980-01-01

    Bidirectional Manchester repeater is inserted at periodic intervals along single bidirectional twisted pair transmission line to detect, amplify, and transmit bidirectional Manchester 11 code signals. Requiring only 18 TTL 7400 series IC's, some line receivers and drivers, and handful of passive components, circuit is simple and relatively inexpensive to build.

  12. Repeat Gamma Knife Radiosurgery for Trigeminal Neuralgia

    Energy Technology Data Exchange (ETDEWEB)

    Aubuchon, Adam C., E-mail: acaubuchon@gmail.com [Department of Radiation Oncology, Wake Forest University School of Medicine, Winston-Salem, NC (United States); Chan, Michael D. [Department of Radiation Oncology, Wake Forest University School of Medicine, Winston-Salem, NC (United States); Lovato, James F. [Department of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC (United States); Balamucki, Christopher J. [Department of Radiation Oncology, University of Florida, Gainesville, FL (United States); Ellis, Thomas L.; Tatter, Stephen B. [Department of Neurosurgery, Wake Forest University School of Medicine, Winston-Salem, NC (United States); McMullen, Kevin P.; Munley, Michael T.; Deguzman, Allan F.; Ekstrand, Kenneth E.; Bourland, J. Daniel; Shaw, Edward G. [Department of Radiation Oncology, Wake Forest University School of Medicine, Winston-Salem, NC (United States)

    2011-11-15

    Purpose: Repeat gamma knife stereotactic radiosurgery (GKRS) for recurrent or persistent trigeminal neuralgia induces an additional response but at the expense of an increased incidence of facial numbness. The present series summarized the results of a repeat treatment series at Wake Forest University Baptist Medical Center, including a multivariate analysis of the data to identify the prognostic factors for treatment success and toxicity. Methods and Materials: Between January 1999 and December 2007, 37 patients underwent a second GKRS application because of treatment failure after a first GKRS treatment. The mean initial dose in the series was 87.3 Gy (range, 80-90). The mean retreatment dose was 84.4 Gy (range, 60-90). The dosimetric variables recorded included the dorsal root entry zone dose, pons surface dose, and dose to the distal nerve. Results: Of the 37 patients, 81% achieved a >50% pain relief response to repeat GKRS, and 57% experienced some form of trigeminal dysfunction after repeat GKRS. Two patients (5%) experienced clinically significant toxicity: one with bothersome numbness and one with corneal dryness requiring tarsorraphy. A dorsal root entry zone dose at repeat treatment of >26.6 Gy predicted for treatment success (61% vs. 32%, p = .0716). A cumulative dorsal root entry zone dose of >84.3 Gy (72% vs. 44%, p = .091) and a cumulative pons surface dose of >108.5 Gy (78% vs. 44%, p = .018) predicted for post-GKRS numbness. The presence of any post-GKRS numbness predicted for a >50% decrease in pain intensity (100% vs. 60%, p = .0015). Conclusion: Repeat GKRS is a viable treatment option for recurrent trigeminal neuralgia, although the patient assumes a greater risk of nerve dysfunction to achieve maximal pain relief.

  13. Repeated low-dose 17β-estradiol treatment prevents activation of apoptotic signaling both in the synaptosomal and cellular fraction in rat prefrontal cortex following cerebral ischemia.

    Science.gov (United States)

    Stanojlović, Miloš; Zlatković, Jelena; Guševac, Ivana; Grković, Ivana; Mitrović, Nataša; Zarić, Marina; Horvat, Anica; Drakulić, Dunja

    2015-01-01

    Disturbance in blood circulation is associated with numerous pathological conditions characterized by cognitive decline and neurodegeneration. Activation of pro-apoptotic signaling previously detected in the synaptosomal fraction may underlie neurodegeneration in the prefrontal cortex of rats submitted to permanent bilateral common carotid arteries occlusion (two-vessel occlusion, 2VO). 17β-Estradiol (E) exerts potent neuroprotective effects in the brain affecting, among other, ischemia-induced pathological changes. As most significant changes in rats submitted to 2VO were observed on 7th day following the insult, of interest was to examine whether 7 day treatment with low dose of E (33.3 µg/kg/day) prevents formerly reported neurodegeneration and may represent additional therapy during the early post-ischemic period. Role of E treatment on apoptotic pathway was monitored on Bcl-2 family members, cytochrome c, caspase 3 and PARP protein level in the synaptosomal (P2) fraction of the prefrontal cortex. Furthermore, changes of these proteins were examined in the cytosolic, mitochondrial and nuclear fraction, with the emphasis on potential involvement of extracellular signal-regulated kinases (ERK) and protein kinase B (Akt) activation and their role in nuclear translocation of transcriptional nuclear factor kappa B (NF-kB) associated with alteration of Bax and Bcl-2 gene expression. The extent of cellular damage was determined using DNA fragmentation and Fluoro-Jade B staining. The absence of activation of apoptotic cascade both in the P2 and cell accompanied with decreased DNA fragmentation and number of degenerating neurons clearly indicates that E treatment ensures the efficient protection against ischemic insult. Moreover, E-mediated modulation of pro-apoptotic signaling in the cortical cellular fractions involves cooperative activation of ERK and Akt, which may be implicated in the observed prevention of neurodegenerative changes.

  14. Object memory impairment at post-drug Day 15 but not at Day 1 after a regimen of repeated treatment with oral methylphenidate.

    Science.gov (United States)

    Taukulis, Harald K; Bigney, Erin E; Fry, Michael D; Hooper, Courtney

    2014-04-30

    Methylphenidate (MPH) is a dopamine and norepinephrine reuptake inhibitor that is widely used for the treatment of attention-deficit/hyperactivity disorder in children and adults. Its similarity to other psychostimulants suggests that, at certain doses, the drug may generate lasting neuroadaptations that can be detrimental to the recipient. Some investigators have found that, in rats, the residual effects of the drug (i.e., following a 10-14 day washout period) can interfere with memory for objects when the retention interval is 3h or more. The present experiment replicated this result and demonstrated the critical importance of the washout period. Long-Evans male rats treated with MPH (5.0mg/kg po b.i.d.) on 21 days (during a post-natal period ranging from Day 29 to Day 57) and then twice-assessed for their performance in an object recognition task were able to recognize a familiar object on Day 1 after the last dose of the drug had been administered, behaving the same as the untreated control group. However, on Day 15 post-drug, the same MPH group failed to distinguish between a familiar and a novel object, exploring both nearly equally, while the control group continued to investigate the novel object to a greater extent than the familiar one. This suggests that, if a test for object recognition is conducted too early after the MPH treatment period ceases, a memory impairment may not be detected. In general, this finding has implications for studies of other behavioral or neurophysiological consequences of MPH that may appear following a drug-free withdrawal period.

  15. 多次利培酮治疗致抗精神病药恶性综合征%Neuroleptic malignant syndrome after repeated treatment with risperidone

    Institute of Scientific and Technical Information of China (English)

    丁跃庆; 李华; 谢振强; 张伟娟; 代俊; 孔君; 吴洪军

    2012-01-01

    1例31岁女性患者因精神分裂症给予利培酮1 mg,2次/d口服,1周后剂量增至2 mg,2次/d.此前患者曾3次间断应用利培酮治疗.本次治疗规律服药49 d,患者精神症状缓解.第50~52天未遵医嘱规律服药.第54天患者出现大汗淋漓,体温达38.5 ℃.第55天出现意识障碍、心动过速、双上肢肌强直、肌张力增高.心电图示窦性心动过速.实验室检查示:白细胞计数12.3×109/L,胆碱酯酶 13 268 U /L,肌酸激酶 1447 U/L,利培酮血液浓度70.5 μg/L.诊断为抗精神病药恶性综合征(NMS).立即停用利培酮,进行物理降温、补液、抗心律失常、抗感染、纠正酸碱平衡、护肝等治疗.6 d后患者体温恢复正常,NMS症状消失.换用奥氮平治疗后,未再出现类似症状.%A 31-year-old woman with schizophrenia received risperidone 1 mg twice daily. One week later, the dose was increased to 2 mg twice daily. The patient had previously received risperidone intermittent treatment for three times. After a 49-day regular treatment, the psychiatric symptoms relieved. On days 50 to 52, she did not adhere to the instructions of the physician for regular use of the drug. On day 54, the patient experienced profuse sweating with a temperature of 38. 5 ℃. On day 55, she developed disturbance of consciousness, tachycardia, muscle rigidity of the upper limbs, and hypermyotonia. Her electrocardiograph showed sinus tachycardia. Laboratory tests showed the following findings: white blood cell count 12. 3 × 109/L, cholinesterase 13 268 U/L, creatine kinase 1447 U/L. The blood concentrations of risperidone was 70. 5 μg/L. Neuroleptic malignant syndrome ( NMS ) was diagnosed. The medication was stopped immediately. Physical methods for lowering body temperature, fluid supplement, antiarrhythmics, anti-infective therapy, correction of the acid-base imbalance, and liver-protective treatment were given. Six days later, the temperature returned to normal, the NMS symptoms

  16. Duct Leakage Repeatability Testing

    Energy Technology Data Exchange (ETDEWEB)

    Walker, Iain [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Sherman, Max [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

    2014-01-01

    Duct leakage often needs to be measured to demonstrate compliance with requirements or to determine energy or Indoor Air Quality (IAQ) impacts. Testing is often done using standards such as ASTM E1554 (ASTM 2013) or California Title 24 (California Energy Commission 2013 & 2013b), but there are several choices of methods available within the accepted standards. Determining which method to use or not use requires an evaluation of those methods in the context of the particular needs. Three factors that are important considerations are the cost of the measurement, the accuracy of the measurement and the repeatability of the measurement. The purpose of this report is to evaluate the repeatability of the three most significant measurement techniques using data from the literature and recently obtained field data. We will also briefly discuss the first two factors. The main question to be answered by this study is to determine if differences in the repeatability of these tests methods is sufficient to indicate that any of these methods is so poor that it should be excluded from consideration as an allowed procedure in codes and standards.

  17. Safety of Repeated Yttrium-90 Radioembolization

    Energy Technology Data Exchange (ETDEWEB)

    Lam, Marnix G. E. H.; Louie, John D. [Stanford University School of Medicine, Division of Interventional Radiology (United States); Iagaru, Andrei H.; Goris, Michael L. [Stanford University School of Medicine, Division of Nuclear Medicine (United States); Sze, Daniel Y., E-mail: dansze@stanford.edu [Stanford University School of Medicine, Division of Interventional Radiology (United States)

    2013-10-15

    Purpose: Repeated radioembolization (RE) treatments carry theoretically higher risk of radiation-induced hepatic injury because of the liver's cumulative memory of previous exposure. We performed a retrospective safety analysis on patients who underwent repeated RE. Methods: From 2004 to 2011, a total of 247 patients were treated by RE. Eight patients (5 men, 3 women, age range 51-71 years) underwent repeated treatment of a targeted territory, all with resin microspheres (SIR-Spheres; Sirtex, Lane Cove, Australia). Adverse events were graded during a standardized follow-up. In addition, the correlation between the occurrence of RE-induced liver disease (REILD) and multiple variables was investigated in univariate and multivariate analyses in all 247 patients who received RE. Results: Two patients died shortly after the second treatment (at 84 and 107 days) with signs and symptoms of REILD. Both patients underwent whole liver treatment twice (cumulative doses 3.08 and 2.66 GBq). The other 6 patients demonstrated only minor toxicities after receiving cumulative doses ranging from 2.41 to 3.88 GBq. All patients experienced objective tumor responses. In the whole population, multifactorial analysis identified three risk factors associated with REILD: repeated RE (p = 0.036), baseline serum total bilirubin (p = 0.048), and baseline serum aspartate aminotransferase (p = 0.043). Repeated RE proved to be the only independent risk factor for REILD in multivariate analysis (odds ratio 9.6; p = 0.002). Additionally, the administered activity per target volume (in GBq/L) was found to be an independent risk factor for REILD, but only in whole liver treatments (p = 0.033). Conclusion: The risk of REILD appears to be elevated for repeated RE. Objective tumor responses were observed, but establishment of safety limits will require improvement in dosimetric measurement and prediction.

  18. Prefrontal cortical and striatal transcriptional responses to the reinforcing effect of repeated methylphenidate treatment in the spontaneously hypertensive rat, animal model of attention-deficit/hyperactivity disorder (ADHD).

    Science.gov (United States)

    dela Peña, Ike; Kim, Hee Jin; Sohn, Aeree; Kim, Bung-Nyun; Han, Doug Hyun; Ryu, Jong Hoon; Shin, Chan Young; Noh, Minsoo; Cheong, Jae Hoon

    2014-05-06

    Methylphenidate is the most commonly used stimulant drug for the treatment of attention-deficit/hyperactivity disorder (ADHD). Research has found that methylphenidate is a "reinforcer" and that individuals with ADHD also abuse this medication. Nevertheless, the molecular consequences of long-term recreational methylphenidate use or abuse in individuals with ADHD are not yet fully known. Spontaneously hypertensive rats (SHR), the most validated and widely used ADHD animal model, were pretreated with methylphenidate (5 mg/kg, i.p.) during their adolescence (post-natal day [PND] 42-48) and tested for subsequent methylphenidate-induced conditioned place preference (CPP) and self-administration. Thereafter, the differentially expressed genes in the prefrontal cortex (PFC) and striatum of representative methylphenidate-treated SHRs, which showed CPP to and self-administration of methylphenidate, were analyzed. Genome-wide transcriptome profiling analyses revealed 30 differentially expressed genes in the PFC, which include transcripts involved in apoptosis (e.g. S100a9, Angptl4, Nfkbia), transcription (Cebpb, Per3), and neuronal plasticity (Homer1, Jam2, Asap1). In contrast, 306 genes were differentially expressed in the striatum and among them, 252 were downregulated. The main functional categories overrepresented among the downregulated genes include those involved in cell adhesion (e.g. Pcdh10, Ctbbd1, Itgb6), positive regulation of apoptosis (Perp, Taf1, Api5), (Notch3, Nsbp1, Sik1), mitochondrion organization (Prps18c, Letm1, Uqcrc2), and ubiquitin-mediated proteolysis (Nedd4, Usp27x, Ube2d2). Together, these changes indicate methylphenidate-induced neurotoxicity, altered synaptic and neuronal plasticity, energy metabolism and ubiquitin-dependent protein degradation in the brains of methylphenidate-treated SHRs, which showed methylphenidate CPP and self-administration. In addition, these findings may also reflect cognitive impairment associated with chronic

  19. Repeatability of Cryogenic Multilayer Insulation

    Science.gov (United States)

    Johnson, W. L.; Vanderlaan, M.; Wood, J. J.; Rhys, N. O.; Guo, W.; Van Sciver, S.; Chato, D. J.

    2017-01-01

    Due to the variety of requirements across aerospace platforms, and one off projects, the repeatability of cryogenic multilayer insulation has never been fully established. The objective of this test program is to provide a more basic understanding of the thermal performance repeatability of MLI systems that are applicable to large scale tanks. There are several different types of repeatability that can be accounted for: these include repeatability between multiple identical blankets, repeatability of installation of the same blanket, and repeatability of a test apparatus. The focus of the work in this report is on the first two types of repeatability. Statistically, repeatability can mean many different things. In simplest form, it refers to the range of performance that a population exhibits and the average of the population. However, as more and more identical components are made (i.e. the population of concern grows), the simple range morphs into a standard deviation from an average performance. Initial repeatability testing on MLI blankets has been completed at Florida State University. Repeatability of five GRC provided coupons with 25 layers was shown to be +/- 8.4 whereas repeatability of repeatedly installing a single coupon was shown to be +/- 8.0. A second group of 10 coupons have been fabricated by Yetispace and tested by Florida State University, through the first 4 tests, the repeatability has been shown to be +/- 16. Based on detailed statistical analysis, the data has been shown to be statistically significant.

  20. Repeated treatment of recurrent uncomplicated Plasmodium falciparum malaria in Senegal with fixed-dose artesunate plus amodiaquine versus fixed-dose artemether plus lumefantrine: a randomized, open-label trial

    Directory of Open Access Journals (Sweden)

    Barry Aichatou

    2011-08-01

    Full Text Available Abstract Background The use of artemisinin-based combination therapy (ACT is currently recommended for treating uncomplicated malaria. The objective was to assess the efficacy and safety of repeated administrations of two fixed-dose presentations of ACT - artesunate plus amodiaquine (ASAQ and artemether-lumefantrine (AL - in subsequent episodes of Plasmodium falciparum malaria. Methods A randomized comparative study was conducted in a rural community of central Senegal from August 2007 to January 2009. Children and adults with uncomplicated P. falciparum malaria were randomized to receive open-label ASAQ once daily or AL twice daily for three days. Drug doses were given according to body weight. Treatments for first episodes were supervised. For subsequent episodes, only the first intake of study drug was supervised. ECGs and audiograms were performed in patients ≥12 years of age. Primary outcome was adequate clinical and parasitological response rate (ACPR after polymerase chain reaction (PCR correction on day 28 for the first episode. Results A total of 366 patients were enrolled in the two groups (ASAQ 184, AL 182 and followed up during two malaria transmission seasons. In the intent-to-treat population, PCR-corrected ACPRs at day 28 for the first episode were 98.4% and 96.2%, respectively, in the ASAQ and AL groups. For the per-protocol population (ASAQ 183, AL 182, PCR-corrected ACPRs at day 28 for the first episode were 98.9% and 96.7%, respectively. A 100% ACPR rate was obtained at day 28 in the 60 and four patients, respectively, who experienced second and third episodes. Treatment-related adverse events were reported in 11.7% of the patients, without significant differences between the two groups. A better improvement of haemoglobin at day 28 was noted in the ASAQ versus the AL group (12.2 versus 11.8 g/dL; p = 0.03. No sign of ototoxicity was demonstrated. A prolongation of the QTc interval was observed in both groups during

  1. Concomitant detection of IFNα signature and activated monocyte/dendritic cell precursors in the peripheral blood of IFNα-treated subjects at early times after repeated local cytokine treatments

    Directory of Open Access Journals (Sweden)

    Rizza Paola

    2011-05-01

    Full Text Available Abstract Background Interferons alpha (IFNα are the cytokines most widely used in clinical medicine for the treatment of cancer and viral infections. Among the immunomodulatory activities possibly involved in their therapeutic efficacy, the importance of IFNα effects on dendritic cells (DC differentiation and activation has been considered. Despite several studies exploiting microarray technology to characterize IFNα mechanisms of action, there is currently no consensus on the core signature of these cytokines in the peripheral blood of IFNα-treated individuals, as well as on the existence of blood genomic and proteomic markers of low-dose IFNα administered as a vaccine adjuvant. Methods Gene profiling analysis with microarray was performed on PBMC isolated from melanoma patients and healthy individuals 24 hours after each repeated injection of low-dose IFNα, administered as vaccine adjuvant in two separate clinical trials. At the same time points, cytofluorimetric analysis was performed on CD14+ monocytes, to detect the phenotypic modifications exerted by IFNα on antigen presenting cells precursors. Results An IFNα signature was consistently observed in both clinical settings 24 hours after each repeated administration of the cytokine. The observed modulation was transient, and did not reach a steady state level refractory to further stimulations. The molecular signature observed ex vivo largely matched the one detected in CD14+ monocytes exposed in vitro to IFNα, including the induction of CXCL10 at the transcriptional and protein level. Interestingly, IFNα ex vivo signature was paralleled by an increase in the percentage and expression of costimulatory molecules by circulating CD14+/CD16+ monocytes, indicated as natural precursors of DC in response to danger signals. Conclusions Our results provide new insights into the identification of a well defined molecular signature as biomarker of IFNα administered as immune adjuvants, and

  2. Episodes of repeated sudden deafness following pregnancies.

    Science.gov (United States)

    Pawlak-Osinska, Katarzyna; Burduk, Pawel K; Kopczynski, Andrzej

    2009-04-01

    Sex hormones influence and provoke changes in hearing levels. Sudden deafness is rarely observed in pregnant women. The effective treatment of sudden deafness in pregnant women is a challenging problem. We present a case of repeatable, completely regressed sudden deafness in a woman during her first and second pregnancies.

  3. Repeated fecal microbiota transplantation in a child with ulcerative colitis.

    Science.gov (United States)

    Shimizu, Hirotaka; Arai, Katsuhiro; Abe, Jun; Nakabayashi, Kazuhiko; Yoshioka, Takako; Hosoi, Kenji; Kuroda, Makoto

    2016-08-01

    We report the case of an 11-year-old girl with ulcerative colitis refractory to conventional therapy, who was subsequently treated successfully with repeated fecal microbiota transplantation (FMT). The patient was steroid dependent despite several infliximab treatments, and colectomy was proposed to improve quality of life. After repeated FMT, she was able to maintain remission with on minimal dose of steroid. Although her fecal microbiota was dysbiotic before FMT, it was restored to a similar pattern as the donor after repeated FMT.

  4. Effect of DNA extraction procedure, repeated extraction and ethidium monoazide (EMA)/propidium monoazide (PMA) treatment on overall DNA yield and impact on microbial fingerprints for bacteria, fungi and archaea in a reference soil.

    Science.gov (United States)

    Wagner, Andreas O; Praeg, Nadine; Reitschuler, Christoph; Illmer, Paul

    2015-09-01

    Different DNA extraction protocols were evaluated on a reference soil. A wide difference was found in the total extractable DNA as derived from different extraction protocols. Concerning the DNA yield phenol-chloroform-isomyl alcohol extraction resulted in high DNA yield but also in a remarkable co-extraction of contaminants making PCR from undiluted DNA extracts impossible. By comparison of two different extraction kits, the Macherey&Nagel SoilExtract II kit resulted in the highest DNA yields when buffer SL1 and the enhancer solution were applied. The enhancer solution not only significantly increased the DNA yield but also the amount of co-extracted contaminates, whereas additional disintegration strategies did not. Although a three times repeated DNA extraction increased the total amount of extracted DNA, microbial fingerprints were merely affected. However, with the 5th extraction this changed. A reduction of total DGGE band numbers was observed for archaea and fungi, whereas for bacteria the diversity increased. The application of ethidium monoazide (EMA) or propidium monoazide (PMA) treatment aiming on the selective removal of soil DNA derived from cells lacking cell wall integrity resulted in a significant reduction of total extracted DNA, however, the hypothesized effect on microbial fingerprints failed to appear indicating the need for further investigations.

  5. Repeatability of Response to Asthma Medications

    Science.gov (United States)

    Wu, Ann; Tantisira, Kelan; Li, Lingling; Schuemann, Brooke; Weiss, Scott

    2010-01-01

    Background Pharmacogenetic studies of drug response in asthma assume that patients respond consistently to a treatment but that treatment response varies across patients, however, no formal studies have demonstrated this. Objective To determine the repeatability of commonly used outcomes for treatment response to asthma medications: bronchodilator response, forced expiratory volume in 1 second (FEV1), and provocative concentration of methacholine producing a 20% decline in FEV1 (PC20). Methods The Childhood Asthma Management Program (CAMP) was a multi-center clinical trial of children randomized to receiving budesonide, nedocromil, or placebo. We determined the intraclass correlation coefficient (ICC) for each outcome over repeated visits over four years in CAMP using mixed effects regression models. We adjusted for the covariates: age, race/ethnicity, height, family income, parental education, and symptom score. We incorporated each outcome for each child as repeated outcome measurements and stratified by treatment group. Results The ICC for bronchodilator response was 0.31 in the budesonide group, 0.35 in the nedocromil group, and 0.40 in the placebo group, after adjusting for covariates. The ICC for FEV1 was 0.71 in the budesonide group, 0.60 in the nedocromil group, and 0.69 in the placebo group, after adjusting for covariates. The ICC for PC20 was 0.67 in the budesonide and placebo groups and 0.73 in the nedocromil group, after adjusting for covariates. Conclusion The within treatment group repeatability of FEV1 and PC20 are high; thus these phenotypes are heritable. FEV1 and PC20 may be better phenotypes than bronchodilator response for studies of treatment response in asthma. PMID:19064281

  6. On balanced minimal repeated measurements designs

    Directory of Open Access Journals (Sweden)

    Shakeel Ahmad Mir

    2014-10-01

    Full Text Available Repeated Measurements designs are concerned with scientific experiments in which each experimental unit is assigned more than once to a treatment either different or identical. This class of designs has the property that the unbiased estimators for elementary contrasts among direct and residual effects are obtainable. Afsarinejad (1983 provided a method of constructing balanced Minimal Repeated Measurements designs p < t , when t is an odd or prime power, one or more than one treatment may occur more than once in some sequences and  designs so constructed no longer remain uniform in periods. In this paper an attempt has been made to provide a new method to overcome this drawback. Specifically, two cases have been considered                RM[t,n=t(t-t/(p-1,p], λ2=1 for balanced minimal repeated measurements designs and  RM[t,n=2t(t-t/(p-1,p], λ2=2 for balanced  repeated measurements designs. In addition , a method has been provided for constructing              extra-balanced minimal designs for special case RM[t,n=t2/(p-1,p], λ2=1.

  7. Expansion of protein domain repeats.

    Directory of Open Access Journals (Sweden)

    Asa K Björklund

    2006-08-01

    Full Text Available Many proteins, especially in eukaryotes, contain tandem repeats of several domains from the same family. These repeats have a variety of binding properties and are involved in protein-protein interactions as well as binding to other ligands such as DNA and RNA. The rapid expansion of protein domain repeats is assumed to have evolved through internal tandem duplications. However, the exact mechanisms behind these tandem duplications are not well-understood. Here, we have studied the evolution, function, protein structure, gene structure, and phylogenetic distribution of domain repeats. For this purpose we have assigned Pfam-A domain families to 24 proteomes with more sensitive domain assignments in the repeat regions. These assignments confirmed previous findings that eukaryotes, and in particular vertebrates, contain a much higher fraction of proteins with repeats compared with prokaryotes. The internal sequence similarity in each protein revealed that the domain repeats are often expanded through duplications of several domains at a time, while the duplication of one domain is less common. Many of the repeats appear to have been duplicated in the middle of the repeat region. This is in strong contrast to the evolution of other proteins that mainly works through additions of single domains at either terminus. Further, we found that some domain families show distinct duplication patterns, e.g., nebulin domains have mainly been expanded with a unit of seven domains at a time, while duplications of other domain families involve varying numbers of domains. Finally, no common mechanism for the expansion of all repeats could be detected. We found that the duplication patterns show no dependence on the size of the domains. Further, repeat expansion in some families can possibly be explained by shuffling of exons. However, exon shuffling could not have created all repeats.

  8. DWI Repeaters and Non-Repeaters: A Comparison.

    Science.gov (United States)

    Weeber, Stan

    1981-01-01

    Discussed how driving-while-intoxicated (DWI) repeaters differed signigicantly from nonrepeaters on 4 of 23 variables tested. Repeaters were more likely to have zero or two dependent children, attend church frequently, drink occasionally and have one or more arrests for public intoxication. (Author)

  9. To Repeat or Not to Repeat a Course

    Science.gov (United States)

    Armstrong, Michael J.; Biktimirov, Ernest N.

    2013-01-01

    The difficult transition from high school to university means that many students need to repeat (retake) 1 or more of their university courses. The authors examine the performance of students repeating first-year core courses in an undergraduate business program. They used data from university records for 116 students who took a total of 232…

  10. Nifty Nines and Repeating Decimals

    Science.gov (United States)

    Brown, Scott A.

    2016-01-01

    The traditional technique for converting repeating decimals to common fractions can be found in nearly every algebra textbook that has been published, as well as in many precalculus texts. However, students generally encounter repeating decimal numerals earlier than high school when they study rational numbers in prealgebra classes. Therefore, how…

  11. Nifty Nines and Repeating Decimals

    Science.gov (United States)

    Brown, Scott A.

    2016-01-01

    The traditional technique for converting repeating decimals to common fractions can be found in nearly every algebra textbook that has been published, as well as in many precalculus texts. However, students generally encounter repeating decimal numerals earlier than high school when they study rational numbers in prealgebra classes. Therefore, how…

  12. All-photonic quantum repeaters

    Science.gov (United States)

    Azuma, Koji; Tamaki, Kiyoshi; Lo, Hoi-Kwong

    2015-01-01

    Quantum communication holds promise for unconditionally secure transmission of secret messages and faithful transfer of unknown quantum states. Photons appear to be the medium of choice for quantum communication. Owing to photon losses, robust quantum communication over long lossy channels requires quantum repeaters. It is widely believed that a necessary and highly demanding requirement for quantum repeaters is the existence of matter quantum memories. Here we show that such a requirement is, in fact, unnecessary by introducing the concept of all-photonic quantum repeaters based on flying qubits. In particular, we present a protocol based on photonic cluster-state machine guns and a loss-tolerant measurement equipped with local high-speed active feedforwards. We show that, with such all-photonic quantum repeaters, the communication efficiency scales polynomially with the channel distance. Our result paves a new route towards quantum repeaters with efficient single-photon sources rather than matter quantum memories. PMID:25873153

  13. Zinc-finger directed double-strand breaks within CAG repeat tracts promote repeat instability in human cells.

    Science.gov (United States)

    Mittelman, David; Moye, Christopher; Morton, Jason; Sykoudis, Kristen; Lin, Yunfu; Carroll, Dana; Wilson, John H

    2009-06-16

    Expanded triplet repeats have been identified as the genetic basis for a growing number of neurological and skeletal disorders. To examine the contribution of double-strand break repair to CAG x CTG repeat instability in mammalian systems, we developed zinc finger nucleases (ZFNs) that recognize and cleave CAG repeat sequences. Engineered ZFNs use a tandem array of zinc fingers, fused to the FokI DNA cleavage domain, to direct double-strand breaks (DSBs) in a site-specific manner. We first determined that the ZFNs cleave CAG repeats in vitro. Then, using our previously described tissue culture assay for identifying modifiers of CAG repeat instability, we found that transfection of ZFN-expression vectors induced up to a 15-fold increase in changes to the CAG repeat in human and rodent cell lines, and that longer repeats were much more sensitive to cleavage than shorter ones. Analysis of individual colonies arising after treatment revealed a spectrum of events consistent with ZFN-induced DSBs and dominated by repeat contractions. We also found that expressing a dominant-negative form of RAD51 in combination with a ZFN, dramatically reduced the effect of the nuclease, suggesting that DSB-induced repeat instability is mediated, in part, through homology directed repair. These studies identify a ZFN as a useful reagent for characterizing the effects of DSBs on CAG repeats in cells.

  14. Analysis of repeated outcome measures from longitudinal studies

    Institute of Scientific and Technical Information of China (English)

    Yuanjia WANG; Naihua DUAN

    2011-01-01

    @@ In many clinical studies repeated measurements of an outcome are collected over time.For example,in an 8-week study of treatment for obsessive compulsive disorder,the severity of the disorder may be measured weekly using the Yale-Brown-Obsessive-Compulsive-Disorder-Scale (YBOCS).For each study participant who completes the study,there will be nine repeated measures of YBOCS (a baseline assessment plus eight assessments during the course of treatment).Such a study in which participants are followed and measured repeatedly over time is called a longitudinal study and the resulting data are called longitudinal data.

  15. Analysis of repeated measures data

    CERN Document Server

    Islam, M Ataharul

    2017-01-01

    This book presents a broad range of statistical techniques to address emerging needs in the field of repeated measures. It also provides a comprehensive overview of extensions of generalized linear models for the bivariate exponential family of distributions, which represent a new development in analysing repeated measures data. The demand for statistical models for correlated outcomes has grown rapidly recently, mainly due to presence of two types of underlying associations: associations between outcomes, and associations between explanatory variables and outcomes. The book systematically addresses key problems arising in the modelling of repeated measures data, bearing in mind those factors that play a major role in estimating the underlying relationships between covariates and outcome variables for correlated outcome data. In addition, it presents new approaches to addressing current challenges in the field of repeated measures and models based on conditional and joint probabilities. Markov models of first...

  16. Mouse repeated electroconvulsive seizure (ECS) does not reverse social stress effects but does induce behavioral and hippocampal changes relevant to electroconvulsive therapy (ECT) side-effects in the treatment of depression

    Science.gov (United States)

    Sigrist, Hannes; Seifritz, Erich; Fikse, Lianne; Bosker, Fokko J.; Schoevers, Robert A.; Klein, Hans C.

    2017-01-01

    Electroconvulsive therapy (ECT) is an effective treatment for depression, but can have negative side effects including amnesia. The mechanisms of action underlying both the antidepressant and side effects of ECT are not well understood. An equivalent manipulation that is conducted in experimental animals is electroconvulsive seizure (ECS). Rodent studies have provided valuable insights into potential mechanisms underlying the antidepressant and side effects of ECT. However, relatively few studies have investigated the effects of ECS in animal models with a depression-relevant manipulation such as chronic stress. In the present study, mice were first exposed to chronic social stress (CSS) or a control procedure for 15 days followed by ECS or a sham procedure for 10 days. Behavioral effects were investigated using an auditory fear conditioning (learning) and expression (memory) test and a treadmill-running fatigue test. Thereafter, immunohistochemistry was conducted on brain material using the microglial marker Iba-1 and the cholinergic fibre marker ChAT. CSS did not increase fear learning and memory in the present experimental design; in both the control and CSS mice ECS reduced fear learning and fear memory expression. CSS induced the expected fatigue-like effect in the treadmill-running test; ECS induced increased fatigue in CSS and control mice. In CSS and control mice ECS induced inflammation in hippocampus in terms of increased expression of Iba-1 in radiatum of CA1 and CA3. CSS and ECS both reduced acetylcholine function in hippocampus as indicated by decreased expression of ChAT in several hippocampal sub-regions. Therefore, CSS increased fatigue and reduced hippocampal ChAT activity and, rather than reversing these effects, a repeated ECS regimen resulted in impaired fear learning-memory, increased fatigue, increased hippocampal Iba-1 expression, and decreased hippocampal ChAT expression. As such, the current model does not provide insights into the

  17. Pharmacokinetic strategies for treatment of drug overdose and addiction.

    Science.gov (United States)

    Gorelick, David A

    2012-02-01

    The pharmacokinetic treatment strategy targets the drug molecule itself, aiming to reduce drug concentration at the site of action, thereby minimizing any pharmacodynamic effect. This approach might be useful in the treatment of acute drug toxicity/overdose and in the long-term treatment of addiction. Phase IIa controlled clinical trials with anticocaine and antinicotine vaccines have shown good tolerability and some efficacy, but Phase IIb and III trials have been disappointing because of the failure to generate adequate antibody titers in most participants. Monoclonal antibodies against cocaine, methamphetamine and phencyclidine have shown promise in animal studies, as has enhancing cocaine metabolism with genetic variants of human butyrylcholinesterase, with a bacterial esterase, and with catalytic monoclonal antibodies. Pharmacokinetic treatments offer potential advantages in terms of patient adherence, absence of medication interactions and benefit for patients who cannot take standard medications.

  18. Repeat Gamma Knife surgery for vestibular schwannomas

    Science.gov (United States)

    Lonneville, Sarah; Delbrouck, Carine; Renier, Cécile; Devriendt, Daniel; Massager, Nicolas

    2015-01-01

    Background: Gamma Knife (GK) surgery is a recognized treatment option for the management of small to medium-sized vestibular schwannoma (VS) associated with high-tumor control and low morbidity. When a radiosurgical treatment fails to stop tumor growth, repeat GK surgery can be proposed in selected cases. Methods: A series of 27 GK retreatments was performed in 25 patients with VS; 2 patients underwent three procedures. The median time interval between GK treatments was 45 months. The median margin dose used for the first, second, and third GK treatments was 12 Gy, 12 Gy, and 14 Gy, respectively. Six patients (4 patients for the second irradiation and 2 patients for the third irradiation) with partial tumor regrowth were treated only on the growing part of the tumor using a median margin dose of 13 Gy. The median tumor volume was 0.9, 2.3, and 0.7 cc for the first, second, and third treatments, respectively. Stereotactic positron emission tomography (PET) guidance was used for dose planning in 6 cases. Results: Mean follow-up duration was 46 months (range 24–110). At the last follow-up, 85% of schwannomas were controlled. The tumor volume decreased, remained unchanged, or increased after retreatment in 15, 8, and 4 cases, respectively. Four patients had PET during follow-up, and all showed a significant metabolic decrease of the tumor. Hearing was not preserved after retreatment in any patients. New facial or trigeminal palsy did not occur after retreatment. Conclusions: Our results support the long-term efficacy and low morbidity of repeat GK treatment for selected patients with tumor growth after initial treatment. PMID:26500799

  19. Tentativa de controle de Hymenolepis nana através de tratamentos clínicos repetidos, com praziquantel, em uma comunidade fechada The use of repeated praziquantel treatments in an attempt to control Hymenolepis nana in an orphanage

    Directory of Open Access Journals (Sweden)

    R. S. Rocha

    1981-08-01

    controle da himenolepíase.Praziquantel was used repeatedly in an orphanage to determine its effectiveness in controlling hymenolepis. At the same time, the possible mechanisms of the transmission of this parasitosis were studied. The first group examined consisted of 161 people of which 109 were the orphanage children, who varied in age from days or months to eight years, and 52 adults, employees of the institution. Stool tests of all were made about every two months, using the Hoffman, Pons and Janer method; cure control was carried out by the same method seven to fourteen days after treatment. Every two weeks, H. nana eggs were searched for under the finger nails of the children, in insects, in domestic wastes, on door knobs and refrigerator handles, and on toilet flush knobs and strings. Water collected from rinsed urinals and shower floors was also tested. Eggs and larva of helminths and protozoa cysts were found in domestic waste and cockroaches and on door knobs. H. nana eggs were found in puddles of water left on shower floors and the rinse water of urinals. Every patient whose feces had H. nana eggs was treated with a single oral 25mg/kg dose of praziquantel, taken after lunch. In the four groups treated (66 patients in all, no important side effects were observed, and follow-up indicated 100% cure. For the 5th and last treatment, a group of both positive and negative (for H. nana people was divided into sub-groups and treated with one (25mg/kg or two doses of the medicine for a period of four days (total: 50mg/kg. Follow-up examination two months after treatment showed that only six patients were still eliminating eggs of the parasite; all belonged to the sub-group treated with a single dose of the drug. In spite of the treatments given an of the high percentage of cure, control of hymenolepiasis was not achieved.

  20. Limitations on quantum key repeaters.

    Science.gov (United States)

    Bäuml, Stefan; Christandl, Matthias; Horodecki, Karol; Winter, Andreas

    2015-04-23

    A major application of quantum communication is the distribution of entangled particles for use in quantum key distribution. Owing to noise in the communication line, quantum key distribution is, in practice, limited to a distance of a few hundred kilometres, and can only be extended to longer distances by use of a quantum repeater, a device that performs entanglement distillation and quantum teleportation. The existence of noisy entangled states that are undistillable but nevertheless useful for quantum key distribution raises the question of the feasibility of a quantum key repeater, which would work beyond the limits of entanglement distillation, hence possibly tolerating higher noise levels than existing protocols. Here we exhibit fundamental limits on such a device in the form of bounds on the rate at which it may extract secure key. As a consequence, we give examples of states suitable for quantum key distribution but unsuitable for the most general quantum key repeater protocol.

  1. Hysteresis of magnetostructural transitions: Repeatable and non-repeatable processes

    Energy Technology Data Exchange (ETDEWEB)

    Provenzano, Virgil [National Institute of Standards and Technology, Gaithersburg, MD 20899 (United States); Della Torre, Edward; Bennett, Lawrence H. [Department of Electrical and Computer Engineering, The George Washington University, Washington, DC 20052 (United States); ElBidweihy, Hatem, E-mail: Hatem@gwmail.gwu.edu [Department of Electrical and Computer Engineering, The George Washington University, Washington, DC 20052 (United States)

    2014-02-15

    The Gd{sub 5}Ge{sub 2}Si{sub 2} alloy and the off-stoichiometric Ni{sub 50}Mn{sub 35}In{sub 15} Heusler alloy belong to a special class of metallic materials that exhibit first-order magnetostructural transitions near room temperature. The magnetic properties of this class of materials have been extensively studied due to their interesting magnetic behavior and their potential for a number of technological applications such as refrigerants for near-room-temperature magnetic refrigeration. The thermally driven first-order transitions in these materials can be field-induced in the reverse order by applying a strong enough field. The field-induced transitions are typically accompanied by the presence of large magnetic hysteresis, the characteristics of which are a complicated function of temperature, field, and magneto-thermal history. In this study we show that the virgin curve, the major loop, and sequentially measured MH loops are the results of both repeatable and non-repeatable processes, in which the starting magnetostructural state, prior to the cycling of field, plays a major role. Using the Gd{sub 5}Ge{sub 2}Si{sub 2} and Ni{sub 50}Mn{sub 35}In{sub 15} alloys, as model materials, we show that a starting single phase state results in fully repeatable processes and large magnetic hysteresis, whereas a mixed phase starting state results in non-repeatable processes and smaller hysteresis.

  2. Cataractogenesis after Repeat Laser in situ Keratomileusis

    Directory of Open Access Journals (Sweden)

    Ahmad M. Mansour

    2012-08-01

    Full Text Available There has been the unsubstantiated clinical impression that laser refractive surgery accelerates cataract development along with solid experimental data about the cataractogenic effects of excimer laser treatment. We present the first documented case of significant cataract formation in a young myope after repeat excimer laser ablation necessitating phacoemulsification with a posterior chamber implant. Proposed explanations include focusing of the ablation wave on the posterior capsule (acoustic wave lens epithelial damage, photooxidative stress of the lens (ultraviolet and inflammatory oxidative stress, and corticosteroid-induced cataract (lens toxicity.

  3. EAMJ Dec. Repeatability.indd

    African Journals Online (AJOL)

    2008-12-12

    Dec 12, 2008 ... Results:Kappa values for four-week repeatability for the wheeze and asthma questions were 0.61 ... for logistic, cultural and ethical reasons, to use ... individual with baseline forced expiratory volume in .... period is likely to also include the effects of true ... data, the writing of the manuscript or the decision.

  4. Value of repeat biopsy in lupus nephritis flares

    Science.gov (United States)

    Greloni, G; Scolnik, M; Marin, J; Lancioni, E; Quiroz, C; Zacariaz, J; De la Iglesia Niveyro, P; Christiansen, S; Pierangelo, M A; Varela, C F; Rosa-Diez, G J; Catoggio, L J; Soriano, E R

    2014-01-01

    Objectives Renal flares are common in lupus nephritis (LN), and class switch is thought to be characteristic. There is no agreement on indications for performing a repeat renal biopsy. Our objective was to retrospectively review patients who had more than one renal biopsy performed on clinical indications, and analyse clinical, pathological and treatment changes after successive biopsies. Methods Forty-five patients with LN and one or more repeat renal biopsies were included, with a total of 116 biopsies. Results Of the 71 repeat biopsies, pathological transition occurred in 39 (54.9%). When having a previous biopsy with a proliferative lesion, class switch occurred in 55.6%, with 24.4% evolving into non-proliferative classes. When previous biopsy was class V, transition to other classes occurred in 58.3% and changes were all into proliferative classes. Conversion from one pure proliferative form to another (class III to class IV or vice versa) happened in 11.3% of the rebiopsies, with 62 rebiopsies (87.3%) leading to a change in the treatment regimen. Conclusions Histological transformations were common, and they occurred when the previous biopsy had non-proliferative lesions as well as when lesions were proliferative. Treatments were modified after repeat renal biopsy in the majority of patients. In this experience, kidney repeat biopsies were useful in guiding treatment of LN flares. PMID:25396056

  5. Directionality switchable gain stabilized linear repeater

    Science.gov (United States)

    Ota, Takayuki; Ohmachi, Tadashi; Aida, Kazuo

    2004-10-01

    We propose a new approach to realize a bidirectional linear repeater suitable for future optical internet networks and fault location in repeater chain with OTDR. The proposed approach is the linear repeater of simple configuration whose directionality is rearranged dynamically by electrical control signal. The repeater is composed of a magneto-optical switch, a circulator, a dynamically gain stabilized unidirectional EDFA, and control circuits. The repeater directionality is rearranged as fast as 0.1ms by an electrical control pulse. It is experimentally confirmed that OTDR with the directionality switchable repeater is feasible for repeater chain. The detailed design and performance of the repeater are also discussed, including the multi-pass interference (MPI) which may arise in the proposed repeater, the effect of the MPI on SNR degradation of the repeater chain and the feed-forward EDFA gain control circuit.

  6. Measurement-based quantum repeaters

    CERN Document Server

    Zwerger, M; Briegel, H J

    2012-01-01

    We introduce measurement-based quantum repeaters, where small-scale measurement-based quantum processors are used to perform entanglement purification and entanglement swapping in a long-range quantum communication protocol. In the scheme, pre-prepared entangled states stored at intermediate repeater stations are coupled with incoming photons by simple Bell-measurements, without the need of performing additional quantum gates or measurements. We show how to construct the required resource states, and how to minimize their size. We analyze the performance of the scheme under noise and imperfections, with focus on small-scale implementations involving entangled states of few qubits. We find measurement-based purification protocols with significantly improved noise thresholds. Furthermore we show that already resource states of small size suffice to significantly increase the maximal communication distance. We also discuss possible advantages of our scheme for different set-ups.

  7. A Repeating Fast Radio Burst

    CERN Document Server

    Spitler, L G; Hessels, J W T; Bogdanov, S; Brazier, A; Camilo, F; Chatterjee, S; Cordes, J M; Crawford, F; Deneva, J; Ferdman, R D; Freire, P C C; Kaspi, V M; Lazarus, P; Lynch, R; Madsen, E C; McLaughlin, M A; Patel, C; Ransom, S M; Seymour, A; Stairs, I H; Stappers, B W; van Leeuwen, J; Zhu, W W

    2016-01-01

    Fast Radio Bursts are millisecond-duration astronomical radio pulses of unknown physical origin that appear to come from extragalactic distances. Previous follow-up observations have failed to find additional bursts at the same dispersion measures (i.e. integrated column density of free electrons between source and telescope) and sky position as the original detections. The apparent non-repeating nature of the fast radio bursts has led several authors to hypothesise that they originate in cataclysmic astrophysical events. Here we report the detection of ten additional bursts from the direction of FRB121102, using the 305-m Arecibo telescope. These new bursts have dispersion measures and sky positions consistent with the original burst. This unambiguously identifies FRB121102 as repeating and demonstrates that its source survives the energetic events that cause the bursts. Additionally, the bursts from FRB121102 show a wide range of spectral shapes that appear to be predominantly intrinsic to the source and wh...

  8. Repeatability of Harris Corner Detector

    Institute of Scientific and Technical Information of China (English)

    HU Lili

    2003-01-01

    Interest point detectors are commonly employed to reduce the amount of data to be processed. The ideal interest point detector would robustly select those features which are most appropriate or salient for the application and data at hand. This paper shows that interest points are geometrically stable under different transformations.This property makes interest points very successful in the context of image matching. To measure this property quantatively, we introduce a evaluation criterion: repeatability rate.

  9. The effects of phencyclidine (PCP) on anxiety-like behavior in the elevated plus maze and the light-dark exploration test are age dependent, sexually dimorphic, and task dependent.

    Science.gov (United States)

    Turgeon, Sarah M; Kim, Daniel; Pritchard, Melissa; Salgado, Sanjay; Thaler, Alison

    2011-11-01

    Previous research in our laboratory revealed sexually dimorphic effects of prior exposure to phencyclidine (PCP) on elevated plus maze behavior. In an attempt to examine the developmental time course of this effect and determine the extent to which it generalizes to other anxiety paradigms, young adult (61-64 days old) and adult (96-107 days old) male and female rats were treated with PCP (15 mg/kg) or saline. Following a two week withdrawal period, animals were tested in either the elevated plus maze (EPM) or a light-dark exploration (LD) test. In adults, both tests revealed a sexually dimorphic effect driven by PCP-induced decreases in anxiety in females as indicated by increased time spent in the open arms of the EPM and in the lit compartment of the LD test and increased anxiety in males as indicated by decreased time spent in the lit compartment of the LD. In young animals, PCP pretreatment decreased open arm exploration in the elevated plus maze, indicating increased anxiety. However, PCP increased time spent in the light compartment in the light-dark exploration test, indicating decreased anxiety. Corticosterone levels measured 15 min after the onset of the EPM failed to reveal an association between the behavioral effects of PCP and corticosterone levels. The results in adults substantiate the previously observed sexually dimorphic effect of PCP on elevated plus maze behavior in adults and indicate that the effect generalizes to another anxiety paradigm. The results in the younger animals suggest an age dependent effect of PCP on anxiety in general and indicate that behaviors in the elevated plus maze and the light-dark exploration test reflect dissociable psychobiological states. Copyright © 2011 Elsevier Inc. All rights reserved.

  10. Blonanserin Ameliorates Phencyclidine-Induced Visual-Recognition Memory Deficits: the Complex Mechanism of Blonanserin Action Involving D3-5-HT2A and D1-NMDA Receptors in the mPFC

    Science.gov (United States)

    Hida, Hirotake; Mouri, Akihiro; Mori, Kentaro; Matsumoto, Yurie; Seki, Takeshi; Taniguchi, Masayuki; Yamada, Kiyofumi; Iwamoto, Kunihiro; Ozaki, Norio; Nabeshima, Toshitaka; Noda, Yukihiro

    2015-01-01

    Blonanserin differs from currently used serotonin 5-HT2A/dopamine-D2 receptor antagonists in that it exhibits higher affinity for dopamine-D2/3 receptors than for serotonin 5-HT2A receptors. We investigated the involvement of dopamine-D3 receptors in the effects of blonanserin on cognitive impairment in an animal model of schizophrenia. We also sought to elucidate the molecular mechanism underlying this involvement. Blonanserin, as well as olanzapine, significantly ameliorated phencyclidine (PCP)-induced impairment of visual-recognition memory, as demonstrated by the novel-object recognition test (NORT) and increased extracellular dopamine levels in the medial prefrontal cortex (mPFC). With blonanserin, both of these effects were antagonized by DOI (a serotonin 5-HT2A receptor agonist) and 7-OH-DPAT (a dopamine-D3 receptor agonist), whereas the effects of olanzapine were antagonized by DOI but not by 7-OH-DPAT. The ameliorating effect was also antagonized by SCH23390 (a dopamine-D1 receptor antagonist) and H-89 (a protein kinase A (PKA) inhibitor). Blonanserin significantly remediated the decrease in phosphorylation levels of PKA at Thr197 and of NR1 (an essential subunit of N-methyl-D-aspartate (NMDA) receptors) at Ser897 by PKA in the mPFC after a NORT training session in the PCP-administered mice. There were no differences in the levels of NR1 phosphorylated at Ser896 by PKC in any group. These results suggest that the ameliorating effect of blonanserin on PCP-induced cognitive impairment is associated with indirect functional stimulation of the dopamine-D1-PKA-NMDA receptor pathway following augmentation of dopaminergic neurotransmission due to inhibition of both dopamine-D3 and serotonin 5-HT2A receptors in the mPFC. PMID:25120077

  11. Blonanserin ameliorates phencyclidine-induced visual-recognition memory deficits: the complex mechanism of blonanserin action involving D₃-5-HT₂A and D₁-NMDA receptors in the mPFC.

    Science.gov (United States)

    Hida, Hirotake; Mouri, Akihiro; Mori, Kentaro; Matsumoto, Yurie; Seki, Takeshi; Taniguchi, Masayuki; Yamada, Kiyofumi; Iwamoto, Kunihiro; Ozaki, Norio; Nabeshima, Toshitaka; Noda, Yukihiro

    2015-02-01

    Blonanserin differs from currently used serotonin 5-HT₂A/dopamine-D₂ receptor antagonists in that it exhibits higher affinity for dopamine-D₂/₃ receptors than for serotonin 5-HT₂A receptors. We investigated the involvement of dopamine-D₃ receptors in the effects of blonanserin on cognitive impairment in an animal model of schizophrenia. We also sought to elucidate the molecular mechanism underlying this involvement. Blonanserin, as well as olanzapine, significantly ameliorated phencyclidine (PCP)-induced impairment of visual-recognition memory, as demonstrated by the novel-object recognition test (NORT) and increased extracellular dopamine levels in the medial prefrontal cortex (mPFC). With blonanserin, both of these effects were antagonized by DOI (a serotonin 5-HT₂A receptor agonist) and 7-OH-DPAT (a dopamine-D₃ receptor agonist), whereas the effects of olanzapine were antagonized by DOI but not by 7-OH-DPAT. The ameliorating effect was also antagonized by SCH23390 (a dopamine-D₁ receptor antagonist) and H-89 (a protein kinase A (PKA) inhibitor). Blonanserin significantly remediated the decrease in phosphorylation levels of PKA at Thr(197) and of NR1 (an essential subunit of N-methyl-D-aspartate (NMDA) receptors) at Ser(897) by PKA in the mPFC after a NORT training session in the PCP-administered mice. There were no differences in the levels of NR1 phosphorylated at Ser(896) by PKC in any group. These results suggest that the ameliorating effect of blonanserin on PCP-induced cognitive impairment is associated with indirect functional stimulation of the dopamine-D₁-PKA-NMDA receptor pathway following augmentation of dopaminergic neurotransmission due to inhibition of both dopamine-D₃ and serotonin 5-HT₂A receptors in the mPFC.

  12. Origin and fate of repeats in bacteria.

    Science.gov (United States)

    Achaz, G; Rocha, E P C; Netter, P; Coissac, E

    2002-07-01

    We investigated 53 complete bacterial chromosomes for intrachromosomal repeats. In previous studies on eukaryote chromosomes, we proposed a model for the dynamics of repeats based on the continuous genesis of tandem repeats, followed by an active process of high deletion rate, counteracted by rearrangement events that may prevent the repeats from being deleted. The present study of long repeats in the genomes of Bacteria and Archaea suggests that our model of interspersed repeats dynamics may apply to them. Thus the duplication process might be a consequence of very ancient mechanisms shared by all three domains. Moreover, we show that there is a strong negative correlation between nucleotide composition bias and the repeat density of genomes. We hypothesise that in highly biased genomes, non-duplicated small repeats arise more frequently by random effects and are used as primers for duplication mechanisms, leading to a higher density of large repeats.

  13. Improving repeatability by improving quality

    Energy Technology Data Exchange (ETDEWEB)

    Ronen, Shuki; Ackers, Mark; Schlumberger, Geco-Prakla; Brink, Mundy

    1998-12-31

    Time lapse (4-D) seismic is a promising tool for reservoir characterization and monitoring. The method is apparently simple: to acquire data repeatedly over the same reservoir, process and interpret the data sets, then changes between the data sets indicate changes in the reservoir. A problem with time lapse seismic data is that reservoirs are a relatively small part of the earth and important reservoir changes may cause very small differences to the time lapse data. The challenge is to acquire and process economical time lapse data such that reservoir changes can be detected above the noise of varying acquisition and environment. 7 refs., 9 figs.

  14. Coordinated hybrid automatic repeat request

    KAUST Repository

    Makki, Behrooz

    2014-11-01

    We develop a coordinated hybrid automatic repeat request (HARQ) approach. With the proposed scheme, if a user message is correctly decoded in the first HARQ rounds, its spectrum is allocated to other users, to improve the network outage probability and the users\\' fairness. The results, which are obtained for single- and multiple-antenna setups, demonstrate the efficiency of the proposed approach in different conditions. For instance, with a maximum of M retransmissions and single transmit/receive antennas, the diversity gain of a user increases from M to (J+1)(M-1)+1 where J is the number of users helping that user.

  15. Considerations on repeated repairing of weldments in Inconel 718 alloy

    Science.gov (United States)

    Bayless, E. O.; Lovoy, C. V.; Mcilwain, M. C.; Munafo, P.

    1981-01-01

    The effects of repeated weld repairs on the metallurgical characteristics, high cycle fatigue (HCF), and tensile properties of Inconel 718 butt weld joints were determined. A 1/4 in thick plate and a 1/2 in thick plate were used as well as tungsten inert gas welding, and Inconel 718 filler wire. Weld panels were subjected to 2, 6, and 12 repeated repairs and were made in a highly restrained condition. Post weld heat treatments were also conducted with the welded panel in the highly restrained condition. Results indicate that no significant metallurgical anomaly is evident as a result of up to twelve repeated weld repairs. No degradation in fatigue life is noted for up to twelve repeated repairs. Tensile results from specimens which contained up to twelve repeated weld repairs revealed no significant degradation in UTS and YS. However, a significant decrease in elongation is evident with specimens (solution treated and age hardened after welding) which contained twelve repeated repairs. The elongation loss is attributed to the presence of a severe notch on each side (fusion line) of the repair weld bead reinforcement.

  16. Comparative analysis of repeated skin dilation in the treatment of scarring baldness%重复皮肤扩张术治疗瘢痕性秃发的对比分析

    Institute of Scientific and Technical Information of China (English)

    李继洋; 惠雷; 盖亚; 郭力

    2014-01-01

    Objective To investigate the clinical effect of repeated skin expansion technique on scarring alopecia. Methods Twenty-eight cases of scarring alopecia underwent repeated relay skin ex-pansion technique were chosen,and 21 cases of scarring alopecia underwent repeated delay skin expan-sion technique were chose. The times of operations,length of hospital stay,expenses and times of anes-thesia were compared between the two methods. Results Relay dilatation was used to repair scarring al-opecia in 28 cases,26 patients had good repairment,the average length of hospital stay was(24 ± 6)d, the average hospitalization expenses were(26 ± 3)thousand yuan. Delay skin expansion was used to re-pair scarring alopecia in 21 cases,20 cases of had good reparrment,the average length of hospital stay was(32 ± 4)d,the average hospitalization expenses were(38 ± 4)thousand yuan. There were signifi-cant differences in the average length of hospital stay and the average hospitalization expenses between the two methods( P<0 . 01 ). Conclusions Delayed skin expansion and relayed expansion both can better repair scarring alopecia,but relayed expansion is feasible,and has fewer operation times,shorter length of hospital stay,little costs and pain.%目的:探讨重复皮肤扩张术治疗瘢痕性秃发的临床效果。方法选择本科重复接力皮肤扩张术治疗瘢痕性秃发28例,重复延期皮肤扩张术治疗瘢痕性秃发21例,对两种治疗方法的手术次数、住院时间、手术费用、麻醉次数等进行比较分析。结果接力扩张术修复瘢痕性秃发28例,修复良好26例,平均住院时间(24±6)d,平均住院费用(2.6±0.3)万元;延期皮肤扩张修复瘢痕秃发21例,修复良好20例,平均住院时间(32±4)d,平均住院费用(3.8±0.4)万元。两种治疗方式的平均住院时间及平均住院费比较差异有统计学意义(P<0.01)。结论延期皮肤扩张和接力扩

  17. Crowding by a repeating pattern.

    Science.gov (United States)

    Rosen, Sarah; Pelli, Denis G

    2015-01-01

    Theinability to recognize a peripheral target among flankers is called crowding. For a foveal target, crowding can be distinguished from overlap masking by its sparing of detection, linear scaling with eccentricity, and invariance with target size.Crowding depends on the proximity and similarity of the flankers to the target. Flankers that are far from or dissimilar to the target do not crowd it. On a gray page, text whose neighboring letters have different colors, alternately black and white, has enough dissimilarity that it might escape crowding. Since reading speed is normally limited by crowding, escape from crowding should allow faster reading. Yet reading speed is unchanged (Chung & Mansfield, 2009). Why? A recent vernier study found that using alternating-color flankers produces strong crowding (Manassi, Sayim, & Herzog, 2012). Might that effect occur with letters and reading? Critical spacing is the minimum center-to-center target-flanker spacing needed to correctly identify the target. We measure it for a target letter surrounded by several equidistant flanker letters of the same polarity, opposite polarity, or mixed polarity: alternately white and black. We find strong crowding in the alternating condition, even though each flanker letter is beyond its own critical spacing (as measured in a separate condition). Thus a periodic repeating pattern can produce crowding even when the individual elements do not. Further, in all conditions we find that, once a periodic pattern repeats (two cycles), further repetition does not affect critical spacing of the innermost flanker.

  18. Repeat microvascular decompression for recurrent idiopathic trigeminal neuralgia

    NARCIS (Netherlands)

    Bakker, Nicolaas A.; van Dijk, J. Marc C.; Immenga, Steven; Wagemakers, Michiel; Metzemaekers, Jan D. M.

    2014-01-01

    Object. Microvascular decompression (MVD) is considered the method of choice to treat idiopathic trigeminal neuralgia (TN) refractory to medical treatment. However, repeat MVD for recurrent TN is not well established. In this paper, the authors describe a large case series in which patients underwen

  19. Effectiveness of Repeated Gonorrhea Cultures in the Third Trimester

    Directory of Open Access Journals (Sweden)

    Juan G. Torres

    1993-01-01

    Full Text Available Objective: With the high cost of health care today, the universal prophylactic measures recommended, and the availability of effective treatment should infection occur, the practice of routinely repeating the endocervical gonorrhea (GC culture in the third trimester of pregnancy may be unwarranted.

  20. Repeat microvascular decompression for recurrent idiopathic trigeminal neuralgia

    NARCIS (Netherlands)

    Bakker, Nicolaas A.; van Dijk, J. Marc C.; Immenga, Steven; Wagemakers, Michiel; Metzemaekers, Jan D. M.

    2014-01-01

    Object. Microvascular decompression (MVD) is considered the method of choice to treat idiopathic trigeminal neuralgia (TN) refractory to medical treatment. However, repeat MVD for recurrent TN is not well established. In this paper, the authors describe a large case series in which patients

  1. Automatization and familiarity in repeated checking

    NARCIS (Netherlands)

    Dek, Eliane C P; van den Hout, Marcel A.; Giele, Catharina L.; Engelhard, Iris M.

    2014-01-01

    Repeated checking paradoxically increases memory uncertainty. This study investigated the underlying mechanism of this effect. We hypothesized that as a result of repeated checking, familiarity with stimuli increases, and automatization of the checking procedure occurs, which should result in decrea

  2. CDC Vital Signs: Preventing Repeat Teen Births

    Science.gov (United States)

    ... file Error processing SSI file Preventing Repeat Teen Births Recommend on Facebook Tweet Share Compartir On this ... Too many teens, ages 15–19, have repeat births. Nearly 1 in 5 births to teens, ages ...

  3. Treatment

    National Research Council Canada - National Science Library

    Safaa M. Raghab; Ahmed M. Abd El Meguid; Hala A. Hegazi

    2013-01-01

    .... This paper presents the results of the analyses of leachate treatment from the solid waste landfill located in Borg El Arab landfill in Alexandria using an aerobic treatment process which was applied...

  4. Expanded complexity of unstable repeat diseases

    OpenAIRE

    Polak, Urszula; McIvor, Elizabeth; Dent, Sharon Y.R.; Wells, Robert D.; Napierala, Marek.

    2012-01-01

    Unstable Repeat Diseases (URDs) share a common mutational phenomenon of changes in the copy number of short, tandemly repeated DNA sequences. More than 20 human neurological diseases are caused by instability, predominantly expansion, of microsatellite sequences. Changes in the repeat size initiate a cascade of pathological processes, frequently characteristic of a unique disease or a small subgroup of the URDs. Understanding of both the mechanism of repeat instability and molecular consequen...

  5. 47 CFR 97.205 - Repeater station.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 5 2010-10-01 2010-10-01 false Repeater station. 97.205 Section 97.205... SERVICE Special Operations § 97.205 Repeater station. (a) Any amateur station licensed to a holder of a Technician, General, Advanced or Amateur Extra Class operator license may be a repeater. A holder of...

  6. 47 CFR 22.1015 - Repeater operation.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 2 2010-10-01 2010-10-01 false Repeater operation. 22.1015 Section 22.1015... Offshore Radiotelephone Service § 22.1015 Repeater operation. Offshore central stations may be used as repeater stations provided that the licensee is able to maintain control of the station, and in...

  7. ProtRepeatsDB: a database of amino acid repeats in genomes

    Directory of Open Access Journals (Sweden)

    Chauhan Virander S

    2006-07-01

    Full Text Available Abstract Background Genome wide and cross species comparisons of amino acid repeats is an intriguing problem in biology mainly due to the highly polymorphic nature and diverse functions of amino acid repeats. Innate protein repeats constitute vital functional and structural regions in proteins. Repeats are of great consequence in evolution of proteins, as evident from analysis of repeats in different organisms. In the post genomic era, availability of protein sequences encoded in different genomes provides a unique opportunity to perform large scale comparative studies of amino acid repeats. ProtRepeatsDB http://bioinfo.icgeb.res.in/repeats/ is a relational database of perfect and mismatch repeats, access to which is designed as a resource and collection of tools for detection and cross species comparisons of different types of amino acid repeats. Description ProtRepeatsDB (v1.2 consists of perfect as well as mismatch amino acid repeats in the protein sequences of 141 organisms, the genomes of which are now available. The web interface of ProtRepeatsDB consists of different tools to perform repeat s; based on protein IDs, organism name, repeat sequences, and keywords as in FASTA headers, size, frequency, gene ontology (GO annotation IDs and regular expressions (REGEXP describing repeats. These tools also allow formulation of a variety of simple, complex and logical queries to facilitate mining and large-scale cross-species comparisons of amino acid repeats. In addition to this, the database also contains sequence analysis tools to determine repeats in user input sequences. Conclusion ProtRepeatsDB is a multi-organism database of different types of amino acid repeats present in proteins. It integrates useful tools to perform genome wide queries for rapid screening and identification of amino acid repeats and facilitates comparative and evolutionary studies of the repeats. The database is useful for identification of species or organism specific

  8. Pentatricopeptide repeat proteins in plants.

    Science.gov (United States)

    Barkan, Alice; Small, Ian

    2014-01-01

    Pentatricopeptide repeat (PPR) proteins constitute one of the largest protein families in land plants, with more than 400 members in most species. Over the past decade, much has been learned about the molecular functions of these proteins, where they act in the cell, and what physiological roles they play during plant growth and development. A typical PPR protein is targeted to mitochondria or chloroplasts, binds one or several organellar transcripts, and influences their expression by altering RNA sequence, turnover, processing, or translation. Their combined action has profound effects on organelle biogenesis and function and, consequently, on photosynthesis, respiration, plant development, and environmental responses. Recent breakthroughs in understanding how PPR proteins recognize RNA sequences through modular base-specific contacts will help match proteins to potential binding sites and provide a pathway toward designing synthetic RNA-binding proteins aimed at desired targets.

  9. Two-dimensional quantum repeaters

    Science.gov (United States)

    Wallnöfer, J.; Zwerger, M.; Muschik, C.; Sangouard, N.; Dür, W.

    2016-11-01

    The endeavor to develop quantum networks gave rise to a rapidly developing field with far-reaching applications such as secure communication and the realization of distributed computing tasks. This ultimately calls for the creation of flexible multiuser structures that allow for quantum communication between arbitrary pairs of parties in the network and facilitate also multiuser applications. To address this challenge, we propose a two-dimensional quantum repeater architecture to establish long-distance entanglement shared between multiple communication partners in the presence of channel noise and imperfect local control operations. The scheme is based on the creation of self-similar multiqubit entanglement structures at growing scale, where variants of entanglement swapping and multiparty entanglement purification are combined to create high-fidelity entangled states. We show how such networks can be implemented using trapped ions in cavities.

  10. General benchmarks for quantum repeaters

    CERN Document Server

    Pirandola, Stefano

    2015-01-01

    Using a technique based on quantum teleportation, we simplify the most general adaptive protocols for key distribution, entanglement distillation and quantum communication over a wide class of quantum channels in arbitrary dimension. Thanks to this method, we bound the ultimate rates for secret key generation and quantum communication through single-mode Gaussian channels and several discrete-variable channels. In particular, we derive exact formulas for the two-way assisted capacities of the bosonic quantum-limited amplifier and the dephasing channel in arbitrary dimension, as well as the secret key capacity of the qubit erasure channel. Our results establish the limits of quantum communication with arbitrary systems and set the most general and precise benchmarks for testing quantum repeaters in both discrete- and continuous-variable settings.

  11. Hungarian repeat station survey, 2010

    Directory of Open Access Journals (Sweden)

    Péter Kovács

    2013-03-01

    Full Text Available The last Hungarian repeat station survey was completed between October 2010 and February 2011. Declination, inclination and the total field were observed using one-axial DMI fluxgate magnetometer mounted on Zeiss20A theodolite and GSM 19 Overhauser magnetometer. The magnetic elements of the sites were reduced to the epoch of 2010.5 on the basis of the continuous recordings of Tihany Geophysical Observatory. In stations located far from the reference observatory, the observations were carried out in the morning and afternoon in order to decrease the effect of the distant temporal correction. To further increase the accuracy, on-site dIdD variometer has also been installed near the Aggtelek station, in the Baradla cave, during the survey of the easternmost sites. The paper presents the technical details and the results of our last campaign. The improvement of the accuracy of the temporal reduction by the use of the local variometer is also reported.

  12. Quality control during repeated fryings

    Directory of Open Access Journals (Sweden)

    Cuesta, C.

    1998-08-01

    Full Text Available Most of the debate ¡s about how the slow or frequent turnover of fresh fat affects the deterioration, of fat used in frying. Then, the modification of different oils used in repeated fryings of potatoes without or with turnover of fresh oil, under similar frying conditions, was evaluated by two criteria: by measuring the total polar component isolated by column chromatography and by the evaluation of the specific compounds related to thermoxidative and hydrolytic alteration by High Performance Size Exclusion Chromatography (HPSEC. The results indicate that with frequent turnover of fresh oil, the critical level of 25% of polar material is rarely reached, and there are fewer problems with fat deterioration because the frying tended to increase the level of polar material and thermoxidative compounds (polymers and dimers of triglycerides and oxidized triglycerides in the fryer oil during the first fryings, followed by minor changes and a tendency to reach a near-steady state in successive fryings. However, in repeated frying of potatoes using a null turnover the alteration rate was higher being linear the relationship found between polar material or the different thermoxidative compounds and the number of fryings. On the other hand chemical reactions produced during deep-fat frying can be minimized by using proper oils. In addition the increased level of consumers awareness toward fat composition and its impact on human health could had an impact on the selection of fats for snacks and for industry. In this way monoenic fats are the most adequate from a nutritional point of view and for its oxidative stability during frying.

  13. Mouse repeated electroconvulsive seizure (ECS) does not reverse social stress effects but does induce behavioral and hippocampal changes relevant to electroconvulsive therapy (ECT) side-effects in the treatment of depression

    NARCIS (Netherlands)

    van Buel, Erin M; Sigrist, Hannes; Seifritz, Erich; Fikse, Lianne; Bosker, Fokko J; Schoevers, Robert A; Klein, Hans C; Pryce, Christopher R; Eisel, Ulrich Lm

    2017-01-01

    Electroconvulsive therapy (ECT) is an effective treatment for depression, but can have negative side effects including amnesia. The mechanisms of action underlying both the antidepressant and side effects of ECT are not well understood. An equivalent manipulation that is conducted in experimental

  14. Efficacy and tolerance of repeated oral doses of tolperisone hydrochloride in the treatment of painful reflex muscle spasm: results of a prospective placebo-controlled double-blind trial.

    Science.gov (United States)

    Pratzel, H G; Alken, R G; Ramm, S

    1996-10-01

    The efficacy and safety of oral tolperisone hydrochloride (Mydocalm) in the treatment of painful reflex muscle spasm was assessed in a prospective, randomized, double-blind, placebo-controlled trial. A total of 138 patients, aged between 20 and 75 years, with painful reflex muscle spasm associated with diseases of the spinal column or proximal joints were enrolled in eight rehabilitation centers. Patients were randomized to receive either 300 mg tolperisone hydrochloride or placebo for a period of 21 days. Both treatment groups recovered during the 3 weeks rehabilitation program. However, tolperisone hydrochloride proved to be significantly superior to placebo: the change score of the pressure pain threshold as the primary target parameter significantly increased during therapy with tolperisone hydrochloride (P = 0.03, valid-case-analysis) compared to the results obtained on placebo treatment. The overall assessment of efficacy by the patient also demonstrated significant differences in favor of tolperisone hydrochloride. Best results were seen in patients aged between 40 and 60 years with a history of complaints shorter than 1 year and with concomitant physical therapy. The evaluation of safety data, i.e., adverse events, biochemical and hematological laboratory parameters, demonstrated no differences between tolperisone hydrochloride and placebo. As a conclusion tolperisone hydrochloride represents an effective and safe treatment of painful reflex muscle spasm without the typical side effects of centrally active muscle relaxants.

  15. Decomposition of Straw in Soil after Stepwise Repeated Additions

    DEFF Research Database (Denmark)

    Sørensen, Lasse Holst

    1979-01-01

    of laboratory incubation, following the first repeated application, by determination of the total amount of labelled C in the soils and labelled C in the soil amino acids. The overall pattern of decomposition was similar whether the soil was amended with one or with several successive applications. Four years...... after the first repeated addition of labelled straw the soils were subjected to a number of “stress” treatments: addition of unlabelled glucose, air-drying, oven-drying, grinding and fumigation with vapour of chloroform, respectively. The CO2 that developed during the first 10 days after the treatments...... accounted for 2.6% of the labelled C in the soil amended with one repeated addition, and 1.0% in the soil amended with 4 repeated additions. The increase in the evolution of labelled CO2-C caused by the stress treatments ranged from 0.3 to 1.7% of the labelled C in the soil: air-drying had the least effect...

  16. A Prospective Study of Psychiatric Comorbidity and Recidivism Among Repeat DUI Offenders

    OpenAIRE

    Nelson, Sarah E.; Belkin, Katerina; LaPlante, Debi A.; Bosworth, Leslie; Shaffer, Howard J.

    2015-01-01

    Psychiatric comorbidity has emerged as a key element distinguishing DUI offenders from others, and, in some cases, distinguishing repeat offenders from first-time offenders. This paper utilizes a prospective design to determine whether the comorbid disorders identified among repeat DUI offenders can predict recidivism. Seven hundred forty-three repeat DUI offenders were recruited from a two-week inpatient treatment program at which they received a standardized mental health assessment and fol...

  17. Negative modulation of GABAA α5 receptors by RO4938581 attenuates discrete sub-chronic and early postnatal phencyclidine (PCP)-induced cognitive deficits in rats.

    Science.gov (United States)

    Redrobe, John P; Elster, Lisbeth; Frederiksen, Kristen; Bundgaard, Christoffer; de Jong, Inge E M; Smith, Garrick P; Bruun, Anne Techau; Larsen, Peter H; Didriksen, Michael

    2012-06-01

    A growing body of evidence suggests that negative modulation of γ-aminobutyric acid (GABA) GABA(A) α5 receptors may be a promising strategy for the treatment of certain facets of cognitive impairment; however, selective modulators of GABA(A) α5 receptors have not yet been tested in "schizophrenia-relevant" cognitive assay/model systems in animals. The objectives of this study were to investigate the potential of RO4938581, a negative modulator of GABA(A) α5 receptors, and to attenuate cognitive impairments induced following sub-chronic (sub-PCP) and early postnatal PCP (neo-PCP) administration in the novel object recognition (NOR) and intra-extradimensional shift (ID/ED) paradigms in rats. Complementary in vitro, ex vivo and in vivo studies were performed to confirm negative modulatory activity of RO4938581 and to investigate animal model validity, concept validity and potential side effect issues, respectively. In vitro studies confirmed the reported negative modulatory activity of RO4938581, whilst immunohistochemical analyses revealed significantly reduced parvalbumin-positive cells in the prefrontal cortex of sub-PCP- and neo-PCP-treated rats. RO4938581 (1 mg/kg) ameliorated both sub-PCP- and neo-PCP-induced cognitive deficits in NOR and ID/ED performance, respectively. In contrast, QH-II-066 (1 and 3 mg/kg), a GABA(A) α5 receptor positive modulator, impaired cognitive performance in the NOR task when administered to vehicle-treated animals. Additional studies revealed that both RO4938581 (1 mg/kg) and QH-II-066 (1 and 3 mg/kg) attenuated amphetamine-induced hyperactivity in rats. Taken together, these novel findings suggest that negative modulation of GABA(A) α5 receptors may represent an attractive treatment option for the cognitive impairments, and potentially positive symptoms, associated with schizophrenia.

  18. [Study of personal best value of peak expiratory flow in patients with asthma--comparison of the highest value of daily PEF under good control and the highest value of daily PEF obtained after using repeated inhaled beta2-agonist during high-dose inhaled steroid treatment].

    Science.gov (United States)

    Watanabe, Naoto; Makino, Sohei; Kihara, Norio; Fukuda, Takeshi

    2008-12-01

    In the guideline for asthma management, it is important to find the personal best value of peak expiratory flow (best PEF). Recently, we have substituted the highest value of PEF in daily life under good control (daily highest PEF) for the best PEF. In the present study, we considered whether the daily highest PEF could be used as the best PEF or not. Subjects were 30 asthmatics who were well controlled but whose baseline PEF values were less than 80 percent of predicted values. We compared the daily highest PEF and the highest of PEF obtained after repeated inhaled beta2-agonist (salbutamol MDI every 20 minutes three times). All subjects then received 1600 microg/day of beclomethasone dipropionate (BDP) for 4 to 8 weeks. We studied the effect of high-dose inhaled steroid treatment on each PEF value and compared the daily highest PEF and the highest PEF obtained after using repeated salbutamol MDI during high dose inhaled steroid therapy on the examination day again. The baseline PEF, daily highest PEF and the highest PEF obtained after salbutamol MDI were significantly less than the each values obtained after high-dose BDP. The best PEF value of them was the value obtained after repeated salbutamol MDI during high dose BDP. We suggest that the daily highest PEF under good control is not a substitute for best PEF because it changes according to the degree of improvement of airway inflammation. We recommend that a course of high dose inhaled steroid is effective in finding the best value of PEF for each individual with moderate asthma.

  19. Repeat urine cultures in children with urinary tract infection

    Directory of Open Access Journals (Sweden)

    Risky Vitria Prasetyo

    2012-05-01

    Full Text Available Background Urinary tract infections (UTIs are the second leading cause of infection in children, following respiratory tract infections. Repeat urine cultures after antibiotic treatment are routinely obtained in clinical practice to verify proof of bacteriologic cure. The American Academy of Pediatrics does not recommended repeat cultures, due to increased cost and discomfort to patients. Objective To determine the frequency of positive repeat urine cultures after 3 days of antibiotics in children with UTIs. Methods We conducted a retrospective study on children with UTIs who visited the Division of Pediatric Nephrology, Department of Child Health at Dr. Soetomo Hospital, Surabaya from January 2006 to December 2011. Results of repeat urine cultures were obtained after 3 days of antibiotic treatment. Descriptive statistics were used to analyze the data. Results Of the 779 pediatric UTI cases, repeat urine cultures were performed in 264 (33.9% cases. Of the 264 patients who comprised our study, there were similar numbers of girls and boys (50.4% vs. 49.6%, respectively. The mean age of patients was 43.9 (SD 1.59 months and 35.5% of subjects were aged under 1 year. In the initial urine cultures of our subjects, Escherichia coli was the most common organism found, with 92 cases (34.8%, compared to 58 cases (21.9% of Klebsiella pneumoniae and 29 cases (10.9% of Pseudomonas aeruginosa. Rrepeat urine cultures showed no bacterial growth in 168 cases (63.6%. Conclusion Mostly negative repeat urine cultures will probably obviate the need of this test in daily routine practice. [Paediatr Indones. 2012;52:170-4].

  20. Strengthening concept learning by repeated testing.

    Science.gov (United States)

    Wiklund-Hörnqvist, Carola; Jonsson, Bert; Nyberg, Lars

    2014-02-01

    The aim of this study was to examine whether repeated testing with feedback benefits learning compared to rereading of introductory psychology key-concepts in an educational context. The testing effect was examined immediately after practice, after 18 days, and at a five-week delay in a sample of undergraduate students (n = 83). The results revealed that repeated testing with feedback significantly enhanced learning compared to rereading at all delays, demonstrating that repeated retrieval enhances retention compared to repeated encoding in the short- and the long-term. In addition, the effect of repeated testing was beneficial for students irrespectively of working memory capacity. It is argued that teaching methods involving repeated retrieval are important to consider by the educational system.

  1. A Comparison of Two Reading Fluency Methods: Repeated Readings to a Fluency Criterion and Interval Sprinting

    Science.gov (United States)

    Kostewicz, Douglas E.; Kubina, Richard M., Jr.

    2010-01-01

    Teachers have used the method of repeated readings to build oral reading fluency in students with and without special needs. A new fluency building intervention called interval sprinting uses shorter timing intervals (i.e., sprints) across a passage. This study used an alternating treatment design to compare repeated readings and interval…

  2. Repeat concussions in the national football league.

    Science.gov (United States)

    Casson, Ira R; Viano, David C; Powell, John W; Pellman, Elliot J

    2011-01-01

    Repeat concussion is an important issue in the National Football League (NFL). An initial description of repeat injuries was published for 6 years (1996-2001). The characteristics and frequency of repeat concussion in the NFL have not changed in the subsequent 6 years (2002-2007). Case control. From 1996 to 2007, concussions were reported using a standardized form documenting signs and symptoms, loss of consciousness and medical action taken. Data on repeat concussions were analyzed for the 12 years and compared between the 2 periods. In 2002-2007, 152 players had repeat concussions (vs 160 in 1996-2001); 44 had 3+ head injuries (vs 52). The positions most often associated with repeat concussion in 2002-2007 were the defensive secondary, kick unit, running back, and linebacker. The odds for repeat concussion were elevated for wide receivers, tight ends, and linebackers but lower than in the earlier period. During 2002-2007, over half of players with repeat concussion were removed from play, and fewer immediately returned (vs 1996-2001). The average duration between concussions was 1.25 years for 2002-2007 and 1.65 years for the 12-year period. Over 12 years, 7.6% of all repeat concussions occurred within 2 weeks of the prior concussion. The defensive secondary, kick unit, running back, and linebacker have the highest incidence of repeat concussion. During 2002-2007, more than half of players with repeat concussion were removed from play, and only a fraction immediately returned. Although concussion was managed more conservatively by team physicians in the recent 6 years, repeat concussions occurred at similar rates during both periods.

  3. Automated quality checks on repeat prescribing.

    OpenAIRE

    Rogers, Jeremy E; Wroe, Christopher J; Roberts, Angus; Swallow, Angela; Stables, David; Cantrill, Judith A; Rector, Alan L.

    2003-01-01

    BACKGROUND: Good clinical practice in primary care includes periodic review of repeat prescriptions. Markers of prescriptions that may need review have been described, but manually checking all repeat prescriptions against the markers would be impractical. AIM: To investigate the feasibility of computerising the application of repeat prescribing quality checks to electronic patient records in United Kingdom (UK) primary care. DESIGN OF STUDY: Software performance test against benchmark manual...

  4. Short Tandem Repeat DNA Internet Database

    Science.gov (United States)

    SRD 130 Short Tandem Repeat DNA Internet Database (Web, free access)   Short Tandem Repeat DNA Internet Database is intended to benefit research and application of short tandem repeat DNA markers for human identity testing. Facts and sequence information on each STR system, population data, commonly used multiplex STR systems, PCR primers and conditions, and a review of various technologies for analysis of STR alleles have been included.

  5. Fatal Renal Failure in a Spinal Cord Injury Patient with Vesicoureteric Reflux Who Underwent Repeated Ureteric Reimplantations Unsuccessfully: Treatment Should Focus on Abolition of High Intravesical Pressures rather than Surgical Correction of Reflux

    Directory of Open Access Journals (Sweden)

    Subramanian Vaidyanathan

    2012-01-01

    Full Text Available A 29-year-old man developed paraplegia at T-10 level due to road traffic accident in 1972. Both kidneys were normal and showed good function on intravenous urography. Division of external urethral sphincter was performed in 1973. In 1974, cystogram showed retrograde filling of left renal tract, which was hydronephrotic. Left ureteric reimplantation was performed. Following surgery, cystogram revealed marked retrograde filling of left renal tract as before. Penile sheath drainage was continued. In 1981, intravenous urography revealed bilateral severe hydronephrosis. Left ureteric reimplantation was performed again in 1983. Blood pressure was 220/140 mm Hg; this patient was prescribed atenolol. Cystogram showed gross left vesicoureteral reflux. Intermittent catheterisation was commenced in 2001. In 2007, proteinuria was 860 mg/day. This patient developed progressive renal failure and expired in 2012. In a spinal cord injury patient with vesicoureteral reflux, the treatment should focus on abolition of high intravesical pressures rather than surgical correction of vesicoureteric reflux. Detrusor hyperactivity and high intravesical pressures are the basic causes for vesicoureteral reflux in spinal cord injury patients. Therefore, it is important to manage spinal cord injury patients with neuropathic bladder by intermittent catheterisations along with antimuscarinic drug therapy in order to abolish high detrusor pressures and prevent vesicoureteral reflux. Angiotensin-converting enzyme inhibitors or angiotensin-receptor-blocking agents should be prescribed even in the absence of hypertension when a spinal cord injury patient develops vesicoureteral reflux and proteinuria.

  6. Repeated Nrf2 stimulation using sulforaphane protects fibroblasts from ionizing radiation

    Energy Technology Data Exchange (ETDEWEB)

    Mathew, Sherin T.; Bergström, Petra; Hammarsten, Ola, E-mail: ola.hammarsten@clinchem.gu.se

    2014-05-01

    Most of the cytotoxicity induced by ionizing radiation is mediated by radical-induced DNA double-strand breaks. Cellular protection from free radicals can be stimulated several fold by sulforaphane-mediated activation of the transcription factor Nrf2 that regulates more than 50 genes involved in the detoxification of reactive substances and radicals. Here, we report that repeated sulforaphane treatment increases radioresistance in primary human skin fibroblasts. Cells were either treated with sulforaphane for four hours once or with four-hour treatments repeatedly for three consecutive days prior to radiation exposure. Fibroblasts exposed to repeated-sulforaphane treatment showed a more pronounced dose-dependent induction of Nrf2-regulated mRNA and reduced amount of radiation-induced free radicals compared with cells treated once with sulforaphane. In addition, radiation- induced DNA double-strand breaks measured by gamma-H2AX foci were attenuated following repeated sulforaphane treatment. As a result, cellular protection from ionizing radiation measured by the 5-ethynyl-2′-deoxyuridine (EdU) assay was increased, specifically in cells exposed to repeated sulforaphane treatment. Sulforaphane treatment was unable to protect Nrf2 knockout mouse embryonic fibroblasts, indicating that the sulforaphane-induced radioprotection was Nrf2-dependent. Moreover, radioprotection by repeated sulforaphane treatment was dose-dependent with an optimal effect at 10 uM, whereas both lower and higher concentrations resulted in lower levels of radioprotection. Our data indicate that the Nrf2 system can be trained to provide further protection from radical damage. - Highlights: • Repeated treatment with sulforaphane protects fibroblasts from ionizing radiation • Repeated sulforaphane treatment attenuates radiation induced ROS and DNA damage • Sulforaphane mediated protection is Nrf2 dependent.

  7. Modelling repeatedly flaring delta-sunspots

    CERN Document Server

    Chatterjee, Piyali; Carlsson, Mats

    2016-01-01

    Active regions (AR) appearing on the surface of the Sun are classified into $\\alpha$, $\\beta$, $\\gamma$, and $\\delta$ by the rules of the Mount Wilson Observatory, California on the basis of their topological complexity. Amongst these, the $\\delta$-sunspots are known to be super-active and produce the most X-ray flares. Here, we present results from a simulation of the Sun by mimicking the upper layers and the corona, but starting at a more primitive stage than any earlier treatment. We find that this initial state consisting of only a thin sub-photospheric magnetic sheet breaks into multiple flux-tubes which evolve into a colliding-merging system of spots of opposite polarity upon surface emergence, similar to those often seen on the Sun. The simulation goes on to produce many exotic $\\delta$-sunspot associated phenomena: repeated flaring in the range of typical solar flare energy release and ejective helical flux ropes with embedded cool-dense plasma filaments resembling solar coronal mass ejections.

  8. Repeatability & Workability Evaluation of SIGMOD 2009

    KAUST Repository

    Manegold, Stefan

    2010-12-15

    SIGMOD 2008 was the first database conference that offered to test submitters\\' programs against their data to verify the repeatability of the experiments published [1]. Given the positive feedback concerning the SIGMOD 2008 repeatability initiative, SIGMOD 2009 modified and expanded the initiative with a workability assessment.

  9. 19 CFR 10.474 - Repeated false or unsupported preference claims.

    Science.gov (United States)

    2010-04-01

    ... States-Chile Free Trade Agreement Origin Verifications and Determinations § 10.474 Repeated false or... qualifies as originating, CBP may deny subsequent claims for preferential tariff treatment on...

  10. Reward modulation of contextual cueing: Repeated context overshadows repeated target location.

    Science.gov (United States)

    Sharifian, Fariba; Contier, Oliver; Preuschhof, Claudia; Pollmann, Stefan

    2017-08-07

    Contextual cueing can be enhanced by reward. However, there is a debate if reward is associated with the repeated target-distractor configurations or with the repeated target locations that occur in both repeated and new displays. Based on neuroimaging evidence, we hypothesized that reward becomes associated with the target location only in new displays, but not in repeated displays, where the repeated target location is overshadowed by the more salient repeated target-distractor configuration. To test this hypothesis, we varied the reward value associated with the same target location in repeated and new displays. The results confirmed the overshadowing hypothesis in that search facilitation in repeated target-distractor configurations was modulated by the variable value associated with the target location. This effect was observed mainly in early learning.

  11. Childhood experiences and repeated suicidal behavior

    DEFF Research Database (Denmark)

    Krarup, Gertrud; Nielsen, Bent; Rask, P

    1991-01-01

    The aim of this study was to elucidate the influence of various events in childhood on suicidal behavior in adult age. For this purpose, 99 patients admitted to the Department of Psychiatry of Odense University Hospital after making a suicide attempt were followed for 5 years, to register repeated...... suicidal behavior. The results showed that three fourths of the patients attempted suicide more than once (62% nonfatal and 14% fatal outcome). The sex distribution was about the same among the first-evers as among the repeaters. Most repeaters were younger people in their twenties and thirties......, and the first-evers on average were past the age of 40. Somewhat unexpectedly, significantly more repeaters than first-evers had grown up with both their parents. However, the results also showed that significantly more repeaters than first-evers had had an unhappy childhood. This indicates...

  12. UK 2009-2010 repeat station report

    Directory of Open Access Journals (Sweden)

    Thomas J.G. Shanahan

    2013-03-01

    Full Text Available The British Geological Survey is responsible for conducting the UK geomagnetic repeat station programme. Measurements made at the UK repeat station sites are used in conjunction with the three UK magnetic observatories: Hartland, Eskdalemuir and Lerwick, to produce a regional model of the local field each year. The UK network of repeat stations comprises 41 stations which are occupied at approximately 3-4 year intervals. Practices for conducting repeat station measurements continue to evolve as advances are made in survey instrumentation and as the usage of the data continues to change. Here, a summary of the 2009 and 2010 UK repeat station surveys is presented, highlighting the measurement process and techniques, density of network, reduction process and recent results.

  13. A Prospective Study of Psychiatric Comorbidity and Recidivism Among Repeat DUI Offenders.

    Science.gov (United States)

    Nelson, Sarah E; Belkin, Katerina; LaPlante, Debi A; Bosworth, Leslie; Shaffer, Howard J

    2015-04-13

    Psychiatric comorbidity has emerged as a key element distinguishing DUI offenders from others, and, in some cases, distinguishing repeat offenders from first-time offenders. This paper utilizes a prospective design to determine whether the comorbid disorders identified among repeat DUI offenders can predict recidivism. Seven hundred forty-three repeat DUI offenders were recruited from a two-week inpatient treatment program at which they received a standardized mental health assessment and followed across five years post-treatment to track DUI offense, motor vehicle-related offenses, and general criminal offenses. Psychiatric comorbidity, though it did not predict DUI recidivism specifically, predicted criminal re-offense more generally. In addition, there was a specific relationship between lifetime attention deficit disorder and repeated motor vehicle-related offenses. These findings suggest that for many repeat offenders, DUI is one outlet in a constellation of criminal behavior, and that psychiatric comorbidity increases vulnerability for criminal re-offense.

  14. Improving Oral Reading Fluency through Response Opportunities: A Comparison of Phrase Drill Error Correction with Repeated Readings

    Science.gov (United States)

    Begeny, John C.; Daly, Edward J., III; Valleley, Rachel J.

    2006-01-01

    The purpose of this study was to compare two oral reading fluency treatments (repeated readings and phrase drill error correction) which differ in the way they prompt student responding. Repeated readings (RR) and phrase drill (PD) error correction were alternated with a baseline and a reward condition within an alternating treatments design with…

  15. Strabismus: Botox Treatment

    Medline Plus

    Full Text Available ... 4 months. However, after repeat treatments the effect can be longer lasting. The reason why the effect ... restored. In adults and cooperative teenagers Botox treatment can be carried out in clinic using anesthetic drops ...

  16. Strabismus: Botox Treatment

    Medline Plus

    Full Text Available ... treatment. The muscle will normally regain its normal function after 3-4 months. However, after repeat treatments ... 2017 Stargardt Disease (STGD) Aug 21, 2017 Surgical Management of Strabismus Jun 10, 2017 Binocular Vision and ...

  17. Mid-Childhood Bone Mass After Exposure to Repeat Doses of Antenatal Glucocorticoids: A Randomized Trial.

    Science.gov (United States)

    McKinlay, Christopher J D; Cutfield, Wayne S; Battin, Malcolm R; Dalziel, Stuart R; Crowther, Caroline A; Harding, Jane E

    2017-05-01

    Treatment of women at risk for preterm birth with repeat doses of glucocorticoids reduces neonatal morbidity, but could have adverse effects on skeletal development. We assessed whether exposure to repeat antenatal betamethasone alters bone mass in children whose mothers participated in the Australasian Collaborative Trial of Repeat Doses of Corticosteroids. Women were randomized to a single dose of betamethasone or placebo, ≥7 days after an initial course of glucocorticoids, repeated each week that they remained at risk for preterm birth at children underwent whole-body dual-energy radiograph absorptiometry at 6 to 8 years' corrected age. Of 212 eligible childhood survivors, 185 were studied (87%; 91 repeat betamethasone group; 94 placebo [single course] group). Children exposed to repeat antenatal betamethasone and those exposed to placebo had similar whole-body bone mineral content (median repeat betamethasone: 553 g, interquartile range: 442-712 g; placebo: 567 g, interquartile range: 447-750 g; geometric mean ratio: 0.99; 95% confidence interval: 0.94-1.03, P = .55) and bone area (median repeat betamethasone 832 cm(2), interquartile range: 693-963 cm(2); placebo: 822 cm(2), interquartile range: 710-1020 cm(2); geometric mean ratio: 0.99, 95% confidence interval: 0.92-1.07, P = .75). Exposure to repeat doses of antenatal betamethasone compared with a single course of glucocorticoids does not alter bone mass in mid-childhood. Copyright © 2017 by the American Academy of Pediatrics.

  18. The Moral Maturity of Repeater Delinquents.

    Science.gov (United States)

    Petronio, Richard J.

    1980-01-01

    Differences in moral development (as conceived by Kohlberg) were examined in a sample of delinquent teenagers. The repeater group was not found, as had been hypothesized, to be lower on moral maturity than those who engaged in less delinquency. (GC)

  19. Star repeaters for fiber optic links.

    Science.gov (United States)

    McMahon, D H; Gravel, R L

    1977-02-01

    A star repeater combines the functions of a passive star coupler and a signal regenerating amplifier. By more effectively utilizing the light power radiated by a light emitting diode, the star repeater can, when used with small diameter channels, couple as much power to all receivers of a multiterminal link as would be coupled to the single receiver of a simple point-to-point link.

  20. Digital repeat analysis; setup and operation.

    Science.gov (United States)

    Nol, J; Isouard, G; Mirecki, J

    2006-06-01

    Since the emergence of digital imaging, there have been questions about the necessity of continuing reject analysis programs in imaging departments to evaluate performance and quality. As a marketing strategy, most suppliers of digital technology focus on the supremacy of the technology and its ability to reduce the number of repeats, resulting in less radiation doses given to patients and increased productivity in the department. On the other hand, quality assurance radiographers and radiologists believe that repeats are mainly related to positioning skills, and repeat analysis is the main tool to plan training needs to up-skill radiographers. A comparative study between conventional and digital imaging was undertaken to compare outcomes and evaluate the need for reject analysis. However, digital technology still being at its early development stages, setting a credible reject analysis program became the major task of the study. It took the department, with the help of the suppliers of the computed radiography reader and the picture archiving and communication system, over 2 years of software enhancement to build a reliable digital repeat analysis system. The results were supportive of both philosophies; the number of repeats as a result of exposure factors was reduced dramatically; however, the percentage of repeats as a result of positioning skills was slightly on the increase for the simple reason that some rejects in the conventional system qualifying for both exposure and positioning errors were classified as exposure error. The ability of digitally adjusting dark or light images reclassified some of those images as positioning errors.

  1. Quantum Key Distribution over Probabilistic Quantum Repeaters

    CERN Document Server

    Amirloo, Jeyran; Majedi, A Hamed

    2010-01-01

    A feasible route towards implementing long-distance quantum key distribution (QKD) systems relies on probabilistic schemes for entanglement distribution and swapping as proposed in the work of Duan, Lukin, Cirac, and Zoller (DLCZ) [Nature 414, 413 (2001)]. Here, we calculate the conditional throughput and fidelity of entanglement for DLCZ quantum repeaters, by accounting for the DLCZ self-purification property, in the presence of multiple excitations in the ensemble memories as well as loss and other sources of inefficiency in the channel and measurement modules. We then use our results to find the generation rate of secure key bits for QKD systems that rely on DLCZ quantum repeaters. We compare the key generation rate per logical memory employed in the two cases of with and without a repeater node. We find the cross-over distance beyond which the repeater system outperforms the non-repeater one. That provides us with the optimum inter-node distancing in quantum repeater systems. We also find the optimal exci...

  2. Remarkable selective constraints on exonic dinucleotide repeats.

    Science.gov (United States)

    Haasl, Ryan J; Payseur, Bret A

    2014-09-01

    Long dinucleotide repeats found in exons present a substantial mutational hazard: mutations at these loci occur often and generate frameshifts. Here, we provide clear and compelling evidence that exonic dinucleotides experience strong selective constraint. In humans, only 18 exonic dinucleotides have repeat lengths greater than six, which contrasts sharply with the genome-wide distribution of dinucleotides. We genotyped each of these dinucleotides in 200 humans from eight 1000 Genomes Project populations and found a near-absence of polymorphism. More remarkably, divergence data demonstrate that repeat lengths have been conserved across the primate phylogeny in spite of what is likely considerable mutational pressure. Coalescent simulations show that even a very low mutation rate at these loci fails to explain the anomalous patterns of polymorphism and divergence. Our data support two related selective constraints on the evolution of exonic dinucleotides: a short-term intolerance for any change to repeat length and a long-term prevention of increases to repeat length. In general, our results implicate purifying selection as the force that eliminates new, deleterious mutants at exonic dinucleotides. We briefly discuss the evolution of the longest exonic dinucleotide in the human genome--a 10 x CA repeat in fibroblast growth factor receptor-like 1 (FGFRL1)--that should possess a considerably greater mutation rate than any other exonic dinucleotide and therefore generate a large number of deleterious variants. © 2014 The Author(s). Evolution © 2014 The Society for the Study of Evolution.

  3. Dynamic combinatorial libraries of artificial repeat proteins.

    Science.gov (United States)

    Eisenberg, Margarita; Shumacher, Inbal; Cohen-Luria, Rivka; Ashkenasy, Gonen

    2013-06-15

    Repeat proteins are found in almost all cellular systems, where they are involved in diverse molecular recognition processes. Recent studies have suggested that de novo designed repeat proteins may serve as universal binders, and might potentially be used as practical alternative to antibodies. We describe here a novel chemical methodology for producing small libraries of repeat proteins, and screening in parallel the ligand binding of library members. The first stage of this research involved the total synthesis of a consensus-based three-repeat tetratricopeptide (TPR) protein (~14 kDa), via sequential attachment of the respective peptides. Despite the effectiveness of the synthesis and ligation steps, this method was found to be too demanding for the production of proteins containing variable number of repeats. Additionally, the analysis of binding of the individual proteins was time consuming. Therefore, we designed and prepared novel dynamic combinatorial libraries (DCLs), and show that their equilibration can facilitate the formation of TPR proteins containing up to eight repeating units. Interestingly, equilibration of the library building blocks in the presence of the biologically relevant ligands, Hsp90 and Hsp70, induced their oligomerization into forming more of the proteins with large recognition surfaces. We suggest that this work presents a novel simple and rapid tool for the simultaneous screening of protein mixtures with variable binding surfaces, and for identifying new binders for ligands of interest.

  4. Effects of repeated regrouping on horse behaviour and injuries

    DEFF Research Database (Denmark)

    Christensen, Janne Winther; Søndergaard, Eva; Thodberg, Karen;

    2011-01-01

    Domestic horses are faced with social challenges throughout their lives due to limitations in social contact, space restrictions and frequent changes in social companionship. This is in contrast to natural conditions where horses live in relatively stable harem bands. Currently, little is known...... about how repeated regrouping affect horse behaviour and welfare, and it is unknown whether horses may adapt to regrouping. In this study, we aimed to investigate the effects of an unstable group structure, caused by weekly regroupings, on behaviour and frequency of injuries in young horses. Forty......, to repeated regrouping. Compared to horses in Stable groups, more agonistic behaviour was shown by horses in Unstable groups (i.e. non-contact agonistic; F1,65 = 5.60, P = 0.02), whereas there was no treatment effect on other variables. The level of play behaviour appeared, however, to be more variable...

  5. Caffeine Ingestion Improves Repeated Freestyle Sprints in Elite Male Swimmers

    Directory of Open Access Journals (Sweden)

    Paul S.R. Goods, Grant Landers, Sacha Fulton

    2017-03-01

    Full Text Available The purpose of this investigation was to determine the efficacy of a moderate dose of caffeine to improve repeat-sprint performance in elite freestyle sprinters. Nine highly trained male swimmers performed 6 x 75 m freestyle sprints on two occasions 1-h after consuming either 3 mg·kg-1 caffeine (CAF, or placebo, in a cross-over manner. Capillary blood samples for the analysis of blood lactate concentration and pH were collected after the 1st, 3rd, and 5th sprint, while heart rate and perceived exertion (RPE were collected after every sprint. There was a moderate effect for improved mean sprint time in the CAF condition (0.52 s; 1.3%; d = 0.50. When assessed individually, there was a large effect for improved performance in sprints 3 (1.00 s; 2.5%; d = 1.02 and 4 (0.84 s; 2.1%; d = 0.84 in CAF compared to placebo, with worthwhile performance improvement found for each of the first 5 sprints. There was a significant treatment effect for higher blood lactate concentration for CAF (p = 0.029, and a significant treatment*time effect for reduced pH in the CAF condition (p = 0.004. Mean heart rate (167 ± 9 bpm vs 169 ± 7 bpm and RPE (17 ± 1 vs 17 ± 1 were not different between placebo and CAF trials, respectively. This investigation is the first to demonstrate enhanced repeat-sprint ability in swimmers following acute caffeine ingestion. It appears likely that the combination of a moderate dose of caffeine (3-6 mg·kg-1 with trained athletes is most likely to enhance repeat-sprint ability in various athletic populations; however, the exact mechanism(s for an improved repeat-sprint ability following acute caffeine ingestion remain unknown.

  6. Metabolic rate variation over adult lifetime in the butterfly Vanessa cardui (Nymphalidae: Nymphalinae): aging, feeding, and repeatability.

    Science.gov (United States)

    Woods, William A; Wood, C A L; Ebersole, John; Stevenson, R D

    2010-01-01

    Questions about the adaptive importance of metabolic rate can be approached only when measurements of differences between individuals are repeatable. We made daily measurements of CO(2) production, body mass, and food uptake over the adult life span of unmated Vanessa cardui kept under constant environmental conditions in both fed and unfed treatments. Mass and CO(2) production generally declined with age in both treatments, though with much day-to-day variability in the fed treatment. For the full samples, metabolic rate was repeatable for the unfed treatment (repeatability r = 0.60) but not for the fed treatment (r = 0.03). Differences between fed and unfed individuals of the same age range were repeatable for the unfed treatment (r = 0.39) but not for the fed treatment (r = -0.20). Removing age effects on CO(2) production yielded still higher repeatability in the unfed treatment (r = 0.83), though not in fed butterflies of the same age range (r = -0.02). However, repeatability of CO(2) production of fed butterflies increased sharply with age, rising to 0.82 for butterflies age 8-10 d. Although food uptake mass was repeatable (r = 0.52), feeding history explained little variation in CO(2) production. We conclude that for V. cardui and possibly for other insects of similar feeding habit, variation in metabolic rate between individuals is best represented by measurements of unfed individuals of the same age or of older fed individuals.

  7. Automated genotyping of dinucleotide repeat markers

    Energy Technology Data Exchange (ETDEWEB)

    Perlin, M.W.; Hoffman, E.P. [Carnegie Mellon Univ., Pittsburgh, PA (United States)]|[Univ. of Pittsburgh, PA (United States)

    1994-09-01

    The dinucleotide repeats (i.e., microsatellites) such as CA-repeats are a highly polymorphic, highly abundant class of PCR-amplifiable markers that have greatly streamlined genetic mapping experimentation. It is expected that over 30,000 such markers (including tri- and tetranucleotide repeats) will be characterized for routine use in the next few years. Since only size determination, and not sequencing, is required to determine alleles, in principle, dinucleotide repeat genotyping is easily performed on electrophoretic gels, and can be automated using DNA sequencers. Unfortunately, PCR stuttering with these markers generates not one band for each allele, but a pattern of bands. Since closely spaced alleles must be disambiguated by human scoring, this poses a key obstacle to full automation. We have developed methods that overcome this obstacle. Our model is that the observed data is generated by arithmetic superposition (i.e., convolution) of multiple allele patterns. By quantitatively measuring the size of each component band, and exploiting the unique stutter pattern associated with each marker, closely spaced alleles can be deconvolved; this unambiguously reconstructs the {open_quotes}true{close_quotes} allele bands, with stutter artifact removed. We used this approach in a system for automated diagnosis of (X-linked) Duchenne muscular dystrophy; four multiplexed CA-repeats within the dystrophin gene were assayed on a DNA sequencer. Our method accurately detected small variations in gel migration that shifted the allele size estimate. In 167 nonmutated alleles, 89% (149/167) showed no size variation, 9% (15/167) showed 1 bp variation, and 2% (3/167) showed 2 bp variation. We are currently developing a library of dinucleotide repeat patterns; together with our deconvolution methods, this library will enable fully automated genotyping of dinucleotide repeats from sizing data.

  8. Repeated Renal Biopsy - A Predictive Tool to Assess the Probability of Renal Flare in Lupus Nephritis.

    Science.gov (United States)

    Piñeiro, Gastón J; Arrizabalaga, Pilar; Solé, Manel; Abellana, Rosa M; Espinosa, Gerard; Cervera, Ricard

    2016-01-01

    How one responds to treatment of lupus nephritis (LN) is based on clinical features, but the activity in renal biopsy (RB) is uncertain. We have described the therapeutic decisions after performing a repeated RB on the assessment of response to intravenous cyclophosphamide (IC) and the possible prognostic role of this repeated RB. Clinical, laboratory and histological features at the initial RB and repeated RB were analyzed in 35 patients. Data in the initial versus the repeated RB were serum creatinine 1.23 ± 1.08 and 0.96 ± 0.45 mg/dl (p < 0.05), glomerular filtration rate <60 ml/min in 12 and 5% patients and proteinuria 4.1 ± 2.8 vs. 0.6 1.1 g/day (p < 0.05). Significant differences were detected in hematuria, nephrotic syndrome and serological immune features. Complete renal remission was reached in 60% (n = 21) at the time of the repeated RB, partial remission in 31.4% (n = 11), and no response IC in 8.6% (n = 3). Nine patients showed proliferative forms in the repeated RB, 3 of them had proteinuria <1 g/day. Just after the repeated RB, 34.3% increased or started a new immunosuppressive therapy, 17.1% remained with the same complementary IST, and 14.3% decreased or stopped it. In the follow-up post repeated RB, 34.5% without active lesions showed a renal flare versus 77.8% with active lesions (p = 0.04). The mean time was 120 and 45 months, respectively. A repeated biopsy in LN distinguishes patients in true remission from those in apparent remission. By doing this, we can identify patients who could benefit from intensified treatment and for whom unnecessary treatment methods can be modified or eliminated. © 2016 S. Karger AG, Basel.

  9. Genome-Wide Demethylation Promotes Triplet Repeat Instability Independently of Homologous Recombination

    Science.gov (United States)

    Dion, Vincent; Lin, Yunfu; Price, Brandee A.; Fyffe, Sharyl L.; Seluanov, Andrei; Gorbunova, Vera; Wilson, John H.

    2008-01-01

    Trinucleotide repeat instability is intrinsic to a family of human neurodegenerative diseases. The mechanism leading to repeat length variation is unclear. We previously showed that treatment with the demethylating agent 5-aza-2′-deoxycytidine (5-aza-CdR) dramatically increases triplet repeat instability in mammalian cells. Based on previous reports that demethylation increases homologous recombination (HR), and our own observations that HR destabilizes triplet repeats, we hypothesized that demethylation alters repeat stability by stimulating HR. Here, we test that hypothesis at the Aprt (adenosine phosphoribosyl transferase) locus in CHO cells, where CpG demethylation and HR have both been shown to increase CAG repeat instability. We find that the rate of HR at the Aprt locus is not altered by demethylation. The spectrum of recombinants, however, was shifted from the usual 6:1 ratio of conversions to crossovers to more equal proportions in 5-aza-CdR-treated cells. The subtle influences of demethylation on HR at the Aprt locus are not sufficient to account for its dramatic effects on repeat instability. We conclude that 5-aza-CdR promotes triplet repeat instability independently of HR. PMID:18083071

  10. Mining of simple sequence repeats in the Genome of Gentianaceae

    Directory of Open Access Journals (Sweden)

    R Sathishkumar

    2011-01-01

    Full Text Available Simple sequence repeats (SSRs or short tandem repeats are short repeat motifs that show high level of length polymorphism due to insertion or deletion mutations of one or more repeat types. Here, we present the detection and abundance of microsatellites or SSRs in nucleotide sequences of Gentianaceae family. A total of 545 SSRs were mined in 4698 nucleotide sequences downloaded from the National Center for Biotechnology Information (NCBI. Among the SSR sequences, the frequency of repeat type was about 429 -mono repeats, 99 -di repeats, 15 -tri repeats, and 2 --hexa repeats. Mononucleotide repeats were found to be abundant repeat types, about 78%, followed by dinucleotide repeats (18.16% among the SSR sequences. An attempt was made to design primer pairs for 545 identified SSRs but these were found only for 169 sequences.

  11. PolyQ repeat expansions in ATXN2 associated with ALS are CAA interrupted repeats.

    Directory of Open Access Journals (Sweden)

    Zhenming Yu

    Full Text Available Amyotrophic lateral sclerosis (ALS is a devastating, rapidly progressive disease leading to paralysis and death. Recently, intermediate length polyglutamine (polyQ repeats of 27-33 in ATAXIN-2 (ATXN2, encoding the ATXN2 protein, were found to increase risk for ALS. In ATXN2, polyQ expansions of ≥ 34, which are pure CAG repeat expansions, cause spinocerebellar ataxia type 2. However, similar length expansions that are interrupted with other codons, can present atypically with parkinsonism, suggesting that configuration of the repeat sequence plays an important role in disease manifestation in ATXN2 polyQ expansion diseases. Here we determined whether the expansions in ATXN2 associated with ALS were pure or interrupted CAG repeats, and defined single nucleotide polymorphisms (SNPs rs695871 and rs695872 in exon 1 of the gene, to assess haplotype association. We found that the expanded repeat alleles of 40 ALS patients and 9 long-repeat length controls were all interrupted, bearing 1-3 CAA codons within the CAG repeat. 21/21 expanded ALS chromosomes with 3CAA interruptions arose from one haplotype (GT, while 18/19 expanded ALS chromosomes with <3CAA interruptions arose from a different haplotype (CC. Moreover, age of disease onset was significantly earlier in patients bearing 3 interruptions vs fewer, and was distinct between haplotypes. These results indicate that CAG repeat expansions in ATXN2 associated with ALS are uniformly interrupted repeats and that the nature of the repeat sequence and haplotype, as well as length of polyQ repeat, may play a role in the neurological effect conferred by expansions in ATXN2.

  12. Repeatability and heritability of response to superovulation in Holstein cows.

    Science.gov (United States)

    Tonhati, H; Lôbo, R B; Oliveira, H N

    1999-04-15

    The objective of this study was to estimate the relative effects of genetic and phenotypic factors on the efficacy and efficiency of superovulation for Holstein-Friesian cows reared in Brazil. A database, established by the Associacao Brasileira de Criadores de Bovinos da Raca Holandesa, consisting of a total of 5387 superovulations of 2941 cows distributed over 473 herds and sired by 690 bulls was used for the analysis. The records were analyzed by MTDFREML (Multiple Trait Derivative-Free Restricted Maximum Likelihood), using a repeatability animal model. The fixed effects included in the model were contemporaneous group (veterinarian, herd, year and season of the superovulation); number of semen doses; cow age; and superovulation order. The estimated repeatability of the number of the transferable embryos was low (0.13), and the estimated heritability was 0.03. These results indicate that environmental factors play a critical role in the response of a cow to a superovulation treatment. There is little evidence that future responses to superovulation by individual females can be predicted by previous treatment(s) or that superovulation response is an heritable trait.

  13. Repeatability of peripheral aberrations in young emmetropes.

    Science.gov (United States)

    Baskaran, Karthikeyan; Theagarayan, Baskar; Carius, Staffan; Gustafsson, Jörgen

    2010-10-01

    The purpose of this study is to assess the intrasession repeatability of ocular aberration measurements in the peripheral visual field with a commercially available Shack-Hartmann aberrometer (complete ophthalmic analysis system-high definition-vision research). The higher-order off-axis aberrations data in young healthy emmetropic eyes are also reported. The aberrations of the right eye of 18 emmetropes were measured using an aberrometer with an open field of view that allows peripheral measurements. Five repeated measures of ocular aberrations were obtained and assessed in steps of 10° out to ±40° in the horizontal visual field (nasal + and temporal -) and -20° in the inferior visual field. The coefficient of repeatability, coefficient of variation, and the intraclass correlation coefficient were calculated as a measure of intrasession repeatability. In all eccentric angles, the repeatability of the third- and fourth-order aberrations was better than the fifth and sixth order aberrations. The coefficient of variation was coefficient was >0.90 for the third and fourth order but reduced gradually for higher orders. There was no statistical significant difference in variance of total higher-order root mean square between on- and off-axis measurements (p > 0.05). The aberration data in this group of young emmetropes showed that the horizontal coma (C(3)(1)) was most positive at 40° in the temporal field, decreasing linearly toward negative values with increasing off-axis angle into the nasal field, whereas all other higher-order aberrations showed little or no change. The complete ophthalmic analysis system-high definition-vision research provides fast, repeatable, and valid peripheral aberration measurements and can be used efficiently to measure off-axis aberrations in the peripheral visual field.

  14. Repeat Descemetopexy after Descemet's Membrane Detachment following Phacoemulsification

    Directory of Open Access Journals (Sweden)

    Sameer Datar

    2014-07-01

    Full Text Available Descemet's membrane detachment (DMD is an uncommon condition with a wide range of possible etiologies. Probably the commonest cause is a localized detachment occurring after cataract extraction surgery. Descemetopexy gives good anatomic attachment rates and visual outcomes and has become the standard treatment for DMD. However, in cases with failed initial descemetopexy, the next step in the management of such cases remains unclear. Before initiating a complex surgical procedure like keratoplasty, which requires good postoperative care and regular follow-ups, repeat descemetopexy with a long-term tamponade using 14% C3F8 gas for recurrent DMD is definitely a worthwhile attempt.

  15. Caffeine Ingestion Improves Repeated Freestyle Sprints in Elite Male Swimmers

    Science.gov (United States)

    Goods, Paul S.R.; Landers, Grant; Fulton, Sacha

    2017-01-01

    The purpose of this investigation was to determine the efficacy of a moderate dose of caffeine to improve repeat-sprint performance in elite freestyle sprinters. Nine highly trained male swimmers performed 6 x 75 m freestyle sprints on two occasions 1-h after consuming either 3 mg·kg-1 caffeine (CAF), or placebo, in a cross-over manner. Capillary blood samples for the analysis of blood lactate concentration and pH were collected after the 1st, 3rd, and 5th sprint, while heart rate and perceived exertion (RPE) were collected after every sprint. There was a moderate effect for improved mean sprint time in the CAF condition (0.52 s; 1.3%; d = 0.50). When assessed individually, there was a large effect for improved performance in sprints 3 (1.00 s; 2.5%; d = 1.02) and 4 (0.84 s; 2.1%; d = 0.84) in CAF compared to placebo, with worthwhile performance improvement found for each of the first 5 sprints. There was a significant treatment effect for higher blood lactate concentration for CAF (p = 0.029), and a significant treatment*time effect for reduced pH in the CAF condition (p = 0.004). Mean heart rate (167 ± 9 bpm vs 169 ± 7 bpm) and RPE (17 ± 1 vs 17 ± 1) were not different between placebo and CAF trials, respectively. This investigation is the first to demonstrate enhanced repeat-sprint ability in swimmers following acute caffeine ingestion. It appears likely that the combination of a moderate dose of caffeine (3-6 mg·kg-1) with trained athletes is most likely to enhance repeat-sprint ability in various athletic populations; however, the exact mechanism(s) for an improved repeat-sprint ability following acute caffeine ingestion remain unknown. Key points A moderate dose of caffeine (3 mg·kg-1) ingested 1 h before a repeat-sprint freestyle set significantly improves mean sprint time in elite swimmers. The combination of at least a moderate dose of caffeine (>3 mg·kg-1) with trained athletes appears the most likely to result in ergogenic benefit to anaerobic

  16. Copy number of tandem direct repeats within the inverted repeats of Marek's disease virus DNA.

    Science.gov (United States)

    Kanamori, A; Nakajima, K; Ikuta, K; Ueda, S; Kato, S; Hirai, K

    1986-12-01

    We previously reported that DNA of the oncogenic strain BC-1 of Marek's disease virus serotype 1 (MDV1) contains three units of tandem direct repeats with 132 base pair (bp) repeats within the inverted repeats of the long regions of the MDV1 genome, whereas the attenuated, nononcogenic viral DNA contains multiple units of tandem direct repeats (Maotani et al., 1986). In the present study, the difference in the copy numbers of 132 bp repeats of oncogenic and nononcogenic MDV1 DNAs in other strains of MDV1 was investigated by Southern blot hybridization. The main copy numbers in different oncogenic MDV1 strains differed: those of BC-1, JM and highly oncogenic Md5 were 3, 5 to 12 and 2, respectively. The viral DNA population with two units of repeats was small, but detectable, in cells infected with either the oncogenic BC-1 or JM strain. The MDV1 DNA in various MD cell lines contained either two units or both two and three units of repeats. The significance of the copy number of repeats in oncogenicity of MDV1 is discussed.

  17. 再次置入药物洗脱支架治疗经皮冠状动脉支架置入术后早期与晚期支架内再狭窄的对比研究%Comparison of repeated drug eluting stent for treatment of early and late in-stent restenosis after drug eluting stent implantation

    Institute of Scientific and Technical Information of China (English)

    朱玮玮; 赵林; 郭成军; 方冬平; 何东方; 张晓江; 迟云鹏; 刘梅颜; 吴小凡

    2014-01-01

    目的 比较再次置入药物洗脱支架(DES)治疗置入DES后早期(≤1年)与晚期(>1年)支架内再狭窄(ISR)患者的临床疗效.方法 收集2008年10月至2011年12月在北京安贞医院因DES置入术后ISR接受再次DES置人治疗并完成临床随访的患者资料.根据DES置入术后发生ISR的时间分为早期ISR组和晚期ISR组.对比2组随访期间的主要不良心血管事件(MACE)[包括全因死亡、心肌梗死和靶病变血运重建(TLR)].结果 总计107例患者入选本研究,其中早期ISR组43例,晚期ISR组64例.2组的患者基线资料、靶病变部位、类型、长度、置入支架特征及ISR类型、再次置入支架特征差异均无统计学意义(P>0.05).早期ISR组糖尿病患病率明显低于晚期ISR组[22.7% (10/44)比42.9% (27/63),P<0.01].晚期ISR组MACE发生率明显低于早期ISR组[15.9% (10/63)比47.7% (21/44),P<0.01];晚期ISR组TLR率明显低于早期ISR组[12.7% (8/63))比43.2% (19/44),P<0.01].Logistic回归分析显示,DES术后早期ISR(OR=6.47,95% CI:2.26~18.50,P<0.01)是DES治疗ISR后再次TLR的唯一预测因素.结论 再次DES置入治疗DES置入后ISR安全有效,但治疗早期ISR时TLR明显升高.%Objective To compare the efficiency and safety of repeated drug eluting stent (DES) for treatment of early and late DES in-stent restenosis(ISR).Methods Patients treated with repeated DES for DES ISR in Beijing anzhen hospital between October 2008 and December 2011 were followed up.All lesions were divided into early ISR group(within 1 year) (43 cases)and late ISR group (in > 1 year) (64 cases) by the period ISR occurring after initial DES implantation.Major adverse cardiovascular events (MACE) including all-cause death,myocardial infarction and clinical target lesion revascularization (TLR) were the primary endpoints.Results There were not differences between early ISR group and late ISR group in clinical and angiographic characteristics(P >0

  18. Efficacy and safety of long-term repeated treatment of facial wrinkles with botulinum toxin A%长期重复应用A型肉毒毒素面部除皱的疗效和安全性评价

    Institute of Scientific and Technical Information of China (English)

    潘卫利; 陆威; 陶小华

    2010-01-01

    目的 评价长期重复多次应用A型肉毒毒素(botulinum toxin A,BTXA)进行面部除皱的疗效和安全性.方法 对52例多次使用国产A型肉毒毒素注射面部除皱者进行了回顾性分析总结.每次注射除皱部位均包括额纹、鱼尾纹、眉间纹、鼻背横纹.于注射前和注射后1周、1个月、3个月及再次注射时,分别进行疗效和安全性评价.结果 每例均注射除皱共8次,每次注射后开始起效时间都在3~4 d,1个月左右是最佳表现时间.疗效评价1级为很好的比例依次是额纹100%、鱼尾纹97.1%、眉间纹99.8%、鼻背横纹99.0%,评价2级为好的比例依次是额纹0、鱼尾纹2.9%、眉间纹0.2%、鼻背横纹1.0%,评价为一般、较差、差这3个等级者为0.随着注射次数增多,疗效等级不断提高.平均疗效维持时间有所延长(r=0.256,P=0.02),为(7.8±1.1)个月,呈正态分布.随着注射次数增加后,不良反应轻微,仅部分受注射者个别注射部位出现瘀斑、额部紧绷感、一定程度的表情僵化和鱼尾纹注射后下眼睑邻近部位皱纹加重.不良反应发生率随注射次数下降(r=0.850,P=0.01).所有被注射者均未出现严重不良反应.结论 长期多次应用A型肉毒毒素除皱安全可靠,且疗效不受影响,因此可以多次使用.%Objective To evaluate the clinical efficacy and safety of long-term repeated treatment of facial wrinkles with application of botulinum toxin A (BTXA). Methods A total of 52 patients had received 8 injections in seven years with BTXA against facial wrinkles, including forehead wrinkles, fishtail lines, glabellas wrinkles, and nasal dorsum transverse wrinkles. Besides day 1 (baseline) and day for the next injection (end-point), follow-up visits were scheduled on 1 week, 1 month, and 3 months after every injection. The therapy effect and safety were evaluated. Results For all the patients, it began to take effect on day 3 or 4 after the treatment and best effect

  19. Y Se Repite = And It Repeats Itself

    Science.gov (United States)

    Katzew, Adriana

    2010-01-01

    In this article, the author discusses Y Se Repite [And It Repeats Itself], a project she conceptualized due to the growing number of Latino/a Mexican migrant workers in dairy farms in the state of Vermont. In 2006, approximately 2,000 Latinos/as--most of them undocumented Mexican migrant workers--worked throughout the state's dairy farms, yet…

  20. Repeater For A Digital-Communication Bus

    Science.gov (United States)

    Torres-Guzman, Esteban; Olson, Stephen; Heaps, Tim

    1993-01-01

    Digital repeater circuit designed to extend range of communication on MIL-STD-1553 bus beyond original maximum allowable length of 300 ft. Circuit provides two-way communication, one way at time, and conforms to specifications of MIL-STD-1553. Crosstalk and instability eliminated.

  1. Repeated sprint training in normobaric hypoxia.

    Science.gov (United States)

    Galvin, Harvey M; Cooke, Karl; Sumners, David P; Mileva, Katya N; Bowtell, Joanna L

    2013-12-01

    Repeated sprint ability (RSA) is a critical success factor for intermittent sport performance. Repeated sprint training has been shown to improve RSA, we hypothesised that hypoxia would augment these training adaptations. Thirty male well-trained academy rugby union and rugby league players (18.4 ± 1.5 years, 1.83 ± 0.07 m, 88.1 ± 8.9 kg) participated in this single-blind repeated sprint training study. Participants completed 12 sessions of repeated sprint training (10 × 6 s, 30 s recovery) over 4 weeks in either hypoxia (13% FiO₂) or normoxia (21% FiO₂). Pretraining and post-training, participants completed sports specific endurance and sprint field tests and a 10 × 6 s RSA test on a non-motorised treadmill while measuring speed, heart rate, capillary blood lactate, muscle and cerebral deoxygenation and respiratory measures. Yo-Yo Intermittent Recovery Level 1 test performance improved after RS training in both groups, but gains were significantly greater in the hypoxic (33 ± 12%) than the normoxic group (14 ± 10%, prepeated aerobic high intensity workout than an equivalent normoxic training. Performance gains are evident in the short term (4 weeks), a period similar to a preseason training block.

  2. Adaptation and complexity in repeated games

    DEFF Research Database (Denmark)

    Maenner, Eliot Alexander

    2008-01-01

    The paper presents a learning model for two-player infinitely repeated games. In an inference step players construct minimally complex inferences of strategies based on observed play, and in an adaptation step players choose minimally complex best responses to an inference. When players randomly ...

  3. A Structured Group Program for Repeat Dieters.

    Science.gov (United States)

    McNamara, Kathleen

    1989-01-01

    Describes a structured group program for women who repeatedly diet and may be at risk of developing more serious eating disorders. Discusses sessions focusing on eating behavior as well as internal factors that contribute to low body esteem and food and weight preoccupation. Evaluates effectiveness of program by self-reports of members of two…

  4. Why Do Students Repeat Admissions Tests?

    Science.gov (United States)

    Jones, Martha S.

    Attitudes and beliefs about the admissions process, especially the role of standardized testing in admissions, were examined for students who took a standardized admissions test more than once. Their attitudes were compared with those of students who did not repeat the test. About 200 preveterinary students who had taken the Veterinary Aptitude…

  5. The Effect of Repeaters on Equating

    Science.gov (United States)

    Kim, HeeKyoung; Kolen, Michael J.

    2010-01-01

    Test equating might be affected by including in the equating analyses examinees who have taken the test previously. This study evaluated the effect of including such repeaters on Medical College Admission Test (MCAT) equating using a population invariance approach. Three-parameter logistic (3-PL) item response theory (IRT) true score and…

  6. Triggering of repeating earthquakes in central California

    Science.gov (United States)

    Wu, Chunquan; Gomberg, Joan; Ben-Naim, Eli; Johnson, Paul

    2014-01-01

    Dynamic stresses carried by transient seismic waves have been found capable of triggering earthquakes instantly in various tectonic settings. Delayed triggering may be even more common, but the mechanisms are not well understood. Catalogs of repeating earthquakes, earthquakes that recur repeatedly at the same location, provide ideal data sets to test the effects of transient dynamic perturbations on the timing of earthquake occurrence. Here we employ a catalog of 165 families containing ~2500 total repeating earthquakes to test whether dynamic perturbations from local, regional, and teleseismic earthquakes change recurrence intervals. The distance to the earthquake generating the perturbing waves is a proxy for the relative potential contributions of static and dynamic deformations, because static deformations decay more rapidly with distance. Clear changes followed the nearby 2004 Mw6 Parkfield earthquake, so we study only repeaters prior to its origin time. We apply a Monte Carlo approach to compare the observed number of shortened recurrence intervals following dynamic perturbations with the distribution of this number estimated for randomized perturbation times. We examine the comparison for a series of dynamic stress peak amplitude and distance thresholds. The results suggest a weak correlation between dynamic perturbations in excess of ~20 kPa and shortened recurrence intervals, for both nearby and remote perturbations.

  7. A Repeater in the Language Laboratory

    Science.gov (United States)

    Griffiths, B. T.

    1969-01-01

    Discusses the feasilility of the use of repeater devices in the language laboratory in order to enable the student to "recapitulate effortlessly and and indefinitely any utterance of any length which is causing him difficulty or is of special interest. (FWB)

  8. The Differential Effects of Repeating Kindergarten

    Science.gov (United States)

    Burkam, David T.; LoGerfo, Laura; Ready, Doug; Lee, Valerie E.

    2007-01-01

    We use the Early Childhood Longitudinal Study to investigate national patterns addressing (a) who repeats kindergarten, and (b) the subsequent cognitive effects of this event. Using OLS regression techniques, we investigate 1st-time kindergartners who are promoted, 1st-time kindergartners who are retained, and children who are already repeating…

  9. Preventing Repeat Teen Births PSA (:60)

    Centers for Disease Control (CDC) Podcasts

    2013-04-02

    This 60 second public service announcement is based on the April 2013 CDC Vital Signs report, which discusses repeat teen births and ways teens, parents and guardians, health care providers, and communities can help prevent them.  Created: 4/2/2013 by Centers for Disease Control and Prevention (CDC).   Date Released: 4/2/2013.

  10. Epigenetics and triplet repeat neurological diseases

    Directory of Open Access Journals (Sweden)

    Sathiji eNageshwaran

    2015-12-01

    Full Text Available The term ‘junk DNA’ has been reconsidered following the delineation of the functional significance of repetitive DNA regions. Typically associated with centromeres and telomeres, DNA repeats are found in nearly all organisms throughout their genomes. Repetitive regions are frequently heterchromatinised resulting in silencing of intrinsic and nearby genes. However, this is not a uniform rule, with several genes known to require such an environment to permit transcription. Repetitive regions frequently exist as dinucleotide, trinucleotide and tetranucleotide repeats. The association between repetitive regions and disease was emphasised following the discovery of abnormal trinucleotide repeats underlying spinal and bulbar muscular atrophy (Kennedy’s disease and fragile X syndrome of mental retardation (FRAXA in 1991. In this review we provide a brief overview of epigenetic mechanisms and then focus on several diseases caused by DNA triplet-repeat expansions, which exhibit diverse epigenetic effects. It is clear that the emerging field of epigenetics is already generating novel potential therapeutic avenues for this group of largely incurable diseases.

  11. Costly renegotiation in repeated Bertand games

    DEFF Research Database (Denmark)

    Andersson, Ola; Wengström, Erik Roland

    2010-01-01

    This paper extends the concept of weak renegotiation-proof equilibrium (WRP) to allow for costly renegotiation and shows that even small renegotiation costs can have dramatic effects on the set of equilibria. More specifically, the paper analyzes the infinitely repeated Bertrand game. It is shown...

  12. EVOLUTION AND RECOMBINATION OF BOVINE DNA REPEATS

    NARCIS (Netherlands)

    JOBSE, C; BUNTJER, JB; HAAGSMA, N; BREUKELMAN, HJ; BEINTEMA, JJ; LENSTRA, JA

    The history of the abundant repeat elements in the bovine genome has been studied by comparative hybridization and PCR. The Bov-A and Bov-B SINE elements both emerged just after the divergence of the Camelidae and the true ruminants. A 31-bp subrepeat motif in satellites of the Bovidae species

  13. Building Fluency through the Repeated Reading Method

    Science.gov (United States)

    Cohen, Joshua

    2011-01-01

    For the last two years the author has used Repeated Reading (RR) to teach reading fluency in English as a Foreign Language classrooms in colleges and universities in Japan. RR is a method where the student reads and rereads a text silently or aloud from two to four times to reach a predetermined level of speed, accuracy, and comprehension. RR…

  14. History repeats itself: genomic divergence in copepods.

    Science.gov (United States)

    Renaut, Sébastien; Dion-Côté, Anne-Marie

    2016-04-01

    Press stop, erase everything from now till some arbitrary time in the past and start recording life as it evolves once again. Would you see the same tape of life playing itself over and over, or would a different story unfold every time? The late Steven Jay Gould called this experiment replaying the tape of life and argued that any replay of the tape would lead evolution down a pathway radically different from the road actually taken (Gould 1989). This thought experiment has puzzled evolutionary biologists for a long time: how repeatable are evolutionary events? And if history does indeed repeat itself, what are the factors that may help us predict the path taken? A powerful means to address these questions at a small evolutionary scale is to study closely related populations that have evolved independently, under similar environmental conditions. This is precisely what Pereira et al. (2016) set out to do using marine copepods Tigriopus californicus, and present their results in this issue of Molecular Ecology. They show that evolution can be repeatable and even partly predictable, at least at the molecular level. As expected from theory, patterns of divergence were shaped by natural selection. At the same time, strong genetic drift due to small population sizes also constrained evolution down a similar evolutionary road, and probably contributed to repeatable patterns of genomic divergence.

  15. Costly renegotiation in repeated Bertand games

    DEFF Research Database (Denmark)

    Andersson, Ola; Wengström, Erik Roland

    2010-01-01

    This paper extends the concept of weak renegotiation-proof equilibrium (WRP) to allow for costly renegotiation and shows that even small renegotiation costs can have dramatic effects on the set of equilibria. More specifically, the paper analyzes the infinitely repeated Bertrand game. It is shown...

  16. Photometric Repeatability of Scanned Imagery: UVIS

    Science.gov (United States)

    Shanahan, Clare E.; McCullough, Peter; Baggett, Sylvia

    2017-08-01

    We provide the preliminary results of a study on the photometric repeatability of spatial scans of bright, isolated white dwarf stars with the UVIS channel of the Wide Field Camera 3 (WFC3) on the Hubble Space Telescope (HST). We analyze straight-line scans from the first pair of identical orbits of HST program 14878 to assess if sub 0.1% repeatability can be attained with WFC3/UVIS. This study is motivated by the desire to achieve better signal-to-noise in the UVIS contamination and stability monitor, in which observations of standard stars in staring mode have been taken from the installation of WFC3 in 2009 to the present to assess temporal photometric stability. Higher signal to noise in this program would greatly benefit the sensitivity to detect contamination, and to better characterize the observed small throughput drifts over time. We find excellent repeatability between identical visits of program 14878, with sub 0.1% repeatability achieved in most filters. These! results support the initiative to transition the staring mode UVIS contamination and photometric stability monitor from staring mode images to spatial scans.

  17. Repeat surgery after failed midurethral slings

    DEFF Research Database (Denmark)

    Foss Hansen, Margrethe; Lose, Gunnar; Kesmodel, Ulrik Schiøler

    2016-01-01

    MUS from 1998 through 2007. The outcome was repeat surgery with any subsequent procedure code for urinary incontinence within a 5-year period of the first procedure. RESULTS: A total of 5,820 women (mean age 55.4 years, ± 12.1) were registered with a synthetic MUS, and 354 (6 %) underwent reoperation...

  18. EVOLUTION AND RECOMBINATION OF BOVINE DNA REPEATS

    NARCIS (Netherlands)

    JOBSE, C; BUNTJER, JB; HAAGSMA, N; BREUKELMAN, HJ; BEINTEMA, JJ; LENSTRA, JA

    1995-01-01

    The history of the abundant repeat elements in the bovine genome has been studied by comparative hybridization and PCR. The Bov-A and Bov-B SINE elements both emerged just after the divergence of the Camelidae and the true ruminants. A 31-bp subrepeat motif in satellites of the Bovidae species cattl

  19. Multivariate linear models and repeated measurements revisited

    DEFF Research Database (Denmark)

    Dalgaard, Peter

    2009-01-01

    Methods for generalized analysis of variance based on multivariate normal theory have been known for many years. In a repeated measurements context, it is most often of interest to consider transformed responses, typically within-subject contrasts or averages. Efficiency considerations leads...

  20. One repeat of the cell wall binding domain is sufficient for anchoring the Lactobacillus acidophilus surface layer protein

    NARCIS (Netherlands)

    Smit, E.; Pouwels, P.H.

    2002-01-01

    The N-terminal repeat (SAC1) of the S-protein of Lactobacillus acidophilus bound efficiently and specifically to cell wall fragments (CWFs) when fused to green fluorescent protein, whereas the C-terminal repeat (SAC2) did not. Treatment of CWFs with hydrofluoric acid, but not phenol, prevented bindi

  1. Repeated Nrf2 stimulation using sulforaphane protects fibroblasts from ionizing radiation.

    Science.gov (United States)

    Mathew, Sherin T; Bergström, Petra; Hammarsten, Ola

    2014-05-01

    Most of the cytotoxicity induced by ionizing radiation is mediated by radical-induced DNA double-strand breaks. Cellular protection from free radicals can be stimulated several fold by sulforaphane-mediated activation of the transcription factor Nrf2 that regulates more than 50 genes involved in the detoxification of reactive substances and radicals. Here, we report that repeated sulforaphane treatment increases radioresistance in primary human skin fibroblasts. Cells were either treated with sulforaphane for four hours once or with four-hour treatments repeatedly for three consecutive days prior to radiation exposure. Fibroblasts exposed to repeated-sulforaphane treatment showed a more pronounced dose-dependent induction of Nrf2-regulated mRNA and reduced amount of radiation-induced free radicals compared with cells treated once with sulforaphane. In addition, radiation- induced DNA double-strand breaks measured by gamma-H2AX foci were attenuated following repeated sulforaphane treatment. As a result, cellular protection from ionizing radiation measured by the 5-ethynyl-2'-deoxyuridine (EdU) assay was increased, specifically in cells exposed to repeated sulforaphane treatment. Sulforaphane treatment was unable to protect Nrf2 knockout mouse embryonic fibroblasts, indicating that the sulforaphane-induced radioprotection was Nrf2-dependent. Moreover, radioprotection by repeated sulforaphane treatment was dose-dependent with an optimal effect at 10 uM, whereas both lower and higher concentrations resulted in lower levels of radioprotection. Our data indicate that the Nrf2 system can be trained to provide further protection from radical damage. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. RepeatsDB 2.0: improved annotation, classification, search and visualization of repeat protein structures

    Science.gov (United States)

    Paladin, Lisanna; Hirsh, Layla; Piovesan, Damiano; Andrade-Navarro, Miguel A.; Kajava, Andrey V.; Tosatto, Silvio C.E.

    2017-01-01

    RepeatsDB 2.0 (URL: http://repeatsdb.bio.unipd.it/) is an update of the database of annotated tandem repeat protein structures. Repeat proteins are a widespread class of non-globular proteins carrying heterogeneous functions involved in several diseases. Here we provide a new version of RepeatsDB with an improved classification schema including high quality annotations for ∼5400 protein structures. RepeatsDB 2.0 features information on start and end positions for the repeat regions and units for all entries. The extensive growth of repeat unit characterization was possible by applying the novel ReUPred annotation method over the entire Protein Data Bank, with data quality is guaranteed by an extensive manual validation for >60% of the entries. The updated web interface includes a new search engine for complex queries and a fully re-designed entry page for a better overview of structural data. It is now possible to compare unit positions, together with secondary structure, fold information and Pfam domains. Moreover, a new classification level has been introduced on top of the existing scheme as an independent layer for sequence similarity relationships at 40%, 60% and 90% identity. PMID:27899671

  3. Tailor-made RNAi knockdown against triplet repeat disease-causing alleles.

    Science.gov (United States)

    Takahashi, Masaki; Watanabe, Shoko; Murata, Miho; Furuya, Hirokazu; Kanazawa, Ichiro; Wada, Keiji; Hohjoh, Hirohiko

    2010-12-14

    Nucleotide variations, including SNPs, in the coding regions of disease genes are important targets for RNAi treatment, which is a promising medical treatment for intractable diseases such as triplet repeat diseases. However, the identification of such nucleotide variations and the design of siRNAs conferring disease allele-specific RNAi are quite difficult. In this study we developed a pull-down method to rapidly identify coding SNP (cSNP) haplotypes of triple repeat, disease-causing alleles, and we demonstrated disease allele-specific RNAi that targeted cSNP sites in mutant Huntingtin alleles, each of which possessed a different cSNP haplotype. Therefore, the methods presented here allow for allele-specific RNAi knockdown against disease-causing alleles by using siRNAs specific to disease-linked cSNP haplotypes, and advanced progress toward tailor-made RNAi treatments for triplet repeat diseases.

  4. 47 CFR 80.1179 - On-board repeater limitations.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 5 2010-10-01 2010-10-01 false On-board repeater limitations. 80.1179 Section... On-board repeater limitations. When an on-board repeater is used, the following limitations must be met: (a) The on-board repeater antenna must be located no higher than 3 meters (10 feet) above...

  5. Effect of repeated manipulation on range of motion in patients with stiff total knee arthroplasty.

    Science.gov (United States)

    Choi, Ho-Rim; Siliski, John M; Malchau, Henrik; Kwon, Young-Min

    2015-03-01

    Although manipulation under anesthesia (MUA) has been considered effective first-line treatment for stiff total knee arthroplasty (TKA), there is no consensus regarding the usefulness of repeated MUA. The purpose of this study was to investigate the usefulness of repeated MUA performed for patients in whom satisfactory range of motion (ROM) was not achieved by MUA. The authors retrospectively reviewed 15 patients who underwent repeated MUA after failure of initial MUA for stiff TKA. Demographic and ROM data were collected. A final ROM of less than 90° was considered a failed manipulation (failure group) and a final ROM of 90° or more was considered a successful manipulation (success group). Average pre-repeated MUA ROM (72.3°±19.5°) immediately improved to 112.3°±9.7° (Pstiff TKA. The success rate of repeated MUA was less than that of primary MUA; however, it is a useful treatment modality for stiff TKA. Decreased pre-TKA ROM appeared to be associated with poor outcomes after repeated MUA.

  6. Stability of dental waxes following repeated heatings.

    Science.gov (United States)

    Kotsiomiti, E; McCabe, J F

    1995-02-01

    The flow and strength properties of dental waxes were examined following excessive and repeated heatings of the materials. For one product, the flow at 40 +/- 0.5 degrees C was reduced by 25.3% following heating above 200 degrees C. A decrease of the elastic modulus at 20 +/- 1 degree C by approximately 66% was observed in some cases after the heating temperature had been increased to 300 degrees C. Property variations were related to compositional changes, which were investigated by infrared spectoscopy and thermal analysis. Exposure of dental waxes to temperatures higher than 200 degrees C, particularly if it is repeated, may affect the composition and properties, resulting in inferior materials.

  7. Learning with repeated-game strategies.

    Science.gov (United States)

    Ioannou, Christos A; Romero, Julian

    2014-01-01

    We use the self-tuning Experience Weighted Attraction model with repeated-game strategies as a computer testbed to examine the relative frequency, speed of convergence and progression of a set of repeated-game strategies in four symmetric 2 × 2 games: Prisoner's Dilemma, Battle of the Sexes, Stag-Hunt, and Chicken. In the Prisoner's Dilemma game, we find that the strategy with the most occurrences is the "Grim-Trigger." In the Battle of the Sexes game, a cooperative pair that alternates between the two pure-strategy Nash equilibria emerges as the one with the most occurrences. In the Stag-Hunt and Chicken games, the "Win-Stay, Lose-Shift" and "Grim-Trigger" strategies are the ones with the most occurrences. Overall, the pairs that converged quickly ended up at the cooperative outcomes, whereas the ones that were extremely slow to reach convergence ended up at non-cooperative outcomes.

  8. Learning With Repeated-Game Strategies

    Directory of Open Access Journals (Sweden)

    Christos A. Ioannou

    2014-07-01

    Full Text Available We use the self-tuning Experience Weighted Attraction model with repeated-game strategies as a computer testbed to examine the relative frequency, speed of convergence and progression of a set of repeated-game strategies in four symmetric 2x2 games: Prisoner's Dilemma, Battle of the Sexes, Stag-Hunt, and Chicken. In the Prisoner's Dilemma game, we fi□nd that the strategy with the most occurrences is the Grim-Trigger. In the Battle of the Sexes game, a cooperative pair that alternates between the two pure-strategy Nash equilibria emerges as the one with the most occurrences. In the Stag-Hunt and Chicken games, the Win-Stay, Lose-Shift and Grim-Trigger strategies are the ones with the most occurrences. Overall, the pairs that converged quickly ended up at the cooperative outcomes, whereas the ones that were extremely slow to reach convergence ended up at non-cooperative outcomes.

  9. Quantum repeaters with entangled coherent states

    CERN Document Server

    Sangouard, Nicolas; Gisin, Nicolas; Laurat, Julien; Tualle-Brouri, Rosa; Grangier, Philippe

    2009-01-01

    Entangled coherent states can be prepared remotely by subtracting non-locally a single photon from two quantum superpositions of coherent states, the so-called "Schroedinger's cat" state. Such entanglement can further be distributed over longer distances by successive entanglement swapping operations using linear optics and photon-number resolving detectors. The aim of this paper is to evaluate the performance of this approach to quantum repeaters for long distance quantum communications. Despite many attractive features at first sight, we show that, when using state-of-the-art photon counters and quantum memories, they do not achieve higher entanglement generation rates than repeaters based on single-photon entanglement. We discuss potential developments which may take better advantage of the richness of entanglement based on continuous variables, including in particular efficient parity measurements.

  10. Quantum repeaters based on heralded qubit amplifiers

    CERN Document Server

    Minář, Jiří; Sangouard, Nicolas

    2011-01-01

    We present a quantum repeater scheme based on the recently proposed qubit amplifier [N. Gisin, S. Pironio and N. Sangouard, Phys. Rev. Lett. 105, 070501 (2010)]. It relies on a on-demand entangled-photon pair source which uses on-demand single-photon sources, linear optical elements and atomic ensembles. Interestingly, the imperfections affecting the states created from this source, caused e.g. by detectors with non-unit efficiencies, are systematically purified from an entanglement swapping operation based on a two-photon detection. This allows the distribution of entanglement over very long distances with a high fidelity, i.e. without vacuum components and multiphoton errors. Therefore, the resulting quantum repeater architecture does not necessitate final postselections and thus achieves high entanglement distribution rates. This also provides unique opportunities for device-independent quantum key distribution over long distances with linear optics and atomic ensembles.

  11. Nonparametric additive regression for repeatedly measured data

    KAUST Repository

    Carroll, R. J.

    2009-05-20

    We develop an easily computed smooth backfitting algorithm for additive model fitting in repeated measures problems. Our methodology easily copes with various settings, such as when some covariates are the same over repeated response measurements. We allow for a working covariance matrix for the regression errors, showing that our method is most efficient when the correct covariance matrix is used. The component functions achieve the known asymptotic variance lower bound for the scalar argument case. Smooth backfitting also leads directly to design-independent biases in the local linear case. Simulations show our estimator has smaller variance than the usual kernel estimator. This is also illustrated by an example from nutritional epidemiology. © 2009 Biometrika Trust.

  12. Repeat-PPM Super-Symbol Synchronization

    Science.gov (United States)

    Connelly, J.

    2016-11-01

    To attain a wider range of data rates in pulse position modulation (PPM) schemes with constrained pulse durations, the sender can repeat a PPM symbol multiple times, forming a super-symbol. In addition to the slot and symbol synchronization typically required for PPM, the receiver must also properly align the noisy super-symbols. We present a low-complexity approximation of the maximum-likelihood method for performing super-symbol synchronization without use of synchronization sequences. We provide simulation results demonstrating performance advantage when PPM symbols are spread by a pseudo-noise sequence, as opposed to simply repeating. Additionally, the results suggest that this super-symbol synchronization technique requires signal levels below those required for reliable communication. This validates that the PPM spreading approach proposed to CCSDS can work properly as part of the overall scheme.

  13. High-bandwidth hybrid quantum repeater.

    Science.gov (United States)

    Munro, W J; Van Meter, R; Louis, Sebastien G R; Nemoto, Kae

    2008-07-25

    We present a physical- and link-level design for the creation of entangled pairs to be used in quantum repeater applications where one can control the noise level of the initially distributed pairs. The system can tune dynamically, trading initial fidelity for success probability, from high fidelity pairs (F=0.98 or above) to moderate fidelity pairs. The same physical resources that create the long-distance entanglement are used to implement the local gates required for entanglement purification and swapping, creating a homogeneous repeater architecture. Optimizing the noise properties of the initially distributed pairs significantly improves the rate of generating long-distance Bell pairs. Finally, we discuss the performance trade-off between spatial and temporal resources.

  14. EGFR CA repeat polymorphism predict clinical outcome in EGFR mutation positive NSCLC patients treated with erlotinib

    DEFF Research Database (Denmark)

    Winther Larsen, Anne; Nissen, Peter Henrik; Meldgaard, Peter;

    2014-01-01

    OBJECTIVES: Somatic mutations in the epidermal growth factor receptor (EGFR) are predictors of efficacy for treatment with the EGFR tyrosine kinase inhibitor erlotinib in non-small cell lung cancer (NSCLC). A CA repeat polymorphism in intron 1 of the EGFR gene influences the transcription...... of the EGFR gene. This study evaluates the association between the CA repeat polymorphism and outcome in NSCLC patients treated with erlotinib.MATERIALS AND METHODS: Number of CA repeats in the EGFR gene was evaluated with PCR-fragment length analysis by capillary electrophoresis in 432 advanced NSCLC...... patients treated with erlotinib irrespective of EGFR mutation status. Patients were dichotomized into harboring short allele (CA≤16 in any allele) or long alleles (CA>16 in both alleles). Number of repeats was correlated with clinical characteristic and outcome. A subgroup analysis was performed based...

  15. Do Gamma-Ray Burst Sources Repeat?

    OpenAIRE

    Meegan, Charles A.; Hartmann, Dieter H.; Brainerd, J. J.; Briggs, Michael S.; Paciesas, William S.; Pendleton, Geoffrey; Kouveliotou, Chryssa; Fishman, Gerald; Blumenthal, George; Brock, Martin

    1995-01-01

    The demonstration of repeated gamma-ray bursts from an individual source would severely constrain burst source models. Recent reports (Quashnock and Lamb 1993; Wang and Lingenfelter 1993) of evidence for repetition in the first BATSE burst catalog have generated renewed interest in this issue. Here, we analyze the angular distribution of 585 bursts of the second BATSE catalog (Meegan et al. 1994). We search for evidence of burst recurrence using the nearest and farthest neighbor statistic and...

  16. 2D Metals by Repeated Size Reduction.

    Science.gov (United States)

    Liu, Hanwen; Tang, Hao; Fang, Minghao; Si, Wenjie; Zhang, Qinghua; Huang, Zhaohui; Gu, Lin; Pan, Wei; Yao, Jie; Nan, Cewen; Wu, Hui

    2016-10-01

    A general and convenient strategy for manufacturing freestanding metal nanolayers is developed on large scale. By the simple process of repeatedly folding and calendering stacked metal sheets followed by chemical etching, free-standing 2D metal (e.g., Ag, Au, Fe, Cu, and Ni) nanosheets are obtained with thicknesses as small as 1 nm and with sizes of the order of several micrometers.

  17. Repeatability and Workability Evaluation of SIGMOD 2011

    DEFF Research Database (Denmark)

    Bonnet, Philippe

    2011-01-01

    SIGMOD has offered, since 2008, to verify the experiments published in the papers accepted at the conference. This year, we have been in charge of reproducing the experiments provided by the authors (repeatability), and exploring changes to experiment parameters (workability). In this paper, we a...... find that most experiments are distributed as Linux packages accompanied by instructions on how to setup and run the experiments. We are still far from the vision of executable papers...

  18. Repeated extraction of DNA from FTA cards

    DEFF Research Database (Denmark)

    Stangegaard, Michael; Ferrero, Laura; Børsting, Claus

    2011-01-01

    Extraction of DNA using magnetic bead based techniques on automated DNA extraction instruments provides a fast, reliable and reproducible method for DNA extraction from various matrices. However, the yield of extracted DNA from FTA-cards is typically low. Here, we demonstrate that it is possible...... to repeatedly extract DNA from the processed FTA-disk. The method increases the yield from the nanogram range to the microgram range....

  19. Repeated extraction of DNA from FTA cards

    OpenAIRE

    Stangegaard, Michael; Ferrero, Laura; Børsting, Claus; Frank-Hansen, Rune; Hansen, Anders Johannes; Morling, Niels

    2011-01-01

    Extraction of DNA using magnetic bead based techniques on automated DNA extraction instruments provides a fast, reliable and reproducible method for DNA extraction from various matrices. However, the yield of extracted DNA from FTA-cards is typically low. Here, we demonstrate that it is possible to repeatedly extract DNA from the processed FTA-disk. The method increases the yield from the nanogram range to the microgram range.

  20. Repeated extraction of DNA from FTA cards

    DEFF Research Database (Denmark)

    Stangegaard, Michael; Ferrero, Laura; Børsting, Claus

    2011-01-01

    Extraction of DNA using magnetic bead based techniques on automated DNA extraction instruments provides a fast, reliable and reproducible method for DNA extraction from various matrices. However, the yield of extracted DNA from FTA-cards is typically low. Here, we demonstrate that it is possible...... to repeatedly extract DNA from the processed FTA-disk. The method increases the yield from the nanogram range to the microgram range....

  1. A Central Limit Theorem for Repeating Patterns

    CERN Document Server

    Abrams, Aaron; Landau, Henry; Landau, Zeph; Pommersheim, James

    2012-01-01

    This note gives a central limit theorem for the length of the longest subsequence of a random permutation which follows some repeating pattern. This includes the case of any fixed pattern of ups and downs which has at least one of each, such as the alternating case considered by Stanley in [2] and Widom in [3]. In every case considered the convergence in the limit of long permutations is to normal with mean and variance linear in the length of the permutations.

  2. Repeatability and Workability Evaluation of SIGMOD 2011

    DEFF Research Database (Denmark)

    Bonnet, Philippe

    2011-01-01

    SIGMOD has offered, since 2008, to verify the experiments published in the papers accepted at the conference. This year, we have been in charge of reproducing the experiments provided by the authors (repeatability), and exploring changes to experiment parameters (workability). In this paper, we a...... find that most experiments are distributed as Linux packages accompanied by instructions on how to setup and run the experiments. We are still far from the vision of executable papers...

  3. Epigenetics and Triplet-Repeat Neurological Diseases

    OpenAIRE

    Nageshwaran, Sathiji; Festenstein, Richard

    2015-01-01

    The term “junk DNA” has been reconsidered following the delineation of the functional significance of repetitive DNA regions. Typically associated with centromeres and telomeres, DNA repeats are found in nearly all organisms throughout their genomes. Repetitive regions are frequently heterochromatinized resulting in silencing of intrinsic and nearby genes. However, this is not a uniform rule, with several genes known to require such an environment to permit transcription. Repetitive regions f...

  4. Epigenetics and triplet repeat neurological diseases

    OpenAIRE

    Sathiji eNageshwaran; Richard eFestenstein

    2015-01-01

    The term ‘junk DNA’ has been reconsidered following the delineation of the functional significance of repetitive DNA regions. Typically associated with centromeres and telomeres, DNA repeats are found in nearly all organisms throughout their genomes. Repetitive regions are frequently heterchromatinised resulting in silencing of intrinsic and nearby genes. However, this is not a uniform rule, with several genes known to require such an environment to permit transcription. Repetitive regions fr...

  5. Comparison of behavioral effects after single and repeated administrations of four benzodiazepines in three mice behavioral models.

    Science.gov (United States)

    Bourin, M; Hascoet, M; Mansouri, B; Colombel, M C; Bradwejn, J

    1992-01-01

    The behavioral and clinical profiles of various benzodiazepines after acute and chronic treatment are not well defined and may differ. The aim of this study was to evaluate the behavioral profiles of alprazolam, bromazepam, diazepam and lorazepam in mice after single and repeated (every half-life for seven half-lives) administrations using a stimulation-sedation test (actimeter), a myorelaxation test (rotarod), and an anxiolysis test ("four plates"). A dose range from 0.03 to 4 mg/kg was used. A single administration of alprazolam showed stimulating and anxiolytic effects which diminished after repeated administration. Lorezapam's sedative effect diminished but its anxiolytic effect increased upon repeated administration. Except for lorazepam, the myorelaxing effect of all four drugs increased after repeated treatment. These results suggest that the behavioral profile of benzodiazepines may not be identical during acute and chronic treatment. These differences may be present in clinical treatment and warrant investigation in humans. PMID:1637802

  6. Comparison of behavioral effects after single and repeated administrations of four benzodiazepines in three mice behavioral models.

    Science.gov (United States)

    Bourin, M; Hascoet, M; Mansouri, B; Colombel, M C; Bradwejn, J

    1992-06-01

    The behavioral and clinical profiles of various benzodiazepines after acute and chronic treatment are not well defined and may differ. The aim of this study was to evaluate the behavioral profiles of alprazolam, bromazepam, diazepam and lorazepam in mice after single and repeated (every half-life for seven half-lives) administrations using a stimulation-sedation test (actimeter), a myorelaxation test (rotarod), and an anxiolysis test ("four plates"). A dose range from 0.03 to 4 mg/kg was used. A single administration of alprazolam showed stimulating and anxiolytic effects which diminished after repeated administration. Lorezapam's sedative effect diminished but its anxiolytic effect increased upon repeated administration. Except for lorazepam, the myorelaxing effect of all four drugs increased after repeated treatment. These results suggest that the behavioral profile of benzodiazepines may not be identical during acute and chronic treatment. These differences may be present in clinical treatment and warrant investigation in humans.

  7. Primary malignant melanoma of the vagina with repeated local recurrences and brain metastasis

    Directory of Open Access Journals (Sweden)

    Li-Te Lin

    2011-08-01

    Full Text Available Malignant melanoma of the vagina, a very rare malignancy, has a notoriously aggressive behavior associated with a high risk of local recurrence and distant metastasis. At present, there are various treatment options for this disease but no standard guideline. We describe a case of a 54-year-old woman with a locally advanced melanoma of the vagina, who underwent radical surgery, biochemotherapy with interferon-α-2b, chemotherapy, radiotherapy, and repeat excision of local recurrent lesions and brain metastasis. In conclusion, malignant melanoma of the vagina has a high risk for local recurrence. Repeated local excision followed by biochemotherapy is a tolerable treatment.

  8. Repeated-sprint ability and aerobic fitness.

    Science.gov (United States)

    Thébault, Nicolas; Léger, Luc A; Passelergue, Philippe

    2011-10-01

    The purpose of this study was to reinvestigate the relationship between aerobic fitness and fatigue indices of repeated-sprint ability (RSA), with special attention to methodological normalization. Soldiers were divided into low (n = 10) and high (n = 9) fitness groups according to a preset maximal aerobic speed (MAS) of 17 km·h(-1) (∼60 ml O2·kg(-1)·min) measured with the University of Montreal Track Test (UMTT). Subjects' assessment included the RSA test (3 sets of 5 40-m sprints with 1-minute rest between sprints and 1.5 minutes between sets), a 40-m sprint (criterion test used in the computation of fatigue indices for the RSA test), strength and power measurement of the lower limbs, and the 20-m shuttle run test (20-m SRT) and the UMTT, which are measures of maximal aerobic power. The highest correlation with the RSA fatigue indices was obtained with the 20-m SRT (r = 0.90, p = 0.0001, n = 19), a test with 180° direction changes and accelerations and decelerations. The lower correlation (r = 0.66, p repeated sprints and achieved better recovery between series. A MAS of at least 17 km·h(-1) favors constant and high speed level during repeated sprints. From a practical point of view, a high aerobic fitness is a precious asset in counteracting fatigue in sports with numerous sprint repetitions.

  9. Histone deacetylase complexes promote trinucleotide repeat expansions.

    Directory of Open Access Journals (Sweden)

    Kim Debacker

    2012-02-01

    Full Text Available Expansions of DNA trinucleotide repeats cause at least 17 inherited neurodegenerative diseases, such as Huntington's disease. Expansions can occur at frequencies approaching 100% in affected families and in transgenic mice, suggesting that specific cellular proteins actively promote (favor expansions. The inference is that expansions arise due to the presence of these promoting proteins, not their absence, and that interfering with these proteins can suppress expansions. The goal of this study was to identify novel factors that promote expansions. We discovered that specific histone deacetylase complexes (HDACs promote CTG•CAG repeat expansions in budding yeast and human cells. Mutation or inhibition of yeast Rpd3L or Hda1 suppressed up to 90% of expansions. In cultured human astrocytes, expansions were suppressed by 75% upon inhibition or knockdown of HDAC3, whereas siRNA against the histone acetyltransferases CBP/p300 stimulated expansions. Genetic and molecular analysis both indicated that HDACs act at a distance from the triplet repeat to promote expansions. Expansion assays with nuclease mutants indicated that Sae2 is one of the relevant factors regulated by Rpd3L and Hda1. The causal relationship between HDACs and expansions indicates that HDACs can promote mutagenesis at some DNA sequences. This relationship further implies that HDAC3 inhibitors being tested for relief of expansion-associated gene silencing may also suppress somatic expansions that contribute to disease progression.

  10. Landauer's Principle in Repeated Interaction Systems

    Science.gov (United States)

    Hanson, Eric P.; Joye, Alain; Pautrat, Yan; Raquépas, Renaud

    2017-01-01

    We study Landauer's Principle for Repeated Interaction Systems (RIS) consisting of a reference quantum system S in contact with a structured environment E made of a chain of independent quantum probes; S interacts with each probe, for a fixed duration, in sequence. We first adapt Landauer's lower bound, which relates the energy variation of the environment E to a decrease of entropy of the system S during the evolution, to the peculiar discrete time dynamics of RIS. Then we consider RIS with a structured environment E displaying small variations of order {T^{-1}} between the successive probes encountered by S, after {n ˜eq T} interactions, in keeping with adiabatic scaling. We establish a discrete time non-unitary adiabatic theorem to approximate the reduced dynamics of S in this regime, in order to tackle the adiabatic limit of Landauer's bound. We find that saturation of Landauer's bound is related to a detailed balance condition on the repeated interaction system, reflecting the non-equilibrium nature of the repeated interaction system dynamics. This is to be contrasted with the generic saturation of Landauer's bound known to hold for continuous time evolution of an open quantum system interacting with a single thermal reservoir in the adiabatic regime.

  11. A Unified Model for Repeating and Non-repeating Fast Radio Bursts

    Science.gov (United States)

    Bagchi, Manjari

    2017-04-01

    The model that fast radio bursts (FRBs) are caused by plunges of asteroids onto neutron stars can explain both repeating and non-repeating bursts. If a neutron star passes through an asteroid belt around another star, there would be a series of bursts caused by a series of asteroid impacts. Moreover, the neutron star would cross the same belt repetitively if it were in a binary with the star hosting the asteroid belt, leading to a repeated series of bursts. I explore the properties of neutron star binaries that could lead to the only known repeating FRB so far (FRB121102). In this model, the next two epochs of bursts are expected around 2017 February 27 and 2017 December 18. On the other hand, if the asteroid belt is located around the neutron star itself, then a chance fall of an asteroid from that belt onto the neutron star would lead to a non-repeating burst. Even a neutron star grazing an asteroid belt can lead to a non-repeating burst caused by just one asteroid plunge during the grazing. This is possible even when the neutron star is in a binary with the asteroid-hosting star, if the belt and the neutron star orbit are non-coplanar.

  12. Carbohydrate mouth rinse does not improve repeated sprint performance

    Directory of Open Access Journals (Sweden)

    Leandro Ricardo Altimari

    2013-09-01

    Full Text Available The objective of this study was to evaluate the effect of a carbohydrate mouth rinse on the repeated sprint ability (RSA of young soccer players. Nine youth soccer players (15.0 ± 1.5 years; 60.7 ± 4.84 kg; 1.72 ± 0.05 m; 20.5 ± 1.25 kg/m2 were selected. The athletes were submitted to an RSA test consisting of six sprints of 40 m (going/return = 20 m + 20 m, separated by 20 s of passive recovery, under three experimental conditions: carbohydrate mouth rinse (CHO or placebo (PLA and control (CON. The mouth rinses containing CHO or PLA were administered 5 min and immediately before the beginning of the test in doses of 100 mL. The best sprint time (RSAbest, mean sprint time (RSAmean, and drop-off in sprint performance (fatigue index were determined for the different treatments. One-not identify significant differences (p> 0.05 in RSAbest (CHO way ANOVA for repeated measures did = 7.30 ± 0.31 s; PLA = 7.30 ± 0.30 s; CON = 7.26 ±0.16 s, RSA mean (CHO = 7.71 ± 0.30 s; PLA = 7.71 ± 0.25 s; CON = 7.66 ± 0.24s, or fatigue index (CHO = 5.58 ± 2.16%; PLA = 5.77 ± 3.04%; CON = 5.55 ±3.72%. The results suggest that a carbohydrate mouth rinse does not improve the repeated sprint performance of young soccer players.

  13. A case of repeated intracerebral hemorrhages secondary to ventriculoperitoneal shunt

    Directory of Open Access Journals (Sweden)

    Jinbing Zhao

    2015-03-01

    Full Text Available Ventriculoperitoneal shunt is a routinely performed treatment in neurosurgical department. Intracerebral hemorrhage, as a complication after shunt catheterization, is really rare but with high mortality. In this study, we reported a case of a 74-year-old man who suffered from repeated intracerebral hemorrhage after ventriculoperitoneal shunt. The first hemorrhage happened 63 h after the 1st surgery, and most hematomas were located in the ipsilateral occipital lobe and intraventricles, along the ventricular catheter. Fresh blood clot casts blocked the external ventricular draining catheter, which was inserted into the right front horn during the 3rd surgery, indicating new intraventricular bleeding happened. A large hematoma in ipsilateral frontal lobe was detected on the 3rd day after the removal of external ventricular draining catheter. Different hemorrhagic locations and time points were encountered on the same case. We discussed the possible causes of repeated hemorrhage for this case, and the pre-operative preparation including risk evaluation in future clinical work.

  14. Repeatability and Reproducibility of Virtual Subjective Refraction.

    Science.gov (United States)

    Perches, Sara; Collados, M Victoria; Ares, Jorge

    2016-10-01

    To establish the repeatability and reproducibility of a virtual refraction process using simulated retinal images. With simulation software, aberrated images corresponding with each step of the refraction process were calculated following the typical protocol of conventional subjective refraction. Fifty external examiners judged simulated retinal images until the best sphero-cylindrical refraction and the best visual acuity were achieved starting from the aberrometry data of three patients. Data analyses were performed to assess repeatability and reproducibility of the virtual refraction as a function of pupil size and aberrometric profile of different patients. SD values achieved in three components of refraction (M, J0, and J45) are lower than 0.25D in repeatability analysis. Regarding reproducibility, we found SD values lower than 0.25D in the most cases. When the results of virtual refraction with different pupil diameters (4 and 6 mm) were compared, the mean of differences (MoD) obtained were not clinically significant (less than 0.25D). Only one of the aberrometry profiles with high uncorrected astigmatism shows poor results for the M component in reproducibility and pupil size dependence analysis. In all cases, vision achieved was better than 0 logMAR. A comparison between the compensation obtained with virtual and conventional subjective refraction was made as an example of this application, showing good quality retinal images in both processes. The present study shows that virtual refraction has similar levels of precision as conventional subjective refraction. Moreover, virtual refraction has also shown that when high low order astigmatism is present, the refraction result is less precise and highly dependent on pupil size.

  15. Oxygen uptake during repeated-sprint exercise.

    Science.gov (United States)

    McGawley, Kerry; Bishop, David J

    2015-03-01

    Repeated-sprint ability appears to be influenced by oxidative metabolism, with reductions in fatigue and improved sprint times related to markers of aerobic fitness. The aim of the current study was to measure the oxygen uptake (VO₂) during the first and last sprints during two, 5 × 6-s repeated-sprint bouts. Cross-sectional study. Eight female soccer players performed two, consecutive, 5 × 6-s maximal sprint bouts (B1 and B2) on five separate occasions, in order to identify the minimum time (trec) required to recover total work done (Wtot) in B1. On a sixth occasion, expired air was collected during the first and last sprint of B1 and B2, which were separated by trec. The trec was 10.9 ± 1.1 min. The VO₂ during the first sprint was significantly less than the last sprint in each bout (psprint (measured in kJ) was significantly related to VO₂max in both B1 (r=0.81, p=0.015) and B2 (r=0.93, p=0.001). In addition, the VO₂ attained in the final sprint was not significantly different from VO₂max in B1 (p=0.284) or B2 (p=0.448). The current study shows that the VO₂ increases from the first to the last of 5 × 6-s sprints and that VO₂max may be a limiting factor to performance in latter sprints. Increasing V˙O₂max in team-sport athletes may enable increased aerobic energy delivery, and consequently work done, during a bout of repeated sprints. Copyright © 2014 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

  16. Mechanical processes with repeated attenuated impacts

    CERN Document Server

    Nagaev, R F

    1999-01-01

    This book is devoted to considering in the general case - using typical concrete examples - the motion of machines and mechanisms of impact and vibro-impact action accompanied by a peculiar phenomenon called "impact collapse". This phenomenon is that after the initial collision, a sequence of repeated gradually quickening collisions of decreasing-to-zero intensity occurs, with the final establishment of protracted contact between the interacting bodies. The initiation conditions of the impact collapse are determined and calculation techniques for the quantitative characteristics of the corresp

  17. Source coding model for repeated snapshot imaging

    CERN Document Server

    Li, Junhui; Yang, Dongyue; wu, Guohua; Yin, Longfei; Guo, Hong

    2016-01-01

    Imaging based on successive repeated snapshot measurement is modeled as a source coding process in information theory. The necessary number of measurement to maintain a certain level of error rate is depicted as the rate-distortion function of the source coding. Quantitative formula of the error rate versus measurement number relation is derived, based on the information capacity of imaging system. Second order fluctuation correlation imaging (SFCI) experiment with pseudo-thermal light verifies this formula, which paves the way for introducing information theory into the study of ghost imaging (GI), both conventional and computational.

  18. REPEAT facility. Report for May, June, July

    Science.gov (United States)

    Winn, C. B.

    1981-08-01

    The construction of the REPEAT facility, a test facility for passive and hybrid solar heating systems is reported. The development of a simulation program for envelope type passive solar systems, constructing an envelope test cell, collecting data to validate the program, and application of the program to determine the best envelope type design are discussed. A low cost monitoring system using a dedicated microprocessor system, an inexpensive, high accuracy A/D converter, and minimum system hardware is developed. A method to determine the average temperature and the average daily temperature variation inside a passively heated solar building is presented.

  19. Multiplicatively Repeated Non-Binary LDPC Codes

    CERN Document Server

    Kasai, Kenta; Poulliat, Charly; Sakaniwa, Kohichi

    2010-01-01

    We propose non-binary LDPC codes concatenated with multiplicative repetition codes. By multiplicatively repeating the (2,3)-regular non-binary LDPC mother code of rate 1/3, we construct rate-compatible codes of lower rates 1/6, 1/9, 1/12,... Surprisingly, such simple low-rate non-binary LDPC codes outperform the best low-rate binary LDPC codes so far. Moreover, we propose the decoding algorithm for the proposed codes, which can be decoded with almost the same computational complexity as that of the mother code.

  20. Improving repeated sprint ability in young elite soccer players: repeated shuttle sprints vs. explosive strength training.

    Science.gov (United States)

    Buchheit, Martin; Mendez-Villanueva, Alberto; Delhomel, Gregory; Brughelli, Matt; Ahmaidi, Said

    2010-10-01

    To compare the effects of explosive strength (ExpS) vs. repeated shuttle sprint (RS) training on repeated sprint ability (RSA) in young elite soccer players, 15 elite male adolescents (14.5 ± 0.5 years) performed, in addition to their soccer training program, RS (n = 7) or ExpS (n = 8) training once a week for a total of 10 weeks. RS training consisted of 2-3 sets of 5-6 × 15- to 20-m repeated shuttle sprints interspersed with 14 seconds of passive or 23 seconds of active recovery (≈2 m·s⁻¹); ExpS training consisted of 4-6 series of 4-6 exercises (e.g., maximal unilateral countermovement jumps (CMJs), calf and squat plyometric jumps, and short sprints). Before and after training, performance was assessed by 10 and 30 m (10 and 30 m) sprint times, best (RSAbest) and mean (RSAmean) times on a repeated shuttle sprint ability test, a CMJ, and a hopping (Hop) test. After training, except for 10 m (p = 0.22), all performances were significantly improved in both groups (all p's repeated shuttle sprint test were only observed after RS training, whereas CMJ height was only increased after ExpS. Because RS and ExpS were equally efficient at enhancing maximal sprinting speed, RS training-induced improvements in RSA were likely more related to progresses in the ability to change direction.

  1. Repeated vitrification/warming of human sperm gives better results than repeated slow programmable freezing

    Institute of Scientific and Technical Information of China (English)

    Teraporn Vutyavanich; Worashorn Lattiwongsakorn; Waraporn Piromlertamorn; Sudarat Samchimchom

    2012-01-01

    In this study,we compared the effects of repeated freezing/thawing of human sperm by our in-house method of rapid freezing with slow programmable freezing.Sperm samples from 11 normozoospermic subjects were processed through density gradients and divided into three aliquots:non-frozen,rapid freezing and slow programmable freezing.Sperm in the rapid freezing group had better motility and viability than those in the slow freezing group (P<O.01) after the first,second and third cycles of freezing/thawing,but there was no difference in morphology.In the second experiment,rapid freezing was repeated three times in 20 subjects.The samples from each thawing cycle were evaluated for DNA fragmentation using the alkaline comet assay.DNA fragmentation began to increase considerably after the second cycle of freezing/thawing,but to a level that was not clinically important.In the third experiment,rapid freezing was done repeatedly in 10 subjects,until no motile sperm were observed after thawing.The median number of repeated freezing/thawing that yielded no motile sperm was seven (range:5-8,mean:6.8).In conclusion,we demonstrated that repeated freezing/thawing of processed semen using our rapid freezing method gave better results than standard slow programmable freezing.This method can help maximize the usage of precious cryopreserved sperm samples in assisted reproduction technology.

  2. Repeated trauma exposure does not impair distress reduction during imaginal exposure for posttraumatic stress disorder.

    Science.gov (United States)

    Jerud, Alissa B; Farach, Frank J; Bedard-Gilligan, Michele; Smith, Hillary; Zoellner, Lori A; Feeny, Norah C

    2017-08-01

    Based on experimental research on threat extinction, individuals exposed to repeated traumatic events may have impaired outcome in exposure therapy compared to those who have experienced a single trauma (Lang & McTeague, ). This study examined whether repeated trauma exposure predicts smaller changes in self-reported distress during imaginal exposure and worse outcomes for patients with posttraumatic stress disorder (PTSD). Adults (N = 116) with chronic PTSD received up to 10 sessions of prolonged exposure (PE) therapy. Trauma exposure was assessed via interview and number of traumatic events were summed for each participant. To examine reductions in distress during treatment, mean and peak values of distress during imaginal exposure were calculated for the first imaginal session (initial distress activation) and subsequent sessions (between-session change in distress). Change in PTSD symptoms from pre- to posttreatment and follow-up provided an additional index of outcome. In-session distress during imaginal exposure decreased over the course of treatment. PTSD symptoms also decreased over treatment, with gains being maintained through follow-up. Repeated trauma exposure was not significantly correlated with initial distress activation. Additionally, linear mixed-model analyses showed no significant association between repeated trauma exposure and between-session change in distress or PTSD symptoms. Contrary to recent speculation, repeated trauma exposure did not predict less change in self-reported distress during imaginal exposure or worse PTSD outcomes. The bench-to-bedside linkage of threat extinction to exposure therapy is discussed, noting strengths and weaknesses. Patients with repeated trauma exposure show reductions in distress with exposure treatment and benefit from PE as much as patients with single-exposure trauma histories. © 2016 Wiley Periodicals, Inc.

  3. Comparative genomics and molecular dynamics of DNA repeats in eukaryotes.

    Science.gov (United States)

    Richard, Guy-Franck; Kerrest, Alix; Dujon, Bernard

    2008-12-01

    Repeated elements can be widely abundant in eukaryotic genomes, composing more than 50% of the human genome, for example. It is possible to classify repeated sequences into two large families, "tandem repeats" and "dispersed repeats." Each of these two families can be itself divided into subfamilies. Dispersed repeats contain transposons, tRNA genes, and gene paralogues, whereas tandem repeats contain gene tandems, ribosomal DNA repeat arrays, and satellite DNA, itself subdivided into satellites, minisatellites, and microsatellites. Remarkably, the molecular mechanisms that create and propagate dispersed and tandem repeats are specific to each class and usually do not overlap. In the present review, we have chosen in the first section to describe the nature and distribution of dispersed and tandem repeats in eukaryotic genomes in the light of complete (or nearly complete) available genome sequences. In the second part, we focus on the molecular mechanisms responsible for the fast evolution of two specific classes of tandem repeats: minisatellites and microsatellites. Given that a growing number of human neurological disorders involve the expansion of a particular class of microsatellites, called trinucleotide repeats, a large part of the recent experimental work on microsatellites has focused on these particular repeats, and thus we also review the current knowledge in this area. Finally, we propose a unified definition for mini- and microsatellites that takes into account their biological properties and try to point out new directions that should be explored in a near future on our road to understanding the genetics of repeated sequences.

  4. Repeatability Using Automatic Tracing with Canon OCT- HS100 and Zeiss Cirrus HD-OCT 5000.

    Directory of Open Access Journals (Sweden)

    Rune Brautaset

    Full Text Available Optical coherence tomography (OCT, can be used in clinical practice to provide high resolution cross-sectional images of the retina, optic disc and macula structure. These measurements can be useful for early detection, diagnosis, monitoring and treatment guidance for retinal diseases. Therefore, repeatability of measurements in OCT is of great importance.Macula and optic disc parameters from the right eye of 30 healthy subjects were obtained twice with the Canon OCT-HS100 and Zeiss Cirrus HD-OCT 5000. Repeatability was evaluated by use of the coefficient of repeatability (CR and the coefficient of repeatability as a percentage of the mean (CR%, and the obtained measurements were compared between the instruments.CR% of optic disc parameters ranged between 0.90 and 22.22% and 0.00 and 16.00% with the Canon and Zeiss OCT respectively. For macular parameters CR% ranged between 0.62 and 2.81% and 0.99 and 1.81% with the Canon and Zeiss OCT respectively. No statistical difference could be found when comparing the CR of all macular and disc measurements between the instruments. Compared to our previously published data repeatability has significantly improved with the inclusion of automatic tracking systems with both the Canon and Zeiss OCT.Automatic tracking function improves repeatability in both Canon OCT-HS100 and Zeiss Cirrus HD-OCT 5000. However, measurements generated by the two instruments are still not interchangeable.

  5. Transcription-induced CAG repeat contraction in human cells is mediated in part by transcription-coupled nucleotide excision repair.

    Science.gov (United States)

    Lin, Yunfu; Wilson, John H

    2007-09-01

    Expansions of CAG repeat tracts in the germ line underlie several neurological diseases. In human patients and mouse models, CAG repeat tracts display an ongoing instability in neurons, which may exacerbate disease symptoms. It is unclear how repeats are destabilized in nondividing cells, but it cannot involve DNA replication. We showed previously that transcription through CAG repeats induces their instability (Y. Lin, V. Dion, and J. H. Wilson, Nat. Struct. Mol. Biol. 13:179-180). Here, we present a genetic analysis of the link between transcription-induced repeat instability and nucleotide excision repair (NER) in human cells. We show that short interfering RNA-mediated knockdown of CSB, a component specifically required for transcription-coupled NER (TC-NER), and knockdowns of ERCC1 and XPG, which incise DNA adjacent to damage, stabilize CAG repeat tracts. These results suggest that TC-NER is involved in the pathway for transcription-induced CAG repeat instability. In contrast, knockdowns of OGG1 and APEX1, key components involved in base excision repair, did not affect repeat instability. In addition, repeats are stabilized by knockdown of transcription factor IIS, consistent with a requirement for RNA polymerase II (RNAPII) to backtrack from a transcription block. Repeats also are stabilized by knockdown of either BRCA1 or BARD1, which together function as an E3 ligase that can ubiquitinate arrested RNAPII. Treatment with the proteasome inhibitor MG132, which stabilizes repeats, confirms proteasome involvement. We integrate these observations into a tentative pathway for transcription-induced CAG repeat instability that can account for the contractions observed here and potentially for the contractions and expansions seen with human diseases.

  6. Extending Teach and Repeat to Pivoting Wheelchairs

    Directory of Open Access Journals (Sweden)

    Guillermo Del Castillo

    2003-02-01

    Full Text Available The paper extends the teach-and-repeat paradigm that has been successful for the control of holonomic robots to nonholonomic wheelchairs which may undergo pivoting action over the course of their taught movement. Due to the nonholonomic nature of the vehicle kinematics, estimation is required -- in the example given herein, based upon video detection of wall-mounted cues -- both in the teaching and the tracking events. In order to accommodate motion that approaches pivoting action as well as motion that approaches straight-line action, the estimation equations of the Extended Kalman Filter and the control equations are formulated using two different definitions of a nontemporal independent variable. The paper motivates the need for pivoting action in real-life settings by reporting extensively on the abilities and limitations of estimation-based teach-and-repeat action where pivoting and near-pivoting action is disallowed. Following formulation of the equations in the near-pivot mode, the paper reports upon experiments where taught trajectories which entail a seamless mix of near-straight and near-pivot action are tracked.

  7. The Perpetual Repeater: an Educative Musical Experience.

    Directory of Open Access Journals (Sweden)

    Svetlana Skriagina

    2014-05-01

    Full Text Available To commemorate the 40th anniversary of the Music Undergraduate Program of the Universidad Pedagógica Nacional (National Pedagogic University, two musical events were planned: an original work written for choir, soloists and symphonic band, and an opera for children. As a result, the cantata ‘The Perpetual Repeater” has been created as an adaptation of a work named “50 Milions de Segons” (50 Millions of Seconds, staged by the CATANIA project of the Barcelona Servei Educatiu de L’Auditori. This work tells the story of those school teachers who, paradoxically enough repeat the same course year after year. After visiting L’Auditori of Barcelona to participate in the pedagogic musical work carried out with school children, we considered the possibility of developing an analogous project, in a similar sociocultural and educational environment, within our Music Undergraduate Program. So, this article deals with two fundamental moments which are essential to understand the educational work implemented with the ISPA students of sixth degree, as well as with a group of the program’s students: The Purpose, which describes in detail the planning of the musical work for children, and The Experience, in which the way the process of The Perpetual Repeater Cantatawas carried out is described.

  8. Airborne Radar Interferometric Repeat-Pass Processing

    Science.gov (United States)

    Hensley, Scott; Michel, Thierry R.; Jones, Cathleen E.; Muellerschoen, Ronald J.; Chapman, Bruce D.; Fore, Alexander; Simard, Marc; Zebker, Howard A.

    2011-01-01

    Earth science research often requires crustal deformation measurements at a variety of time scales, from seconds to decades. Although satellites have been used for repeat-track interferometric (RTI) synthetic-aperture-radar (SAR) mapping for close to 20 years, RTI is much more difficult to implement from an airborne platform owing to the irregular trajectory of the aircraft compared with microwave imaging radar wavelengths. Two basic requirements for robust airborne repeat-pass radar interferometry include the ability to fly the platform to a desired trajectory within a narrow tube and the ability to have the radar beam pointed in a desired direction to a fraction of a beam width. Uninhabited Aerial Vehicle Synthetic Aperture Radar (UAVSAR) is equipped with a precision auto pilot developed by NASA Dryden that allows the platform, a Gulfstream III, to nominally fly within a 5 m diameter tube and with an electronically scanned antenna to position the radar beam to a fraction of a beam width based on INU (inertial navigation unit) attitude angle measurements.

  9. Aggregating quantum repeaters for the quantum internet

    Science.gov (United States)

    Azuma, Koji; Kato, Go

    2017-09-01

    The quantum internet holds promise for accomplishing quantum teleportation and unconditionally secure communication freely between arbitrary clients all over the globe, as well as the simulation of quantum many-body systems. For such a quantum internet protocol, a general fundamental upper bound on the obtainable entanglement or secret key has been derived [K. Azuma, A. Mizutani, and H.-K. Lo, Nat. Commun. 7, 13523 (2016), 10.1038/ncomms13523]. Here we consider its converse problem. In particular, we present a universal protocol constructible from any given quantum network, which is based on running quantum repeater schemes in parallel over the network. For arbitrary lossy optical channel networks, our protocol has no scaling gap with the upper bound, even based on existing quantum repeater schemes. In an asymptotic limit, our protocol works as an optimal entanglement or secret-key distribution over any quantum network composed of practical channels such as erasure channels, dephasing channels, bosonic quantum amplifier channels, and lossy optical channels.

  10. Automated Planning in Repeated Adversarial Games

    CERN Document Server

    de Cote, Enrique Munoz; Sykulski, Adam M; Jennings, Nicholas R

    2012-01-01

    Game theory's prescriptive power typically relies on full rationality and/or self-play interactions. In contrast, this work sets aside these fundamental premises and focuses instead on heterogeneous autonomous interactions between two or more agents. Specifically, we introduce a new and concise representation for repeated adversarial (constant-sum) games that highlight the necessary features that enable an automated planing agent to reason about how to score above the game's Nash equilibrium, when facing heterogeneous adversaries. To this end, we present TeamUP, a model-based RL algorithm designed for learning and planning such an abstraction. In essence, it is somewhat similar to R-max with a cleverly engineered reward shaping that treats exploration as an adversarial optimization problem. In practice, it attempts to find an ally with which to tacitly collude (in more than two-player games) and then collaborates on a joint plan of actions that can consistently score a high utility in adversarial repeated gam...

  11. Chromosome-specific DNA Repeat Probes

    Energy Technology Data Exchange (ETDEWEB)

    Baumgartner, Adolf; Weier, Jingly Fung; Weier, Heinz-Ulrich G.

    2006-03-16

    In research as well as in clinical applications, fluorescence in situ hybridization (FISH) has gained increasing popularity as a highly sensitive technique to study cytogenetic changes. Today, hundreds of commercially available DNA probes serve the basic needs of the biomedical research community. Widespread applications, however, are often limited by the lack of appropriately labeled, specific nucleic acid probes. We describe two approaches for an expeditious preparation of chromosome-specific DNAs and the subsequent probe labeling with reporter molecules of choice. The described techniques allow the preparation of highly specific DNA repeat probes suitable for enumeration of chromosomes in interphase cell nuclei or tissue sections. In addition, there is no need for chromosome enrichment by flow cytometry and sorting or molecular cloning. Our PCR-based method uses either bacterial artificial chromosomes or human genomic DNA as templates with {alpha}-satellite-specific primers. Here we demonstrate the production of fluorochrome-labeled DNA repeat probes specific for human chromosomes 17 and 18 in just a few days without the need for highly specialized equipment and without the limitation to only a few fluorochrome labels.

  12. Repeat-induced gene silencing in mammals.

    Science.gov (United States)

    Garrick, D; Fiering, S; Martin, D I; Whitelaw, E

    1998-01-01

    In both plants and Drosophila melanogaster, expression from a transgenic locus may be silenced when repeated transgene copies are arranged as a concatameric array. This repeat-induced gene silencing is frequently manifested as a decrease in the proportion of cells that express the transgene, resulting in a variegated pattern of expression. There is also some indication that, in transgenic mammals, the number of transgene copies within an array can exert a repressive influence on expression, with several mouse studies reporting a decrease in the level of expression per copy as copy number increases. However, because these studies compare different sites of transgene integration as well as arrays with different numbers of copies, the expression levels observed may be subject to varying position effects as well as the influence of the multicopy array. Here we describe use of the lox/Cre system of site-specific recombination to generate transgenic mouse lines in which different numbers of a transgene are present at the same chromosomal location, thereby eliminating the contribution of position effects and allowing analysis of the effect of copy number alone on transgene silencing. Reduction in copy number results in a marked increase in expression of the transgene and is accompanied by decreased chromatin compaction and decreased methylation at the transgene locus. These findings establish that the presence of multiple homologous copies of a transgene within a concatameric array can have a repressive effect upon gene expression in mammalian systems.

  13. Radiotherapy for a repeatedly recurrent ameloblastoma with malignant transformation.

    Science.gov (United States)

    Huang, Chun-Ming; Chen, Jin-Yi; Chen, Chung-Ho; Huang, Chih-Jen

    2014-01-01

    The role of radiation therapy (RT) for ameloblastoma remains controversial and undetermined due to the rarity of the disease. A case of repeatedly recurrent ameloblastoma with malignant transformation is presented. The clinical course and managements are described. The 63-year-old man had a recurrent ameloblastoma in the left mandible. Five years after the first surgical resection, he underwent 8 more rounds of surgical excision of the recurrent tumors. The malignant transformation occurred and the unresectable tumor invaded the masticator space, parapharyngeal space, and skull base. He received 3-dimensional conformal RT, at the dose of 66 Gray (Gy) in 33 fractions. The ulcerative exophytic mass had regressed gradually. After follow-up of 28 months, the tumor was well controlled. RT seems to be a feasible treatment option for recurrent ameloblastoma with malignant transformation. Copyright © 2013 Wiley Periodicals, Inc.

  14. Reactivity to nicotine cues over repeated cue reactivity sessions

    Science.gov (United States)

    LaRowe, Steven D.; Saladin, Michael E.; Carpenter, Matthew J.; Upadhyaya, Himanshu P.

    2009-01-01

    The present study investigated whether reactivity to nicotine-related cues would attenuate across four experimental sessions held one week apart. Participants were nineteen non-treatment seeking, nicotine-dependent males. Cue reactivity sessions were performed in an outpatient research center using in vivo cues consisting of standardized smoking-related paraphernalia (e.g., cigarettes) and neutral comparison paraphernalia (e.g., pencils). Craving ratings were collected before and after both cue presentations while physiological measures (heart rate, skin conductance) were collected before and during the cue presentations. Although craving levels decreased across sessions, smoking-related cues consistently evoked significantly greater increases in craving relative to neutral cues over all four experimental sessions. Skin conductance was higher in response to smoking cues, though this effect was not as robust as that observed for craving. Results suggest that, under the described experimental parameters, craving can be reliably elicited over repeated cue reactivity sessions. PMID:17537583

  15. REPEATED RECURRENCE OF OSTEOSARCOMA TREATED BY RESECTIONS AND CHEMOTHERAPY

    Institute of Scientific and Technical Information of China (English)

    刘国平; 杜靖远; 陈汝轻; 罗怀灿; 叶开华

    1996-01-01

    This paper presents 5 patients with repeated recurrence of osteoeareoma (RROS). The primary focus of 3 patients were in the distal portion of femur, and 2 patients were in the proximal portion of tibia. Three patients, whose chest X ray film were negative, were treated by amputation and chemotherapy. Two patients had isolated metastatic focus 1.5cm in diameter in lung, were treated by amputation after 1 week of chemotherapy and then treated by lobectomy after 2 weeks of chemotherapy. After operation, the chemotherapy was carried out for 3 courses of treatment. The roentgenogram of chest and affected limb were taken once every two months. There were metastatic focuses found in the lung of 1 patient and in the distal portion of femur of 2 patients. One patient was operated on for 4 times. Up to now, 3 patients havebeen living for 5 years and 2 patients for 6 years after operation.

  16. Reactivity to nicotine cues over repeated cue reactivity sessions.

    Science.gov (United States)

    LaRowe, Steven D; Saladin, Michael E; Carpenter, Matthew J; Upadhyaya, Himanshu P

    2007-12-01

    The present study investigated whether reactivity to nicotine-related cues would attenuate across four experimental sessions held 1 week apart. Participants were nineteen non-treatment seeking, nicotine-dependent males. Cue reactivity sessions were performed in an outpatient research center using in vivo cues consisting of standardized smoking-related paraphernalia (e.g., cigarettes) and neutral comparison paraphernalia (e.g., pencils). Craving ratings were collected before and after both cue presentations while physiological measures (heart rate, skin conductance) were collected before and during the cue presentations. Although craving levels decreased across sessions, smoking-related cues consistently evoked significantly greater increases in craving relative to neutral cues over all four experimental sessions. Skin conductance was higher in response to smoking cues, though this effect was not as robust as that observed for craving. Results suggest that, under the described experimental parameters, craving can be reliably elicited over repeated cue reactivity sessions.

  17. Repeated blood flow restriction induces muscle fiber hypertrophy.

    Science.gov (United States)

    Sudo, Mizuki; Ando, Soichi; Kano, Yutaka

    2017-02-01

    We recently developed an animal model to investigate the effects of eccentric contraction (ECC) and blood flow restriction (BFR) on muscle tissue at the cellular level. This study clarified the effects of repeated BFR, ECC, and BFR combined with ECC (BFR+ECC) on muscle fiber hypertrophy. Male Wistar rats were assigned to 3 groups: BFR, ECC, and BFR+ECC. The contralateral leg in the BFR group served as a control (CONT). Muscle fiber cross-sectional area (CSA) of the tibialis anterior was determined after the respective treatments for 6 weeks. CSA was greater in the BFR+ECC group than in the CONT (P muscle fiber hypertrophy at the cellular level. Muscle Nerve 55: 274-276, 2017. © 2016 Wiley Periodicals, Inc.

  18. [Chlamydia: from population screening to individual repeated screening].

    Science.gov (United States)

    Bally, F; Quach, A

    2014-10-08

    Chlamydia trachomatis is a frequent sexually transmitted infection especially in young adults and adolescents. Its complications can impair a woman's reproductive potential. chlamydia control has several challenges. These include asymptomatic infections; a long duration of untreated infections; re-infections and partner treatments. Any person with infection is at high risk of re-infection. Repeated screening would decrease, at an individual level, the risk of complications. General practitioners, gynaecologists and centres for sexual health could participate in Chlamydia screening for asymptomatic infections, in Switzerland, the cost of the laboratory test is fixed by national tariff regulations. The cost is high and prohibitive for many, especially adolescents and young adults and needs to be lowered.

  19. Seizure threshold to lidocaine is decreased following repeated ECS (electroconvulsive shock)

    DEFF Research Database (Denmark)

    Kragh, J; Seidelin, J; Bolwig, T G

    1993-01-01

    Seizure susceptibility to lidocaine was investigated in rats which had received repeated ECS (electroconvulsive shock). In the first experiment three groups of rats received an ECS daily for 18 days, an ECS weekly for 18 weeks, and 18 sham treatments, respectively. Twelve weeks after the last ECS...

  20. No hearing loss after repeated courses of tobramycin in cystic fibrosis patients

    NARCIS (Netherlands)

    Scheenstra, Renske J; Heijerman, Harry G M; Zuur, Charlotte L; Touw, Daan J; Rijntjes, Evert

    2010-01-01

    CONCLUSION: Our results indicate that repeated treatment courses with tobramycin 10 mg/kg (twice daily for 3 weeks) may be safely applied in cystic fibrosis (CF) patients with respect to ototoxicity. The risk of hearing loss in this patient group is less than expected, which could be explained by ei

  1. Comparing the Efficiency of Repeated Reading and Listening-While-Reading to Improve Fluency and Comprehension

    Science.gov (United States)

    Hawkins, Renee O.; Marsicano, Richard; Schmitt, Ara J.; McCallum, Elizabeth; Musti-Rao, Shobana

    2015-01-01

    An alternating treatments design was used to compare the effects of two reading fluency interventions on the oral reading fluency and maze accuracy of four fourth-grade students. Also, by taking into account time spent in intervention, the efficiency of the two interventions was compared. In the adult-mediated repeated reading (RR) condition,…

  2. Repeated Time-to-event Analysis of Consecutive Analgesic Events in Postoperative Pain

    DEFF Research Database (Denmark)

    Juul, Rasmus Vestergaard; Rasmussen, Sten; Kreilgaard, Mads;

    2015-01-01

    BACKGROUND: Reduction in consumption of opioid rescue medication is often used as an endpoint when investigating analgesic efficacy of drugs by adjunct treatment, but appropriate methods are needed to analyze analgesic consumption in time. Repeated time-to-event (RTTE) modeling is proposed as a w...

  3. Seizure threshold to lidocaine is decreased following repeated ECS (electroconvulsive shock)

    DEFF Research Database (Denmark)

    Kragh, J; Seidelin, J; Bolwig, T G

    1993-01-01

    Seizure susceptibility to lidocaine was investigated in rats which had received repeated ECS (electroconvulsive shock). In the first experiment three groups of rats received an ECS daily for 18 days, an ECS weekly for 18 weeks, and 18 sham treatments, respectively. Twelve weeks after the last ECS...

  4. Discrepancies in reporting the CAG repeat lengths for Huntington's disease

    DEFF Research Database (Denmark)

    Quarrell, Oliver W; Handley, Olivia; O'Donovan, Kirsty

    2011-01-01

    Huntington's disease results from a CAG repeat expansion within the Huntingtin gene; this is measured routinely in diagnostic laboratories. The European Huntington's Disease Network REGISTRY project centrally measures CAG repeat lengths on fresh samples; these were compared with the original...

  5. Cardiovascular risk factors in children after repeat doses of antenatal glucocorticoids: an RCT.

    Science.gov (United States)

    McKinlay, Christopher J D; Cutfield, Wayne S; Battin, Malcolm R; Dalziel, Stuart R; Crowther, Caroline A; Harding, Jane E

    2015-02-01

    Treatment of women at risk for preterm birth with repeat doses of glucocorticoids reduces neonatal morbidity but could have adverse long-term effects on cardiometabolic health in offspring. We assessed whether exposure to repeat antenatal betamethasone increased risk factors for later cardiometabolic disease in children whose mothers participated in the Australasian Collaborative Trial of Repeat Doses of Corticosteroids. Women were randomized to betamethasone or placebo treatment, ≥ 7 days after an initial course of glucocorticoids, repeated each week that they remained at risk for preterm birth at children were assessed at 6 to 8 years' corrected age for body composition, insulin sensitivity, ambulatory blood pressure, and renal function. Of 320 eligible childhood survivors, 258 were studied (81%; 123 repeat betamethasone group; 135 placebo [single course] group). Children exposed to repeat antenatal betamethasone and those exposed to placebo had similar total fat mass (geometric mean ratio 0.98, 95% confidence interval [CI] 0.78 to 1.23), minimal model insulin sensitivity (geometric mean ratio 0.89, 95% CI 0.74 to 1.08), 24-hour ambulatory blood pressure (mean difference systolic 0 mm Hg, 95% CI -2 to 2; diastolic 0 mm Hg, 95% CI -1 to 1), and estimated glomerular filtration rate (mean difference 1.2 mL/min/1.73 m(2), 95% CI -3.2 to 5.6). Exposure to repeat doses of antenatal betamethasone compared with a single course of glucocorticoids does not increase risk factors for cardiometabolic disease at early school age. Copyright © 2015 by the American Academy of Pediatrics.

  6. Results of repeated transsphenoidal surgery in Cushing's disease. Long-term follow-up.

    Science.gov (United States)

    Valderrábano, Pablo; Aller, Javier; García-Valdecasas, Leopoldo; García-Uría, José; Martín, Laura; Palacios, Nuria; Estrada, Javier

    2014-04-01

    Transsphenoidal surgery (TSS) is the treatment of choice for Cushing's disease (CD). However, the best treatment option when hypercortisolism persists or recurs remains unknown. The aim of this study was to analyze the short and long-term outcome of repeat TSS in this situation and to search for response predictors. Data from 26 patients with persistent (n=11) or recurrent (n=15) hypercortisolism who underwent repeat surgery by a single neurosurgeon between 1982 and 2009 were retrospectively analyzed. Remission was defined as normalization of urinary free cortisol (UFC) levels, and recurrence as presence of elevated UFC levels after having achieved remission. The following potential outcome predictors were analyzed: adrenal status (persistence or recurrence) after initial TSS, tumor identification in imaging tests, degree of hypercortisolism before repeat TSS, same/different surgeon in both TSS, and time to repeat surgery. Immediate postoperative remission was achieved in 12 patients (46.2%). Five of the 10 patients with available follow-up data relapsed after surgery (median time to recurrence, 13 months). New hormone deficiencies were seen in seven patients (37%), and two patients had cerebrospinal fluid leakage. No other major complications occurred. None of the preoperative factors analyzed was predictive of surgical outcome. When compared to initial surgery, repeat TSS for CD is associated to a lower remission rate and a higher risk of recurrence and complications. Further studies are needed to define outcome predictors. Copyright © 2013 SEEN. Published by Elsevier Espana. All rights reserved.

  7. Androgen receptor gene CAG repeat polymorphism and ovarian cancer risk: A meta-analysis.

    Science.gov (United States)

    Deng, Yang; Wang, Jue; Wang, Ling; Du, Yan

    2017-02-28

    Ovarian cancer is one of the common gynecological malignancies worldwide. It is usually diagnosed at a later stage, thus missing the best opportunity for treatment. Despite the advancement of ovarian cancer treatment, the prognosis is still poor. Androgen receptor (AR) may play a role in ovarian carcinogenesis. Previous studies regarding the association between AR CAG repeat length and ovarian cancer risk reported inconsistent results. Therefore, we conducted a meta-analysis to evaluate the association between AR CAG repeat length and ovarian cancer risk following the MOOSE guidelines. PubMed, Web of Science, EBSCO and other databases were searched up to September 15(th) 2016. Case control studies with clear definition of CAG repeat length and detailed genotype information were included. Two authors independently reviewed and extracted data. Pooled analysis and subgroup analysis stratified by ethnicity were performed for different genetic models. Begg's funnel plot and Egger's test were performed for publication bias estimation. Overall, there was no association between the AR CAG repeat polymorphism and ovarian cancer risk. However, short CAG repeat polymorphism was associated with increased ovarian cancer risk in African Americans and Chinese under the dominant model, whereas a reverse association was observed in Caucasians and Italians under the other three models. Our study results should be interpreted with caution. Further well-designed epidemiological and functional studies are needed to elucidate the role of AR in ovarian carcinogenesis.

  8. Repeated Intraperitoneal alpha-Radioimmunotherapy of Ovarian Cancer in Mice

    DEFF Research Database (Denmark)

    Elgqvist, Jörgen; Andersson, Håkan; Jensen, Holger

    2010-01-01

    The aim of this study was to investigate the therapeutic efficacy of alpha-radioimmunotherapy of ovarian cancer in mice using different fractionated treatment regimens. The study was performed using the monoclonal antibody MX35 F(ab')(2) labeled with the alpha-particle emitter (211)At. Methods....... Nude mice were intraperitoneally inoculated with ~1 x 10(7) cells of the cell line NIH:OVCAR-3. Four weeks later 6 groups of animals were given 400 kBq (211)At-MX35 F(ab')(2) as a single or as a repeated treatment of up to 6 times (n = 18 in each group). The fractionated treatments were given every...... seventh day. Control animals were treated with unlabeled MX35 F(ab')(2) (n = 12). Eight weeks posttreatment the animals were sacrificed and the presence of macro- and microscopic tumors and ascites was determined. Results. The tumor-free fractions (TFFs) of the animals, defined as the fraction of animals...

  9. 47 CFR 90.247 - Mobile repeater stations.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 5 2010-10-01 2010-10-01 false Mobile repeater stations. 90.247 Section 90.247... MOBILE RADIO SERVICES Non-Voice and Other Specialized Operations § 90.247 Mobile repeater stations. A... repeater to extend the communications range of hand-carried units subject to the following: (a)...

  10. Polymorphic GGC repeat differentially regulates human reelin gene expression levels.

    Science.gov (United States)

    Persico, A M; Levitt, P; Pimenta, A F

    2006-10-01

    The human gene encoding Reelin (RELN), a pivotal protein in neurodevelopment, includes a polymorphic GGC repeat in its 5' untranslated region (UTR). CHO cells transfected with constructs encompassing the RELN 5'UTR with 4-to-13 GGC repeats upstream of the luciferase reporter gene show declining luciferase activity with increasing GGC repeat number (P autism.

  11. CGG repeat in the FMR1 gene: Size matters

    NARCIS (Netherlands)

    R.A. Willemsen (Ralph); G.J. Levenga (Josien); B.A. Oostra (Ben)

    2011-01-01

    textabstractThe FMR1 gene contains a CGG repeat present in the 5'-untranslated region which can be unstable upon transmission to the next generation. The repeat is up to 55 CGGs long in the normal population. In patients with fragile X syndrome (FXS), a repeat length exceeding 200 CGGs (full

  12. Antihypertensive treatment

    DEFF Research Database (Denmark)

    Christensen, Cramer; Mogensen, C E

    1987-01-01

    This study was undertaken to clarify whether antihypertensive treatment has any effect on the rate of progression of kidney disease in patients with incipient diabetic nephropathy. Six insulin-dependent diabetic men with incipient nephropathy (urinary albumin excretion above 15 micrograms....../min and total protein excretion below 0.5 g/24 h) were first given metoprolol (200 mg daily) with the subsequent addition of hydroflumethiazide. At the start of antihypertensive treatment, mean patient age was 32 +/- 4.2 years (SD) and mean duration of diabetes was 18 +/- 1.2 years. The patients were followed...... with repeated measurements of urinary albumin excretion for a mean of 5.4 +/- 3.1 years prior to, and for 4.7 +/- 1.3 years (SD) during treatment. Mean arterial blood pressure declined significantly during treatment, e.g., the values at 6 months before initiation of treatment being compared with values during...

  13. Differences between youth with a single suicide attempt and repeaters regarding their and their parents history of psychiatric illness.

    Science.gov (United States)

    Jakobsen, Ida Skytte; Christiansen, Erik; Larsen, Kim Juul; Waaktaar, Trine

    2011-01-01

    The objective of this study was to determine predictors of repeated suicide attempts in young people, focusing on psychiatric illness. A longitudinal population-based register study of all adolescents born in Denmark between 1984 and 2006 was conducted. Greater numbers of hospitalizations, psychiatric diagnoses, and psychopharmacological medications prescribed to youth before and after the index attempt were risk factors for repeated suicide attempts. Parental diagnoses and drug prescriptions following a child's first suicide attempt moderated the risk of repeated attempts. Psychiatric illness is a strong predictor of repeated suicide attempts in young people, and those with co-morbid diagnoses are at increased risk of repeated suicide attempts. Treatment of psychiatric illness in the parents after their child's first suicide attempt is a potential protective factor.

  14. Repeat Testing Effects on Credentialing Exams: Are Repeaters Misinformed or Uninformed?

    Science.gov (United States)

    Feinberg, Richard A.; Raymond, Mark R.; Haist, Steven A.

    2015-01-01

    To mitigate security concerns and unfair score gains, credentialing programs routinely administer new test material to examinees retesting after an initial failing attempt. Counterintuitively, a small but growing body of recent research suggests that repeating the identical form does not create an unfair advantage. This study builds upon and…

  15. Who Repeats Algebra, and How Does Initial Performance Relate to Improvement When the Course Is Repeated?

    Science.gov (United States)

    Fong, Anthony; Jaquet, Karina; Finkelstein, Neal

    2016-01-01

    The information provided in this report shows how students perform when they repeat algebra I and how the level of improvement varies depending on initial course performance and the academic measure (course grades or CST scores). This information can help inform decisions and policies regarding whether and under what circumstances students should…

  16. Hybrid quantum repeater using bright coherent light.

    Science.gov (United States)

    van Loock, P; Ladd, T D; Sanaka, K; Yamaguchi, F; Nemoto, Kae; Munro, W J; Yamamoto, Y

    2006-06-23

    We describe a quantum repeater protocol for long-distance quantum communication. In this scheme, entanglement is created between qubits at intermediate stations of the channel by using a weak dispersive light-matter interaction and distributing the outgoing bright coherent-light pulses among the stations. Noisy entangled pairs of electronic spin are then prepared with high success probability via homodyne detection and postselection. The local gates for entanglement purification and swapping are deterministic and measurement-free, based upon the same coherent-light resources and weak interactions as for the initial entanglement distribution. Finally, the entanglement is stored in a nuclear-spin-based quantum memory. With our system, qubit-communication rates approaching 100 Hz over 1280 km with fidelities near 99% are possible for reasonable local gate errors.

  17. Quantum repeaters using continuous-variable teleportation

    Science.gov (United States)

    Dias, Josephine; Ralph, T. C.

    2017-02-01

    Quantum optical states are fragile and can become corrupted when passed through a lossy communication channel. Unlike for classical signals, optical amplifiers cannot be used to recover quantum signals. Quantum repeaters have been proposed as a way of reducing errors and hence increasing the range of quantum communications. Current protocols target specific discrete encodings, for example quantum bits encoded on the polarization of single photons. We introduce a more general approach that can reduce the effect of loss on any quantum optical encoding, including those based on continuous variables such as the field amplitudes. We show that in principle the protocol incurs a resource cost that scales polynomially with distance. We analyze the simplest implementation and find that while its range is limited it can still achieve useful improvements in the distance over which quantum entanglement of field amplitudes can be distributed.

  18. Statistical Properties of repeating FRB 121102

    CERN Document Server

    Wang, F Y

    2016-01-01

    Fast radio bursts (FRBs) are millisecond-duration radio signals possibly occurring at cosmological distances. However the physical model of FRBs is mystery, many models have been proposed. Here we study the frequency distributions of peak flux, fluence, duration and waiting time for repeating FRB 121102. The cumulative distributions of peak flux, fluence and duration show power-law forms. The waiting time distribution also shows power-law distribution, and is consistent with a non-stationary Poisson process. We also use the statistical results to test the proposed models for FRBs. Comparing with the model predications, we find that the theoretical models proposed by Dai et al. (2016) and Katz (2016) are favored. These distributions are consistent with the predications from avalanche models of driven systems.

  19. Simple sequence repeats in mycobacterial genomes

    Indian Academy of Sciences (India)

    Vattipally B Sreenu; Pankaj Kumar; Javaregowda Nagaraju; Hampapathalu A Nagarajaram

    2007-01-01

    Simple sequence repeats (SSRs) or microsatellites are the repetitive nucleotide sequences of motifs of length 1–6 bp. They are scattered throughout the genomes of all the known organisms ranging from viruses to eukaryotes. Microsatellites undergo mutations in the form of insertions and deletions (INDELS) of their repeat units with some bias towards insertions that lead to microsatellite tract expansion. Although prokaryotic genomes derive some plasticity due to microsatellite mutations they have in-built mechanisms to arrest undue expansions of microsatellites and one such mechanism is constituted by post-replicative DNA repair enzymes MutL, MutH and MutS. The mycobacterial genomes lack these enzymes and as a null hypothesis one could expect these genomes to harbour many long tracts. It is therefore interesting to analyse the mycobacterial genomes for distribution and abundance of microsatellites tracts and to look for potentially polymorphic microsatellites. Available mycobacterial genomes, Mycobacterium avium, M. leprae, M. bovis and the two strains of M. tuberculosis (CDC1551 and H37Rv) were analysed for frequencies and abundance of SSRs. Our analysis revealed that the SSRs are distributed throughout the mycobacterial genomes at an average of 220–230 SSR tracts per kb. All the mycobacterial genomes contain few regions that are conspicuously denser or poorer in microsatellites compared to their expected genome averages. The genomes distinctly show scarcity of long microsatellites despite the absence of a post-replicative DNA repair system. Such severe scarcity of long microsatellites could arise as a result of strong selection pressures operating against long and unstable sequences although influence of GC-content and role of point mutations in arresting microsatellite expansions can not be ruled out. Nonetheless, the long tracts occasionally found in coding as well as non-coding regions may account for limited genome plasticity in these genomes.

  20. The excess of small inverted repeats in prokaryotes.

    Science.gov (United States)

    Ladoukakis, Emmanuel D; Eyre-Walker, Adam

    2008-09-01

    Recent analyses have shown that there is a large excess of perfect inverted repeats in many prokaryotic genomes but not in eukaryotic ones. This difference could be due to a genuine difference between prokaryotes and eukaryotes or to differences in the methods and types of data analyzed--full genome versus protein coding sequences. We used simulations to show that the method used previously tends to underestimate the expected number of inverted repeats. However, this bias is not large and cannot explain the excess of inverted repeats observed in real data. In contrast, our method is unbiased. When both methods are applied to bacterial protein coding sequences they both detect an excess of inverted repeats, which is much lower than previously reported in whole prokaryotic genomes. This suggests that the reported large excess of inverted repeats is due to repeats found in intergenic regions. These repeats could be due to transcription factor binding sites, or other types of repetitive DNA, on opposite strands of the DNA sequence. In contrast, the smaller, but significant, excess of inverted repeats that we report in protein coding sequences may be due to sequence-directed mutagenesis (SDM). SDM is a process where one copy of a small, imperfect, inverted repeat corrects the other copy via strand misalignment, resulting in a perfect repeat and a series of mutations. We show by simulation that even very low levels of SDM, relative to the rate of point mutation, can generate a substantial excess of inverted repeats.

  1. Studies of an expanded trinucleotide repeat in transgenic mice

    Energy Technology Data Exchange (ETDEWEB)

    Bingham, P.; Wang, S.; Merry, D. [Univ. of Pennsylvania, Philadelphia, PA (United States)

    1994-09-01

    Spinal and bulbar muscular atrophy (SBMA) is a progressive motor neuron disease caused by expansion of a trinucleotide repeat in the androgen receptor gene (AR{sup exp}). AR{sup exp} repeats expand further or contract in approximately 25% of transmissions. Analogous {open_quotes}dynamic mutations{close_quotes} have been reported in other expanded trinucleotide repeat disorders. We have been developing a mouse model of this disease using a transgenic approach. Expression of the SBMA AR was documented in transgenic mice with an inducible promoter. No phenotypic effects of transgene expression were observed. We have extended our previous results on stability of the expanded trinucleotide repeat in transgenic mice in two lines carrying AR{sup exp}. Tail DNA was amplified by PCR using primers spanning the repeat on 60 AR{sup exp} transgenic mice from four different transgenic lines. Migration of the PCR product through an acrylamide gel showed no change of the 45 CAG repeat length in any progeny. Similarly, PCR products from 23 normal repeat transgenics showed no change from the repeat length of the original construct. Unlike the disease allele in humans, the expanded repeat AR cDNA in transgenic mice showed no change in repeat length with transmission. The relative stability of CAG repeats seen in the transgenic mice may indicate either differences in the fidelity of replicative enzymes, or differences in error identification and repair between mice and humans. Integration site or structural properties of the transgene itself might also play a role.

  2. Role of DNA Polymerases in Repeat-Mediated Genome Instability

    Directory of Open Access Journals (Sweden)

    Kartik A. Shah

    2012-11-01

    Full Text Available Expansions of simple DNA repeats cause numerous hereditary diseases in humans. We analyzed the role of DNA polymerases in the instability of Friedreich’s ataxia (GAAn repeats in a yeast experimental system. The elementary step of expansion corresponded to ∼160 bp in the wild-type strain, matching the size of Okazaki fragments in yeast. This step increased when DNA polymerase α was mutated, suggesting a link between the scale of expansions and Okazaki fragment size. Expandable repeats strongly elevated the rate of mutations at substantial distances around them, a phenomenon we call repeat-induced mutagenesis (RIM. Notably, defects in the replicative DNA polymerases δ and ∊ strongly increased rates for both repeat expansions and RIM. The increases in repeat-mediated instability observed in DNA polymerase δ mutants depended on translesion DNA polymerases. We conclude that repeat expansions and RIM are two sides of the same replicative mechanism.

  3. ADHD-like hyperactivity, with no attention deficit, in adult rats after repeated hypoxia during the equivalent of extreme prematurity.

    Science.gov (United States)

    Oorschot, Dorothy E; Voss, Logan; Covey, Matthew V; Bilkey, David K; Saunders, Sarah E

    2007-11-30

    The most common behavioural disorder seen in children and adolescents born extremely prematurely is attention deficit hyperactivity disorder (ADHD). The hyperactive/impulsive sub-type of ADHD or the inattentive sub-type or the hyperactive/impulsive/inattentive sub-type can be evident. These sub-types of ADHD can persist into adulthood. The aim of this study was to investigate the relevance of a new immature rat model of repeated hypoxic exposure to these behavioural characteristics of extreme prematurity. More specifically, this study aimed to measure ADHD-like hyperactivity in response to delayed reward, and inattention, in repeated hypoxic versus repeated normoxic rats. Sprague-Dawley rats were exposed to either repeated hypoxia or repeated normoxia during postnatal days (PN) 1-3. The rat brain during PN1-3 is generally considered to be developmentally equivalent to the human brain during extreme prematurity. The rats were then behaviourally tested at 16 months-of-age on a multiple component fixed interval-extinction test. This test detects ADHD-like hyperactivity in response to delayed reward, as well as inattention. It was found that the repeated hypoxic rats exhibited ADHD-like hyperactivity in response to delayed reward, but no attention deficit, when compared to repeated normoxic rats. These findings provide a new animal model to investigate the biological mechanisms and treatment of ADHD-like hyperactivity due to repeated hypoxia during the equivalent of extreme prematurity.

  4. Differences between youth with a single suicide attempt and repeaters regarding their and their parents history of psychiatric illness

    DEFF Research Database (Denmark)

    Jakobsen, Ida Skytte; Christiansen, Erik; Juul Larsen, Kim

    2011-01-01

    The objective of this study was to determine predictors of repeated suicide attempts in young people, focusing on psychiatric illness. A longitudinal population-based register study of all adolescents born in Denmark between 1984 and 2006 was conducted. Greater numbers of hospitalizations, psychi...... is a strong predictor of repeated suicide attempts in young people, and those with co-morbid diagnoses are at increased risk of repeated suicide attempts. Treatment of psychiatric illness in the parents after their child's first suicide attempt is a potential protective factor....

  5. [Effects of Ward Interventions on Repeated Critical Incidents in Child and Adolescent Psychiatric Inpatient Care].

    Science.gov (United States)

    Ulke, Christine; Klein, Annette M; von Klitzing, Kai

    2014-01-01

    Effects of Ward Interventions on Repeated Critical Incidents in Child and Adolescent Psychiatric Inpatient Care. The aim of this study was to evaluate the effects of several ward interventions (transition to an open ward concept, individualized treatment plans, tiered crisis-management, staff training, quality control) on repeated critical incidents, non-restrictive and restrictive measures. The outcome variables were compared in two time periods, 2007 and 2011. The study included 74 critical incident reports of 51 child and adolescent inpatients that had at least one hospital stay and one critical incident in the selected time periods. Aggressive, self-harming, and absconding incidents were included. The quantitative results suggest that ward interventions can contribute to a reduction of repeated critical incidents and restrictive measures. The qualitative evaluation suggests a cultural change of crisis management.

  6. Five-Year, Disease-Free Survival after Repeat Palliative Multimodality Therapy in a Patient with Recurrent Metastastic Bladder Cancer

    Directory of Open Access Journals (Sweden)

    Sebastian Fetscher

    2007-01-01

    Full Text Available In appropriately selected cases, palliative therapeutic strategies can be adapted to those special features of cancer biographies that indicate an atypical course of disease. Elucidating these features, and adapting multimodal treatment strategies to them, can lead to significantly superior effects when compared to the routine application of conventional treatment algorhythms. A case of regionally metastactic bladder cancer is presented that documents the value of repeat debulking-surgery and repeat radiotherapy leading to unexpected short-term and long-term treatment results.

  7. Repeated predictable stress causes resilience against colitis-induced behavioral changes in mice

    Science.gov (United States)

    Hassan, Ahmed M.; Jain, Piyush; Reichmann, Florian; Mayerhofer, Raphaela; Farzi, Aitak; Schuligoi, Rufina; Holzer, Peter

    2014-01-01

    Inflammatory bowel disease is associated with an increased risk of mental disorders and can be exacerbated by stress. In this study which was performed with male 10-week old C57Bl/6N mice, we used dextran sulfate sodium (DSS)-induced colitis to evaluate behavioral changes caused by intestinal inflammation, to assess the interaction between repeated psychological stress (water avoidance stress, WAS) and colitis in modifying behavior, and to analyze neurochemical correlates of this interaction. A 7-day treatment with DSS (2% in drinking water) decreased locomotion and enhanced anxiety-like behavior in the open field test and reduced social interaction. Repeated exposure to WAS for 7 days had little influence on behavior but prevented the DSS-induced behavioral disturbances in the open field and SI tests. In contrast, repeated WAS did not modify colon length, colonic myeloperoxidase content and circulating proinflammatory cytokines, parameters used to assess colitis severity. DSS-induced colitis was associated with an increase in circulating neuropeptide Y (NPY), a rise in the hypothalamic expression of cyclooxygenase-2 mRNA and a decrease in the hippocampal expression of NPY mRNA, brain-derived neurotrophic factor mRNA and mineralocorticoid receptor mRNA. Repeated WAS significantly decreased the relative expression of corticotropin-releasing factor mRNA in the hippocampus. The effect of repeated WAS to blunt the DSS-evoked behavioral disturbances was associated with a rise of circulating corticosterone and an increase in the expression of hypothalamic NPY mRNA. These results show that experimental colitis leads to a particular range of behavioral alterations which can be prevented by repeated WAS, a model of predictable chronic stress, while the severity of colitis remains unabated. We conclude that the mechanisms underlying the resilience effect of repeated WAS involves hypothalamic NPY and the hypothalamic-pituitary-adrenal axis. PMID:25414650

  8. Repeated Predictable Stress Causes Resilience against Colitis-Induced Behavioral Changes in Mice

    Directory of Open Access Journals (Sweden)

    Ahmed M Hassan

    2014-11-01

    Full Text Available Inflammatory bowel disease is associated with an increased risk of mental disorders and can be exacerbated by stress. In this study which was performed with male 10-week old C57Bl/6N mice, we used dextran sulfate sodium (DSS-induced colitis to evaluate behavioral changes caused by intestinal inflammation, to assess the interaction between repeated psychological stress (water avoidance stress, WAS and colitis in modifying behavior, and to analyze neurochemical correlates of this interaction. A 7-day treatment with DSS (2 % in drinking water decreased locomotion and enhanced anxiety-like behavior in the open field test and reduced social interaction. Repeated exposure to WAS for 7 days had little influence on behavior but prevented the DSS-induced behavioral disturbances in the open field and social interaction tests. In contrast, repeated WAS did not modify colon length, colonic myeloperoxidase content and circulating proinflammatory cytokines, parameters used to assess colitis severity. DSS-induced colitis was associated with an increase in circulating neuropeptide Y (NPY, a rise in the hypothalamic expression of cyclooxygenase-2 mRNA and a decrease in the hippocampal expression of NPY mRNA, brain-derived neurotrophic factor mRNA and mineralocorticoid receptor mRNA. Repeated WAS significantly decreased the relative expression of corticotropin-releasing factor mRNA in the hippocampus. The effect of repeated WAS to blunt the DSS-evoked behavioral disturbances was associated with a rise of circulating corticosterone and an increase in the expression of hypothalamic NPY mRNA. These results show that experimental colitis leads to a particular range of behavioral alterations which can be prevented by repeated WAS, a model of predictable chronic stress, while the severity of colitis remains unabated. We conclude that the mechanisms underlying the resilience effect of repeated WAS involves hypothalamic NPY and the hypothalamic-pituitary-adrenal axis.

  9. Repeated-dose liver micronucleus test of 4,4'-methylenedianiline using young adult rats.

    Science.gov (United States)

    Sanada, Hisakazu; Koyama, Naomi; Wako, Yumi; Kawasako, Kazufumi; Hamada, Shuichi

    2015-03-01

    Liver micronucleus (MN) tests using partial hepatectomized rats or juvenile rats have been shown to be useful for the detection of hepatic carcinogens. Moreover, Narumi et al. established the repeated-dose liver MN test using young adult rats for integration into general toxicity. In the present study, in order to examine the usefulness of the repeated-dose liver MN test, we investigated MN induction with a 14 or 28 day treatment protocol using young adult rats treated with 4,4′-methylenedianiline (MDA), a known hepatic carcinogen. MDA dose-dependently induced micronuclei in hepatocytes in 14- and 28-day repeated-dose tests. However, although statistically significant increases in micronuclei were observed in bone marrow cells at two dose levels in the 14-day study, there was no dose response and no increases in micronuclei in the 28-day study. These results indicate that the evaluation of genotoxic effects using hepatocytes is effective in cases where chromosomal aberrations are not clearly detectable in bone marrow cells. Moreover, the repeated-dose liver MN test allows evaluation at a dose below the maximum tolerable dose, which is required for the conventional MN test because micronucleated hepatocytes accumulate. The repeated-dose liver MN test employed in the present study can be integrated into the spectrum of general toxicity tests without further procedural modifications.

  10. Heart failure re-admission: measuring the ever shortening gap between repeat heart failure hospitalizations.

    Directory of Open Access Journals (Sweden)

    Jeffrey A Bakal

    Full Text Available Many quality-of-care and risk prediction metrics rely on time to first rehospitalization even though heart failure (HF patients may undergo several repeat hospitalizations. The aim of this study is to compare repeat hospitalization models. Using a population-based cohort of 40,667 patients, we examined both HF and all cause re-hospitalizations using up to five years of follow-up. Two models were examined: the gap-time model which estimates the adjusted time between hospitalizations and a multistate model which considered patients to be in one of four states; community-dwelling, in hospital for HF, in hospital for any reason, or dead. The transition probabilities and times were then modeled using patient characteristics and number of repeat hospitalizations. We found that during the five years of follow-up roughly half of the patients returned for a subsequent hospitalization for each repeat hospitalization. Additionally, we noted that the unadjusted time between hospitalizations was reduced ∼40% between each successive hospitalization. After adjustment each additional hospitalization was associated with a 28 day (95% CI: 22-35 reduction in time spent out of hospital. A similar pattern was seen when considering the four state model. A large proportion of patients had multiple repeat hospitalizations. Extending the gap between hospitalizations should be an important goal of treatment evaluation.

  11. Effects of repeated applications of fungicide carbendazim on its persistence and microbial community in soil

    Institute of Scientific and Technical Information of China (English)

    YU Yunlong; CHU Xiaoqiang; PANG Guohui; XIANG Yueqin; FANG Hua

    2009-01-01

    Carbendazim, a systemic benzimidazole fungicide, is applied repeatedly to control of plant diseases including soilborne diseases, over a growing season. Studies were carried out under laboratory conditions to assess the effects of repeated carbendazim applications on its persistence and microbial community in soil. The results indicate that dissipation of carbendazim in soil was accelerated with its application frequency. The degradation rate constant of carbendazim was increased significantly from 0.074 d-1 to 0.79 d-1. The corresponding half-life was shorten markedly from 9.3 d to 0.9 d after four repeated applications. No significant inhibitory effect of carbendazim on soil microbial utilization of the carbon sources was observed after first treatment, but a slight increase in average well color development (AWCD) was shown after second, third, and fourth applications. It suggested that soil microorganisms become adapted to carbendazim after repeated application. Simpson and Shannon indexes of soil microbial community from carbendazim treated soil were also similar to those from the control soil, indicating that the richness and dominant character of soil microorganisms remain unchangeable after repeated application. However, after first, second, and third addition of carbendazim, McIntosh indexes on day 21 were significantly increased as compared with the control, suggesting that balance of soil microorganisms was altered due to the enrichment of the specific carbendazim-adapting strains in soil.

  12. Effects of repeated concentric and eccentric contractions on tendon blood circulation.

    Science.gov (United States)

    Kubo, K

    2015-06-01

    Previous studies demonstrated that treatment involving eccentric training was effective in the conservative management of chronic tendinosis. However, the mechanisms for these phenomena are unknown. The purpose of this study was to compare changes in blood circulation of the tendons after the repeated concentric and eccentric contractions. 11 healthy males volunteered for this study. Subjects performed the repeated concentric (CON) and eccentric (ECC) contractions (5 sets of 10 maximal voluntary contractions) of the plantar flexors. During and after repeated contractions, oxyhemoglobin (Oxy), deoxyhemoglobin (Deoxy), total hemoglobin (THb), and oxygen saturation (StO2) of the Achilles tendons were measured using red laser lights. Oxy and THb increased during and after ECC, but not CON. Deoxy decreased during both CON and ECC. Increase in StO2 during and after ECC was greater than that during and after CON. These results suggested that changes in blood circulation of the Achilles tendon during and after repeated eccentric contractions were more remarkable than those during and after repeated concentric contractions.

  13. Two-year follow-up of a randomised trial with repeated antenatal betamethasone.

    Science.gov (United States)

    Peltoniemi, O M; Kari, M A; Lano, A; Yliherva, A; Puosi, R; Lehtonen, L; Tammela, O; Hallman, M

    2009-11-01

    Weekly repeated antenatal corticosteroid treatment improves respiratory outcome but decreases fetal growth and may impair neurodevelopmental outcome. We have previously reported that a single repeat betamethasone (BM) dose neither decreased fetal growth nor improved the outcome of preterm infants during the first hospitalisation. To study prospectively whether a single repeat dose of BM influences neurodevelopment and growth within 2 years. Women with imminent delivery before 34.0 gestational weeks were eligible if they remained undelivered for >7 days after a single course of antenatal BM. After stratification, a single repeat dose of BM (12 mg) or placebo was given. The children underwent neurological and psychometric examinations and a speech evaluation at a corrected age of 2 years. Prospective, blinded evaluation following the randomised multicentre trial. 259 (82%) surviving infants completed the 2-year follow-up, 120 in the BM group and 139 in the placebo group. The rate of survival without severe neurodevelopmental impairment was similar in both groups (BM 98%, placebo 99%). The risk of cerebral palsy (BM 2%, placebo 1%), growth or re-hospitalisation rates (BM 60%, placebo 50%) did not differ between the groups. A single repeat dose of antenatal BM tended not to influence physical growth or neurodevelopment at 2 years of age.

  14. REPdenovo: Inferring De Novo Repeat Motifs from Short Sequence Reads.

    Directory of Open Access Journals (Sweden)

    Chong Chu

    Full Text Available Repeat elements are important components of eukaryotic genomes. One limitation in our understanding of repeat elements is that most analyses rely on reference genomes that are incomplete and often contain missing data in highly repetitive regions that are difficult to assemble. To overcome this problem we develop a new method, REPdenovo, which assembles repeat sequences directly from raw shotgun sequencing data. REPdenovo can construct various types of repeats that are highly repetitive and have low sequence divergence within copies. We show that REPdenovo is substantially better than existing methods both in terms of the number and the completeness of the repeat sequences that it recovers. The key advantage of REPdenovo is that it can reconstruct long repeats from sequence reads. We apply the method to human data and discover a number of potentially new repeats sequences that have been missed by previous repeat annotations. Many of these sequences are incorporated into various parasite genomes, possibly because the filtering process for host DNA involved in the sequencing of the parasite genomes failed to exclude the host derived repeat sequences. REPdenovo is a new powerful computational tool for annotating genomes and for addressing questions regarding the evolution of repeat families. The software tool, REPdenovo, is available for download at https://github.com/Reedwarbler/REPdenovo.

  15. Repeated-sprint and effort ability in rugby league players.

    Science.gov (United States)

    Johnston, Rich D; Gabbett, Tim J

    2011-10-01

    The aim of this study was to (a) investigate the influence of tackling on repeated-sprint performance; (b) determine whether repeated-sprint ability (RSA) and repeated-effort ability (REA) are 2 distinct qualities; and (c) assess the test-retest reliability of repeated-sprint and repeated-effort tests in rugby league. Twelve rugby league players performed a repeated-sprint (12 × 20-m sprints performed on a 20-second cycle) and a repeated-effort (12 × 20-m sprints with intermittent tackling, performed on a 20-second cycle) test 7 days apart. The test-retest reliability of these tests was also established. Heart rate and rating of perceived exertion were recorded throughout the tests. There was a significantly greater (p ≤ 0.05) and large effect size (ES) differences for total sprint time (ES = 1.19), average heart rate (ES = 1.64), peak heart rate (ES = 1.35), and perceived exertion (ES = 3.39) for the repeated-effort test compared with the repeated-sprint test. A large difference (ES = 1.02, p = 0.06) was detected for percentage decrement between the 2 tests. No significant relationship was found between the repeated-sprint and repeated-effort tests for any of the dependent variables. Both tests proved reliable, with total sprint time being the most reliable method of assessing performance. This study demonstrates that the addition of tackling significantly increases the physiological response to repeated-sprint exercise and reduces repeated-sprint performance in rugby league players. Furthermore, RSA and REA appear to be 2 distinct qualities that can be reliably assessed with total time being the most reliable measure of performance.

  16. Multineuronal Spike Sequences Repeat with Millisecond Precision

    Directory of Open Access Journals (Sweden)

    Koki eMatsumoto

    2013-06-01

    Full Text Available Cortical microcircuits are nonrandomly wired by neurons. As a natural consequence, spikes emitted by microcircuits are also nonrandomly patterned in time and space. One of the prominent spike organizations is a repetition of fixed patterns of spike series across multiple neurons. However, several questions remain unsolved, including how precisely spike sequences repeat, how the sequences are spatially organized, how many neurons participate in sequences, and how different sequences are functionally linked. To address these questions, we monitored spontaneous spikes of hippocampal CA3 neurons ex vivo using a high-speed functional multineuron calcium imaging technique that allowed us to monitor spikes with millisecond resolution and to record the location of spiking and nonspiking neurons. Multineuronal spike sequences were overrepresented in spontaneous activity compared to the statistical chance level. Approximately 75% of neurons participated in at least one sequence during our observation period. The participants were sparsely dispersed and did not show specific spatial organization. The number of sequences relative to the chance level decreased when larger time frames were used to detect sequences. Thus, sequences were precise at the millisecond level. Sequences often shared common spikes with other sequences; parts of sequences were subsequently relayed by following sequences, generating complex chains of multiple sequences.

  17. A Repeated Signal Difference for Recognising Patterns

    Directory of Open Access Journals (Sweden)

    Kieran Greer

    2016-08-01

    Full Text Available This paper describes a new mechanism that might help with defining pattern sequences, by the fact that it can produce an upper bound on the ensemble value that can persistently oscillate with the actual values produced from each pattern. With every firing event, a node also receives an on/off feedback switch. If the node fires then it sends a feedback result depending on the input signal strength. If the input signal is positive or larger, it can store an ‘on’ switch feedback for the next iteration. If the signal is negative or smaller it can store an ‘off’ switch feedback for the next iteration. If the node does not fire, then it does not affect the current feedback situation and receives the switch command produced by the last active pattern event for the same neuron. The upper bound therefore also represents the largest or most enclosing pattern set and the lower value is for the actual set of firing patterns. If the pattern sequence repeats, it will oscillate between the two values, allowing them to be recognised and measured more easily, over time. Tests show that changing the sequence ordering produces different value sets, which can also be measured.

  18. A novel PCR-based approach for the detection of the Huntington disease associated trinucleotide repeat expansion.

    Science.gov (United States)

    Panagopoulos, I; Lassen, C; Kristoffersson, U; Aman, P

    1999-01-01

    Huntington disease (HD) is an autosomal dominant neurodegenerative disorder associated with expansions of an unstable CAG trinucleotide repeat in exon 1 of the IT15 gene. In normal individuals, IT15 contains up to 35 CAG repeats, while in affected the repeat length is >36. Polymerase chain reaction (PCR) is used to estimate the number of CAG repeats but may be inefficient in long repeats because of the high C+G content of the HD locus. We present a novel PCR approach for the diagnosis of HD, which permits direct visualization of the amplified products on agarose gel, using ethidium bromide. It is based on the methylation-sensitive conversion of C residues to U by bisulfite treatment of single-stranded DNA and subsequent amplification of the sense strand with specific primers. The bisulfite treatment dramatically reduces the C + G content of the region; thus, the high Tm and stable secondary structures are no longer obstacles to PCR. In both normal and affected individuals, UAG repeats (5'- CAG-3', before bisulfite treatment) in the sense strand can easily be amplified and visualized on a gel by ethidium bromide staining. The method has considerable advantages compared with other described PCR-based diagnostic tests for HD.

  19. Hypoxic Repeat Sprint Training Improves Rugby Player's Repeated Sprint but Not Endurance Performance.

    Science.gov (United States)

    Hamlin, Michael J; Olsen, Peter D; Marshall, Helen C; Lizamore, Catherine A; Elliot, Catherine A

    2017-01-01

    This study aims to investigate the performance changes in 19 well-trained male rugby players after repeat-sprint training (six sessions of four sets of 5 × 5 s sprints with 25 s and 5 min of active recovery between reps and sets, respectively) in either normobaric hypoxia (HYP; n = 9; FIO2 = 14.5%) or normobaric normoxia (NORM; n = 10; FIO2 = 20.9%). Three weeks after the intervention, 2 additional repeat-sprint training sessions in hypoxia (FIO2 = 14.5%) was investigated in both groups to gauge the efficacy of using "top-up" sessions for previously hypoxic-trained subjects and whether a small hypoxic dose would be beneficial for the previously normoxic-trained group. Repeated sprint (8 × 20 m) and Yo-Yo Intermittent Recovery Level 1 (YYIR1) performances were tested twice at baseline (Pre 1 and Pre 2) and weekly after (Post 1-3) the initial intervention (intervention 1) and again weekly after the second "top-up" intervention (Post 4-5). After each training set, heart rate, oxygen saturation, and rate of perceived exertion were recorded. Compared to baseline (mean of Pre 1 and Pre 2), both the hypoxic and normoxic groups similarly lowered fatigue over the 8 sprints 1 week after the intervention (Post 1: -1.8 ± 1.6%, -1.5 ± 1.4%, mean change ± 90% CI in HYP and NORM groups, respectively). However, from Post 2 onwards, only the hypoxic group maintained the performance improvement compared to baseline (Post 2: -2.1 ± 1.8%, Post 3: -2.3 ± 1.7%, Post 4: -1.9 ± 1.8%, and Post 5: -1.2 ± 1.7%). Compared to the normoxic group, the hypoxic group was likely to have substantially less fatigue at Post 3-5 (-2.0 ± 2.4%, -2.2 ± 2.4%, -1.6 ± 2.4% Post 3, Post 4, Post 5, respectively). YYIR1 performances improved throughout the recovery period in both groups (13-37% compared to baseline) with unclear differences found between groups. The addition of two sessions of "top-up" training after intervention 1, had little effect on either group. Repeat-sprint training in

  20. Hypoxic Repeat Sprint Training Improves Rugby Player's Repeated Sprint but Not Endurance Performance

    Science.gov (United States)

    Hamlin, Michael J.; Olsen, Peter D.; Marshall, Helen C.; Lizamore, Catherine A.; Elliot, Catherine A.

    2017-01-01

    This study aims to investigate the performance changes in 19 well-trained male rugby players after repeat-sprint training (six sessions of four sets of 5 × 5 s sprints with 25 s and 5 min of active recovery between reps and sets, respectively) in either normobaric hypoxia (HYP; n = 9; FIO2 = 14.5%) or normobaric normoxia (NORM; n = 10; FIO2 = 20.9%). Three weeks after the intervention, 2 additional repeat-sprint training sessions in hypoxia (FIO2 = 14.5%) was investigated in both groups to gauge the efficacy of using “top-up” sessions for previously hypoxic-trained subjects and whether a small hypoxic dose would be beneficial for the previously normoxic-trained group. Repeated sprint (8 × 20 m) and Yo-Yo Intermittent Recovery Level 1 (YYIR1) performances were tested twice at baseline (Pre 1 and Pre 2) and weekly after (Post 1–3) the initial intervention (intervention 1) and again weekly after the second “top-up” intervention (Post 4–5). After each training set, heart rate, oxygen saturation, and rate of perceived exertion were recorded. Compared to baseline (mean of Pre 1 and Pre 2), both the hypoxic and normoxic groups similarly lowered fatigue over the 8 sprints 1 week after the intervention (Post 1: −1.8 ± 1.6%, −1.5 ± 1.4%, mean change ± 90% CI in HYP and NORM groups, respectively). However, from Post 2 onwards, only the hypoxic group maintained the performance improvement compared to baseline (Post 2: −2.1 ± 1.8%, Post 3: −2.3 ± 1.7%, Post 4: −1.9 ± 1.8%, and Post 5: −1.2 ± 1.7%). Compared to the normoxic group, the hypoxic group was likely to have substantially less fatigue at Post 3–5 (−2.0 ± 2.4%, −2.2 ± 2.4%, −1.6 ± 2.4% Post 3, Post 4, Post 5, respectively). YYIR1 performances improved throughout the recovery period in both groups (13–37% compared to baseline) with unclear differences found between groups. The addition of two sessions of “top-up” training after intervention 1, had little effect on either

  1. An Expanded CAG Repeat in Huntingtin Causes +1 Frameshifting.

    Science.gov (United States)

    Saffert, Paul; Adamla, Frauke; Schieweck, Rico; Atkins, John F; Ignatova, Zoya

    2016-08-26

    Maintenance of triplet decoding is crucial for the expression of functional protein because deviations either into the -1 or +1 reading frames are often non-functional. We report here that expression of huntingtin (Htt) exon 1 with expanded CAG repeats, implicated in Huntington pathology, undergoes a sporadic +1 frameshift to generate from the CAG repeat a trans-frame AGC repeat-encoded product. This +1 recoding is exclusively detected in pathological Htt variants, i.e. those with expanded repeats with more than 35 consecutive CAG codons. An atypical +1 shift site, UUC C at the 5' end of CAG repeats, which has some resemblance to the influenza A virus shift site, triggers the +1 frameshifting and is enhanced by the increased propensity of the expanded CAG repeats to form a stem-loop structure. The +1 trans-frame-encoded product can directly influence the aggregation of the parental Htt exon 1.

  2. Repeats in transforming acidic coiled-coil (TACC) genes.

    Science.gov (United States)

    Trivedi, Seema

    2013-06-01

    Transforming acidic coiled-coil proteins (TACC1, 2, and 3) are essential proteins associated with the assembly of spindle microtubules and maintenance of bipolarity. Dysregulation of TACCs is associated with tumorigenesis, but studies of microsatellite instability in TACC genes have not been extensive. Microsatellite or simple sequence repeat instability is known to cause many types of cancer. The present in silico analysis of SSRs in human TACC gene sequences shows the presence of mono- to hexa-nucleotide repeats, with the highest densities found for mono- and di-nucleotide repeats. Density of repeats is higher in introns than in exons. Some of the repeats are present in regulatory regions and retained introns. Human TACC genes show conservation of many repeat classes. Microsatellites in TACC genes could be valuable markers for monitoring numerical chromosomal aberrations and or cancer.

  3. Survey of simple sequence repeats in woodland strawberry (Fragaria vesca).

    Science.gov (United States)

    Guan, L; Huang, J F; Feng, G Q; Wang, X W; Wang, Y; Chen, B Y; Qiao, Y S

    2013-07-30

    The use of simple sequence repeats (SSRs), or microsatellites, as genetic markers has become popular due to their abundance and variation in length among individuals. In this study, we investigated linkage groups (LGs) in the woodland strawberry (Fragaria vesca) and demonstrated variation in the abundances, densities, and relative densities of mononucleotide, dinucleotide, and trinucleotide repeats. Mononucleotide, dinucleotide, and trinucleotide repeats were more common than longer repeats in all LGs examined. Perfect SSRs were the predominant SSR type found and their abundance was extremely stable among LGs and chloroplasts. Abundances of mononucleotide, dinucleotide, and trinucleotide repeats were positively correlated with LG size, whereas those of tetranucleotide and hexanucleotide SSRs were not. Generally, in each LG, the abundance, relative abundance, relative density, and the proportion of each unique SSR all declined rapidly as the repeated unit increased. Furthermore, the lengths and frequencies of SSRs varied among different LGs.

  4. Quasimonomorphic Mononucleotide Repeats for High-Level Microsatellite Instability Analysis

    Directory of Open Access Journals (Sweden)

    Olivier Buhard

    2004-01-01

    Full Text Available Microsatellite instability (MSI analysis is becoming more and more important to detect sporadic primary tumors of the MSI phenotype as well as in helping to determine Hereditary Non-Polyposis Colorectal Cancer (HNPCC cases. After some years of conflicting data due to the absence of consensus markers for the MSI phenotype, a meeting held in Bethesda to clarify the situation proposed a set of 5 microsatellites (2 mononucleotide repeats and 3 dinucleotide repeats to determine MSI tumors. A second Bethesda consensus meeting was held at the end of 2002. It was discussed here that the 1998 microsatellite panel could underestimate high-level MSI tumors and overestimate low-level MSI tumors. Amongst the suggested changes was the exclusive use of mononucleotide repeats in place of dinucleotide repeats. We have already proposed a pentaplex MSI screening test comprising 5 quasimonomorphic mononucleotide repeats. This article compares the advantages of mono or dinucleotide repeats in determining microsatellite instability.

  5. Assembly of Repeat Content Using Next Generation Sequencing Data

    Energy Technology Data Exchange (ETDEWEB)

    labutti, Kurt; Kuo, Alan; Grigoriev, Igor; Copeland, Alex

    2014-03-17

    Repetitive organisms pose a challenge for short read assembly, and typically only unique regions and repeat regions shorter than the read length, can be accurately assembled. Recently, we have been investigating the use of Pacific Biosciences reads for de novo fungal assembly. We will present an assessment of the quality and degree of repeat reconstruction possible in a fungal genome using long read technology. We will also compare differences in assembly of repeat content using short read and long read technology.

  6. Neuropathological diagnosis and CAG repeat expansion in Huntington's disease.

    OpenAIRE

    Xuereb, J H; MacMillan, J C; Snell, R; Davies, P.; Harper, P S

    1996-01-01

    OBJECTIVE--To correlate the degree of CAG repeat expansion with neuropathological findings in Huntington's disease. METHODS--The CAG repeat polymorphism was analysed in a large series of brain samples from 268 patients with a clinical diagnosis of Huntington's disease in which full neuropathological data was available. RESULTS--Analysis by polymerase chain reaction was successful in 63% of samples (169 of 268). Repeat expansions were detected in 152 of 153 (99%) samples with a neuropathologic...

  7. The evolution of filamin – A protein domain repeat perspective

    OpenAIRE

    Light, Sara; Sagit, Rauan; Ithychanda, Sujay S.; Qin, Jun; Elofsson, Arne

    2012-01-01

    Particularly in higher eukaryotes, some protein domains are found in tandem repeats, performing broad functions often related to cellular organization. For instance, the eukaryotic protein filamin interacts with many proteins and is crucial for the cytoskeleton. The functional properties of long repeat domains are governed by the specific properties of each individual domain as well as by the repeat copy number. To provide better understanding of the evolutionary and functional history of rep...

  8. Artificial leucine rich repeats as new scaffolds for protein design.

    Science.gov (United States)

    Baabur-Cohen, Hemda; Dayalan, Subashini; Shumacher, Inbal; Cohen-Luria, Rivka; Ashkenasy, Gonen

    2011-04-15

    The leucine rich repeat (LRR) motif that participates in many biomolecular recognition events in cells was suggested as a general scaffold for producing artificial receptors. We describe here the design and first total chemical synthesis of small LRR proteins, and their structural analysis. When evaluating the tertiary structure as a function of different number of repeating units (1-3), we were able to find that the 3-repeats sequence, containing 90 amino acids, folds into the expected structure.

  9. Exploring bacterial community structure and function associated with atrazine biodegradation in repeatedly treated soils.

    Science.gov (United States)

    Fang, Hua; Lian, Jianjun; Wang, Huifang; Cai, Lin; Yu, Yunlong

    2015-04-09

    Substantial application of the herbicide atrazine in agriculture leads to persistent contamination, which may damage the succeeding crops and pose potential threats to soil ecology and environmental health. Here, the degradation characteristics of atrazine and dynamic change of soil bacterial community structure and function as well as their relations were studied during three repeated treatments at the recommended, double, and five-fold doses. The results showed that the degradation half-life of atrazine obviously decreased with increased treatment frequency. Soil microbial functional diversity displayed a variation trend of suppression-recovery-stimulation, which was associated with increased degradation rate of atrazine. 16S amplicon sequencing was conducted to explore bacterial community structure and correlate the genus to potential atrazine degradation. A total of seven potentially atrazine-degrading bacterial genera were found including Nocardioides, Arthrobacter, Bradyrhizobium, Burkholderia, Methylobacterium, Mycobacterium, and Clostridium. These bacterial genera showed almost complete atrazine degradation pathways including dechlorination, dealkylation, hydroxylation, and ring cleavage. Furthermore, the relative abundance of four of them (i.e., Nocardioides, Arthrobacter, Methylobacterium, and Bradyrhizobium) increased with treatment frequency and atrazine concentration, suggesting that they may participate in atrazine degradation during repeated treatments. Our findings reveal the potential relationship between atrazine degradation and soil bacterial community structure in repeatedly treated soils. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Coexistence of 3G repeaters with LTE base stations.

    Science.gov (United States)

    Yeo, Woon-Young; Lee, Sang-Min; Hwang, Gyung-Ho; Kim, Jae-Hoon

    2013-01-01

    Repeaters have been an attractive solution for mobile operators to upgrade their wireless networks at low cost and to extend network coverage effectively. Since the first LTE commercial deployment in 2009, many mobile operators have launched LTE networks by upgrading their 3G and legacy networks. Because all 3G frequency bands are shared with the frequency bands for LTE deployment and 3G mobile operators have an enormous number of repeaters, reusing 3G repeaters in LTE networks is definitely a practical and cost-efficient solution. However, 3G repeaters usually do not support spatial multiplexing with multiple antennas, and thus it is difficult to reuse them directly in LTE networks. In order to support spatial multiplexing of LTE, the role of 3G repeaters should be replaced with small LTE base stations or MIMO-capable repeaters. In this paper, a repeater network is proposed to reuse 3G repeaters in LTE deployment while still supporting multilayer transmission of LTE. Interestingly, the proposed network has a higher cluster throughput than an LTE network with MIMO-capable repeaters.

  11. Mononucleotide repeats are asymmetrically distributed in fungal genes

    Directory of Open Access Journals (Sweden)

    de Graaff Leo H

    2008-12-01

    Full Text Available Abstract Background Systematic analyses of sequence features have resulted in a better characterisation of the organisation of the genome. A previous study in prokaryotes on the distribution of sequence repeats, which are notoriously variable and can disrupt the reading frame in genes, showed that these motifs are skewed towards gene termini, specifically the 5' end of genes. For eukaryotes no such intragenic analysis has been performed, though this could indicate the pervasiveness of this distribution bias, thereby helping to expose the selective pressures causing it. Results In fungal gene repertoires we find a similar 5' bias of intragenic mononucleotide repeats, most notably for Candida spp., whereas e.g. Coccidioides spp. display no such bias. With increasing repeat length, ever larger discrepancies are observed in genome repertoire fractions containing such repeats, with up to an 80-fold difference in gene fractions at repeat lengths of 10 bp and longer. This species-specific difference in gene fractions containing large repeats could be attributed to variations in intragenic repeat tolerance. Furthermore, long transcripts experience an even more prominent bias towards the gene termini, with possibly a more adaptive role for repeat-containing short transcripts. Conclusion Mononucleotide repeats are intragenically biased in numerous fungal genomes, similar to earlier studies on prokaryotes, indicative of a similar selective pressure in gene organization.

  12. Huntington's disease as caused by 34 CAG repeats.

    Science.gov (United States)

    Andrich, Jürgen; Arning, Larissa; Wieczorek, Stefan; Kraus, Peter H; Gold, Ralf; Saft, Carsten

    2008-04-30

    Huntington's disease (HD) is an autosomal dominantly inherited neurodegenerative disorder caused by an abnormal expansion of a polymorphic stretch of CAG repeats in the coding 5' part of the HD gene on chromosome 4p. Expansions of CAG blocks beyond 35 repeats are associated with the clinical presentation of HD. There is an intermediate range of rare alleles between 27 and 35 CAG repeats with a higher risk for further expansion in subsequent generations. Here, we report a 75-year-old male with clinical features of HD and 34 CAG repeat units.

  13. Intragenic tandem repeat variation between Legionella pneumophila strains

    Directory of Open Access Journals (Sweden)

    Jarraud Sophie

    2008-12-01

    Full Text Available Abstract Background Bacterial genomes harbour a large number of tandem repeats, yet the possible phenotypic effects of those found within the coding region of genes are only beginning to be examined. Evidence exists from other organisms that these repeats can be involved in the evolution of new genes, gene regulation, adaptation, resistance to environmental stresses, and avoidance of the immune system. Results In this study, we have investigated the presence and variability in copy number of intragenic tandemly repeated sequences in the genome of Legionella pneumophila, the etiological agent of a severe pneumonia known as Legionnaires' disease. Within the genome of the Philadelphia strain, we have identified 26 intragenic tandem repeat sequences using conservative selection criteria. Of these, seven were "polymorphic" in terms of repeat copy number between a large number of L. pneumophila serogroup 1 strains. These strains were collected from a wide variety of environments and patients in several geographical regions. Within this panel of strains, all but one of these seven genes exhibited statistically different patterns in repeat copy number between samples from different origins (environmental, clinical, and hot springs. Conclusion These results support the hypothesis that intragenic tandem repeats could play a role in virulence and adaptation to different environments. While tandem repeats are an increasingly popular focus of molecular typing studies in prokaryotes, including in L. pneumophila, this study is the first examining the difference in tandem repeat distribution as a function of clinical or environmental origin.

  14. Genus-specific protein binding to the large clusters of DNA repeats (short regularly spaced repeats) present in Sulfolobus genomes

    DEFF Research Database (Denmark)

    Peng, Xu; Brügger, Kim; Shen, Biao

    2003-01-01

    Short regularly spaced repeats (SRSRs) occur in multiple large clusters in archaeal chromosomes and as smaller clusters in some archaeal conjugative plasmids and bacterial chromosomes. The sequence, size, and spacing of the repeats are generally constant within a cluster but vary between clusters...... that are identical in sequence to one of the repeat variants in the S. solfataricus chromosome. Repeats from the pNOB8 cluster were amplified and tested for protein binding with cell extracts from S. solfataricus. A 17.5-kDa SRSR-binding protein was purified from the cell extracts and sequenced. The protein is N...... terminally modified and corresponds to SSO454, an open reading frame of previously unassigned function. It binds specifically to DNA fragments carrying double and single repeat sequences, binding on one side of the repeat structure, and producing an opening of the opposite side of the DNA structure. It also...

  15. Cardiorespiratory Coordination in Repeated Maximal Exercise

    Directory of Open Access Journals (Sweden)

    Sergi Garcia-Retortillo

    2017-06-01

    Full Text Available Increases in cardiorespiratory coordination (CRC after training with no differences in performance and physiological variables have recently been reported using a principal component analysis approach. However, no research has yet evaluated the short-term effects of exercise on CRC. The aim of this study was to delineate the behavior of CRC under different physiological initial conditions produced by repeated maximal exercises. Fifteen participants performed 2 consecutive graded and maximal cycling tests. Test 1 was performed without any previous exercise, and Test 2 6 min after Test 1. Both tests started at 0 W and the workload was increased by 25 W/min in males and 20 W/min in females, until they were not able to maintain the prescribed cycling frequency of 70 rpm for more than 5 consecutive seconds. A principal component (PC analysis of selected cardiovascular and cardiorespiratory variables (expired fraction of O2, expired fraction of CO2, ventilation, systolic blood pressure, diastolic blood pressure, and heart rate was performed to evaluate the CRC defined by the number of PCs in both tests. In order to quantify the degree of coordination, the information entropy was calculated and the eigenvalues of the first PC (PC1 were compared between tests. Although no significant differences were found between the tests with respect to the performed maximal workload (Wmax, maximal oxygen consumption (VO2 max, or ventilatory threshold (VT, an increase in the number of PCs and/or a decrease of eigenvalues of PC1 (t = 2.95; p = 0.01; d = 1.08 was found in Test 2 compared to Test 1. Moreover, entropy was significantly higher (Z = 2.33; p = 0.02; d = 1.43 in the last test. In conclusion, despite the fact that no significant differences were observed in the conventionally explored maximal performance and physiological variables (Wmax, VO2 max, and VT between tests, a reduction of CRC was observed in Test 2. These results emphasize the interest of CRC

  16. Cardiorespiratory Coordination in Repeated Maximal Exercise.

    Science.gov (United States)

    Garcia-Retortillo, Sergi; Javierre, Casimiro; Hristovski, Robert; Ventura, Josep L; Balagué, Natàlia

    2017-01-01

    Increases in cardiorespiratory coordination (CRC) after training with no differences in performance and physiological variables have recently been reported using a principal component analysis approach. However, no research has yet evaluated the short-term effects of exercise on CRC. The aim of this study was to delineate the behavior of CRC under different physiological initial conditions produced by repeated maximal exercises. Fifteen participants performed 2 consecutive graded and maximal cycling tests. Test 1 was performed without any previous exercise, and Test 2 6 min after Test 1. Both tests started at 0 W and the workload was increased by 25 W/min in males and 20 W/min in females, until they were not able to maintain the prescribed cycling frequency of 70 rpm for more than 5 consecutive seconds. A principal component (PC) analysis of selected cardiovascular and cardiorespiratory variables (expired fraction of O2, expired fraction of CO2, ventilation, systolic blood pressure, diastolic blood pressure, and heart rate) was performed to evaluate the CRC defined by the number of PCs in both tests. In order to quantify the degree of coordination, the information entropy was calculated and the eigenvalues of the first PC (PC1) were compared between tests. Although no significant differences were found between the tests with respect to the performed maximal workload (Wmax), maximal oxygen consumption (VO2 max), or ventilatory threshold (VT), an increase in the number of PCs and/or a decrease of eigenvalues of PC1 (t = 2.95; p = 0.01; d = 1.08) was found in Test 2 compared to Test 1. Moreover, entropy was significantly higher (Z = 2.33; p = 0.02; d = 1.43) in the last test. In conclusion, despite the fact that no significant differences were observed in the conventionally explored maximal performance and physiological variables (Wmax, VO2 max, and VT) between tests, a reduction of CRC was observed in Test 2. These results emphasize the interest of CRC evaluation in

  17. Is immunotherapy an opportunity for effective treatment of drug addiction?

    Science.gov (United States)

    Zalewska-Kaszubska, Jadwiga

    2015-11-27

    Immunotherapy has a great potential of becoming a new therapeutic strategy in the treatment of addiction to psychoactive drugs. It may be used to treat addiction but also to prevent neurotoxic complications of drug overdose. In preclinical studies two immunological methods have been tested; active immunization, which relies on the administration of vaccines and passive immunization, which relies on the administration of monoclonal antibodies. Until now researchers have succeeded in developing vaccines and/or antibodies against addiction to heroin, cocaine, methamphetamine, nicotine and phencyclidine. Their effectiveness has been confirmed in preclinical studies. At present, clinical studies are being conducted for vaccines against nicotine and cocaine and also anti-methamphetamine monoclonal antibody. These preclinical and clinical studies suggest that immunotherapy may be useful in the treatment of addiction and drug overdose. However, there are a few problems to be solved. One of them is controlling the level of antibodies due to variability between subjects. But even obtaining a suitable antibody titer does not guarantee the effectiveness of the vaccine. Additionally, there is a risk of intentional or unintentional overdose. As vaccines prevent passing of drugs through the blood/brain barrier and thereby prevent their positive reinforcement, some addicted patients may erroneously seek higher doses of psychoactive substances to get "high". Consequently, vaccination should be targeted at persons who have a strong motivation to free themselves from drug dependency. It seems that immunotherapy may be an opportunity for effective treatment of drug addiction if directed to adequate candidates for treatment. For other addicts, immunotherapy may be a very important element supporting psycho- and pharmacotherapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. How repeated 15-minute assertiveness training sessions reduce wrist cutting in patients with borderline personality disorder.

    Science.gov (United States)

    Hayakawa, Masaya

    2009-01-01

    The aim of this work was to examine a possible treatment for patients with borderline personality disorder who have wrist-cutting syndrome, a condition characterized by repeated, superficial wrist cutting in a non-suicidal fashion. Within the current healthcare system in Japan, the average amount of time a doctor can spend with a psychiatric outpatient is about 8 to 15 minutes. We, therefore, examined whether repeated 15-minute psychotherapy sessions to improve patient assertiveness would be effective for reducing wrist cutting and possibly other forms of self-mutilation. We treated 13 patients diagnosed with borderline personality disorder and wrist-cutting syndrome with assertiveness training during 15-minute, biweekly therapy sessions over a course of one to four years. At the conclusion of psychotherapeutic treatment, 69% of outpatients showed a statistically significant reduction in wrist-cutting behavior.

  19. Safety of Moxifloxacin following repeated intramuscular administration in Wistar rats

    Directory of Open Access Journals (Sweden)

    K.A. Sadariya

    Full Text Available Moxifloxacin is a novel fourth generation fluoroquinolone with broad spectrum of antibacterial activity. The study was conducted to evaluate the safety of Moxifloxacin (5.0 mg/kg after repeated intramuscular administration at 24 h interval for 14 days in male and female wistar rats. Hematological (Haemoglobin, RBC, WBC, MCV, MCH, MCHC, HCT and DLC, blood biochemical parameters (AST, ALT, ALP, Total Bilirubin, Total Serum Protein, Serum Albumin, Globulin, Serum Creatinine, Urea, Uric acid and Blood glucose and histopathological examination of various tissues were carried out in the present study. Male and female animals of any group did not reveal any clinical symptoms and mortality attributable to the 14 days intramuscular administration of Moxifloxacin. The data were compared by unpaired two tail `t` test using Graph Pad Prism (Version 4.00. All above hematological and blood biochemical parameters were found to fluctuate within normal range during treatment period and the mean values were not significantly differ (p < 0.05 from corresponding control values. Moreover, no gross or microscopic changes were found in the liver, kidney, heart, spleen, stomach, intestine and joint cartilages of the treated wistar rats. Results indicate that daily administration of Moxifloxacin for 14 days seems to be safe and well tolerated in rats. [Veterinary World 2010; 3(10.000: 449-452

  20. Repeated use of ion-exchange resin membranes in calcareous soils

    Science.gov (United States)

    Sherrod, S.K.; Belnap, J.; Miller, M.E.

    2003-01-01

    This study compared the consistency of nutrient extraction among repeated cycles of ion-exchange resin membrane use. Two sandy calcareous soils and different equilibration temperatures were tested. No single nutrient retained consistent values from cycle to cycle in all treatments, although both soil source and temperature conferred some influence. It was concluded that the most conservative use of resin membranes is single-use.

  1. Effect of tramadol on metamizol pharmacokinetics and pharmacodynamics after single and repeated administrations in arthritic rats.

    Science.gov (United States)

    Moreno-Rocha, Luis Alfonso; López-Muñoz, Francisco Javier; Medina-López, José Raúl; Domínguez-Ramírez, Adriana Miriam

    2016-11-01

    Combined administration of certain doses of opioid compounds with a non-steroidal anti-inflammatory drug can produce additive or supra-additive effects while reducing unwanted effects. We have recently reported that co-administration of metamizol with tramadol produces antinociceptive effect potentiation, after acute treatment. However, none information about the effect produced by the combination after chronic or repeated dose administration exists. The aims of this study were to investigate whether the antinociceptive synergism produced by the combination of metamizol and tramadol (177.8 + 17.8 mg/kg, s.c. respectively) is maintained after repeated treatment and whether the effects observed are primarily due to pharmacodynamic interactions or may be related to pharmacokinetics changes. Administration of metamizol plus tramadol acute treatment significantly enhanced the antinociceptive effect of the drugs given alone (P metamizol and tramadol was found under acute treatment (P > 0.05). The mechanism involved in the synergism of the antinociceptive effect observed with the combination of metamizol and tramadol in single dose cannot be attributed to a pharmacokinetic interaction, and other pharmacodynamic interactions have to be considered. On the other hand, when metamizol and tramadol were co-administered under repeated administrations, a pharmacokinetic interaction and tolerance development occurred. Differences found in metamizol active metabolites' pharmacokinetics (P < 0.05) were related to the development of tolerance produced by the combination after repeated doses. This work shows an additional preclinical support for the combination therapy. The clinical utility of this combination in a suitable dose range should be evaluated in future studies.

  2. Brexpiprazole Alters Monoaminergic Systems following Repeated Administration: an in Vivo Electrophysiological Study

    OpenAIRE

    Oosterhof, Chris A.; Mansari, Mostafa El; Bundgaard, Christoffer; Blier, Pierre

    2015-01-01

    Background: Brexpiprazole was recently approved as adjunctive therapy for depression and treatment of schizophrenia in adults. To complement results from a previous study in which its acute effects were characterized, the present study assessed the effect of repeated brexpiprazole administration on monoaminergic systems. Methods: Brexpiprazole (1mg/kg, subcutaneous) or vehicle was administered once daily for 2 and 14 days. Single-unit electrophysiological recordings from noradrenaline neurons...

  3. Repeatability Using Automatic Tracing with Canon OCT- HS100 and Zeiss Cirrus HD-OCT 5000

    OpenAIRE

    Rune Brautaset; Ulrika Birkeldh; Petra Frehr Alstig; Petra Wikén; Maria Nilsson

    2016-01-01

    Background Optical coherence tomography (OCT), can be used in clinical practice to provide high resolution cross-sectional images of the retina, optic disc and macula structure. These measurements can be useful for early detection, diagnosis, monitoring and treatment guidance for retinal diseases. Therefore, repeatability of measurements in OCT is of great importance. Methods Macula and optic disc parameters from the right eye of 30 healthy subjects were obtained twice with the Canon OCT-HS10...

  4. Turkish population data on the short tandem repeat locus TPOX

    DEFF Research Database (Denmark)

    Vural, B; Poda, M; Atlioglu, E;

    1998-01-01

    Allele and genotype frequencies were determined for the STR (short tandem repeat) locus TPOX in a random Turkish population sample of 200 individuals.......Allele and genotype frequencies were determined for the STR (short tandem repeat) locus TPOX in a random Turkish population sample of 200 individuals....

  5. PILER-CR: Fast and accurate identification of CRISPR repeats

    Directory of Open Access Journals (Sweden)

    Edgar Robert C

    2007-01-01

    Full Text Available Abstract Background Sequencing of prokaryotic genomes has recently revealed the presence of CRISPR elements: short, highly conserved repeats separated by unique sequences of similar length. The distinctive sequence signature of CRISPR repeats can be found using general-purpose repeat- or pattern-finding software tools. However, the output of such tools is not always ideal for studying these repeats, and significant effort is sometimes needed to build additional tools and perform manual analysis of the output. Results We present PILER-CR, a program specifically designed for the identification and analysis of CRISPR repeats. The program executes rapidly, completing a 5 Mb genome in around 5 seconds on a current desktop computer. We validate the algorithm by manual curation and by comparison with published surveys of these repeats, finding that PILER-CR has both high sensitivity and high specificity. We also present a catalogue of putative CRISPR repeats identified in a comprehensive analysis of 346 prokaryotic genomes. Conclusion PILER-CR is a useful tool for rapid identification and classification of CRISPR repeats. The software is donated to the public domain. Source code and a Linux binary are freely available at http://www.drive5.com/pilercr.

  6. Repeatable mechanochemical activation of dynamic covalent bonds in thermoplastic elastomers.

    Science.gov (United States)

    Imato, Keiichi; Kanehara, Takeshi; Nojima, Shiki; Ohishi, Tomoyuki; Higaki, Yuji; Takahara, Atsushi; Otsuka, Hideyuki

    2016-08-18

    Repeated mechanical scission and recombination of dynamic covalent bonds incorporated in segmented polyurethane elastomers are demonstrated by utilizing a diarylbibenzofuranone-based mechanophore and by the design of the segmented polymer structures. The repeated mechanochemical reactions can accompany clear colouration and simultaneous fading.

  7. PCR-free digital minisatellite tandem repeat genotyping.

    Science.gov (United States)

    Chen, Yuchao; Seo, Tae Seok

    2011-06-01

    We demonstrated a proof-of-concept for novel minisatellite tandem repeat typing, called PCR-free digital VNTR (variable number tandem repeat) typing, which is composed of three steps: a ligation reaction instead of PCR thermal cycling, magnetic bead-based solid-phase capture for purification, and an elongated sample stacking microcapillary electrophoresis (μCE) for sensitive digital coding of repeat number. We designed a 16-bp fluorescently labeled ligation probe which is complementary to a repeat unit of a biotinylated synthetic template mimicking the human D1S80 VNTR locus and is randomly hybridized with the minisatellite tandem repeats. A quick isothermal ligation reaction was followed to link the adjacent ligation probes on the DNA templates, and then the ligated products were purified by streptavidin-coated magnetic beads. After a denaturing step, a large amount of ligated products whose size difference was equivalent to the repeat unit were released and recovered. Through the elongated sample stacking μCE separation on a microdevice, the fluorescence signal of the ligated products was generated in the electropherogram and the peak number was directly counted which was exactly matched with the repeat number of VNTR locus. We could successfully identify the minisatellite tandem repeat number with only 5 fmol of DNA template in 30 min.

  8. Development of Repeated Sprint Ability in Talented Youth Basketball Players

    NARCIS (Netherlands)

    te Wierike, Sanne C. M.; de Jong, Mark C.; Tromp, Eveline J. Y.; Vuijk, Pieter J.; Lemmink, Koen A. P. M.; Malina, Robert M.; Elferink-Gemser, Marije T.; Visscher, Chris

    te Wierike, SCM, de Jong, MC, Tromp, EJY, Vuijk, PJ, Lemmink, KAPM, Malina, RM, Elferink-Gemser, MT, and Visscher, C. Development of repeated sprint ability in talented youth basketball players. J Strength Cond Res 28(4): 928-934, 2014-Factors affecting repeated sprint ability (RSA) were evaluated

  9. Vocabulary Learning through Assisted and Unassisted Repeated Reading

    Science.gov (United States)

    Webb, Stuart; Chang, Anna C-S.

    2012-01-01

    Previous research investigating the effects of unassisted and assisted repeated reading has primarily focused on how each approach may contribute to improvement in reading comprehension and fluency. Incidental learning of the form and meaning of unknown or partially known words encountered through assisted and unassisted repeated reading has yet…

  10. Impact of Inclusion or Exclusion of Repeaters on Test Equating

    Science.gov (United States)

    Puhan, Gautam

    2011-01-01

    This study examined the effect of including or excluding repeaters on the equating process and results. New forms of two tests were equated to their respective old forms using either all examinees or only the first timer examinees in the new form sample. Results showed that for both tests used in this study, including or excluding repeaters in the…

  11. Effect of Repeated Simulations by Standardized Patients on Intercase Reliability.

    Science.gov (United States)

    Colliver, Jerry A.; And Others

    1991-01-01

    A study using five Southern Illinois University senior medical school classes (n=350 students) investigated whether having a standardized patient simulate a case repeatedly in postclerkship medical student evaluation affects the measure's reliability. Results suggest that repeated simulation had little or no effect on intercase reliability of…

  12. Analysis of CR1 Repeats in the Zebra Finch Genome

    Directory of Open Access Journals (Sweden)

    George E. Liu

    2013-06-01

    Full Text Available Most bird species have smaller genomes and fewer repeats than mammals. Chicken Repeat 1 (CR1 repeat is one of the most abundant families of repeats, ranging from ~133,000 to ~187,000 copies accounting for ~50 to ~80% of the interspersed repeats in the zebra finch and chicken genomes, respectively. CR1 repeats are believed to have arisen from the retrotransposition of a small number of master elements, which gave rise to multiple CR1 subfamilies in the chicken. In this study, we performed a global assessment of the divergence distributions, phylogenies, and consensus sequences of CR1 repeats in the zebra finch genome. We identified and validated 34 CR1 subfamilies and further analyzed the correlation between these subfamilies. We also discovered 4 novel lineage-specific CR1 subfamilies in the zebra finch when compared to the chicken genome. We built various evolutionary trees of these subfamilies and concluded that CR1 repeats may play an important role in reshaping the structure of bird genomes.

  13. Repeated Witnessing of Conspecifics in Pain : Effects on Emotional Contagion

    NARCIS (Netherlands)

    Carrillo, Maria; Migliorati, Filippo; Bruls, Rune; Han, Yingying; Heinemans, Mirjam; Pruis, Ilanah; Gazzola, V.; Keysers, C.

    2015-01-01

    Witnessing of conspecifics in pain has been shown to elicit socially triggered freezing in rodents. It is unknown how robust this response is to repeated exposure to a cage-mate experiencing painful stimulation. To address this question, shock-experienced Observer rats repeatedly witnessed familiar

  14. Secret key rates for an encoded quantum repeater

    Science.gov (United States)

    Bratzik, Sylvia; Kampermann, Hermann; Bruß, Dagmar

    2014-03-01

    We investigate secret key rates for the quantum repeater using encoding [L. Jiang et al., Phys. Rev. A 79, 032325 (2009), 10.1103/PhysRevA.79.032325] and compare them to the standard repeater scheme by Briegel, Dür, Cirac, and Zoller. The former scheme has the advantage of a minimal consumption of classical communication. We analyze the trade-off in the secret key rate between the communication time and the required resources. For this purpose we introduce an error model for the repeater using encoding which allows for input Bell states with a fidelity smaller than one, in contrast to the model given by L. Jiang et al. [Phys. Rev. A 79, 032325 (2009), 10.1103/PhysRevA.79.032325]. We show that one can correct additional errors in the encoded connection procedure of this repeater and develop a suitable decoding algorithm. Furthermore, we derive the rate of producing entangled pairs for the quantum repeater using encoding and give the minimal parameter values (gate quality and initial fidelity) for establishing a nonzero secret key. We find that the generic quantum repeater is optimal regarding the secret key rate per memory per second and show that the encoded quantum repeater using the simple three-qubit repetition code can even have an advantage with respect to the resources compared to other recent quantum repeater schemes with encoding.

  15. CTG trinucleotide repeat "big jumps": large expansions, small mice.

    Directory of Open Access Journals (Sweden)

    Mário Gomes-Pereira

    2007-04-01

    Full Text Available Trinucleotide repeat expansions are the genetic cause of numerous human diseases, including fragile X mental retardation, Huntington disease, and myotonic dystrophy type 1. Disease severity and age of onset are critically linked to expansion size. Previous mouse models of repeat instability have not recreated large intergenerational expansions ("big jumps", observed when the repeat is transmitted from one generation to the next, and have never attained the very large tract lengths possible in humans. Here, we describe dramatic intergenerational CTG*CAG repeat expansions of several hundred repeats in a transgenic mouse model of myotonic dystrophy type 1, resulting in increasingly severe phenotypic and molecular abnormalities. Homozygous mice carrying over 700 trinucleotide repeats on both alleles display severely reduced body size and splicing abnormalities, notably in the central nervous system. Our findings demonstrate that large intergenerational trinucleotide repeat expansions can be recreated in mice, and endorse the use of transgenic mouse models to refine our understanding of triplet repeat expansion and the resulting pathogenesis.

  16. Development of Repeated Sprint Ability in Talented Youth Basketball Players

    NARCIS (Netherlands)

    te Wierike, Sanne C. M.; de Jong, Mark C.; Tromp, Eveline J. Y.; Vuijk, Pieter J.; Lemmink, Koen A. P. M.; Malina, Robert M.; Elferink-Gemser, Marije T.; Visscher, Chris

    2014-01-01

    te Wierike, SCM, de Jong, MC, Tromp, EJY, Vuijk, PJ, Lemmink, KAPM, Malina, RM, Elferink-Gemser, MT, and Visscher, C. Development of repeated sprint ability in talented youth basketball players. J Strength Cond Res 28(4): 928-934, 2014-Factors affecting repeated sprint ability (RSA) were evaluated i

  17. Monotone missing data and repeated controls of fallible authors

    NARCIS (Netherlands)

    Raats, V.M.

    2004-01-01

    Chapters 2 and 3 focus on repeated audit controls with categorical variables. Chapter 4 and 5 introduce and analyse a very general multivariate regression model for (monotone) missing data. In the final Chapter 6 the previous chapters are combined into a more realistic model for repeated audit contr

  18. Development of Repeated Sprint Ability in Talented Youth Basketball Players

    NARCIS (Netherlands)

    te Wierike, Sanne C. M.; de Jong, Mark C.; Tromp, Eveline J. Y.; Vuijk, Pieter J.; Lemmink, Koen A. P. M.; Malina, Robert M.; Elferink-Gemser, Marije T.; Visscher, Chris

    2014-01-01

    te Wierike, SCM, de Jong, MC, Tromp, EJY, Vuijk, PJ, Lemmink, KAPM, Malina, RM, Elferink-Gemser, MT, and Visscher, C. Development of repeated sprint ability in talented youth basketball players. J Strength Cond Res 28(4): 928-934, 2014-Factors affecting repeated sprint ability (RSA) were evaluated i

  19. Contraceptive Use among Women Seeking Repeat Abortion in ...

    African Journals Online (AJOL)

    AJRH Managing Editor

    Compared with women seeking their first abortion, significantly more repeat abortion clients had ever used ... social sigma24, repeat abortion may be as well, perhaps even .... 0.1198. aIncludes hostess, cleaner, waitress, housemaid, commercial sex worker, and cook ..... be made to support the process by strengthening.

  20. Witness recall across repeated interviews in a case of repeated abuse.

    Science.gov (United States)

    Brubacher, Sonja P; La Rooy, David

    2014-02-01

    In this illustrative case study we examine the three forensic interviews of a girl who experienced repeated sexual abuse from ages 7 to 11. She disclosed the abuse after watching a serialized television show that contained a storyline similar to her own experience. This triggered an investigation that ended in successful prosecution of the offender. Because this case involved abuse that was repeated on a weekly basis for 4 years we thus investigated the degree to which the child's narrative reflected specific episodes or generic accounts, and both the interviewer's and child's attempts to elicit and provide, respectively, specific details across the 3 interviews collected in a 1 month period. Across the 3 interviews, the child's account was largely generic, yet on a number of occasions she provided details specific to individual incidents (episodic leads) that could have been probed further. As predicted: earlier interviews were characterized more by episodic than generic prompts and the reverse was true for the third interview; the child often responded using the same style of language (episodic or generic) as the interviewer; and open questions yielded narrative information. We discuss the importance of adopting children's words to specify occurrences, and the potential benefits of permitting generic recall in investigative interviews on children's ability to provide episodic leads. Despite the fact that the testimony was characterized by generic information about what usually happened, rather than specific episodic details about individual occurrences, this case resulted in successful prosecution.

  1. Consequences of amygdala kindling and repeated withdrawal from ethanol on amphetamine-induced behaviours.

    Science.gov (United States)

    Ripley, Tamzin L; Dunworth, Sarah J; Stephens, David N

    2002-09-01

    It has been shown previously that chronic ethanol treatment in mice leads to accelerated behavioural sensitization to psychomotor stimulants [Manley & Little (1997) J. Pharmacol. Exp. Ther., 281, 1330-1339], whilst repeated experience of ethanol withdrawal sensitizes pathways underlying seizure activity (Becker & Hale (1993) Alcohol Clin. Exp. Res., 17, 94-98]. The aim of the current experiment was to investigate the consequences of repeated withdrawal from ethanol on amphetamine-induced behaviours in the rat and compare this with animals with electrical kindling of the amygdala, a procedure that has been shown to enhance alcohol withdrawal seizures [Pinel et al. (1975) Can. J. Neurol. Sci., 2, 467-475]. For the kindling experiments, electrodes were surgically implanted in the left basolateral amygdala and were stimulated daily at the afterdischarge threshold until a criterion of three consecutive stage 5 seizures was reached. Fully kindled rats showed a marginally significant reduction in sensitivity to the locomotor stimulant effects of acute amphetamine compared with sham and partially kindled rats which had experienced subthreshold stimulation of the amygdala. Sham and partially kindled rats sensitized readily to the locomotor activating effects of amphetamine (0.125 mg/kg) following repeated treatments, but the fully kindled rats did not. Fully kindled rats also failed to show place preference conditioning to amphetamine (0.5 mg/kg). Rats, withdrawn three times from chronic ethanol (liquid-diet), kindled more quickly to PTZ (30 mg/kg, i.p.) than rats with the same overall exposure to ethanol (24 days) followed by a single withdrawal or control animals. However, there was no difference in the locomotor stimulating effects of acute amphetamine (0.25-1 mg/kg, i.p.), the rate of sensitization to amphetamine (0.125 mg/kg, i.p.) or amphetamine induced conditioned place preference (1 mg/kg, i.p.). These observations suggest that, in rats, repeated withdrawal from a

  2. Effects of 3-repeat tau on taxol mobility through microtubules

    Science.gov (United States)

    Park, Hyunjoo; Fygenson, Deborah; Kim, Mahn Won

    2005-03-01

    Both the anti-cancer drug taxol and the microtubule-associated protein tau suppress dynamics of microtubules (MT). We have observed taxol mobility with full-length 3-repeat tau, one of six tau isoforms, using fluorescence recovery after photobleaching (FRAP) on MTs and compare with earlier results on recombinant full-length adult 4-repeat tau. Taxol mobility becomes highly sensitive to taxol concentration in the presence of 3-repeat tau (up to 1:1 molar ratio) as it does in the presence of 4-repeat tau, but is 2 to 3 times faster at low taxol concentrations. Fitting to a mean-field binding reaction model [J.L. Ross et.al, PNAS 101:12910-5 (2004)] suggests that the presence of 3-repeat tau enhances taxol movement through pores in the MT walls.

  3. Melatonin prevents the development of hyperplastic urothelium induced by repeated doses of cyclophosphamide.

    Science.gov (United States)

    Zupancic, Dasa; Vidmar, Gaj; Jezernik, Kristijan

    2009-06-01

    Repeated cyclophosphamide (CP) chemotherapy increases the risk of developing bladder cancer, which could be due to the extremely rapid proliferation of urothelial cells observed in hyperplastic urothelium induced by CP treatment. We investigated the effect of melatonin on the development of urothelial hyperplasia induced by repeated CP treatment. Male ICR mice were injected with CP (150 mg/kg) or melatonin (10 mg/kg) with CP once a week for 3, 4 and 5 weeks. Transmission and scanning electron microscopy, immunohistochemistry and Western blot analysis were used to study the ultrastructure, apoptosis, proliferation and differentiation of urothelial cells. Repeated doses of CP caused the development of hyperplastic urothelium with up to ten cell layers and increased proliferation and apoptotic indices regarding Ki-67 and active caspase-3 immunohistochemistry, respectively. Scanning electron microscopy observations, cytokeratin and asymmetrical unit membrane immunohistochemistry and Western blot analysis showed a lower differentiation state of superficial urothelial cells. Melatonin co-treatment prevented the development of hyperplastic urothelium, statistically significantly decreased proliferation and apoptotic indices after four and five doses of CP and caused higher differentiation state of superficial urothelial cells.

  4. Polymeric photosensitizer-embedded self-expanding metal stent for repeatable endoscopic photodynamic therapy of cholangiocarcinoma.

    Science.gov (United States)

    Bae, Byoung-chan; Yang, Su-Geun; Jeong, Seok; Lee, Don Haeng; Na, Kun; Kim, Joon Mee; Costamagna, Guido; Kozarek, Richard A; Isayama, Hiroyuki; Deviere, Jacques; Seo, Dong Wan; Nageshwar Reddy, D

    2014-10-01

    Photodynamic therapy (PDT) is a new therapeutic approach for the palliative treatment of malignant bile duct obstruction. In this study, we designed photosensitizer-embedded self-expanding nonvascular metal stent (PDT-stent) which allows repeatable photodynamic treatment of cholangiocarcinoma without systemic injection of photosensitizer. Polymeric photosensitizer (pullulan acetate-conjugated pheophorbide A; PPA) was incorporated in self-expanding nonvascular metal stent. Residence of PPA in the stent was estimated in buffer solution and subcutaneous implantation on mouse. Photodynamic activity of PDT-stent was evaluated through laserexposure on stent-layered tumor cell lines, HCT-116 tumor-xenograft mouse models and endoscopic intervention of PDT-stent on bile duct of mini pigs. Photo-fluorescence imaging of the PDT-stent demonstrated homogeneous embedding of polymeric Pheo-A (PPA) on stent membrane. PDT-stent sustained its photodynamic activities at least for 2 month. And which implies repeatable endoscopic PDT is possible after stent emplacement. The PDT-stent after light exposure successfully generated cytotoxic singlet oxygen in the surrounding tissues, inducing apoptotic degradation of tumor cells and regression of xenograft tumors on mouse models. Endoscopic biliary in-stent photodynamic treatments on minipigs also suggested the potential efficacy of PDT-stent on cholangiocarcinoma. In vivo and in vitro studies revealed our PDT-stent, allows repeatable endoscopic biliary PDT, has the potential for the combination therapy (stent plus PDT) of cholangiocarcinoma. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. Consistency of Repeated Naming in Aphasia

    Directory of Open Access Journals (Sweden)

    Elizabeth E. Galletta

    2015-09-01

    Full Text Available Background People with mild aphasia and healthy elderly often exhibit similar impairments on language tests of word retrieval. However, variable practice effects in object naming by three individuals with aphasia compared to young and elderly adults have been reported (Wingfield et al. 2006. Wingfield et al. (2006 found that naming of the same pictures of objects over five trials demonstrated decreasing response latencies over repeated trials for both older and younger adults, but not for individuals with aphasia. In fact, among their three participants with aphasia, response latencies in the consecutive trials differed considerably. The authors suggested that different underlying processes may be involved in word retrieval for people with aphasia compared to adults without brain injuries. In our study we aimed to further consider the effect of practice on both object and action naming in individuals with mild aphasia. Method One woman with anomic aphasia (age 38 years; WAB Aphasia Quotient = 88 and one healthy woman (age 25 years participated. Both were native English speakers and reported 18 years of formal education. Participants were tested individually, with a set of 27 object pictures and a set of 27 action pictures presented one at a time on a computer screen. The participants were instructed to name each picture as quickly as possible as soon as each picture appeared on the screen. There were 10 trials of each set of pictures, with different random orders for each trial. The order of presentation of the object and action picture sets alternated across participants. Naming responses were recorded to computer sound files for later measurements of response latencies. A brief tone was presented simultaneous with the picture onset, allowing later measurement of response latencies from the onset of picture presentation to the onset of the participant’s correct response. Results Our findings resembled those reported in Wingfield et al. (2006

  6. CAG trinucleotide RNA repeats interact with RNA-binding proteins

    Energy Technology Data Exchange (ETDEWEB)

    McLaughlin, B.A.; Eberwine, J.; Spencer, C. [Univ. of Pennsylvania, Philadelphia, PA (United States)

    1996-09-01

    Genes associated with several neurological diseases are characterized by the presence of an abnormally long trinucleotide repeat sequence. By way of example, Huntington`s disease (HD), is characterized by selective neuronal degeneration associated with the expansion of a polyglutamine-encoding CAG tract. Normally, this CAG tract is comprised of 11-34 repeats, but in HD it is expanded to >37 repeats in affected individuals. The mechanism by which CAG repeats cause neuronal degeneration is unknown, but it has been speculated that the expansion primarily causes abnormal protein functioning, which in turn causes HD pathology. Other mechanisms, however, have not been ruled out. Interactions between RNA and RNA-binding proteins have previously been shown to play a role in the expression of several eukaryotic genes. Herein, we report the association of cytoplasmic proteins with normal length and extended CAG repeats, using gel shift and LJV crosslinking assays. Cytoplasmic protein extracts from several rat brain regions, including the striatum and cortex, sites of neuronal degeneration in HD, contain a 63-kD RNA-binding protein that specifically interacts with these CAG-repeat sequences. These protein-RNA interactions are dependent on the length of the CAG repeat, with longer repeats binding substantially more protein. Two CAG repeat-binding proteins are present in human cortex and striatum; one comigrates with the rat protein at 63 kD, while the other migrates at 49 kD. These data suggest mechanisms by which RNA-binding proteins may be involved in the pathological course of trinucleotide repeat-associated neurological diseases. 47 refs., 5 figs.

  7. Repeatability Evaluation of Finger Tapping Device with Magnetic Sensors

    Science.gov (United States)

    Sano, Yuko; Kandori, Akihiko; Shima, Keisuke; Tamura, Yasuhiro; Takagi, Hiroshi; Tsuji, Toshio; Noda, Masafumi; Higashikawa, Fumiko; Yokoe, Masaru; Sakoda, Saburo

    We tested the repeatability of a finger tapping device with magnetic sensors to determine its reliability. This device, which was developed to assist in the diagnosis of movement disorders such as Parkinson's disease (PD) and strokes, measures the distance between the first and index fingers during finger tapping movements (opening and closing the fingers repeatedly). We evaluated three types of repeatability based on ICC (interclass correlation coefficient) and Welch's test (test for equal means in a oneway layout): repeatability when measured at different times, when using different devices, and when using different measurers. We calculated these three types for three finger tapping tasks on both hands for 21 characteristics calculated from finger tapping waveforms. Results demonstrated that the repeatability when using different devices is high regardless of the task or hand. The repeatability when measuring at different times and when using different measurers is high at some tasks, but not all. One of the finger tapping tasks (finger tapping movement with the largest amplitude and highest velocity), which is used in a conventional PD diagnosis method (UPDRS), does not have enough repeatability, while other tasks show high repeatability. Results also showed that five characteristics have the highest repeatability (ICC ≥ 0.5 or significance probability of Welch's test ≥ 5% in all tasks): “total moving distance,” “average of local minimum acceleration in opening motion,” “average of local minimum acceleration in closing motion,” “average of local maximum distance” and “average of local minimum velocity”. These results clearly demonstrate the strong repeatability of this device and lead to more precise diagnosis of movement disorders.

  8. Criminality and continued DUI offense: criminal typologies and recidivism among repeat offenders.

    Science.gov (United States)

    LaBrie, Richard A; Kidman, Rachel C; Albanese, Mark; Peller, Allyson J; Shaffer, Howard J

    2007-01-01

    We examined over 20,000 arraignment records to define criminal typologies and post-treatment driving under the influence of alcohol (DUI) convictions for a select cohort of 1,281 repeat DUI offenders who were offered and elected treatment as an alternative to incarceration; we compared this information with a similar data analysis collected 20 years previously. Analyses of 8,600 prior-to-treatment convictions defined four basic crime profiles: only DUI and other substance-related offenses (60%), plus crimes against property (18%), plus crimes against people (8%), plus crimes against both property and people (13%). During the six years after inpatient treatment, 15.5% of the cohort was convicted of another DUI. The reoffense rate was significantly different across criminal types and was not related to the time post treatment years at risk. The findings show there has been no significant improvement in treatment outcome over the last 20 years. New and innovative DUI offender policies and practices are needed to better engage the heterogeneous offender population, and reduce the incidence of repeat DUI.

  9. New prospects for antipsychotic treatment - the role of the kynurenine pathway

    Directory of Open Access Journals (Sweden)

    Hanna Karakuła-Juchnowicz

    2014-12-01

    Full Text Available The mechanism of action of antipsychotic drugs is mainly associated with changes in dopaminergic system. The application of antipsychotic agents simultaneously produces changes in concentrations of metabolites (e.g. kynurenic acid – KYNA, 3-hydroxykynurenine – 3-OHKYN, kynurenine – KYN of the kynurenine pathway, the pathway engaged in glutamatergic transmission. The increase in KYNA levels in certain areas of the central nervous system results in inhibition of glutamatergic transmission. Pharmacologically induced elevation of KYNA levels produces effects similar to those observed after administering ketamine or phencyclidine (the noncompetitive NMDA receptor antagonist, concerning increased activity of mesolimbic dopamine neurons, as well as reduction in dopamine release from the prefrontal cortex. Recent research results confirm the predictive value of changes in concentrations of kynurenine pathway metabolites for assessment of effectiveness of antipsychotic treatment. Significant relationships were found 1 in schizophrenia between the reduction of psychopathological symptoms and variations in 3-OHKYN levels as well as changes in KYNA/3-OHKYN and KYN/KYNA ratios, 2 in mania between varying tryptophan concentrations and the reduction in manic symptoms achieved with antipsychotic treatment. The research as well presented the possibilities of kynurenine pathway modifications, raising high hopes for their future application as target points for the action of novel antipsychotic agents.

  10. Strategy When Faced with Failure: Persistence and Degree Attainment of Course Repeaters versus Non-Repeaters. AIR 2002 Forum Paper.

    Science.gov (United States)

    Fenton, Kathleen S.

    Graduation and persistence rates were compared for 184 students, 92 of whom had repeated multiple courses or at least 1 course 3 times. A control group of 92 nonrepeating students was drawn from the remaining 303 students of the entire 1996 cohort. There was no difference between the graduation rate of repeaters and nonrepeaters. The persistence…

  11. Image analysis as a non-destructive method to assess regrowth of weeds after repeated flame weeding

    DEFF Research Database (Denmark)

    Rask, Anne Merete; Kristoffersen, Palle; Andreasen, Christian

    2013-01-01

    Efficient non-chemical weed control like flame weeding often requires repeated treatments. In weed control experiments the effect of each treatment may be estimated by removing and weighing the remaining weed biomass after the treatment, but the method influences the weed plants ability to regrow......, and therefore it may influence the long-term effect of repeated treatments. Visual assessment of weed cover or image analysis do not affect the remaining parts of the weed plants after treatment, but the methods may have other disadvantages. In order to evaluate and compare three methods we measured changes...... in vegetation cover of perennial ryegrass after flaming by (1) a simple image analysis programme counting green pixels, (2) visual assessment of images and (3) by taking biomass samples. Plants were flame treated with eight different dosages (0, 20, 30, 35, 45, 60, 90 and 180 kg propane ha-1) and with various...

  12. Treatment Intensity and Childhood Apraxia of Speech

    Science.gov (United States)

    Namasivayam, Aravind K.; Pukonen, Margit; Goshulak, Debra; Hard, Jennifer; Rudzicz, Frank; Rietveld, Toni; Maassen, Ben; Kroll, Robert; van Lieshout, Pascal

    2015-01-01

    Background: Intensive treatment has been repeatedly recommended for the treatment of speech deficits in childhood apraxia of speech (CAS). However, differences in treatment outcomes as a function of treatment intensity have not been systematically studied in this population. Aim: To investigate the effects of treatment intensity on outcome…

  13. Repeating earthquakes recorded by Liaoning Regional Seismograph Network

    Institute of Scientific and Technical Information of China (English)

    LI Yu-tong; WU Zhong-liang; JIANG Chang-sheng; LI Guang-ping

    2008-01-01

    In the list of 'repeating pairs' or 'doublets' of earthquakes in China identified by Schaff and Richards using tele-seismic waveform cross-correlation, there were 23 repeating pairs located in Liaoning Province. In this study the waveforms of these events were cross-correlated using records from Liaoning Regional Seismograph Network (LRSN), and the 'repeating events' in the sense of regional waveform cross-correlation were obtained. The result was compared with that of Schaff and Richards and was used for the assessment of the seismic phase picking and event location practice of LRSN. The result shows that 'repeating events' in the sense of teleseismic waveform cross-correlation and those in the sense of regional waveform cross-correlation have significant difference, al-though with some overlap. However, the overall assessment of the location accuracy and the phase pick errors of LRSN by using these two sets of 'repeating events', respectively, provides similar results, while 'repeating events' in the sense of regional waveform cross-correlation seem to be better performing in such an assessment. With the assumption that the separation between the 'repeaters' be less than 1 km, the uncertainty in routine earthquake location of LRSN is estimated to be below 5 km, with the average of 2 km. In the observational bulletins of LRSN the time error in phase picking is estimated to be within±Is for 94% Pg readings and for 88% Sg readings.

  14. Repeat breeding: Incidence, risk factors and diagnosis in buffaloes

    Directory of Open Access Journals (Sweden)

    Chandra Shekher Saraswat

    2016-04-01

    Full Text Available Repeat breeding in buffaloes was evaluated in terms of incidence, risk factors and diagnosis. The incidence of repeat breeding is low in buffaloes however in different studies the incidence varied from 0.70% to 30%. Because of seasonal suppression of fertility repeat breeding in buffaloes should be limited to the breeding season. Spring and winter calving, first parity, peri-parturient disease and lactation are significant risk factors for repeat breeding in buffaloes. The etiologies of repeat breeding in buffaloes can be failure of fertilization and early embryonic deaths. Only a few of causes of failure of fertilization have been identified in buffaloes. Ovulatory disturbances and ovarian cysts are uncommon in buffaloes and cysts have poor clinical manifestation. Endometritis is the common female cause of fertilization failures in buffaloes whereas poor semen quality and improper insemination are the bull side factors for fertilization failures. Early embryonic deaths are common in buffaloes mated/inseminated during the end of the breeding season due to a low luteal progesterone however embryonic deaths occur late (<25 days in buffaloes. Diagnostic approaches for repeat breeding include vaginoscopic and transrectal examination and uterine cytology for genital health. More precise evaluations of the ovarian and uterine function can be obtained by ultrasonographic and hysteroscopic examinations performed sequentially however, precise diagnosis of the cause of repeat breeding seems difficult.

  15. Exploring the repeat protein universe through computational protein design.

    Science.gov (United States)

    Brunette, T J; Parmeggiani, Fabio; Huang, Po-Ssu; Bhabha, Gira; Ekiert, Damian C; Tsutakawa, Susan E; Hura, Greg L; Tainer, John A; Baker, David

    2015-12-24

    A central question in protein evolution is the extent to which naturally occurring proteins sample the space of folded structures accessible to the polypeptide chain. Repeat proteins composed of multiple tandem copies of a modular structure unit are widespread in nature and have critical roles in molecular recognition, signalling, and other essential biological processes. Naturally occurring repeat proteins have been re-engineered for molecular recognition and modular scaffolding applications. Here we use computational protein design to investigate the space of folded structures that can be generated by tandem repeating a simple helix-loop-helix-loop structural motif. Eighty-three designs with sequences unrelated to known repeat proteins were experimentally characterized. Of these, 53 are monomeric and stable at 95 °C, and 43 have solution X-ray scattering spectra consistent with the design models. Crystal structures of 15 designs spanning a broad range of curvatures are in close agreement with the design models with root mean square deviations ranging from 0.7 to 2.5 Å. Our results show that existing repeat proteins occupy only a small fraction of the possible repeat protein sequence and structure space and that it is possible to design novel repeat proteins with precisely specified geometries, opening up a wide array of new possibilities for biomolecular engineering.

  16. Effect of tramadol on metamizol pharmacokinetics and pharmacodynamics after single and repeated administrations in arthritic rats

    Directory of Open Access Journals (Sweden)

    Luis Alfonso Moreno-Rocha

    2016-11-01

    Full Text Available Combined administration of certain doses of opioid compounds with a non-steroidal anti-inflammatory drug can produce additive or supra-additive effects while reducing unwanted effects. We have recently reported that co-administration of metamizol with tramadol produces antinociceptive effect potentiation, after acute treatment. However, none information about the effect produced by the combination after chronic or repeated dose administration exists. The aims of this study were to investigate whether the antinociceptive synergism produced by the combination of metamizol and tramadol (177.8 + 17.8 mg/kg, s.c. respectively is maintained after repeated treatment and whether the effects observed are primarily due to pharmacodynamic interactions or may be related to pharmacokinetics changes. Administration of metamizol plus tramadol acute treatment significantly enhanced the antinociceptive effect of the drugs given alone (P  0.05. The mechanism involved in the synergism of the antinociceptive effect observed with the combination of metamizol and tramadol in single dose cannot be attributed to a pharmacokinetic interaction, and other pharmacodynamic interactions have to be considered. On the other hand, when metamizol and tramadol were co-administered under repeated administrations, a pharmacokinetic interaction and tolerance development occurred. Differences found in metamizol active metabolites’ pharmacokinetics (P < 0.05 were related to the development of tolerance produced by the combination after repeated doses. This work shows an additional preclinical support for the combination therapy. The clinical utility of this combination in a suitable dose range should be evaluated in future studies.

  17. Repeated administration of imipramine modifies GABAergic transmission in rat frontal cortex.

    Science.gov (United States)

    Wabno, Joanna; Hess, Grzegorz

    2013-05-01

    Alterations in the functions of brain gamma-aminobutyric acid (GABA) inhibitory system and a distortion in the balance between excitatory and inhibitory synaptic transmission have been hypothesized to be possible causes of mood disorders. Experimental evidence points to modifications of GABAergic transmission as a result of prolonged treatment with antidepressant drugs, however, the influence of the tricyclic antidepressant imipramine on inhibitory synaptic transmission in the rat cerebral cortex has not yet been investigated. Therefore, in the present study the effects of single and repeated administration of imipramine were evaluated ex vivo in slices of the rat frontal cortex using electrophysiological approach. In slices prepared 2 days after the last drug administration from animals receiving imipramine for 14 days (dose 10 mg/kg p.o., twice daily) the mean frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) recorded from layer II/III pyramidal neurons was decreased, while the mean amplitude of sIPSCs was increased. These effects were absent in slices obtained from rats which received imipramine once. Application of N,N'-dibenzhydrylethane-1,2-diamine dihydrochloride (AMN 082), a selective mGluR7 allosteric agonist, to the slice incubation medium resulted in a decrease in the mean frequency of sIPSCs in preparations obtained from repeated imipramine-treated animals, in contrast to slices originating from control rats where no AMN 082-induced effects were observed. Repeated imipramine treatment reduced protein density levels of the three tested GABAA receptor subunits: α 1, β 2 and γ 2. These data indicate that repeated treatment of normal rats with imipramine results in a modification of the release mechanism of GABA from presynaptic terminals and its modulation by mGluR7 receptors as well as in an alteration in GABAA receptor subunit protein levels in the rat cerebral cortex.

  18. Repeat Whole Brain Radiation Therapy with a Simultaneous Infield Boost: A Novel Technique for Reirradiation

    Directory of Open Access Journals (Sweden)

    William A. Hall

    2014-01-01

    Full Text Available The treatment of patients who experience intracranial progression after whole brain radiation therapy (WBRT is a clinical challenge. Novel radiation therapy delivery technologies are being applied with the objective of improving tumor and symptom control in these patients. The purpose of this study is to describe the clinical outcomes of the application of a novel technology to deliver repeat WBRT with volume modulated arc therapy (VMAT and a simultaneous infield boost (WB-SIB to gross disease. A total of 16 patients were initially treated with WBRT between 2000 and 2008 and then experienced intracranial progression, were treated using repeat WB-SIB, and were analyzed. The median dose for the first course of WBRT was 35 Gy (range: 30–50.4 Gy. Median time between the initial course of WBRT and repeat WB-SIB was 11.3 months. The median dose at reirradiation was 20 Gy to the whole brain with a median boost dose of 30 Gy to gross disease. A total of 2 patients demonstrated radiographic disease progression after treatment. The median overall survival (OS time from initial diagnosis of brain metastases was 18.9 months (range: 7.1–66.6 (95% CI: 0.8–36.9. The median OS time after initiation of reirradiation for all patients was 2.7 months (range: 0.46–14.46 (95% CI: 1.3–8.7. Only 3 patients experienced CTCAE grade 3 fatigue. No other patients experienced any ≥ CTCAE grade 3 toxicity. This analysis reports the result of a novel RT delivery technique for the treatment of patients with recurrent brain metastases. Side effects were manageable and comparable to other conventional repeat WBRT series. Repeat WB-SIB using the VMAT RT delivery technology is feasible and appears to have acceptable short-term acute toxicity. These results may provide a foundation for further exploration of the WB-SIB technique for repeat WBRT in future prospective clinical trials.

  19. ACCA phosphopeptide recognition by the BRCT repeats of BRCA1.

    Science.gov (United States)

    Ray, Hind; Moreau, Karen; Dizin, Eva; Callebaut, Isabelle; Venezia, Nicole Dalla

    2006-06-16

    The tumour suppressor gene BRCA1 encodes a 220 kDa protein that participates in multiple cellular processes. The BRCA1 protein contains a tandem of two BRCT repeats at its carboxy-terminal region. The majority of disease-associated BRCA1 mutations affect this region and provide to the BRCT repeats a central role in the BRCA1 tumour suppressor function. The BRCT repeats have been shown to mediate phospho-dependant protein-protein interactions. They recognize phosphorylated peptides using a recognition groove that spans both BRCT repeats. We previously identified an interaction between the tandem of BRCA1 BRCT repeats and ACCA, which was disrupted by germ line BRCA1 mutations that affect the BRCT repeats. We recently showed that BRCA1 modulates ACCA activity through its phospho-dependent binding to ACCA. To delineate the region of ACCA that is crucial for the regulation of its activity by BRCA1, we searched for potential phosphorylation sites in the ACCA sequence that might be recognized by the BRCA1 BRCT repeats. Using sequence analysis and structure modelling, we proposed the Ser1263 residue as the most favourable candidate among six residues, for recognition by the BRCA1 BRCT repeats. Using experimental approaches, such as GST pull-down assay with Bosc cells, we clearly showed that phosphorylation of only Ser1263 was essential for the interaction of ACCA with the BRCT repeats. We finally demonstrated by immunoprecipitation of ACCA in cells, that the whole BRCA1 protein interacts with ACCA when phosphorylated on Ser1263.

  20. Secure quantum network coding for controlled repeater networks

    Science.gov (United States)

    Shang, Tao; Li, Jiao; Liu, Jian-wei

    2016-07-01

    To realize efficient quantum communication based on quantum repeater, we propose a secure quantum network coding scheme for controlled repeater networks, which adds a controller as a trusted party and is able to control the process of EPR-pair distribution. As the key operations of quantum repeater, local operations and quantum communication are designed to adopt quantum one-time pad to enhance the function of identity authentication instead of local operations and classical communication. Scheme analysis shows that the proposed scheme can defend against active attacks for quantum communication and realize long-distance quantum communication with minimal resource consumption.

  1. Instability of trinucleotidic repeats during chromatin remodeling in spermatids.

    Science.gov (United States)

    Simard, Olivier; Grégoire, Marie-Chantal; Arguin, Mélina; Brazeau, Marc-André; Leduc, Frédéric; Marois, Isabelle; Richter, Martin V; Boissonneault, Guylain

    2014-11-01

    Transient DNA breaks and evidence of DNA damage response have recently been reported during the chromatin remodeling process in haploid spermatids, creating a potential window of enhanced genetic instability. We used flow cytometry to achieve separation of differentiating spermatids into four highly purified populations using transgenic mice harboring 160 CAG repeats within exon 1 of the human Huntington disease gene (HTT). Trinucleotic repeat expansion was found to occur immediately following the chromatin remodeling steps, confirming the genetic instability of the process and pointing to the origin of paternal anticipation observed in some trinucleotidic repeats diseases.

  2. Frequency Bandwidth of Half-Wave Impedance Repeater

    Directory of Open Access Journals (Sweden)

    Marek Dvorsky

    2012-01-01

    Full Text Available This article brings in the second part general information about half-wave impedance repeater. The third part describes the basic functional principles of the half-wave impedance repeater using Smith chart. The main attention is focused in part four on the derivation of repeater frequency bandwidth depending on characteristics and load impedance of unknown feeder line. Derived dependences are based on the elementary features of the feeder lines with specific length. The described functionality is proved in part 4.3 by measurement of transformed impedance using vector several unbalanced feeder lines and network analyzer VNWA3+.

  3. Varenicline impairs extinction and enhances reinstatement across repeated cycles of nicotine self-administration in rats.

    Science.gov (United States)

    Macnamara, Claire L; Holmes, Nathan M; Westbrook, R Fred; Clemens, Kelly J

    2016-06-01

    Varenicline is a partial nicotine receptor agonist widely prescribed as a smoking cessation medication. Repeated (or long-term) use of varenicline has been proposed as a treatment option for tobacco addiction. However the effect of repeated varenicline use on motivation for nicotine is unknown. Here the intravenous nicotine self-administration paradigm in rats was used to model the consequences of varenicline treatment across repeated cycles of administration, extinction and reinstatement. Rats acquired nicotine self-administration across 20 days before undergoing 6 days of extinction, where each extinction session was preceded by a single injection of varenicline or saline. This was followed by a single varenicline-free nicotine-primed reinstatement test. All rats then reacquired nicotine self-administration for 10 days followed by a second cycle of extinction. Across this period, rats either received a second cycle of varenicline (VAR-VAR) or saline (SAL-SAL), or the alternative treatment (SAL-VAR, VAR-SAL), followed by a final reinstatement test. Treatment with varenicline increased responding across the first cycle of extinction, but did not affect responding in the reinstatement test. Across the second cycle, varenicline again increased responding across extinction, and critically, rats treated with varenicline across cycle 1 and saline across cycle 2 (Group VAR-SAL) exhibited more reinstatement than rats in any other group. The effect of VAR on nicotine seeking was not due to its effects on locomotor activity. Instead, the results suggest that a history of VAR can increase vulnerability to reinstatement/relapse when its treatment is discontinued. The possible mechanisms of this increased vulnerability are discussed.

  4. Combination of repeated single-session percutaneous ethanol injection and transarterial chemoembolisation compared to repeated single-session percutaneous ethanol injection in patients with non-resectable hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Arne Dettmer; Susanne Krusche; Sonja Merkesdal; Michael Galanski; Michael P Manns; Joerg S Bleck; Timm D Kirchhoff; Michael Gebel; Lars Zender; Nisar P Malek; Bernhard Panning; Ajay Chavan; Herbert Rosenthal; Stefan Kubicka

    2006-01-01

    AIM: To evaluate the treatment effect of percutaneous ethanol injection (PEI) for patients with advanced,non-resectable HCC compared with combination of transarterial chemoembolisation (TACE) and repeated single-session PEI, repeated single-session PEI alone,repeated TACE alone, or best supportive care.METHODS: All patients who received PEI treatment during the study period were included and stratified to one of the following treatment modalities according to physical status and tumor extent: combination of TACE and repeated single-session PEI, repeated single-session PEI alone, repeated TACE alone, or best supportive care. Prognostic value of clinical parameters including Okuda-classification, presence of portal vein thrombosis,presence of ascites, number of tumors, maximum tumor diameter, and serum cholinesterase (CHE), as well as Child-Pugh stage, α-fetoprotein (AFP), fever, incidence of complications were assessed and compared between the groups. Survival was determined using Kaplan-Meier and multivariate regression analyses.RESULTS: The 1- and 3-year survival of all patients was 73% and 47%. In the subgroup analyses, the combination of TACE and PEI (1) was associated with a longer survival (1-, 3-, 5-year survival: 90%, 52%,and 43%) compared to PEI treatment alone (2) (1-, 3-,5-year survival:65%, 50%, and 37%). Secondary PEI after initial stratification to TACE (3) yielded comparable results (1-, 3-, 5-year survival: 91%, 40%, and 30%)while PEI after stratification to best supportive care (4)was associated with decreased survival (1-, 3-, 5-year survival: 50%, 23%, 12%). Apart from the chosen treatment modalities, predictors for better survival were tumor number (n<5), tumor size (<5cm), no ascites before PEI, and stable serum cholinesterase after PEI (P<0.05). The mortality within 2 wk after PEI was 2.8%(n=3). There were 24 (8.9%) major complications after PEI including segmental liver infarction, focal liver necrosis, and liver abscess. All

  5. The Effect of Repeated Heating on Fatty Acid Profile of Beef and Spices of Rendang

    Directory of Open Access Journals (Sweden)

    Rina Yenrina

    2015-03-01

    Full Text Available Rendang is a traditional Minangkabau cuisine with the main ingredient of beef or buffalo meat which is cooked using coconut milk and some spices. Rendang is cooked more than 2 hours, and after that do the repeated heating. This study aimed to determine the effect of repeated heating on fatty acid profiles of beef and spices of rendang. The analysis carried out at Chemistry Lab. and Biochemistry Lab. In  Fateta Unand and Integrated Lab in IPB Bogor. This  study   designed  used a completely  randomized  design  with 5 treatments and 3 replications.  The treatments that used in this study were A (raw beef, B (freshly cooked rendang, C (first heating, D (second heating, E (third heating where the heating was done every 2 days. Data were collected for  fatty acids profile of beef and spices of rendang. Analysis of the Type of  Fatty Acid by HPLC method (AOAC, 1984. The results shown that repeated heating of beef and spice of rendang had significantly different effect on the type of fatty acids and an increased trans fatty Acid of rendang.

  6. Effects of Carbohydrate Ingestion and Carbohydrate Mouth Rinse on Repeat Sprint Performance.

    Science.gov (United States)

    Krings, Ben M; Peterson, Timothy J; Shepherd, Brandon D; McAllister, Matthew J; Smith, JohnEric W

    2017-06-01

    The purpose of this investigation was to examine to the influence of carbohydrate ingestion (CHOI) and carbohydrate mouth rinse (CHOR) on acute repeat maximal sprint performance. Fourteen healthy males (age: 21.7 ± 1.8 years, mass: 82.3 ± 12.3 kg) completed a total of five 15-s maximal repeat sprints on a cycle ergometer against 0.075 kg ・ kg(-1) body mass each separated by 4 min of active recovery. Subjects completed four experimental trials and were randomly assigned one of four treatments: (1) CHOI, (2) CHOR, (3) placebo mouth rinse (PLAR), (4) placebo ingestion (PLAI). Subjects rinsed or ingested six 50 mL 10% CHO solutions throughout each trial. Performance variables measured included rating of perceived exertion, peak heart rate, peak and mean power output, fatigue index, and total work. Significant treatment main effects were observed for mean power output (p = 0.026), total work (p = 0.020), fatigue index (p = 0.004), and heart rate (p = 0.013). Overall mean power output and total work were significantly greater with CHOI (659.3 ± 103.0 watts, 9849.8 ± 1598.8 joules) compared with CHOR (645.8 ± 99.7 watts, 9447.5 ± 1684.9 joules, p PLAI, and PLAR. Athletes required to complete repeat bouts of high intensity exercise may benefit from CHOI.

  7. Myricetin Attenuates Depressant-Like Behavior in Mice Subjected to Repeated Restraint Stress

    Directory of Open Access Journals (Sweden)

    Zegang Ma

    2015-11-01

    Full Text Available Increasing evidence has shown that oxidative stress may be implicated in chronic stress-induced depression. Several flavonoids with anti-oxidative effects have been proved to be anti-depressive. Myricetin is a well-defined flavonoid with the anti-oxidative, anti-inflammatory, anti-apoptotic, and neuroprotective properties. The aim of the present study is to investigate the possible effects of chronic administration of myricetin on depressant-like behaviors in mice subjected to repeated restraint (4 h/day for 21 days. Our results showed that myricetin administration specifically reduced the immobility time in mice exposed to chronic stress, as tested in both forced swimming test and tail suspension test. Myricetin treatment improved activities of glutathione peroxidase (GSH-PX in the hippocampus of stressed mice. In addition, myricetin treatment decreased plasma corticosterone levels of those mice subjected to repeated restraint stress. The effects of myricetin on the brain-derived neurotrophic factor (BDNF levels in hippocampus were also investigated. The results revealed that myricetin normalized the decreased BDNF levels in mice subjected to repeated restraint stress. These findings provided more evidence that chronic administration of myricetin improves helpless behaviors. The protective effects of myricetin might be partially mediated by an influence on BDNF levels and might be attributed to myricetin-mediated anti-oxidative stress in the hippocampus.

  8. Repeated transcranial direct current stimulation prevents abnormal behaviors associated with abstinence from chronic nicotine consumption.

    Science.gov (United States)

    Pedron, Solène; Monnin, Julie; Haffen, Emmanuel; Sechter, Daniel; Van Waes, Vincent

    2014-03-01

    Successful available treatments to quit smoking remain scarce. Recently, the potential of transcranial direct current stimulation (tDCS) as a tool to reduce craving for nicotine has gained interest. However, there is no documented animal model to assess the neurobiological mechanisms of tDCS on addiction-related behaviors. To address this topic, we have developed a model of repeated tDCS in mice and used it to validate its effectiveness in relieving nicotine addiction. Anodal repeated tDCS was applied over the frontal cortex of Swiss female mice. The stimulation electrode (anode) was fixed directly onto the cranium, and the reference electrode was placed onto the ventral thorax. A 2 × 20 min/day stimulation paradigm for five consecutive days was used (0.2 mA). In the first study, we screened for behaviors altered by the stimulation. Second, we tested whether tDCS could alleviate abnormal behaviors associated with abstinence from nicotine consumption. In naive animals, repeated tDCS had antidepressant-like properties 3 weeks after the last stimulation, improved working memory, and decreased conditioned place preference for nicotine without affecting locomotor activity and anxiety-related behavior. Importantly, abnormal behaviors associated with chronic nicotine exposure (ie, depression-like behavior, increase in nicotine-induced place preference) were normalized by repeated tDCS. Our data show for the first time in an animal model that repeated tDCS is a promising, non-expensive clinical tool that could be used to reduce smoking craving and facilitate smoking cessation. Our animal model will be useful to investigate the mechanisms underlying the effects of tDCS on addiction and other psychiatric disorders.

  9. Highly Informative Simple Sequence Repeat (SSR) Markers for Fingerprinting Hazelnut

    Science.gov (United States)

    Simple sequence repeat (SSR) or microsatellite markers have many applications in breeding and genetic studies of plants, including fingerprinting of cultivars and investigations of genetic diversity, and therefore provide information for better management of germplasm collections. They are repeatab...

  10. On the role of memory errors in quantum repeaters

    CERN Document Server

    Hartmann, L; Dür, W; Kraus, B

    2006-01-01

    We investigate the influence of memory errors in the quantum repeater scheme for long-range quantum communication. We show that the communication distance is limited in standard operation mode due to memory errors resulting from unavoidable waiting times for classical signals. We show how to overcome these limitations by (i) improving local memory, and (ii) introducing two new operational modes of the quantum repeater. In both operational modes, the repeater is run blindly, i.e. without waiting for classical signals to arrive. In the first scheme, entanglement purification protocols based on one-way classical communication are used allowing to communicate over arbitrary distances. However, the error thresholds for noise in local control operations are very stringent. The second scheme makes use of entanglement purification protocols with two-way classical communication and inherits the favorable error thresholds of the repeater run in standard mode. One can increase the possible communication distance by an o...

  11. Analysis of Simple Sequence Repeats in Genomes of Rhizobia

    Institute of Scientific and Technical Information of China (English)

    GAO Ya-mei; HAN Yi-qiang; TANG Hui; SUN Dong-mei; WANG Yan-jie; WANG Wei-dong

    2008-01-01

    Simple sequence repeats (SSRs) or microsatellites, as genetic markers, are ubiquitous in genomes of various organisms. The analysis of SSR in rhizobia genome provides useful information for a variety of applications in population genetics of rhizobia. We analyzed the occurrences, relative abundance, and relative density of SSRs, the most common in Bradyrhizobium japonicum, Mesorhizobium loti, and Sinorhizobium meliloti genomes se-quenced in the microorganisms tandem repeats database, and SSRs in the three species genomes were compared with each other. The result showed that there were 1 410, 859, and 638 SSRs in B. japonicum, M. loti, and 5. meliloti genomes, respectively. In the genomes of B. japonicum, M. loti, and 5. meliloti, tetranucleotide, pentanucleotide, and hexanucleotide repeats were more abundant and indicated higher mutation rates in these species. The least abundance was mononucleotide repeat. The SSRs type and distribution were similar among these species.

  12. simple sequence repeat (SSR) markers in genetic analysis of

    African Journals Online (AJOL)

    Yomi

    2012-08-28

    Aug 28, 2012 ... In the present study, 78 mapped simple sequence repeat (SSR) markers representing 11 ... mean (UPGMA) with each cluster representing a particular Vigna species. ..... were reported to be more frequent than the compound.

  13. Study of simple sequence repeat (SSR) polymorphism for biotic ...

    African Journals Online (AJOL)

    home

    2013-10-02

    Oct 2, 2013 ... back cross breeding; SSRs, simple sequence repeats; PIC, polymorphism ..... PIC values were reported in barley wheat and rice (Gu et ... doubled-haploid rice population. Theor. ... Grover A, Aishwarya V, Sharma PC (2007).

  14. Markerless modification of trinucleotide repeat loci in BACs.

    Science.gov (United States)

    Benzow, Kellie A; Koob, Michael D

    2013-01-01

    Transcription and splicing of human genes are regulated by nucleotide sequences encoded across large segments of our genome, and trinucleotide repeat expansion mutations can have both profound and subtle effects on these processes. In the course of our work to understand the impact of the Spinocerebellar Ataxia type 8 (SCA8) CTG repeat expansion on the transcription and splicing of the RNAs encoded near the SCA8 locus, we have developed a set of reagents and protocols for modifying large genomic BAC clones of this region. We describe the two-step procedure that allows us to precisely replace unexpanded trinucleotide repeats with expanded variants of these repeat sequences without leaving any exogenous sequences in the final constructs, and we discuss how this approach can be adapted to make other desired sequence changes to these genomic clones.

  15. Discriminant analysis for repeated measures data: a review

    Directory of Open Access Journals (Sweden)

    Lisa Lix

    2010-09-01

    Full Text Available Discriminant analysis (DA encompasses procedures for classifying observations into groups (i.e., predictive discriminative analysis and describing the relative importance of variables for distinguishing amongst groups (i.e., descriptive discriminative analysis. In recent years, a number of developments have occurred in DA procedures for the analysis of data from repeated measures designs. Specifically, DA procedures have been developed for repeated measures data characterized by missing observations and/or unbalanced measurement occasions, as well as high-dimensional data in which measurements are collected repeatedly on two or more variables. This paper reviews the literature on DA procedures for univariate and multivariate repeated measures data, focusing on covariance pattern and linear mixed-effects models. A numeric example illustrates their implementation using SAS software.

  16. Bayesian model selection of informative hypotheses for repeated measurements

    NARCIS (Netherlands)

    Mulder, Joris; Klugkist, I.G.; Schoot, Rens van de; Meeus, W.H.J.; Selfhout, Maarten; Hoijtink, Herbert

    2010-01-01

    When analyzing repeated measurements data, researchers often have expectations about the relations between the measurement means. The expectations can often be formalized using equality and inequality constraints between (i) the measurement means over time, (ii) the measurement means between

  17. Bayesian model selection of informative hypotheses for repeated measurements

    NARCIS (Netherlands)

    Mulder, J.|info:eu-repo/dai/nl/304823031; Klugkist, I.G.|info:eu-repo/dai/nl/27330089X; Van de Schoot, R.|info:eu-repo/dai/nl/304833207; Meeus, W.H.J.|info:eu-repo/dai/nl/070442215; van Zalk, M.H.W.|info:eu-repo/dai/nl/304836214; Hoijtink, H.J.A.|info:eu-repo/dai/nl/075184427

    2009-01-01

    When analyzing repeated measurements data, researchers often have expectations about the relations between the measurement means. The expectations can often be formalized using equality and inequality constraints between (i) the measurement means over time, (ii) the measurement means between groups,

  18. Correct use of repeated measures analysis of variance.

    Science.gov (United States)

    Park, Eunsik; Cho, Meehye; Ki, Chang-Seok

    2009-02-01

    In biomedical research, researchers frequently use statistical procedures such as the t-test, standard analysis of variance (ANOVA), or the repeated measures ANOVA to compare means between the groups of interest. There are frequently some misuses in applying these procedures since the conditions of the experiments or statistical assumptions necessary to apply these procedures are not fully taken into consideration. In this paper, we demonstrate the correct use of repeated measures ANOVA to prevent or minimize ethical or scientific problems due to its misuse. We also describe the appropriate use of multiple comparison tests for follow-up analysis in repeated measures ANOVA. Finally, we demonstrate the use of repeated measures ANOVA by using real data and the statistical software package SPSS (SPSS Inc., USA).

  19. Pharmacology of ayahuasca administered in two repeated doses.

    Science.gov (United States)

    Dos Santos, Rafael G; Grasa, Eva; Valle, Marta; Ballester, Maria Rosa; Bouso, José Carlos; Nomdedéu, Josep F; Homs, Rosa; Barbanoj, Manel J; Riba, Jordi

    2012-02-01

    Ayahuasca is an Amazonian tea containing the natural psychedelic 5-HT(2A/2C/1A) agonist N,N-dimethyltryptamine (DMT). It is used in ceremonial contexts for its visionary properties. The human pharmacology of ayahuasca has been well characterized following its administration in single doses. To evaluate the human pharmacology of ayahuasca in repeated doses and assess the potential occurrence of acute tolerance or sensitization. In a double-blind, crossover, placebo-controlled clinical trial, nine experienced psychedelic drug users received PO the two following treatment combinations at least 1 week apart: (a) a lactose placebo and then, 4 h later, an ayahuasca dose; and (b) two ayahuasca doses 4 h apart. All ayahuasca doses were freeze-dried Amazonian-sourced tea encapsulated to a standardized 0.75 mg DMT/kg bodyweight. Subjective, neurophysiological, cardiovascular, autonomic, neuroendocrine, and cell immunity measures were obtained before and at regular time intervals until 12 h after first dose administration. DMT plasma concentrations, scores in subjective and neurophysiological variables, and serum prolactin and cortisol were significantly higher after two consecutive doses. When effects were standardized by plasma DMT concentrations, no differences were observed for subjective, neurophysiological, autonomic, or immunological effects. However, we observed a trend to reduced systolic blood pressure and heart rate, and a significant decrease for growth hormone (GH) after the second ayahuasca dose. Whereas there was no clear-cut tolerance or sensitization in the psychological sphere or most physiological variables, a trend to lower cardiovascular activation was observed, together with significant tolerance to GH secretion.

  20. Repeated bedside echocardiography in children with respiratory failure

    Directory of Open Access Journals (Sweden)

    Jehlicka Petr

    2011-04-01

    Full Text Available Abstract Background The aim of this study was to verify the benefits and limitations of repeated bedside echocardiographic examinations in children during mechanical ventilation. For the purposes of this study, we selected the data of over a time period from 2006 to 2010. Methods A total of 235 children, average age 3.21 (SD 1.32 years were included into the study and divided into etiopathogenic groups. High-risk groups comprised: Acute lung injury and acute respiratory distress syndrome (ALI/ARDS, return of spontaneous circulation after cardiopulmonary resuscitation (ROSC, bronchopulmonary dysplasia (BPD, cardiomyopathy (CMP and cardiopulmonary disease (CPD. Transthoracic echocardiography was carried out during mechanical ventilation. The following data were collated for statistical evaluation: right and left ventricle myocardial performance indices (RV MPI; LV MPI, left ventricle shortening fraction (SF, cardiac output (CO, and the mitral valve ratio of peak velocity of early wave (E to the peak velocity of active wave (A as E/A ratio. The data was processed after a period of recovery, i.e. one hour after the introduction of invasive lines (time-1 and after 72 hours of comprehensive treatment (time-2. The overall development of parameters over time was compared within groups and between groups using the distribution-free Wilcoxons and two-way ANOVA tests. Results A total of 870 echocardiographic examinations were performed. At time-1 higher average values of RV MPI (0.34, SD 0.01 vs. 0.21, SD 0.01; p Conclusion Echocardiography complements standard monitoring of valuable information regarding cardiac load in real time. Chest excursion during mechanical ventilation does not reduce the quality of the acquired data.