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Sample records for oligomers impair long-term

  1. Alpha synuclein oligomers oppose long-term potentiation and impair memory through a calcineurin-dependent mechanism: relevance to human synucleopathic diseases

    PubMed Central

    Martin, Zane S.; Neugebauer, Volker; Dineley, Kelly T.; Kayed, Rakez; Zhang, Wenru; Reese, Lindsay C.; Taglialatela, Giulio

    2011-01-01

    Intracellular deposition of fibrillar aggregates of alpha synuclein (αSyn) characterizes neurodegenerative diseases such as Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). However, recent evidence indicates that small αSyn oligomeric aggregates that precede fibril formation may be the most neurotoxic species and can be found extracellularly. This new evidence has changed the view of pathological αSyn aggregation from a self-contained cellular phenomenon to an extracellular event and prompted investigation of the putative effects of extracellular αSyn oligomers. Here, we report that extracellular application of αSyn oligomers detrimentally impacts neuronal welfare and memory function. We found that oligomeric αSyn increased intracellular Ca2+ levels, induced calcineurin (CaN) activity, decreased cAMP response element binding protein (CREB) transcriptional activity and resulted in calcineurin-dependent death of human neuroblastoma cells. Similarily, CaN induction and CREB inhibition were observed when αSyn oligomers were applied to organotypic brain slices, which opposed hippocampal long-term potentiation (LTP). Furthermore, αSyn oligomers induced CaN, inhibited CREB and evoked memory impairments in mice that received acute intracerebroventricular injections. Notably, all these events were reversed by pharmacological inhibition of CaN. Moreover, we found decreased active calcineurin (CaN) and reduced levels of phosphorylated CREB in autopsy brain tissue from patients affected by DLB, which is characterized by deposition of αSyn aggregates and progressive cognitive decline. These results indicate that exogenously-applied αSyn oligomers impact neuronal function and produce memory deficits through mechanisms that involve CaN activation. PMID:22060133

  2. Long-Term Cognitive Impairment in Kleine-Levin Syndrome

    PubMed Central

    Uguccioni, Ginevra; Lavault, Sophie; Chaumereuil, Charlotte; Golmard, Jean-Louis; Gagnon, Jean-François; Arnulf, Isabelle

    2016-01-01

    Study Objectives: In Kleine-Levin syndrome (KLS), episodes of hypersomnia, cognitive, and behavioral disturbances alternate with asymptomatic periods. Because 50% of patients report decreased academic performances, we evaluated their cognitive status during asymptomatic periods, determinants of deficits, and changes during follow-up. Methods: The cognitive assessment during asymptomatic periods in all consecutive patients with typical KLS and healthy controls included the non-verbal intelligence quotient (Raven Progressive Matrices), the Trail Making Test, the Stroop Color-Word Test, the Wechsler Memory Test, verbal fluencies, the Free and Cued Learning Memory Test, and the Rey-Osterreith Complex Figure. Cognitive status was reevaluated after 0.5 to 2 y in 44 patients. Results: At baseline, compared with the 42 controls, the 122 patients with KLS exhibited lower non-verbal intelligence quotient, speed of processing, attention, and reduced retrieval strategies in episodic memory. Higher episode frequency, shorter episode duration, shorter time since last episode, deeper sleep, and megaphagia during episodes predicted impaired memory. The visuoconstructional abilities and non-verbal memory were intact. After a mean follow-up of 1.7 ± 1.0 y, the episode frequency decreased from 4.6 ± 4.8 to 1.7 ± 1.9/y. The logical reasoning and attention improved, the processing speed remained low, and the retrieval strategies in verbal memory further worsened. Conclusions: In this field study, one-third of patients with KLS have long-term cognitive deficits affecting retrieval and processing speed. Cognitive function should be systematically tested in patients with KLS, which appears important to help patients in their academic studies. Citation: Uguccioni G, Lavault S, Chaumereuil C, Golmard JL, Gagnon JF, Arnulf I. Long-term cognitive impairment in kleine-levin syndrome. SLEEP 2016;39(2):429–438. PMID:26414895

  3. 40 CFR 51.306 - Long-term strategy requirements for reasonably attributable visibility impairment.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... preventing future impairment. (b) The State must coordinate its long-term strategy for an area with existing... 40 Protection of Environment 2 2012-07-01 2012-07-01 false Long-term strategy requirements for... IMPLEMENTATION PLANS Protection of Visibility § 51.306 Long-term strategy requirements for...

  4. 40 CFR 51.306 - Long-term strategy requirements for reasonably attributable visibility impairment.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... preventing future impairment. (b) The State must coordinate its long-term strategy for an area with existing... 40 Protection of Environment 2 2014-07-01 2014-07-01 false Long-term strategy requirements for... IMPLEMENTATION PLANS Protection of Visibility § 51.306 Long-term strategy requirements for...

  5. Dopaminergic neurotransmission dysfunction induced by amyloid-β transforms cortical long-term potentiation into long-term depression and produces memory impairment.

    PubMed

    Moreno-Castilla, Perla; Rodriguez-Duran, Luis F; Guzman-Ramos, Kioko; Barcenas-Femat, Alejandro; Escobar, Martha L; Bermudez-Rattoni, Federico

    2016-05-01

    Alzheimer's disease (AD) is a neurodegenerative condition manifested by synaptic dysfunction and memory loss, but the mechanisms underlying synaptic failure are not entirely understood. Although dopamine is a key modulator of synaptic plasticity, dopaminergic neurotransmission dysfunction in AD has mostly been associated to noncognitive symptoms. Thus, we aimed to study the relationship between dopaminergic neurotransmission and synaptic plasticity in AD models. We used a transgenic model of AD (triple-transgenic mouse model of AD) and the administration of exogenous amyloid-β (Aβ) oligomers into wild type mice. We found that Aβ decreased cortical dopamine levels and converted in vivo long-term potentiation (LTP) into long-term depression (LTD) after high-frequency stimulation delivered at basolateral amygdaloid nucleus-insular cortex projection, which led to impaired recognition memory. Remarkably, increasing cortical dopamine and norepinephrine levels rescued both high-frequency stimulation -induced LTP and memory, whereas depletion of catecholaminergic levels mimicked the Aβ-induced shift from LTP to LTD. Our results suggest that Aβ-induced dopamine depletion is a core mechanism underlying the early synaptopathy and memory alterations observed in AD models and acts by modifying the threshold for the induction of cortical LTP and/or LTD. PMID:27103531

  6. Dopaminergic neurotransmission dysfunction induced by amyloid-β transforms cortical long-term potentiation into long-term depression and produces memory impairment.

    PubMed

    Moreno-Castilla, Perla; Rodriguez-Duran, Luis F; Guzman-Ramos, Kioko; Barcenas-Femat, Alejandro; Escobar, Martha L; Bermudez-Rattoni, Federico

    2016-05-01

    Alzheimer's disease (AD) is a neurodegenerative condition manifested by synaptic dysfunction and memory loss, but the mechanisms underlying synaptic failure are not entirely understood. Although dopamine is a key modulator of synaptic plasticity, dopaminergic neurotransmission dysfunction in AD has mostly been associated to noncognitive symptoms. Thus, we aimed to study the relationship between dopaminergic neurotransmission and synaptic plasticity in AD models. We used a transgenic model of AD (triple-transgenic mouse model of AD) and the administration of exogenous amyloid-β (Aβ) oligomers into wild type mice. We found that Aβ decreased cortical dopamine levels and converted in vivo long-term potentiation (LTP) into long-term depression (LTD) after high-frequency stimulation delivered at basolateral amygdaloid nucleus-insular cortex projection, which led to impaired recognition memory. Remarkably, increasing cortical dopamine and norepinephrine levels rescued both high-frequency stimulation -induced LTP and memory, whereas depletion of catecholaminergic levels mimicked the Aβ-induced shift from LTP to LTD. Our results suggest that Aβ-induced dopamine depletion is a core mechanism underlying the early synaptopathy and memory alterations observed in AD models and acts by modifying the threshold for the induction of cortical LTP and/or LTD.

  7. 40 CFR 51.306 - Long-term strategy requirements for reasonably attributable visibility impairment.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... every 3 years until the date of submission of the State's first plan addressing regional haze visibility... and regional haze visibility impairment, and the State must submit the first such coordinated long... first regional haze plan. In addition, the plan must provide for review of the long-term strategy as...

  8. Post-learning REM sleep deprivation impairs long-term memory: reversal by acute nicotine treatment.

    PubMed

    Aleisa, A M; Alzoubi, K H; Alkadhi, K A

    2011-07-15

    Rapid eye movement sleep deprivation (REM-SD) is associated with spatial learning and memory impairment. During REM-SD, an increase in nicotine consumption among habitual smokers and initiation of tobacco use by non-smokers have been reported. We have shown recently that nicotine treatment prevented learning and memory impairments associated with REM-SD. We now report the interactive effects of post-learning REM-SD and/or nicotine. The animals were first trained on the radial arm water maze (RAWM) task, then they were REM-sleep deprived using the modified multiple platform paradigm for 24h. During REM-SD period, the rats were injected with saline or nicotine (1mg/kg s.c. every 12h: a total of 3 injections). The animals were tested for long-term memory in the RAWM at the end of the REM-SD period. The 24h post-learning REM-SD significantly impaired long-term memory. However, nicotine treatment reversed the post-learning REM-SD-induced impairment of long-term memory. On the other hand, post-learning treatment of normal rats with nicotine for 24h enhanced long-term memory. These results indicate that post-learning acute nicotine treatment prevented the deleterious effect of REM-SD on cognitive abilities.

  9. Literacy Outcomes for Students with Speech Impairment: Long-Term Follow-Up

    ERIC Educational Resources Information Center

    Leitao, Suze; Fletcher, Janet

    2004-01-01

    Background: Theoretical and empirical support now exists for the finding that many children with expressive phonological impairment experience problems in acquiring phonological awareness and early literacy skills. Few studies, however, have examined the long-term academic and literacy outcomes for this population, in particular as the…

  10. Long-term reproductive impairment in a seabird after the Prestige oil spill.

    PubMed

    Barros, Alvaro; Alvarez, David; Velando, Alberto

    2014-01-01

    Large oil spills are dramatic perturbations on marine ecosystems, and seabirds are one of the worst affected organisms in such events. It has been argued that oil spills may have important long-term consequences on marine organisms, but supporting evidence remains scarce. The European shag (Phalacrocorax aristotelis) was strongly impacted at population level by the Prestige oil spill, the biggest spillage in the eastern North Atlantic. In this paper, we report on the long-term consequences on reproduction of this coastal seabird, using temporal and spatial replicated data (before-after-control-impact design). Our study revealed long-term reproductive impairment during at least the first 10 years since the Prestige oil spill. Annual reproductive success did not differ before the impact, but after the impact it was reduced by 45% in oiled colonies compared with unoiled ones. This is a rare documentation of long-term effects after a major oil spill, highlighting the need for long-term monitoring in order to assess the real impact of this type of disturbance on marine organisms.

  11. Long-term reproductive impairment in a seabird after the Prestige oil spill

    PubMed Central

    Barros, Álvaro; Álvarez, David; Velando, Alberto

    2014-01-01

    Large oil spills are dramatic perturbations on marine ecosystems, and seabirds are one of the worst affected organisms in such events. It has been argued that oil spills may have important long-term consequences on marine organisms, but supporting evidence remains scarce. The European shag (Phalacrocorax aristotelis) was strongly impacted at population level by the Prestige oil spill, the biggest spillage in the eastern North Atlantic. In this paper, we report on the long-term consequences on reproduction of this coastal seabird, using temporal and spatial replicated data (before–after–control–impact design). Our study revealed long-term reproductive impairment during at least the first 10 years since the Prestige oil spill. Annual reproductive success did not differ before the impact, but after the impact it was reduced by 45% in oiled colonies compared with unoiled ones. This is a rare documentation of long-term effects after a major oil spill, highlighting the need for long-term monitoring in order to assess the real impact of this type of disturbance on marine organisms. PMID:24789139

  12. [Alcohol impaired drivers after completion of a long-term model IVT-Hö rehabilitation].

    PubMed

    Höcher, G

    1994-07-01

    The "Individualpsychologische Verkehrstherapie (IVT-Hö)" is a psychotherapeutic long-term rehabilitation for alcohol impaired drivers. The therapy is mainly for the benefit of people for whom re-training (BASt model) is unsuitable because of their extreme alcohol problems. 3 years after having completed the treatment and after having been re-granted their driving licences, 3.6% of the drivers had a relapse.

  13. Tooth root growth impairment after mantle radiation in long-term survivors of Hodgkin's disease

    SciTech Connect

    McGinnis, J.P. Jr.; Hopkins, K.P.; Thompson, E.I.; Hustu, H.O.

    1985-10-01

    The tooth root growth impairment that resulted from 35 to 37 Gy mantle port radiation in 47 long-term survivors of childhood Hodgkin's disease was quantified and related to specific age groups and categories of teeth. Root measurements of the mandibular permanent canines, first and second premolars, and first and second molars were made from sequential panoramic radiographs taken at the time of radiation therapy and after the closure of root apexes. The severity of root growth impairment was greatest in patients who received radiation during the early stages of odontogenesis. With later stages of odontogenesis, and as the age increased at the time of treatment, less impairment occurred. The potential difficulties of using repeated panoramic radiographs to assess tooth lengths in longitudinal studies also were discussed.

  14. Social stress in male mice impairs long-term antiviral immunity selectively in wounded subjects.

    PubMed

    de Groot, Johanna; Boersma, Wim J A; Scholten, Jan Willem; Koolhaas, Jaap M

    2002-03-01

    An important property of the antiviral immune response is its time-dependent character. Beginning with a few antigen-specific cells upon infection, it evolves to a stage where there is an abundance of antigen-specific cells and antibodies that are needed to clear the pathogen, and ends with circulating antibodies and a population of virus-specific memory cells to protect the animal from reinfection. Short-term effects of stress on the immune system have been investigated extensively, showing that stress acutely changes many aspects of immunity. However, relatively little is known about the consequences of stress for the quality and quantity of long-term immunological memory. In the present study, we have investigated the effect of social stress, applied in mice at Days 1, 2 and 3 after inoculation with a herpes virus, on long-term antibody and memory cytokine responses to the virus. Male mice were subjected to three 5-min confrontations with an aggressive conspecific. Approximately half of the mice was wounded by bites of the aggressor during this stress procedure, and these mice were analyzed separately from nonwounded mice. It appeared that wounded mice showed suppressed protective antibody responses and impaired memory for virus-specific IL-4 and IL-10 production, whereas mice that were not wounded showed intact long-term immune responses and memory. It is concluded that the combination of wounds and the social stress of repeated confrontations is associated with impaired protective immunity as a consequence of suppressed antibody levels and impairment of some aspects of antiviral immunological memory. PMID:11897253

  15. Altered neural network supporting declarative long-term memory in mild cognitive impairment.

    PubMed

    Poettrich, Katrin; Weiss, Peter H; Werner, Annett; Lux, Silke; Donix, Markus; Gerber, Johannes; von Kummer, Rüdiger; Fink, Gereon R; Holthoff, Vjera A

    2009-02-01

    Autobiographical episodic memory represents a subsystem of declarative long-term memory and largely depends on combining information from multiple sources. The purpose of this study was to assess neural correlates of declarative long-term memory in patients with amnestic mild cognitive impairment (MCI) and controls using fMRI and a task requiring autobiographical and semantic memory retrieval. Comparison of the network supporting episodic autobiographical and semantic memory irrespective of remoteness (recent and remote) revealed significant activations in right parietal cortex and precuneus bilaterally in the patients. Autobiographical episodic versus semantic memory retrieval in the controls led to significant bilateral activations of the parietal-temporal junction, left temporal pole, anterior cingulate, retrosplenial cortex and cerebellum. In contrast, MCI patients activated left supplementary motor area, left premotor and superior temporal cortex. In MCI patients compared to controls a dysfunction of the retrosplenial cortex during memory retrieval was revealed by a lack of differential activation in relation to recency of memories and memory type. Our data suggest that MCI leads to a loss of specificity in the neural network supporting declarative long-term memory.

  16. Caffeine and diphenyl diselenide improve long-term memory impaired in middle-aged rats.

    PubMed

    Leite, Marlon R; Marcondes Sari, Marcel Henrique; de Freitas, Mayara L; Oliveira, Lia P; Dalmolin, Laíza; Brandão, Ricardo; Zeni, Gilson

    2014-05-01

    The aim of the present study was to evaluate the effects of diphenyl diselenide (PhSe)2 supplemented diet (10ppm) associated to the administration of caffeine (15mg/kg; i.g.) for 30days on the novel object recognition memory in middle-aged rats. The present findings showed that (PhSe)2-supplemented diet enhanced short-term memory, but not long-term memory, of middle-aged rats in the novel object recognition task. The (PhSe)2 supplemented diet associated with caffeine administration improved long-term memory, but did not alter short-term memory, impaired in middle-aged rats. Daily caffeine administration to middle-aged rats had no effect on the memory tasks. Diet supplemented with (PhSe)2 plus caffeine administration increased the number of crossings and rearings reduced in middle-aged rats. Caffeine administration plus (PhSe)2 diets were effective in increasing the number of rearings and crossings, respectively, in middle-aged rats, [(3)H] glutamate uptake was reduced in hippocampal slices of rats from (PhSe)2 and caffeine plus (PhSe)2 groups. In addition, animals supplemented with (PhSe)2 showed an increase in the pCREB/CREB ratio whereas pAkt/Akt ratio was not modified. These results suggest that the effects of (PhSe)2 on the short-term memory may be related to its ability to decrease the uptake of glutamate, influencing the increase of CREB phosphorylation. (PhSe)2-supplemented diet associated to the administration of caffeine improved long-term memory impaired in middle-aged rats, an effect independent of CREB and Akt phosphorylation.

  17. Long-term exposure to microgravity impairs vestibulo-cardiovascular reflex.

    PubMed

    Morita, Hironobu; Abe, Chikara; Tanaka, Kunihiko

    2016-01-01

    The vestibular system is known to have an important role in controlling blood pressure upon posture transition (vestibulo-cardiovascular reflex, VCR). However, under a different gravitational environment, the sensitivity of the vestibular system may be altered. Thus, the VCR may become less sensitive after spaceflight because of orthostatic intolerance potentially induced by long-term exposure to microgravity. To test this hypothesis in humans, we investigated the ability of the VCR to maintain blood pressure upon head-up tilt before and after a 4-6 months stay on the International Space Station. To detect the functional state of the VCR, galvanic vestibular stimulation (GVS) was applied. As GVS transiently interrupts the vestibular-mediated pressor response, impaired VCR is detected when the head-up tilt-induced blood pressure response does not depend on GVS. During the first 20 s of head-up tilt, a transient blood pressure increase (11.9 ± 1.6 mmHg) was observed at pre-spaceflight but not at 1-4 days after return from spaceflight. The magnitude of VCR recovered to the pre-spaceflight levels within 2 months after return. These results indicate that long-term exposure to microgravity induces VCR impairment, which may be involved in a mechanism of spaceflight-induced orthostatic intolerance. PMID:27634181

  18. Long-term exposure to microgravity impairs vestibulo-cardiovascular reflex

    PubMed Central

    Morita, Hironobu; Abe, Chikara; Tanaka, Kunihiko

    2016-01-01

    The vestibular system is known to have an important role in controlling blood pressure upon posture transition (vestibulo-cardiovascular reflex, VCR). However, under a different gravitational environment, the sensitivity of the vestibular system may be altered. Thus, the VCR may become less sensitive after spaceflight because of orthostatic intolerance potentially induced by long-term exposure to microgravity. To test this hypothesis in humans, we investigated the ability of the VCR to maintain blood pressure upon head-up tilt before and after a 4–6 months stay on the International Space Station. To detect the functional state of the VCR, galvanic vestibular stimulation (GVS) was applied. As GVS transiently interrupts the vestibular-mediated pressor response, impaired VCR is detected when the head-up tilt-induced blood pressure response does not depend on GVS. During the first 20 s of head-up tilt, a transient blood pressure increase (11.9 ± 1.6 mmHg) was observed at pre-spaceflight but not at 1–4 days after return from spaceflight. The magnitude of VCR recovered to the pre-spaceflight levels within 2 months after return. These results indicate that long-term exposure to microgravity induces VCR impairment, which may be involved in a mechanism of spaceflight-induced orthostatic intolerance. PMID:27634181

  19. Involvement of Microglia Activation in the Lead Induced Long-Term Potentiation Impairment

    PubMed Central

    Wang, Wen; Shen, Xue-Feng; Che, Hong-Lei; Guo, Yan-Yan; Zhao, Ming-Gao; Chen, Jing-Yuan; Luo, Wen-Jing

    2012-01-01

    Exposure of Lead (Pb), a known neurotoxicant, can impair spatial learning and memory probably via impairing the hippocampal long-term potentiation (LTP) as well as hippocampal neuronal injury. Activation of hippocampal microglia also impairs spatial learning and memory. Thus, we raised the hypothesis that activation of microglia is involved in the Pb exposure induced hippocampal LTP impairment and neuronal injury. To test this hypothesis and clarify its underlying mechanisms, we investigated the Pb-exposure on the microglia activation, cytokine release, hippocampal LTP level as well as neuronal injury in in vivo or in vitro model. The changes of these parameters were also observed after pretreatment with minocycline, a microglia activation inhibitor. Long-term low dose Pb exposure (100 ppm for 8 weeks) caused significant reduction of LTP in acute slice preparations, meanwhile, such treatment also significantly increased hippocampal microglia activation as well as neuronal injury. In vitro Pb-exposure also induced significantly increase of microglia activation, up-regulate the release of cytokines including tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β) and inducible nitric oxide synthase (iNOS) in microglia culture alone as well as neuronal injury in the co-culture with hippocampal neurons. Inhibiting the microglia activation with minocycline significantly reversed the above-mentioned Pb-exposure induced changes. Our results showed that Pb can cause microglia activation, which can up-regulate the level of IL-1β, TNF-α and iNOS, these proinflammatory factors may cause hippocampal neuronal injury as well as LTP deficits. PMID:22952811

  20. Long-term Biological Monitoring of an Impaired Stream: Synthesis and Environmental Management Implications

    SciTech Connect

    Peterson, Mark J; Efroymson, Rebecca Ann; Adams, Marshall

    2011-01-01

    The long-term ecological recovery of an impaired stream in response to an industrial facility's pollution abatement actions and the implications of the biological monitoring effort to environmental management is the subject of this special issue of Environmental Management. This final article focuses on the synthesis of the biological monitoring program's components and methods, the efficacy of various biological monitoring techniques to environmental management, and the lessons learned from the program that might be applicable to the design and application of other programs. The focus of the 25-year program has been on East Fork Poplar Creek, an ecologically impaired stream in Oak Ridge, Tennessee with varied and complex stressors from a Department of Energy facility in its headwaters. Major components of the long-term program included testing and monitoring of invertebrate and fish toxicity, bioindicators of fish health, fish contaminant accumulation, and instream communities (including periphyton, benthic macroinvertebrate, and fish). Key parallel components of the program include water chemistry sampling and data management. Multiple lines of evidence suggested positive ecological responses during three major pollution abatement periods. Based on this case study and the related literature, effective environmental management of impaired streams starts with program design that is consistent across space and time, but also adaptable to changing conditions. The biological monitoring approaches used for the program provided a strong basis for assessments of recovery from remedial actions, and the likely causes of impairment. This case study provides a unique application of multidisciplinary and quantitative techniques to address multiple and complex regulatory and programmatic goals, environmental stressors, and remedial actions.

  1. Long-Term Biological Monitoring of an Impaired Stream: Implications for Environmental Management [Special Issue

    SciTech Connect

    Adams, Marshall; Brandt, Craig C; Christensen, Sigurd W; Efroymson, Rebecca Ann; Greeley Jr, Mark Stephen; Ham, Kenneth; Kszos, Lynn A; Loar, James M; McCracken, Kitty; Morris, Gail Wright; Peterson, Mark J; Ryon, Michael G; Smith, John G; Southworth, George R; Stewart, Arthur J

    2011-01-01

    The long-term ecological recovery of an impaired stream in response to an industrial facility's pollution abatement actions and the implications of the biological monitoring effort to environmental management is the subject of this special issue of Environmental Management. This final article focuses on the synthesis of the biological monitoring program's components and methods, the efficacy of various biological monitoring techniques to environmental management, and the lessons learned from the program that might be applicable to the design and application of other programs. The focus of the 25-year program has been on East Fork Poplar Creek, an ecologically impaired stream in Oak Ridge, Tennessee with varied and complex stressors from a Department of Energy facility in its headwaters. Major components of the long-term program included testing and monitoring of invertebrate and fish toxicity, bioindicators of fish health, fish contaminant accumulation, and instream communities (including periphyton, benthic macroinvertebrate, and fish). Key parallel components of the program include water chemistry sampling and data management. Multiple lines of evidence suggested positive ecological responses during three major pollution abatement periods. Based on this case study and the related literature, effective environmental management of impaired streams starts with program design that is consistent across space and time, but also adaptable to changing conditions. The biological monitoring approaches used for the program provided a strong basis for assessments of recovery from remedial actions, and the likely causes of impairment. This case study provides a unique application of multidisciplinary and quantitative techniques to address multiple and complex regulatory and programmatic goals, environmental stressors, and remedial actions.

  2. Compartmentalized PDE4A5 Signaling Impairs Hippocampal Synaptic Plasticity and Long-Term Memory

    PubMed Central

    Park, Alan J.; Tolentino, Rosa E.; Bruinenberg, Vibeke M.; Tudor, Jennifer C.; Lee, Yool; Hansen, Rolf T.; Guercio, Leonardo A.; Linton, Edward; Neves-Zaph, Susana R.; Meerlo, Peter; Baillie, George S.; Houslay, Miles D.

    2016-01-01

    Alterations in cAMP signaling are thought to contribute to neurocognitive and neuropsychiatric disorders. Members of the cAMP-specific phosphodiesterase 4 (PDE4) family, which contains >25 different isoforms, play a key role in determining spatial cAMP degradation so as to orchestrate compartmentalized cAMP signaling in cells. Each isoform binds to a different set of protein complexes through its unique N-terminal domain, thereby leading to targeted degradation of cAMP in specific intracellular compartments. However, the functional role of specific compartmentalized PDE4 isoforms has not been examined in vivo. Here, we show that increasing protein levels of the PDE4A5 isoform in mouse hippocampal excitatory neurons impairs a long-lasting form of hippocampal synaptic plasticity and attenuates hippocampus-dependent long-term memories without affecting anxiety. In contrast, viral expression of a truncated version of PDE4A5, which lacks the unique N-terminal targeting domain, does not affect long-term memory. Further, overexpression of the PDE4A1 isoform, which targets a different subset of signalosomes, leaves memory undisturbed. Fluorescence resonance energy transfer sensor-based cAMP measurements reveal that the full-length PDE4A5, in contrast to the truncated form, hampers forskolin-mediated increases in neuronal cAMP levels. Our study indicates that the unique N-terminal localization domain of PDE4A5 is essential for the targeting of specific cAMP-dependent signaling underlying synaptic plasticity and memory. The development of compounds to disrupt the compartmentalization of individual PDE4 isoforms by targeting their unique N-terminal domains may provide a fruitful approach to prevent cognitive deficits in neuropsychiatric and neurocognitive disorders that are associated with alterations in cAMP signaling. SIGNIFICANCE STATEMENT Neurons exhibit localized signaling processes that enable biochemical cascades to be activated selectively in specific subcellular

  3. Cerebral Malaria in Children Is Associated With Long-term Cognitive Impairment

    PubMed Central

    John, Chandy C.; Bangirana, Paul; Byarugaba, Justus; Opoka, Robert O.; Idro, Richard; Jurek, Anne M.; Wu, Baolin; Boivin, Michael J.

    2008-01-01

    OBJECTIVE Cerebral malaria affects >785 000 African children every year. We previously documented an increased frequency of cognitive impairment in children with cerebral malaria 6 months after their initial malaria episode. This study was conducted to determine the long-term effects of cerebral malaria on the cognitive function of these children. METHODS Children who were 5 to 12 years of age and presented to Mulago Hospital, Kampala, Uganda, with cerebral malaria (n = 44) or uncomplicated malaria (n = 54), along with healthy, asymptomatic community children (n = 89), were enrolled in a prospective cohort study of cognition. Cognitive testing was performed at enrollment and 2 years later. The primary outcome was presence of a deficit in ≥1 of 3 cognitive areas tested. RESULTS At 2-year follow-up testing, 26.3% of children with cerebral malaria and 12.5% with uncomplicated malaria had cognitive deficits in ≥1 area, as compared with 7.6% of community children. Deficits in children with cerebral malaria were primarily in the area of attention (cerebral malaria, 18.4%, vs community children, 2.5%). After adjustment for age, gender, nutrition, home environment, and school level, children with cerebral malaria had a 3.67-fold increased risk for a cognitive deficit compared with community children. Cognitive impairment at 2-year follow-up was associated with hyporeflexia on admission and neurologic deficits 3 months after discharge. CONCLUSIONS Cerebral malaria is associated with long-term cognitive impairments in 1 of 4 child survivors. Future studies should investigate the mechanisms involved so as to develop interventions aimed at prevention and rehabilitation. PMID:18541616

  4. Chronic dietary chlorpyrifos causes long-term spatial memory impairment and thigmotaxic behavior.

    PubMed

    López-Granero, Caridad; Ruiz-Muñoz, Ana M; Nieto-Escámez, Francisco A; Colomina, María T; Aschner, Michael; Sánchez-Santed, Fernando

    2016-03-01

    Little is known about the long-term effects of chronic exposure to low-level organophosphate (OP) pesticides, and the role of neurotransmitter systems, other than the cholinergic system, in mediating OP neurotoxicity. In this study, rats were administered 5mg/kg/day of chlorpyrifos (CPF) for 6 months commencing at 3-months-of-age. The animals were examined 7 months later (at 16-months-of-age) for spatial learning and memory in the Morris water maze (MWM) and locomotor activity. In addition, we assessed the chronic effects of CPF on glutamatergic and gamma-aminobutyric acid (GABAergic) function using pharmacological challenges with dizocilpine (MK801) and diazepam. Impaired performance related to altered search patterns, including thigmotaxis and long-term spatial memory was noted in the MWM in animals exposed to CPF, pointing to dietary CPF-induced behavioral disturbances, such as anxiety. Twenty-four hours after the 31st session of repeated acquisition task, 0.1mg/kg MK801, an N-methyl-d-aspartate (NMDA) antagonist was intraperitoneally (i.p.) injected for 4 consecutive days. Decreased latencies in the MWM in the control group were noted after two sessions with MK801 treatment. Once the MWM assessment was completed, animals were administered 0.1 or 0.2mg/kg of MK801 and 1 or 3mg/kg of diazepam i.p., and tested for locomotor activity. Both groups, the CPF dietary and control, displayed analogous performance in motor activity. In conclusion, our data point to a connection between the long-term spatial memory, thigmotaxic response and CPF long after the exposure ended.

  5. Relationship between cognitive impairment and nutritional assessment on functional status in Calabrian long-term-care

    PubMed Central

    Malara, Alba; Sgrò, Giovanni; Caruso, Chiara; Ceravolo, Francesco; Curinga, Giuseppe; Renda, Grazia Francesca; Spadea, Fausto; Garo, Michele; Rispoli, Vincenzo

    2014-01-01

    Objective The interaction between dementia and nutritional state is very complex and not yet fully understood. The aim of the present study was to assess the interaction between cognitive impairment and nutritional state in a cohort of residential elderly in relationship with functional condition of patients and their load of assistance in long-term-care facilities of the National Association of Third Age Structures (ANASTE) Calabria. Methods One hundred seventy-four subjects (122 female and 52 male) were admitted to the long-term-care ANASTE Calabria study. All patients underwent multidimensional geriatric assessment. Nutritional state was assessed with the Mini Nutritional Assessment (MNA), whereas cognitive performance was evaluated by the Mini-Mental State Examination (MMSE). The functional state was assessed by Barthel Index (BI) and Activity Daily Living (ADL). The following nutritional biochemical parameters were also evaluated: albumin, cholesterol, iron, and hemoglobin. All patients were reassessed 180 days later. Results A severe cognitive impairment in MMSE performance was displayed in 49.7% patients, while 39.8% showed a moderate deficit; 6.9% had a slight deficit; and 3.4% evidenced no cognitive impairment. In MNA, 30% of patients exhibited an impairment of nutritional state; 56% were at risk of malnutrition; and 14% showed no nutritional problems. Malnutrition was present in 42% of patients with severe cognitive impairment, but only 4% of malnourished patients showed moderate cognitive deficit. The statistical analysis displayed a significant correlation between MNA and MMSE (P<0.001), as did MMSE correlated with Activity Daily Living (P<0.001) and BI (P<0.05). MNA correlated with BI (P<0.001) and albumin (P<0.001). The follow-up showed a strong correlation between cognitive deterioration and worsening of nutritional state (P<0.005) as well as with the functional state (P<0.05) and mortality (P<0.01). Conclusion The present study clearly shows that

  6. Impaired long-term potentiation-like cortical plasticity in presymptomatic genetic frontotemporal dementia.

    PubMed

    Benussi, Alberto; Cosseddu, Maura; Filareto, Ilaria; Dell'Era, Valentina; Archetti, Silvana; Sofia Cotelli, Maria; Micheli, Anna; Padovani, Alessandro; Borroni, Barbara

    2016-09-01

    Neurophysiological biomarkers were assessed using a transcranial magnetic stimulation multiparadigm approach in 13 presymptomatic (n = 13 Granulin) and 14 symptomatic (n = 11 Granulin, n = 3 C9orf72) subjects with a pathogenic mutation for frontotemporal dementia (FTD). Intracortical facilitation and long-term potentiation-like plasticity were impaired in presymptomatic carriers, compared to healthy controls, more than 15 years before expected symptom onset. In symptomatic carriers, a decrease in short-interval intracortical inhibition, compared to presymptomatic carriers, was found. In conclusion, these biomarkers could provide the footprints of specific physiopathological processes in the development of this disease and possibly support the diagnosis of autosomal-dominant FTD. Ann Neurol 2016;80:472-476. PMID:27438089

  7. Antidepressants that inhibit both serotonin and norepinephrine reuptake impair long-term potentiation in hippocampus

    PubMed Central

    Cooke, Jennifer D.; Cavender, Hannah M.; Lima, Hope K.; Grover, Lawrence M.

    2014-01-01

    Rationale Monoamine reuptake inhibitors can stimulate expression of brain-derived neurotrophic factor (BDNF) and alter long-term potentiation (LTP), a widely used model for the synaptic mechanisms that underlie memory formation. BDNF expression is up-regulated during LTP, and BDNF in turn positively modulates LTP. Previously, we found that treatment with venlafaxine, a serotonin and norepinephrine reuptake inhibitor (SNRI), but not citalopram, a selective serotonin reuptake inhibitor (SSRI) reduced LTP in hippocampal area CA1 without changing hippocampal BDNF protein expression. Objectives We tested the hypothesis that combined serotonin and norepinephrine reuptake inhibition is necessary for LTP impairment, and we reexamined the potential role of BNDF by testing for region-specific changes in areas CA1, CA3 and dentate gyrus. We also tested whether early events in the LTP signaling pathway were altered to impair LTP. Methods Animals were treated for 21 days with venlafaxine, imipramine, fluoxetine, or maprotiline. In vitro hippocampal slices were used for electrophysiological measurements. Protein expression was measured by enzyme-linked immunosorbent assay (ELISA) and western blotting. Results LTP was impaired only following treatment with combined serotonin and norepinephrine reuptake inhibitors (venlafaxine, imipramine) but not with selective serotonin (fluoxetine) or norepinephrine (maprotiline) reuptake inhibitors. BDNF protein expression was not altered by venlafaxine or imipramine treatment, nor were postsynaptic depolarization during LTP inducing stimulation or synaptic membrane NMDA receptor subunit expression affected. Conclusions LTP is impaired by chronic treatment with antidepressant that inhibit both serotonin and norepinephrine reuptake; this impairment results from changes that are downstream of postsynaptic depolarization and calcium-influx. PMID:24781518

  8. Extracellular Tau Oligomers Produce An Immediate Impairment of LTP and Memory

    PubMed Central

    Fá, M.; Puzzo, D.; Piacentini, R.; Staniszewski, A.; Zhang, H.; Baltrons, M. A.; Li Puma, D. D.; Chatterjee, I.; Li, J.; Saeed, F.; Berman, H. L.; Ripoli, C.; Gulisano, W.; Gonzalez, J.; Tian, H.; Costa, J. A.; Lopez, P.; Davidowitz, E.; Yu, W. H.; Haroutunian, V.; Brown, L. M.; Palmeri, A.; Sigurdsson, E. M.; Duff, K. E.; Teich, A. F.; Honig, L. S.; Sierks, M.; Moe, J. G.; D’Adamio, L.; Grassi, C.; Kanaan, N. M.; Fraser, P. E.; Arancio, O.

    2016-01-01

    Non-fibrillar soluble oligomeric forms of amyloid-β peptide (oAβ) and tau proteins are likely to play a major role in Alzheimer’s disease (AD). The prevailing hypothesis on the disease etiopathogenesis is that oAβ initiates tau pathology that slowly spreads throughout the medial temporal cortex and neocortices independently of Aβ, eventually leading to memory loss. Here we show that a brief exposure to extracellular recombinant human tau oligomers (oTau), but not monomers, produces an impairment of long-term potentiation (LTP) and memory, independent of the presence of high oAβ levels. The impairment is immediate as it raises as soon as 20 min after exposure to the oligomers. These effects are reproduced either by oTau extracted from AD human specimens, or naturally produced in mice overexpressing human tau. Finally, we found that oTau could also act in combination with oAβ to produce these effects, as sub-toxic doses of the two peptides combined lead to LTP and memory impairment. These findings provide a novel view of the effects of tau and Aβ on memory loss, offering new therapeutic opportunities in the therapy of AD and other neurodegenerative diseases associated with Aβ and tau pathology. PMID:26786552

  9. Extracellular Tau Oligomers Produce An Immediate Impairment of LTP and Memory.

    PubMed

    Fá, M; Puzzo, D; Piacentini, R; Staniszewski, A; Zhang, H; Baltrons, M A; Li Puma, D D; Chatterjee, I; Li, J; Saeed, F; Berman, H L; Ripoli, C; Gulisano, W; Gonzalez, J; Tian, H; Costa, J A; Lopez, P; Davidowitz, E; Yu, W H; Haroutunian, V; Brown, L M; Palmeri, A; Sigurdsson, E M; Duff, K E; Teich, A F; Honig, L S; Sierks, M; Moe, J G; D'Adamio, L; Grassi, C; Kanaan, N M; Fraser, P E; Arancio, O

    2016-01-20

    Non-fibrillar soluble oligomeric forms of amyloid-β peptide (oAβ) and tau proteins are likely to play a major role in Alzheimer's disease (AD). The prevailing hypothesis on the disease etiopathogenesis is that oAβ initiates tau pathology that slowly spreads throughout the medial temporal cortex and neocortices independently of Aβ, eventually leading to memory loss. Here we show that a brief exposure to extracellular recombinant human tau oligomers (oTau), but not monomers, produces an impairment of long-term potentiation (LTP) and memory, independent of the presence of high oAβ levels. The impairment is immediate as it raises as soon as 20 min after exposure to the oligomers. These effects are reproduced either by oTau extracted from AD human specimens, or naturally produced in mice overexpressing human tau. Finally, we found that oTau could also act in combination with oAβ to produce these effects, as sub-toxic doses of the two peptides combined lead to LTP and memory impairment. These findings provide a novel view of the effects of tau and Aβ on memory loss, offering new therapeutic opportunities in the therapy of AD and other neurodegenerative diseases associated with Aβ and tau pathology.

  10. Extracellular Tau Oligomers Produce An Immediate Impairment of LTP and Memory.

    PubMed

    Fá, M; Puzzo, D; Piacentini, R; Staniszewski, A; Zhang, H; Baltrons, M A; Li Puma, D D; Chatterjee, I; Li, J; Saeed, F; Berman, H L; Ripoli, C; Gulisano, W; Gonzalez, J; Tian, H; Costa, J A; Lopez, P; Davidowitz, E; Yu, W H; Haroutunian, V; Brown, L M; Palmeri, A; Sigurdsson, E M; Duff, K E; Teich, A F; Honig, L S; Sierks, M; Moe, J G; D'Adamio, L; Grassi, C; Kanaan, N M; Fraser, P E; Arancio, O

    2016-01-01

    Non-fibrillar soluble oligomeric forms of amyloid-β peptide (oAβ) and tau proteins are likely to play a major role in Alzheimer's disease (AD). The prevailing hypothesis on the disease etiopathogenesis is that oAβ initiates tau pathology that slowly spreads throughout the medial temporal cortex and neocortices independently of Aβ, eventually leading to memory loss. Here we show that a brief exposure to extracellular recombinant human tau oligomers (oTau), but not monomers, produces an impairment of long-term potentiation (LTP) and memory, independent of the presence of high oAβ levels. The impairment is immediate as it raises as soon as 20 min after exposure to the oligomers. These effects are reproduced either by oTau extracted from AD human specimens, or naturally produced in mice overexpressing human tau. Finally, we found that oTau could also act in combination with oAβ to produce these effects, as sub-toxic doses of the two peptides combined lead to LTP and memory impairment. These findings provide a novel view of the effects of tau and Aβ on memory loss, offering new therapeutic opportunities in the therapy of AD and other neurodegenerative diseases associated with Aβ and tau pathology. PMID:26786552

  11. Serious renal impairment is associated with long-term parenteral nutrition.

    PubMed

    Buchman, A L; Moukarzel, A; Ament, M E; Gornbein, J; Goodson, B; Carlson, C; Hawkins, R A

    1993-01-01

    Thirty-three current long-term total parenteral nutrition (TPN) patients (13 men, 20 women) aged 21 to 79 years were prospectively studied to evaluate their change in glomerular filtration rate since beginning TPN. Creatinine clearance (CrCl) from the subject's initial home TPN clinic visit and at present were estimated from standard formulas and compared. The CrCl in 12 patients who had received home TPN for > 10 years was estimated retrospectively on a yearly basis. The estimated CrCl as an accurate measure of glomerular filtration rate was confirmed by measuring plasma indium-111 diethylenetriamine pentaacetic acid clearance. The mean daily intravenous protein intake and days during which nephrotoxic medications were used and number of bacteremic/fungemic episodes were determined for each subject. CrCl declined by 3.5 +/- 6.3% per year (p = .004). Twenty-nine of 33 patients had decreases of 0.6% to 15.4% per year. Tubular function, as determined by the tubular reabsorption of phosphate, was impaired in 52% of the subjects. The intravenous protein load averaged 1.28 +/- 0.32 g/kg per day, nephrotoxic drug use averaged 3.4 +/- 4.0% of all days on home TPN, and each patient averaged 2.3 episodes of bacteremia or fungemia since home TPN was started (0.5 +/- 0.5 episodes per year). When all factors were assessed simultaneously, nephrotoxic drug use, episodes of bacteremia/fungemia, and age accounted for approximately 46% of the variability in CrCl. When bacteremia/fungemia was expressed as a yearly rate, nephrotoxic drug use assumed no role in the glomerular filtration rate determination; infection rate and age alone accounted for 53% of the CrCl variability. We describe a profound decrease in renal function associated with long-term TPN, most of which is largely unexplained.

  12. Cannabinoids decrease excitatory synaptic transmission and impair long-term depression in rat cerebellar Purkinje cells.

    PubMed

    Lévénés, C; Daniel, H; Soubrié, P; Crépel, F

    1998-08-01

    1. CB-1 cannabinoid receptors are strongly expressed in the molecular layer of the cerebellar cortex. We have analysed, in patch-clamped Purkinje cells (PCs) in rat cerebellar slices, the effect of the selective CB-1 agonists WIN55,212-2 and CP55,940 and of the selective CB-1 antagonist SR141716-A on excitatory synaptic transmission and synaptic plasticity. 2. Bath application of both agonists markedly depressed parallel fibre (PF) EPSCs. This effect was reversed by SR141716-A. In contrast, responses of PCs to ionophoretic application of glutamate were not affected by WIN55, 212-2. 3. The coefficient of variation and the paired-pulse facilitation of these PF-mediated EPSCs increased in the presence of WIN55,212-2. 4. WIN55,212-2 decreased the frequency of miniature EPSCs and of asynchronous synaptic events evoked in the presence of strontium in the bath, but did not affect their amplitude. 5. WIN55, 212-2 did not change the excitability of PFs. 6. WIN55,212-2 impaired long-term depression induced by pairing protocols in PCs. This effect was antagonized by SR141716-A. The same impairment of LTD was produced by 2-chloroadenosine, a compound that decreases the probability of release of glutamate at PF-PC synapses. 7. The present study demonstrates that cannabinoids inhibit synaptic transmission at PF-PC synapses by decreasing the probability of release of glutamate, and thereby impair LTD. These two effects might represent a plausible cellular mechanism underlying cerebellar dysfunction caused by cannabinoids.

  13. Early Impairment of Long-Term Depression in the Perirhinal Cortex of a Mouse Model of Alzheimer's Disease

    PubMed Central

    Tamagnini, Francesco; Burattini, Costanza; Casoli, Tiziana; Balietti, Marta; Fattoretti, Patrizia

    2012-01-01

    Abstract Visual recognition memory is early impaired in Alzheimer's disease. Long-term depression of synaptic transmission in the perirhinal cortex is critically involved in this form of memory. We found that synaptic transmission was impaired in perirhinal cortex slices obtained from 3-month-old Tg2576 mice, and that 3,000 pulses at 5 Hz induced long-term depression in perirhinal cortex slices from age-matched control mice, but not in those from Tg2576 mice. To our knowledge, these data provide the first evidence of synaptic transmission and long-term depression impairment in the perirhinal cortex in an animal model of Alzheimer's disease, and the earliest synaptic deficit in Tg2576 mice. PMID:22533438

  14. Subregion-Specific p300 Conditional Knock-Out Mice Exhibit Long-Term Memory Impairments

    ERIC Educational Resources Information Center

    Oliveira, Ana M. M.; Estevez, Marcel A.; Hawk, Joshua D.; Grimes, Shannon; Brindle, Paul K.; Abel, Ted

    2011-01-01

    Histone acetylation plays a critical role during long-term memory formation. Several studies have demonstrated that the histone acetyltransferase (HAT) CBP is required during long-term memory formation, but the involvement of other HAT proteins has not been extensively investigated. The HATs CBP and p300 have at least 400 described interacting…

  15. Impaired long-term habituation is dissociated from increased locomotor activity after sensorimotor cortex compression.

    PubMed

    Moreira, Tiago; Cebers, Gvido; Salehi, Mehdi; Wägner, Anna; Liljequist, Sture

    2006-02-15

    Behavioural habituation to a novel environment is a simple form of learning in rodents. We studied the habituation and locomotor activity (LMA) of Wistar rats subjected to unilateral, transient (30min) extradural compression (EC) of the right sensorimotor cortex. One group of rats was tested every 24h during the first 5 days (D1-D5) post-EC. Two other groups were tested for the first time in the LMA boxes on D3 and D6 post-EC and their performance was compared with the group tested on D1 (activity in a novel environment). Total and center locomotion, vertical activity and time spent in the center of the LMA box were reduced on D1 post-EC and normalized by D2. The EC-induced motor paresis was undetectable on the rotarod by D2 and on the beam-walking by D3. Total locomotion, vertical activity and time spent in the center of EC-rats significantly increased from D1 to D3. EC caused neurodegeneration in the cortex, caudate putamen and thalamus as detected by Fluoro-Jade staining. The size of the cortical damage decreased from D2 to D5 in the medial and caudal regions of the compressed hemisphere, in accordance with recovery of motor function. LMA provided additional information in the follow-up of recovery from brain injury and habituation to the environment. Thus, long-term, inter-session habituation was impaired from D1 to D3 but dissociated from increased LMA intra-session on D3, when the motor deficits provoked by EC were already undetectable in the rotarod and beam-walking tests. PMID:16337698

  16. Cognitive flexibility and long-term depression (LTD) are impaired following β-catenin stabilization in vivo.

    PubMed

    Mills, Fergil; Bartlett, Thomas E; Dissing-Olesen, Lasse; Wisniewska, Marta B; Kuznicki, Jacek; Macvicar, Brian A; Wang, Yu Tian; Bamji, Shernaz X

    2014-06-10

    The cadherin/β-catenin adhesion complex is a key mediator of the bidirectional changes in synapse strength which are believed to underlie complex learning and memory. In the present study, we demonstrate that stabilization of β-catenin in the hippocampus of adult mice results in significant impairments in cognitive flexibility and spatial reversal learning, including impaired extinction during the reversal phase of the Morris water maze and deficits in a delayed nonmatch to place T-maze task. In accordance with these deficits, β-catenin stabilization was found to abolish long-term depression by stabilizing cadherin at the synaptic membrane and impairing AMPA receptor endocytosis, while leaving basal synaptic transmission and long-term potentiation unaffected. These results demonstrate that the β-catenin/cadherin adhesion complex plays an important role in learning and memory and that aberrant increases in synaptic adhesion can have deleterious effects on cognitive function.

  17. The compensatory effect of regular exercise on long-term memory impairment in sleep deprived female rats.

    PubMed

    Salari, Maryam; Sheibani, Vahid; Saadati, Hakimeh; Pourrahimi, Alimohammad; khaksarihadad, Mohammad; Esmaeelpour, Khadijeh; Khodamoradi, Mehdi

    2015-10-01

    Previous studies have been shown that exercise can improve short-term spatial learning, memory and synaptic plasticity impairments in sleep deprived female rats. The aim of the present study was to investigate the effects of treadmill exercise on sleep deprivation (SD) induced impairment in hippocampal dependent long-term memory in female rats. Intact and ovariectomized female rats were used in the current study. Exercise protocol was 4 weeks treadmill running. Twenty four hour SD was induced by using multiple platform apparatus after learning phase. Spatial learning and long-term memory was examined by using the Morris Water Maze (MWM) test. Our results indicated that sleep deprivation impaired long term memory in the intact and ovariectomized female rats, regardless of reproductive status (p<0.05) and treadmill exercise compensated this impairment (p<0.05). In conclusion the results of the current study confirmed the negative effect of SD on cognitive functions and regular exercise seems to protect rats from these factors, however more investigations need to be done.

  18. The compensatory effect of regular exercise on long-term memory impairment in sleep deprived female rats.

    PubMed

    Salari, Maryam; Sheibani, Vahid; Saadati, Hakimeh; Pourrahimi, Alimohammad; khaksarihadad, Mohammad; Esmaeelpour, Khadijeh; Khodamoradi, Mehdi

    2015-10-01

    Previous studies have been shown that exercise can improve short-term spatial learning, memory and synaptic plasticity impairments in sleep deprived female rats. The aim of the present study was to investigate the effects of treadmill exercise on sleep deprivation (SD) induced impairment in hippocampal dependent long-term memory in female rats. Intact and ovariectomized female rats were used in the current study. Exercise protocol was 4 weeks treadmill running. Twenty four hour SD was induced by using multiple platform apparatus after learning phase. Spatial learning and long-term memory was examined by using the Morris Water Maze (MWM) test. Our results indicated that sleep deprivation impaired long term memory in the intact and ovariectomized female rats, regardless of reproductive status (p<0.05) and treadmill exercise compensated this impairment (p<0.05). In conclusion the results of the current study confirmed the negative effect of SD on cognitive functions and regular exercise seems to protect rats from these factors, however more investigations need to be done. PMID:26190016

  19. Intrahippocampal Glutamine Administration Inhibits mTORC1 Signaling and Impairs Long-Term Memory

    ERIC Educational Resources Information Center

    Rozas, Natalia S.; Redell, John B.; Pita-Almenar, Juan D.; McKenna, James, III.; Moore, Anthony N.; Gambello, Michael J.; Dash, Pramod K.

    2015-01-01

    The mechanistic Target of Rapamycin Complex 1 (mTORC1), a key regulator of protein synthesis and cellular growth, is also required for long-term memory formation. Stimulation of mTORC1 signaling is known to be dependent on the availability of energy and growth factors, as well as the presence of amino acids. In vitro studies using serum- and amino…

  20. Adoption reverses the long-term impairment in glucocorticoid feedback induced by prenatal stress.

    PubMed

    Maccari, S; Piazza, P V; Kabbaj, M; Barbazanges, A; Simon, H; Le Moal, M

    1995-01-01

    The development of the organism is subjected to critical and complex influences during the perinatal period. Prenatal and postnatal stresses can have different long-term behavioral effects, and appropriate postnatal manipulations can counteract the behavioral effects of prenatal stress. In the present study, we investigated the involvement of changes in the activity of the hypothalamo-pituitary-adrenal (HPA) axis in the long-term effects of prenatal and postnatal events and of interactions between them. We investigated stress-induced corticosterone secretion and hippocampal corticosteroid receptors in male adult rats submitted to prenatal and/or postnatal manipulations. Repeated restraint during the last week of pregnancy was used as prenatal stressor, and adoption at birth was used to change the postnatal environment. We found that (1) prenatal stress prolongs stress-induced corticosterone secretion in adult rats, which was attributed to the observed decrease in central corticosteroid receptors; (2) adoption, irrespective of the stress experience of the foster mother, reverses the effects of prenatal stress; and (3) adoption per se increases maternal behavior and decreases the stress-induced corticosterone secretion peak in the adult offspring. In conclusion, certain prenatal and postnatal manipulations appear to have opposite long-term effects on the activity of the HPA axis, and adoption, probably by modifying maternal behavior, can protect against the effects of prenatal stress. Thus, changes in the activity of the HPA axis may be one of the biological substrates of the long-term effects of certain perinatal events. PMID:7823121

  1. Rescue of Impaired Long-Term Facilitation at Sensorimotor Synapses of Aplysia following siRNA Knockdown of CREB1

    PubMed Central

    Zhou, Lian; Zhang, Yili; Liu, Rong-Yu; Smolen, Paul; Cleary, Leonard J.

    2015-01-01

    Memory impairment is often associated with disrupted regulation of gene induction. For example, deficits in cAMP response element-binding protein (CREB) binding protein (CBP; an essential cofactor for activation of transcription by CREB) impair long-term synaptic plasticity and memory. Previously, we showed that small interfering RNA (siRNA)-induced knockdown of CBP in individual sensory neurons significantly reduced levels of CBP and impaired 5-HT-induced long-term facilitation (LTF) in sensorimotor cocultures from Aplysia. Moreover, computational simulations of the biochemical cascades underlying LTF successfully predicted training protocols that restored LTF following CBP knockdown. We examined whether simulations could also predict a training protocol that restores LTF impaired by siRNA-induced knockdown of the transcription factor CREB1. Simulations based on a previously described model predicted rescue protocols that were specific to CREB1 knockdown. Empirical studies demonstrated that one of these rescue protocols partially restored impaired LTF. In addition, the effectiveness of the rescue protocol was enhanced by pretreatment with rolipram, a selective cAMP phosphodiesterase inhibitor. These results provide further evidence that computational methods can help rescue disruptions in signaling cascades underlying memory formation. Moreover, the study demonstrates that the effectiveness of computationally designed training protocols can be enhanced with complementary pharmacological approaches. PMID:25632137

  2. Rescue of impaired long-term facilitation at sensorimotor synapses of Aplysia following siRNA knockdown of CREB1.

    PubMed

    Zhou, Lian; Zhang, Yili; Liu, Rong-Yu; Smolen, Paul; Cleary, Leonard J; Byrne, John H

    2015-01-28

    Memory impairment is often associated with disrupted regulation of gene induction. For example, deficits in cAMP response element-binding protein (CREB) binding protein (CBP; an essential cofactor for activation of transcription by CREB) impair long-term synaptic plasticity and memory. Previously, we showed that small interfering RNA (siRNA)-induced knockdown of CBP in individual sensory neurons significantly reduced levels of CBP and impaired 5-HT-induced long-term facilitation (LTF) in sensorimotor cocultures from Aplysia. Moreover, computational simulations of the biochemical cascades underlying LTF successfully predicted training protocols that restored LTF following CBP knockdown. We examined whether simulations could also predict a training protocol that restores LTF impaired by siRNA-induced knockdown of the transcription factor CREB1. Simulations based on a previously described model predicted rescue protocols that were specific to CREB1 knockdown. Empirical studies demonstrated that one of these rescue protocols partially restored impaired LTF. In addition, the effectiveness of the rescue protocol was enhanced by pretreatment with rolipram, a selective cAMP phosphodiesterase inhibitor. These results provide further evidence that computational methods can help rescue disruptions in signaling cascades underlying memory formation. Moreover, the study demonstrates that the effectiveness of computationally designed training protocols can be enhanced with complementary pharmacological approaches. PMID:25632137

  3. Long-term cognitive impairments in adult rats treated neonatally with beta-N-Methylamino-L-Alanine.

    PubMed

    Karlsson, Oskar; Roman, Erika; Brittebo, Eva B

    2009-11-01

    Most cyanobacteria (blue-green algae) can produce the neurotoxin beta-N-methylamino-L-alanine (BMAA). Dietary exposure to BMAA has been suggested to be involved in the etiology of the neurodegenerative disease amyotrophic lateral sclerosis/Parkinsonism-dementia complex (ALS/PDC). Little is known about BMAA-induced neurotoxicity following neonatal administration. Our previous studies have revealed an uptake of BMAA in the hippocampus and striatum of neonatal mice. Furthermore, rats treated with BMAA during the neonatal period displayed acute but transient motoric disturbances and failed to show habituation at juvenile age suggesting impairments in learning functions. In the present study, the aim was to investigate long-term behavioral effects of BMAA administration in neonatal rats. BMAA was administered on postnatal days 9-10 (200 or 600 mg/kg; subcutaneous injection). Spatial learning and memory was investigated in adulthood using the radial arm maze test. The results revealed impaired learning but not memory in BMAA-treated animals. The observed impairments were not due to alterations in motoric capacity, general activity, or behavioral profiles, as assessed in the multivariate concentric square field (MCSF) and open field tests. An aversive stimulus in the MCSF test revealed impairments in avoidance learning and/or memory. There was no difference in basal serum corticosterone levels in BMAA-treated animals, indicating that the observed long-term effects were not secondary to an altered basal hypothalamic-pituitary-adrenal axis function. The present data demonstrated long-term learning impairments following neonatal BMAA administration. Further studies on biochemical effects in various brain regions and subsequent behavioral alterations are needed to elucidate the mechanisms of BMAA-induced developmental neurotoxicity.

  4. The IkappaB kinase inhibitor sulfasalazine impairs long-term memory in the crab Chasmagnathus.

    PubMed

    Merlo, E; Freudenthal, R; Romano, A

    2002-01-01

    Evidence for the participation of Rel/NF-kappaB transcription factors in long-term memory has recently been reported in the context-signal learning paradigm of the crab Chasmagnathus, in which a high correlation between long-term memory formation and NF-kappaB activation was observed. Two components of the NF-kappaB pathway in the crab brain have now been identified by cross-immunoreactivity using mammalian antibodies for IkappaB-alpha and IkappaB kinase alpha. Furthermore, IkappaB kinase-like phosphotransferase activity, which was inhibited by the IkappaB kinase inhibitor sulfasalazine, was detected in brain extracts. We have evaluated the effect of sulfasalazine administration on long-term memory tested at 48 h. Amnesia was found when sulfasalazine was administered pre-training and 5 h after training but not at 0 or 24 h after training. Thus, two periods for sulfasalazine-induced amnesia were found in coincidence with the two phases of NF-kappaB activation previously described (immediately and 6 h after training). The cyclooxygenase inhibitor indomethacin did not induce amnesia when administered pre-training. Thus, the possibility that sulfasalazine induces amnesia by means of cyclooxygenase inhibition is unlikely to be tenable. In vivo sulfasalazine inhibition of basal NF-kappaB activity was found between 30 and 45 min after injection, as assessed by electrophoretic mobility shift assay. On the other hand, in vivo sulfasalazine administration 6 h after training inhibited the second phase of training-induced NF-kappaB activation, providing evidence that the sulfasalazine effect on memory is due to a direct effect of the drug on the NF-kappaB pathway. These results provide the first evidence that IkappaB kinase and NF-kappaB activation are necessary for memory formation.

  5. Docosahexaenoic Acid Rescues Synaptogenesis Impairment and Long-Term Memory Deficits Caused by Postnatal Multiple Sevoflurane Exposures.

    PubMed

    Tao, Guorong; Luo, Yan; Xue, Qingsheng; Li, Guohui; Tan, Yongchang; Xiao, Jinglei; Yu, Buwei

    2016-01-01

    Sevoflurane exposures were demonstrated to induce neurotoxicity in the developing brain in both human and animal studies. However, there is no effective approach to reverse it. The present study aimed to evaluate the feasibility of utilizing docosahexaenoic acid (DHA) to prevent sevoflurane-induced neurotoxicity. P6 (postnatal 6 days) mice were administrated DHA after exposure to 3% sevoflurane for two hours daily in three consecutive days. Molecular expressions of synaptic makers (PSD95, synaptophysin) and synaptic morphological changes were investigated by Western blot analysis and transmission electron microscopy, respectively. Meanwhile, Morris water maze test was used to assess spatial memory of mice at P31 (postnatal 31 days). DHA restored sevoflurane-induced decreased level of PSD95 and synaptophysin expressions and increased PSD areas and also improved long-term spatial memory. These results suggest that DHA could rescue synaptogenesis impairment and long-term memory deficits in postnatal caused by multiple sevoflurane exposures. PMID:27597963

  6. Docosahexaenoic Acid Rescues Synaptogenesis Impairment and Long-Term Memory Deficits Caused by Postnatal Multiple Sevoflurane Exposures

    PubMed Central

    Tao, Guorong; Luo, Yan; Xue, Qingsheng; Li, Guohui; Tan, Yongchang

    2016-01-01

    Sevoflurane exposures were demonstrated to induce neurotoxicity in the developing brain in both human and animal studies. However, there is no effective approach to reverse it. The present study aimed to evaluate the feasibility of utilizing docosahexaenoic acid (DHA) to prevent sevoflurane-induced neurotoxicity. P6 (postnatal 6 days) mice were administrated DHA after exposure to 3% sevoflurane for two hours daily in three consecutive days. Molecular expressions of synaptic makers (PSD95, synaptophysin) and synaptic morphological changes were investigated by Western blot analysis and transmission electron microscopy, respectively. Meanwhile, Morris water maze test was used to assess spatial memory of mice at P31 (postnatal 31 days). DHA restored sevoflurane-induced decreased level of PSD95 and synaptophysin expressions and increased PSD areas and also improved long-term spatial memory. These results suggest that DHA could rescue synaptogenesis impairment and long-term memory deficits in postnatal caused by multiple sevoflurane exposures. PMID:27597963

  7. Docosahexaenoic Acid Rescues Synaptogenesis Impairment and Long-Term Memory Deficits Caused by Postnatal Multiple Sevoflurane Exposures

    PubMed Central

    Tao, Guorong; Luo, Yan; Xue, Qingsheng; Li, Guohui; Tan, Yongchang

    2016-01-01

    Sevoflurane exposures were demonstrated to induce neurotoxicity in the developing brain in both human and animal studies. However, there is no effective approach to reverse it. The present study aimed to evaluate the feasibility of utilizing docosahexaenoic acid (DHA) to prevent sevoflurane-induced neurotoxicity. P6 (postnatal 6 days) mice were administrated DHA after exposure to 3% sevoflurane for two hours daily in three consecutive days. Molecular expressions of synaptic makers (PSD95, synaptophysin) and synaptic morphological changes were investigated by Western blot analysis and transmission electron microscopy, respectively. Meanwhile, Morris water maze test was used to assess spatial memory of mice at P31 (postnatal 31 days). DHA restored sevoflurane-induced decreased level of PSD95 and synaptophysin expressions and increased PSD areas and also improved long-term spatial memory. These results suggest that DHA could rescue synaptogenesis impairment and long-term memory deficits in postnatal caused by multiple sevoflurane exposures.

  8. Long-term social isolation in the adulthood results in CA1 shrinkage and cognitive impairment.

    PubMed

    Pereda-Pérez, Inmaculada; Popović, Natalija; Otalora, Beatriz Baño; Popović, Miroljub; Madrid, Juan Antonio; Rol, Maria Angeles; Venero, César

    2013-11-01

    Social isolation in adulthood is a psychosocial stressor that can result in endocrinological and behavioral alterations in different species. In rodents, controversial results have been obtained in fear conditioning after social isolation at adulthood, while neural substrates underlying these differences are largely unknown. Neural cell adhesion molecule (NCAM) and its polysialylated form (PSA-NCAM) are prominent modulators of synaptic plasticity underlying memory processes in many tasks, including fear conditioning. In this study, we used adult female Octodon degus to investigate the effects of long-term social isolation on contextual and cued fear conditioning, and the possible modulation of the synaptic levels of NCAM and PSA-NCAM in the hippocampus. After 6½ months of social isolation, adult female degus showed a normal auditory-cued fear memory, but a deficit in contextual fear memory, a hippocampal dependent task. Subsequently, we observed reduced hippocampal synaptic levels of PSA-NCAM in isolated compared to grouped-housed female degus. No significant differences were found between experimental groups in hippocampal levels of the three main isoforms of NCAM (NCAM180, NCAM140 and NCAM120). Interestingly, social isolation reduced the volume of the hippocampal CA1 subfield, without affecting the volume of the CA3 subregion or the total hippocampus. Moreover, attenuated body weight gain and reduced number of granulocytes were detected in isolated animals. Our findings indicate for the first time, that long-term social isolation of adult female animals induces a specific shrinkage of CA1 and a decrease in synaptic levels of PSA-NCAM in the hippocampus. These effects may be related to the deficit in contextual fear memory observed in isolated female degus.

  9. Repeated Isoflurane Exposures Impair Long-Term Potentiation and Increase Basal GABAergic Activity in the Basolateral Amygdala

    PubMed Central

    Long II, Robert P.; Aroniadou-Anderjaska, Vassiliki; Prager, Eric M.; Pidoplichko, Volodymyr I.; Figueiredo, Taiza H.; Braga, Maria F. M.

    2016-01-01

    After surgery requiring general anesthesia, patients often experience emotional disturbances, but it is unclear if this is due to anesthetic exposure. In the present study, we examined whether isoflurane anesthesia produces long-term pathophysiological alterations in the basolateral amygdala (BLA), a brain region that plays a central role in emotional behavior. Ten-week-old, male rats were administered either a single, 1 h long isoflurane (1.5%) anesthesia or three, 1 h long isoflurane exposures, separated by 48 h. Long-term potentiation (LTP) and spontaneous GABAergic activity in the BLA were studied 1 day, 1 week, and 1 month later. Single isoflurane anesthesia had no significant effect on the magnitude of LTP. In contrast, after repeated isoflurane exposures, LTP was dramatically impaired at both 1 day and 1 week after the last exposure but was restored by 1 month after the exposures. Spontaneous GABAA receptor-mediated IPSCs were increased at 1 day and 1 week after repeated exposures but had returned to control levels by 1 month after exposure. Thus, repeated exposures to isoflurane cause a long-lasting—but not permanent—impairment of synaptic plasticity in the BLA, which could be due to increased basal GABAergic activity. These pathophysiological alterations may produce emotional disturbances and impaired fear-related learning. PMID:27313904

  10. Repeated Isoflurane Exposures Impair Long-Term Potentiation and Increase Basal GABAergic Activity in the Basolateral Amygdala.

    PubMed

    Long Ii, Robert P; Aroniadou-Anderjaska, Vassiliki; Prager, Eric M; Pidoplichko, Volodymyr I; Figueiredo, Taiza H; Braga, Maria F M

    2016-01-01

    After surgery requiring general anesthesia, patients often experience emotional disturbances, but it is unclear if this is due to anesthetic exposure. In the present study, we examined whether isoflurane anesthesia produces long-term pathophysiological alterations in the basolateral amygdala (BLA), a brain region that plays a central role in emotional behavior. Ten-week-old, male rats were administered either a single, 1 h long isoflurane (1.5%) anesthesia or three, 1 h long isoflurane exposures, separated by 48 h. Long-term potentiation (LTP) and spontaneous GABAergic activity in the BLA were studied 1 day, 1 week, and 1 month later. Single isoflurane anesthesia had no significant effect on the magnitude of LTP. In contrast, after repeated isoflurane exposures, LTP was dramatically impaired at both 1 day and 1 week after the last exposure but was restored by 1 month after the exposures. Spontaneous GABAA receptor-mediated IPSCs were increased at 1 day and 1 week after repeated exposures but had returned to control levels by 1 month after exposure. Thus, repeated exposures to isoflurane cause a long-lasting-but not permanent-impairment of synaptic plasticity in the BLA, which could be due to increased basal GABAergic activity. These pathophysiological alterations may produce emotional disturbances and impaired fear-related learning.

  11. Repeated Isoflurane Exposures Impair Long-Term Potentiation and Increase Basal GABAergic Activity in the Basolateral Amygdala.

    PubMed

    Long Ii, Robert P; Aroniadou-Anderjaska, Vassiliki; Prager, Eric M; Pidoplichko, Volodymyr I; Figueiredo, Taiza H; Braga, Maria F M

    2016-01-01

    After surgery requiring general anesthesia, patients often experience emotional disturbances, but it is unclear if this is due to anesthetic exposure. In the present study, we examined whether isoflurane anesthesia produces long-term pathophysiological alterations in the basolateral amygdala (BLA), a brain region that plays a central role in emotional behavior. Ten-week-old, male rats were administered either a single, 1 h long isoflurane (1.5%) anesthesia or three, 1 h long isoflurane exposures, separated by 48 h. Long-term potentiation (LTP) and spontaneous GABAergic activity in the BLA were studied 1 day, 1 week, and 1 month later. Single isoflurane anesthesia had no significant effect on the magnitude of LTP. In contrast, after repeated isoflurane exposures, LTP was dramatically impaired at both 1 day and 1 week after the last exposure but was restored by 1 month after the exposures. Spontaneous GABAA receptor-mediated IPSCs were increased at 1 day and 1 week after repeated exposures but had returned to control levels by 1 month after exposure. Thus, repeated exposures to isoflurane cause a long-lasting-but not permanent-impairment of synaptic plasticity in the BLA, which could be due to increased basal GABAergic activity. These pathophysiological alterations may produce emotional disturbances and impaired fear-related learning. PMID:27313904

  12. Event-related Functional Magnetic Resonance Imaging of a Low Dose of Dexmedetomidine that Impairs Long-term Memory

    PubMed Central

    Hayama, Hiroki R.; Drumheller, Kristin. M.; Mastromonaco, Mark; Reist, Christopher; Cahill, Lawrence F.; Alkire, Michael. T.

    2012-01-01

    Background Work suggests the amnesia of Dexmedetomidine (an α2-adrenergic agonist) is caused by a failure of information to be encoded into long-term memory and that dexmedetomidine might differentially affect memory for emotionally arousing material. We investigated these issues in humans using event-related neuroimaging to reveal alterations in brain activity and subsequent memory effects associated with drug exposure. Methods Forty-eight healthy volunteers received a computer-controlled infusion of either placebo or low-dose dexmedetomidine (target = 0.15ng/ml plasma) during neuroimaging while they viewed and rated 80 emotionally arousing (e.g., graphic war wound) and 80 nonarousing neutral (e.g., cup) pictures for emotional arousal content. Long-term picture memory was tested 4 days later without neuroimaging. Imaging data were analyzed for drug effects, emotional processing differences and memory related changes with statistical parametric mapping-8. Results Dexmedetomidine impaired overall (mean ± SEM) picture memory (Placebo: 0.58 ± 0.03 vs. a dexmedetomidine: 0.45 ± 0.03, p = 0.001), but did not differentially modulate memory as a function of item arousal. Arousing pictures were better remembered for both groups. Dexmedetomidine had regionally heterogeneous effects on brain activity, primarily decreasing it in the cortex while increasing it in thalamic and posterior hippocampal regions. Nevertheless, a single subsequent memory effect for item memory common to both groups was identified only in the left hippocampus/amygdala. Much of this effect was found to be larger for the placebo than dexmedetomidine group. Conclusion Dexmedetomidine impaired long-term picture memory, but did not disproportionately block memory for emotionally arousing items. The memory impairment on dexmedetomidine corresponds with a weakened hippocampal subsequent memory effect. PMID:22929730

  13. Long-Term Habituation to Repeated Loud Noise Is Impaired by Relatively Short Interstressor Intervals in Rats

    PubMed Central

    Masini, Cher V.; Day, Heidi E. W.; Campeau, Serge

    2008-01-01

    The phenomenon of spaced (longer intertrial interval) compared with massed (shorter intertrial interval) training leading to better long-term habituation and associative learning is well documented. However, the effects of intertrial intervals on response habituation to repeated stress exposures have not been previously examined. The present experiments found that massed (six 30-min exposures of 95 dB white noise in 6 hr) and spaced (one 30-min exposure daily for 6 days) noise exposures led to similar habituation of plasma corticosterone and ACTH responses, heart rate, and core body temperature after the 6th exposure in male Sprague–Dawley rats. However, these habituated responses were not retained in the massed group on a similar noise re-exposure 48 hr later, compared with the spaced group. The habituated responses found in the massed group after the 6 noise exposures were not due to differential hearing threshold shifts, as examined with modifications of the acoustic startle reflex. These data indicate that relatively short interstressor intervals impair long-term stress adaptation. This series of studies supports the idea of distinct short- and long-term habituation processes to stress responsiveness. PMID:18298264

  14. Stress Administered Prior to Encoding Impairs Neutral but Enhances Emotional Long-Term Episodic Memories

    ERIC Educational Resources Information Center

    Payne, Jessica D.; Jackson, Eric D.; Hoscheidt, Siobhan; Ryan, Lee; Jacobs, W. Jake; Nadel, Lynn

    2007-01-01

    Stressful events frequently comprise both neutral and emotionally arousing information, yet the impact of stress on emotional and neutral events is still not fully understood. The hippocampus and frontal cortex have dense concentrations of receptors for stress hormones, such as cortisol, which at high levels can impair performance on hippocampally…

  15. Depletion of Serotonin Selectively Impairs Short-Term Memory without Affecting Long-Term Memory in Odor Learning in the Terrestrial Slug "Limax Valentianus"

    ERIC Educational Resources Information Center

    Santa, Tomofumi; Kirino, Yutaka; Watanabe, Satoshi; Shirahata, Takaaki; Tsunoda, Makoto

    2006-01-01

    The terrestrial slug "Limax" is able to acquire short-term and long-term memories during aversive odor-taste associative learning. We investigated the effect of the selective serotonergic neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) on memory. Behavioral studies indicated that 5,7-DHT impaired short-term memory but not long-term memory. HPLC…

  16. Spatial Memory and Long-Term Object Recognition Are Impaired by Circadian Arrhythmia and Restored by the GABAAAntagonist Pentylenetetrazole

    PubMed Central

    Ruby, Norman F.; Fernandez, Fabian; Garrett, Alex; Klima, Jessy; Zhang, Pei; Sapolsky, Robert; Heller, H. Craig

    2013-01-01

    Performance on many memory tests varies across the day and is severely impaired by disruptions in circadian timing. We developed a noninvasive method to permanently eliminate circadian rhythms in Siberian hamsters (Phodopussungorus) so that we could investigate the contribution of the circadian system to learning and memory in animals that are neurologically and genetically intact. Male and female adult hamsters were rendered arrhythmic by a disruptive phase shift protocol that eliminates cycling of clock genes within the suprachiasmatic nucleus (SCN), but preserves sleep architecture. These arrhythmic animals have deficits in spatial working memory and in long-term object recognition memory. In a T-maze, rhythmic control hamsters exhibited spontaneous alternation behavior late in the day and at night, but made random arm choices early in the day. By contrast, arrhythmic animals made only random arm choices at all time points. Control animals readily discriminated novel objects from familiar ones, whereas arrhythmic hamsters could not. Since the SCN is primarily a GABAergic nucleus, we hypothesized that an arrhythmic SCN could interfere with memory by increasing inhibition in hippocampal circuits. To evaluate this possibility, we administered the GABAA antagonist pentylenetetrazole (PTZ; 0.3 or 1.0 mg/kg/day) to arrhythmic hamsters for 10 days, which is a regimen previously shown to produce long-term improvements in hippocampal physiology and behavior in Ts65Dn (Down syndrome) mice. PTZ restored long-term object recognition and spatial working memory for at least 30 days after drug treatment without restoring circadian rhythms. PTZ did not augment memory in control (entrained) animals, but did increase their activity during the memory tests. Our findings support the hypothesis that circadian arrhythmia impairs declarative memory by increasing the relative influence of GABAergic inhibition in the hippocampus. PMID:24009680

  17. Spatial memory and long-term object recognition are impaired by circadian arrhythmia and restored by the GABAAAntagonist pentylenetetrazole.

    PubMed

    Ruby, Norman F; Fernandez, Fabian; Garrett, Alex; Klima, Jessy; Zhang, Pei; Sapolsky, Robert; Heller, H Craig

    2013-01-01

    Performance on many memory tests varies across the day and is severely impaired by disruptions in circadian timing. We developed a noninvasive method to permanently eliminate circadian rhythms in Siberian hamsters (Phodopus sungorus) [corrected] so that we could investigate the contribution of the circadian system to learning and memory in animals that are neurologically and genetically intact. Male and female adult hamsters were rendered arrhythmic by a disruptive phase shift protocol that eliminates cycling of clock genes within the suprachiasmatic nucleus (SCN), but preserves sleep architecture. These arrhythmic animals have deficits in spatial working memory and in long-term object recognition memory. In a T-maze, rhythmic control hamsters exhibited spontaneous alternation behavior late in the day and at night, but made random arm choices early in the day. By contrast, arrhythmic animals made only random arm choices at all time points. Control animals readily discriminated novel objects from familiar ones, whereas arrhythmic hamsters could not. Since the SCN is primarily a GABAergic nucleus, we hypothesized that an arrhythmic SCN could interfere with memory by increasing inhibition in hippocampal circuits. To evaluate this possibility, we administered the GABAA antagonist pentylenetetrazole (PTZ; 0.3 or 1.0 mg/kg/day) to arrhythmic hamsters for 10 days, which is a regimen previously shown to produce long-term improvements in hippocampal physiology and behavior in Ts65Dn (Down syndrome) mice. PTZ restored long-term object recognition and spatial working memory for at least 30 days after drug treatment without restoring circadian rhythms. PTZ did not augment memory in control (entrained) animals, but did increase their activity during the memory tests. Our findings support the hypothesis that circadian arrhythmia impairs declarative memory by increasing the relative influence of GABAergic inhibition in the hippocampus.

  18. Repeated Neonatal Propofol Administration Induces Sex-Dependent Long-Term Impairments on Spatial and Recognition Memory in Rats

    PubMed Central

    Gonzales, Edson Luck T.; Yang, Sung Min; Choi, Chang Soon; Mabunga, Darine Froy N.; Kim, Hee Jin; Cheong, Jae Hoon; Ryu, Jong Hoon; Koo, Bon-Nyeo; Shin, Chan Young

    2015-01-01

    Propofol is an anesthetic agent that gained wide use because of its fast induction of anesthesia and rapid recovery post-anesthesia. However, previous studies have reported immediate neurodegeneration and long-term impairment in spatial learning and memory from repeated neonatal propofol administration in animals. Yet, none of those studies has explored the sex-specific long-term physical changes and behavioral alterations such as social (sociability and social preference), emotional (anxiety), and other cognitive functions (spatial working, recognition, and avoidance memory) after neonatal propofol treatment. Seven-day-old Wistar-Kyoto (WKY) rats underwent repeated daily intraperitoneal injections of propofol or normal saline for 7 days. Starting fourth week of age and onwards, rats were subjected to behavior tests including open-field, elevated-plus-maze, Y-maze, 3-chamber social interaction, novel-object-recognition, passive-avoidance, and rotarod. Rats were sacrificed at 9 weeks and hippocampal protein expressions were analyzed by Western blot. Results revealed long-term body weight gain alterations in the growing rats and sex-specific impairments in spatial (female) and recognition (male) learning and memory paradigms. A markedly decreased expression of hippocampal NMDA receptor GluN1 subunit in female- and increased expression of AMPA GluR1 subunit protein expression in male rats were also found. Other aspects of behaviors such as locomotor activity and coordination, anxiety, sociability, social preference and avoidance learning and memory were not generally affected. These results suggest that neonatal repeated propofol administration disrupts normal growth and some aspects of neurodevelopment in rats in a sex-specific manner. PMID:25995824

  19. Ultrafiltration Failure and Impaired Sodium Sieving During Long-Term Peritoneal Dialysis: More Than Aquaporin Dysfunction?

    PubMed

    Morelle, Johann; Sow, Amadou; Hautem, Nicolas; Devuyst, Olivier; Goffin, Eric

    2016-01-01

    Fifteen years ago, our group reported the case of a 67-year-old man on peritoneal dialysis for 11 years, in whom ultrafiltration failure and impaired sodium sieving were associated with an apparently normal expression of aquaporin-1 (AQP1) water channels in peritoneal capillaries. At that time, AQP1 dysfunction was suggested as the cause of impaired free-water transport. However, recent data from computer simulations, and structural and functional analysis of the peritoneal membrane of patients with encapsulating peritoneal sclerosis, demonstrated that changes in the peritoneal interstitium directly alter osmotic water transport. In light of these insights, we challenge the initial hypothesis and provide several lines of evidence supporting the diagnosis of encapsulating peritoneal sclerosis in this patient and suggesting that severe peritoneal fibrosis accounted for the loss of osmotic conductance developed during the course of peritoneal dialysis. PMID:27006441

  20. Long-term caloric restriction in mice may prevent age-related learning impairment via suppression of apoptosis.

    PubMed

    Ma, Lina; Wang, Rong; Dong, Wen; Li, Yun; Xu, Baolei; Zhang, Jingshuang; Zhao, Zhiwei

    2016-12-15

    Caloric restriction (CR) is the most reliable intervention to extend lifespan and prevent age-related disorders in various species from yeast to rodents. However, the underlying mechanisms have not yet been clearly defined. Therefore, we aimed to identify the underlying mechanisms of long-term CR on age-related learning impairment in C57/BL mice. Thirty six-week-old male C57/BL mice were randomly divided into three groups: normal control group (NC group, n=10), high energy group (HE group, n=10), and CR group (n=10). After 10 months, the Morris water maze test was performed to monitor learning abilities. Western blotting, immunohistochemistry and real-time polymerase chain reaction were used to monitor changes in protein and mRNA levels associated with apoptosis-related proteins in the hippocampus. The average escape latency was lower in the CR group compared with the NC group, and the average time taken to first cross the platform in the CR group was significantly shorter than the HE group. Both Bcl-2 protein and mRNA expression levels in the CR group were significantly higher than those of the NC group and HE group. The expression of Bax, Caspase-3 and PARP protein in the CR group was significantly lower than the NC group. Our findings demonstrate that long-term CR may prevent age-related learning impairments via suppressing apoptosis in mice. PMID:27452805

  1. Overexpression of SIRT6 in the hippocampal CA1 impairs the formation of long-term contextual fear memory

    PubMed Central

    Yin, Xi; Gao, Yuan; Shi, Hai-Shui; Song, Li; Wang, Jie-Chao; Shao, Juan; Geng, Xu-Hong; Xue, Gai; Li, Jian-Li; Hou, Yan-Ning

    2016-01-01

    Histone modifications have been implicated in learning and memory. Our previous transcriptome data showed that expression of sirtuins 6 (SIRT6), a member of Histone deacetylases (HDACs) family in the hippocampal cornu ammonis 1 (CA1) was decreased after contextual fear conditioning. However, the role of SIRT6 in the formation of memory is still elusive. In the present study, we found that contextual fear conditioning inhibited translational expression of SIRT6 in the CA1. Microinfusion of lentiviral vector-expressing SIRT6 into theCA1 region selectively enhanced the expression of SIRT6 and impaired the formation of long-term contextual fear memory without affecting short-term fear memory. The overexpression of SIRT6 in the CA1 had no effect on anxiety-like behaviors or locomotor activity. Also, we also found that SIRT6 overexpression significantly inhibited the expression of insulin-like factor 2 (IGF2) and amounts of proteins and/or phosphoproteins (e.g. Akt, pAkt, mTOR and p-mTOR) related to the IGF2 signal pathway in the CA1. These results demonstrate that the overexpression of SIRT6 in the CA1 impaired the formation of long-term fear memory, and SIRT6 in the CA1 may negatively modulate the formation of contextual fear memory via inhibiting the IGF signaling pathway. PMID:26732053

  2. Long-term Behavioral Impairment Following Acute Embryonic Ethanol Exposure in Zebrafish

    PubMed Central

    Bailey, JM; Oliveri, AN; Zhang, C; Frazier, JM; Mackinnon, S; Cole, GJ; Levin, ED

    2015-01-01

    BACKGROUND Developmental exposure to ethanol has long been known to cause persisting neurobehavioral impairment. However, the neural and behavioral mechanisms underlying these deficits and the importance of exposure timing are not well-characterized. Given the importance of timing and sequence in neurodevelopment it would be expected that alcohol intoxication at different developmental periods would result in distinct neurobehavioral consequences. METHODS Zebrafish embryos were exposed to ethanol (0%, 1%, 3%) at either 8-10 or 24-27 hours post-fertilization (hpf) then reared to adolescence and evaluated on several behavioral endpoints. Habituation to a repeated environmental stimulus and overall sensorimotor function were assessed using a tap startle test; measurements of anxiety and exploration behavior were made following introduction to a novel tank; and spatial discrimination learning was assessed using aversive control in a three-chambered apparatus. Overt signs of dysmorphogenesis were also scored (i.e. craniofacial malformations, including eye diameter and midbrain-hindbrain boundary morphology). RESULTS Ethanol treated fish were more active both at baseline and following a tap stimulus compared to the control fish and were hyperactive when placed in a novel tank. These effects were more prominent following exposure at 24-27 hpf than with the earlier exposure window, for both dose groups. Increases in physical malformation were only present in the 3% ethanol group; all malformed fish were excluded from behavioral testing. DISCUSSION These results suggest specific domains of behavior are affected following ethanol exposure, with some but not all of the tests revealing significant impairment. The behavioral phenotypes following distinct exposure windows described here can be used to help link cellular and molecular mechanisms of developmental ethanol exposure to functional neurobehavioral effects. PMID:25599606

  3. Associations between Depressive State and Impaired Higher-Level Functional Capacity in the Elderly with Long-Term Care Requirements.

    PubMed

    Ogata, Soshiro; Hayashi, Chisato; Sugiura, Keiko; Hayakawa, Kazuo

    2015-01-01

    Depressive state has been reported to be significantly associated with higher-level functional capacity among community-dwelling elderly. However, few studies have investigated the associations among people with long-term care requirements. We aimed to investigate the associations between depressive state and higher-level functional capacity and obtain marginal odds ratios using propensity score analyses in people with long-term care requirements. We conducted a cross-sectional study based on participants aged ≥ 65 years (n = 545) who were community dwelling and used outpatient care services for long-term preventive care. We measured higher-level functional capacity, depressive state, and possible confounders. Then, we estimated the marginal odds ratios (i.e., the change in odds of impaired higher-level functional capacity if all versus no participants were exposed to depressive state) by logistic models using generalized linear models with the inverse probability of treatment weighting (IPTW) for propensity score and design-based standard errors. Depressive state was used as the exposure variable and higher-level functional capacity as the outcome variable. The all absolute standardized differences after the IPTW using the propensity scores were < 10% which indicated negligible differences in the mean or prevalence of the covariates between non-depressive state and depressive state. The marginal odds ratios were estimated by the logistic models with IPTW using the propensity scores. The marginal odds ratios were 2.17 (95%CI: 1.13-4.19) for men and 2.57 (95%CI: 1.26-5.26) for women. Prevention of depressive state may contribute to not only depressive state but also higher-level functional capacity.

  4. Hippocampal inactivation with TTX impairs long-term spatial memory retrieval and modifies brain metabolic activity.

    PubMed

    Conejo, Nélida María; Cimadevilla, José Manuel; González-Pardo, Héctor; Méndez-Couz, Marta; Arias, Jorge Luis

    2013-01-01

    Functional inactivation techniques enable studying the hippocampal involvement in each phase of spatial memory formation in the rat. In this study, we applied tetrodotoxin unilaterally or bilaterally into the dorsal hippocampus to evaluate the role of this brain structure in retrieval of memories acquired 28 days before in the Morris water maze. We combined hippocampal inactivation with the assessment of brain metabolism using cytochrome oxidase histochemistry. Several brain regions were considered, including the hippocampus and other related structures. Results showed that both unilateral and bilateral hippocampal inactivation impaired spatial memory retrieval. Hence, whereas subjects with bilateral hippocampal inactivation showed a circular swim pattern at the side walls of the pool, unilateral inactivation favoured swimming in the quadrants adjacent to the target one. Analysis of cytochrome oxidase activity disclosed regional differences according to the degree of hippocampal functional blockade. In comparison to control group, animals with bilateral inactivation showed increased CO activity in CA1 and CA3 areas of the hippocampus during retrieval, while the activity of the dentate gyrus substantially decreased. However, unilateral inactivated animals showed decreased CO activity in Ammon's horn and the dentate gyrus. This study demonstrated that retrieval recruits differentially the hippocampal subregions and the balance between them is altered with hippocampal functional lesions.

  5. Hippocampal inactivation with TTX impairs long-term spatial memory retrieval and modifies brain metabolic activity.

    PubMed

    Conejo, Nélida María; Cimadevilla, José Manuel; González-Pardo, Héctor; Méndez-Couz, Marta; Arias, Jorge Luis

    2013-01-01

    Functional inactivation techniques enable studying the hippocampal involvement in each phase of spatial memory formation in the rat. In this study, we applied tetrodotoxin unilaterally or bilaterally into the dorsal hippocampus to evaluate the role of this brain structure in retrieval of memories acquired 28 days before in the Morris water maze. We combined hippocampal inactivation with the assessment of brain metabolism using cytochrome oxidase histochemistry. Several brain regions were considered, including the hippocampus and other related structures. Results showed that both unilateral and bilateral hippocampal inactivation impaired spatial memory retrieval. Hence, whereas subjects with bilateral hippocampal inactivation showed a circular swim pattern at the side walls of the pool, unilateral inactivation favoured swimming in the quadrants adjacent to the target one. Analysis of cytochrome oxidase activity disclosed regional differences according to the degree of hippocampal functional blockade. In comparison to control group, animals with bilateral inactivation showed increased CO activity in CA1 and CA3 areas of the hippocampus during retrieval, while the activity of the dentate gyrus substantially decreased. However, unilateral inactivated animals showed decreased CO activity in Ammon's horn and the dentate gyrus. This study demonstrated that retrieval recruits differentially the hippocampal subregions and the balance between them is altered with hippocampal functional lesions. PMID:23724089

  6. Hippocampal Inactivation with TTX Impairs Long-Term Spatial Memory Retrieval and Modifies Brain Metabolic Activity

    PubMed Central

    Conejo, Nélida María; Cimadevilla, José Manuel; González-Pardo, Héctor; Méndez-Couz, Marta; Arias, Jorge Luis

    2013-01-01

    Functional inactivation techniques enable studying the hippocampal involvement in each phase of spatial memory formation in the rat. In this study, we applied tetrodotoxin unilaterally or bilaterally into the dorsal hippocampus to evaluate the role of this brain structure in retrieval of memories acquired 28 days before in the Morris water maze. We combined hippocampal inactivation with the assessment of brain metabolism using cytochrome oxidase histochemistry. Several brain regions were considered, including the hippocampus and other related structures. Results showed that both unilateral and bilateral hippocampal inactivation impaired spatial memory retrieval. Hence, whereas subjects with bilateral hippocampal inactivation showed a circular swim pattern at the side walls of the pool, unilateral inactivation favoured swimming in the quadrants adjacent to the target one. Analysis of cytochrome oxidase activity disclosed regional differences according to the degree of hippocampal functional blockade. In comparison to control group, animals with bilateral inactivation showed increased CO activity in CA1 and CA3 areas of the hippocampus during retrieval, while the activity of the dentate gyrus substantially decreased. However, unilateral inactivated animals showed decreased CO activity in Ammon's horn and the dentate gyrus. This study demonstrated that retrieval recruits differentially the hippocampal subregions and the balance between them is altered with hippocampal functional lesions. PMID:23724089

  7. Inhibition of the Motor Protein Eg5/Kinesin-5 in Amyloid β-Mediated Impairment of Hippocampal Long-Term Potentiation and Dendritic Spine Loss.

    PubMed

    Freund, Ronald K; Gibson, Emily S; Potter, Huntington; Dell'Acqua, Mark L

    2016-05-01

    Alzheimer's disease (AD) is characterized by neurofibrillary tangles, amyloid plaques, and neurodegeneration. However, this pathology is preceded by increased soluble amyloid beta (Aβ) 1-42 oligomers that interfere with the glutamatergic synaptic plasticity required for learning and memory, includingN-methyl-d-aspartate receptor (NMDAR)-dependent long-term potentiation (LTP). In particular, soluble Aβ(1-42) acutely inhibits LTP and chronically causes synapse loss. Many mechanisms have been proposed for Aβ-induced synaptic dysfunction, but we recently found that Aβ(1-42) inhibits the microtubule motor protein Eg5/kinesin-5. Here we compared the impacts of Aβ(1-42) and monastrol, a small-molecule Eg5 inhibitor, on LTP in hippocampal slices and synapse loss in neuronal cultures. Acute (20-minute) treatment with monastrol, like Aβ, completely inhibited LTP at doses >100 nM. In addition, 1 nM Aβ(1-42) or 50 nM monastrol inhibited LTP #x223c;50%, and when applied together caused complete LTP inhibition. At concentrations that impaired LTP, neither Aβ(1-42) nor monastrol inhibited NMDAR synaptic responses until #x223c;60 minutes, when only #x223c;25% inhibition was seen for monastrol, indicating that NMDAR inhibition was not responsible for LTP inhibition by either agent when applied for only 20 minutes. Finally, 48 hours of treatment with either 0.5-1.0μM Aβ(1-42) or 1-5μM monastrol reduced the dendritic spine/synapse density in hippocampal cultures up to a maximum of #x223c;40%, and when applied together at maximal concentrations, no additional spine loss resulted. Thus, monastrol can mimic and in some cases occlude the impact of Aβon LTP and synapse loss, suggesting that Aβinduces acute and chronic synaptic dysfunction in part through inhibiting Eg5.

  8. Oxaloacetate restores the long-term potentiation impaired in rat hippocampus CA1 region by 2-vessel occlusion.

    PubMed

    Marosi, Máté; Fuzik, János; Nagy, Dávid; Rákos, Gabriella; Kis, Zsolt; Vécsei, László; Toldi, József; Ruban-Matuzani, Angela; Teichberg, Vivian I; Farkas, Tamás

    2009-02-14

    Various acute brain pathological conditions are characterized by the presence of elevated glutamate concentrations in the brain interstitial fluids. It has been established that a decrease in the blood glutamate level enhances the brain-to-blood efflux of glutamate, removal of which from the brain may prevent glutamate excitotoxicity and its contribution to the long-lasting neurological deficits seen in stroke. A decrease in blood glutamate level can be achieved by exploiting the glutamate-scavenging properties of the blood-resident enzyme glutamate-oxaloacetate transaminase, which transforms glutamate into 2-ketoglutarate in the presence of the glutamate co-substrate oxaloacetate. The present study had the aim of an evaluation of the effects of the blood glutamate scavenger oxaloacetate on the impaired long-term potentiation (LTP) induced in the 2-vessel occlusion ischaemic model in rat. Transient (30-min) incomplete forebrain ischaemia was produced 72 h before LTP induction. Although the short transient brain hypoperfusion did not induce histologically identifiable injuries in the CA1 region (Fluoro-Jade B, S-100 and cresyl violet), it resulted in an impaired LTP function in the hippocampal CA1 region without damaging the basal synaptic transmission between the Schaffer collaterals and the pyramidal neurons. This impairment could be fended off in a dose-dependent manner by the intravenous administration of oxaloacetate in saline (at doses between 1.5 mmol and 0.1 mumol) immediately after the transient hypoperfusion. Our results suggest that oxaloacetate-mediated blood and brain glutamate scavenging contributes to the restoration of the LTP after its impairment by brain ischaemia.

  9. Post ischemia intermittent hypoxia induces hippocampal neurogenesis and synaptic alterations and alleviates long-term memory impairment.

    PubMed

    Tsai, Yi-Wei; Yang, Yea-Ru; Sun, Synthia H; Liang, Keng-Chen; Wang, Ray-Yau

    2013-05-01

    Adult hippocampal neurogenesis is important for learning and memory, especially after a brain injury such as ischemia. Newborn hippocampal neurons contribute to memory performance by establishing functional synapses with target cells. This study demonstrated that the maturation of hippocampal neurons is enhanced by postischemia intermittent hypoxia (IH) intervention. The effects of IH intervention in cultured neurons were mediated by increased synaptogenesis, which was primarily regulated by brain-derived neurotrophic factor (BDNF)/PI3K/AKT. Hippocampal neo-neurons expressed BDNF and exhibited enhanced presynaptic function as indicated by increases in the pSynapsin expression, synaptophysin intensity, and postsynapse density following IH intervention after ischemia. Postischemia IH-induced hippocampal neo-neurons were affected by presynaptic activity, which reflected the dynamic plasticity of the glutamatergic receptors. These alterations were also associated with the alleviation of ischemia-induced long-term memory impairment. Our results suggest that postischemia IH intervention rescued ischemia-induced spatial learning and memory impairment by inducing hippocampal neurogenesis and functional synaptogenesis via BDNF expression.

  10. Long-term reading and spelling outcome in Italian adolescents with a history of specific language impairment.

    PubMed

    Brizzolara, Daniela; Gasperini, Filippo; Pfanner, Lucia; Cristofani, Paola; Casalini, Claudia; Chilosi, Anna M

    2011-09-01

    Specific language impairment (SLI) diagnosed in the pre-school years is frequently associated with reading and writing difficulties at school age. The nature of this relationship is unclear, despite the availability of a large number of studies, mostly on English speaking children. Phonological processing deficits have been considered the prominent cause of both difficulties. However recent findings in both children with SLI and in children with reading difficulties are not easily accommodated within a single dimensional model explaining the relationship between oral and written language deficits. Our study focuses on the long-term reading and spelling outcome in relation to preschool oral language skills in a group of Italian adolescents with a documented history of SLI. Sixteen Italian adolescents diagnosed as SLI at our Hospital in the pre-school years and 32 normal controls were submitted to an extensive assessment of oral and written language skills. At a group level SLI adolescents had weak oral and written language skills in almost all tests. Results show that reading difficulties have some features in common with those of Italian developmental dyslexics but also have distinct characteristics, since reading accuracy and written comprehension, usually relatively spared in Italian developmental dyslexics, were impaired in adolescents with SLI. Longitudinal analyses showed that expressive morpho-syntactic and lexical abilities at pre-school age were the oral language skills that best predicted reading and spelling outcomes in adolescents with SLI. However, also children with severe phonological impairment in the absence of other oral language deficits showed later literacy difficulties, although less severe and mainly limited to reading accuracy. Our study supports the notion that there is a complex relationship between oral and written language difficulties which may change at different developmental time points, not captured by a single deficit model, but

  11. Impaired long-term memory retention: common denominator for acutely or genetically reduced hippocampal neurogenesis in adult mice.

    PubMed

    Ben Abdallah, Nada M-B; Filipkowski, Robert K; Pruschy, Martin; Jaholkowski, Piotr; Winkler, Juergen; Kaczmarek, Leszek; Lipp, Hans-Peter

    2013-09-01

    In adult rodents, decreasing hippocampal neurogenesis experimentally using different approaches often impairs performance in hippocampus-dependent processes. Nonetheless, functional relevance of adult neurogenesis is far from being unraveled, and deficits so far described in animal models often lack reproducibility. One hypothesis is that such differences might be the consequence of the extent of the methodological specificity used to alter neurogenesis rather than the extent to which adult neurogenesis is altered. To address this, we focused on cranial irradiation, the most widely used technique to impair hippocampal neurogenesis and consequentially induce hippocampus-dependent behavioral deficits. To investigate the specificity of the technique, we thus exposed 4-5 months old female cyclin D2 knockout mice, a model lacking physiological levels of olfactory and hippocampal neurogenesis, to an X-ray dose of 10 Gy, reported to specifically affect transiently amplifying precursors. After a recovery period of 1.5 months, behavioral tests were performed and probed for locomotor activity, habituation, anxiety, and spatial learning and memory. Spatial learning in the Morris water maze was intact in all experimental groups. Although spatial memory retention assessed 24h following acquisition was also intact in all mice, irradiated wild type and cyclin D2 knockout mice displayed memory deficits one week after acquisition. In addition, we observed significant differences in tests addressing anxiety and locomotor activity dependent on the technique used to alter neurogenesis. Whereas irradiated mice were hyperactive regardless of their genotype, cyclin D2 knockout mice were hypoactive in most of the tests and displayed altered habituation. The present study emphasizes that different approaches aimed at decreasing adult hippocampal neurogenesis may result in distinct behavioral impairments related to locomotion and anxiety. In contrast, spatial long-term memory retention is

  12. Long-term reading and spelling outcome in Italian adolescents with a history of specific language impairment.

    PubMed

    Brizzolara, Daniela; Gasperini, Filippo; Pfanner, Lucia; Cristofani, Paola; Casalini, Claudia; Chilosi, Anna M

    2011-09-01

    Specific language impairment (SLI) diagnosed in the pre-school years is frequently associated with reading and writing difficulties at school age. The nature of this relationship is unclear, despite the availability of a large number of studies, mostly on English speaking children. Phonological processing deficits have been considered the prominent cause of both difficulties. However recent findings in both children with SLI and in children with reading difficulties are not easily accommodated within a single dimensional model explaining the relationship between oral and written language deficits. Our study focuses on the long-term reading and spelling outcome in relation to preschool oral language skills in a group of Italian adolescents with a documented history of SLI. Sixteen Italian adolescents diagnosed as SLI at our Hospital in the pre-school years and 32 normal controls were submitted to an extensive assessment of oral and written language skills. At a group level SLI adolescents had weak oral and written language skills in almost all tests. Results show that reading difficulties have some features in common with those of Italian developmental dyslexics but also have distinct characteristics, since reading accuracy and written comprehension, usually relatively spared in Italian developmental dyslexics, were impaired in adolescents with SLI. Longitudinal analyses showed that expressive morpho-syntactic and lexical abilities at pre-school age were the oral language skills that best predicted reading and spelling outcomes in adolescents with SLI. However, also children with severe phonological impairment in the absence of other oral language deficits showed later literacy difficulties, although less severe and mainly limited to reading accuracy. Our study supports the notion that there is a complex relationship between oral and written language difficulties which may change at different developmental time points, not captured by a single deficit model, but

  13. Photoperiod-mediated impairment of long-term potention and learning and memory in male white-footed mice.

    PubMed

    Walton, J C; Chen, Z; Weil, Z M; Pyter, L M; Travers, J B; Nelson, R J

    2011-02-23

    Adult mammalian brains are capable of some structural plasticity. Although the basic cellular mechanisms underlying learning and memory are being revealed, extrinsic factors contributing to this plasticity remain unspecified. White-footed mice (Peromyscus leucopus) are particularly well suited to investigate brain plasticity because they show marked seasonal changes in structure and function of the hippocampus induced by a distinct environmental signal, viz., photoperiod (i.e. the number of hours of light/day). Compared to animals maintained in 16 h of light/day, exposure to 8 h of light/day for 10 weeks induces several phenotypic changes in P. leucopus, including reduction in brain mass and hippocampal volume. To investigate the functional consequences of reduced hippocampal size, we examined the effects of photoperiod on spatial learning and memory in the Barnes maze, and on long-term potentiation (LTP) in the hippocampus, a leading candidate for a synaptic mechanism underlying spatial learning and memory in rodents. Exposure to short days for 10 weeks decreased LTP in the Schaffer collateral-CA1 pathway of the hippocampus and impaired spatial learning and memory ability in the Barnes maze. Taken together, these results demonstrate a functional change in the hippocampus in male white-footed mice induced by day length. PMID:21145376

  14. CB2 Cannabinoid Receptor Knockout in Mice Impairs Contextual Long-Term Memory and Enhances Spatial Working Memory.

    PubMed

    Li, Yong; Kim, Jimok

    2016-01-01

    Neurocognitive effects of cannabinoids have been extensively studied with a focus on CB1 cannabinoid receptors because CB1 receptors have been considered the major cannabinoid receptor in the nervous system. However, recent discoveries of CB2 cannabinoid receptors in the brain demand accurate determination of whether and how CB2 receptors are involved in the cognitive effects of cannabinoids. CB2 cannabinoid receptors are primarily involved in immune functions, but also implicated in psychiatric disorders such as schizophrenia and depression. Here, we examined the effects of CB2 receptor knockout in mice on memory to determine the roles of CB2 receptors in modulating cognitive function. Behavioral assays revealed that hippocampus-dependent, long-term contextual fear memory was impaired whereas hippocampus-independent, cued fear memory was normal in CB2 receptor knockout mice. These mice also displayed enhanced spatial working memory when tested in a Y-maze. Motor activity and anxiety of CB2 receptor knockout mice were intact when assessed in an open field arena and an elevated zero maze. In contrast to the knockout of CB2 receptors, acute blockade of CB2 receptors by AM603 in C57BL/6J mice had no effect on memory, motor activity, or anxiety. Our results suggest that CB2 cannabinoid receptors play diverse roles in regulating memory depending on memory types and/or brain areas.

  15. DCP-LA neutralizes mutant amyloid beta peptide-induced impairment of long-term potentiation and spatial learning.

    PubMed

    Nagata, Tetsu; Tomiyama, Takami; Tominaga, Takemi; Mori, Hiroshi; Yaguchi, Takahiro; Nishizaki, Tomoyuki

    2010-01-01

    Long-term potentiation (LTP) was monitored from the CA1 region of the intact rat hippocampus by delivering high frequency stimulation (HFS) to the Schaffer collateral commissural pathway. Intraventricular injection with mutant amyloid beta(1-42) peptide lacking glutamate-22 (Abeta(1-42)E22Delta), favoring oligomerization, 10 min prior to HFS, inhibited expression of LTP, with the potency more than wild-type amyloid beta(1-42) peptide. Intraperitoneal injection with the linoleic acid derivative 8-[2-(2-pentyl-cyclopropylmethyl)-cyclopropyl]-octanoic acid (DCP-LA) 70 min prior to HFS neutralized mutant Abeta(1-42)E22Delta peptide-induced LTP inhibition. In the water maze test, continuous intraventricular injection with mutant Abeta(1-42)E22Delta peptide for 14 days prolonged the acquisition latency as compared with that for control, with the potency similar to wild-type Abeta(1-42) peptide, and intraperitoneal injection with DCP-LA shortened the prolonged latency to control levels. The results of the present study indicate that DCP-LA neutralizes mutant Abeta(1-42)E22Delta peptide-induced impairment of LTP and spatial learning.

  16. CB2 Cannabinoid Receptor Knockout in Mice Impairs Contextual Long-Term Memory and Enhances Spatial Working Memory

    PubMed Central

    Li, Yong; Kim, Jimok

    2016-01-01

    Neurocognitive effects of cannabinoids have been extensively studied with a focus on CB1 cannabinoid receptors because CB1 receptors have been considered the major cannabinoid receptor in the nervous system. However, recent discoveries of CB2 cannabinoid receptors in the brain demand accurate determination of whether and how CB2 receptors are involved in the cognitive effects of cannabinoids. CB2 cannabinoid receptors are primarily involved in immune functions, but also implicated in psychiatric disorders such as schizophrenia and depression. Here, we examined the effects of CB2 receptor knockout in mice on memory to determine the roles of CB2 receptors in modulating cognitive function. Behavioral assays revealed that hippocampus-dependent, long-term contextual fear memory was impaired whereas hippocampus-independent, cued fear memory was normal in CB2 receptor knockout mice. These mice also displayed enhanced spatial working memory when tested in a Y-maze. Motor activity and anxiety of CB2 receptor knockout mice were intact when assessed in an open field arena and an elevated zero maze. In contrast to the knockout of CB2 receptors, acute blockade of CB2 receptors by AM603 in C57BL/6J mice had no effect on memory, motor activity, or anxiety. Our results suggest that CB2 cannabinoid receptors play diverse roles in regulating memory depending on memory types and/or brain areas. PMID:26819779

  17. Impaired decision making on the Balloon Analogue Risk Task as a result of long-term alcohol use.

    PubMed

    Campbell, James A; Samartgis, Jodi R; Crowe, Simon F

    2013-01-01

    The Balloon Analogue Risk Task (BART) is an experimental measure of risk taking that has commonly been employed to measure the risk taking behavior of nonclinical populations. Previous research has indicated that the task measures a unique aspect of behavioral disinhibition, but there has not as yet been focus upon the possible impact of other aspects of cognitive processing on performance. The current study investigated the cognitive factors related to performance of the BART in an alcohol-using sample. Seventeen individuals with long-term alcohol use were matched for age and education to a group of 17 nonusing participants. The results indicated that the alcohol-using group pumped the balloons on the BART to a lesser extent than did the nonusing group across all trials on the task. The results indicate that the alcohol-using group made less "optimal" decisions on the BART most notably due to neuropsychological impairment in the domains of immediate memory and executive functioning. PMID:24215387

  18. Impaired spatial memory and enhanced long-term potentiation in mice with forebrain-specific ablation of the Stim genes.

    PubMed

    Garcia-Alvarez, Gisela; Shetty, Mahesh S; Lu, Bo; Yap, Kenrick An Fu; Oh-Hora, Masatsugu; Sajikumar, Sreedharan; Bichler, Zoë; Fivaz, Marc

    2015-01-01

    Recent findings point to a central role of the endoplasmic reticulum-resident STIM (Stromal Interaction Molecule) proteins in shaping the structure and function of excitatory synapses in the mammalian brain. The impact of the Stim genes on cognitive functions remains, however, poorly understood. To explore the function of the Stim genes in learning and memory, we generated three mouse strains with conditional deletion (cKO) of Stim1 and/or Stim2 in the forebrain. Stim1, Stim2, and double Stim1/Stim2 cKO mice show no obvious brain structural defects or locomotor impairment. Analysis of spatial reference memory in the Morris water maze revealed a mild learning delay in Stim1 cKO mice, while learning and memory in Stim2 cKO mice was indistinguishable from their control littermates. Deletion of both Stim genes in the forebrain resulted, however, in a pronounced impairment in spatial learning and memory reflecting a synergistic effect of the Stim genes on the underlying neural circuits. Notably, long-term potentiation (LTP) at CA3-CA1 hippocampal synapses was markedly enhanced in Stim1/Stim2 cKO mice and was associated with increased phosphorylation of the AMPA receptor subunit GluA1, the transcriptional regulator CREB and the L-type Voltage-dependent Ca(2+) channel Cav1.2 on protein kinase A (PKA) sites. We conclude that STIM1 and STIM2 are key regulators of PKA signaling and synaptic plasticity in neural circuits encoding spatial memory. Our findings also reveal an inverse correlation between LTP and spatial learning/memory and suggest that abnormal enhancement of cAMP/PKA signaling and synaptic efficacy disrupts the formation of new memories.

  19. General Anesthesia Causes Long-term Impairment of Mitochondrial Morphogenesis and Synaptic Transmission in Developing Rat Brain

    PubMed Central

    Sanchez, Victoria; Feinstein, Shawn D.; Lunardi, Nadia; Joksovic, Pavle M.; Boscolo, Annalisa; Todorovic, Slobodan M.; Jevtovic-Todorovic, Vesna

    2011-01-01

    Background Clinically used general anesthetics, alone or in combination, are damaging to the developing mammalian brain. In addition to causing widespread apoptotic neurodegeneration in vulnerable brain regions, exposure to general anesthesia at the peak of synaptogenesis causes learning and memory deficiencies later in life. Our in-vivo rodent studies have suggested that activation of the intrinsic (mitochondria-dependent) apoptotic pathway is the earliest warning sign of neuronal damage, suggesting that a disturbance in mitochondrial integrity and function could be the earliest triggering events. Methods Since proper and timely mitochondrial morphogenesis is critical for brain development, we examined the long-term effects of a commonly used anesthesia combination (isoflurane, nitrous oxide, and midazolam) on the regional distribution, ultrastructural properties, and electron transport chain function of mitochondria, as well as synaptic neurotransmission, in the subiculum of rat pups. Results This anesthesia, administered at the peak of synaptogenesis, causes protracted injury to mitochondria, including significant enlargement of mitochondria (over 30%, p < 0.05), impairment of their structural integrity, about 28% increase in their complex IV activity (p < 0.05) and two-fold decrease in their regional distribution in presynaptic neuronal profiles (p < 0.05) where their presence is crucially important for the normal development and functioning of synapses. Consequently, we showed that impaired mitochondrial morphogenesis is accompanied by heightened autophagic activity, decrease in mitochondrial density (about 27%, p < 0.05) and long-lasting disturbances in inhibitory synaptic neurotransmission. The interrelation of these phenomena remains to be established. Conclusion Developing mitochondria are exquisitely vulnerable to general anesthesia and may be important early target of anesthesia-induced developmental neurodegeneration. PMID:21909020

  20. Long-term trends in visibility and impacts of aerosol composition on visibility impairment in Baoji, China

    NASA Astrophysics Data System (ADS)

    Xiao, S.; Wang, Q. Y.; Cao, J. J.; Huang, R.-J.; Chen, W. D.; Han, Y. M.; Xu, H. M.; Liu, S. X.; Zhou, Y. Q.; Wang, P.; Zhang, J. Q.; Zhan, C. L.

    2014-11-01

    Visibility impairment has become an important environmental issue receiving great attention from both the scientific community and the public. Long-term meteorological data from Baoji, China, were collected to investigate the trend in visibility change from 1980 to 2012. The 33-year average visual range is 12.0 km. The best 20% of the visibility observations in a calendar year shows a general decreasing trend from 1994 onwards, while the worst 20% exhibits a slight increasing trend from 1997 onwards. These results suggest the progressive degradation of air quality in Baoji in recent years. Intensive PM2.5 measurements were conducted from March 2012 to February 2013 to determine the causes of visibility impairment. An analysis based on IMPROVE equation reveals that PM2.5 organic matter (OM) contributes to 34.2% of the light extinction coefficient (bext) on an annual basis, followed by (NH4)2SO4 (30.0%), NH4NO3 (20.1%), elemental carbon (9.2%) and soil dust (6.5%). The largest contributor to bext for the Worst 20% group is (NH4)2SO4, and the contribution of NH4NO3 for the Worst 20% group increases by a factor of ~ 3 compared with the Best 20% group. Source apportionment using a positive matrix factorization receptor model indicates that secondary sulfate is the main source of PM2.5 (23.0%), followed by fugitive dust (20.5%), coal combustion (19.9%), secondary nitrate (15.5%), biomass burning (14.3%) and motor vehicle emissions (6.8%). These quantitative results could be useful for policy makers to take effective measures to control the haze pollution in Baoji. Further, the results also are likely to be relevant for other mid-sized cities in China.

  1. Impaired Global Right Ventricular Longitudinal Strain Predicts Long-Term Adverse Outcomes in Patients with Pulmonary Arterial Hypertension

    PubMed Central

    Park, Jae-Hyeong; Park, Margaret M.; Farha, Samar; Sharp, Jacqueline; Lundgrin, Erika; Comhair, Suzy; Tang, Wai Hong; Erzurum, Serpil C.

    2015-01-01

    Background New 2-dimensional strain echocardiography enables quantification of right ventricular (RV) mechanics by assessing global longitudinal strain of RV (GLSRV) in patients with pulmonary arterial hypertension (PAH). However, the prognostic significance of impaired GLSRV is unclear in these patients. Methods Comprehensive echocardiography was performed in 51 consecutive PAH patients without atrial fibrillation (40 females, 48 ± 14 years old) with long-term follow-up. GLSRV was measured with off-line with velocity vector imaging (VVI, Siemens Medical System, Mountain View, CA, USA). Results GLSRV showed significant correlation with RV fractional area change (r = -0.606, p < 0.001), tricuspid annular plane systolic excursion (r = -0.579, p < 0.001), and RV Tei index (r = 0.590, p < 0.001). It showed significant correlations with pulmonary vascular resistance (r = 0.469, p = 0.001) and B-natriuretic peptide concentration (r = 0.351, p = 0.012). During a clinical followup time (45 ± 15 months), 20 patients experienced one or more adverse events (12 death, 2 lung transplantation, and 15 heart failure hospitalization). After multivariate analysis, age [hazard ratio (HR) = 2.343, p = 0.040] and GLSRV (HR = 2.122, p = 0.040) were associated with adverse clinical events. Age (HR = 3.200, p = 0.016) and GLSRV (HR = 2.090, p = 0.042) were also significant predictors of death. Impaired GLSRV (≥ -15.5%) was associated with lower event-free survival (HR = 4.906, p = 0.001) and increased mortality (HR = 8.842, p = 0.005). Conclusion GLSRV by VVI showed significant correlations with conventional echocardiographic parameters indicating RV systolic function. Lower GLSRV (≥ -15.5%) was significantly associated with presence of adverse clinical events and deaths in PAH patients. PMID:26140151

  2. Anisomycin injection in area CA3 of the hippocampus impairs both short-term and long-term memories of contextual fear.

    PubMed

    Remaud, Jessica; Ceccom, Johnatan; Carponcy, Julien; Dugué, Laura; Menchon, Gregory; Pech, Stéphane; Halley, Helene; Francés, Bernard; Dahan, Lionel

    2014-05-15

    Protein synthesis is involved in the consolidation of short-term memory into long-term memory. Previous electrophysiological data concerning LTP in CA3 suggest that protein synthesis in that region might also be necessary for short-term memory. We tested this hypothesis by locally injecting the protein synthesis inhibitor anisomycin in hippocampal area CA1 or CA3 immediately after contextual fear conditioning. As previously shown, injections in CA1 impaired long-term memory but spared short-term memory. Conversely, injections in CA3 impaired both long-term and short-term memories. We conclude that early steps of experience-induced plasticity occurring in CA3 and underlying short-term memory require protein synthesis.

  3. Anisomycin injection in area CA3 of the hippocampus impairs both short-term and long-term memories of contextual fear.

    PubMed

    Remaud, Jessica; Ceccom, Johnatan; Carponcy, Julien; Dugué, Laura; Menchon, Gregory; Pech, Stéphane; Halley, Helene; Francés, Bernard; Dahan, Lionel

    2014-06-01

    Protein synthesis is involved in the consolidation of short-term memory into long-term memory. Previous electrophysiological data concerning LTP in CA3 suggest that protein synthesis in that region might also be necessary for short-term memory. We tested this hypothesis by locally injecting the protein synthesis inhibitor anisomycin in hippocampal area CA1 or CA3 immediately after contextual fear conditioning. As previously shown, injections in CA1 impaired long-term memory but spared short-term memory. Conversely, injections in CA3 impaired both long-term and short-term memories. We conclude that early steps of experience-induced plasticity occurring in CA3 and underlying short-term memory require protein synthesis. PMID:25171422

  4. Exposure to Kynurenic Acid during Adolescence Increases Sign-Tracking and Impairs Long-Term Potentiation in Adulthood

    PubMed Central

    DeAngeli, Nicole E.; Todd, Travis P.; Chang, Stephen E.; Yeh, Hermes H.; Yeh, Pamela W.; Bucci, David J.

    2015-01-01

    Changes in brain reward systems are thought to contribute significantly to the cognitive and behavioral impairments of schizophrenia, as well as the propensity to develop co-occurring substance abuse disorders. Presently, there are few treatments for persons with a dual diagnosis and little is known about the neural substrates that underlie co-occurring schizophrenia and substance abuse. One goal of the present study was to determine if a change in the concentration of kynurenic acid (KYNA), a tryptophan metabolite that is increased in the brains of people with schizophrenia, affects reward-related behavior. KYNA is an endogenous antagonist of NMDA glutamate receptors and α7 nicotinic acetylcholine receptors, both of which are critically involved in neurodevelopment, plasticity, and behavior. In Experiment 1, rats were treated throughout adolescence with L-kynurenine (L-KYN), the precursor of KYNA. As adults, the rats were tested drug-free in an autoshaping procedure in which a lever was paired with food. Rats treated with L-KYN during adolescence exhibited increased sign-tracking behavior (lever pressing) when they were tested as adults. Sign-tracking is thought to reflect the lever acquiring incentive salience (motivational value) as a result of its pairing with reward. Thus, KYNA exposure may increase the incentive salience of cues associated with reward, perhaps contributing to an increase in sensitivity to drug-related cues in persons with schizophrenia. In Experiment 2, we tested the effects of exposure to KYNA during adolescence on hippocampal long-term potentiation (LTP). Rats treated with L-KYN exhibited no LTP after a burst of high-frequency stimulation that was sufficient to produce robust LTP in vehicle-treated rats. This finding represents the first demonstrated consequence of elevated KYNA concentration during development and provides insight into the basis for cognitive and behavioral deficits that result from exposure to KYNA during adolescence

  5. Immune recovery in HIV-infected patients after Candida esophagitis is impaired despite long-term antiretroviral therapy

    PubMed Central

    Stuehler, Claudia; Bernardini, Claudia; Elzi, Luigia; Stoeckle, Marcel; Zimmerli, Stefan; Furrer, Hansjakob; Günthard, Huldrych F.; Leibundgut-Landmann, Salomé; Battegay, Manuel; Khanna, Nina

    2016-01-01

    Objective: Candida esophagitis belongs to the most common AIDS-defining diseases; however, a comprehensive immune pathogenic concept is lacking. Design: We investigated the immune status of 37 HIV-1-infected patients from the Swiss HIV cohort study at diagnosis of Candida esophagitis, 1 year before, 1 year later and after 2 years of suppressed HIV RNA. We compared these patients with three groups: 37 HIV-1-infected patients without Candida esophagitis but similar CD4+ cell counts as the patients at diagnosis (advanced HIV group), 15 HIV-1-infected patients with CD4+ cell counts higher than 500 cells/μl, CD4+ cell nadirs higher than 350 cells/μl and suppressed HIV RNA under combination antiretroviral therapy (cART) (early cART group) and 20 healthy individuals. Methods: We investigated phenotype, cytokine production and proliferative capacity of different immune cells by flow cytometry and enzyme-linked immunosorbent spot. Results: We found that patients with Candida esophagitis had nearly abolished CD4+ cell proliferation in response to Candida albicans, significantly increased percentages of dysfunctional CD4+ cells, significantly decreased cytotoxic natural killer cell counts and peripheral innate lymphoid cell counts and significantly reduced IFN-γ and IL-17 production compared with the early cART group and healthy individuals. Most of these defects remained for more than 2 years despite viral suppression. The advanced HIV group without opportunistic infection showed partly improved immune recovery. Conclusion: Our data indicate that Candida esophagitis in HIV-1-infected patients is caused by an accumulation of multiple, partly Candida-specific immunological defects. Long-term immune recovery is impaired, illustrating that specific immunological gaps persist despite cART. These data also support the rationale for early cART initiation to prevent irreversible immune defects. PMID:27149086

  6. Long-Term Memory: A Review and Meta-Analysis of Studies of Declarative and Procedural Memory in Specific Language Impairment

    ERIC Educational Resources Information Center

    Lum, Jarrad A. G.; Conti-Ramsden, Gina

    2013-01-01

    This review examined the status of long-term memory systems in specific language impairment (SLI)--declarative memory and aspects of procedural memory in particular. Studies included in the review were identified following a systematic search of the literature and findings combined using meta-analysis. This review showed that individuals with SLI…

  7. Long-term moderate calorie restriction inhibits inflammation without impairing cell-mediated immunity: a randomized controlled trial in non obese humans

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Calorie restriction (CR) inhibits inflammation and slows aging in many animal species, but in rodents housed in pathogen-free facilities, CR impairs immunity against certain pathogens. However, little is known about the effects of long-term moderate CR on immune function in humans. In this multi-cen...

  8. Natural amyloid-β oligomers acutely impair the formation of a contextual fear memory in mice.

    PubMed

    Kittelberger, Kara A; Piazza, Fabrizio; Tesco, Giuseppina; Reijmers, Leon G

    2012-01-01

    Memory loss is one of the hallmark symptoms of Alzheimer's disease (AD). It has been proposed that soluble amyloid-beta (Abeta) oligomers acutely impair neuronal function and thereby memory. We here report that natural Abeta oligomers acutely impair contextual fear memory in mice. A natural Abeta oligomer solution containing Abeta monomers, dimers, trimers, and tetramers was derived from the conditioned medium of 7PA2 cells, a cell line that expresses human amyloid precursor protein containing the Val717Phe familial AD mutation. As a control we used 7PA2 conditioned medium from which Abeta oligomers were removed through immunodepletion. Separate groups of mice were injected with Abeta and control solutions through a cannula into the lateral brain ventricle, and subjected to fear conditioning using two tone-shock pairings. One day after fear conditioning, mice were tested for contextual fear memory and tone fear memory in separate retrieval trials. Three experiments were performed. For experiment 1, mice were injected three times: 1 hour before and 3 hours after fear conditioning, and 1 hour before context retrieval. For experiments 2 and 3, mice were injected a single time at 1 hour and 2 hours before fear conditioning respectively. In all three experiments there was no effect on tone fear memory. Injection of Abeta 1 hour before fear conditioning, but not 2 hours before fear conditioning, impaired the formation of a contextual fear memory. In future studies, the acute effect of natural Abeta oligomers on contextual fear memory can be used to identify potential mechanisms and treatments of AD associated memory loss.

  9. Proteasome Inhibition Enhances the Induction and Impairs the Maintenance of Late-Phase Long-Term Potentiation

    ERIC Educational Resources Information Center

    Dong, Chenghai; Upadhya, Sudarshan C.; Ding, Lan; Smith, Thuy K.; Hegde, Ashok N.

    2008-01-01

    Protein degradation by the ubiquitin-proteasome pathway plays important roles in synaptic plasticity, but the molecular mechanisms by which proteolysis regulates synaptic strength are not well understood. We investigated the role of the proteasome in hippocampal late-phase long-term potentiation (L-LTP), a model for enduring synaptic plasticity.…

  10. Impairment and Abuse of Elderly by Staff in Long-Term Care in Michigan: Evidence from Structural Equation Modeling

    ERIC Educational Resources Information Center

    Conner, Tom; Prokhorov, Artem; Page, Connie; Fang, Yu; Xiao, Yimin; Post, Lori A.

    2011-01-01

    Elder abuse in long-term care has become a very important public health concern. Recent estimates of elder abuse prevalence are in the range of 2% to 10% (Lachs & Pillemer, 2004), and current changes in population structure indicate a potential for an upward trend in prevalence (Malley-Morrison, Nolido, & Chawla, 2006; Post et al., 2006). More…

  11. Risk of long term renal impairment and duration of follow up recommended for Henoch-Schönlein purpura with normal or minimal urinary findings: a systematic review

    PubMed Central

    Narchi, H

    2005-01-01

    Background: The duration of follow up to assess the risk of long term renal impairment in Henoch-Schönlein purpura (HSP) without nephritic or nephrotic syndrome or renal failure on diagnosis remains undetermined. Aims: To undertake a systematic review of the literature to assess whether the risk of long term renal impairment without renal involvement on diagnosis could be estimated and to determine the time period when renal involvement is very unlikely after the diagnosis of HSP. Methods: Search of studies of unselected children with HSP, and available information on urinary findings, renal involvement, and long term renal function follow up. Studies of selected children with HSP nephropathy at diagnosis were excluded. Results: Twelve studies of 1133 children were reviewed. The follow up period ranged from 6 weeks to 36 years. Proteinuria and/or haematuria, which occurred in 34.2%, of which only one fifth were in association with nephritic or nephrotic syndrome, developed in 85% of cases within 4 weeks of the diagnosis of HSP, in 91% within 6 weeks, and in 97% within 6 months. Permanent renal impairment never developed after normal urinalysis; it occurred in 1.6% of those with isolated urinary abnormalities, and in 19.5% of those who developed nephritic or nephrotic syndrome. Conclusion: No long term renal impairment occurred after normal urinalysis. Even if urinalysis is normal at presentation, the testing should be continued for six months. There is no need to follow up after the first six months those whose urinalysis remains normal. PMID:15871983

  12. Anthracycline-containing chemotherapy causes long-term impairment of mitochondrial respiration and increased reactive oxygen species release in skeletal muscle

    PubMed Central

    Gouspillou, Gilles; Scheede-Bergdahl, Celena; Spendiff, Sally; Vuda, Madhusudanarao; Meehan, Brian; Mlynarski, Heather; Archer-Lahlou, Elodie; Sgarioto, Nicolas; Purves-Smith, Fennigje M.; Konokhova, Yana; Rak, Janusz; Chevalier, Stéphanie; Taivassalo, Tanja; Hepple, Russell T.; Jagoe, R. Thomas

    2015-01-01

    Anticancer treatments for childhood acute lymphoblastic leukaemia (ALL) are highly effective but are now implicated in causing impaired muscle function in long-term survivors. However, no comprehensive assessment of skeletal muscle mitochondrial functions in long-term survivors has been performed and the presence of persistent chemotherapy-induced skeletal muscle mitochondrial dysfunction remains a strong possibility. Non-tumour-bearing mice were treated with two drugs that have been used frequently in ALL treatment (doxorubicin and dexamethasone) for up to 4 cycles at 3-week intervals and euthanized 3 months after the 4th cycle. Treated animals had impaired growth and lower muscle mass as well as reduced mitochondrial respiration and increased reactive oxygen species production per unit oxygen consumption. Mitochondrial DNA content and protein levels of key mitochondrial membrane proteins and markers of mitochondrial biogenesis were unchanged, but protein levels of Parkin were reduced. This suggests a novel pattern of chemotherapy-induced mitochondrial dysfunction in skeletal muscle that persists because of an acquired defect in mitophagy signaling. The results could explain the observed functional impairments in adult survivors of childhood ALL and may also be relevant to long-term survivors of other cancers treated with similar regimes. PMID:25732599

  13. Protein Carbamylation in Chronic Systolic Heart Failure: Relation to Renal Impairment and Adverse Long-Term Outcomes

    PubMed Central

    Wilson Tang, W. H.; Shrestha, Kevin; Wang, Zeneng; Borowski, Allen G.; Troughton, Richard W.; Klein, Allan L.; Hazen, Stanley L.

    2013-01-01

    Background Protein carbamylation, a post-translational modification promoted during uremia and catalyzed by myeloperoxidase (MPO) at sites of inflammation, is linked to altered protein structure, vascular dysfunction, and poor prognosis. We examine the relationship between plasma protein-bound homocitrulline (PBHCit) levels, a marker of protein lysine residue carbamylation, with cardio-renal function and long-term outcomes in chronic systolic heart failure. Methods and Results In 115 patients with chronic systolic HF (LVEF≤35%), we measured plasma PBHCit by quantitative mass spectrometry and performed comprehensive echocardiography with assessment of cardiac structure and performance. Adverse long-term events (death, cardiac transplant) were tracked for 5 years. In our study cohort, the median PBHCit level was 87 [IQR: 59, 128] μmol/mol Lysine. Higher plasma PBHcit levels were associated with poorer renal function (eGFR Spearman’s r= −0.37, p<0.001); cystatin C (r=0.31, p=0.001), and elevated plasma NT-proBNP levels (r= 0.26, 0.006), but not with markers of systemic inflammation or oxidant stress (hsCRP and MPO, p>0.10 for each). Furthermore, elevated plasma PBHCit levels were not related to indices of cardiac structure or function (p>0.10 for all examined) except modestly with increased right atrial volume index (RAVi; r=0.31, p=0.002). PBHCit levels predicted adverse long-term events (Hazard ratio [HR]: 1.8, 95% CI 1.3– 2.6, p<0.001), including following adjustment for age, eGFR, MPO and NT-proBNP (HR: 1.9, 95% CI: 1.2–3.1, p=0.006). Conclusions In chronic systolic HF, protein carbamylation is associated with poorer renal but not cardiac function, and portends poorer long-term adverse clinical outcomes even when adjusted for cardio-renal indices of adverse prognosis. PMID:23582087

  14. Regular Exercise Prevents Sleep Deprivation Associated Impairment of Long-Term Memory and Synaptic Plasticity in The CA1 Area of the Hippocampus

    PubMed Central

    Zagaar, Munder; Dao, An; Levine, Amber; Alhaider, Ibrahim; Alkadhi, Karim

    2013-01-01

    Study Objectives: The present study aimed to investigate the effects of treadmill exercise on sleep deprivation (S-D)-induced impairment of hippocampal dependent long-term memory, late phase long-term potentiation (L-LTP) and its signaling cascade in the cornu ammonis 1 (CA1) area. Experimental Design: Animals were conditioned to run on treadmills for 4 weeks then deprived of sleep for 24 h using the columns-in-water method. We tested the effect of exercise and/or S-D on behavioral performance using a post-learning paradigm in the radial arm water maze (RAWM) and in vivo extracellular recording in the CA1 area. The levels of L-LTP-related molecules in the CA1 area were then assessed both before and after L-LTP induction. Measurements and Results: After 24 h of S-D, spatial long-term memory impairment in the RAWM and L-LTP suppression was prevented by 4 weeks of regular exercise. Regular exercise also restored the S-D-associated decreases in the basal levels of key signaling molecules such as: calcium/calmodulin kinase IV (CaMKIV), mitogen-activated protein kinase (MAPK/ERK), phosphorylated cAMP response element-binding protein (P-CREB) and brain derived neurotrophic factor (BDNF), in the CA1 area. After L-LTP induction, regular exercise also prevented the S-D-induced down regulation of BDNF and P-CREB protein levels. Conclusions: The results suggest that our exercise protocol may prevent 24-h S-D-induced impairments in long-term memory and LTP by preventing deleterious changes in the basal and post-stimulation levels of P-CREB and BDNF associated with S-D. Citation: Zagaar M; Dao A; Levine A; Alhaider I; Alkadhi K. Regular exercise prevents sleep deprivation associated impairment of long-term memory and synaptic plasticity in the CA1 area of the hippocampus. SLEEP 2013;36(5):751-761. PMID:23633758

  15. Mice lacking the PSD-95-interacting E3 ligase, Dorfin/Rnf19a, display reduced adult neurogenesis, enhanced long-term potentiation, and impaired contextual fear conditioning.

    PubMed

    Park, Hanwool; Yang, Jinhee; Kim, Ryunhee; Li, Yan; Lee, Yeunkum; Lee, Chungwoo; Park, Jongil; Lee, Dongmin; Kim, Hyun; Kim, Eunjoon

    2015-11-10

    Protein ubiquitination has a significant influence on diverse aspects of neuronal development and function. Dorfin, also known as Rnf19a, is a RING finger E3 ubiquitin ligase implicated in amyotrophic lateral sclerosis and Parkinson's disease, but its in vivo functions have not been explored. We report here that Dorfin is a novel binding partner of the excitatory postsynaptic scaffolding protein PSD-95. Dorfin-mutant (Dorfin(-/-)) mice show reduced adult neurogenesis and enhanced long-term potentiation in the hippocampal dentate gyrus, but normal long-term potentiation in the CA1 region. Behaviorally, Dorfin(-/-) mice show impaired contextual fear conditioning, but normal levels of cued fear conditioning, fear extinction, spatial learning and memory, object recognition memory, spatial working memory, and pattern separation. Using a proteomic approach, we also identify a number of proteins whose ubiquitination levels are decreased in the Dorfin(-/-) brain. These results suggest that Dorfin may regulate adult neurogenesis, synaptic plasticity, and contextual fear memory.

  16. EphrinA4 mimetic peptide targeted to EphA binding site impairs the formation of long-term fear memory in lateral amygdala.

    PubMed

    Dines, M; Lamprecht, R

    2014-09-30

    Fear conditioning leads to long-term fear memory formation and is a model for studying fear-related psychopathologies conditions such as phobias and posttraumatic stress disorder. Long-term fear memory formation is believed to involve alterations of synaptic efficacy mediated by changes in synaptic transmission and morphology in lateral amygdala (LA). EphrinA4 and its cognate Eph receptors are intimately involved in regulating neuronal morphogenesis, synaptic transmission and plasticity. To assess possible roles of ephrinA4 in fear memory formation we designed and used a specific inhibitory ephrinA4 mimetic peptide (pep-ephrinA4) targeted to EphA binding site. We show that this peptide, composed of the ephrinA4 binding domain, interacts with EphA4 and inhibits ephrinA4-induced phosphorylation of EphA4. Microinjection of the pep-ephrinA4 into rat LA 30 min before training impaired long- but not short-term fear conditioning memory. Microinjection of a control peptide derived from a nonbinding E helix site of ephrinA4, that does not interact with EphA, had no effect on fear memory formation. Microinjection of pep-ephrinA4 into areas adjacent to the amygdala had no effect on fear memory. Acute systemic administration of pep-ephrinA4 1 h after training also impaired long-term fear conditioning memory formation. These results demonstrate that ephrinA4 binding sites in LA are essential for long-term fear memory formation. Moreover, our research shows that ephrinA4 binding sites may serve as a target for pharmacological treatment of fear and anxiety disorders.

  17. Apolipoprotein E4 impairs in vivo hippocampal long-term synaptic plasticity by reducing the phosphorylation of CaMKIIα and CREB.

    PubMed

    Qiao, Feng; Gao, Xiu-Ping; Yuan, Li; Cai, Hong-Yan; Qi, Jin-Shun

    2014-01-01

    Inheritance of the apolipoprotein E genotype ε4 (APOE4) is a powerful risk factor for most cases of late-onset Alzheimer's disease (AD). However, the effects of ApoE4 on the long-term synaptic plasticity and its underlying mechanism have not clearly investigated. In the present study, we examined the effects of ApoE4 on the hippocampal late-phase long-term potentiation (L-LTP) and investigated its probable molecular mechanisms by using in vivo field potential recording, immunohistochemistry, and western blotting. The results showed that: (1) intra-hippocampal injection of 0.2 μg ApoE4, but not ApoE2, before high frequency stimulations (HFSs) attenuated the induction of hippocampal L-LTP in the CA1 region, while injection of the same concentration of ApoE4 after HFSs, even at a higher concentration (2 μg), did not affect the long term synaptic plasticity; (2) ApoE4 injection did not affect the paired pulse facilitation in the hippocampal CA1 region; (3) ApoE4 injection before, not after, HFSs significantly decreased the levels of phosphorylated Ca2+/calmodulin-dependent protein kinase IIα (p-CaMKIIα) and phosphorylated cAMP response element-binding protein (p-CREB) in the hippocampus. These results demonstrated for the first time that ApoE4 could impair hippocampal L-LTP by reducing p-CaMKIIα and p-CREB, suggesting that the ApoE4-induced suppression of hippocampal long-term synaptic plasticity may contribute to the cognitive impairments in genetic AD; and both CaMKIIα and CREB are important intracellular targets of the neurotoxic ApoE4.

  18. Soluble amyloid-β oligomers as synaptotoxins leading to cognitive impairment in Alzheimer's disease.

    PubMed

    Ferreira, Sergio T; Lourenco, Mychael V; Oliveira, Mauricio M; De Felice, Fernanda G

    2015-01-01

    Alzheimer's disease (AD) is the most common form of dementia in the elderly, and affects millions of people worldwide. As the number of AD cases continues to increase in both developed and developing countries, finding therapies that effectively halt or reverse disease progression constitutes a major research and public health challenge. Since the identification of the amyloid-β peptide (Aβ) as the major component of the amyloid plaques that are characteristically found in AD brains, a major effort has aimed to determine whether and how Aβ leads to memory loss and cognitive impairment. A large body of evidence accumulated in the past 15 years supports a pivotal role of soluble Aβ oligomers (AβOs) in synapse failure and neuronal dysfunction in AD. Nonetheless, a number of basic questions, including the exact molecular composition of the synaptotoxic oligomers, the identity of the receptor(s) to which they bind, and the signaling pathways that ultimately lead to synapse failure, remain to be definitively answered. Here, we discuss recent advances that have illuminated our understanding of the chemical nature of the toxic species and the deleterious impact they have on synapses, and have culminated in the proposal of an Aβ oligomer hypothesis for Alzheimer's pathogenesis. We also highlight outstanding questions and challenges in AD research that should be addressed to allow translation of research findings into effective AD therapies. PMID:26074767

  19. The representational consequences of intentional forgetting: Impairments to both the probability and fidelity of long-term memory.

    PubMed

    Fawcett, Jonathan M; Lawrence, Michael A; Taylor, Tracy L

    2016-01-01

    We investigated whether intentional forgetting impacts only the likelihood of later retrieval from long-term memory or whether it also impacts the fidelity of those representations that are successfully retrieved. We accomplished this by combining an item-method directed forgetting task with a testing procedure and modeling approach inspired by the delayed-estimation paradigm used in the study of visual short-term memory (STM). Abstract or concrete colored images were each followed by a remember (R) or forget (F) instruction and sometimes by a visual probe requiring a speeded detection response (E1-E3). Memory was tested using an old-new (E1-E2) or remember-know-no (E3) recognition task followed by a continuous color judgment task (E2-E3); a final experiment included only the color judgment task (E4). Replicating the existing literature, more "old" or "remember" responses were made to R than F items and RTs to postinstruction visual probes were longer following F than R instructions. Color judgments were more accurate for successfully recognized or recollected R than F items (E2-E3); a mixture model confirmed a decrease to both the probability of retrieving the F items as well as the fidelity of the representation of those F items that were retrieved (E4). We conclude that intentional forgetting is an effortful process that not only reduces the likelihood of successfully encoding an item for later retrieval, but also produces an impoverished memory trace even when those items are retrieved; these findings draw a parallel between the control of memory representations within working and long-term memory. PMID:26709589

  20. Environmental enrichment improves age-related immune system impairment: long-term exposure since adulthood increases life span in mice.

    PubMed

    Arranz, Lorena; De Castro, Nuria M; Baeza, Isabel; Maté, Ianire; Viveros, Maria Paz; De la Fuente, Mónica

    2010-08-01

    Age-related changes in immunity have been shown to highly influence morbidity and mortality. The aim of the present work was to study the effects of environmental enrichment (EE) (8-16 weeks) on several functions and oxidative stress parameters of peritoneal leukocytes, previously described as health and longevity markers, in mice at different ages, namely adult (44 +/- 4 weeks), old (69 +/- 4 weeks), and very old (92 +/- 4 weeks). Mortality rates were monitored in control and enriched animals, and effects on survival of long-term exposure to EE until natural death were determined. The results showed that exposure to EE was efficient in improving the function (i.e., macrophage chemotaxis and phagocytosis, lymphocyte chemotaxis and proliferation, natural killer cell activity, interleukin-2 and tumor necrosis factor-alpha levels) and decreasing the oxidative-inflammatory stress (i.e., lowered oxidized glutathione content, xanthine oxidase activity, expression of Toll-like receptors 2 and 4 on CD4 and CD8 cells, and increased reduced glutathione and glutathione peroxidase and catalase activities) of immune cells. These positive effects of EE were especially remarkable in animals at older ages. Importantly, long-term exposure to EE from adult age and until natural death stands out as a useful strategy to extend longevity. Thus, the present work confirms the importance of maintaining active mental and/or physical activity aiming to improve quality of life in terms of immunity, and demonstrates that this active life must be initiated at early stages of the aging process and preserved until death to improve life span.

  1. The Representational Consequences of Intentional Forgetting: Impairments to Both the Probability and Fidelity of Long-Term Memory

    PubMed Central

    2016-01-01

    We investigated whether intentional forgetting impacts only the likelihood of later retrieval from long-term memory or whether it also impacts the fidelity of those representations that are successfully retrieved. We accomplished this by combining an item-method directed forgetting task with a testing procedure and modeling approach inspired by the delayed-estimation paradigm used in the study of visual short-term memory (STM). Abstract or concrete colored images were each followed by a remember (R) or forget (F) instruction and sometimes by a visual probe requiring a speeded detection response (E1–E3). Memory was tested using an old–new (E1–E2) or remember-know-no (E3) recognition task followed by a continuous color judgment task (E2–E3); a final experiment included only the color judgment task (E4). Replicating the existing literature, more “old” or “remember” responses were made to R than F items and RTs to postinstruction visual probes were longer following F than R instructions. Color judgments were more accurate for successfully recognized or recollected R than F items (E2–E3); a mixture model confirmed a decrease to both the probability of retrieving the F items as well as the fidelity of the representation of those F items that were retrieved (E4). We conclude that intentional forgetting is an effortful process that not only reduces the likelihood of successfully encoding an item for later retrieval, but also produces an impoverished memory trace even when those items are retrieved; these findings draw a parallel between the control of memory representations within working and long-term memory. PMID:26709589

  2. The representational consequences of intentional forgetting: Impairments to both the probability and fidelity of long-term memory.

    PubMed

    Fawcett, Jonathan M; Lawrence, Michael A; Taylor, Tracy L

    2016-01-01

    We investigated whether intentional forgetting impacts only the likelihood of later retrieval from long-term memory or whether it also impacts the fidelity of those representations that are successfully retrieved. We accomplished this by combining an item-method directed forgetting task with a testing procedure and modeling approach inspired by the delayed-estimation paradigm used in the study of visual short-term memory (STM). Abstract or concrete colored images were each followed by a remember (R) or forget (F) instruction and sometimes by a visual probe requiring a speeded detection response (E1-E3). Memory was tested using an old-new (E1-E2) or remember-know-no (E3) recognition task followed by a continuous color judgment task (E2-E3); a final experiment included only the color judgment task (E4). Replicating the existing literature, more "old" or "remember" responses were made to R than F items and RTs to postinstruction visual probes were longer following F than R instructions. Color judgments were more accurate for successfully recognized or recollected R than F items (E2-E3); a mixture model confirmed a decrease to both the probability of retrieving the F items as well as the fidelity of the representation of those F items that were retrieved (E4). We conclude that intentional forgetting is an effortful process that not only reduces the likelihood of successfully encoding an item for later retrieval, but also produces an impoverished memory trace even when those items are retrieved; these findings draw a parallel between the control of memory representations within working and long-term memory.

  3. NLRP3 inflammasome activation by mitochondrial reactive oxygen species plays a key role in long-term cognitive impairment induced by paraquat exposure.

    PubMed

    Chen, Liuji; Na, Ren; Boldt, Erin; Ran, Qitao

    2015-09-01

    Exposure to environmental toxins such as pesticides is implicated in increasing Alzheimer's disease risk. In this study, we investigated the long-term effects of paraquat exposure on cognition of Alzheimer's disease animal model APP/PS1 mice and wild-type (WT) mice. Our results showed that APP/PS1 mice had exacerbated cognition impairment and elevated Aβ levels at 5 months after paraquat exposure, and that WT mice had cognition impairment at 5 and 16 months after paraquat exposure. In addition, increased mitochondrial oxidative stress and augmented brain inflammation were observed in both paraquat-exposed APP/PS1 mice and WT mice. Interestingly, activation of NLRP3 inflammasome, which triggers inflammation in response to mitochondrial stress, was enhanced in paraquat-exposed mice. Moreover, transgenic mice overexpressing Prdx3, a key enzyme in detoxifying mitochondrial H2O2, had suppressed NLRP3 inflammasome activation, reduced brain inflammation, and attenuated cognition impairment after paraquat exposure. Together, our results indicate that NLRP3 inflammasome activation induced by mitochondrial reactive oxygen species plays a key role in mediating paraquat-induced long-term cognition decline by elevating brain inflammation. PMID:26119225

  4. Reconsolidation of a long-term spatial memory is impaired by cycloheximide when reactivated with a contextual latent learning trial in male and female rats.

    PubMed

    Flint, R W; Valentine, S; Papandrea, D

    2007-09-21

    Reconsolidation of long-term memory has become a topic of great interest in recent years, and has the potential to provide important information regarding memory processes and the treatment of memory-related disorders. The present study examined the role of systemic protein synthesis inhibition in reconsolidation of a long-term spatial memory reactivated by a contextual latent learning trial in male and female rats. Using the Morris water maze, we demonstrate that: 1) a contextual latent reactivation treatment enhances memory, 2) systemic protein synthesis inhibition selectively impairs test performance when administered in conjunction with a memory reactivation treatment, and 3) that these effects are more pronounced in female rats. These findings indicate a role for protein synthesis in the reconsolidation of a contextually reactivated long-term spatial memory using the water maze, and a potential differential effect of sex in this apparatus. The role of the strength of the memory trace is discussed and the relevance of these findings to theories of reconsolidation and therapeutic treatment of post-traumatic stress disorder is discussed. PMID:17766047

  5. Reconsolidation of a long-term spatial memory is impaired by cycloheximide when reactivated with a contextual latent learning trial in male and female rats.

    PubMed

    Flint, R W; Valentine, S; Papandrea, D

    2007-09-21

    Reconsolidation of long-term memory has become a topic of great interest in recent years, and has the potential to provide important information regarding memory processes and the treatment of memory-related disorders. The present study examined the role of systemic protein synthesis inhibition in reconsolidation of a long-term spatial memory reactivated by a contextual latent learning trial in male and female rats. Using the Morris water maze, we demonstrate that: 1) a contextual latent reactivation treatment enhances memory, 2) systemic protein synthesis inhibition selectively impairs test performance when administered in conjunction with a memory reactivation treatment, and 3) that these effects are more pronounced in female rats. These findings indicate a role for protein synthesis in the reconsolidation of a contextually reactivated long-term spatial memory using the water maze, and a potential differential effect of sex in this apparatus. The role of the strength of the memory trace is discussed and the relevance of these findings to theories of reconsolidation and therapeutic treatment of post-traumatic stress disorder is discussed.

  6. Impairment of basal forebrain cholinergic neurons associated with aging and long-term loss of ovarian function.

    PubMed

    Gibbs, R B

    1998-06-01

    Recent studies suggest that women are at greater risk for Alzheimer's disease than men and that estrogen replacement can help to reduce the risk and severity of Alzheimer's-related dementia in postmenopausal women. We have hypothesized that the increased risk for Alzheimer's-related dementia is due, in part, to the loss of ovarian function in postmenopausal women and to the effects that decreased levels of ovarian hormones have on basal forebrain cholinergic function. In the present study, the effects of aging and ovariectomy on cholinergic neurons in the rat basal forebrain were examined to determine (1) whether aging differentially affects cholinergic neurons in the basal forebrain of males vs females, and (2) whether long-term loss of ovarian function produces deficits in basal forebrain cholinergic function beyond those associated with aging and sex. In part I of the study, gonadally intact male and female rats were sacrificed at 13, 19, and 25 months of age and the effects of aging on cholinergic neurons in the medial septum (MS) and nucleus basalis magnocellularis (NBM) were compared. In part II of the study, female rats were ovariectomized at 13 months of age and then sacrificed 3 and 6 months later along with gonadally intact, age-matched controls. Adjacent sections through the MS and NBM were processed for either immunocytochemical detection of choline acetyltransferase (ChAT) and p75NTR-like immunoreactivity or for in situ hybridization detection and quantification of ChAT and trkA mRNA. Results from part I revealed no significant effects of age on the relative size or density of cholinergic neurons in the MS and NBM of gonadally intact animals. Likewise, no significant effects on the relative numbers of cholinergic neurons expressing p75NTR protein were detected. However, a significant decrease in trkA mRNA was detected in the MS of gonadally intact females, but not males, between 13 and 25 months of age. No significant effects of aging on ChAT mRNA were

  7. Long-term but not short-term blockade of dopamine release in Drosophila impairs orientation during flight in a visual attention paradigm.

    PubMed

    Ye, Yizhou; Xi, Wang; Peng, Yueqing; Wang, Yizheng; Guo, Aike

    2004-08-01

    Dopamine is a major neuromodulator in both vertebrates and invertebrates and has profound effects on many physiological processes, including the regulation of attention. Most studies of the functions of dopamine use models with long-term blockade of dopamine release and few effects of transient blockade have yet been reported. The goal of the present study was to determine the role of dopamine in attention-like behavior in Drosophila by taking advantage of the fly's orientation behavior during flight. The examination of several different transgenic flies in a single-target visual attention paradigm showed that flies lost their orientation ability if dopamine release was blocked from the beginning of the development of dopaminergic neurons. This is similar to the attention loss in mammals. However, if the blockade of dopamine release was induced during the experimental procedure, flies performed normally. Statistical analysis of the behavioral assessment showed a significant difference between long-term and transient blockade. Using the RNA interference approach, we generated flies with down-regulated J-domain protein, which is a potential cochaperone in synaptic vesicle release, to make an alternative form of long-term dopamine-blockade mutant. Behavioral assays revealed that flies with permanent J-domain protein down-regulation specifically in dopaminergic neurons have an attention defect similar to that induced by long-term blockade of dopamine release. Furthermore, dopamine depletion beginning at eclosion also caused an attention deficit. Our results indicate that prolonged but not transient blockade of dopamine release impairs visual attention-like behavior in Drosophila.

  8. Long-term exposure to decabrominated diphenyl ether impairs CD8 T-cell function in adult mice

    PubMed Central

    Zeng, Weihong; Wang, Ying; Liu, Zhicui; Khanniche, Asma; Hu, Qingliang; Feng, Yan; Ye, Weiyi; Yang, Jianglong; Wang, Shujun; Zhou, Lin; Shen, Hao; Wang, Yan

    2014-01-01

    Polybrominated diphenyl ethers (PBDEs) are ubiquitous environmental pollutants that accumulate to high levels in human populations that are subject to occupational or regional industry exposure. PBDEs have been shown to affect human neuronal, endocrine and reproductive systems, but their effect on the immune system is not well understood. In this study, experimental adult mice were intragastrically administered 2,2′,3,3′,4,4′,5,5′,6,6′-decabromodiphenyl ether (BDE-209) at doses of 8, 80 or 800 mg/kg of body weight (bw) at 2-day intervals. Our results showed that continuous exposure to BDE-209 resulted in high levels of BDE-209 in the plasma that approached the levels found in people who work in professions with high risks of PDBE exposure. Reduced leukocytes, decreased cytokine (IFN-γ, IL-2 and TNF-α) production and lower CD8 T-cell proliferation were observed in the mice exposed to BDE-209. Additionally, mice with long-term BDE-209 exposure had lower numbers of antigen-specific CD8 T cells after immunization with recombinant Listeria monocytogenes expressing ovalbumin (rLm-OVA) and the OVA-specific CD8 T cells had reduced functionality. Taken together, our study demonstrates that continuous BDE-209 exposure causes adverse effects on the number and functionality of immune cells in adult mice. PMID:24705197

  9. Neuronal fibrillogenesis: amyloid fibrils from primary neuronal cultures impair long-term memory in the crab Chasmagnathus.

    PubMed

    Romano, Arturo; Serafino, Annalucia; Krasnowska, Ewa; Ciotti, Maria Teresa; Calissano, Pietro; Ruberti, Francesca; Galli, Cinzia

    2003-12-17

    Amyloid beta protein (Abeta) fibrillogenesis is considered one of the crucial steps of Alzheimer's disease (AD) pathogenesis. The effect of endogenous neuronal amyloid fibrils on memory processes is unknown. To investigate this issue, we first characterised the Abeta fibrillar aggregates secreted by cerebellar granule cells and then we evaluated the effect of neuronal fibrils on an invertebrate model of memory. An increase of fibril formation, assessed by Thioflavin T (ThT) fluorescence, was observed in the conditioned medium of apoptotic neurons during 48 h of the apoptotic process. Moreover, the depolarisation-stimulated secretion of cerebellar granule cells contains monomers of endogenous Abeta, which undergo cell-free fibrillogenesis over several days of incubation. The pattern of single endogenous fibrils, examined by electron microscopy, was similar to that of synthetic Abeta while a tighter and more complex interfibrillar organization was observed in endogenous fibrils. The biological effect of neuronal fibrils was studied in a long-term memory (LTM) paradigm, namely the context-signal learning of the crab Chasmagnathus. Pre-training injection of neuronal fibril extract (protein concentration, 1 microg/ml) induced amnesia in a dose-dependent manner. On the contrary, no effect on retention was observed with the administration of two orders higher doses (100 microg/ml) of synthetic Abeta1-40. These results indicate that only naturally secreted fibrils, but not synthetic Abeta, clearly interfere with memory process.

  10. Impaired recruitment of seizure-generated neurons into functional memory networks of the adult dentate gyrus following long-term amygdala kindling.

    PubMed

    Fournier, Neil M; Botterill, Justin J; Marks, Wendie N; Guskjolen, Axel J; Kalynchuk, Lisa E

    2013-06-01

    Epileptic seizures increase the birth of new neurons in the adult hippocampus. Although the consequences of aberrant neurogenesis on behavior are not fully understood, one hypothesis is that seizure-generated neurons might form faulty circuits that disrupt hippocampal functions, such as learning and memory. In the present study, we employed long-term amygdala kindling (i.e., rats receive 99-electrical stimulations) to examine the effect of repeated seizures on hippocampal neurogenesis and behavior. We labeled seizure-generated cells with the proliferation marker BrdU after 30-stimulations and continued kindling for an additional 4weeks to allow newborn neurons to mature under conditions of repeated seizures. After kindling was complete, rats were tested in a trace fear conditioning task and sacrificed 2h later to examine if 4-week old newborn cells were recruited into circuits involved in the retrieval of emotional memory. Compared to non-kindled controls, long-term kindled rats showed significant impairments in fear memory reflected in a decrease in conditioned freezing to both tone and contextual cues during testing. Moreover, long-term kindling also prevented the activation of 4-week old newborn cells in response to fear memory retrieval. These results indicate that the presence of seizure activity during cell maturation impedes the ability of new neurons to integrate properly into circuits important in memory formation. Together, our findings suggest that aberrant seizure-induced neurogenesis might contribute to the development of learning impairments in chronic epilepsy and raise the possibility that targeting the reduced activation of adult born neurons could represent a beneficial strategy to reverse cognitive deficits in some epileptic patients.

  11. Long-term moderate calorie restriction inhibits inflammation without impairing cell-mediated immunity: a randomized controlled trial in non-obese humans.

    PubMed

    Meydani, Simin N; Das, Sai K; Pieper, Carl F; Lewis, Michael R; Klein, Sam; Dixit, Vishwa D; Gupta, Alok K; Villareal, Dennis T; Bhapkar, Manjushri; Huang, Megan; Fuss, Paul J; Roberts, Susan B; Holloszy, John O; Fontana, Luigi

    2016-07-01

    Calorie restriction (CR) inhibits inflammation and slows aging in many animal species, but in rodents housed in pathogen-free facilities, CR impairs immunity against certain pathogens. However, little is known about the effects of long-term moderate CR on immune function in humans. In this multi-center, randomized clinical trial to determine CR's effect on inflammation and cell-mediated immunity, 218 healthy non-obese adults (20-50 y), were assigned 25% CR (n=143) or an ad-libitum (AL) diet (n=75), and outcomes tested at baseline, 12, and 24 months of CR. CR induced a 10.4% weight loss over the 2-y period. Relative to AL group, CR reduced circulating inflammatory markers, including total WBC and lymphocyte counts, ICAM-1 and leptin. Serum CRP and TNF-α concentrations were about 40% and 50% lower in CR group, respectively. CR had no effect on the delayed-type hypersensitivity skin response or antibody response to vaccines, nor did it cause difference in clinically significant infections. In conclusion, long-term moderate CR without malnutrition induces a significant and persistent inhibition of inflammation without impairing key in vivo indicators of cell-mediated immunity. Given the established role of these pro-inflammatory molecules in the pathogenesis of multiple chronic diseases, these CR-induced adaptations suggest a shift toward a healthy phenotype. PMID:27410480

  12. Post-Weaning Protein Malnutrition in the Rat Produces Short and Long Term Metabolic Impairment, in Contrast to Earlier and Later Periods

    PubMed Central

    del Carmen Miñana-Solis, María; Escobar, Carolina

    2008-01-01

    Malnutrition during gestation and lactation modifies metabolic strategies and leads to metabolic disease in adult life. Studies in human populations suggest that malnutrition during infancy may also induce long term metabolic disorders. The present study investigated if post-weaning and a late period of development might be sensitive for long term metabolic impairment. Hereto male Wistar rats were malnourished with a low protein diet (6%), during gestation and lactation (MGL), from weaning to 55 days (MPW) or during adulthood from 90 to 120 days (MA). Control rats (C) were fed with a regular diet (23% protein). We determine plasma concentrations of insulin, glucagon, triacylglycerols (TAG), free fatty acids (FFA), and liver glycogen after a Glucose Tolerance Test (GTT). Independent of the age of onset, malnutrition induced low body weight. Early and post-weaning malnutrition produced impaired glucose tolerance and low values of TAG, also in MPW induced low values of insulin and glucagon. At 90 days, after balanced diet rehabilitation, the MGL group showed a similar glucose tolerance test as the controls but display low values of insulin, while the MPW group exhibited high levels of glucose and TAG, and low values of insulin, glucagon, FFA and hepatic glycogen. At 180 days, after balanced rehabilitation only MPW rats showed metabolic alterations. Malnutrition during adult life (MA) did not produce metabolic disturbances. Surprisingly the results uncover the post-weaning stage as a vulnerable period to malnutrition that induces long lasting metabolic alterations and deficiency in pancreatic function. PMID:19043606

  13. Long-term moderate calorie restriction inhibits inflammation without impairing cell-mediated immunity: a randomized controlled trial in non-obese humans.

    PubMed

    Meydani, Simin N; Das, Sai K; Pieper, Carl F; Lewis, Michael R; Klein, Sam; Dixit, Vishwa D; Gupta, Alok K; Villareal, Dennis T; Bhapkar, Manjushri; Huang, Megan; Fuss, Paul J; Roberts, Susan B; Holloszy, John O; Fontana, Luigi

    2016-07-01

    Calorie restriction (CR) inhibits inflammation and slows aging in many animal species, but in rodents housed in pathogen-free facilities, CR impairs immunity against certain pathogens. However, little is known about the effects of long-term moderate CR on immune function in humans. In this multi-center, randomized clinical trial to determine CR's effect on inflammation and cell-mediated immunity, 218 healthy non-obese adults (20-50 y), were assigned 25% CR (n=143) or an ad-libitum (AL) diet (n=75), and outcomes tested at baseline, 12, and 24 months of CR. CR induced a 10.4% weight loss over the 2-y period. Relative to AL group, CR reduced circulating inflammatory markers, including total WBC and lymphocyte counts, ICAM-1 and leptin. Serum CRP and TNF-α concentrations were about 40% and 50% lower in CR group, respectively. CR had no effect on the delayed-type hypersensitivity skin response or antibody response to vaccines, nor did it cause difference in clinically significant infections. In conclusion, long-term moderate CR without malnutrition induces a significant and persistent inhibition of inflammation without impairing key in vivo indicators of cell-mediated immunity. Given the established role of these pro-inflammatory molecules in the pathogenesis of multiple chronic diseases, these CR-induced adaptations suggest a shift toward a healthy phenotype.

  14. Long-term moderate calorie restriction inhibits inflammation without impairing cell-mediated immunity: a randomized controlled trial in non-obese humans

    PubMed Central

    Meydani, Simin N.; Das, Sai K.; Pieper, Carl F.; Lewis, Michael R.; Klein, Sam; Dixit, Vishwa D.; Gupta, Alok K.; Villareal, Dennis T.; Bhapkar, Manjushri; Huang, Megan; Fuss, Paul J.; Roberts, Susan B.; Holloszy, John O.; Fontana, Luigi

    2016-01-01

    Calorie restriction (CR) inhibits inflammation and slows aging in many animal species, but in rodents housed in pathogen-free facilities, CR impairs immunity against certain pathogens. However, little is known about the effects of long-term moderate CR on immune function in humans. In this multi-center, randomized clinical trial to determine CR's effect on inflammation and cell-mediated immunity, 218 healthy non-obese adults (20-50 y), were assigned 25% CR (n=143) or an ad-libitum (AL) diet (n=75), and outcomes tested at baseline, 12, and 24 months of CR. CR induced a 10.4% weight loss over the 2-y period. Relative to AL group, CR reduced circulating inflammatory markers, including total WBC and lymphocyte counts, ICAM-1 and leptin. Serum CRP and TNF-α concentrations were about 40% and 50% lower in CR group, respectively. CR had no effect on the delayed-type hypersensitivity skin response or antibody response to vaccines, nor did it cause difference in clinically significant infections. In conclusion, long-term moderate CR without malnutrition induces a significant and persistent inhibition of inflammation without impairing key in vivo indicators of cell-mediated immunity. Given the established role of these pro-inflammatory molecules in the pathogenesis of multiple chronic diseases, these CR-induced adaptations suggest a shift toward a healthy phenotype. PMID:27410480

  15. Levothyroxine rescues the lead-induced hypothyroidism and impairment of long-term potentiation in hippocampal CA1 region of the developmental rats

    SciTech Connect

    Wu Chuanyun; Liu Bing; Wang Huili; Ruan Diyun

    2011-10-15

    Lead (Pb) exposure during development has been associated with impaired long-term potentiation (LTP). Hypothyroidism happening upon subjects with occupational exposure to Pb is suggestive of an adverse effect of Pb on thyroid homeostasis, leading to the hypothesis that Pb exposure may alter thyroid hormone homeostasis. Hippocampus is one of the targets of Pb exposure, and is sensitive to and dependent on thyroid hormones, leading us to explore whether levothyroxine (L-T{sub 4}) administration could alter the thyroid disequilibrium and impairment of LTP in rat hippocampus caused by Pb exposure. Our results show that Pb exposure caused a decrease in triiodothyronine (T{sub 3}) and tetraiodothyronine (T{sub 4}) levels accompanied by a dramatic decrease of TSH and application of L-T{sub 4} restored these changes to about control levels. Hippocampal and blood Pb concentration were significantly reduced following L-T{sub 4} treatment. L-T{sub 4} treatment rescued the impairment of LTP induced by the Pb exposure. These results suggest that Pb exposure may lead to thyroid dysfunction and induce hypothyroidism and provide a direct electrophysiological proof that L-T{sub 4} relieves chronic Pb exposure-induced impairment of synaptic plasticity. - Highlights: > Lead may interfere with thyroid hormone homeostasis and induce hypothyroidism. > Levothyroxine decreases the hippocampal and blood Pb concentration. > Levothyroxine amends the T{sub 3}, T{sub 4} and TSH levels in blood. > Levothyroxine rescues the impaired LTP in CA1.

  16. Overexpression of αCaMKII impairs behavioral flexibility and NMDAR-dependent long-term depression in the medial prefrontal cortex.

    PubMed

    Ma, J; Duan, Y; Qin, Z; Wang, J; Liu, W; Xu, M; Zhou, S; Cao, X

    2015-12-01

    The medial prefrontal cortex (mPFC) participates in the behavioral flexibility. As a major downstream molecule in the NMDA receptor signaling, alpha-Ca(2+)/calmodulin-dependent protein kinase II (αCaMKII) is crucial for hippocampal long-term potentiation (LTP) and hippocampus-related memory. However, the role of αCaMKII in mPFC-related behavioral flexibility and mPFC synaptic plasticity remains elusive. In the present study, using chemical-genetic approaches to temporally up-regulate αCaMKII activity, we found that αCaMKII-F89G transgenic mice exhibited impaired behavioral flexibility in Y-water maze arm reversal task. Notably, in vitro electrophysiological analysis showed normal basal synaptic transmission, LTP and depotentiation, but selectively impaired NMDAR-dependent long-term depression (LTD) in the mPFC of αCaMKII-F89G transgenic mice. In accordance with the deficit in NMDAR-dependent LTD, αCaMKII-F89G transgenic mice exhibited impaired AMPAR internalization during NMDAR-dependent chemical LTD expression in the mPFC. Furthermore, the above deficits in behavioral flexibility, NMDAR-dependent LTD and AMPAR internalization could all be reversed by 1-naphthylmethyl (NM)-PP1, a specific inhibitor of exogenous αCaMKII-F89G activity. Taken together, our results for the first time indicate that αCaMKII overexpression in the forebrain impairs behavioral flexibility and NMDAR-dependent LTD in the mPFC, and supports the notion that there is a close relationship between NMDAR-dependent LTD and behavioral flexibility.

  17. Neurotoxicity of developmental hypothyroxinemia and hypothyroidism in rats: Impairments of long-term potentiation are mediated by phosphatidylinositol 3-kinase signaling pathway

    SciTech Connect

    Wang, Yi; Wei, Wei; Wang, Yuan; Dong, Jing; Song, Binbin; Min, Hui; Teng, Weiping; Chen, Jie

    2013-09-01

    Neurotoxicity of iodine deficiency-induced hypothyroidism during developmental period results in serious impairments of brain function, such as learning and memory. These impairments are largely irreversible, and the underlying mechanisms remain unclear. In addition to hypothyroidism, iodine deficiency may cause hypothyroxinemia, a relatively subtle form of thyroid hormone deficiency. Neurotoxicity of developmental hypothyroxinemia also potentially impairs learning and memory. However, more direct evidence of the associations between developmental hypothyroxinemia and impairments of learning and memory should be provided, and the underlying mechanisms remain to be elucidated. Thus, in the present study, we investigated the effects of developmental hypothyroxinemia and hypothyroidism on long-term potentiation (LTP), a widely accepted cellular model of learning and memory, in the hippocampal CA1 region. The activation of the phosphatidylinositol 3-kinase (PI3K) signaling pathway – a pathway closely associated with synaptic plasticity and learning and memory – was also investigated. Wistar rats were treated with iodine deficient diet or methimazole (MMZ) to induce developmental hypothyroxinemia or hypothyroidism. The results showed that developmental hypothyroxinemia caused by mild iodine deficiency and developmental hypothyroidism caused by severe iodine deficiency or MMZ significantly reduced the field-excitatory postsynaptic potential (f-EPSP) slope and the population spike (PS) amplitude. Decreased activation of the PI3K signaling pathway was also observed in rats subjected to developmental hypothyroxinemia or hypothyroidism. Our results may support the hypothesis that neurotoxicity of both developmental hypothyroxinemia and hypothyroidism causes damages to learning and memory. Our results also suggest that decreased activation of the PI3K signaling pathway may contribute to impairments of LTP caused by neurotoxicity of both developmental hypothyroxinemia and

  18. Endothelin-1 Mediates Brain Microvascular Dysfunction Leading to Long-Term Cognitive Impairment in a Model of Experimental Cerebral Malaria

    PubMed Central

    Freeman, Brandi D.; Martins, Yuri C.; Akide-Ndunge, Oscar B.; Bruno, Fernando P.; Wang, Hua; Tanowitz, Herbert B.; Spray, David C.; Desruisseaux, Mahalia S.

    2016-01-01

    Plasmodium falciparum infection causes a wide spectrum of diseases, including cerebral malaria, a potentially life-threatening encephalopathy. Vasculopathy is thought to contribute to cerebral malaria pathogenesis. The vasoactive compound endothelin-1, a key participant in many inflammatory processes, likely mediates vascular and cognitive dysfunctions in cerebral malaria. We previously demonstrated that C57BL6 mice infected with P. berghei ANKA, our fatal experimental cerebral malaria model, sustained memory loss. Herein, we demonstrate that an endothelin type A receptor (ETA) antagonist prevented experimental cerebral malaria-induced neurocognitive impairments and improved survival. ETA antagonism prevented blood-brain barrier disruption and cerebral vasoconstriction during experimental cerebral malaria, and reduced brain endothelial activation, diminishing brain microvascular congestion. Furthermore, exogenous endothelin-1 administration to P. berghei NK65-infected mice, a model generally regarded as a non-cerebral malaria negative control for P. berghei ANKA infection, led to experimental cerebral malaria-like memory deficits. Our data indicate that endothelin-1 is critical in the development of cerebrovascular and cognitive impairments with experimental cerebral malaria. This vasoactive peptide may thus serve as a potential target for adjunctive therapy in the management of cerebral malaria. PMID:27031954

  19. Long-Term Air Pollution and Traffic Noise Exposures and Mild Cognitive Impairment in Older Adults: A Cross-Sectional Analysis of the Heinz Nixdorf Recall Study

    PubMed Central

    Tzivian, Lilian; Dlugaj, Martha; Winkler, Angela; Weinmayr, Gudrun; Hennig, Frauke; Fuks, Kateryna B.; Vossoughi, Mohammad; Schikowski, Tamara; Weimar, Christian; Erbel, Raimund; Jöckel, Karl-Heinz; Moebus, Susanne; Hoffmann, Barbara

    2016-01-01

    Background: Mild cognitive impairment (MCI) describes the intermediate state between normal cognitive aging and dementia. Adverse effects of air pollution (AP) on cognitive functions have been proposed, but investigations of simultaneous exposure to noise are scarce. Objectives: We analyzed the cross-sectional associations of long-term exposure to AP and traffic noise with overall MCI and amnestic (aMCI) and nonamnestic (naMCI) MCI. Methods: At the second examination of the population-based Heinz Nixdorf Recall study, cognitive assessment was completed in 4,086 participants who were 50–80 years old. Of these, 592 participants were diagnosed as having MCI (aMCI, n = 309; naMCI, n = 283) according to previously published criteria using five neuropsychological subtests. We assessed long-term residential concentrations for size-fractioned particulate matter (PM) and nitrogen oxides with land use regression, and for traffic noise [weighted 24-hr (LDEN) and night-time (LNIGHT) means]. Logistic regression models adjusted for individual risk factors were calculated to estimate the association of environmental exposures with MCI in single- and two-exposure models. Results: Most air pollutants and traffic noise were associated with overall MCI and aMCI. For example, an interquartile range increase in PM2.5 and a 10 A-weighted decibel [dB(A)] increase in LDEN were associated with overall MCI as follows [odds ratio (95% confidence interval)]: 1.16 (1.05, 1.27) and 1.40 (1.03, 1.91), respectively, and with aMCI as follows: 1.22 (1.08, 1.38) and 1.53 (1.05, 2.24), respectively. In two-exposure models, AP and noise associations were attenuated [e.g., for aMCI, PM2.5 1.13 (0.98, 1.30) and LDEN 1.46 (1.11, 1.92)]. Conclusions: Long-term exposures to air pollution and traffic noise were positively associated with MCI, mainly with the amnestic subtype. Citation: Tzivian L, Dlugaj M, Winkler A, Weinmayr G, Hennig F, Fuks KB, Vossoughi M, Schikowski T, Weimar C, Erbel R, Jöckel KH

  20. The Impact of Renal Impairment on Long-Term Safety and Effectiveness of Drug-Eluting Stents

    PubMed Central

    Stefanini, Giulio G.; Taniwaki, Masanori; Kalesan, Bindu; Räber, Lorenz; Stortecky, Stefan; Pilgrim, Thomas; Onuma, Yoshinobu; Silber, Sigmund; Serruys, Patrick W.; Meier, Bernhard; Jüni, Peter; Windecker, Stephan

    2014-01-01

    Background Renal impairment (RI) is associated with impaired prognosis in patients with coronary artery disease. Clinical and angiographic outcomes of patients undergoing percutaneous coronary intervention (PCI) with the use of drug-eluting stents (DES) in this patient population are not well established. Methods We pooled individual data for 5,011 patients from 3 trials with the exclusive and unrestricted use of DES (SIRTAX - N = 1,012, LEADERS - N = 1,707, RESOLUTE AC - N = 2,292). Angiographic follow-up was available for 1,544 lesions. Outcomes through 2 years were stratified according to glomerular filtration rate (normal renal function: GFR≥90 ml/min; mild RI: 90impaired among patients with moderate/severe RI. PMID:25184244

  1. Mice deficient for striatal Vesicular Acetylcholine Transporter (VAChT) display impaired short-term but normal long-term object recognition memory.

    PubMed

    Palmer, Daniel; Creighton, Samantha; Prado, Vania F; Prado, Marco A M; Choleris, Elena; Winters, Boyer D

    2016-09-15

    Substantial evidence implicates Acetylcholine (ACh) in the acquisition of object memories. While most research has focused on the role of the cholinergic basal forebrain and its cortical targets, there are additional cholinergic networks that may contribute to object recognition. The striatum contains an independent cholinergic network comprised of interneurons. In the current study, we investigated the role of this cholinergic signalling in object recognition using mice deficient for Vesicular Acetylcholine Transporter (VAChT) within interneurons of the striatum. We tested whether these striatal VAChT(D2-Cre-flox/flox) mice would display normal short-term (5 or 15min retention delay) and long-term (3h retention delay) object recognition memory. In a home cage object recognition task, male and female VAChT(D2-Cre-flox/flox) mice were impaired selectively with a 15min retention delay. When tested on an object location task, VAChT(D2-Cre-flox/flox) mice displayed intact spatial memory. Finally, when object recognition was tested in a Y-shaped apparatus, designed to minimize the influence of spatial and contextual cues, only females displayed impaired recognition with a 5min retention delay, but when males were challenged with a 15min retention delay, they were also impaired; neither males nor females were impaired with the 3h delay. The pattern of results suggests that striatal cholinergic transmission plays a role in the short-term memory for object features, but not spatial location. PMID:27233822

  2. Mice deficient for striatal Vesicular Acetylcholine Transporter (VAChT) display impaired short-term but normal long-term object recognition memory.

    PubMed

    Palmer, Daniel; Creighton, Samantha; Prado, Vania F; Prado, Marco A M; Choleris, Elena; Winters, Boyer D

    2016-09-15

    Substantial evidence implicates Acetylcholine (ACh) in the acquisition of object memories. While most research has focused on the role of the cholinergic basal forebrain and its cortical targets, there are additional cholinergic networks that may contribute to object recognition. The striatum contains an independent cholinergic network comprised of interneurons. In the current study, we investigated the role of this cholinergic signalling in object recognition using mice deficient for Vesicular Acetylcholine Transporter (VAChT) within interneurons of the striatum. We tested whether these striatal VAChT(D2-Cre-flox/flox) mice would display normal short-term (5 or 15min retention delay) and long-term (3h retention delay) object recognition memory. In a home cage object recognition task, male and female VAChT(D2-Cre-flox/flox) mice were impaired selectively with a 15min retention delay. When tested on an object location task, VAChT(D2-Cre-flox/flox) mice displayed intact spatial memory. Finally, when object recognition was tested in a Y-shaped apparatus, designed to minimize the influence of spatial and contextual cues, only females displayed impaired recognition with a 5min retention delay, but when males were challenged with a 15min retention delay, they were also impaired; neither males nor females were impaired with the 3h delay. The pattern of results suggests that striatal cholinergic transmission plays a role in the short-term memory for object features, but not spatial location.

  3. Etomidate Impairs Long-Term Potentiation In Vitro by Targeting α5-Subunit Containing GABAA Receptors on Nonpyramidal Cells

    PubMed Central

    Rodgers, F. Clifford; Zarnowska, Ewa D.; Laha, Kurt T.; Engin, Elif; Zeller, Anja; Keist, Ruth; Rudolph, Uwe

    2015-01-01

    Previous experiments using genetic and pharmacological manipulations have provided strong evidence that etomidate impairs synaptic plasticity and memory by modulating α5-subunit containing GABAA receptors (α5-GABAARs). Because α5-GABAARs mediate tonic inhibition (TI) in hippocampal CA1 pyramidal cells and etomidate enhances TI, etomidate enhancement of TI in pyramidal cells has been proposed as the underlying mechanism (Martin et al., 2009). Here we tested this hypothesis by selectively removing α5-GABAARs from pyramidal neurons (CA1–pyr–α5–KO) and comparing the ability of etomidate to enhance TI and block LTP in fl–α5 (WT), global–α5–KO (gl–α5–KO), and CA1–pyr–α5–KO mice. Etomidate suppressed LTP in slices from WT and CA1–pyr–α5–KO but not gl–α5–KO mice. There was a trend toward reduced TI in both gl–α5–KO and CA1–pyr–α5–KO mice, but etomidate enhanced TI to similar levels in all genotypes. The dissociation between effects of etomidate on TI and LTP in gl–α5–KO mice indicates that increased TI in pyramidal neurons is not the mechanism by which etomidate impairs LTP and memory. Rather, the ability of etomidate to block LTP in WT and CA1–pyr–α5–KO mice, but not in gl–α5–KO mice, points toward α5-GABAARs on nonpyramidal cells as the essential effectors controlling plasticity in this in vitro model of learning and memory. PMID:26134653

  4. Long-term ambient air pollution and lung function impairment in Chinese children from a high air pollution range area: The Seven Northeastern Cities (SNEC) study

    NASA Astrophysics Data System (ADS)

    Zeng, Xiao-Wen; Vivian, Elaina; Mohammed, Kahee A.; Jakhar, Shailja; Vaughn, Michael; Huang, Jin; Zelicoff, Alan; Xaverius, Pamela; Bai, Zhipeng; Lin, Shao; Hao, Yuan-Tao; Paul, Gunther; Morawska, Lidia; Wang, Si-Quan; Qian, Zhengmin; Dong, Guang-Hui

    2016-08-01

    Epidemiological studies have reported inconsistent and inconclusive associations between long-term exposure to ambient air pollution and lung function in children from Europe and America, where air pollution levels were typically low. The aim of the present study is to examine the relationship between air pollutants and lung function in children selected from heavily industrialized and polluted cities in northeastern China. During 2012, 6740 boys and girls aged 7-14 years were recruited in 24 districts of seven northeastern cities. Portable electronic spirometers were used to measure lung function. Four-year average concentrations of particulate matter with an aerodynamic diameter ≤10 μm (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), and ozone (O3) were measured at monitoring stations in the 24 districts. Two-staged regression models were used in the data analysis, controlling for covariates. Overall, for all subjects, the increased odds of lung function impairment associated with exposure to air pollutants, ranged from 5% (adjusted odds ratio [aOR] = 1.05; 95% confidence interval [CI] = 1.01, 1.10) for FVC < 85% predicted per 46.3 μg/m3 for O3 to 81% (aOR = 1.81; 95%CI = 1.44, 2.28) for FEV1 < 85% predicted per 30.6 μg/m3 for PM10. The linear regression models consistently showed a negative relationship between all air pollutants and lung function measures across subjects. There were significant interaction terms indicating gender differences for lung function impairment and pulmonary function from exposure to some pollutants (P < 0.10). In conclusion, long term exposure to high concentrations of ambient air pollution is associated with decreased pulmonary function and lung function impairment, and females appear to be more susceptible than males.

  5. Long-Term Care

    MedlinePlus

    ... this page please turn Javascript on. Long-Term Care What Is Long-Term Care? Long-term care involves a variety of services ... the Escape (Esc) button on your keyboard.) Most Care Provided at Home Long-term care is provided ...

  6. Long-term central pathology and cognitive impairment are exacerbated in a mixed model of Alzheimer's disease and type 2 diabetes.

    PubMed

    Infante-Garcia, Carmen; Ramos-Rodriguez, Juan Jose; Galindo-Gonzalez, Lucia; Garcia-Alloza, Monica

    2016-03-01

    Type 2 diabetes (T2D) is a well-characterized risk factor for Alzheimer's disease (AD), the most common cause of dementia. Since both, T2D and dementia are closely related to aging and they chronically coexist in elderly patients, it is of particular relevance to know whether long-term evolution of T2D and dementia interfere with each other years after the onset of the diseases. In order to elucidate this interaction, we have characterized a mixed model of T2D and AD, the APP/PS1xdb/db mouse, at 36 weeks of age, when both diseases have long coexisted and evolved. In aged APP/PS1xdb/db mice we observed dysfunctional metabolic control, when compared with diabetic mice alone, suggesting that AD may also contribute to T2D pathology in the long-term. Learning and memory were severely impaired in APP/PS1xdb/db mice, accompanied by reduced cortical size, neuronal branching simplification and reduction of dendritic spine density. Increased tau phosphorylation was also observed in old APP/PS1xdb/db mice. A shift in amyloid-β (Aβ) pathology was detected, and while insoluble Aβ was reduced, more toxic soluble species were favoured. Microglia burden was significantly increased in the proximity of senile plaques and an overall increase of spontaneous haemorrhages was also observed in APP/PS1xdb/db mice, suggesting a possible disruption of the blood brain barrier in the mixed model. It is therefore feasible that strict metabolic control may slow or delay central complications when T2D and dementia coexist in the long term. PMID:26708068

  7. Immunization with DAT fragments is associated with long-term striatal impairment, hyperactivity and reduced cognitive flexibility in mice

    PubMed Central

    2012-01-01

    Background Possible interactions between nervous and immune systems in neuro-psychiatric disorders remain elusive. Levels of brain dopamine transporter (DAT) have been implicated in several impulse-control disorders, like attention deficit / hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD). Here, we assessed the interplay between DAT auto-immunity and behavioural / neurochemical phenotype. Methods Male CD-1 mice were immunized with DAT peptide fragments (DAT-i), or vehicle alone (VEH), to generate elevated circulating levels of DAT auto-antibodies (aAbs). Using an operant delay-of-reward task (20 min daily sessions; timeout 25 sec), mice had a choice between either an immediate small amount of food (SS), or a larger amount of food after a delay (LL), which increased progressively across sessions (from 0 to 150 sec). Results DAT-i mice exhibited spontaneous hyperactivity (2 h-longer wake-up peak; a wake-up attempt during rest). Two sub-populations differing in behavioural flexibility were identified in the VEH control group: they showed either a clear-cut decision to select LL or clear-cut shifting towards SS, as expected. Compared to VEH controls, choice-behaviour profile of DAT-i mice was markedly disturbed, together with long-lasting alterations of the striatal monoamines. Enhanced levels of DA metabolite HVA in DAT-i mice came along with slower acquisition of basal preferences and with impaired shifting; elevation also in DOPAC levels was associated with incapacity to change a rigid selection strategy. This scarce flexibility of performance is indicative of a poor adaptation to task contingencies. Conclusions Hyperactivity and reduced cognitive flexibility are patterns of behaviour consistent with enduring functional impairment of striatal regions. It is yet unclear how anti-DAT antibodies could enter or otherwise affect these brain areas, and which alterations in DAT activity exactly occurred after immunization. Present neuro

  8. Toxoplasma gondii Infection in Mice Impairs Long-Term Fear Memory Consolidation through Dysfunction of the Cortex and Amygdala.

    PubMed

    Ihara, Fumiaki; Nishimura, Maki; Muroi, Yoshikage; Mahmoud, Motamed Elsayed; Yokoyama, Naoaki; Nagamune, Kisaburo; Nishikawa, Yoshifumi

    2016-10-01

    Chronic infection with Toxoplasma gondii becomes established in tissues of the central nervous system, where parasites may directly or indirectly modulate neuronal function. Epidemiological studies have revealed that chronic infection in humans is a risk factor for developing mental diseases. However, the mechanisms underlying parasite-induced neuronal dysfunction in the brain remain unclear. Here, we examined memory associated with conditioned fear in mice and found that T. gondii infection impairs consolidation of conditioned fear memory. To examine the brain pathology induced by T. gondii infection, we analyzed the parasite load and histopathological changes. T. gondii infects all brain areas, yet the cortex exhibits more severe tissue damage than other regions. We measured neurotransmitter levels in the cortex and amygdala because these regions are involved in fear memory expression. The levels of dopamine metabolites but not those of dopamine were increased in the cortex of infected mice compared with those in the cortex of uninfected mice. In contrast, serotonin levels were decreased in the amygdala and norepinephrine levels were decreased in the cortex and amygdala of infected mice. The levels of cortical dopamine metabolites were associated with the time spent freezing in the fear-conditioning test. These results suggest that T. gondii infection affects fear memory through dysfunction of the cortex and amygdala. Our findings provide insight into the mechanisms underlying the neurological changes seen during T. gondii infection. PMID:27456832

  9. Toxoplasma gondii Infection in Mice Impairs Long-Term Fear Memory Consolidation through Dysfunction of the Cortex and Amygdala.

    PubMed

    Ihara, Fumiaki; Nishimura, Maki; Muroi, Yoshikage; Mahmoud, Motamed Elsayed; Yokoyama, Naoaki; Nagamune, Kisaburo; Nishikawa, Yoshifumi

    2016-10-01

    Chronic infection with Toxoplasma gondii becomes established in tissues of the central nervous system, where parasites may directly or indirectly modulate neuronal function. Epidemiological studies have revealed that chronic infection in humans is a risk factor for developing mental diseases. However, the mechanisms underlying parasite-induced neuronal dysfunction in the brain remain unclear. Here, we examined memory associated with conditioned fear in mice and found that T. gondii infection impairs consolidation of conditioned fear memory. To examine the brain pathology induced by T. gondii infection, we analyzed the parasite load and histopathological changes. T. gondii infects all brain areas, yet the cortex exhibits more severe tissue damage than other regions. We measured neurotransmitter levels in the cortex and amygdala because these regions are involved in fear memory expression. The levels of dopamine metabolites but not those of dopamine were increased in the cortex of infected mice compared with those in the cortex of uninfected mice. In contrast, serotonin levels were decreased in the amygdala and norepinephrine levels were decreased in the cortex and amygdala of infected mice. The levels of cortical dopamine metabolites were associated with the time spent freezing in the fear-conditioning test. These results suggest that T. gondii infection affects fear memory through dysfunction of the cortex and amygdala. Our findings provide insight into the mechanisms underlying the neurological changes seen during T. gondii infection.

  10. Self-reported cognitive impairment after breast cancer treatment in young women from the ELIPPSE40 cohort: the long-term impact of chemotherapy.

    PubMed

    Rey, Dominique; Bouhnik, Anne-Déborah; Mancini, Julien; Bendiane, Marc-Karim; Séror, Valérie; Viens, Patrice

    2012-09-01

    Cognitive impairment (CI) is common after cancer treatments, but little is known about the long-term evolution of CI, especially in premenopausal women. Since September 2005, all consecutive women included in the French National Health Insurance Fund registry with a diagnosis of primary breast cancer, aged 18-40 years and living in South Eastern France, were asked to participate in a cohort study, including telephone interviews, medical data, and prescription refills of psychotropic drugs and adjuvant endocrine therapy. At each interview, CI is defined as self-report of frequent memory loss and attention deficits. As of February 2010, 222 women with available medical data had taken part in the 10-, 16-, and 28-month telephone interviews, with CI being reported by 37.4%, 36.5%, and 42.3% of participants, respectively. Tranquilizers' dispensation was associated with CI self-report at all three interviews; chemotherapy was reported only at the 28-month interview. At 28 months, besides chemotherapy and tranquilizer's dispensation, having a low educational level and not being a native French woman were also independently associated with CI. Reports of CI were common in young women and primarily related to psycho-social vulnerabilities and cancer treatment. As they affect quality of life, long-term CI complaints deserve greater consideration.

  11. Impaired immunity in harbour seals (Phoca vitulina) exposed to bioaccumulated environmental contaminants: review of a long-term feeding study.

    PubMed Central

    de Swart, R L; Ross, P S; Vos, J G; Osterhaus, A D

    1996-01-01

    Mass mortalities among seals and dolphins inhabiting contaminated marine regions have led to speculation about a possible involvement of immunosuppression associated with environmental pollution. To evaluate whether contaminants at ambient environmental levels can affect immune function of seals, we carried out an immunotoxicological study under semifield conditions. Two groups of 11 harbour seals (Phoca vitulina) originating from a relatively uncontaminated area were fed herring from either the highly polluted Baltic Sea or the relatively uncontaminated Atlantic Ocean. Changes in immune function were monitored over a 2 1/2-year period. The seals that were fed contaminated Baltic herring developed significantly higher body burdens of potentially immunotoxic organochlorines and displayed impaired immune responses as demonstrated by suppression of natural killer cell activity and specific T-cell responses. During a 2-week fasting experiment performed at the end of the feeding study, mobilization of organochlorines from the blubber did not lead to a strong increase of contaminant levels in the blood, and no enhancement of the existing immunosuppression was observed. These results demonstrate that chronic exposure to environmental contaminants accumulated through the food chain affects immune function in harbour seals, whereas short-term fasting periods, which are normal for seals, do not seem to pose an additional risk. The seals of this study were not exposed perinatally to high levels of environmental chemicals, and body burdens of organochlorines measured near the end of the study were lower than those generally observed in free-ranging seals inhabiting many contaminated regions. Therefore, it may be expected that environmental contaminants adversely affect immune function of free-ranging seals inhabiting contaminated regions at least as seriously as observed in these studies. PMID:8880005

  12. Discovery of MK-0952, a selective PDE4 inhibitor for the treatment of long-term memory loss and mild cognitive impairment.

    PubMed

    Gallant, Michel; Aspiotis, Renee; Day, Stephen; Dias, Rebecca; Dubé, Daniel; Dubé, Laurence; Friesen, Richard W; Girard, Mario; Guay, Daniel; Hamel, Pierre; Huang, Zheng; Lacombe, Patrick; Laliberté, Sebastien; Lévesque, Jean-François; Liu, Susana; Macdonald, Dwight; Mancini, Joseph; Nicholson, Donald W; Styhler, Angela; Townson, Karen; Waters, Kerry; Young, Robert N; Girard, Yves

    2010-11-15

    The structure-activity relationship of a novel series of 8-biarylnaphthyridinones acting as type 4 phosphodiesterase (PDE4) inhibitors for the treatment of long-term memory loss and mild cognitive impairment is described herein. The manuscript describes a new paradigm for the development of PDE4 inhibitor targeting CNS indications. This effort led to the discovery of the clinical candidate MK-0952, an intrinsically potent inhibitor (IC(50)=0.6 nM) displaying limited whole blood activity (IC(50)=555 nM). Supporting in vivo results in two preclinical efficacy tests and one test assessing adverse effects are also reported. The comparative profiles of MK-0952 and two other Merck compounds are described to validate the proposed hypothesis.

  13. The inflammatory response of two different kinds of anesthetics on vascular cognitive impairment rats and the effect on long term cognitive function.

    PubMed

    Xu, Bing; Yang, Jia; Kang, Fang; Li, Juan

    2015-01-01

    Vascular cognitive impairment, caused by vascular injury and inflammation, affects brain function. Present treatment for vascular injury primarily relies on combination therapy of surgery with anesthesia. In this study, we sought to determine the effects of anesthetics, sevoflurane and fentanyl, on long-term cognitive function in brain tissue of rats, and potential correlations with inflammatory factors such as VEGF, IL-1β, TNF-α. We used shuttle box and water maze tests to study the cognitive function of Wistar rats. The results demonstrated that rats treated with sevoflurane or fentanyl performed less shock times and more active escape times compared with rats model undergoing vascular cognitive impairment. Treatment of anesthetics also shortened the periods of learning and memory incubation, suggesting a protective role in cognitive function. In addition, our results unraveled a reducing expression of TNF-α and IL-1β but an increasing level of VEGF in head tissues of rats implemented with anesthetics. These findings underscore the improving role of sevoflurane and fentanyl in the recovery of vascular cognitive impairment rats as well as the cognitive function in rats, by regulating the expression of inflammatory factors. PMID:26629205

  14. The inflammatory response of two different kinds of anesthetics on vascular cognitive impairment rats and the effect on long term cognitive function

    PubMed Central

    Xu, Bing; Yang, Jia; Kang, Fang; Li, Juan

    2015-01-01

    Vascular cognitive impairment, caused by vascular injury and inflammation, affects brain function. Present treatment for vascular injury primarily relies on combination therapy of surgery with anesthesia. In this study, we sought to determine the effects of anesthetics, sevoflurane and fentanyl, on long-term cognitive function in brain tissue of rats, and potential correlations with inflammatory factors such as VEGF, IL-1β, TNF-α. We used shuttle box and water maze tests to study the cognitive function of Wistar rats. The results demonstrated that rats treated with sevoflurane or fentanyl performed less shock times and more active escape times compared with rats model undergoing vascular cognitive impairment. Treatment of anesthetics also shortened the periods of learning and memory incubation, suggesting a protective role in cognitive function. In addition, our results unraveled a reducing expression of TNF-α and IL-1β but an increasing level of VEGF in head tissues of rats implemented with anesthetics. These findings underscore the improving role of sevoflurane and fentanyl in the recovery of vascular cognitive impairment rats as well as the cognitive function in rats, by regulating the expression of inflammatory factors. PMID:26629205

  15. Impaired long-term memory retention and working memory in sdy mutant mice with a deletion in Dtnbp1, a susceptibility gene for schizophrenia

    PubMed Central

    Takao, Keizo; Toyama, Keiko; Nakanishi, Kazuo; Hattori, Satoko; Takamura, Hironori; Takeda, Masatoshi; Miyakawa, Tsuyoshi; Hashimoto, Ryota

    2008-01-01

    Background Schizophrenia is a complex genetic disorder caused by multiple genetic and environmental factors. The dystrobrevin-binding protein 1 (DTNBP1: dysbindin-1) gene is a major susceptibility gene for schizophrenia. Genetic variations in DTNBP1 are associated with cognitive functions, general cognitive ability and memory function, and clinical features of patients with schizophrenia including negative symptoms and cognitive decline. Since reduced expression of dysbindin-1 has been observed in postmortem brains of patients with schizophrenia, the sandy (sdy) mouse, which has a deletion in the Dtnbp1 gene and expresses no dysbindin-1 protein, could be an animal model of schizophrenia. To address this issue, we have carried out a comprehensive behavioral analysis of the sdy mouse in this study. Results In a rotarod test, sdy mice did not exhibit motor learning whilst the wild type mice did. In a Barnes circular maze test both sdy mice and wild type mice learned to selectively locate the escape hole during the course of the training period and in the probe trial conducted 24 hours after last training. However, sdy mice did not locate the correct hole in the retention probe tests 7 days after the last training trial, whereas wild type mice did, indicating impaired long-term memory retention. A T-maze forced alternation task, a task of working memory, revealed no effect of training in sdy mice despite the obvious effect of training in wild type mice, suggesting a working memory deficit. Conclusion Sdy mouse showed impaired long-term memory retention and working memory. Since genetic variation in DTNBP1 is associated with both schizophrenia and memory function, and memory function is compromised in patients with schizophrenia, the sdy mouse may represent a useful animal model to investigate the mechanisms of memory dysfunction in the disorder. PMID:18945333

  16. Neurotoxicity of developmental hypothyroxinemia and hypothyroidism in rats: Impairments of long-term potentiation are mediated by phosphatidylinositol 3-kinase signaling pathway.

    PubMed

    Wang, Yi; Wei, Wei; Wang, Yuan; Dong, Jing; Song, Binbin; Min, Hui; Teng, Weiping; Chen, Jie

    2013-09-01

    Neurotoxicity of iodine deficiency-induced hypothyroidism during developmental period results in serious impairments of brain function, such as learning and memory. These impairments are largely irreversible, and the underlying mechanisms remain unclear. In addition to hypothyroidism, iodine deficiency may cause hypothyroxinemia, a relatively subtle form of thyroid hormone deficiency. Neurotoxicity of developmental hypothyroxinemia also potentially impairs learning and memory. However, more direct evidence of the associations between developmental hypothyroxinemia and impairments of learning and memory should be provided, and the underlying mechanisms remain to be elucidated. Thus, in the present study, we investigated the effects of developmental hypothyroxinemia and hypothyroidism on long-term potentiation (LTP), a widely accepted cellular model of learning and memory, in the hippocampal CA1 region. The activation of the phosphatidylinositol 3-kinase (PI3K) signaling pathway - a pathway closely associated with synaptic plasticity and learning and memory - was also investigated. Wistar rats were treated with iodine deficient diet or methimazole (MMZ) to induce developmental hypothyroxinemia or hypothyroidism. The results showed that developmental hypothyroxinemia caused by mild iodine deficiency and developmental hypothyroidism caused by severe iodine deficiency or MMZ significantly reduced the field-excitatory postsynaptic potential (f-EPSP) slope and the population spike (PS) amplitude. Decreased activation of the PI3K signaling pathway was also observed in rats subjected to developmental hypothyroxinemia or hypothyroidism. Our results may support the hypothesis that neurotoxicity of both developmental hypothyroxinemia and hypothyroidism causes damages to learning and memory. Our results also suggest that decreased activation of the PI3K signaling pathway may contribute to impairments of LTP caused by neurotoxicity of both developmental hypothyroxinemia and

  17. Single fluoxetine treatment before but not after stress prevents stress-induced hippocampal long-term depression and spatial memory retrieval impairment in rats.

    PubMed

    Han, Huili; Dai, Chunfang; Dong, Zhifang

    2015-07-28

    A growing body of evidence has shown that chronic treatment with fluoxetine, a widely prescribed medication for treatment of depression, can affect synaptic plasticity in the adult central nervous system. However, it is not well understood whether acute fluoxetine influences synaptic plasticity, especially on hippocampal CA1 long-term depression (LTD), and if so, whether it subsequently impacts hippocampal-dependent spatial memory. Here, we reported that LTD facilitated by elevated-platform stress in hippocampal slices was completely prevented by fluoxetine administration (10 mg/kg, i.p.) 30 min before stress. The LTD was not, however, significantly inhibited by fluoxetine administration immediately after stress. Similarly, fluoxetine incubation (10 μM) during electrophysiological recordings also displayed no influence on the stress-facilitated LTD. In addition, behavioral results showed that a single fluoxetine treatment 30 min before but not after acute stress fully reversed the impairment of spatial memory retrieval in the Morris water maze paradigm. Taken together, these results suggest that acute fluoxetine treatment only before, but not after stress, can prevent hippocampal CA1 LTD and spatial memory retrieval impairment caused by behavioral stress in adult animals.

  18. Lgr4 protein deficiency induces ataxia-like phenotype in mice and impairs long term depression at cerebellar parallel fiber-Purkinje cell synapses.

    PubMed

    Guan, Xin; Duan, Yanhong; Zeng, Qingwen; Pan, Hongjie; Qian, Yu; Li, Dali; Cao, Xiaohua; Liu, Mingyao

    2014-09-19

    Cerebellar dysfunction causes ataxia characterized by loss of balance and coordination. Until now, the molecular and neuronal mechanisms of several types of inherited cerebellar ataxia have not been completely clarified. Here, we report that leucine-rich G protein-coupled receptor 4 (Lgr4/Gpr48) is highly expressed in Purkinje cells (PCs) in the cerebellum. Deficiency of Lgr4 leads to an ataxia-like phenotype in mice. Histologically, no obvious morphological changes were observed in the cerebellum of Lgr4 mutant mice. However, the number of PCs was slightly but significantly reduced in Lgr4(-/-) mice. In addition, in vitro electrophysiological analysis showed an impaired long term depression (LTD) at parallel fiber-PC (PF-PC) synapses in Lgr4(-/-) mice. Consistently, immunostaining experiments showed that the level of phosphorylated cAMP-responsive element-binding protein (Creb) was significantly decreased in Lgr4(-/-) PCs. Furthermore, treatment with forskolin, an adenylyl cyclase agonist, rescued phospho-Creb in PCs and reversed the impairment in PF-PC LTD in Lgr4(-/-) cerebellar slices, indicating that Lgr4 is an upstream regulator of Creb signaling, which is underlying PF-PC LTD. Together, our findings demonstrate for first time an important role for Lgr4 in motor coordination and cerebellar synaptic plasticity and provide a potential therapeutic target for certain types of inherited cerebellar ataxia. PMID:25063812

  19. Streptozotocin Induces Mild Cognitive Impairment at Appropriate Doses in Mice as Determined by Long-Term Potentiation and the Morris Water Maze.

    PubMed

    Li, Dong; Huang, Yan; Cheng, Bin; Su, Jie; Zhou, Wen-Xia; Zhang, Yong-Xiang

    2016-07-27

    Alzheimer's disease (AD) is a progressive neurodegenerative disease, and effective therapeutic drugs in the clinic are still lacking. Ideally, AD progression could be stopped at an early stage, such as at the mild cognitive impairment (MCI) stage. MCI refers to the clinical condition between normal aging and dementia. Patients with MCI experience memory loss but do not meet the criteria for the diagnosis of clinically probable AD. However, few MCI animal models have been established. Here, we used in vivo long-term potentiation (LTP) recording and the Morris water maze (MWM) to evaluate the effects of intracerebroventricular injection of streptozotocin (ICV-STZ) in mice. We found a relationship between cognitive behavior and LTP in vivo and determined the appropriate doses of STZ for a putative MCI animal model. Animals that received≥150μg of STZ exhibited cognitive impairment in the MWM test, and few changes in behavior tests were observed in animals receiving less than 150μg of STZ. In vivo LTP recordings revealed that the induction of LTP decreased significantly in STZ-treated animals, even at the lowest dose (25μg/mouse), in a dose-dependent manner. Pathology analysis revealed STZ-induced neuron loss in a dose-dependent manner, both in the cortex and in the hippocampus, as evidenced by a significantly decreased neuronal number in the cohort treated with 75μg of STZ/mouse. Our study indicated that a low dose (25μg/mouse) of STZ impaired neural plasticity; at a higher dose of 75μg/mouse STZ, further LTP deficits were noted along with induced neuronal loss in both the cortex and the hippocampus, which could be considered a possible MCI or pre-MCI animal model; and finally, at 150μg/mouse STZ, dementia was induced, feasibly indicating a state of AD.

  20. Cocaine Withdrawal Impairs mGluR5-Dependent Long-Term Depression in Nucleus Accumbens Shell Neurons of Both Direct and Indirect Pathways.

    PubMed

    Huang, Chiung-Chun; Liang, Ying-Ching; Lee, Cheng-Che; Hsu, Kuei-Sen

    2015-12-01

    We previously reported that animals withdrawn from repeated cocaine exposure exhibited a selective deficit in the ability to elicit metabotropic glutamate receptor 5 (mGluR5)-dependent long-term depression (LTD) in the nucleus accumbens (NAc) shell. To determine whether such impairment occurs in the NAc in a cell-type-specific manner, we used bacterial artificial chromosome (BAC) transgenic mice expressing enhanced green fluorescent protein (eGFP) under the control of gene regulatory elements for the dopamine D1 receptor (Drd1) or dopamine D2 receptor (Drd2) to identify distinct subpopulations of medium spiny neurons (MSNs). We found that bath application of group I mGluR agonist (S)-3,5-dihydroxyphenylglycine (DHPG) reliably induced LTD in both NAc shell and core MSNs of wild-type, hemizygous Drd1-eGFP, and Drd2-eGFP mice. Confirming our previous results, cocaine withdrawal selectively impaired DHPG-LTD in NAc shell Drd1-expressing direct and Drd2-expressing indirect pathway MSNs. We also found that the expression of DHPG-LTD in NAc MSNs was not affected by the Ca(2+)-permeable α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist 1-naphthyl acetyl spermine. Furthermore, systemic administration of mGluR5-negative allosteric modulator fenobam before the daily injection of cocaine preserved mGluR5 function and significantly reduced the expression of cocaine-induced behavioral sensitization. These results reveal that withdrawal from repeated cocaine exposure may result in the impairment of NAc mGluR5-LTD in a subregion- but not cell-type-specific manner and suggests that pharmacological antagonism of mGluR5 may represent a potential strategy for reducing cocaine-induced addictive behaviors.

  1. Caspase-cleaved tau exhibits rapid memory impairment associated with tau oligomers in a transgenic mouse model.

    PubMed

    Kim, YoungDoo; Choi, Hyunwoo; Lee, WonJae; Park, Hyejin; Kam, Tae-In; Hong, Se-Hoon; Nah, Jihoon; Jung, Sunmin; Shin, Bora; Lee, Huikyong; Choi, Tae-Yong; Choo, Hyosun; Kim, Kyung-Keun; Choi, Se-Young; Kayed, Rakez; Jung, Yong-Keun

    2016-03-01

    In neurodegenerative diseases like AD, tau forms neurofibrillary tangles, composed of tau protein. In the AD brain, activated caspases cleave tau at the 421th Asp, generating a caspase-cleaved form of tau, TauC3. Although TauC3 is known to assemble rapidly into filaments in vitro, a role of TauC3 in vivo remains unclear. Here, we generated a transgenic mouse expressing human TauC3 using a neuron-specific promoter. In this mouse, we found that human TauC3 was expressed in the hippocampus and cortex. Interestingly, TauC3 mice showed drastic learning and spatial memory deficits and reduced synaptic density at a young age (2-3months). Notably, tau oligomers as well as tau aggregates were found in TauC3 mice showing memory deficits. Further, i.p. or i.c.v. injection with methylene blue or Congo red, inhibitors of tau aggregation in vitro, and i.p. injection with rapamycin significantly reduced the amounts of tau oligomers in the hippocampus, rescued spine density, and attenuated memory impairment in TauC3 mice. Together, these results suggest that TauC3 facilitates early memory impairment in transgenic mice accompanied with tau oligomer formation, providing insight into the role of TauC3 in the AD pathogenesis associated with tau oligomers and a useful AD model to test drug candidates.

  2. Long-term decrease of CD4+CD45RA+ T cells and impaired primary immune response after post-traumatic splenectomy.

    PubMed

    Wolf, H M; Eibl, M M; Georgi, E; Samstag, A; Spatz, M; Uranüs, S; Passl, R

    1999-10-01

    Congenital or acquired absence of the spleen and functional hyposplenism are associated with abnormalities of host defence such as an increased susceptibility to infection with encapsulated bacteria. The effects of the lack of the spleen on cell-mediated immunity are largely unknown. In the present study we have investigated peripheral blood lymphocyte subpopulations in healthy adults who had undergone splenectomy because of severe abdominal trauma > 4 years before the study. The results show a significant reduction in the percentage of CD4+ T cells due to a selective and long-term decrease in the percentage of CD4+CD45RA+ lymphocytes, the CD4+ T-cell subset mainly involved in primary immune responses to newly encountered antigens. Levels of the reciprocal CD45RO+CD4+ T-cell subset were comparable between splenectomized and control individuals, as were lymphoproliferative responses and IFN-gamma production to recall antigens. Decreased levels of CD4+CD45RA+ cells were accompanied by an impairment in primary immune responsiveness, as assessed by investigating T-cell proliferation to stimulation with keyhole limpet haemocyanin and by measuring antibody responses following primary immunization with a clinically relevant T-dependent antigen, hepatitis A vaccine, in vivo. These findings suggest a possible role of the spleen in the generation, maintenance and/or differentiation of naive, unprimed T cells or their precursors, which might have a possible functional relevance for primary immune responses following splenectomy. PMID:10520025

  3. Methylglyoxal (MG) and cerebro-renal interaction: does long-term orally administered MG cause cognitive impairment in normal Sprague-Dawley rats?

    PubMed

    Watanabe, Kimio; Okada, Kana; Fukabori, Ryoji; Hayashi, Yoshimitsu; Asahi, Koichi; Terawaki, Hiroyuki; Kobayashi, Kazuto; Watanabe, Tsuyoshi; Nakayama, Masaaki

    2014-01-07

    Methylglyoxal (MG), one of the uremic toxins, is a highly reactive alpha-dicarbonyl compound. Recent clinical studies have demonstrated the close associations of cognitive impairment (CI) with plasma MG levels and presence of kidney dysfunction. Therefore, the present study aims to examine whether MG is a direct causative substance for CI development. Eight-week-old male Sprague-Dawley (SD) rats were divided into two groups: control (n = 9) and MG group (n = 10; 0.5% MG in drinking water), and fed a normal diet for 12 months. Cognitive function was evaluated by two behavioral tests (object exploration test and radial-arm maze test) in early (4-6 months of age) and late phase (7-12 months of age). Serum MG was significantly elevated in the MG group (495.8 ± 38.1 vs. 244.8 ± 28.2 nM; p < 0.001) at the end of study. The groups did not differ in cognitive function during the course of study. No time-course differences were found in oxidative stress markers between the two groups, while, antioxidants such as glutathione peroxidase and superoxide dismutase activities were significantly increased in the MG group compared to the control. Long-term MG administration to rats with normal kidney function did not cause CI. A counter-balanced activation of the systemic anti-oxidant system may offset the toxicity of MG in this model. Pathogenetic significance of MG for CI requires further investigation.

  4. Nicotine prevents synaptic impairment induced by amyloid-β oligomers through α7-nicotinic acetylcholine receptor activation.

    PubMed

    Inestrosa, Nibaldo C; Godoy, Juan A; Vargas, Jessica Y; Arrazola, Macarena S; Rios, Juvenal A; Carvajal, Francisco J; Serrano, Felipe G; Farias, Ginny G

    2013-09-01

    An emerging view on Alzheimer disease's (AD) pathogenesis considers amyloid-β (Aβ) oligomers as a key factor in synaptic impairment and rodent spatial memory decline. Alterations in the α7-nicotinic acetylcholine receptor (α7-nAChR) have been implicated in AD pathology. Herein, we report that nicotine, an unselective α7-nAChR agonist, protects from morphological and synaptic impairments induced by Aβ oligomers. Interestingly, nicotine prevents both early postsynaptic impairment and late presynaptic damage induced by Aβ oligomers through the α7-nAChR/phosphatidylinositol-3-kinase (PI3K) signaling pathway. On the other hand, a cross-talk between α7-nAChR and the Wnt/β-catenin signaling pathway was revealed by the following facts: (1) nicotine stabilizes β-catenin, in a concentration-dependent manner; (2) nicotine prevents Aβ-induced loss of β-catenin through the α7-nAChR; and (3) activation of canonical Wnt/β-catenin signaling induces α7-nAChR expression. Analysis of the α7-nAChR promoter indicates that this receptor is a new Wnt target gene. Taken together, these results demonstrate that nicotine prevents memory deficits and synaptic impairment induced by Aβ oligomers. In addition, nicotine improves memory in young APP/PS1 transgenic mice before extensive amyloid deposition and senile plaque development, and also in old mice where senile plaques have already formed. Activation of the α7-nAChR/PI3K signaling pathway and its cross-talk with the Wnt signaling pathway might well be therapeutic targets for potential AD treatments.

  5. Long-Term Feeding of Chitosan Ameliorates Glucose and Lipid Metabolism in a High-Fructose-Diet-Impaired Rat Model of Glucose Tolerance.

    PubMed

    Liu, Shing-Hwa; Cai, Fang-Ying; Chiang, Meng-Tsan

    2015-12-10

    This study was designed to investigate the effects of long-term feeding of chitosan on plasma glucose and lipids in rats fed a high-fructose (HF) diet (63.1%). Male Sprague-Dawley rats aged seven weeks were used as experimental animals. Rats were divided into three groups: (1) normal group (normal); (2) HF group; (3) chitosan + HF group (HF + C). The rats were fed the experimental diets and drinking water ad libitum for 21 weeks. The results showed that chitosan (average molecular weight was about 3.8 × 10⁵ Dalton and degree of deacetylation was about 89.8%) significantly decreased body weight, paraepididymal fat mass, and retroperitoneal fat mass weight, but elevated the lipolysis rate in retroperitoneal fats of HF diet-fed rats. Supplementation of chitosan causes a decrease in plasma insulin, tumor necrosis factor (TNF)-α, Interleukin (IL)-6, and leptin, and an increase in plasma adiponectin. The HF diet increased hepatic lipids. However, intake of chitosan reduced the accumulation of hepatic lipids, including total cholesterol (TC) and triglyceride (TG) contents. In addition, chitosan elevated the excretion of fecal lipids in HF diet-fed rats. Furthermore, chitosan significantly decreased plasma TC, low-density lipoprotein cholesterol (LDL-C), very-low-density lipoprotein cholesterol (VLDL-C), the TC/high-density lipoprotein cholesterol (HDL-C) ratio, and increased the HDL-C/(LDL-C + VLDL-C) ratio, but elevated the plasma TG and free fatty acids concentrations in HF diet-fed rats. Plasma angiopoietin-like 4 (ANGPTL4) protein expression was not affected by the HF diet, but it was significantly increased in chitosan-supplemented, HF-diet-fed rats. The high-fructose diet induced an increase in plasma glucose and impaired glucose tolerance, but chitosan supplementation decreased plasma glucose and improved impairment of glucose tolerance and insulin tolerance. Taken together, these results indicate that supplementation with chitosan can improve the impairment of

  6. Long-Term Treatment of Clonidine, Atenolol, Amlodipine and Dihydrochlorothiazide, but Not Enalapril, Impairs the Sexual Function in Male Spontaneously Hypertensive Rats

    PubMed Central

    Lin, Li-Li; Wang, Dong; Wang, Wei; Cheng, Yan-Qiong; Su, Ding-Feng; Liu, Ai-Jun

    2015-01-01

    This study was designed to investigate the impact of representative antihypertensive drugs of 5 classes on the sexual function in male spontaneously hypertensive rats (SHR) at doses that achieved similar blood pressure (BP) reduction. The experiment was performed in 6 groups of male SHR. The dose are 20 μg/kg/day for clonidine, 3 mg/kg/day for enalapril, 20 mg/kg/day for atenolol, 2 mg/kg/day for amlodipine, and 10 mg/kg/day for dihydrochlorothiazide. SHR were treated for 3 months, and then the penile erection and sexual behavior were detected. After BP recording, SHR were killed to evaluate the organ-damage, weight of accessory sex organs and levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH) and testosterone in serum. Five drugs had the similar efficacy on BP reduction. All drugs except of enalapril, significantly prolonged the mount latency, and decreased the mount frequency (P<0.05). Clonidine also reduced the conception rate (45% vs. 80% in control group, P<0.05). Amlodipine and dihydrochlorothiazide significantly increased the testosterone level (0.79±0.30, 0.80±0.34 vs. 0.49±0.20 in control group, unit: ng/dl, P<0.05). Enalapril, atenolol and amlodipine also significantly decreased the BP variability (systolic, 8.2±2.5, 7.6±1.8, 8.9±2.0 vs. 12.2±3.8 in control group, unit: mm Hg). All these drugs significantly decreased the organ-damage (P<0.05). In conclusion, long-term treatment with 5 common antihypertensive drugs possessed obvious organ protection in SHR. Clonidine, atenolol, amlodipine and dihydrochlorothiazide, but not enalapril, impair sexual function. PMID:25615941

  7. Significant long-term, but not short-term, hippocampal-dependent memory impairment in adult rats exposed to alcohol in early postnatal life.

    PubMed

    Goodfellow, Molly J; Lindquist, Derick H

    2014-09-01

    In rodents, ethanol exposure in early postnatal life is known to induce structural and functional impairments throughout the brain, including the hippocampus. Herein, rat pups were administered one of three ethanol doses over postnatal days (PD) 4-9, a period of brain development comparable to the third trimester of human pregnancy. As adults, control and ethanol rats were trained and tested in a variant of hippocampal-dependent one-trial context fear conditioning. In Experiment 1, subjects were placed into a novel context and presented with an immediate footshock (i.e., within ∼8 sec). When re-exposed to the same context 24 hr later low levels of conditioned freezing were observed. Context pre-exposure 24 hr prior to the immediate shock reversed the deficit in sham-intubated and unintubated control rats, enhancing freezing behavior during the context retention test. Even with context pre-exposure, however, significant dose-dependent reductions in contextual freezing were seen in ethanol rats. In Experiment 2, the interval between context pre-exposure and the immediate shock was shortened to 2 hr, in addition to the standard 24 hr. Ethanol rats trained with the 2 hr, but not 24 hr, interval displayed retention test freezing levels roughly equal to controls. Results suggest the ethanol rats can encode a short-term context memory and associate it with the aversive footshock 2 hr later. In the 24 hr ethanol rats the short-term context memory is poorly transferred or consolidated into long-term memory, we propose, impeding the memory's subsequent retrieval and association with shock.

  8. Rescue of Cyclic AMP Mediated Long Term Potentiation Impairment in the Hippocampus of Mecp2 Knockout (Mecp2-/y) Mice by Rolipram

    PubMed Central

    Balakrishnan, Saju; Niebert, Marcus; Richter, Diethelm W.

    2016-01-01

    Rett syndrome (RTT) patients experience learning difficulties and memory loss. Analogous deficits of hippocampal plasticity are reported in mouse models of RTT. To elucidate the underlying pathophysiology, we studied long term potentiation (LTP) at the CA3 to CA1 synapses in the hippocampus in acute brain slices from WT and Mecp2-/y mice, by either activating cAMP dependent pathway or using high frequency stimulation, by means of patch clamp. We have observed that, the NMDA channel current characteristics remain unchanged in the Mecp2-/y mice. The adenylyl cyclase (AC) agonist forskolin evoked a long lasting potentiation of evoked EPSCs in WT CA1 neurons, but only minimally enhanced the EPSCs in the Mecp2-/y mice. This weaker potentiation in Mecp2-/y mice was ameliorated by application of phosphodiesterase 4 inhibitor rolipram. The hyperpolarization activated cyclic nucleotide gated channel current (Ih) was potentiated to similar extent by forskolin in both phenotypes. Multiple tetanus induced cAMP-dependent plasticity was also impaired in the Mecp2-/y mice, and was also partially rescued by rolipram. Western blot analysis of CA region of Mecp2-/y mice hippocampus revealed more than twofold up-regulation of protein kinase A (PKA) regulatory subunits, while the expression of the catalytic subunit remained unchanged. We hypothesize that the overexpressed PKA regulatory subunits buffer cAMP and restrict the PKA mediated phosphorylation of target proteins necessary for LTP. Blocking the degradation of cAMP, thereby saturating the regulatory subunits alleviated this defect. PMID:26869885

  9. Lack of the metabotropic glutamate receptor subtype 7 selectively impairs short-term working memory but not long-term memory.

    PubMed

    Hölscher, Christian; Schmid, Susanne; Pilz, Peter K D; Sansig, Gilles; van der Putten, Herman; Plappert, Claudia F

    2004-10-01

    Metabotropic glutamate receptors (mGluRs), and in particular the mGluR group III receptors (subtypes 4, 6, 7, 8) are known to play a role in synaptic plasticity and learning. Here, we report the effect of mGluR7 gene ablation in different learning paradigms. In the acoustic startle response (ASR), no differences were seen between knockout (KO) mice and wildtype (WT) littermates in parameters including prepulse inhibition and habituation. In an open field test, no differences were seen between genotypes in motor activity, exploratory behaviour, and fearful behaviour. In a T-maze reinforced alternation working memory (WM) task, again no difference was seen between groups. However, when increasing the demands on working-memory in a 4-arm and 8-arm maze task, KO mice committed more WM errors than WT littermates thereby uncovering a highly significant difference between the two groups that persisted every day for the whole 9 days of the experiment. In a 4-arm maze with 2 arms baited, KO and wildtype mice committed the same number of LTM errors, whereas KOs committed more WM errors. Altogether, these findings suggest that a lack of mGluR7 mainly impairs short-term working but not long-term memory performance while having no effect on sensorimotor processing, non-associative learning, motor activity and spatial orientation. The effects on WM are task-dependent and become apparent in more complex but not simple learning tasks. We discuss how mGluR7 could influence WM.

  10. Long-term Treatment of Teicoplanin for Methicillin-resistant Staphylococcus aureus Sternal Osteomyelitis with Renal Impairment: A Case of High Teicoplanin Trough Levels Maintained by Therapeutic Drug Monitoring.

    PubMed

    Shiohira, Hideo; Nakamatsu, Masashi; Kise, Yuya; Higa, Futoshi; Tateyama, Masao; Hokama, Nobuo; Kuniyoshi, Yukio; Ueda, Shinichiro; Nakamura, Katsunori; Fujita, Jiro

    2016-01-01

    Teicoplanin, a glycopeptide antibiotic for methicillin-resistant Staphylococcus aureus, is recommended for therapeutic drug monitoring during treatment. Maintaining a high trough range of teicoplanin is also recommended for severe infectious disease. However, the optimal dose and interval of treatment for severe renal impairment is unknown. We report a 79-year-old man who received long-term teicoplanin treatment for methicillin-resistant Staphylococcus aureus bacteremia due to postoperative sternal osteomyelitis with renal impairment. Plasma teicoplanin trough levels were maintained at a high range (20-30 μg/mL). Although the patient required long-term teicoplanin treatment, a further decline in renal function was not observed, and blood culture remained negative after the start of treatment. Teicoplanin treatment that is maintained at a high trough level by therapeutic drug monitoring might be beneficial for severe methicillin-resistant Staphylococcus aureus infection accompanied by renal impairment. PMID:27592834

  11. The coumarin scopoletin potentiates acetylcholine release from synaptosomes, amplifies hippocampal long-term potentiation and ameliorates anticholinergic- and age-impaired memory

    PubMed Central

    Hornick, A.; Lieb, A.; Vo, N.P.; Rollinger, J.M.; Stuppner, H.; Prast, H.

    2011-01-01

    In a previous study the simple, naturally derived coumarin scopoletin (SCT) was identified as an inhibitor of acetylcholinesterase (AChE), using a pharmacophore-based virtual screening approach. In this study the potential of SCT as procholinergic and cognition-enhancing therapeutic was investigated in a more detailed way, using different experimental approaches like measuring newly synthesized acetylcholine (ACh) in synaptosomes, long-term potentiation (LTP) experiments in hippocampal slices, and behavior studies. SCT enhanced the K+-stimulated release of ACh from rat frontal cortex synaptosomes, showing a bell-shaped dose effect curve (Emax: 4 μM). This effect was blocked by the nicotinic ACh receptor (nAChR) antagonists mecamylamine (MEC) and dihydro-β-erythroidine (DHE). The nAChR agonist (and AChE inhibitor) galantamine induced a similar increase in ACh release (Emax: 1 μM). SCT potentiated LTP in hippocampal slices of rat brain. The high-frequency stimulation (HFS)-induced, N-methyl-D-aspartate (NMDA) receptor dependent LTP of field excitatory postsynaptic potentials at CA3-CA1 synapses was greatly enhanced by pre-HFS application of SCT (4 μM for 4 min). This effect was mimicked by nicotine (2 μM) and abolished by MEC, suggesting an effect on nAChRs. SCT did not restore the total inhibition of LTP by NMDA receptor antagonist d, l-2-amino-5-phosphonopentanoic acid (AP-5). SCT (2 μg, i.c.v.) increased T-maze alternation and ameliorated novel object recognition of mice with scopolamine-induced cholinergic deficit. It also reduced age-associated deficits in object memory of 15–18-month-old mice (2 mg/kg sc). Our findings suggest that SCT possesses memory-improving properties, which are based on its direct nAChR agonistic activity. Therefore, SCT might be able to rescue impaired cholinergic functions by enhancing nAChR-mediated release of neurotransmitters and promoting neural plasticity in hippocampus. PMID:21945033

  12. Anisomycin Injection in Area CA3 of the Hippocampus Impairs Both Short-Term and Long-Term Memories of Contextual Fear

    ERIC Educational Resources Information Center

    Remaud, Jessica; Ceccom, Johnatan; Carponcy, Julien; Dugué, Laura; Menchon, Gregory; Pech, Stéphane; Halley, Helene; Francés, Bernard; Dahan, Lionel

    2014-01-01

    Protein synthesis is involved in the consolidation of short-term memory into long-term memory. Previous electrophysiological data concerning LTP in CA3 suggest that protein synthesis in that region might also be necessary for short-term memory. We tested this hypothesis by locally injecting the protein synthesis inhibitor anisomycin in hippocampal…

  13. [Interventions based on exercise and physical environment for preventing falls in cognitively impaired older people living in long-term care facilities: A systematic review and meta-analysis].

    PubMed

    González-Román, Loreto; Bagur-Calafat, Caritat; Urrútia-Cuchí, Gerard; Garrido-Pedrosa, Jèssica

    2016-01-01

    This systematic review aims to report the effectiveness of interventions based on exercise and/or physical environment for reducing falls in cognitively impaired older adults living in long-term care facilities. In July 2014, a literature search was conducted using main databases and specialised sources. Randomised controlled trials assessing the effectiveness of fall prevention interventions, which used exercise or physical environment among elderly people with cognitive impairment living in long-term care facilities, were selected. Two independent reviewers checked the eligibility of the studies, and evaluated their methodological quality. If it was adequate, data were gathered. Fourteen studies with 3,539 participants using exercise and/or physical environment by a single or combined approach were included. The data gathered from studies that used both interventions showed a significant reduction in fall rate. Further research is needed to demonstrate the effectiveness of those interventions for preventing falls in the elderly with cognitive impairment living in long-term care establishments.

  14. [Interventions based on exercise and physical environment for preventing falls in cognitively impaired older people living in long-term care facilities: A systematic review and meta-analysis].

    PubMed

    González-Román, Loreto; Bagur-Calafat, Caritat; Urrútia-Cuchí, Gerard; Garrido-Pedrosa, Jèssica

    2016-01-01

    This systematic review aims to report the effectiveness of interventions based on exercise and/or physical environment for reducing falls in cognitively impaired older adults living in long-term care facilities. In July 2014, a literature search was conducted using main databases and specialised sources. Randomised controlled trials assessing the effectiveness of fall prevention interventions, which used exercise or physical environment among elderly people with cognitive impairment living in long-term care facilities, were selected. Two independent reviewers checked the eligibility of the studies, and evaluated their methodological quality. If it was adequate, data were gathered. Fourteen studies with 3,539 participants using exercise and/or physical environment by a single or combined approach were included. The data gathered from studies that used both interventions showed a significant reduction in fall rate. Further research is needed to demonstrate the effectiveness of those interventions for preventing falls in the elderly with cognitive impairment living in long-term care establishments. PMID:26811122

  15. Impaired long-term expansion and self-renewal potential of pediatric acute myeloid leukemia-initiating cells by PTK787/ZK 222584.

    PubMed

    Weidenaar, Alida C; Ter Elst, Arja; Kampen, Kim R; Meeuwsen-de Boer, Tiny; Kamps, Willem A; Schuringa, Jan Jacob; de Bont, Eveline S J M

    2013-04-01

    Although most children with acute myeloid leukemia (AML) achieve complete remission, the relapse rate is 30% to 40%. Because it is thought that leukemia-initiating cells (LIC) are responsible for AML relapses, targeting these cells might improve outcome. Treatment of pediatric AML blasts with the receptor tyrosine kinase (RTK) inhibitor PTK787/ZK 222584 (PTK/ZK) induces cell death in vitro. However, the role of PTK/ZK inhibition on outgrowth of (pediatric) LICs is unknown. In this study, we cultured CD34+ cells from pediatric patients with AML on MS5 stromal cells in long-term cocultures. In analogy to adult AML, long-term expansion of leukemic cells up to 10 weeks could be generated in 9 of 13 pediatric AMLs. Addition of PTK/ZK to long-term cocultures significantly inhibited leukemic expansion in all samples, ranging from 4% to 80% growth inhibition at week 5 compared with untreated samples. In 75% of the samples, the inhibitory effect was more pronounced at week 10. Proteome profiler array analysis of downstream kinases revealed that PTK/ZK reduced activation of PI3K/Akt kinase signaling. Although main targets of PTK/ZK are VEGF receptors (VEGFR), no effect was seen on outgrowth of LICs when cultured with bevacizumab (monoclonal VEGFA-antibody), specific antibodies against VEGFR2 or VEGFR3, or exposed to stroma-derived VEGFA. These data suggest that the effect of PTK/ZK on LICs is not only dependent on inhibition of VEGFA/VEGFR signaling. Taken together, our data elucidated antileukemic properties of PTK/ZK in long-term expansion cultures, and suggest that targeting multiple RTKs by PTK/ZK might be a potential effective approach in eradicating (pediatric) LICs. PMID:23393162

  16. Traumatic injury to the immature frontal lobe: a new murine model of long-term motor impairment in the absence of psychosocial or cognitive deficits.

    PubMed

    Chen, Chien-Yi; Noble-Haeusslein, Linda J; Ferriero, Donna; Semple, Bridgette D

    2013-01-01

    Traumatic brain injury in children commonly involves the frontal lobes and is associated with distinct structural and behavioral changes. Despite the clinical significance of injuries localized to this region during brain development, the mechanisms underlying secondary damage and long-term recovery are poorly understood. Here, we have characterized the first model of unilateral focal traumatic injury to the developing frontal lobe. Male C57Bl/6J mice at postnatal day (p)21, an age approximating a toddler-aged child, received a controlled cortical impact or sham surgery to the left frontal lobe and were euthanized 1 or 7 days later. A necrotic cavity and local inflammatory response were largely confined to the unilateral frontal lobe, dorsal corpus callosum and striatum anterior to the bregma. While cell death and accumulated β-amyloid precursor protein were characteristic features of the pericontusional motor cortex, corpus callosum, cingulum and dorsal striatum, underlying structures including the hippocampus showed no overt pathology. To determine the long-term functional consequences of injury at p21, two additional cohorts were subjected to a battery of behavioral tests in adolescence (p35-45) or adulthood (p70-80). In both cohorts, brain-injured mice showed normal levels of anxiety, sociability, spatial learning and memory. The signature phenotypic features were deficits in motor function and motor learning, coincident with a reduction in ipsilateral cortical brain volumes. Together, these findings demonstrate classic morphological features of a focal traumatic injury, including early cell death and axonal injury, and long-term volumetric loss of cortical volumes. The presence of deficits in sensorimotor function and coordination in the absence of abnormal findings related to anxiety, sociability and memory likely reflects several variables, including the unique location of the injury and the emergence of favorable compensatory mechanisms during subsequent

  17. The clearance of oral high-risk human papillomavirus infection is impaired by long-term persistence of cervical human papillomavirus infection.

    PubMed

    Louvanto, K; Rautava, J; Syrjänen, K; Grénman, S; Syrjänen, S

    2014-11-01

    Persistence of high-risk (HR-) human papillomavirus (HPV) infection of the uterine cervix increases the risk of cervical cancer. Oral HPV infections are among potential covariates of long-term genotype-specific persistent cervical HR-HPV infections. It is not known whether this persistence reflects inability of the host to reject HPV infections in general. A case-control setting was designed to estimate the covariates of long-term persistent cervical HR-HPV infections using multivariate generalized estimating equation (GEE) models. HPV was detected with PCR using GP05+/GP06+-primers and genotyped for 24 HPVs with a Multimetrix-kit. The cases (n=43) included women who had genotype-specific persistent cervical HR-HPV infection for at least 24 months (24M+) and controls were women who tested repeatedly HPV-negative in their cervical samples (n=52). These women represent a sub-cohort of the Finnish Family HPV Study. The cases differed significantly from the HPV-negative controls in several aspects: they were younger, had a longer mean time to incident oral HPV infection (40.7 versus 23.6 months), longer duration of oral HPV persistence (38.4 versus 14.1 months), and longer time to clearance of their oral HPV infection (50.0 versus 28.2 months). In multivariate GEE analysis, the second pregnancy during the follow up was the only independent predictor with significant protective effect against 24M+ persistent cervical HR-HPV infections, OR of 0.15 (95% CI 0.07-0.34). To conclude, long-term persistent cervical HR-HPV infections are associated with a prolonged clearance of oral HR-HPV infections while new pregnancy protects against persistent cervical HR-HPV infections.

  18. Short-Term and Working Memory Impairments in Early-Implanted, Long-Term Cochlear Implant Users Are Independent of Audibility and Speech Production

    PubMed Central

    AuBuchon, Angela M.; Pisoni, David B.; Kronenberger, William G.

    2015-01-01

    OBJECTIVES Determine if early-implanted, long-term cochlear implant (CI) users display delays in verbal short-term and working memory capacity when processes related to audibility and speech production are eliminated. DESIGN Twenty-three long-term CI users and 23 normal-hearing controls each completed forward and backward digit span tasks under testing conditions which differed in presentation modality (auditory or visual) and response output (spoken recall or manual pointing). RESULTS Normal-hearing controls reproduced more lists of digits than the CI users, even when the test items were presented visually and the responses were made manually via touchscreen response. CONCLUSIONS Short-term and working memory delays observed in CI users are not due to greater demands from peripheral sensory processes such as audibility or from overt speech-motor planning and response output organization. Instead, CI users are less efficient at encoding and maintaining phonological representations in verbal short-term memory utilizing phonological and linguistic strategies during memory tasks. PMID:26496666

  19. [The Impact of Diseases (ICD-10) and Impairments of Activity and Participation (ICF) on the Long-Term Care Insurance in Germany (SGB XI)].

    PubMed

    Schmitt, J

    2006-07-01

    On the basis of a representative sample of expert records from the Medical Review Board of the statutory care insurance funds (MDK) it could be shown that in the year 2003 more diseases of dementia had been examined for the long-term care insurance. The diagnois of dementia is statistically significant as a determinat of exposition related to get benefit from the care insuance. Help assistance which is needed after suffering form fraturs of bones are significant too, but related to get no benefits. In Germany the expert records of the long-term care insurance investigate the help assistance defined by the Social Code (SGB XI) which is needed in the daily live of the disabled and handicaped people. The classification of the SGB XI for daily performances offers the required transparency by using the mulitvariate logistic regression analysis with the predictor to get benefits from the care insurance. The help assistance estimated in the sample was recoded with the International Classification of Functioning, Disability and Health (ICF). Within this classification activity and participation in daily life of disabled and handicapped people are investigated. It was found that there could be more subdivions for these performances. A new analysis of the body function recorded in the ICF could be of interest to explain significant variables relating to the amount of help assistance.

  20. PERSISTENT IMPAIRMENTS IN SHORT-TERM BUT ENHANCED LONG-TERM SYNAPTIC PLASTICITY IN HIPPOCAMPAL AREA CA1 FOLLOWING DEVELOPMENTAL HYPOTHYROIDISM.

    EPA Science Inventory

    Thyroid hormones (TH) are critical for nervous system development. Deficiency of TH during development impair performance on tasks of learning and memory that rely upon the hippocampus, but the mechanism underlying this impairment is not well understood. The present study was ...

  1. Resistance of Dynamin-related Protein 1 Oligomers to Disassembly Impairs Mitophagy, Resulting in Myocardial Inflammation and Heart Failure.

    PubMed

    Cahill, Thomas J; Leo, Vincenzo; Kelly, Matthew; Stockenhuber, Alexander; Kennedy, Nolan W; Bao, Leyuan; Cereghetti, Grazia; Harper, Andrew R; Czibik, Gabor; Lao, Chunyan; Bellahcene, Mohamed; Steeples, Violetta; Ghaffari, Safar; Yavari, Arash; Mayer, Alice; Poulton, Joanna; Ferguson, David J P; Scorrano, Luca; Hettiarachchi, Nishani T; Peers, Chris; Boyle, John; Hill, R Blake; Simmons, Alison; Watkins, Hugh; Dear, T Neil; Ashrafian, Houman

    2015-10-23

    We have reported previously that a missense mutation in the mitochondrial fission gene Dynamin-related protein 1 (Drp1) underlies the Python mouse model of monogenic dilated cardiomyopathy. The aim of this study was to investigate the consequences of the C452F mutation on Drp1 protein function and to define the cellular sequelae leading to heart failure in the Python monogenic dilated cardiomyopathy model. We found that the C452F mutation increased Drp1 GTPase activity. The mutation also conferred resistance to oligomer disassembly by guanine nucleotides and high ionic strength solutions. In a mouse embryonic fibroblast model, Drp1 C452F cells exhibited abnormal mitochondrial morphology and defective mitophagy. Mitochondria in C452F mouse embryonic fibroblasts were depolarized and had reduced calcium uptake with impaired ATP production by oxidative phosphorylation. In the Python heart, we found a corresponding progressive decline in oxidative phosphorylation with age and activation of sterile inflammation. As a corollary, enhancing autophagy by exposure to a prolonged low-protein diet improved cardiac function in Python mice. In conclusion, failure of Drp1 disassembly impairs mitophagy, leading to a downstream cascade of mitochondrial depolarization, aberrant calcium handling, impaired ATP synthesis, and activation of sterile myocardial inflammation, resulting in heart failure. PMID:26370078

  2. Alzheimer's therapeutics targeting amyloid beta 1-42 oligomers II: Sigma-2/PGRMC1 receptors mediate Abeta 42 oligomer binding and synaptotoxicity.

    PubMed

    Izzo, Nicholas J; Xu, Jinbin; Zeng, Chenbo; Kirk, Molly J; Mozzoni, Kelsie; Silky, Colleen; Rehak, Courtney; Yurko, Raymond; Look, Gary; Rishton, Gilbert; Safferstein, Hank; Cruchaga, Carlos; Goate, Alison; Cahill, Michael A; Arancio, Ottavio; Mach, Robert H; Craven, Rolf; Head, Elizabeth; LeVine, Harry; Spires-Jones, Tara L; Catalano, Susan M

    2014-01-01

    Amyloid beta (Abeta) 1-42 oligomers accumulate in brains of patients with Mild Cognitive Impairment (MCI) and disrupt synaptic plasticity processes that underlie memory formation. Synaptic binding of Abeta oligomers to several putative receptor proteins is reported to inhibit long-term potentiation, affect membrane trafficking and induce reversible spine loss in neurons, leading to impaired cognitive performance and ultimately to anterograde amnesia in the early stages of Alzheimer's disease (AD). We have identified a receptor not previously associated with AD that mediates the binding of Abeta oligomers to neurons, and describe novel therapeutic antagonists of this receptor capable of blocking Abeta toxic effects on synapses in vitro and cognitive deficits in vivo. Knockdown of sigma-2/PGRMC1 (progesterone receptor membrane component 1) protein expression in vitro using siRNA results in a highly correlated reduction in binding of exogenous Abeta oligomers to neurons of more than 90%. Expression of sigma-2/PGRMC1 is upregulated in vitro by treatment with Abeta oligomers, and is dysregulated in Alzheimer's disease patients' brain compared to age-matched, normal individuals. Specific, high affinity small molecule receptor antagonists and antibodies raised against specific regions on this receptor can displace synthetic Abeta oligomer binding to synaptic puncta in vitro and displace endogenous human AD patient oligomers from brain tissue sections in a dose-dependent manner. These receptor antagonists prevent and reverse the effects of Abeta oligomers on membrane trafficking and synapse loss in vitro and cognitive deficits in AD mouse models. These findings suggest sigma-2/PGRMC1 receptors mediate saturable oligomer binding to synaptic puncta on neurons and that brain penetrant, small molecules can displace endogenous and synthetic oligomers and improve cognitive deficits in AD models. We propose that sigma-2/PGRMC1 is a key mediator of the pathological effects of

  3. Caffeine treatment prevents rapid eye movement sleep deprivation-induced impairment of late-phase long-term potentiation in the dentate gyrus.

    PubMed

    Alhaider, Ibrahim A; Alkadhi, Karim A

    2015-11-01

    The CA1 and dentate gyrus (DG) are physically and functionally closely related areas of the hippocampus, but they differ in various respects, including their reactions to different insults. The purpose of this study was to determine the protective effects of chronic caffeine treatment on late-phase long-term potentiation (L-LTP) and its signalling cascade in the DG area of the hippocampus of rapid eye movement sleep-deprived rats. Rats were chronically treated with caffeine (300 mg/L drinking water) for 4 weeks, after which they were sleep-deprived for 24 h. L-LTP was induced in in anaesthetized rats, and extracellular field potentials from the DG area were recorded in vivo. The levels of L-LTP-related signalling proteins were assessed by western blot analysis. Sleep deprivation markedly reduced L-LTP magnitude, and basal levels of total cAMP response element-binding protein (CREB), phosphorylated CREB (P-CREB), and calcium/calmodulin kinase IV (CaMKIV). Chronic caffeine treatment prevented the reductions in the basal levels of P-CREB, total CREB and CaMKIV in sleep-deprived rats. Furthermore, caffeine prevented post-L-LTP sleep deprivation-induced downregulation of P-CREB and brain-derived neurotrophic factor in the DG. The current findings show that caffeine treatment prevents acute sleep deprivation-induced deficits in brain function.

  4. Gulf War agent exposure causes impairment of long-term memory formation and neuropathological changes in a mouse model of Gulf War Illness.

    PubMed

    Zakirova, Zuchra; Tweed, Miles; Crynen, Gogce; Reed, Jon; Abdullah, Laila; Nissanka, Nadee; Mullan, Myles; Mullan, Michael J; Mathura, Venkatarajan; Crawford, Fiona; Ait-Ghezala, Ghania

    2015-01-01

    Gulf War Illness (GWI) is a chronic multisymptom illness with a central nervous system component such as memory deficits, neurological, and musculoskeletal problems. There are ample data that demonstrate that exposure to Gulf War (GW) agents, such as pyridostigmine bromide (PB) and pesticides such as permethrin (PER), were key contributors to the etiology of GWI post deployment to the Persian GW. In the current study, we examined the consequences of acute (10 days) exposure to PB and PER in C57BL6 mice. Learning and memory tests were performed at 18 days and at 5 months post-exposure. We investigated the relationship between the cognitive phenotype and neuropathological changes at short and long-term time points post-exposure. No cognitive deficits were observed at the short-term time point, and only minor neuropathological changes were detected. However, cognitive deficits emerged at the later time point and were associated with increased astrogliosis and reduction of synaptophysin staining in the hippocampi and cerebral cortices of exposed mice, 5 months post exposure. In summary, our findings in this mouse model of GW agent exposure are consistent with some GWI symptom manifestations, including delayed onset of symptoms and CNS disturbances observed in GWI veterans.

  5. Caffeine treatment prevents rapid eye movement sleep deprivation-induced impairment of late-phase long-term potentiation in the dentate gyrus.

    PubMed

    Alhaider, Ibrahim A; Alkadhi, Karim A

    2015-11-01

    The CA1 and dentate gyrus (DG) are physically and functionally closely related areas of the hippocampus, but they differ in various respects, including their reactions to different insults. The purpose of this study was to determine the protective effects of chronic caffeine treatment on late-phase long-term potentiation (L-LTP) and its signalling cascade in the DG area of the hippocampus of rapid eye movement sleep-deprived rats. Rats were chronically treated with caffeine (300 mg/L drinking water) for 4 weeks, after which they were sleep-deprived for 24 h. L-LTP was induced in in anaesthetized rats, and extracellular field potentials from the DG area were recorded in vivo. The levels of L-LTP-related signalling proteins were assessed by western blot analysis. Sleep deprivation markedly reduced L-LTP magnitude, and basal levels of total cAMP response element-binding protein (CREB), phosphorylated CREB (P-CREB), and calcium/calmodulin kinase IV (CaMKIV). Chronic caffeine treatment prevented the reductions in the basal levels of P-CREB, total CREB and CaMKIV in sleep-deprived rats. Furthermore, caffeine prevented post-L-LTP sleep deprivation-induced downregulation of P-CREB and brain-derived neurotrophic factor in the DG. The current findings show that caffeine treatment prevents acute sleep deprivation-induced deficits in brain function. PMID:26449851

  6. Gulf War Agent Exposure Causes Impairment of Long-Term Memory Formation and Neuropathological Changes in a Mouse Model of Gulf War Illness

    PubMed Central

    Zakirova, Zuchra; Tweed, Miles; Crynen, Gogce; Reed, Jon; Abdullah, Laila; Nissanka, Nadee; Mullan, Myles; Mullan, Michael J.; Mathura, Venkatarajan; Crawford, Fiona; Ait-Ghezala, Ghania

    2015-01-01

    Gulf War Illness (GWI) is a chronic multisymptom illness with a central nervous system component such as memory deficits, neurological, and musculoskeletal problems. There are ample data that demonstrate that exposure to Gulf War (GW) agents, such as pyridostigmine bromide (PB) and pesticides such as permethrin (PER), were key contributors to the etiology of GWI post deployment to the Persian GW. In the current study, we examined the consequences of acute (10 days) exposure to PB and PER in C57BL6 mice. Learning and memory tests were performed at 18 days and at 5 months post-exposure. We investigated the relationship between the cognitive phenotype and neuropathological changes at short and long-term time points post-exposure. No cognitive deficits were observed at the short-term time point, and only minor neuropathological changes were detected. However, cognitive deficits emerged at the later time point and were associated with increased astrogliosis and reduction of synaptophysin staining in the hippocampi and cerebral cortices of exposed mice, 5 months post exposure. In summary, our findings in this mouse model of GW agent exposure are consistent with some GWI symptom manifestations, including delayed onset of symptoms and CNS disturbances observed in GWI veterans. PMID:25785457

  7. Posttraining activation of CB1 cannabinoid receptors in the CA1 region of the dorsal hippocampus impairs object recognition long-term memory.

    PubMed

    Clarke, Julia R; Rossato, Janine I; Monteiro, Siomara; Bevilaqua, Lia R M; Izquierdo, Iván; Cammarota, Martín

    2008-09-01

    Evidence indicates that brain endocannabinoids are involved in memory processing. However, the participation of CB1 and CB2 cannabinoid receptors in recognition memory has not been yet conclusively determined. Therefore, we evaluated the effect of the posttraining activation of hippocampal cannabinoid receptors on the consolidation of object recognition memory. Rats with infusion cannulae stereotaxically aimed to the CA1 region of the dorsal hippocampus were trained in an object recognition learning task involving exposure to two different stimulus objects. Memory retention was assessed at different times after training. In the test sessions, one of the objects presented during training was replaced by a novel one. When infused in the CA1 region immediately after training, the non-selective cannabinoid receptor agonist WIN-55,212-2 and the endocannabinoid membrane transporter inhibitor VDM-11 blocked long-term memory retention in a dose-dependent manner without affecting short-term memory, exploratory behavior, anxiety state or the functionality of the hippocampus. The amnesic effect of WIN-55,212-2 and VDM-11 was not due to state-dependency and was completely reversed by co-infusion of the CB1 receptor antagonist AM-251 and mimicked by the CB1 receptor agonist ACEA but not by the CB2 receptor agonists JWH-015 and palmitoylethanolamide. Our data indicate that activation of hippocampal CB1 receptors early after training hampers consolidation of object recognition memory.

  8. Deleting Both PHLPP1 and CANP1 Rescues Impairments in Long-Term Potentiation and Learning in Both Single Knockout Mice

    ERIC Educational Resources Information Center

    Liu, Yan; Sun, Jiandong; Wang, Yubin; Lopez, Dulce; Tran, Jennifer; Bi, Xiaoning; Baudry, Michel

    2016-01-01

    Calpain-1 (CANP1) has been shown to play a critical role in synaptic plasticity and learning and memory, as its deletion in mice results in impairment in theta-burst stimulation (TBS)-induced LTP and various forms of learning and memory. Likewise, PHLPP1 (aka SCOP) has also been found to participate in learning and memory, as PHLPP1 overexpression…

  9. Long-term safety and efficacy of dalfampridine for walking impairment in patients with multiple sclerosis: Results of open-label extensions of two Phase 3 clinical trials

    PubMed Central

    Goodman, Andrew D; Bethoux, Francois; Brown, Theodore R; Schapiro, Randall T; Cohen, Ron; Marinucci, Lawrence N; Henney, Herbert R

    2015-01-01

    Background: In Phase 3 double-blind trials (MS-F203 and MS-F204), dalfampridine extended release tablets 10 mg twice daily (dalfampridine-ER; prolonged-release fampridine in Europe; fampridine modified or sustained release elsewhere) improved walking speed relative to placebo in patients with multiple sclerosis (MS). Objectives: Evaluation of long-term safety and efficacy of dalfampridine-ER in open-label extensions (MS-F203EXT, MS-F204EXT). Methods: Patients received dalfampridine-ER 10 mg twice daily; and had Timed 25-Foot Walk (T25FW) assessments at 2, 14 and 26 weeks, and then every 6 months. Subjects were categorized as dalfampridine-ER responders or non-responders, based on their treatment response in the double-blind parent trials that assessed T25FW. Results: We had 269 patients enter MS-F203EXT and 154 patients complete it; for a maximum exposure of 5 years. We had 214 patients enter MS-F204EXT and 146 complete it; for a maximum exposure of 3.3 years. No new safety signals emerged and dalfampridine-ER tolerability was consistent with the double-blind phase. Improvements in walking speed were lost after dalfampridine-ER was discontinued in the parent trial, but returned by the 2-week assessment after re-initiation of the drug. Throughout the extensions, mean improvement in walking speed declined, but remained improved, among the double-blind responders as compared with non-responders. Conclusions: The dalfamipridine-ER safety profile was consistent with the parent trials. Although walking speed decreased over time, dalfampridine-ER responders continued to show improved walking speed, which was sustained compared with non-responders. PMID:25583832

  10. A decision aid regarding long-term tube feeding targeting substitute decision makers for cognitively impaired older persons in Japan: A small-scale before-and-after study

    PubMed Central

    2014-01-01

    Background In Japan, there is no decision-making guide regarding long-term tube feeding that specifically targets individuals making decisions on behalf of cognitively impaired older persons (substitute decision makers). The objective of this study was to describe the development and evaluation of such a decision aid. Methods In this before-and-after study, participants comprised substitute decision makers for 13 cognitively impaired inpatients aged 65 years and older who were being considered for placement of a percutaneous endoscopic gastrostomy tube in acute care hospitals and mixed-care hospitals in Japan. Questionnaires were used to compare substitute decision makers’ knowledge, decisional conflict, and predisposition regarding feeding tube placement before and after exposure to a decision aid. The acceptability of the decision aid was also assessed. Paired t-tests were used to compare participants’ knowledge and decisional conflict scores before and after using the decision aid. Results Substitute decision makers showed significantly increased knowledge (P < .001) and decreased decisional conflict (P < .01) regarding long-term tube feeding after using the decision aid. All substitute decision makers found the decision aid helpful and acceptable. Conclusions The decision aid facilitated the decision-making process of substitute decision makers by decreasing decisional conflict and increasing knowledge. PMID:24495735

  11. Long-term study of patients with type 2 diabetes and moderate renal impairment shows that dapagliflozin reduces weight and blood pressure but does not improve glycemic control

    PubMed Central

    Kohan, Donald E; Fioretto, Paola; Tang, Weihua; List, James F

    2014-01-01

    In patients with diabetes, glycemic improvement by sodium-glucose cotransporter-2 inhibition depends on the kidney's ability to filter glucose. Dapagliflozin, a sodium-glucose cotransporter-2 inhibitor, reduces hyperglycemia in patients with diabetes and normal or mildly impaired renal function. In this randomized, double-blind, placebo-controlled study we assessed daily treatment with dapagliflozin in 252 patients with inadequately controlled type 2 diabetes and moderate renal impairment. The primary endpoint, the mean change in HbA1c, was not statistically different from placebo after 24 weeks (−0.41% and −0.44% for 5- and 10-mg doses, respectively, and −0.32% for placebo). The mean weight change from baseline was −1.54 and −1.89 kg for the 5- and 10-mg doses, respectively, and +0.21 kg for placebo. The mean systolic and diastolic blood pressure decreased in the dapagliflozin groups compared to placebo. Through 104 weeks, 13 patients receiving dapagliflozin and no patients receiving placebo experienced bone fracture. At 1 week, the mean serum creatinine increased with dapagliflozin 5 mg (+0.13 mg/dl) and 10 mg (+0.18 mg/dl) and did not change further after 104 weeks. Mean serum electrolytes did not change in any group, and there were fewer episodes of hyperkalemia with dapagliflozin than placebo. Thus, in patients with moderate renal impairment, dapagliflozin did not improve glycemic control, but reduced weight and blood pressure. PMID:24067431

  12. Developmental exposure to di(2-ethylhexyl) phthalate impairs endocrine pancreas and leads to long-term adverse effects on glucose homeostasis in the rat.

    PubMed

    Lin, Yi; Wei, Jie; Li, Yuanyuan; Chen, Jun; Zhou, Zhao; Song, Liqiong; Wei, Zhengzheng; Lv, Ziquan; Chen, Xi; Xia, Wei; Xu, Shunqing

    2011-09-01

    -Di(2-ethylhexyl) phthalate (DEHP), a typical endocrine-disrupting chemical (EDC), is widely used as plasticizer. DEHP exposure in humans is virtually ubiquitous, and those undergoing certain medical procedures can be especially high. In this study, we investigated whether developmental DEHP exposure disrupted glucose homeostasis in the rat and whether this was associated with the early impairment in endocrine pancreas. Pregnant Wistar rats were administered DEHP (1.25 and 6.25 mg·kg(-1)·day(-1)) or corn oil throughout gestation and lactation by oral gavage. Body weight, glucose and insulin tolerance, and β-cell morphometry and function were examined in offspring during the growth. In this study, developmental DEHP exposure led to abnormal β-cell ultrastructure, reduced β-cell mass, and pancreatic insulin content as well as alterations in the expression of genes involved in pancreas development and β-cell function in offspring at weaning. At adulthood, female DEHP-exposed offspring exhibited elevated blood glucose, reduced serum insulin, impaired glucose tolerance, and insulin secretion. Male DEHP-exposed offspring had increased serum insulin, although there were no significant differences in blood glucose at fasting and during glucose tolerance test. In addition, both male and female DEHP-exposed offspring had significantly lower birth weight and maintained relatively lower body weight up to 27 wk of age. These results suggest that developmental exposure to DEHP gives rise to β-cell dysfunction and the whole body glucometabolic abnormalities in the rat. DEHP exposure in critical periods of development can be a potential risk factor, at least in part, for developing diabetes.

  13. Reproduction impairment and endocrine disruption in female zebrafish after long-term exposure to MC-LR: A life cycle assessment.

    PubMed

    Hou, Jie; Li, Li; Wu, Ning; Su, Yujing; Lin, Wang; Li, Guangyu; Gu, Zemao

    2016-01-01

    Microcystin-LR (MC-LR) has been found to cause reproductive and developmental impairments as well as to disrupt sex hormone homeostasis of fish during acute and sub-chronic toxic experiments. However, fish in natural environments are continuously exposed to MC-LR throughout their entire life cycle as opposed to short-term exposure. Here, we tested the hypothesis that the mechanism by which MC-LR harms female fish reproduction and development within natural water bodies is through interference of the reproductive endocrine system. In the present study, zebrafish hatchlings (5 d post-fertilization) were exposed to 0, 0.3, 3 and 30 μg/L MC-LR for 90 d until reaching sexual maturity. Female zebrafish were selected, and the changes in growth and developmental indicators, ovarian ultrastructure as well as the levels of gonadal steroid hormones and vitellogenin (VTG) were examined along with the transcription of related genes in the hypothalamic-pituitary-gonadal-liver axis (HPGL-axis). The results showed for the first time, a life cycle exposure to MC-LR caused growth inhibition, decreased ovary weight and ovarian ultra-pathological lesions. Decreased ovarian testosterone levels indicated that MC-LR disrupted sex steroid hormone balance. Significantly up-regulated transcription of brain FSHβ and LHβ along with ovarian ERα, FSHR and LHR suggested positive feedback regulation in the HPGL-axis was induced as a compensatory mechanism for MC-LR damage. It was also noted that ovarian VTG content and hepatic ERα and VTG1 expression were all down-regulated, which might be responsible for reduced vitellus storage noted in our histological observations. Our findings indicate that a life cycle exposure to MC-LR impairs the development and reproduction of female zebrafish by disrupting the transcription of related HPGL-axis genes, suggesting that MC-LR has potential adverse effects on fish reproduction and thus population dynamics in MCs-contaminated aquatic environment.

  14. Reproduction impairment and endocrine disruption in female zebrafish after long-term exposure to MC-LR: A life cycle assessment.

    PubMed

    Hou, Jie; Li, Li; Wu, Ning; Su, Yujing; Lin, Wang; Li, Guangyu; Gu, Zemao

    2016-01-01

    Microcystin-LR (MC-LR) has been found to cause reproductive and developmental impairments as well as to disrupt sex hormone homeostasis of fish during acute and sub-chronic toxic experiments. However, fish in natural environments are continuously exposed to MC-LR throughout their entire life cycle as opposed to short-term exposure. Here, we tested the hypothesis that the mechanism by which MC-LR harms female fish reproduction and development within natural water bodies is through interference of the reproductive endocrine system. In the present study, zebrafish hatchlings (5 d post-fertilization) were exposed to 0, 0.3, 3 and 30 μg/L MC-LR for 90 d until reaching sexual maturity. Female zebrafish were selected, and the changes in growth and developmental indicators, ovarian ultrastructure as well as the levels of gonadal steroid hormones and vitellogenin (VTG) were examined along with the transcription of related genes in the hypothalamic-pituitary-gonadal-liver axis (HPGL-axis). The results showed for the first time, a life cycle exposure to MC-LR caused growth inhibition, decreased ovary weight and ovarian ultra-pathological lesions. Decreased ovarian testosterone levels indicated that MC-LR disrupted sex steroid hormone balance. Significantly up-regulated transcription of brain FSHβ and LHβ along with ovarian ERα, FSHR and LHR suggested positive feedback regulation in the HPGL-axis was induced as a compensatory mechanism for MC-LR damage. It was also noted that ovarian VTG content and hepatic ERα and VTG1 expression were all down-regulated, which might be responsible for reduced vitellus storage noted in our histological observations. Our findings indicate that a life cycle exposure to MC-LR impairs the development and reproduction of female zebrafish by disrupting the transcription of related HPGL-axis genes, suggesting that MC-LR has potential adverse effects on fish reproduction and thus population dynamics in MCs-contaminated aquatic environment. PMID

  15. Loss of GluN2B-containing NMDA receptors in CA1 hippocampus and cortex impairs long-term depression, reduces dendritic spine density and disrupts learning

    PubMed Central

    Brigman, Jonathan L.; Wright, Tara; Talani, Giuseppe; Prasad-Mulcare, Shweta; Jinde, Seiichiro; Seabold, Gail K.; Mathur, Poonam; Davis, Margaret I.; Bock, Roland; Gustin, Richard M.; Colbran, Roger J.; Alvarez, Veronica A.; Nakazawa, Kazu; Delpire, Eric; Lovinger, David M.; Holmes, Andrew

    2010-01-01

    N-methyl-D-aspartate receptors (NMDARs) are key mediators of certain forms of synaptic plasticity and learning. NMDAR complexes are heteromers composed of an obligatory GluN1 subunit and one or more GluN2 (GluN2A- GluN2D) subunits. Different subunits confer distinct physiological and molecular properties to NMDARs, but their contribution to synaptic plasticity and learning in the adult brain remains uncertain. Here, we generated mice lacking GluN2B in pyramidal neurons of cortex and CA1 subregion of hippocampus. We found that hippocampal principal neurons of adult GluN2B mutants had faster decaying NMDAR-mediated excitatory postsynaptic currents (EPSCs) than non-mutant controls, and were insensitive to GluN2B but not NMDAR antagonism. A sub-saturating form of hippocampal long-term potentiation (LTP) was impaired in the mutants, whereas a saturating form of LTP was intact. A NMDAR-dependent form of long-term depression (LTD) produced by low-frequency stimulation combined with glutamate transporter inhibition was abolished in the mutants. Additionally, mutants exhibited decreased dendritic spine density in CA1 hippocampal neurons as compared to controls. On multiple assays for corticohippocampal-mediated learning and memory (hidden platform Morris water maze, T-maze spontaneous alternation, Pavlovian trace fear conditioning), mutants were impaired. These data further demonstrate the importance of GluN2B for synaptic plasticity in the adult hippocampus and suggest a particularly critical role in LTD, at least the form studied here. The finding that loss of GluN2B was sufficient to cause learning deficits illustrates the contribution of GluN2B-mediated forms of plasticity to memory formation, with implications for elucidating NMDAR-related dysfunction in disease-related cognitive impairment. PMID:20357110

  16. Mice lacking the PSD-95–interacting E3 ligase, Dorfin/Rnf19a, display reduced adult neurogenesis, enhanced long-term potentiation, and impaired contextual fear conditioning

    PubMed Central

    Park, Hanwool; Yang, Jinhee; Kim, Ryunhee; Li, Yan; Lee, Yeunkum; Lee, Chungwoo; Park, Jongil; Lee, Dongmin; Kim, Hyun; Kim, Eunjoon

    2015-01-01

    Protein ubiquitination has a significant influence on diverse aspects of neuronal development and function. Dorfin, also known as Rnf19a, is a RING finger E3 ubiquitin ligase implicated in amyotrophic lateral sclerosis and Parkinson’s disease, but its in vivo functions have not been explored. We report here that Dorfin is a novel binding partner of the excitatory postsynaptic scaffolding protein PSD-95. Dorfin-mutant (Dorfin−/−) mice show reduced adult neurogenesis and enhanced long-term potentiation in the hippocampal dentate gyrus, but normal long-term potentiation in the CA1 region. Behaviorally, Dorfin−/− mice show impaired contextual fear conditioning, but normal levels of cued fear conditioning, fear extinction, spatial learning and memory, object recognition memory, spatial working memory, and pattern separation. Using a proteomic approach, we also identify a number of proteins whose ubiquitination levels are decreased in the Dorfin−/− brain. These results suggest that Dorfin may regulate adult neurogenesis, synaptic plasticity, and contextual fear memory. PMID:26553645

  17. Long-term follow up of patients with implantable cardioverter-defibrillators and mild, moderate, or severe impairment of left ventricular function.

    PubMed Central

    Trappe, H. J.; Wenzlaff, P.; Pfitzner, P.; Fieguth, H. G.

    1997-01-01

    OBJECTIVE: To determine whether patients with life threatening ventricular tachyarrhythmias, impaired left ventricular function, and severe heart failure will benefit from implantable cardioverter-defibrillator (ICD) treatment. DESIGN: 410 patients were followed up after ICD implant. Left ventricular function was assessed by the New York Heart Association (NYHA) functional class of heart failure: 50 patients (12%) were in NYHA I-II, 151 (37%) in NYHA II, 117 (29%) in NYHA II-III, and 92 (22%) in NYHA III. Epicardial ICD implantation was performed in 209 patients (51%) and 201 patients (49%) received non-thoracotomy ICDs. RESULTS: Perioperatively, 12 patients (3%) died, more often after epicardial ICD implant (11/209 patients, 5%) than after transvenous implant (1/201 patients, < 1%) (P < 0.05). During a mean (SD) follow up of 28 (24) months (range < 1 to 114 months), 90 patients (23%) died: nine (2%) died from sudden arrhythmia; five (1%) also died suddenly but probably not from arrhythmic causes; 55 (14%) died from cardiac causes (congestive heart failure, myocardial reinfarction); 21 (5%) died from non-cardiac causes. The three year, five year, and seven year survival was 92-96% for arrhythmic mortality in NYHA class I, II and III, compared to a three year survival of 94% and a five year and seven year survival of 84% for patients in NYHA class II-III. 338 patients (82%) received ICD shocks (21 (SD 43) shocks per patient); patients in NYHA class II (83%), class II-III (84%), and class III (90%) received ICD discharges more often than those in class I-II (64%) (P < 0.05). The mean (SD) time interval between ICD implant and the first ICD shock was shorter in NYHA class II (16 (17) months), class II-III (19 (27) months), and class III (16 (19) months) than in class 0-I (22 (24) months) (P < 0.05). CONCLUSIONS: Patients with mild, moderate, and severe left ventricular dysfunction benefit from ICD treatment and these patients survive for a considerable time after the

  18. Long-term acarbose administration alleviating the impairment of spatial learning and memory in the SAMP8 mice was associated with alleviated reduction of insulin system and acetylated H4K8.

    PubMed

    Yan, Wen-Wen; Chen, Gui-Hai; Wang, Fang; Tong, Jing-Jing; Tao, Fei

    2015-04-01

    Age-associated memory impairment (AAMI) not only reduces the quality of life for the elderly but also increases the costs of healthcare for society. Methods that can regulate glucose metabolism, insulin/insulin-like growth factor 1 (IGF-1) system and acetylated histone H4 lysine 8 (H4K8ac), one of the most well-researched facets of histone acetylation modification associating with cognition, tend to ameliorate the AAMI. Here, we used SAMP8 mice, the excellent animal model of aging and AAMI, to study the effect of long-term treatment with acarbose, an inhibitor of a-glucosidase, on AAMI and explore whether blood glucose, insulin/IGF-1 system and H4K8ac are associated with potential effects. The treatment group received acarbose (20mg/kg/d, dissolved in drinking water) at the age of 3-month until 9-month old before the behavioral test, and the controls only received water. Compared to the young controls (3-month-old, n=11), the old group (9-month-old, n=8) had declined abilities of spatial learning and memory and levels of serum insulin, hippocampal insulin receptors (InsRs) and H4K8ac. Interestingly, the acarbose group (9-month-old, n=9) showed better abilities of spatial learning and memory and higher levels of insulin, InsRs and H4K8ac relative to the old controls. Good performance of spatial learning and memory was positively correlated with the elevated insulin, InsRs and H4K8ac. All these results suggested that long-term administration of acarbose could alleviate the age-related impairment of spatial learning and memory in the SAMP8 mice, and the alleviated reduction of an insulin system and H4K8ac might be associated with the alleviation.

  19. Long-term environmental stewardship.

    SciTech Connect

    Nagy, Michael David

    2010-08-01

    The purpose of this Supplemental Information Source Document is to effectively describe Long-Term Environmental Stewardship (LTES) at Sandia National Laboratories/New Mexico (SNL/NM). More specifically, this document describes the LTES and Long-Term Stewardship (LTS) Programs, distinguishes between the LTES and LTS Programs, and summarizes the current status of the Environmental Restoration (ER) Project.

  20. Presynaptic long-term plasticity

    PubMed Central

    Yang, Ying; Calakos, Nicole

    2013-01-01

    Long-term synaptic plasticity is a major cellular substrate for learning, memory, and behavioral adaptation. Although early examples of long-term synaptic plasticity described a mechanism by which postsynaptic signal transduction was potentiated, it is now apparent that there is a vast array of mechanisms for long-term synaptic plasticity that involve modifications to either or both the presynaptic terminal and postsynaptic site. In this article, we discuss current and evolving approaches to identify presynaptic mechanisms as well as discuss their limitations. We next provide examples of the diverse circuits in which presynaptic forms of long-term synaptic plasticity have been described and discuss the potential contribution this form of plasticity might add to circuit function. Finally, we examine the present evidence for the molecular pathways and cellular events underlying presynaptic long-term synaptic plasticity. PMID:24146648

  1. Day Care as a Long-Term Care Service Study.

    ERIC Educational Resources Information Center

    Zaki, Gamel; Zaki, Sylvia

    Day care is a growing service in the field of long-term care, increasing the options available to the impaired elderly. To study the development of adult day care centers in southeastern New England, and to identify the relationship of day care centers to the long term care network of services, the 11 day care centers in the catchment area of the…

  2. Early beneficial effect of matrix metalloproteinase inhibition on blood-brain barrier permeability as measured by magnetic resonance imaging countered by impaired long-term recovery after stroke in rat brain.

    PubMed

    Sood, Rohit R; Taheri, Saeid; Candelario-Jalil, Eduardo; Estrada, Eduardo Y; Rosenberg, Gary A

    2008-02-01

    Proteolytic disruption of the extracellular matrix with opening of the blood-brain barrier (BBB) because of matrix metalloproteinases (MMPs) occurs in reperfusion injury after stroke. Matrix metalloproteinase inhibition blocks the early disruption of the BBB, but the long-term consequences of short-term MMP inhibition are not known. Recently, a method to quantify BBB permeability by graphical methods was described, which provides a way to study both early disruption of the BBB and long-term effects on recovery in the same animal. We used a broad-spectrum MMP inhibitor, BB1101, to determine both the usefulness of the Magnetic resonance imaging (MRI) method for treatment studies and the long-term effects on recovery. Magnetic resonance imaging studies were performed in control (N=6) and drug-treated (N=8) groups on a dedicated 4.7-T MRI scanner. Adult Wistar-Kyoto underwent a 2-h middle cerebral artery occlusion followed by an MRI study after 3 h of reperfusion, which consisted of T2- and diffusion-weighted techniques. Additionally, a rapid T1 mapping protocol was also implemented to acquire one pre-gadolinium-diethylenetriaminepentaacetic acid baseline data set followed by postinjection data sets at 3-min intervals for 45 mins. The same animal was imaged again at 48 h for lesion size estimation. Data was postprocessed pixel-wise to generate apparent diffusion coefficient and permeability coefficient maps. Treatment with BB-1101 significantly reduced BBB permeability at 3 h, but failed to reduce lesion size at 48 h. Behavioral studies showed impairment in recovery in treated rats. Magnetic resonance imaging allowed for the monitoring of multiple parameters in the same animal. Our studies showed that BB-1101 was an excellent inhibitor of the BBB damage. However, results show that BB-1101 may be responsible for significant deterioration in neurologic status of treated animals. Although these preliminary results suggest that BB-1101 is useful in reducing early BBB

  3. Long term complications of diabetes

    MedlinePlus

    ... this page: //medlineplus.gov/ency/patientinstructions/000327.htm Long term complications of diabetes To use the sharing ... sores and infections. If it goes on too long, your toes, foot, or leg may need to ...

  4. Abdominal Pain, Long-Term

    MedlinePlus

    MENU Return to Web version Abdominal Pain, Long-term See complete list of charts. Ongoing or recurrent abdominal pain, also called chronic pain, may be difficult to diagnose, causing frustration for ...

  5. Long-term biomass research

    SciTech Connect

    Not Available

    1981-03-01

    Some of DOE's long term R and D programs for biomass are summarized in this article. These include research efforts in the fields of anaerobic digestion, energy farming, short rotation cultivation and aquatic farming. (DMC)

  6. Long-term consequences of anorexia nervosa.

    PubMed

    Meczekalski, Blazej; Podfigurna-Stopa, Agnieszka; Katulski, Krzysztof

    2013-07-01

    Anorexia nervosa (AN) is a psychiatric disorder that occurs mainly in female adolescents and young women. The obsessive fear of weight gain, critically limited food intake and neuroendocrine aberrations characteristic of AN have both short- and long-term consequences for the reproductive, cardiovascular, gastrointestinal and skeletal systems. Neuroendocrine changes include impairment of gonadotropin releasing-hormone (GnRH) pulsatile secretion and changes in neuropeptide activity at the hypothalamic level, which cause profound hypoestrogenism. AN is related to a decrease in bone mass density, which can lead to osteopenia and osteoporosis and a significant increase in fracture risk in later life. Rates of birth complications and low birth weight may be higher in women with previous AN. The condition is associated with fertility problems, unplanned pregnancies and generally negative attitudes to pregnancy. During pregnancy, women with the condition have higher rates of hyperemesis gravidarum, anaemia and obstetric complications, as well as impaired weight gain and compromised intrauterine foetal growth. It is reported that 80% of AN patients are affected by a cardiac complications such as sinus bradycardia, a prolonged QT interval on electrocardiography, arrythmias, myocardial mass modification and hypotension. A decrease in bone mineral density (BMD) is one of the most important medical consequences of AN. Reduced BMD may subsequently lead to a three- to seven-fold increased risk of spontaneous fractures. Untreated AN is associated with a significant increase in the risk of death. Better detection and sophisticated therapy should prevent the long-term consequences of this disorder. The aims of treatment are not only recovery but also prophylaxis and relief of the long-term effects of this disorder. Further investigations of the long-term disease risk are needed. PMID:23706279

  7. Long-term parenteral nutrition

    PubMed Central

    Ladefoged, Karin; Jarnum, Stig

    1978-01-01

    Nineteen patients (11 women and eight men) aged 20-68 received long-term parenteral nutrition, mostly at home, for six to 63 months (mean 19 months). Indications for LTPN were extensive, active Crohn's disease in three patients, intestinocutaneous fistulas in three, and short-bowel syndrome in the remaining 13 patients. Subclavian or intra-atrial (Broviac) catheters were most commonly used, for which the average life was four and seven months respectively. Complications of long-term parenteral nutrition included pneumothorax in four out of 48 subclavian vein punctures. Catheter-induced thrombosis of central veins was shown by phlebography 17 times in nine patients, and eight episodes of total occlusion occurred. Two of these patients had pulmonary infarction. Nineteen episodes of catheter sepsis occurred in 11 patients, but only one was fatal. Complications related to intestinal disease included intra-abdominal abscesses and intestinal fistulas, and disturbances of liver function. Five patients died, though in only two was death related to long-term parenteral nutrition. One of these patients died from catheter sepsis, the other had subdural haematoma possibly caused by anticoagulant treatment. Eight of the 14 surviving patients still needed parenteral nutrition. All received a disability pension, but six had an acceptable quality of life with almost normal social activities. Despite problems such as difficulties in maintaining standardised infusion programmes, it was concluded that long-term parenteral nutrition at home is practicable and consistent with an acceptable quality of life. ImagesFIG 2 PMID:98199

  8. Blood glucose concentration for predicting poor outcomes in patients with and without impaired glucose metabolism undergoing off-pump coronary artery bypass surgery – long-term observational study

    PubMed Central

    Majstrak, Franciszek; Opolski, Grzegorz; Filipiak, Krzysztof J.

    2016-01-01

    Introduction Strict glucose control is an everyday practice in the perioperative period. Elevated glucose level has a deleterious impact on clinical results, but a therapeutic target has not been stated yet. Aim To determine a glucose concentration range affecting long-term outcomes after coronary artery bypass surgery (CABG). Material and methods This study is a retrospective evaluation of consecutive patients treated in a university hospital in Poland from 2004 to 2008. Patients were divided into 2 groups: an impaired glucose metabolism group (IGM) if they had 1) known DM or 2) perioperative hyperglycaemia defined as ≥ 200 mg/dl; and a non-IGM group. The end point (EP) was all-cause mortality. Results One thousand two hundred and eleven patients were covered by the analysis. The observation time was from 01.01.2004 until 01.08.2012. Patients who had maximal glucose concentrations < 242 mg/dl had the lowest mortality risk (EP in 21.1%); a higher risk was noted in the group with glucose concentrations 242–324 mg/dl (EP in 30.8%); and a very high risk was found for the group where glucose concentration was > 324 mg/dl (EP in 44.2%) (p = 0.041). Patients with IGM had a shorter survival at the end of the study (p < 0.001). The longest survival was observed in patients whose maximal glucose level was ≤ 242 mg/dl (p < 0.001) and the minimal glucose concentration was in the range 61–110 mg/dl (p < 0.001). Conclusions Tight glucose concentration control should be performed irrespective of a diabetes diagnosis and proper treatment introduced when necessary. Maximal glucose concentration should be kept < 242 mg/dl, while the minimum should be in the range 60–110 mg/dl. PMID:27625687

  9. Blood glucose concentration for predicting poor outcomes in patients with and without impaired glucose metabolism undergoing off-pump coronary artery bypass surgery – long-term observational study

    PubMed Central

    Majstrak, Franciszek; Opolski, Grzegorz; Filipiak, Krzysztof J.

    2016-01-01

    Introduction Strict glucose control is an everyday practice in the perioperative period. Elevated glucose level has a deleterious impact on clinical results, but a therapeutic target has not been stated yet. Aim To determine a glucose concentration range affecting long-term outcomes after coronary artery bypass surgery (CABG). Material and methods This study is a retrospective evaluation of consecutive patients treated in a university hospital in Poland from 2004 to 2008. Patients were divided into 2 groups: an impaired glucose metabolism group (IGM) if they had 1) known DM or 2) perioperative hyperglycaemia defined as ≥ 200 mg/dl; and a non-IGM group. The end point (EP) was all-cause mortality. Results One thousand two hundred and eleven patients were covered by the analysis. The observation time was from 01.01.2004 until 01.08.2012. Patients who had maximal glucose concentrations < 242 mg/dl had the lowest mortality risk (EP in 21.1%); a higher risk was noted in the group with glucose concentrations 242–324 mg/dl (EP in 30.8%); and a very high risk was found for the group where glucose concentration was > 324 mg/dl (EP in 44.2%) (p = 0.041). Patients with IGM had a shorter survival at the end of the study (p < 0.001). The longest survival was observed in patients whose maximal glucose level was ≤ 242 mg/dl (p < 0.001) and the minimal glucose concentration was in the range 61–110 mg/dl (p < 0.001). Conclusions Tight glucose concentration control should be performed irrespective of a diabetes diagnosis and proper treatment introduced when necessary. Maximal glucose concentration should be kept < 242 mg/dl, while the minimum should be in the range 60–110 mg/dl.

  10. Long-term data archiving

    SciTech Connect

    Moore, David Steven

    2009-01-01

    Long term data archiving has much value for chemists, not only to retain access to research and product development records, but also to enable new developments and new discoveries. There are some recent regulatory requirements (e.g., FDA 21 CFR Part 11), but good science and good business both benefit regardless. A particular example of the benefits of and need for long term data archiving is the management of data from spectroscopic laboratory instruments. The sheer amount of spectroscopic data is increasing at a scary rate, and the pressures to archive come from the expense to create the data (or recreate it if it is lost) as well as its high information content. The goal of long-term data archiving is to save and organize instrument data files as well as any needed meta data (such as sample ID, LIMS information, operator, date, time, instrument conditions, sample type, excitation details, environmental parameters, etc.). This editorial explores the issues involved in long-term data archiving using the example of Raman spectral databases. There are at present several such databases, including common data format libraries and proprietary libraries. However, such databases and libraries should ultimately satisfy stringent criteria for long term data archiving, including readability for long times into the future, robustness to changes in computer hardware and operating systems, and use of public domain data formats. The latter criterion implies the data format should be platform independent and the tools to create the data format should be easily and publicly obtainable or developable. Several examples of attempts at spectral libraries exist, such as the ASTM ANDI format, and the JCAMP-DX format. On the other hand, proprietary library spectra can be exchanged and manipulated using proprietary tools. As the above examples have deficiencies according to the three long term data archiving criteria, Extensible Markup Language (XML; a product of the World Wide Web

  11. Influenza in long-term care facilities: preventable, detectable, treatable.

    PubMed

    Mossad, Sherif B

    2009-09-01

    Influenza in long-term care facilities is an ever more challenging problem. Vaccination of residents and health care workers is the most important preventive measure. Although vaccine efficacy has been questioned, the preponderance of data favors vaccination. Antiviral resistance complicates postexposure chemoprophylaxis and treatment. Factors that limit the choice of antiviral agents in this patient population include limited vaccine supplies and impaired dexterity and confusion in long-term care residents. PMID:19726556

  12. Soluble amyloid beta oligomers block the learning-induced increase in hippocampal sharp wave-ripple rate and impair spatial memory formation.

    PubMed

    Nicole, Olivier; Hadzibegovic, Senka; Gajda, Judyta; Bontempi, Bruno; Bem, Tiaza; Meyrand, Pierre

    2016-01-01

    Post-learning hippocampal sharp wave-ripples (SWRs) generated during slow wave sleep are thought to play a crucial role in memory formation. While in Alzheimer's disease, abnormal hippocampal oscillations have been reported, the functional contribution of SWRs to the typically observed spatial memory impairments remains unclear. These impairments have been related to degenerative synaptic changes produced by soluble amyloid beta oligomers (Aβos) which, surprisingly, seem to spare the SWR dynamics during routine behavior. To unravel a potential effect of Aβos on SWRs in cognitively-challenged animals, we submitted vehicle- and Aβo-injected mice to spatial recognition memory testing. While capable of forming short-term recognition memory, Aβ mice exhibited faster forgetting, suggesting successful encoding but an inability to adequately stabilize and/or retrieve previously acquired information. Without prior cognitive requirements, similar properties of SWRs were observed in both groups. In contrast, when cognitively challenged, the post-encoding and -recognition peaks in SWR occurrence observed in controls were abolished in Aβ mice, indicating impaired hippocampal processing of spatial information. These results point to a crucial involvement of SWRs in spatial memory formation and identify the Aβ-induced impairment in SWRs dynamics as a disruptive mechanism responsible for the spatial memory deficits associated with Alzheimer's disease. PMID:26947247

  13. Soluble amyloid beta oligomers block the learning-induced increase in hippocampal sharp wave-ripple rate and impair spatial memory formation

    PubMed Central

    Nicole, Olivier; Hadzibegovic, Senka; Gajda, Judyta; Bontempi, Bruno; Bem, Tiaza; Meyrand, Pierre

    2016-01-01

    Post-learning hippocampal sharp wave-ripples (SWRs) generated during slow wave sleep are thought to play a crucial role in memory formation. While in Alzheimer’s disease, abnormal hippocampal oscillations have been reported, the functional contribution of SWRs to the typically observed spatial memory impairments remains unclear. These impairments have been related to degenerative synaptic changes produced by soluble amyloid beta oligomers (Aβos) which, surprisingly, seem to spare the SWR dynamics during routine behavior. To unravel a potential effect of Aβos on SWRs in cognitively-challenged animals, we submitted vehicle- and Aβo-injected mice to spatial recognition memory testing. While capable of forming short-term recognition memory, Aβ mice exhibited faster forgetting, suggesting successful encoding but an inability to adequately stabilize and/or retrieve previously acquired information. Without prior cognitive requirements, similar properties of SWRs were observed in both groups. In contrast, when cognitively challenged, the post-encoding and -recognition peaks in SWR occurrence observed in controls were abolished in Aβ mice, indicating impaired hippocampal processing of spatial information. These results point to a crucial involvement of SWRs in spatial memory formation and identify the Aβ-induced impairment in SWRs dynamics as a disruptive mechanism responsible for the spatial memory deficits associated with Alzheimer’s disease. PMID:26947247

  14. Wnt signaling is required for long-term memory formation

    PubMed Central

    Tan, Ying; Yu, Dinghui; Busto, Germain U.; Wilson, Curtis; Davis, Ronald L.

    2013-01-01

    SUMMARY Wnt signaling regulates synaptic plasticity and neurogenesis in the adult nervous system, suggesting a potential role in behavioral processes. Here, we probed the requirement for Wnt signaling during olfactory memory formation in Drosophila using an inducible RNA interference approach. Interfering with β-catenin expression in the adult mushroom body neurons specifically impaired long-term memory without altering short-term memory. The impairment was reversible, rescued with expression of a wild-type β-catenin transgene, and correlated with a disruption of a cellular long-term memory trace. Inhibition of wingless, a Wnt ligand, and arrow, a Wnt co-receptor, also impaired long-term memory. Wingless expression in wild type flies was transiently elevated in the brain after long-term memory conditioning. Thus, inhibiting three key components of the Wnt signaling pathway in the adult mushroom bodies impairs long-term memory, collectively indicating that this pathway mechanistically underlies this specific form of memory. PMID:24035392

  15. Long-term Outcomes of Childhood Onset Nephrotic Syndrome

    PubMed Central

    Hjorten, Rebecca; Anwar, Zohra; Reidy, Kimberly Jean

    2016-01-01

    There are limited studies on long-term outcomes of childhood onset nephrotic syndrome (NS). A majority of children with NS have steroid-sensitive nephrotic syndrome (SSNS). Steroid-resistant nephrotic syndrome (SRNS) is associated with a high risk of developing end-stage renal disease. Biomarkers and analysis of genetic mutations may provide new information for prognosis in SRNS. Frequently relapsing and steroid-dependent NS is associated with long-term complications, including dyslipidemia, cataracts, osteoporosis and fractures, obesity, impaired growth, and infertility. Long-term complications of SSNS are likely to be under-recognized. There remain many gaps in our knowledge of long-term outcomes of childhood NS, and further study is indicated. PMID:27252935

  16. Spinosin, a C-Glucosylflavone, from Zizyphus jujuba var. spinosa Ameliorates Aβ1–42 Oligomer-Induced Memory Impairment in Mice

    PubMed Central

    Ko, Sang Yoon; Lee, Hyung Eun; Park, Se Jin; Jeon, Se Jin; Kim, Boseong; Gao, Qingtao; Jang, Dae Sik; Ryu, Jong Hoon

    2015-01-01

    Alzheimer’s disease (AD) is a neurodegenerative disorder associated with progressive memory loss and neuronal cell death. Although numerous previous studies have been focused on disease progression or reverse pathological symptoms, therapeutic strategies for AD are limited. Alternatively, the identification of traditional herbal medicines or their active compounds has received much attention. The aims of the present study were to characterize the ameliorating effects of spinosin, a C-glucosylflavone isolated from Zizyphus jujuba var. spinosa, on memory impairment or the pathological changes induced through amyloid-β1–42 oligomer (AβO) in mice. Memory impairment was induced by intracerebroventricular injection of AβO (50 μM) and spinosin (5, 10, and 20 mg/kg) was administered for 7 days. In the behavioral tasks, the subchronic administration of spinosin (20 mg/kg, p.o.) significantly ameliorated AβO-induced cognitive impairment in the passive avoidance task or the Y-maze task. To identify the effects of spinosin on the pathological changes induced through AβO, immunohistochemistry and Western blot analyses were performed. Spinosin treatment also reduced the number of activated microglia and astrocytes observed after AβO injection. In addition, spinosin rescued the AβO-induced decrease in choline acetyltransferase expression levels. These results suggest that spinosin ameliorated memory impairment induced through AβO, and these effects were regulated, in part, through neuroprotective activity via the anti-inflammatory effects of spinosin. Therefore, spinosin might be a useful agent against the amyloid b protein-induced cognitive dysfunction observed in AD patients. PMID:25767684

  17. Long Term Surface Salinity Measurements

    NASA Technical Reports Server (NTRS)

    Schmitt, Raymond W.; Brown, Neil L.

    2005-01-01

    Our long-term goal is to establish a reliable system for monitoring surface salinity around the global ocean. Salinity is a strong indicator of the freshwater cycle and has a great influence on upper ocean stratification. Global salinity measurements have potential to improve climate forecasts if an observation system can be developed. This project is developing a new internal field conductivity cell that can be protected from biological fouling for two years. Combined with a temperature sensor, this foul-proof cell can be deployed widely on surface drifters. A reliable in-situ network of surface salinity sensors will be an important adjunct to the salinity sensing satellite AQUARIUS to be deployed by NASA in 2009. A new internal-field conductivity cell has been developed by N Brown, along with new electronics. This sensor system has been combined with a temperature sensor to make a conductivity - temperature (UT) sensor suitable for deployment on drifters. The basic sensor concepts have been proven on a high resolution CTD. A simpler (lower cost) circuit has been built for this application. A protection mechanism for the conductivity cell that includes antifouling protection has also been designed and built. Mr. A.Walsh of our commercial partner E-Paint has designed and delivered time-release formulations of antifoulants for our application. Mr. G. Williams of partner Clearwater Instrumentation advised on power and communication issues and supplied surface drifters for testing.

  18. Long-term equilibrium tides

    NASA Astrophysics Data System (ADS)

    Shaffer, John A.; Cerveny, Randall S.

    1998-08-01

    Extreme equilibrium tides, or ``hypertides,'' are computed in a new equilibrium tidal model combining algorithms of a version of the Chapront ELP-2000/82 Lunar Theory with the BER78 Milankovitch astronomical expansions. For the recent past, a high correspondence exists between computed semidiurnal tide levels and a record of coastal flooding demonstrating that astronomical alignment is a potential influence on such flooding. For the Holocene and near future, maximum tides demonstrate cyclic variations with peaks at near 5000 B.P. and 4000 A.P. On the late Quaternary timescale, variations in maximum equilibrium tide level display oscillations with periods of approximately 10,000, 100,000 and 400,000 years, because of precessional shifts in tidal maxima between vernal and autumnal equinoxes. While flooding occurs under the combined effects of tides and storms via ``storm surges,'' the most extensive flooding will occur with the coincidence of storms and the rarer hypertides and is thus primarily influenced by hypertides. Therefore we suggest that astronomical alignment's relationship to coastal flooding is probabilistic rather than deterministic. Data derived from this model are applicable to (1) archaeological and paleoclimatic coastal reconstructions, (2) long-term planning, for example, radioactive waste site selection, (3) sealevel change and paleoestuarine studies or (4) ocean-meteorological interactions.

  19. Platelet/lymphocyte ratio was associated with impaired myocardial perfusion and both in-hospital and long-term adverse outcome in patients with ST-segment elevation acute myocardial infarction undergoing primary coronary intervention

    PubMed Central

    Tabakci, Mehmet M.; Simsek, Zeki; Arslantas, Ugur; Durmus, Halil I.; Ocal, Lutfi; Demirel, Muhittin; Ozturkeri, Burak; Ozal, Ender; Kargin, Ramazan

    2015-01-01

    Introduction Platelet/lymphocyte ratio (PLR) has been shown to be an inflammatory and thrombotic biomarker for coronary heart disease, but its prognostic value in ST-segment elevation myocardial infarction (STEMI) has not been fully investigated. Aim To investigate the relationship between PLR and no-reflow, along with the in-hospital and long-term outcomes in patients with STEMI. Material and methods In the present study, we included 304 consecutive patients suffering from STEMI who underwent primary percutaneous coronary intervention (p-PCI). Patients were stratified according to PLR tertiles based on the blood samples obtained in the emergency room upon admission. No-reflow after p-PCI was defined as a coronary thrombolysis in myocardial infarction (TIMI) flow grade ≤ 2 after vessel recanalization, or TIMI flow grade 3 together with a final myocardial blush grade (MBG) < 2. Results The mean follow-up period was 24 months (range: 22–26 months). The number of patients characterized with no-reflow was counted to depict increments throughout successive PLR tertiles (14% vs. 20% vs. 45%, p < 0.001). In-hospital major adverse cardiovascular events and death increased as the PLR increased (p < 0.001, p < 0.001). Long-term MACE and death also increased as the PLR increased (p < 0.001, p < 0.001). Multivariable logistic regression analysis revealed that PLR remained an independent predictor for both in-hospital (OR = 1.01, 95% CI: 1.00–1.01; p = 0.002) and major long-term (OR = 1.01, 95% CI: 1.00–1.01; p < 0.001) adverse cardiac events. Conclusions Platelet/lymphocyte ratio on admission is a strong and independent predictor of both the no-reflow phenomenon and long-term prognosis following p-PCI in patients with STEMI. PMID:26677378

  20. The antineoplastic drug flavopiridol reverses memory impairment induced by Amyloid-ß1-42 oligomers in mice.

    PubMed

    Leggio, Gian Marco; Catania, Maria Vincenza; Puzzo, Daniela; Spatuzza, Michela; Pellitteri, Rosalia; Gulisano, Walter; Torrisi, Sebastiano Alfio; Giurdanella, Giovanni; Piazza, Cateno; Impellizzeri, Agata Rita; Gozzo, Lucia; Navarria, Andrea; Bucolo, Claudio; Nicoletti, Ferdinando; Palmeri, Agostino; Salomone, Salvatore; Copani, Agata; Caraci, Filippo; Drago, Filippo

    2016-04-01

    The ectopic re-activation of cell cycle in neurons is an early event in the pathogenesis of Alzheimer's disease (AD), which could lead to synaptic failure and ensuing cognitive deficits before frank neuronal death. Cytostatic drugs that act as cyclin-dependent kinase (CDK) inhibitors have been poorly investigated in animal models of AD. In the present study, we examined the effects of flavopiridol, an inhibitor of CDKs currently used as antineoplastic drug, against cell cycle reactivation and memory loss induced by intracerebroventricular injection of Aß1-42 oligomers in CD1 mice. Cycling neurons, scored as NeuN-positive cells expressing cyclin A, were found both in the frontal cortex and in the hippocampus of Aβ-injected mice, paralleling memory deficits. Starting from three days after Aβ injection, flavopiridol (0.5, 1 and 3mg/kg) was intraperitoneally injected daily, for eleven days. Here we show that a treatment with flavopiridol (0.5 and 1mg/kg) was able to rescue the loss of memory induced by Aβ1-42, and to prevent the occurrence of ectopic cell-cycle events in the mouse frontal cortex and hippocampus. This is the first evidence that a cytostatic drug can prevent cognitive deficits in a non-transgenic animal model of AD. PMID:26875816

  1. Aβ42-oligomer Interacting Peptide (AIP) neutralizes toxic amyloid-β42 species and protects synaptic structure and function

    PubMed Central

    Barucker, Christian; Bittner, Heiko J.; Chang, Philip K.-Y.; Cameron, Scott; Hancock, Mark A.; Liebsch, Filip; Hossain, Shireen; Harmeier, Anja; Shaw, Hunter; Charron, François M.; Gensler, Manuel; Dembny, Paul; Zhuang, Wei; Schmitz, Dietmar; Rabe, Jürgen P.; Rao, Yong; Lurz, Rudi; Hildebrand, Peter W.; McKinney, R. Anne; Multhaup, Gerhard

    2015-01-01

    The amyloid-β42 (Aβ42) peptide is believed to be the main culprit in the pathogenesis of Alzheimer disease (AD), impairing synaptic function and initiating neuronal degeneration. Soluble Aβ42 oligomers are highly toxic and contribute to progressive neuronal dysfunction, loss of synaptic spine density, and affect long-term potentiation (LTP). We have characterized a short, L-amino acid Aβ-oligomer Interacting Peptide (AIP) that targets a relatively well-defined population of low-n Aβ42 oligomers, rather than simply inhibiting the aggregation of Aβ monomers into oligomers. Our data show that AIP diminishes the loss of Aβ42-induced synaptic spine density and rescues LTP in organotypic hippocampal slice cultures. Notably, the AIP enantiomer (comprised of D-amino acids) attenuated the rough-eye phenotype in a transgenic Aβ42 fly model and significantly improved the function of photoreceptors of these flies in electroretinography tests. Overall, our results indicate that specifically “trapping” low-n oligomers provides a novel strategy for toxic Aβ42-oligomer recognition and removal. PMID:26510576

  2. Aβ42-oligomer Interacting Peptide (AIP) neutralizes toxic amyloid-β42 species and protects synaptic structure and function

    NASA Astrophysics Data System (ADS)

    Barucker, Christian; Bittner, Heiko J.; Chang, Philip K.-Y.; Cameron, Scott; Hancock, Mark A.; Liebsch, Filip; Hossain, Shireen; Harmeier, Anja; Shaw, Hunter; Charron, François M.; Gensler, Manuel; Dembny, Paul; Zhuang, Wei; Schmitz, Dietmar; Rabe, Jürgen P.; Rao, Yong; Lurz, Rudi; Hildebrand, Peter W.; McKinney, R. Anne; Multhaup, Gerhard

    2015-10-01

    The amyloid-β42 (Aβ42) peptide is believed to be the main culprit in the pathogenesis of Alzheimer disease (AD), impairing synaptic function and initiating neuronal degeneration. Soluble Aβ42 oligomers are highly toxic and contribute to progressive neuronal dysfunction, loss of synaptic spine density, and affect long-term potentiation (LTP). We have characterized a short, L-amino acid Aβ-oligomer Interacting Peptide (AIP) that targets a relatively well-defined population of low-n Aβ42 oligomers, rather than simply inhibiting the aggregation of Aβ monomers into oligomers. Our data show that AIP diminishes the loss of Aβ42-induced synaptic spine density and rescues LTP in organotypic hippocampal slice cultures. Notably, the AIP enantiomer (comprised of D-amino acids) attenuated the rough-eye phenotype in a transgenic Aβ42 fly model and significantly improved the function of photoreceptors of these flies in electroretinography tests. Overall, our results indicate that specifically “trapping” low-n oligomers provides a novel strategy for toxic Aβ42-oligomer recognition and removal.

  3. Aβ42-oligomer Interacting Peptide (AIP) neutralizes toxic amyloid-β42 species and protects synaptic structure and function.

    PubMed

    Barucker, Christian; Bittner, Heiko J; Chang, Philip K-Y; Cameron, Scott; Hancock, Mark A; Liebsch, Filip; Hossain, Shireen; Harmeier, Anja; Shaw, Hunter; Charron, François M; Gensler, Manuel; Dembny, Paul; Zhuang, Wei; Schmitz, Dietmar; Rabe, Jürgen P; Rao, Yong; Lurz, Rudi; Hildebrand, Peter W; McKinney, R Anne; Multhaup, Gerhard

    2015-01-01

    The amyloid-β42 (Aβ42) peptide is believed to be the main culprit in the pathogenesis of Alzheimer disease (AD), impairing synaptic function and initiating neuronal degeneration. Soluble Aβ42 oligomers are highly toxic and contribute to progressive neuronal dysfunction, loss of synaptic spine density, and affect long-term potentiation (LTP). We have characterized a short, L-amino acid Aβ-oligomer Interacting Peptide (AIP) that targets a relatively well-defined population of low-n Aβ42 oligomers, rather than simply inhibiting the aggregation of Aβ monomers into oligomers. Our data show that AIP diminishes the loss of Aβ42-induced synaptic spine density and rescues LTP in organotypic hippocampal slice cultures. Notably, the AIP enantiomer (comprised of D-amino acids) attenuated the rough-eye phenotype in a transgenic Aβ42 fly model and significantly improved the function of photoreceptors of these flies in electroretinography tests. Overall, our results indicate that specifically "trapping" low-n oligomers provides a novel strategy for toxic Aβ42-oligomer recognition and removal. PMID:26510576

  4. Long-Term Planning in Higher Education.

    ERIC Educational Resources Information Center

    United Nations Educational, Scientific and Cultural Organization, Bangkok (Thailand). Principal Regional Office for Asia and the Pacific.

    This report presents the concepts and issues discussed at a Regional Symposium on Long-term Planning in Higher Education held in Dhaka, Bangladesh, September 21-30, 1986. Chapter 1 explores some fundamental issues about the rationale for the objectives of long-term planning. It defines long-term planning in higher education, considers its…

  5. Predictors of Home Based Long-Term Care Services.

    ERIC Educational Resources Information Center

    Luppens, Jean; And Others

    An attempt was made to determine predictors of service need, use, and outcome among chronically impaired adults and aged who were living in the community and using the home-based, long term care services of the Chronic Illness Center (CIC) of the Cuyahoga County Hospitals (Ohio). Randomly selected consumer service records (N=200) were coded for…

  6. Prion-Protein-interacting Amyloid-β Oligomers of High Molecular Weight Are Tightly Correlated with Memory Impairment in Multiple Alzheimer Mouse Models*

    PubMed Central

    Kostylev, Mikhail A.; Kaufman, Adam C.; Nygaard, Haakon B.; Patel, Pujan; Haas, Laura T.; Gunther, Erik C.; Vortmeyer, Alexander; Strittmatter, Stephen M.

    2015-01-01

    Alzheimer disease (AD) is characterized by amyloid-β accumulation, with soluble oligomers (Aβo) being the most synaptotoxic. However, the multivalent and unstable nature of Aβo limits molecular characterization and hinders research reproducibility. Here, we characterized multiple Aβo forms throughout the life span of various AD mice and in post-mortem human brain. Aβo exists in several populations, where prion protein (PrPC)-interacting Aβo is a high molecular weight Aβ assembly present in multiple mice and humans with AD. Levels of PrPC-interacting Aβo match closely with mouse memory and are equal or superior to other Aβ measures in predicting behavioral impairment. However, Aβo metrics vary considerably between mouse strains. Deleting PrPC expression in mice with relatively low PrPC-interacting Aβo (Tg2576) results in partial rescue of cognitive performance as opposed to complete recovery in animals with a high percentage of PrPC-interacting Aβo (APP/PSEN1). These findings highlight the relative contributions and interplay of Aβo forms in AD. PMID:26018073

  7. Long-term solar-terrestrial observations

    NASA Technical Reports Server (NTRS)

    1988-01-01

    The results of an 18-month study of the requirements for long-term monitoring and archiving of solar-terrestrial data is presented. The value of long-term solar-terrestrial observations is discussed together with parameters, associated measurements, and observational problem areas in each of the solar-terrestrial links (the sun, the interplanetary medium, the magnetosphere, and the thermosphere-ionosphere). Some recommendations are offered for coordinated planning for long-term solar-terrestrial observations.

  8. Hippocampal Focal Knockout of CBP Affects Specific Histone Modifications, Long-Term Potentiation, and Long-Term Memory

    PubMed Central

    Barrett, Ruth M; Malvaez, Melissa; Kramar, Eniko; Matheos, Dina P; Arrizon, Abraham; Cabrera, Sara M; Lynch, Gary; Greene, Robert W; Wood, Marcelo A

    2011-01-01

    To identify the role of the histone acetyltransferase (HAT) CREB-binding protein (CBP) in neurons of the CA1 region of the hippocampus during memory formation, we examine the effects of a focal homozygous knockout of CBP on histone modifications, gene expression, synaptic plasticity, and long-term memory. We show that CBP is critical for the in vivo acetylation of lysines on histones H2B, H3, and H4. CBP's homolog p300 was unable to compensate for the loss of CBP. Neurons lacking CBP maintained phosphorylation of the transcription factor CREB, yet failed to activate CREB:CBP-mediated gene expression. Loss of CBP in dorsal CA1 of the hippocampus resulted in selective impairments to long-term potentiation and long-term memory for contextual fear and object recognition. Together, these results suggest a necessary role for specific chromatin modifications, selectively mediated by CBP in the consolidation of memories. PMID:21508930

  9. Financing long-term care in Canada.

    PubMed

    Jacobs, P; Mills, C; Hollander, M

    1997-06-01

    Financial policies relating to long-term care in Canada are changing rapidly in response to demands for health care reform. This chapter focuses on the financial structure of institutional care, primarily nursing homes, in the western provinces of Alberta and British Columbia. Community-based long-term care is discussed briefly.

  10. Virtual Models of Long-Term Care

    ERIC Educational Resources Information Center

    Phenice, Lillian A.; Griffore, Robert J.

    2012-01-01

    Nursing homes, assisted living facilities and home-care organizations, use web sites to describe their services to potential consumers. This virtual ethnographic study developed models representing how potential consumers may understand this information using data from web sites of 69 long-term-care providers. The content of long-term-care web…

  11. Long-term preservation of Anammox bacteria

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Deposit of useful microorganisms in culture collections requires long-term preservation and successful reactivation techniques. The goal of this study was to develop a simple preservation protocol for the long-term storage and reactivation of the anammox biomass. To achieve this, anammox biomass w...

  12. Paying for long-term care.

    PubMed Central

    Estes, C L; Bodenheimer, T

    1994-01-01

    Everyone agrees that insurance for long-term care is inadequate in the United States. Disagreement exists, however, on whether such insurance should be provided through the private or public sector. Private insurance generally uses the experience-rating principle that persons with higher risk of illness are charged higher premiums. For private insurance for long-term care, this principle creates a dilemma. Most policies will be purchased by the elderly; yet, because the elderly have a high risk of needing long-term care, only about 20% of them can afford the cost of premiums. A public-private partnership by which the government partially subsidizes private long-term-care insurance is unlikely to resolve this dilemma. Only a social insurance program for long-term care can provide universal, affordable, and equitable coverage. PMID:8128712

  13. Short- and Long-Term Outcomes for Extremely Preterm Infants.

    PubMed

    Patel, Ravi Mangal

    2016-02-01

    Prematurity is the leading cause of infant mortality worldwide. In developed countries, extremely preterm infants contribute disproportionately to both neonatal and infant mortality. Survival of this high-risk population has incrementally improved in recent years. Despite these improvements, approximately one in four extremely preterm infants dies during the birth hospitalization. Among those who survive, respiratory and other morbidities are common, although their effect on quality of life is variable. In addition, long-term neurodevelopmental impairment is a large concern for patients, clinicians, and families. However, the interplay of multiple factors contributes to neurodevelopmental impairment, with measures that change over time and outcomes that can be difficult to define and predict. Understanding outcomes of extremely preterm infants can help better counsel families regarding antenatal and postnatal care and guide strategies to improve survival without morbidity. This review summarizes recent evidence to provide an overview into the short- and long-term outcomes for extremely preterm infants.

  14. Enhanced Long-Term and Impaired Short-Term Spatial Memory in GluA1 AMPA Receptor Subunit Knockout Mice: Evidence for a Dual-Process Memory Model

    ERIC Educational Resources Information Center

    Sanderson, David J.; Good, Mark A.; Skelton, Kathryn; Sprengel, Rolf; Seeburg, Peter H.; Rawlins, J. Nicholas P.; Bannerman, David M.

    2009-01-01

    The GluA1 AMPA receptor subunit is a key mediator of hippocampal synaptic plasticity and is especially important for a rapidly-induced, short-lasting form of potentiation. GluA1 gene deletion impairs hippocampus-dependent, spatial working memory, but spares hippocampus-dependent spatial reference memory. These findings may reflect the necessity of…

  15. Disrupted caring attachments: implications for long-term care.

    PubMed

    Flannery, Raymond B

    2002-01-01

    Caring attachments or social supports are the positive psychological and physical contacts and relationships between people. These attachments have been associated with improved health, well-being, and longevity. It is also true that disrupted caring attachments are associated with impaired health and well-being. This paper reviews the general medical and elder medical findings of disrupted caring attachments and negative health outcomes. The implications of these findings for dementia sufferers, caregivers, and long-term care staff are examined.

  16. Post-Training Intrahippocampal Inhibition of Class I Histone Deacetylases Enhances Long-Term Object-Location Memory

    ERIC Educational Resources Information Center

    Hawk, Joshua D.; Florian, Cedrick; Abel, Ted

    2011-01-01

    Long-term memory formation involves covalent modification of the histone proteins that package DNA. Reducing histone acetylation by mutating histone acetyltransferases impairs long-term memory, and enhancing histone acetylation by inhibiting histone deacetylases (HDACs) improves long-term memory. Previous studies using HDAC inhibitors to enhance…

  17. Fimbria-fornix lesions impair spatial performance and induce epileptic-like activity but do not affect long-term potentiation in the CA1 region of rat hippocampal slices.

    PubMed

    Kleschevnikov, A M; Sinden, J D; Marchbanks, R

    1994-09-12

    Groups of rats were given bilateral fimbria-fornix lesions and one month later grafted into the hippocampus with fetal cholinergic and non-cholinergic (hippocampal) neural tissue. Three weeks and 3 months after transplantation the animals were trained to find and then to retain the location of a hidden platform in the Morris water maze. After the final behavioral testing phase, electrophysiological studies of the short- and long-term potentiation (STP and LTP) and epileptiform activity of evoked responses were performed in vitro in the CA1 region of the hippocampus. The lesions produced a marked deficit in spatial function in the early testing phase which showed some recovery at the three month time point. Neither the cholinergic nor the non-cholinergic grafts improved spatial performance; indeed, on some measures these groups showed a significantly greater deficit than the lesion-alone group. Epileptiform activity, which was defined as the ratio of the sum of amplitudes of second and third population spikes to the amplitude of the first, before tetanization was not significantly different for all groups. After tetanization of the radiatum input, however, the epileptiform activity in the FFL group was significantly higher in comparison to that of the control groups. Grafting of cholinergic tissue decreased this parameter to the control level, but non-cholinergic grafts did not modify the lesion-induced epileptiform activity. Epileptiform activity after tetanization of the oriens input was approximately equal for all groups. There were no significant differences between surgical groups in STP and LTP for both the oriens and radiatum inputs.(ABSTRACT TRUNCATED AT 250 WORDS)

  18. Long Term Effects of Food Poisoning

    MedlinePlus

    ... develop chronic arthritis. Brain and nerve damage A Listeria infection can lead to meningitis, an inflammation of ... brain. If a newborn infant is infected with Listeria , long-term consequences may include mental retardation, seizures, ...

  19. Asthma Medicines: Long-Term Control

    MedlinePlus

    ... Español Text Size Email Print Share Asthma Medicines: Long-term Control Page Content Article Body Corticosteroids Synthetic ... and sprinkle forms are available for young children. Long-Acting Beta2-Agonists Medications in the beta 2 - ...

  20. Long-term stable lung function and second uncomplicated pregnancy on sirolimus in lymphangioleiomyomatosis (LAM).

    PubMed

    Faehling, Martin; Wienhausen-Wilke, Vera; Fallscheer, Sabine; Trinajstic-Schulz, B; Weber, J; Leschke, Matthias

    2015-01-01

    We present a patient with lymphangioleiomyomatosis (LAM) on long-term sirolimus (now 79 months) who has had a second successful pregnancy. The second pregnancy on uninterrupted low-dose sirolimus (plasma levels 3-5 mg/L) was uncomplicated both with respect to mother and child suggesting that low-dose sirolimus might be safe in selected pregnant patients with stable LAM. The long-term time course in this patient is in agreement with recent reports of a long-term beneficial effect of sirolimus in LAM. In this patient, the pregnancies did not seem to impair the long-term improvement of lung-function on sirolimus.

  1. Long Term Outcomes after Pediatric Liver Transplantation

    PubMed Central

    2013-01-01

    Long term outcomes after liver transplantation are major determinants of quality of life and of the value of this heroic treatment. As short term outcomes are excellent, our community is turning to take a harder look at long term outcomes. The purpose of this paper is to review these outcomes, and highlight proposed treatments, as well as pressing topics needing to be studied. A systemic review of the English literature was carried in PubMed, covering all papers addressing long term outcomes in pediatric liver transplant from 2000-2013. Late outcomes after pediatric liver transplant affect the liver graft in the form of chronic liver dysfunction. The causes include rejection particularly humoral rejection, but also de novo autoimmune hepatitis, and recurrent disease. The metabolic syndrome is a major factor in long term cardiovascular complication risk. Secondary infections, kidney dysfunction and malignancy remain a reality of those patients. There is growing evidence of late cognitive and executive function delays affecting daily life productivity as well as likely adherence. Finally, despite a good health status, quality of life measures are comparable to those of children with chronic diseases. Long term outcomes are the new frontier in pediatric liver transplantation. Much is needed to improve graft survival, but also to avoid systemic morbidities from long term immunosuppression. Quality of life is a new inclusive measure that will require interventions and innovative approaches respectful not only on the patients but also of their social circle. PMID:24511516

  2. Long-term home care research.

    PubMed

    Green, J H

    1989-11-01

    The population of seniors is growing and health service reimbursement is shrinking. Long-term home health care services were developed with an assumption that the services would decrease costs. This assumption has not been validated. What has been recognized is that long-term home health care targets a new and growing population of frail seniors who need services but are probably not at risk for institutionalization. The impact of long-term home care services on the health status and quality of life of seniors and caregivers has been limited by outcome measurement problems. There are indications that the services improved life satisfaction and reduced services needs, but further evaluations need to replicate the outcomes. In effect, long-term outcomes have not been sufficiently explored. Further research also needs to assist us in identifying outcomes for certain services with precise target populations. Public policy questions are ahead. Should a program that can increase costs, has demonstrated some but not dramatic impacts on quality of life and health status, and has the possibility of expansion, be funded? The question is obviously debatable. From a nursing perspective of health promotion and prevention, the answer is "yes." Funding should be continued in conjunction with increased research on the program impacts. In Kane's (1988) analysis of the Channeling experiments, she summarized the situation effectively: Knowing these facts, we are now in a position to reformulate public policies to design a system of long-term care that satisfies the preferences of consumers and protects them from catastrophic long-term expenses, while promoting the triple virtues of acceptable, quality, equitable access, and defensible costs. . . Nothing in the Channeling results should prevent us from going ahead and trying to develop both community based and institutionally based long-term services in which this country can take pride.

  3. Long-term outcomes of autoimmune pancreatitis.

    PubMed

    Ikeura, Tsukasa; Miyoshi, Hideaki; Shimatani, Masaaki; Uchida, Kazushige; Takaoka, Makoto; Okazaki, Kazuichi

    2016-09-14

    Autoimmune pancreatitis (AIP) has been considered a favorable-prognosis disease; however, currently, there is limited information on natural course of AIP during long-term follow-up. Recently published studies regarding the long-term outcomes of AIP has demonstrated the developments of pancreatic stone formation, exocrine insufficiency, and endocrine insufficiency are observed in 5%-41%, 34%-82%, and 38%-57% of patients having the disease. Furthermore, the incidence rate of developing pancreatic cancer ranges from 0% to 4.8% during the long-term follow-up. The event of death from AIP-related complications other than accompanying cancer is likely to be rare. During follow-up of AIP patients, careful surveillance for not only relapse of the disease but also development of complications at regular intervals is needed. PMID:27678359

  4. Long-term outcomes of autoimmune pancreatitis

    PubMed Central

    Ikeura, Tsukasa; Miyoshi, Hideaki; Shimatani, Masaaki; Uchida, Kazushige; Takaoka, Makoto; Okazaki, Kazuichi

    2016-01-01

    Autoimmune pancreatitis (AIP) has been considered a favorable-prognosis disease; however, currently, there is limited information on natural course of AIP during long-term follow-up. Recently published studies regarding the long-term outcomes of AIP has demonstrated the developments of pancreatic stone formation, exocrine insufficiency, and endocrine insufficiency are observed in 5%-41%, 34%-82%, and 38%-57% of patients having the disease. Furthermore, the incidence rate of developing pancreatic cancer ranges from 0% to 4.8% during the long-term follow-up. The event of death from AIP-related complications other than accompanying cancer is likely to be rare. During follow-up of AIP patients, careful surveillance for not only relapse of the disease but also development of complications at regular intervals is needed. PMID:27678359

  5. Long-term outcomes of autoimmune pancreatitis

    PubMed Central

    Ikeura, Tsukasa; Miyoshi, Hideaki; Shimatani, Masaaki; Uchida, Kazushige; Takaoka, Makoto; Okazaki, Kazuichi

    2016-01-01

    Autoimmune pancreatitis (AIP) has been considered a favorable-prognosis disease; however, currently, there is limited information on natural course of AIP during long-term follow-up. Recently published studies regarding the long-term outcomes of AIP has demonstrated the developments of pancreatic stone formation, exocrine insufficiency, and endocrine insufficiency are observed in 5%-41%, 34%-82%, and 38%-57% of patients having the disease. Furthermore, the incidence rate of developing pancreatic cancer ranges from 0% to 4.8% during the long-term follow-up. The event of death from AIP-related complications other than accompanying cancer is likely to be rare. During follow-up of AIP patients, careful surveillance for not only relapse of the disease but also development of complications at regular intervals is needed.

  6. Long-Term Use of Benzodiazepines

    PubMed Central

    Potts, Nicholas L.S.; Krishnan, K. Ranga R.

    1992-01-01

    Problems associated with physical dependence and abuse of benzodiazepines by a small percentage of patients have reduced their popularity from the most commonly prescribed psychoactive drug in the 1970s to being prescribed for mainly short periods. Patients who benefit from long-term benzodiazepine use are nearly ignored by the medical community as a whole. This article details what patient population can improve from long-term benzodiazepine therapy, the risks and benefits of treatment, and how to select appropriate candidates. PMID:21229127

  7. Long-term outcomes after severe shock.

    PubMed

    Pratt, Cristina M; Hirshberg, Eliotte L; Jones, Jason P; Kuttler, Kathryn G; Lanspa, Michael J; Wilson, Emily L; Hopkins, Ramona O; Brown, Samuel M

    2015-02-01

    Severe shock is a life-threatening condition with very high short-term mortality. Whether the long-term outcomes among survivors of severe shock are similar to long-term outcomes of other critical illness survivors is unknown. We therefore sought to assess long-term survival and functional outcomes among 90-day survivors of severe shock and determine whether clinical predictors were associated with outcomes. Seventy-six patients who were alive 90 days after severe shock (received ≥1 μg/kg per minute of norepinephrine equivalent) were eligible for the study. We measured 3-year survival and long-term functional outcomes using the Medical Outcomes Study 36-Item Short-Form Health Survey, the EuroQOL 5-D-3L, the Hospital Anxiety and Depression Scale, the Impact of Event Scale-Revised, and an employment instrument. We also assessed the relationship between in-hospital predictors and long-term outcomes. The mean long-term survival was 5.1 years; 82% (62 of 76) of patients survived, of whom 49 were eligible for follow-up. Patients who died were older than patients who survived. Thirty-six patients completed a telephone interview a mean of 5 years after hospital admission. The patients' Physical Functioning scores were below U.S. population norms (P < 0.001), whereas mental health scores were similar to population norms. Nineteen percent of the patients had symptoms of depression, 39% had symptoms of anxiety, and 8% had symptoms of posttraumatic stress disorder. Thirty-six percent were disabled, and 17% were working full-time. Early survivors of severe shock had a high 3-year survival rate. Patients' long-term physical and psychological outcomes were similar to those reported for cohorts of less severely ill intensive care unit survivors. Anxiety and depression were relatively common, but only a few patients had symptoms of posttraumatic stress disorder. This study supports the observation that acute illness severity does not determine long-term outcomes. Even extremely

  8. Scenarios for long-term analysis

    SciTech Connect

    Wolbers, Stephen; /Fermilab

    2009-01-01

    Data Preservation and Long-Term Analysis of High Energy Physics (HEP) Experiments data is described and summarized in this talk. The summary covers information presented at the First Workshop on Data Preservation and Long-Term Analysis. Experiments representing e{sup +}e{sup -} collisions (LEP, B Factories and CLEO), ep collisions (H1 and ZEUS), p{bar p} collisions (CDF and D0) and others presented interesting information related to utilizing the large datasets collected over many years at these HEP facilities. Many questions and issues remain to be explored.

  9. The effects of long-term sleep deprivation on the long-term potentiation in the dentate gyrus and brain oxidation status in rats.

    PubMed

    Süer, Cem; Dolu, Nazan; Artis, A Seda; Sahin, Leyla; Yilmaz, Alpaslan; Cetin, Aysun

    2011-05-01

    Some evidence suggests that sleep deprivation might impair synaptic plasticity and produce oxidative stress in the hippocampus. However it is not clear whether impairment of long-term potentiation depends on the oxidative stress evoked by sleep deprivation protocol. In this study we aimed to investigate the effects of a 21-day sleep deprivation period on long-term plasticity taking into account the stressful effect of sleep deprivation. Sleep deprivation was carried out using the multiple platforms method on adult male Wistar rats. Long-term potentiation was studied in the medial perforant pathway-dentate gyrus synapses. Elevated T test was applied, and blood corticosterone levels were measured. Lipid peroxidation products in whole brain and hippocampus were determined. No significant difference was found between the sleep deprived, pedestal and cage control groups at the end of the 21-day period when corticosterone levels were compared. The results of the elevated T test indicated that sleep deprivation did not change the anxiety-like behavior of the animals. When compared with cage or pedestal control groups, sleep deprived rats displayed elevated malondialdehyde levels, and decreased superoxide dismutase and glutathione peroxidase activities together with impaired long-term potentiation maintenance. It can be argued that 21-day SD may impair the maintenance of long-term potentiation evoked in the dentate gyrus, and the balance between oxidant and antioxidant defenses of the hippocampus. PMID:21256900

  10. Outcomes of long-term audiological rehabilitation in charge syndrome.

    PubMed

    Trevisi, P; Ciorba, A; Aimoni, C; Bovo, R; Martini, A

    2016-06-01

    The aim of this paper is to assess the long-term audiological features and outcomes of hearing rehabilitation in a large group of individuals with CHARGE Syndrome. The study has been conducted retrospectively, on a paediatric patient database, at the Audiology Department of the University Hospitals of Ferrara and Padua. The study sample included 31 children presenting with different degrees of hearing impairment associated with CHARGE syndrome. Hearing was assessed using auditory brainstem responses (ABRs) and/or electrocochleography, or conditioned audiometry (visual reinforcement audiometry [VRA] or play audiometry). Auditory-perceptual outcomes in terms of communication skills and expressive language were also recorded. The effects of hearing rehabilitation (with hearing aids or cochlear implants) in this group of children and language outcomes after rehabilitation were monitored during long-term follow-up. The outcomes of rehabilitation measures differed in relation to the heterogeneous and often severe disabilities associated with CHARGE syndrome, e.g. developmental delay, intellectual delay, visual impairment, thin 8(th) nerve with retrocochlear auditory dysfunction (as described in cases of auditory neuropathy/dyssynchrony). Oral expressive language was severely impaired in most cases, even after lengthy follow-up, suggesting the need for alternative augmentative communication modes. The early identification of sensorineural hearing loss, and carefully planned rehabilitation treatments, can be of some benefit in children with CHARGE syndrome. PMID:27214832

  11. Characteristics of Long-Term First Marriages.

    ERIC Educational Resources Information Center

    Fenell, David L.

    1993-01-01

    Investigated characteristics of long-term first marriages (over 20 years). Findings from 147 couples revealed: lifetime commitment to marriage, loyalty to spouse, strong moral values, respect for spouse as best friend, commitment to sexual fidelity, desire to be good parent, faith in God, desire to please and support spouse, good companion to…

  12. Long Term Transfer Effect of Metaphoric Allusion.

    ERIC Educational Resources Information Center

    Hayes, David A.; Mateja, John A.

    A study was conducted to investigate the long term transfer effect of metaphoric allusion used to clarify unfamiliar subject matter. Forty-nine high school students were given unfamiliar prose materials variously augmented by metaphoric allusion. The subjects' immediate performance on a transfer task was compared to their performance on an…

  13. Long-Term Stability of Social Participation

    ERIC Educational Resources Information Center

    Hyyppa, Markku T.; Maki, Juhani; Alanen, Erkki; Impivaara, Olli; Aromaa, Arpo

    2008-01-01

    The long-term stability of social participation was investigated in a representative urban population of 415 men and 579 women who had taken part in the nationwide Mini-Finland Health Survey in the years 1978-1980 and were re-examined 20 years later. Stability was assessed by means of the following tracking coefficients: kappa, proportion of…

  14. Evaluating Long-Term Disability Insurance Plans.

    ERIC Educational Resources Information Center

    Powell, Jan

    1992-01-01

    This report analyzes the factors involved in reviewing benefits and services of employer-sponsored group long-term disability plans for higher education institutions. Opening sections describe the evolution of disability insurance and its shape today. Further sections looks at the complex nature of "value" within a plan, relationship between plan…

  15. The long term characteristics of greenschist

    NASA Astrophysics Data System (ADS)

    Jang, Bo-An

    2016-04-01

    The greenschist in the Jinping II Hydropower Station in southwest China exhibits continuous creep behaviour because of the geological conditions in the region. This phenomenon illustrates the time-dependent deformation and progressive damage that occurs after excavation. In this study, the responses of greenschist to stress over time were determined in a series of laboratory tests on samples collected from the access tunnel walls at the construction site. The results showed that the greenschist presented time-dependent behaviour under long-term loading. The samples generally experienced two stages: transient creep and steady creep, but no accelerating creep. The periods of transient creep and steady creep increased with increasing stress levels. The long-term strength of the greenschist was identified based on the variation of creep strain and creep rate. The ratio of long-term strength to conventional strength was around 80% and did not vary much with confining pressures. A quantitative method for predicting the failure period of greenschist, based on analysis of the stress-strain curve, is presented and implemented. At a confining pressure of 40 MPa, greenschist was predicted to fail in 5000 days under a stress of 290 MPa and to fail in 85 days under the stress of 320 MPa, indicating that the long-term strength identified by the creep rate and creep strain is a reliable estimate.

  16. LONG TERM HYDROLOGICAL IMPACT ASSESSMENT (LTHIA)

    EPA Science Inventory

    LTHIA is a universal Urban Sprawl analysis tool that is available to all at no charge through the Internet. It estimates impacts on runoff, recharge and nonpoint source pollution resulting from past or proposed land use changes. It gives long-term average annual runoff for a lan...

  17. Long-Term Memory and Learning

    ERIC Educational Resources Information Center

    Crossland, John

    2011-01-01

    The English National Curriculum Programmes of Study emphasise the importance of knowledge, understanding and skills, and teachers are well versed in structuring learning in those terms. Research outcomes into how long-term memory is stored and retrieved provide support for structuring learning in this way. Four further messages are added to the…

  18. Who Recommends Long-Term Care Matters

    ERIC Educational Resources Information Center

    Kane, Robert L.; Bershadsky, Boris; Bershadsky, Julie

    2006-01-01

    Purpose: Making good consumer decisions requires having good information. This study compared long-term-care recommendations among various types of health professionals. Design and Methods: We gave randomly varied scenarios to a convenience national sample of 211 professionals from varying disciplines and work locations. For each scenario, we…

  19. Long-term lysimeter data on evapotranspiration

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Long term crop evapotranspiration (ET) data measured using large weighing lysimeters have only been gathered in a few places in the world, yet are of great importance for ground truthing of many models of plant water use, mesoscale climate, remote sensing estimation of ET, climate change and climate...

  20. Professionalism in Long-Term Care Settings

    ERIC Educational Resources Information Center

    Lubinski, Rosemary

    2006-01-01

    Speech-language pathologists who serve elders in a variety of long-term care settings have a variety of professional skills and responsibilities. Fundamental to quality service is knowledge of aging and communication changes and disorders associated with this process, institutional alternatives, and the changing nature of today's elders in…

  1. Plutonium packaging and long-term storage

    NASA Astrophysics Data System (ADS)

    Lloyd, Jane A.; Wedman, Douglas E.

    2000-07-01

    It has been demonstrated that the Advanced Recovery and Integrated Extraction System (ARIES) packaging line at Los Alamos National Laboratory can successfully package plutonium to meet DOE requirements for safe long-term storage. The ARIES system has just completed the disassembly and conversion of its first cores ("pits") for nuclear weapons.

  2. Long-Term Sequelae of Stroke

    PubMed Central

    Teasell, Robert W.

    1992-01-01

    Scant attention has been paid to the long-term consequences and complications resulting from a stroke. Many stroke survivors go on to develop a variety of medical, musculoskeletal, and psychosocial complications, years after the acute stroke. The family physician is regularly called upon to deal with these problems, but is often hampered by a lack of resources. PMID:21221264

  3. Experimental selection of long-term intracellular mycobacteria.

    PubMed

    Vázquez, Cristina L; Lerner, Thomas R; Kasmapour, Bahram; Pei, Gang; Gronow, Achim; Bianco, Maria V; Blanco, Federico C; Bleck, Christopher K E; Geffers, Robert; Bigi, Fabiana; Abraham, Wolf-Rainer; Gutierrez, Maximiliano G

    2014-09-01

    Some intracellular bacteria are known to cause long-term infections that last decades without compromising the viability of the host. Although of critical importance, the adaptations that intracellular bacteria undergo during this long process of residence in a host cell environment remain obscure. Here, we report a novel experimental approach to study the adaptations of mycobacteria imposed by a long-term intracellular lifestyle. Selected Mycobacterium bovis BCG through continuous culture in macrophages underwent an adaptation process leading to impaired phenolic glycolipids (PGL) synthesis, improved usage of glucose as a carbon source and accumulation of neutral lipids. These changes correlated with increased survival of mycobacteria in macrophages and mice during re-infection and also with the specific expression of stress- and survival-related genes. Our findings identify bacterial traits implicated in the establishment of long-term cellular infections and represent a tool for understanding the physiological states and the environment that bacteria face living in fluctuating intracellular environments. PMID:24779357

  4. Experimental selection of long-term intracellular mycobacteria

    PubMed Central

    Vázquez, Cristina L; Lerner, Thomas R; Kasmapour, Bahram; Pei, Gang; Gronow, Achim; Bianco, Maria V; Blanco, Federico C; Bleck, Christopher K E; Geffers, Robert; Bigi, Fabiana; Abraham, Wolf-Rainer; Gutierrez, Maximiliano G

    2014-01-01

    Some intracellular bacteria are known to cause long-term infections that last decades without compromising the viability of the host. Although of critical importance, the adaptations that intracellular bacteria undergo during this long process of residence in a host cell environment remain obscure. Here, we report a novel experimental approach to study the adaptations of mycobacteria imposed by a long-term intracellular lifestyle. Selected Mycobacterium bovis BCG through continuous culture in macrophages underwent an adaptation process leading to impaired phenolic glycolipids (PGL) synthesis, improved usage of glucose as a carbon source and accumulation of neutral lipids. These changes correlated with increased survival of mycobacteria in macrophages and mice during re-infection and also with the specific expression of stress- and survival-related genes. Our findings identify bacterial traits implicated in the establishment of long-term cellular infections and represent a tool for understanding the physiological states and the environment that bacteria face living in fluctuating intracellular environments. PMID:24779357

  5. Inhibition promotes long-term potentiation at cerebellar excitatory synapses

    PubMed Central

    Binda, F.; Dorgans, K.; Reibel, S.; Sakimura, K.; Kano, M.; Poulain, B.; Isope, P.

    2016-01-01

    The ability of the cerebellar cortex to learn from experience ensures the accuracy of movements and reflex adaptation, processes which require long-term plasticity at granule cell (GC) to Purkinje neuron (PN) excitatory synapses. PNs also receive GABAergic inhibitory inputs via GCs activation of interneurons; despite the involvement of inhibition in motor learning, its role in long-term plasticity is poorly characterized. Here we reveal a functional coupling between ionotropic GABAA receptors and low threshold CaV3 calcium channels in PNs that sustains calcium influx and promotes long-term potentiation (LTP) at GC to PN synapses. High frequency stimulation induces LTP at GC to PN synapses and CaV3-mediated calcium influx provided that inhibition is intact; LTP is mGluR1, intracellular calcium store and CaV3 dependent. LTP is impaired in CaV3.1 knockout mice but it is nevertheless recovered by strengthening inhibitory transmission onto PNs; promoting a stronger hyperpolarization via GABAA receptor activation leads to an enhanced availability of an alternative Purkinje-expressed CaV3 isoform compensating for the lack of CaV3.1 and restoring LTP. Accordingly, a stronger hyperpolarization also restores CaV3-mediated calcium influx in PNs from CaV3.1 knockout mice. We conclude that by favoring CaV3 channels availability inhibition promotes LTP at cerebellar excitatory synapses. PMID:27641070

  6. Inhibition promotes long-term potentiation at cerebellar excitatory synapses.

    PubMed

    Binda, F; Dorgans, K; Reibel, S; Sakimura, K; Kano, M; Poulain, B; Isope, P

    2016-01-01

    The ability of the cerebellar cortex to learn from experience ensures the accuracy of movements and reflex adaptation, processes which require long-term plasticity at granule cell (GC) to Purkinje neuron (PN) excitatory synapses. PNs also receive GABAergic inhibitory inputs via GCs activation of interneurons; despite the involvement of inhibition in motor learning, its role in long-term plasticity is poorly characterized. Here we reveal a functional coupling between ionotropic GABAA receptors and low threshold CaV3 calcium channels in PNs that sustains calcium influx and promotes long-term potentiation (LTP) at GC to PN synapses. High frequency stimulation induces LTP at GC to PN synapses and CaV3-mediated calcium influx provided that inhibition is intact; LTP is mGluR1, intracellular calcium store and CaV3 dependent. LTP is impaired in CaV3.1 knockout mice but it is nevertheless recovered by strengthening inhibitory transmission onto PNs; promoting a stronger hyperpolarization via GABAA receptor activation leads to an enhanced availability of an alternative Purkinje-expressed CaV3 isoform compensating for the lack of CaV3.1 and restoring LTP. Accordingly, a stronger hyperpolarization also restores CaV3-mediated calcium influx in PNs from CaV3.1 knockout mice. We conclude that by favoring CaV3 channels availability inhibition promotes LTP at cerebellar excitatory synapses. PMID:27641070

  7. Inhibition promotes long-term potentiation at cerebellar excitatory synapses.

    PubMed

    Binda, F; Dorgans, K; Reibel, S; Sakimura, K; Kano, M; Poulain, B; Isope, P

    2016-09-19

    The ability of the cerebellar cortex to learn from experience ensures the accuracy of movements and reflex adaptation, processes which require long-term plasticity at granule cell (GC) to Purkinje neuron (PN) excitatory synapses. PNs also receive GABAergic inhibitory inputs via GCs activation of interneurons; despite the involvement of inhibition in motor learning, its role in long-term plasticity is poorly characterized. Here we reveal a functional coupling between ionotropic GABAA receptors and low threshold CaV3 calcium channels in PNs that sustains calcium influx and promotes long-term potentiation (LTP) at GC to PN synapses. High frequency stimulation induces LTP at GC to PN synapses and CaV3-mediated calcium influx provided that inhibition is intact; LTP is mGluR1, intracellular calcium store and CaV3 dependent. LTP is impaired in CaV3.1 knockout mice but it is nevertheless recovered by strengthening inhibitory transmission onto PNs; promoting a stronger hyperpolarization via GABAA receptor activation leads to an enhanced availability of an alternative Purkinje-expressed CaV3 isoform compensating for the lack of CaV3.1 and restoring LTP. Accordingly, a stronger hyperpolarization also restores CaV3-mediated calcium influx in PNs from CaV3.1 knockout mice. We conclude that by favoring CaV3 channels availability inhibition promotes LTP at cerebellar excitatory synapses.

  8. Relationship between short- and long-term memory and short- and long-term extinction.

    PubMed

    Cammarota, Martín; Bevilaqua, Lia R M; Rossato, Janine I; Ramirez, Maria; Medina, Jorge H; Izquierdo, Iván

    2005-07-01

    Both the acquisition and the extinction of memories leave short- and long-term mnemonic traces. Here, we show that in male Wistar rats, the short-term memory for a step-down inhibitory avoidance task (IA) is resistant to extinction, and that its expression does not influence retrieval or extinction of long-term memory. It has been known for some time that short- and long-term inhibitory avoidance memory involve separate and parallel processes. Here we show that, instead, short-term extinction of IA long-term memory is the first step towards its long-term extinction, and that this link requires functional NMDA receptors and protein synthesis in the CA1 region of the dorsal hippocampus at the time of the first CS-no US presentation.

  9. Tiagabine Improves Hippocampal Long-Term Depression in Rat Pups Subjected to Prenatal Inflammation

    PubMed Central

    Rideau Batista Novais, Aline; Crouzin, Nadine; Cavalier, Mélanie; Boubal, Mathilde; Guiramand, Janique; Cohen-Solal, Catherine; de Jesus Ferreira, Marie-Céleste; Cambonie, Gilles; Vignes, Michel; Barbanel, Gérard

    2014-01-01

    Maternal inflammation during pregnancy is associated with the later development of cognitive and behavioral impairment in the offspring, reminiscent of the traits of schizophrenia or autism spectrum disorders. Hippocampal long-term potentiation and long-term depression of glutamatergic synapses are respectively involved in memory formation and consolidation. In male rats, maternal inflammation with lipopolysaccharide (LPS) led to a premature loss of long-term depression, occurring between 12 and 25 postnatal days instead of after the first postnatal month, and aberrant occurrence of long-term potentiation. We hypothesized this would be related to GABAergic system impairment. Sprague Dawley rats received either LPS or isotonic saline ip on gestational day 19. Male offspring's hippocampus was studied between 12 and 25 postnatal days. Morphological and functional analyses demonstrated that prenatal LPS triggered a deficit of hippocampal GABAergic interneurons, associated with presynaptic GABAergic transmission deficiency in male offspring. Increasing ambient GABA by impairing GABA reuptake with tiagabine did not interact with the low frequency-induced long-term depression in control animals but fully prevented its impairment in male offspring of LPS-challenged dams. Tiagabine furthermore prevented the aberrant occurrence of paired-pulse triggered long-term potentiation in these rats. Deficiency in GABA seems to be central to the dysregulation of synaptic plasticity observed in juvenile in utero LPS-challenged rats. Modulating GABAergic tone may be a possible therapeutic strategy at this developmental stage. PMID:25184226

  10. Tiagabine improves hippocampal long-term depression in rat pups subjected to prenatal inflammation.

    PubMed

    Rideau Batista Novais, Aline; Crouzin, Nadine; Cavalier, Mélanie; Boubal, Mathilde; Guiramand, Janique; Cohen-Solal, Catherine; de Jesus Ferreira, Marie-Céleste; Cambonie, Gilles; Vignes, Michel; Barbanel, Gérard

    2014-01-01

    Maternal inflammation during pregnancy is associated with the later development of cognitive and behavioral impairment in the offspring, reminiscent of the traits of schizophrenia or autism spectrum disorders. Hippocampal long-term potentiation and long-term depression of glutamatergic synapses are respectively involved in memory formation and consolidation. In male rats, maternal inflammation with lipopolysaccharide (LPS) led to a premature loss of long-term depression, occurring between 12 and 25 postnatal days instead of after the first postnatal month, and aberrant occurrence of long-term potentiation. We hypothesized this would be related to GABAergic system impairment. Sprague Dawley rats received either LPS or isotonic saline ip on gestational day 19. Male offspring's hippocampus was studied between 12 and 25 postnatal days. Morphological and functional analyses demonstrated that prenatal LPS triggered a deficit of hippocampal GABAergic interneurons, associated with presynaptic GABAergic transmission deficiency in male offspring. Increasing ambient GABA by impairing GABA reuptake with tiagabine did not interact with the low frequency-induced long-term depression in control animals but fully prevented its impairment in male offspring of LPS-challenged dams. Tiagabine furthermore prevented the aberrant occurrence of paired-pulse triggered long-term potentiation in these rats. Deficiency in GABA seems to be central to the dysregulation of synaptic plasticity observed in juvenile in utero LPS-challenged rats. Modulating GABAergic tone may be a possible therapeutic strategy at this developmental stage.

  11. Phenylethynyl terminated imide oligomers

    NASA Technical Reports Server (NTRS)

    Hergenrother, Paul M. (Inventor); Bryant, Robert G. (Inventor); Jensen, Brian J. (Inventor); Havens, Stephen J. (Inventor)

    1995-01-01

    Four phenylethynyl amine compounds - 3 and 4-aminophenoxy-4'-phenylethynylbenzophenone, and 3 and 4-amino-4'-phenylethynylbenzophenone - were readily prepared and were used to endcap imide oligomers. Phenylethynyl-terminated amide acid oligomers and phenylethynyl-terminated imide oligomers with various molecular weights and compositions were prepared and characterized. These oligomers were cured at 300 to 400 C to provide crosslinked polyimides with excellent solvent resistance, high strength and modulus, and good high temperature properties. Adhesive panels, composites, films, and moldings from these phenylethynyl terminated imide oligomers gave excellent mechanical performance.

  12. Long-term changes in Saturn's troposphere

    SciTech Connect

    Trafton, L.

    1985-09-01

    Attention is given to the results of a long term monitoring study of Saturn's H/sub 2/ quadrupole and CH/sub 4/ band absorptions outside the equatorial zone, over an interval of half a Saturn year that covers most of the perihelion half of Saturn's elliptical orbit (which is approximately bounded by the equinoxes). Marked long term changes are noted in the CH/sub 4/ absorption, accompanied by weakly opposite changes in the H/sub 2/ absorption. Seasonal changes are inferred on the basis of temporal variations in absorption. Spatial measurements have also been made in the 6450 A NH/sub 3/ band since the 1980 equinox. 42 references.

  13. Long-term reinforced fixed provisional restorations.

    PubMed

    Galindo, D; Soltys, J L; Graser, G N

    1998-06-01

    Extensive prosthodontic treatment often requires fabrication of long-term provisional restorations. Numerous materials and techniques have been described for prolonged insertion of interim restorations. This article describes a procedure for fabrication of long-term reinforced heat-processed provisional restorations based on a diagnostic wax-up. Reinforced heat-processed provisional restorations reduced flexure, which minimizes progressive loss of cement and diminished the possibility of recurrent decay. Occlusal stability and vertical dimension were maintained because of greater wear resistance. Occlusion, tooth contours, and pontic design developed in the provisional restoration were duplicated in the definitive restoration. The use of a matrix from a diagnostic wax-up facilitated fabrication of the prosthesis, and made the procedure less time-consuming and more predictable.

  14. Working Memory, Long-Term Memory, and Medial Temporal Lobe Function

    ERIC Educational Resources Information Center

    Jeneson, Annette; Squire, Larry R.

    2012-01-01

    Early studies of memory-impaired patients with medial temporal lobe (MTL) damage led to the view that the hippocampus and related MTL structures are involved in the formation of long-term memory and that immediate memory and working memory are independent of these structures. This traditional idea has recently been revisited. Impaired performance…

  15. [Taiwan long-term care insurance and the evolution of long-term care in Japan].

    PubMed

    Huang, Hui-Wen; Liu, Shu-Hui; Pai, Yu-Chu

    2010-08-01

    The proportion of elderly (65 years of age and older) in Taiwan has exceeded 10% since 2008. With more elderly, the number of patients suffering from dementia and disabilities has also been rapidly increasing. Japan also has been facing increasing demand for long-term care due to an aging society. Prior to 2000, social welfare programs in Japan, working to cope with changing needs, typically provided insufficient services, and geriatric patients were hospitalized unnecessarily, wasting medical resources and causing undue patient hardship. In response, Japan launched its long-term care insurance program in April 2000. Under the program, city, town and village-based organizations should take responsibility for providing care to the elderly in their place of residence. The program significantly improved previous financial shortfalls and long-term care supply and demand has been met by existing social welfare organization resources. In Taiwan, the provision of long-term care by county / city authorities has proven inconsistent, with performance deemed poor after its first decade of long-term care operations. Service was found to be affected by differences in available resources and insufficient long-term care administration. The cultures of Taiwan and Japan are similar. The authors visited the Japan Long-Term Care Insurance Institute in August 2009. Main issues involved in the implementation and evolution of the Japan long-term Care Insurance are reported on in this paper. We hope such may be useful information to those working to develop long-term care programs in Taiwan. PMID:20661859

  16. Cutaneous oxalosis after long-term hemodialysis.

    PubMed

    Abuelo, J G; Schwartz, S T; Reginato, A J

    1992-07-01

    A 27-year-old woman undergoing long-term hemodialysis developed cutaneous calcifications on her fingers. A skin biopsy specimen showed that the deposits were calcium oxalate. To our knowledge, only one previous article has reported pathologic and crystallographic studies on calcifications of the skin resulting from dialysis oxalosis. We speculate that vitamin C supplements, liberal tea consumption, an increased serum ionized calcium concentration, and the long duration of hemodialysis contributed to the production of these deposits.

  17. Long-term course of opioid addiction.

    PubMed

    Hser, Yih-Ing; Evans, Elizabeth; Grella, Christine; Ling, Walter; Anglin, Douglas

    2015-01-01

    Opioid addiction is associated with excess mortality, morbidities, and other adverse conditions. Guided by a life-course framework, we review the literature on the long-term course of opioid addiction in terms of use trajectories, transitions, and turning points, as well as other factors that facilitate recovery from addiction. Most long-term follow-up studies are based on heroin addicts recruited from treatment settings (mostly methadone maintenance treatment), many of whom are referred by the criminal justice system. Cumulative evidence indicates that opioid addiction is a chronic disorder with frequent relapses. Longer treatment retention is associated with a greater likelihood of abstinence, whereas incarceration is negatively related to subsequent abstinence. Over the long term, the mortality rate of opioid addicts (overdose being the most common cause) is about 6 to 20 times greater than that of the general population; among those who remain alive, the prevalence of stable abstinence from opioid use is low (less than 30% after 10-30 years of observation), and many continue to use alcohol and other drugs after ceasing to use opioids. Histories of sexual or physical abuse and comorbid mental disorders are associated with the persistence of opioid use, whereas family and social support, as well as employment, facilitates recovery. Maintaining opioid abstinence for at least five years substantially increases the likelihood of future stable abstinence. Recent advances in pharmacological treatment options (buprenorphine and naltrexone) include depot formulations offering longer duration of medication; their impact on the long-term course of opioid addiction remains to be assessed.

  18. Consequences of long-term hyperparathyroidism.

    PubMed

    Graal, M B; Wolffenbuttel, B H

    1998-07-01

    We describe a young woman with long-term untreated hyperparathyroidism with a superimposed vitamin D deficiency and an extremely decreased bone mineral density that was complicated by a vertebral fracture. Despite pretreatment with intravenous pamidronate and short-term vitamin D supplementation, severe and long-standing hypocalcaemia ('hungry bone syndrome') developed after parathyroidectomy. We discuss the consequences of hyperparathyroidism, especially the effects on bone, the complications of parathyroidectomy and the possibilities of preoperative treatment with bisphosphonates.

  19. Propofol effects on cerebellar long-term depression.

    PubMed

    Lee, Kwan Young; Kim, Young Im; Kim, Se Hoon; Park, Hyung Seo; Park, Youn Joon; Ha, Myung Sook; Jin, Yunju; Kim, Dong Kwan

    2015-11-16

    Propofol is an intravenously administered anesthetic that induces γ-aminobutyric acid-mediated inhibition in the central nervous system. It has been implicated in prolonged movement disorders. Since the cerebellum is important for motor coordination and learning, we investigated the potential effects of propofol on cerebellar circuitry. Using the whole-cell patch-clamp technique in Wister rat cerebellar slices, we demonstrated that propofol administration impaired long-term depression from the parallel fiber (PF) to Purkinje cell (PC) synapses (PF-LTD). Also, propofol reduced metabotropic glutamate receptor 1 (mGluR1)-mediated and group I mGluR agonist-induced slow currents in PCs. These results suggest that the propofol-induced PF-LTD impairment may be related to an alteration in mGluR1 signaling, which is essential to motor learning.

  20. Electrodes for long-term esophageal electrocardiography.

    PubMed

    Niederhauser, Thomas; Haeberlin, Andreas; Marisa, Thanks; Jungo, Michael; Goette, Josef; Jacomet, Marcel; Abacherli, Roger; Vogel, Rolf

    2013-09-01

    The emerging application of long-term and high-quality ECG recording requires alternative electrodes to improve the signal quality and recording capability of surface skin electrodes. The esophageal ECG has the potential to overcome these limitations but necessitates novel recorder and lead designs. The electrode material is of particular interest, since the material has to ensure conflicting requirements like excellent biopotential recording properties and inertness. To this end, novel electrode materials like PEDOT and silver-PDMS as well as established electrode materials such as stainless steel, platinum, gold, iridium oxide, titanium nitride, and glassy carbon were investigated by long-term electrochemical impedance spectroscopy and model-based signal analysis using the derived in vitro interfacial properties in conjunction with a dedicated ECG amplifier. The results of this novel approach show that titanium nitride and iridium oxide featuring microstructured surfaces did not degrade when exposed to artificial acidic saliva. These materials provide low electrode potential drifts and insignificant signal distortion superior to surface skin electrodes making them compatible with accepted standards for ambulatory ECG. They are superior to the noble and polarizable metals such as platinum, silver, and gold that induced more signal distortions and are superior to esophageal stainless steel electrodes that corrode in artificial saliva. The study provides rigorous criteria for the selection of electrode materials for prolonged ECG recording by combining long-term in vitro electrode material properties with ECG signal quality assessment.

  1. [Long-term survival after severe trauma].

    PubMed

    Mutschler, W; Mutschler, M; Graw, M; Lefering, R

    2016-07-01

    Long-term survival after severe trauma is rarely addressed in German trauma journals although knowledge of life expectancy and identification of factors contributing to increased mortality are important for lifetime care management, development of service models, and targeting health promotion and prevention interventions. As reliable data in Germany are lacking, we compiled data mainly from the USA and Australia to describe life expectancy, risk factors, and predictors of outcome in patients experiencing traumatic spinal cord injury, traumatic brain injury, and polytrauma. Two years after trauma, life expectancy in all three categories was significantly lower than that of the general population. It depends strongly on severity of disability, age, and gender and is quantifiable. Whereas improvements in medical care have led to a marked decline in short-term mortality, surprisingly long-term survival in severe trauma has not changed over the past 30 years. Therefore, there is need to intensify long-term trauma patient care and to find new strategies to limit primary damage. PMID:27342106

  2. Titanium for long-term tritium storage

    SciTech Connect

    Heung, L.K.

    1994-12-01

    Due to the reduction of nuclear weapon stockpile, there will be an excess of tritium returned from the field. The excess tritium needs to be stored for future use, which might be several years away. A safe and cost effective means for long term storage of tritium is needed. Storing tritium in a solid metal tritide is preferred to storing tritium as a gas, because a metal tritide can store tritium in a compact form and the stored tritium will not be released until heat is applied to increase its temperature to several hundred degrees centigrade. Storing tritium as a tritide is safer and more cost effective than as a gas. Several candidate metal hydride materials have been evaluated for long term tritium storage. They include uranium, La-Ni-Al alloys, zirconium and titanium. The criteria used include material cost, radioactivity, stability to air, storage capacity, storage pressure, loading and unloading conditions, and helium retention. Titanium has the best combination of properties and is recommended for long term tritium storage.

  3. Long-term EEG in children.

    PubMed

    Montavont, A; Kaminska, A; Soufflet, C; Taussig, D

    2015-03-01

    Long-term video-EEG corresponds to a recording ranging from 1 to 24 h or even longer. It is indicated in the following situations: diagnosis of epileptic syndromes or unclassified epilepsy, pre-surgical evaluation for drug-resistant epilepsy, follow-up of epilepsy or in cases of paroxysmal symptoms whose etiology remains uncertain. There are some specificities related to paediatric care: a dedicated pediatric unit; continuous monitoring covering at least a full 24-hour period, especially in the context of pre-surgical evaluation; the requirement of presence by the parents, technician or nurse; and stronger attachment of electrodes (cup electrodes), the number of which is adapted to the age of the child. The chosen duration of the monitoring also depends on the frequency of seizures or paroxysmal events. The polygraphy must be adapted to the type and topography of movements. It is essential to have at least an electrocardiography (ECG) channel, respiratory sensor and electromyography (EMG) on both deltoids. There is no age limit for performing long-term video-EEG even in newborns and infants; nevertheless because of scalp fragility, strict surveillance of the baby's skin condition is required. In the specific context of pre-surgical evaluation, long-term video-EEG must record all types of seizures observed in the child. This monitoring is essential in order to develop hypotheses regarding the seizure onset zone, based on electroclinical correlations, which should be adapted to the child's age and the psychomotor development.

  4. Infective endocarditis: determinants of long term outcome

    PubMed Central

    Netzer, R O M; Altwegg, S C; Zollinger, E; Täuber, M; Carrel, T; Seiler, C

    2002-01-01

    Objective: To evaluate predictors of long term prognosis in infective endocarditis. Design: Retrospective cohort study. Setting: Tertiary care centre. Patients: 212 consecutive patients with infective endocarditis between 1980 and 1995 Main outcome measures: Overall and cardiac mortality; event-free survival; and the following events: recurrence, need for late valve surgery, bleeding and embolic complications, cerebral dysfunction, congestive heart failure. Results: During a mean follow up period of 89 months (range 1–244 months), 56% of patients died. In 180 hospital survivors, overall and cardiac mortality amounted to 45% and 24%, respectively. By multivariate analysis, early surgical treatment, infection by streptococci, age < 55 years, absence of congestive heart failure, and > 6 symptoms or signs of endocarditis during active infection were predictive of improved overall long term survival. Independent determinants of event-free survival were infection by streptococci and age < 55 years. Event-free survival was 17% at the end of follow up both in medically–surgically treated patients and in medically treated patients. Conclusions: Long term survival following infective endocarditis is 50% after 10 years and is predicted by early surgical treatment, age < 55 years, lack of congestive heart failure, and the initial presence of more symptoms of endocarditis. PMID:12067947

  5. Can We Optimize Long-Term Outcomes in Acute Respiratory Distress Syndrome by Targeting Normoxemia?

    PubMed Central

    Anderson, Brian; Christie, Jason D.; Hopkins, Ramona O.; Lanken, Paul N.

    2014-01-01

    Since its original description in 1967, acute respiratory distress syndrome (ARDS) has been recognized as a devastating condition associated with significant morbidity and mortality. Advances in critical care medicine and ARDS management have led to a substantial increase in the number of ARDS survivors. Long-term cognitive impairment after critical illness is a significant public health concern. ARDS survivors frequently experience long-term cognitive impairment, as well as physical impairment, psychiatric morbidity, and reduced health-related quality of life. At present, no intensive care unit–based intervention has been proven to reduce the risk of long-term cognitive impairment after ARDS. To address the urgent need to identify strategies to preserve long-term health, investigators have advocated the measurement of short- and long-term outcomes in clinical trials. Maintaining adequate oxygen delivery to preserve organ function is of vital importance in ARDS management. The optimal target range for arterial oxygenation in ARDS remains unknown, due in part to the challenge to maintain adequate tissue oxygenation and to minimize harm, such as oxygen toxicity. An approach targeted to subnormal oxygenation values (partial pressure of arterial oxygen, 55–80 mm Hg) has emerged as a means to accomplish these aims. In this perspective, we critically evaluate this strategy from short- and long-term perspectives, with a focus on the potential long-term cognitive effects of the strategy. We conclude with a proposal to consider resetting the target range for arterial oxygenation higher (85–110 mm Hg) as a potential strategy to improve the long-term outcomes of ARDS survivors. PMID:24621125

  6. Evaluation of Long-Term Migration Testing from Can Coatings into Food Simulants: Polyester Coatings.

    PubMed

    Paseiro-Cerrato, Rafael; Noonan, Gregory O; Begley, Timothy H

    2016-03-23

    FDA guidance for food contact substances recommends that for food packaging intended for use at sterilized, high temperature processed, or retorted conditions, a migration test with a retort step at 121 °C for 2 h followed by a 10 day migration test at 40 °C should be performed. These conditions are in intended to simulate processing and long-term storage. However, can coatings may be in contact with food for years, and there are very few data evaluating if this short-term testing accurately simulates migration over extended time periods. A long-term migration test at 40 °C with retorted and non-retorted polyester cans using several food simulants (water, 3% acetic acid, 10% ethanol, 50% ethanol, and isooctane) was conducted to verify whether traditional migration testing protocols accurately predict migration from food contact materials used for extended time periods. Time points were from 1 day to 515 days. HPLC-MS/MS was used to analyze polyester monomers, and oligomer migration was monitored using HPLC-DAD/CAD and HPLC-MS. Concentrations of monomers and oligomers increased during the migration experiments, especially in ethanol food simulants. The data suggest that current FDA migration protocols may need to be modified to address changes in migrants as a result of long-term storage conditions.

  7. Long-term EARLINET dust observations

    NASA Astrophysics Data System (ADS)

    Mona, Lucia; Amiridis, Vassilis; Amodeo, Aldo; Binietoglou, Ioannis; D'Amico, Giuseppe; Schwarz, Anja; Papagiannopoulos, Nikolaos; Papayannis, Alexandros; Sicard, Michael; Comeron, Adolfo; Pappalardo, Gelsomina

    2015-04-01

    Systematic observations of Saharan dust events over Europe are performed from May 2000 by EARLINET, the European Aerosol Research LIdar NETwork. EARLINET is a coordinated network of stations that make use of advanced lidar methods for the vertical profiling of aerosols. The backbone of EARLINET network is a common schedule for performing the measurements and the quality assurance of instruments/data. Particular attention is paid to monitoring the Saharan dust intrusions over the European continent. The geographical distribution of the EARLINET stations is particularly appealing for the dust observation, with stations located all around the Mediterranean and in the center of the Mediterranean (Italian stations) where dust intrusions are frequent, and with several stations in the central Europe where dust penetrates occasionally. All aerosol backscatter and extinction profiles related to observations collected during these alerts are grouped in the devoted "Saharan dust" category of the EARLINET database. This category consists of about 4700 files (as of December 2013). Case studies involving several stations around Europe selected from this long-term database have been provided the opportunity to investigate dust modification processes during transport over the continent. More important, the long term EARLINET dust monitoring allows the investigation of the horizontal and vertical extent of dust outbreaks over Europe and the climatological analysis of dust optical intensive and extensive properties at continental scale. This long-term database is also a unique tool for a systematic comparison with dust model outputs and satellite-derived dust products. Because of the relevance for both dust modeling and satellite retrievals improvement, results about desert dust layers extensive properties as a function of season and source regions are investigated and will be presented at the conference. First comparisons with models outputs and CALIPSO dust products will be

  8. Human Behaviour in Long-Term Missions

    NASA Technical Reports Server (NTRS)

    1997-01-01

    In this session, Session WP1, the discussion focuses on the following topics: Psychological Support for International Space Station Mission; Psycho-social Training for Man in Space; Study of the Physiological Adaptation of the Crew During A 135-Day Space Simulation; Interpersonal Relationships in Space Simulation, The Long-Term Bed Rest in Head-Down Tilt Position; Psychological Adaptation in Groups of Varying Sizes and Environments; Deviance Among Expeditioners, Defining the Off-Nominal Act in Space and Polar Field Analogs; Getting Effective Sleep in the Space-Station Environment; Human Sleep and Circadian Rhythms are Altered During Spaceflight; and Methodological Approach to Study of Cosmonauts Errors and Its Instrumental Support.

  9. Long Term Analysis for the BAM device

    NASA Astrophysics Data System (ADS)

    Bonino, D.; Gardiol, D.

    2011-02-01

    Algorithms aimed at the evaluation of critical quantities are based on models with many parameters, which values are estimated from data. The knowledge, with high accuracy, of these values and the control of their temporal evolution are important features. In this work, we focus on the latter subject, and we show a proposed pipeline for the BAM (Basic Angle Monitoring) Long Term Analysis, aimed at the study of the calibration parameters of the BAM device and of the Basic Angle variation, searching for unwanted trends, cyclic features, or other potential unexpected behaviours.

  10. Long-term outcomes in multiple gestations.

    PubMed

    Rand, Larry; Eddleman, Keith A; Stone, Joanne

    2005-06-01

    Children born from a multiple gestation are at increased risk for cerebral palsy, learning disability, and language and neurobehavioral deficits. With the increased incidence of multiple pregnancies and use of assisted reproductive technology (ART), these issues are more commonly affecting parents. Long-term outcomes are a critical part of preconceptual and early pregnancy counseling for parents faced with a multiple gestation or considering ART, and the provider should be well versed on issues surrounding zygosity, gestational age, higher-order multiples, and the effects of options such as multifetal pregnancy reduction. PMID:15922795

  11. Long-Term Wind Power Variability

    SciTech Connect

    Wan, Y. H.

    2012-01-01

    The National Renewable Energy Laboratory started collecting wind power data from large commercial wind power plants (WPPs) in southwest Minnesota with dedicated dataloggers and communication links in the spring of 2000. Over the years, additional WPPs in other areas were added to and removed from the data collection effort. The longest data stream of actual wind plant output is more than 10 years. The resulting data have been used to analyze wind power fluctuations, frequency distribution of changes, the effects of spatial diversity, and wind power ancillary services. This report uses the multi-year wind power data to examine long-term wind power variability.

  12. Long-term effects of sibling incest.

    PubMed

    Daie, N; Witztum, E; Eleff, M

    1989-11-01

    Although sexual abuse of children is recognized as a serious problem, sibling incest has received relatively little attention. A distinction has been made between power-oriented sibling incest and nurturance-oriented incest. The authors review the relevant literature and present four clinical examples. The cases illustrate the broad range of sibling incest and demonstrate its effects, including the long-term consequences for the perpetrator. Lasting difficulties in establishing and maintaining close relationships, especially sexual ones, are prominent features of each case. Without denying the occurrences of benign sex-play between siblings, the authors emphasize exploitation and abuse as pathogenic aspects of sibling incest.

  13. Performance considerations in long-term spaceflight

    NASA Technical Reports Server (NTRS)

    Akins, F. R.

    1979-01-01

    Maintenance of skilled performance during extended space flight is of critical importance to both the health and safety of crew members and to the overall success of mission goals. An examination of long term effects and performance requirements is therefore a factor of immense importance to the planning of future missions. Factors that were investigated include: definition of performance categories to be investigated; methods for assessing and predicting performance levels; in-flight factors which can affect performance; and factors pertinent to the maintenance of skilled performance.

  14. Long-term space flights - personal impressions

    NASA Astrophysics Data System (ADS)

    Polyakov, V. V.

    During a final 4-month stage of a 1-year space flight of cosmonauts Titov and Manarov, a physician, Valery Polyakov was included on a crew for the purpose of evaluating their health, correcting physical status to prepare for the spacecraft reentry and landing operations. The complex program of scientific investigations and experiments performed by the physician included an evaluation of adaptation reactions of the human body at different stages of space mission using clinicophysiological and biochemical methods; testing of alternative regimes of exercise and new countermeasures to prevent an unfavourable effect of long-term weightlessness.

  15. 17 CFR 256.224 - Other long-term debt.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 17 Commodity and Securities Exchanges 3 2011-04-01 2011-04-01 false Other long-term debt. 256.224... COMPANY ACT OF 1935 6. Long-Term Debt § 256.224 Other long-term debt. This account shall include all long-term debt to nonassociates and not subject to current settlement. Note: Subaccounts shall be...

  16. 17 CFR 256.224 - Other long-term debt.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Other long-term debt. 256.224... COMPANY ACT OF 1935 6. Long-Term Debt § 256.224 Other long-term debt. This account shall include all long-term debt to nonassociates and not subject to current settlement. Note: Subaccounts shall be...

  17. 47 CFR 54.303 - Long term support.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 3 2010-10-01 2010-10-01 false Long term support. 54.303 Section 54.303... SERVICE Universal Service Support for High Cost Areas § 54.303 Long term support. (a) Beginning January 1... shall receive Long Term Support. Beginning July 1, 2004, no carrier shall receive Long Term Support....

  18. 47 CFR 54.303 - Long term support.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 3 2011-10-01 2011-10-01 false Long term support. 54.303 Section 54.303... SERVICE Universal Service Support for High Cost Areas § 54.303 Long term support. (a) Beginning January 1... shall receive Long Term Support. Beginning July 1, 2004, no carrier shall receive Long Term Support....

  19. Long-term outcome of abusive head trauma.

    PubMed

    Chevignard, Mathilde P; Lind, Katia

    2014-12-01

    Abusive head trauma is a severe inflicted traumatic brain injury, occurring under the age of 2 years, defined by an acute brain injury (mostly subdural or subarachnoidal haemorrhage), where no history or no compatible history with the clinical presentation is given. The mortality rate is estimated at 20-25% and outcome is extremely poor. High rates of impairments are reported in a number of domains, such as delayed psychomotor development; motor deficits (spastic hemiplegia or quadriplegia in 15-64%); epilepsy, often intractable (11-32%); microcephaly with corticosubcortical atrophy (61-100%); visual impairment (18-48%); language disorders (37-64%), and cognitive, behavioral and sleep disorders, including intellectual deficits, agitation, aggression, tantrums, attention deficits, memory, inhibition or initiation deficits (23-59%). Those combined deficits have obvious consequences on academic achievement, with high rates of special education in the long term. Factors associated with worse outcome include demographic factors (lower parental socioeconomic status), initial severe presentation (e.g., presence of a coma, seizures, extent of retinal hemorrhages, presence of an associated cranial fracture, extent of brain lesions, cerebral oedema and atrophy). Given the high risk of severe outcome, long-term comprehensive follow-up should be systematically performed to monitor development, detect any problem and implement timely adequate rehabilitation interventions, special education and/or support when necessary. Interventions should focus on children as well as families, providing help in dealing with the child's impairment and support with psychosocial issues. Unfortunately, follow-up of children with abusive head trauma has repeatedly been reported to be challenging, with very high attrition rates. PMID:25501726

  20. Toward a comprehensive long term nicotine policy

    PubMed Central

    Gray, N; Henningfield, J; Benowitz, N; Connolly, G; Dresler, C; Fagerstrom, K; Jarvis, M; Boyle, P

    2005-01-01

    Global tobacco deaths are high and rising. Tobacco use is primarily driven by nicotine addiction. Overall tobacco control policy is relatively well agreed upon but a long term nicotine policy has been less well considered and requires further debate. Reaching consensus is important because a nicotine policy is integral to the target of reducing tobacco caused disease, and the contentious issues need to be resolved before the necessary political changes can be sought. A long term and comprehensive nicotine policy is proposed here. It envisages both reducing the attractiveness and addictiveness of existing tobacco based nicotine delivery systems as well as providing alternative sources of acceptable clean nicotine as competition for tobacco. Clean nicotine is defined as nicotine free enough of tobacco toxicants to pass regulatory approval. A three phase policy is proposed. The initial phase requires regulatory capture of cigarette and smoke constituents liberalising the market for clean nicotine; regulating all nicotine sources from the same agency; and research into nicotine absorption and the role of tobacco additives in this process. The second phase anticipates clean nicotine overtaking tobacco as the primary source of the drug (facilitated by use of regulatory and taxation measures); simplification of tobacco products by limitation of additives which make tobacco attractive and easier to smoke (but tobacco would still be able to provide a satisfying dose of nicotine). The third phase includes a progressive reduction in the nicotine content of cigarettes, with clean nicotine freely available to take the place of tobacco as society's main nicotine source. PMID:15923465

  1. Long term changes in the polar vortices

    NASA Astrophysics Data System (ADS)

    Braathen, Geir O.

    2015-04-01

    As the amount of halogens in the stratosphere is slowly declining and the ozone layer slowly recovers it is of interest to see how the meteorological conditions in the vortex develop over the long term since such changes might alter the foreseen ozone recovery. In conjunction with the publication of the WMO Antarctic and Arctic Ozone Bulletins, WMO has acquired the ERA Interim global reanalysis data set for several meteorological parameters. This data set goes from 1979 - present. These long time series of data can be used for several useful studies of the long term development of the polar vortices. Several "environmental indicators" for vortex change have been calculated, and a climatology, as well as trends, for these parameters will be presented. These indicators can act as yardsticks and will be useful for understanding past and future changes in the polar vortices and how these changes affect polar ozone depletion. Examples of indicators are: vortex mean temperature, vortex minimum temperature, vortex mean PV, vortex "importance" (PV*area), vortex break-up time, mean and maximum wind speed. Data for both the north and south polar vortices have been analysed at several isentropic levels from 350 to 850 K. A possible link between changes in PV and sudden stratospheric warmings will be investigated, and the results presented.

  2. Long-Term Care Policy: Singapore's Experience.

    PubMed

    Chin, Chee Wei Winston; Phua, Kai-Hong

    2016-01-01

    Singapore, like many developed countries, is facing the challenge of a rapidly aging population and the increasing need to provide long-term care (LTC) services for elderly in the community. The Singapore government's philosophy on care for the elderly is that the family should be the first line of support, and it has relied on voluntary welfare organizations (VWOs) or charities for the bulk of LTC service provision. For LTC financing, it has emphasized the principles of co-payment and targeting of state support to the low-income population through means-tested government subsidies. It has also instituted ElderShield, a national severe disability insurance scheme. This paper discusses some of the challenges facing LTC policy in Singapore, particularly the presence of perverse financial incentives for hospitalization, the pitfalls of over-reliance on VWOs, and the challenges facing informal family caregivers. It discusses the role of private LTC insurance in LTC financing, bearing in mind demand- and supply-side failures that have plagued the private LTC insurance market. It suggests the need for more standardized needs assessment and portable LTC benefits, with reference to the Japanese Long-Term Care Insurance program, and also discusses the need to provide more support to informal family caregivers. PMID:26808468

  3. Long-term anticoagulation. Indications and management.

    PubMed Central

    Stults, B M; Dere, W H; Caine, T H

    1989-01-01

    Each year half a million persons in the United States receive long-term anticoagulant therapy to prevent venous and arterial thromboembolism. Unfortunately, the relative benefits and risks of anticoagulant therapy have not been adequately quantified for many thromboembolic disorders, and the decisions as to whether, for how long, and how intensely to administer anticoagulation are often complex and controversial. Several expert panels have published recommendations for anticoagulant therapy for different thromboembolic disorders; the primary area of disagreement among these panels concerns the optimal intensity of anticoagulation. Recent research and analytic reviews have helped to clarify both the risk factors for and the appropriate diagnostic evaluation of anticoagulant-induced hemorrhage. Clinicians must be aware of the nonhemorrhagic complications of anticoagulant therapy, particularly during pregnancy. The administration of anticoagulants is difficult both in relation to dosing and long-term monitoring. Knowledge of the pharmacology of the anticoagulants, an organized approach to ongoing monitoring, and thorough patient education may facilitate the safe and effective use of these drugs. PMID:2686173

  4. Long-term outcome in personality disorders.

    PubMed

    Stone, M H

    1993-03-01

    Personality disorders meeting DSM or ICD criteria represent the severe end of the broad spectrum of personality configurations involving maladaptive traits. The literature regarding long-term outcome of personality disorders is sparse. Most attention is devoted to formerly institutionalised patients with borderline, antisocial, or schizotypal disorders. Borderline patients at 10-25-year follow-up have a wide range of outcomes, from clinical recovery (50-60%) to suicide (3-9%). Certain factors (e.g. artistic talent) conduce to higher recovery rates, others (e.g. parental cruelty) to lower rates. Schizoid and schizotypal patients tend to remain isolated, and to lead marginal lives. The long-term outcome in antisocial persons is bleak if psychopathic traits are prominent. Personality traits and their corresponding disorders are egosyntonic, harden into habit, and are both slow to change and hard to modify. There is no one treatment of choice. Psychoanalysis and related methods work best within the anxious/inhibited group; cognitive/behavioural techniques are well suited to the disorders requiring limit setting and the amelioration of maladaptive habits. PMID:8453424

  5. Long term perfusion system supporting adipogenesis.

    PubMed

    Abbott, Rosalyn D; Raja, Waseem K; Wang, Rebecca Y; Stinson, Jordan A; Glettig, Dean L; Burke, Kelly A; Kaplan, David L

    2015-08-01

    Adipose tissue engineered models are needed to enhance our understanding of disease mechanisms and for soft tissue regenerative strategies. Perfusion systems generate more physiologically relevant and sustainable adipose tissue models, however adipocytes have unique properties that make culturing them in a perfusion environment challenging. In this paper we describe the methods involved in the development of two perfusion culture systems (2D and 3D) to test their applicability for long term in vitro adipogenic cultures. It was hypothesized that a silk protein biomaterial scaffold would provide a 3D framework, in combination with perfusion flow, to generate a more physiologically relevant sustainable adipose tissue engineered model than 2D cell culture. Consistent with other studies evaluating 2D and 3D culture systems for adipogenesis we found that both systems successfully model adipogenesis, however 3D culture systems were more robust, providing the mechanical structure required to contain the large, fragile adipocytes that were lost in 2D perfused culture systems. 3D perfusion also stimulated greater lipogenesis and lipolysis and resulted in decreased secretion of LDH compared to 2D perfusion. Regardless of culture configuration (2D or 3D) greater glycerol was secreted with the increased nutritional supply provided by perfusion of fresh media. These results are promising for adipose tissue engineering applications including long term cultures for studying disease mechanisms and regenerative approaches, where both acute (days to weeks) and chronic (weeks to months) cultivation are critical for useful insight. PMID:25843606

  6. Long Term Changes in the Polar Vortices

    NASA Astrophysics Data System (ADS)

    Braathen, Geir O.

    2016-04-01

    As the amount of halogens in the stratosphere is slowly declining and the ozone layer slowly recovers it is of interest to see how the meteorological conditions in the vortex develop over the long term since such changes might alter the foreseen ozone recovery. In conjunction with the publication of the WMO Antarctic and Arctic Ozone Bulletins, WMO has acquired the ERA Interim global reanalysis data set for several meteorological parameters. This data set goes from 1979 - present. These long time series of data can be used for several useful studies of the long term development of the polar vortices. Several "environmental indicators" for vortex change have been calculated, and a climatology, as well as trends, for these parameters will be presented. These indicators can act as yardsticks and will be useful for understanding past and future changes in the polar vortices and how these changes affect polar ozone depletion. Examples of indicators are: vortex mean temperature, vortex minimum temperature, vortex mean PV, vortex "importance" (PV*area), vortex break-up time, mean and maximum wind speed. Data for both the north and south polar vortices have been analysed at several isentropic levels from 350 to 850 K. A possible link between changes in PV and sudden stratospheric warmings will be investigated, and the results presented. The unusual meteorological conditions of the 2015 south polar vortex and the 2010/11 and 2015/16 north polar vortices will be compared to other recent years.

  7. Long term perfusion system supporting adipogenesis

    PubMed Central

    Abbott, Rosalyn D.; Raja, Waseem K.; Wang, Rebecca Y.; Stinson, Jordan A.; Glettig, Dean L.; Burke, Kelly A.; Kaplan, David L.

    2015-01-01

    Adipose tissue engineered models are needed to enhance our understanding of disease mechanisms and for soft tissue regenerative strategies. Perfusion systems generate more physiologically relevant and sustainable adipose tissue models, however adipocytes have unique properties that make culturing them in a perfusion environment challenging. In this paper we describe the methods involved in the development of two perfusion culture systems (2D and 3D) to test their applicability for long term in vitro adipogenic cultures. It was hypothesized that a silk protein biomaterial scaffold would provide a 3D framework, in combination with perfusion flow, to generate a more physiologically relevant sustainable adipose tissue engineered model than 2D cell culture. Consistent with other studies evaluating 2D and 3D culture systems for adipogenesis we found that both systems successfully model adipogensis, however 3D culture systems were more robust, providing the mechanical structure required to contain the large, fragile adipocytes that were lost in 2D perfused culture systems. 3D perfusion also stimulated greater lipogenesis and lipolysis and resulted in decreased secretion of LDH compared to 2D perfusion. Regardless of culture configuration (2D or 3D) greater glycerol was secreted with the increased nutritional supply provided by perfusion of fresh media. These results are promising for adipose tissue engineering applications including long term cultures for studying disease mechanisms and regenerative approaches, where both acute (days to weeks) and chronic (weeks to months) cultivation are critical for useful insight. PMID:25843606

  8. Long-term mechanical ventilation and nutrition.

    PubMed

    Ambrosino, Nicolino; Clini, Enrico

    2004-05-01

    Mechanical ventilation (MV) in chronic situations is commonly used, either delivered invasively or by means of non-invasive interfaces, to control hypoventilation in patients with chest wall, neuromuscular or obstructive lung diseases (either in adulthood or childhood). The global prevalence of ventilator-assisted individuals (VAI) in Europe ranges from 2 to 30 per 100000 population according to different countries. Nutrition is a common problem to face with in patients with chronic respiratory diseases: nonetheless, it is a key component in the long-term management of underweight COPD patients whose muscular disfunction may rapidly turn to peripheral muscle waste. Since long-term mechanical ventilation (LTMV) is usually prescribed in end-stage respiratory diseases with poor nutritional status, nutrition and dietary intake related problems need to be carefully assessed and corrected in these patients. This paper aims to review the most recent innovations in the field of nutritional status and food intake-related problems of VAI (both in adulthood and in childhood).

  9. Toward a comprehensive long term nicotine policy.

    PubMed

    Gray, N; Henningfield, J E; Benowitz, N L; Connolly, G N; Dresler, C; Fagerstrom, K; Jarvis, M J; Boyle, P

    2005-06-01

    Global tobacco deaths are high and rising. Tobacco use is primarily driven by nicotine addiction. Overall tobacco control policy is relatively well agreed upon but a long term nicotine policy has been less well considered and requires further debate. Reaching consensus is important because a nicotine policy is integral to the target of reducing tobacco caused disease, and the contentious issues need to be resolved before the necessary political changes can be sought. A long term and comprehensive nicotine policy is proposed here. It envisages both reducing the attractiveness and addictiveness of existing tobacco based nicotine delivery systems as well as providing alternative sources of acceptable clean nicotine as competition for tobacco. Clean nicotine is defined as nicotine free enough of tobacco toxicants to pass regulatory approval. A three phase policy is proposed. The initial phase requires regulatory capture of cigarette and smoke constituents liberalising the market for clean nicotine; regulating all nicotine sources from the same agency; and research into nicotine absorption and the role of tobacco additives in this process. The second phase anticipates clean nicotine overtaking tobacco as the primary source of the drug (facilitated by use of regulatory and taxation measures); simplification of tobacco products by limitation of additives which make tobacco attractive and easier to smoke (but tobacco would still be able to provide a satisfying dose of nicotine). The third phase includes a progressive reduction in the nicotine content of cigarettes, with clean nicotine freely available to take the place of tobacco as society's main nicotine source. PMID:15923465

  10. Long-term Trend of Sunspot Numbers

    NASA Astrophysics Data System (ADS)

    Gao, P. X.

    2016-10-01

    Using the Hilbert–Huang Transform method, we investigate the long-term trend of yearly mean total sunspot numbers in the time interval of 1700–2015, which come from the World Data Center—the sunspot Index and long-term solar observations. The main findings of this study are summarized below. (1) From the adaptive trend, which is extracted from the yearly mean total sunspot numbers, we can find that the value gradually increases during the time period 1700–1975, then decreases gradually from 1975 to 2015. (2) The Centennial Gleissberg Cycle is extracted from the yearly mean total sunspot numbers and confirms that a new grand minimum is in progress; the Dalton Minimum, the Gleissberg Minimum, and low level of solar activity during solar cycle 24 (the part of the new grand minimum) all can be understood as minima of the Centennial Gleissberg Cycle. (3) Based on the adaptive (overall) trend, and the 100-year and longer timescale trend of yearly mean total sunspot numbers, we can infer that the level of solar activity during the new grand minimum may be close to that during the Gleissberg Minimum, slightly higher than that during the Dalton Minimum, and significantly higher than that during the Maunder Minimum. Our results do not support the suggestion that a new grand minimum, somewhat resembling the Maunder Minimum, is in progress.

  11. Long term perfusion system supporting adipogenesis.

    PubMed

    Abbott, Rosalyn D; Raja, Waseem K; Wang, Rebecca Y; Stinson, Jordan A; Glettig, Dean L; Burke, Kelly A; Kaplan, David L

    2015-08-01

    Adipose tissue engineered models are needed to enhance our understanding of disease mechanisms and for soft tissue regenerative strategies. Perfusion systems generate more physiologically relevant and sustainable adipose tissue models, however adipocytes have unique properties that make culturing them in a perfusion environment challenging. In this paper we describe the methods involved in the development of two perfusion culture systems (2D and 3D) to test their applicability for long term in vitro adipogenic cultures. It was hypothesized that a silk protein biomaterial scaffold would provide a 3D framework, in combination with perfusion flow, to generate a more physiologically relevant sustainable adipose tissue engineered model than 2D cell culture. Consistent with other studies evaluating 2D and 3D culture systems for adipogenesis we found that both systems successfully model adipogenesis, however 3D culture systems were more robust, providing the mechanical structure required to contain the large, fragile adipocytes that were lost in 2D perfused culture systems. 3D perfusion also stimulated greater lipogenesis and lipolysis and resulted in decreased secretion of LDH compared to 2D perfusion. Regardless of culture configuration (2D or 3D) greater glycerol was secreted with the increased nutritional supply provided by perfusion of fresh media. These results are promising for adipose tissue engineering applications including long term cultures for studying disease mechanisms and regenerative approaches, where both acute (days to weeks) and chronic (weeks to months) cultivation are critical for useful insight.

  12. LONG-TERM RESULTS OF BODY AND NECK TALUS FRACTURES

    PubMed Central

    Gomes de Sousa, Ricardo Jorge; Teixeira de Oliveira Massada, Marta Maria; Gonçalves Pereira, Manuel Alexandre Negrais Pinho; Gonçalves Costa, Isabel Maria; da Costa e Castro, José Fernando Souzellas

    2015-01-01

    Objectives: Talar neck and body fractures are unusual fractures. The purpose of this study is to determine the prevalence of long term results. Material and Methods: A retrospective analysis was carried out including 11 patients that underwent surgical treatment for body or neck talus fractures between January 1997 and December 2005. Final follow-up examination included a clinical evaluation (AOFAS score) and standard radiographs. Results: The mean follow-up time was 58.5 months. The prevalence of associated fractures was 60% (6/10). Overall AOFAS score averaged 72 [19-100]. Avascular necrosis and post-traumatic arthritis were present in half of the patients. Quality of surgical reduction, body fractures and absence of degenerative changes were correlated with better functional results. Neck fractures, osteonecrosis and posttraumatic arthritis led to inferior results. Conclusion: There is a great potential for long term functional impairment due to posttraumatic arthritis and chronic pain in this kind of fracture. Anatomic surgical reduction is the best chance to avoid them but it is not infallible. The avascular necrosis rate correlates with initial fracture displacement, but its occurrence in each specific case is unpredictable. PMID:27004192

  13. Long-term sensitization and environmental conditioning in terrestrial snails.

    PubMed

    Balaban, P; Bravarenko, N

    1993-01-01

    The hypothesis that a long-term increase of behavioural responses in snails (over a period of days) might be due to environmental conditioning was examined. Training consisted of delivering electric shocks non-contingently with test stimuli twice per day for 5 days to freely moving snails on a ball floating in water. After training, a significant difference in amplitude of a withdrawal reaction to tactile test stimulation appeared between shocked and control snails. Responses were significantly facilitated in shocked animals for up to 12 days after training, but only if the animals were tested in the environment used for training. Testing of the same groups of animals crawling freely on the glass lid of a tank in which they lived between experimental sessions revealed no difference in responses to the same stimuli between shocked and control snails. Injection of the neurotoxin 5,7-dihydroxytryptamine, which selectively impairs serotonergic cells, eliminated the differences between shocked and control animals. Changing the pH of the water in which the ball floated, by addition of citric acid, led to a significant selective increase of responsiveness in snails sensitized in this environment relative to the responsiveness of the same snails with normal water in the tank. The results suggest that the long-term sensitization of withdrawal reactions observed is at least in part a manifestation of an associative process, namely environmental conditioning.

  14. Long-term performance of filtration layer

    NASA Astrophysics Data System (ADS)

    Radfar, A.; Rockaway, T. D.

    2013-12-01

    Permeable pavements are commonly employed to capture and divert stormwater before it enters the stormwater or sewer conveyance systems. During a storm event, runoff water passes through the permeable pavement surface, enters a storage gallery and finally exfiltrates into the surrounding soil. Thus, the ability of the system to store an appropriate volume of runoff water is an important consideration for stormwater control design. Traditionally, crushed stone or other porous material has been used to provide the necessary interstitial void space to store the runoff water. Unfortunately, over time the available void space within the storage gallery is reduced due to settlement, biological growth and sediment accumulation. This gradual reduction in void space reduces the long-term effectiveness of these stormwater controls by limiting its ability to store and pass runoff water. This study examined the long-term performance of the storage gallery layer with respect to its ability to both store and pass runoff water. As the porosity within the storage gallery decreased, it was anticipated that volumetric water content within the gallery would increase and that time necessary to drain the gallery would increase as well. The effects of the gallery porosity were assessed over a one-year study using both laboratory experimentation and monitoring data from naturally occurring rain events. Changes in gallery porosity were first assessed by correlating monitoring piezometer data with surface infiltration testing; building a relation between know volume of poured water being used for the test and the associated pressure head at the base of the gallery. As a known volume of water enters the system, volume change in the gallery directly correlate to increases in pressure head. Second, the time required for water to permeate through pavers and gallery layer to trigger the TDRs in the filtration layer and the time to drain it from the crushed stone were calculated and compared by

  15. Managing soils for long-term productivity

    PubMed Central

    Syers, J. K.

    1997-01-01

    Meeting the goal of long-term agricultural productivity requires that soil degradation be halted and reversed. Soil fertility decline is a key factor in soil degradation and is probably the major cause of declining crop yields. There is evidence that the contribution of declining soil fertility to soil degradation has been underestimated.
    Sensitivity to soil degradation is implicit in the assessment of the sustainability of land management practices, with wide recognition of the fact that soils vary in their ability to resist change and recover subsequent to stress. The concept of resilience in relation to sustainability requires further elaboration and evaluation.
    In the context of soil degradation, a decline in soil fertility is primarily interpreted as the depletion of organic matter and plant nutrients. Despite a higher turnover rate of organic matter in the tropics there is no intrinsic difference between the organic matter content of soils from tropical and temperate regions. The level of organic matter in a soil is closely related to the above and below ground inputs. In the absence of adequate organic material inputs and where cultivation is continuous, soil organic matter declines progressively. Maintaining the quantity and quality of soil organic matter should be a guiding principle in developing management practices.
    Soil microbial biomass serves as an important reservoir of nitrogen (N), phosphorus (P) and sulphur (S), and regulates the cycling of organic matter and nutrients. Because of its high turnover rate, microbial biomass reacts quickly to changes in management and is a sensitive indicator for monitoring and predicting changes in soil organic matter. Modelling techniques have been reasonably successful in predicting changes in soil organic matter with different organic material inputs, but there is little information from the tropics.
    Nutrient depletion through harvested crop components and residue removal, and by leaching and soil

  16. Cushing's syndrome: a structured short- and long-term management plan for patients in remission.

    PubMed

    Ragnarsson, Oskar; Johannsson, Gudmundur

    2013-11-01

    One hundred years have passed since Harvey Williams Cushing presented the first patient with the syndrome that bears his name. In patients with Cushing's syndrome (CS), body composition and lipid, carbohydrate and protein metabolism are dramatically affected and psychopathology and cognitive dysfunction are frequently observed. Untreated patients with CS have a grave prognosis with an estimated 5-year survival of only 50%. Remission can be achieved by surgery, radiotherapy and sometimes with medical therapy. Recent data indicate that the adverse metabolic consequences of CS are present for years after successful treatment.In addition, recent studies have demonstrated that health-related quality of life and cognitive function are impaired in patients with CS in long-term remission. The focus of specialised care should therefore be not only on the diagnostic work-up and the early postoperative management but also on the long-term follow-up. In this paper, we review the long-term consequences in patients with CS in remission with focus on the neuropsychological effects and discuss the importance of these findings for long-term management. We also discuss three different phases in the postoperative management of surgically-treated patients with CS, each phase distinguished by specific challenges: the immediate postoperative phase, the glucocorticoid dose tapering phase and the long-term management. The focus of the long-term specialised care should be to identify cognitive impairments and psychiatric disorders, evaluate cardiovascular risk, follow pituitary function and detect possible recurrence of CS. PMID:23985132

  17. Emotional behavior in long-term marriage.

    PubMed

    Carstensen, L L; Gottman, J M; Levenson, R W

    1995-03-01

    In exploring the emotional climate of long-term marriages, this study used an observational coding system to identify specific emotional behaviors expressed by middle-aged and older spouses during discussions of a marital problem. One hundred and fifty-six couples differing in age and marital satisfaction were studied. Emotional behaviors expressed by couples differed as a function of age, gender, and marital satisfaction. In older couples, the resolution of conflict was less emotionally negative and more affectionate than in middle-aged marriages. Differences between husbands and wives and between happy and unhappy marriages were also found. Wives were more affectively negative than husbands, whereas husbands were more defensive than wives, and unhappy marriages involved greater exchange of negative affect than happy marriages.

  18. Long-term monitoring for closed sites

    SciTech Connect

    Golchert, N.W.; Sedlet, J.; Veluri, V.R.

    1985-01-01

    A procedure is presented for planning and implementing a long-term environmental monitoring program for closed low-level radioactive waste disposal sites. The initial task in this procedure is to collect the available information on the legal/regulatory requirements, site and area characteristics, source term, pathway analysis, and prior monitoring results. This information is coupled with parameters such as half-life and retardation factors to develop a monitoring program. As examples, programs are presented for a site that has had little or no waste migration, and for sites where waste has been moved by suface water, by ground water, and by air. Sampling techniques and practices are discussed relative to how a current program would be structured and projections are made on techniques and practices expected to be available in the future. 8 refs., 2 figs.

  19. Long term evolution of comet Halleys orbit.

    NASA Astrophysics Data System (ADS)

    Dvorak, R.; Kribbel, J.

    1987-03-01

    The aim of the paper is to study the long term evolution of comet Halleys orbit taking into account small errors in the initial conditions. Recent papers deal with mapping methods to model cometary dynamics; (e.g. Petrosky and Broucke, 1987 and Chirikov and Vecheslavov, 1986). They will be discussed critically and compared with our own results. We then tested the model using numerical integration methods. For the moment we limited our calculation to 2.105 years, but a 106 year integration is still in progress. We show the expected dynamical evolution of Hallyes orbit taking into account also smaller and larger errors of the initial conditions (nongravitational effects are only roughly estimated). Finally we discuss alsothe controversal opinions concerning the role of the planets (especially the earth).

  20. Long-term control of root growth

    DOEpatents

    Burton, Frederick G.; Cataldo, Dominic A.; Cline, John F.; Skiens, W. Eugene

    1992-05-26

    A method and system for long-term control of root growth without killing the plants bearing those roots involves incorporating a 2,6-dinitroaniline in a polymer and disposing the polymer in an area in which root control is desired. This results in controlled release of the substituted aniline herbicide over a period of many years. Herbicides of this class have the property of preventing root elongation without translocating into other parts of the plant. The herbicide may be encapsulated in the polymer or mixed with it. The polymer-herbicide mixture may be formed into pellets, sheets, pipe gaskets, pipes for carrying water, or various other forms. The invention may be applied to other protection of buried hazardous wastes, protection of underground pipes, prevention of root intrusion beneath slabs, the dwarfing of trees or shrubs and other applications. The preferred herbicide is 4-difluoromethyl-N,N-dipropyl-2,6-dinitro-aniline, commonly known as trifluralin.

  1. Energy medicine for long-term disabilities.

    PubMed

    Trieschmann, R B

    1999-01-01

    Energy medicine techniques derive from traditional Chinese medicine and are based upon the concept that health and healing are dependent upon a balance of vital energy, a still mind, and controlled emotions. Physical dysfunctions result from disordered patterns of energy of long standing and reversal of the physical problem requires a return to balanced and ordered energy. Qi Gong (Chi Kung) is a system which teaches an individual to live in a state of energy balance. Shen Qi is a sophisticated form of Qi Gong which relies on no external physical interventions but rather relies on mind control to prevent illness, heal existing physical and emotional problems, and promote health and happiness. This paper will describe the use of these techniques with people who have long-term physical disabilities.

  2. [Enteral nutrition through long-term jejunostomy].

    PubMed

    Fernández, T; Neira, P; Enríquez, C

    2008-01-01

    We present the case of a female patient suffering a peritonitis episode after subtotal gastrectomy due to gastric neoplasm in relation to lesser curvature necrosis extending to the anterior esophageal wall. This an uncommon andsevere complication that made mandatory further aggressive surgery: transection of the abdominal esophagus, transection of the gastric stump, and cervical esophagostomy with creation of a jejunostomy with a needle catheter for feeding. This digestive tube access technique is generally used during major abdominal post-surgery until oral intake is reestablished. Our patient has been 187 days with this therapy since reconstruction of the GI tract was ruled out due to tumoral infiltration of the colon and tumor recurrence at the gastrohepatic omentum. To date, there has been no complication from permanence and/or long-term use of this technique.

  3. Radiation risk during long-term spaceflight

    NASA Astrophysics Data System (ADS)

    Petrov, V. M.

    Cosmonauts` exposure to cosmic rays during long-term spaceflight can cause unfavorable effects in health and risk for the crew members` lives. All unfavorable effects induced by exposure should be taken into consideration for the risk estimation. They should include both the acute deterministic effects and delayed effects called stochastic. On the ground the limitation of unfavorable consequences of acute exposure is achieved by means of establishing dose limits. But in space applications this approach can't be acceptable. Establishing a fixed dose limit is adequate to introducing indefinite reserve coefficient and therefore ineffective usage of spacecraft resource. The method of radiation risk calculation caused by acute and delayed effects of cosmonauts' exposure is discussed and substantiated in the report. Peculiarities of the impact of permanent radiation sources (galactic cosmic rays and trapped radiation) and the variable one (solar cosmic rays) are taken into consideration.

  4. Long-term control of root growth

    SciTech Connect

    Burton, F.G.; Cataldo, D.A.; Cline, J.F.; Skiens, W.E.

    1992-05-26

    A method and system for long-term control of root growth without killing the plants bearing those roots involves incorporating a 2,6-dinitroaniline in a polymer and disposing the polymer in an area in which root control is desired. This results in controlled release of the substituted aniline herbicide over a period of many years. Herbicides of this class have the property of preventing root elongation without translocating into other parts of the plant. The herbicide may be encapsulated in the polymer or mixed with it. The polymer-herbicide mixture may be formed into pellets, sheets, pipe gaskets, pipes for carrying water, or various other forms. The invention may be applied to other protection of buried hazardous wastes, protection of underground pipes, prevention of root intrusion beneath slabs, the dwarfing of trees or shrubs and other applications. The preferred herbicide is 4-difluoromethyl-N,N-dipropyl-2,6-dinitro-aniline, commonly known as trifluralin. 7 figs.

  5. Reducing long-term reservoir performance uncertainty

    SciTech Connect

    Lippmann, M.J.

    1988-04-01

    Reservoir performance is one of the key issues that have to be addressed before going ahead with the development of a geothermal field. In order to select the type and size of the power plant and design other surface installations, it is necessary to know the characteristics of the production wells and of the produced fluids, and to predict the changes over a 10--30 year period. This is not a straightforward task, as in most cases the calculations have to be made on the basis of data collected before significant fluid volumes have been extracted from the reservoir. The paper describes the methodology used in predicting the long-term performance of hydrothermal systems, as well as DOE/GTD-sponsored research aimed at reducing the uncertainties associated with these predictions. 27 refs., 1 fig.

  6. Radiation risk during long-term spaceflight.

    PubMed

    Petrov, V M

    2002-01-01

    Cosmonauts' exposure to cosmic rays during long-term spaceflight can cause unfavorable effects in health and risk for the crew members' lives. All unfavorable effects induced by exposure should be taken into consideration for the risk estimation. They should include both the acute deterministic effects and delayed effects called stochastic. On the ground the limitation of unfavorable consequences of acute exposure is achieved by means of establishing dose limits. But in space applications this approach can't be acceptable. Establishing a fixed dose limit is adequate to introducing indefinite reserve coefficient and therefore ineffective usage of spacecraft resource. The method of radiation risk calculation caused by acute and delayed effects of cosmonauts' exposure is discussed and substantiated in the report. Peculiarities of the impact of permanent radiation sources (galactic cosmic rays and trapped radiation) and the variable one (solar cosmic rays) are taken into consideration. PMID:12539775

  7. Safety of long-term PPI therapy.

    PubMed

    Reimer, Christina

    2013-06-01

    Proton pump inhibitors have become the mainstay of medical treatment of acid-related disorders. Long-term use is becoming increasingly common, in some cases without a proper indication. A large number of mainly observational studies on a very wide range of possible associations have been published in the past decade and are critically reviewed in this article and the existing evidence is evaluated and translated into possible clinical consequences. Based on the existing evidence the benefits of PPI treatment seem to outweigh potential risks in the large majority of patients especially if PPI use is based on a relevant indication. The concern for complications should primarily be directed at elderly, malnourished with significant co-morbidity. In this population an increased risk for enteric infections, fractures and nutritional deficiencies might have clinical consequences and should lead to a careful evaluation of the indication for PPI treatment. PMID:23998981

  8. Long term performance of radon mitigation systems

    SciTech Connect

    Prill, R.; Fisk, W.J.

    2002-03-01

    Researchers installed radon mitigation systems in 12 houses in Spokane, Washington and Coeur d'Alene, Idaho during the heating season 1985--1986 and continued to monitor indoor radon quarterly and annually for ten years. The mitigation systems included active sub-slab ventilation, basement over-pressurization, and crawlspace isolation and ventilation. The occupants reported various operational problems with these early mitigation systems. The long-term radon measurements were essential to track the effectiveness of the mitigation systems over time. All 12 homes were visited during the second year of the study, while a second set 5 homes was visited during the fifth year to determine the cause(s) of increased radon in the homes. During these visits, the mitigation systems were inspected and measurements of system performance were made. Maintenance and modifications were performed to improve system performance in these homes.

  9. Advanced long term cryogenic storage systems

    NASA Technical Reports Server (NTRS)

    Brown, Norman S.

    1987-01-01

    Long term, cryogenic fluid storage facilities will be required to support future space programs such as the space-based Orbital Transfer Vehicle (OTV), Telescopes, and Laser Systems. An orbital liquid oxygen/liquid hydrogen storage system with an initial capacity of approximately 200,000 lb will be required. The storage facility tank design must have the capability of fluid acquisition in microgravity and limit cryogen boiloff due to environmental heating. Cryogenic boiloff management features, minimizing Earth-to-orbit transportation costs, will include advanced thick multilayer insulation/integrated vapor cooled shield concepts, low conductance support structures, and refrigeration/reliquefaction systems. Contracted study efforts are under way to develop storage system designs, technology plans, test article hardware designs, and develop plans for ground/flight testing.

  10. Brodie's abscess. A long-term review.

    PubMed

    Stephens, M M; MacAuley, P

    1988-09-01

    In 20 patients with 21 Brodie's abscesses, a long-term review revealed that 13 occurred in the second decade of life. All had local symptoms for six weeks or more. The tibia was involved in 11 cases and seven of these were in the proximal metaphysis. The erythrocyte sedimentation rate (ESR) was elevated in only six cases. When the ESR was more than 40 mm per hour, recurrence was more likely. Staphylococcus aureus was cultured from 11 abscesses. Curettage and antibiotics for six weeks were adequate for treatment in most cases. However, lesions larger than 3 cm in diameter should be grafted, and patients with an elevated ESR require more aggressive decompression and prolonged antibiotic therapy. Lesions within the neck of the femur pose particular anatomic problems and should not be approached laterally. All cases were followed to full bone maturity. No significant leg length inequality was clinically or roentgenologically apparent. If an abscess was juxtaphyseal, deformity of the epiphysis could develop.

  11. Managing Records for the Long Term - 12363

    SciTech Connect

    Montgomery, John V.; Gueretta, Jeanie

    2012-07-01

    The U.S. Department of Energy (DOE) is responsible for managing vast amounts of information documenting historical and current operations. This information is critical to the operations of the DOE Office of Legacy Management. Managing legacy records and information is challenging in terms of accessibility and changing technology. The Office of Legacy Management is meeting these challenges by making records and information management an organizational priority. The Office of Legacy Management mission is to manage DOE post-closure responsibilities at former Cold War weapons sites to ensure the future protection of human health and the environment. These responsibilities include environmental stewardship and long-term preservation and management of operational and environmental cleanup records associated with each site. A primary organizational goal for the Office of Legacy Management is to 'Preserve, Protect, and Share Records and Information'. Managing records for long-term preservation is an important responsibility. Adequate and dedicated resources and management support are required to perform this responsibility successfully. Records tell the story of an organization and may be required to defend an organization in court, provide historical information, identify lessons learned, or provide valuable information for researchers. Loss of records or the inability to retrieve records because of poor records management processes can have serious consequences and even lead to an organisation's downfall. Organizations must invest time and resources to establish a good records management program because of its significance to the organization as a whole. The Office of Legacy Management will continue to research and apply innovative ways of doing business to ensure that the organization stays at the forefront of effective records and information management. DOE is committed to preserving records that document our nation's Cold War legacy, and the Office of Legacy

  12. Long-term dynamics of Typha populations

    USGS Publications Warehouse

    Grace, J.B.; Wetzel, R.G.

    1998-01-01

    The zonation of Typha populations in an experimental pond in Michigan was re-examined 15 years after the original sampling to gain insight into the long-term dynamics. Current distributions of Typha populations were also examined in additional experimental ponds at the site that have been maintained for 23 years. The zonation between T. latifolia and T. angustifolia in the previously studied pond 15 years after the initial sampling revealed that the density and distribution of shoots had not changed significantly. Thus, it appears that previously reported results (based on 7- year old populations) have remained consistent over time. Additional insight into the interaction between these two taxa was sought by comparing mixed and monoculture stands in five experimental ponds that have remained undisturbed for their 23-year history. The maximum depth of T. latifolia, the shallow- water species, was not significantly reduced when growing in the presence of the more flood tolerant T. angustifolia. In contrast, the minimum depth of T. angustifolia was reduced from 0 to 37 cm when in the presence of T. latifolia. When total populations were compared between monoculture and mixed stands, the average density of T. angustifolia shoots was 59.4 percent lower in mixed stands while the density of T. latifolia was 32 percent lower, with T. angustifolia most affected at shallow depths (reduced by 92 percent) and T. latifolia most affected at the deepest depths (reduced by 60 percent). These long-term observations indicate that competitive displacement between Typha taxa has remained stable over time.

  13. Long-term effects of dynamic aortomyoplasty.

    PubMed

    Chachques, J C; Haab, F; Cron, C; Fischer, E C; Grandjean, P; Bruneval, P; Acar, C; Jebara, V A; Fontaliran, F; Carpentier, A F

    1994-07-01

    Aortomyoplasty consists of wrapping the latissimus dorsi muscle (LDM) around the ascending aorta and electrostimulating it during diastole. The ascending aorta will act as an ectopic neo-ventricle compressed during diastole, thus reproducing the effects of long-term diastolic counterpulsation. In 5 goats, the right LDM was transferred to the thoracic cavity after removal of the second rib. The ascending aorta was enlarged by a pericardial patch and wrapped with the LDM. Postoperative electrostimulation was delivered in a counterpulsating manner. Hemodynamic studies were performed at 12 and 24 months postoperatively. Percent increase in the subendocardial viability index (diastolic pressure-time index/systolic tension-time index) was calculated using unassisted and assisted cardiac cycles with the stimulator off versus the stimulator on at a 1:1 ratio in the basal state and after acute heart failure was induced by the administration of high doses of propranolol hydrochloride. Diastolic counterpulsation of the ascending aorta resulted in significant improvement in the subendocardial viability index long term, both in basal state conditions and after induced cardiac failure. During heart failure, aortomyoplasty increased the cardiac output and decreased systemic vascular resistance. Histopathologic studies up to 24 months showed preservation of the histologic structure of the aortic wall and no evidence of thromboembolism. Tight adhesions developed between the aortic wall (including the pericardial patch) and the LDM. The diameters of the enlarged aortas showed no significant differences compared with diameters immediately postoperatively. In conclusion, aortomyoplasty produces chronic diastolic augmentation with preservation of aortic structure. After induction of heart failure, aortomyoplasty offers efficient circulatory support.

  14. SCOP/PHLPP1β mediates circadian regulation of long-term recognition memory

    PubMed Central

    Shimizu, Kimiko; Kobayashi, Yodai; Nakatsuji, Erika; Yamazaki, Maya; Shimba, Shigeki; Sakimura, Kenji; Fukada, Yoshitaka

    2016-01-01

    Learning and memory depend on the time of day in various organisms, but it is not clear whether and how the circadian clock regulates memory performance. Here we show that consolidation of long-term recognition memory is a circadian-regulated process, which is blunted by disruption of the hippocampal clock. We focused on SCOP, a key molecule regulating hippocampus-dependent long-term memory for objects. The amounts of SCOP and its binding partner K-Ras in the hippocampal membrane rafts exhibit robust circadian changes, and SCOP knockdown in the hippocampal CA1 impairs long-term memory at night. Circadian changes in stimulus-dependent activation of ERK in the hippocampal neurons are dependent on the SCOP levels in the membrane rafts, while Scop knockout abrogates the activation rhythm. We conclude that long-term memory formation is regulated by the circadian clock through SCOP dynamics in the membrane rafts of the hippocampal CA1. PMID:27686624

  15. The evaluation of the National Long Term Care Demonstration. 3. Recruitment and characteristics of channeling clients.

    PubMed

    Applebaum, R A

    1988-04-01

    The National Long Term Care Demonstration (channeling) was designed to provide coordinated community-based long-term care services to those older persons at high risk of nursing home placement. A key component of the program was the process established to accomplish this targeting effort. In this article, the outreach and eligibility procedures developed in the demonstration are described. Characteristics of channeling clients are compared to those of clients from other long-term care demonstrations, a national nursing home sample, and a simulated national sample of functionally impaired older persons. Results indicate that the channeling clients were quite frail, more so than the clients served in most of the other long-term care demonstrations, but were younger, slightly less disabled, and more likely to be married than a national sample of nursing home residents.

  16. Long-term follow up of workers exposed to solvents.

    PubMed Central

    Edling, C; Ekberg, K; Ahlborg, G; Alexandersson, R; Barregård, L; Ekenvall, L; Nilsson, L; Svensson, B G

    1990-01-01

    Long term occupational exposure to organic solvents may cause adverse effects to the central nervous system. This collaborative study between six Swedish departments of occupational medicine examines the overall prognosis in terms of working capacity, symptoms, and psychometric test performance for individuals occupationally exposed to organic solvents. After re-analyses of the data from an initial clinical investigation of 111 men, the subjects were divided into two subgroups: one group of 65 with symptoms but no impairment on the tests and one group of 46 with toxic encephalopathy (symptoms and test impairment). At least five years after the initial examination the subjects were asked to attend a re-examination that included a structured medical interview and a psychometric investigation. The results indicate that effects on the central nervous system persist even when exposure has ceased. In the group of 46 more men had stopped working and were receiving sickness or early retirement pensions. This group also had reduced activity levels with regard to everyday life, leisure activities, and education or training and more neuropsychiatric symptoms. There was no support for the view that a solvent induced toxic encephalopathy is a progressive disease comparable with presenile dementia such as Alzheimer's disease or Pick's disease. If a worker was removed from exposure when he presented symptoms without signs of impairment in intellectual function recovery was seen in most cases. PMID:2178676

  17. Financing Long Term Care. Selected Topics in Long Term Care. Volume 3.

    ERIC Educational Resources Information Center

    Greenberg, Jay; Doth, David

    This document, one in a series developed to provide technical assistance to 22 Long-Term Care Gerontology Centers, is designed to be a financial resource guide. Current major funding sources are detailed, followed by an examination of the issues and problems associated with current financing systems. Programmatic issues associated with Medicare…

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

    PubMed Central

    Bliss, Timothy V.P.; Cooke, Sam F

    2011-01-01

    Long-term potentiation and long-term depression are enduring changes in synaptic strength, induced by specific patterns of synaptic activity, that have received much attention as cellular models of information storage in the central nervous system. Work in a number of brain regions, from the spinal cord to the cerebral cortex, and in many animal species, ranging from invertebrates to humans, has demonstrated a reliable capacity for chemical synapses to undergo lasting changes in efficacy in response to a variety of induction protocols. In addition to their physiological relevance, long-term potentiation and depression may have important clinical applications. A growing insight into the molecular mechanisms underlying these processes, and technological advances in non-invasive manipulation of brain activity, now puts us at the threshold of harnessing long-term potentiation and depression and other forms of synaptic, cellular and circuit plasticity to manipulate synaptic strength in the human nervous system. Drugs may be used to erase or treat pathological synaptic states and non-invasive stimulation devices may be used to artificially induce synaptic plasticity to ameliorate conditions arising from disrupted synaptic drive. These approaches hold promise for the treatment of a variety of neurological conditions, including neuropathic pain, epilepsy, depression, amblyopia, tinnitus and stroke. PMID:21779718

  19. LONG-TERM MONITORING SENSOR NETWORK

    SciTech Connect

    Stephen P. Farrington; John W. Haas; Neal Van Wyck

    2003-10-16

    Long-term monitoring (LTM) associated with subsurface contamination sites is a key element of Long Term Stewardship and Legacy Management across the Department of Energy (DOE) complex. However, both within the DOE and elsewhere, LTM is an expensive endeavor, often exceeding the costs of the remediation phase of a clean-up project. The primary contributors to LTM costs are associated with labor. Sample collection, storage, preparation, analysis, and reporting can add a significant financial burden to project expense when extended over many years. Development of unattended, in situ monitoring networks capable of providing quantitative data satisfactory to regulatory concerns has the potential to significantly reduce LTM costs. But survival and dependable operation in a difficult environment is a common obstacle to widespread use across the DOE complex or elsewhere. Deploying almost any sensor in the subsurface for extended periods of time will expose it to chemical and microbial degradation. Over the time-scales required for in situ LTM, even the most advanced sensor systems may be rendered useless. Frequent replacement or servicing (cleaning) of sensors is expensive and labor intensive, offsetting most, if not all, of the cost savings realized with unattended, in situ sensors. To enable facile, remote monitoring of contaminants and other subsurface parameters over prolonged periods, Applied Research Associates, Inc has been working to develop an advanced LTM sensor network consisting of three key elements: (1) an anti-fouling sensor chamber that can accommodate a variety of chemical and physical measurement devices based on electrochemical, optical and other techniques; (2) two rapid, cost effective, and gentle means of emplacing sensor packages either at precise locations directly in the subsurface or in pre-existing monitoring wells; and (3) a web browser-based data acquisition and control system (WebDACS) utilizing field-networked microprocessor-controlled smart

  20. Robotics for Long-Term Monitoring

    SciTech Connect

    Shahin, Sarkis; Duran, Celso

    2002-07-01

    While long-term monitoring and stewardship means many things to many people, DOE has defined it as The physical controls, institutions, information, and other mechanisms needed to ensure protection of people and the environment at sites where DOE has completed or plans to complete cleanup (e.g., landfill closures, remedial actions, and facility stabilization). Across the United States, there are thousands of contaminated sites with multiple contaminants released from multiple sources where contaminants have transported and commingled. The U.S. government and U.S. industry are responsible for most of the contamination and are landowners of many of these contaminated properties. These sites must be surveyed periodically for various criteria including structural deterioration, water intrusion, integrity of storage containers, atmospheric conditions, and hazardous substance release. The surveys, however, are intrusive, time-consuming, and expensive and expose survey personnel to radioactive contamination. In long-term monitoring, there's a need for an automated system that will gather and report data from sensors without costly human labor. In most cases, a SCADA (Supervisory Control and Data Acquisition) unit is used to collect and report data from a remote location. A SCADA unit consists of an embedded computer with data acquisition capabilities. The unit can be configured with various sensors placed in different areas of the site to be monitored. A system of this type is static, i.e., the sensors, once placed, cannot be moved to other locations within the site. For those applications where the number of sampling locations would require too many sensors, or where exact location of future problems is unknown, a mobile sensing platform is an ideal solution. In many facilities that undergo regular inspections, the number of video cameras and air monitors required to eliminate the need for human inspections is very large and far too costly. HCET's remote harsh

  1. Treatment for childhood cancer -- long-term risks

    MedlinePlus

    ... ency/patientinstructions/000849.htm Treatment for childhood cancer - long-term risks To use the sharing features on ... has. Being aware of your child's risk of long-term health problems can help you follow-up ...

  2. Intermediate- and long-term earthquake prediction.

    PubMed

    Sykes, L R

    1996-04-30

    Progress in long- and intermediate-term earthquake prediction is reviewed emphasizing results from California. Earthquake prediction as a scientific discipline is still in its infancy. Probabilistic estimates that segments of several faults in California will be the sites of large shocks in the next 30 years are now generally accepted and widely used. Several examples are presented of changes in rates of moderate-size earthquakes and seismic moment release on time scales of a few to 30 years that occurred prior to large shocks. A distinction is made between large earthquakes that rupture the entire downdip width of the outer brittle part of the earth's crust and small shocks that do not. Large events occur quasi-periodically in time along a fault segment and happen much more often than predicted from the rates of small shocks along that segment. I am moderately optimistic about improving predictions of large events for time scales of a few to 30 years although little work of that type is currently underway in the United States. Precursory effects, like the changes in stress they reflect, should be examined from a tensorial rather than a scalar perspective. A broad pattern of increased numbers of moderate-size shocks in southern California since 1986 resembles the pattern in the 25 years before the great 1906 earthquake. Since it may be a long-term precursor to a great event on the southern San Andreas fault, that area deserves detailed intensified study.

  3. Transuranic waste: long-term planning

    SciTech Connect

    Young, K.C.

    1985-07-01

    Societal concerns for the safe handling and disposal of toxic waste are behind many of the regulations and the control measures in effect today. Transuranic waste, a specific category of toxic (radioactive) waste, serves as a good example of how regulations and controls impact changes in waste processing - and vice versa. As problems would arise with waste processing, changes would be instituted. These changes improved techniques for handling and disposal of transuranic waste, reduced the risk of breached containment, and were usually linked with regulatory changes. Today, however, we face a greater public awareness of and concern for toxic waste control; thus, we must anticipate potential problems and work on resolving them before they can become real problems. System safety analyses are valuable aids in long-term planning for operations involving transuranic as well as other toxic materials. Examples of specific system safety analytical methods demonstrate how problems can be anticipated and resolution initiated in a timely manner having minimal impacts upon allocation of resource and operational goals. 7 refs., 1 fig.

  4. Long-term data storage in diamond

    PubMed Central

    Dhomkar, Siddharth; Henshaw, Jacob; Jayakumar, Harishankar; Meriles, Carlos A.

    2016-01-01

    The negatively charged nitrogen vacancy (NV−) center in diamond is the focus of widespread attention for applications ranging from quantum information processing to nanoscale metrology. Although most work so far has focused on the NV− optical and spin properties, control of the charge state promises complementary opportunities. One intriguing possibility is the long-term storage of information, a notion we hereby introduce using NV-rich, type 1b diamond. As a proof of principle, we use multicolor optical microscopy to read, write, and reset arbitrary data sets with two-dimensional (2D) binary bit density comparable to present digital-video-disk (DVD) technology. Leveraging on the singular dynamics of NV− ionization, we encode information on different planes of the diamond crystal with no cross-talk, hence extending the storage capacity to three dimensions. Furthermore, we correlate the center’s charge state and the nuclear spin polarization of the nitrogen host and show that the latter is robust to a cycle of NV− ionization and recharge. In combination with super-resolution microscopy techniques, these observations provide a route toward subdiffraction NV charge control, a regime where the storage capacity could exceed present technologies.

  5. Long-term adequacy of metal resources

    USGS Publications Warehouse

    Singer, D.A.

    1977-01-01

    Although the earth's crust contains vast quantities of metals, extraction technologies and associated costs are inextricably bound to three fundamental geological factors - the amount of metal available in the earth's crust in each range of grades, the mineralogical form and chemical state of the metal, and the spatial distribution of the metal. The energy required to recover a given amount of metal increases substantially as grade declines. Most metal is produced from sulphide or oxide minerals, whereas most metal in the crust may be locked in the structures of the more refractory silicates. Recovery from silicate minerals could require orders of magnitude more energy than that used at present as also could exploitation of small, widely scattered or thin, deeply buried deposits. Although specific information on the fundamental factors is not available, each factor must in turn tend to further restrict exploitation. Independence of average grade and tonnage for many deposit types further reduces the availability of rock as a source of metal. In the long term, effects of these factors will be large increases in price for many metals. ?? 1977.

  6. Intermediate- and long-term earthquake prediction.

    PubMed Central

    Sykes, L R

    1996-01-01

    Progress in long- and intermediate-term earthquake prediction is reviewed emphasizing results from California. Earthquake prediction as a scientific discipline is still in its infancy. Probabilistic estimates that segments of several faults in California will be the sites of large shocks in the next 30 years are now generally accepted and widely used. Several examples are presented of changes in rates of moderate-size earthquakes and seismic moment release on time scales of a few to 30 years that occurred prior to large shocks. A distinction is made between large earthquakes that rupture the entire downdip width of the outer brittle part of the earth's crust and small shocks that do not. Large events occur quasi-periodically in time along a fault segment and happen much more often than predicted from the rates of small shocks along that segment. I am moderately optimistic about improving predictions of large events for time scales of a few to 30 years although little work of that type is currently underway in the United States. Precursory effects, like the changes in stress they reflect, should be examined from a tensorial rather than a scalar perspective. A broad pattern of increased numbers of moderate-size shocks in southern California since 1986 resembles the pattern in the 25 years before the great 1906 earthquake. Since it may be a long-term precursor to a great event on the southern San Andreas fault, that area deserves detailed intensified study. Images Fig. 1 PMID:11607658

  7. Long-term corrosion testing pan.

    SciTech Connect

    Wall, Frederick Douglas; Brown, Neil R.

    2008-08-01

    This document describes the testing and facility requirements to support the Yucca Mountain Project long-term corrosion testing needs. The purpose of this document is to describe a corrosion testing program that will (a) reduce model uncertainty and variability, (b) reduce the reliance upon overly conservative assumptions, and (c) improve model defensibility. Test matrices were developed for 17 topical areas (tasks): each matrix corresponds to a specific test activity that is a subset of the total work performed in a task. A future document will identify which of these activities are considered to be performance confirmation activities. Detailed matrices are provided for FY08, FY09 and FY10 and rough order estimates are provided for FY11-17. Criteria for the selection of appropriate test facilities were developed through a meeting of Lead Lab and DOE personnel on October 16-17, 2007. These criteria were applied to the testing activities and recommendations were made for the facility types appropriate to carry out each activity. The facility requirements for each activity were assessed and activities were identified that can not be performed with currently available facilities. Based on this assessment, a total of approximately 10,000 square feet of facility space is recommended to meet all future testing needs, given that all testing is consolidated to a single location. This report is a revision to SAND2007-7027 to address DOE comments and add a series of tests to address NWTRB recommendations.

  8. Long-term corrosion testing plan.

    SciTech Connect

    Wall, Frederick Douglas; Brown, Neil R.

    2009-02-01

    This document describes the testing and facility requirements to support the Yucca Mountain Project long-term corrosion testing program. The purpose of this document is to describe a corrosion testing program that will (a) reduce model uncertainty and variability, (b) reduce the reliance upon overly conservative assumptions, and (c) improve model defensibility. Test matrices were developed for 17 topical areas (tasks): each matrix corresponds to a specific test activity that is a subset of the total work performed in a task. A future document will identify which of these activities are considered to be performance confirmation activities. Detailed matrices are provided for FY08, FY09 and FY10 and rough order estimates are provided for FY11-17. Criteria for the selection of appropriate test facilities were developed through a meeting of Lead Lab and DOE personnel on October 16-17, 2007. These criteria were applied to the testing activities and recommendations were made for the facility types appropriate to carry out each activity. The facility requirements for each activity were assessed and activities were identified that can not be performed with currently available facilities. Based on this assessment, a total of approximately 10,000 square feet of facility space is recommended to accommodate all future testing, given that all testing is consolidated to a single location. This report is a revision to SAND2008-4922 to address DOE comments.

  9. Long-term changes in Saturn's troposphere

    NASA Astrophysics Data System (ADS)

    Trafton, L.

    1985-09-01

    The author reports the results of monitoring Saturn's H2 quadrupole and CH4 band absorptions outside of the equatorial zone over one-half of Saturn's year. This interval covers most of the perihelion half of Saturn's elliptical orbit, which happens to be approximately bounded by the equinoxes. Marked long-term changes occur in the CH4 absorption accompanied by weakly opposite changes in the H2 absorption. Around the 1980 equinox, the H2 and CH4 absorptions in the northern hemisphere appear to be discontinuous with those in the southern hemisphere. This discontinuity and the temporal variation of the absorptions are evidence for seasonal changes. The absorption variations can be attributed to a variable haze in Saturn's troposphere, responding to changes in temperature and insolation through the processes of sublimation and freezing. The author models the vertical haze distribution of Saturn's south temperate latitudes during 1971 - 1977 in terms of a distribution having a particle scale height equal to a fraction of the atmospheric scale height. He also reports spatial measurements of the absorption in the 6450 Å NH3 band made annually since the 1980 equinox.

  10. Long-term plutonium storage: Design concepts

    SciTech Connect

    Wilkey, D.D.; Wood, W.T.; Guenther, C.D.

    1994-08-01

    An important part of the Department of Energy (DOE) Weapons Complex Reconfiguration (WCR) Program is the development of facilities for long-term storage of plutonium. The WCR design goals are to provide storage for metals, oxides, pits, and fuel-grade plutonium, including material being held as part of the Strategic Reserve and excess material. Major activities associated with plutonium storage are sorting the plutonium inventory, material handling and storage support, shipping and receiving, and surveillance of material in storage for both safety evaluations and safeguards and security. A variety of methods for plutonium storage have been used, both within the DOE weapons complex and by external organizations. This paper discusses the advantages and disadvantages of proposed storage concepts based upon functional criteria. The concepts discussed include floor wells, vertical and horizontal sleeves, warehouse storage on vertical racks, and modular storage units. Issues/factors considered in determining a preferred design include operational efficiency, maintenance and repair, environmental impact, radiation and criticality safety, safeguards and security, heat removal, waste minimization, international inspection requirements, and construction and operational costs.

  11. Long-term predictions using natural analogues

    SciTech Connect

    Ewing, R.C.

    1995-09-01

    One of the unique and scientifically most challenging aspects of nuclear waste isolation is the extrapolation of short-term laboratory data (hours to years) to the long time periods (10{sup 3}-10{sup 5} years) required by regulatory agencies for performance assessment. The direct validation of these extrapolations is not possible, but methods must be developed to demonstrate compliance with government regulations and to satisfy the lay public that there is a demonstrable and reasonable basis for accepting the long-term extrapolations. Natural systems (e.g., {open_quotes}natural analogues{close_quotes}) provide perhaps the only means of partial {open_quotes}validation,{close_quotes} as well as data that may be used directly in the models that are used in the extrapolation. Natural systems provide data on very large spatial (nm to km) and temporal (10{sup 3}-10{sup 8} years) scales and in highly complex terranes in which unknown synergisms may affect radionuclide migration. This paper reviews the application (and most importantly, the limitations) of data from natural analogue systems to the {open_quotes}validation{close_quotes} of performance assessments.

  12. The long-term variability of Vega

    NASA Astrophysics Data System (ADS)

    Butkovskaya, V.; Plachinda, S.; Valyavin, G.; Baklanova, D.; Lee, B.-C.

    2011-12-01

    Over the time of 60 years Vega (α Lyrae = HD 172167, A0V) has been generally accepted as a standard star in the near-infrared, optical, and ultraviolet regions. But is the spectrophotometric standard Vega really non-variable star? Researchers give very different answers to this question. We aim to search a periodicity in our results of spectropolarimetric study of Vega, namely periodic variations in equivalent width of the spectral lines and longitudinal magnetic field measurements. High-accuracy spectropolarimetric observations of Vega have been performed during 26 nights from 1997 to 2010 using the Coudé spectrograph of the 2.6-m Shain reflector at the Crimean Astrophysical Observatory (CrAO, Ukraine) and during 4 nights in 2007 and 2008 using the echelle spectrograph BOES at the Bohyunsan Optical Astronomy Observatory (BOAO, South Korea). The long-term (year-to-year) variability of Vega was confirmed. It was concluded that this variability does not have magnetic nature. The paper is dedicated to the memory of V.P. Merezhin.

  13. Long-term potentiation: peeling the onion.

    PubMed

    Nicoll, Roger A; Roche, Katherine W

    2013-11-01

    Since the discovery of long-term potentiation (LTP), thousands of papers have been published on this phenomenon. With this massive amount of information, it is often difficult, especially for someone not directly involved in the field, not to be overwhelmed. The goal of this review is to peel away as many layers as possible, and probe the core properties of LTP. We would argue that the many dozens of proteins that have been implicated in the phenomenon are not essential, but rather modulate, often in indirect ways, the threshold and/or magnitude of LTP. What is required is NMDA receptor activation followed by CaMKII activation. The consequence of CaMKII activation is the rapid recruitment of AMPA receptors to the synapse. This recruitment is independent of AMPA receptor subunit type, but absolutely requires an adequate pool of surface receptors. An important unresolved issue is how exactly CaMKII activation leads to modifications in the PSD to allow rapid enrichment. This article is part of the Special Issue entitled 'Glutamate Receptor-Dependent Synaptic Plasticity'. PMID:23439383

  14. Long-term observations of siamang behaviour.

    PubMed

    Chivers, D J; Raemaekers, J J; Aldrich-Blake, F P

    1975-01-01

    Long-term observations are presented on the behaviour of the siamang ape, Symphalangus syndactylus, in the lowland forest of central Malaya. The data were collected during two dry and three fruiting seasons between 1969 and 1973 inclusive on two groups with adjacent ranges; comparisons are made within and between sample periods, and between groups. The influence of weather on daily activities is considered. Food intake is analysed in terms of number of food trees, number of visits to these trees, and the cumulative time spent feeding on various food categories. Ranging behaviour is investigated in terms of distance travelled, area covered, and distribution of time and of food trees about the range. The occurrence of calling is described and compared with that of the white-handed gibbon in the same area. A discussion ensues on each of these aspects of behaviour in turn. Emphasis is laid on the similarity of behaviour of the two groups at any one time, and on the degree of their response to the fluctuations of environment variables. Finally, the application to siamang of ranging concepts currently used in animal behaviour is considered briefly.

  15. Long-Term Consequences of Neonatal Injury

    PubMed Central

    Beggs, Simon

    2015-01-01

    The maturation of the central nervous system’s (CNS’s) sensory connectivity is driven by modality-specific sensory input in early life. For the somatosensory system, this input is the physical, tactile interaction with the environment. Nociceptive circuitry is functioning at the time of birth; however, there is still considerable organization and refinement of this circuitry that occurs postnatally, before full discrimination of tactile and noxious input is possible. This fine-tuning involves separation of tactile and nociceptive afferent input to the spinal cord’s dorsal horn and the maturation of local and descending inhibitory circuitry. Disruption of that input in early postnatal life (for example, by tissue injury or other noxious stimulus), can have a profound influence on subsequent development, and consequently the mature functioning of pain systems. In this review, the impact of neonatal surgical incision on nociceptive circuitry is discussed in terms of the underlying developmental neurobiology. The changes are complex, occurring at multiple anatomical sites within the CNS, and including both neuronal and glial cell populations. The altered sensory input from neonatal injury selectively modulates neuronal excitability within the spinal cord, disrupts inhibitory control, and primes the immune system, all of which contribute to the adverse long-term consequences of early pain exposure. PMID:26174217

  16. Long-term outcome in aqueductal stenosis.

    PubMed

    Villani, R; Tomei, G; Gaini, S M; Grimoldi, N; Spagnoli, D; Bello, L

    1995-03-01

    In this study, 78 patients with aqueductal stenosis were submitted to detailed neurodevelopmental assessment with a follow-up of 5-25 years. Sixty-eight percent of patients were categorized as normal; they either attended normal school courses or had regular jobs. Among these, 34% had some motor abnormalities (ataxia, mild hemiparesis, visual disturbances). Twenty-four percent (19 cases) were moderately disabled (trainable retardation) and 8% (6 cases) were severely handicapped. Epilepsy was observed in 13% of the cases. Incidence of recurrent and generalized seizures paralleled neurodevelopmental outcome (5% in normal, 16% in moderately disabled and 50% in severely disabled patients). Endocrine dysfunctions were evident in 28% of the cases and were characterized by precocious or delayed puberty, amenorrhea and somatic underdevelopment. No patient with ventricular enlargement and a cortical mantle width below 20 mm showed a good outcome. Large ventricles were compatible with normal mental development when compensated with a corresponding cranial vault enlargement. In patients with normal mental status and motor abnormalities, long-term CT scan findings revealed the presence of focal brain abnormalities (poroencephaly, brain atrophy, calcifications, extracerebral collections). PMID:7773981

  17. Long-term oxygen therapy: battling breathlessness.

    PubMed

    Wick, Jeannette Y

    2012-12-01

    Approximately 1 million of the 1.4 million Americans (71%) receiving long-term oxygen therapy (LTOT) are Medicare beneficiaries, confirming that LTOT is most often prescribed for individuals 65 years of age or older. Although several conditions create a need for supplemental oxygen, the majority of patients have chronic obstructive pulmonary disease (COPD). People with healthy lungs can extract the oxygen from air, while those with damaged lungs need higher oxygen concentrations. They can supplement their oxygen using one of three options: high-pressure oxygen tanks, liquid oxygen, or oxygen concentrators. The multicenter Nocturnal Oxygen Therapy Trial and the smaller Medical Research Council study identified LTOT as an intervention that improved survival in patients with COPD or chronic respiratory failure, approximately doubling survival at 19 months in patients who were adherent to oxygen. Despite its advantages, LTOT is plagued with problems: compliance with clinical guidelines, patient adherence, and cost. Fires associated with smoking in the vicinity of supplemental oxygen are the leading cause of residential fire deaths in the United States.

  18. Long term prediction of flood occurrence

    NASA Astrophysics Data System (ADS)

    Aguilar, Cristina; Montanari, Alberto; José Polo, María

    2016-05-01

    How long a river remembers its past is still an open question. Perturbations occurring in large catchments may impact the flow regime for several weeks and months, therefore providing a physical explanation for the occasional tendency of floods to occur in clusters. The research question explored in this paper may be stated as follows: can higher than usual river discharges in the low flow season be associated to a higher probability of floods in the subsequent high flow season? The physical explanation for such association may be related to the presence of higher soil moisture storage at the beginning of the high flow season, which may induce lower infiltration rates and therefore higher river runoff. Another possible explanation is persistence of climate, due to presence of long-term properties in atmospheric circulation. We focus on the Po River at Pontelagoscuro, whose catchment area amounts to 71 000 km2. We look at the stochastic connection between average river flows in the pre-flood season and the peak flows in the flood season by using a bivariate probability distribution. We found that the shape of the flood frequency distribution is significantly impacted by the river flow regime in the low flow season. The proposed technique, which can be classified as a data assimilation approach, may allow one to reduce the uncertainty associated to the estimation of the flood probability.

  19. Neurological long term consequences of deep diving.

    PubMed

    Todnem, K; Nyland, H; Skeidsvoll, H; Svihus, R; Rinck, P; Kambestad, B K; Riise, T; Aarli, J A

    1991-04-01

    Forty commercial saturation divers, mean age 34.9 (range 24-49) years, were examined one to seven years after their last deep dive (190-500 metres of seawater). Four had by then lost their divers' licence because of neurological problems. Twenty seven (68%) had been selected by neurological examination and electroencephalography before the deep dives. The control group consisted of 100 men, mean age 34.0 (range 22-48) years. The divers reported significantly more symptoms from the nervous system. Concentration difficulties and paraesthesia in feet and hands were common. They had more abnormal neurological findings by neurological examination compatible with dysfunction in the lumbar spinal cord or roots. They also had a larger proportion of abnormal electroencephalograms than the controls. The neurological symptoms and findings were highly significantly correlated with exposure to deep diving (depth included), but even more significantly correlated to air and saturation diving and prevalence of decompression sickness. Visual evoked potentials, brainstem auditory evoked potentials, and magnetic resonance imaging of the brain did not show more abnormal findings in the divers. Four (10%) divers had had episodes of cerebral dysfunction during or after the dives; two had had seizures, one had had transitory cerebral ischaemia and one had had transitory global amnesia. It is concluded that deep diving may have a long term effect on the nervous system of the divers.

  20. Long-term treatment outcome in acromegaly.

    PubMed

    Holdaway, I M; Rajasoorya, C R; Gamble, G D; Stewart, A W

    2003-08-01

    A number of groups have developed guidelines to indicate whether an individual with acromegaly has been cured by treatment. However, studies to date do not provide a robust definition of biochemical remission of the disorder based on correlation with long-term outcome. Available data suggest that those with a random serum growth hormone (GH) level of <2.5 microg/l, or a glucose-suppressed GH level of <1 microg/l following treatment have mortality figures indistinguishable from the general population. However, the confidence limits for these mortality estimates are quite wide. It remains possible that growth hormone levels lower than 1 microg/l for random samples, or even lower when using ultrasensitive GH assays, may indicate superior outcome, but this remains to be confirmed. There are limited data relating serum insulin-like growth factor-I (IGF-I) levels to outcome, although normalisation of serum IGF-I clearly improves outcome compared with continued elevation of measurements after treatment. Current evidence suggests that a post-treatment random serum GH <2.5 microg/l and a normal serum IGF-I value defines biochemical cure. Available data suggest that achieving similar growth hormone levels after treatment also reduces the prevalence of chronic complications of the disorder, which is subsequently reflected in improved mortality. PMID:12914751

  1. Long Term Storage of Lyophilized Liposomal Formulations

    PubMed Central

    Payton, N.M.; Wempe, M.F.; Xu, Y.; Anchordoquy, T.J.

    2014-01-01

    Because aqueous liposomal formulations containing multiply unsaturated lipids are susceptible to chemical degradation, these formulations are often lyophilized. Despite their limited chemical stability, interest in the use of multiply unsaturated lipids to promote intracellular delivery has increased considerably in recent years. The goal of the current study was to examine the long term storage stability of lyophilized formulations containing lipids with increasing levels of unsaturation, and various strategies which can be employed to improve stability. Aqueous lipid-trehalose formulations containing 1,2-dilinolenoyl-sn-glycero-3-phosphocholine (DLPC), 1,2-dilinoleoyl-sn-glycero-3-phosphocholine (DLinPC) or 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) were lyophilized and stored at temperatures ranging from 4°C to 60°C. We observed that the lipid degradation rate increased as the storage temperature and unsaturation level were increased. Even the cleanest sugars which are available commercially contain iron contaminants, and it was observed that the chelation of these iron contaminants significantly improved the stability of DLPC during storage. However, the glass transition temperature of the sugar which was included in the formulation, the reduction of the oxygen in the aqueous sample prior to lyophilization, the inclusion of helper lipids (i.e., cholesterol), and the rate of freezing did not significantly improve stability. PMID:25308534

  2. Long-term behavior of ceramic materials

    SciTech Connect

    Anson, D.; Ramesh, K.S.

    1992-02-19

    This topical report has been prepared in response to the need to address the question of long term durability of high-strength structural ceramic materials. In a new project to demonstrate the use of such materials as replacements for metals in the hot gas path of industrial gas turbines, the longest projected test bed run will be 1000 hours. Creep in ceramic materials seldom exceeds one percent strain before failure, but the strain takes place almost entirely in the intergranular regions, which can be severely weakened by accumulated damage as creep occurs. In this report, we discuss the nature of creep in silicon nitride and silicon carbide ceramic materials, the method of evaluating creep, and the interpretation of data obtained under various creep test conditions. A review of creep data illustrates the importance of intergranular phases and of the history of the material. Also, in most cases, the histories applying to laboratory investigations are different from those that will apply to engineering situations in which measurable creep will be generally unacceptable. Fatigue in ceramic materials usually is assessed in static fatigue tests, which are dependent on the same types of grain boundary damage as those occurring in creep, but over shorter time periods. Corrosion of silicon-based ceramics by oxygen and water vapor results in the formation of protective SiO{sub 2} under gas turbine operating conditions.

  3. 22 CFR 228.12 - Long-term leases.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Long-term leases. 228.12 Section 228.12 Foreign... Transactions for USAID Financing § 228.12 Long-term leases. Any commodity obtained under a long-term lease..., a long-term lease is defined as a single lease of more than 180 days, or repetitive or...

  4. 22 CFR 228.12 - Long-term leases.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 22 Foreign Relations 1 2011-04-01 2011-04-01 false Long-term leases. 228.12 Section 228.12 Foreign... Transactions for USAID Financing § 228.12 Long-term leases. Any commodity obtained under a long-term lease..., a long-term lease is defined as a single lease of more than 180 days, or repetitive or...

  5. Legislation on Long-Term Care Insurance. Report No. 11.

    ERIC Educational Resources Information Center

    Wisconsin State Legislative Council, Madison.

    This report presents Wisconsin state legislation on long-term care insurance. Part I summarizes key provisions of six 1987 assembly bills concerned with long-term care insurance. Part II describes activities of the Wisconsin State Legislative Council's Special Committee on Long-Term Health Care Insurance. Part III provides background information…

  6. 22 CFR 228.18 - Long-term leases.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 22 Foreign Relations 1 2012-04-01 2012-04-01 false Long-term leases. 228.18 Section 228.18 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT RULES FOR PROCUREMENT OF COMMODITIES AND SERVICES FINANCED BY... USAID Financing § 228.18 Long-term leases. Any commodity obtained under a long-term lease agreement...

  7. 22 CFR 228.18 - Long-term leases.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 22 Foreign Relations 1 2014-04-01 2014-04-01 false Long-term leases. 228.18 Section 228.18 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT RULES FOR PROCUREMENT OF COMMODITIES AND SERVICES FINANCED BY... USAID Financing § 228.18 Long-term leases. Any commodity obtained under a long-term lease agreement...

  8. 22 CFR 228.18 - Long-term leases.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 22 Foreign Relations 1 2013-04-01 2013-04-01 false Long-term leases. 228.18 Section 228.18 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT RULES FOR PROCUREMENT OF COMMODITIES AND SERVICES FINANCED BY... USAID Financing § 228.18 Long-term leases. Any commodity obtained under a long-term lease agreement...

  9. Scientific Understanding from Long Term Observations: Insights from the Long Term Ecological Research (LTER) Program

    NASA Astrophysics Data System (ADS)

    Gosz, J.

    2001-12-01

    The network dedicated to Long Term Ecological Research (LTER) in the United States has grown to 24 sites since it was formed in 1980. Long-term research and monitoring are performed on parameters thatare basic to all ecosystems and are required to understand patterns, processes, and relationship to change. Collectively, the sites in the LTER Network provide opportunities to contrast marine, coastal, and continental regions, the full range of climatic gradients existing in North America, and aquatic and terrestrial habitats in a range of ecosystem types. The combination of common core areas and long-term research and monitoring in many habitats have allowed unprecedented abilities to understand and compare complex temporal and spatial dynamics associated with issues like climate change, effects of pollution, biodiversity and landuse. For example, McMurdo Dry Valley in the Antarctic has demonstrated an increase in glacier mass since 1993 which coincides with a period of cooler than normal summers and more than average snowfall. In contrast, the Bonanza Creek and Toolik Lake sites in Alaska have recorded a warming period unprecedented in the past 200 years. Nitrogen deposition effects have been identified through long-term watershed studies on biogeochemical cycles, especially at Coweeta Hydrological Lab, Harvard Forest, and the Hubbard Brook Experimental Forest. In aquatic systems, such as the Northern Temperate Lakes site, long-term data revealed time lags in effects of invaders and disturbance on lake communities. Biological recovery from an effect such as lake acidification was shown to lag behind chemical recovery. The long-term changes documented over 2 decades have been instrumental in influencing management practices in many of the LTER areas. In Puerto Rico, the Luquillo LTER demonstrated that dams obstruct migrations of fish and freshwater shrimp and water abstraction at low flows can completely obliterate downstream migration of juveniles and damage

  10. The neuronal response at extended timescales: long-term correlations without long-term memory

    PubMed Central

    Soudry, Daniel; Meir, Ron

    2014-01-01

    Long term temporal correlations frequently appear at many levels of neural activity. We show that when such correlations appear in isolated neurons, they indicate the existence of slow underlying processes and lead to explicit conditions on the dynamics of these processes. Moreover, although these slow processes can potentially store information for long times, we demonstrate that this does not imply that the neuron possesses a long memory of its input, even if these processes are bidirectionally coupled with neuronal response. We derive these results for a broad class of biophysical neuron models, and then fit a specific model to recent experiments. The model reproduces the experimental results, exhibiting long term (days-long) correlations due to the interaction between slow variables and internal fluctuations. However, its memory of the input decays on a timescale of minutes. We suggest experiments to test these predictions directly. PMID:24744724

  11. Laminin degradation by plasmin regulates long-term potentiation.

    PubMed

    Nakagami, Y; Abe, K; Nishiyama, N; Matsuki, N

    2000-03-01

    Plasmin is converted from its zymogen plasminogen by tissue type or urokinase type plasminogen activator (PA) and degrades many components of the extracellular matrix (ECM). To explore the possibility that the PA-plasmin system regulates synaptic plasticity, we investigated the effect of plasmin on degradation of ECM and synaptic plasticity by using organotypic hippocampal cultures. High-frequency stimulation produced long-term potentiation (LTP) in control slices, whereas the potentiation was induced but not maintained in slices pretreated with 100 nM plasmin for 6 hr. The baseline synaptic responses were not affected by pretreatment with plasmin. The impairment of LTP maintenance was not observed in slices pretreated with 100 nM plasmin for 6 hr, washed, and then cultured for 24-48 hr in the absence of plasmin. To identify substrates of plasmin, the expression of three major components of ECM, laminin, fibronectin, and type IV collagen, was investigated by immunofluorescence imaging. The three ECM components were widely distributed in the hippocampus, and only laminin was degraded by plasmin pretreatment. The expression level of laminin returned to normal levels when the slices were cultured for 24-48 hr after washout of plasmin. Furthermore, preincubation with anti-laminin antibodies prevented both the degradation of laminin and the impairment of LTP maintenance by plasmin. These results suggest that the laminin-mediated cell-ECM interaction may be necessary for the maintenance of LTP.

  12. Long-term infrared photometry of Seyferts

    NASA Astrophysics Data System (ADS)

    Glass, I. S.

    2004-05-01

    Long-term (up to 10 000 d) monitoring has been undertaken for 41 Seyferts in the near-infrared (1.25-3.45 μm). All but two showed variability, with amplitudes at K in the range <0.1 to >1.1 mag. The time-scale for detectable change is from about one week to a few years. Where contemporary observations of variability in X-rays, ultraviolet (UV) or visible light exist, it is found that the near-infrared varies in a similar way, though in some cases the shorter-wavelength infrared (IR) bands are diluted by underlying galaxy radiation. A simple cross-correlation study indicates that there is evidence for delays of up to several hundred d between the variations seen at the shortest wavelengths (U or J) and the longest (L) in many galaxies. In particular, the data for Fairall 9 now extend to twice the interval covered in earlier publications and the delay between its UV and IR outputs is seen to persist. An analysis of the fluxes shows that, for any given galaxy, the colours of the variable component of its nucleus are usually independent of the level of activity. The state of activity of the galaxy can be parameterized. Taken over the whole sample, the colours of the variable components fall within moderately narrow ranges. In particular, the H-K colour is appropriate to a blackbody of temperature 1600 K. The H-K excess for a heavily reddened nucleus can be determined and used to find EB-V, which can be compared to the values found from the visible region broad line ratios. Using flux-flux diagrams, the flux within the aperture from the underlying galaxies can often be determined without the need for model surface brightness profiles. In many galaxies it is apparent that there must be an additional constant contribution from warm dust.

  13. LONG TERM IN SITU DISPOSAL ENGINEERING STUDY

    SciTech Connect

    ADAMS; CARLSON; BROCKMAN

    2003-07-23

    Patent application pulled per Ken Norris (FH General Counsel). The objective of this study is to devise methods, produce conceptual designs, examine and select alternatives, and estimate costs for the demonstration of long-term (300-year) in situ disposal of an existing waste disposal site. The demonstration site selected is the 216-A-24 Crib near the 200 East Area. The site contains a fission product inventory and has experienced plant, animal, and inadvertent than intrusion. Of the potential intrusive events and transport pathways at the site, potential human intrusion has been given primary consideration in barrier design. Intrusion by wind, plants, and animals has been given secondary consideration. Groundwater modeling for a number of barrier configurations has been carried out to help select a barrier that will minimize water infiltration and waste/water contact time. The estimated effective lifetime and cost of 20 barrier schemes, using a variety of materials, have been evaluated. The schemes studied include single component surface barriers, multicomponent barriers, and massively injected grout barriers. Five barriers with high estimated effective lifetimes and relatively low costs have been selected for detailed evaluation. They are basalt riprap barriers, massive soil barriers, salt basin barriers, multi-component fine/coarse barriers, and cemented basalt barriers. A variety of materials and configurations for marking the site have also been considered. A decision analysis was completed to select a barrier scheme for demonstration. The analysis indicated that the basalt riprap alternative would be the preferred choice for a full-scale demonstration. The recommended approach is to demonstrate the basalt riprap barrier at the 216-A-24 Crib as soon as possible. Methods and costs of assessing effectiveness of the demonstration are also described. Preliminary design modifications and costs for applying the five selected barrier schemes to other site types are

  14. Hormonal changes during long-term isolation.

    PubMed

    Custaud, M A; Belin de Chantemele, E; Larina, I M; Nichiporuk, I A; Grigoriev, A; Duvareille, M; Gharib, C; Gauquelin-Koch, G

    2004-05-01

    Confinement and inactivity induce considerable psychological and physiological modifications through social and sensory deprivation. The aim of the SFINCSS-99 experiment was to determine the cardiovascular and hormonal pattern of blood volume regulation during long-term isolation and confinement. Simulation experiments were performed in pressurized chambers similar in size to the volumes of modern space vehicles. Group I consisted of four Russian male volunteers, who spent 240 days in a 100-m(3 )chamber. Group II included four males (one German and three Russians) who spent 110 days in isolation (200-m(3) module). The blood samples, taken before, during and after the isolation period, were used to determine haematocrit (Ht), growth hormone (GH), active renin, aldosterone, and osmolality levels. From the urine samples, electrolytes, osmolality, nitrites, nitrates, cortisol, antidiuretic hormone (ADH), aldosterone, normetanephrine and metanephrine levels were determined. The increase in plasma volume (PV) that is associated with a tendency for a decrease in plasma active renin is likely to be due to decreased sympathetic activity, and concords with the changes in urinary catecholamine levels during confinement. Urinary catecholamine levels were significantly higher during the recovery period than during confinement. This suggests that the sympathoadrenal system was activated, and concords with the increase in heart rate. Vascular resistance is determined by not only the vasoconstrictor but also vasodilator systems. The ratio of nitrite/nitrate in urine, as an indicator of nitric oxide release, did not reveal any significant changes. Analysis of data suggests that the duration of the isolation was a main factor involved in the regulation of hormones.

  15. Long term cultivation of larger benthic Foraminifera

    NASA Astrophysics Data System (ADS)

    Wöger, Julia; Eder, Wolfgang; Kinoshita, Shunichi; Antonino, Briguglio; Carles, Ferrandes-Cañadell; Hohenegger, Johann

    2015-04-01

    Benthic Foraminifera are used in a variety of applications employing numerous different methods, i.e. ecological monitoring, studying the effects of ocean acidification, reconstructing palaeo-bathymetry or investigating palaeo-salinity and palaeo-temperature to name only a few. To refine our understanding of ecological influences on larger benthic foraminiferal biology and to review inferences from field observations, culture experiments have become an indispensable tool. While culture experiments on smaller benthic foraminifera have become increasingly frequent in the past century, reports of the cultivation of symbiont bearing larger Foraminifera are rare. Generally, cultivation experiments can be divided into two groups: Culturing of populations and cultivation of single specimens allowing individual investigation. The latter differ form the former by several restrictions resulting from the need to limit individual motility without abridging microenvironmental conditions in the Foraminiferans artificial habitat, necessary to enable the individual to development as unfettered as possible. In this study we present first experiences and preliminary results of the long-term cultivation of larger benthic Foraminifera conducted at the 'Tropical Biosphere Research Station Sesoko Island, University of the Ryukyus', Japan, trying to reproduce natural conditions as closely as possible. Individuals of three species of larger benthic Foraminifera (Heterostegina depressa, Palaeonummulites venosus and Operculina complanata) have been cultured since April 2014. At the time of the general assembly the cultivation experiments will have been going on for more than one year, with the aim to investigate growth rates, longevities and reproduction strategies for comparison with results statistically inferred from application of the of the 'natural laboratory' method. The most important factor influencing foraminiferal health and development was found to be light intensity and light

  16. A new long-term care manifesto.

    PubMed

    Kane, Robert L

    2015-04-01

    This article argues for a fresh look at how we provide long-term care (LTC) for older persons. Essentially, LTC offers a compensatory service that responds to frailty. Policy debate around LTC centers on costs, but we are paying for something we really don't want. Building societal enthusiasm (or even support) for LTC will require re-inventing and re-branding. LTC has three basic components: personal care, housing, and health care (primarily chronic disease management). They can be delivered in a variety of settings. It is rare to find all three done well simultaneously. Personal care (PC) needs to be both competent and compassionate. Housing must provide at least minimal amenities and foster autonomy; when travel time for PC raises costs dramatically, some form of clustered housing may be needed. Health care must be proactive, aimed at preventing exacerbations of chronic disease and resultant hospitalizations. Enhancing preferences means allowing taking informed risks. Payment incentives should reward both quality of care and quality of life, but positive outcomes must be defined as slowing decline. Paying for services but not for housing under Medicaid would automatically level the playing field between nursing homes (NH) and community-based services. Regulations should achieve greater parity between NH and community care and include both positive and negative feedback. Providing post-acute care should be separate from LTC. Using the tripartite LTC framework, we can create innovative flexible approaches to providing needed services for frail older persons in formats that are both desirable and affordable. Such care will be more socially desirable and hence worth paying for.

  17. Balancing cure and long-term risks in acute lymphoblastic leukemia.

    PubMed

    Silverman, Lewis B

    2014-12-01

    Cure rates for children and adolescents with acute lymphoblastic leukemia (ALL) have improved dramatically over the last few decades. With this success has come increasing recognition of the adverse late effects of treatment. The significant long-term sequelae in the earliest cohort of long-term survivors treated in the 1970s and 1980s are well documented. To reduce the incidence of these late effects, the majority of pediatric patients treated on more contemporary regimens receive less intensive treatment than did those treated 30-40 years ago. However, current therapies are not risk free; children treated with contemporary regimens remain at risk for developing long-term toxicities, including cardiac dysfunction, osteonecrosis, neurocognitive impairment, and second malignant neoplasms. One of the great challenges facing clinical investigators today is to identify interventions that will reduce the frequency and severity of long-term toxicities without adversely affecting cure rates. The use of dexrazoxane as a cardioprotectant (to prevent anthracycline-associated cardiotoxicity) and alternate-week dosing of dexamethasone (to reduce the risk of osteonecrosis) are examples of 2 such successful strategies. This article provides an overview of the long-term toxicities associated with current therapies and reviews results of clinical trials designed to minimize the burden of cure in long-term survivors.

  18. Long-term and preventative treatment for seasonal affective disorder.

    PubMed

    Westrin, Asa; Lam, Raymond W

    2007-01-01

    Recurrent major depressive disorder with regular seasonal patterns, commonly known as seasonal affective disorder (SAD), has evoked substantial research in the last two decades. It is now recognised that SAD is a common condition with prevalence rates between 0.4% and 2.9% of the general population, and that patients with SAD experience significant morbidity and impairment in psychosocial function. There is good evidence that bright light therapy and antidepressant medications are effective for the short-term treatment of SAD; however, given that SAD is characterised by recurrent major depressive episodes, long-term and maintenance treatment must be considered. Unfortunately, there are few studies of longer term (>8 weeks) and maintenance (preventative) treatments for SAD. The weight of evidence suggests that light therapy usually needs to be continued daily throughout the winter season because of rapid relapse when light is stopped too early in the treatment period. However, some studies support the use of antidepressants to continue the response from a brief (1-2 weeks) course of light therapy early in the depressive episode, as soon as the first symptoms emerge in autumn. Only small studies have examined preventative treatment (before onset of symptoms) with light therapy, all of which have methodological limitations. The best evidence for preventative treatment in SAD comes from antidepressant studies. Three large, randomised, placebo-controlled studies have shown that preventative treatment with bupropion XL reduces the recurrence rate of depressive episodes in patients with SAD. Given the limitations in the evidence base and the inconsistent recurrence rate of winter depressive episodes, clinical recommendations for long-term and preventative treatment must individualise treatment choices and weigh potential benefits against possible adverse effects. PMID:17927295

  19. Long term evolution of patients treated in a TIA unit

    PubMed Central

    2013-01-01

    Background Transient ischemic attacks (TIA) entail a high risk of stroke recurrence, which depends on the etiology. New organizational models have been created, but there is not much information about the long-term evolution of patients managed according to these premises. Our aim is to refer the follow-up of patients attended according to our model of TIA Unit. Methods TIA Unit is located in the Emergency Department and staffed by vascular neurologists. Patients admitted during the Neurology night shift stayed in such Unit <48h with complete etiological study. Preventive treatment is instituted in patients discharged to a high resolution Neurology consult, in order to review in <2 weeks and subsequent follow-up. Results During a year 161 patients were attended, being admitted to the hospital 8.6%. A total of 1470 hospital days were avoided. Recurrence at 90 days was of 0.6%. Mean follow-up was 18.14 ± 8.02 months (0–34), total recurrence 6.2% (70% cardioembolic strokes). There were no complications derived from treatment. Cardiological events were recorded in 10.6%, neoplastic in 5%, cognitive impairment in 11%. There were 3 deaths unrelated nor to the stroke or its treatment. Conclusions This model allows an early diagnosis and treatment of TIA, preventing recurrences of stroke in a long term. It detects atherothrombotic strokes, most of them admitted to the hospital, and it shows a greater difficulty for detecting all cardioembolic strokes. TIA Unit appeared to be safe in using anticoagulation therapy, as the follow-up shows. It shows the same quality of management than hospital admission, with a significant saving in hospital stays. PMID:23635082

  20. Long term property prediction of polyethylene nanocomposites

    NASA Astrophysics Data System (ADS)

    Shaito, Ali Al-Abed

    properties of the nanocomposites was analyzed by examining tensile and creep-recovery behavior of the films at temperatures in the range of 25 to -100°C. Within the measured temperature range, the materials showed a nonlinear temperature dependent response. The time-temperature superposition principle was successfully used to predict the long term behavior of LLDPE nanocomposites.

  1. Long-Term Space Astrophysics Program

    NASA Technical Reports Server (NTRS)

    Nowark, Michael A.

    2001-01-01

    This is the final report for our Long-Term Space Astrophysics Program (NRA 94-OSS-12) grant NAG 5-3225. The proposal is entitled 'Spectral and Temporal Properties of Black Hole Candidates', and began funding in May 1995, and ran through 31 Aug 2000. The project summary from the original proposal was as follows: 'We will study the spectral and temporal properties of black hole candidates (BHC) by using data from archival sources (e.g., EXOSAT, Ginga, ROSAT) and proposed follow-up observations with modern instruments (e.g., ASCA, XTE). Our spectral studies will focus on identifying the basic characteristics and luminosities of the emission components in the various 'states' of BHC. We hope to understand and quantify the global energetics of these states. Our temporal studies will focus on expanding and classifying our knowledge of BHC variability properties in each state. We will explore the nature of quasi-periodic oscillations in BHC. We will combine our spectral and temporal studies by analyzing time lags and variability coherence between energy channels. In addition, we will investigate ways of correlating observed variability behavior with specific emission components.' We have accomplished many of these goals laid out within the original proposal. As originally proposed, we have utilized both archival and proprietary satellite data. In terms of archival data, we have utilized data from the Advanced Satellite for Cosmology and Astrophysics (ASCA), ROSAT, and the Rossi X-ray Timing Explorer (RXTE). We also obtained proprietary data from ASCA, RXTE, and the Extreme Ultraviolet Explorer (EUVE). In terms of sources, we have examined a wide variety of both galactic black hole candidates and extra-galactic black holes. For the galactic black holes we have observed and analyzed both the low/hard state and the high/soft state. We have performed both spectral and timing analyses on all of these objects. In addition, we have also examined a number of neutron stars or

  2. Long term prognosis of reactive salmonella arthritis

    PubMed Central

    Leirisalo-Repo, M; Helenius, P; Hannu, T; Lehtinen, A; Kreula, J; Taavitsainen, M; Koskimies, S

    1997-01-01

    OBJECTIVES—Reactive joint complications triggered by salmonella gastroenteritis are increasingly reported, but the outcome and long term prognosis of the patients is incompletely known. This study looked at the prognosis of salmonella arthritis in patients hospitalised in 1970-1986.
METHODS—Hospital records from two hospitals in southern Finland were screened for patients with the discharge diagnosis of salmonellosis or reactive, postinfectious arthritis or Reiter's disease. For the patients with confirmed diagnosis of reactive salmonella arthritis, data about the acute disease were collected from the hospital records. A follow up study was performed.
RESULTS—There were 63 patients (28 women, 35 men, mean age 36.5 years) with salmonella arthritis. Urethritis occurred in 27%, eye inflammation in 13%, and low back pain in 44% of the patients. HLA-B27 was present in 88%. More men than women were HLA-B27 positive. HLA-B27 positive patients had higher erythrocyte sedimentation rate (mean 80.9 v 46.5 mm 1st h, p = 0.0180). Also, extra-articular features and radiological sacroiliitis were seen only in HLA-B27 positive patients. A follow up study was performed on 50 patients mean 11.0 (range 5-22 years) later. Twenty patients had recovered completely. Ten patients had mild joint symptoms, 11 patients had had a new acute transient arthritis, and five acute iritis. Eight patients had developed chronic spondyloarthropathy. Radiological sacroiliitis was seen in six of 44 patients, more frequently in male than in female patients (32% v 0%; p = 0.0289). Recurrent or chronic arthritis, iritis or radiological sacroiliitis developed only in HLA-B27 positive patients.
CONCLUSION—Joint symptoms are common after reactive salmonella arthritis. HLA-B27 contributes to the severity of acute disease and to the late prognosis.

 PMID:9370874

  3. Long-term Nicotine Replacement Therapy

    PubMed Central

    Schnoll, Robert A.; Goelz, Patricia M.; Veluz-Wilkins, Anna; Blazekovic, Sonja; Powers, Lindsay; Leone, Frank T.; Gariti, Peter; Wileyto, E. Paul; Hitsman, Brian

    2015-01-01

    and extended treatment arms (20.3% vs 23.8%; OR, 1.17 [95% CI, 0.69-1.98]; P = .57). Similarly, we found no difference in week 52 abstinence rates between participants in the extended and standard treatment arms (26.0% vs 21.7%; OR, 1.33 [95% CI, 0.72-2.45]; P = .36). Treatment duration was not associated with any adverse effects or adherence to the counseling regimen, but participants in the maintenance treatment arm reported lower adherence to the nicotine patch regimen compared with those in the standard and extended treatment arms (mean [SD], 3.94 [2.5], 4.61 [2.0], and 4.7 [2.4] patches/wk, respectively; F2,522 = 6.03; P = .003). CONCLUSIONS AND RELEVANCE The findings support the safety of long-term use of nicotine patch treatment, although they do not support efficacy beyond 24 weeks of treatment in a broad group of smokers. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01047527 PMID:25705872

  4. Long-term functional recovery and compensation after cerebral ischemia in rats

    PubMed Central

    Girard, Sylvie; Murray, Katie N.; Rothwell, Nancy J.; Metz, Gerlinde A.S.; Allan, Stuart M.

    2014-01-01

    Cerebral ischemia is one of the most common causes of disabilities in adults and leads to long-term motor and cognitive impairments with limited therapeutic possibilities. Treatment options have proven efficient in preclinical models of cerebral ischemia but have failed in the clinical setting. This limited translation may be due to the suitability of models used and outcomes measured as most studies have focused on the early period after injury with gross motor scales, which have limited correlation to the clinical situation. The aim of this study was to determine long-term functional outcomes after cerebral ischemia in rats, focusing on fine motor function, social and depressive behavior as clinically relevant measures. A secondary objective was to evaluate the effects of an anti-inflammatory treatment (interleukin-1 receptor antagonist (IL-1Ra)) on functional recovery and compensation. Infarct volume was correlated with long-term (25 days) impairments in fine motor skills, but not with emotional components of behavior. Motor impairments could not be detected using conventional neurological tests and only detailed analysis allowed differentiation between recovery and compensation. Acute systemic administration of IL-1Ra (at reperfusion) led to a faster and more complete recovery, but delayed (24 h) IL-1Ra treatment had no effect. In summary functional assessment after brain injury requires detailed motor tests in order to address long-term impairments and compensation processes that are mediated by intact tissues. Functional deficits in skilled movement after brain injury represent ideal predictors of long-term outcomes and should become standard measures in the assessment of preclinical animal models. PMID:24821402

  5. Stochastic Induction of Long-Term Potentiation and Long-Term Depression.

    PubMed

    Antunes, G; Roque, A C; Simoes-de-Souza, F M

    2016-01-01

    Long-term depression (LTD) and long-term potentiation (LTP) of granule-Purkinje cell synapses are persistent synaptic alterations induced by high and low rises of the intracellular calcium ion concentration ([Ca(2+)]), respectively. The occurrence of LTD involves the activation of a positive feedback loop formed by protein kinase C, phospholipase A2, and the extracellular signal-regulated protein kinase pathway, and its expression comprises the reduction of the population of synaptic AMPA receptors. Recently, a stochastic computational model of these signalling processes demonstrated that, in single synapses, LTD is probabilistic and bistable. Here, we expanded this model to simulate LTP, which requires protein phosphatases and the increase in the population of synaptic AMPA receptors. Our results indicated that, in single synapses, while LTD is bistable, LTP is gradual. Ca(2+) induced both processes stochastically. The magnitudes of the Ca(2+) signals and the states of the signalling network regulated the likelihood of LTP and LTD and defined dynamic macroscopic Ca(2+) thresholds for the synaptic modifications in populations of synapses according to an inverse Bienenstock, Cooper and Munro (BCM) rule or a sigmoidal function. In conclusion, our model presents a unifying mechanism that explains the macroscopic properties of LTP and LTD from their dynamics in single synapses. PMID:27485552

  6. Stochastic Induction of Long-Term Potentiation and Long-Term Depression

    PubMed Central

    Antunes, G.; Roque, A. C.; Simoes-de-Souza, F. M.

    2016-01-01

    Long-term depression (LTD) and long-term potentiation (LTP) of granule-Purkinje cell synapses are persistent synaptic alterations induced by high and low rises of the intracellular calcium ion concentration ([Ca2+]), respectively. The occurrence of LTD involves the activation of a positive feedback loop formed by protein kinase C, phospholipase A2, and the extracellular signal-regulated protein kinase pathway, and its expression comprises the reduction of the population of synaptic AMPA receptors. Recently, a stochastic computational model of these signalling processes demonstrated that, in single synapses, LTD is probabilistic and bistable. Here, we expanded this model to simulate LTP, which requires protein phosphatases and the increase in the population of synaptic AMPA receptors. Our results indicated that, in single synapses, while LTD is bistable, LTP is gradual. Ca2+ induced both processes stochastically. The magnitudes of the Ca2+ signals and the states of the signalling network regulated the likelihood of LTP and LTD and defined dynamic macroscopic Ca2+ thresholds for the synaptic modifications in populations of synapses according to an inverse Bienenstock, Cooper and Munro (BCM) rule or a sigmoidal function. In conclusion, our model presents a unifying mechanism that explains the macroscopic properties of LTP and LTD from their dynamics in single synapses. PMID:27485552

  7. Reforming long-term care financing through insurance

    PubMed Central

    Meiners, Mark R.

    1988-01-01

    Until recently, insurance for long-term care was not viewed as feasible. This perception has changed dramatically in the past few years. Several models of long-term care insurance have begun to be tested. Although the application of insurance principles to long-term care is still new, the emergence of private market interest in developing long-term care insurance has been a catalyst to renewed public-policy support for reforming the way we pay for long-term care. States, in particular, have become interested in developing public-private partnerships to support the emergence of long-term care insurance that could help relieve the mounting pressure on Medicaid budgets. PMID:10312962

  8. Short-term Gains with Long-term Consequences: The Evolving Story of Sepsis Survivorship.

    PubMed

    Maley, Jason H; Mikkelsen, Mark E

    2016-06-01

    Sepsis is an acute, life-threatening condition that afflicts millions of patients annually. Advances in care and heightened awareness have led to substantial declines in short-term mortality. An expanding body of literature describes the long-term impact of sepsis, revealing long-term cognitive and functional impairments, sustained inflammation and immune dysfunction, increased healthcare resource use, reduced health-related quality of life, and increased mortality. The evidence challenges the notion that sepsis is an acute, transient illness, revealing rather that sepsis is an acute illness with lingering consequences. This article provides a state-of-the-art review of the emerging literature of the long-term consequences of sepsis. PMID:27229651

  9. Long-Term Monitoring of Global Climate Forcings and Feedbacks

    NASA Technical Reports Server (NTRS)

    Hansen, J. (Editor); Rossow, W. (Editor); Fung, I. (Editor)

    1993-01-01

    A workshop on Long-Term Monitoring of Global Climate Forcings and Feedbacks was held February 3-4, 1992, at NASA's Goddard Institute for Space Studies to discuss the measurements required to interpret long-term global temperature changes, to critique the proposed contributions of a series of small satellites (Climsat), and to identify needed complementary monitoring. The workshop concluded that long-term (several decades) of continuous monitoring of the major climate forcings and feedbacks is essential for understanding long-term climate change.

  10. Information exchange between short term and long term operations

    NASA Astrophysics Data System (ADS)

    Weijs, Steven

    2016-04-01

    This research focuses on the interactions between optimal short term and long term operations of managed water systems. Stochastic Dynamic Programming is used as a framework to find and analyze optimal operations. When considering optimal operations under uncertainty, the short term operations are influenced by the long term optimal policy through the value function of the end-state at the short term horizon. Conversely, the optimal long-term operations are influenced by the value of future decisions, which is partly determined by the short term operations. This leads to a two-way information flow between short and long term operations. The implications of this information flow are discussed.

  11. Long-Term Monitoring of Global Climate Forcings and Feedbacks

    SciTech Connect

    Hansen, J.; Rossow, W.; Fung, I.

    1993-09-01

    A workshop on Long-Term Monitoring of Global Climate Forcings and Feedbacks was held February 3-4, 1992, at NASA's Goddard Institute for Space Studies to discuss the measurements required to interpret long-term global temperature changes, to critique the proposed contributions of a series of small satellites (Climsat), and to identify needed complementary monitoring. The workshop concluded that long-term (several decades) of continuous monitoring of the major climate forcings and feedbacks is essential for understanding long-term climate change. Separate abstracts have been prepared for articles from this report.

  12. Deficits in long-term recognition memory reveal dissociated subtypes in congenital prosopagnosia.

    PubMed

    Stollhoff, Rainer; Jost, Jürgen; Elze, Tobias; Kennerknecht, Ingo

    2011-01-25

    The study investigates long-term recognition memory in congenital prosopagnosia (CP), a lifelong impairment in face identification that is present from birth. Previous investigations of processing deficits in CP have mostly relied on short-term recognition tests to estimate the scope and severity of individual deficits. We firstly report on a controlled test of long-term (one year) recognition memory for faces and objects conducted with a large group of participants with CP. Long-term recognition memory is significantly impaired in eight CP participants (CPs). In all but one case, this deficit was selective to faces and didn't extend to intra-class recognition of object stimuli. In a test of famous face recognition, long-term recognition deficits were less pronounced, even after accounting for differences in media consumption between controls and CPs. Secondly, we combined test results on long-term and short-term recognition of faces and objects, and found a large heterogeneity in severity and scope of individual deficits. Analysis of the observed heterogeneity revealed a dissociation of CP into subtypes with a homogeneous phenotypical profile. Thirdly, we found that among CPs self-assessment of real-life difficulties, based on a standardized questionnaire, and experimentally assessed face recognition deficits are strongly correlated. Our results demonstrate that controlled tests of long-term recognition memory are needed to fully assess face recognition deficits in CP. Based on controlled and comprehensive experimental testing, CP can be dissociated into subtypes with a homogeneous phenotypical profile. The CP subtypes identified align with those found in prosopagnosia caused by cortical lesions; they can be interpreted with respect to a hierarchical neural system for face perception.

  13. Deficits in Long-Term Recognition Memory Reveal Dissociated Subtypes in Congenital Prosopagnosia

    PubMed Central

    Stollhoff, Rainer; Jost, Jürgen; Elze, Tobias; Kennerknecht, Ingo

    2011-01-01

    The study investigates long-term recognition memory in congenital prosopagnosia (CP), a lifelong impairment in face identification that is present from birth. Previous investigations of processing deficits in CP have mostly relied on short-term recognition tests to estimate the scope and severity of individual deficits. We firstly report on a controlled test of long-term (one year) recognition memory for faces and objects conducted with a large group of participants with CP. Long-term recognition memory is significantly impaired in eight CP participants (CPs). In all but one case, this deficit was selective to faces and didn't extend to intra-class recognition of object stimuli. In a test of famous face recognition, long-term recognition deficits were less pronounced, even after accounting for differences in media consumption between controls and CPs. Secondly, we combined test results on long-term and short-term recognition of faces and objects, and found a large heterogeneity in severity and scope of individual deficits. Analysis of the observed heterogeneity revealed a dissociation of CP into subtypes with a homogeneous phenotypical profile. Thirdly, we found that among CPs self-assessment of real-life difficulties, based on a standardized questionnaire, and experimentally assessed face recognition deficits are strongly correlated. Our results demonstrate that controlled tests of long-term recognition memory are needed to fully assess face recognition deficits in CP. Based on controlled and comprehensive experimental testing, CP can be dissociated into subtypes with a homogeneous phenotypical profile. The CP subtypes identified align with those found in prosopagnosia caused by cortical lesions; they can be interpreted with respect to a hierarchical neural system for face perception. PMID:21283572

  14. Distinctions between orthographic long-term memory and working memory

    PubMed Central

    Buchwald, Adam; Rapp, Brenda

    2011-01-01

    Research in the cognitive and neural sciences has long posited a distinction between the long-term memory (LTM) storage of information and the short-term buffering of information that is being actively manipulated in working memory (WM). This basic type of distinction has been posited in a variety of domains, including written language production—spelling. In the domain of spelling, the primary source of empirical evidence regarding this distinction has been cognitive neuropsychological studies reporting deficits selectively affecting what the cognitive neuropsychological literature has referred to as the orthographic lexicon (LTM) or the graphemic buffer (WM). Recent papers have reexamined several of the hallmark characteristics of impairment affecting the graphemic buffer, with implications for our understanding of the nature of the orthographic LTM and WM systems. In this paper, we present a detailed case series study of 4 individuals with acquired spelling deficits and report evidence from both error types and factors influencing error rates that support the traditional distinction between these cognitive systems involved in spelling. In addition, we report evidence indicating possible interaction between these systems, which is consistent with a variety of recent findings in research on spelling. PMID:20425660

  15. Long-term outcomes of children after solid organ transplantation

    PubMed Central

    Kim, Jon Jin; Marks, Stephen D.

    2014-01-01

    Solid organ transplantation has transformed the lives of many children and adults by providing treatment for patients with organ failure who would have otherwise succumbed to their disease. The first successful transplant in 1954 was a kidney transplant between identical twins, which circumvented the problem of rejection from MHC incompatibility. Further progress in solid organ transplantation was enabled by the discovery of immunosuppressive agents such as corticosteroids and azathioprine in the 1950s and ciclosporin in 1970. Today, solid organ transplantation is a conventional treatment with improved patient and allograft survival rates. However, the challenge that lies ahead is to extend allograft survival time while simultaneously reducing the side effects of immunosuppression. This is particularly important for children who have irreversible organ failure and may require multiple transplants. Pediatric transplant teams also need to improve patient quality of life at a time of physical, emotional and psychosocial development. This review will elaborate on the long-term outcomes of children after kidney, liver, heart, lung and intestinal transplantation. As mortality rates after transplantation have declined, there has emerged an increased focus on reducing longer-term morbidity with improved outcomes in optimizing cardiovascular risk, renal impairment, growth and quality of life. Data were obtained from a review of the literature and particularly from national registries and databases such as the North American Pediatric Renal Trials and Collaborative Studies for the kidney, SPLIT for liver, International Society for Heart and Lung Transplantation and UNOS for intestinal transplantation. PMID:24860856

  16. [Long-term functional outcomes of cochlear implants in children].

    PubMed

    Laszig, R; Aschendorff, A; Beck, R; Schild, C; Kröger, S; Wesarg, T; Arndt, S

    2009-07-01

    The treatment of deaf and hearing-impaired children with cochlear implants has been established for several years. Nonetheless, no long-term results exist for studies of a representatively large number of children in the German-speaking area. These are necessary in order to formulate prognoses regarding the development and results of children undergoing implantation at various ages. In a retrospective study, we assessed the data of 156 children with various implantation ages and a minimum follow-up period of 5 years for whom speech and audiological data (Oldenburg Sentence Test, Freiburg words/numbers test) were available. Our findings confirm the assumption that early-implanted children (<2 years) achieve the best speech-comprehension results. For this reason, support for a sufficient universal neonate hearing screen should be emphatically given so that implantation, after a hearing test phase, can be targeted in the first year of life. The surgical, anesthesiological, and rehabilitation conditions must be fulfilled, and surgical experience is required for operation on infants and small children. PMID:19517077

  17. Hypoxia-induced phrenic long-term facilitation: emergent properties

    PubMed Central

    Devinney, Michael J.; Huxtable, Adrianne G.; Nichols, Nicole L.; Mitchell, Gordon S.

    2013-01-01

    Just as in other neural systems, plasticity is a hallmark of the neural system controlling breathing. One spinal mechanism of respiratory plasticity is phrenic long-term facilitation (pLTF) following acute intermittent hypoxia. Although cellular mechanisms giving rise to pLTF occur within the phrenic motor nucleus, different signaling cascades elicit pLTF in different conditions. These cascades, referred to as “Q” and “S" pathways to phrenic motor facilitation (pMF), interact via cross-talk inhibition. Whereas the Q pathway dominates pLTF after mild to moderate hypoxic episodes, the S pathway dominates after severe hypoxic episodes. The biological significance of multiple pathways to pMF is not known. We discuss the possibility that interactions between pathways confer emergent properties to pLTF, including: 1) pattern sensitivity and 2) metaplasticity. Understanding these mechanisms and their interactions may enable us to optimize intermittent hypoxia induced plasticity as a treatment for patients that suffer from ventilatory impairment or other motor deficits. PMID:23531012

  18. Long term sleep disturbance due to traffic noise

    NASA Astrophysics Data System (ADS)

    Vallet, M.; Gagneux, J.-M.; Blanchet, V.; Favre, B.; Labiale, G.

    1983-09-01

    This contribution to the evaluation of the effects of traffic noise on sleep disturbance is focused on the responses of people living near a main road. Experiments were carried out in the homes of subjects who had habitually been exposed to noise for periods of more than four years. The chronic changes in overall sleep patterns and the temporary sleep responses to particular noise events caused by traffic are demonstrated. Young people show mainly stage 3 and 4 deficits whilst older people show REM sleep deficits. The cardiac response to noise during sleep was also examined. These results highlight that both long term average and peak levels are important in assessing sleep disturbance. The threshold levels, measured inside the bedroom and above which sleep quality starts to become impaired, are 37 Leq(A) and 45 dB (A) Lp max , respectively. For the type of traffic studied these two levels are coherent and it is therefore possible that a single noise index, Leq(A), is sufficient to scale sleep disturbance.

  19. Long-term outcomes of children after solid organ transplantation.

    PubMed

    Kim, Jon Jin; Marks, Stephen D

    2014-01-01

    Solid organ transplantation has transformed the lives of many children and adults by providing treatment for patients with organ failure who would have otherwise succumbed to their disease. The first successful transplant in 1954 was a kidney transplant between identical twins, which circumvented the problem of rejection from MHC incompatibility. Further progress in solid organ transplantation was enabled by the discovery of immunosuppressive agents such as corticosteroids and azathioprine in the 1950s and ciclosporin in 1970. Today, solid organ transplantation is a conventional treatment with improved patient and allograft survival rates. However, the challenge that lies ahead is to extend allograft survival time while simultaneously reducing the side effects of immunosuppression. This is particularly important for children who have irreversible organ failure and may require multiple transplants. Pediatric transplant teams also need to improve patient quality of life at a time of physical, emotional and psychosocial development. This review will elaborate on the long-term outcomes of children after kidney, liver, heart, lung and intestinal transplantation. As mortality rates after transplantation have declined, there has emerged an increased focus on reducing longer-term morbidity with improved outcomes in optimizing cardiovascular risk, renal impairment, growth and quality of life. Data were obtained from a review of the literature and particularly from national registries and databases such as the North American Pediatric Renal Trials and Collaborative Studies for the kidney, SPLIT for liver, International Society for Heart and Lung Transplantation and UNOS for intestinal transplantation. PMID:24860856

  20. Insulin signaling is acutely required for long-term memory in Drosophila.

    PubMed

    Chambers, Daniel B; Androschuk, Alaura; Rosenfelt, Cory; Langer, Steven; Harding, Mark; Bolduc, Francois V

    2015-01-01

    Memory formation has been shown recently to be dependent on energy status in Drosophila. A well-established energy sensor is the insulin signaling (InS) pathway. Previous studies in various animal models including human have revealed the role of insulin levels in short-term memory but its role in long-term memory remains less clear. We therefore investigated genetically the spatial and temporal role of InS using the olfactory learning and long-term memory model in Drosophila. We found that InS is involved in both learning and memory. InS in the mushroom body is required for learning and long-term memory whereas long-term memory specifically is impaired after InS signaling disruption in the ellipsoid body, where it regulates the level of p70s6k, a downstream target of InS and a marker of protein synthesis. Finally, we show also that InS is acutely required for long-term memory formation in adult flies.

  1. Long-Term Treatment with Low Doses of Methamphetamine Promotes Neuronal Differentiation and Strengthens Long-Term Potentiation of Glutamatergic Synapses onto Dentate Granule Neurons.

    PubMed

    Baptista, Sofia; Lourenço, Joana; Milhazes, Nuno; Borges, Fernanda; Silva, Ana Paula; Bacci, Alberto

    2016-01-01

    Methamphetamine (METH) is a psychostimulant, affecting hippocampal function with disparate cognitive effects, which depends on the dose and time of administration, ranging from improvement to impairment of memory. Importantly, in the United States, METH is approved for the treatment of attention deficit hyperactivity disorder. Modifications of long-term plasticity of synapses originating from the entorhinal cortex onto dentate granule cells (DGCs) have been proposed to underlie cognitive alterations similar to those seen in METH users. However, the effects of METH on synaptic plasticity of the dentate gyrus are unknown. Here, we investigated the impact of long-term administration of METH (2 mg/kg/d) on neurogenesis and synaptic plasticity of immature and mature DGCs of juvenile mice. We used a mouse model of neurogenesis (the G42 line of GAD67-GFP), in which GFP is expressed by differentiating young DGCs. METH treatment enhanced the differentiation of GFP(+) cells, as it increased the fraction of GFP(+) cells expressing the neuronal marker NeuN, and decreased the amount of immature DGCs coexpressing doublecortin. Interestingly, METH did not change the magnitude of long-term potentiation (LTP) in more immature neurons, but facilitated LTP induction in more differentiated GFP(+) and strengthened plasticity in mature GFP(-) DGCs. The METH-induced facilitation of LTP in GFP(+) neurons was accompanied with spine enlargement. Our results reveal a specific action of long-term use of METH in the long-term plasticity of excitatory synapses onto differentiating DGCs and might have important implications toward the understanding of the synaptic basis of METH-induced cognitive alterations. PMID:27419216

  2. Long-Term Treatment with Low Doses of Methamphetamine Promotes Neuronal Differentiation and Strengthens Long-Term Potentiation of Glutamatergic Synapses onto Dentate Granule Neurons

    PubMed Central

    Milhazes, Nuno

    2016-01-01

    Abstract Methamphetamine (METH) is a psychostimulant, affecting hippocampal function with disparate cognitive effects, which depends on the dose and time of administration, ranging from improvement to impairment of memory. Importantly, in the United States, METH is approved for the treatment of attention deficit hyperactivity disorder. Modifications of long-term plasticity of synapses originating from the entorhinal cortex onto dentate granule cells (DGCs) have been proposed to underlie cognitive alterations similar to those seen in METH users. However, the effects of METH on synaptic plasticity of the dentate gyrus are unknown. Here, we investigated the impact of long-term administration of METH (2 mg/kg/d) on neurogenesis and synaptic plasticity of immature and mature DGCs of juvenile mice. We used a mouse model of neurogenesis (the G42 line of GAD67-GFP), in which GFP is expressed by differentiating young DGCs. METH treatment enhanced the differentiation of GFP+ cells, as it increased the fraction of GFP+ cells expressing the neuronal marker NeuN, and decreased the amount of immature DGCs coexpressing doublecortin. Interestingly, METH did not change the magnitude of long-term potentiation (LTP) in more immature neurons, but facilitated LTP induction in more differentiated GFP+ and strengthened plasticity in mature GFP− DGCs. The METH-induced facilitation of LTP in GFP+ neurons was accompanied with spine enlargement. Our results reveal a specific action of long-term use of METH in the long-term plasticity of excitatory synapses onto differentiating DGCs and might have important implications toward the understanding of the synaptic basis of METH-induced cognitive alterations. PMID:27419216

  3. Factors Affecting Long-Term Abstinence from Substances Use

    ERIC Educational Resources Information Center

    Elsheikh, Salah Elgaily

    2008-01-01

    Objective: The purpose of this study is to explore the attitudes of abstainers from drug use that relate to the factors leading to long-term abstinence. Materials and Methods: Cross-sectional study was carried out in Al-Amal Hospital to examine, which attitudes of abstainers related to long-term abstinence. A random survey was conducted on 62…

  4. Long Term Agroecosystem Research in the southern plains

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The Southern Plains (SP) site of the Long Term Agroecosystem Research (LTAR) network is headquartered at USDA-ARS’s Grazinglands Research Laboratory (GRL) in El Reno, Oklahoma. The GRL was established in 1948. A long-term watershed and climate research program was established in the Little Washita ...

  5. Helping People Make Better Long-Term-Care Decisions

    ERIC Educational Resources Information Center

    Kane, Robert L.; Boston, Krista; Chilvers, Mary

    2007-01-01

    Purpose: The purpose of this article is to describe an innovative online system to support long-term-care decision making. Design and Methods: The Long-Term Care Choices tool is a web-based system that uses expert opinion and structures decision making. Results: The system has been well accepted, and most users find it easy to use. Implications:…

  6. 78 FR 36449 - State Long-Term Care Ombudsman Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-18

    ... from the Long- Term Care Ombudsman program with less variation in the quality, efficiency, and... State Long-Term Care Ombudsman programs (Ombudsman programs) serve as advocates for residents of nursing homes, board and care homes, assisted living facilities and similar adult care facilities. They work...

  7. 7 CFR 1773.44 - Long-term debt.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 12 2011-01-01 2011-01-01 false Long-term debt. 1773.44 Section 1773.44 Agriculture...-term debt. The CPA's workpapers must document that he/she: (a) Confirmed RUS, FFB, and RTB debt to the...); (b) Confirmed other long-term debt directly with the lender; (c) Examined notes executed or...

  8. 7 CFR 1773.44 - Long-term debt.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 12 2010-01-01 2010-01-01 false Long-term debt. 1773.44 Section 1773.44 Agriculture...-term debt. The CPA's workpapers must document that he/she: (a) Confirmed RUS, FFB, and RTB debt to the...); (b) Confirmed other long-term debt directly with the lender; (c) Examined notes executed or...

  9. 3 CFR - Long-Term Gulf Coast Restoration Support Plan

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 3 The President 1 2011-01-01 2011-01-01 false Long-Term Gulf Coast Restoration Support Plan... Restoration Support Plan Memorandum for the Heads of Executive Departments and Agencies The oil spill in the... a plan of Federal support for the long-term economic and environmental restoration of the Gulf...

  10. 41 CFR 51-6.3 - Long-term procurements.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 41 Public Contracts and Property Management 1 2012-07-01 2009-07-01 true Long-term procurements. 51-6.3 Section 51-6.3 Public Contracts and Property Management Other Provisions Relating to Public... § 51-6.3 Long-term procurements. (a) Contracting activities are encouraged to investigate...

  11. 41 CFR 51-6.3 - Long-term procurements.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 41 Public Contracts and Property Management 1 2013-07-01 2013-07-01 false Long-term procurements. 51-6.3 Section 51-6.3 Public Contracts and Property Management Other Provisions Relating to Public... § 51-6.3 Long-term procurements. (a) Contracting activities are encouraged to investigate...

  12. 7 CFR 1773.44 - Long-term debt.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 12 2012-01-01 2012-01-01 false Long-term debt. 1773.44 Section 1773.44 Agriculture... (CONTINUED) POLICY ON AUDITS OF RUS BORROWERS RUS Required Audit Procedures and Documentation § 1773.44 Long... 691, Confirmation Schedule—Long-term Obligation to RUS as of; or RTB Form 12, Confirmation...

  13. 7 CFR 1773.44 - Long-term debt.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 12 2014-01-01 2013-01-01 true Long-term debt. 1773.44 Section 1773.44 Agriculture... (CONTINUED) POLICY ON AUDITS OF RUS BORROWERS RUS Required Audit Procedures and Documentation § 1773.44 Long... 691, Confirmation Schedule—Long-term Obligation to RUS as of; or RTB Form 12, Confirmation...

  14. 7 CFR 1773.44 - Long-term debt.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 12 2013-01-01 2013-01-01 false Long-term debt. 1773.44 Section 1773.44 Agriculture... (CONTINUED) POLICY ON AUDITS OF RUS BORROWERS RUS Required Audit Procedures and Documentation § 1773.44 Long... 691, Confirmation Schedule—Long-term Obligation to RUS as of; or RTB Form 12, Confirmation...

  15. 41 CFR 51-6.3 - Long-term procurements.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 41 Public Contracts and Property Management 1 2011-07-01 2009-07-01 true Long-term procurements. 51-6.3 Section 51-6.3 Public Contracts and Property Management Other Provisions Relating to Public... § 51-6.3 Long-term procurements. (a) Contracting activities are encouraged to investigate...

  16. 41 CFR 51-6.3 - Long-term procurements.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 41 Public Contracts and Property Management 1 2014-07-01 2014-07-01 false Long-term procurements. 51-6.3 Section 51-6.3 Public Contracts and Property Management Other Provisions Relating to Public... § 51-6.3 Long-term procurements. (a) Contracting activities are encouraged to investigate...

  17. Standards for Psychological Services in Long-Term Care Facilities.

    ERIC Educational Resources Information Center

    Morrow-Howell, Nancy; Lichtenberg, Peter A.; Smith, Michael; Frazer, Deborah; Molinari, Victor; Rosowsky, Erlene; Crose, Royda; Stillwell, Nick; Kramer, Nanette; Hartman-Stein, Paula; Qualls, Sara; Salamon, Michael; Duffy, Michael; Parr, Joyce; Gallagher-Thompson, Dolores

    1998-01-01

    Describes the development of standards for psychological practice in long-term care facilities. The standards, which were developed by Psychologists in Long-Term Care, address provider characteristics, methods of referral, assessment practices, treatment, and ethical issues. Offers suggestions for use of the standards. (MKA)

  18. Developmental Dyslexia and Explicit Long-Term Memory

    ERIC Educational Resources Information Center

    Menghini, Deny; Carlesimo, Giovanni Augusto; Marotta, Luigi; Finzi, Alessandra; Vicari, Stefano

    2010-01-01

    The reduced verbal long-term memory capacities often reported in dyslexics are generally interpreted as a consequence of their deficit in phonological coding. The present study was aimed at evaluating whether the learning deficit exhibited by dyslexics was restricted only to the verbal component of the long-term memory abilities or also involved…

  19. Elder Rights and the Long-Term Care Ombudsman Program.

    ERIC Educational Resources Information Center

    Netting, F. Ellen; And Others

    1995-01-01

    Examines important issues facing the Long-Term Care Ombudsman Program. Provides a historical overview of the policy and programmatic and research issues that surround the Older Americans Act. Explains ombudsmen's activities in their local communities and explores social workers' roles under the auspices of long-term care ombudsman programs. (RJM)

  20. The relationship between interannual and long-term cloud feedbacks

    SciTech Connect

    Zhou, Chen; Zelinka, Mark D.; Dessler, Andrew E.; Klein, Stephen A.

    2015-12-11

    The analyses of Coupled Model Intercomparison Project phase 5 simulations suggest that climate models with more positive cloud feedback in response to interannual climate fluctuations also have more positive cloud feedback in response to long-term global warming. Ensemble mean vertical profiles of cloud change in response to interannual and long-term surface warming are similar, and the ensemble mean cloud feedback is positive on both timescales. However, the average long-term cloud feedback is smaller than the interannual cloud feedback, likely due to differences in surface warming pattern on the two timescales. Low cloud cover (LCC) change in response to interannual and long-term global surface warming is found to be well correlated across models and explains over half of the covariance between interannual and long-term cloud feedback. In conclusion, the intermodel correlation of LCC across timescales likely results from model-specific sensitivities of LCC to sea surface warming.

  1. Long-Term Dynamics of Autonomous Fractional Differential Equations

    NASA Astrophysics Data System (ADS)

    Liu, Tao; Xu, Wei; Xu, Yong; Han, Qun

    This paper aims to investigate long-term dynamic behaviors of autonomous fractional differential equations with effective numerical method. The long-term dynamic behaviors predict where systems are heading after long-term evolution. We make some modification and transplant cell mapping methods to autonomous fractional differential equations. The mapping time duration of cell mapping is enlarged to deal with the long memory effect. Three illustrative examples, i.e. fractional Lotka-Volterra equation, fractional van der Pol oscillator and fractional Duffing equation, are studied with our revised generalized cell mapping method. We obtain long-term dynamics, such as attractors, basins of attraction, and saddles. Compared with some existing stability and numerical results, the validity of our method is verified. Furthermore, we find that the fractional order has its effect on the long-term dynamics of autonomous fractional differential equations.

  2. [Long-term care insurance in taiwan: theory and challenges].

    PubMed

    Lee, Jwo-Leun; Lung, Chi-Hsuan; Liu, Li-Fan

    2010-08-01

    Long-term care insurance, now being intensively discussed as part of the formal governmental agenda, is widely expected to be inaugurated by 2011. As all entitled citizens will be enrolled compulsorily in accordance with social insurance rules, tight scrutiny in the planning process is strongly advised. Equity of financial mechanisms and the efficiency of the delivery system for long-term care should also be carefully considered and maximized. This study explores major empirical suggestions for Taiwan's long-term care insurance scheme from a primarily theoretical point of view. The three relevant issues deliberated in this paper include risk sharing and financial equity in long-term care insurance and long-term care system delivery efficiency. Content focuses on concepts that may be easily misunderstood or misinterpreted by medical professionals.

  3. Environmental Management Long-Term Stewardship Transition Guidance

    SciTech Connect

    Kristofferson, Keith

    2001-11-01

    Long-term stewardship consists of those actions necessary to maintain and demonstrate continued protection of human health and the environment after the completion of facility cleanup. Long-term stewardship is administered and overseen by the U.S. Department of Energy Environmental Management Office of Science and Technology. This report describes the background of long-term stewardship and gives general guidance about considerations when ownership and/or responsibility of a site should be transferred to a long-term stewardship program. This guidance document will assist the U.S. Department of Energy in: (a) ensuring that the long-term stewardship program leads transition planning with respect to facility and site areas, and (b) describing the classes and types of criteria and data required to initiate transition for areas and sites where the facility mission has ended and cleanup is complete.

  4. The relationship between interannual and long-term cloud feedbacks

    NASA Astrophysics Data System (ADS)

    Zhou, Chen; Zelinka, Mark D.; Dessler, Andrew E.; Klein, Stephen A.

    2015-12-01

    Analyses of Coupled Model Intercomparison Project phase 5 simulations suggest that climate models with more positive cloud feedback in response to interannual climate fluctuations also have more positive cloud feedback in response to long-term global warming. Ensemble mean vertical profiles of cloud change in response to interannual and long-term surface warming are similar, and the ensemble mean cloud feedback is positive on both timescales. However, the average long-term cloud feedback is smaller than the interannual cloud feedback, likely due to differences in surface warming pattern on the two timescales. Low cloud cover (LCC) change in response to interannual and long-term global surface warming is found to be well correlated across models and explains over half of the covariance between interannual and long-term cloud feedback. The intermodel correlation of LCC across timescales likely results from model-specific sensitivities of LCC to sea surface warming.

  5. Deficit in long-term synaptic plasticity is rescued by a computationally predicted stimulus protocol.

    PubMed

    Liu, Rong-Yu; Zhang, Yili; Baxter, Douglas A; Smolen, Paul; Cleary, Leonard J; Byrne, John H

    2013-04-17

    Mutations in the gene encoding CREB-binding protein (CBP) cause deficits in long-term plasticity, learning, and memory. Here, long-term synaptic facilitation (LTF) at Aplysia sensorimotor synapses in cell culture was used as a model system to investigate methods for overcoming deficits in LTF produced by a CBP knockdown. Injecting CBP-siRNA into individual sensory neurons reduced CBP levels and impaired LTF produced by a standard protocol of five 5-min pulses of serotonin (5-HT) delivered at 20 min interstimulus intervals. A computational model, which simulated molecular processes underlying LTF induction, predicted a rescue protocol of five pulses of 5-HT at non-uniform interstimulus intervals that overcame the consequences of reduced CBP and restored LTF. These results suggest that complementary empirical and computational studies can identify methods for ameliorating impairments of learning attributable to molecular lesions.

  6. Deficit in long-term synaptic plasticity is rescued by a computationally predicted stimulus protocol.

    PubMed

    Liu, Rong-Yu; Zhang, Yili; Baxter, Douglas A; Smolen, Paul; Cleary, Leonard J; Byrne, John H

    2013-04-17

    Mutations in the gene encoding CREB-binding protein (CBP) cause deficits in long-term plasticity, learning, and memory. Here, long-term synaptic facilitation (LTF) at Aplysia sensorimotor synapses in cell culture was used as a model system to investigate methods for overcoming deficits in LTF produced by a CBP knockdown. Injecting CBP-siRNA into individual sensory neurons reduced CBP levels and impaired LTF produced by a standard protocol of five 5-min pulses of serotonin (5-HT) delivered at 20 min interstimulus intervals. A computational model, which simulated molecular processes underlying LTF induction, predicted a rescue protocol of five pulses of 5-HT at non-uniform interstimulus intervals that overcame the consequences of reduced CBP and restored LTF. These results suggest that complementary empirical and computational studies can identify methods for ameliorating impairments of learning attributable to molecular lesions. PMID:23595752

  7. Numerical simulation of gender differences in a long-term microgravity exposure

    NASA Astrophysics Data System (ADS)

    Perez-Poch, Antoni

    The objective of this work is to analyse and simulate gender differences when individuals are exposed to long-term microgravity. Risk probability of a health impairment which may put in jeopardy a long-term mission is also evaluated. Computer simulations are becoming a promising research line of work, as physiological models become more and more sophisticated and reliable. Technological advances in state-of-the-art hardware technology and software allow nowadays for better and more accurate simulations of complex phenomena, such as the response of the human cardiovascular system to long-term exposure to microgravity. Experimental data for long-term missions are difficult to achieve and reproduce, therefore the predictions of computer simulations are of a major importance in this field. Our approach is based on a previous model developed and implemented in our laboratory (NELME: Numerical Evaluation of Long-term Microgravity Effects). The software simulates the behaviour of the cardiovascular system and different human organs, has a modular architecture, and allows to introduce perturbations such as physical exercise or countermeasures. The implementation is based on a complex electricallike model of this control system, using inexpensive software development frameworks, and has been tested and validated with the available experimental data. Gender differences have been implemented for this specific work, as an adjustment of a number of parameters that are included in the model. Women versus men physiological differences have been therefore taken into account, based upon estimations from the physiology bibliography. A number of simulations have been carried out for long-term exposure to microgravity. Gravity varying from Earth-based to zero, and time exposure are the two main variables involved in the construction of results, including responses to patterns of physical aerobical exercise, and also thermal stress simulating an extra-vehicular activity. Results show

  8. Quaternary structure defines a large class of amyloid-β oligomers neutralized by sequestration

    PubMed Central

    Liu, Peng; Reed, Miranda N.; Kotilinek, Linda A.; Grant, Marianne K.O.; Forster, Colleen L.; Qiang, Wei; Shapiro, Samantha L.; Reichl, John H.; Chiang, Angie C.A.; Jankowsky, Joanna L.; Wilmot, Carrie M.; Cleary, James P.; Zahs, Kathleen R.; Ashe, Karen H.

    2015-01-01

    Summary The accumulation of amyloid-β (Aβ) as amyloid fibrils and toxic oligomers is an important step in the development of Alzheimer's disease (AD). However, there are numerous potentially toxic oligomers and little is known about their neurological effects when generated in the living brain. Here, we show that Aβ oligomers can be assigned to one of at least two classes (Type 1 and Type 2) based on their temporal, spatial and structural relationships to amyloid fibrils. The Type 2 oligomers are related to amyloid fibrils and represent the majority of oligomers generated in vivo, but remain confined to the vicinity of amyloid plaques and do not impair cognition at levels relevant to AD. Type 1 oligomers are unrelated to amyloid fibrils and may have greater potential to cause global neural dysfunction in AD because they are dispersed. These results refine our understanding of the pathogenicity of Aβ oligomers in vivo. PMID:26051935

  9. The Womanly World of Long Term Care: The Plight of the Long Term Care Worker. Gray Paper.

    ERIC Educational Resources Information Center

    Older Women's League, Washington, DC.

    Long-term care workers (those who are paid to provide custodial care for long-term patients in nursing homes or at home) must care for a growing number of increasingly disabled or dependent persons. They are working for agencies and institutions under growing pressure to increase productivity. They face new training and competency requirements,…

  10. Dopamine favours the emergence of long-term depression versus long-term potentiation in slices of rat prefrontal cortex.

    PubMed

    Law-Tho, D; Desce, J M; Crepel, F

    1995-03-24

    In the present study, we have investigated possible interactions between dopamine and long-term changes in synaptic efficacy induced in layer V pyramidal cells by tetanization of afferents from layer I-II. In the absence of dopamine, we confirmed that high frequency stimulation of excitatory afferents induced long-term potentiation, long-term depression or no change. Inversely, in the presence of dopamine, we have found that the same tetanus led to long-term depression in synaptic transmission in a majority of cells, but no more long-term potentiation. These results suggest that in rat prefrontal cortex, dopamine may determine the direction of activity dependent changes in synaptic efficacy and therefore, plays a functional role in the physiology of this structure.

  11. Role of healthcare in Korean long-term care insurance.

    PubMed

    Kang, Im-Oak; Park, Chong Yon; Lee, Yunhwan

    2012-05-01

    With the rapid aging of the population, Korea introduced public long-term care insurance for older people in 2008. The long-term care insurance was designed as a separate scheme from the national health insurance, with eligibility qualifications and the certification process based on functional disability, benefits and coverage of community-based and institutional care, and a financing structure through multi-party contributions. Delivering appropriate health services to long-term care beneficiaries who manifest a high prevalence of comorbid chronic conditions with rising healthcare costs, however, presents a particular challenge. The lack of coordination between the health and long-term care sectors, limited consideration of physicians' assessments in the certification process, inadequate provision of health services in long-term care facilities, and overlapping and inefficient use of care resources act as barriers to providing comprehensive healthcare for older beneficiaries. Through active participation in the long-term care system, health professionals can help older patients navigate through the complex long-term care terrain to obtain quality healthcare.

  12. Long-Term Stewardship Baseline Report and Transition Guidance

    SciTech Connect

    Kristofferson, Keith

    2001-11-01

    Long-term stewardship consists of those actions necessary to maintain and demonstrate continued protection of human health and the environment after facility cleanup is complete. As the Department of Energy’s (DOE) lead laboratory for environmental management programs, the Idaho National Engineering and Environmental Laboratory (INEEL) administers DOE’s long-term stewardship science and technology efforts. The INEEL provides DOE with technical, and scientific expertise needed to oversee its long-term environmental management obligations complexwide. Long-term stewardship is administered and overseen by the Environmental Management Office of Science and Technology. The INEEL Long-Term Stewardship Program is currently developing the management structures and plans to complete INEEL-specific, long-term stewardship obligations. This guidance document (1) assists in ensuring that the program leads transition planning for the INEEL with respect to facility and site areas and (2) describes the classes and types of criteria and data required to initiate transition for areas and sites where the facility mission has ended and cleanup is complete. Additionally, this document summarizes current information on INEEL facilities, structures, and release sites likely to enter long-term stewardship at the completion of DOE’s cleanup mission. This document is not intended to function as a discrete checklist or local procedure to determine readiness to transition. It is an overarching document meant as guidance in implementing specific transition procedures. Several documents formed the foundation upon which this guidance was developed. Principal among these documents was the Long-Term Stewardship Draft Technical Baseline; A Report to Congress on Long-Term Stewardship, Volumes I and II; Infrastructure Long-Range Plan; Comprehensive Facility Land Use Plan; INEEL End-State Plan; and INEEL Institutional Plan.

  13. Clinical and radiological assessment of effects of long-term corticosteroid therapy on oral health

    PubMed Central

    Beeraka, Swapna Sridevi; Natarajan, Kannan; Patil, Rajendra; Manne, Rakesh Kumar; Prathi, Venkata Sarath; Kolaparthi, Venkata Suneel Kumar

    2013-01-01

    Background: Corticosteroids (Cs) are used widely for their anti-inflammatory and immunosuppressive properties. They have the potential to cause dramatic improvement as well as produce equally dramatic adverse effects. The clinical misuse like over prescription of the drug should be avoided. Long-term administration may cause many adverse effects leading to impaired oral health. Oral health is usually not considered during management of patients on long-term corticosteroid therapy. The aim of this study was to assess the oral health status and radiological changes in the jaw bones of the patients under long-term corticosteroid therapy. Materials and Methods: Oral health of 100 patients under long-term corticosteroid therapy with a minimum of 3 months duration was compared with sex- and age-matched 100 healthy controls. The clinical examination included complete examination of the mouth and periodontal status. Radiographic evaluation of bone with the help of intra oral periapical radiograph and digital orthopantomograph and levels of serum calcium, alkaline phosphatase, and random blood sugar were assessed. ‘Chi-square test’, ‘Kolmogorov-Smirnov test’ and ‘Mann-Whitney U test’ were used for statistical analysis. P > 0.05 was considered significant. Results: Patients on steroids exhibited significantly higher levels of candidiasis and clinical attachment loss of the periodontal ligament, probing pocket depth. Bone density was significantly lower in the study group than that in the control group. Random blood glucose was significantly higher and significant lower levels of calcium were observed in patients on steroids. Conclusion: Long-term use of Cs may affect oral health adversely leading to candidiasis as well as impair bone metabolism leading to a considerable decrease in the mandibular bone mineral density. PMID:24348627

  14. Space ventures and society long-term perspectives

    NASA Technical Reports Server (NTRS)

    Brown, W. M.

    1985-01-01

    A futuristic evaluation of mankind's potential long term future in space is presented. Progress in space will not be inhibited by shortages of the Earth's physical resources, since long term economic growth will be focused on ways to constrain industrial productivity by changing social values, management styles, or government competence. Future technological progress is likely to accelerate with an emphasis on international cooperation, making possible such large joint projects as lunar colonies or space stations on Mars. The long term future in space looks exceedingly bright even in relatively pessimistic scenarios. The principal driving forces will be technological progress, commercial and public-oriented satellites, space industrialization, space travel, and eventually space colonization.

  15. Nitric oxide-dependent long-term depression but not endocannabinoid-mediated long-term potentiation is crucial for visual recognition memory

    PubMed Central

    Tamagnini, Francesco; Barker, Gareth; Warburton, E Clea; Burattini, Costanza; Aicardi, Giorgio; Bashir, Zafar I

    2013-01-01

    Synaptic plasticity in perirhinal cortex is essential for recognition memory. Nitric oxide and endocannabinoids (eCBs), which are produced in the postsynaptic cell and act on the presynaptic terminal, are implicated in mechanisms of long-term potentiation (LTP) and long-term depression (LTD) in other brain regions. In this study, we examine these two retrograde signalling cascades in perirhinal cortex synaptic plasticity and in visual recognition memory in the rat. We show that inhibition of NO-dependent signalling prevented both carbachol- and activity (5 Hz)-dependent LTD but not activity (100 Hz theta burst)-dependent LTP in the rat perirhinal cortex in vitro. In contrast, inhibition of the eCB-dependent signalling prevented LTP but not the two forms of LTD in vitro. Local administration into perirhinal cortex of the nitric oxide synthase inhibitor NPA (2 μm) disrupted acquisition of long-term visual recognition memory. In contrast, AM251 (10 μm), a cannabinoid receptor 1 antagonist, did not impair visual recognition memory. The results of this study demonstrate dissociation between putative retrograde signalling mechanisms in LTD and LTP in perirhinal cortex. Thus, LTP relies on cannabinoid but not NO signalling, whilst LTD relies on NO- but not eCB-dependent signalling. Critically, these results also establish, for the first time, that NO- but not eCB-dependent signalling is important in perirhinal cortex-dependent visual recognition memory. PMID:23671159

  16. Phenylethynyl terminated reactive oligomer

    NASA Technical Reports Server (NTRS)

    Bryant, Robert G. (Inventor); Jensen, Brian J. (Inventor); Hergenrother, Paul M. (Inventor)

    1995-01-01

    A composition of matter having the general structure: ##STR1## (wherein X is F, Cl, or NO.sub.2, and Y is CO, SO.sub.2 or C(CF.sub.3).sub.2) is employed to terminate a nucleophilic reagent, resulting in the exclusive production of phenylethynyl terminated reactive oligomers which display unique thermal characteristics. A reactive diluent having the general structure: ##STR2## (wherein R is any aliphatic or aromatic moiety) is employed to decrease the melt viscosity of a phenylethynyl terminated reactive oligomer and to subsequently react therewith to provide a thermosetting material of enhanced density. These materials have features which make them attractive candidates for use as composite matrices and adhesives.

  17. Earth's Long-Term Warming Trend, 1880-2015

    NASA Video Gallery

    This visualization illustrates Earth’s long-term warming trend, showing temperature changes from 1880 to 2015 as a rolling five-year average. Orange colors represent temperatures that are warmer th...

  18. Malaria prophylaxis in long-term expatriate mineworkers in Ghana.

    PubMed

    Fegan, D; Glennon, J

    1993-08-01

    The role of malaria chemoprophylaxis for long-term expatriates has not been re-evaluated since the emergence of widespread multidrug resistance. A survey of 106 expatriates working in a mine in Ghana (holoendemic for malaria) was conducted to determine the compliance with malaria chemoprophylaxis. Overall 64 per cent took regular chemoprophylaxis. Of the long-term expatriates (5 or more years in areas with holoendemic malaria), 48.4 per cent either took malaria prophylaxis very irregularly or not at all. The main reasons for failing to comply were fear of long-term side effects and conflicting advice on prophylaxis. This reluctance to take long-term chemoprophylaxis highlights the need to re-emphasise the importance of anti-mosquito measures, prompt treatment of fevers, and perhaps consider abandoning chemoprophylaxis in those expatriate workers with ready access to hospital care.

  19. Biogeochemistry: Long-term effects of permafrost thaw

    NASA Astrophysics Data System (ADS)

    Zona, Donatella

    2016-09-01

    Carbon emissions from the Arctic tundra could increase drastically as global warming thaws permafrost. Clues now obtained about the long-term effects of such thawing on carbon dioxide emissions highlight the need for more data.

  20. Long-Term Quiescent Fibroblast Cells Transit into Senescence

    PubMed Central

    Marthandan, Shiva; Priebe, Steffen; Hemmerich, Peter; Klement, Karolin; Diekmann, Stephan

    2014-01-01

    Cellular senescence is described to be a consequence of telomere erosion during the replicative life span of primary human cells. Quiescence should therefore not contribute to cellular aging but rather extend lifespan. Here we tested this hypothesis and demonstrate that cultured long-term quiescent human fibroblasts transit into senescence due to similar cellular mechanisms with similar dynamics and with a similar maximum life span as proliferating controls, even under physiological oxygen conditions. Both, long-term quiescent and senescent fibroblasts almost completely fail to undergo apoptosis. The transition of long-term quiescent fibroblasts into senescence is also independent of HES1 which protects short-term quiescent cells from becoming senescent. Most significantly, DNA damage accumulates during senescence as well as during long-term quiescence at physiological oxygen levels. We suggest that telomere-independent, potentially maintenance driven gradual induction of cellular senescence during quiescence is a counterbalance to tumor development. PMID:25531649

  1. Long-term memories in online users' selecting activities

    NASA Astrophysics Data System (ADS)

    Pan, Xue; Hou, Lei; Stephen, Mutua; Yang, Huijie

    2014-07-01

    In this paper, we investigate the long-term memory effect in the behavior of online users. Two user-oriented online movie systems are used in this study. Due to the short length of the series, the balanced estimation of diffusion entropy approach is used to evaluate scaling-invariance in selecting activities of users in the two online movie systems. Our results indicate that persistence (long-term memory) exists widely in the movie selecting series. However, there is generally significant difference between a user's objective and subjective behaviors. Additionally, statistically, the long-term memory depends on activity levels, as results show that the much more active a users' group, the stronger the long-term memory will be. These findings provide a new criterion for constructing reasonable models, and can help understand how individuals' behaviors form a collective behavior of an online society.

  2. Long-Term Ecological Monitoring Field Sampling Plan for 2007

    SciTech Connect

    T. Haney R. VanHorn

    2007-07-31

    This field sampling plan describes the field investigations planned for the Long-Term Ecological Monitoring Project at the Idaho National Laboratory Site in 2007. This plan and the Quality Assurance Project Plan for Waste Area Groups 1, 2, 3, 4, 5, 6, 7, 10, and Removal Actions constitute the sampling and analysis plan supporting long-term ecological monitoring sampling in 2007. The data collected under this plan will become part of the long-term ecological monitoring data set that is being collected annually. The data will be used t determine the requirements for the subsequent long-term ecological monitoring. This plan guides the 2007 investigations, including sampling, quality assurance, quality control, analytical procedures, and data management. As such, this plan will help to ensure that the resulting monitoring data will be scientifically valid, defensible, and of known and acceptable quality.

  3. Long-term monitoring for nanomedicine implants and drugs

    NASA Astrophysics Data System (ADS)

    Kendall, Michaela; Lynch, Iseult

    2016-03-01

    Increasing globalization means that traditional occupational epidemiological approaches may no longer apply, suggesting a need for an alternative model to assess the long-term impact of nanomaterial exposure on health.

  4. The market for long-term care services.

    PubMed

    Grabowski, David C

    2008-01-01

    Although a large literature has established the importance of market and regulatory forces within the long-term care sector, current research in this field is limited by a series of data, measurement, and methodological issues. This paper provides a comprehensive review of these issues with an emphasis on identifying initiatives that will increase the volume and quality of long-term care research. Recommendations include: the construction of standard measures of long-term care market boundaries, the broader dissemination of market and regulatory data, the linkage of survey-based data with market measures, the encouragement of further market-based studies of noninstitutional long-term care settings, and the standardization of Medicaid cost data. PMID:18524292

  5. Examining Long-Term Global Climate Change on the Web.

    ERIC Educational Resources Information Center

    Huntoon, Jacqueline E.; Ridky, Robert K.

    2002-01-01

    Describes a web-based, inquiry-oriented activity that enables students to examine long-term global climate change. Supports instruction in other topics such as population growth. (Contains 34 references.) (DDR)

  6. The Long Term Agroecosystem Research Network - Shared research strategy

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Agriculture faces tremendous challenges in meeting multiple societal goals, including a safe and plentiful food supply; climate change adaptation and mitigation; supplying sources of bioenergy; improving water, air, and soil quality; and maintaining biodiversity. The Long Term Agroecosystem Research...

  7. Long-term Career Goals for Professional Women in Agriculture.

    ERIC Educational Resources Information Center

    Klepper, Betty

    1986-01-01

    Encourages the formation of long-term career goals for women in agronomy. Offers perspectives and practical suggestions for obtaining positions, maintaining professional credentials, and managing personal and career related obligations. (ML)

  8. The role of spatial boundaries in shaping long-term event representations.

    PubMed

    Horner, Aidan J; Bisby, James A; Wang, Aijing; Bogus, Katrina; Burgess, Neil

    2016-09-01

    When remembering the past, we typically recall 'events' that are bounded in time and space. However, as we navigate our environment our senses receive a continuous stream of information. How do we create discrete long-term episodic memories from continuous input? Although previous research has provided evidence for a role of spatial boundaries in the online segmentation of our sensory experience within working memory, it is not known how this segmentation contributes to subsequent long-term episodic memory. Here we show that the presence of a spatial boundary at encoding (a doorway between two rooms) impairs participants' later ability to remember the order that objects were presented in. A sequence of two objects presented in the same room in a virtual reality environment is more accurately remembered than a sequence of two objects presented in adjoining rooms. The results are captured by a simple model in which items are associated to a context representation that changes gradually over time, and changes more rapidly when crossing a spatial boundary. We therefore provide the first evidence that the structure of long-term episodic memory is shaped by the presence of a spatial boundary and provide constraints on the nature of the interaction between working memory and long-term memory. PMID:27295330

  9. Conversion of short-term to long-term memory in the novel object recognition paradigm.

    PubMed

    Moore, Shannon J; Deshpande, Kaivalya; Stinnett, Gwen S; Seasholtz, Audrey F; Murphy, Geoffrey G

    2013-10-01

    It is well-known that stress can significantly impact learning; however, whether this effect facilitates or impairs the resultant memory depends on the characteristics of the stressor. Investigation of these dynamics can be confounded by the role of the stressor in motivating performance in a task. Positing a cohesive model of the effect of stress on learning and memory necessitates elucidating the consequences of stressful stimuli independently from task-specific functions. Therefore, the goal of this study was to examine the effect of manipulating a task-independent stressor (elevated light level) on short-term and long-term memory in the novel object recognition paradigm. Short-term memory was elicited in both low light and high light conditions, but long-term memory specifically required high light conditions during the acquisition phase (familiarization trial) and was independent of the light level during retrieval (test trial). Additionally, long-term memory appeared to be independent of stress-mediated glucocorticoid release, as both low and high light produced similar levels of plasma corticosterone, which further did not correlate with subsequent memory performance. Finally, both short-term and long-term memory showed no savings between repeated experiments suggesting that this novel object recognition paradigm may be useful for longitudinal studies, particularly when investigating treatments to stabilize or enhance weak memories in neurodegenerative diseases or during age-related cognitive decline.

  10. Learning, memory and long-term potentiation are altered in Nedd4 heterozygous mice.

    PubMed

    Camera, Daria; Coleman, Harold A; Parkington, Helena C; Jenkins, Trisha A; Pow, David V; Boase, Natasha; Kumar, Sharad; Poronnik, Philip

    2016-04-15

    The consolidation of short-term memory into long-term memory involves changing protein level and activity for the synaptic plasticity required for long-term potentiation (LTP). AMPA receptor trafficking is a key determinant of LTP and recently ubiquitination by Nedd4 has been shown to play an important role via direct action on the GluA1 subunit, although the physiological relevance of these findings are yet to be determined. We therefore investigated learning and memory in Nedd4(+/-) mice that have a 50% reduction in levels of Nedd4. These mice showed decreased long-term spatial memory as evidenced by significant increases in the time taken to learn the location of and subsequently find a platform in the Morris water maze. In contrast, there were no significant differences between Nedd4(+/+) and Nedd4(+/-) mice in terms of short-term spatial memory in a Y-maze test. Nedd4(+/-) mice also displayed a significant reduction in post-synaptic LTP measured in hippocampal brain slices. Immunofluorescence of Nedd4 in the hippocampus confirmed its expression in hippocampal neurons of the CA1 region. These findings indicate that reducing Nedd4 protein by 50% significantly impairs LTP and long-term memory thereby demonstrating an important role for Nedd4 in these processes.

  11. Endoscopic Management of Attic Cholesteatoma: Long-Term Results.

    PubMed

    Alicandri-Ciufelli, Matteo; Marchioni, Daniele; Kakehata, Seiji; Presutti, Livio; Villari, Domenico

    2016-10-01

    The main application of endoscopic surgery relies on the middle ear cholesteatoma surgical treatment, although for a definitive validation and acceptance by scientific community, long-term results are needed about recurrent and residual rates of the pathology. The aim of the present paper was to analyze the single institution experience with the long-term results of surgical treatment of attic cholesteatoma. PMID:27565391

  12. Long-term effects of sludge application to land

    SciTech Connect

    Geertsema, W.S. ); Knocke, W.R.; Novak, J.T.; Dove, D. . Dept. of Civil Engineering)

    1994-11-01

    The purpose of this study was to evaluate the long-term environmental effects of applying alum sludge to land. Investigations at the original field site included soil analysis, soil water monitoring, groundwater monitoring, and analysis of tissues from pine needles. No long-term (30 months) effects were observed, and the authors conclude that alum coagulant sludges can be applied to forest lands at loading rates of at least 1.5 to 2.5% by dry weight without adverse effect.

  13. Maintaining Engagement in Long-term Interventions with Relational Agents

    PubMed Central

    Bickmore, Timothy; Schulman, Daniel; Yin, Langxuan

    2011-01-01

    We discuss issues in designing virtual humans for applications which require long-term voluntary use, and the problem of maintaining engagement with users over time. Concepts and theories related to engagement from a variety of disciplines are reviewed. We describe a platform for conducting studies into long-term interactions between humans and virtual agents, and present the results of two longitudinal randomized controlled experiments in which the effect of manipulations of agent behavior on user engagement was assessed. PMID:21318052

  14. Musical and verbal memory in Alzheimer's disease: a study of long-term and short-term memory.

    PubMed

    Ménard, Marie-Claude; Belleville, Sylvie

    2009-10-01

    Musical memory was tested in Alzheimer patients and in healthy older adults using long-term and short-term memory tasks. Long-term memory (LTM) was tested with a recognition procedure using unfamiliar melodies. Short-term memory (STM) was evaluated with same/different judgment tasks on short series of notes. Musical memory was compared to verbal memory using a task that used pseudowords (LTM) or syllables (STM). Results indicated impaired musical memory in AD patients relative to healthy controls. The deficit was found for both long-term and short-term memory. Furthermore, it was of the same magnitude for both musical and verbal domains whether tested with short-term or long-term memory tasks. No correlation was found between musical and verbal LTM. However, there was a significant correlation between verbal and musical STM in AD participants and healthy older adults, which suggests that the two domains may share common mechanisms. PMID:19398148

  15. Commentary: The Broader Context of Long-Term Care Ethics.

    PubMed

    Lesandrini, Jason; O'Connell, Carol

    2016-07-01

    Ethical issues in long-term care settings, although having received attention in the literature, have not in our opinion received the appropriate level they require. Thus, we applaud the Cambridge Quarterly for publishing this case. We can attest to the significance of ethical issues arising in long-term care facilities, as Mr. Hope's case is all too familiar to those practicing in these settings. What is unique about this case is that an actual ethics consult was made in a long-term care setting. We have seen very little in the published literature on the use of ethics structures in long-term care populations. Our experience is that these healthcare settings are ripe for ethical concerns and that providers, patients, families, and staff need/desire ethics resources to actively and preventively address ethical concerns. The popular press has begun to recognize the ethical issues involved in long-term care settings and the need for ethics structures. Recently, in California a nurse refused to initiate CPR for an elderly patient in a senior residence. In that case, the nurse was quoted as saying that the facility had a policy that nurses were not to start CPR for elderly patients. 1 Although this case is not exactly the same as that of Mr. Hope, it highlights the need for developing robust ethics program infrastructures in long-term care settings that work toward addressing ethical issues through policy, education, and active consultation.

  16. Private Financing Options for Long-term Care

    PubMed Central

    Brody, Barbara L.; Simon, Harold J.; Smallwood, Dennis E.

    1987-01-01

    Private financing for long-term care now comes almost exclusively from out-of-pocket payments. Long-term-care costs quickly impoverish most elderly, resulting in Medicaid dependency. The consequences are profound for the western Sun Belt with its rapidly growing elderly population. Key private financing options are long-term-care individual retirement accounts (LTC/IRAs), home equity conversion, social-health maintenance organizations and long-term-care insurance. Study of data from the past half century suggests that the LTC/IRA approach would prove unsatisfactory for the purpose despite the intuitive appeal of this mechanism. Experience with home equity conversions is still very limited, and unresolved questions limit this approach to the role of a reserve option for now. While promising, social-health maintenance organizations are still in the experimental stages and not yet commercially available. Long-term-care insurance is currently sold on a thin market and emphasizes nursing home coverage. New approaches to private financing through long-term-care insurance seem to offer the best approach for immediate implementation. PMID:3118576

  17. Long-term care insurance in Japan: implications for U.S. long-term care policy.

    PubMed

    Houde, Susan Crocker; Gautam, Ramraj; Kai, Ichiro

    2007-01-01

    The purpose of this article is to review the long-term care insurance program in Japan and the present system of payment of long-term care services in the United States. The long-term care insurance system in Japan was implemented in 2001 for the purpose of promoting independence in older adults with functional disability. It reimburses for both home and institutional care. Several concerns expressed about the Japanese system include increasing applications for nursing home placement, lower use of home care services than anticipated, limited coverage for disabilities for those under 65, regional variations in service, educational preparation for case managers, and access to care for older adults. Revisions to the Japanese system and implications for U.S. long-term care policy are discussed.

  18. Structural studies on HCN oligomers.

    PubMed

    Ferris, J P; Edelson, E H; Auyeung, J M; Joshi, P C

    1981-01-01

    NMR spectral studies on the HCN oligomers suggest the presence of carboxamide and urea groupings. The release of CO2, H2O, HCN, CH3CN, HCONH2 and pyridine on pyrolysis is consistent with the presence of these groupings as well as carboxylic acid groups. No basic primary amine groupings could be detected with fluorescamine. Hydrazinolysis of the HCN oligomers releases 10% of the amino acids normally released by acid hydrolysis. The oligomers give a positive biuret test but this is not due to the presence of peptide bonds. There is no conclusive evidence for the presence of peptide bonds in the HCN oligomers. No diglycine was detected on partial hydrolysis of the HCN oligomers at pH 8.5 suggesting that HCN oligomers were not a source of prebiotic peptides.

  19. mTORC2 controls actin polymerization required for consolidation of long-term memory.

    PubMed

    Huang, Wei; Zhu, Ping Jun; Zhang, Shixing; Zhou, Hongyi; Stoica, Loredana; Galiano, Mauricio; Krnjević, Krešimir; Roman, Gregg; Costa-Mattioli, Mauro

    2013-04-01

    A major goal of biomedical research is the identification of molecular and cellular mechanisms that underlie memory storage. Here we report a previously unknown signaling pathway that is necessary for the conversion from short- to long-term memory. The mammalian target of rapamycin (mTOR) complex 2 (mTORC2), which contains the regulatory protein Rictor (rapamycin-insensitive companion of mTOR), was discovered only recently and little is known about its function. We found that conditional deletion of Rictor in the postnatal murine forebrain greatly reduced mTORC2 activity and selectively impaired both long-term memory (LTM) and the late phase of hippocampal long-term potentiation (L-LTP). We also found a comparable impairment of LTM in dTORC2-deficient flies, highlighting the evolutionary conservation of this pathway. Actin polymerization was reduced in the hippocampus of mTORC2-deficient mice and its restoration rescued both L-LTP and LTM. Moreover, a compound that promoted mTORC2 activity converted early LTP into late LTP and enhanced LTM. Thus, mTORC2 could be a therapeutic target for the treatment of cognitive dysfunction.

  20. Metabolic Profiles in Ovine Carotid Arteries with Developmental Maturation and Long-Term Hypoxia

    PubMed Central

    Goyal, Ravi; Longo, Lawrence D.

    2015-01-01

    Background Long-term hypoxia (LTH) is an important stressor related to health and disease during development. At different time points from fetus to adult, we are exposed to hypoxic stress because of placental insufficiency, high-altitude residence, smoking, chronic anemia, pulmonary, and heart disorders, as well as cancers. Intrauterine hypoxia can lead to fetal growth restriction and long-term sequelae such as cognitive impairments, hypertension, cardiovascular disorders, diabetes, and schizophrenia. Similarly, prolonged hypoxic exposure during adult life can lead to acute mountain sickness, chronic fatigue, chronic headache, cognitive impairment, acute cerebral and/or pulmonary edema, and death. Aim LTH also can lead to alteration in metabolites such as fumarate, 2-oxoglutarate, malate, and lactate, which are linked to epigenetic regulation of gene expression. Importantly, during the intrauterine life, a fetus is under a relative hypoxic environment, as compared to newborn or adult. Thus, the changes in gene expression with development from fetus to newborn to adult may be as a consequence of underlying changes in the metabolic profile because of the hypoxic environment along with developmental maturation. To examine this possibility, we examined the metabolic profile in carotid arteries from near-term fetus, newborn, and adult sheep in both normoxic and long-term hypoxic acclimatized groups. Results Our results demonstrate that LTH differentially regulated glucose metabolism, mitochondrial metabolism, nicotinamide cofactor metabolism, oxidative stress and antioxidants, membrane lipid hydrolysis, and free fatty acid metabolism, each of which may play a role in genetic-epigenetic regulation. PMID:26110419

  1. Forced vital capacity predicts long-term survival for curative-resected NSCLC.

    PubMed

    Guo, Xi; Cao, Hongxin; Xu, Jun; Yu, Jianyu; Zheng, Chunlong; Meng, Long; Du, Jiajun

    2014-09-01

    We conducted a retrospective study in patients with non-small cell lung cancer (NSCLC) who underwent curative lung resection to seek for better lung function parameters associated with long-term survival after lung resection. From January 2006 to December 2008, 470 patients who underwent lung resection with a postoperative diagnosis of NSCLC were studied. Median survival time was 60 months. Patients with pulmonary function values <80 % of predicted were defined as lung function impairment. Patients with impaired vital capacity, maximal voluntary ventilation, forced vital capacity (FVC), forced expiratory volume in one second (FEV1) or diffusion capacity for carbon monoxide (DLCO) had significant shorter overall survival time (P = 0.024; P = 0.026; P < 0.001; P = 0.027; P = 0.007). In univariate analysis, VC, FVC, FEV1 and DLCO were found to have significant effect on overall survival. In multivariate analysis, FVC (HR, 2.029; 95 % CI 1.126-3.659; P = 0.019) was found to be an independent prognostic predictor of long-term overall survival. For cancer-specific survival, FVC (HR 2.404; 95 % CI 1.300-4.445; P = 0.005) was also found to be an independent prognostic predictor in multivariable analysis. Preoperative FVC, rather than FEV1 or DLCO, is an independent prognostic predictor for long-term survival. FVC is not only an indicator of lung function but also of great value for surgeons to predict survival after lung resection.

  2. Rare individual amyloid-β oligomers act on astrocytes to initiate neuronal damage.

    PubMed

    Narayan, Priyanka; Holmström, Kira M; Kim, Dong-Hyun; Whitcomb, Daniel J; Wilson, Mark R; St George-Hyslop, Peter; Wood, Nicholas W; Dobson, Christopher M; Cho, Kwangwook; Abramov, Andrey Y; Klenerman, David

    2014-04-22

    Oligomers of the amyloid-β (Aβ) peptide have been implicated in the neurotoxicity associated with Alzheimer's disease. We have used single-molecule techniques to examine quantitatively the cellular effects of adding well characterized Aβ oligomers to primary hippocampal cells and hence determine the initial pathway of damage. We found that even picomolar concentrations of Aβ (1-40) and Aβ (1-42) oligomers can, within minutes of addition, increase the levels of intracellular calcium in astrocytes but not in neurons, and this effect is saturated at a concentration of about 10 nM of oligomers. Both Aβ (1-40) and Aβ (1-42) oligomers have comparable effects. The rise in intracellular calcium is followed by an increase in the rate of ROS production by NADPH oxidase in both neurons and astrocytes. The increase in ROS production then triggers caspase-3 activation resulting in the inhibition of long-term potentiation. Our quantitative approach also reveals that only a small fraction of the oligomers are damaging and that an individual rare oligomer binding to an astrocyte can initiate the aforementioned cascade of responses, making it unlikely to be due to any specific interaction. Preincubating the Aβ oligomers with an extracellular chaperone, clusterin, sequesters the oligomers in long-lived complexes and inhibits all of the physiological damage, even at a ratio of 100:1, total Aβ to clusterin. To explain how Aβ oligomers are so damaging but that it takes decades to develop Alzheimer's disease, we suggest a model for disease progression where small amounts of neuronal damage from individual unsequestered oligomers can accumulate over time leading to widespread tissue-level dysfunction. PMID:24717093

  3. Making memories: the development of long-term visual knowledge in children with visual agnosia.

    PubMed

    Metitieri, Tiziana; Barba, Carmen; Pellacani, Simona; Viggiano, Maria Pia; Guerrini, Renzo

    2013-01-01

    There are few reports about the effects of perinatal acquired brain lesions on the development of visual perception. These studies demonstrate nonseverely impaired visual-spatial abilities and preserved visual memory. Longitudinal data analyzing the effects of compromised perceptions on long-term visual knowledge in agnosics are limited to lesions having occurred in adulthood. The study of children with focal lesions of the visual pathways provides a unique opportunity to assess the development of visual memory when perceptual input is degraded. We assessed visual recognition and visual memory in three children with lesions to the visual cortex having occurred in early infancy. We then explored the time course of visual memory impairment in two of them at 2  years and 3.7  years from the initial assessment. All children exhibited apperceptive visual agnosia and visual memory impairment. We observed a longitudinal improvement of visual memory modulated by the structural properties of objects. Our findings indicate that processing of degraded perceptions from birth results in impoverished memories. The dynamic interaction between perception and memory during development might modulate the long-term construction of visual representations, resulting in less severe impairment.

  4. Parishin C's prevention of Aβ 1-42-induced inhibition of long-term potentiation is related to NMDA receptors.

    PubMed

    Liu, Zhihui; Wang, Weiping; Feng, Nan; Wang, Ling; Shi, Jiangong; Wang, Xiaoliang

    2016-05-01

    The rhizome of Gastrodia elata (GE), a herb medicine, has been used for treatment of neuronal disorders in Eastern Asia for hundreds of years. Parishin C is a major ingredient of GE. In this study, the i.c.v. injection of soluble Aβ 1-42 oligomers model of LTP injury was used. We investigated the effects of parishin C on the improvement of LTP in soluble Aβ 1-42 oligomer-injected rats and the underlying electrophysiological mechanisms. Parishin C (i.p. or i.c.v.) significantly ameliorated LTP impairment induced by i.c.v. injection of soluble Aβ 1-42 oligomers. In cultured hippocampal neurons, soluble Aβ 1-42 oligomers significantly inhibited NMDAR currents while not affecting AMPAR currents and voltage-dependent currents. Pretreatment with parishin C protected NMDA receptor currents from the damage induced by Aβ. In summary, parishin C improved LTP deficits induced by soluble Aβ 1-42 oligomers. The protection by parishin C against Aβ-induced LTP damage might be related to NMDA receptors.

  5. Changes in the default mode networks of individuals with long-term unilateral sensorineural hearing loss.

    PubMed

    Zhang, G-Y; Yang, M; Liu, B; Huang, Z-C; Chen, H; Zhang, P-P; Li, J; Chen, J-Y; Liu, L-J; Wang, J; Teng, G-J

    2015-01-29

    Hearing impairment contributes to cognitive dysfunction. Previous studies have found changes of functional connectivity in the default mode network (DMN) associated with cognitive processing in individuals with sensorineural hearing loss (SNHL). Whereas the changes in the DMN in patients with long-term unilateral SNHL (USNHL) is still not entirely clear. In this work, we analyzed resting-state functional magnetic resonance imaging (fMRI) data and neuropsychological test scores from normal hearing subjects (n = 11) and patients (n = 21) with long-term USNHL. Functional connectivity and nodal topological properties were computed for every brain region in the DMN. Analysis of covariance (ANCOVA) and post hoc analyses were conducted to identify differences between normal controls and patients for each measure. Results indicated that the left USNHL presented enhanced connectivity (p < 0.05, false discovery rate (FDR) corrected), and significant changes (p < 0.05, Bonferroni corrected) of the nodal topological properties in the DMN compared with the control. More changes in the DMN have been found in the left than right long-term USNHL (RUSNHL). However, the neuropsychological tests did not show significant differences between the USNHL and the control. These findings suggest that long-term USNHL contributes to changes in the DMN, and these changes might affect cognitive abilities in patients with long-term USNHL. Left hearing loss affects the DMN more than the right hearing loss does. The fMRI measures might be more sensitive for observing cognitive changes in patients with hearing loss than clinical neuropsychological tests. This study provides some insights into the mechanisms of the association between hearing loss and cognitive function.

  6. C-reactive protein and long-term ischemic stroke prognosis.

    PubMed

    VanGilder, Reyna L; Davidov, Danielle M; Stinehart, Kyle R; Huber, Jason D; Turner, Ryan C; Wilson, Karen S; Haney, Eric; Davis, Stephen M; Chantler, Paul D; Theeke, Laurie; Rosen, Charles L; Crocco, Todd J; Gutmann, Laurie; Barr, Taura L

    2014-04-01

    C-reactive protein (CRP) is an inflammatory biomarker of inflammation and may reflect progression of vascular disease. Conflicting evidence suggests CRP may be a prognostic biomarker of ischemic stroke outcome. Most studies that have examined the relationship between CRP and ischemic stroke outcome have used mortality or subsequent vascular event as the primary outcome measure. Given that nearly half of stroke patients experience moderate to severe functional impairments, using a biomarker like CRP to predict functional recovery rather than mortality may have clinical utility for guiding acute stroke treatments. The primary aim of this study was to systematically and critically review the relationship between CRP and long-term functional outcome in ischemic stroke patients to evaluate the current state of the literature. PubMed and MEDLINE databases were searched for original studies which assessed the relationship between acute CRP levels measured within 24 hours of symptom onset and long-term functional outcome. The search yielded articles published between 1989 and 2012. Included studies used neuroimaging to confirm ischemic stroke diagnosis, high-sensitivity CRP assay, and a functional outcome scale to assess prognosis beyond 30 days after stroke. Study quality was assessed using the REMARK recommendations. Five studies met all inclusion criteria. Results indicate a significant association between elevated baseline high sensitivity CRP and unfavorable long-term functional outcome. Our results emphasize the need for additional research to characterize the relationship between acute inflammatory markers and long-term functional outcome using well-defined diagnostic criteria. Additional studies are warranted to prospectively examine the relationship between high sensitivity CRP measures and long-term outcome.

  7. Subjective Memory Ability and Long-Term Forgetting in Patients Referred for Neuropsychological Assessment.

    PubMed

    van der Werf, Sieberen P; Geurts, Sofie; de Werd, Maartje M E

    2016-01-01

    It has been suggested that the memory complaints of patients who are not impaired on formal memory tests may reflect accelerated forgetting. We examined this hypothesis by comparing the 1-week delayed recall and recognition test performance of outpatients who were referred for neuropsychological assessment and who had normal memory performance during standard memory assessment with that of a non-patient control group. Both groups performed equally in verbal learning and delayed recall. However, after 1 week, the patients performed worse than controls on both recall and recognition tests. Although subjective memory ability predicted short-term memory function in patients, it did not predict long-term delayed forgetting rates in either the patients or controls. Thus, long-term delayed recall and recognition intervals provided no additional value to explain poor subjective memory ability in the absence of objective memory deficits. PMID:27199838

  8. Subjective Memory Ability and Long-Term Forgetting in Patients Referred for Neuropsychological Assessment

    PubMed Central

    van der Werf, Sieberen P.; Geurts, Sofie; de Werd, Maartje M. E.

    2016-01-01

    It has been suggested that the memory complaints of patients who are not impaired on formal memory tests may reflect accelerated forgetting. We examined this hypothesis by comparing the 1-week delayed recall and recognition test performance of outpatients who were referred for neuropsychological assessment and who had normal memory performance during standard memory assessment with that of a non-patient control group. Both groups performed equally in verbal learning and delayed recall. However, after 1 week, the patients performed worse than controls on both recall and recognition tests. Although subjective memory ability predicted short-term memory function in patients, it did not predict long-term delayed forgetting rates in either the patients or controls. Thus, long-term delayed recall and recognition intervals provided no additional value to explain poor subjective memory ability in the absence of objective memory deficits. PMID:27199838

  9. Subjective Memory Ability and Long-Term Forgetting in Patients Referred for Neuropsychological Assessment.

    PubMed

    van der Werf, Sieberen P; Geurts, Sofie; de Werd, Maartje M E

    2016-01-01

    It has been suggested that the memory complaints of patients who are not impaired on formal memory tests may reflect accelerated forgetting. We examined this hypothesis by comparing the 1-week delayed recall and recognition test performance of outpatients who were referred for neuropsychological assessment and who had normal memory performance during standard memory assessment with that of a non-patient control group. Both groups performed equally in verbal learning and delayed recall. However, after 1 week, the patients performed worse than controls on both recall and recognition tests. Although subjective memory ability predicted short-term memory function in patients, it did not predict long-term delayed forgetting rates in either the patients or controls. Thus, long-term delayed recall and recognition intervals provided no additional value to explain poor subjective memory ability in the absence of objective memory deficits.

  10. Long-term persistence of vaccine-derived aluminum hydroxide is associated with chronic cognitive dysfunction.

    PubMed

    Couette, Maryline; Boisse, Marie-Françoise; Maison, Patrick; Brugieres, Pierre; Cesaro, Pierre; Chevalier, Xavier; Gherardi, Romain K; Bachoud-Levi, Anne-Catherine; Authier, François-Jérôme

    2009-11-01

    Macrophagic myofasciitis (MMF) is an emerging condition, characterized by specific muscle lesions assessing long-term persistence of aluminum hydroxide within macrophages at the site of previous immunization. Affected patients mainly complain of arthromyalgias, chronic fatigue, and cognitive difficulties. We designed a comprehensive battery of neuropsychological tests to prospectively delineate MMF-associated cognitive dysfunction (MACD). Compared to control patients with arthritis and chronic pain, MMF patients had pronounced and specific cognitive impairment. MACD mainly affected (i) both visual and verbal memory; (ii) executive functions, including attention, working memory, and planning; and (iii) left ear extinction at dichotic listening test. Cognitive deficits did not correlate with pain, fatigue, depression, or disease duration. Pathophysiological mechanisms underlying MACD remain to be determined. In conclusion, long-term persistence of vaccine-derived aluminum hydroxide within the body assessed by MMF is associated with cognitive dysfunction, not solely due to chronic pain, fatigue and depression.

  11. Rural long-term care work, gender, and restructuring.

    PubMed

    Leach, Belinda; Joseph, Gillian

    2011-06-01

    Restructuring--the introduction of changes that alter the way health care is delivered for maximum efficiency and least cost--layered with rurality and with rural gender ideologies and practices, results in rural long-term care settings that have particular consequences for the women working in them, and for the residents and communities that they serve. This research investigated how rurality affects the implementation of patient classification in Ontario long-term care homes. Methods involved interviews and focus groups with front-line long-term care workers, administrators, and key participants. The findings revealed that rural long-term care delivery takes place when a restructured work environment intersects with gender ideologies and practices that take on particular characteristics when developed and sustained in a rural context. These factors shape the labor market and working conditions for rural women. We argue that this produces a uniquely rural experience for long-term care workers and conclude that those implementing classification systems must consider contextual factors as well as practical and financial exigencies. PMID:24650670

  12. The relationship between interannual and long-term cloud feedbacks

    DOE PAGES

    Zhou, Chen; Zelinka, Mark D.; Dessler, Andrew E.; Klein, Stephen A.

    2015-12-11

    The analyses of Coupled Model Intercomparison Project phase 5 simulations suggest that climate models with more positive cloud feedback in response to interannual climate fluctuations also have more positive cloud feedback in response to long-term global warming. Ensemble mean vertical profiles of cloud change in response to interannual and long-term surface warming are similar, and the ensemble mean cloud feedback is positive on both timescales. However, the average long-term cloud feedback is smaller than the interannual cloud feedback, likely due to differences in surface warming pattern on the two timescales. Low cloud cover (LCC) change in response to interannual andmore » long-term global surface warming is found to be well correlated across models and explains over half of the covariance between interannual and long-term cloud feedback. In conclusion, the intermodel correlation of LCC across timescales likely results from model-specific sensitivities of LCC to sea surface warming.« less

  13. Epilepsy-related long-term amnesia: anatomical perspectives.

    PubMed

    Butler, Chris; Kapur, Narinder; Zeman, Adam; Weller, Roy; Connelly, Alan

    2012-11-01

    There are few clues as to the neural basis of selective long-term amnesia. We report group and single-case data to shed light on this issue. In a group study of patients with transient epileptic amnesia, there were no significant correlations between volumetric measures of the hippocampus and indices of accelerated long-term forgetting or longer-term autobiographical memory loss. Post-mortem investigations in a patient with temporal lobe epilepsy who showed accelerated long-term forgetting, together with a degree of autobiographical memory loss, yielded evidence of neuronal loss and gliosis in regions of both the right and the left hippocampus. Neuronal loss and gliosis were more evident in anterior than posterior hippocampus. These results indicate that the unusual forms of long-term forgetting seen in some patients with temporal lobe epilepsy have no gross anatomical correlate. The findings leave open the possibilities that subtle structural damage or subtle functional disturbance, perhaps in the form of subclinical epileptiform activity, underly epilepsy-related long-term amnesia.

  14. Characteristics of Long-Term Survivors of Epithelial Ovarian Cancer

    PubMed Central

    Cress, Rosemary D.; Chen, Yingjia S.; Morris, Cyllene R.; Petersen, Megan; Leiserowitz, Gary S.

    2015-01-01

    Objective To identify characteristics associated with long-term survival forepithelial ovarian cancer patients using the California Cancer Registry. Methods A descriptive analysis of survival of all California residents diagnosed with epithelial ovarian cancer between 1994 and 2001 was conducted using patients identified through the cancer registry with follow up through 2011. Characteristics of the patients who survived more than 10 years (long-term survivors) were compared to three other cohorts: patients who survived less than 2 years, those who survived at least 2 but no more than 5 years, and those who survived at least 5 but no more than 10 years. Results A total of 3,582 out of 11,541 (31% CI=30.2%, 31.8%) of the patients survived more than 10 years. Younger age, early stage, low-grade, and non-serous histology were significant predictors of long-term survival, but long-term survivors also included women with high-risk cancer. Conclusion Long-term survival is not unusual in patients with epithelial ovarian cancer, even in those with high-risk disease. Many of the prognostic factors are well known, but it remains to be determined why some patients with advanced stage high-grade cancers survive longer than others with the same histology. These findings are important for patient counseling. PMID:26244529

  15. Method for Water Management Considering Long-term Probabilistic Forecasts

    NASA Astrophysics Data System (ADS)

    Hwang, J.; Kang, J.; Suh, A. S.

    2015-12-01

    This research is aimed at predicting the monthly inflow of the Andong-dam basin in South Korea using long-term probabilistic forecasts to apply long-term forecasts to water management. Forecasted Cumulative Distribution Functions (CDFs) of monthly precipitation are plotted by combining the range of monthly precipitation based on proper Probability Density Function (PDF) in past data with probabilistic forecasts in each category. Ensembles of inflow are estimated by entering generated ensembles of precipitation based on the CDFs into the 'abcd' water budget model. The bias and RMSE between averages in past data and observed inflow are compared to them in forecasted ensembles. In our results, the bias and RMSE of average precipitation in the forecasted ensemble are bigger than in past data, whereas the average inflow in the forecasted ensemble is smaller than in past data. This result could be used for reference data to apply long-term forecasts to water management, because of the limit in the number of forecasted data for verification and differences between the Andong-dam basin and the forecasted regions. This research has significance by suggesting a method of applying probabilistic information in climate variables from long-term forecasts to water management in Korea. Original data of a climate model, which produces long-term probabilistic forecasts should be verified directly as input data of a water budget model in the future, so that a more scientific response in water management against uncertainty of climate change could be reached.

  16. Wastewater treatment by soil infiltration: Long-term phosphorus removal.

    PubMed

    Eveborn, David; Kong, Deguo; Gustafsson, Jon Petter

    2012-10-01

    Phosphorus (P) leaching from on-site wastewater treatment systems may contribute to eutrophication. In developed countries the most common on-site treatment technique is septic systems with soil infiltration. However, the current knowledge about long term P removal in soil treatment systems is not well developed and the data used for estimation of P losses from such systems are unreliable. In this study we sampled four filter beds from community-scale soil treatment systems with an age of between 14 and 22years to determine the long-term P removal and to investigate the chemical mechanisms behind the observed removal. For one site the long-term P removal was calculated using a mass balance approach. After analysis of the accumulated P, it was estimated that on average 12% of the long-term P load had been removed by the bed material. This indicates a low overall capacity of soil treatment systems to remove phosphorus. Batch experiments and chemical speciation modelling indicated that calcium phosphate precipitation was not an important long-term P removal mechanism, with the possible exception of one of the sites. More likely, the P removal was induced by AlPO(4) precipitation and/or sorption to poorly ordered aluminium compounds, as evidenced by strong relationships between oxalate-extractable Al and P. PMID:22982614

  17. Long-Term Prognosis of Ischemic Stroke in Young Adults

    PubMed Central

    Varona, Jose F.

    2011-01-01

    There is limited information about long-term prognosis of ischemic stroke in young adults. Giving the potentially negative impact in physical, social, and emotional aspects of an ischemic stroke in young people, providing early accurate long-term prognostic information is very important in this clinical setting. Moreover, detection of factors associated with bad outcomes (death, recurrence, moderate-to-severe disability) help physicians in optimizing secondary prevention strategies. The present paper reviews the most relevant published information concerning long-term prognosis and predictors of unfavorable outcomes of ischemic stroke affecting young adults. As a summary, we can conclude that, in the long term, stroke in the young adult increases slightly the risk of mortality, implies higher risk of future cardiovascular events, and determines functional limitations in a significant percentage of patients. Nevertheless, in every individual case the prognosis has to be considered depending on several factors (stroke subtype, initial severity, cardiovascular risk factors) that determine the long-term outcomes. PMID:21197408

  18. Long-Term Stewardship Program Science and Technology Requirements

    SciTech Connect

    Joan McDonald

    2002-09-01

    Many of the United States’ hazardous and radioactively contaminated waste sites will not be sufficiently remediated to allow unrestricted land use because funding and technology limitations preclude cleanup to pristine conditions. This means that after cleanup is completed, the Department of Energy will have long-term stewardship responsibilities to monitor and safeguard more than 100 sites that still contain residual contamination. Long-term stewardship encompasses all physical and institutional controls, institutions, information, and other mechanisms required to protect human health and the environment from the hazards remaining. The Department of Energy Long-Term Stewardship National Program is in the early stages of development, so considerable planning is still required to identify all the specific roles and responsibilities, policies, and activities needed over the next few years to support the program’s mission. The Idaho National Engineering and Environmental Laboratory was tasked with leading the development of Science and Technology within the Long-Term Stewardship National Program. As part of that role, a task was undertaken to identify the existing science and technology related requirements, identify gaps and conflicts that exist, and make recommendations to the Department of Energy for future requirements related to science and technology requirements for long-term stewardship. This work is summarized in this document.

  19. Common Calibration Source for Monitoring Long-term Ozone Trends

    NASA Technical Reports Server (NTRS)

    Kowalewski, Matthew

    2004-01-01

    Accurate long-term satellite measurements are crucial for monitoring the recovery of the ozone layer. The slow pace of the recovery and limited lifetimes of satellite monitoring instruments demands that datasets from multiple observation systems be combined to provide the long-term accuracy needed. A fundamental component of accurately monitoring long-term trends is the calibration of these various instruments. NASA s Radiometric Calibration and Development Facility at the Goddard Space Flight Center has provided resources to minimize calibration biases between multiple instruments through the use of a common calibration source and standardized procedures traceable to national standards. The Facility s 50 cm barium sulfate integrating sphere has been used as a common calibration source for both US and international satellite instruments, including the Total Ozone Mapping Spectrometer (TOMS), Solar Backscatter Ultraviolet 2 (SBUV/2) instruments, Shuttle SBUV (SSBUV), Ozone Mapping Instrument (OMI), Global Ozone Monitoring Experiment (GOME) (ESA), Scanning Imaging SpectroMeter for Atmospheric ChartographY (SCIAMACHY) (ESA), and others. We will discuss the advantages of using a common calibration source and its effects on long-term ozone data sets. In addition, sphere calibration results from various instruments will be presented to demonstrate the accuracy of the long-term characterization of the source itself.

  20. Wastewater treatment by soil infiltration: Long-term phosphorus removal

    NASA Astrophysics Data System (ADS)

    Eveborn, David; Kong, Deguo; Gustafsson, Jon Petter

    2012-10-01

    Phosphorus (P) leaching from on-site wastewater treatment systems may contribute to eutrophication. In developed countries the most common on-site treatment technique is septic systems with soil infiltration. However, the current knowledge about long term P removal in soil treatment systems is not well developed and the data used for estimation of P losses from such systems are unreliable. In this study we sampled four filter beds from community-scale soil treatment systems with an age of between 14 and 22 years to determine the long-term P removal and to investigate the chemical mechanisms behind the observed removal. For one site the long-term P removal was calculated using a mass balance approach. After analysis of the accumulated P, it was estimated that on average 12% of the long-term P load had been removed by the bed material. This indicates a low overall capacity of soil treatment systems to remove phosphorus. Batch experiments and chemical speciation modelling indicated that calcium phosphate precipitation was not an important long-term P removal mechanism, with the possible exception of one of the sites. More likely, the P removal was induced by AlPO4 precipitation and/or sorption to poorly ordered aluminium compounds, as evidenced by strong relationships between oxalate-extractable Al and P.

  1. Accelerated long-term forgetting in children with temporal lobe epilepsy.

    PubMed

    Gascoigne, Michael B; Smith, Mary Lou; Barton, Belinda; Webster, Richard; Gill, Deepak; Lah, Suncica

    2014-07-01

    Adults with temporal lobe epilepsy (TLE) have been found to have accelerated long-term forgetting, but this phenomenon has not yet been investigated in children. Although deficits in recall of materials after short (20- to 30-minute) delays have been shown to slowly emerge from childhood to adolescence in patients with TLE, it is unknown whether such a trend will also be found in recall of materials after long delays. This study examined the presence of accelerated long-term forgetting in children with TLE and how it relates to chronological age. Twenty-three children with TLE and 58 healthy controls of similar age, sex distribution and socioeconomic status completed a battery of neuropsychological tests, including standardised tests of story recall and design location, as well as two experimental tests requiring the learning of words and design locations to a criterion, both of which assessed recall after short (30-min) and long (7-day) delays. Word recall at the 7-day delay (relative to the 30-min recall) was significantly poorer in the TLE group, compared to the control group. The TLE group also exhibited worse 30-min recall performance on a standardised test of story recall. Individual patient analyses revealed dissociation between performance on the experimental and standardised verbal memory tests; children who were impaired on the experimental test (7-day delay) were not impaired on the standardised test (30-min delay). Compared to controls, patients with a left-hemisphere seizure focus recalled fewer words at short and long delays while patients with an abnormal hippocampus recalled fewer words at the long delay. No between-group differences were found with respect to the design location task. Age negatively correlated with the recall of words after short- and long-term delays within the TLE group, where older age was associated with worse memory. This association was not present in the control group. To our knowledge, this is the first study to show

  2. The Chronicity of Self-Injurious Behaviour: A Long-Term Follow-Up of a Total Population Study

    ERIC Educational Resources Information Center

    Taylor, Lorne; Oliver, Chris; Murphy, Glynis

    2011-01-01

    Background: Self-injurious behaviour (SIB) is a relatively common problem for people with intellectual disabilities and it is known to be associated with various risk markers, such as degree of disability, sensory impairments, and autism (McClintock "et al." 2003). Less is known about its long-term course however. Method: The present study was…

  3. Stirling engine - Approach for long-term durability assessment

    NASA Technical Reports Server (NTRS)

    Tong, Michael T.; Bartolotta, Paul A.; Halford, Gary R.; Freed, Alan D.

    1992-01-01

    The approach employed by NASA Lewis for the long-term durability assessment of the Stirling engine hot-section components is summarized. The approach consists of: preliminary structural assessment; development of a viscoplastic constitutive model to accurately determine material behavior under high-temperature thermomechanical loads; an experimental program to characterize material constants for the viscoplastic constitutive model; finite-element thermal analysis and structural analysis using a viscoplastic constitutive model to obtain stress/strain/temperature at the critical location of the hot-section components for life assessment; and development of a life prediction model applicable for long-term durability assessment at high temperatures. The approach should aid in the provision of long-term structural durability and reliability of Stirling engines.

  4. Long-term Synoptic Observations of the Sun.

    NASA Astrophysics Data System (ADS)

    Pevtsov, Alexei

    2015-08-01

    Does the solar activity vary with time, or it remains constant? How systematic or intermittent solar cycles are? Long-term observations of the Sun are the reason we know answers to these questions. Ultimately, the development of a better understanding of stellar cycles will require similar long-term observations of other sun-like stars. To facilitate international collaboration on synoptic long-term solar observations, IAU created a working group on “Coordination of Synoptic Observations of the Sun.” The working group provides a forum for discussion of all issues relevant to past, current, and future synoptic programs, preservation, calibration, and access to synoptic solar data products. This talk will provide a summary of recent activity by this IAU WG. It will also present a brief overview of recent research on sun-as-a-star conducted at the US National Solar Observatory.

  5. Forecasting demand for long-term care services.

    PubMed Central

    Lane, D; Uyeno, D; Stark, A; Kliewer, E; Gutman, G

    1985-01-01

    This article analyzes three methods used to forecast the transition of long-term care clients through a variety of possible home and facility placements and levels of care. The test population (N = 1,653) is derived from the larger population of clients admitted in 1978 to British Columbia's newly established Long-Term Care program. The investigators have accumulated 5 years of service-generated data on moves, discharges, and deaths of these clients. Results show that the first-order Markov chain with stationary transition probabilities yields a superior forecast to state-by-state moving average growth and state-by-state regression analyses. The results of these analyses indicate that the Markov method should receive serious consideration as a tool for resource planning and allocation in long-term care. PMID:3932260

  6. Winning market positioning strategies for long term care facilities.

    PubMed

    Higgins, L F; Weinstein, K; Arndt, K

    1997-01-01

    The decision to develop an aggressive marketing strategy for its long term care facility has become a priority for the management of a one-hundred bed facility in the Rocky Mountain West. Financial success and lasting competitiveness require that the facility in question (Deer Haven) establish itself as the preferred provider of long term care for its target market. By performing a marketing communications audit, Deer Haven evaluated its present market position and created a strategy for solidifying and dramatizing this position. After an overview of present conditions in the industry, we offer a seven step process that provides practical guidance for positioning a long term care facility. We conclude by providing an example application. PMID:10179063

  7. Long-term RNA persistence in postmortem contexts

    PubMed Central

    2013-01-01

    Ribonucleic acids (RNA) are generally considered fragile molecules that are readily degraded. However, there is growing documentation of long-term (from days to centuries) RNA persistence in a variety of contexts and tissue types, and as such a number of academic disciplines are beginning to exploit degraded RNA. While the reasons for its survival are not fully understood, there are several plausible mechanisms that would safeguard this molecule against degradation. However, after examining the literature available on the postmortem instability and decay mechanisms of RNA, it has become clear that limited experimental studies and no reviews offer an overview of these mechanisms. Hence in this review we outline molecular reasons for RNA surviving long-term postmortem, and provide specific examples of RNA survival in forensic, archival and archaeological contexts. A better understanding of the mechanisms of RNA decay will be crucial for developing expectations on its long-term survival. PMID:23618361

  8. Long-term Internship through Cooperative Education with Regional Industries

    NASA Astrophysics Data System (ADS)

    Takahashi, Kenzo; Hase, Hiroyuki

    The long term internship is one of special educational programs for graduate students of Graduate School of Engineering in University of Fukui. This is a collaborative program between university and industries where selected post-graduate students are dispatched to companies for a long term and educated in real business environments. It is the final goal of the program to develop sophisticated specialists who would be able to catch the business strategy in industries and solve any problems by themselves. The program is managed in a semester (6 months) and contains 1.5 month prior education of preliminary special knowledge, ethics and secrecy, about 3 month dispatch with long-term internship, and 1.5 month post-education for complementary education and presentation. This paper presents the effect of this program which has been evolving since 2005.

  9. Marijuana effects on long-term memory assessment and retrieval.

    PubMed

    Darley, C F; Tinklenberg, J R; Roth, W T; Vernon, S; Kopell, B S

    1977-05-01

    The ability of 16 college-educated male subjects to recall from long-term memory a series of common facts was tested during intoxication with marijuana extract calibrated to 0.3 mg/kg delta-9-tetrahydrocannabinol and during placebo conditions. The subjects' ability to assess their memory capabilities was then determined by measuring how certain they were about the accuracy of their recall performance and by having them predict their performance on a subsequent recognition test involving the same recall items. Marijuana had no effect on recall or recognition performance. These results do not support the view that marijuana provides access to facts in long-term storage which are inaccessible during non-intoxication. During both marijuana and placebo conditions, subjects could accurately predict their recognition memory performance. Hence, marijuana did not alter the subjects' ability to accurately assess what information resides in long-term memory even though they did not have complete access to that information.

  10. An approach to long-term sedative-hypnotic use

    PubMed Central

    Shahid, Azmeh; Chung, Sharon A; Phillipson, Ron; Shapiro, Colin M

    2012-01-01

    Insomnia is a common, often chronic medical disorder with significant medical and socioeconomic repercussions. However, unlike other medical conditions, there is intense debate as to whether the long-term treatment of insomnia is clinically appropriate. The perceived deleterious side effect of sedative-hypnotic medications may result in patients remaining untreated or undertreated. This review proposes that a more subtle approach needs to be taken in the management of patients with chronic insomnia and that long-term use of the newer sedative-hypnotics may be a feasible and effective treatment option when used in conjunction with thorough medical assessment and regular patient follow-up. This review discusses these issues and discusses the pros and cons of long-term sedative-hypnotic use. PMID:23620678

  11. Sexuality and Physical Intimacy in Long Term Care

    PubMed Central

    Lichtenberg, Peter A.

    2015-01-01

    Sexuality and sexual needs in older adults remains a neglected area of clinical intervention, particularly so in long term care settings. Because older adults in medical rehabilitation and long term care beds present with significant frailties, and often significant neurocognitive disorders it makes it difficult for occupational therapists and other staff to evaluate the capacity of an older adult resident to participate in sexual relationships. The current paper reviews the current literature on sexuality and aging, examines some of the clinical practices and guidelines regarding sexual expression in long term care and presents two case examples. A semi-structured interview and decision tree is presented to assist therapists in making careful and informed decisions and thereby balancing needs for protection with needs for autonomy. PMID:24354331

  12. Long-term management of patients with multiple sclerosis.

    PubMed

    Weightman, Cherie

    2006-07-01

    This article explores the challenges of long-term case management for patients who have multiple sclerosis (MS). Currently there is scant research into district nursing input into long-term management of patients who have MS. Until now the role of the community nurses has been confined to palliation or terminal care, focusing on the more physical manifestations of MS. The contemporary role of district nurse is going to evolve to include proactive approaches. Governmental initiatives demand proactive services, and place emphasis on self-care for patients with MS. Themes that emerge from this article relate to the pre-existing skills--such as managing patients with complex needs and the advanced assessment skills--that will be required to achieve this. What is clear is that community nurses already possess many of the prerequisite skills needed for long-term management, and they should not be daunted by this prospect.

  13. Long-term Use of Opioids for Complex Chronic Pain

    PubMed Central

    Von Korff, Michael R.

    2014-01-01

    Increased opioid prescribing for back pain and other chronic musculoskeletal pain conditions has been accompanied by dramatic increases in prescription opioid addiction and fatal overdose. Opioid-related risks appear to increase with dose. While short-term randomized trials of opioids for chronic pain have found modest analgesic benefits (a one-third reduction in pain intensity on average), the long-term safety and effectiveness of opioids for chronic musculoskeletal pain is unknown. Given the lack of large, long-term randomized trials, recent epidemiologic data suggests the need for caution when considering long-term use of opioids to manage chronic musculoskeletal pain, particularly at higher dosage levels. Principles for achieving more selective and cautious use of opioids for chronic musculoskeletal pain are proposed. PMID:24315147

  14. Data Analysis in the LOFAR Long Term Archive

    NASA Astrophysics Data System (ADS)

    Holties, H. A.; van Diepen, G.; van Dok, D.; Dijkstra, F.; Loose, M.; Renting, G. A.; Schrijvers, C.; Vriend, W.-J.

    2012-09-01

    The LOFAR Long Term Archive (LTA) is a distributed information system that provides integrated services for data analysis as well as long term preservation of astronomical datasets and their provenance. The data analysis capabilities are provided by a federated system that integrates a central catalog and client user interfaces provided by Astro-Wise with processing pipelines running on Grid based and University HPC clusters. The framework used for data analysis ensures that proper authorization and access rules are applied and that generated data products are ingested into the storage part of the Long Term Archive. The ingest process includes information about data provenance. This paper presents the architecture of the processing framework of the LTA.

  15. Inflammatory markers in relation to long-term air pollution.

    PubMed

    Mostafavi, Nahid; Vlaanderen, Jelle; Chadeau-Hyam, Marc; Beelen, Rob; Modig, Lars; Palli, Domenico; Bergdahl, Ingvar A; Vineis, Paolo; Hoek, Gerard; Kyrtopoulos, Soterios Α; Vermeulen, Roel

    2015-08-01

    Long-term exposure to ambient air pollution can lead to chronic health effects such as cancer, cardiovascular and respiratory disease. Systemic inflammation has been hypothesized as a putative biological mechanism contributing to these adverse health effects. We evaluated the effect of long-term exposure to air pollution on blood markers of systemic inflammation. We measured a panel of 28 inflammatory markers in peripheral blood samples from 587 individuals that were biobanked as part of a prospective study. Participants were from Varese and Turin (Italy) and Umea (Sweden). Long-term air pollution estimates of nitrogen oxides (NOx) were available from the European Study of Cohorts for Air Pollution Effects (ESCAPE). Linear mixed models adjusted for potential confounders were applied to assess the association between NOx and the markers of inflammation. Long-term exposure to NOx was associated with decreased levels of interleukin (IL)-2, IL-8, IL-10 and tumor necrosis factor-α in Italy, but not in Sweden. NOx exposure levels were considerably lower in Sweden than in Italy (Sweden: median (5th, 95th percentiles) 6.65 μg/m(3) (4.8, 19.7); Italy: median (5th, 95th percentiles) 94.2 μg/m(3) (7.8, 124.5)). Combining data from Italy and Sweden we only observed a significant association between long-term exposure to NOx and decreased levels of circulating IL-8. We observed some indication for perturbations in the inflammatory markers due to long-term exposure to NOx. Effects were stronger in Italy than in Sweden, potentially reflecting the difference in air pollution levels between the two cohorts.

  16. Morphodynamic length scale and long term river meandering dynamics

    NASA Astrophysics Data System (ADS)

    Lanzoni, S.; Frascati, A.

    2009-12-01

    The fully nonlinear simulation of the lateral migration of meandering channels, combined with an analytical description of the linearized flow field, gives a powerful and yet computationally accessible tool to investigate short and long term evolution of alluvial rivers. In the present contribution we focus on the long term behavior of meandering rivers. This class of dynamical systems is driven by the coexistence of various intrinsically nonlinear mechanisms which determine the possible occurrence of two different morphodynamic regimes: the sub-resonant and the super-resonant regime. Investigating the full range of morphodynamic conditions, we end up with a new morphodynamic length scale associated with spatially oscillating disturbances, accounting for both curvature-forced variations in velocity and depth and alternate bars. Once normalized with this length scale, the relevant morphologic features of the simulated long term patterns (i.e. the probability density function of the local channel curvature and the geometric characteristics of the oxbow lakes) tend to collapse on two distinct behaviors, depending on the dominant morphologic regime. The long term river meandering dynamics is then investigated. The occurrence of cutoff events is a key mechanism in the dynamics of these systems. They introduce a strong source of nonlinearity in the evolution of river meandering, which strongly contributes to the formation of the complex planform patterns usually observed in nature. To detect the possible signatures of a chaotic behavior or a self-organized criticality state triggered in river meandering dynamics by the repeated occurrence of cutoffs, some robust nonlinear methodologies have been applied to both the spatial series of local curvatures and the time series of long term channel sinuosity. The temporal distribution of cutoff inter-arrivals is also investigated. The results are consistent and show that, at least from a modelling point of view, no evidence of

  17. A basic strategy for financing long term care.

    PubMed

    Greenberg, J A; Leutz, W N

    1984-02-01

    As pressure mounts to contain Medicaid long term care spending, short-range "quick fixes" must be avoided. Three such false solutions in particular have shortcomings that may actually exacerbate long term care's financial dilemma because they are based on inadequate definitions of the problem. Two of these proposals--legislation to broaden family responsibility toward institutionalized elders on Medicaid and expanded state power to put liens on such elders' real property--err by trying to mandate "caring" and are predicated on a misunderstanding of the "spend-down" problem. The other proposal--to provide tax incentives to family members who care for elders--requires a large administrative apparatus, assumes an elasticity of supply that may not exist, and could disrupt the "gift relationship" on which family exchanges are often based. What is needed is a strategy with short term, intermediate, and long term objectives that move toward an insurance approach. The short term plan should lay the groundwork for intermediate strategy and control costs by changing rate-setting methods and putting limits on facility construction. The intermediate plan should change the problem's definition from one of merely controlling Medicaid long term care expenditures to one of efficiently managing state resources for the elderly through the development of state financing and local delivery systems that target older persons in greatest need. An effective means of doing this is through the creation of social/HMOs, which have five key features: integration of service responsibility and authority; flexibility in organizational design; balanced clientele; pooled prepaid funding; and financial risk for the provider organization. Finally, the long term strategy should transfer much of the long term care financial burden from individuals and state Medicaid agencies to insurance mechanisms. Many individuals would thus avoid impoverishment caused by health care spending and Medicaid would

  18. Auditory Discrimination Using Frequency-Modulated Amplification with Long-Term Amplitude Compression.

    NASA Astrophysics Data System (ADS)

    Shea, Bernard David

    This dissertation considers the effects of long -term amplitude compression used in narrow-band frequency modulated (FM) assistive listening devices on the auditory discrimination of severely and profoundly hearing-impaired individuals. Compression has been used in narrow-band FM transmitters for hearing-impaired children in educational programs for over twenty years. It restricts the peak deviation of the FM signal to within allowable limits. Narrow -band FM equipment can vary in peak limitation approaches via compression, i.e., using a form of compression limiting or using long-term compression (automatic volume control). Numerous investigations have studied the benefits of FM system use, but none have tested the benefits or deleterious effects of these compression forms on the auditory discrimination of hearing-impaired individuals. Despite the marked limitations associated with severe or profound sensorineural hearing impairment in children, spoken language development is possible. Research and experience have suggested that the auditory system represents the best sensory input channel for these children. With appropriate amplification and educational intervention they can achieve dramatic improvements in speech perception, speech production, language development, and educational achievement (Boothroyd, 1985; Hudgins, 1953, 1954; Ling & Milne, 1981; Wedenberg, 1954). Most hearing-impaired children in educational programs across the United States receive the amplified teacher's speech signal via narrow-band frequency modulated (FM) transmission, yet a controlled investigation of the input compression used in these systems has never been conducted. This dissertation reviews and discusses narrow -band frequency modulated (FM) radio wave systems and the use of audio compression. The experiment tested 32 students with severe to profound sensorineural hearing loss under two narrow -band FM transmitter conditions. The FM transmitter conditions were varied on the basis

  19. 18. Uniform cost accounting in long-term care.

    PubMed

    Sorensen, J E

    1976-05-01

    Uniform cost data are essential for managing health services, establishing billing and reimbursement rates, and measuring effectiveness and impact. Although it is especially difficult in the case of long-term health care to develop standard cost accounting procedures because of the varied configurations of inpatient, intermediate, and ambulatory services, the overall approaches to cost accounting and its content can be made more uniform. With this purpose in mind, a general model of cost accounting is presented for a multilevel program of long-term services, together with a special method for ambulatory services using "hours accounted for" as the basic measure.

  20. Long-term results after intentional tooth reimplantation in monkeys.

    PubMed

    Caffesse, R G; Nasjleti, C E; Castelli, W A

    1977-11-01

    The purpose of this study was to evaluate histologically the long-term response to intentional tooth reimplantation in six rhesus monkeys. The study revealed that cervical and apical root resorption is a universal complication after tooth reimplantation and that arrested areas of resorption will show repair by deposition of cementum. A highly cellular periodontal membrane usually will develop. Periodontal fibers will reattach to reparative bone and cementum but seldom regain functional orientation. Partial or complete ankylosis may result. A further complication is progressive undermining resorption of the ankylosed teeth. Long-term studies are mandatory to evaluate the response to intentional tooth reimplantation.

  1. Leadership: the Winnipeg Community and Long-Term Care Authority.

    PubMed

    Suski, M; Hack, T; Heaman, M

    1999-01-01

    The Winnipeg Community and Long Term Care Authority (WCA) was established in 1998 under the Regional Health Authorities Act of the Province of Manitoba. The WCA's role is to provide for the successful integration of Winnipeg's community-based healthcare delivery services through its three main portfolios: Community Care and Public Health, Home Care and Mental Health, and Long Term Care and Specialized Services. The WCA is dedicated to building a quality health future for Winnipeg. Various initiatives undertaken in the pursuit of quality are described.

  2. Neurohumoral reactions to long-term vestibular stimulation in man.

    PubMed

    Nichiporuk, I A; Rapotkov, A N; Orlov, O I; Grigoriev, A I

    1993-02-01

    The main purposes of present work were: 1) to examine neurohumoral reactions to long-term vestibular stimulation provocative for MS symptoms in man; 2) to compare the peculiarities of neuroendocrine reactions to short-term and to long-term vestibular stimulation; 3) to analyze the received results from the position of neuroendocrine adaptive reactions biological conformity to natural laws, and its physiological importance for human organisms; 4) to make some prognostic points of neurohumoral reaction changes on health and capacity for work in subjects influenced by professional conditions, provocative for MS manifestation development.

  3. Long-term stability test of a triple GEM detector

    NASA Astrophysics Data System (ADS)

    Adak, R. P.; Biswas, S.; Das, S.; Ghosal, D.; Ghosh, S. K.; Mondal, A.; Nag, D.; Nayak, T. K.; Patra, R. N.; Prasad, S. K.; Raha, S.; Sahu, P. K.; Sahu, S.; Swain, S.

    2016-10-01

    The main aim of the study is to perform the long-term stability test of gain of the single mask triple GEM detector. A simple method is used for this long-term stability test using a radioactive X-ray source with high activity. The test is continued till accumulation of charge per unit area > 12.0 mC/mm2. The details of the chamber fabrication, the test set-up, the method of measurement and the test results are presented in this paper.

  4. Intrahepatic haematoma in a patient on long-term haemodialysis.

    PubMed

    Lai, K N; Disney, A P; Mathew, T H

    Spontaneous intrahepatic haematoma is an uncommon potentially fatal complication in uraemic patients receiving long-term haemodialysis, particularly in those taking anticoagulant and antiplatelet drugs. Prompt diagnosis, withdrawal of anticoagulant and antiplatelet therapy, cautious transfusion, and careful dialysis with regional heparinisation are essential in the management and may help to avoid surgical intervention in the presence of a tendency to bleed. Noninvasive organ imaging such as ultrasonography and computerised axial tomography are helpful in diagnosis and monitoring of progress. A case of intrahepatic haematoma in a 37-year-old man who had been receiving long-term haemodialysis since 1976 is described.

  5. Human sperm chromosomes. Long-term effect of cancer treatment

    SciTech Connect

    Genesca, A.; Caballin, M.R.; Miro, R.; Benet, J.; Bonfill, X.; Egozcue, J. )

    1990-06-01

    The long-term cytogenetic effect of radio- or chemotherapy or both on male germ cells was evaluated by study of the chromosomal abnormalities in spermatozoa of four men treated for cancer 5-18 years earlier. The cytogenetic analysis of 422 sperm metaphases showed no differences in the aneuploidy rate. The incidence of structural chromosome aberrations was 14.0%, however, which is much higher than in controls. Thus, the high incidence of structurally aberrant spermatozoa observed in our long-term study indicates that antitumoral treatments affect stem-cell spermatogonia and that aberrant cells can survive germinal selection and produce abnormal spermatozoa.

  6. Thermospheric density long-term trend at high latitude

    NASA Astrophysics Data System (ADS)

    Yamazaki, Yosuke; Kosch, Michael

    2016-07-01

    We present a novel technique that has been recently developed to estimate the thermospheric oxygen density using ionospheric measurements from EISCAT radars. The technique is based on an ion momentum equation, which takes into account the collisional interaction between neutrals and ions. We apply the technique to a 30-year long data set from the Tromso UHF radar, which for the first time allows us to evaluate the thermospheric density long-term trend at high latitude. The results are compared with the trend derived from satellite drag, which represents the long-term trend at lower latitudes.

  7. 18. Uniform cost accounting in long-term care.

    PubMed

    Sorensen, J E

    1976-05-01

    Uniform cost data are essential for managing health services, establishing billing and reimbursement rates, and measuring effectiveness and impact. Although it is especially difficult in the case of long-term health care to develop standard cost accounting procedures because of the varied configurations of inpatient, intermediate, and ambulatory services, the overall approaches to cost accounting and its content can be made more uniform. With this purpose in mind, a general model of cost accounting is presented for a multilevel program of long-term services, together with a special method for ambulatory services using "hours accounted for" as the basic measure. PMID:819732

  8. [Long-term-management of organ transplant recipients].

    PubMed

    Bürger, Christin; Schmidt, Martina; Maschmeier, Miriam; Stella, Jaqueline; Hüsing, Anna; Wilms, Christian; Schmidt, Hartmut Hans-Jürgen; Kabar, Iyad

    2016-07-01

    Due to advances in immunosuppressive therapy and surgical techniques, survival rates after solid organ transplantation have constantly improved over the last decades. In long-term care after transplantation, physicians need to focus as much on diagnosis and treatment of allograft-related complications as they should consider comorbidities and evaluate risk-factors and adverse events of immunosuppressive agents to prevent secondary diseases. In particular, cardiovascular and metabolic diseases, malignancy and infection play a major role in long-term survival. Therefore, screening of organ transplant recipients in regard to these complications and adverse events is a crucial part of follow up in these patients. PMID:27359310

  9. Long-term Outcomes in Youth with Diabetes Mellitus

    PubMed Central

    White, Neil H.

    2015-01-01

    Synopsis In this chapter, I will review the long-term outcomes and their precursors of type 1 diabetes (T1D) starting in youth. I will also contrast the changing incidence of these long-term complications as we have moved from the pre-DCCT to the post-DCCT standard of care and will review the emerging data related to complications in youth with type 2 diabetes (T2D). Finally, I will review the recent understanding related to the effects of diabetes on the brain and cognition. PMID:26210623

  10. Elder rights and the Long-Term Care Ombudsman Program.

    PubMed

    Netting, F E; Huber, R; Paton, R N; Kautz, J R

    1995-05-01

    Since 1975 the Long-Term Care Ombudsman Program has grown and developed under the Older Americans Act (OAA) of 1965. With the passage of the Older Americans Act Amendments of 1992, this program was combined with other advocacy functions and placed in Title VII--Vulnerable Elder Rights Protection Activities. This article provides a historical overview of the policy, programmatic, and research issues that surround OAA and explains the activities of ombudsmen in their local communities and the roles many social workers perform under the auspices of long-term care ombudsman programs.

  11. Long-term use of benzodiazepines and related drugs among community-dwelling individuals with and without Alzheimer's disease.

    PubMed

    Taipale, Heidi; Koponen, Marjaana; Tanskanen, Antti; Tolppanen, Anna-Maija; Tiihonen, Jari; Hartikainen, Sirpa

    2015-07-01

    The aim of this study was to investigate the prevalence of benzodiazepine and related drug (BZDR) use, especially long-term use, and associated factors among community-dwelling individuals with and without Alzheimer's disease (AD). We utilized data from the MEDALZ-2005 cohort, which includes all community-dwelling individuals diagnosed with AD in Finland at the end of 2005 and matched comparison individuals without AD. Register-based data included prescription drug purchases, comorbidities, and hospital discharge diagnoses. In this study, 24,966 individuals with AD and 24,985 individuals without AD were included. During the 4-year follow-up, we found that 45% (N = 11,312) of individuals with AD and 38% (N = 9534) of individuals without AD used BZDRs. The prevalence of long-term (≥ 180 days) BZDR use was more common among individuals with AD (30%) than individuals without AD (26%). The median durations of the first long-term use periods of BZDRs were 1.5 and 2 years for individuals with and without AD, respectively. Factors associated with long-term BZDR use included female sex, AD, schizophrenia, bipolar disorder, depression, coronary artery disease, and asthma/chronic obstructive pulmonary disease. The high prevalence of long-term BZDR use among individuals with AD is especially a cause for concern because long-term use may further impair cognition and may be associated with serious adverse events. PMID:26011780

  12. Dissociation of short- and long-term face memory: evidence from long-term recency effects in temporal lobe epilepsy.

    PubMed

    Bengner, T; Malina, T

    2007-07-01

    We tested whether memory deficits in temporal lobe epilepsy (TLE) are better described by a single- or dual-store memory model. To this aim, we analyzed the influence of TLE and proactive interference (PI) on immediate and 24-h long-term recency effects during face recognition in 16 healthy participants and 18 right and 21 left non-surgical TLE patients. PI in healthy participants or TLE erased the long-term recency effect, but left the immediate recency effect unaffected. Although the immediate recency effect was still visible in right TLE patients, the number of detected recency items during immediate recognition was decreased in right TLE compared to left TLE. Right TLE was also related to decreased detection of pre-recency items during delayed recognition compared to left TLE, and decreased detection of pre-recency items during immediate recognition under PI. The results show that the temporal lobes are necessary for the long-term recency effect, but not for the immediate recency effect, and thus speak for a dissociation of short- and long-term memory for faces. Right TLE is related to more severe long-term memory deficits than left TLE and is also related to additional short-term memory deficits for faces.

  13. 42 CFR 412.536 - Special payment provisions for long-term care hospitals and satellites of long-term care...

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... hospitals and satellites of long-term care hospitals that discharged Medicare patients admitted from a hospital not located in the same building or on the same campus as the long-term care hospital or satellite... payment provisions for long-term care hospitals and satellites of long-term care hospitals that...

  14. 42 CFR 412.536 - Special payment provisions for long-term care hospitals and satellites of long-term care...

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... hospitals and satellites of long-term care hospitals that discharged Medicare patients admitted from a hospital not located in the same building or on the same campus as the long-term care hospital or satellite... payment provisions for long-term care hospitals and satellites of long-term care hospitals that...

  15. 42 CFR 412.536 - Special payment provisions for long-term care hospitals and satellites of long-term care...

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... hospitals and satellites of long-term care hospitals that discharged Medicare patients admitted from a hospital not located in the same building or on the same campus as the long-term care hospital or satellite... payment provisions for long-term care hospitals and satellites of long-term care hospitals that...

  16. 42 CFR 412.536 - Special payment provisions for long-term care hospitals and satellites of long-term care...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... hospitals and satellites of long-term care hospitals that discharged Medicare patients admitted from a hospital not located in the same building or on the same campus as the long-term care hospital or satellite... payment provisions for long-term care hospitals and satellites of long-term care hospitals that...

  17. 42 CFR 412.536 - Special payment provisions for long-term care hospitals and satellites of long-term care...

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... hospitals and satellites of long-term care hospitals that discharged Medicare patients admitted from a hospital not located in the same building or on the same campus as the long-term care hospital or satellite... payment provisions for long-term care hospitals and satellites of long-term care hospitals that...

  18. Hippocampal long term memory: effect of the cholinergic system on local protein synthesis.

    PubMed

    Lana, Daniele; Cerbai, Francesca; Di Russo, Jacopo; Boscaro, Francesca; Giannetti, Ambra; Petkova-Kirova, Polina; Pugliese, Anna Maria; Giovannini, Maria Grazia

    2013-11-01

    The present study was aimed at establishing a link between the cholinergic system and the pathway of mTOR and its downstream effector p70S6K, likely actors in long term memory encoding. We performed in vivo behavioral experiments using the step down inhibitory avoidance test (IA) in adult Wistar rats to evaluate memory formation under different conditions, and immunohistochemistry on hippocampal slices to evaluate the level and the time-course of mTOR and p70S6K activation. We also examined the effect of RAPA, inhibitor of mTORC1 formation, and of the acetylcholine (ACh) muscarinic receptor antagonist scopolamine (SCOP) or ACh nicotinic receptor antagonist mecamylamine (MECA) on short and long term memory formation and on the functionality of the mTOR pathway. Acquisition test was performed 30 min after i.c.v. injection of RAPA, a time sufficient for the drug to diffuse to CA1 pyramidal neurons, as demonstrated by MALDI-TOF-TOF imaging. Recall test was performed 1 h, 4 h or 24 h after acquisition. To confirm our results we performed in vitro experiments on live hippocampal slices: we evaluated whether stimulation of the cholinergic system with the cholinergic receptor agonist carbachol (CCh) activated the mTOR pathway and whether the administration of the above-mentioned antagonists together with CCh could revert this activation. We found that (1) mTOR and p70S6K activation in the hippocampus were involved in long term memory formation; (2) RAPA administration caused inhibition of mTOR activation at 1 h and 4 h and of p70S6K activation at 4 h, and long term memory impairment at 24 h after acquisition; (3) scopolamine treatment caused short but not long term memory impairment with an early increase of mTOR/p70S6K activation at 1 h followed by stabilization at longer times; (4) mecamylamine plus scopolamine treatment caused short term memory impairment at 1 h and 4 h and reduced the scopolamine-induced increase of mTOR/p70S6K activation at 1 h and 4 h; (5

  19. Commitment and the Long-Term Marriage Relationship.

    ERIC Educational Resources Information Center

    Swensen, Clifford H.; Trahaug, Geir

    1985-01-01

    Examined the relationship of commitment in marriage and change in commitment over marriage to the expression of love and marriage problems among long-term Norwegian married couples. Results indicated that those who were committed to their spouses as persons had significantly fewer marriage problems. Those whose commitment increased expressed more…

  20. The Jornada Basin long term ecological research program

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Chihuahuan Desert landscapes exemplify the ecological conditions, vulnerability, and management challenges in arid and semi-arid regions around the world. The goal of the Jornada Basin Long Term Ecological Research program (JRN LTER) established in 1982 is to understand and quantify the key factors ...